Acne.

Rosacea
Autoimmune skin diseases
Tadas Raudonis
Exam topics

24. Discoid lupus: definition, etiopathogenesis, clinical features, diagnosis,

treatment, prevention
25. Morphea: definition, etiopathogenesis, clinical features, diagnosis, treatment
26. Vitiligo: definition, etiopathogenesis, clinical features, diagnosis, treatment
27. Acne vulgaris: definition, etiopathogenesis, classification, clinical features,
diagnosis, treatment

28. Rosacea: definition, etiopathogenesis, classification, clinical features, diagnosis,

treatment
24. Pemphigus vulgaris : definition, etiopathogenesis, clinical features, diagnosis,
treatment
25. Bullous pemphigoid : definition, etiopathogenesis, clinical features, diagnosis,
treatment
Acne vulgaris
ACNE
myths
 Myth #1:

Your diet is not associated with acne

 Myth #3:

Acne – problem only for adolescents

 Myth #4:

Make-up always worsens acne

 Myth #6:

Tooth paste improves acne

 Myth #7:

Sun has a positive impct on acne

 Myth #8:

Comedones = dirty skin

Acne: definition, epidemiology

Definition:

¤ Chronic, inflammatory, polyetiologic skin disorder, affecting the pilosebaceus unit, and presenting with
polymorphic lesions on the face, chest and back

Epidemiology:
• One of the most common skin disorders in the dermatology practice
• Common positive family history
• Typically begins around 8- 12 y.o., peaks at 15- 18 y.o., remission up to 25 years
• Due to earlier onset of puberty acne begins at earlier age
• Acne tarda – may develop in females around 20- 35 y.o. (s. „acne in adult females“)
• High impact on quality of life: acne causes social, psychological and emotional impact comparable to epilepsy,
asthma, diabetes and arthritis
Acne: etiopathogenesis (1)
Important acne pathophysiology factors:

¤ Androgen mediated hyperproliferation and hyperactivity of skin sebaceous

glands

¤ Changes in hair follicle keratinocyte differentiation and hyperkeratinization

¤ Cutibacterium acnes colonisation in the hair follicle

¤ Inflammatory cytokine excretion and changes in skin immune response

Factors influencing acne onset and / or exacerbation:

• Genetic factors
• Dietary habits and poor diet
• Climate, air humidity
• UV rays
• Environmental toxins
• Stress
• Certain medications
• Irregular menstrual cycle, pregnancy
Acne: etiopathogenesis (2)

Androgen mediated hyperproliferation and hyperactivity of skin sebaceous glands:

¤ Patients with seborrhea or acne have larger sebaceous glands with more lobules in a single gland

¤ Patients with acne have a higher density of androgen receptors and higher 5α-reductase activity (compared to
healthy skin) → „peripheral hyperandrogenism“

¤ Local androgen excess and / or pronounced androgen receptor expression and sensitivity in the skin influence
formation of acne lesions

¤ Most patients with acne have normal levels of circulating androgens in the blood
Acne: etiopathogenesis (3)

Changes in hair follicle keratonocyte differentiation and hyperkeratinization:

¤ Keratinocyte hyperproliferation

¤ Slow korneocyte separation

¤ Changes in hair follicle environment

¤ Infundibulum of the hair follicle – „bottle neck“ phenomenon

Acne: etiopathogenesis(4)

Cutibacterium acnes colonisation in the hair follicle:

¤ Formerly Propionibacterium acnes (P. acnes)

¤ G+ anaerobe

¤ Produces porphyrins

¤ Produces inflammatory cytokines: IL-1, TNF-α, lipazes

Endogenous factor
influence on acne
Endocrine system influence

• Menstrual cycle: frequent exacerbations before

menses

• Pregnancy: lesions are the most severe during the

first three months of pregnancy

• Endocrine disorders: polycystic ovary syndrome,

hereditary adrenal hyperplasia, etc.
Stress
• Studies prove that stress worsens acne

• Stress induced hormones activate sebaceous glands in

the skin

• Self monitoring helps determine if stress has an impact

on acne lesions

• Increased stress can be associated with certain habits:

use of coffee, energy drinks, smoking
Lifestyle impact
on acne
Acne diet

Acne is negatively affected by:

• High glycemic index food products and fast food
• Dairy products
Acne diet

Acne is positively affected by:

• Omega-3 fatty acids

• Products rich in fiber
Impact of high glycemic index and dairy products

• Use of low glycemic index products improves acne

• People with normal BMI have a lower tendency to

develop acne

• The amount of consumed dairy especially low-fat

milk worsens acne, especially in moderate and
severe acne
Impact of omega-3 fatty acids and fiber

Omega-3 fatty acids slow inflammatory process,

including inflammatory acne lesions

Products high in fiber (selenium, fresh and dried fruit, vegetables) maintain gut microbiota
balance à help improve acne lesions
Ultraviolet irradiation

Impact on acne:
• Epidermal and dermal thickening à ↑ hair follicle keratinization
• Decreased amount of dermal fibers à ↑ sebum production
• Eradication of C. acnes à ↓ C. acnes in follicles
• Immunosuppression à ↓ inflammation
• Erythema, burns, skin cancer
• Wrinkles, aging
• Vit D. production
• Phototoxic reactions to medication
Other factors with negative impact

• Excessive use of Vit. B, protein and other supplements

• Occlusive bandages, splints, bras

• Cosmetics, various hair products, etc.

• Medication:
o Glucocorticosteroids
o Lithium
o Antiepilectics
o Medication for thyroid hyperfunction
o Anabolic steroids
o Neuroleptics
 ACNE
clinical features
Acne: clinical features (1)

Distribution:
¤ 99 proc. of cases develop acne on the face, less commonly on chest, back
¤ In severe cases shoulders, neck, buttocks are affected

Primary skin lesions:

Non-inflammatory:
• Microcomedones (the main skin lesion, may be present in healthy-looking
skin, which may develop into closed comedones)
• Closed comedones
• Open comedones
Inflammatory:
• Papules
• Pustules
• Nodules
Acne lesions

Open Closed
Papules Pustules Nodules, cysts
comedones comedones
 Acne: clinical features (3)
Secondary skin lesions:

¤ Crusts

¤ Cysts

¤ Fistulated comedones

¤ Fistula

¤ Scars (atrophic, hypertrophic or keloids)

Acne: lesion morphology

¤ Initially: „clogged pores“ (pore = pilosebaceous unit)

¤ Main initial acne lesions - microcomedones

¤ Closed comedones influence further development of acne

¤ Polymorphic lesions = lesions of different stages

¤ Skin lesion „evolution“:

– Comedone → nodules → pustule → node →cyst → scars, pigmentary changes

Acne severity grading

Mild form – comedonal acne

Moderate form – papulopustular acne
Severe form – nodules and conglobate acne

Mild Moderate Severe

Acne: severity subtypes
Acne comedonica Papulopustular acne Nodulocystic and conglobate acne

• Comedones
• Inflammatory skin lesions (forms
from comedones)
Accelerated keratinocyte corneation at the
lower part of the hair follicle causes • Multiples grouped fistular
microcomedone formation, followed by a comedones, papules, pustules,
closed comedone. nodules, painful nodes that form
When corneated cells fill the fair follicle and fistula
reach its opening, an open comedone forms • Common signs of feeling unwell
• Torso, shoulders, upper arms are
affected
• Heals with scarring
• More common in 20- 30 y.o. males
Acne complications

Atrophic scars Hypertrophic scars Hyperpigmentation

Adult acne

• Onset at 20–35 y.o or older age

• 5-10 proc. have acne until 40-50 years

• Usually develops in women (80 proc. of cases)

• Closely related to hormonal changes

• Distribution – mandible and neck

• In males may worsen due to shaving, excessive sweating

Other types of acne

Excoriation acne: Mallorca acne:

- usually affects young females - Develops following intensive sun
exposure, i.e. winter holidays in warm
- scratch marks and scars
climate
- usually with psychiatric disorders - Provoked by heat and sweating,
occlusive sunscreens
Acne: other subtypes

¤ Acne fulminans – severe acne with a sudden onset, usually affecting the face and torso, followed by signs of
systemic sickness

¤ Comestic, contact acne – caused by cosmetics, lesions – comedones and papules (pustules not common)

¤ Chloracne - develops followinf contact with halogen aromatic substances, presents with multiple comedones

¤ Neonatal and infant acne (acne neonatorum et infantum) – develops during the first year with monomorphic
lesions on the cheeks

¤ Hidradenitis suppurativa (acne inversa) – chronic inflammatory skin disorder presenting in sites with apocrine
sweat glands (armpits, inguinal, groin, perianal areas)

¤ Solar, senile, tropical, mechanical, medication-induced, professional, smokers acne, etc.

Acne diagnosis

¤ History

¤ Clinical presentation (comedones!)

¤ Additional tests performed:

– Suspicion of atypical forms

– When long-term systemic treatment is prescribed

ACNE TREATMENT
and skin care
Acne treatment

¤ Targeted to maximum supression of pathogenesis

¤ Adequate combined treatment:

– Topical

– Systemic

– Light therapy (lasers, IPL, PDT etc.)

– Cosmetic procedures

– Psychotherapy
Acne treatment guidelines
 Skin care at home
¤ Detergents

¤ Creams, lotions, serums

¤ Peels

¤ Masking products
Detergents
¤ Choose a mild detergent (pH 5,5-7)

¤ Do not scrub the skin, soft massage

using fingertips is sufficient

¤ Wash the face no more than twice daily

 Creams and cosmetics
• Choose a dermatological cream for acne-prone skin (non-comedogenic)
• Water-based products are less comedogenic than oil-based
• Substances acting on acne pathogenesis are recommended

• DO NOT go to bed wearing make-up

• Use a special mask of non-aggressive peel

or serum a few times per week
Recommended substances

• Keratolytics:

o Glycolic acid, lactic acid, salicylic acid

• Sebum production suppressing substances:

o Zinc acetate, nicotinamide (B3)

• Substances with anti-inflammatory and antibacterial action:

o Benzoyl peroxide, triclosan, azelaic racid, salycillic acid, nicotinamide,

phytosfingozine, etil-lactate, resveratrol

 Skincare routine
Morning:

¤ Wash the face with lukewarm water

¤ Mild detergents without irritating substances

¤ Dry with a soft towel, do not rub

¤ Cream according to skin type

¤ Physician-prescribed topical medication

¤ Sun protection SPF 30+

¤ Concealers
 Skincare routine
Evening:

¤ Micellar water to clean the make-up

¤ Mild detergents without irritating substances

¤ Dry with a soft towel, do not rub

¤ Cream according to skin type

¤ Physician-prescribed topical medication

Mechanical lesion manipulation

¤ Do not try to extract acne

lesions by yourself:
¥ Scarring promotion
¥ Infection promotion

¤ With comedones present, a

cosmetologist might extract
them mechanically
 Acne treatment: topical
¤ For mild forms

¤ Moderate to severe forms: combined with systemic treatment

¤ Maintenance therapy following systemic treatment

¤ Long-term therapy

Retinoids Antiinflammatory medications

• Adapalene, tretinoin • Benzoyl peroxide (BPO), azelaic acid
• I-st line therapy for most forms of acne • BPO:
• Comedolytic (normalizes desquamation) – Bactericidic, does not cause MO resistance
• Supresses inflammation – Supresses inflammation, keratolytic

Antibiotics
Keratolytics
• Clindamycin, erythromycin, tetracycline
• BPO, salicylic acid
• Not prescribed as monotherapy → only
combination medications (Duac®, Treclinac®)
• Reduces the number of MO supresses inflammation
 Azelaic acid
• Antimicrobial, anti-inflammatory and comedone-reducing properties

• Reduces post-inflammatory hyperpigmentation

• For mild and moderate acne

• Must be used with a sunscreen SPF 50+

 Benzoyl peroxide

• Reduces C. acnes colonisation on facial skin

• Comedolytic action

• May cause skin irritation → start with small amounts

• May stain clothing and bed sheets (bleaching)

 Topical antibiotics
• Commonly used: clindamycin and erythromycin

• Reduces C. acnes colonisation

• Antiinflammatory action

• Combination with benzoylperoxide or retinoids

 Topical retinoids
• Vitamin A derivates (adapalene, tazarotene, tretinoin)

• Antiinflammatory action, normalizes follicular keratinization

• Applied once daily (tretinoin used in the evening due to photosensitivity)

• Applied on lesional skin

• Sun pretection during the day SPF 50+

• May cause irritation, burning sensation, itching, erythema

• Not recommended during pregnancy

 Acne treatment: systemic
¤ For moderate / severe acne

¤ Also in patients where mild and sparse lesions cause major psychoemotional discomfort

¤ Excoriation acne

¤ G- folicullitis

Retinoids Antibiotics

Isotretinoin Doxycycline, tetracycline, minocycline, erythromycin

• Reduces sebum production, normalizes desquamation • Reduces the number of MO (number of superficial C. acnes colonies)
• Inhibits C. acnes growth • Supresses inflammation
• Supresses inflammation • Low-dose, long-term treatment

• Pathogenetic medication – acts on all 4 acne pathogenesis • ↑ resistance to AB

factors
Hormonal antiandrogens
• Crosses placenta
Oral contraceptives
• Teratogenic
• Reduces production of sebum, normalizes desquamation
• Hepatotoxic
• ↑ breast, cervical, embolus risk
• Prescribed for severe forms / resistant to other treatment
• Ovarian / adrenal hyperandrogenism signs, POS
• When contraception is desired / treatment with isotretinoin
 Oral antibiotics
• Moderate or severe acne, when topical treatment is not effective

• Prescribed for 3 - 4 months with topical retinoids (usually)

• Side effects: vaginal candidiasis, diarrhea

 Oral retinoids
Prescribed for severe acne

Laboratory investigations necessary

At least for 20 weeks (individually determined) → maintenance treatment

Possible side effects:

Cholesterol increase
Lip dryness, cheilitis
Skin and mucous membrane dryness, irritation, itch

Teratogenic – absolute contraindication during pregnancy

Not recommended in younger than 12 y.o. patients

 Hormonal therapy
• Good effect in patients prone to hyperandrogenism
• Irregular menses
• Facial hypertrichosis
• Ovarian cysts

• Estrogen, progestin

• Supresses androgen production à reduced activity of sebaceous

glands
Other treatment methods
Chemical peels
Intense pulsed light, laser therapy
Light therapy
 Chemical peeling
• Chemical peel – acidic products of various concentration used on the
surface of the skin cause controlled epidermal and dermal destruction

• Used for mild to moderate acne, scarring

• Usually well-tolerated

• Commonly used products: BHA (salicylic), AHA (glycolic, lactic, mandelic),

TCA, Jessner, kojic acid

• Side effects: skin burning, erythema, dryness, flaking, edema

 Blue light therapy
• Blue light 400-495 nm
Mechanism of action:
• Affects C. acnes
• Forms reactive oxygen species (ROS)
• ROS act on C. acnes or sebaceous glands
• à reduces inflammation, sebum production

Not enough large studies to prove efficacy!

Treatment of acne scars

Atrophic/hypotrophic:
• Filler injections
• Laser treatment
• Moderate depth chemical peels

Hypertrophic scars:
• Glucocorticosteroid injections
• Silicone gels
• Laser therapy
• Cryotherapy
 Treatment of acne hyperpigmentation
Recommended:
• Use of sun protection SPF 50+ during the day
• Topical medications with azelaic acid or retinoids

• Use products with skin lightening substances (hydroquinone, retinol, arbutin)

• Superficial chemical peels (with glycolic or salicylic acid)
 Treatment side effects
Irritation, dryness, flaking:
possible complications with oral retinoids and topical agents

Recommended:

• Start with low concentration → increase to maximum tolerated dose

• Use mild detergents, cleansers

• Use creams specially formulated for acne prone skin

• Apply moisturizer before topical medication

• Use topical medication every 2–3 days

• If severe irritation, wash the medication off after a few minutes and prolong application time
gradually
 Treatment side effects
• Photosensitivity: skin tans faster and stronger, may flake, blisters may form

• Medication with possible photosensitivity:

• Topical retinoids
• Benzoylperoxide
• Oral antibiotics and retinoids

• Other substances, than can cause sensitivity: AHA, chemical peels, microdermabrasion,
laser procedures

! Use sun protection daily (SPF > 30), avoid tanning beds
 Patience and time!
¤ At the beginning most medication may irritate the skin
à change treatment regimen

¤ Coadministration of a moisturizing and calming cream,

formulated for dried out oily skin

¤ After achieving derised results the treatment should not

be stopped, because untreated acne may flare-upà
maintenance treatment is necessary

¤ Treatment efficacy should be evaluated at least after 2–

3 months!
Conclusions

¤ Acne – very mythic, one of the most common dermatological disorders, may develop at any age

¤ Pathogenesis :

¥ Inflammation, hair follicle keratinization, increased sebum production and C. acnes excess

¤ Acne onset and severity is influeced by genetic, hormonal, stress and lifestyle factors

¤ Selection of suitable skincare products is key!

¤ Long-term treatment, efficacy evaluated after 2-3 months

Rosacea
MITAS ar TIESA? Myths
apie rožinę
about rosacea
#2. Frequent alcohol use – cause of rosacea

Alcohol may worsen the condition, however it is not the main cause
 #4. Rosacea is caused by poor hygiene

On the contrary – frequent skin cleasing and washing may

worsen the condition of dry and sensitive skin
 #6. Rosacea is curable

Even though rosacea cannot be cured , treatment helps control or even fully suppress
signs and symptoms of rosacea

Rožinė???
We
Rosacea???
can!!!
#7. Rosacea will subside without treatment

No. During the initial phases erythema may be transient,

but as it progresses, symptoms eventually become constant
 #10. Skin gets used to medication and they become ineffective

¤ Topical medication is designed for long-term use

¤ Usually there is no need to change the treatment due to tolerance

 #11. I can stop the treatment when symptoms subside

¤ False. Rosacea has a remitting relapsing course

¤ Long-term treatment prolongs remission and reduces the number of relapses

¤ Proactive treatment may help avoid this

Rosacea: definition

¤ Chronic inflammatory skin disorder

¤ Distribution: face (central part)

¤ Affects adults

¤ Relapses/remissions

¤ Various clinical stages

Rosacea: prevalance

¤ 30 – 60 y.o.

¤ Females > males

¤ Predisposing factors: bright skin (I-II

skin type)

¤ Distribution: ♀ cheeks, ♂ nose

¤ Males develop more severe forms

¤ Rarely seen in childhood

¤ 1/10 of UK residents

¤ In 20 proc. of cases eyes are affected

Rosacea: etiopathogenesis (1)

¤ Not completely clear

¤ No histological or serological markers

¤ Prominent genetic component (46%)/ hereditary sensitivity to triggers

¤ Sign variability – consequence of chronic skin inflammation, which may not bet clinically visible, but detected

histologically and biochemically

¤ Signs:

– Sudden flushing and constant centrofacial erythema

– papules/pustules

– Possible development of phymatous skin changes

 Rosacea: etiopathogenesis (2)
Provocative factors
(factors, that increase blood flow to the facial blood vessels, cause damage to the connective tissue of blood vessels and dermis)

Environment (exogenous) irritants:

¤ Temperature changes: cold – warm, cold wind, humidity, hyperthermia, saunas...

¤ UV, solar heat/sun burns, tanning beds

¤ Cosmetic procedures / make-up (microdermabrasion, chemical peels, skincare products containing alcohol, menthol, peppermint,
eucaliptus and other irritants)

Emotional: stress, anxiety

Physiological:

¤ Hormonal changes (females – menopause, “flushing”)

¤ Certain food, medication (amiodarone), other chemical substances (vit. B-6 and B-12)

¤ Intensive physical activity

¤ ↑ feritin levels (oxidative stress)

Rosacea: etiopathogenesis (3)

Associations with other disorders

GI Neurologic CVD Metabolic- endocine Onkologic

Ulcerative colitis Depression CHD Dislipidemia Thyroid Ca

Crohns disease Migraine AH Diabetes Glioma
Celiac disease Alzheimer‘s Rheumatoid arthritis
H. pylori Parkinson‘s Hormonal imbalance in
GERD Multiple sclerosis females (age)
 Rosacea: etiopathogenesis (4)

Trigger impact on the skin:

Increased blood flow to the blood vessels closer to the skin surface:
• erythema = dilation of superficial blood vessels

Damage to the connective tissue of blood vessels and dermis:

• Papillary dermal atrophy = capillary visualization

Perivascular inflammation:
• edema = increased blood vessel permeability
• edema may cause fibrosis and rhinophyma
Rosacea: Demodex

¤ Part of natural skin microbiota, residing on human skin

¤ Found in healthy and sick persons
¤ Rosacea-affected skin has a larger number of ticks
¤ Role of ticks and rosacea:
- Occlusion of the hair follicle
- Immune reaction to Demodex byproducts upon their death
- Disruption of skin barrier

Proof of central part of Demodex ticks in rosacea, is indirect

Demodex may be a provocative factor in rosacea-prone patients
Rosacea symptoms

• Sudden episodes of facial flushing, burning

• Persistant facial flushing, telangiectasia

• Inflammatory lesions

• Erythema and hyperplasia of nasal tissue

• Conjunctiva erythema, tear production, burning sensation

Rosacea clinical features

Blood vessel reaction Inflammation

Erythema Lesions
Teleangiectasia Damage to sebaceous
glands and connective
Skin burning tissue
 Rosacea: clinical features (1)

¤ Chronic course: relapses / remission

¤ Distribution: cheeks, perioral, nasal ares, forehead

¤ Facial burning, transient or persistant erythema

¤ Blood vessel dilation = telangiectasia

¤ Papules, pustules, nodules (rarely)

¤ Facial skin sensitivity, dryness, flaking

¤ Local eye symptoms

¤ Proliferation of connective tissue and sebaceous glands → phyma (rhinophyma, gnatophyma, otophyma etc.)
 Different forms of rosacea
Transient erythema

Persistant erythema + teleangiectasia

Erythema
+ teleangiectasia
+ skin lesions

Erythema
+ teleangiectasia
+ skin lesions
+ changes in fatty
tissue
 Rosacea: clinical features (2)

Persistent facial erythema Papules, pustules Teleangiectasia

Rhinophyma Teleangiectasia Papules, pustules, erythema

Rosacea: eye symptoms
No association between eye and skin symptoms!

Main symptoms – not specific:

¤ Increased eye sensitivity, dryness, fatigue, tearing

¤ Relapsing styes, meibomiitis

¤ Burning, pain, edema (scleritis)

¤ Eyelid border erythema, edema, teleangiectasia

¤ Blepharitis, conjunctivitis, keratitis

¤ Cornea ulceration, neovascularization

¤ Damage of tear ducts

¤ Blurred vission, photosensitivity ↑ (anterior uveitis)

Rosacea: diagnosis

¤ History (family history, provocative factors, genetic

disorders etc.)

¤ No diagnostic laboratory tests

¤ Clinical presentation:
¥ Typical complaints

¥ Typical signs

¥ No comedones
Rosacea and other skin disorders
Some patients with rosacea also have:

• acne

• perioral dermatitis

• seborrheic dermatitis

• atopic dermatitis

• psoriasis

• folliculitis
How to take care of your skin?
Main rules

Determine and
avoid
Sun protection Procedures
provocative
factors

Suitable skin
Medication
care
Rosacea provocative factors Genetics
Environ-
Food mental
factors

Rosacea
Cosmetics Seasons

Medication Stress
Food and drinks to be avoided

e
• C h ees
• Ch
ocolate
S p i c y food
•

o y s a uce
• S
• Vanilla
• D
airy
• Li v
er
• Re
d w i ne
H o t d rinks
•
pirits
• Other s
Suitable products
Medication to be avoided

Oral
• Niacin
• Nitrogl
ycerin

Topical
• Cortico
steroids
• Retinoi
ds
• Aceton
e
• Alcoho
l
 Environmental factors to be avoided

H eat t b aths
•
o
S a u na, h
ating
•
ve rh e
• O

• S
un
i n g b ed s
• T
ann
y
H u midit
•
g w i nd s
• S
tron
• C
ol d
Even emotions

er
• A ng
ss
• Stre
r i um
• Deli
A nx iety
•
Main rules

Determine and
avoid
Sun protection Procedures
provocative
factors

Suitable
Medication
skincare
DAILY
SKIN CARE
Skincare routine: morning

• Physician prescribed topical

¤ High quality sleep
medication
¤ Lukewarm water for face
washing
• Skincare for sensitive and
¤ Mild detergents without any
flushing skin
irritants
• Sun protection
¤ Pat dry with a towel
• Easily applied make-up
(green tinted
Skincare routine: evening

• Clean make-up with micellar water

• Mild detergents without irritating substancs

• Physician-prescribed topical medication

• Skincare for sensitive and flushing skin

• Facial massage
Correct skin cleansing

¤ Avoid irritants: tonics and other products containing sodium laureth sulfate,
SLES, menthol, camphar

¤ Avoid abrasive or peeling, sensitizing substances

¤ Detergents: mild, without soap, slightly acidic pH

¤ Wash the skin very lightly, do not rub

¤ Use lukewarm water

¤ Tap-dry with a clean and soft towel

 Skin tonic vs. micellar water
• Micellar water – product designed to clean the skin
• Micelles provide multiple action:
- decontaminate toxic substances on the skin surface
- soothes irritation, erythema, inflammation
- absorbs and removes dirt and sebum excess
- contracts skin pores
- moiturises the skin
• Tonic is intended to freshen the skin, restore the skin pH and prepare the skin for other cosmetics
Suitable cosmetic es
F ra g ra n c
substances ¤

¤ Alc
ohol
¤ M e nthol
¤ C a m p ha r
! Avoid cosmetics which contain: ¤ E u c a li p tus oil

¤ Ace
tone
F o r m a ldehyde
¤

¤ La n
olin
¤ Urea
Do not use stimulating facial masks and tonics
¤ F ru
it acids
containing alcohol cid
¤ Glycolic a
Choice of cosmetics

¤ Use cosmetics suitable for sensitive, flushing skin

¤ Choose creams containing soothing,

antiinflammatory, vessel stabilizing agents: kinetin,
retinaldehyde, likochalcone A

¤ Skin muisturising creams are essential

(hydrophyllic formula without or only a small number
of lipids)
Shaving

• Avoid shaving foam

containing soaps

• Most suitable – “dry”

shaving
Make-up

¤ Do not use waterproof make-up or heavy foundation that is difficult to remove

¤ Heavily concealing make-up is not suitable for rosacea

¤ Green pigment masks erythema

Main rules

Determine and
avoid
Sun protection Procedures
provocative
factors

Suitable
Medication
skincare
Sun protection

¤ Avoid sun between 10:00 – 16:00

¤ Wear a wide hat, sunglasses, protective clothing,

reapply sunscreen every 2 hours (SPF>30)

¤ Dimethicone, cyklomethicone – skin soothing

substances

¤ Sunscreens containing zinc oxide or titanium

dioxide – well-tolerated
Pagrindinės taisyklės

Determine and
avoid
Sun protection Procedures
provocative
factors

Suitable
Medication
skincare
Rosacea: treatment (1)
¤ Rosacea rarely dissappears by itself

¤ Chronic course

¤ Controllable, but incurable

¤ Untreated disease worserns gradually

¤ Treatment is usually necessary, because complete avoidance of provocative factors is difficult

¤ Choise of treatment depends on symptoms and disease severity

 Rosacea: treatment (2)
Topical:
Antiinflammatory, antimicrobial:
¤ 1 proc. ivermectin gel
¤ 0,75 proc. or 1 proc. metronidazole gel
¤ Clindamycin, erythromycin, tetracycline
Azelaic acid (15 proc.)
¤ Antimicrobial, antiinflammatory, keratinization suppresive action, does not cause resistance
Brimonidine (0,33 proc.)
¤ Alfa 2 adrenergic receptor agonist

Systemic (antibiotics):
• Antiinflammatory
• Doxycycline (100 mg/d, 40 mg/d)
• Minocycline, erythromycin, metronidazole
• Treatment is longterm, initially – 8-12 weeks (until inflammatory lesions dissappear)
Ivermectin

¤ Prescription medication

¤ Applied once daily in the evening

¤ Pea-sized amount of cream is applied on each of the zones: forehead, chin, nose and cheeks

• Improvement visible in 4 weeks, used for at least 3

months
• Side effects: skin burning sensation
Metronidazole

¤ Prescription medication, antibiotic

¤ Used for treatment of rosacea lesions and flushing, pustules, small papules on the
nose

¤ Longterm use in the morning and / or evening

¤ Do not apply close to eyes

¤ Usual treatment duration – 3 – 4 months

¤ Side effects: skin dryness, erythema, pruritus, skin discomfort, pain, tingling), skin
irritation, worsening of the condition
Azelaic acid

¤ Prescription medication

¤ Reduces inflammatory skin lesions

¤ Used longterm, morning and / or evening on affected skin

¤ Treatment duration – individual, depends on severity

• Improvement usually seen after 4 weeks

• May be used for many months

• Side effects: skin irritation (i.e. burning sensation, pruritus)

Brimonidine
¤ Prescription medication, gel

¤ Constricts blood vessels on the skin surface

¤ Efficacy lasts up to 12 hours

¤ Gel is applied on clean skin

¤ Other skincare products after the product dries

¤ Medication efficacy is transient, therefore should be

used regularly
Tips

#1. Do not use cosmetics before applying medication

#2. Cosmetics may be used once the medication dries

#3. Wash hands immediately after applying it

#4. During treatment, avoid other possibly irritating skincare

products:
n soaps
n alcohol-containing skin cleansers, pore constricting agents

n peels
Oral antibiotics

¤ Most commonly: low-dose doxycycline

¤ Inflammation (erythema) reducing action

¤ Efficacy evaluated after at least 8 weeks

¤ Safe for longterm use (up to 6 months)

¤ Side effects: GI upset, diarrhea, photosensitivity

Main rules

Determine and
avoid
Sun protection Procedures
provocative
factors

Suitable
Medication
skincare
Facial massage

¤ 1951 m. Danish dermatologist P. Sobye described therapeutic

massage

¤ Massage stimulates intercelullar fluid transport from the connective

tissue into the bloodstream, this reduces inflammation and erythema

¤ Therapeutic massages promote lymph drainage:

¥ Reduces inflammation, edema, erythema

¥ Improves tissue bloodflow, medication penetration into deeper tissues

 Laser treatment
¤ Reduces erythema by destroying dilated blood vessels

¤ Multiple procedures might be necessary (1 - 6), procedures repeated every 3 – 8

weeks

¤ Lasers: Nd: YAG, PDL, IPL

¤ During treatment – avoid sun SPF 50+

Efficacy after 3
laser procedures
Chemical peels

¤ Chemical peels of low concentration may be used as a supplementary treatment

¤ Dermatologist should choose a suitable peeling and intervals between procedures, after
evaluating the skin condition

¤ Suitable peels – salicylic acid (20-30 proc.), azelaic acid, mandelic acid

¤ During exacerbation peels containing glycolic acid and fruit acid are not recommended

¤ Procedure performed every 2-6 weeks

¤ Mandaroty sun protection SPF 50+

Ocular rosacea treatment

• Eyelid hygiene with lukewarm water

twice daily
• Artificial tears
• Cyclosporine 0,05 proc. eye drops
• Antibiotics

! Not associated with skin symptoms

Rhinophyma treatment

• Topical retinoids

• Antibiotics

• Oral retinoids

• Laser treatment

• Cryotherapy

• Surgery

Before and after CO2 laser treatment

Autoimmune skin diseases
Examination topics

33. Cutaneous discoid lupus erythematosus: definition, etiopathogenesis, classification, clinical

features, diagnosis, treatment, prevention

34. Scleroderma: definition, etiopathogenesis, classification, clinical features, diagnosis, treatment

35. Vitiligo: definition, etiopathogenesis, clinical features, diagnosis, treatment

36. Pemphigus vulgaris: definition, etiopathogenesis, clinical features, diagnosis, treatment

37. Bullous pemphigoid: definition, etiopathogenesis, clinical features, diagnosis, treatment

Autoimmune connective tissue disorders

¤ A group of disorders with similar etiopathogenesis and symptoms:

¥ Lupus erythematosus
¥ Scleroderma
¥ Vitiligo
¥ Blistering disorders

¤ Circulating autoantibodies (autoAb) against certain nuclear components (ANA)

Discoid lupus erythematosus
Lupus erythematosus: definition, classification

¤ Polyetiological autoimmune connective tissue disorder affecting 1 or more organ systems:

¥ skin, vessels, kidneys, other systems
¤ Acute or chronic course

¤ Cutaneous lupus erythematosus variants:

¥ Acute
¥ Subacute
¥ Chronic:
¥ Discoid
¥ LE tumidus
¥ LE profundus
¥ Other variants: newborn, cold, medication induced

¤ AutoAb against intracellular components (anti-Ro/SSA)

Cutaneous lupus erythematosus: etiopathogenesis
¤ Genetic factors influence the risk of developing LE during one lifetime
¥ HLA – histocompatibility antigens
¥ HLA-B8, -DR2, -DR3, -DQwl, -DRB1

¥ Complement gene variations / mutations especially cause photosensitivity, anti-Ro/SSA production

¤ Risk factors
¥ Exogenous
¥ UV exposure

¥ Viral infections (EBV)

¥ Chemical compounds: medication (minocycline, antiepileptics), farming chemicals

¥ Smoking

¥ Individual
¥ Hormonal imbalance

¥ Immune response

¥ Mothers anti-SSA, anti-SSB transport through the placenta

¤ Autoantibodies may be detected a few year before any symptoms develop, exposure to risk factors
accelerates disease development
Discoid lupus erythematosus: definition, etiopathogeneses

¤ Chronic cicatricial erythrosquamous skin disorder that extends into the epidermi, upper and lower
dermis and skin appendages
¤ Usually develops in sun exposed areas

¤ Rarely any systemic disease findings, ANA negative

¤ F>M
¤ 15–60 y.o.

¤ Lasts for months – years

¥ 50 proc. recover
¥ 10 proc. progress into subacute stage
¥ 2 proc. progress into SLE
Discoid lupus erythematosus: pathogenesis
Discoid lupus erythematosus : clinical presentation

¤ Red clearly demarcated papules and plaques

¤ Hyperkeratosis, very adherent scale

¤ Atrophy, scarring

¤ Telangiectasia

¤ Central hipopigmentation, periferal hyperpigmentation

¤ Scalp – cicatricial alopecia

¤ Rough and indurated upon palpation

¤ Distribution
¥ Scalp, forehead, cheeks, nose, chin

¥ Chest, neck, back, upper arms

Discoid lupus erythematosus: clinical presentation
 Discoid lupus erythematosus: diagnostic investigations
¤ Clinical signs
¤ Skin biopsy
¥ Epidermal atrophy, vacuolar degeneration of basal keratinocytes,
Civatte bodies
¥ Hair follicle hyperkeratosis
¥ Lymphocytic dermal infiltrate, mucin deposits
¤ Direct immunofluorescence
¤ Laboratory: ANA negative or low titers
¤ SLE exclusion
Discoid lupus erythematosus: treatment

¤ Leads to scarring, permanent alopecia, pigmentary changes when untreated

¤ Sun protection, SPF50+, vit. D supplements
¤ Topical treatment:
¥ Topical CCS – first choice treatment, works on all subtypes of CLE
¥ Used for several weeks (especially face)

¥ Calcineurin inhibitors (pimecrolimus, tacrolimus)

¥ Triamcinolone injections
¥ Topical retirnoids (adapalene) – treatment-resistant lesions (second choice)

¤ Systemic treatment – disseminated lesions and/or scarring risk

¥ Antimalarials
¥ Hydroxychloroquine 200–400 mg/d. (max. dose up to 5 mg/kg/d)

n Oftalmological monitoring every 6–12 months

n Slow tapering if efficacy achieved
¥ Systemic CCS – severe and disseminated lesions together with antimalarials
n Dose slowly tapered down to lowest effective and discontinued when disease is controlled
Scleroderma
Scleroderma: definition, classification

¤ Chronic inflammatory skin disorder that causes local or disseminated skin sclerosis and/or internal
organ damage

¤ Local (morphea) – limited lesion with skin sclerosis

¥ Scleroderma circumscripta
¥ Scleroderma linearis
¥ Scleroderma ictus gladii, en coup de sabre
¤ Generalized – multiple large areas of sclerosis
¤ Systemic

¤ Risk factors:
¥ Environmental factors
¥ SiO2
¥ Solvents (vinyl chloride, trichlorethylene, epoxy resins, carbon tetrachloride)
¥ Xray
¥ CMV, HHV–5, parvovirus B19
¥ Mechanical skin trauma
Local scleroderma (morphea): etiopathogenesis
¤ Skin sclerosis without systemic involvement, multiple
disease variants, chronic inflammation

¤ Etiology is not exactly clear

¤ Prevalence increases with age (30–50 y.o.)
¥ Rare in children (linear type)

¤ Females are 4–9x more affected

¤ Induced and activated immune and inflammatory cells in

people with genetic predisposition
¥ Secretion of cytokines (IL-4, TNF-β), chemokines, growth
factors

¥ AutoAb: anti-ssDNR, fibrillin I, histone Ab

¤ Fibroblast activation, promotion of epithelial and

endothelial cell differentiation into myofibroblasts
¥ Myofibroblasts produce vast amounts of extracellular matter

-> tissue fibrosis

Classic local scleroderma (morphea): clinical presentation

¤ >1 cm oval asymmetric painless lesions

¤ Trunk, under breasts, lower back, inguinal areas
¤ Erythematous lesions –> firm in the the centre and
whitish
¤ Active lesions have a „lilac ring“
¤ During the late phase lesions soften, become partly
atrophic, hyper/hypopigmented
¤ Hair and other skin appendages dissappear
Morphea: clinical types

¤ Plaque – large discrete lesions

¤ Atrophoderma of Pasini and Pierini – superficial erythematous morphea variant, usually in young
females on the trunk, heals with atrophy and hyperpigmentation but without sclerosis. Clinically
presents with abrupt transformation from healthy skin to concave lesion
Morphea: clinical types

¤ Guttate – multiple small hypopigmented lesions

¤ Nodular – convex, keloid-like lesions

¤ Linear – single lesion, usually on the leg, more common in children, causes bone atrophy,
shortening of the limb, decreased function
Morphea: clinical types

¤ Coup de sabre – lesion usually found on the forehead, resembling a sword stroke

¤ Hemifacial atrophy (Parry-Romberg syndrome) – very severe form of linear morphea forma, may
also cause seizures and trigeminal neuralgia

¤ Mutilating generalized pansclerotic morphea – generalized morphea, presents with muscle

atrophy, loss of limb function, possibly lethal
Morphea: diagnostic investications

¤ Skin biopsy may confirm the diagnosis, but

cannot exclude systemic scleroderma, therefore,
clinical evaluation is crucial

¥ Acute phase: endothelial edema, perivascular

infiltration (T lymphocytes)

¥ Sclerotic phase: avascularisation, degradation of

skin appendages, abundant homogeneous
collagen fibers

¤ ANA and anti-ssDNR may be (+) in linear and

disseminated morphea

¤ In patients with disseminated form, esophagus

and joint examination is necessary
36 m. moteris

Kairiojo
pakinklio srityje
atrofinė
plokštelė.
Siuntimo diagnozė:
Skleroderma?

Galutinė diagnozė:
Lokali skleroderma

Balkšva bestruktūrė
sritis (O)
Local morphea: treatment

¤ Discrete lesions are treated with potent

CCS
¥ Occlusion, intralesional injection possible
¤ Tacrolimus
¤ Bath PUVA or UVA1
¤ Generalized or fast spreading type:
¥ Systemic CCS
¥ MTX
Systemic sclerosis

¤ Autoimmune disorder affecting multiple organ systems (skin, lungs, GI, kidneys) characterized by
diffuse connective tissue sclerosis

¤ Epidemiology:
¥ Usual onset 30–50 y.o., increases with age
¥ Women affected 5 x more often, males have a worse prognosis

¤ Pathogenesis:
¥ Small vessel vasculopathy, fibrosis, immune activation
¥ Genetic predisposition (HLA-DR3, -DR5, -DRw6, -DRws52)
¥ Autoreactive T cells are produced (as in GVHD)
¥ Increased production of type I, III, IV collagen, deposition in connective tissue
Systemic sclerosis: clinical presentation

¤ Diffuse
¤ Acral – sclerodactyly
¤ CREST syndrome
¥ C alcinosis of the soft tissue
¥ Hard nodules which produce white substance

¥ Raynaud’s phenomenon
¥ Finger blanching, cyanosis due to cold
¥ E sophagus dysfunction
¥ Sclerodactyly
¥ Finger edema –> sclerodactyly –> painful ulcers on the
fingertips
¥ T eleangiectasia
Systemic sclerosis: clinical presentation

¤ Skin is unable to be pinched, wax-coloured

¤ Face – mask: no mimics, microstomia, sharp nose, narrow lips,
yellowish skin, tense
¤ GI: tongue tie sclerosis, dysphagia, atrophic gastritis,
malabsorption
¤ Lung, renal fibrosis
¤ Heart: constrictive pericarditis, myocardial, valve sclerosis
¤ Musculoskeletal: arthralgia, muscle pain
Systemic scleroderma: treatment

¤ Systemic CCS: prednisone 0,5 mg/kg/d.

¥ Until remission achieved, then dose is tapered slowly
¤ Azathioprine 1–2 mg/d.
¤ MTX 20–30 mg/sav.
¤ Cyclophosphamide
¤ Cyclosporine
Vitiligo
Vitiligo: definition, epidemiology

¤ Aquired chronic multifactorial pigmentation disorder characterized by white

macules due to significant loss of functional epidermal (and sometimes hair
follicle) melanocytes
¤ Affects 0,5–2 proc. of population
¤ Same prevalence between genders, age groups and races
¤ 50 proc. onset before 20 y.o.
¤ Females seek treatment 2x more often due to social stigma
¤ Positive family history 6,25–38 proc.
Vitiligo: etiopathogenesis

¤ Various mechanisms cause loss of functional melanocytes:

¥ Metabolic disorders, oxidative stress, production of inflammatory mediators (IL-6, IL-8), cell separation
and autoimmune response (CD8 T-cells)
¤ Main etiologic theory – melanocyte-affecting autoimmune response in genetically predisposed
persons

4. Altered
1. Genetic 3. Melanocyte
2. Risk factos immune
predisposition stress
response
Vitiligo: etiopathogenesis

1. Genetic predisposition
¥ Vitiligo is associated with gene polymorphism of immune response and melanogenesis
¥ Polygenic inheritance
¥ Autoimmune disease predisposition
¥ Autoimmune thyroiditis, type I diabetes, Adison disease, alopecia areata, psoriasis
¥ Patient with vitiligo have limited ability to combat oxidative stress
2. Risk factors
¥ Internal factors
¥ Emotional distress
¥ Malnutrition
¥ External factors
¥ Sun burns
¥ Chemical exposition – phenols, diluents, hair dye
¥ Medication (skin brightening creams with rhododendron)
¥ Infections
Vitiligo: etiopathogenesis
 Vitiligo: classification
Segmental Non segmental
¤ Onset – before 12 y.o. ¤ Onset at any age
¤ A few small lesions ¤ Different body areas affected:
¤ One macule in one body area (90 proc.) ¥ Local: single or multiple macules in the same area
(10–15 cm2)
¤ Does not cross the midline
¥ Generalized:
¤ Distribution: head, neck, trunk, limbs ¥ Vulgaris: disseminated lesions without an obvious
¤ Acute onset and stabilisation main area
¥ Acrofacial distribution: distal fingertips and
¤ Not associated with thyroid or other
periorbital/oral areas
autoimmune disorders
¥ Universal: (almost) complete depigmentation
¥ Mucous membrane: around body orifices (lips,
Mixed genitalia, gingiva, nipples)
¤ Onset as segmental ¤ Symmetric, bilateral distribution
¤ Transforms into ¤ Associated with autoimmune and inflammatory
non segmental markers
Vitiligo: clinical presentation

¤ Clearly demarcated hypopigmented macules or

plaques surrounded by healthy skin
¤ Chalk or milk white
¤ Oval, round, linear from a few mm to a few cm
¤ Spreading speed unpredictable
¤ Inflammatory vitiligo: itch, elevated plaques, erythemic
borders
¤ Leukotrichia – white hairs in the affected area
¤ Koebner phenomenon
¤ May develop around a nevus (Halo nevus)
Vitiligo: segmental and non segmental types
Vitiligo: diagnostic investigations

¤ Vitiligo is almost always diagnosed only by clinical examination

¤ Wood’s lamp – better visualization of loss of pigment and intensiveness of
hypopigmentation
¥ Milky white luminescence
¤ Skin biopsy – to exclude other depigmenting disorders
¥ No melanocytes (special staining), slight MMN infiltration at the lesion borders
¤ Lab – exclusion of endocrine disorders (ANA, ATPO)
Vitiligo: treatment

¤ Treatment goals: ¤ Local treatment:

¥ Melanocyte stabilization ¥ GKS
¥ Suppresion of autoimmune response ¥ Calcineurin inhibitors
¥ Stimulation of melanocyte regeneration, ¥ Vitamin D analogues
proliferation
¤ Phototherapy:
¥ UVB-311 nm
¤ General measures:
¥ PUVA
¥ SPF50+: protection against sunburns, avoidance
of Koebner phenomenon ¥ Excimer laser (308 nm)
Camouflage makeup
¥
¤ Systemic:
¥ Camouflage tattoos on the lips, nipples
¥ CCS pulse therapy
¥ Self tanning lotions
¤ Surgical:
¥ Melanocyte transplantation
Vitiligo: treatment

¤ Topical CCS:
¥ First choice for lesions not on the face
¥ Potent (betnovate, mometasone) and super potent (clobetasol)
¥ Monitor for atrophy and teleangiectasia

¥ Applied daily, no more than 3 months

¤ Topical calcineurin inhibitors (tacrolimus and pimecrolimus):

¥ Especially face
¥ Safer for long-term use
¥ Initially prescribed for 6 moths, short sun exposure recommended
¥ With positive response continue for 12 months
Vitiligo: treatment

¤ UVB-311 nm
¥ First choice in active / disseminated vitiligo
¥ Whole body may be treated
¥ Treatment must be long-term
¥ Discontinued if no efficacy in 3 months
¥ With positive response continued up to 1–2 years

¤ Laser treatment – Excimer laser (308 nm)

¥ Single stable macules
¥ 2 times per week, 24–48 procedures

¤ Autologous skin transplant – only in stable disease (2

y.), with no tendency for keloids or Koebner
phenomenon
¥ When medical treatment is not effective
¥ Efficacy up to 87 proc.
Vitiligo: depigmentation

¤ For patients with treatment resistant or very generalized vitiligo

¤ Remaining pigmented areas are destroyed using chemical substances or physical properties
¤ Monobenzone ethyl ester (Benoquin, MBEH) – hidrochinone derivate
¥ Almost always causes permanent skin depigmentation
¥ Best candidates with V, VI phototype
¥ MBEH used as 20 proc. cream 2–3 x/d. 1–4 months, sun avoidance mandatory
¤ Q-switched 755 nm Ruby laser – destroys melanin and cells containing it
¥ Together with MBEH or alone
JAK inhibitors

¤ Janus kinase (JAK) inhibitors act on janus kinase enzymes (JAK1, JAK2, JAK3, JAK4) therefore
interfering with the JAK-STAT signaling pathway in lymphocytes
¥ First generation drugs – tofacitinib and ruxolutinib lacked subtype selectivity, affecting JAK1/JAK3 and
JAK1/JAK2 respectively – unlikely to reach Baltics
¥ Second generation drugs – upadacitinib, baricitinib, abrocitinib, deucravacitinib

¤ Oral medications, fast onset of action

¥ patients had less itch as early as 2 days after starting the medication
¥ clearer skin in as little as 2 weeks

¤ Indications:
¥ Atopic dermatitis (upadacitinib, baricitinib, abrocitinib)
¥ Alopecia areata (first-line in the latest guidelines!) (baricitinib)
¥ Psoriasis (deucravacitinib) (EMA approval 2023 Mar)
¥ Psoriatic arthritis (upadacitinib, tofacitinib)
¥ Vitiligo (ruxolitinib)
Blistering skin diseases
Bullous skin diseases
¤ Blistering autoimmune diseases – group of autoimmune skin and mucous membrane disorders,
associated with IgG or IgA antibodies against different skin adhesion molecules
¤ Autoimmune mechanism determines the location of bullae formation and clinical presentation
¤ Disease course is severe and life-threatening
¤ Classification:
¥ Bullous disease group (loss of ¥ Pemphigoid group (loss of subepidermal
intraepidermal adhesion) adhesion
¥ Pemphigus vulgaris ¥ Bullous pemphigoid

¥ Vegetative ¥ Cicatricial pemphigoid

¥ Foliaceus ¥ Duhrings dermatitis herpetiformis

¥ Erythematous ¥ Linear IgA dermatosis
¥ Medication induced

¥ Paraneoplastic
Pemphigus vulgaris
Pemphigus vulgaris: definition, epidemiology

¤ Severe, potentially life-threatening autoimmune disorder affecting the skin and mucous
membranes, characterized by intraepidermal acantholytic blisters above the basal membrane,
which area caused by autoAb against desmogleins
¤ Prevalence 0,1–0,5/100 000 annually, usually certain ethnicities are affected
¤ Onset 40–60 y.o., females=males
Pemphigus vulgaris: definition and etiopathogenesis

¤ IgG autoAb against keratinocyte surface structures circulate in the blood and accumulate in
intercellular space –> IgG autoAb adhere to epidermal desmosomes –> acantholysis
¥ AutoAb against desmoglein-3 and 1
¥ Desmosomal complex is attacked, which holds keratinocytes connected together
Pemphigus vulgaris: clinical presentation

¤ Unaffected skin / mucous membrane –> soft unstable blisters –> easy tearing–> very painful and
slowly healing erosions –> bleeding –> crusting
¤ Distribution:
¥ Mucous membranes, head, chest, back, skin folds
¤ Severe cases – dissemination throughout the whole body –> loss of fluids and protein –>
electrolyte imbalance –> secondary infection –> sepsis, death
Pemphigus vulgaris: clinical presentation

¤ Three stages:
¥ Oral mucosa – 70 proc. begin in the mouth with painful erosions
¥ Additional localized lesions, usually on the scalp
¥ Generalized disorder
Pemphigus vulgaris: diagnostic investigations

¤ Nikolsky sign (+):

¥ indirect – pinching and pulling the epidermal border removes healthy looking epidermis
¥ direct – pressing the blister causes it to spread to the healthy tissue
¤ Cytology:
¥ Acantholytic cells
¤ Histology:
¥ intraepidermal bullae (above basal membrane)
Pemphigus vulgaris: diagnostic investigations

¤ Direct immunofluorescence – histology

¥ IgG (100 proc.), C3 (80 proc.), IgA (20 proc.) deposition around keratinocyte in the early blisters
¤ Indirect immunofluorescence – patient serum reaction with monkey esophagus epithelium
¥ Circulating IgG autoAb in serum against desmogleins
¤ Bloodwork:
¥ HGB ↓, ESR ↑, hypoproteinemia, electrolyte, fluid imbalance
Pemphigus vulgaris: treatment

¤ Systemic standard
¥ CCS: prednisone 1–3 mg/kg/d. –> slow tapering to maintenance dose (15–25 mg)

¤ Systemic agressive
¥ Methyl prednisone pulse therapy 1 g/d. in 2–3 hours, 3–5 d.
¥ Prednisone 1,5–2 mg/kg/d. + azathioprine (AZT) 2–4 mg/kg/d, slow tapering
¥ Methotrexate (MTX) 25–50 mg/week
¥ Cyclophosphamide 1–3 mg/kg/d. slow tapering

¤ Topical
¥ Wound care – promotion of epithelization, secondary infection prevention
¥ Local oral anesthetics before meals
¥ Antiseptic and antifungal medication
Rituximab

• Monoclonal antibody against B lymphocyte CD20 surface molecule

• Complete remission à 89% rituximab vs. 34% prednizolone
Induces:
- apoptosis,
- complement-dependent cytotoxicity
- antibody-dependent cytotoxicity
~70% of patients can stop taking prednisone after 6 months
AE: fever, leukopenia, neutropenia, agammaglobulinemia
Moderate and severe pemphigus vulgaris treatment

First line
• Rituximab: two infusions of 1 g every two weeks with systemic CCS 1.0 mg/kg/d tapered over 6 months
• Systemic CCS: p/os prednizolone 1.0-1.5 mg/kg/d with/without azathioprine 1–2.5 mg/kg/d, MMF 2 g/d

Remission achieved

Maintenance after 6 months Maintenance after 12 and 18 months

• Rituximab 500 mg or 1 g • Rituximab 500 mg on 12th and 18th month
If in complete remission If complete remission on/off therapy
AND Patients with still detectable anti-desmoglein antibodies
Initially severe pemphigus or high levels of anti-Dsg
after 3 months

• Rituximab 2 g (1 g Q2W)
- If remission incomplete
Klinikinis atvejis

• 35 m. ♀
• Pūslės pradėjo formuotis nuo 2015 m. visame kūne, veide, gleivinėse
• Gydyta Prednisolonu 60 – 80 mg, lokaliais AB, azatioprinu 100 mg/d
• Keletą kartų taikyti plazmaferezių kursai
• Dėl ilgalaikio GKS vartojimo išsivystė Kušingo sindromas, raumenų atrofija,
hiperglikemija
• Burnos gleivinėje formuojasi erozijos à sunku valgyti maistą à hipoproteinemija
Bullous pemphigoid
Bullous pemphigoid: definition

¤ Acquired autoimmune subepidermal blistering disease caused by autoAb against basal membrane
zone (BMZ) hemidesmosomal components
¤ Most common autoimmune blistering disease
¤ More common in the elderly 60–80 y.o.
¤ Males affected twice as often as females
Bullous pemphigoid: pathogenesis

¤ AutoAb (mostly IgG) against

hemidesmosomes (epidermal and dermal
adhesion complex)
¤ AutoAb act on two hemidesmosomal
proteins :
¥ Bullous pemphigoid (BP) 230
¥ BP 180
¤ When autoAb are connected, complement
is activated –> attraction of eosinophils and
neutrophils –> protease secretion –> blister
formation
Bullous pemphigoid: clinical presentation

¤ Nonbullous phase:
¥ Before formation of bullae
¥ Nonspecific polymorphic rash, prodrome symptoms
¥ Urticarial lesions

¥ Eczema-like lesions
¥ Itch
¥ May last weeks – months

¤ Bullous phase:
¥ Bullae form on healthy or erythematous skin
¥ May be accompanied by urticarial, popular lesions
Bullous pemphigoid: clinical presentation

¤ Very stable (roof is comprised of whole epidermis), tense, difficult

to puncture bullae
¤ Often filled with serous fluid, may be up to 10 cm
¤ Last for a few days, gets covered with a scab, heals without
scarring
¤ Nikolsky sign (–)
¤ Rarely affects the oral mucosa (< 20 proc.)
¤ Intense itching
¤ Symmetric distribution:
¥ Limb flexor surfaces, abdomen, folds
Bullous pemphigoid: diagnostic investigations

¤ Histology:
¥ Subepidermal bullae, inflammatory infiltrate with eosinophils
¤ Bloodwork:
¥ Eosinophilia (50 proc.), ESR ↑, IgE ↑ (50 proc.)
¤ Direct immunofluorescence:
¥ IgG, C3 deposit band on the basal membrane
¤ Indirect immunofluorescence:
¥ AutoAb in the blood against BP230 and BP180 adhere to the roof of the bulla
Bullous pemphigoid: treatment

¤ Goal – reduce clinical symptoms to individually tolerated (suppression of bullae formation, urticarial
lesions and itch)

¤ Systemic:
¥ CCS: prednisone 40–80 mg/d., slow tapering
¥ Azathioprine 100–150 mg/d.
¥ Methotrexate 15–20 mg/week
¥ May be combined with topical potent CCS during the induction 4–6 week phase
¥ Dapsone 100–150 mg/d.

¤ Topical:
¥ Wound care – promotion of epithelization, secondary infection prevention
Thank you

Questions?