Pedro Jaén Olasolo
A healthy 17-year-old male presented with a 2-week history of an erythematous, slightly painful plaque on the right lower leg that was preceded by an injury to the area. He was otherwise asymptomatic and appeared well. Medical history was unremarkable.
Physical examination revealed an erythematous plaque with cribriform erosions on its surface and a crusty edge (Figure 1). Laboratory tests were normal, except for the erythrocyte sedimentation rate (ESR) which was slightly high (31 mm/hr; normal range for men: 0–22 mm/hr). A skin biopsy was performed and showed a perivascular and perifollicular mixed infiltrate of neutrophils and lymphocytes from the epidermis to the subcutis. No bacterial or fungal micro-organisms were identified on culture.
The patient was treated empirically with topical antifungal therapy and followed up the next day. By this time, the superficial erosions were more pronounced and crusts had appeared on the surface of the lesion (Figure 2). After 3 days, the lesion was completely necrotic with a deeply ulcerated centre (Figure 3).
Figure 1. Erythematous plaque with cribriform erosions on its surface
Figure 2. Poor response to topical antifungal treatment
Figure 3. The lesion appears necrotic 3 days postbiopsy
What is the most likely diagnosis?
What differential diagnoses should be considered?
Why did the necrotic ulceration appear after the biopsy?
What are the treatment options for pyoderma gangrenosum?
Pyoderma gangrenosum (PG) is a painful, ulcerative, necrotic skin lesion with distinctive clinical features. The aetiology is uncertain and the pathophysiology is poorly understood, but dysfunction of the immune system is believed to play a role. Approximately one-half of cases are associated with an underlying systemic disease (Table 1), most commonly inflammatory bowel disease, arthritis, or a lymphoproliferative disorder.1 The diagnosis is made by excluding differential diagnoses (see Question 2).2 The lesions may be single or multiple; they are usually chronic and/or recurrent. They occur most commonly on the legs, especially the pretibial area, but can develop on any area of the body (eg. the abdominal wall adjacent to a stoma following a colectomy).
Table 1. Systemic diseases associated with pyoderma gangrenosum
|Inflammatory bowel disease: ulcerative colitis, Crohn disease
|Arthritis: classic rheumatoid arthritis (RA), seronegative RA-like syndrome, non-destructive monoarticular arthritis of large joints
|Monoclonal gammopathy: 75% IgA, 25% IgG, rarely myeloma
|Immunologic dysfunction: leukaemia, transplants, HIV infection, congenital and acquired hypogammaglobulinaemia
|Haematologic and malignant: leukaemia, IgA myeloma, myelofibrosis, polycythaemia rubra vera, lymphoma, solid tumours of colon, adrenal gland, bladder, breast, lung, ovary
|Others: acne conglobate, Behçet disease, chronic active hepatitis, gastric ulceration, Hashimoto thyroiditis, Hidradenitis suppurativa, hyperthyroidism, primary billary cirrhosis, sarcoidosis, systemic lupus erythematosis, Wegener granulomatosis
The differential diagnoses of PG include deep mycoses, bacterial infections (including mycobacteria), chronic ulcerative herpes simplex virus, vasculitis and insect bite reaction among others (Table 2). Histopathologic findings may help distinguish between these disorders, but there are no investigation results that are pathognomonic for PG.
Table 2. Differential diagnosis of pyoderma gangrenosum
|Bacterial infections (including mycobacteria)2
|Deep fungal infections
||Insect bite: spider
|Viral infections (herpes simplex virus, varicella-zoster virus in immunosuppressed patients)
- systemic vasculitis
||Warfarin skin necrosis
This event is explained by the phenomenon of pathergy that was first described by Blobner in 1937.3 Pathergy refers to the formation of a papule, sterile pustule or ulceration 24–48 hours after a needleprick to the skin. It has long been used in the diagnosis of Behçet disease, but the phenomenon is also associated with PG, eosinophilic pustular folliculitis, cutaneous ulcerative lichen planus, bowel-associated dermatosis-arthritis syndrome, rheumatoid arthritis, leukocytoclastic vasculitis, non-Hodgkin lymphoma and chronic myeloid leukaemia treated with interferon alfa.4 Many patients with PG report previous trauma to the sites of their lesions, however, pathergy, in the absence of other clinical criteria, is not sufficient to make a diagnosis of PG.
Treatments for PG include local and systemic approaches (Figure 4). Local or topical therapies include colloidal membrane occlusive dressings, whirlpool baths, topical antiseptics (benzoyl peroxide, silver sulfadiazine), topical or intralesional glucocorticoids5 and topical tacrolimus ointment. Where systemic treatments are required, systemic glucocorticoids are generally first line (eg. prednisolone 0.5–2.0 mg/kg/day).6
Figure 4. Treatment algorithm for pyoderma gangrenosum
For lesions that are refractory to oral glucocorticoids alone, additional treatment options include azathioprine (50–150 mg/day), mycophenolate mofetil (1–2 g twice daily),7,8 cyclophosphamide (2–3 mg/kg/day), cyclosporin (5 mg/kg/day, with target trough serum levels of 150–350 ng/mL).9,10
High dose intravenous immunoglobulin has been reported to be effective in some cases.11 In addition, biologic agents have shown efficacy in the treatment of PG. Infliximab therapy was superior to placebo in a randomised trial of 30 patients.12 Clinical improvement has also been reported in several patients treated with adalimumab and in one patient who received ustekinumab.13,14
Competing interests: None.
Provenance and peer review: Not commissioned; externally peer reviewed.
- Mir-Madjlessi SH, Taylor JS, Farmer RG. Clinical course and evolution of erythema nodosum and pyoderma gangrenosum in chronic ulcerative colitis: a study of 42 patients. Am J Gastroenterol 1985;80:615–20.
- Weenig RH, Davis MD, Dahl PR, Su WP. Skin ulcers misdiagnosed as pyoderma gangrenosum. N Engl J Med 2002;347:1412–8.
- Blobner F. Zur rezidivierenden hypopyon-iritis. Z Augenheilk 1937;91:129.
- Frank C Powell, W.P Daniel Su, Harold O Perry. Pyoderma gangrenosum: classification and management. J Am Acad Dermatol 1996;34:395–409.
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- Galun E, Flugelman MY, Rachmilewitz D. Pyoderma gangrenosum complicating ulcerative colitis: successful treatment with methylprednisolone pulse therapy and dapsone. Am J Gastroenterol 1986;81:988–9.
- Wollina U, Karamfilov T. Treatment of recalcitrant ulcers in pyoderma gangrenosum with mycophenolate mofetil and autologous keratinocyte transplantation on a hyaluronic acid matrix. J Eur Acad Dermatol Venereol 2000;14:187–90.
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- Curley RK, Macfarlane AW, Vickers CF. Pyoderma gangrenosum treated with cyclosporin A. Br J Dermatol 1985;113:601–4.
- Matis WL, Ellis CN, Griffiths CE, Lazarus GS. Treatment of pyoderma gangrenosum with cyclosporine. Arch Dermatol 1992;128:1060–4.
- Gupta AK, Shear NH, Sauder DN. Efficacy of human intravenous immune globulin in pyoderma gangrenosum. J Am Acad Dermatol 1995;32:140–2.
- Brooklyn TN, Dunnill MG, Shetty A, et al. Infliximab for the treatment of pyoderma gangrenosum: a randomised, double blind, placebo controlled trial. Gut 2006;55:505–9.
- Guenova E, Teske A, Fehrenbacher B, et al. Interleukin 23 expression in pyoderma gangrenosum and targeted therapy with ustekinumab. Arch Dermatol 2011;147:1203–5.
- Cariñanos I, Acosta MB, Domènech E. Adalimumab for pyoderma gangrenosum associated with inflammatory bowel disease. Inflamm Bowel Dis 2011;17:E153–E4.