AUTOIMMUNE SKIN DISEASES

1. What is autoimmune disease?

2. What skin diseases caused by

autoimmune mechanism?

3. How is the pathogenesis of autoimmune

skin disease?

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 AUTOIMMUNE DISEASE
 Occurs as a result of breakdown in tolerance to self

 Characterized by immune system “attack” against self

antigens that lead to tissue damage
– Inflammation and hypersensitivity reactions
 Mediated by B-lymphocytes that produce antibodies to
self antigens
And / or
 T-lymphocytes with T-cell receptors that recognize self
antigens
– Autoreactive CD4 Th and autoreactive CD8
cytotoxic T cells
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 Pathogenesis
• Genetics
• Environmental:
– Infection
– Stress
– Hormonal

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 AUTOIMMUNE SKIN DISEASES
• BULLOUS DISEASES GROUP
• RHEUMATIC DISEASES GROUP
• OTHER

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 Bullous Disease Group
• Pemphigus
• Bullous pemhigoid
• Herpes gestationes
• Epidermolysis bullosa
• Dermatitis herpetiformis
• Chronic Bullous Dermatosis of Childhood
(CBDC)

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 Rheumatic Disease Group
• Lupus Eryhtematosus
• Dermatomyositis
• Systemic Sclerosis
• Localized Scleroderma (Morphea)
• Mixed Collagen-vascular Diseases (MCD)
• Others

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 Others
• Vitiligo
• Alopecia areata
• Chronic urticaria
• Etc.

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 Autoimmune Skin Diseases and Target
Antigens
Disease Autoantigen Clinical manifestations

Pemphigus Desmoglein-1 Intraepidermal blisters

Desmoglein-3
Bullous Pemphigoid BPAG-1(230 kD) Subepidermal blisters
BPAG-2 (180 kD)
Dermatitis Transglutaminases Subepidermal blisters
herpetiformis
Psoriasis Epidermal keratin Ki-16 Epidermal
Hyperproliferation
Vitiligo Melanocytes
Depigmentation
Alopecia areata Hair follicle
Patchy baldness
SLE DNA, Histone, ribosomes,
snRNP, scRNP Multiorgans involvement
 Bullous Disease Group
• Pemphigus
• Bullous pemhigoid
• Dermatitis herpetiformis
• Herpes gestationes
• Epidermolysis bullosa
• Chronic Bullous Dermatosis of Childhood
(CBDC)

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 PEMPHIGUS
• A group of disorders with loss of intra-epidermal
adhesion
• Cause: autoantibodies directed against proteins of
desmosomal complex that hold keratinocytes
together.
• Classification:
• Pemphigus vulgaris
• Pemphigus foliaceus
• Pemphigus erythematosus
• Pemphigus vegetans

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 Pemphigus vulgaris
• severe and potentially fatal autoimmune
blistering disorder affecting the skin and mucous
membranes caused by autoantibodies against
desmogleins.
• Incidence : 0.1-0.5/100,000 population/yr
• Pathogenesis:
– Genetic predisposition: HLA-DRQ402, -DQ0505
– Autoantibodies against desmoglein 3 (Dsg3), and
desmoglein 1(Dsg1)
– The bound antibodies activate proteases that
damage the desmosome  acantholysis
– Serum Ab titer correlates with severity of disease
and course

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Skin biology

Damages of desmoglein in Pemphigus

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 Diseases caused by desmosomal disturbances
Protein Disease
Desmoglein 1 Pemphigus foliaseus, striate palmoplantar
keratoderma, S4, bullous impetigo
Desmoglein 3 Pemphigus vulgaris
Desmoglein 4 Autosomal recessive hypotrichosis
Plakoglobin Palmoplantar keratoderma with wooly hair and
arrythmogenic right ventricular cardiomyopathy
(Naxos disease)
Plakophilin 1 Ectodermal dysplasia/skin fragility syndrome (skin
erosions, dystrophic nails, sparse hair, and painful
palmoplantar keratoderma)
Plakophilin 2 arrythmogenic right ventricular cardiomyopathy
Desmoplakin Lethal acantholytic epidermolysis bullosa, striate
palmoplantar keratoderma type I, Palmoplantar
keratoderma with left ventricular cardiomyopathy and
wooly hair, autosomal dominant arrythmogenic right
ventricular cardiomyopathy
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 Clinical pictures
• Predilection : scalp, face, intertriginous
areas, mechancal stressed areas, nail fold,
oral mucosa
• The blisters are not stable, as he
epidermis falls apart --> erosion & crusts
• 3 stages:
– Oral involvement -- 70 %
– Localized areas (e.g. scalp)
– Generalized disease

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 Diagnosis
• Clinical pictures
• Nikolsky sign :
– Gentle rubbing results in development of new
blisters
• Asboe-Hansen sign :
– Pressure at edge of blister makes it spread
• Histology
• Immunofluorescence

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 Differential diagnosis
• Skin lesions:
– Erytema multiforme/ Stevens Johnson
Syndrome
– Bullous impetigo
– Hailey-Hailey disease
• Oral lesions:
– Erosive candidiasis
– Chronic recurrent aphthae
– Herpetic gingivo-stomatitis
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 Pemphigus foliaceus
• Represent 10 – 20 % all pemphigus
• Clinical pictures :
– Recurrent crops of vesicles/blisters easily rupture,
leaving crusted erosion
– Predilection: head, neck, upper trunk, and rarely
mucous membrane
– Mostly affect adult usually midlife
• Nikolsky sign positive
• Histopathology :
– Superficial blisters with split in the granular layer or
directly beneath the stratum corneum

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 Differential Diagnosis
• Seborrhoic dermatitis
• Photodermatoses
• Lupus erythematosus
• Erythroderma
• Drug eruption

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 Management
• Systemic :
– Corticosteroids (1-2 mg/kg/day)
– Cyclophosphamide (7.5-10 mg/kg/day)
– Cycloporine (5.0-7.5 mg/kg/day
– Azathioprine (2.5 mgkg/day)
• Topical:
– Antiseptic and anticandidal
– Oral anesthetic gel

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 Bullous Pemphigoid
• Subepidermal blistering disease caused by
autoantibodies against components of the
hemidesmosomes in the basement membrane
zone (BMZ) (i.e. BPAG1/BP230 and
BPAG2/BP180)
• Incidence:
– Most frequent autoimmune bullous disease,
affects more elder people (50-60 yrs)
– Men more common affected

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 Bullous Pemphigoid
• Clinical pictures:
– Initialized by pruritus, urticarial lesions then
followed by development of blisters
– The blisters are stable and tense as the roof
are entire epidermis, contain fluid serum
– Oralmucosa involvement <20%
– Nikolsky sign negative

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 Bullous Pemphigoid
• Histology:
– Subepidermal blisters containing eosinophils
– Lamina lucida remains on the roof,and
lamina densa on the floor
• Immunofluorescence:
– Band of IgG and C3 along BMZ

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 Management

• Systemic:
– Prednisolone 1 mg/kg daily --> tappered to
maintenance dose 8 mg/day
– Sparing agents :
• Azathioprine, mycophenolate mofetil
– Methotrexate 15-20 mg/ week
• Topical;
– High potent corticosteroids
– Antiseptics (Povidone iodine)

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 Rheumatic Disease Group
• Lupus Eryhtematosus
• Dermatomyositis
• Systemic Sclerosis
• Localized Scleroderma (Morphea)
• Mixed Collagen-vascular Diseases (MCD)
• Others

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Lupus erythematosus
• Is an autoimune disease with a
broad clinical spectrum ranging
from mainly cutaneous lesions
(Cutaneous LE) to a severe
systemic disease (systemic LE).

• Clinical manifestation of
Cutaneous LE (CLE) is
heterogenous and primarily
defined to the skin

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Spectrum Lupus Erythematosus

SCLE

SLE

HL
E CCLE ACLE

LET

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Classification of Cutaneous LE (CLE)
 Acute cutaneous lupus erythematosus (ACLE)
 Localized form
 Generalized form
 Subacute cutaneous lupus erythematosus (SCLE)
 Annular
 Papulosquamous
 Chronic cutaneous lupus erythematosus (CCLE)
 Discoid lupus erythematosus (localized/ disseminated)
 Lupus erythematosus profundus (LEP)
 Chilblain lupus erythematosus (CHLE)
 Intermittent cutaneous lupus erythematosus (ICLE)
 Lupus erythematosus tumidus (LET)
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Malar rash
Alopecia

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Reaksi fotosensitivitas pada SLE
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Lesi psoriasiformis pada SCLE Lesi annular pada SCLE

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Lesi Koebner pada SCLE Ulserasi oral pada SLE
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Lesi fotosensitivitas pada SCLE
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Chronic discoid LE
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Classification of Cutaneous LE (CLE)

Histologically specific Histologically non-specific

• Discoid CLE • Histologically non-
• Subacute CLE specific:
• Acute CLE – Urticarial vasculitis
• LE Panniculitis (LEP) – Psoriasiform
• LE tumidus – Annular erythema
• Chilblain lupus (CL) – Raynaud phenomena
• Neonatal lupus – Alopecia
syndrome
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 Epidemiology

• Incidence 4 / 100.000 population in Sweden

• Female : male ratio varies 5.3 – 8 : 1
• CLE occurs in 72 – 85 % patients with SLE
• No data from Indonesia

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 Diagnostic criteria for CLE
ARA criteria SLE EADV
• Malar rash • Autoantibodies
• Discoid LE • LE band NS, LE band LS
• Photosensitivity • Low complement
• Oral ulcers • Hypergammaglobulinemia
• Arthritis • Finger vascular changes
• Serositis • Urticarial vasculitis
• Renal disorder • Psoriasiform, annular
• Neurologic • Raynaud phenomenon
• Hematologic • Alopecia
• Immunologic • Myalgia
• ANA positive • High ESR
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(Immuno)-Pathogenesis
• UV irradiation
• Autoantibodies
• Disregulation of T-cells
• Dendritic cells
• Cytokines and chemokines
• Epigenetics

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 Autoimmunity

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 Others
• Vitiligo
• Alopecia areata
• Chronic urticaria
• Etc.

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 Vitiligo
• Acquired localized depigmentation of skin, hair, and
occasionally mucosa, characterized by complete
loss of melanocytes
• Etiology not well understood, evidence
autoimmune mechanism

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 Alopecia areata
• Sudden localized hair loss without
clinically visible inflammation
• Organ-specific autoimmune disorder
with autoaggresive T cells directed
against anagen hair follicles
• Classification:
– Circumscripta
– Totalis
– Universalis
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