A Case Report of Concurrent Pyostomatitis Vegetans-Like/Intercellular Immunoglobulin A Dermatosis and Uveitic Macular Edema Reacting Exclusively with Desmocollins: A Possible Common Pathogenesis

Dear Editor:

We describe a patient with concomitant intercellular immunoglobulin (Ig) A dermatosis (IAD) and uveitic macular edema (UME). Moreover, we review the literature of IAD with exclusively IgA anti-desmocollin (Dsc) antibodies cases to raise the question of the possible common role of anticadherin antibodies.

A male in his 50s had been seen by his dentist for vegetating gingivitis which had caused the loss of several teeth since November 2017. With the clinical suspicion of pyodermatitis-pyostomatitis vegetans (PPV), a gingival biopsy was performed. Because histopathology reinforced this diagnosis, inflammatory bowel disease was ruled out. In June 2018, he was diagnosed with bilateral UME treated with intravitreal bevacizumab/dexamethasone, oral steroids and mycophenolate mofetil, with transitory improvement. In September 2018, he presented at our department with gingival hyperplasia and small pustules on the gingivae and hard palate (Fig. 1A). A CT scan revealed severe bone loss. A new gingival biopsy showed marked acanthosis, pseudoepitheliomatous hyperplasia, spongiosis with neutrophils and intraepidermal neutrophilic microabscesses (Fig. 1B). Direct immunofluorescence and indirect immunofluorescence (IIF) examination on sections of only human skin, 1M NaCl split human skin and monkey esophagus for both IgG and IgA antibodies were all negative. Commercial ELISA for desmoglein 1 and 3 (MBL, Nagoya, Japan) were negative for both IgG and IgA antibodies. In contrast, ELISAs of eukaryotic recombinant proteins of human Dsc IgA antibodies were positive for Dsc1 (0.224, positive >0.123), weakly positive for Dsc2 (0.058, positive >0.048), while IgG antibodies were negative. We started dapsone with poor results, so initiated intravenous Ig with good response. Repeated IIF on monkey esophagus showed positive intercellular IgA antibodies.

Fig. 1. Clinicopathological features. (A) Vegetating gingivitis with small pustules on the upper gingivae. (B) Acanthosis, pseudoepitheliomatous hyperplasia, spongiosis with prominent neutrophils and intraepidermal neutrophilic microabscesses (H&E, ×100).

IAD, also known as IgA pemphigus, is a rare immunobullous disease. There are two clinicopathological variants, an intraepidermal neutrophilic dermatosis-type and a subcorneal pustular dermatosis-type; its target antigen is Dsc-1, a cadherin family adhesion molecule¹. There are 9 reported IAD cases with exclusively IgA anti-Dsc antibodies (Table 1). Almost all of them presented with cutaneous pustules and only one also had mucosal involvement². Two cases were associated with lymphoid neoplasms^2,3 and no patient had concomitant autoimmune diseases.

Table 1. Clinical, histological and molecular characteristics of patients reported with intercellular IgA dermatosis with exclusively IgA anti-Dsc antibodies.

Ig: immunoglobulin, Dsc: desmocollin, PMID: PubMed identifier, DIF: direct immunofluorescence, M: male, F: female, ELISA: enzyme-linked immunosorbent assays, IIF: indirect immunofluorescence, IB: Immunoblotting. ^*Current case patient. ^†cDNA transfection tests on unfixed COS-7.

Although PPV shares clinicopathological findings with IAD, IgA anti-Dsc autoantibodies have not been previously reported⁴. Moreover, intercellular IgA antibodies were detected by IIF, so we finally diagnosed this case as PPV-like IAD with IgA anti-Dsc antibodies. The pathogenic role of IgA antibodies is unknown. As gingival mucosa have low expression of Dsc1 and high of Dsc2, we think that anti-Dsc2 must account for the pathogenic antibodies in our patient.

UME occurs due to an imbalance of extracellular fluid caused by blood-retinal barrier (BRB) breaches. It could complicate an uveitis secondary to infections, neoplasms or autoimmune disorders. BRB is formed by tight junctions between retinal pigment epithelial and endothelial cells, which contain occludins and cadherin-5. Single nucleotide polymorphism of cadherin-5 in combination with triggering events has been associated with central serous chorioretinopathy, a disorder which, like UME, is characterized by serous central retinal detachment⁵.

This, then, is an IAD case with exclusively IgA anti-Dsc antibodies, only mucous involvement and simultaneous UME. It may be that this association is accidental, but although we do not have evidence of anti-cadherin-5 antibodies in our patient, we hypothesize a possible common pathogenesis through anti-Dsc/cadherin antibodies. Further studies on the possible presence of anti-cadherin-5 antibodies may serve to clarify this issue.