The genetics of pyoderma gangrenosum and implications for treatment: a systematic review

• Published in: British journal of dermatology (1951) Vol. 172; no. 6; pp. 1487 - 1497
• Main Authors: DeFilippis, E.M., Feldman, S.R., Huang, W.W.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.06.2015; Oxford University Press
• Subjects: Acne; Acne Vulgaris - complications; Acne Vulgaris - genetics; Arthritis; Arthritis - complications; Arthritis - genetics; Child; Child, Preschool; Drug development; Forecasting; Hematologic Diseases - complications; Hematologic Diseases - genetics; Humans; Inflammatory bowel diseases; Intestine; Irritable Bowel Syndrome - complications; Irritable Bowel Syndrome - genetics; Janus kinase 2; Janus Kinase 2 - genetics; Leukocytes (neutrophilic); Methylenetetrahydrofolate reductase; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; Mutation; Mutation - genetics; Myelodysplastic syndrome; Patients; Polyarthritis; Pyoderma; Pyoderma gangrenosum; Pyoderma Gangrenosum - complications; Pyoderma Gangrenosum - genetics; Skin; Skin diseases; Thalidomide; Vitamins
• ISSN: 0007-0963; 1365-2133
• DOI: 10.1111/bjd.13493

Summary Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by painful skin ulcerations for which treatment can be challenging. The genetic basis of PG may provide a better understanding of the disease and new targets for treatment. We systematically reviewed the published literature regarding the syndromes and genetic mutations associated with PG. A literature search was performed through the clinical queries PubMed (National Library of Medicine) database and the Cochrane database. The studies were assessed and then categorized as relating to syndromes or specific gene mutations. Two hundred and eight articles were identified, describing 823 cases of PG. A total of 537 (65·2%) cases were associated with inflammatory bowel disease, 133 (16·1%) with polyarthritis and 103 (12·5%) with haematological disorders. Thirty‐one cases of pyogenic arthritis, pyoderma gangrenosum and acne, and its variants, were identified. Two patients had mutations in MTHFR and two had mutations in JAK2. Fourteen (1·7%) cases were familial. PG responded to different treatments depending on the setting. For example, treatment with B vitamins improved PG in cases of mutations in MTHFR, whereas patients with myelodysplastic syndrome improved with thalidomide treatment. PG can occur in isolation, associated with systemic disease or as part of various syndromes. Different genetic causes may be best treated with particular treatments. Understanding its genetic basis can help elucidate new potential targets for drug development. What's already known about this topic? Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by painful skin ulcerations for which treatment can be challenging. What does this study add? This study reviews over 823 cases of PG and its associated gene mutations and syndromes. The various treatments of PG, depending on the underlying disease association, are discussed.