Pyoderma gangrenosum and pathergy

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Pyoderma gangrenosum is a neutrophilic dermatosis, not a bacterial pyoderma. Classic ulcerative PG favours lower legs but can affect postoperative wounds, breasts, abdomen, genital skin and stomas. A small sterile pustule or painful papule can enlarge over hours to days, with central necrosis and an overhanging boggy border. Purulent exudate and fever can accompany sterile inflammation, yet secondary infection is also possible. The diagnosis therefore depends on disciplined parallel assessment rather than choosing either infection or inflammation from appearance alone.

Trauma can amplify neutrophilic inflammation. Repeated aggressive debridement may enlarge the ulcer and create a cycle in which each postoperative deterioration prompts further surgery. Conversely, a patient with crepitus, shock or fascial gas cannot be protected from necessary surgical source control by a provisional PG label. Photograph the edge and rate of change with consent, take blood and tissue cultures from clinically credible infection, and coordinate an edge biopsy that includes inflamed border and adjacent skin. Histology commonly shows neutrophilic inflammation but primarily excludes vasculitis, infection and malignancy.

Management has four strands: suppress active inflammation, maintain a low-trauma moist wound environment, control pain and treat associated disease. Choice between potent local therapy and systemic prednisolone or ciclosporin depends on size and speed, not merely ulcer duration. Biologics may be selected with gastroenterology, rheumatology or dermatology for resistant PG and an associated inflammatory disorder. Healing leaves a thin cribriform or wrinkled scar; recurrence risk and future surgical planning remain relevant after closure.

Key points

Classic pyoderma gangrenosum begins as a tender pustule, papule or nodule and expands into an exquisitely painful ulcer with a dusky violaceous undermined border and purulent-looking sterile base.
On brown or black skin the active border may look deep purple, grey, brown or black; palpated overhang, warmth, oedema and rapid centrifugal change help when erythema is subtle.
Pathergy is lesion induction or worsening after minor trauma, cannulation, biopsy, stoma friction or debridement; it supports PG but is neither universal nor unique.
There is no single confirmatory test. Diagnosis combines characteristic evolution, edge biopsy, exclusion of infection and vascular disease, systemic associations and response to appropriate immune treatment.
Inflammatory bowel disease, inflammatory arthritis and haematological disorders are important associations; bullous superficial disease should prompt urgent blood count and myeloid-malignancy assessment.
First-line small localised disease may use a superpotent topical corticosteroid or tacrolimus with atraumatic wound care; rapidly progressive or extensive ulceration needs systemic therapy.
Prednisolone and ciclosporin had similar healing in the UK STOP GAP trial; choose by infection, diabetes, bone, blood pressure, kidney, malignancy and interaction risk rather than assuming one is universally superior.
Avoid sharp debridement of active inflammatory borders, but do not use pathergy fear to withhold life-saving drainage of proven deep infection or removal of clearly non-viable tissue after inflammation is controlled.
Pain, wound exudate, steroid toxicity and the associated disease need parallel management; apparent surface improvement alone is not enough.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Autoinflammatory neutrophil disease

Dysregulated innate immune signalling recruits and activates neutrophils in skin without a primary bacterial cause, producing sterile pustulation and ulceration.

Inflammatory disease association

Ulcerative colitis, Crohn disease, inflammatory arthritis and autoinflammatory syndromes share immune pathways and may flare alongside or independently of skin disease.

Haematological association

Myelodysplasia, acute myeloid leukaemia, monoclonal gammopathy and other blood disorders are important, particularly with bullous or atypically distributed disease.

Trauma amplification

Surgery, needles, dressings and stoma leakage can provoke pathergy in susceptible skin, although many procedures heal normally and trauma is not the root cause.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Neutrophils are over-recruited
Cytokine and chemokine imbalance draws activated neutrophils into dermis, creating tender papules and sterile pustules at the expanding edge.
2
Inflammation destroys tissue
Proteases and reactive inflammatory mediators break down dermis and vessels secondarily, producing rapid central necrosis and undermining beneath apparently viable skin.
3
Trauma restarts the cascade
Tissue injury releases danger signals that intensify neutrophilic recruitment, explaining new lesions at puncture sites and expansion after unnecessary debridement.
4
Healing follows edge arrest
Once peripheral inflammation is suppressed, granulation and epithelial migration fill the defect and leave thin fibrotic cribriform architecture.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Painful pustule-to-ulcer evolution

A sterile inflammatory papule, pustule or nodule breaks down and expands rapidly, with pain commonly exceeding what the initial surface area suggests.

Undermined active border

The ulcer edge is swollen, tender, overhanging and violaceous, grey-brown or dusky, often with peripheral pustules marking centrifugal progression.

Pathergic worsening

New lesions or sudden expansion follows needle sites, surgery, stoma appliance trauma, biopsy or sharp debridement, although other inflammatory diseases can also pathergy.

Cribriform scar

Healed ulcers can leave thin wrinkled sieve-like scars with irregular pigment, offering retrospective support but not proving the original diagnosis.

Peristomal phenotype

Painful undermined ulceration develops beside a stoma where leakage, appliance pressure and inflammatory bowel disease provide both pathergy and diagnostic confounding.

Bullous haematological patternRed flag

Superficial blue-grey bullae and erosions, often on upper limbs or face, are associated with myeloid malignancy and require urgent haematological assessment.

Deep infection discordanceRed flag

Crepitus, shock, anaesthetic skin, fascial spread or gas is not safely attributed to PG and requires immediate infection and surgical evaluation.

Red flags requiring action

Shock, crepitus, spreading deep pain, exposed tendon or bone, critical ischaemia, uncontrolled bleeding, sepsis, ocular disease, stoma breakdown, rapidly expanding bullae, cytopenia or constitutional loss requires same-day multidisciplinary assessment.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Serial examination and photographsFirst step
Why
Document rate, edge morphology and treatment response while reducing repeated traumatic handling.
Interpretation and limitations
Measure ulcer dimensions, undermining, satellite pustules, pain and surrounding heat using consistent images; rapid enlargement supports activity but occurs in infection too.
02
Deep edge biopsy
Why
Exclude infection, vasculitis, occlusion and malignancy and seek compatible neutrophilic inflammation.
Interpretation and limitations
Sample the active border with enough depth, warn about pathergy and send separately for histology and cultures when needed; no histological feature alone confirms PG.
03
Tissue and blood microbiology
Why
Identify primary or secondary infection before escalating immune treatment.
Interpretation and limitations
Prefer tissue over a superficial chronic-wound swab for deep concern and obtain blood cultures when febrile; colonising organisms do not explain an expanding pathergic border by themselves.
04
Perfusion and venous assessment
Why
Find arterial ischaemia, venous hypertension or mixed ulceration that changes wound safety.
Interpretation and limitations
Examine pulses and refill and use ABPI, toe pressure or duplex as indicated; a normal inflammatory biopsy cannot make compression safe in critically impaired circulation.
05
FBC, film, CRP, renal and liver profile
Why
Find inflammation, infection, cytopenia, haematological malignancy and a systemic-treatment baseline.
Interpretation and limitations
Blasts, unexplained cytopenias or a bullous phenotype require urgent haematology; inflammatory markers are useful for trajectory but cannot separate sterile PG from infection alone.
06
Association-directed assessment
Why
Detect IBD, inflammatory arthritis, paraprotein and other disease that may share treatment.
Interpretation and limitations
Use bowel history, calprotectin or endoscopy, joint examination, immunoglobulins and electrophoresis from the phenotype rather than ordering every test for every local ulcer.
07
Imaging for deep threat
Why
Evaluate gas, abscess, fasciitis, osteomyelitis or another anatomical process when examination raises concern.
Interpretation and limitations
CT or MRI supports planning but must not delay operative assessment in unstable necrotising infection; chronic ulcer contact with bone lowers the threshold for osteomyelitis evaluation.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Necrotising soft-tissue infection

Shock, rapidly spreading deep pain, crepitus, gas and fascial damage demand immediate antimicrobial and surgical management even when PG is possible.

Venous or arterial ulcer

Gaiter oedema and pigmentation or distal punched-out ischaemic wounds with abnormal perfusion indicate haemodynamic causes that can coexist with inflammation.

Vasculitis or thrombotic disease

Purpura, livedo, retiform infarction, renal signs and histological vessel-wall inflammation or thrombosis redirect causal testing and treatment.

Infectious ulcer

Bacterial ecthyma, deep fungus, atypical mycobacteria and leishmaniasis require exposure history, tissue culture and organism-specific treatment before immune suppression.

Ulcerated malignancy

Squamous cancer, lymphoma and other tumours can mimic inflammatory ulcers and require representative edge biopsy when growth, induration or bleeding persists.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01First emergency decisionHold infection and PG in view togetherFirst stepA painful ulcer is expanding quickly or worsens after a procedure.

1Assess ABCDE, pain, crepitus, perfusion, fascial signs and systemic toxicity and take photographs and cultures without slowing treatment of suspected sepsis.
2Convene surgical, dermatology and infection review early; operate urgently for credible necrotising infection while avoiding serial margin debridement driven only by sterile postoperative expansion.
3Take coordinated viable-edge tissue for histology and bacterial, fungal or mycobacterial studies and record prior antibiotics, corticosteroids and trauma.

02First-line local treatmentCalm a small active border atraumaticallyFirst linePG is localised and slowly progressive without deep exposure or major systemic illness.

1Apply a dermatologist-directed superpotent topical corticosteroid or tacrolimus to the active edge and reassess within days to weeks for pain and expansion.
2Use non-adherent absorbent dressings, gentle cleansing, adequate analgesia and adhesive or stoma modifications that minimise stripping, leakage and pressure.
3EscalationDo not sharply debride the inflamed undermined edge; remove loose devitalised material only through an agreed wound plan and escalate if the ulcer continues to enlarge.

03First-line systemic treatmentChoose prednisolone or ciclosporin by comorbidityFirst lineUlceration is rapidly progressive, extensive, deeply painful or failing an adequate local approach.

1Exclude uncontrolled infection and establish wound, blood pressure, renal, liver, glucose, bone and vaccination baselines before systemic immune treatment.
2Select oral prednisolone or ciclosporin with dermatology, using the STOP GAP regimens as evidence-informed options and choosing toxicity rather than assuming efficacy differs greatly.
3Measure pain and edge arrest early, taper or modify once healing is established and consider IBD-aligned biologic or another steroid-sparing therapy for refractory disease.

04Associated-disease routeLook beyond the ulcer without delaying itBowel, joint, haematological or constitutional features accompany PG or the phenotype is bullous.

1Investigate IBD and inflammatory arthritis from symptoms and examine the complete blood count and film, paraprotein and marrow pathway when haematological disease is plausible.
2Coordinate a treatment that can control both disorders where possible, while preserving rapid skin suppression, wound care and infection surveillance.
3EscalationEscalate bullous PG with cytopenia, blasts or systemic decline urgently because an underlying myeloid malignancy changes prognosis and treatment ownership.

05Future-procedure planReduce pathergy without denying necessary careA patient with current or previous PG requires surgery, stoma revision, vascular access or biopsy.

1Confirm whether disease is active, map previous pathergy, optimise associated inflammation and involve dermatology and the procedural team before the planned trauma.
2Use the least traumatic effective technique, careful haemostasis, non-stripping dressings and a clear postoperative plan for infection versus inflammatory deterioration.
3Consider peri-procedural immune management only through specialist agreement and avoid listing all procedures as contraindicated when clinical benefit is substantial.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

A first-line potent local anti-inflammatory option for limited PG alongside atraumatic dressings and pain control.

Clobetasol propionate 0.05% local therapy

Apply a thin dermatologist-directed layer once daily to the active inflammatory border of a small ulcer for a defined two-to-four-week induction, then reassess before continuing or tapering.

Do not let topical treatment delay reassessment of an enlarging wound or infection. Monitor atrophy, absorption, delayed epithelialisation and contact sensitivity and avoid indiscriminate application to untreated infected tissue.

Provides rapid systemic suppression for extensive or progressive ulcerative PG when local treatment is insufficient.

Prednisolone systemic induction

The UK STOP GAP regimen used 0.75 mg/kg by mouth once daily, capped at 75 mg daily, with subsequent adjustment and taper according to inflammatory arrest and healing.

Exclude or treat infection and monitor glucose, blood pressure, mood, bone, eye, gastrointestinal and adrenal risk. Repeated or prolonged exposure requires prevention planning, steroid-card advice and a steroid-sparing strategy.

An efficacy-comparable systemic alternative to prednisolone when renal, blood-pressure, infection, malignancy and metabolic trade-offs favour calcineurin inhibition.

Ciclosporin systemic induction

The UK STOP GAP regimen used 4 mg/kg by mouth per day, capped at 400 mg daily, with dose adjustment to response, formulation and specialist safety monitoring.

Check blood pressure, renal and liver function, magnesium, potassium, lipids, infection and skin-cancer risk. Avoid interacting CYP3A4 medicines, grapefruit and unplanned live vaccines and review pregnancy and malignancy context.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Rapid tissue loss

Unchecked peripheral inflammation can expose fascia, tendon or bone, impair mobility and require prolonged reconstruction after disease control.

Secondary infection

A large immunosuppressed wound can develop cellulitis, abscess, osteomyelitis or sepsis despite an initially sterile disease mechanism.

Severe persistent pain

Inflammatory, wound and neuropathic pain disrupts sleep, mobility, dressing tolerance and mental health and may persist into scar formation.

Pathergy-related expansion

Biopsy, cannulation, stoma leakage or repeated surgery can generate new ulcers and increase surface area before diagnosis and inflammation are controlled.

Immune-treatment toxicity

Glucocorticoid and ciclosporin expose patients to infection, metabolic, renal, hypertensive, neurological and malignancy harms requiring close structured surveillance.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Measure pain, new peripheral pustules, border advance, depth, undermining and epithelialisation with consented serial photographs rather than relying on exudate colour.
At every systemic review screen for fever, spreading cellulitis, malodour with clinical decline, exposed structures and osteomyelitis while recognising that colonisation is common.
Track prednisolone weight, glucose, pressure, mood, infection, bone and adrenal risks and record a taper plan and steroid-card status.
Track ciclosporin pressure and renal function closely after initiation and dose changes, alongside electrolytes, liver tests, interactions and malignancy surveillance.
Review bowel, joint and blood symptoms and ensure abnormal counts, paraprotein or constitutional loss have a named specialty owner.
After healing, document pathergy history, cribriform scar, recurrence warning signs and a procedure plan without encouraging avoidance of necessary healthcare.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Purulence can be sterile

Neutrophils and liquefied tissue make convincing pus, so microbiology and clinical infection behaviour matter more than appearance alone.

Pathergy is bidirectional risk

Trauma may worsen PG, yet refusing essential source control in true necrotising infection is equally dangerous; multidisciplinary judgement resolves the conflict.

Biopsy excludes more than confirms

Compatible neutrophils support the diagnosis, but the greatest value of tissue is often demonstrating that infection, vasculitis or malignancy is more or less likely.

Pain leads the edge

A fall in pain and cessation of peripheral expansion can precede obvious filling of a large defect and provide early evidence of immune control.

Bullae change the work-up

A superficial bullous phenotype is disproportionately linked to myeloid disease and deserves urgent scrutiny of the blood count and film.

Healing has a signature

Thin cribriform wrinkling can remain after closure, but a scar pattern is supportive history rather than permission to skip assessment of a new ulcer.

11Common pitfallsFrequent interpretation and management errors.

01
Repeatedly debriding a sterile expanding undermined edge because the wound looks purulent.
02
Calling every postoperative deterioration pathergy and missing necrotising infection, abscess or ischaemia.
03
Using a superficial chronic-wound swab as the sole evidence for or against deep infection.
04
Biopsying only the dead centre and omitting active border, depth, cultures and clinical photographs.
05
Starting systemic immunosuppression without baseline infection, renal, pressure, blood, glucose and malignancy assessment.
06
Treating the ulcer while ignoring bowel symptoms, arthritis, cytopenia or a bullous myeloid phenotype.
07
Continuing a toxic systemic regimen despite ongoing border expansion without diagnostic and adherence review.