PARK CITY, UTAH — If a leg ulcer worsens after debridement, the patient may have pyoderma gangrenosum, Dr. John Zone told physicians at a clinical dermatology seminar sponsored by Medicis.
“When a surgeon calls to say, 'we debrided, and it got bigger,' that is a hallmark of PG [pyoderma gangrenosum],” said Dr. Zone, chairman of the dermatology department at the University of Utah in Salt Lake City.
A rare skin disease caused by an intense, uncontrolled inflammatory response, PG presents with pathergy in about 20%–30% of patients, according to Dr. Zone. They develop PG at the site of a trauma, such as a needle stick, and the resulting ulcer worsens after debridement.
PG is one of a group of conditions (vasculitis, neoplastic disease, drug-induced hydroxyurea, necrobiosis lipoidica, panniculitis, and hypercoagulable state) that may cause a leg ulcer to not heal within 3 months of first-line treatment. “The most important thing in leg ulcers is keeping a differential diagnosis in place,” he said.
“These people won't get better until you figure out what they have,” he advised.
About 75% of PG cases are classic or ulcerative. In 50%–70% of these cases, he said PG is associated with an underlying systemic disease. Inflammatory bowel disease is the most common, followed by arthritis, hematologic disorders, hepatitis C, lupus, and sarcoidosis.
“The development of PG does not parallel systemic disease activity,” he said. PG can present in a patient who has not yet developed inflammatory bowel disease, as well as in a patient who has been cured of bowel disease.
About half of PG patients have multiple lesions, and a similar proportion have multiple episodes, according to Dr. Zone.
The morphology of ulcerative PG is distinct, a tender papulopustule ulcerating within days to a week, he said, noting that it may be associated with a fever. In classic cases with acute lesions, the ulcers are purulent, painful, and violaceous with black borders that may appear necrotic, he said. They are surrounded by erythema. The ulcer may extend beneath the skin edges with tissue destruction by intense inflammatory response.
Dr. Zone recommended gastrointestinal studies in symptomatic patients. He also advised doing the following laboratory tests: a complete blood count with differential, a chemistry panel, rheumatoid factor, serum protein electrophoresis (SPEP), hepatitis B and C antibodies, and antinuclear antibody, antineutrophil cytoplasmic antibodies, and antiphospholipid antibodies.
Treatment needs to suppress the inflammatory tissue response locally or systematically, Dr. Zone said, recommending aggressive treatments of secondary bacterial infections.
Local wound care should be nonaggressive, however. Only gentle debridement should be used, he said. He suggested silver dressings to suppress bacterial infection and allografts or xenografts to encourage granulation tissue.
There are no controlled studies of PG therapies, according to Dr. Zone. For mild disease, he suggested superpotent topical steroids, intralesional steroids, and topical tacrolimus or pimecrolimus.
In severe cases, he said prednisone is a standard initial therapy but with substantial side effects. He said he prefers to “pulse” steroids, giving 1 g intravenous methylprednisolone once a day for 5 days. “I'm 100% sure what they got, how much they got, and when they got it,” he said.
Additional options mentioned by Dr. Zone included calcineurin inhibitors, anti-inflammatory/immunosuppressive agents, tumor necrosis factor-α inhibitors, and steroid-sparing agents, in particular, cyclosporine. He cited a retrospective study in which 13 patients had complete healing with infliximab, (Am. J. Gastroenterology 2003;98:1821–6). Dr. Zone said his department also had good results but has tried the agent in only four patients.
Surgery is also an option, once the patient is immunosuppressed and inflammation is resolved, but Dr. Zone warned that there could still be a pathergic response.