IMMUNOBULLOUS DISEASES کنفرانس ضایعات تاولی پوست 25/12/94 Dr: E. Salimi. Dermatologist Kermanshah university of medical sciences

Key features. Pemphigus is a group of autoimmune blistering diseasesof the skin and mucous membranes that is characterized by:. histologically, intraepidermal blisters due to the loss of cell- cell adhesion of keratinocytes. immunopathologically, the finding of in vivo bound and circulating IgG autoantibodies directed against the cell surface of keratinocytes. Pemphigus is divided into three major forms: pemphigus vulgaris,pemphigus foliaceus and para neoplastic pemphigus

Patients with pemphigus vulgaris and pemphigus foliaceus have IgG autoantibodies against desmoglein 3 and desmoglein 1, respectively, while patients with para neoplastic pemphigus have IgG autoantibodies against plakin molecules in addition to autoantibodies against desmogleins. IgAautoantibodies directed against the keratinocyte cell surface define IgA pemphigus, the pathophysiology of which is yet to be clarified

pemphigus vulgaris: CLINICAL FEATURES: pemphigus vulgaris develop painful erosions of the oral mucosa. More than half of the patients also develop flaccid blisters and widespread cutaneous erosions. Pemphigus vulgaris divided into two subgroups: (1) mucosal dominant with mucosal erosions but minimal skin involvement; (2) mucocutaneous type with extensive skin blisters and erosions in addition to mucosal involvement.

Mucous membrane lesions:  may be seen anywhere in the oral cavity, scattered or extensive erosions  most common sites are the buccal and palatine mucosa.  painful erosions  Intact blisters are rare and fragile and break easily  erosions arc of different sizes with an irregular ill- defined border,

The lesions may extend out onto the vermilion lip and lead to fissured hemorrhagic crusts. Involvement of the throat produces hoarseness and difficulty in swallowing. The esophagus also may be involved The conjunctivae, nasal mucosa, vagina, penis, anus and labia can develop lesions as well. Cytology vaginal cells may be misread as a malignancy when vaginal lesions are present.

The primary skin lesions of pemphibus vulgaris are flaccid, thin walled,easily ruptured blisters The fluid within the bullae is initially clear but may become hemorrhagic, turbid, or even seropurulent These erosions often attain a large size and can become generalized.

Those lesions that do heal often leave hyperpigmented patches with no scarring. Associated pruritus is uncommon. Pemphigus Vegetans: is a rare variant of pemphigus vulgaris represent a reactive pattern of the skin to the autoimmune of pemphigus vulgaris. characterized by flaccid blisters that become erosions and then form fungoid vegetations or papillomatous proliferations, soon progress to vegetative plaques. especially in intertriginous areas and on the scalp or face

Pemphigus Foliaceus They complain of burning and pain in association with the skin lesions. develop scaly, crusted cutaneous erosions, often on an erythematous base, do not have clinically apparent mucosal involvement even with widespread diseas The onset of disease is often subtle, with a few scattered crusted lesions that are transient

They are usually well demarcated and have a seborrhcic distribution, they favor the face, scalp and upper trunk the vesicle is so superficial and fragile, often only the resultant crust and scale are seen The disease may  stay localized for years or  it may rapidly progress, in some cases to generalized involvcment and an exfoliative erythroderma  oral lesions is extremely rare,

Pemphigus Erythematosus (Senear-Usher Syndrome localized variant of pemphigus foliaceus In the malar region of the face Typical scaly and crusted lesions of pemphigus foliaceus patients with immunologic features of:  both lupus erythematosus and pemphigus,  IgG and C3 deposition on cell surfaces of keratinocytes  as well as the basement membrane zone,  in circulating antinuclear antibodies'

Paraneoplastic Pemphigus with underlying neoplasms,both malignant and benign. The most commonly associated neoplasms are:  non-Hodgkin lymphoma (40)  chronic lymphocytic leukemia(30%),  Castleman's disease (10%),  malignant and benign thymomas(6%), sarcomas (6%) and Waldenstri)m's macroglobulinemia (6%) The most constant clinical feature of paraneoplastic pemphigus is the presence of intractable stomatitis. This stomatitis consists of erosions and ulcerations that affect all surfaces of the oropharynx and characteristically extend onto the vermilion lip

Cutaneous findings are polymorphic:  may present as erythematous macules,  flaccid blisters and erosions resembling pemphigus vulgaris,  tense blisters resembling bullous pemphigoid,  erythema multiforme-like lesions  lichenoid eruptions

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease; it predominantly affects the elderly Clinical Features Non-bullous phase: In the prodromal, non-bullous phase,signs and symptoms are frequently nonspecific, mild to severe intractable pruritus alone or in association with excoriated, eczematous, papular and/or urticarial lesions that may persist for several weeks or months. These nonspecific skin findings may remain as the only signs of the disease

Bullous phase:  vesicles and bullae on apparently normal or erythematous skin together with urticarial and, eczematous papules and plaques  The blisters are tense, up to 1-4 cm in diameter,  contain a clear fluid, and may persist for several days,  Occasionally becomes blood-tinged.  leaving eroded and crusted areas.  The lesions frequently have a symmetrical distribution pattern,  they predominate on the flexural aspects of the limbs and the lower trunk, and abdomen.

The mucosae of the eyes, nose,pharynx, esophagus and anogenital region are more rarely affected. In approximately 50% of patients, a peripheral blood eosinophilia. The association of internal malignancies with BP is probably related primarily to the older age of the patient In some patients, BP appears to be triggered by trauma, burns, radiotherapy or UV irradiation (including PUVA)

Immunofluorescence microscopy (indirect) salt-split. BP patients bind to the epidermal side (roof) B EBA react with the dermal side (floor) of the blister

MUCOUS MEMBRANE (CICATRICIAL) PEMPHIGOID: Mucous membrane pemphigoid is a chronic, autoimmune, subepithelial blistering disorder characterized by predominant involvement of the external mucosal surfaces and a tendency for scarring that favor the mucosal surfaces and, less frequently,the skin When scarring and fibrosis affect the conjunctivae, the disorder can be devastating and ultimately lead to blindness Circulating anti-basement membrane autoantibodies are detected in the serum of some patients (20-30% by standard indirect IF), usually at a low titer.

EPIDERMOLYSIS BULLOSA ACQUISITA Epidermolysis bullosa acquisita is a rare, acquired, subepidermal bullous disease associated with autoimmunity to type VII collagen,the major component of the anchoring fibrils of the dermalepidermal junction present either with a mechanobullous disorder,mimicking dystrophic epidermolysis bullosa, or with clinical features indistinguishable from bullous pemphigoid The disease is usually chronic and more refractory to treatment than is BP

Dermatitis Herpetiformis: Dermatitis herpetiformis (DH) is a cutaneous manifestation of gluten sensitivity Although over 90% of DH patients have evidence of a gluten- sensitive enteropathy, only about 20% have intestinal symptoms of celiac disease (CD). Both the skin disease and the intestinal disease respond to gluten restriction and recur with institution of a gluten containing diet.

Four findings support the diagnosis of DH: 1-pruritic papulovesicles or excoriated papules on extensor surfaces 2-neutrophilic infiltration of the dermal papillae with vesicle formation at the dermal-epidermal junction 3-granular deposition of IgA within the dermal papillae of clinically normal-appearing skin adjacent to a lesion 4-response to dapsone therapy of the skin disease, but not the intestinal disease,.  Although DH is usually a lifelong condition, the course may wax and wane.  A spontaneous remission may occur in up to 10% of patients,

Clinical Features: symmetric distribution Favors the elbows, extensor forearms,back, buttocks and knees The primary lesions are pleomorphic, with urticarial plaques, papules and vesicles Grouped or "herpetiform" papulovesicles with an erythematous base Intense pruritus leads to secondary excoriation and crusting. Less common presentations are isolated facial involvement

Lupus Erythematosus There are several variants of cutaneous lupus, defined in part by the location and depth of the inflammatory infiltrate Acute cutaneous lupus involves primarily the epidermis and upper dermis and is usually associated with systemic disease Subacute cutaneous lupus involves primarily the epidermis and upper dermis and is associated with anti-Ro/SSA autoantibodies and photosensitivity; the majority of patients do not have significant systemic disease

Discoid lesions of lupus: involve the epidermis, upper and lower dermis, and adnexal structures, and they can scar; the majority of patients do not have significant systemic disease Lupus erythematosus tumidus :involves the dermis but there is no prominent epidermal or adnexal involvement Lupus panniculitis : involves the subcutaneous tissue and may result in disfiguring depressed scars

skin lesions into :specific and not specific lupus bullous lesions may appear for several reasons. Result of the intensity of the basal cell damage in lesions of ACLE or SCLE or, possibly, DLE. Rarely, a dramatic, acute eruption similar to erythema multiforme major or toxic epidermal necrolysis(TEN) may occur in patients with preexisting ACLE or SCLE

blistering disease due to autoantibodies to a component of the basement membrane zone The term bullous eruption of SLE, or bullous SLE, has been used to describe a blistering eruption that consists of vesicles and bullae histopathology often resembles dermatitis herpetiform is, with a primarily neutrophilic infiltrate and microabscesses within the dermal papillae In some patients, the clinical and histologic features may resemble bullous pemphigoid or epidermolysis bullosa acquisita.