Case of shift from linear immunoglobulin A bullous dermatosis to pemphigus herpetiformis for a short period of time

Abstract

Pemphigus herpetiformis (PH) is a rare variant of pemphigus characterized by erythemas and vesicles, tending to present with annular-shaped lesions. Immunologically, immunoglobulin (Ig)G deposition at the keratinocyte cell surfaces is observed. Linear IgA bullous dermatosis (LABD) is a rare subepidermal blistering disease with linear IgA deposits at the epidermal basement membrane zone (BMZ). The annular-shaped skin lesions in PH mimic clinical manifestation of other autoimmune bullous diseases, including LABD, although PH and LABD have different immunological and histopathological features. Herein, we report the first case of a shift from LABD to PH. A 70-year-old Japanese man presented annular erythemas surrounded by vesicles on the trunk and extremities. Histopathological examination revealed subepidermal bullae and eosinophilic spongiosis. Direct immunofluorescence demonstrated linear IgA deposits at the epidermal BMZ. Immunoblot analyses of normal human epidermal and dermal extracts, supernatant of HaCaT cells, recombinant proteins of BP180 NC16a and C-terminal domains, and purified laminin-332 showed no reactivity for either IgG or IgA. IgG chemiluminescent enzyme immunoassays for desmogleins 1 and 3, and BP180 were all negative. These findings led to the diagnosis of sole LABD. Although oral prednisolone temporarily improved the skin lesions, annular erythema without vesicles remained. A new skin biopsy revealed subcorneal pustules with eosinophils, but no subepidermal bullae. Direct immunofluorescence revealed IgG and C3 deposition at the keratinocyte cell surfaces. IgG enzyme-linked immunosorbent assay for mammalian desmocollins 1-3 revealed desmocollin 1 reactivity. Based on these findings, we made a diagnosis of sole PH.

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

“…Dsg1 was usually the target (32%), less commonly Dsg3 (7%) and Dsg1 and 3 (4%). Anti‐Dscs were also detected in a few cases, showing a variable combination of anti‐Dsg1 and 3 with anti‐Dsc 1, 2, and 3 (Table ) …”

“…The initial search yielded 371 publications: 284 from the PubMed database and 87 from the Ovid Medline database. We identified 96 publications (88 from PubMed and 63 from Ovid Medline [55 duplicates between the two databases]) reporting 158 individual cases that fulfilled the inclusion criteria. We also report an additional three unpublished cases diagnosed at our institution.…”

“…Both intercellular IgG and IgA deposits with/without C3 were mentioned for seven patients with pemphigus herptiformis; however, other cases of pemphigus have been described as IgG/ Table 3). [20][21][22][23][24][25][26][27][28][29][30][31][32] Association with other diseases As shown in Table 1, PH is seldom associated with other diseases, but its most frequent reported association was with other immunobullous disorders, especially other types of pemphigus (8%). Initially, PH was thought to be an unusual clinical and pathologic presentation of classical pemphigus (pemphigus vulgaris or pemphigus foliaceus) that could precede or occur during the course of these diseases.…”

“…The pathophysiologic characteristics of PH are unclear. Some patients show immunoreactivity not only to desmogleins (Dsgs), as in classic forms of pemphigus, but also to desmocollins (Dscs) . Many mechanisms by which autoantibodies produce characteristic skin lesions of PH have been proposed, including autoantibody‐augmented signaling pathways that lead to increases in proinflammatory cytokines and chemokines and to subsequent epitope spreading …”

“…Some patients show immunoreactivity not only to desmogleins (Dsgs), as in classic forms of pemphigus, but also to desmocollins (Dscs). [20][21][22][23][24][25][26][27][28][29][30][31][32] Many mechanisms by which autoantibodies produce characteristic skin lesions of PH have been proposed, including autoantibody-augmented signaling pathways that lead to increases in proinflammatory cytokines and chemokines and to subsequent epitope spreading. 14 Pemphigus herpetiformis generally has a benign course, and most cases respond well to treatment with systemic corticosteroids or dapsone (or other sulfones), although other immunosuppressants may sometimes be required.…”