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Pyoderma Gangrenosum_0912 Derm Dx
A 56-year-old female undergoing chemotherapy for acute myelogenous leukemia is admitted to the hospital with a small purulent ulceration. General surgery services debrides the lesion, and broad-spectrum antibiotics are started, but the ulceration continues to expand rapidly.
Two more debridements are performed and antibiotic coverage is broadened. Despite these measures, the ulceration continues to expand, and the patient complains of exquisite pain. All wound cultures are negative. A biopsy demonstrates collections of neutrophils, but special stains for infectious organisms are negative.
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Pyoderma gangrenosum is a chronic, recurrent ulcerative cutaneous disease with a distinctive clinical appearance. In classic pyoderma gangrenosum cases, a small pustule develops and then ulcerates. Frequently, lesions appear at sites of trauma and worsen with manipulation, for example after debridement. This phenomenon is called “pathergy.”
Satellite ulcerations may appear at the border of the main ulcer, ultimately fusing with central ulcer and causing peripheral expansion. A fully developed classic pyoderma gangrenosum ulceration is painful and has sharply delineated, undermined, violaceous or steely blue borders. The most common location is the lower extremities. Lesions heal with thin, atrophic or cribriform scarring.
In addition to the aforementioned classic presentation, other variants of pyoderma gangrenosum include pustular pyoderma gangrenosum, bullous pyoderma gangrenosum and vegetative pyoderma gangrenosum. In pustular pyoderma gangrenosum, lesions remain as pustules without ulceration. This form of pyoderma gangrenosum is frequently associated with inflammatory bowel disease (IBD).
Bullous pyoderma is a superficial variant of the disease and is less destructive and less painful than the classical ulcerative type. Bullous pyoderma gangrenosum is commonly associated with leukemia or polycythemia vera.
Vegetative pyoderma gangrenosum is also called superficial granulomatous pyoderma. Lesions present as superficial ulcerations on the trunk that slowly enlarge. In contrast to classical pyoderma gangrenosum, lesions are rarely painful and are usually not associated with an underlying disease.
Pyoderma gangrenosum most commonly occurs in adults aged 40 to 60 years. Many patients have an underlying systemic disease — 50% to 70% — most commonly inflammatory bowel disease (IBD), including both Crohn’s disease and ulcerative colitis. As many as 5% of IBD patients develop pyoderma gangrenosum. Classical and pustular variants are most commonly seen in this setting. The lesions of pyoderma gangrenosum may completely remit after surgical removal of the diseased intestine, but unfortunately this is not always the case and the skin ulcerations may persist.
After IBD, the next most common systemic diseases associated with pyoderma gangrenosum are arthritis and hematologic disease. Arthritis subtypes seen in association with pyoderma gangrenosum include seronegative arthritis and rheumatoid arthritis. Hematologic diseases most commonly associated with pyoderma gangrenosum are acute myelogenous leukemia, myelodysplastic syndrome and monoclonal gammopathy.
As many as 15% of patients will have monoclonal gammopathy, most commonly of the IgA subtype. Pyogenic arthritis pyoderma gangrenosum and acne (PAPA) is an autosomal dominant genetic condition due to mutated CD2 binding protein 1, associated with pyoderma gangrenosum.
Diagnosis
An undermined ulceration with steely-grey or violaceous borders is characteristic of the classical ulcerative pyoderma gangrenosum. One should maintain a high level of suspicious for pyoderma gangrenosum when patients present with underlying systemic disease such as IBD, rheumatoid arthritis or a hematologic disorder. Worsening condition despite debridement and antibiotics are further signs of the disease; however, in all cases pyoderma gangrenosum remains a diagnosis of exclusion.
There are no specific diagnostic serologic or histologic features of pyoderma gangrenosum. Biopsy will show ulceration with neutrophilic abscesses, a feature that can also be seen with a multitude of infectious causes. Therefore, it is important to rule out infection with cultures and special stains for infectious organisms. Infections that may mimic pyoderma gangrenosum include deep fungi, mycobacteria, gummatous syphilis, and others.
Other conditions that mimic pyoderma gangrenosum include large vessel cutaneous vasculitis, certain spider bites, venous insufficiency ulcers, or a factitial disease in which the patient injects caustic substances into the skin. In each case, complete history, physical, and special studies or biopsies should be performed as indicated.
See the Derm Dx on ecthyma for an explanation of ecthyma and ecthyma gangrenosum.
Treatment
Once a diagnosis of pyoderma gangrenosum is established, both the patient and the managing physicians should be educated about the concept of “pathergy” – that is the both the development and worsening of pyodema gangrenosum with trauma. This means that incision, drainage and debridement should be avoided, and other forms of iatrogenic trauma, such as needle sticks, should be minimized.
Severity of presentation determines treatment. Mild cases of vegetative pyoderma gangrenosum may respond to conservative topical measures, whereas rapidly progressive and ulcerative cases should be managed with early implementation of aggressive systemic therapy to limit morbidity associated with the disease.
The gold standard for systemic therapy is systemic steroids. The initial dose of prednisone is approximately 1 mg/kg of ideal body weight. When control is achieved, the steroid may be tapered. If steroid tapering is not possible, addition of a steroid-sparing agent should be considered.
Cyclosporine and infliximab results in faster healing than other immunosuppressive agents. Cyclosporine is initiated at 5mg/kg daily in three divided doses. Infliximab is an intravenous infusion that targets TNF-alpha. Infliximab may be the treatment of choice in aggressive cases associated with IBD, as the therapy will benefit both cutaneous and gastrointestinal symptoms. Azathioprine, cyclophosphamide and chlorambucil are other medications that have been used effectively as steroid-sparing agents.
Once the disease is controlled, skin grafting may be performed if indicated. If the patient is on sufficient immunosupression, pathergy is unlikely to occur at the donor site.
In this case once the pyoderma gangrenosum diagnosis was established, all surgical manipulations were stopped immediately. Prednisone was initiated at 60mg daily.
Within several days the patient reported less pain, and the ulceration began to slowly improve within three weeks. At eight weeks, steroids were tapered, and by three months the lesion had completely healed, albeit with significant scarring. Unfortunately, the patient died 18 months later due complications from her underlying leukemia.
Adam Rees, MD, is a graduate of the University of California Los Angeles School of Medicine and a resident in the Department of Dermatology at Baylor College of Medicine in Houston.
References
1. Bolognia J, Jorizzo JL, Rapini RP.”Chapter 27: Neutrophilic Dermatoses.” Dermatology. St. Louis, Mo.: Mosby/Elsevier, 2008.
2. James WD, Berger TG, Elston DM et al.”Chapter 7: Erythema and Urticaria.” Andrews’ Diseases of the Skin: Clinical Dermatology. Philadelphia: Saunders Elsevier, 2006.
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