IgG/IgA pemphigus in a patient with a history of pemphigus vulgaris: An example of epitope spreading?

Abstract

We report a case of IgG/IgA pemphigus presenting as pemphigus foliaceus following diagnosis and treatment of classic IgG‐mediated pemphigus vulgaris. The dual presentation of IgG and IgA positivity on direct immunofluorescence (DIF) constitutes a rare form of pemphigus with a wide variety of clinicopathologic manifestations. The progression of pemphigus vulgaris is commonly because of epitope spreading. However, the patient's disease was partially refractory to rituximab and showed a change in the DIF with dual staining for IgG and IgA. This indicates that class‐switching may have occurred with epitope spreading or that there was autoreactive IgA at the onset of disease below the threshold of detection by DIF. Our case indicates that in progressive autoimmune disease refractory to treatment, re‐evaluation of the patient for antibody isotypes absent on initial diagnosis may offer key information in better identifying the cause of progression as well as in directing the necessary treatment.

Persistent Scattered Pustules: Vesiculopustular IgA Pemphigus Arising in a Patient With Ulcerative Colitis

“…4 A case of IgG pemphigus evolving to express both IgG and IgA suggests that epitope spreading may occur and should be considered in the differential diagnosis. 5 Systemic steroids and dapsone are generally considered first-line therapy, but mycophenolate mofetil and other systemic immunosuppressive agents may be helpful in refractory cases. Diagnosis can be difficult because widespread pustular lesions often raise concerns for folliculitis, scabies, or other types of dermatoses associated with pustules.…”

“…4 A case of IgG pemphigus evolving to express both IgG and IgA suggests that epitope spreading may occur and should be considered in the differential diagnosis. 5…”

IgG/IgA pemphigus with differing regional presentations

“… 4 Whether it represents an intermediate form of pemphigus, a distinctive pemphigus variant arising from inflammation-associated epitope spreading, or a novel entity secondary to antibody class-switching within an altered immunological milieu remains uncertain. 3 , 5 , 6 , 7 Intertriginous distribution, pustular lesions, acantholysis, and intercellular C3 deposition in the epidermis were reported as features common to IgG/IgA pemphigus. 5 Circulating autoantibodies against the desmoglein and desmocollin isoforms could be demonstrated by ELISA.…”

Pemphigus—The Crux of Clinics, Research, and Treatment during the COVID-19 Pandemic

“…One explanation for this heterogeneity, which is shown to be a characteristic of IgG/IgA pemphigus, is the epitope spreading phenomenon in which an inflammatory event releases new target antigens, exposes them to the immune system, and then induces subsequent autoimmunity to new related antigens [ 48 ]. However, it is thought that a class switching of antibodies does not occur with epitope spreading as the limiting of the occurrence of epitope spreading to only class-switched cells is a mechanism by which the body limits the damage experienced as a result of the autoimmune disease [ 49 ]. Another explanation of the IgG/IgA heterogeneity is the existence of IgA antibodies at the onset of IgG pemphigus, however, at below the threshold for detection by DIF.…”