What are the causes of Pyoderma gangrenosum?

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From the Guidelines

Pyoderma gangrenosum is caused by an abnormal immune system response that leads to severe skin inflammation, often triggered by underlying systemic conditions such as inflammatory bowel diseases, autoimmune diseases, or trauma to the skin. It is an autoinflammatory neutrophilic dermatosis where the body's immune system mistakenly attacks healthy skin tissue. The exact trigger is often unknown, but pyoderma gangrenosum frequently occurs in association with underlying systemic conditions, including inflammatory bowel diseases (ulcerative colitis and Crohn's disease), rheumatoid arthritis, hematologic disorders (leukemia, lymphoma, monoclonal gammopathy), and other autoimmune diseases 1. In some cases, trauma or injury to the skin (pathergy) can initiate lesion development, as noted in the context of postsurgical stomas or trauma to the shins 1. Genetic factors may also play a role in susceptibility. At the cellular level, there is dysregulation of neutrophil function and inflammatory cytokines, particularly TNF-alpha, IL-1, and IL-17, which contribute to the characteristic painful, rapidly expanding ulcers with undermined violaceous borders.

Some key points to consider in the diagnosis and understanding of pyoderma gangrenosum include:

  • The condition can occur anywhere on the body, including the genitalia, but the most common sites are the shins and adjacent to stomas 1.
  • Pyoderma gangrenosum is usually diagnosed clinically, based on the characteristic appearance of the lesions following exclusion of other possible skin diseases 1.
  • The therapeutic goal should be rapid healing, as pyoderma gangrenosum can be a debilitating skin disorder 1.
  • Treatment focuses on controlling the inflammatory response and addressing any underlying conditions that may be driving the immune dysregulation, with options including systemic corticosteroids, infliximab, adalimumab, or topical or oral calcineurin inhibitors 1.

From the Research

Causes of Pyoderma Gangrenosum

The causes of Pyoderma gangrenosum (PG) are not fully understood, but several factors have been identified as contributing to the development of the disease. These include:

  • Underlying systemic diseases, such as inflammatory bowel disease, rheumatological disorders, hematological malignancies, or other autoimmune conditions, which are associated with PG in 50-70% of cases 2, 3, 4, 5
  • Immune dysregulation, characterized by the presence of abnormal neutrophils and T-cells, leading to the production of inflammatory mediators such as IL-1β, IL-8, IL-17, and TNF-α 6
  • Trauma, which can trigger the onset of PG in 20-30% of patients, a phenomenon known as pathergy 4
  • Genetic factors, as PG can occur as part of an inherited inflammatory syndrome 6
  • Other potential triggers, such as infections or malignancies, although these are less common 2, 3

Associated Conditions

PG is often associated with other conditions, including:

  • Inflammatory bowel disease, such as Crohn's disease or ulcerative colitis 2, 3, 4, 5
  • Rheumatological disorders, such as rheumatoid arthritis 3, 5
  • Hematological malignancies, such as leukemia or lymphoma 2, 3, 4, 5
  • Other autoimmune conditions, such as chronic hepatitis or paraproteinemias 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Clinical management of pyoderma gangrenosum.

American journal of clinical dermatology, 2002

Research

Pyoderma gangrenosum: a systematic review.

Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia, 2014

Research

Pyoderma Gangrenosum: A Current Problem as Much as an Unknown One.

The international journal of lower extremity wounds, 2017

Research

Pyoderma gangrenosum: a review of pathogenesis and treatment.

Expert review of clinical immunology, 2018

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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