title: Drug-induced pyoderma gangrenosum: a model to understand the pathogenesis of pyoderma gangrenosum.
abstract: Pyoderma gangrenosum (PG) is a rare autoinflammatory condition in which the alteration of neutrophil function and the innate immune response play key roles in its pathogenesis. Cases of PG have been reported in patients being treated with certain medications, which may help us to understand some of the possible pathways involved in the aetiology of PG. The aim of this review is to review the cases of PG triggered by certain drugs and try to thoroughly understand the pathogenesis of the disease. To accomplish this, a PubMed search was completed using the following words: pyoderma gangrenosum, neutrophilic dermatosis, pathophysiology, drug-induced pyoderma gangrenosum. In total, we found 43 cases of drug-induced PG. Most of them were caused by colony-stimulating factors and small-molecule tyrosine kinase inhibitors. We propose that drugs induce PG through various mechanisms such as dysfunctional neutrophil migration and function, dysregulated inflammatory response, promotion of keratinocyte apoptosis and alteration of epigenetic mechanisms. PG is a rare condition with complex pathophysiology and drug-induced cases are even more scarce; this is the main limitation of this review. Understanding the possible mechanisms of drug-induced PG, via abnormal neutrophil migration and function, abnormal inflammation, keratinocyte apoptosis and alteration of epigenetic mechanisms would help to better understand the pathogenesis of PG and ultimately to optimize targeted therapy.
authors.affiliation: Department of Medicine, Drexel University College of Medicine/Hahnemann University Hospital, Philadelphia, PA, U.S.A.
authors.forename: B C
authors.initials: BC
authors.lastname: Wu
authors.affiliation: Virginia Commonwealth University School of Medicine, Richmond, VA, U.S.A.
authors.forename: E D
authors.initials: ED
authors.lastname: Patel
authors.affiliation: Center for Wound and Healing, Department of Dermatology, Oregon Health & Science University, 3303 SW Bond Avenue, CHD 16D, Portland, OR, 97034, U.S.A.
authors.forename: A G
authors.initials: AG
authors.lastname: Ortega-Loayza
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000627:therapeutic use; D003879:Dermatologic Agents / Q000627:therapeutic use; D003875:Drug Eruptions / Q000209:etiology*; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors; D044127:Epigenesis, Genetic / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D015603:Keratinocytes / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D056687:Off-Label Use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D017511:Pyoderma Gangrenosum / Q000139:chemically induced*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D003115:Colony-Stimulating Factors; D003879:Dermatologic Agents; D014409:Tumor Necrosis Factor-alpha; D004815:Epidermal Growth Factor; D011505:Protein-Tyrosine Kinases