Skin & Subcutaneous Tissue

Pyoderma gangrenosum: diagnosis and management

Clinical Overview and When to Suspect Pyoderma Gangrenosum

— Incidence ~3–10 per million/year; peaks in adults aged 20–50, slight female predominance

— Associated systemic disease in 50–70% of cases — drives the workup

— Inflammatory bowel disease (ulcerative colitis > Crohn) — most common GI link

— Inflammatory arthritis (seronegative, RA)

— Hematologic disease: IgA monoclonal gammopathy, MDS, AML, CML

— Autoinflammatory syndromes: PAPA, PASH, PAPASH

— Drug-induced: cocaine/levamisole, propylthiouracil, isotretinoin, G-CSF, TNF inhibitors (paradoxical)

— Rapidly enlarging ulcer (days to weeks) with disproportionate pain

— Ulcer worsens after debridement or surgery (pathergy)

— Patient with known IBD, RA, or hematologic disorder develops a leg ulcer

— Failed antibiotic courses for presumed "cellulitis" or "infected wound"

— 45-year-old with ulcerative colitis develops a pretibial pustule that breaks down into a 10-cm ulcer with violaceous, overhanging edges over 2 weeks; cultures negative; pain out of proportion.

Board pearl: PG is a diagnosis of exclusion — there is no confirmatory test. The single most important early action is to rule out infection and vascular causes before immunosuppressing. Also: avoid surgical debridement — pathergy will make it dramatically worse, a favorite Step 3 trap question where the wrong answer is "wide local excision."

Step 3 management: Once suspected, simultaneously initiate workup for an underlying systemic association (CBC, SPEP, colonoscopy if GI symptoms) because treating the trigger improves outcomes and changes long-term immunosuppressive choice.

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by rapidly progressive, painful, sterile ulcers with violaceous undermined borders — not an infection despite the misleading name.

Epidemiology and demographics:

Core associations to memorize:

When to suspect on Step 3:

Classic clinical scenario:

Presentation Patterns and Key History

— Ulcerative (classic): deep ulcer, violaceous undermined border, lower extremities (pretibial most common); ~85% of cases

— Bullous (atypical): superficial hemorrhagic bullae on dorsal hands/extensor arms; strongly linked to hematologic malignancy (AML, MDS) — workup must include bone marrow consideration

— Pustular: discrete sterile pustules with halo; most associated with active IBD; may resolve with bowel disease control

— Vegetative (superficial granulomatous): solitary, less painful, superficial ulcer; often no systemic association; best prognosis

— Onset: starts as a papule, pustule, or insect-bite–like lesion that ulcerates within days

— Pain out of proportion to exam — hallmark

— Pathergy: new lesions at sites of minor trauma, venipuncture, IV lines

— Prior "wounds that won't heal" despite antibiotics or debridement

— Systemic symptoms: fever, malaise, arthralgias in ~50%

— GI: bloody diarrhea, tenesmus, weight loss → IBD

— MSK: morning stiffness, joint swelling → seronegative arthropathy

— Heme: fatigue, recurrent infections, bleeding → MDS/leukemia

— Med list: recent TNF inhibitor, hydralazine, cocaine

Key distinction: Bullous PG on the upper extremity in an older adult should prompt immediate CBC with differential and peripheral smear — this variant is the one most likely to herald undiagnosed hematologic malignancy, and missing it is a high-yield Step 3 error.

Board pearl: Postoperative PG classically appears 4–11 days after surgery, mimics necrotizing infection, but blood/tissue cultures are negative — re-operation worsens it. Recognize and switch to systemic steroids.

Four classic clinical variants — recognize each because treatment intensity varies:

Other recognized variants: peristomal PG (around ostomies in IBD patients — often misdiagnosed as irritant dermatitis), genital/vulvar PG, and postoperative PG (surgical incision breaks down 1–2 weeks post-op).

Key history points to elicit:

Targeted ROS for associations:

Physical Exam Findings and Wound Assessment

— Violaceous, undermined border — purple-gray edge that overhangs the ulcer base

— Necrotic, purulent or boggy base with granulation tissue

— Erythematous halo extending several cm beyond the edge

— Cribriform scarring as ulcers heal (sieve-like pattern) — pathognomonic remnant

— Most commonly pretibial, but can occur anywhere; often multiple lesions

— Peristomal location in IBD patients with ileostomy/colostomy

— Mucosal involvement is rare (helps distinguish from Behçet)

— Severe, often opioid-requiring, disproportionate to ulcer size

— Tenderness extends beyond visible erythema

— Positive in ~25–50% — new lesions develop at sites of minor skin injury (BP cuff bruise, venipuncture, surgical site)

— Document carefully; informs avoidance of biopsies at active edges if possible

— Abdominal tenderness, perianal tags/fistulas → IBD

— Synovitis, dactylitis → spondyloarthropathy

— Pallor, petechiae, lymphadenopathy, splenomegaly → hematologic disease

— Track marks, nasal septal perforation → cocaine/levamisole-induced

— Palpate pedal pulses, check ABI if any suspicion of PAD

— Assess for venous stasis changes (hemosiderin, lipodermatosclerosis) — common comorbidity that complicates wound healing

— Document size, depth, undermining in cm; photograph at each visit to track response to therapy

CCS pearl: On a CCS case, order wound photography, ABI, and venous duplex alongside biopsy and labs — PAD/CVI not only mimic PG but coexist and limit healing; missing them means topical therapy will fail.

Board pearl: The cribriform "atrophic, wrinkled, sieve-like" scar is the post-healing visual signature — if a stem describes it, the prior ulcer was PG.

Cardinal ulcer morphology — high-yield visual identification:

Distribution and number:

Pain assessment:

Pathergy sign:

Systemic exam to anchor associations:

Vascular exam (must do):

Wound measurement:

Diagnostic Workup — Initial Labs, Imaging, and Biopsy Strategy

— Major criterion (required): biopsy of ulcer edge showing neutrophilic infiltrate

— Minor criteria (need ≥4 of 8): exclusion of infection; pathergy; history of IBD or inflammatory arthritis; history of papule/pustule/vesicle ulcerating within 4 days; peripheral erythema, undermining border, tenderness at ulcer site; multiple ulcerations (≥1 on anterior lower leg); cribriform scars at healed sites; decreased ulcer size within 1 month of immunosuppressive therapy

— CBC with differential and peripheral smear — screen for MDS/leukemia, especially in bullous variant

— CMP — baseline renal/hepatic before immunosuppression

— ESR, CRP — often elevated, supports inflammatory etiology

— HbA1c — diabetes affects wound healing and steroid use

— HIV, hepatitis B and C serologies — required before biologics

— QuantiFERON-TB Gold — required before TNF inhibitors

— SPEP/UPEP with immunofixation — screen for IgA monoclonal gammopathy (classic PG association)

— ANA, RF, anti-CCP — if joint symptoms

— ANCA — exclude vasculitis (especially GPA, microscopic polyangiitis)

— Aerobic, anaerobic, fungal, mycobacterial — must be negative or show only colonization

— Tissue Gram stain and special stains on biopsy

— Plain X-ray if osteomyelitis suspected at deep ulcers

— Colonoscopy if any GI symptoms or unexplained iron-deficiency anemia

— Chest imaging if granulomatous disease in differential

Step 3 management: Always biopsy the ulcer edge (not the necrotic center) for both H&E and tissue culture simultaneously. The biopsy itself can trigger pathergy, but is essential — cover the site with topical steroids post-procedure to minimize this.

Board pearl: Histology is nonspecific (dense dermal neutrophilic infiltrate) — its role is to exclude mimics, not confirm PG.

PG is a clinical diagnosis of exclusion — no specific biomarker. The 2018 Delphi criteria (Maverakis) are the current standard:

Initial labs to order:

Wound cultures:

Imaging:

Diagnostic Workup — Advanced and Confirmatory Studies

— Ankle-brachial index (ABI): rule out arterial insufficiency (ABI <0.9 abnormal; >1.3 calcified)

— Venous duplex ultrasound: chronic venous insufficiency commonly coexists

— CT/MR angiography if ABI abnormal and revascularization may be needed

— Special stains: GMS, PAS (fungi); AFB and Fite (mycobacteria); Gram (bacteria)

— Direct immunofluorescence (DIF) — usually negative; helps exclude vasculitis and autoimmune blistering disease

— Tissue cultures for bacteria, atypical mycobacteria, fungi (especially in immunosuppressed)

— Colonoscopy with biopsies — diagnose IBD; mandatory if GI symptoms, iron-deficiency anemia, or peristomal PG

— Bone marrow biopsy — if cytopenias, abnormal smear, IgA gammopathy, or bullous PG variant

— Rheumatology referral — if inflammatory arthritis features

— Cocaine/levamisole urine screen if clinical suspicion (purpuric ear lesions, ANCA positivity)

— PAPA syndrome (PSTPIP1 mutation): pyogenic arthritis, PG, acne — pediatric/young adult

— PASH (PG, acne, suppurative hidradenitis); PAPASH adds arthritis

— Cryoglobulins, complement, hepatitis serologies if vasculitis suspected

— Coagulopathy panel (antiphospholipid, protein C/S) if ulcer pattern suggests vasculopathy

Key distinction: A positive response to systemic immunosuppression within 1–2 weeks is itself a diagnostic minor criterion and is often the clinching evidence — but only after infection is excluded. Empiric steroids before culture results can mask infection if you haven't biopsied and cultured first.

CCS pearl: In CCS, sequence orders as biopsy + cultures + ABI/duplex + CBC/SPEP on day 1; start systemic therapy day 2–3 once infection is reasonably excluded. Document the diagnostic reasoning in your notes.

Vascular workup — essential to exclude/identify confounders:

Tissue studies beyond routine H&E:

Workup for systemic associations (drives long-term management):

Genetic considerations (uncommon but high-yield):

Differential-driven testing:

Risk Stratification and First-Line Management Logic

— Limited/mild disease: single small ulcer (<2 cm), no rapid progression, no systemic symptoms → consider topical/intralesional therapy

— Moderate disease: multiple lesions, larger ulcers (2–10 cm), moderate pain → systemic therapy required

— Severe/rapidly progressive: large (>10 cm), multifocal, mucosal involvement, systemic inflammatory response, functional impairment → high-dose systemics ± biologics, inpatient management

— Immunosuppression of the neutrophilic inflammation

— Wound care (gentle, non-debriding) and pain control

— Treat the underlying disease (IBD, malignancy, drug withdrawal)

— Avoid sharp debridement — pathergy worsens disease

— Gentle cleansing with saline; moist wound healing dressings (hydrocolloid, alginate, silicone foam)

— Compression therapy cautiously for lower extremity disease if no arterial compromise

— Adequate analgesia — often requires opioids initially

— Topical antiseptics for colonization without true infection

— Expected course: healing takes weeks to months, with cribriform scarring

— Recurrence rate up to 30–50%, often at new sites

— Avoid elective surgery during active disease — pathergy risk

— Smoking cessation, glycemic control to optimize healing

— Dermatology (lead), gastroenterology, rheumatology, hematology as indicated; wound care nursing; pain management

Step 3 management: The first-line systemic therapy for moderate-to-severe PG is systemic corticosteroids OR cyclosporine — RCT data (STOP-GAP trial) show comparable efficacy at 6 months. Choice depends on patient comorbidities: avoid cyclosporine in uncontrolled hypertension or significant CKD; avoid high-dose steroids in poorly controlled diabetes or osteoporosis.

Board pearl: "Treat the wound, treat the inflammation, treat the underlying disease" — missing any of the three causes treatment failure.

Severity stratification guides therapy ladder:

Management framework — three parallel tracks must run simultaneously:

General wound care principles — distinct from typical ulcer care:

Patient counseling at diagnosis:

Multidisciplinary team:

Pharmacotherapy — First-Line and Second-Line Regimens

— Prednisone 0.5–1 mg/kg/day (typically 40–80 mg) PO; rapid response often within days

· Taper slowly over 3–6 months based on ulcer healing

· IV methylprednisolone pulse 1 g/day × 3–5 days for fulminant disease

— Cyclosporine 4–5 mg/kg/day divided BID — equivalent efficacy to prednisone in STOP-GAP trial

· Monitor BP, creatinine, magnesium, potassium, lipids every 2 weeks initially

· Avoid if eGFR <60, uncontrolled HTN, or concurrent nephrotoxins

— Topical/intralesional triamcinolone (10–40 mg/mL) for small or early lesions

— Topical tacrolimus 0.1% or clobetasol for peristomal and superficial variants

— Dapsone 50–150 mg/day — useful adjunct; check G6PD before starting; monitor for methemoglobinemia and hemolysis

— Minocycline, sulfasalazine, colchicine — mild adjuncts

— Infliximab 5 mg/kg IV at weeks 0, 2, 6 then q8 weeks — strongest RCT evidence among biologics; first-choice biologic, especially with IBD

— Adalimumab, certolizumab (pregnancy-friendly) — alternatives

— Ustekinumab (IL-12/23) — emerging, useful in Crohn-associated PG

— IL-1 blockade (anakinra, canakinumab) — for autoinflammatory syndromes (PAPA, PASH)

— IVIG 2 g/kg/cycle — refractory cases, pregnancy

— JAK inhibitors (tofacitinib, upadacitinib) — emerging evidence

— Mycophenolate, azathioprine, methotrexate, cyclophosphamide — steroid-sparing

— TB testing (QuantiFERON), HBV/HCV serologies, HIV, baseline CBC/CMP, age-appropriate cancer screening

Step 3 management: For a PG patient with active Crohn disease, infliximab is preferred because it treats both diseases simultaneously — avoid prolonged steroid monotherapy.

Board pearl: Cyclosporine is the right answer when the stem highlights diabetes, osteoporosis, or psychiatric history that makes high-dose steroids problematic, provided renal function and BP are acceptable.

First-line systemic therapy (moderate–severe PG):

Adjunctive/steroid-sparing agents:

Second-line and refractory therapy:

Pre-biologic screening (mandatory):

Wound Management, Local Therapy, and Surgical Considerations

— No sharp/aggressive debridement — pathergy. Autolytic debridement with hydrogels or enzymatic agents (collagenase) is acceptable for adherent slough

— Non-adherent dressings: silicone foam, hydrocolloid, alginate; change atraumatically

— Negative pressure wound therapy (NPWT) — only after disease is controlled with immunosuppression; can be useful for healing large defects but pathergy is a risk if started during active inflammation

— Compression therapy for venous-stasis comorbid disease, once arterial flow confirmed (ABI >0.8)

— Multimodal: scheduled acetaminophen, topical lidocaine, gabapentinoids

— Opioids commonly required initially; taper as inflammation controlled

— Local intralesional steroid injections also reduce pain

— Surveillance for superimposed infection (especially on immunosuppression): new fever, purulent change, increased pain

— Culture-directed antibiotics only — avoid empiric long courses

— Clobetasol 0.05% BID under occlusion

— Tacrolimus 0.1% ointment BID (especially peristomal)

— Intralesional triamcinolone at ulcer edge

— Avoid elective surgery during active PG — pathergy

— If surgery is unavoidable (e.g., colectomy for fulminant UC), cover with perioperative immunosuppression (steroids or biologic continuation)

— Skin grafting and reconstruction only after disease is quiescent for several months and on continued maintenance immunosuppression

— Optimize stomal appliance fit; barrier rings; consider stoma relocation only after immunosuppression fails

CCS pearl: Ordering "surgical debridement" on a CCS PG case is a scoring penalty — the correct order set is biopsy edge, gentle wound care, topical clobetasol, systemic immunosuppression, pain control.

Board pearl: A patient with PG needing urgent abdominal surgery should be continued on immunosuppression perioperatively — abrupt withdrawal triggers flares at the incision.

Wound care principles (PG-specific):

Pain management:

Infection control:

Topical and intralesional options for limited disease or as adjuncts:

Surgical considerations — handle carefully:

Stoma considerations in peristomal PG:

Special Populations — Elderly and Renal/Hepatic Impairment

— Higher prevalence of comorbid MDS, monoclonal gammopathy, RA — workup must include SPEP and CBC with smear

— Polypharmacy increases adverse event risk from steroids and cyclosporine

— Steroid risks: osteoporotic fractures, hyperglycemia, delirium, infection, cataracts

· Initiate calcium 1200 mg/day, vitamin D 800–1000 IU/day, and bisphosphonate if anticipated steroid use ≥3 months at prednisone-equivalent ≥7.5 mg/day

· DEXA scan baseline if not done in past 2 years

— PJP prophylaxis (TMP-SMX) when prednisone ≥20 mg/day for ≥4 weeks, especially with second immunosuppressant

— Glycemic monitoring: check fasting glucose, HbA1c at baseline and during steroid therapy

— Cyclosporine contraindicated/cautioned at eGFR <60 — nephrotoxic, vasoconstrictive

— NSAIDs avoided — used for pain elsewhere but contribute to renal injury and may not help PG pain anyway

— Dose adjust: mycophenolate (no adjustment usually); methotrexate avoid if eGFR <30; dapsone caution

— TMP-SMX prophylaxis dose-adjust per eGFR

— Azathioprine — check TPMT or NUDT15 activity before starting; reduced activity → severe myelosuppression

— Methotrexate contraindicated in significant liver disease; avoid alcohol; baseline hepatitis serologies

— Infliximab/adalimumab — screen HBV; treat latent TB; risk of hepatitis B reactivation

— Cyclosporine raises BP and lipids — optimize antihypertensives before/during therapy

— Steroids contribute to fluid retention, worsening HF

Step 3 management: Before starting prolonged steroids in an elderly patient, bundle bone-protective therapy + PJP prophylaxis + glucose monitoring + GI ulcer prophylaxis (PPI if NSAID/anticoagulant overlap or ulcer history) as a single order set — frequently tested.

Board pearl: In an elderly patient with new PG and macrocytic anemia or pancytopenia, order a bone marrow biopsy — MDS is the underlying driver and changes everything.

Elderly patients:

Renal impairment:

Hepatic impairment:

Cardiovascular comorbidity:

Special Populations — Pregnancy, Pediatrics, and Drug-Induced PG

— PG can flare or first present in pregnancy/postpartum

— Safe options: systemic corticosteroids (prednisone preferred, minimal placental transfer), certolizumab pegol (PEGylated Fc-free TNF inhibitor — minimal placental transfer, preferred biologic), IVIG, cyclosporine (category C, used when needed)

— Avoid: methotrexate (teratogenic), mycophenolate (teratogenic — pregnancy prevention required, washout 6 weeks before conception), cyclophosphamide

— Dapsone is generally considered acceptable; monitor for hemolysis

— Coordinate with MFM; vaginal delivery preferred — avoid C-section if possible due to pathergy risk at incision

— Rare; <4% of all cases

— Strong association with IBD, immunodeficiency, and autoinflammatory syndromes (PAPA, deficiency of IL-1 receptor antagonist [DIRA])

— Consider genetic testing (PSTPIP1, IL1RN) in early-onset or syndromic cases

— Treatment: systemic steroids, cyclosporine, IL-1 blockade (anakinra) for autoinflammatory variants, anti-TNF for IBD-associated

— Growth and development monitoring on chronic immunosuppression

— Cocaine/levamisole — classic ear/cheek necrosis with ANCA positivity

— Propylthiouracil, hydralazine, isotretinoin, gefitinib, rituximab, G-CSF/GM-CSF

— Paradoxical PG on TNF inhibitors (used for other indications) — counterintuitive but documented; may need switching biologic class

— Management: discontinue offending agent; most cases resolve with withdrawal ± short steroid course

— Onset 4–14 days after surgery, often breast/abdominal procedures

— Misdiagnosed as necrotizing infection — re-operation worsens; steroids resolve

Key distinction: In a postpartum patient with a breakdown of a C-section wound and negative cultures, think postoperative PG, not necrotizing fasciitis — re-operating is the wrong move.

Board pearl: Certolizumab is the biologic of choice in pregnancy for PG due to minimal placental transfer.

Pregnancy:

Pediatric PG:

Drug-induced PG (recognize the trigger):

Postoperative PG:

Complications and Adverse Outcomes

— Chronic non-healing ulcers with disfiguring cribriform scarring

— Functional impairment: limited mobility from lower-extremity ulcers, work disability

— Chronic pain with opioid dependence risk

— Secondary infection/cellulitis — particularly on immunosuppression; can progress to sepsis

— Osteomyelitis if ulcer extends to bone

— Tendon/muscle exposure in deep ulcers; rare amputation

— Recurrence: 30–50% lifetime risk, often at new sites or sites of new trauma

— Psychosocial: depression, anxiety, social withdrawal — screen and refer

— Corticosteroid toxicity: hyperglycemia, hypertension, weight gain, osteoporosis, avascular necrosis, cataracts, glaucoma, psychiatric (mania, psychosis), adrenal suppression, immunosuppression

— Cyclosporine toxicity: nephrotoxicity, hypertension, hyperkalemia, hypomagnesemia, hirsutism, gingival hyperplasia, tremor, neurotoxicity, increased malignancy risk

— TNF inhibitors: reactivation of latent TB, HBV; opportunistic infections; demyelinating disease; rare lymphoma; injection/infusion reactions; paradoxical psoriasis or PG

— Mycophenolate/azathioprine: cytopenias, GI intolerance, infection, skin cancer (long-term), azathioprine + TPMT/NUDT15 deficiency → severe myelosuppression

— Dapsone: hemolytic anemia (G6PD), methemoglobinemia, hypersensitivity syndrome (DRESS), agranulocytosis

— PJP, CMV, fungal infections on combined immunosuppression

— Direct mortality is uncommon

— Excess mortality driven by underlying disease (MDS, leukemia, severe IBD) and infections from immunosuppression

— Mortality higher in elderly and bullous variant

CCS pearl: Patients on combined immunosuppression presenting with new fever warrant broad workup: cultures, chest imaging, β-D-glucan, CMV PCR — don't anchor on "PG flare." Also recheck for cellulitis at the ulcer.

Board pearl: Acute psychosis or mania within 1–2 weeks of starting high-dose prednisone is a known adverse effect — lower dose, consider antipsychotic, do not abruptly stop.

Disease-related complications:

Treatment-related complications:

Mortality:

When to Escalate — ICU, Consult, and Inpatient Triage

— Rapidly progressive or fulminant PG (large ulcers, multifocal, rapid expansion over days)

— Uncontrolled pain requiring parenteral analgesia

— Suspected superimposed infection or sepsis

— Inability to maintain hydration/nutrition; severe IBD flare driving PG

— Need for IV pulse steroid or infliximab loading

— Diagnostic uncertainty requiring multidisciplinary evaluation and rapid workup

— Sepsis with hemodynamic instability

— Toxic megacolon or severe IBD complication in IBD-associated PG

— Acute renal injury from cyclosporine or sepsis

— Severe steroid-related complications (DKA, perforation, psychosis with safety risk)

— Dermatology — primary diagnostic and management lead

— Gastroenterology — IBD workup/optimization; colonoscopy planning

— Hematology/Oncology — if cytopenias, IgA gammopathy, suspected MDS/leukemia

— Rheumatology — inflammatory arthritis or autoinflammatory syndromes

— Wound care/ostomy nursing — peristomal PG, complex dressings

— Pain management — opioid stewardship and multimodal pain control

— Infectious disease — if opportunistic infection on immunosuppression

— MFM — pregnancy

— Psychiatry/social work — chronic disease coping, opioid risk, disability

— Admit, NPO if surgery considered (usually no), IV access, vitals q4h

— Labs: CBC, CMP, ESR, CRP, blood cultures if febrile

— Biopsy edge for histology + tissue culture (bact/fungal/AFB)

— IV methylprednisolone or PO prednisone 1 mg/kg

— Pain regimen: scheduled acetaminophen + opioid PRN

— Wound care: saline cleanse, silicone foam dressing, no debridement

— VTE prophylaxis; PPI; bowel regimen; glucose monitoring

— Consults as above

Step 3 management: Severe steroid-refractory PG → escalate to infliximab 5 mg/kg IV (after TB/HBV/HIV screening) within days, not weeks. Don't repeatedly increase steroid dose when biologic add-on is indicated.

Indications for inpatient admission:

ICU criteria:

Consultations to obtain:

Inpatient order set essentials (CCS-style):

Key Differentials — Same-Category (Ulcerative/Neutrophilic) Causes

— Sweet syndrome (acute febrile neutrophilic dermatosis): tender, erythematous plaques/papules (not deep ulcers), fever, neutrophilia; same disease spectrum as PG; can coexist; associated with AML, IBD

— Behçet disease: recurrent oral and genital aphthous ulcers, uveitis, pathergy, vascular involvement (DVT, aneurysm); HLA-B51; mucosal involvement distinguishes from PG

— Bowel-associated dermatosis-arthritis syndrome: pustular/vesicular lesions in bypass/IBD patients

— Necrotizing fasciitis: rapidly spreading, systemic toxicity, crepitus, "pain out of proportion" too — but cultures positive, gas on imaging, requires emergent debridement (opposite of PG)

— Ecthyma gangrenosum: Pseudomonas in neutropenic patients; "gun-metal gray" eschar with erythematous halo; blood cultures positive

— Atypical mycobacterial ulcers (M. marinum, M. ulcerans/Buruli): exposure history

— Cutaneous leishmaniasis, blastomycosis, sporotrichosis: travel/exposure history; biopsy with special stains

— Syphilitic gumma, cutaneous TB, deep fungal: chronic indolent ulcers; tissue cultures and stains

— GPA, microscopic polyangiitis, EGPA: ANCA-positive; pulmonary-renal syndrome; biopsy shows true vasculitis

— Polyarteritis nodosa (cutaneous): livedo, nodules, ulcers on lower extremities

— Cryoglobulinemic vasculitis: HCV, palpable purpura, cold-induced

— Levamisole-induced vasculopathy: ear/cheek purpura, ANCA+, cocaine use

— Antiphospholipid syndrome, calciphylaxis (CKD/dialysis, painful purpuric plaques to ulcers, vascular calcifications on biopsy)

— Warfarin-induced skin necrosis, heparin-induced skin necrosis (HIT)

Key distinction: Behçet vs PG — both have pathergy and neutrophilic infiltrates, but Behçet has recurrent oral and genital aphthae, uveitis, and HLA-B51; PG typically spares mucosa.

Board pearl: Painful purpuric plaques on the abdomen of a dialysis patient evolving to ulcers = calciphylaxis, not PG — treat with sodium thiosulfate, optimize Ca/PO4, avoid warfarin.

Other neutrophilic dermatoses:

Infectious ulcers:

Vasculitic ulcers:

Thrombotic/vasculopathic:

Key Differentials — Other-Category Causes

— Venous stasis ulcers: medial malleolus, shallow, irregular margins, hemosiderin staining, lipodermatosclerosis, painless to mildly tender; ABI normal

— Arterial (ischemic) ulcers: lateral malleolus/toes, "punched-out," dry necrotic base, very painful, diminished pulses, ABI <0.9

— Mixed venous-arterial disease common in elderly

— Martorell hypertensive ischemic ulcer: lateral pretibial, severe pain, very tender, in poorly controlled HTN/diabetes — frequently misdiagnosed as PG

— Bony prominences, immobile patients, no undermining of inflammatory border

— Squamous cell carcinoma (especially Marjolin ulcer in chronic wounds), basal cell, cutaneous lymphoma (mycosis fungoides ulcerating), Kaposi sarcoma

— Any non-healing ulcer >3 months warrants biopsy to rule out malignancy — including suspected PG that fails therapy

— Geometric/linear ulcers in accessible areas; psychiatric history; "la belle indifférence"

— Brown recluse envenomation; chemical burns; injection site necrosis (illicit drug use)

— Verrucous plaques with pustules; usually infectious or IBD-associated

— Granulomatous skin ulcers and fissures distant from GI tract; biopsy shows non-caseating granulomas (distinct from PG's neutrophilic infiltrate)

Step 3 management: Any "PG" ulcer not responding to appropriate immunosuppression at 4–6 weeks mandates re-biopsy to exclude SCC, lymphoma, atypical infection, or vasculopathy — anchor bias is the most common pitfall.

Board pearl: Martorell ulcer: a lateral lower-extremity, exquisitely painful ulcer in an older hypertensive/diabetic patient with intact pulses — don't immunosuppress; treat BP, perform skin grafting, manage as ischemic subcutaneous arteriolosclerosis.

Vascular ulcers:

Pressure injuries (decubitus ulcers):

Malignancy:

Factitial dermatitis (dermatitis artefacta):

Trauma/burns/spider bite mimics:

Pyoderma vegetans / blastomycosis-like pyoderma:

Cutaneous Crohn disease (metastatic Crohn):

Secondary Prevention, Discharge Medications, and Long-Term Plan

— Continue first-line agent until ulcer fully healed, then taper slowly over months

— Add steroid-sparing agent (mycophenolate, azathioprine, dapsone, or maintenance biologic) for patients requiring prolonged therapy

— In IBD-PG: continue TNF inhibitor or ustekinumab indefinitely as IBD maintenance — covers both diseases

— In MDS/leukemia-associated PG: treat the hematologic disorder; PG often resolves with disease control

— Drug-induced PG: discontinue offending agent; brief immunosuppression while healing

— Tapering prednisone schedule with written instructions

— Bone protection: calcium, vitamin D, bisphosphonate if steroid ≥3 months at ≥7.5 mg/day

— PJP prophylaxis (TMP-SMX SS daily or DS three times weekly) if prednisone ≥20 mg ≥4 weeks or combined immunosuppression

— PPI if NSAID use or peptic ulcer history

— Pain regimen with opioid taper plan

— Vaccination updates before biologic initiation when possible: inactivated influenza annually, pneumococcal (PCV20 or PCV15+PPSV23), recombinant zoster (Shingrix) ≥18 if immunosuppressed, COVID-19; avoid live vaccines on immunosuppression

— Avoid skin trauma, elective cosmetic procedures, unnecessary venipuncture at involved sites

— Inform all future surgeons/proceduralists of PG history

— Smoking cessation; glycemic control; weight management

— Compression stockings if venous insufficiency contributes

— Annual CBC, SPEP in patients without identified association — late emergence of MDS/myeloma documented

— Age-appropriate cancer screening (colonoscopy, mammography, cervical, skin) — chronic immunosuppression elevates risk

— Annual TB screening on TNF inhibitors

Step 3 management: A patient leaving the hospital on prednisone 40 mg/day after PG diagnosis should depart with: PPI, calcium/vit D, bisphosphonate plan, TMP-SMX, glucose log, taper schedule, dermatology follow-up in 1–2 weeks, and updated vaccinations — bundle this on every Step 3 outpatient transition question.

Maintenance immunosuppression strategy:

Discharge medication checklist:

Trigger avoidance and self-management:

Surveillance for systemic associations:

Follow-Up, Monitoring Parameters, and Counseling

— Initial: dermatology visit at 1–2 weeks post-discharge to assess response; weekly–biweekly until clear improvement

— Stabilization phase: every 2–4 weeks with photographs and measurements

— Maintenance: every 3 months once healed and on stable therapy

— Primary care: integrate steroid taper and comorbidity management

— Prednisone: weight, BP, glucose (HbA1c q3 months), DEXA at baseline and annually if prolonged, ophthalmologic exam annually, mood screen

— Cyclosporine: BP at every visit; creatinine, K+, Mg++, lipid panel every 2 weeks initially, then monthly when stable; trough levels not routinely needed for dermatologic dosing

— Mycophenolate: CBC, LFTs monthly initially; pregnancy testing in females of childbearing potential

— Azathioprine: TPMT/NUDT15 before starting; CBC, LFTs at 2, 4, 8 weeks then q3 months

— Methotrexate: CBC, LFTs, creatinine every 2–3 months; folate 1 mg daily

— Dapsone: G6PD before start; CBC weekly × 4 weeks, then monthly; methemoglobin if symptomatic

— TNF inhibitors: annual TB screening; CBC, LFTs periodically; surveillance for new infections, demyelinating symptoms, lupus-like reaction

— Serial photographs; measure length × width × depth

— >30% reduction in size at 1 month indicates therapy response

— Watch for signs of infection, new lesions (pathergy), inadequate pain control

— Disease chronicity and recurrence risk

— Adherence to medication and follow-up

— Trigger avoidance and pre-procedure notification

— Mental health: depression/anxiety common; refer

— Opioid risk and tapering plan

— Pregnancy planning if on teratogens

— Vaccination, infection precautions

— Identify and treat the underlying systemic disease longitudinally

CCS pearl: Schedule explicit follow-up orders: "dermatology in 2 weeks, primary care in 4 weeks, GI in 4–6 weeks if IBD, labs (CBC/CMP) in 2 weeks" — Step 3 CCS rewards specific transition-of-care orders.

Board pearl: Lack of size reduction by 4 weeks despite adequate first-line therapy → escalate to biologic and re-biopsy.

Follow-up cadence:

Monitoring on systemic therapy:

Wound monitoring:

Counseling priorities:

Ethical, Legal, and Patient Safety Considerations

— Discuss infection risk, malignancy risk (especially long-term TNF and azathioprine — skin cancer, NMSC, lymphoma), teratogenicity (methotrexate, mycophenolate), reproductive implications

— Pregnancy prevention counseling required for mycophenolate (REMS program for many formulations) and methotrexate — document in chart

— Discuss alternative regimens (steroid vs cyclosporine vs biologic) — shared decision-making

— PG is a diagnosis of exclusion — over-diagnosis leads to inappropriate immunosuppression of infection or malignancy

— Under-diagnosis leads to harmful surgical debridement and disease progression

— Document the diagnostic reasoning (Delphi criteria met, infection/malignancy excluded) carefully — medicolegally protective

— Communicate PG diagnosis to all surgical/procedural teams — high-risk transition; pathergy can cause catastrophic wound breakdown after unrelated surgery (e.g., joint replacement, C-section). Provide written notification card if possible

— Medication reconciliation at every transition — steroid taper errors and missed PJP prophylaxis are common

— Opioid stewardship: written taper plan, PDMP check, avoid simultaneous benzodiazepines, naloxone co-prescription where appropriate

— Cocaine/levamisole-induced PG: addiction counseling and treatment referral; consider social work; not mandatory reporting in adults unless pediatric exposure

— Pediatric PG with autoinflammatory syndrome: ensure family genetic counseling

— Disability documentation for severe disease affecting work capacity

— Address vaccine hesitancy directly; document discussion

— Live vaccines (MMR, varicella, yellow fever, intranasal influenza) contraindicated on immunosuppression; plan ahead before initiating biologic

— Biologics often require prior authorization; document failure of first-line therapy; partner with specialty pharmacy

— Cost may drive nonadherence — screen and address

Step 3 management: A PG patient scheduled for elective hernia repair → recommend deferring surgery until disease quiescent, document discussion, communicate with surgeon; if urgent, plan perioperative immunosuppression continuation and inform OR team of pathergy risk.

Informed consent for immunosuppression:

Diagnostic-uncertainty ethics:

Patient safety and transitions of care:

Mandatory reporting and special situations:

Vaccination ethics:

Health-systems and access issues:

High-Yield Associations and Rapid-Fire Clinical Facts

— IBD (UC > CD) — most common; PG activity often parallels bowel activity (especially pustular variant)

— Inflammatory arthritis — RA, seronegative spondyloarthropathies

— Hematologic: IgA monoclonal gammopathy (classic), MDS, AML, CML, hairy cell leukemia, myeloma

— Solid tumors — less common; colon, breast, prostate

— Autoinflammatory syndromes: PAPA (PSTPIP1), PASH, PAPASH, DIRA, DITRA

— Takayasu arteritis — rare but reported

— TNF inhibitors (paradoxical), G-CSF/GM-CSF, propylthiouracil, hydralazine, cocaine/levamisole, isotretinoin, gefitinib, sunitinib, rituximab, pembrolizumab

— Pathergy positivity: ~25–50% of PG; ~60–70% in Behçet

— STOP-GAP trial: prednisone vs cyclosporine — equal efficacy at 6 months; cyclosporine fewer serious infections

— Infliximab: only biologic with RCT-level evidence (small but positive)

— Histology: dense dermal neutrophilic infiltrate, leukocytoclasis, no vasculitis (unless secondary)

— Healing leaves cribriform atrophic scar

— Most common ulcer site: pretibial

— Most pregnancy-friendly biologic: certolizumab pegol

— Bullous PG: think AML/MDS

— Peristomal PG: think active IBD

— Postoperative PG: surgical wound breakdown 4–14 days post-op, mimics necrotizing infection — DO NOT re-operate

— Cribriform scar = pathognomonic post-PG

— Pre-biologic: TB, HBV, HCV, HIV, age-appropriate cancer screen, vaccines

— Diagnostic framework: Maverakis (PARACELSUS for severity) Delphi criteria — biopsy + 4/8 minor

— Sharp debridement (procedural, not drug, but board favorite)

— Skin grafts during active disease

Board pearl: When the stem mentions "ulcer began as a pustule, expanded rapidly, has a violaceous undermined border, biopsy shows neutrophilic infiltrate, cultures negative, patient has bloody diarrhea" → diagnosis is PG with IBD; best treatment is infliximab (single agent treating both).

Systemic disease associations (memorize):

Trigger drugs (high yield):

Rapid-fire facts:

Drugs to avoid in PG:

Board Question Stem Patterns

— 38-year-old with ulcerative colitis develops a pretibial ulcer with violaceous border after a minor scratch. Cultures negative. Best next step?

— Answer: Skin biopsy of ulcer edge + systemic corticosteroids (or infliximab if active IBD); avoid debridement

— Day 7 after C-section, wound dehisces with rapid expansion and violaceous edges; cultures negative; debridement made it worse.

— Answer: Postoperative PG → systemic corticosteroids; do NOT re-debride

— 65-year-old with hemorrhagic bullae on dorsal hands, pancytopenia.

— Answer: Bone marrow biopsy — bullous PG associated with MDS/AML

— PG patient with diabetes, osteoporosis → choose cyclosporine over high-dose prednisone (assuming normal renal function and BP)

— PG patient with CKD stage 3 → choose prednisone, not cyclosporine

— PG with active Crohn → choose infliximab

— PG in pregnancy → prednisone or certolizumab

— IBD patient with ulcers around ileostomy site, painful, not responding to barrier dressings.

— Answer: Topical/intralesional corticosteroid or tacrolimus, optimize stoma appliance; treat IBD; avoid stoma revision

— Purpuric ulcers on ears/nose, ANCA positive, cocaine use.

— Answer: Levamisole-induced vasculopathy (PG-like) — discontinue cocaine; supportive care

— Before infliximab → TB screen (QFT or PPD), HBV serologies, HIV, vaccinations

— PG not improving on prednisone at 6 weeks → re-biopsy to exclude malignancy/infection, escalate to biologic

— "Wide surgical debridement" — almost always wrong in PG

— "Empiric vancomycin and piperacillin-tazobactam" — wrong if cultures negative and clinical picture is PG

— "Skin grafting" during active disease — wrong; defer until quiescent

Step 3 management: When two answer choices are reasonable systemic therapies, match the drug to the comorbidity — that's the discriminator (DM/osteoporosis → cyclosporine; CKD → steroids; IBD → infliximab; pregnancy → certolizumab/prednisone).

Stem pattern 1 — IBD plus skin ulcer:

Stem pattern 2 — Postoperative wound breakdown:

Stem pattern 3 — Bullous variant + cytopenias:

Stem pattern 4 — Therapy choice based on comorbidity:

Stem pattern 5 — Peristomal PG:

Stem pattern 6 — Cocaine user with ear necrosis:

Stem pattern 7 — Pre-biologic screening:

Stem pattern 8 — Failure to respond:

Stem pattern 9 — Wrong answer to recognize:

One-Line Recap

Pyoderma gangrenosum is a neutrophilic, ulcerative, pathergy-prone dermatosis diagnosed clinically after excluding infection, vasculitis, and malignancy, treated with systemic corticosteroids or cyclosporine (equivalent first-line) and escalated to infliximab — especially when IBD coexists — while strictly avoiding surgical debridement and concurrently treating the underlying systemic association.

Board pearl: If the stem features rapid pretibial ulceration with violaceous undermined edges, severe pain, negative cultures, and a history of UC — the answer is PG, the workup is biopsy plus systemic disease screen, and the treatment is systemic steroids or, if active IBD, infliximab — never the scalpel.

Diagnosis: clinical, supported by Maverakis Delphi criteria — biopsy of ulcer edge (neutrophilic infiltrate, mandatory) plus ≥4 of 8 minor criteria including pathergy, IBD/arthritis history, rapid ulceration from pustule, peripheral erythema/undermining/tenderness, multiple lesions, cribriform scarring, and response to immunosuppression within 1 month; rule out infection, vasculitis, vascular ulcers, and malignancy first.

Treatment cornerstones: prednisone 0.5–1 mg/kg/day or cyclosporine 4–5 mg/kg/day (STOP-GAP equivalence) for moderate–severe disease; infliximab for IBD-associated or refractory disease; topical/intralesional steroids or tacrolimus for limited/peristomal disease; dapsone, mycophenolate, azathioprine as steroid-sparing; never sharp-debride.

Associations: IBD (most common), inflammatory arthritis, IgA monoclonal gammopathy, MDS/AML (especially bullous variant), autoinflammatory syndromes (PAPA, PASH); drug triggers include TNF inhibitors (paradoxical), G-CSF, cocaine/levamisole, propylthiouracil, hydralazine.

Critical traps: postoperative PG mimicking necrotizing infection (do not re-operate); pathergy worsening after debridement; bullous PG flagging hematologic malignancy; Martorell hypertensive ulcer being misdiagnosed as PG; failure to escalate to biologic at 4–6 weeks of nonresponse; missing PJP prophylaxis, bone protection, vaccination, and TB screen on prolonged immunosuppression; not communicating PG diagnosis to surgical teams at care transitions.