Infliximab: A Treatment Option for Ulcerative Pyoderma Gangrenosum
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Infliximab (Remicade®, Centocor Inc., Malvern, Pennsylvania) is a chimeric monoclonal antibody with high affinity for tumor necrosis factor-alpha (TNFa). The United States Food and Drug Administration (FDA) has approved infliximab for the treatment of rheumatoid arthritis and Crohn’s disease. Infliximab appears to be efficacious in the treatment of a variety of inflammatory dermatological diseases, such as psoriasis,[1,2] subcorneal pustular dermatosis, hidradenitis suppurativa, acute graft vs. host disease, Behçet’s disease,[6,7] refractory sarcoidosis,8 and orofacial and perineal cutaneous Crohn’s disease.[9,10] Additionally, recent reports suggest its utility to treat pyoderma gangrenosum.[11,12]
Pyoderma gangrenosum (PG) is a rare idiopathic inflammatory disease of undetermined cause. Most commonly affecting adults between 40 and 60 years of age, PG is characterized by erythematous, edematous, undermined, necrotic skin ulcers. The recurring and destructive ulcerations may begin as pustules, rapidly develop into necrotic ulcers with irregular borders, and may resolve with cribriform scars.[11,15,16] PG is associated with certain systemic disorders in up to 75 percent of patients, most commonly inflammatory bowel disease. Other common associated conditions include rheumatoid or seronegative arthritis, monoclonal gammopathy, and hematologic malignancies.
PG is often found to localize at the site of trauma or an operative procedure, a response termed pathergy. Susceptible patients may mount an inappropriate cellular immune response to the tissue that has been antigenically modified as a result of trauma or operation. As PG is often mistaken for an infectious process, it may be mistreated with debridement and antibiotics.
Therapy includes corticosteroids, antibiotics with anti-inflammatory properties, and/or immunosuppressive medications. With mild disease, topical or intralesional steroids are useful[11,15,18] but with more severe disease, systemic therapies are needed. PG is often refractory to treatment and a host of treatments, including cyclosporine, mycophenolate mofetil, methotrexate, and chlorambucil, has been reported. Infliximab may be a potentially useful treatment for PG. The authors report their experience with five patients with PG treated with infliximab.
A retrospective chart review was performed for patients who received infliximab for PG at the University of Miami Department of Dermatology (Miami, Florida). Demographic and disease-specific data, including sex, age, previous treatments, adjunctive medications, and therapeutic response, were tabulated (Table 1). Ulcer size was recorded before and after treatment.
A total of five patients with 13 ulcers were treated with infliximab. Their mean age was 60 (range 35 to 94 years of age). The mean initial size of the ulcers was 6.4cm2. The mean disease duration was 6.6 months (range 1 to 17 months) (Table 1). Past therapies included oral and intravenous antimicrobials; oral, intralesional, and intravenous steroids; and colchicine, pentoxifylline, cyclosporin A, stanozolol, clofazimine, mycophelate mofetil, and dapsone. At the time of initial administration, all patients were free of known acute or chronic infections and had negative chest X-rays and/or purified protein derivative (PPD) tests for tuberculosis. Associated conditions included ulcerative colitis, hidradenitis suppurativa, and seronegative arthritis, among others (Table 1).
All patients received initial infusions of infliximab 5mg/kg. The infusions were given over a several hour time period. Of the five patients, the number of infusions ranged from one to three (Figure 1).
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