Pyoderma gangrenosum (PG) is a rare but potentially severe inflammatory skin disorder characterized by painful, rapidly enlarging ulcers. Although its dramatic name suggests infection or gangrene, pyoderma gangrenosum is neither infectious nor directly related to true gangrene. Instead, it represents a form of neutrophilic dermatosis — a group of conditions defined by the accumulation of neutrophils in the skin, leading to tissue damage. 

First described in the early 20th century, PG remains a diagnostic and therapeutic challenge. It can mimic other conditions, and inappropriate management — particularly unnecessary surgical interventions — may worsen tissue destruction. Timely recognition and appropriate immunosuppressive treatment are crucial to prevent complications such as chronic ulcers, disfigurement, and disability. 

Pyoderma gangrenosum is an uncommon, ulcerative skin condition characterized by neutrophilic infiltration leading to tissue necrosis. The defining feature is the development of painful ulcers with undermined, violaceous (bluish-purple) borders. These ulcers typically begin as small pustules, nodules, or papules that rapidly break down and expand. 

Although PG most often affects the lower extremities, especially the pretibial region, lesions can develop anywhere on the body, including the abdomen (often around surgical sites), upper limbs, head, neck, and genitalia. The disease may be idiopathic or associated with systemic disorders such as inflammatory bowel disease (IBD), arthritis, or hematologic malignancies. 

The precise cause of PG remains incompletely understood, but it is believed to represent an abnormal immune response in genetically predisposed individuals. Several mechanisms have been proposed: 

• Neutrophil dysfunction: Abnormal activation, chemotaxis, or degranulation of neutrophils contributes to tissue destruction. 

• Immune dysregulation: Overproduction of pro-inflammatory cytokines such as TNF-α, IL-1, and IL-8 perpetuates inflammation. 

• Genetic factors: Rare familial cases and associations with certain HLA types suggest genetic susceptibility. 

PG often occurs with systemic conditions, including: 

• Inflammatory bowel disease (ulcerative colitis, Crohn’s disease) 

• Arthritis (rheumatoid arthritis, seronegative spondyloarthropathies) 

• Hematologic diseases (myeloproliferative disorders, monoclonal gammopathy, leukemia) 

• Other autoimmune diseases (e.g., Behçet’s disease, systemic lupus erythematosus) 

In 30–50% of cases, no underlying cause is identified (idiopathic PG). A hallmark feature is pathergy — the appearance of new lesions at sites of minor trauma or surgery. 

At the cellular level, PG is marked by dysregulated neutrophilic infiltration into the dermis and subcutaneous tissue. The sequence of events typically involves: 

• Disruption of normal skin barriers (often from minor trauma or surgery) 

• Excessive recruitment and activation of neutrophils 

• Release of proteolytic enzymes, reactive oxygen species, and cytokines 

• Collateral damage to blood vessels and connective tissue 

• Progressive ulceration and necrosis 

Histopathology is non-specific but usually shows dense neutrophilic infiltrates, dermal edema, and sometimes leukocytoclastic vasculitis. The pathergy phenomenon highlights how even small injuries can provoke destructive immune responses. 

Recognizing PG early is essential, as prompt treatment can prevent severe complications. Its presentation varies, but some key features are consistent. 

Classic Presentation: 

• Ulcer with undermined, violaceous border 

• Purulent or necrotic base 

• Surrounding erythema and induration 

• Intense pain, often out of proportion to ulcer size 

• Rapid progression over days to weeks 

The lower limbs are the most frequent sites, though ulcers can also develop in surgical wounds or on the trunk and upper body. 

Variants of PG: 

• Ulcerative (classic): Deep, rapidly enlarging ulcers; often linked to IBD and arthritis. 

• Bullous (atypical): Superficial bullae that ulcerate; seen with hematologic malignancies. 

• Pustular: Multiple sterile pustules that may or may not ulcerate; usually associated with active IBD. 

• Vegetative (superficial granulomatous): Slowly progressing, less destructive ulcers with minimal pain. 

Systemic Symptoms: 

• Low-grade fever 

• Malaise 

• Arthralgia 

• Symptoms of associated disease (e.g., diarrhea in IBD) 

Diagnosis of PG is clinical and made by exclusion, since no single test is definitive. 

Key Diagnostic Clues: 

• Rapidly progressing painful ulcer with undermined border 

• Lesions appear at trauma or surgical sites (pathergy) 

• Lack of improvement or worsening with antibiotics or debridement 

• Patient history of systemic disease 

Investigations: 

• Laboratory tests: Elevated ESR/CRP, CBC, serum protein electrophoresis, autoimmune markers, GI evaluation if IBD suspected 

• Biopsy: Helps rule out mimics; shows sterile dermal neutrophilic infiltrates with or without vasculitis 

• Microbiology: Wound cultures usually sterile or show colonizing flora 

• Imaging: Ultrasound or MRI if deep involvement or osteomyelitis suspected 

Differential Diagnosis: Conditions that mimic PG include necrotizing fasciitis, vasculitis, cutaneous lymphoma, chronic venous ulcers, diabetic ulcers, and squamous cell carcinoma (Marjolin’s ulcer). 

Emerging tools such as dermoscopy, diagnostic criteria (e.g., PARACELSUS score, Delphi guidelines), and advanced imaging may improve diagnostic accuracy, though none are universally adopted. 

Managing PG requires careful immunosuppression and supportive care. Early intervention helps control inflammation and promote healing. 

General Principles: 

• Early, aggressive immunosuppression prevents progression 

• Avoid unnecessary surgical debridement (can worsen PG due to pathergy) 

• Gentle wound care with non-adherent dressings 

Pharmacologic Therapy: 

• First-line: Systemic corticosteroids (prednisone 1–2 mg/kg/day) or cyclosporine (3–5 mg/kg/day) 

• Other options: Methotrexate, mycophenolate mofetil, azathioprine, dapsone 

• Biologics: Infliximab, adalimumab, ustekinumab (especially in IBD-associated PG) 

• Topical therapies: High-potency corticosteroids, tacrolimus ointment, intralesional steroids for localized lesions 

Supportive Measures: 

• Pain management 

• Nutritional support 

• Treatment of underlying systemic disease 

• Physiotherapy for mobility if limb ulcers are present 

• Psychosocial support for the emotional burden of chronic ulcers 

Adjunctive wound therapies (e.g., negative pressure wound therapy) may be used cautiously, but manipulation should be minimized due to risk of pathergy. 

Without treatment, PG can result in: 

• Chronic non-healing ulcers 

• Severe scarring and contractures 

• Secondary infections 

• Functional impairment 

• Emotional and psychological distress 

Rare complications include sepsis from infection and limb function loss in advanced disease. 

The outlook depends on disease extent, associated conditions, and response to therapy. 

• Many patients achieve remission with treatment. 

• Recurrences are common, especially if underlying disease persists. 

• Some patients may need long-term maintenance immunosuppression. 

There are no specific preventive measures, but risk may be reduced by: 

• Early treatment of associated systemic diseases 

• Careful surgical planning in patients with PG history 

• Minimizing trauma to skin in susceptible individuals 

Patients with known PG should be educated about early signs of recurrence, and preemptive immunosuppression may be considered before surgery in high-risk cases. 

Pyoderma gangrenosum is an uncommon but significant cause of skin ulceration, notable for rapid progression and serious complications. Because it can mimic infection or other ulcers, clinicians must maintain high suspicion to ensure timely diagnosis and immunosuppressive therapy. Advances in biologic treatment offer hope for refractory cases, and multidisciplinary care involving dermatology, rheumatology, gastroenterology, and wound care specialists is often essential for optimal outcomes. 

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