PREPARING FOR THE MBBS | CHAPTER FOUR

Medicine Long Cases

the clinical questions approach

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MEDICINE LONG CASES: THE CLINICAL QUESTIONS APPROACH CONTENTS

Contents

Overall Strategy 234

Cardiology:
ADULT Atrial Fibrillation 239
PAEDS Congenital Heart Disease 241
ADULT Heart Failure 244
ADULT Ischaemic Heart Disease 248

Dermatology:
ADULT & PAEDS Psoriasis 252

Endocrinology:
ADULT & PAEDS Cushing’s Syndrome 254
ADULT & PAEDS Diabetes 256
ADULT & PAEDS Graves’ Disease 260

Gastroenterology:
PAEDS Biliary Atresia 263
ADULT Chronic Hepatitis 265
ADULT & PAEDS Liver Cirrhosis 269
ADULT & PAEDS Inflammatory Bowel Disease 272

Genetics:
PAEDS The Syndromic Child 276

Haematology:
PAEDS Hemophilia 281
ADULT & PAEDS Idiopathic Thrombocytopenic Purpura 283
PAEDS Thalassaemia 285

Infectious Diseases:
ADULT Tuberculosis 289
ADULT HIV 292
ADULT & PAEDS Infective Endocarditis 296

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MEDICINE LONG CASES: THE CLINICAL QUESTIONS APPROACH CONTENTS

Neurology:
ADULT Acute Stroke 300
PAEDS Cerebral Palsy 305
ADULT & PAEDS Headache & Migraine 307
ADULT Multiple Sclerosis 312
PAEDS Muscular Dystrophy 315
ADULT & PAEDS Myasthenia Gravis 317
ADULT Parkinsons’ Disease 320
ADULT & PAEDS Seizure, First Seizure 324
ADULT & PAEDS Seizure, Epilepsy 327
PAEDS Spina Bifida 329
PAEDS Spinal Muscular Atrophy 332

Renal Medicine:
ADULT & PAEDS Chronic Kidney Disease & ESRF 335
ADULT & PAEDS Nephrotic Syndrome 340

Respiratory Medicine:
ADULT & PAEDS Asthma 342
ADULT & PAEDS Bronchiectasis 346
ADULT Chronic Obstructive Pulmonary Disease 349

Rheumatology:
ADULT Gout 352
PAEDS Henoch-Schonlein Purpura 356
PAEDS Juvenile Idiopathic Arthritis 358
ADULT Rheumatoid Arthritis 360
ADULT & PAEDS Systemic Lupus Erythematosus 363

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MEDICINE LONG CASES: THE CLINICAL QUESTIONS APPROACH STRATEGY

Strategy
What are medical long cases like? 25 minutes for history and examination, 2 minutes for
consolidation, and 10 minutes for presentation and discussion. 2 examiners are present
throughout. This seems to be designed to reflect an outpatient consultation of a chronic
condition, although you can at times get acute conditions / inpatients. 80% of cases are adult
and 20% are paediatric.

Examiners want you to:

• Identify the issues and formulate a problem list
• Assess each issue in terms of etiology – complications – management – control.
• If there is a new issue (diagnostic cases), demonstrate a sound approach to arrive at
diagnosis and differentials.
• Have a holistic approach: not only deal with medical issues, but also how these have
impacted the patient functionally and socially. You should be interested in the patient’s
life, delving deep into social, financial emotional, and psychological aspects.
• Consider interactions between issues: e.g. disease-disease, drug-drug, drug-disease
interactions, how disease affects patient, and how patient / environment affects
disease.
• Presentation: give problem list and your assessment of each problem, instead of
presenting the entire history.
• Discuss your management plan, tailored to this patient’s problems and unique
circumstances. You should show awareness of community resources and strategies
to deal with the social problems.

Your strategy: Medical patients often have multiple problems (some acute, some chronic),
multiple interactions between issues, and a complex social history. Unlike the surgical long
case, the focus is on managing this patient (and his/her multiple issues) as a whole as you
would in a clinic consult, rather than going in depth into one specific acute problem. You will
need to deal with whatever the patient throws at you – a new complaint (whether related or
not to old issues), follow-up management of chronic issues (which may be very well controlled
or a total wreck), complications of existing issues or medications, specific concerns and
worries, and social issues, or a combination of the above. It should be apparent by now that
the medical long case requires an organized thought process to sort out the issues, the mental
flexibility to multitask, and a good deal of clinical acumen. Note:

• The twin exhortations discussed in the surgical long cases – to be comfortable with
clerking real patients, and to think through cases you have seen – are just as important
here. Please refer to the surgical long case strategy for that discussion.

• This chapter should be read with Approaches to Symptoms of Disease. Approaches

takes you from presentation to diagnosis, while this chapter takes you from diagnosis
to assessment and management.

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MEDICINE LONG CASES: THE CLINICAL QUESTIONS APPROACH STRATEGY

A suggested toolbox to deal with the medicine long case is as follows:

1: CORRECTLY IDENTIFY THE CLINICAL PROBLEM

This is a necessary to proceed. Be aware that an ‘issue’ may reflect different clinical problems.
For example, a patient with seizure might be (1) a first seizure, or a (2) known epileptic with
breakthrough seizures. The management tasks are very different: in (1), the goal is to look
hard for precipitating causes, in (2) the goal is antiepileptic drug titration.

2: FOR A NEW COMPLAINT, THINK THROUGH DIFFERENTIALS

Think in terms of ddx related to existing issues, or entirely unrelated. See the separate notes
on Approaches to Symptoms of Disease. When you have shortlisted differentials, think
through by filling in this table –

Differential What is in favour? What is against? What is expected What other info do
but absent? I need?

Ddx #1

Ddx #2

3: FOR A CHRONIC ISSUE: APPLY A ‘CLINICAL QUESTIONS’ APPROACH

Aim: this is a tool to assess a chronic issue, identify management tasks (‘what do I have to
do for this patient today’), and improve holistic management (‘how can we do better’).

Basic premise: each chronic issue can be broken down into a series of clinical questions
(generally a variation of etiology – severity – complications – management tasks). For
example, COPD can be considered in terms of –
1. Is the diagnosis COPD?
2. What is the COPD stage?
3. What is the risk and history of exacerbations, and how is this mitigated?
4. What are the baseline symptoms and how are these managed?
5. Are there any complications and how are these managed?
6. How is the patient’s general health and comorbids?
7. How is the patient coping in general?

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Using the clinical questions approach: As you go through history / examination /

investigations / management, think through each question in turn. For example,
• On history: (1) clarify the symptomology and rule out asthma, (3) explore previous
admissions, (4) ask about baseline oxygenation, functional status, (5) screen for red
flags of lung cancer, and so on.
• Investigations: spirometry for (1) diagnosis and (2) staging, rule out (5) pneumothorax
in acute exacerbation
• Management: (2) consider GOLD guideline, (3) strategies to prevent exacerbations
e.g. inhaled steroid, vaccinations, (4) symptomatic management including smoking
cessation, bronchodilation, etc.

Benefit of this approach: We begin with the premise that every patient is very different and
has to be carefully assessed (e.g. the well-controlled diabetic on OHGA is vastly different from
the diabetic with ESRF and amputations). We have found this approach incredibly helpful in
dissecting complex issues into simple questions, allowing comprehensive assessment of each
patient without remembering checklists, making necessary investigations and management
plans obvious, and even allowing identification of gaps in management so that they can be
improved.

In this notes: This set of notes is organized along this ‘clinical questions’ approach, which will
become clearer as you use these notes. Rather than learn separate adult and paediatric
approaches, we have as far as possible integrated the adult and pediatric questions, and
highlighted how they differ. The range of possible medicine/paediatric cases is wide and we
cover perhaps 70-80% of the possible issues (but you can get combinations and variations of
these issues).

4: SUMMARIZE ISSUES AND PRESENT – A WORKED EXAMPLE

The history you take:

Mr Akbar is a 49 year old Indian gentleman with a background of Child's C alcoholic cirrhosis,
recently admitted for hematemesis and discharged 2 weeks ago.

He had been well for 1 week on discharge but now presents with a 1-week history of altered
mental status, manifesting as increased lethargy and difficulty expressing himself. Given the
background of Child C cirrhosis the first thought would be hepatic encephalopathy, but pure
aphasia with alertness is not typical for hepatic encephalopathy. There are no neurological
deficits on history or physical examination, and there are no infective symptoms. In terms of
possible precipitants for hepatic encephalopathy, I do not note any malena, hematemesis,
recent alcohol ingestion, constipation, or new medications.

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In terms of his background of cirrhosis, this was diagnosed 1 year ago when he presented
with lower limb edema. This is most likely alcoholic on the basis of significant alcohol
consumption and negative tests or family history of hepatitis. He has never had a liver biopsy,
which I would expect if other etiologies such as autoimmune hepatitis were suspected.

In terms of complications, he has had 2 admissions for symptomatic ascites requiring tapping,
1 admission for hematemesis requiring intubation, status post endoscopic variceal ligation. He
does not have other bleeding symptoms.

Otherwise he has very good social support.

The examination you do:

Examination was remarkable for stigmata of chronic liver disease such as shifting dullness,
loss of axillary hair, telangiectasia. There was also an umbilical hernia. Although distended,
abdomen was non-tender; i expect splenomegaly but was not able to palpate for the spleen
through the ascites. There was no asterixes and the patient was alert although he has
expressive aphasia. I did not note any focal neurological deficit or lateralizing sign. There is
no ataxia or opthalmoplegia to suggest Wernicke's. The patient is eating french fries at the
bedside in spite of a distended abdomen. I would like to complete my examination with digital
rectal exam looking for malena or hard impacted faeces.

What you actually present:

Sir, presenting Mr Akbar, a 49 year old Indian gentleman with Child’s C alcoholic cirrhosis and
complications of variceal bleeding requiring ICU stay, as well as symptomatic ascites, who
now presents a 1-week history of altered mental state. My main issues are:
1. Altered mental state - possibly decompensated cirrhosis but need to rule out structural
lesion of left cortical region as it may be an aphasia.
2. Child C's cirrhosis cx ascites and hematemesis
3. Poor compliance to salt restriction as evidenced by eating french fries

Investigations include:
1. Rule out ddx for altered mental state (septic w/u for infection, CT or MRI brain for CVA,
electrolytes, glucose for hypoglycaemia); LFT to trend, ammonia. If he later develops
abdo pain to do ascitic tap for spontaneous bacterial peritonitis.
2. Also to look for precipitant for hepatic encephalopathy - ensure no drop in Hb to
suggest BGIT, consider AFP and liver US to rule out interval development of HCC,
unless these were very recently done. GGT & MCV for evidence of continued alcohol
ingestion
3. Child's C alcoholic cirrhosis: hep B/C unless already done, look for other complications
(platelets, creatinine, PT/PTT)

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My management includes
1. For AMS: If no reversible ppt found, to manage as for hepatic encephalopathy, give
lots of lactulose, ensure BO 2x a day. Consider thiamine and benzodiazepine if any
suspicion that he is still drinking. Put on CIWA charting to watch for delirium tremens.
2. For Child C alcoholic cirrhosis, ascites and varices: need to ensure pt stopped alcohol,
consider pharmacotherapy for alcohol use disorder if pt has not stopped alcohol, and
vaccinate against hep A/B. Treat complicaitons - may need re-scope to ensure all
varices banded, propanolol to reduce portal pressures, spironolactone and furosemide
for ascites. Consideration can be given to liver transplant.
3. Noncompliance to salt restriction: need to counsel, find out ideas and expectations.
Good social support so need to explain the purpose of salt restriction especially when
he has had two ascitic taps.

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MEDICINE LONG CASES: THE CLINICAL QUESTIONS APPROACH CARDIO: ATRIAL FIBRILLATION

MEDICAL LONG CASES

Cardio: Atrial Fibrillation

ADULTS
Atrial fibrillation is less commonly a standalone case (palpitations), than part of another case
(e.g. stroke, valvular heart disease, ischaemic heart disease, cardiac failure, thyrotoxicosis)

Is this atrial fibrillation?

! In most cases quite a straightforward diagnosis once you palpate an irregularly
irregular pulse or have the ECG
! To look for paroxysmal AF (not an innocent disease) → do 24h Holter
! For the patient complaining of palpitations → see approaches notes

What is the etiology of AF?

! Explore the cardiac status on hx, examination, and inx.
○ Ischaemic heart disease → symptoms, 2DE for SWMA
○ Valvular heart disease → Auscultate for murmurs, do 2DE. This changes
management.
○ Cardiac failure → symptoms, 2DE, NTBNP
○ Recent cardiac surgery.
! Systemic disease: thyroid, sepsis, pulmonary problems
○ If recent onset, look for any precipitant.
○ Do CXR, TFT, septic workup

What is this AF causing?

! Symptoms: palpitations, poor effort tolerance
! Complications e.g. stroke

Do I do rate or rhythm control?

! Choice between rate and rhythm control: similar morbidity and mortality, rhythm control
better exercise tolerance for young patients
! Rhythm control: if attempting cardioversion and AF >48h be sure not to cause a stroke
-- need transesophageal echo to look for LA thrombus, or at least 3 weeks of
anticoagulation before attempting.
○ Electrical: more effective but requires sedation
○ Pharmacological: e.g. flecainide, procainamide (amiodarone less effective)
○ Give maintenance Rx (don’t cardiovert and send home - some recur)

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! If rate control: is the patient in heart failure?

○ Heart failure: digoxin (less effective), amiodarone (risk cardioversion)
○ No heart failure: beta-blockade (beware asthma), verapamil/diltiazam
○ Please make sure there is no Wolff-Parkinson-White before using AV nodal
blockers (beta blocker, CCB, digoxin; caution in amiodarone)
! If drugs fail and symptomatic → consider catheter ablation therapy.
! Complications:
○ E.g. for amiodarone: lung toxicity, thyroid status, liver toxicity, gynaecomastia,
photosensitivity, GI side effect
○ All drugs: monitor ECG (brady, QTc prolongation, arrhythmia), electrolytes

Do I need to anticoagulate, and how?

! Anticoagulation is a cornerstone of stroke prevention
! Initiating: decide based on the clinical judgement of risk vs benefit
○ Stroke risk - CHADS-VASc scoring: CCF, HTN, Age (75+: 2 pts, 60-75: 1 pt),
DM, past Stroke/TIA (2pt), Vascular disease (AMI, PVD), Sex Cat (female 1pt)
○ Bleed risk - HASBLED scoring: HTN, Abnormal renal/liver function (1pt each),
Stroke, Bleeding, Labile INR, Elderly (>65), Drugs/alcohol (1pt each)
! What anticoagulation to use?
○ Aspirin usually not preferred, consider if CHADS-VASc 0-1 or refuse warfarin.
○ Warfarin is 1st line → discuss with patient
○ NOACs: apixaban, dabigatran, rivoxaban → more convenient and no need to
monitor but has issues (not for valvular AF, more expensive, no reversal agent)
! Monitoring; how is the patient coping
○ Any bleeding
○ Is INR on target (2-3)? Is it labile?
○ Lifestyle: frequent blood test, food and drug interaction → explore patient
knowledge of disease, awareness to tell any GP

What are the comorbids

! AF is rarely the lone disease → Manage the comorbids as well
! Consider drug drug and drug disease interactions esp if patient is on warfarin.

How is the patient coping?

! Function
! Social
! Financial

Sample summary: see heart failure

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MEDICINE LONG CASES: THE CLINICAL QUESTIONS APPROACH CARDIO: CONGENITAL HEART DISEASE

MEDICAL LONG CASES

Cardio: Congenital Heart Disease

PAEDIATRICS

What congenital heart disease is this; how did the child present?
! May be picked up in the neonatal period e.g. cyanosis from birth in ToF.
! Worsening cyanosis and breathless at day 2 of life characterises a duct dependent
circulation (e.g. TGA, tricuspid atresia without VSD, hypoplastic left heart). In these
conditions, mixing of pulmonary and systemic circulations through the ductus
arteriosus is critical to sustain life, physiological closure at day 2 of life causes
worsening symptoms.
! Hypotension, poor feeding developing in first 2 weeks characterises defects like CoA
(where defect is present at birth and exacerbated once ductus arteriosus closes).
! Symptoms of heart failure (dyspnoea, fluid overload) developing at 2 months
characterises a large L > R shunt (e.g. VSD, PDA); at birth, high pulmonary pressures
cause little shunting, it is only when pulmonary pressures fall that shunting occurs and
symptoms develop.
! Mild disease (e.g. VSD, AS, PDA) may be asymptomatic and/or present with an
incidental murmur.

Presentation Anatomy Examples

Cyanotic, not breathless R > L shunt - Tetralogy of Fallot: Overriding aorta, PS, RV
> Cyanosis may not be visible, hypertrophy, VSD.
but SpO2 low. - Pulmonary atresia with hypoplastic RV and
VSD.
- Hypoplastic left heart (RV supplies aorta)

Cyanotic, breathless Common - Transposition of great arteries (TGA)

mixing - Complete AVSD / single ventricle

Acyanotic, not breathless Outflow - AS

> Severe: hypotension obstruction - Coarctation of aorta
> Moderate: syncope - Totally anomalous pulmonary venous return
> Mild: asymptomatic with pulm outflow obstruction

Acyanotic, breathless L > R shunt - ASD

> Severe: dyspnoea - VSD
> Mild: asymptomatic - PDA

Please also refer to the table in Medical Short Case > Cardiovascular System (paediatric)

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How was diagnosis confirmed?

! ECG: e.g. RVH in ToF
! CXR: e.g. boot shaped heart in ToF, evidence of CCF, LV hypertrophy
! 2DE
! Cardiac catheterization study

Is there any associated syndrome

! Down’s
! VACTERL → ask if there are other Vertebral, Anorectal, (Cardiac), Tracheo-
esophageal, Renal, and Limb abnormalities

Clinical course & management to date

! Infants with cyanotic heart disease receive extensive neonatal care and may have
prolonged NICU care. Duct dependent circulation requires prostaglandin to maintain
ductus arteriosus patency.
! Surgical repair may be performed in infancy e.g. TGA (arterial switch), severe CoA
! Surgical repair may also be performed later e.g. AS/PS, CoA, VSD/ASD, specific
operations for right heart disease
! Surgery for right heart disease (pulmonary flow obstruction or hypoplastic RV) is often
a staged procedure e.g.
○ Blalock-Taussig shunt: subclavian > pulmonary artery (can be done 2x, one on
each side)
○ Hemi-Fontan: SVC to PA
○ Fontan completion: IVC to PA.
! Minimally invasive methods are sometimes used e.g. device closure (e.g. VSD, ASD),
balloon valvuloplasy (AS, PS), coil embolization (PDA)

Current issues

(1) CCF
! Are there still symptoms of CCF: shortness of breath, fluid overload.
! Management: fluid restrict, diuretics, digoxin -- how effective have these been?

(2) Is there pulmonary hypertension?

! Can contribute to SOB, lethargy
! If left to right shunt > is Eisenmenger’s threatened? → Eisenmenger means that
closure can no longer be attempted and prognosis is limited.

(3) Growth and development

! Infants: feeding difficulties in infancy are common and may result in failure to thrive.
! Children: may have poor growth, missed milestones.

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Further issues in cyanotic heart diseases:

(4) Endocarditis & prophylaxis

! Incompletely repaired cyanotic heart disease may require Abx prophylaxis

(5) Cyanosis and hypoxia

! Tet spells in ToF: restless, agitated, squat. RVOT spasm worsens obstruction and
worsens shunt, causing hypoxia.

(6) R > L embolism in R > L shunts

! Cerebral thromboembolism
! Cerebral abscesses.

Prognosis and support

! Children with cyanotic heart disease often have a stormy course with multiple
surgeries, multiple hospitalizations. How is the family coping with this?
! Explore social setup and financial situation.
! If child is of childcare age or beyond, explore coping in school environment; daily
activity.

Sample summary: Valentine is a 2 year old girl with congenital cyanotic heart disease, noted
to be cyanosed and increasingly breathless on day 2-3 of life which improved with
prostaglandin, status post bilateral blalock taussig shunt. She is currently admitted for
decompensated congestive cardiac failure secondary to fever for investigation to rule out
infective endocarditis. I note that she is failing to thrive, being at the 1st percentile for both
height and weight, and that she has isolated gross motor delay. Her fever has responded to
empiric broad spectrum antibiotics, and her dyspnea has improved with diuretics so that she
was able to take feeds orally today. Plan now is to continue current management, arrange for
2DE and dietician review today, and await results of full septic workup.

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MEDICINE LONG CASES: THE CLINICAL QUESTIONS APPROACH CARDIO: HEART FAILURE

MEDICAL LONG CASES

Cardio: Heart Failure

ADULTS

Is this heart failure?

! Presentation of heart failure (forward failure: low output, backward failure: congestion)
varies according to its etiology and time course:
○ Acute presentation: an acute cardiac event (e.g. AMI, acute valve regurgitation,
arrhythmia, hypertensive emergency) may result in hypotension, pulmonary
edema, fluid overload.
○ Subacute presentation: mainly exertional dyspnoea, paroxysmal nocturnal
dyspnoea, orthopnoea.
○ Chronic presentation: fluid overload presentation, fatigue
! Each presentation requires that differentials are excluded-
○ Acute hypotension → consider other causes of shock (hypovolaemic,
haemorrhagic, septic, anaphylatic, PE, etc).
○ Shortness of breath → consider respiratory disease (COPD, interstitial lung
disease), anaemia
○ Fluid overload → consider renal disease (ESRF, nephrotic syndrome), cirrhosis
! There is no single diagnostic test; diagnosis is made on the cluster of symptoms
(dyspnoea, fatigue), signs (fluid overload, hypoperfusion), and evidence of cardiac
dysfunction (e.g. NT-proBNP, 2DE, CXR)

How bad is this patient’s heart failure?

! NYHA class: what is the extent of the patient’s symptoms?
○ Class 1: no SOB on ordinary activity
○ Class 2: SOB on ordinary activity (e.g. housework, walking to bus stop)
○ Class 3: SOB on less than ordinary activity (e.g. bathing, eating)
○ Class 4: SOB at rest
! Latest 2DE -- what is the ejection fraction?
○ Some patients may have heart failure with preserved ejection fraction (≥50%)
-- diastolic heart failure.
! Time course of exacerbations
○ How severe → requiring admission, ICU?
○ What was the exacerbation like? Conceptually think of the acute hemodynamic
state as an intersection of cardiac output and fluid overload:

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Minimal fluid overload Fluid overloaded

- Well compensated - Pulm congestion

Good cardiac output Warm and Dry Warm and Wet

> Good BP > Continue current Mx > Diuresis
> Peripheries perfused > Vasodilators e.g. nitrates

Poor cardiac output Cold and Dry Cold and Wet

> Low BP > Fluids (judiciously) > Diuresis +/- nitrates
> AKI, cold peripheries > Inotropes > Peripheries perfused
> Inotropes eg dobutamine

What are my clinical tasks:

(1) Identify etiology of heart failure → and treat.

! This may be obvious clinically or require workup; may be multifactorial.
! Ischaemic heart disease and its risk factors
○ This may be apparent from history (previous AMI, PCI, CABG) or symptoms
(angina)
○ Nonetheless all patients should be worked up for IHD (ECG, echo, stress test),
and screen for underlying risk factors (fasting glucose, lipids, BP)
○ Any IHD should be treated: antiplatelet, statin [see topic on IHD]
○ Modify risk factors aggressively: stop smoking, lose weight, control sugars, BP
! Valvular heart disease
○ Assessment: 2DE, cardiac MRI
○ Treatment specific to valve: heart failure is often an indication for definitive rx
e.g. surgery [see topic on valve dysfunction]
! Arrhythmias
○ Assess ECG
○ Treat if any present e.g. atrial fibrillation → rate vs rhythm control +
anticoagulation [see topic on AF]
! Hypertensive heart disease → hypertension increases afterload on the failing ventricle
○ Treat hypertension using evidence-based drugs: ACE-I, beta blocker,
aldosterone antagonist (see (3))
○ Consider workup for secondary causes (especially young patient) [see topic on
hypertension]
! Thyroid heart disease
○ Measure T4/TSH
○ Treat if present [see topic on Graves’ disease]
! Others: cardiomyopathies, infiltrative disease (amyloidosis, hemochromatosis), drugs
(e.g. doxorubicin), infection (myocarditis, HIV)

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(2) Relieve symptoms and maximise function

! In addition to NYHA class, evaluate function -- of great importance to quality of life.
! Nonpharmacological
○ Dietary modification: salt and fluid restriction, plus as appropriate for risk factor
(e.g. DM diet, low fat). Monitor weight
○ Exercise → Does the patient exercise? If no, explore why e.g. fear of cardiac
event. Consider formal cardiac rehabilitation programmes
! Pharmacological - initiate carefully and titrate:
○ 1st line -- Furosemide → check K, postural BP, fall risk
○ Digoxin if (1) still symptomatic despite optimal diuresis, ACE-I, beta blocker,
and aldosterone antagonist, or (2) AF with inadequate rate control despite beta
blockade
! If the patient has exceptionally poor response → re-evaluate diagnosis of heart failure.

(3) Inhibit cardiac remodelling and reduce risk.

! Activated neurohormonal mechanisms initially maintain cardiac output by increasing
filling pressures, however, in the chronic state, they cause detrimental remodelling
! Pharmacological therapy for heart failure with reduced EF (not evidence based for
preserved EF) - initiate carefully and titrate:
○ ACE-inhibition or ARB: beware renal artery stenosis, monitor for hyperkalemia
○ Beta blocker: use an evidence based beta blocker e.g. carvedilol metoprolol
bisoprolol, beware initial worsening of symptoms and asthma
○ Aldosterone antagonist e.g. spironolactone (evidence if NYHA 2 EF ≤30%,
NYHA 3-4 EF <35%, or previous STEMI EF ≤40%), monitor for hyperkalemia
○ Additional drugs in certain situations: ivabradine
! Device therapy:
○ Cardiac resynchronization therapy (biventricular pacing): improves survival in
patients who are still NYHA class 3-4 despite maximal medical rx
○ Automated implanted cardioverter-defibrillator: as secondary prevention
(survivors of sudden cardiac arrest) and as primary prevention in certain cases
(very poor EF, hx of dangerous arrhythmia).

(4) Prevent exacerbations

! Explore the precipitants for previous exacerbations
○ New cardiac insult: ischaemia, arrhythmia
○ Non-cardiac disease: renal disease, infection
○ Noncompliance to fluid restriction or medication: hypertension, fluid overload.
! Address precipitant accordingly e.g.
○ Immunizations
! Avoid drugs that worsen heart failure: NSAIDs, thiazolidinediones, metformin if eGFR
≤30

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(5) Treat comorbids and medication issues

! Heart failure patients are often older, with multiple medical problems and
polypharmacy; a holistic multidisciplinary approach is particularly crucial
! Explore medication compliance and motivation → if not compliant, why?
! Explore medication side effects e.g. postural hypotension, falls
! Be wary of disease-disease, drug-disease, drug-drug interactions. Red flags:
○ Interactions with warfarin
○ Drugs acting on potassium levels
○ Nitrates and sildenafil

How is this affecting the patient?

! Ability to stay employed or engage in leisure activity
! Social interaction
! Psychological: medications, uncertainty of prognosis, activity and diet restrictions often
take a toll
! Financial

Sample summary: Mdm Poh Xin Men is a 85 year old lady with NYHA II congestive cardiac
failure secondary to severe mitral stenosis and atrial fibrillation on a background of rheumatic
heart disease. She has had innumerable admissions for decompensated CCF over past 15-
20 years, usually precipitated by intercurrent illnesses or non-adherence to salt and fluid
restriction. Her latest ejection fraction is 25%. She is already on best medical therapy
(furosemide for symptoms; ACE-I, beta blockers and spironolactone to prevent disease
remodelling; beta blockers for rate control of AF and warfarin for anticoagulation) and has
already previously decided she does not want to go for mitral valve replacement. She is ADL-
independent and able to take her own medicines, but is mostly home bound. She stays with
her daughter and son-in-law, both of whom dote on her and support her financially. My issues
for her are:
(1) Decompensated CCF
(2) Severe mitral stenosis complicated by AF
(3) B/g rheumatic heart disease
(4) Non compliance to salt and water restriction

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MEDICAL LONG CASES

Cardio: Ischaemic Heart Disease

ADULTS

Where in the spectrum of IHD is this patient?

! IHD rears its head in many ways - it is crucial to accurately understand this patient’s
disease because management tasks are drastically different in each:
! Which chest pain syndrome does the patient have?
○ Stable Angina: episodic chest pain triggered by exertion, relieved with 3-5min
of rest or sublingual nitrates → Continue chronic Mx.
○ Unstable Angina: increasingly severe angina (more severe, more frequent,
takes less to precipitate), angina at rest, or new-onset angina → This portends
a coming AMI so Investigate and treat intensely.
○ Acute coronary syndrome: acute chest pain, worse than usual angina, lasting
>30min, with dyspnoea, diaphoresis, vomiting. This includes unstable angina,
NSTEMI, and STEMI → See acute management.
! What is this patient’s cardiac history?
○ Previous episodes of AMI
○ Previous coronary intervention → Stent or bypass can still thrombose!
○ Previous episodes of dangerous arrhythmias, collapse (e.g. VT, VF)

What is the patient’s cardiac status and complications?

! Functional status and change over time.
! Heart failure: any symptoms (dyspnoea, LL swelling), what is latest EF? (see heart
failure section)
! Arrhythmias: e.g. atrial fibrillation
! What are the latest investigations
○ Imaging: echocardiography, MRI/MIBI
○ Stress testing: treadmill ECG vs stress echo (exercise or pharmacological)

How can I optimise this patient’s cardiac status?

! Goal of therapy in stable IHD: alleviate symptoms, prevent progression, decrease the
risk of adverse outcomes (death, AMI, heart failure)

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(1) Symptomatic relief

! 1st line -- Beta blockers, preferring cardioselective agents (metoprolol, atenolol)
○ Evidence-based to improve survival post-MI
○ Cautions: asthma, heart failure, bradycardia or heart block.
○ Safe in DM, amiodarone use
! 2nd line -- calcium channel blockers, if beta blocker unsuccessful, or contraindicated,
or not tolerated (diltiazem, verapamil, amlodipine; avoid nifedipine
! Nitrates -- 1st line for acute angina (GTN), 2nd line as add on chronic therapy to beta
blockers (isosorbide dinitrite, transdermal nitroglycerin)
○ Avoid in right ventricular MI
○ Please make sure patient does not take sildenafil

(2) Risk factor modification

! Assess for and modify cardiac risk factors
! Low-hanging fruits:
○ Smoking → Stop smoking, refer to cessation clinics
○ Obesity → Lose weight
○ Diet → Reduce salt, reduce fat, reduce sugar.
○ Sedentary lifestyle → Exercise prescription, refer cardiac rehab
○ Hyperlipidemia → Invasive statins regardless of LDL levels
! DM → Screen and treat; see DM text
! Hypertension
○ Look for secondary cause, especially if young patient: renal artery stenosis
(renal artery doppler), GN or CKD (UECr), Conn’s syndrome (UECr for hypoK),
Cushing syndrome (look), obstructive sleep apnoea (ask), coarctation of aorta
(measure 4 limb BP).
○ Watch for fragile patients → those prone to postural hypotension and falls, as
well as those who tend to present with hypertensive urgency (or emergency
e.g. CVA, dissection, AKI, retinopathy)
○ Patients who have had an MI should receive ACE-I and beta blocker regardless
of BP control

(3) Secondary prevention

! 1st line -- Aspirin 100mg OM + omeprazole cover
! Clopidogrel if allergic to aspirin.

(4) Revascularization
! May be performed in acute setting -- NSTEMI, STEMI
! Elective revascularization in -
○ Activity limiting angina despite best medical therapy
○ High risk lesion (likely survival benefit from revascularization): left main
disease, triple vessel disease, two vessel disease with severe LAD stenosis
○ Active patients who prefer revascularization for improved quality of life
compared to medical therapy

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! Options: PCI vs CABG

○ PCI: single vessel disease involving the right or circumflex coronary arteries,
short segment, anatomically feasible for PCI.
○ CABG: triple vessel disease, left main disease, two vessel disease with severe
proximal LAD stenosis
! After revascularization give dual antiplatelet therapy: e.g. 1 year (drug eluting stent) or
3 months (bare metal stent), thereafter single antiplatelet. (although latest evidence
suggests DAPT is for life).

(5) Treat comorbidities and complications

! Treat heart failure (see heart failure) → very often the same drugs above
! Treat arrhythmias e.g. AF (see AF)
! Other comorbidities

How is the patient affecting the disease?

! Worth exploring patient perceptions about disease
! Consider compliance to lifestyle and pharmacological measures.

How is the disease affecting the patient?

! ADL, ambulation status - has it been deteriorating? Is this affecting his function?
! Psychologically, how is the patient dealing?
○ Patient’s understanding and attitude towards condition is important as this
influences patient motivation to participate in rehabilitation AND control control
cardiovascular risk factors
! Social support?
! Financial support?

Sample summary: Ee Li Fen is a 70 year old retiree who presents with episodic chest pain
which worsened in frequency and severity over 2 months. She was diagnosed to have
unstable angina and received percutaneous coronary intervention a week ago, after which
she has been symptom-free. She had no prior past medical history but on workup was found
to be hypertensive and diabetic; otherwise she has no peripheral vascular disease, strokes;
her renal function is normal and she is not proteinuric; she does not have peripheral
neuropathy; she also has no symptoms of exertional dyspnoea or pedal edema. She is on
long-term aspirin, bisoprolol, losartan, metformin, glipizide, and atorvastatin. Functionally she
is now symptom free and has no functional limitation. She has good social support.

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Appendix: acute management of acute coronary syndrome

Immediate Management
! Assess ABC, attach cardiac and oxygen saturation monitors, give supplemental
oxygen as needed to keep SpO2 >90%, ensure IV access
! Obtain 12 lead ECG within 10min of arrival, repeat 10-15min if initial ECG
nondiagnostic but clinical suspicion high
○ Treat sustained ventricular arrhythmias according to ACLS
! Send bloods: cardiac enzymes, RP, FBC, PT/PTT
! Load aspirin 300mg, chewed and swallowed (unless aortic dissection is being
considered)
! Give sublingual GTN tablets (0.4mg tablet every 5 min x3) or spray (one spray every
5 min x3) for relief of acute angina
○ If patient has persistent chest discomfort, hypertension, signs of heart failure
○ And if NO right ventricular infarction on ECG, no hemodynamic compromise
! STAT dose of atorvastatin 80mg preferably before PCI
! Give cardioselective beta blocker (PO metoprolol 25mg)
○ If no signs of heart failure, no bradycardia, no hemodynamic compromise, or
severe reactive airway disease
! Give morphine for persistent pain (2-4mg slow IV push every 5-15min)

Definitive Management

(A) STEMI
! Decide if patient is for revascularization
○ Percutaneous coronary intervention within 90 minutes (door to balloon
time)
○ IV thrombolysis within 12 hours of symptoms
! Oral antiplatelet therapy for all patients
○ Prasugrel 60mg stat, 10mg OM continue for 3/12
- Age <75, BW60kg, no prior CVA, TIA, ICH
○ Clopidogrel 600mg stat, 75mg om continue for 1 year
- Age >75, BW <60, prior CVA, TIA, ICH

! Anticoagulation therapy for all patients

(B) NSTEMI/Unstable angina

! Decide if patient is for early revascularization (cath within 48 hours)
! Oral antiplatelet therapy for all patients
○ If patient is for early cath: Ticagrelor 180mg stat, 90mg BD continue
ticagrelor 90mg BD x 1 year (for raised CE (high risk), no prior CVA TIA
or ICH)
○ If patient is NOT for early cath: Clopidogrel 600mg stat, 75mg om
continue for 1 year (for Negative CEs (low risk), no prior CVA TIA ICH)
! Anticoagulation therapy for all patients: SC clexane 1.5mg/kg

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MEDICINE LONG CASES: THE CLINICAL QUESTIONS APPROACH DERM: PSORIASIS

MEDICAL LONG CASES

Derm: Psoriasis

ADULTS & PAEDIATRICS

Is this psoriasis?
! Describe and delineate the extent & distribution of skin lesions
! Classic description: erythematous papules or plaques with silvery scales, classically
affecting scalp, elbows, knees, back, usually in a rather symmetrical distribution.
Positive auspitz sign (removal of scales reveals small bleeding points) and
demonstrates Koebner phenomenon (skin trauma aggravates lesions).
! Identify the subtype and consider ddx.
○ Chronic plaque psoriasis: ddx discoid eczema, tinea corporis (offer to scrape)
○ Erythrodermic psoriasis:ddx eczemas, drug eruption, cutaneous lymphoma
○ Guttate psoriasis: ddx pityriasis rosea, secondary syphillis
○ Palms and soles psoriasis: ddx hand/feet eczema
○ Scalp psoriasis: ddx seborrheic dermatitis
○ Pustular psoriasis: ddx AGEP (drug reaction)

Are there any other manifestations?

! Psoriatic onychodystrophy: pitting, onycholysis, discolouration
! Psoriatic arthropathy (5 subtypes):
○ Asymmetrical oligoarticular
○ RA-type
○ OA-type
○ Spondyloarthritic/AS-type
○ Arthritis mutilans

What has the course and management so far been like?

! Has the patient required admission before? Any flares?
○ Triggers: infections, withdrawal of systemic steroids (any TCM?), post-partum
detioriation, trauma, HIV infection
! What treatment has the patient received so far? Have the skin lesions/arthropathy
responded?

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How can I optimize treatment?

(a) Nonpharmacological
! Patient education & correct misconceptions. Disease is noncontagious, unpredictable,
not scarring, treatable, incurable, not influenced by diet.
! Control/screening for comorbidities (DM, HTN, HLD, metabolic syndrome)
! Avoid smoking and alcohol
! Avoid precipitants of flares

(b) Specific therapy

! Topicals: Coal tar, Dithranol, Topical steroids, Calcipotriol/calcitrol, Topical calcineurin
inhibitors (and as always, emollients)
! Phototherapy: 1st line for moderate-severe psoriasis (>10% BSA) or poor response to
topicals or severe impact on quality of life.
○ Usually narrow band ultraviolet B, alternative psoralen + ultraviolet A (PUVA).
○ 2-3x/week, slowly build up from 1 min → 1.5min → 5 min per session to overcome
skin’s natural resistance to light
! Systemic: methotrexate (esp if joint involvement), retinoids, cyclosporine A, biologics
(e.g. infliximab, adalimumab)

Have there been any complications of treatment?

! Phototherapy: SCC
! Liver toxicity on methotrexate or retinoid
○ Monitor LFT
! Agranulocytosis on methotrexate
○ Monitor FBC
○ Give folic acid
○ Check - does patient know what to do if fever?
! Complications of immunosuppression
○ Are there recurrent infections?
○ Prophylaxis: vaccinate
! If young female on retinoids or methotrexate - is the patient planning pregnancy? Both
are teratogenic so if considering pregnancy need to switch; if not considering, check
that contraception is adequate

How is the patient coping overall?

! Patient’s understanding: of disease -- what are the concerns and fears? and of
treatment -- competent?
! Psychological: (esp in young female patients) how affected is the patient by the skin
lesions? does the patient resort to hiding the lesions?
! Social: does the patient face discrimination from friends, in school or at work? does
being mindful of the skin lesions limit the clothes/activities the patient is willing to try?
! Functional: Able to work? Able to take care of self?
! Financial

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MEDICINE LONG CASES: THE CLINICAL QUESTIONS APPROACH ENDOCRINE: CUSHING’S SYNDROME

MEDICAL LONG CASES

Endocrine: Cushing’s Syndrome

ADULTS & PAEDIATRICS

What are the visible features of Cushing’s Syndrome?

! Central obesity
! Facial adiposity, supraclavicular adiposity, dorsal-cervical adiposity
! Thinned skin, easy bruising, abdominal striae, acne, female balding
! Hirsuitism (rapid development of deepening of voice, frontal balding, male pattern hair,
acne, increased muscle bulk, oligomenorrhoea, clitoromegaly, etc) should prompt
suspicion of an adrenal tumor.
! Hyperpigmentation indicates high ACTH.

What is the cause of Cushing’s?

(a) Are there any exogenous sources of corticosteroids?

! ***Always rule out exogenous causes first***
! Any co-morbid conditions that require long term use of steroids?
○ Autoimmune (RA, SLE, IBD, MS), Renal (Nephrotic, RPGN), Respi: Asthma,
Haem (ITP), Transplant patients
○ Is there any way to use steroid sparing agents instead?
! Does the patient take TCM or other supplements?

(b) If no exogenous source, likely endogenous source - proceed with workup for
Cushing’s syndrome.
! Endogenous causes include pituitary adenoma, ectopic ACTH secreting tumour,
adrenal tumour.
! Confirm Cushing’s: high 24h urinary free cortisol, or failure to suppress cortisol
secretion with low dose dexamethasone.
! Localize source of hypercortisolism: serum ACTH levels (also looking for
hyperpigmentation) and high dose dexamethasone test or CRH stimulation.
○ Adrenal tumor: Low ACTH (suppressed by high cortisol levels) -- may be
adrenal adenoma or carcinoma > CT adrenal.
○ Pituitary adenoma: High ACTH, but suppressible with high dose
dexamethasone (since pituitary is still responsive to high dose dex) > MRI
pituitary, test other pituitary hormones (may be low)
○ Ectopic ACTH: High ACTH, not suppressed by high dose dexamethasone >
often a lung primary, CT thorax.

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How shall we proceed with management?

! If exogenous source, but patient is steroid dependant:
○ Attempt steroid sparing agents
○ If need to continue steroids, deal with complications of Cushing’s syndrome as
they come
○ Give patient stress doses of steroids during any procedure to avoid adrenal
insufficiency
! If exogenous source which can be tailed down (e.g. steroid sparing agents, can stop
TCM): gently tail down to prevent adrenal insufficiency.
! If endogenous source: surgery

What are the other complications of Cushing’s Syndrome? --- often additional issues
that need to be addressed.
! Metabolic: Hypertension, hyperglycemia --- screen and treat.
! MSK: Osteoporosis, avascular necrosis of hip, proximal myopathy --- should be on vit
D / calcium, screen for osteoporosis, treat if osteoporotic.
! CNS: agitated depression, anxiety, irritability, emotional lability, psychosis, impaired
cognition
! GI – steroid induced ulcers and BGIT
! Immune: immunocompromised state --- vaccinations (influenza, pneumococcal),
screen hep B/C/HIV, TB, if high dose steroid need to know what to do if sick.
! Menstrual irregularity, increased libido
! Eye: glaucoma, cataracts -- may need ophthalmology screening

Sample summary: Yue Liang is a 32 year old lady with immune mediated thrombocytopenia
which first presented 10 years ago with non-palpable purpura, menorrhagia, and gum
bleeding. In terms of ITP she has been very stable with a baseline platelet count maintained
around 50-60s, on prednisolone 20mg/day. However she is very steroid dependant; each time
her haematologist attempts to tail down steroids her platelets plunge below 10 and she bleeds.
Indeed she has become Cushingoid, and she is particularly concerned about her large body
habitus, acne, and gradual hirsuitism has had negative ramifications on her dating life. The
other issue is that she has had symptoms of polyuria/polydipsia recently which I wonder could
be steroid-induced hyperglycemia.

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MEDICAL LONG CASES

Endocrine: Diabetes

ADULTS & PAEDIATRICS

What is the patient’s clinical course to date?

! When was the patient diagnosed?
○ Fulminant presentation with DKA/HHS, stupor → type 1
○ Indolent presentation: polyuria, polydipsia, +/- lethargy → often type 2
○ On screening or on admission for a comorbidity.
○ Pregnancy: gestational DM.
! Diagnostic criteria: 1 test if symptomatic or 2 tests if asymptomatic -- Random glucose
>11.1 mmol/L, OGTT >11.1 mmol/L, fasting glucose >7.0 mmol/L
! Distinguish T1DM vs T2DM
○ Body habitus, age of onset, insulin requirement, acanthosis nigracans (T1DM)
○ Review diagnostic workup: e.g. if suspecting T1DM, anti-islet cell antibody, anti
glutamic acid decarboxylase antibody, insulin levels (low in T1DM) C-peptide
levels (low in T1DM)
! Any contributory factors to hyperglycaemia e.g. chronic steroid use, TCM?
! Have there been any admissions for diabetic emergencies?
○ If so, why? Non-compliance? Triggered by intercurrent illness?
○ DKA = BG >15mmol/L, pH<7.3 or HCO3 <18, ketones>0.6
○ HHS = BG >33, serum osmolality >320 (2Na + glucose)

How has the control been?

! Lifestyle: has there been lifestyle modification: diet, exercise, weight loss
! What pharmacological therapy is the patient currently on
○ OHGAs: start with metformin, then a 2nd drug
○ Insulin: basal-bolus vs mixtard vs OHGA + topup regimen (mixtard not
appropriate for T1DM)
○ Does this fit well into lifestyle?
○ Is patient competent in taking medicine?
○ Is patient compliant to medicine and home glucose monitoring?
! What is the daily glucose trend and HbA1c?
! For T1DM: is patient aware of what to do if he/she is sick and unable to eat? (NOT
stop insulin -- give basal doses only and monitor with glucometer, smarter patients can
be taught to titrate accordingly)

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Do I need to adjust therapy?

! Adjustment of pharmacological therapy proceeds concomitant to lifestyle measures
! First address the ‘hypos’
○ Does have hypo episodes e.g. giddy, diaphoresis?
○ If yes, why? > Irregular meals?
○ If no, true no or hypoglycaemic unawareness? → do home glucose monitoring.
○ Is the patient aware of what to do in hypoglycaemic episode?
○ Any hypos, change regimen (e.g. early morning hypo -- decrease night dose)
! Then look at the ‘hypers’
○ Why hyper? Missed meds dose, patient gave himself a sweet treat?
○ If post-meal hyper, there is insufficient pre-meal insulin
! Look at overall glucose control: HbA1c (target <7% in most,<8% in old)
! Do we need to step-up therapy?
○ If on OHGA, is patient amenable to insulin?
○ If on mixtard BD, this is often difficult to titrate with post-lunch hypers and early
morning hypos > is that acceptable or change to basal-bolus?
○ Consider convenient options e.g. insulin pens, pumps esp younger well-
educated pts (but costly)

What DM complications are present and how are they managed?

! Microvascular: regular screening starting 5 yr after diagnosis (T1DM) or immediately
(T2DM) is important because intervention can be performed
○ Retinopathy: has DM eye screen been done, if not, do.
○ Neuropathy: yearly DM foot screen; any ulcers?
○ Nephropathy: is there established CKD? If no, screen albumin-creatinine ratio
for microalbuminaemia (abnormal: >3 mg albumin per mmol creatinine) →
inhibit proteinuria with ACE-I
! Macrovascular: strokes, ischemic heart disease, peripheral vascular disease
! Immunopathy e.g. recurrent abscesses, DM foot infections

What comorbids are present?

! [Adult] Other cardiovascular risk factors: HTN, HLD and the medications/control for
those --- treat everything.
! [Child] Other autoimmune conditions: myasthenia gravis, grave’s/hashimoto’s,
pernicious anemia (and family history for those)

How is the overall condition of the patient?

! [Child] Growth and development, participation in school
! Interference with work and function: e.g. having to inject insulin, complications
(amputation, strokes)
! Social setup
! Financial situation

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! Young ladies -- issue of pregnancy

○ Existing children -- any issues?
○ Is the patient sexually active and what contraception is used?
○ Is patient aware that pregnancy may be hazardous to mother and baby If DM
control is poor?
○ Refer to high risk pregnancy specialist.
! Patient understanding of the condition and treatment

Appendix: Worked examples in titrating diabetes meds based on patient’s trend.

Notes:
! These are for outpatient use -- inpatient DM goals are different -- simply to avoid DM
emergencies, not to stabilize outpatient management.
! Don’t titrate based on a single day’s reading, look at several readings and the HbA1c
(beware: patients often control their diet very well when it’s monitoring day, and cut
some slack otherwise!)
! Assume that diet factors are taken out → e.g. patient did not miss a meal, treat himself
to ice cream, etc.

Examples:

Current Rx Breakfast Lunch Dinner 10pm

Pre Post Pre Post Pre Post
1. Metformin (max dose) 10 14 10 15 11 16 10
2. Metformin + Glipizide BD (max dose) 10 14 10 15 11 16 10
3. Metformin + Glipizide BD (max dose) 3 9 5 10 4 8 5
4. Mixtard BD 3.5 9 11 17 11 13 9
5. Mixtard BD 10 14 10 15 11 16 10
6. Lispro TDS premeal + Detemir ON 10 14 10 15 11 16 10
7. Lispro TDS premeal + Detemir ON 6 12 7 16 6 17 6
8. Lispro TDS premeal + Detemir ON 4 7 3.5 8 4 9 6

1 & 2: overall control is poor, glucose is too high throughout. Check diet, remove steroids, and
consider step-up therapy e.g. add glipizide to (1), add a 3rd OHGA or basal long-acting insulin
to (2), switch (2) to insulin regimen.

3: Control is too tight. Loosen up a bit! Reduce glipizide especially > metformin does not cause
hypo.

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4: This is the usual difficulty with mixtard: post-lunch hyperglycaemia and early morning hypo.
This is because each mixtard dose is a calculated trade-off to avoid a 2nd injection, e.g. for
the morning dose, the actrapid covers the breakfast glucose, while the insulatard covers the
lunchtime sugar intake; for the evening dose, the actrapid covers dinner and insulatard tides
through the night. Hence, for example, an insufficient evening mixtard dose results in post-
dinner hyperglycaemia, while too high a evening mixtard causes nocturnal / early morning
hypos. In this situation the principle is to tackle the hypos first -- reduce the evening dose!
However this will cause post-dinner glucose to go too high. If acceptable control cannot be
achieved without significant hypoglycaemia risk, it may be better to switch to basal bolus
regimen.

5: All readings too high throughout the day > increase both am and pm mixtard dose (if only
high post-breakfast till pre-dinner, increase morning dose only; if only high post-dinner till pre-
breakfast, increase evening dose only)

6: All readings too high > Increase basal insulin. Increasing basal insulin will result in a global
decrease in all readings (since basal acts all the time), while increasing bolus insulin will only
decrease post-meal readings (since this is short acting).

7: Post-meal readings too high but pre-meal acceptable > Increase bolus i.e. pre-meal insulin.

8: All readings too low > decrease basal insulin. This often arises as CKD progresses and
insulin excretion falls.

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MEDICAL LONG CASES

Endocrine: Graves’ Disease

ADULTS & PAEDIATRICS

How did this patient present?

! Classic Graves’ disease in a young lady who presents with an insidious onset of
symptoms of hyperthyroidism (heat intolerance, sweating palpitations, anxiety, weight
loss, diarrhoea, oligomenorrhoea; tremors, tachycardia), a soft diffuse goitre, and
Graves’ eye signs.
! Older patients present less classically, at times simply with weight loss or atrial
fibrillation
! The occasional unfortunate patient presents with a complication e.g. thyroid storm or
stroke due to atrial fibrillation.
! Some patients may have +ve family history, or personal history of other autoimmune
disease.
! Initial workup → is the diagnosis of Graves confirmed?
○ Expect: high T4 low TSH with positive thyroid stimulating antibody
○ If initially hyperthyroid then hypothyroid, consider thyroiditis e.g. Hashimoto
which has initial hyperthyroid phase.

What is the current thyroid status & can I optimise?

! What is the treatment to date
○ Options are: thioamides (carbimazole superior to PTU) vs radioactive iodine vs
surgery
○ Explore patient preference, why was this chosen.
! What is the current thyroid status
○ Is the patient clinically euthyroid: are there symptoms & signs of hyper or
hypothyroidism?
○ Is the patient biochemically euthyroid: what is latest TSH/T4?
○ Is there a large bothersome goitre?
! Any complications of treatment
○ Agranulocytosis
○ Liver toxicity
○ Does patient know what to do if fever?

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How can I optimise management?

! If patient on medical Rx is not euthyroid --
○ Due to noncompliance? > Explore compliance, if not, why?
○ Due to dosing? Titrate thioamide + add beta blocker if hyperthyroid
○ Difficult to control → Consider RAI.
! If maintained on medical Rx or new diagnosis:
○ If long-term medical Rx > can I try stopping? (50% will not relapse)
○ Is there a role for radioactive iodine? > Especially if difficult to titrate medical
therapy, patient bothered by burden of compliance, and pt non pregnant.
○ Is there a role for surgery? > Especially if fail RAI, bothersome goitre.
○ Discuss patient preference, esp understanding that RAI may result in
hypothyroidism later → requiring replacement thyroxine.

Are there complications:

(1) Eye disease:

! Assessment: Is there exopthalmos, opthalmoplegia? Is the patient troubled by
cosmesis, diplopia?
! Are there serious complications e.g. corneal ulceration due to proptosis, threatened
loss of vision?
! Management: eye disease may take a separate course from systemic thyroid status.
Consider opthalmology referral.
○ Stop smoking
○ Artificial teardrops
○ Avoid radioactive iodine: worsen eye disease.
○ Prednisolone
○ If necessary - rituximab, orbital decompression surgery

(2) Atrial fibrillation or cardiac disease

! Is this AF in un- or under-treated disease (often resolves once T4 normalise), or
persistent AF in euthyroid state (may not resolve)?
! Any complications e.g. stroke; any impairment of function
! Manage as per non-valvular AF in other patients → rate vs rhythm control +
anticoagulation.

(3) Any past episodes of thyroid storm?

! What was the precipitant? → noncompliance, infection
! Any complications -- congestive cardiac failure, requiring ICU stay, etc
! Acute management: thioamide, hydrocortisone, beta blocker (controversial), lugol’s
iodine (1h after thioamide)

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Is patient considering pregnancy?

! If yes → thioamides may be teratogenic
○ Consider radioactive iodine before pregnancy, or use propylthiouracil over
carbimazole in 1st trimester.
○ Refer to O&G who specializes in high risk pregnancy.
! If no → counsel on teratogenicity of thioamides, use of contraception

How is the patient coping?

! Function: ability to work
! Social interactions: any issues due to anxiety, irritability?
! Financial status

Sample summary: Mr Kan Chiong is a 44 year old Chinese driver who was diagnosed 3
months ago with Grave’s disease when he presented with fever, diarrhea, heat intolerance,
mood changes. He was initiated on carbimazole and sent home, but defaulted follow up and
medications as he felt he could not afford them. He has currently re-presented with
thyrotoxicosis complicated by congestive cardiac failure secondary to atrial fibrillation, likely
precipitated by URTI and non-compliance. CCF has resolved and symptoms have improved
with carbimazole and propanolol, but he is persistently hyperthyroid and in rate controlled atrial
fibrillation. Warfarin was initiated. The team has give him the option of RAI to achieve better
control, especially since he is not keen on lifelong carbimazole and warfarin, and he does not
have thyroid ophthalmopathy. My issues for him are:
(1) Thyrotoxicosis
(2) Atrial fibrillation secondary to thyrotoxicosis, complicated by CCF
(3) URTI (resolved)
(4) Non-compliance to medications secondary to financial issues
(5) Financial issues, a/w MSW input

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MEDICINE LONG CASES: THE CLINICAL QUESTIONS APPROACH GASTRO: BILIARY ATRESIA

MEDICAL LONG CASES

Gastro: Biliary Atresia

PAEDIATRICS

How did this child present?

! Classic presentation is prolonged neonatal jaundice with pale stools, conjugated
hyperbilirubinaemia.
! Is the diagnosis of biliary atresia confirmed -- if not, consider ddx (see end)
○ Ultrasound: CBD not visible, triangular cord sign, abnormal GB size/shape
○ Hepatobiliary scintigraphy (HIDA scan) - failed excretion of tracer from liver to
bowel
○ Intra-op cholangiogram
! Differential diagnoses for biliary atresia: consider based on time of onset (early <24h
vs prolonged >2 weeks) and whether conjugated (pale stools, >15% direct bilirubin)
○ Early onset: hemolysis (ABO, Rh, G6PD, spherocytosis), TORCH -- antenatal
history and maternal blood types.
○ Prolonged & conjugated: Biliary atresia; neonatal hepatitis
○ 24h-2wk: Infection e.g. UTI, Hypothyroidism, hepatitis
○ Physiological jaundice, breast milk jaundice

Has the child gone for Kasai procedure?

! Kasai is a hepato portoenterostomy (create roux loup and anastomose to liver hilum)
! At which day is Kasai done? This is prognostically important, Kasai < 60 days has
better outcome

Was Kasai successful?

! Success rate: 1 in 3 succeed, 1 in 3 progress to cirrhosis, 1 in 3 fail from outset --
require transplant.
! Is there residual jaundice? > Ursodeoxycholic acid may help (no evidence)

How has the patient’s course been post-op

! Cirrhosis and its complications: Ask if the child has had variceal bleeding, ascites,
coagulopathy, or is puritic. Examine for stigmata of chronic liver disease. Intervene as
for cirrhosis (see cirrhosis approach)
! Cholangitis is common due to altered biliary tree anatomy and stasis in ascending limb
of roux-en-Y. Ask how many episodes have occurred and how were they treated?
Inquire whether parents know what to do

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Is the child’s growth and development otherwise alright?

! Poor nutrition is common due to cholestasis and liver inflammation.
○ How has the child’s growth been?
○ What has been done -- concentrated feeds, fat soluble vitamin supplements,
nasogastric feeds?
! Developmental milestones
! School performance
! Puberty

Is transplant necessary and has it been considered?

! Necessity of transplant depends on development of cirrhosis, complications, and poor
growth
! If considered -- has transplant workup been done, any donor available?

How is the patient and family coping with this illness?

! Time off school/work
! Financial cost can be immense
! Psychological cost - a child who feeds poorly on good days and gets cholangitic on
bad days is very draining.

Sample: Xiao Huang is a 6-month old Chinese boy who first presented with prolonged
neonatal jaundice at 1 month of age. Workup revealed biliary atresia and he underwent Kasai
procedure at 6 weeks with resolution of jaundice. Since then he has had two episodes of
cholangitis. He has been growing well and meeting all milestones. He has a supportive social
setup. My main issues are:
1. Recurrent cholangitis
2. Biliary atresia s/p Kasai

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MEDICINE LONG CASES: THE CLINICAL QUESTIONS APPROACH GASTRO: CHRONIC HEPATITIS

MEDICAL LONG CASES

Gastro: Chronic Hepatitis

ADULTS

How did this patient present?

! Asymptomatic on screening
! Acute hepatitis
○ This may be a flare of previously immunotolerant disease (more common), or
represent new infection
○ How severe? Usually mild, occasionally fulminant liver failure with
encephalopathy, coagulopathy.
○ Consider ddx: obstructive jaundice, cholangitis, alcoholic, drugs, autoimmune
! Other manifestation: e.g. glomerulonerphritis
! How was the diagnosis made?
! Is this hepatitis B or C?

Why does this patient have hepatitis?

! Vertical transmission most common unless young → ask for family history
! Acquired infection → not all present as icteric hepatitis (Hep B > Hep C); 5% of new
Hep B and 60% of new Hep C develop chronic hepatitis. Look for:
○ High-risk sexual behaviour → take sexual hx
○ IV drug use
○ Blood transfusions e.g. overseas.
○ Occupational
! If there are risk factors, screen for other blood bourne viruses
! For hep B: was the patient vaccinated?

Where is this patient in the course of disease?

! Hepatitis B: at each visit evaluate LFTs, serology and viral load to gauge where in the
disease this patient is (see chart and text below)
! Hepatitis C: these patients do not usually get ‘flares’, disease progresses slowly to
cirrhosis.

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The natural history of Hepatitis B

• Immune-tolerant phase: young patient with perinatal infection and has never had flares
(immune system does not recognize disease) -- LFTs normal, HBeAg +ve, high viral
load (can be HBeAg negative if pre-core mutant)
• Immune clearance phase: immune system has started recognizing virus causing
episodes of flares -- LFTs fluctuate, HBeAg +ve then seroconverts to HBeAg -ve, viral
load falls (can be HBeAg negative if pre-core mutant)
• Nonreplicative / carrier phase: a patient who has had episodes of flares during which
HBeAg seroconversion occurred, and is now flare-free -- LFTs normal, HBeAg -ve,
viral load low. Some of these patients may go on to lose the HBsAg and are considered
cured.
• End-stage with liver damage and cirrhosis: see approach to cirrhosis

What are the issues and how to manage?

(1) Flares
! Ensure that it is purely a hepatitis viral flare
○ Expect hepatocellular pattern of LFT derangement
○ Rule out alcohol use, autoimmune liver disease, non-hepatitis viruses (e.g.
dengue), drug induced liver toxicity.
! Avoid precipitating flares
○ Vaccinations: hepatitis A vaccination, hepatitis B vaccination (if hep C)
○ Avoid hepatotoxic drugs.
○ Is the patient still drinking? → Stop! Get help if cannot stop.

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(2) Complications and their management

! Cirrhosis
○ If no cirrhosis: monitor clinically, fibroscan, biopsy
○ If cirrhosis: manage complications (see cirrhosis document)
! Screening for hepatocellular carcinoma (various protocols) e.g. ultrasound, AFP
! Look for extra-hepatic manifestations: the hepatitis viruses can cause a wide range of
extrahepatic manifestations, e.g.
○ Membranous glomerulonephritis
○ Palpable purpura / vasculitic rash.
○ Hep C is associated with other autoimmune diseases e.g. thyroiditis, ITP, etc.

(3) Direct viral control

! New breakthroughs in antiviral drugs have transformed the management of chronic
hepatitis however cost is a big issue. Drugs include (will not discuss how to choose
between the drugs)
○ Hep B: interferon, lamivudine, entecavir, tenofovir (check HIV first, don’t
inadvertently give HIV monotherapy and cause resistance!)

! Approach for hepatitis B: treatment is long-term, controls disease and reduces risk of
progression to cirrhosis - but not a cure. Need to think carefully who to treat, and
discuss with patient; once committed to treatment it can be for life.
○ If advanced fibrosis with high viral load, cirrhosis → Treat
○ Acute liver failure → Treat
○ Patient will need chemotherapy or immunosuppression → Treat (prevent flare)
○ Recurrent flares → Discuss with patient:
■ HBeAg positive: Rx reduces flares but is likely a long-term affair; without
Rx such patients have the potential to spontaneously undergo ‘e’
seroconversion and move to immune carrier phase, but this is unlikely
to happen on treatment
■ HBeAg negative: may be pre-core mutant likely -- body is unlikely able
to control disease by ‘e seroconversion’
○ Immune tolerant phase, inactive carrier phase → Do not treat

! Approach for hepatitis C: antiviral therapy can eradicate HCV RNA and lead to a cure
○ Need to know genotype → determines choice of direct acting antiviral
○ Direct acting antivirals are given for a fixed duration and result in excellent SVR
rates 80-100%.
○ SVR: Test for HCV RNA at 12-24 weeks after stopping treatment, if none, this
is sustained virologic response = cure (99% chance of being HCV RNA
negative during long-term follow-up).
○ Treatment benefits almost all patients but high cost is a big issue

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(4) Public health and transmission

! Vaccinate household members
! No blood donation → Explore awareness and counsel
! Is patient sexually active?
○ Committed partnership: for hep B, partner should be vaccinated and test
antibody
○ Casual partners: counsel on use of protection (even if partner is immune, risks
other STDs)
! Does patient intend pregnancy?
○ Neonate must be vaccinated with active immunization, plus passive
immunization if ‘e’ antigen positive (i.e. transmissible)
○ Need to discuss with obstetrician.

How is the patient coping?

! This depends greatly on where the patient is in the disease course
! Occupation: time off, flare episodes, implications if healthcare staff
! Financial: important because of the high cost of antiviral drugs - is the patient able to
afford it?

Sample summary: Gan Yan is a 30 year old Chinese lady with chronic liver cirrhosis
secondary to hepatitis B infection, likely vertically transmitted. She was diagnosed during a
recent admission for what turned out to be acute cholecystitis, and her liver function test was
noted to be markedly deranged. She is otherwise asymptomatic, slightly icteric, She has never
had complications of liver cirrhosis, and US HBS showed no lesions in the liver. She is
currently Hbe positive with high viral load. She is still undecided as to whether to initiate
antiviral treatment or allow spontaneous “e” seroconversion. Newly married, she is under great
pressure to produce grandchildren by her mother-in-law. She is relieved that her husband is
already vaccinated against Hep B with healthy antibody titres, and that it is possible to prevent
vertical transmission to her children with active + passive vaccination perinatally. Otherwise
she is able to work as per normal, no social or financial problems.

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MEDICAL LONG CASES

Gastro: Liver Cirrhosis

ADULTS

Does this patient have cirrhosis?

! Asymptomatic in the early stages: detected on LFT, fibroscan (e.g. monitoring in
patients with known hepatitis)
! In later stages, our beloved stigmata of chronic liver disease: jaundice, clubbing,
palmar erythema, scleral icterus, gynaecomastia, spider naevi, loss of axillary hair,
testicular atrophy; with elevated LFTs.
! Some patients also receive imaging or liver biopsy.

What is the etiology of this patient’s cirrhosis?

! Knowing the etiology is important because this can change management.
! Some etiologies may be obvious on history, examination, and confirmed on initial
investigation
○ Alcohol: history of alcoholism → look at MCV, GGT.
○ Hepatitis: known status, immunization, family hx, high risk sexual behaviour, IV
drug use, received blood products in another country → do HBsAg, HBsAb,
HBcAg, HCV IgM
○ Congenital: e.g. biliary atresia.
! Other etiologies are less obvious although there may be clinical suspicion
○ Wilson’s disease: neurologic symptoms, family hx, kayser-fleischer rings →
measure serum copper, ceruloplasmin (low), urinary copper (high), may need
biopsy.
○ Hemochromatosis: known transfusion-dependent hemolytic anaemia → do
ferritin, TIBC,
○ Cardiac cirrhosis
○ Budd-Chiari
! Yet other etiologies are only investigated when none of the obvious ones fit -- often a
biopsy is needed, but does a biopsy change management?
○ Non-alcoholic steatohepatitis (may be responsible for a lot of ‘cryptogenic’
cirrhosis)
○ Autoimmune hepatitis → IgG, ANA, liver biopsy.
○ Glycogen storage diseases
! Finally, in some patients, no obvious etiology is found and the cirrhosis is labelled
‘cryptogenic’

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What is the severity of this patient’s cirrhosis?

! Use Child’s-Pugh Scoring: Child’s A = 5-6, Child’s B = 7-9, Child’s C = 10-15

1 point 2 points 3 points

Albumin g/L >35 28-35 <28

Bilirubin µmol/L <34 34-51 >51

Coag: PT prolongation (INR) <4 (<1.7) 4-6 (1.7-2.3) >6 (>2.3)

Distension (ascites); None Controlled on diuretics Refractory to diuretics

Encephalopathy None West Haven 1-2 West Haven 3-4

1: Change in 3: Marked confusion,
behaviour alone mostly sleeping
2: Disorientation, but arousable
drowsy, asterixes 4: Comatose

What complications has this patient had → how can I optimise management?
! Consider complications in terms of portal hypertension (variceal bleed, ascites), loss
of catabolic function (encephalopathy, puritus, jaundice), loss of synthetic function
(coagulopathy, hypoglycaemia). Hepatocellular CA discussed below.
! Variceal bleeds
○ Any previous hematemesis, melena?
○ How severe, did the patient need TIPS, required ICU?
○ Emergent Mx: ABC, Abx, IV PPI, somatostatin, transfusion, endoscopic
hemostasis.
○ Follow up: prophylaxis with propranolol, treat portal hypertension, interval
variceal band ligation to eliminate all remaining varices
○ Treat portal hypertension: nonselective beta blockers (propranolol),
transjugular intrahepatic portosystemic shunt insertion (TIPS) if recurrent.
! Ascites:
○ Symptomatic with abdominal distension, SOB on lying supine (diaphragmatic
splinting), hernias? → Ddx cardiac, renal
○ If abdo pain → consider spontaneous bacterial peritonitis and treat
○ Low salt diet and fluid restriction
○ Pharmacological: furosemide and spironolactone in 5:2 ratio
○ Abdominal tap with IV albumin cover
! Hepatic encephalopathy: drowsiness/confusion, sleep wake reversal, asterixis
○ Low protein diet and nutritional supplementation
○ Lots of lactulose to ensure BO at least 2 times a day
! Others: puritus, coagulopathy, hypoglycaemia (usually occurs late)

How often does this patient decompensate, why?

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! Trace how many admissions - how often, what reason

○ How severe? > E.g. the symptomatic ascites requiring tap, vs the patient with
variceal bleed and hepatorenal syndrome requiring ICU care!
○ What was response to treatment?
! Identify trigger of decompensation and treat
○ Non-compliance to low salt diet or fluid restriction
○ Acute liver injury e.g. alcohol, hepatotoxic drugs, acute hepatitis infection
○ Acute intercurrent illness e.g. URTI, GE
○ Newly developed hepatocellular carcinoma (refer to GS long case section on
HCC)

Can I treat the underlying cause?

! Stop all further insults to the liver
○ No more alcohol → refer NAMS
○ Avoid hepatotoxic drugs, no TCM.
○ Vaccinate against hepatitis A and B
! Treat hepatitis B/C - indication to start treatment (see document on hepatitis)
! Non-alcoholic steatotic hepatitis → supportive mx, lose weight, treat other cardiac risk
factors
! Autoimmune hepatitis → induction therapy with glucocorticoids alone, KIV tail after
remission for 18 months or maintenance azathioprine
! Is the patient a transplant candidate; any donor available?

Is there hepatocellular carcinoma?

! Regular monitoring with ultrasound liver, alphafetoprotein needed
! Both hepatitis B and any cause of hepatocellular inflammation increases risk of HCC

How is the patient coping?

! Personal: Cirrhotics come in different sorts - the ‘bo chup’ still-drinking alcoholic, vs
the young autoimmune or hemochromatosis patient. Explore the patient’s disease
understanding, motivation, and compliance (especially salt and water restriction)
! Functional: is the patient able to work, is he ADL independent?
! Social: often flavourful and worth some time delving into. Consider home setup,
‘drinking buddies’, sexual history (if hepatitis B/C - need to counsel)
! Financial: almost all will say they have financial issues.
! May need advanced care planning if end stage cirrhotic.

Sample Summary: see worked example of ‘How to summarise Issues’ (Medical Long Cases
> strategy)

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MEDICAL LONG CASES

Gastro: Inflammatory Bowel Dx

ADULTS & PAEDIATRICS

How did this patient present & how was the diagnosis made?
! Presentation is usually inflammatory diarrhoea (bloody +/- systemic symptoms), abdo
colic +/- weight loss or growth failure, +/- perianal skin tags (Crohns)
○ Exclude ddx: infections (travel history, stool OCP, C diff toxin), ischaemic (any
AF?), neoplastic (scope), steatorrhoea.
! Initial workup: high TW, CRP, ESR; stool calprotectin +ve; ASCA (Crohn), pANCA
(UC) not for routine diagnosis
! Colonoscopy and biopsy would have been done, this distinguished UC vs Crohn’s.
○ Distribution: UC always starts from the rectum, proximal extension is
continuous and may continue until the terminal ileum i.e. backwash ileitis
(extent of proximal extension is prognostically important). Crohn’s spares the
rectum, has skip lesions, and can involve the entire GIT.
○ Appearance: Crohn’s has a cobblestone appearance with deep ulcers and
fissures; UC has shallow ulcers, pseudo-polyps and mucosal bridges.
○ Biopsy: UC shows shallow ulcers and crypt abscesses. Crohn’s shows
transmural inflammation with non-caseating granulomas.
! Small bowel workup may also be necessary for Crohns: e.g. CT or MR enterography.

Assess disease course and current issues / management tasks in terms of:

(1) Colonic flares

! History: Have there been any severe flares or emergencies?
○ UC: SIRS, anaemia <10.5, rapid weight loss → toxic megacolon (SIRS, bowel
>5.5cm, pneumatosis intestinalis) → perforation
○ Crohns: IO → closed loop → perforation
○ Crohns: intra-abdominal abscess → peritonitis
! Patient in remission: The natural history is that of intermittent exacerbations.
○ Assess the tempo of flares and what maintenance drugs are required to sustain
remission: none, 5-ASA alone, steroids (steroid-dependent), or other drugs?
○ Inquire compliance and motivation -- less of a problem with UC/CD than with
many other chronic conditions because noncompliance quite easily leads to an
unpleasant flare.

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! Patient with flare: assess frequency and severity of flares (general guides below),
induce remission then continue as per maintenance therapy.
○ Mild: tolerates orally, mild abdo pain, no SIRS
○ Moderate: prominent symptoms (fever, weight loss, abdo pain)
○ Severe / fulminant: SIRS or an emergency (toxic megacolon, perforation,
severe IO) → perforation should manage according to surgical lines.
! Examine current management strategy and whether there is a need to step up or down
- a sample approach is below (but evidence shifts quickly and exact choice is highly
patient and consultant dependent)

Ulcerative Colitis Crohn’s disease

Mild flare [Paeds] Exclusive enteral nutrition [Paeds] Exclusive enteral nutrition
Rectal 5-aminosalicylate (5-ASA) PO 5-ASA - efficacy debated (not
(sulfasalazine, mesalazine) rectal, Crohns involves entire GI)
Rectal steroid (budesonide) PO Abx

Moderate flare PO 5-ASA

PO steroids (budesonide preferred PO steroids (budesonide preferred
due to high first-pass metabolism due to high first-pass metabolism
in liver, lower systemic effects) in liver, lower systemic effects)
Steroid dependant or refractory: 6- Steroid dependant or refractory: 6-
MP or azathioprine. MP or azathioprine.

Severe flare PO 5-ASA

IV hydrocortisone / methylpred IV hydrocortisone / methylpred
IV Abx IV Abx esp if suspecting abscess
No response: No response:
Cyclosporine or infliximab Cyclosporine or infliximab
Fulminant or toxic megacolon:
Panproctocolectomy & end
ileostomy

Regular Stop smoking (reduces relapse) Stop smoking (reduces relapse)

maintenance 5-ASA: sulfasalazine > mesalazine 5-ASA: sulfasalazine, mesalazine
+/- Abx

Difficult Try azathioprine or 6MP Try azathioprine or 6MP

maintenance Try biologics e.g. infliximab, Try biologics e.g. infliximab,
Relapse often adalimumab adalimumab
Steroid Medically refractory disease: Minimise surgery: repeated SB
dependant proctocolectomy + ileal pouch resection can lead to short gut
anal anastamosis

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(2) Chronic colonic complications

! Colorectal cancer
○ Patient should receive screening with biopsies
○ Recommendations for screening differ - e.g. American gastroenterological
society recommendations for both UC and Crohns are to start 8 years
(pancolitis) or 15 years (left colitis) after diagnosis, repeat every 1-2 years.
! Strictures causing IO
○ Rule out malignant strictures
○ Attempt to resolve with medical Rx and bowel rest, if not, surgical resection
may be required
! [Crohn] Fistulation - enteroenteric (mass), enterovesical (pneumaturia, UTIs),
enterovaginal (discharge), enterocutaneous (discharge), sinus tracts (intra-abdominal
abscess, perianal disease (perianal abscess, fistula-in-ano)
○ Medical: immunosuppression esp infliximab, azathioprine, 6-MP
○ Surgical resection if medical Rx fails (attempt to minimise resected bowel)
! Malabsorption, malnutrition, vitamin ADEK deficiency.

(3) Extraintestinal manifestations & systemic complications

! Uveitis
! Joints: IBD associated arthritis
○ Use NSAIDs with caution
○ 5-ASA drugs, azathioprine, 6-MP, MTX, steroids, and biologics are helpful for
both bowel and peripheral joints
○ Spine disease: manage like AS with physiotherapy +/- biologics.
! Skin: erythema nodosum, pyoderma gangrenosum.
○ Responds to immunosuppression.
! Liver: Primary sclerosing cholangitis → jaundice, RHC pain, raised ALP
○ Give ursodeoxycholic acid
○ Monitor for cancer
! Anaemia: due to BGIT and B12 deficiency
○ Periodically monitor Hb.
! [Crohn’s] Oral ulcerations → topical steroids

(4) Complications of treatment

! Steroid side effects → see Cushing’s approach
○ Osteoporosis monitoring (DEXA) and prophylaxis (replace calcium / vitamin D),
KIV treatment
! Immunosuppression & myelosuppression
○ Check Hep B/C/HIV, TB status before starting potent immunosuppression
○ Vaccinations
○ Patient education - what to do if fever? (Come A&E and get FBC)
! Other side effects: liver toxicity, renal toxicity (ASA)

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How is this affecting the patient?

! [Paeds] Growth & Development
! Able to work / school?
! Financial
! Social: esp if fistulating disease with enterocutaneous fistula, resection required,
troublesome symptoms -- has social interaction been impaired?
! Psychological care: how does the patient feel about the illness?

Sample summary:
Lao Sai is a 12 year old boy with ulcerative colitis, who first presented at age 10 with bloody
diarrhea of 2 months duration associated with low grade fever, fatigue, colicky abdominal pain
and loss of weight, diagnosis confirmed on colonoscopy. He has been steroid-dependant
since the time of diagnosis, developing moderately severe flares each of the 3 times his
physician tails his steroids down. He is still currently in remission, and has just been started
on infliximab in addition to azathioprine and steroids. Otherwise he also has joint pain in the
wrists and ankles as well as skin lesions, both of which have improved with his medications.
He is has been in and out of school, and struggling to keep up with his studies. He is also self-
conscious that he is smaller sized than all this peers (in spite of all his vitamin supplementation
and efforts to tolerate exclusive enteral nutrition) and Cushingoid from the steroids. The family
is barely keeping with the financial burden of his admissions and infliximab combined, but
want to give him the best shot at regaining a normal quality of life. They are considering the
option of an elective panproctocolectomy with ileal pouch anal anastomosis.

Please also refer to Surgical Long Case > Crohn’s disease

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MEDICINE LONG CASES: THE CLINICAL QUESTIONS APPROACH GENETIC: THE SYNDROMIC CHILD

MEDICAL LONG CASES

Genetic: The Syndromic Child

PAEDIATRICS

A short short time ago in a galaxy next door … a professor once said during an ill-fated MBBS long
case, “This child has Goldenhar syndrome (??), please take a history (!!!!)”. Most students foamed.
Are we expected to know all these rare syndromes? → You are probably expected to know
something about the common ones (especially Down’s), but for the rare ones, probably not.
Regardless, you should have an overall approach to the syndromic child -- whatever the specific
syndrome there are commonalities; the underlying cause cannot be treated so your task is to
identify, in a systematic fashion, organ-based manifestations and how they have been managed,
and what the current issues are.

How did this syndrome present and how was it diagnosed?

! Antenatal diagnosis may have been done: e.g. thickened nuchal fold (Down’s),
maternal serum screening (Down’s), amniocentesis and karyotyping (Down’s)
! The condition may be picked up in the neonatal period, as an abnormal neonatal
examination or due to particular complications.
! It may have been picked up upon noting developmental delay.
! If features are mild, it may only be noted in adolescence or adulthood > e.g. short
stature, delayed puberty (Turner’s syndrome).
! The need to consider differentials depends on how obvious the presentation is, the
more vague the presentation (e.g. microcephaly, vague dysmorphisms), the wider the
net that should be cast – e.g. other syndromes, TORCH infection

Are there any visible features I can observe?

! The most important is to recognize that the child is ‘dysmorphic’. If you recognize a
specific syndrome and are confident, call it. If not, simply list the dysmorphic features.

Syndrome Visible features Diagnostic criteria

Down’s Eyes: upslanting palpebral fissures, Karyotype > trisomy 21

prominent epicanthic folds,
hypertelorism, flat nasal bridge.
Ears: low-set
Neck: short, excessive skin
Hands: single palmar crease,
incurved 5th finger
Legs: widened sandal gap,
hypotonia

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Syndrome Visible features Diagnostic criteria

Turner’s Short stature (short and fat) Karyotype > XO

Neck: webbed
Body: widely-spaced nipples,
cubitus valgus

Klinefelter Tall stature Karyotype > XXY

Gonads: Small testes,
gynaecomastia

Neurofibroma- Skin: Cafe-au-lait, neurofibromas, Two of the following:

tosis type 1 axillary freckles ≥6 cafe au lait >5mm (pre-) or
>15mm (postpubertal)
Neurofibromas, ≥2 or 1 plexiform
Axillary / inguinal freckling
Optic glioma, ≥2
Lisch nodule (iris hamartoma)
Sphenoid dysplasia
1st degree relative with NF.

Sturge-Weber Face: Port-wine stain MRI brain.

Tuberous Face: adenoma sebaceum Clinical diagnostic criteria, or

Sclerosis (appears in adolescence) Gene testing.
Skin: ash-leaf spot, shagreen
patch,

Prader-Willi Neonate: hypotonia, feeding Clinical criteria, or

difficulty, failure to thrive Molecular testing (complex);
Older: almond shaped eyes, need to identify which is
obesity, hyperphagia, maternal or paternal
hypogonadism chromosome.

Noonan Face: hypertelorism, low-set ears

Neck: short, webbed
Short stature
Chest: pectus excavatum

William’s Elfin facies: periorbital fullness, Karyotype > 7q deletion

hypertelorism, long philtrum,
thick lips, wide mouth, small jaw

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Why is this child syndromic?

! Knowledge of the genetics of each condition is helpful but even if such knowledge is
not available, following the broad principles of paediatric history taking will uncover
much information.
! Broadly, take a deep interest in the family history. Ask if parents or relatives are
affected. Also ask if the parents related to each other (consanguinity)
! When considering non-heritable conditions or de-novo mutations, delve into antenatal
history and consider maternal risk factors e.g. advanced maternal age.

What are the complications and current (medical) issues?

! Approach: If you know the specific syndrome, look for its particular manifestation (see
table); alternatively the patient/parent may volunteer the information.
! Regardless, some concerns are common to all syndromes (probably all children) so
you should spend time looking into these.
! How is the child growing? → Plot height and weight on the percentile charts
○ Any feeding and nutrition issues? (Especially if unable to feed self)
! How is the child’s development? → Do a developmental assessment
○ Neurodevelopment, intellectual disability → If present, how has the family been
coping? Special school, early intervention? Care needs? (see below)
○ Motor development → Any motor disability
○ Speech and language → Hearing aids? Early intervention?
○ Sensory impairment: blindness, deafness → Any special school or other
intervention?
! Any seizures? (Neurocutaneous syndromes) → If so, what is the mx, any
breakthroughs? (see approach to seizure)

Syndrome Organ-based complication Directed management

Down’s (Trisomy CNS: developmental milestones, behaviour

21) CVS: VSD (most common), AVSD (most Gauge severity ?surgery
pathognomonic)
GI: duodenal atresia, anorectal malformations ? Surgical correction
Eye: nystagmus, strabismus,
Hearing impairment Hearing aids
Endocrine: hypothyroidism, DM Replacement
Leukemia Monitoring
Immunodeficiency

Turner’s Endocrine: short stature, hypothyroid Screen TFT, KIV GH

CVM: aortic valve disease, aortic dissection 2DE KIV MRI
Renal: malformations → UTI, hypertension. Do Cr, US, treat UTI,
Metabolic syndrome Monitor glucose, lipids
Gynae: amenorrhoea, infertility, osteoporosis Exogenous estrogen.
Increased risk of autoimmune disease.

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Syndrome Organ-based complication Directed management

Klinefelter Endocrine: tall stature, infertility,

hypogonadism
Psych: usually normal IQ but may have
behaviour problems.

Neurofibromatosis Malignant peripheral nerve sheath tumors Monitor neurofibromas.

Hypertension: coarctation of aorta, renal artery Measure BP KIV renal
stenosis, pheochromocytoma. artery US.
CNS: intellectual disability, seizures. MRI brain if seizure- ?tumor
Eye: optic glioma Eye screen
MSK: skeletal deformities (bowed legs, Examine MSK.
pseudoarthrosis, bone cysts)

Sturge-Weber CNS: Seizure, focal neuro deficits, low IQ

Eye: glaucoma, choroidal haemangioma, Refer eye, screen glaucoma
visual field defect
Endocrine: growth hormone deficiency Inx if not growing.

Tuberous CNS: Brain tubers, seizures, behaviour Treat seizures, MRI brain
Sclerosis problems
CVS: rhabdomyoma Usually asymptomatic, 2DE
Renal: angiomyolipoma, HTN, cancer Measure BP, surveillance
with MRI

Prader-Willi CNS: low IQ, behaviour problems

Hyperphagia, stealing food --> choking Limitation of food
episodes
Endocrine: short stature, hypogonadism Growth hormone.
Complications of obesity: DM, hyperlipid, Monitor and manage
OSA, IHD accordingly

Noonan CNS: low IQ

CVM: PS, ASD, HOCM 2DE
Bleeding diathesis

William’s CNS: moderate intellectual disability but good

language, ADHD
Hearing: loss Audiology evaluation
CVS: AS, PS
Renal: renal artery stenosis Renal artery ultrasound
GIT: constipation

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How is this affecting the child & family?

! Special care arrangements
! Special school: MINDS, rainbow centre, special school
! Social: stigma, integration with society, what the relatives think
! Psychological: caregiver stress, lost hope (if know prognosis), guilt,
! Financial cost

Genetic implications
! Stance on future childbearing? → Genetic counselling?
! Generally it is necessary to first test parents for the mutation. NF and TS are AD, so if
parents are unaffected, consider new mutation, mosaicism, or incomplete penetrance
(if TS).
! Genetic counselling depends on the inheritance and penetrance and can be complex.
For example,
○ NF: AD with high penetrance, low-risk if parents are not affected.
○ TS: AD with variable expression, need to test if parents are affected.
○ Sturge Weber: it is not heritable.
○ Down’s syndrome: most are new mutations due to non-disjunction (risk of
recurrence is 1 in 200 for <35 yr old mother and equal to age-specific risk in
>35 yr old mother), however parents may also be balanced translocation
carriers (risk of recurrence depends on what translocation)

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MEDICINE LONG CASES: THE CLINICAL QUESTIONS APPROACH HAEM: HEMOPHILIA

MEDICAL LONG CASES

Haem: Hemophilia

PAEDIATRICS (less likely adult)

How was the diagnosis made?

! At what age did this boy present, and how? E.g. known FHx, haemarthrosis, bruising,
hematuria
○ Ddx for haemarthrosis: septic arthritis.
○ Often mistaken as non-accidental injury
! Laboratory confirmation is prolonged aPTT, correctable with mixing, reduced factor
VIII (Hemophilia A) or IX (Hemophilia B)
! What is the factor activity level? > Defines severity
! There is usually a significant family history (X linked recessive inheritance): only boys
are affected, apparently affected females either have lyonization or something else
e.g. von willibrand disease.

Have there been any clinically serious bleeding & what is the sequelae?
! Intracranial bleeds
○ Any residual neurological impairment?
! Hemarthrosis
○ Any hemophiliac arthropathy, what is current motor function
○ Any orthopaedic interventions necessary?

What is the treatment to date & any complications?

! How many active bleeds or injuries in the last year?
○ Mild bleed: Give desmopressin i.e. DDAVP (only for hemophilia A - releases
factor VIII) and tranexamic acid (fibrinolytic)
○ Serious bleed: factor replacement to at least 40-50% of normal. All head
injuries (including minor knocks) must be taken seriously.
! Has the patient needed surgery or faced any other hemostatic challenge, how were
these dealt with?
! Is patient on baseline prophylaxis with factor replacement? -- if not on, why?
○ Primary prophylaxis indicated for severe hemophilia: reduces risk of
arthropathy compared to on-demand treatment
○ Secondary prophylaxis if there is already hemophiliac arthropathy
○ Options: Purified plasma concentrate or recombinant
! Complications:
○ Have factor inhibitors developed? -- Give bypass agent (very expensive!)
○ Any transmission of blood bourne infectious disease? (Common in past, rare
now)

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How is the patient’s life affected?

! What is the patient bothered by: any troublesome bruising, serious bleeding? Is the
boy able to brush teeth?
! How is the patient’s knowledge of disease: Know how to come in for on-demand factor
replacement, know what to do if “minor” head injury?
! Functional limitation: is the boy able to exercise? Does he disregard restrictions in a
bid to ‘have fun’ with friends?
! Social limitation: does inability to participate in some activity lead to social
ostracization?
! Financial limitation: factor replacement is costly
! [Paeds] How is growth and development otherwise?

Genetic counselling
! Are other family members involved?
! Do parents understand implication for future pregnancies: X-linked recessive,
therefore half of all male children are affected (i.e. 25% of all children), and half of all
female children are carriers.
! Are patient’s sisters aware that they may be carriers?
○ Ethical issue: should parent test the child before child is 21? What if the child
does not want to know?
○ Implications for future relationships

Sample summary:
Humpty Dumpty is a 17 year old boy with hemophilia A, diagnosed at the age of 1.5 years old
when he presented with painless right knee swelling with no history of trauma/fall. Since then
he has never had any major bleeding episodes especially intracranially or from the GIT that
required admission for desmopressin, and underwent an uneventful appendectomy last year
with FFP supplementation. He is not on primary prophylaxis. In the past year however, he has
been working out hard at the gym (against doctor’s advice) to impress a girl he likes at school.
He notices mild bilateral elbow swelling after every workout involving free weights and bench
presses, but dismissed it as insignificant as they are painless and self-resolve. More recently
though he has noticed stiffness and reduced range of movement in both elbows. Otherwise
he is well-accepted in school and is thankful for the understanding he has from his friends
when he sits out of PE class. Family is supportive and financially able to afford factor
replacement treatment should he ever need it. His younger sisters (15, 16) are aware they
that may be carriers of the gene, but only want to decide on testing when they turn 21.

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MEDICAL LONG CASES

Haem: ITP

ADULTS & PAEDIATRICS

What type of bleeding is this?

! Classic ITP presents with a thrombocytopenic bleeding pattern: non-palpable purpura
(not blanchable) on bilateral lower limbs, with mucocutaneous bleeding (epistaxis, gum
bleeding, ecchymosis on lips, menorrhagia).
! Distinguish from the vasculitic rash which is a palpable purpura.
! In contrast the hemophilias and other coagulopathies present as haemarthrosis,
intramuscular hematomas hours after minor trauma

Is the diagnosis just ITP?

(a) Is the patient sick

! ITP patients are completely well. A sick patient does not have ITP.
! Consider: DIVC, meningitis, vasculitis, TTP-HUS, liver failure.

(b) Is there isolated thrombocytopenia, no other cell lines involved?

! The expected picture is isolated thrombocytopenia with normal RBC, normal WBC,
normal coagulation profiles.
○ Patient should not have symptomatic anaemia, pallor, or recurrent infections.
○ Ask if patient is on warfarin or any NOACs.
! If other cell lines are involved → consider
○ All low: aplastic anaemia, megaloblastic anaemia, marrow infiltration, other
causes of myelosuppression (e.g. drugs)
○ Low Hb, low platelets → B12 deficiency,
○ Look for the raised TW of leukaemia.
! If the clinical picture is that of ITP but Plt is ‘normal’ → likely von willibrand disease, do
VWF antigen, VWF activity (ristocetin cofactor activity)

(c) Is there a secondary cause of thrombocytopenia?

! Infection: HIV, HCV can present as thrombocytopenia -- risk profile and order workup.
Rule out dengue in acute setting. Sometimes no infection is identified but “ITP” remits
spontaneously very soon > many of these are viral
! Rheumato: ask for symptoms of SLE, vasculitis -- if suspicious workup ANA, dsDNA.
! Exclude drug induced: heparin, antibiotics, antiepileptics -- take full drug hx, stop
drugs, also inquire supplements and traditional meds.
! Liver disease -- ensure not jaundiced, LFTs normal.

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ITP is a diagnosis of exclusion; exclusion of secondary causes is required for diagnosis.

Complications: Is there any clinically significant bleeding?

! Dangerous bleeds: Intracranial hemorrhage, PR bleed
! Past hemostatic challenges: surgeries, pregnancy & delivery.
! Patient education
○ Do patients know what to do if they get a bleed?
○ Are there dangerous occupational and leisure activities?

How has it been treated?

! Goal of ITP treatment: to prevent clinically important bleeding rather than to normalize
the platelet count. Treatment is not always required.
! Acute admission for low Plt -- supportive mx:
○ Complete rest in bed, no IM injections, no brushing teeth
○ Daily platelet counts
○ FFP, platelet transfusions for patients with clinically impt bleeding or Plt <20
○ IV fluid resuscitation
! 1st line therapy: glucocorticoids -- in the chronic setting the question is often titration
to achieve an acceptable Plt count with no bleeding, and minimise side effects -
○ Cushings syndrome
○ Any immunosuppression -- vaccinate, counsel pt on what to do.
○ Osteoporosis: monitor DEXA, give Ca/VitD, treat if necessary
! 2nd line: IVIG -- raises platelet count more rapidly than glucocorticoids. Use for active
bleeding, pts who need an urgent invasive procedure.
! Other therapies: splenectomy, rituximab, thrombopoietin receptor agonist,
immunosuppressive therapy

What is the prognosis?

! Adults: ITP is generally a chronic disease with only 10% remitting spontaneously. The
majority have stable disease with normal life expectancy.
! Children: up to 50% remit spontaneously, especially those <10 years old.

How is the patient’s function, overall health, and quality of life?

! Child: Growth and development
! Is his/her function/participation in activities limited by the disease
! Social setup
! Financial

Sample case: Lolita is a 29 year old Filipino maid who presents with non-palpable purpura,
mucocutaneous bleeding, and menorrhagia. She was otherwise very well and has no
suggestion of autoimmune disease, chronic viral infection, liver disease, and is not on any
long-term medications or supplements. She was diagnosed with ITP and required FFP. Her
platelet counts have come up once she was started on prednisolone.

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MEDICAL LONG CASES

Haem: Thalassaemia

PAEDIATRICS (less likely adult)

How did thalassaemia present > what clinical phenotype?

! Thal major: well at birth, presents at 6-12 months (when HbF production switched to
HbA) with pallor, irritability, growth retardation, hepatosplenomegaly, and jaundice.
Thereafter they require 3-4 weekly transfusions. Genetically they are β0β0
! Thal intermedia: presents in late first decade often as lethargy or difficulty exercising.
Unlike thal major, these kids do not require hypertransfusion, only require intermittent
or no transfusion. The underlying genetic abnormality is heterogeneous e.g. abnormal
beta globin chains which produce some but not zero beta-chains, HbE-beta thal, or
HbH disease (α-/--).
! N.B. Thalassemia minor is asymptomatic (α-/α-, αα/-- or αα/α-), Bart’s hydrops (--/--
with no alpha allele) dies in utero

How was the diagnosis confirmed?

! Blood: hypochromic microcytic anaemia with low RDW, evidence of hemolysis
(unconjugated hyperbilirubinemia, raised LDH, decreased haptoglobin)
! Gel electrophoresis distinguishes the type of thalassaemia: HbH (β4) in α-thalassemia,
HbF (α2γ2) and HbA2 (α2δ2) in β-thalassemia, HbE, and HbS.

How is the child’s anaemia managed?

! Transfusion requirements: how often and how much?
! Is there residual anaemia?
○ What is the usual Hb?
○ Any symptoms: Pallor, lightheadedness, lethargy, poor exercise tolerance
! Is there residual extramedullary hematopoiesis? > look for chipmunk facies, hepato-
splenomegaly.
! Are transfusion requirements increasing? (increasing frequency and volume) > is there
hypersplenism?
○ Usual indication for splenectomy is hypersplenism causing accelerated RBC
destruction and increasing transfusion requirements
○ If splenectomised, any infective complications, are the child’s pneumococcal
and meningococcal and HiB vaccinations up to date?
! Any complications from transfusion? > E.g. blood borne virus, antibody production
making it hard to find suitable blood.

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Is the child receiving adequate chelation?

! In the past thalassaemia kids used to die in their teenage years due to iron overload.
! What chelation is the child receiving?
○ SQ/IV slow infusion deferoxamine 8-24 hours every day
○ PO deferasirox (OD) or deferiprone (TDS) > more convenient but expensive.
! How is the compliance? > If poor, why, what are the issues? (Medical / financial / social
/ psychological)
○ Typically no problems while the child is young and parents administer the
treatment. Compliance becomes a problem when the child becomes a
teenager and the chelation regime clashes with hectic schedules packed with
extra-curricular activities or late-night suppers with friends
○ PO deferasirox may be a more palatable option, but it is expensive so do also
explore the family’s financial situation when you offer that alternative

Is there iron overload?

! This is especially so for transfusion dependent thalassaemia but non transfusion
dependence does not exclude iron overload because extramedullary hematopoiesis
itself stimulates increased iron absorption from the gut.
! What are the latest monitoring parameters?
○ Target ferritin: 300-500 mcg/L (normal 200-300)
○ MRI T2* (cardiac, liver)
! Any end-organ damage?
○ Heart: any arrhythmias or heart failure?
○ Liver: any chronic liver disease?
○ Pancreas: any diabetes? Latest OGTT
○ Gonads: any delayed puberty? Latest serum FSH/LH, estrogen, testosterone
○ Thyroid: any symptoms of hypothyroidism? Last TFT
○ Pituitary: short stature/shorter than peers? Latest height and weight percentile

How is the overall coping of the child?

! Growth and development
! Is he/she able to participate fully in school?
! Social setup
! Financial

Genetic aspects: how about the siblings / family / future children?

! There is often a family history +/- other involved siblings
! Do parents want more children? > Have they gone for genetic counselling?
○ Beta-thal is autosomal recessive i.e. if parents are both β++β0, the risks are:
beta thal major 25%, carrier 50%, normal 25%; genetic counselling is more
tricky in alpha thalassaemia.
○ First need to do genetic testing to confirm they are carrying the alleles (most
parents would have received Hb as baseline screen, then offered
electrophoresis if Hb low)

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○ Can consider antenatal testing via chorionic villus sampling (10 to 12 weeks of
gestation), or amniocentesis (>15 weeks of gestation); risk miscarriage. But
consider parental values -- will they abort? If no, don’t bother testing.

Sample summary: Alvin is a 15 year old Chinese boy who presented at

5 years old with lethargy and shortness of breath and was diagnosed with
beta thalassaemia intermedia. He receives transfusions about q2-3
monthly and knows how to come in for transfusion should he feel
unusually lethargic. His mum had all along ensured compliance to
subcutaneous chelation therapy and I note that he has hit puberty last
year, with no cardiac or liver complications. This year, however, his
parents divorced with custody going to the dad - while he is a bright kid
who understand his disease and is motivated to comply, he appears
somewhat affected by the divorce and I worry whether he would keep up with regular chelation
without his mum’s watchful eye. I don’t think they can afford oral chelation. Hence my issues
are (1) parental divorce, and (2) thalassaemia intermedia requiring 2-3 monthly transfusion
and no iron overload thus far.

ADDENUM: Hereditary Spherocytosis

Definition: HS is a hemolytic anemia due to a red cell membrane defect. It is a result of

heterogeneous alterations in one of six genes (most often the ankyrin gene) that encode for
proteins involved in vertical associations that tie the membrane skeleton to the lipid bilayer.
Autosomal dominance in 75% patients, recessive inheritance for the rest.

When to suspect hereditary spherocytosis as a differential?

! Presents very similarly to thalassaemia → with anaemia, jaundice, splenomegaly, +/-
positive family history of hemolytic anaemia. Blood work will also show anaemia with
low MCV, high reticulocytes, and evidence of hemolysis (unconjugated bilirubinemia,
high LDH, low haptoglobin)
! However unlike thalassaemia, there is
○ More hemolysis and less ineffective erythropoiesis, less extramedullary
hematopoiesis → spleen is usually larger and liver smaller than thalassaemia
○ High RDW
○ Spherocytes on peripheral blood film with negative coomb’s test (Ddx:
alloimmune and autoimmune hemolytic anemia can also have spherocytes, but
both are associated with a positive Coombs test)

How to confirm diagnosis?

! Classic: osmotic fragility test
! More accurate: eosin-5-maleimide binding test +/- a second test e.g. acidified glycerol
lysis time or the cryohemolysis test.

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What do I need to do for this patient?

! Asymptomatic or mild: nothing
! Symptomatic anaemia:
○ Blood transfusions
○ Consider splenectomy: recommended for symptomatic HS and moderate to
severe hemolysis and anemia (reduces hemolysis, reduces gallstone
formation)
! If splenectomized, risk of infection with encapsulated bacteria
○ Vaccinate: pneumococcal and meningococcal and HiB
○ If under 6 yrs old, consider partial splenectomy (temporary relief of hemolysis
while still providing freedom from sepsis)
! Symptomatic gallstone disease: cholecystectomy

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MEDICAL LONG CASES

ID: Tuberculosis

ADULTS (less likely paediatrics) contributions from David Ng

How did this patient present, is it TB?

! TB can cause anything except pregnancy → there is a million ways TB can present,
and quite insidiously too, so always think of it as a ddx
! Pulmonary TB: cough +/- fever, loss of weight, pleural effusion
○ Always consider ddx e.g. CA lung
○ Start with CXR: classically infiltrates with upper lobe cavitation; other
appearances possible e.g. collapse, consolidation, pleural effusion, cavitations,
fibrosis, bronchiectatic changes, reticulonodular opacities (miliary TB)
○ Obtain at least 3 sputum samples (either coughed or induced with hypertonic
saline nebuliser, at least one specimen obtained in early morning) for AFB
smear, cultures, TB nuclear acid amplification test (NAAT) i.e. PCR (also has
advantage of testing TB strain for drug resistance)*; if unable to obtain sputum
consider bronchoalveolar lavage (also has added advantage of biopsy if there
is a lesion favourably located)
○ If pleural effusion then tap; some institutions favour sending for ADA in addition
to AFB and culture
○ Presumptive clinical diagnosis is sufficient to initiate therapy.
! Extrapulmonary TB e.g. lymphadenopathy +/- fever, loss of weight
○ Intracranial: CT/MRI. lumbar puncture
○ Lymph node: biopsy and AFB stain/culture
! Interferon gamma release assays (T-spot, quantiferon) are used to diagnose latent TB
infection and should not be used to diagnose active TB (cannot distinguish latent vs
active TB, in acute infection there is temporary anergy and negative T-spot)

*Interpretation of AFB / NAAT results:

NAAT +ve NAAT -ve

AFB +ve Diagnostic. treat with RHEZ Check if inhibitors to NAAT are present.
Repeat AFB. If 2nd AFB also +, consider
non-tuberculous mycobacteria.

AFB -ve Repeat NAAT (if 2x +ve, can be Cannot rule out TB
diagnostic) Clinical judgment whether to treat.
Start treatment if clinically
suspecting TB

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Why does this patient have TB?

! Most often it is an elderly patient with reactivation disease
! But look for any immunocompromised state
○ HIV - in TB always look for HIV and in HIV always look for TB
○ Is patient on any immunosuppressive drugs (e.g. transplant, autoimmune
conditions)
! Work out any contact history, foreign country of origin.

Is this patient receiving treatment?

! Drugs available:
○ 1st line drugs are R (rifampicin), H (isoniazid), E (ethambutol), Z (pyrazinamide)
- R and H are bacteriocidal
○ 2nd line include streptomycin, levofloxacin
○ Give H with pyridoxine.
! What is the patient on: for non-HIV patient a possible regimes is
○ Lung TB: 2 weeks of daily RHEZ, then twice weekly for 6 weeks, then RH twice
weekly till 6 months
○ Extrapulmonary disease may require longer duration of treatment
○ Patient considered contagious until 2 weeks of treatment have been completed
or sputum is negative → isolate until then
! How is the treatment response
○ Compliance to treatment? → Consider Direct Observed Therapy? Taking less
than recommended is a recipe for MDR and treatment failure
○ Follow up sputum smears: repeat 2 months after starting therapy and again if
still positive. Positive cultures after three months of effective treatment must be
evaluated carefully to identify the cause of the delayed conversion. Positive
cultures after 4 months define treatment failure
○ If treatment failure, don’t just add single drug (will breed resistance); retreat
using at least 3 new 2nd line drugs.

Are there any complications of treatment?

! Rifampicin: hepatitis/cholestasis, orange discolouration of urine/tears → monitor LFT,
stop if bil rises
! Isoniazid: peripheral neuropathy → ensure pt is taking pyridoxine 10mg/day
! Ethambutol: optic neuritis → Monitor Ishihara chart
! Pyrazinamide: hepatitis, gout → monitor LFT
! GI side effects can be significant, may affect patient’s ability to take retain meds and
obtain adequate nutrition

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Is there a need for contact tracing?

! Consider chemoprophylaxis for individuals with significant exposure to patient while
pTB was active
○ Consider Mantoux testing (result interpretation depends on prior BCG
vaccination)
○ Or do interferon gamma release assays.
! Isoniazid 300mg OD X 9/12 + pyridoxine 50mg/day

How has the patient been affected? How is the patient coping overall?
! Patient will be unable to work for a period of time (loss of income) and may be difficult
to have to keep going back to polyclinic for DOT
! Funciton: ADL, ambulation
! Nutrition: important to be well nourished to respond to anti tuberculous therapy.
! Financial, social situation: TB treatment is free in Singapore.

Sample summary: Mdm Xiu is a 70 year old lady with non insulin dependant diabetes and
diabetic nephropathy CKD3, admitted for 3 weeks of cough with fever and weight loss. Chest
X ray showed upper lobe cavitation with a small right-sided pleural effusion, and sputum AFB
cultures were positive. She was isolated and commenced on direct observed therapy with
RHEZ. There was symptomatic improvement and weight gain, follow up chest X ray showed
resolution of disease with no residual nodularity. However she lost her job due to her
admission and having to attend direct observed therapy thereafter, and as a result has
significant financial and emotional concerns.

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MEDICINE LONG CASES: THE CLINICAL QUESTIONS APPROACH ID: HIV

MEDICAL LONG CASES

ID: HIV

ADULTS

What is this patient’s disease course / where is he in the natural hx of HIV?

! Antiretroviral therapy has dramatically altered the disease course of HIV, offering the
potential of normal life expectancy. The majority of HIV patients are well outpatients,
but some progress to end stage because of late presentation or failure to receive
treatment
! When and how was this patient diagnosed with HIV?
○ Asymptomatic, incidental diagnosis: e.g. admission for unrelated illness, at NS
screening, employment screening etc.
○ Primary HIV infection: an infectious mononucleosis like syndrome (ddx: EBV,
CMV) with fever, lethargy, myalgia, rash, lymphadenopathy, pharyngitis,
headache
○ Symptomatic HIV infection without AIDS: patients with persistent generalized
lymphadenopathy, other organ-based complications (e.g. thrombocytopenia,
glomerulonephritis) who were found to have HIV → Need to consider ddx.
○ Late-stage presentation with AIDS-defining illnesses e.g. pneumocystis
pneumonia
! Where in the course of disease is this patient? The stage of HIV is of crucial importance
because it determines the likely issues
○ What is the latest CD4? CDC definition: >500 (stage 1), 200-499 (stage 2),
<200 (stage 3) during which AIDS defining illnesses appear.
○ Are there any AIDS-defining complications?

What are the issues and how to manage?

(1) Antiretroviral therapy

! Is the patient on ART?
○ ART is now indicated regardless of CD4 count: increases chance of immune
reconstitution to near normal CD4 levels, reduces transmission
○ If not on, why? → Is the patient ready to start? Need compliance, commitment
to lifelong Rx.
○ If initiating → beware immune reconstitution inflammatory syndrome.

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! What ARTs has the patient had / what is he currently on?

○ Usually start with a backbone of 2 NRTIs (tenofovir, emtricitabine, abacavir -
must test HLAB5701, lamivudine) plus an NNRTI (efavirenz, nevirapine)
○ NNRTIs have low genetic barrier to resistance → Once resistance develops,
switch to a protease inhibitor which has a higher barrier (e.g. lopinavir,
atazanavir, +/- boosting with ritonavir)
○ Choice often depends on comorbids (specialist topic).
! Any issues with ART?
○ Side effects and other issues? > e.g. renal (tenofovir), liver (nevirapine)
○ Compliance is very important as drug-resistance mutations will invariably
emerge if HIV replicates in the presence of antiretroviral drug concentrations
insufficient to exert complete suppression → if noncompliant, explore why.
Consider combination tablets for easier dosing
! What are the response to therapy
○ Any resistance to Rx?
○ Check viral load: prognostically important, goal is to reduce HIV replication
below which the virus does not evolve. If rising → Check compliance, genotype
resistance testing.

(2) Opportunistic infections

! What are the patient’s baseline serologies? > hepatitis, toxo, CMV
! What is the patient’s history of infections?
○ Any respiratory infections: PCP, MAC, TB
○ Any skin infections: HSV,
○ Any chronic diarrhoea: cryptosporidium
○ Any dysphagia: candidiasis
○ Any eye disease: e.g. CMV retinitis (need eye screen)
○ Intracranial infections: toxoplasmosis, cryptococcus, PML (JC virus)
○ Any septicaemia: any bacteria e.g. salmonella
! Prevention of infections
○ Vaccinations: an advanced discussion -- in general vaccinations are impt due
to immunocompromise, but response to vaccine may be poor, also avoid live
vaccines if CD4 low. Consider vaccinating against influenza, tetanus,
pneumococcus, hepatitis B.
○ Precautions if CD4 <200: beware undercooked food including soft boiled eggs
(salmonella, toxoplasma), bartonella (cats)
○ Prophylaxis if CD4 <200: depending on CD4 level, prophylaxis against PCP
(bactrim), toxoplasma (bactrim), MAC (azithromycin)

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(3) Non-infectious disease manifestations

! HIV is itself an inflammatory syndrome and can cause other organ involvement
! Malignant: lymphoma, kaposi sarcoma
! Skin: psoriasis
! Cardiac: HIV cardiomyopathy, inflammatory state increasing risk of IHD
! Neurologic: gullian barre syndrome, peripheral neuropathy
! Haematologic: anemia, leukopenia, lymphopenia, or thrombocytopenia
! Renal: membranous glomerulonephritis
! Psychiatric: depression, HIV related neurocognitive disorders (ddx: intracranial
infection)

(4) Infectivity and public health

! How did the patient acquire disease?
○ Sexual hx: no. of partners, type (homosexual vs heterosexual), casual vs
committed
○ IVDU
○ Occupational
○ Overseas blood transfusion
! Is the patient currently sexually active
○ Must inform partner (by law)
○ If good adherence to ART, viral load <400 → low risk of transmission (Partner
study). If formed partnership, no need condom (acceptable psychologically?).
If casual sex, still need to protect against other STD
○ If viral load high and sexually active → need counselling
! Pregnancy: If female patient, any intentions?
○ Good adherence to ART and well control of viral load → pregnancy is usually
safe
○ Discuss with physician and obgyn → Planned pregnancy

Are there any other comorbid conditions?

! With increasing life expectancy many patients are more likely to die of a comorbid
condition than of AIDS
○ Address comorbids aggressively.
! Beware of disease-disease and drug-disease interactions
○ On ritonavir: statins contraindicated
○ On atazanavir: no PPIs (needs acidic pH for absorption)
○ Tenofovir causes renal side effects
○ Protease inhibitors cause hyperlipidemia, DM → must screen

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How is this affecting the patient?

! Function and employment
! Social stigma is great → look into emotional and psychiatric issues.
! Does the family know and what do they think?
! Financial burden → if cannot afford drugs, join buyer’s club to buy generics from
Thailand.

Sample summary: Anonymous is a 68-year-old Chinese gentleman who was diagnosed 2

years ago with HIV when he first presented with pneumothorax secondary to pneumocystis
pneumonia. CD4 count then was 100. He was started on antiretroviral therapy, to which his
he has been absolutely compliant, and his CD4 count has climbed up to 300. He has not had
any other opportunistic infections, or any other non-infectious HIV complications. He has
developed hyperlipidemia and diabetes mellitus secondary to the antiretroviral therapy, for
which he is on medical treatment. Unfortunately, as he had acquired the infection from one of
his many previous illicit affairs, his wife divorced him after he broke the news to her (she has
thankfully tested negative). He is socially isolated, having been ostracized by family and too
ashamed to tell his friends. He now stays alone in a rented room, supporting himself
comfortably as he continues work as a security guard.

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MEDICINE LONG CASES: THE CLINICAL QUESTIONS APPROACH ID: INFECTIVE ENDOCARDITIS

MEDICAL LONG CASES

ID: Infective Endocarditis

ADULTS (less likely paediatrics) contributions from David Ng

Approach to non-specific fever

The best thing to do is be systematic. A overview is repeated below, a more comprehensive
approach can be found in Approaches to Symptoms of Disease > Fever

History Physical Exam Investigations

Fever Hx (duration, pattern, onset, frequency) Go head to toe Routine: FBC, RP, LFT
Any localising symptoms?
Head: Cultures:
a) Infection - CN palsies, - Blood: 3 sets 3 sites
- Cranial (AMS/Headache/BoV) - Oral: ulcer, fungus - Sputum Cultures
- Ear (tinnitus/giddyness/LoH)
- Pulmonary (Cough, SOB) Lymph Nodes (cervical, CXR
- Cardiac (murmur/IE signs) axillary, inguinal) 2DEcho for I/E
- Intraabdominal (Pain/Vomit/Diarrhea) CT (TAP)
- Hepatic (Jaundice/RUQ pain) Heart & Lungs
- OM/TB Spine (point tenderness) - Murmurs Serologies
- Urine (pyuria/dysuria/flank pain) - Consolidation, collapse - ANA
- GU (PV d/c, urethritis, low abd pain) - Effusion - RF
- Ulcers (numbness/calluses/d/c) - Complement
- vector-borne diseases (malaria) Abdomen: - ESR
- Organomegaly / mass - CRP
b) Malignancy - Tenderness - IFN-γ assay
- constitutional & B symptoms - Genitalia: sores?
- system specific symptoms Additional tests
Bones/limbs: any point - CTD serologies
c) Connective tissue disorder tenderness - Bacterial serologies
- rash, ulcers, joint pains - KIV biopsies
Skin: any infection, bites, - Thick/thin film (malaria)
Risk profile patient: ulcers - HIV serology
- Any risk of immunosuppresion?
- Travel history
- Contact history (including animals)
- sexual history - HIV/STIs
- Drug History
- Vaccination
- FHx of cancer or CTD

Social history and function

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Could this be infective endocarditis?

! Determine onset as acute vs subacute vs chronic involve different organisms
! Clinical manifestations
○ Most commonly PUO, initial 1st line investigations come up empty and time to
look closely for more occult sources
○ New murmur
○ Extra-cardiac manifestations
○ Complications: Heart failure, stroke
! Ddx
○ Common: sepsis (any source) complicated by AMI and/or CCF (esp if pt has
cardiac disease)
○ Other occult infections: deep seated intra-abdominal/pelvic abscess, pocket
site infection from permanent pacemaker or intra-cardiac device

How could this patient have gotten infective endocarditis? Is this a high risk
individual?
! Previous episode of infective endocarditis | Ask for dentition,
! Congenital heart disease | recent dental op
! Prosthetic valves (entirely different ballgame altogether) | Abx prophylaxis
! History of cardiac lesion causing turbulent flow e.g. hx of rheumatic heart dx
! Known IV drug abuser
○ When was last IV use? Shared or re-used needles? Other friends also fever?
! Long-standing catheter e.g. perm cath in renal patient
○ Find out about perm cath care, hx of perm cath infections, MSSA/MRSA
bacteremia

How do I confirm the diagnosis?

! Modified Duke’s Criteria --- please look up
! Translation: what do I need to do on the ground?
○ Thorough clinical examination! Including fundoscopy for Roth spots and urine
dipstick for microscopic hematuria
○ Take 3 blood cultures from different peripheral veins under aseptic technique
over 30 minute intervals, BEFORE initiating IV Abx
○ Arrange for transthoracic echocardiogram (1st line) or transesophageal
echocardiogram (if TTE negative but high index of suspicion, prosthetic valve
or intra-cardiac device causing acoustic shadows)

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What are the complications of IE I need to watch for/manage?

! Congestive cardiac failure
○ Secondary to sudden regurgitant lesion (chord rupture or dehision of
prosthesis), valve obstruction by vegetation, or fistula creating a shunt
! Periannular extension
○ I.e. Formation of abscess, fistula, valvular dehiscence
○ Is there heart block (due to invasion involving conduction bundles)? → serial
ECGs please!
○ Common in prosthetic valve IE, aortic valve most often affected
! Systemic embolization
○ CNS (stroke), kidneys (AKI), spleen (splenic infarct), spine (anterior cord
syndrome)
○ Risk factors: left sided IE, vegetations that are mobile, large (>10mm) or
increasing in size
○ Majority occur within 1-2 weeks of initiating antibiotic treatment → keep
inpatient for at least 1st 2 weeks, before considering OPAT,
! Acute renal failure
○ Multifactorial: multiorgan failure from septic shock or cardiogenic shock, renal
infarct from systemic embolization, immune complex glomerulonephritis,
interstitial nephritis from gentamycin or vancomycin
○ Monitor urine output and renal panel closely, may need renal replacement
therapy

How do I manage this patient?

(a) Medical
! Management is multidisciplinary involving ID physician, cardiologist, +/- cardiothoracic
surgeon
! Begin empiric IV antibiotics covering suspected organisms (e.g. viridans Streptococci,
Streptococcus bovis, S. aureus, Enterococcus). Regimens e.g. benzylpenicillin +
gentamicin, vancomycin if suspect MRSA.
! Antibiotics should thereafter be guided by culture results
! Fever should resolve within days of starting IV antibiotics
! Refer to dentist if suspecting dental source for IE.

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(b) Surgical
! May be necessary for total removal of infected tissue and reconstruction of cardiac
morphology
! Early surgery (during initial hospitalization before completion of full therapeutic
course of antibiotics) may be required if
○ Heart failure from valve dysfunction
○ Periannular extension: Heart block, abscess, destructive lesion
○ Persistent infection: fever or bacteremia in spite of 5-7 days of IV appropriate
Abx
○ Difficult to treat: Left sided IE caused by S. aureus, fungi or highly resistant
organisms
○ Recurrent emboli and persistent vegetation in spite of appropriate antibiotics
! If not for early surgery, ensure fully treating extra-cardiac infection so that new
implant does not get infected. Can consider doing bypass at same time if needed.

(c) Subsequent antibiotic prophylaxis

! Only for cardiac conditions highest risk for IE: prosthetic valve, previous IE,
unrepaired cyanotic congenital heart disease
! Only for procedures high risk for IE:
○ Dental operation
○ Biopsy of respiratory mucosa (tonsillectomy, etc)
○ Surgery involving infected skin or tissue
○ NOT required for routine scopes
! Regimens: amoxicillin 2g PO once, ampicillin 2g IV once, clindamycin 600mg PO
once (if penicilin allergic)

(d) Treatment of source

! Streptococcus bovis IE: associated with CA colon, do colonoscope

(D )

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MEDICINE LONG CASES: THE CLINICAL QUESTIONS APPROACH NEURO: ACUTE STROKE

MEDICAL LONG CASES

Neuro: Acute Stroke

ADULTS
Patients may be at different timepoints of disease: acute stroke – post-stroke follow-up – old
stroke + cardiovascular risk factors; in each case the clinical focus is different. This topic
discusses the whole range but be sure to tailor it to ‘your’ patient.

Is this a stroke?
• Diagnosis is clinical not based on ‘scan’
• Typical presentation:
o Acute onset (minutes) → characterizes a vascular lesion
o Unilateral neurological deficit → e.g. weakness of face and/or limbs
o UMN signs (hyperreflexia, hypertonia, Babinski): take hours-weeks to develop,
in acute setting paralysis is flaccid
• If symptoms appear transient → consider transient ischaemic attack (see appendix)
• Do not forget to consider and exclude stroke mimics:

Stroke Mimic Feature

Hypoglycemia Patient on DM medications

Always do hypocount → excellent mimic of stroke.

Epilepsy - partial seizure with Noted seizure: witnessed or past episodes

Todd’s paralysis Improves rapidly, no lasting neuro deficit.

Structural intracranial lesion

- AVM Can’t tell: need scan
- Subdural hematoma Hx of head trauma
- Tumour Chronic progressive hemiparesis and/or headache.

Infection - meningitis, Fever, photophobia, neck stiffness

encephalitis

Migraine Hx of migraines (but beware of the headache of a

different nature that could be a SAH)

Inflammatory - Multiple sclerosis Younger females, more subacute in presentation

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Where is the stroke?

• Anterior circulation
o Cortical: suggestive in the presence of dense hemiplegia and cortical signs
(aphasia, hemineglect, sensory/visual extinction, apraxia, agnosia,
hemianopia, drowsiness)
o Subcortical (lacunar strokes): no cortical signs, known lacunar stroke syndrome
which involves at least 2 contiguous areas (FAL, FA or AL):
- Pure sensory
- Pure motor
- Sensorimotor
- Ataxic - weakness and ataxia on ipsilat side
- Dysarthria clumsy-hand
• Posterior circulation: brainstem, cerebellar or isolated occipital lobe involvement, e.g.
o Crossed hemiparesis
o Disorder of conjugate eye movements
o Ataxia without weakness on ipsilat side
o Isolated hemianopia or cortical blindness
o Drowsiness

What is the mechanism/underlying etiology?

• Workup - see individual sections.
• Clinical suspicion of likely stroke etiology is based on patient’s risk factors as well as
the localization of stroke -

Ischemic Hemorrhagic

Thrombotic Embolic Hypoperfusion

CVM risk factors: Cardioembolic: AF Systemic shock: Uncontrolled

DM, HTN, HLD, Artery-to-artery haemorrhagic, hypertension
smoking emboli: carotid cardiogenic, septic Coagulopathy
Vasculopath: IHD, stenosis Known AVM
PVD, CKD

Lacunar infarcts Large vessel territory Infarct seen in Bleed visible on

Unilateral well- (e.g. MCA infarct) watershed area scan
defined territory Multifocal infarcts
e.g. MCA infarct (spray of emboli)

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Acute stroke - early management:

(1) Immediate resuscitation

• ABC, Q1H paras & consciousness level, hypocount, supplemental oxygen, NBM and
NG tube, IV drip 2 litres
• Is there any raised ICP: worsening headache and vomiting, drop in GCS, Cushing’s
reflex (late), papilloedema on fundoscopy, false localizing CN6
o Supportive: elevate head 30 degrees, IV mannitol 20% 0.25-0.5g/kg over
20min Q6-8H up to x 3/7, hyperventilate PCO2 25-30mmHg,
o KIV intubate esp patient drowsy and unable to maintain saturation,
o KIV call neurosurgery for decompression

(2) Definitive treatment

• Send for CT brain or MRI stroke protocol early: to distinguish ischaemic stroke vs
haemorrhagic stroke, not for diagnosis.

(a) Ischemic
• Does the patient qualify for IV thrombolysis? (recombinant tissue plasminogen
activator)
o Onset of symptoms within 4.5h - if unsure (e.g. woke up weak), take time
patient last seen to be neurologically normal?
o Measurable neurological deficit
o Age > 18 yrs
o No high-risk for bleed: no recent stroke, neurosurgery, brain tumor, AVM,
bleeding diathesis, active internal bleed, massive infarct, platelet <100, INR
>1.7
• If not for thrombolysis, are clot retrieval techniques e.g. Solitaire, TREVO, MERCI
(subject to availability) possible?
• Early secondary prevention: antiplatelet therapy with either aspirin or clopidogrel
o If aspirin: 300mg stat, 100mg OD thereafter. Add dipyridamole for high risk
patients
o If clopidogrel: 75mg stat and OD thereafter.
o Give PPI cover
• Be wary of complications: cerebra edema, haemorrhagic conversion if thrombolysis
given
o If patient becomes more drowsy or neurologically deterioriates post
thrombolysis → re-CT for haemorrhagic conversion.
o Early decompression for malignant MCA infarct (50% MCA territory, NIHSS
>15, drowsy) → within 48 hours of onset, 18-60 years old

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(b) Hemorrhagic
• Rx is mostly supportive
• Monitoring of GCS and ICP, maintaining oxygenation
• Surgical decompression in selected cases
• Consider seizure prophylaxis.

(3) Manage BP
• Concept is to allow permissive hypertension so as to maintain cerebral perfusion.
• Targets:
o Ischaemic stroke, no thrombolysis: keep <220/120 (lower 15% in 1st 24h)
o Ischaemic stroke, for thrombolysis: keep <185/110
o Haemorrhagic stroke: target 160/90 (if raised ICP, difficult situation -- monitor
ICP and titrate BP according to ICP)
• Unusual situations
o If hypotensive → find out why
o If other indication for aggressive BP reduction e.g. aortic dissection → treat BP
regardless of above targets

(4) Treat underlying cause

• Treatment depends on underlying mechanism of stroke. Identify the clinically likely
stroke mechanism and workup as:
o Neurovascular imaging: MRI/CT angiography, carotid ultrasound (anterior
circulation stroke), MRI neck (posterior circulation stroke)
o Cardiac evaluation: echocardiogram, Holter monitoring for AF.
• Thrombotic and embolic stroke: Control vascular risk factors (DM, HTN, HLD), start
statins regardless of lipid levels
• Embolic stroke: search hard for AF (including paroxysmal), rate control
o Anticoagulate → first ensure no haemorrhagic conversion; repeat CT before
initiation, delay initiation for 2 weeks if hemorrhage is evident
• Haemorrhagic stroke: control hypertension, treat coagulopathy
• Young stroke: workup e.g. prothrombotic disease, vasculitis (out of scope of this text).

(5) Aggressive early rehabilitation

• Often neglected, but crucial to maximise functional recovery.
• If non-ambulant or other impairment: be wary of aspiration pneumonia (speech therapy
assessment), decubitus ulcers.

Acute TIA - early management:

• Clinical significance of a TIA: portends a high risk of stroke
o ABCD2 scoring to risk stratify: age, BP, clinical feature, duration, diabetes.
o May require hospitalization for workup if moderate to high risk.
• Needs urgent workup to determine etiology of TIA - as for a stroke
• Treat identified etiologies urgently.

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Post-stroke follow-up - issues & management:

• Has all the above been done? > Find and treat etiology and risk factors, prevent re-
stroke
• Follow up on rehabilitation progress and function
• Lifestyle adjustments to cope with new functional status
o Swallowing impairment → diet adjustment, NG tube or PEG
o Mobility assistance devices
o Nursing care

All patients - social issues

(1) How has this affected the patient?

• Pre-morbid status (ADL, ambulation) vs current status: is there a big drop?
• Occupation: how badly will this impact patient’s ability to work? E.g. taxi drivers cannot
drive for a year post-stroke
• Hobbies: how badly will this prevent patient from enjoying them? QoL
• Psychologically, how is the patient dealing?
o Reactive/post-stroke depression is common
o Patient’s understanding and attitude towards condition is important as this
influences patient motivation to participate in rehabilitation AND control control
cardiovascular risk factors

(2) How is the patient’s social and financial support?

• Who does the patient stay with?
• Will the patient be able to take care of himself on discharge home? If not, does he
have competent caregivers?
• Does the patient have the financial reserve to put himself through this period of loss of
income? If not, does he receive financial support from anyone else?

Sample summary: Mr Muthu is a 70 year old Indian gentleman with significant past medical
history of poorly-controlled diabetes, hypertension, ischaemic heart disease. He presented
two weeks ago with acute onset left hemiparesis and left facial droop. I understand he received
thrombolysis for ischaemic stroke. Thereafter he underwent rehabilitation and has currently
regained a good deal of left-sided motor function with power 4/5 in most areas. He is able to
ambulate and has no swallowing impairment. In terms of the underlying cause, he was noted
to have an irregularly irregular pulse, and has since been started on warfarin. My main issues
for this gentleman are
1. Right cortical/subcortical ischaemic stroke, s/p thrombolysis
2. Left hemiparesis undergoing rehabilitation.
3. Newly diagnosed atrial fibrillation, on warfarin.
4. Poor patient understanding of disease, likely poor compliance if not addressed.
5. Social isolation: stays alone, divorced, and estranged from children.

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MEDICINE LONG CASES: THE CLINICAL QUESTIONS APPROACH NEURO: CEREBRAL PALSY

MEDICAL LONG CASES

Neuro: Cerebral Palsy

PAEDIATRICS

How did this present > is it cerebral palsy?

! Definition: Cerebral palsy is a heterogenous group of permanent, non-progressive
clinical syndromes characterized by motor and posture dysfunction, secondary to an
insult to the developing brain before the age of 2 years.
! Implication: Trace the developmental hx of the child carefully > it is a static insult,
before 2 years of age. Regression after 2 years is not CP
! Presentations include developmental delay, difficulty walking, etc.

Which type of cerebral palsy?

! Spastic: diplegic, quadriplegic, and less commonly hemiplegic. Elicit UMN signs.
! Dyskinetic: dystonic vs choreoathetotic (observe the involuntary movements).
! Ataxic

What is the etiology of CP in this child?

! Antenatal: TORCH infections, chorioamnionitis, congenital brain malformations,
prematurity -- careful antenatal history.
! Perinatal: hypoxic ischemic encephalopathy
! Postnatal: stroke/intracranial hemorrhage, meningitis, severe drowning, kernicterus --
ask in hx, examine for any VP shunt

What are the issues - prioritise - and how are they managed?
! Motherhood statement (but particularly critical in CP): management requires a
multidisciplinary team with a holistic approach - working with the family to maximize
the child's social and emotional development, communication, education, nutrition,
mobility, and ADL independence

(a) Intellectual & Communication

! The degree to which intellectual development is affected varies - spastic diplegics may
be pretty smart, while others may not even communicate. Visual disorders, hearing
impairment, and speech disorders are also common.
! Special schools: e.g. Cerebral Palsy Association and Rainbow Centre (Yishun,
Margaret Drive) for patients up to 18 years old -- but what happens after the child turns
18?
! Technology has allowed development of augmentative communication strategies for
nonverbal children or those with poor language skills - e.g. picture symbols and voice
output device

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(b) Motor: mobility and ADL independence

! Again, the range of mobility is quite wide -- get to know the child; access function both
in biological (can stand) and social terms (can walk in the house)
! The relatively mobile child may benefit from PT, OT, and motorized wheelchairs.
! Is spasticity bothersome? Try PO antispasmodics (baclofen, dantrolene), botulinum
toxin injection, selective dorsal rhizotomy (interrupt afferent limb of reflex arc)
! Are there contractures? Try muscle tendon release surgery
! Hip dislocations: conservative or reconstruction
! The immobile: management of complications e.g. sacral sores.

(c) Nutrition
! Feeding problems are common in children with cerebral palsy
! Any aspiration pneumonias and how have they been managed?
! Is intake adequate? > Growth of child
! Is there a need for NG tube or PEG feeding? If so, have they been carried out? If not,
why?

(d) Seizures
! A common comorbidity in CP > refer to discussion on seizure.

What are the care arrangements?

! Especially child is ADL dependent
! What are the concerns with the care arrangement?
! Is there caregiver stress? > Special schools provide some reprieve.
! Social and financial concerns.

Have others been able to accept the child?

! E.g. family members, peers
! Drooling can be quite disconcerting. Consider behavioural therapy (oral motor skills
training to improve lip and jaw closure), anticholinergics (e.g. glycopyrrolate).........
! Urinary incontinence: toileting schedule, diapers, clean intermittent catheterization.

Sample summary: See P. is a 12 year old boy with spastic diplegic cerebral palsy. He was a
32-weeker, requiring prolonged neonatal ICU care, and was diagnosed with cerebral palsy
when he failed to walk at 1.5 years of age. He also suffers from epilepsy with monthly
breakthrough seizures. Functionally, he engages in simple communication, is able to assist
with self-care, is able to get around on a motorized wheelchair. He attends a special school.
He has a good social setup with a supportive mother, however she seems to be suffering from
some caregiver stress. My problem list is
1. Epilepsy with breakthrough seizures - mother does not know how to give rectal
diazepam and tries to stuff spoon in mouth when he seizes.
2. Caregiver stress
3. Spastic diplegic cerebral palsy

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MEDICAL LONG CASES

Neuro: Headache & Migraine

ADULTS & PAEDIATRICS

What is my diagnosis?
! The key to diagnosis is characterizing the nature of pain (a classic use of the
‘SOCRATES’ mnemonic - not an exhaustive list of what to consider, but things you
have to be able to answer by the time you finish the consult).
! Time course is important - distinguish acute vs chronic vs recurrant/episodic
! Note: Any new onset headache in a patient >50 years old → worry about tumor, giant
cell arteritis

(1) Have I ruled out dangerous causes?

! Acute generalized headache:

Cause Characteristic Workup Treatment

Subarachnoid Thunderclap: sudden CT brain (best Coiling (radiology)

haemorrhage onset, max at onset within 12h) Clipping (neurosurg)
Worst headache ever had LP if CT -ve > for
Suspect in ADPKD pts xanthochromia

Meningitis Fever, photophobia, neck LP Ceftriaxone, vanco +/-

stiff Blood c/s ampicillin (listeria)
Altered mental state Steroids
Purpuric rash

Haemorrhagic Neurological deficit CT brain See stroke

stroke

Hypertensive Uncontrolled BP CT brain (ddx BP management

crisis SAH)

Venous sinus Acute: like SAH Prothrombotic screen

thrombosis Subacute: raised ICP, CNS/ENT cancer
focal signs, seizure, Autoimmune screen
encephalopathy Anticoagulation (clexane
CT and LP negative then warfarin)

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! Chronic progressive headache

○ Tumour: worse on supine position / coughing / sex, associated nausea &
vomiting +/- progressive focal neurological deficits (e.g. CN6, hemiplegia,
seizure). In pituitary tumours, look for bitemporal hemianopia and features of
acromegaly

(2) Are there other possible secondary causes?

These can either be acute first episode localized (consider together with acute first episode
generalized group), or recurrent episodic (consider together with primary headache group).
! Under this category, the next important thing to rule out is if there are any vision
threatening causes: Giant cell arteririts, glaucoma
! Giant cell arteritis: >50yo, subacute throbbing headache over superficial occipital or
temporal arteries, a/w jaw claudication on chewing
○ 75% raised CRP and ESR, diagnosis confirmed on biopsy (within 2 weeks),
○ Treat with prednisolone to prevent blindness
! Glaucoma: unilateral painful red eye with fixed mid-dilated pupil, diminished peripheral
vision, hx of glaucoma
! Sinusitis: hx upper respiratory symptoms, pain behind browbone or cheekbones
! Trigeminal neuralgia
! Benign idiopathic intracranial hypertension: young fat female, headache worse on
supine position/coughing/sex. Look for papilloedema.
○ Usually CT brain done first TRO intracranial lesion
○ Dx confirmed with high opening pressure on LP

(3) If likely primary headache, which type?

! There are three primary causes of episodic recurrent headaches (>5-10 episodes) with
characteristic differences (see table: diagnostic criteria marked by *)
! Always re-explore the diagnosis to avoid missing ddx.
○ If any change in character or response to treatment of previous headaches →
do not simply blame primary headache disorders, worry about other sinister
causes

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The primary headache disorders: characteristics and diagnostic criteria

Tension headache Migraine Cluster headache

Duration & At least 5 attacks At least 5 attacks

frequency * Each 30min-7d Each 4-72h Each 15-180min

Frequency: between
EOD to 8x/day for
>half of the time when
the disorder is active

Characteristic At least 2 of At least 2 of Unilateral

of pain * - Bilateral - Unilateral Severe pain
- Nonpulsating - Pulsating
- Mild or moderate - Moderate or severe
- Not worse on - Worse on physical
physical activity activity
Classic
description Pressing/tightening Sharp boring pain
band around head focused in an around
the eye

Associated None of Either or both of Sense of restlessness

features* - Photophobia - Photophobia or ≥1 ipsilateral
- Nausea/vomiting - Nausea/vomiting autonomic feature
- Conjunctival injection
or tearing
- Eyelid edema
- Nasal congestion
- Facial sweating
- Facial flushing
- Fullness in ear
- Miosis / ptosis

Some May or may not have May be chronic or

subtypes also aura: visual, sensory, episodic (lasts 7d-1y,
have aphasia, hemiplegia, separated by pain-free
brainstem dysfunction remissions of ≥1m)
(dysarthria, vertigo,
ataxia, diplopia;
exclude stroke)

* Diagnostic criteria

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Management issues

(1) Trigger avoidance

! Most patients know their trigger e.g. work stress, certain foods (cheese, chocolate,
alcohol), flashing lights → can this be avoided?
! Behavioural management strategies; lifestyle modification
○ Regular sleep, exercise, meals
○ Stress management
○ Cognitive behavioural therapy
! Rule out medication overuse headache: if headache is persistent or worsens during
medication use, ≥15 days/month for at least 3 months
○ Establish pattern of medication use: consider medication overuse headache if
using for ≥10 days a month (ergot, triptan, opioids) or ≥15 days (simple
analgesics)
○ If medication overuse headache, need to withdraw overused drug + give
pharmacological and nonpharmacological support through withdrawal
headaches (antiemetics, antipsychotics, rescue analgesic other than the one
overused)

(2) Pain control

! How much is this affecting the patient?
○ Patient satisfaction with current Rx
○ Migraine Disability Assessment Scale: guides stratified approach to
pharmacological treatment (low, moderate and high need)
! Acute treatment: principle is to start Rx early and whack hard (better outcome than
escalation if not improving).
○ Simple analgesics: paracetamol, NSAIDs +/- caffeine as adjuvant
○ Migraine: serotonin agonists (triptans > ergots), antiemetics (metoclopramide,
chlorpromazine)
○ Cluster headache: oxygen (100% 10L for 20min), SC sumatriptan
○ Be wary of side effects and contraindications: e.g. renal disease and NSAIDs,
ischaemic heart or cerebrovascular disease and triptans/ergots
○ Adjunctive dexamethasone reduces risk of recurrence.
○ Generally try to avoid opiates → high risk of early recurrence
! Prophylaxis
○ Start if recurrent attacks → cannot use acute treatment >10 days a month
○ Start low dose and titrate up
○ Tension headache: antidepressants e.g. amitriptyline, mirtazapine
○ Migraine: antiepileptics (e.g. valproate), antidepressants (e.g. amitriptyline),
beta-blockers e.g. propranolol
○ Cluster headache: verapamil, steroids, lithium.

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(3) Therapeutic relationship

! Headache diary: frequency, duration, disability, response, adverse effects to meds
! Establish partnership with patient:
○ Address patient expectations
! Education and collaborative management.
○ Educate on nature and mechanism of disorder
○ Strategies for identifying and avoiding triggers
○ Importance of limiting days of acute Rx to prevent medication overuse
headache
○ Maximize compliance by discussing rationale for treatment, when/how to take
medications, adverse effects

How is this affecting the patient?

! Personal: how is the patient’s mood? Chronic pain predisposes to depression
! Function: is the patient able to work? how often does he need to take leave?
! Elicit any concerns, especially that of brain tumour

Sample summary: Jitter is a 35-year old lady with a 4 year history of episodic recurrent
headache; this is severe, unilateral, throbbing, and associated with photophobia. She was
diagnosed as migraine and given ergots plus propranolol prophylaxis. In the last half year,
however, she complains of progressively worsening headache. She had been under
significant work stress and has been taking ergots plus panadol almost daily. My main issues
for her are:
1. Medication overuse headache - she is aware of medication overuse headache but
feels crippled without medications, and unable to meet work deadlines.
2. Migraine

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MEDICINE LONG CASES: THE CLINICAL QUESTIONS APPROACH NEURO: MULTIPLE SCLEROSIS

MEDICAL LONG CASES

Neuro: Multiple Sclerosis

ADULTS

What is the clinical presentation?

! Begin by eliciting a history of previous episodes of CNS dysfunction
! Where is the lesion? For example common MS lesions include -
○ Optic neuritis: eye pain accentuated by eye movements, central visual loss,
RAPD, disc edema +/- pallor
○ Brainstem disease: Internuclear opthalmoplegia (bilateral - highly likely MS),
hemiparesis.
○ Cerebellar disease: slurred speech, gait imbalance, dysmetria
○ Spine disease: long tract sensory symptoms, diplegia/paraplegia,
bladder/bowel dysfunction
! What is the lesion: is it inflammatory?
○ Onset is characteristic: inflammatory diseases like MS have subacute onset
over hours-days. In contrast vascular lesions have an acute onset over
minutes, while chronic onset (days-weeks) characterises a neoplastic lesion
○ Ddx: infective lesions (meningitis, abscess), episodic lesions (seizure) - ensure
no fever and no seizure symptoms.

Is this MS?
! Diagnosis of MS requires demonstrating dissemination in space (DIS) and
dissemination in time (DIT), clinically or by MRI criteria (McDonald 2010), with
exclusion of ddx
○ Clinical diagnosis: two attacks that localize to two locations
○ MRI evidence of DIS: T2 lesions in ≥2 of 4 typical regions (periventricular,
juxtacortical, infratentorial, spinal cord)
○ MRI evidence of DIT: new lesion on follow-up scan, or simultaneous enhancing
and non-enhancing lesions
○ Disease felt to be MS but not meeting criteria is called ‘possible MS’.
! LP is not necessary but if done shows oligoclonal bands

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! Be wary of differential diagnoses

○ Neuromyelitis optica (NMO): visual defect more likely bilateral, altitudinal (vs
unilateral, central), myelitis more likely longitudinally extensive and affecting
entire cross section (vs discrete, affecting part of cross section) → worse
prognosis (60% blind and 30% die in 5 years) → do NMO-IgG (AQP4), look at
Wingerchuk criteria
○ Acute disseminated encephalomyelitis (ADEM): post-infectious presentation,
monophasic illness, lesions on MRI all same age.
○ Autoimmune disease e.g. SLE: joint pains, rash, seizures → do ANA, dsDNA,
ANCA, etc.
○ HIV

What is the course of MS?

! MS has four defined clinical courses
! Clinically isolated syndrome: a single monosymptomatic attack compatible with MS is
often the first presentation
○ Diagnose MS if there is MRI evidence of DIS/DIT
○ Else observe -- it may subsequently develop into MS
! Relapsing-remitting MS (85%): episodes of relapse (which may recover or have
sequelae) and intervening periods without disease progression
! Secondary progressive MS: A longstanding relapsing-remitting MS may secondarily
progress i.e. gradually worsen during intervening periods, with minor remissions
between episodes
! Primary progressive MS (10%): progression of disability from the beginning, without
significant remissions; there may be superimposed relapses/flares

What are the issues and what treatment has the patient received?

(1) Flares
! What is the course of flares: how often, how troublesome, what is the response to
treatment? → Rule out ddx.
! Acute Rx: first line glucocorticoids → no effect in disease activity or disability. Plasma
exchange if no response.
! Disease modifying therapy for RRMS e.g. injection (inteferon), infusion (natalizumab),
and oral
○ If not on → why not
○ Consider starting -- reduces flare frequency although(effect on disability
uncertain)

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(2) Disability
! MS inevitably progresses to disability, but quite slowly (RRMS: median time to needing
walking aid is 28 years; faster in PPMS)
! Elicit if there are gait problems or other disability
○ Supportive measures - physiotherapy, walking aids
○ Spasticity - e.g. baclofen
! Bladder dysfunction
○ Anticholinergics (oxybutynin), intermittent catheterization

How is the patient coping?

! Function: disability, fatigue, ability to work, disruption to life.
! Psychological: depression, anxiety at disease course
! Pregnancy: any intention? > MS gets better during pregnancy but worse post-partum.
! Financial issues

Sample summary: Ms Claire Rose is a 23 year old Caucasian lady with relapsing remitting
multiple sclerosis. She was diagnosed 3 years ago when she presented with one-sided
weakness/numbness and difficulty coordinating worsening over 3 weeks. MRI brain showed
2 lesions of different ages. She has had 2 relapses since, one of which had additional spine
involvement. Her symptoms respond to high dose steroids in all 3 admissions, but her pre-
morbid function takes a small dip with every relapse. She now needs a walking aid to ambulate
independently and some assistance for her ADLs, but is still able to write and type. Otherwise
her vision is unaffected and she is still bladder/bowel continent. She is still hopeful that she
can complete her university education and hold a job that is clerical or that allows her to work
remotely from home. Her family is extremely supportive - although they cannot afford
interferon injections for her at the moment, they are working hard to save up so she has the
best shot at preserving her function.

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MEDICAL LONG CASES

Neuro: Muscular Dystrophy

PAEDIATRICS

How did this boy present?

! Duchenne Muscular Dystrophy: weakness is first clinically noticeable ~ 2-3 years old
and progresses thereafter, patients are usually wheelchair bound by 12 years.
! Becker Muscular Dystrophy: weakness starts later and is milder. Patients do not
become wheelchair bound before 15 years old.
! Ddx:
○ Consider non X-linked etiologies e.g. limb-girdle muscular dystrophy.
○ Rule out fatigability in myasthenia gravis.
! There will often be a +ve family history.
! Clinical findings are LMN LL weakness affecting proximal before distal muscles, calf
pseudohypertrophy, Gower’s sign, waddling gait, lumbar hyperlordosis → findings
should still be present.
! Initial investigations would have showed: elevated CK, abnormal ECG, myopathic
EMG; diagnostic confirmation is via genetic testing (dystrophin) or muscle biopsy.

What are his current status?

! Lower limb motor function: is the patient still ambulant? > Usually wheelchair bound
by 12 years old.
! Respiratory function: any respiratory failure, pneumonias?
! Cardiomyopathy: any heart failure, arrhythmiass
! Cognitive development: often associated with mild intellectual disability
! Overall health: growth & development

How is he managed?
! Disease modifying therapy: Steroids prolong walking years and delay mortality. Start
at 4-5 years old;
! Mobility aids: orthoses, braces, eventually wheelchair
! Vaccinations
! Management of heart failure.

How is the child & family coping?

! Physical: Function, ambulation, and self care.
! Emotional: Awareness of disability, social interactions, self esteem
! Financial issues

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Have end of life issues been explored?

! Duchenne patients lose mobility by 12 years and die in late teens or 20s while Becker
patients lose mobility after 16 years and can survive beyond 30s.
! Advanced care planning and palliative management is often helpful.
! Gently probe patient's and family’s understanding of prognosis and if not adequate,
should refer for ACP.

Genetic counselling
! Are other family members involved?
! Do parents understand implication for future pregnancies: X-linked recessive,
therefore half of all male children are affected (i.e. 25% of all children), and half of all
female children are carriers.
! Are patient’s sisters aware that they may be carriers?
○ Ethical issue: should parent test the child before child is 21? What if the child
does not want to know?
○ Implications for future relationships

Sample summary: Da Tui is a 12 year old boy with Duchenne’s muscular dystrophy,
diagnosed at the age of 3 when his parents brought him to a pediatrician for delayed gross
motor milestones (he started to pull to stand at 1.5 years, walk at 2 years and run at 3 years).
He was able to ambulate and participate fully at Rainbow Centre with his walking aids up til
the age of 9, and became wheelchair bound by 11. He has never had any cardiac or
respiratory complications, but is cushingoid from the steroids he has been taking since 5 years
old. Da Tui is accepting of the fact that he will never be strong like the other children, but is
still quite happy in school where there are other peers like himself. His parents plan to break
the news about his prognosis soon and start advanced care planning. Da Tui has 2 other
younger sisters who have not been tested for carrier status -- the parents intend to let them
decide on whether to test for carrier status older in life.

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MEDICAL LONG CASES

Neuro: Myasthenia Gravis

ADULTS AND PAEDIATRICS

How did this patient present → is this MG?

! MG is characterized by a fluctuating degree and variable combination of fatigable
weakness which may first affect --
○ Ocular involvement only (50%): non-conforming pattern of ophthalmoplegia
(does not fit CN3, CN6, or INO pattern - but sometimes can mimic) + ptosis
○ Generalized involvement (see table)
! For each presentation consider differentials (see table). In particular,
○ Sensory involvement is not a feature of MG
○ Lambert-Eaton myasthenic syndrome (LEMS): important not to miss as it is
paraneoplastic. In LEMS, weakness and reflexes improve on exercise (vs
fatigue in MG); it tends not to first present occular-only disease. If suspicious,
test for antibodies to voltage-gated calcium channel (VGCC) and do
electrophysiology. If LEMS is confirmed, look hard for a cancer e.g. lung.

Presentation Classic for MG Differentials & their features

Ocular Non-conforming Brainstem & cranial nerve lesions: known pattern of

opthalmoplegia opthalmoplegia (CN3, CN6, INO), other CN palsy
Ptosis (uni or bilat) Horner's syn: Miosis, unilateral ptosis, anhidrosis.
Pupils are spared Thyroid ophthalmopathy: Proptosis, Exopthalmos,
symptoms and signs of hyperthyroidism

Bulbar Fatigable chewing Brainstem & cranial nerve lesions: other CN palsy
Dysphagia Cortical lesion (e.g. stroke): long tract signs
Dysarthria Motor neuron disease: mixed UMN & LMN signs.
Nasopharyngeal CA

Limb Proximal weakness Lambert-Eaton myasthenic syndrome (see above)

Fatigable Motor neuron disease: mixed UMN & LMN signs
Sensation spared Peripheral nerve: motor neuropathies e.g. CIDP
Myopathies: muscle pain, percussion myotonia

Face & Neck Expressionless face Bilateral CN 7 palsy

Myasthenic sneer Brainstem disease
Dropped head syn

Respiratory Type 2 respi failure Motor neuron disease

Dyspnoea. Myopathies

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! Confirm diagnosis of MG via:

○ Bedside tests: Tensilon test (edrophonium), ice pack test
○ Electrophysiologic tests: Repetitive nerve stimulation, single fibre
electromyography
○ Serum antibodies: anti-acetylcholine receptor antibody, anti-MuSK (muscle
specific receptor tyrosine kinase) antibody

What is this patient’s disease course?

! 50% of patients who present as ocular MG may develop generalized myasthenia by
two years; no way to predict who will generalize
! Where in the ‘classic’ trajectory of disease is the patient? → But each case is unique.
○ Early MG: transient symptoms, may even remit spontaneously for weeks
○ Active phase: symptoms progress (in frequency, severity, distribution). This
occurs 5-7 years after onset (peak at 3yr). Myasthenic crises may occur.
○ Second phase: symptoms stable but persist; occasional exacerbations
precipitated by infection, medication taper, etc
○ Third phase: many patients eventually remit (on meds or off)
! Risk assessment - Hx of myasthenic crisis?
○ How severe → respiratory failure, intubation?
○ What was the trigger? (e.g. infection)
! Is this patient progressing: increasing drug requirements or symptoms?
! What is the functional status now?

What is the patient’s treatment, can I improve it?

! What is current mx, is it optimal?
○ Acetylcholinesterase inhibitor: pyridostigmine → symptomatic relief
○ Chronic immunomodulators: steroids, azathioprine, mycophenolate,
cyclosporine → indicated if symptomatic on pyridostigmine or respond only
temporarily
○ Rapid immunomodulators: plasmapheresis, IVIg → for myasthenic crisis, as a
bridge to initiating other immunotherapies, or pre-surgery for mod-severe MG
! Is there a need to offer thymectomy?
○ CT scan for a thymoma → If present, should resect
○ Even if no thymoma, recommend thymectomy in generalized MG: increases
chance of becoming asymptomatic or achieving medication-free remission
○ Controversial in ocular MG
! Prevent mortality & morbidity from myasthenic crisis
○ Patient education -- when to seek help
○ Early recognition → generalized weakness can mask respiratory distress
○ Monitoring e.g. negative inspiratory force
○ Careful when stepping down medication

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Are there any comorbids?

! Other autoimmune disease: e.g. Grave’s disease, RA, SLE
! Is the patient on other drugs?
○ A lot of drug-disease interactions, need to look up
○ Avoid fluoroquinolones, aminoglycosides, Mg sulfate.
! Is the patient going for surgery? > Beware of anaesthesia in the MG patient
○ Avoid neuromuscular blocking agents if possible: MG patients have
unpredictable resistance to depolarizing NMBA (succinylcholine), and
unpredictable sensitivity to nondepolarizing NMBAs (eg rocuronium,
vecuroniume. Anticholinesterases prolong the effect of succinylcholine and
delay the onset of nondepolarizing NMBAs.
○ Use short-acting sedatives, hypnotics, and anesthetic agents

How is the patient coping?

! Functional status: able to work?
! Social support: if stay alone -- what happens if enters crisis?
! Financial

Sample summary: Floppy is a 45-year old housewife who presented to the ophthalmologist
three years ago with ocular myasthenia. Six months ago her myasthenia generalized to
involved her limbs, and she has found it increasingly difficult to do heavy housework. She
presented one week ago with increasing weakness and shortness of breath, although on
admission her negative inspiratory force and PCO2 were within normal values. She was
managed as for threatened myasthenic crisis with steroids and IVIg and has since improved,
although she remains slightly symptomatic. Workup also revealed a thymoma for which she
will undergo surgery next week. My issues for her are:
1. Generalized myasthenia gravis with threatened crisis → Need to monitor, educate
patient, vaccinate
2. Thymoma in myasthenia gravis for resection

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MEDICAL LONG CASES

Neuro: Parkinsons’ Disease

ADULTS

Is this parkinsonism?
Relatively easy to identify: Tremor, Rigidity, Bradykinesia, Postural instability

Is this idiopathic Parkinson’s disease or something else?

! Features supporting / suggesting idiopathic Parkinson’s disease (PD)
○ Unilateral onset, persistent asymmetry of signs
○ Resting tremor 4-6 Hz
○ A clear and dramatic beneficial response to dopaminergic therapy
○ Presence of levodopa-induced dyskinesia
○ Progressive clinical course of 10 years or more
! Are there any features to suggest “Parkinsons-Plus” syndromes?
○ Lack of response to levodopa or dopamine agonists in early stages of disease
○ Marked symmetry of signs in early stages of the disease
○ Rapid progression
○ Features specific to each “Parkinson’s Plus” syndrome:

Multi-System Pyramidal signs unexplained by previous stroke or spinal cord lesions

Atrophy (MSA) Autonomic symptoms e.g. postural hypotension, incontinence early in
disease course (may occur late in PD)
Cerebellar involvement

Progressive Ocular: impaired vertical gaze overcome with doll’s eye, eyelid freezing
Supranuclear Limbs: Severe postural instability, rigidity trunk > limb, tremor is rare
Palsy (PSP) Early onset of dementia

Corticobasal Cortico: Pyramidal tract signs not explained by previous stroke or spinal
Degeneration cord lesions, progressive aphasia
Basal: Prominent (myoclonus) apraxia, alien limb phenomenon

Lewy-Body Early onset hallucinations or psychosis, precipitated by initiation of low-

Dementia dose levodopa or dopamine agonists
Early onset of dementia (occurs late in PD)

Vascular History of cardiovascular risk factors, multiple lacunar strokes

Parkinsonism Marked symmetry of signs

Extrapyramidal History of anti-psychotic use or psychiatric disorder

side effect

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Where is the patient in the course of disease?

! Identify where in the natural course is the patient: PD begins indolently and progresses
over years.
○ Motor function is initially good but disability eventually sets in (25% severely
disabled at 5 years, 67% at 5-9 years, 80% at 10-14 years).
○ Non-motor manifestations develop late in the course of disease
! Staging systems include Hoehn and Yahr (motor only) and unified Parkinson Disease
Rating Scale (more complicated, looks at all aspects)

What are this patient’s manifestations & management tasks?

! The main goal of Rx is to preserve the patient’s mobility and function for as long as
possible, and manage symptomatic non-motor manifestations as they come.
! Hence Rx is all about what is bothering the patient → find out!

(1) Maximise motor function

! Difficulty walking: a product of bradykinesia (shuffling gait, freezing, festination, turning
in numbers), rigidity (stooped posture), and postural instability (falls)
! Difficulty communicating: hypomimia (mask-like facies), speech impairment
(hypokinetic dysarthria, hypophonia, palilalia), micrographia
! Other features: decreased spontaneous eye blink rate, dysphagia and sialorrhea

(a) Treat dopamine deficiency

! Early PD: <65yo, milder motor symptoms → Try dopamine agonists (Bromocriptine,
ropinirole) first
○ Less efficacious but postpone levodopa use and save it for later; long term
levodopa inevitably leads to reduced response, motor fluctuations, dyskinesia.
○ Alternative: anticholinergics.
! Later PD: >65yo or any age with prominent motor symptoms: Levodopa-carbidopa
(madopar).
○ Assess side effects: e.g. postural hypotension, nausea/vomiting (carbidopa is
a peripheral decarboxylase inhibitor, reduces side effects by reducing
peripheral levodopa to dopamine conversion)
○ Assess response: progression of motor symptoms, any reduced response or
increasing requirements for madopar
○ Assess dyskinesias
○ Assess motor fluctuations: any difficulty titrating dosing to reduce dyskinesias
when “on” drug and bradykinesia when “off” drug
! Later lines of therapy - other drugs available as add-on therapy, but no miracles.

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(b) Adjuncts to mitigate reduced motor ability

! Walking aids
○ Walking sticks - built in lasers project lines on the floor to break freezing
episodes
○ Walker with wheels (please do not give walking frame! PD patients cannot do
the many steps to walk with a frame)
○ Wheelchair
! Manage fall risk
! Home modifications
! Social interactions: are these inhibited due to hypomimia, speech difficulties, and
writing difficulties?

2. Assess & manage non-motor features

(a) Incontinence
! Usually more due to inability to reach toilet in time, than true incontinence
! Options include use of diapers, bedside potty/pan, or caregiver to wheel patient to toilet
every time

(b) Nutrition and swallowing

! Is the patient getting enough nutrition?
! Difficult issues in end stages → anorexia, dysphagia
○ Loss of interest in food
○ Dysphagia
○ Aspiration risk → pneumonias
! Get speech therapist input: thickened feeds, NG tube?
! Discuss goal of care!

(c) Psychiatric issues

! Psychiatric complications are the most challenging manifestation of PD to deal with
and are the main culprits of caregiver stress
! Assess what specific psychiatric issues are present and how this affects patient and
carers.
! Pharmacological therapy may be available -- but is this what you want?
○ Dementia: cholinesterase inhibitors (donepazil, mementine)
○ Sleep disturbances → benzodiazepines, non-benzo hypnotics (zolpiclone,
zolpidem)
○ Mood disorders → antidepressants, commonly SSRI
○ Visual hallucinations → reduce PD drugs, consider atypical antipsychotics

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Advanced care planning

! Gently probe patient's and family’s understanding of prognosis and wishes → if
insufficient, need to gradually discuss.
! Do ACP if not done
○ Clarity on goals of care.
! Palliative management of symptoms.

How are the patient and family coping?

! Disease understanding → focus groups
! What is the patient’s current function: ambulation, ADL, ? occupation
! What are the care arrangements?
○ If already has a caregiver → Any carer stress?
○ If not yet → Does he need one?
○ If still ambulant → What is the long-term plan?
! What are the patient and family’s emotional and psychological needs: very often there
is little understanding of the complex issues involved.
! Financial concerns

Sample summary: Mr Park is a 70 year old gentleman who first presented with unilateral
tremor and rigidity upon retirement 7 years ago. He was diagnosed to have idiopathic
parkinson’s disease and treatment was initially withheld. With disease progression treatment
was started 5 years ago, first with bromocriptine and subsequently madopar. Effectiveness
has gradually decreased despite uptitration of dose and dosing frequency, with declining
motor function, dosing-related dyskinesias and pre-dose freezing. Mr Park is no longer able
to walk with a walking stick and spends his days mainly in a wheelchair. He no longer
communicates much with his family. The current issues are:
1. Idiopathic parkinson's disease, failing madopar therapy
2. Behavioural symptoms - sleep-wake reversal and night-time agitation which disturbs
his family’s sleep
3. Care issues - his main caregiver (wife) suffered a stroke last year and is struggling
4. Advanced care planning - goals of care are not established and family does not
understand prognosis.

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MEDICAL LONG CASES

Neuro: Seizure, First Seizure

ADULTS AND PAEDIATRICS

If the presenting complaint is ‘seizure’, be sure to distinguish whether this requires an

approach to first seizure, or is an known epilepsy case.

Is this really a seizure?

! The usual task is to distinguish seizure vs syncope. Obtain history from a witness if
available, if not then it has to be distinguished based on pre and post events.
! Rule out other mimics: hypoglycaemia, anaemia, cardiac events, stroke -- always
check glucose.
! Seizure
○ Pre-ictal: happened in any position, may have preceding aura e.g. flashing
lights, smell, sounds
○ Ictal: loss of consciousness, not responsive to call; witnesses will describe
jerking of limbs, uprolling of eyes, clenching of jaw and arching of back. If
tongue is bitten, usually at the lateral aspects of the tongue. Urinary
incontinence is not a useful feature.
○ Post-ictal: drowsy for up to half an hour, can sometimes have todd’s paralysis
! Syncope:
○ Pre-syncope, happened when suddenly getting up, with a sensation of ‘dark
closing in’ (like James Bond movies)
○ Syncope: witnesses will describe loss of tone and patient sliding to the floor,
can have a jerk or two but otherwise quite motionless
○ Post-syncope: no drowsiness on regaining of consciousness
! Screen for causes of syncope anyway, esp when it may not be so clear whether
seizure vs syncope
○ Cardiac: preceding chest pain, palpitations, SOB, heart murmurs (syncope is a
poor prognostic feature of AS) -- exertional syncope is a bad sign.
○ Postural hypotension: DM, parkinsons, MSA -- do postural BP
○ Drugs: HTN meds (postural hypotension), antidepressants
○ Vasovagal: positional change, on micturation

If likely seizure > what pattern?

! Generalized: Petit mal (absence) vs Grand mal (tonic-clonic)
! Partial: simple partial (normal conscious level) vs complex partial (impaired conscious
level) vs secondary generalization → look for a focal lesion!

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What is the course of seizure thus far & what is response to treatment?
! Abort spontaneously without treatment
! Abort after rectal diazepam or IV benzo (lorazepam 4mg, diazepam 5mg)
! Status epilepticus = seizure ≥5 minutes or 2 seizures without recovery of
consciousness in between → phenytoin, barbiturate coma → ICU.
! Any injury

What is the etiology? > look for any provoking factors present?
! Infection e.g. meningitis - fever, neck stiffness, photophobia
! Metabolic: look for background setup and measure the electrolytes
○ Hypoglycemia: diabetic?
○ Hypercalcaemia: urolithiasis, abdominal pain, hx of parathyroid problems
○ Hyponatremia: poor oral intake, hx liver/cardiac/renal failure, hx TURP
○ Hypokalemia: e.g. gastroenteritis, vomiting.
○ Drugs and alcohol: withdrawal, delirium tremens?
! Intracranial lesion → consider CT brain.
○ Acute stroke, SAH, or cranial trauma
○ Previous strokes now with scar epilepsy
○ Brain tumour - preceding history of constant progressing headache, one-sided
weakness/numbness or difficulty walking
! [Paeds] Is there an underlying syndrome or seizure disorder?
○ Developmental milestones: have they been on time? have they been
regressing?
○ Any dysmorphism?
○ Any neurocutaneous stigmata?
○ Any family history of epilepsies?
○ Any abnormal neurologic findings
! [Paeds] Febrile seizure - Has the child been febrile from intercurrent illness with a rapid
rise in temperature? Any family history of febrile seizures?
○ Simple febrile fit: typical epidemiology (6 months - 6 years), typical seizure
(GTC, <15min, do not recur in 24h), otherwise normal child (normal
development, no neuro findings)
○ Complex febrile fit: does not fit the above.
○ Diagnosis of exclusion so exclude the above causes first.

What is the management?

! Workup and treat precipitant
! If precipitant will persist (e.g. new stroke, trauma), consider antiseizure prophylaxis.
! If apparently idiopathic: do not diagnose epilepsy on a 1st seizure unless there is a
high probability of further seizures (equal to recurrence risk after two unprovoked
seizures i.e. 60% - e.g. if focal brain lesion), or a clear epilepsy syndrome → if
suspicious, consider EEG.

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APPENDIX: Paeds febrile fit – Communication to parents

! What is this condition? Ma’am, what your child has had is called a febrile seizure. It
occurs when temperatures rises rapidly during a fever. It tends to occur in children
between 6 mth old to to 6 yrs old. It must have been very scary for you, but this happens
quite commonly. It does not cause brain damage, or any delay in your child’s
development, as long as it is stopped as soon as possible.

! Can it happen again? Yes - the risk of your child having another febrile seizure is 1 in
3, and a further 1 in 3 will have ≥3 seizures. Recurrence is higher if onset before 1 yr
old and if there is positive family history. But it has a benign course -- only 1% develop
epilepsy, which is the same risk as the general population.

! What to do if it happens?
○ Stay calm, take note of the time it started
○ Clear a space on the floor and position child on side, keep sharp objects away.
Do not restrain child or put objects into mouth.
○ Give rectal diazepam: twist top off, spread open your child’s butt cheeks, insert
the tube into the anus and squeeze in the contents. Then remove the tube and
squeeze the butt cheeks together to prevent the diazepam from spilling out
○ Try to bring the fever down (after the fit has ceased) with paracetamol or
sponging (do not feed any medication orally while your child is still drowsy).
○ Always bring your child to the doctor if in doubt
○ Bring the child to A&E (call ambulance) if: 1st episode, >5min, child unable to
move one side of body, unusual drowsiness after fit, injury during fit.

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MEDICAL LONG CASES

Neuro: Seizure, Epilepsy

ADULTS AND PAEDIATRICS

If the presenting complaint is ‘seizure’, be sure to distinguish whether this requires an

approach to first seizure, or is an known epilepsy case.

Elicit disease course:

! How was the diagnosis made (how does this patient fulfill the definition of epilepsy)?
○ When did the seizures start?
○ How many seizures and their temporal relationship to each other and to the
current moment?
○ ILEA definition: (1) At least two unprovoked (or reflex) seizures occurring >24
h apart, or (2) one unprovoked seizure + probability of further seizures similar
to the general recurrence risk (at least 60%) after two unprovoked seizures, or
(3) Diagnosis of an epilepsy syndrome
! Usual seizure morphology / Seizure signature
! Etiology: idiopathic epilepsy or any known underlying predisposition to recurrent
seizures?
○ Stroke
○ Structural brain malformation
○ Epilepsy syndrome, neurocutaneous syndrome

What has the management been so far?

! Was patient started on AED?
○ If so, what? How many agents, what is the dosage, has regime been stable?
! Have there been any side effects?
○ Bone marrow suppression
○ Liver toxicity
○ Teratogenicity: if female and childbearing age → ask about sexual history, use
of contraception; if intending to get pregnant needs very careful discussion

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How has control of epilepsy been?

! What is the frequency of breakthrough seizures?
! Explore precipitants
○ Drug compliance
○ Precipitants e.g. alcohol, stress, sleep deprivations, new drugs e.g. antibiotics
(cipro), painkillers
○ Any other reversible causes? e.g. hypoglycemia, electrolyte disturbances,
meningitis
! What is the nature of breakthrough seizures
○ Complicated e.g. status epilepticus?
○ Require admission for AED titration?
! Patient education: does the patient know when to go to the hospital?
○ Worrysome for non-epileptic seizure: high fever, localizing neurology, change
in seizure character.
○ Complicated seizure: status epilepticus, prolonged drowsiness after seizure
○ Needs titration: increasing frequency of breakthroughs with no identifiable
triggers.

How has this affected the patient?

! [Paeds] Milestones and development, participation in school, social set-up at home
! Occupation: ability to find a job?
! Social: ability to maintain friendships / relationships / stigma
○ In a lady, has being on AED kept her from childbearing?
! Function and precautions
○ Patients with epilepsy are legally prohibited from driving
○ Should not be allowed to swim
○ Discouraged from cycling, climbing or scuba diving
! Financial situation

Sample Summary: Mr Jerk King is a 30/Chinese/M with epilepsy, diagnosed in his teenage
years, which was deemed idiopathic in etiology. He has always been less than optimally
compliant to antiepileptics, and has had one prior episode of status epilepticus two years ago.
In the past month he has had 5 breakthrough seizures. He has had difficulty holding down
employment, and lost his most recent job 2 months ago, after he had an epileptic fit in front of
his boss. He has also become increasingly socially isolated, and financial issues hinder
compliance to AED. My issues are:
1. Breakthrough seizures 2’ noncompliance to antiepileptic medications 2’ financial
difficulty
2. Social: financial difficulty 2’ unemployment, social isolation
3. Background of idiopathic epilepsy on Keppra

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MEDICAL LONG CASES

Neuro: Spina Bifida

PAEDIATRICS

How did this child present?

! Spina bifida varies in severity: from obvious myelomeningocele to spina bifida occulta.
! Open myelomeningocele may be detected prenatally on AFP screening and
ultrasound, or it may be an obvious lesion noted at birth.
! Spina bifida occulta is usually picked up later. It is difficulty walking, urinary problems,
or orthopaedic issues of the lower limbs (these lesions may progress with age -
tethered cord syndrome) that prompts medical consult; and an astute GP or a
paediatrician who examines the back and finds a sacral dimple or tuft of hair.
Worsening neurology may be indicative of tethered cord syndrome, where the cauda
equina is tethered to more superficial structures and is stretched as the child grows.
! Symptomatic patients would probably have had spine surgery → in the neonatal period
for open myelomeningocele, much later for spina bifida occulta.
! Classic examination findings are: lower limb LMN diplegia with a tuft of hair or surgical
scar on the lumbar spine.

What are the current issues; can we optimise management?

(1) Lower limb function & mobility

! What is the LL neurological function like? → which spinal cord levels are affected and
to what extent is sensation lost?
! Is the child at least partly mobile
○ Will aids help e.g. motorized wheelchair
○ Has received PT/OT?
! If immobile > any complications of immobility?
! There are also associated orthopaedic problems in the lower limb e.g. foot deformities
○ Will the child benefit from orthopaedic intervention?

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(2) Urinary function

! Is there neurogenic bladder?
○ What are the symptoms -- often an insensate bladder with no stretch reflex +/-
overflow incontinence
○ Should be confirmed on urodynamic study.
! How has this been managed
○ If cognitive status is good or if carer is available, clean intermittent
catheterization is probably best. Assess technique and check that the patient
does it frequently enough e.g. 4x a day.
○ Less optimal: permanent IDC, diapers
! Complications
○ Vesicoureteric reflux → Do micturating cystourethrogram; anticholinergic may
help
○ Recurrent UTIs → How severe, any admissions, any resistant organism
colonization. → Do DMSA for renal scarring, consider prophylactic Abx
○ Hydronephrosis, pyelonephritis --> Renal impairment

(3) Bowel function

! Many patients also have bowel issues: constipation and incontinence → does this
patient have it and how is he/she coping?
! Give laxatives, suppository → ensure regular BO and avoid impacted faeces, spurious
diarrhoea.

(4) Associated Chiari malformation

! Myelomeningocele (but not spina bifida occulta) may be associated with Arnold-Chiari
malformation: downward displacement of cerebellar tonsils, causing CSF outflow
obstruction and hydrocephalus.
! This may manifest as hydrocephalus requiring ventriculo-peritoneal shunt
○ In the infant head circumference should be carefully monitored.
○ If a shunt has been done, what complications have arisen? > Infection,
blockage, overshunting
○ At each visit ask for any symptoms -- e.g. headache (classically worse on
recumbancy) → any symptoms warrant a CT brain looking for interval increase
in ventricular size, which would imply shunt malfunction.
! It may also cause brainstem dysfunction e.g. lower cranial nerve palsy, difficulty
swallowing
! Finally Chiari malformation tends to affect cognitive development as well.

How is the child’s growth, development & overall health

! Growth and development
! Schooling: type of school (special or mainstream), any learning problems

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How is the child / family coping with this illness.

! Coping with intermittent catheterization and/or fecal incontinence
! Awareness of disability, self-esteem and peer relationships; social ostracization
! Financial issues
! Mobility and lifestyle

Are future pregnancies protected?

! Explore antenatal risk factors -- spina bifida is a neural tube defect and associated with
folate deficiency (dietary or drug e.g. methotrexate), antiepileptic drug use, as well as
DM.
! Has mum received counselling on this? > Advice for folate supplementation, review of
DM control, stop drugs

Sample summary: Fifi is a 16 year old Chinese girl with background spina bifida occulta,
currently admitted for upper urinary tract infection. She diagnosed at the age of 3 when she
had delayed gross motor milestones with an inability to be potty trained, and an astute GP
noticed a tuft of hair at the small of her back. There has been no progression of her
neurological symptoms to suggest tethered cord syndrome. She is ADL-independent and
community ambulant with her orthosis and currently attending a local secondary school. She
is urine incontinent but bowel continent. She performs self- intermittent catheterization 4 times
a day, and sometimes has trouble keeping aseptic technique when she is rushing to do it while
in school in between classes or extracurricular activities. She gets lower UTIs once or twice a
year treated with oral antibiotics outpatient, but this is the first she has had fever and loin pain.
Since admission she has responded well to IV antibiotics and has been told that her kidney
function is good. Her mother, an epileptic on valproate, decided against having any more
children after being counselled on the link between valproate and her daughter’s spina bifida.

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MEDICAL LONG CASES

Neuro: Spinal Muscular Atrophy

PAEDIATRICS

How did the patient present and how was diagnosis confirmed?
! SMA is characterised by the progressive degeneration of anterior horn cells at various
tempos
! Presentation differs depending on the clinical phenotype of SMA.
○ SMA Type 1: most severe form, presents in neonatal period, does not survive
beyond 1 year due to respiratory failure
○ SMA Type 2: intermediate form, presents between 3-15 months with delayed
gross motor milestones.
○ SMA Type 3: mild form, presents ≥1 year with delayed gross motor milestones,
or more subtly with foot drop or tripping over feet
○ SMA Type 4: adult form, presents in 2nd to 3rd decade of life.
! Outcome depends on severity of muscle weakness at presentation (rather than age of
onset), but earlier onset tends to correlate with greater weakness
! Confirmation of diagnosis would have been performed via:
○ Molecular genetic testing: exon 7 deletion of the SMN gene
○ Electromyography: fasciculations, fibrillations. positive sharp waves, high
amplitude long duration motor units
○ Muscle biopsy: grouped atrophy
○ Creatinine Kinase will be normal or mildly elevated (unlike myopathy)

What are the visible clinical manifestations?

! Elicit a symmetrical LMN (flaccid, areflexic) weakness, greater in proximal than distal
muscles, greater in lower than upper limb. Fasciculations are prominent and best seen
in tongue. Sensation is completely spared.
! Look for manifestations of the issues below

What is the clinical course and current issues?

! No disease modifying treatment for SMA exists. Management is supportive.
! As you explore the common issues below, be mindful of the course of the disease and
the tempo of progression (pegged very closely with patient’s functional status).

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(1) Musculoskeletal
! Muscle weakness is relentlessly progressive and will eventually result in increasing
disability
○ The still-walking child → consider orthoses, walking aids where necessary
○ The non-ambulant child → consider functional aids e.g. motorized wheelchair
○ The bedbound child → watch for complications of immobility e.g. bed sores,
ask about nursing care, turning; contractures and physiotherapy to minimise
contractures
! Orthopaedic issues: e.g. scoliosis secondary to weakness of paravertebral muscles
○ How bad is it? To a point where it is contributing to the patient’s respiratory
problems?
○ Spinal bracing can be used to delay progression, but use with caution as it can
reduce expiratory tidal volume when patient is sitting up

(2) Respiratory muscle weakness

! Respiratory weakness and pneumonia is the ultimate cause of death in many patients,
as SMA patients have difficulty clearing lower respiratory tract secretions + high
aspiration risk
! Infections: what is the course of infections, how have they been treated?
○ Vaccinations
! Secretions: are these troublesome?
○ Buscopan → Reduce secretion
○ Chest physiotherapy and postural drainage (manual or mechanical)
○ Cough assist device or mechanical insufflation/exsufflation device
○ What is the compliance to such assistance?
! In end stage may require ventilatory assistance, especially during sleep where pts are
especially prone to hypoventilation
○ Oxygenation can be aided with non-invasive ventilation or tracheostomy with
traditional ventilation
○ However this should be individualized for each patient in each stage of illness

(3) Maximization of social, language and intellectual skills

! Growth and development
! SMA patients are intellectually normal
! Special schools: e.g. Rainbow Centre (Yishun, Margaret Drive) for patients up to 18
years old -- but what happens after the child turns 18?

How is the child and family coping?

! Function: ADLs, ability to attend school or work
! Care: what is the care arrangement, is there caregiver stress.
! Socially: peer integration, family support,
! Psychologically: awareness of disability, self esteem
! Financial issues.

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Have end of life issues been explored?

! Prognosis: SMA type 1 babies die within 2 years, SMA type 2 patients survive into
adolescence or young adulthood. SMA type 3 patients may live to adulthood.
! Advanced care planning and palliative management is often helpful for SMA type 1
and 2.
! Gently probe patient's and family’s understanding of prognosis and if not adequate,
should refer for ACP.

Genetic counselling
! Are other family members involved?
! Do parents understand implication for future pregnancies → How do they feel?
! Are patient’s siblings aware that they may be carriers?
! Affected individuals and families should be referred for genetic counseling. SMA is
generally autosomal recessive but may have other inheritance patterns as more than
1 gene is involved.

Sample summary: Bohlak is a 23 year old boy who was diagnosed with spinal muscular
atrophy type 2 at 2 years old, when he presented with delayed gross motor development. Over
the years he has progressively lost muscle function, having been wheelchair bound since 12
years old, and in the last 3 years losing most hand movements except finger movements. In
terms of respiratory status, he has suffered recurrent pneumonias and requires required night-
time ventilatory assist. He uses his secretion clearance device (Acapella) regularly.
Functionally, he is mentally intelligent, bedbound but able to occupy himself surfing on a
laptop, and maintains a widely-read blog site. His mother is the main carer and they are
financially tight but coping. My main issues are:
1. Spinal muscular atrophy type 2, bedbound
2. Respiratory muscle weakness with recurrent pneumonias → to vaccinate, improve
chest physiotherapy.
3. Advanced care planning.

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MEDICINE LONG CASES: THE CLINICAL QUESTIONS APPROACH RENAL: CKD & ESRF

MEDICAL LONG CASES

Renal: CKD & ESRF

ADULTS & PAEDIATRICS

Where along the spectrum of CKD is this patient?

! Ensure that the patient’s complaint is CKD and not AKI: by definition renal impairment
>3 months (see approaches notes)
! CKD is a spectrum ranging from asymptomatic CKD to dialysis-dependant ESRF
○ KDIGO classification according to GFR: CKD 1 (>90 ml/min/1.73m2), 2 (60-
89), 3A (45-59), 3B (30-44), 4 (15-29), 5 (<15).
○ KDIGO albuminuria grading (measures kidney damage): A1 (<30 mg/day), A2
(30 - 300), A3 (>300)
! Know how your patient developed and where he is now -
○ Has patient been told to start, or is already on dialysis? → ESRF
○ If on dialysis, was this scheduled or crash-land?
! Subsequent issues and goals of management depend on where along the spectrum
of CKD this patient is:

Task CKD, not yet CKD approaching ESRF on dialysis

approaching ESRF ESRF (not on RRT)

Manage Investigate etiology, Investigate etiology, Need to know etiology

etiology treat & avoid further treat & avoid further and manage as a
renal damage renal damage comorbid

Manage Retard disease Decide HD vs PD Titrate dialysis

progression progression Prepare for dialysis: Manage HD/PD issues

Complica- Usually mild, monitor Close mx of ESRF Manage complications

tions complications (not on of ESRF and dialysis
RRT, vulnerable)

Note: this document describes clinical tasks for all ends of the spectrum but be sure to tailor
your approach to where your patient is (as above). For instance if a patient is clearly CKD3 it
would be quite inappropriate to ask about dialysis planning.

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Why does this patient have CKD/ESRF?

! May be a known obvious cause (e.g. longstanding DM) or require investigation
especially if progressive CKD
! Basic clinical workup: the PMHx is most informative.
○ Pre-renal: diabetes (PMHx, fasting glucose), hypertension (measure)
○ Renal autoimmune disease e.g. glomerulonephritis, SLE, vasculitis → PMHx,
ask for proteinuria or hematuria, other symptoms (joint pain, rash etc), do
UFEME, ANA, etc.
○ Cystic kidney diseases → ballot kidney, ask FHx
○ Postrenal: longstanding obstructive disease → PMHx, palpate bladder
! May require biopsy if cause occult clinically

Managing the patient’s renal function

(1) CKD: how can I retard disease progression?

! Treat cause of CKD: e.g. control DM/HTN, treat urological disease,
immunosuppression for glomerulonephritis
! Inhibit proteinuria e.g. ACE-inhibition, ARB
! Avoid further renal insults: hypovolemia, nephrotoxins, obstructive uropathy

(2) Advanced CKD: do I need to start dialysis?

! Emergent dialysis required if -
○ A - Acidosis pH <7.2 or unresponsive to HCO3
○ E - electrolyte imbalances (refractory hyperK, hypoNa, hyperCa)
○ I - intoxicants (salicylates, methanol, ethylene, glycol, Li, ASA)
○ O - intractable fluid overload
○ U - symptomatic uremia (nausea/vomiting, seizure, pericarditis, bleeding)
! Good to prepare for dialysis early… far too often patients crash-land with a
complication of ESRF requiring emergent dialysis via temporary vascular access,
which has higher complications
○ If patient is approaching ESRF and refusing dialysis → explore why
○ At times in a very elderly patient, poor comorbids, declining dialysis is very
reasonable → do advanced care plan (do you still want vascath if you crash?)
! Discuss options: hemodialysis vs peritoneal dialysis (continuous ambulatory PD or
automated PD)
○ Lifestyle and patient factors: PD good for highly motivated, more educated
patients (need aseptic technique), or patients with competent caregiver; HD
good for patients who require help.
○ Consider comorbids: HD is challenging for patients who cannot tolerate large
fluid shifts (e.g. CCF), PD contraindicated in patients with previous abdominal
surgery
○ Consider long-term outcomes: PD preserves residual urine function longer than
HD; starting with PD preserves vascular access for future HD.
! If HD, need to create AVF → can take 3-6 months to mature

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(3) ESRF already on dialysis

! Explore dialysis route (HD vs PD) and regime (thrice-weekly HD, PD no. of changes)
○ Is patient coping?
○ Has patient been missing dialysis?
○ If on perm cath → patient should not be on perm cath. Why? Any plans for HD?
! Monitor adequacy of dialysis
○ Clinical: dialysis to dry weight (if not at dry weight post-dialysis, may be
inadequate dialysis) → ask about dry weight
○ Biochemical: (1) solute clearance of PO4, K, acidosis, (2) fluid clearance and
blood pressure, (3) Kt/V measurement >1.7 (measures urea clearance)
! Complications of dialysis -- see later.

(4) Is this patient a transplant candidate?

! Explore if the question of transplant has been raised (should be unless patient has bad
comorbids or is old)
○ Are any living related donors available?
○ Is patient on deceased donor waitlist?

What complications of renal failure are there and how are these managed?
Severity of complications increases as GFR falls
! How often has the patient been admitted for complications or required emergent
dialysis?
○ How severe: ICU, intubation?
○ Why? AoCKD (infection, cardiac event), non-compliance to diet restrictions,
missed dialysis

(1) Complications of ESRF

! Anaemia: normocytic normochromic anemia secondary to decreased erythropoietin

production → any symptoms, what is the latest Hb?
○ Target Hb 10.5-12
○ Rule out GI bleed, myeloma (anaemia, CKD, elderly)
○ First ensure iron replete (ferritin >500, transferrin saturation >30%) → Give PO
iron, IV iron e.g. ferrinjet
○ Then top up erythropoietin (recormon)

! Blood pressure → what is the baseline?

○ CKD: ACE-I or ARB (all patients should be on), diuretics
○ ESRF: first titrate dry weight to achieve BP, then add antihypertensives.

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! Calcium / Vitamin D / bone disease: Initially phosphate retention & hypocalcemia from
vitamin D deficiency causes secondary hyperparathyroidism and mineral bone disease
→ Measure Ca / PO4 / PTH; any fractures? Proceed stepwise -
○ Diet control: phosphate restriction
○ Phosphate binders: usually calcium-based unless hypercalcemia (then give
lanthanum or sevalemer)
○ Only when phosphate controlled - activated vitamin D supplementation
(calcitriol)
○ If hypercalcemic - patient may have developed tertiary hyperparathyroidism
and hypercalcemia. Think about cinacalcet, parathyroidectomy.

! Electrolytes: hyperK, acidosis → how many admissions?

○ Diet control: low potassium diet → usually works, is patient compliant?
○ Consider bicarbonate supplementation (but with caution as it comes with Na)

! Fluid overload: dyspnoea, pedal edema → assess clinically. How many admissions?
○ Fluid restriction → usually works, is patient compliant?
○ Diuresis if not ESRF.

! Others: uremia and constitutional symptoms → are there any?

○ Immunosuppresion: Malignancy screening, vaccinations
○ Anorexia, malnutrition: monitor nutrition status, albumin
○ Puritus: usually a late issue.

Are there complications from dialysis?

! How often missed dialysis?
! Symptoms and coping with dialysis:
○ HD: end dialysis symptoms e.g. hypotension, giddiness
○ PD: bloating
○ HD: high output cardiac failure
! HD access issues: managing the vascular access is critical as this is the patient’s
lifeline.
○ On AVF/AVG: any issues with graft stenosis / inability to dialysis etc?
○ On perm cath: why? Any plans for AVF or AVG?
○ Has the patient required new graft creation or perm cath?
○ Does the patient have remaining access options left?
! Infection issues:
○ HD: line sepsis
○ PD: peritonitis → explore aseptic technique, ddx surgical peritonitis

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Managing comorbids
! Cardiac comorbids important to manage -- these patients are vasculopaths and
cardiac is the top cause of death in ESRF
! Remember to adjust medication dosing
○ E.g. diabetes - Stop metformin if CrCl <30, adjust insulin (decreased clearance
leads to hypoglycaemias)
○ If ESRF no concern about nephrotoxicity; if CKD not on dialysis be very
concerned.

How is the patient coping?

! Dialysis patients are always grumpy for a good reason - it takes a large toll on them
○ Explore compliance with dialysis, diet and fluid restrictions
○ Explore emotional / psychological issues → any depression? → Mirtazapine?
○ What is the patient’s function?
! Financial aspects: dialysis is expensive, any subsidy (e.g. NKF?)
! Social aspects: is patient able to maintain any sort of lifestyle between shutting from
dialysis centres to hospital?

Sample summary: Mdm Sian is a 66 year old lady with end-stage renal failure on
hemodialysis secondary to longstanding diabetes. She has had recurrent admissions for
thrombosed AVF and is currently dialysing via a permanent catheter, while awaiting for new
left brachiobasilic AVF to mature. She has had one episode of MRSA line sepsis requiring
permanent catheter change. Apart from ESRF, my outstanding issues for her include…
1. Access problems: currently on PC dialysis awaiting AVF maturity
2. Anaemia: I note she is pale and has exertional dyspnoea, would like to know her Hb,
rule out GI blood loss and myeloma
3. Episodes of fluid overload secondary to noncompliance to fluid restriction
4. Comorbidities: insulin-dependant diabetes with excessively tight control (HbA1c below
6%, hypoglycaemic episodes)
5. Depressive symptoms due to burden of chronic disease
6. Financial problems: she has depleted her medisave and savings.

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MEDICINE LONG CASES: THE CLINICAL QUESTIONS APPROACH RENAL: NEPHROTIC SYNDROME

MEDICAL LONG CASES

Renal: Nephrotic Syndrome

ADULTS & PAEDIATRICS

Do I have a diagnosis of nephrotic syndrome?

! Nephrotic syndrome is the cluster of urinary protein loss (urine total protein >3g/day),
causing hypoalbuminaemia (<25g/L) and generalized edema.
! This contrasts with nephritic syndrome which presents with hematuria, hypertension,
and varying degrees of renal compromise (rise in creatinine).
! Explore how the patient first presented - often leg swelling, shortness of breath,

What is the etiology of this patient’s nephrotic syndrome?

! Etiology includes primary glomerulopathies of various histologies, as well as
secondary causes.
! Explore possible secondary causes on history and subsequently investigation. These
include autoimmune disease like lupus or HSP (joint pain, rash, dsDNA, ANA,
complements), infection (HBsAg, HCV IgM, HIV), and diabetes.
! The primary glomerulopathies are distinguished on renal biopsy. Was this done? If so,
why?
○ The overwhelming majority of paediatric nephrotic syndrome is due to minimal
change disease and hence a biopsy is typically not performed. A biopsy would
have been done if there were atypical features (age <1 or >10), nephritic
features (hypertension, hematuria), poor response to steroid, suspicion of
secondary cause (e.g. joint pain, low complements), worsening renal function
or family history of renal failure.
○ Biopsy is standard in adult nephrotic syndrome - may show minimal change
disease, FSGS, membranoproliferative and membranous GN. Each has
specific disease associations (e.g. membranous with malignancy), and
conditions like lupus can present as any pattern.

How treatment-responsive is this patient’s nephrotic syndrome?

! ***Ask for nephrotic diary!***
! How frequently does the patient relapse? > In remission, infrequently relapsing (<2 in
6/12), frequently relapsing (>2 in 6/12).
○ Relapse = 3 consecutive days of dipstick at least ++ OR edema,
hypoalbuminemia; Remission = 3 consecutive days of dipstick + or less
○ Frequent relapse --- is it because of noncompliance to medication, diet, or
failure of treatment?
! Is there residual proteinuria/edema? > Give ACE-I to all.

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! How well does the patient respond to therapy? Is he steroid-responsive, dependant

(relapse within 2 weeks of stopping steroids or at least 2 relapses while on steroids),
or resistant (failure to achieve remission in spite at least 6-8 weeks of high dose
steroids).
○ If steroid-dependant, try steroid-sparing agents --- e.g. levamisole,
azathioprine, cyclophosphamide (SE infertility), cyclosporine. Have they
worked?
○ If steroid-resistant, have the other immunosuppressants worked?

What complications are there?

! Is renal function OK? (usually OK in nephrotic)
! Immunocompromised state: secondary to treatment (steroids → cushing’s or
immunosuppressants → agranulocytosis) and also as part of nephrotic syndrome (loss
of immunoglobulins through urine)
○ Does patient know what to do if fever?
○ Vaccinate
! Hypercoagulability - venous thromboembolism > prophylaxis with aspirin or warfarin
! Hyperlipidemia and cardiovascular effects > give statin.

How is the patient coping with the medications and diet regimen?
! The nephrotic diet is unpleasant - salt and water is restricted, and due to the risk of
cushings sugars and fats are also restricted. Many patients have difficulty with
compliance which deserves lots of empathy!
! Similar with the medications -- if noncompliant, explore why? Due to poor
understanding of disease / poor motivation / side effect / financial reason / lifestyle
choice?

How is the patient’s general health?

! Comorbids should be managed
! Paeds : growth and development is key.

Sample Summary
Mimi Yen is a 11 year old girl with steroid dependant nephrotic syndrome, diagnosed 2 years
ago when she first presented with bilateral leg swelling and facial edema. She has had 3
relapses since diagnosis, the first within 1 week of tailing down her steroids and the other 2
even while she has been kept on steroids. Her primary physician is starting to bridge her over
to tacrolimus as she is starting to develop features of cushing’s syndrome. Otherwise, she has
not had recurrent infections. Mrs Yen has, with much difficulty, kept Mimi on the recommended
salt, water, sugar and fat restricted diet and ensured that she takes her medications daily.
Mimi is below the 5th percentile in terms of height for her gender and is amongst the shortest
in her class, but is otherwise doing well in the St. Hilda’s gifted education program and able to
participate fully in all activities. She understands that everything she is going through is for her
own good, and has a group of best friends in her class who know about her condition and
support her when the boys tease her about her chubby face.

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MEDICINE LONG CASES: THE CLINICAL QUESTIONS APPROACH RESPI: ASTHMA

MEDICAL LONG CASES

Respi: Asthma

ADULTS & PAEDIATRICS

Is this asthma? What else could it be?

! Classic features: History of variable (over time and in intensity) respiratory symptoms
(wheeze, shortness of breath, chest tightness, cough) often worse at night/on waking,
responds to bronchodilators, usually has a trigger (refer below for usual culprits),
personal history of atopy, family history of atopy
! Asthma variants: cough variant, exercise-induced variant, occupational variant
! Know the different differentials for each age group: a more comprehensive list is
provided below but this requires tailoring to your patient (most important ones *)

Age Differentials Symptoms

0-5 y Viral bronchiolitis also causes wheeze up to 3 years old and hence a diagnosis of
asthma is often held off initially. However if the wheeze is recurrent, occurs even
in the absence of URTI symptoms, or there is a strong family history of asthma or
personal history of atopy, one may lean in favour of diagnosing asthma.

6-11 y Inhaled foreign body Sudden onset dyspnea, unilateral wheeze

Bronchiectasis Recurrent infection, prod cough
Primary ciliary dyskinesia Recurrent infection, prod cough, sinusitis
Congenital heart disease Cardiac murmurs
Bronchopulmonary dysplasia Preterm delivery, symptoms since birth
Cystic fibrosis Cough & mucus production ++, GI sympt

12-39 y Vocal cord dysfunction Dyspnea, stridor

Hyperventilation Dizziness, paresthesia
Bronchiectasis Recurrent infection, prod cough
Cystic fibrosis Cough & mucus production ++, GI sympt
Congenital heart disease Cardiac murmurs
Alpha1-antitrypsin deficiency SOB, family history of early emphysema
Inhaled foreign body Sudden onset, unilat wheeze

40+ y COPD * Cough & sputum, SOBOE, smoking

Heart failure (cardiac asthma) * SOBOE, PND/orthopnea, JVP, LL swelling
Interstitial lung disease * SOBOE, clubbing, non-prod cough
Lung cancer Monophonic, cont wheeze, cachexic, hemopt
Vocal cord dysfunction Dyspnea, stridor
Hyperventilation Dizziness, paresthesia
Bronchiectasis Recurrent infection, prod cough
Medication related cough Hx of ACE inhibitor
Pulmonary embolism Sudden onset dyspnea, chest pain, LL swellin
Churg Strauss Eosinophilia, ENT disease, renal impairment

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Did the patient undergo spirometry?

! Asthma is a clinical diagnosis but spirometry is a useful adjunct for diagnosis
! Classic spirometry finding is an obstructive picture with reduced FEV1/FVC (normally
>0.75–0.80 in adults, >0.90 in children), with documented excessive variability in lung
function, e.g.
○ If initial spirometry shows obstruction → do bronchodilator reversibility; should
increase FEV1 >12% (withhold before test: SABA ≥4 hours, LABA ≥15 hours)
○ If initial spirometry is ‘normal’ → do methacholine challenge test, which should
result in ≥20% fall in FEV1

Etiology: what precipitates asthma and have these been avoided?

! Is there an atopic setup? > Eczema, allergic rhinitis -- should be treated if present.
! Is there a family history?
! What precipitates asthma and has this been avoided?
○ Allergens: pets, dust mites
○ Occupational exposure -- are symptoms better on weekends?
○ Smoking: first hand and second hand --- stop smoking!
○ Environment: cold, haze, etc
○ Exercise
○ Infection: e.g. URTI
○ NSAIDs

How is recent asthma control?

! Course of disease: previous admissions, recent step up/down of therapy
! Are there features of high-risk asthma?
○ Past ICU admission, intubation, near-fatality.
○ Recent poor control (see below), severe exacerbations in last 12 months
! Asthma Control Test: all criteria met = controlled, 1-2 criteria not met = partially
controlled, 3-4 criteria not met = uncontrolled
○ Daytime symptoms i.e. wheeze/cough/difficulty breathing (controlled =
<2/week),
○ Nocturnal symptoms/awakening (controlled = 0)
○ Limitation of activities (controlled = 0)
○ Need for rescue/reliever treatment (controlled = <2/week)

If current exacerbation, what is the severity?

! Clinical: severity of SOB (on walking, on talking, at rest), ability to talk (in sentences,
phrases, or words), ability to walk (yes, needed assistance, needed to be carried),
mental state (alert, confused, or drowsy, ability to eat (too breathless?)
! On PE: SpO2, RR, PR, retractions, conscious level, speech, cyanosis, wheeze
! What has been given so far by GP or A&E? > Level of oxygen supplementation, how
many puffs of rescue inhaler or nebulizations, and response to treatment
! Low threshold to do ABG; PCO2 should be low because of hyperventilation, if it is
“normal” the patient is tiring out.

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How best to manage the asthma?

! Acutely -
○ Ventilatory support: stepup from nasal prongs → face mask → intubate
○ Bronchodilation: inhalers vs nebulizer (1:2:1 ventolin:ipratropium:saline)
○ IV hydrocortisone +/- magnesium if severe
○ +/- antibiotics if clear infection
! Chronically - what is current regimen
○ What is current regimen (prescribed vs actually taken) -- frequent reliever use
without preventer use is worrysome
○ How is compliance to treatment > If poor, why, what are the issues? (Medical
/ financial / social / psychological, perceptions of steroids)
○ Is inhaler technique acceptable
! Is there a need to step up or step down therapy -- not controlled = step up
○ Step 1: SABA PRN
○ Step 2: SABA PRN + low dose ICS
○ Step 3: SABA PRN + low dose ICS + LABA
○ Step 4: SABA PRN + medium/high dose ICS + LABA
○ Step 5: SABA PRN + medium/high dose ICS + LABA + low dose PO CS
! Give a written asthma action plan
! Assess and treat co-morbidities: rhinitis, eczema, sinusitis, GERD, obesity, OSA,
depression, anxiety
! Treat precipitants: stop smoking, avoid allergens (see prior).

Any complications from treatment?

! Cushing’s from long term corticosteroids

How is the overall coping of the child / young adult?

! Growth and development
! Is he/she able to participate fully in school?
○ What sports/hobbies/interests does the child have, at school and in their spare
time? How does the child’s level of activity compare with their peers or siblings?
! Social setup
! Financial

Note: The clinical questions above are more suitable for a chronic follow-up consult. In an
acute setting, consider instead
• Is this really asthma? (rule out other dDx) clinical features of asthma + spirometry
• Assess the severity of the asthma exacerbation - impending resp arrest? disposition?
• Look for etiology of exacerbation - what was the trigger?
• Assess underlying control of asthma - and decide if there is a need to step up

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Sample Summary 1: Little Sniffy is a 3 year old Chinese Boy with a strong family history of
asthma and personal history of atopic dermatitis. He had two episodes of wheeze last year,
associated with fever and rhinorrhoea, which were diagnosed as viral (RSV) bronchiolitis. In
the past 2 months, however, he has had three episodes of wheeze, two of which occured
without any fever or upper respiratory tract infection. I feel that I would label him as asthma
and commence treatment. I also note that his father is a heavy smoker. Otherwise he is
growing well and meeting all milestones. My issues are:
1. Likely asthma (vs bronchiolitis) given atopic setup, family history, and multiple
episodes without viral symptoms -- in an older child I would do spirometry as an adjunct
for diagnosis but it is difficult to in this 3-year old. I would like to commence treatment
with SABA and low-dose ICS.
2. Allergic rhinitis -- I would like to give intranasal corticosteroids.
3. Smoke exposure at home

Sample Summary 2: Biggie Wheezie is a 23 year old Malay lady with high risk asthma. In the
past year alone she was admitted for 4 exacerbations and required intubation once. In the
past month she has had night cough and alternate day exacerbations. She uses her ventolin
heavily but does not comply to ICS - I note also that her inhaler technique is poor. Financially
she is unemployed and not always able to afford her medications. The issues I need to
address for her are:
1. High-risk asthma, poorly controlled with poor compliance to ICS
2. Financial issues

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MEDICAL LONG CASES

Respi: Bronchiectasis

ADULTS & PAEDIATRICS

How did this patient present?

! Adults may present as a longstanding (months-years) hx of cough with purulent
sputum production daily, after repeated lung infections over the years. A COPD-like
picture (wheeze, exertional dyspnoea) is also found in bronchiectasis.
! Children may present as chronic cough +/- failure to thrive
! Diagnostic imaging would have confirmed
○ CXR: tram tracks, ring shadows
○ HRCT: signet ring, bronchiole do not taper to periphery, bronchial wall
thickening ("traction bronchiectasis" seen in pulmonary fibrosis is not
bronchiectasis).

What is the underlying etiology?

! The pathophysiology of bronchiectasis is a vicious cycle of infection → airway damage
→ impaired secretion clearance → more infection; various causes lung infections,
airway damage, or impaired secretion clearance can lead to bronchiectasis.
! Young patient with bronchiectasis or recurrent infections:
○ Is there cystic fibrosis? → Do sweat chloride, CFTR gene
○ Is there ciliary dysmotility? (Kartagener’s) → Look for dextrocardia, infertility,
consider ciliary motility studies
○ Immunodeficiency states → Quantify immunoglobulins
! Is there autoimmune disease?
○ RA, Sjogrens’ (LL bronchiectasis) → Ask about symptoms, kiv workup (see
RA).
○ Inflammatory bowel disease → Ask about symptoms, kiv colonoscope
○ Sarcoidosis (UL bronchiectasis)
! Is there obstructive lung disease?
○ Longstanding asthma with cough, poor response to inhalers: consider allergic
bronchopulmonary aspergillosis (central bronchiectasis) → Do FBC
(eosinophilia), IgE (high), aspergillus precipitins, sputum culture.
○ COPD like picture → consider testing for alpha 1 antitrypsin deficiency

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! What were previous pulmonary infections?

○ TB scarring: UL bronchiectasis
○ Aspiration pneumonia: LL bronchiectasis → Ask about GERD, swallowing
impairment.
○ Previous virulent pneumonia or non-tuberculous mycobacteria infection: focal
bronchiectasis (ML in NTM)
! Very focal crepitations
○ Rule out mechanical obstruction (foreign body, tumor) which is amenable to
resection → chest imaging
! On examination attempt again to localize crepitations.
○ Focal: mechanical obstruction (FB, tumor), local infection (pneumonia, TB)
○ Diffuse UL: radiation, sarcoidosis
○ Diffuse LL: aspiration, immunodeficiency, fibrosis, idiopathic
○ Diffuse ML: NTM, ciliary dysmotility (ask abt fertility)
○ Central: ABPA.
! First-line etiological workup includes: FBC, sputum cultures (bacterial, TB, fungal),
immunoglobulin levels, sweat chloride, CT (also diagnostic) +/- bronchoscopy.

Is underlying etiology treatable?

! Unfortunately, often not.
! Treat: NTM, ABPA
! Control: GERD, rheumatic disease
! Surgery: focal bronchiectasis, tumors, FB.

How is this patient and how is he being managed?

* Prognostic factors

(1) Infection and management

! How many exacerbations in past year? *
○ Frequency: >3, bad
○ Severity: Admission *, ICU?
○ Colonizing bacteria: any pseudomonas*, non-tuberculous mycobacteria?
○ Management: what has been needed?
! Are secretion clearance (bronchial hygiene) strategies being used?
○ Modalities: Chest physiotherapy (postural drainage, clapping), Devices (e.g.
acapella), nebulized agents (hypertonic saline, mannitol, mucolytics)
○ Many are tedious → Explore compliance
! Is there a role for antibiotic suppression therapy? (e.g. ≥2 exacerbations a year)
○ Macrolides are both anti-infective and anti-inflammatory
○ Inhaled antibiotics especially for cystic fibrosis bronchiectasis
! Immunize patient.

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(2) Baseline symptoms & management

! Cough & sputum production → secretion clearance
! Wheeze and exertional dyspnoea *
○ What is latest lung function test: FEV1 *
○ Bronchodilators
○ Stop smoking.
! What is the functional status?
○ Pulmonary rehab
○ Exercise
○ Nutrition, BMI *

(3) Haemoptysis
! Any episodes? Usually due to infection eroding bronchial arterioles.
! How were they managed

How is the patient coping?

! Able to work?
! Social and lifestyle burden of frequent sputum production, cough, need to use
secretion clearance
! Psychological and emotional.
! Financial

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MEDICAL LONG CASES

Respi: COPD

ADULTS

Is the diagnosis COPD?

! Presentation: progressive exertional dyspnoea & chronic cough in a patient with
significant smoke exposure, +/- intermittent exacerbations of SOB and wheeze
! Consider ddx:
○ Asthma → non-smoker, young pt, atopic hx (allergic rhinitis, eczema),
exacerbation with allergen exposure, asymptomatic between exacerbations.
○ Asthma-COPD overlap: Asthma and COPD are a continuum -- these patients
are considered to have Asthma-COPD overlap: (1) the ‘asthmatic’ with
incompletely reversible airway obstruction, (2) the ‘COPD’ with reactive airways
and exacerbations on allergen exposure, (3) the ‘asthmatic’ with chronic
productive cough (‘asthmatic bronchitis’).
○ Bronchiectasis → many similarities with COPD and may occur concurrently.
Suspect if: cough with daily sputum production is the main complaint (rather
than exertional dyspnoea), crepitations, clubbing. Many similarities with COPD
and may occur concurrently.
○ Heart failure
○ Pulmonary fibrosis
! Has COPD been confirmed on spirometry?
○ Expected obstructive picture, FEV1/FVC <70%, bronchodilator response <12%
○ FEV1 is prognostically important (determines ‘risk’)

What is the COPD stage?

! Concept from GOLD - COPD can be staged in the intersection of symptoms and risk
(of exacerbations, and severity of airflow limitation). Summary below, details later –

Higher risk Gold C Gold D

FEV1 < 50% predicted, or ICS + LABA ICS + LABA +/- LAMA
≥2 exacerbations / year

Low risk Gold A Gold B

FEV1 > 50% predicted, and SABA or SAMA prn LABA or LAMA
0-1 exacerbations / year

Less Symptoms More Symptoms

mMRC ≤2, CAT <10 mMRC 2+, CAT ≥10

SABA: short acting beta agonist; SAMA: short acting muscarinic antagonist (anticholinergic); LABA: long
acting beta agonist; LAMA: long acting muscarinic antagonist (anticholinergic)

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What is the risk / hx of exacerbations; and how is this mitigated?

! How frequent?
! How severe?
○ Requiring NIV / intubation?
○ Clinical course with usual mx: PO prednisolone, nebulized SABA, Abx
! What is the precipitating factor?
○ Usually infections → which, CAP or HCAP?
○ At times other complications of COPD e.g. pneumothorax
○ Also comorbids e.g. heart failure
! Prevention of future exacerbations:
○ Inhaled corticosteroids if high risk (GOLD C-D): reduce exacerbations,
symptoms → How compliant?
○ Vaccinations: influenza, pneumococcal
○ Some patients may be on prophylactic Abx: evidence conflicting
○ Measures as below

What are the baseline symptoms and how are these managed?
Assessment:
! What is the functional limitation: e.g. walking speed limited by SOB, having to stop
because of SOB when walking on level ground → qualifies as ‘more symptoms’
! What is the baseline SpO2?
Management: pharmacological and nonpharmacological, in stepwise approach.
! Stop smoking
○ If still smoking, why? Explore motivation and offer cessation therapy
! Mainstay is bronchodilators: beta-agonists or anticholinergics, short or long acting.
○ Evidence based to improve symptoms, reduce risk → if not taking, why?
○ GOLD A: SABA (e.g. albuterol) and/or SAMA (ipratropium)
○ GOLD B-D (inadequate symptom control or high risk): LABA (salmeterol,
formoterol, indacaterol, vilanterol, olodaterol) or LAMA (tiotropium, aclidinium,
umeclidinium, glycopyrronium). Dual bronchodilation if monotherapy
inadequate to control symptoms.
○ Assess inhaler technique
! ICS should be added in GOLD C-D (see above)
! Has gone for pulmonary rehab? → improve functional capacity and QoL.
! Does the patient need LTOT? → evidence based, indicated if SpO2 baseline <88%
○ Machine is not portable, patient will have to be home to use it
! Role of surgery
○ Bullectomy
○ Lung volume reduction surgery
○ Transplant.

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Are there any complications?

! Pneumothorax
! CA lung
○ What is the FHx?
○ Watch for red flags → weight loss, clubbing, chronic cough (concomitant
bronchiectasis), haemoptysis (may be as subtle as blood-tinged sputum)
○ Annual chest CT screening decreases mortality in patients with ≥30 pack-year
history of smoking (including those who quit in the last 15 years).
! Cor Pulmonale → any raised JVP, loud P2, parasternal heave?
! Hypoxaemia
! Polycythaemia

Comorbids and general health

! Address comorbids
○ Especially cardiac → coexistence of CCF/COPD results in difficulty
distinguishing the cause of exacerbations. Selective beta-1 blockers are safe.
! Ability to work
! Social setup → 2nd hand smoke?
! Psychological and emotional overtones: anxiety vs disregard.
! Financial situation

Sample summary: Chimney Chuan is a 65 year old Chinese ex-cook and smoker of 40 pack
years, currently admitted for yet another infective exacerbation of chronic obstructive
pulmonary disease. In the 9 years since diagnosis, he has progressed from GOLD Class A to
D: his exacerbations have been increasing in frequency (once a year to 2-3 times a year) and
severity (most recent one required intubation and ICU), and he has had progressive functional
limitation from his symptoms (walking and wok handling limited by SOB) causing him to resign
as a cook 3 years ago. Clinically he has signs of cor pulmonale but has refused all catheter
angiographies. Otherwise he has never been complicated by pneumothorax, last screening
CT did not show any suspicious lesions or bronchiectatic changes. He has a rather cavalier
attitude towards his condition - he still smokes about 1 pack a day, tends to only take his
bronchodilators when he needs it and does not bother with the ICS. This admission, his
baseline SpO2 was found to be 86% even after resolution of the infection, and has been
counselled for LTOT. He is reluctant for it as he is tight financially and does not like the idea
of having to be at home most of the time to use it. He is eager to go home so he can smoke
without having to sneak out to a stairwell. My issues for him are:
(1) Infective exacerbation of COPD (resolved)
(2) COPD GOLD Class D
(3) Baseline SpO2 86% - KIV LTOT
(4) Ongoing smoking 1 pack a day

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MEDICINE LONG CASES: THE CLINICAL QUESTIONS APPROACH RHEUM: GOUT

MEDICAL LONG CASES

Rheum: Gout

ADULTS

Is this gout?
! Acute gout classically presents as a painful, warm, swollen, erythematous joint. Onset
is usually at night, and severity peaks in 12-24 hours. Gout is often monoarticular
(favouring lower limbs esp. 1st MTPJ - podagra), but can also be polyarticular.
! Natural history of gout: acute gouty arthritis → intercritical/interval gout → chronic
tophaceous gout.
! Important differentials:
○ For acute gouty arthritis: Septic arthritis, trauma, pseudogout
○ For chronic tophaceous gout: rheumatoid arthritis, dactylitis, osteomyelitis
! Confirm diagnosis during an acute flare:
○ Joint aspirate: negatively birefringent needle shaped crystals on polarised light
microscopy
○ XR of affected joint: “punched-out” erosions with sclerotic margins in a marginal
and juxta-articular distribution, with overhanging edges
○ Blood: nonspecific inflammatory picture - leukocytosis, raised CRP, ESR
○ Serum urate levels are hard to interpret during acute gout flare, wait until at
least 2 weeks after flare completely subsides to get baseline value

Any secondary causes of hyperuricemia?

! Is the patient on any uricosuric drugs (e.g. thiazide)? → Take patient off them!
! Hematological malignancy with high cell turnover or s/p initiation of chemotherapy
?tumour lysis syndrome

What is the course of the disease; any complications?

! Acute flares: are they increasing in frequency, severity and duration?
○ What are the usual triggers? High meat and seafood intake?
○ Which joints are involved?
! Intercritical symptoms
○ Is there pain between flares (called intercritical segments)
○ Has the patient developed tophi?
! Complications:
○ Is there joint deformity?
○ Urolithiasis → Chronic kidney disease
○ Infected tophi
○ Superimposed septic arthritis

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How have acute gouty attacks been managed?

! Monotherapy with any one: NSAID, colchicine, systemic corticosteroid
! If inadequate response, switch to alternate monotherapy, or add combination therapy
! Does patient know how to initiate self-treatment of gout flares?
○ Try to take colchicine or NSAID at the onset of flare, before the flare peaks in
severity → more effective
○ For colchicine: load 1.0mg, 0.5mg 1 hour later, 0.5mg 12 hours later

Chronic management

(1) Lifestyle measures and treating comorbids

! Treat metabolic syndrome: DM, HTN, HLD
! Lose weight
! Diet control: no alcohol, decrease red meat and fish, avoid fructose-enhanced
sweetened drinks, reduce fat.

(2) If not on urate lowering treatment: When to initiate?

! All patients: low purine diet
! Indications:
○ Any tophus/tophi on clinical exam or on imaging
○ Frequent attacks of acute gouty arthritis (2 or more in a year)
○ CKD Stage 2 or more
○ Urolithiasis
○ Going for chemotherapy which may precipitate tumor lysis.
! When to initiate: usually wait 2 weeks after acute flare, because urate lowering therapy
can precipitate gout flare (controversial - now disputed)
! What to initiate:
○ 1st line: xanthine oxidase inhibitors (allopurinol or febuxostat) → counsel on
allopurinol risks especially SJS (see counselling)
○ Alternative: uricosurics e.g. probenecid (ensure GFR ok)
○ Treat to individualised serum urate target: <0.36mmol/L usually, <0.3mmol/L if
tophi present
! Give concomitant colchicine for acute gout prophylaxis
○ [Tophi absent] 3 months after achieving target urate level
○ [Tophi present] 6 months after achieving target urate level + resolution of tophi

(3) If already on treatment: how has the patient been coping?

! Any side effects from the medication?
○ Allopurinol: rash, GI symptoms, fever, allopurinol hypersensitivity syndrome
! How has compliance been to medications and to diet?
! How is patient responding to treatment?
○ Is pain under control? Frequency of attacks decreased?

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! What is patient’s understanding of his disease and treatment?

○ Does he understand the importance of compliance to medications and low
purine diet?
○ Does he know how to recognize adverse reactions to his medications?
○ Does he know NOT to stop ULT during a gout flare?

How has this affected the patient?

! Function is extremely important here
○ Is it pain or deformity that is affecting the patient?
○ What is the patient’s occupation, how has this affected his ability to work?
○ ADL and ambulatory status - during flare and in between
! Financial situation, social situation

Sample summary: Ah Pooi is a 50-year old taxi driver with tophaceous gout. He first
presented two years ago with podagra. Since then he flares every 2-3 months, often triggered
by a drinking party. He is on allopurinol and is moderately compliant, missing doses when he
drives late, and he still has tophi. He understands his disease well and can self-initiate NSAIDs
early in an acute flare - although I wonder if NSAIDs should be given as continuous prophylaxis
until his tophi disappear. My main issues for him are:
1. Chronic tophaceous gout
2. Metabolic syndrome: DM, hypertension, obesity.

APPENDIX: how to counsel on allopurinol

Take note because allopurinol has been the cause of Stevens-Johnson-Syndrom and
implicated in multiple lawsuits.

Hi sir, I have been asked to talk to you about this drug called allopurinol. May I just check with
you what you know about your condition, or about this?

I will go through with you (1) what is your current condition, and why allopurinol is indicated
(2) what is allopurinol and how to take it (3) what are the risks and side effects of allopurinol
and (4) alternatives. Please stop me anytime along the way if you have questions!

(1) Current condition, indication

You have a condition called gout, which is where you have too much uric acid in your
blood and it forms crystals around your joint. This can cause irritation and inflammation,
therefore the redness pain and swelling. This has becomes serious enough that you
are getting it 2 or more times a year/forming tophi i.e collections in the skin/damage to
the kidneys/urate stones in the kidney, therefore we recommend to start treatment.

(2) What is allopurinol, how to take it

Allopurinol is a drug that will help lower the uric acid levels in your body. It is taken as
an oral tablet once a day, after meals.

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(3) Side effects

! A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal
necrolysis) may happen. Get medical help right away if you have signs like red,
swollen, blistered, or peeling skin (with or without fever); red or irritated eyes;
or sores in your mouth, throat, nose, or eyes.
! Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or
peeling skin with or without fever; wheezing; tightness in the chest or throat;
trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face,
lips, tongue, or throat. Get medical help right away.
! Allopurinol can ironically cause gout flares in the initial few months
! Fever or chills, sore throat.
! Nausea, vomiting, diarrhea

(4) Alternatives
! There are other drugs like febuxostat and probenecid
! You can also choose not to start therapy at all

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MEDICINE LONG CASES: THE CLINICAL QUESTIONS APPROACH RHEUM: HENOCH-SCHONLEIN PURPURA

MEDICAL LONG CASES

Rheum: Henoch-Schonlein Purpura

PAEDIATRICS

Do I have a diagnosis of Henoch Schonlein Purpura? What else could it be?

! Palpable purpura (usually lower limb) without thrombocytopenia or coagulopathy (do
FBC, ESR, PT/PTT) is mandatory. In addition there is ≥1 of:
○ Abdo pain: diffuse, colicky, acute-onset (can lag behind rash by 1 week) -- if
significant think of intussusception.
○ Arthritis or arthralgia: acute-onset oligoarthritis favouring LL; may be swollen,
tender, ROM limited, but not warm or erythematous; may refuse to ambulate.
○ Renal involvement: hematuria +/- red blood cell casts, no or mild proteinuria
! May be preceded by URTI; significant proportion of cases of HSP are triggered by
streptococcal infections → do antistreptolysin O titres
! If incomplete presentation, esp if purpura is absent -
○ Biopsy kidney (in glomerulonephritis) or skin (vasculitis) -- there is IgA
deposition in HSP. Biopsy is not routine, reserved for unusual presentations
(ie, no rash, or an atypical rash) or significant renal disease
○ Consider ddx:
Differentials Workup

Purpura Cutaneous small vessel vasculitis Plt, PT/PTT, skin biopsy

Systemic small vessel vasculitides ANCA
(Wegener’s, Churg-strauss,
microscopic polyangitis)
Connective tissue disease (SLE) ANA, dsDNA, C3, C4
Hep B/C HBsAg, HCV RNA

Arthralgia SLE, JIA ANA, dsDNA, C3, C4, RF

Arthritis Rheumatic fever Throat c/s, anti-streptolysin O
Septic arthritis KIV joint aspiration

Abdo pain Appendicitis, gastroenteritis, etc.

(see abdo pain approach)

Nephritis IgA nephropathy (common Renal biopsy

pathogen)

What are the organ-based complications and management tasks?

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(1) Overall management

! 90% of HSP occur in paediatrics and are self limiting.
! Most can be treated outpatient with oral hydration, bed rest, and symptomatic relief of
joint and abdominal pain; admit if child is sick (cannot take orally, severe abdo or joint
pain limiting ambulation, altered mental status), complications (significant GI bleed,
significant renal disease)
! Manage joint/abdo pain with NSAIDS such as naproxen with adequate hydration
! Systemic glucocorticoids (PO prednisolone or IV methylprednisolone) if severe
abdominal pain that interferes with oral intake and non-response to NSAIDs;
remember to tail dose.

(2) Renal disease

! Monitor UFEME & Cr → ⅓ of HSP develop renal involvement which may be range from
mild to acute nephritic syndrome (hematuria, hypertension) or renal impairment.
! Some clinicians treat with steroids -- controversial. Glucocorticoids and other steroid
sparing agents not shown to be beneficial unless renal biopsy shows true crescentic
glomerulonephritis.

(3) Abdominal pain +/- complications

! Abdominal pain is a feature of HSP but beware of complications → more commonly
intussusception (severe colic, redcurrent jelly stools), GI bleed, pancreatitis,
gallbladder involvement, bowel perforation
! If suspect intussusception order ultrasound; treatment is first by attempting
radiographic- guided air enema; if fails, open surgery.

(4) Other complications (less common)

! Neurology: headaches, seizures, encephalopathy (both hypertensive encephalopathy
and posterior reversible encephalopathy syndrome [PRES]), focal neurologic deficits,
ataxia, intracerebral hemorrhage, and central and peripheral neuropathy
! Scrotum: rarely, boys can also present with scrotal pain mimics testicular torsion

Long-term follow up
! Prognosis is excellent although the rash may take time to resolve and a small
percentage (<1%) develop long term complications, mainly renal disease.
! Outpatient follow-up: screen BP and for urinary abnormalities to identify patients with
significant and potentially progressive renal involvement.

Sample summary: Pokey is a 6 year old boy who first presented with a 2-week history of
palpable purpura, mild abdominal pain, and hematuria. He was diagnosed with henoch
schonlein purpura and treated outpatient with NSAID analgesia and PO steroids.
Subsequently he developed severe abdominal pain and redcurrent jelly stools; he was
admitted and an ultrasound diagnosed intussusception. Treatment with air enema was
successfully. That episode was four weeks ago and at his latest follow up last week he was
well, feeding well, with no residual abdominal pain.

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MEDICINE LONG CASES: THE CLINICAL QUESTIONS APPROACH RHEUM: JUVENILE IDIOPATHIC ARTHRITIS

MEDICAL LONG CASES

Rheum: Juvenile Idiopathic Arthritis

PAEDIATRICS

What is the clinical presentation > Is it JIA and if so, which subtype?

(a) Pauciarticular JIA: chronic oligoarticular joint pain

! Look at the time course - JIA lasts >6 weeks. If acute, consider septic septic arthritis,
haemarthrosis, and trauma -- do joint aspirate
! Classically, inflammatory pain in ≤4, usually large joints, o/e swollen and tender. But
may not present as “pain”, simply as limp, clumsiness, refusal to play

(b) Polyarticular JIA: chronic polyarticular joint pain

! Look at the time course - JIA lasts >6 weeks. If acute, consider septic septic arthritis,
viral arthritis, henoch schonlein purpura, haemarthrosis, and trauma
! Classically, inflammatory symmetrical polyarthropathy in ≥5 joints (may be preceded
by indolent pain in 1-2 joints esp In younger children <10y). Parallels RA.
! ANA is +ve in younger children <10y, RF +ve in older. Lupus-related antibodies
(dsDNA, etc) should be -ve.

(c) Enthesitis-related arthritis

! Somewhat hard to classify and psoriatic arthritis seems separate?
! Features include spinal pain, HLA-B27 positivity, inflammatory bowel disease;
analogous to spondyloarthropathy in adult.

(d) Systemic onset JIA: sick child with joint pain

! Classically recurrent spiking fever, salmon-coloured rash, hepatosplenomegaly +/-
pleuritis/pericarditis; onset of arthritis may be delayed.
! Laboratory findings are: raised inflammatory markers (neutrophils, thrombocytosis,
ESR, CRP, ferritin), anaemia. RF and ANA usually negative.
! Ensure that malignancy is excluded: ‘normal WBC’, lymphocytosis, neutropenia,
thrombocytopenia, and disproportionate or night pain is worrysome.
! Other ddx: viral arthritis, malaria.

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How has it been treated and is there disease remission?

! Treatment options: NSAIDs, hydroxychloroquine, methotrexate, biologics; bridging
corticosteroids in acute setting, intra-articular corticosteroids for oligoarticular JIA.
! Is pain controlled?
! How is child’s function?
! Is there any deformity? > e.g. contractures, loss of joints space.
! Are there side effects of treatment? E.g. if on MTX, does the child/parent know how to
come to A&E for FBC if there is any fever? These drugs require monitoring.

How is the child’s vision?

! Children with JIA are at risk for uveitis, especially if ANA +ve, pauciarticular JIA.
! Are there symptoms of visual loss? However uveitis can be asymptomatic until vision
is lost.
! Require regular slit-lamp screening -- if not doing, why?

How is the child’s overall health, and quality of life?

! Growth & Development
! Coping with school
! Family support.

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MEDICINE LONG CASES: THE CLINICAL QUESTIONS APPROACH RHEUM: RHEUMATOID ARTHRITIS

MEDICAL LONG CASES

Rheum: Rheumatoid Arthritis

ADULTS

Is this rheumatoid arthritis?

! Classic RA: symmetrical inflammatory polyarthropathy affecting the small joints of the
hands (MCPJ and PIPJ, sparing the DIPJ), associated with morning stiffness lasting
>30min.
○ EULAR/ACR 2010 Criteria: clinical (joints affected, symptom duration),
serological (RF, anti-CCP), acute phase reactants (CRP, ESR)
○ Any inflammatory joint pain has to be taken seriously even if it is not a classic
rheumatological condition → early specialist referral.
! Differentials
○ Psoriatic arthropathy → Look carefully for any psoriatic plaque, onycholysis and
other nail changes.
○ Osteoarthritis of the hand → mainly DIPJ (Heberden node) rather than PIPJ
(Bouchard node), pain is mechanical not inflammatory
○ Polyarticular gout
○ Overlap syndromes: look for features of SLE (rash, systemic organ involvement
not classical for RA e.g. nephritis), scleroderma (sclerodactyly, facial
telangiectasias, pulp atrophy and digital ulcers), do anti-RNP antibody

What has the course and current disease activity?

! Consider how the patient presented, the course of disease and response to treatment,
and where the patient is currently.
○ RA is now aggressively treated with early diagnosis, specialist care, early
DMARD use, and tight control, therefore it is rare to see new RA cases
progress along its natural history to reach an end state with disabling
deformities (the ‘piano key hands’).
○ However longstanding RA patients patients, or older patients who do not seek
help early, may still present with late stage RA
! What is the current disease activity
○ Symptoms: pain, morning stiffness
○ Functional status (very important to assess)
○ Examination findings: bogginess of the joint, erythema and tenderness
○ Serological: trend the CRP, ESR
! What is the accumulated damage?
○ Deformities - e.g. subluxed MCPJ, Z thumb, etc
○ Function is also very relevant here.

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What is the extent of involvement?

! Other joints
○ Larger appendicular joints: wrists, elbows, shoulders, ankles, knees, hip
○ Atlantoaxial instability → any neck pain?
○ Hallux valgus
! Extra-articular manifestations
○ Eyes: episcleritis, scleritis → any eye disease?
○ Skin: rheumatoid nodules, pyoderma gangrenosum
○ Vasculitis
○ Lungs: interstitial lung disease, bronchiectasis
○ Pericarditis
○ Haem: anemia, neutropaenia (felty’s syndrome)
○ Nerves: carpal tunnel syndrome

How can I optimise management?

(1) Symptomatic relief

! NSAIDs, COX2 inhibitors
! Low dose prednisolone
! Is patient satisfied with functional state?

(2) Prevent disease progression

! Corticosteroids for induction of remission
! DMARDs: Methotrexate hydroxychloroquine, sulfasalazine, leflunomide
○ Baseline tests: CXR (pneumonitis, TB), FBC (cytopenias), LFT
(hepatotoxicity), RP for Cr, HBsAg, Anti-HCV
○ Advocate for early DMARD use to prevent damage.
! Biologics: anti-B cell (rituximab), anti-TNF (etanercept, infliximab, adalimumab, etc.)
○ For patients with high disease activity despite DMARDs
○ Long term use can result in antibodies being formed against the drugs and thus
loss of response

(3) Mitigate existing disability

! Orthopaedic intervention e.g.
○ Replace destroyed joints
○ Tendon transfers
○ Carpal tunnel syndrome management
! Functional assistance: e.g. orthotic aids, home modifications, occupational therapy

(4) Manage extra-articular manifestations

! Interstitial lung disease → try glucocorticoids, and if refractory, mycophenolate,
azathioprine, or cyclophosphamide (avoid methotrexate)

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(5) Manage complications of treatment

! Steroid side effects e.g. Cushingoid appearance, osteoporosis, cataracts: see
approach to Cushing’s disease → monitor fasting glucose, lipids, DEXA and treat
osteoporosis
! Agranulocytosis on methotrexate
○ Monitoring
○ Give folic acid
○ Check - does patient know what to do if fever?
! Complications of immunosuppression
○ Are there recurrent infections?
○ Prophylaxis: vaccinate
! If young female on methotrexate - is the patient planning pregnancy? Methotrexate is
teratogenic so if considering pregnancy need to switch; if not considering, check that
contraception is adequate

How is the patient coping overall?

! Patient’s understanding of disease -- what are the concerns and fears
! Functional: Able to work? Able to take care of self?
! Psychological: deformities can be disfiguring and pain debilitating.
! Social: especially if function not as good, what are the care arrangements?
! Financial

Sample summary: Mdm Sang Net is a 60 year old Chinese lady who has a 10-year history
of inflammatory symmetrical polyarthropathy mainly affecting MCPJs, PIPJs, and bilateral
knees, associated with morning stiffness. She was referred to rheumatology and diagnosed
with rheumatoid arthritis but was lost to follow up before she could be started on treatment.
She re-presented three years ago with hand deformities including MCPJ subluxation and ulnar
deviation and swan neck deformities. She was started then on methotrexate and analgesia,
which she is tolerating well. Currently her disease is quiescent with no complaints, minor
functional impairment not causing impediment to lifestyle, therefore she is thinking of stopping
treatment because she feels better. My main issues are -
1. Rheumatoid arthritis on methotrexate
2. Poor patient understanding of disease → need education.

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MEDICINE LONG CASES: THE CLINICAL QUESTIONS APPROACH RHEUM: SLE

MEDICAL LONG CASES

Rheum: SLE

ADULTS & PAEDIATRICS

Is this SLE?
! What is the presenting symptom? > Dr House has a running joke of offering lupus as
a differential in almost every episode -- there is some truth to this, the clinical
manifestations of SLE are protean.
! When to consider SLE: in the presence of suspicious clinical features,
○ Do autoantibodies: ANA, dsDNA, anti-Sm, anti-Ro, anti-La, antiphospholipid
(anticoagulant, anticardiolipin, anti beta-2 microglobulin): beware false +ve
ANA (other rheumatic dx, other autoimmune dx, chronic infection, normal pt)
○ Look for multiorgan involvement: FBC, UECr, CXR, as below.
! What else to consider: consider differentials to the presenting symptom (see approach
to specific symptoms), e.g.
○ Other rheumatic disease: RA, mixed connective tissue dx (RNP +ve),
vasculitides
! When to call it SLE?
○ Ultimately, a clinical diagnosis. Classification criteria (e.g. 2012 SLICC criteria)
are meant for research use; they provide a guide but are insufficiency sensitive
especially in early disease
○ Much more clear-cut if the clinical course is long

What are the manifestations in this patient?

Necessary to do a thorough systematic review and comprehensive physical examination to
look at organ specific manifestations
! Skin: malar rash, discoid rash, alopecia → any rash
! Face: dry eyes/mouth (2’ sjogren’s), red eyes (uveitis), oral ulcers
! Cardiac: any cardiac issues (accelerated atherosclerosis)
! Pulmonary: pleuritis, interstitial lung disease → any cough / chest pain / SOB?
! Renal: nephritic or nephrotic syndrome, CKD → any frothy urine, pedal edema,
hematuria, hypertension?
! Haematological: anaemia, thrombocytopaenia
! Antiphospholipid syndrome: DVT, recurrent obstetrical loss → Any previous children?
Any painful leg swelling?
! Musculoskeletal: joint pain or swelling
! Neurological: stroke (vasculitis), seizures, psychiatric issues → Any weakness /
numbness / difficulty seeing / headache
! Constitutional features: fever, loss of weight, fatigue.

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What are the current management issues?

(1) Disease activity and flares

! What is the tempo of flares - and how serious?
○ Each patient usually has a stereotypical flare -- but note ddx: infection
○ Evidence of flare: complements fall, dsDNA rises. [but CRP normal]
! How were they managed?
○ Major flare: pulse methylpred, cyclophosphamide, mycophenolate, cyclosporin
○ Minor: oral prednisolone, azathioprine, hydroxychloroquine
! Any other evidence of disease activity e.g. active nephritis, difficult to manage
cytopenias
○ Monitor C3, dsDNA Ab, CRP
! Any other symptoms → manage them
○ E.g. arthralgias → NSAIDs if no renal disease
○ Photosensitive skin manifestations: avoid sunlight, sunscreen

(2) Chronic immunosuppression

! What is the patient currently on and what is the response
○ Is response adequate? Any need to step up/down?
! Is the patient smoking? → Stop!
! Can we optimise treatment
○ All patients should be on hydroxychloroquine
○ If on steroids chronically → any role for steroid sparing agents e.g. azathioprine,
mycophenolate, cyclosporin

(3) Complications of medication

! Immunosuppression: predisposition to infections
○ What is the hep B, C, HIV status; baseline CXR
○ Immunizations
! Steroid side effect: e.g. osteoporosis, avascular necrosis, cushingoid features (see
approach to Cushing’s)
! If on hydroxychloroquine: any retinopathy
! Methotrexate if joints involved

(4) End-organ damage and their management

! Monitor: e.g. UECr, UPCR, UFEME, FBC, LFT, malignancy screen
! Renal failure → manage as per CKD (ACE-I), may need dialysis
! DVT/PE → may require anticoagulation.
! DM, hyperlipidemia → manage as per usual

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How is the patient coping?

! In a disease with many manifestations (and further side effects), important to know
exactly what is bothering the patient
! Sexual activity: does the patient intend to become pregnant?
○ If active disease, dangerous materal and fetal outcomes (lupus flare,
miscarriage, preeclampsia, neonatal heart block) → should control disease first
for 6/12 before planned pregnancy
○ If active disease → what contraception is used?
! Function: able to work?
! Social: social interactions, family
! Financial

Sample summary: Ms Seow Ling Ee is a 30 year old Chinese teacher with systemic lupus
erythematosus. She was diagnosed 5 years ago when she first presented with malar rash,
small joint arthritis, lupus nephritis and hemolytic anemia. She has been stable on
hydroxychloroquine and methotrexate, with only 2 flares with the same pattern of involvement
which remitted with pulse steroids. Her kidney function, CKD stage 3 at the moment on ACE-
Is, is being watched closely. She has not experienced any serious side effects from her
medications such as vision problems or recurrent infections. As a patient, Ms Seow is highly
motivated to comply to her treatment as she wants to avoid dialysis. She is also astute and
has a good understanding of her disease, having been able to recognize her flare signature
(fever, malaise, rash, joint pain, lower limb swelling, symptoms of anemia) and know to get
admitted. She and her husband are still undecided as to whether they want to try for children
- they do desire children, but do not want to rock the boat and risk further damage to Ms
Seow’s kidneys. Until then, they understand the importance of continuing contraception when
she is on methotrexate. My main issues for her are:
(1) SLE with lupus nephritis, hemolytic anemia and arthritis - currently in remission
(2) CKD Stage 3 secondary to lupus nephritis
(3) ?possibility of planned pregnancy

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