A Systematic Review of Mendelian Pyoderma Gangrenosum: Clinical and Genetic Characteristics in 120 Published Patients

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterised by sterile, recurrent ulcers with a predominantly multifactorial aetiology. However, in a small subset of patients carrying highly penetrant Mendelian mutations in single genes, PG presents as a part of a genetic syndrome. This study aimed to systematically review Mendelian susceptibilities to PG and summarise the clinical and genetic characteristics of patients. Search criteria encompassed case reports, case series and other original articles focusing on causal sequence variants associated with PG pathogenicity. We screened 1577 articles and selected 79 studies, encompassing 120 PG patients and 19 distinct genes, for quantitative analysis. The most prevalent mode of inheritance was autosomal dominant, and the mean age of onset was 23.39 ± 19.76 years. Seventeen of 19 genes are categorised under the Inborn Errors of Immunity (IEI) compiled by the International Union of Immunological Societies (IUIS). According to this, the most reported genes (37%) belong to 'Autoinflammatory Disorders.' All 19 genes were linked to cutaneous ulcers, with PSTPIP1 and MEFV being the only genes associated with all three lesion types (cutaneous, anogenital, mucosal). PSTPIP1 was the most frequently reported PG-related gene, followed by MEFV, ITGB2, NOD2, NFKB1, RAG1, JAK2, and NCSTN. Pseudomonas aeruginosa was the most frequently identified infectious agent in PG skin lesions. This study identifies at least 19 genes associated with PG susceptibility, emphasising the crucial role of genetic factors in disease pathogenesis. Gaining insight into the genetic basis and molecular mechanisms involved may facilitate the development of more targeted therapeutic strategies for PG.