AUTOIMMUNE SKIN DISEASES

Hardyanto Soebono
Fakultas Kedokteran UGM
 AUTOIMMUNITY

• Ability of immune system to differentiate

between self and non-self antigens
• Immune system response against self antigens
• Autoimmune responses include antibodies
and T cells with specificity for self antigens
AUTOIMMUNITY
• Autoimmunity appears normal part of
immune system
• Healthy people have low concentration of
autoantibodies in serum and tissue
• Auto-antibodies may form antigen-
antibody complex removed by
macrophages as part of tissue damage
removal
 Autoimmune Disease
Autoimmune disease occurs as a result of breakdown
in tolerance to self
Autoimmune disease is 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
 AUTOIMMUNE SKIN DISEASES

 BULLOUS DISEASES GROUP

 RHEUMATIC DISEASES GROUP
 OTHER
 Bullous Disease Group
 Pemphigus
 Bullous pemhigoid
 Herpes gestationes
 Dermatitis herpetiformis
 Epidermolysis bullosa
 Chronic Bullous Dermatosis of Childhood
(CBDC)
Rheumatic Disease Group
Lupus Eryhtematosus
Dermatomyositis
Systemic Sclerosis
Localized Scleroderma (Morphea)
Mixed Collagen-vascular Diseases (MCD)
Others
Others
Psoriasis
Vitiligo
Alopecia areata
Chronic urticaria
Etc.
 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 herpetiformis Transglutaminases Subepidermal blisters

Psoriasis Epidermal keratin Ki-16 Epidermal

Hyperproliferation
Vitiligo Melanocytes
Depigmentation
Alopecia areata Hair follicle
Patchy baldness
SLE DNA, Histone, ribosomes,
snRNP, scRNP Multiorgans involvement
 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
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
Skin biology

Damages of desmoglein in Pemphigus

1
Clinical pictures
 Predilection : scalp, face, intertriginous
areas, mechancal stressed areas, nail fold,
oral mucosa
 The blisters are not stable, as the
epidermis falls apart --> erosion & crusts
 3 stages:
◦ Oral involvement -- 70 %
◦ Localized areas (e.g. scalp)
◦ Generalized disease
 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
 Differential diagnosis
 Skin lesions:
◦ Erytema multiforme/ Stevens Johnson Syndrome
◦ Bullous impetigo
◦ Hailey-Hailey disease
 Oral lesions:
◦ Erosive candidiasis
◦ Chronic recurrent aphthae
◦ Herpetic gingivo-stomatitis
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
Pemphigus foliaceus
Represent 10 – 20 % all pemphigus
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
directlt beneath the stratum corneum
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
 ZONA MEMBRANA BASALIS/DERMO-EPIDERMAL JUNCTION

HD

LL
MB
MB

LD

AF
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
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
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)
 Psoriasis

– Psoriasis is a chronic, inflammatory, immune-mediated skin

disease affecting ~2% of the European population1
– The disease usually occurs in individuals with genetic
susceptibility in conjunction with environmental stimuli, and
may involve an immune response to autoantigens2
– Evidence supports a central role for dendritic cells and T cells
in establishing and maintaining the "vicious cycle" of psoriatic
plaque development2,3

1. Gudjonsson JE, Elder JT. Clin Dermatol. 2007;25(6):535-46. 2. Griffiths CE, Barker JN. Lancet. 2007;370:263-71. 3. Nickoloff BJ,
Nestle FO. J Clin Invest. 2004; 113:1664-75.
Clinical and Histological Appearance
of Psoriatic Plaque

Bar = 200 µm
 Vitiligo
• Acquired localized depigmentation of skin, hair,
and occasionally mucosa, characterized by
complete loss of melanocytes
• Etiology not well understood, evidence
autoimmune mechanism
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
 Sistemic Lupus Erythematosus
(SLE)
Disturbed immune regulation:
•Pathologic antigen presentation
•Increased MHC expression
•Enhanced co stimulation
•Cytokine imbalance (Th1/Th2)
•Decrease of regulatory T cells
•Defective of increased apoptosis

 B cell over activation

 Pathologic autoantibody production
 Impaired clearance of immune complexes
 Accumulation of IC
 Complement activation
 Antigen targets in SLE

 Nuclear antigens:
ssDNA, dsDNA,
histon (H1, H2A, H2B, H3, H4), Sm, RNP,
 Cytoplasmic antigens:
SS-A (Ro), SS-B (LA),
ribosomal p-protein,
ANCA (MPO, PR3),
 Cell surface antigens:
on endothelial cells, erythrocytes, neutrophil cells, lymphocytes
and platelets
 Other antigens:
plasma factors: e.g.beta-2-glicoprotein I,
phospholipids,
immune globulin.
 CRITERIA FOR THE DIAGNOSIS OF SLE ACCORDING
TO THE AMERICAN COLLEGE OF RHEUMATOLOGY
(ACR)

1. Butterfly rush 9. Haematological alterations

2. Discoid lupus
3. Photosensitivity
4. Oral ulceration
5. Polyarthritis
6. Nephritis
a. proteinuria over 0.5g/day
b. cellular casts
7. Pleuritis/pericarditis
8. Neuropsychiatric symptoms
a. convulsions
b. psychosis
4 or more symptoms are required for the diagnosis
a. haemolytic anaemia
b. leucopenia (4.0 G/l)
c. lymphopenia (1.5G/l)
d. thrombocytopenia (100G/l)
10. Immunologic alterations
a. anti-dsDNA
b. anti-Sm
c. anti-CL and/or LA
11. ANA
M Hochberg, 1997
CLASSIFICATION OF SKIN SYMPTOMS IN SLE
(Sontheimer RD.Lupus 6:84-95, 1997)

Lupus specific Lupus non-specific

A. Acute cutan LE /ACLE/ A. Cutan vascular symptoms
• Butterfly rush • Vasculitis
• Generalised ACLE
• Vasculopathy
• photosensitivity.
• Raynaud’s syndrome
B. Subacute cutan LE /SCLE/
• Livedo reticularis
• Annular
• Psoriasiform B. Non-scarring diffuse
alopecia
C. Chronic cutan LE /CCLE/
• Classical discoid lesions C. Urticaria
• Hypertrophic DLE D. Erythema exsudativum
• Lupus panniculitis multiforme
• Mucosal ulceration
• Others (L.tumidus,
Lichenoid)
Acute Cutaneous: Malar Rash Chronic Cutaneous:Discoid
Note Scarring, Hyperpigmentation
Note Sparing of Nasolabial Folds
Subacute Cutaneous Lupus