Clinical, pathologic, and immunologic features of pemphigus herpetiformis: a literature review and proposed diagnostic criteria

Abstract

Pemphigus herpetiformis (PH), a rare type of pemphigus, is characterized by immunologic findings consistent with pemphigus but with a unique clinical and pathologic presentation. PH was first described as resembling dermatitis herpetiformis clinically, but because of its variable presentation, it can also resemble linear immunoglobulin A bullous dermatosis and bullous pemphigoid. We reviewed reported cases to analyze the most frequent clinical, pathologic, and immunologic characteristics and to propose corresponding diagnostic criteria. Through a comprehensive review of Medline and PubMed databases, 96 publications and 158 cases were identified. After reviewing the reported characteristics of PH, we suggest the following diagnostic criteria: Clinical: 1) pruritic herpetiform intact blisters with/without erosions; and/or 2) pruritic annular or urticarial erythematous plaques with/without erosions; Pathologic: 1) intraepidermal eosinophils or neutrophils, or both; and/or 2) intraepidermal split with/without acantholysis; Immunologic: 1) direct immunofluorescence showing immunoglobulin G with/without C3 intercellular deposits; and/or 2) indirect immunofluorescence showing immunoglobulin G to epithelial cell surface; and/or 3) detection of serum autoantibodies against desmogleins (1,3) or desmocollins (1,2,3), or both. Diagnosis requires one clinical, one pathologic, and one immunologic feature. We also report three new cases diagnosed at our institution to demonstrate the applicability of the suggested criteria.

Increased expression of in situ IL‐31RA and circulating CXCL8 and CCL2 in pemphigus herpetiformis suggests participation of the IL‐31 family in the pathogenesis of the disease

“…[1][2][3][4][5][6][7] This disorder is usually associated with marked pruritus and blood eosinophilia, [8][9][10][11] and eosinophilic spongiosis (ES), with or without mild acantholysis, which is invariably present in the classic subtypes of pemphigus. [12][13][14] There is no clear explanation for the mechanisms by which autoantibodies produce the distinct skin lesions of PH, or the pruritus. Although some hypotheses have been postulated, some features of PH are still inconclusive.…”

The clinical, immunological and pathological features for relapse of pemphigus herpetiformis: a univariate analysis of 26 cases

“…Direct immunofluorescence (DIF) and indirect immunofluorescence (IIF; re‐examined using archived serum samples) demonstrated deposition of IgGs (IgG1 and IgG4) or/and C3 on keratinocyte cell surfaces. Diagnosis of PH was confirmed in 26 of the 43 patients, as proposed previously …”

A herpetiform eruption with unexpected immunofluorescence findings

“…1 Since then, a total of 161 cases have been reported in the literature. 2 PH is a challenging diagnosis, owing to the clinical appearance of dermatitis herpetiformis and immunological characteristics of pemphigus. 3 The presentation of grouped pruritic papules, vesicles or bullae in a herpetiform distribution makes PH a diagnosis rarely made on initial clinical evaluation alone.…”

“…There have been recent proposals for diagnostic criteria for PH factoring in clinical, histopathological and immunological characteristics. 2,4 The histopathological presentation of PH is diverse and characterized by spongiosis and intraepidermal pustule formation. The inflammatory cell type varies between predominantly neutrophilic (20%), eosinophilic (20%) and mixed neutrophilic/eosinophilic (60%).…”

“…Disruption of keratinocyte intercellular adhesion has been suggested because of autoreactivity to desmogleins/desmocollins on indirect immunofluorescence. 2 Mechanistic theories involving autoantibody-mediated signalling pathways have also been implicated. 3 PH usually has an indolent course and good prognosis.…”