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 antigenantibody 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
Desmoglein-3

Intraepidermal blisters

Bullous Pemphigoid

BPAG-1(230 kD)
BPAG-2 (180 kD)

Subepidermal blisters

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 intraepidermal 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

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

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 m

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,
lymphocytes and platelets

erythrocytes,

Other antigens:

plasma factors: e.g.beta-2-glicoprotein I,

phospholipids,
immune globulin.

neutrophil

cells,

CRITERIA FOR THE DIAGNOSIS OF SLE ACCORDING

TO THE AMERICAN COLLEGE OF RHEUMATOLOGY
(ACR)

1. Butterfly rush
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

9. Haematological alterations
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
4 or more symptoms are required for the diagnosis

CLASSIFICATION OF SKIN SYMPTOMS IN SLE

(Sontheimer RD.Lupus 6:84-95, 1997)
Lupus specific

Lupus non-specific

A. Acute cutan LE /ACLE/

Butterfly rush
Generalised ACLE
photosensitivity.
B. Subacute cutan LE /SCLE/
Annular
Psoriasiform
C. Chronic cutan LE /CCLE/
Classical discoid lesions
Hypertrophic DLE
Lupus panniculitis
Mucosal ulceration
Others (L.tumidus,
Lichenoid)

A. Cutan vascular symptoms

Vasculitis
Vasculopathy
Raynauds syndrome
Livedo reticularis
B. Non-scarring diffuse
alopecia
C. Urticaria
D. Erythema exsudativum
multiforme

Acute Cutaneous: Malar Rash

Note Sparing of Nasolabial Folds

Chronic Cutaneous:Discoid
Note Scarring, Hyperpigmentation

Subacute Cutaneous Lupus