Pyoderma Gangrenosum: Case Report of Novel Treatment with Topical Steroid and Silver Sulfadiazine

Introduction The pathogenesis of pyoderma gangrenosum remains unknown, and because there are no pathognomonic features, the diagnosis is based on clinical grounds. The disease presents as painful, violaceous, boggy, undermined ulcers, most commonly located on the lower extremities. The wounds usually begin as papulovesicles or pustules occurring either spontaneously or after minor trauma. These areas necrose and progress to a confluent ulcer.1 In the majority of cases, pyoderma gangrenosum has been reported in association with a number of systemic diseases, including inflammatory bowel disease, rheumatoid arthritis, hepatitis, myeloproliferative disorders, and monoclonal gammopathies.2-4 Traditionally, treatment is directed at the associated systemic disease, immune suppression, and local wound care. The treatment remains empiric, and although success has been reported with various therapies, it has not generally been satisfactory. Ideally, a safe, effective, easily used treatment regimen would be desirable. The authors report successful treatment of a patient with wounds secondary to pyoderma gangrenosum by combination therapy of topical steroids and silver sulfadiazine cream. Case Report A 75-year-old Caucasian man with a history of ankylosing spondylitis, ulcerative colitis, hypertension, chronic obstructive pulmonary disease, and IgA myeloma (IgA gammopathy) presented to the wound clinic with a three-month history of left lower-extremity open wounds (Figure 1). Presumptive diagnosis of pyoderma gangrenosum was made. Wound biopsies for histology and quantitative culture were performed and showed chronic granulating wounds consistent with a diagnosis of pyoderma gangrenosum, with bacterial counts less than 105 colonies per gram of tissue. The patient had been treated chronically with oral steroids (prednisone). Initial treatment included topical therapy with silver sulfadiazine cream and varying oral prednisone doses. Over a six-week period, the wounds improved in appearance but did not decrease in size. Topical antimicrobials were discontinued, and a topical steroid was initiated. No progress in healing was noted over the next six-week period. The patient refused treatment with immunosuppressives other than prednisone. Repeat wound quantitative cultures at this point showed greater than 105 colonies of Staphylococcus aureus. A mixture of silver sulfadiazine/methylprednisolone cream (400g silver sulfadiazine/4g methylprednisolone) was started topically twice per day on the wound sites. The wounds rapidly responded and, over the next 10 weeks, progressed to complete healing. The wounds have since remained stable and healed without recurrence or breakdown at five and one-half months (Figure 2). Discussion Pyoderma gangrenosum is a rare, chronic, destructive, ulcerating skin disorder of unknown etiology. Complete and sustained resolution of the lesion is known to occur when the associated systemic disease is treated and cured. In 40 to 50 percent of cases, pyoderma gangrenosum occurs in patients with no known associated systemic disease, and its occurrence is assumed to be sporadic.3,4 Although no consistent immunologic disturbance has been observed, altered immune reactivity and defective leukocytes have been reported.3 No microorganisms have been associated with the disease; however, invasive infection may be a contributory factor to wounds and wound healing. Treatment is traditionally directed toward underlying associated systemic disease, immune system contributions, and the local wound. Steroids given orally and/or intravenously are generally effective at treating systemic immune contributions to the disease. Refractory cases have been successfully treated with cyclosporine and FK-506 along with other lesser used immune suppression drugs, though risk-benefit ratio may limit their use.5-7 Combination therapies of systemic steroids and hyperbaric oxygen in the treatment of wounds associated with pyoderma gangrenosum have been successfully reported.8-10 Presumably, the wounds of pyoderma gangrenosum are caused by immune response and are secondarily infected once the barriers to bacterial balance (skin integrity and normal healing response) are broken down. Robson, et al., have shown failure of parenteral antibiotics to control the bacterial burden in granulating wounds; however, topically applied antibacterials lower bacterial levels.11 Although not proven, topical delivery of steroids in appropriate concentrations could benefit and possibly constitute an improved form of therapy. Although one might think that topical steroids would lower wound resistance, this was not the case for methylprednisolone.12,13 The patient presented in this case report showed rapid improvement and wound resolution with the topical regimen combination of silver sulfadiazine and methylprednisolone. Presumably, the patient's wounds required adequate topical antibacterials along with local immunosuppression to adequately optimize the chronic wound environment to allow healing. Further experimental studies are necessary to show whether effective concentrations of steroids are delivered to wounds by topical and/or parenteral routes, as well as which treatment may be more successful in delivering effective concentrations to the wound tissue. Summary Because the etiology and pathophysiology of pyoderma gangrenosum are still poorly understood, a universal treatment regimen remains to be found. In some instances, local treatment may be sufficient, and thereby, the unwanted side effects of prolonged systemic therapies may be avoided. The authors present a case of pyoderma gangrenosum treated successfully with a combination of topical antibiotic (silver sulfadiazine) and topical steroid (methylprednisolone) therapy. They recommend considering this regimen in instances refractory to conventional treatments and, especially, in cases of refractory pyoderma gangrenosum with wound bacterial quantitative cultures with greater than 105 organisms per gram of tissue.