Laboratory Diagnosis and Clinical Profile of Anti-p200 Pemphigoid

Abstract

IMPORTANCE Anti-p200 pemphigoid is a rare subepidermal autoimmune blistering disease characterized by autoantibodies against a 200-kDa protein in the basement membrane zone. Anti-p200 pemphigoid is probably often misdiagnosed because of low availability of diagnostic assays and expertise and classified as bullous pemphigoid or epidermolysis bullosa acquisita. OBJECTIVE To clinically characterize patients with anti-p200 pemphigoid, identified by using indirect immunofluorescence microscopy on skin substrates deficient in type VII collagen and laminin-332 (knockout analysis), to validate this technique by immunoblot with dermal extract, and to incorporate direct immunofluorescence serration pattern analysis in the diagnostic algorithm. DESIGN, SETTING, AND PARTICIPANTS This was a retrospective study performed from January 2014 to June 2015 with biobank patient materials and clinical data for the period 1998 to 2015 from the single national referral center on autoimmune bullous diseases. Patients were selected based on a dermal side binding on 1-mol/L salt (sodium chloride)-split human skin substrate by indirect immunofluorescence microscopy, not diagnosed epidermolysis bullosa acquisita or anti-laminin-332 mucous membrane pemphigoid. MAIN OUTCOMES AND MEASURES Indirect immunofluorescence microscopy knockout analysis was performed and diagnosis of anti-p200 confirmed by immunoblot with dermal extract. Clinical, histological, and immunological findings were registered. Autoantibodies against laminin γ1 were determined by immunoblot. RESULTS Twelve patients with anti-p200 pemphigoid (7 male and 5 female; mean age, 66.6 years) were identified using the indirect immunofluorescence microscopy knockout analysis. Direct immunofluorescence microscopy showed a linear n-serrated IgG deposition pattern along the basement membrane zone in 9 of 11 patients. The diagnosis was confirmed by immunoblot showing autoantibodies against 200-kDa protein in dermal extract in 12 of 12 patients. Autoantibodies against recombinant laminin γ1 were detected by immunoblot in 8 of 12 patients. Remarkable similarities were seen in clinical features with predominantly tense blisters on hands and feet, resembling dyshidrosiform pemphigoid. Mucosal involvement was seen in 6 (50%) of the patients. CONCLUSIONS AND RELEVANCE Predominance of blisters on hands and feet may be a clinical clue to the diagnosis of anti-p200 pemphigoid. Direct immunofluorescence microscopy serration pattern analysis and indirect immunofluorescence microscopy knockout analysis are valuable additional techniques to facilitate the diagnosis of anti-p200 pemphigoid.

Treatment and clinical outcomes in anti‐p200 pemphigoid: a systematic review

“…The antineutrophil characteristics of dapsone are mediated by the inhibition of calcium‐dependent functions of neutrophils, such as the release of tissue‐damaging oxidants and proteases, as well as the disturbance of neutrophil adherence and inhibition of chemotaxis . Histologically, anti‐p200 pemphigoid is typified by predominantly neutrophilic dermal infiltrates and papillary microabscesses, in contrast to the typically eosinophilic dermal infiltrates in BP . The neutrophil‐rich nature of the dermal infiltrates may account for the high efficacy of dapsone in patients with anti‐p200 pemphigoid.…”

“…The clinical course of anti‐p200 pemphigoid was considered to be of a benign nature as compared with other subepidermal AIBDs . Yet, the rarity of the disease and the lack of large‐scale longitudinal studies restrict a precise assessment of the true clinical outcomes of these patients.…”

Histomorphologic and Direct Immunofluorescence Findings of Autoimmune Bullous Disease

“…An upper dermal infiltrate of eosinophils and neutrophils was seen in nearly all cases. Direct immunofluorescence results displayed IgG and C3 positivity in all cases [9].…”

Pemphigoid variants affecting the skin

“…The diagnosis is made by IIF on SSS (dermal staining) and immunoblotting with a dermal skin extract. Clinical clues for anti‐p200 pemphigoid are the acral distribution of blisters and frequent mucosal involvement (30–50%) …”