Garbanzos, Clint Christian T.

ABSTRACTBackgroundIntercellular IgG4 deposition is variably present on DIF in patients with pemphigus. Whether this feature has clinical, serologic, or histopathologic correlates was unknown.MethodsWe identified 34 patients with pemphigus who had 55 DIF specimens reported to show intercellular IgG, IgG4, and/or C3 deposition (8/22/2017–11/30/2023). Patients and biopsies were stratified by intercellular IgG4 status. Clinical and serologic data were extracted from electronic records, and corresponding biopsy slides were reviewed for histopathologic findings.ResultsAmong the 34 patients with pemphigus, patients with positive IgG4 were significantly more likely to have detectable serum anti‐desmoglein 1/3 antibodies by ELISA (p = 0.014 and p = 0.030, respectively). Paraneoplastic pemphigus (PNP) was more frequent in the IgG4‐negative group (p = 0.037), particularly among patients with ocular involvement. Of 55 DIF biopsy specimens meeting inclusion criteria, 52 (94.5%) had intercellular IgG deposition and 42 (76.4%) had intercellular IgG4 on DIF. Compared to IgG4‐negative specimens, IgG4‐positive specimens were significantly more likely to represent a vesiculobullous lesion (p = 0.024), to be derived from the trunk (p = 0.047), to show histologic acantholysis (p = 0.019) and to lack lichenoid inflammation (p = 0.0004).ConclusionFor pemphigus, DIF IgG4 status correlated with ocular involvement, the clinical morphology selected for biopsy, the likelihood of detecting circulating desmoglein antibodies, the presence of specific histopathologic features such as acantholysis and lichenoid inflammation, and the likelihood of having a final diagnosis of PNP. Further studies are needed to determine whether the presence of tissue‐bound intercellular IgG4 antibodies correlates with particular disease variants or lesion‐specific characteristics.

ABSTRACTBackground/ObjectivesImmune‐mediated skin disorders, such as immunobullous dermatoses and leukocytoclastic vasculitis, rarely affect children. While direct immunofluorescence (DIF) biopsy is a standard diagnostic tool, limited data exist on pediatric DIF patterns, rates of positivity, pretest diagnostic concordance, and the relevance of biopsy site. This study sought to address these gaps.MethodsDIF data from all skin and mucosal specimens interpreted at Mayo Clinic's reference immunodermatology laboratory for patients aged 0–18 years (August 22, 2017 to November 30, 2023) were reviewed. DIF results were classified as positive if a characteristic pattern was seen and negative if the findings were negative or nondiagnostic.ResultsOf 986 pediatric DIF studies, 153 (15.5%) were positive and comparable to adult positivity rates (20.9%) during the same period. The most frequent DIF patterns were IgA‐predominant vasculitis (N = 85/153; 55.5%) and lichenoid tissue reaction (N = 21/153;13.7%). Concordance between pretest diagnosis and positive DIF results was highest for linear IgA bullous dermatosis (N = 7/7; 100%) and dermatitis herpetiformis (N = 6/6; 100%). Excluding these entities, DIF changed the pretest diagnosis in 16.7% (N = 19/114) of cases. While lower extremity biopsies were initially more likely to yield positive DIF results, this association disappeared when IgA vasculitis cases were excluded.ConclusionThe most frequent DIF pattern in children was that of IgA‐predominant vasculitis. Pediatric DIF positivity rates closely mirrored those of adults, supporting similar biopsy thresholds. DIF results differed from the pretest impression in a substantial percentage, supporting the value of DIF in select situations in the pediatric population. After controlling for IgA vasculitis, biopsy site was not associated with DIF positivity.