Pyoderma Gangrenosum · What It Is, Causes, Signs, Symptoms, and More

While the exact cause is not known, pyoderma gangrenosum is thought to be associated with an impaired inflammatory response. Researchers have found several important factors involved in this condition that support this association, including neutrophil dysfunction, increased cytokine response, and a possible genetic component. Neutrophil dysfunction includes abnormal neutrophil chemotaxis (i.e., neutrophil recruitment), migration, phagocytosis (i.e., engulfment), and bactericidal properties. The increased cytokine response may involve the overexpression of inflammatory mediators such as TNF-alpha, chemokines, metalloproteinases, and IL-1. Lastly, deficiencies of the Janus kinase (JAK) pathway, which is involved in the immune system, have also been proposed. 

The onset of pyoderma gangrenosum has been linked to various inflammatory conditions and malignancies. Most commonly, PG is associated with inflammatory bowel disease (i.e., ulcerative colitis and Crohn disease). There are arthritic diseases related to PG, such as psoriatic arthritis (i.e., joint and skin inflammation); polyarthritis (i.e., joint disease of more than five different joints); spondyloarthritis (i.e., arthritis in spine); and rheumatoid arthritis (i.e., an autoimmune disease affecting joints). Additionally, hepatitis (i.e., inflammation of the liver) and primary biliary cirrhosis (i.e., autoimmune disease of bile ducts) are diseases affecting the liver and biliary system that can be associated with PG. Finally, in rare occasions, autoimmune conditions such as systemic lupus erythematosus (i.e., widespread inflammation impacting tissue all around the body) and Sjogren syndrome (i.e., dry eyes and dry mouth) may also co-occur with PG.  

Pyoderma gangrenosum may be diagnosed after a thorough medical history and physical examination. A detailed review of systems is crucial to uncover any other systemic conditions accompanying the PG. PG is a diagnosis of exclusion, meaning that all other possible causes must be ruled out before a conclusion may be reached. 

A provider may want to order various tests to rule out other causes or look for a coinciding systemic illness. A complete blood count (CBC) assesses for anemia and elevated white blood cell count indicating inflammation. A comprehensive metabolic panel (CMP) can determine electrolyte levels, kidney function, and liver function. To look further into blood disorders, serum electrophoresis, blood smear, and bone marrow biopsy may be performed to look for hematologic causes. Antibodies such as an antineutrophil cytoplasmic antibody (ANCA), antinuclear antibody (ANA), and antiphospholipid antibody may be used to rule out other autoimmune conditions.  Tissue cultures and biopsies may be performed to rule out infections (e.g., fungal, bacterial, viral) or malignancy. An ulcer biopsy can show neutrophilic infiltration and necrosis of the epidermis. If an individual is experiencing any gastrointestinal symptoms, a colonoscopy may be considered to assess for inflammatory bowel disease. 

Researchers have recently proposed guidelines to aid healthcare providers in diagnosing PG. Major criteria that must be present include progressive ulcer and excluding all other conditions.  Additionally, four minor criteria might be found, including pathergy or cribriform scarring;  having other coinciding systemic diseases; typical biopsy findings;  and a response to treatment with steroids.