Background

This is a rare autoimmune blistering disease. It is characterized by antibodies directed against a 200kd protein in the lower lamina lucida. Clinically, the lesions resemble the lesions of bullous pemphigoid, dermatitis herpetiformis, or linear IgA disease. The lesions heal without scarring and have a prompt response to treatment.

OUTLINE

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/ Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

DISEASE ASSOCIATIONS	CHARACTERIZATION
PSORIASIS
Coexistence of psoriasis and an unusual IgG-mediated subepidermal bullous dermatosis: identification of a novel 200-kDa lower lamina lucida target antigen. Chen KR, Shimizu S, Miyakawa S, Ishiko A, Shimizu H, Hashimoto T. Division of Dermatology, Kawasaki City Hospital, Japan.	Br J Dermatol 1996 Feb;134(2):340-6 Abstract quote Bullous pemphigoid (BP) is characterized by autoantibodies against 230- and 180-kDa hemidesmosomal antigens located in the most superficial layers of the basement membrane zone (BMZ). Histologically, there is a predominance of eosinophils in the infiltrate. In a psoriatic patient, we identified an unusual autoimmune subepidermal bullous eruption which clinically resembled BP, but which was characterized by IgG autoantibodies against a novel 200-kDa lower lamina lucida component. Histologically there was a predominance of neutrophils in the infiltrate. Direct immunofluorescence showed linear immunoglobulin (Ig)G and C3 deposition at the BMZ. The patient's IgG autoantibodies bound exclusively to the dermal side of salt-split normal human skin. Indirect immunogold electron microscopy showed a marked deposition of IgG at the lower lamina lucida and minimal deposition at the hemidesmosomes. Immunoblot analysis identified a unique 200-kDa autoantigen in dermal extracts and a faint band of the 230-kDa BP antigen in epidermal extracts. The patient responded dramatically well to cyclosporin A. A lthough the patient's serum also reacted slightly with the 230-kDa BP antigen, there were significant findings different from the usual immunopathological changes of BP. These included finding a novel 200-kDa lower lamina lucida target antigen, the binding of IgG autoantibodies exclusively to the dermal side of the split skin and a predominance of neutrophils in blister infiltrate. The IgG autoantibodies against the 200-kDa lamina lucida target antigen seemed to play a major role in the pathogenesis of this unique autoimmune subepidermal dermatosis.

 

PATHOGENESIS	CHARACTERIZATION
Subepidermal blistering disease with autoantibodies to both the p200 autoantigen and the alpha3 chain of laminin 5. Shimanovich I, Petersen EE, Weyers W, Sitaru C, Zillikens D. Department of Dermatology, University of Lubeck, Germany.	J Am Acad Dermatol. 2005 May;52(5 Suppl 1):S90-2. Abstract quote   Anti-p200 pemphigoid and anti-laminin 5 mucous membrane pemphigoid are two distinct autoimmune blistering skin diseases. Patients with anti-p200 pemphigoid demonstrate circulating autoantibodies to an unknown 200-kd acidic noncollagenous glycoprotein of the lower lamina lucida, whereas anti-laminin 5 mucous membrane pemphigoid is characterized by an autoimmune response against the major basement membrane adhesion molecule laminin 5. In this report, we describe a patient who developed a recurrent nonscarring blistering eruption, affecting both skin and mucous membranes. Immunoblotting of dermal extracts and extracellular matrix of cultured keratinocytes revealed circulating autoantibodies directed to the p200 antigen and the alpha3 chain of laminin 5, respectively. The unusual clinical and immunologic profile of this case suggests that molecular specificity of circulating autoantibodies affects the clinical presentation of autoimmune subepidermal blistering skin diseases.
Subepidermal blistering disease with autoantibodies against a novel dermal 200-kDa antigen. Kawahara Y, Zillikens D, Yancey KB, Marinkovich MP, Nie Z, Hashimoto T, Nishikawa T. Department of Dermatology, Keiyu Hospital, 3-7-3 Minatomirai, Nishi-ku, Yokohama, Japan.	J Dermatol Sci 2000 Jun;23(2):93-102 Abstract quote A number of autoimmune subepidermal blistering diseases are characterized by the distinct autoantigens of the cutaneous basement membrane zone. Recently, a few cases with autoantibodies against a novel 200-kDa dermal protein have been reported. We collected nine cases of subepidermal blistering disease with IgG antibodies against this 200-kDa antigen. In this report, we describe the clinical and immunological appearances in these cases. Five cases showed bullous pemphigoid-like features, one case resembled dermatitis herpetiformis, and another case showed mixed features of bullous pemphigoid and linear IgA bullous dermatosis. It was interesting to note that psoriasis coexisted in four cases. By indirect immunofluorescence on 1 M NaCl split skin, IgG antibodies from all sera reacted with the dermal side of the split. By immunoblot analysis, IgG antibodies recognized a 200-kDa protein of dermal extract. IgG affinity-purified antibodies on the 200-kDa immunoblot membrane stained the dermal side of 1 M NaCl split skin. Various examinations suggested that the 200-kDa antigen is not identical to any chains of laminins-1, -5 or -6. This autoimmune subepidermal blistering disease against the dermal 200-kDa protein may form a new distinct entity, which often associates with psoriasis.

 

CLINCAL AND GROSS VARIANTS	CHARACTERIZATION
A subepidermal blistering disease with histopathological features of dermatitis herpetiformis and immunofluorescence characteristics of bullous pemphigoid: a novel subepidermal blistering disease or a variant of bullous pemphigoid? Salmhofer W, Kawahara Y, Soyer HP, Kerl H, Nishikawa T, Hashimoto T. Department of Dermatology, University of Graz, Austria.	Br J Dermatol 1997 Oct;137(4):599-604 Abstract quote A 64-year-old man presented with a bullous eruption which clinically and histopathologically resembled dermatitis herpetiformis. However, direct immunofluorescence analysis showed IgG deposits at the basement membrane zone, indicating a relationship with bullous pemphigoid or epidermolysis bullosa acquisita. Indirect immunofluorescence studies on salt-split skin showed binding of IgG mainly on the dermal side of the blister. Immunoblot analysis revealed a novel 200 kDa dermal antigen that could be associated with a major pathogen in this blistering disease. The histopathological similarity to dermatitis herpetiformis and the immunofluorescence findings indicating bullous pemphigoid or epidermolysis bullosa acquisita seem typical of a distinct subepidermal blistering disease characterized by this 200 kDa antigen. However, the pathogenetic role of autoantibodies against this antigen should be further elucidated before confirming whether this case represents a novel subepidermal blistering disease or a special variant of bullous pemphigoid.
A subepidermal bullous eruption associated with IgG autoantibodies to a 200 kd dermal antigen: the first case report from the United States. Mascaro JM Jr, Zillikens D, Giudice GJ, Caux F, Fleming MG, Katz HM, Diaz LA. Department of Dermatology, Medical College of Wisconsin, Milwaukee 53226, USA.	J Am Acad Dermatol 2000 Feb;42(2 Pt 2):309-15 Abstract quote We describe an 81-year-old white man in whom a subepidermal bullous eruption developed that clinically resembled bullous pemphigoid. The eruption promptly responded to oral tetracycline and niacinamide and topical clobetasol. Histologic examination of perilesional skin revealed neutrophilic infiltration with formation of papillary microabscesses and subepidermal cleavage. Direct immunofluorescence showed linear deposition of IgG and C3 along the basement membrane zone. By indirect immunofluorescence, circulating IgG autoantibodies bound exclusively to the dermal side of salt-split normal human skin. Immunoblot analysis demonstrated that the patient's autoantibodies reacted with a 200 kd dermal protein that was different from type VII collagen, the epidermolysis bullosa acquisita autoantigen. This patient represents the first confirmed case from the United States with a recently reported novel autoimmune subepidermal bullous disease associated with IgG autoantibodies to a 200 kd dermal antigen.
Anti-p200 pemphigoid: Diagnosis and treatment of a case presenting as an inflammatory subepidermal blistering disease. Egan CA, Yee C, Zillikens D, Yancey KB. Dermatology Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, and Department of Dermatology, University of Wurzburg.	J Am Acad Dermatol 2002 May;46(5 Pt 1):786-9 Abstract quote Anti-p200 pemphigoid is a recently defined subepidermal immunobullous disease. It is characterized by the binding of circulating IgG autoantibodies to the dermal side of 1 M NaCl split skin and by reactivity of these autoantibodies to a unique 200-kd antigen on immunoblot of dermal extract. On immunoelectron microscopic examination, these autoantibodies deposit at the lamina lucida-lamina densa interface. We describe the clinical, histologic, and immunopathologic features in a patient with anti-p200 pemphigoid, as well as his favorable response to treatment with systemic glucocorticosteroids and dapsone.

 

SPECIAL STAINS/ IMMUNOPEROXIDASE	CHARACTERIZATION
Direct immunofluorescence (DIF)	Linear deposits of IgG and C3 along the basement membrane zone Immunoblot reactivity to p200, localizing the lower portion of the lamina lucida
Indirect immunofluorescence (IIF)	IgG binding to dermal side of NaCl split skin

J Invest Dermatol 1996;106:1333-1338
Br J Dermatol 1996;134:340-346
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Bullous Pemphigoid

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Last Updated May 25, 2005

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