Erythema multiforme associated with anti‐plakin antibodies: a multicentric retrospective case series

Abstract

Background Erythema multiforme (EM) is a muco‐cutaneous inflammatory disease mainly triggered by herpes simplex virus (HSV) recurrences. Association of EM and circulating auto‐antibodies against plakins (anti‐PLK‐Abs [EM‐PLK+]) has been reported. However, little is known about this subset of EM. Objectives We aimed to describe the clinical and immunological features and response to treatment of EM‐PLK+. Methods We conducted a retrospective multicentric study of EM‐PLK+ selected from the database of the immunological laboratory of Bichat hospital, Paris, France, from January 2009 to December 2020. Anti‐PLK‐Abs were detected in ≥1 immunological tests: immunofluorescence assay, immunoblotting and/or ELISA. Patients with alternative diagnoses were excluded. Results We included 29 patients (16 women, median age 25 [range 2–58] years). EM‐PLK+ were mostly major (EM with ≥2 mucosal involvements; n = 24, 83%) and relapsing (≥2 flares; n = 23, 79%). Cutaneous lesions were target (n = 13, 54%) and target‐like lesions (n = 9, 38%) with usual topography (acral, n = 19, 79%; limbs, n = 21, 88%). Mucosal lesions affected the mouth (n = 27, 96%) and genitalia (n = 19, 68%), with a median of 2 [range 0–5] mucous membranes. EM‐PLK+ were suspected as certain or possible postherpetic (EM‐HSV) in 19 cases (65.5%); no triggering factors were detected in 9 (31%) patients. Desmoplakin‐I/II Abs were the most frequent anti‐PLK‐Abs (n = 20, 69%); envoplakin and periplakin Abs were detected in 11 and 9 cases. Relapsing EM‐PLK+ (n = 23) were still active (≥1 flare within 6 months) in 13 (57%) patients despite immunosuppressive therapy (n = 8, 62%). Antiviral drugs were ineffective in preventing relapse in 15/16 (94%) EM‐HSV. Conclusion The rationale for anti‐PLK‐Ab detection in EM is not elucidated. More systematic research of anti‐PLK‐Abs is warranted to better understand whether this association reflects humoral immune activity in a subset of EM or is fortuitous, related to an epitope spreading process. However, EM‐PLK+ seems to be associated with major and relapsing subtypes, and difficult‐to‐treat cases.

Human Orf with Immune-Mediated Reactions: A Systematic Review

“…No HSV was detected in bullous pemphigoid [ 43 ]. Antiviral therapy has a controversial efficacy in HSV-induced erythema multiforme [ 44 , 45 ].…”

T cell autoimmunity and immune regulation to desmoglein 3, a pemphigus autoantigen

“…Presence of autoantibodies against envoplakin and periplakin is sensitive to the diagnosis of PNP 58 . These antibodies are also detectable in patients with erythema multiforme 64 . The pathogenicity of antibodies against plakin family members that are localized intracellularly is unclear.…”

“… 58 These antibodies are also detectable in patients with erythema multiforme. 64 The pathogenicity of antibodies against plakin family members that are localized intracellularly is unclear. One study reported that purified anti‐desmoplakin antibody from a patient with PNP induced dissociation of keratinocytes in vitro and caused blisters in vivo when transferred to neonatal mice.…”