Drug-induced pyoderma gangrenosum: a model to understand the pathogenesis of pyoderma gangrenosum

Abstract

This study aimed to explore how drug-induced pyoderma gangrenosum develops in the body. Pyoderma gangreno-sum (PG) is a rare autoinflammatory disease (a genetic disease caused by a malfunctioning immune system) that causes tissue cells to die, resulting in severe and painful ulcers. Drug-induced disease is where a disease occurs, or is triggered, as a result of taking medication/drugs. In this study 43 cases of patients diagnosed with drug-induced PG were reviewed. The authors found that most of the medications associated with drug-induced PG affected more the one element in the pathway that leads to a person developing drug-induced PG. Abnormal neutrophil migration and function, dysregulated inflammation, keratinocyte apoptosis, and alteration of epigenetic mechanisms were all found to be associated with the development of drug-induced PG. Abnormal neutrophil migration and function refers to the irregular movement and function of a specific type of white blood cell (which forms part of the body's immune system). Dysregulated inflammation refers to an abnormal inflammation response in the body's cells and tissue. Ker-atinocyte apoptosis means the death of keratinocyte cells (the cells that form the majority of the outer layer of skin). Alteration of epigenetic mechanisms means a change to the way in which a cell reads and understands its own genes, which in turn affects how the cell behaves. The authors conclude that, in order to better understand how PG develops, further research is needed into the immune system, epigenetics (the way in which a cell reads and acts upon its genes) and NETosis (a form of cell death).

Dysregulation of inflammatory gene expression in lesional and nonlesional skin of patients with pyoderma gangrenosum

“…It is often idiopathic but can be associated with systemic conditions . Our recent publications highlight the need for better characterization of the molecular understanding of PG to improve diagnostic accuracy and targeted therapy. Recent reviews suggest that innate immunity may have a causative and consequential role in PG.…”

A case of pyoderma gangrenosum induced by insulin

“…3 The most commonly implicated drugs causing PG are cocaine laced with levamisole followed by isotretinoin, propylthiouracil, and sunitinib. PG is caused by the interplay of multiple factors, that is, genetics, epigenetics, and triggers from the environment, which all result in chemotaxis, migration, and accumulation of neutrophils.…”

“…3 Much molecular work has been performed in recent years to study the pathogenesis of PG. 3 Much molecular work has been performed in recent years to study the pathogenesis of PG.…”

“…Either epigenetic demethylation of DNA or interaction of Toll-like receptors with damage-associated molecular patterns leads to the release of tumor-necrosis factor-α (TNF-α), resulting in the apoptosis of keratinocytes. 3 The most commonly implicated drugs causing PG are cocaine laced with levamisole followed by isotretinoin, propylthiouracil, and sunitinib. All these drugs induce the release of chemokines, mediating chemotaxis and migration of neutrophils; propylthiouracil produces myeloperoxidase anti-neutrophil cytoplasmic antibodies and IgG antibodies, which in turn activate neutrophils, while sunitinib also suppresses anti-apoptotic signals for keratinocytes, which promotes keratinocyte apoptosis.…”

“…Isotretinoin induces the release of matrix metalloproteinases-9 (MMP-9) which mobilises PMNs to the site of inflammation. 3 Much molecular work has been performed in recent years to study the pathogenesis of PG. Other inflammatory mediators involved in PG are interleukins (IL); IL-1β, IL-8, IL-17, and MMP-2.…”