A 14-year multicentric follow-up study of atypical pemphigus variants in Italy: the VARIANT_P study

Background: The clinical, epidemiological and immunopathological profiles of atypical forms of pemphigus remain only partially known. Objectives: To define the clinical, epidemiological and immunological characteristics, therapies and outcomes in patients with atypical pemphigus variants. Methods: This was a 14-year multicentre retrospective observational study (VARIANT_P) on atypical variants of pemphigus across Italy. We collected demographic, immunopathological and clinical data, as well as information on comorbidities and prescribed treatments. Results: We enrolled 61 patients [female/male sex ratio 1.77; 13 paraneoplastic pemphigus (PNP), 26 IgA pemphigus (PIgA), 22 pemphigus herpetiformis (PH)]. The median ages at onset and diagnosis were 70.6 (range 43.1-86.8) and 71.1 (range 46.9-86.9) for PNP; 62.2 (range 3.8-81.0) and 63.6 (range 4.0-82.4) for PIgA; and 49.4 (range 5.4-84.4) and 52.3 (range 5.9-85.9) for PH, respectively. The median diagnostic delay was 3.0 (range 0.0-45.6) months for PNP, 9.5 (range 1.0-140.0) months for PIgA and 2.0 (range 0-30.4) months for PH. The mortality rate was 55% (6/11) for PNP, 4% (1/26) for PIgA and 6% (1/17) for PH. Cutaneous involvement was present in all patients with PIgA and PH, and in 83% (10/12) of the patients with PNP. In contrast, oral mucosal involvement was observed in all patients with PNP with data (n = 12), but only in 8% (2/26) of those with PIgA and 21% (4/19) of those with PH. Histology, direct immunofluorescence, indirect immunofluorescence and enzyme-linked immunosorbent assay data demonstrated variable concordance with previously known data. Comorbidities included mainly solid malignancies for people with PNP, whereas cardiovascular and metabolic diseases were the most prevalent for those with PIgA and PH. Treatment mostly relied on systemic steroids and rituximab. Conclusions: The VARIANT_P study contributes to data collection relating to atypical pemphigus variants in order to promote the development of specific therapeutical guidelines in the future.