Pyoderma gangrenosum

Pyoderma gangrenosum is an inflammatory skin condition characterized by one or more rapidly progressive, painful skin ulcers with neutrophilic infiltration. Pyoderma gangrenosum is likely due to autoimmune dysregulation and is associated with autoimmune conditions such as inflammatory bowel disease (IBD) and rheumatoid arthritis. Pyoderma gangrenosum may be precipitated by trauma, often developing as a result of pathergy. Diagnosis is often based on clinical suspicion and can be confirmed with skin biopsy. Treatment includes supportive care, immunosuppressants, and monitoring.

• Prevalence: 58 cases per million adults in the US ^[1]
• Worldwide incidence: ∼ 3–10 cases per million per year ^[2]
• Most often manifests in individuals ∼ 50 years of age but can occur between 20–60 years of age or older ^[1][3]
• ♀ > ♂ ^[3]
• Often associated with a higher mortality rate than similar groups of the same age ^[1]

Epidemiological data refers to the US, unless otherwise specified.

Pyoderma gangrenosum is likely due to autoimmune dysregulation and may be idiopathic or associated with systemic autoimmune conditions. ^[2]

• Precipitating factors ^[3]
  • Trauma or surgery (often via pathergy)
  • Drugs (e.g., G-CSF, retinoids, TNF inhibitors, imatinib, hydralazine, rituximab, cocaine)
• Associated conditions ^[1][2]
  • Inflammatory bowel disease (e.g., Crohn disease, ulcerative colitis)
  • Autoimmune arthritis (e.g., rheumatoid arthritis)
  • Malignancy (e.g., myelodysplastic syndrome, MGUS, AML)
  • Autoinflammatory syndromes (e.g., SAPHO syndrome)
  • Pregnancy

Distinguishing features

• Skin lesions ^[1][2][3]
  • One or more pustules, papules, or blisters that rapidly progress into deep ulcers with irregular, undermined erythematous, purple (violaceous) edges, central necrosis, and pus
  • Severely painful
  • Marginal edema during acute phase
  • Scarring: cribriform or wrinkled (like cigarette paper)
• Distribution ^[3]
  • Frequently extensor surfaces of lower legs
  • Other possible sites: head, neck, trunk, fingers, vulva, peristomal skin

Disease severity ^[1][2]

The severity of pyoderma gangrenosum can be classified based on ulcer size, number, and/or distribution. ^[4]

• Mild disease
  • Ulcer size ≤ 3 cm
  • ≤ 3 lesions
  • ≤ 5% total body surface area
• Moderate to severe disease
  • Ulcer size > 3 cm
  • > 3 lesions
  • > 5% total body surface area
  • Involvement of the face or genitals
  • Visibility of tendon, bone, and/or muscle

Consult a specialist (e.g., dermatology) early to avoid diagnostic delay and misdiagnosis, as there are no standardized diagnostic criteria.

Skin biopsy ^[1][3]

• Indication: all patients with suspected pyoderma gangrenosum
• Site: preferably taken from the edge of the ulcer
• Histological findings (nonspecific)
  • Neutrophilic infiltration (common) and/or lymphocytic infiltration
  • Dermal edema
  • Bacterial and fungal staining to rule out infection

Biopsy findings alone cannot confirm the diagnosis of pyoderma gangrenosum.

Routine laboratory studies ^[3]

• CBC with differential and PBS:
  • Leukocytosis (often neutrophilic)
  • Leukemoid reaction (rare)
• Inflammatory markers: ↑ ESR and CRP

Additional studies ^[1][3]

Perform age-appropriate cancer screening for all patients and consider the following studies based on clinical suspicion.

• Alternative diagnoses, e.g.:
  • Syphilis testing (e.g., RPR, VDRL)
  • Autoimmune testing (e.g., p-ANCA, c-ANCA)
• Associated conditions, e.g.:
  • Evaluation for IBD (e.g., colonoscopy)
    • See “Diagnosis of Crohn disease.”
    • See “Diagnosis of ulcerative colitis.”
  • X-ray of affected joints to assess for inflammatory arthritis

• Infection, e.g.: ^[1][3]
  • Bacterial or mycobacterial skin infections
  • Deep fungal infections
  • Necrotizing fasciitis
  • Syphilis
  • Parasitic infections (e.g., leishmaniasis)
• Malignancy, e.g.: ^[3]
  • Squamous cell carcinoma
  • Basal cell carcinoma
  • Lymphoma
• Vasculitis, e.g.: ^[3]
  • Polyarteritis nodosa
  • Granulomatosis with polyangiitis
  • Leukocytoclastic vasculitis
  • Rheumatoid vasculitis
• Vascular disease, e.g.: ^[3]
  • Peripheral arterial disease or peripheral venous disease
  • Thromboses (e.g., due to antiphospholipid syndrome)
• Other ^[1]
  • Severe insect bites
  • Factitious ulcers

The differential diagnoses listed here are not exhaustive.

Treatment is largely based on expert opinion as there have been few large-scale clinical trials on pyoderma gangrenosum.

General principles

• All patients
  • Consult dermatology for treatment guidance.
  • Provide supportive care.
  • Manage concurrent associated conditions (e.g., IBD, rheumatoid arthritis) if present.
• Mild disease: Start topical or intralesional therapy with or without prednisone. ^[2]
• Moderate to severe disease: Start prednisone and/or cyclosporine. ^[2]
• Monitoring
  • Reassess after 1–3 weeks or longer for response. ^[1][2]
  • Add additional immunosuppressive therapy if the lesion does not resolve with subsequent reassessments.
  • Consider either tapering off therapy or providing long-term maintenance in patients with complete resolution.

Pharmacological treatment ^[1][2]

• Topical therapy, e.g.:
  • Glucocorticoids (e.g., clobetasol propionate) ^[2]
  • Calcineurin inhibitors (e.g., tacrolimus)
• Intralesional therapy: : e.g., triamcinolone, cyclosporine
• Systemic immunosuppressants
  • Initial therapy (first-line): glucocorticoids (e.g., prednisone) and/or cyclosporine
  • Refractory disease: biologics (e.g., anti-TNF-α agent, IL-17 inhibitor, IL-23 inhibitor) or DMARDs (e.g., mycophenolate mofetil)
• Adjunctive therapies: for refractory disease (e.g., dapsone, IV immunoglobulin, granulocyte and monocyte adsorption apheresis) ^[2]

The size and appearance of the ulcer should be well-documented before starting pharmacological treatment since immunosuppression can alter the characteristic appearance of pyoderma gangrenosum ulcers. ^[1]

Supportive care ^[1]

• Wound care ^[1][2]
  • Daily gentle cleansing
  • Dressings based on wound environment: Avoid drying the wound.
  • Treatment of any superimposed skin and soft tissue infection
  • Consider split-thickness skin graft with negative pressure wound therapy and immunosuppressive therapy.
• Pain management (e.g., NSAIDs or acetaminophen)
• Psychosocial counseling

Avoid debriding the wound as this can exacerbate the ulcer.