Bullous pemphigoid presenting as generalized pruritus: observations in six patients.

BACKGROUND: Bullous pemphigoid is a chronic immunobullous disease of the elderly. Classically, tense, pruritic blisters develop on normal or erythematous skin. These may be preceded by a prodromal pruritic, urticarial, or eczematous eruption. Occasionally, patients may develop generalized pruritus without blisters as a prodrome of bullous pemphigoid. METHODS: The records of the patients were reviewed. Biopsy specimens were studied by light and immunofluorescence microscopy. Serum specimens were studied by indirect immunofluorescence techniques including the salt-split skin technique. RESULTS: We studied six elderly patients presenting with generalized pruritus as the dominant or single presenting feature of early bullous pemphigoid. Two of the six had rare vesicles at presentation. All had excoriations and one each presented with minimal urticarial or eczematous papules. Routine skin biopsies were largely nonspecific. All patients had confirmation of their diagnosis by either indirect or direct immunofluorescence testing or both. All six patients had their disease completely controlled by their treatment. CONCLUSIONS: The clinical presentation of the six patients in our series and the eight previously reported patients should be regarded as an unusual prodromal manifestation of bullous pemphigoid characterized by generalized pruritus without primary skin lesions. This presentation could be described as "pruritic pemphigoid," because it joins the remarkable clinical finding of generalized pruritus with the underlying diagnosis of bullous pemphigoid. Elderly patients with severe or persistent unexplained generalized pruritus merit immunofluorescence testing to exclude bullous pemphigoid as the cause of the generalized pruritus. Establishing an early diagnosis permits the prompt institution of effective therapy with dapsone or systemic corticosteroids with an excellent prognosis for complete control of the disease.

Secondary amyloidosis complicating psoriasis.

BACKGROUND: Amyloidosis is a heterogeneous group of disorders characterized by extracellular deposition of fibrillar protein. Secondary amyloidosis occurs in patients with chronic infectious or inflammatory processes. Only 18 cases of secondary amyloidosis complicating psoriasis have been reported. OBJECTIVE: We characterized secondary amyloidosis complicating psoriasis. METHODS: We reviewed all cases of coexisting psoriasis and amyloidosis seen at the Mayo Clinic from 1950 to 1992. The clinical characteristics were summarized, and the literature was reviewed. RESULTS: There were 28 cases of coexistent disease, and in five of these psoriasis was the only inflammatory condition preceding the development of secondary amyloidosis. Histopathologic confirmation with Congo red staining was available in four cases, and immunohistochemical confirmation of the characteristic amyloid A subtype was performed in two. CONCLUSION: Follow-up of four patients supports the view that amyloidosis associated with psoriasis is an aggressive disease that may be fatal.

Paraneoplastic pemphigus: a case with high titer of circulating anti-basement membrane zone autoantibodies.

Multiple flaccid bullae, erosions, and tense bullae developed in a 67-year-old man with chronic lymphocytic leukemia. A biopsy specimen revealed features of typical pemphigus vulgaris (suprabasilar clefting with acantholysis), paraneoplastic pemphigus (necrotic keratinocytes and hydropic degeneration in addition to acantholysis), and bullous pemphigoid (subepidermal separation and epidermal regeneration). Direct and indirect immunofluorescence studies revealed deposits of immunoglobulins and C3 within the intercellular substance and basement membrane zone in some specimens. Immunoprecipitation of serum revealed four polypeptides with molecular weights of 250, 230, 210, and 190 kd.

Paraneoplastic pemphigus: a subset of patients with pemphigus and neoplasia.

We reviewed the clinical, histologic, and immunofluorescence features of 20 patients with pemphigus and neoplasia and compared them with a control group of 17 patients with pemphigus without neoplasia. Patients with neoplasia were divided according to clinical, histologic, and immunofluorescence findings into those with paraneoplastic pemphigus syndrome (12 patients) and those with classic pemphigus vulgaris or pemphigus foliaceus with neoplasia (8 patients). The histologic findings in patients with paraneoplastic pemphigus included acantholysis, interface dermatitis, spongiosis, and satellite keratinocyte necrosis. Histologic findings in the 8 patients with classic pemphigus and neoplasia included acantholysis and spongiosis. Direct immunofluorescence in both paraneoplastic pemphigus and pemphigus with neoplasia showed IgG staining of cell-surface proteins (intercellular substance) and deposition of immunoglobulin at the basement membrane zone. Indirect immunofluorescence with rat bladder substrate was used to differentiate paraneoplastic pemphigus from classic pemphigus. Circulating IgG anti-cell-surface protein antibodies were detected in 4 patients with paraneoplastic pemphigus syndrome; they were absent in 2 patients with pemphigus and neoplasia. Immunoprecipitation of sera from the 4 patients with epithelial staining showed the complex of bands identified in studies of paraneoplastic pemphigus syndrome. We conclude that paraneoplastic pemphigus syndrome has distinct clinical, histologic, and immunologic features that differentiate it from classic pemphigus with underlying neoplasia.

Cutaneous manifestations of the eosinophilia-myalgia syndrome.

We report the cutaneous manifestations of the eosinophilia-myalgia syndrome in 10 patients, with specific reference to their clinical course, histopathological features, and immunogenetic studies. Cutaneous manifestations could be classified into three groups: morphoea-like sclerosis, urticarial and papular lesions, and generalized sclerosis. Despite this polymorphic clinical presentation, the histopathological abnormalities in all cases were strikingly similar, and consisted of superficial and deep perivascular lymphocytic dermal infiltrates, mucin deposition, and fascial inflammation (often in the absence of sclerosis). Immunoperoxidase studies revealed increased numbers of factor XIIIa- and MAC 387-positive cells in the inflammatory infiltrate. Immunogenetic studies demonstrated that 77% (7/9) of patients possessed the HLA-DR3 or HLA-DR4 phenotypes. Mean follow-up of 24 months after discontinuation of L-tryptophan revealed the presence of persistent severe disabling disease in 30% of patients.

Human autoantibodies against desmoplakins in paraneoplastic pemphigus.

Recently, a previously unrecognized autoantibody mediated blistering disease, paraneoplastic pemphigus has been described. Paraneoplastic pemphigus is associated with lymphoid malignancies, thymomas, and poorly differentiated sarcomas. Serum of affected patients contain pathogenic autoantibodies that immunoprecipitate from normal keratinocytes a characteristic complex of four polypeptides with M(r) of 250, 230, 210, and 190 kD. As our preliminary studies indicated that the 250-kD and the 210-kD antigens comigrated with desmoplakins I and II, we investigated the possibility that autoantibodies against the desmoplakins were a component of this autoimmune syndrome. 11 sera from affected patients were tested by indirect immunofluorescence against desmosome containing tissues, immunoprecipitation of metabolically labeled keratinocytes, and Western immunoblotting of desmoplakins I and II that had been purified to homogeneity from pig tongue epithelium. By indirect immunofluorescence, 9 of 11 sera showed strong binding to epithelial and nonepithelial desmosomes, and 2 were weakly reactive. All 11 immunoprecipitated 250- and 210-kD bands of variable intensity that comigrated with bands identified by a murine monoclonal antidesmoplakin antibody, and immunoblotting confirmed binding of the serum autoantibodies to purified desmoplakins. This demonstrates that paraneoplastic pemphigus is the first human autoimmune syndrome in which autoantibodies against the desmoplakins are a prominent component of the humoral autoimmune response.