Extraintestinal manifestations of inflammatory bowel disease (IBD) have been widely described (1–3). Cutaneous manifestations include pyoderma gangrenosum, erythema nodosum, cutaneous vasculitis, perianal disease, peristomal and perifistular disease, and metastatic Crohn disease (4,5). Pyoderma gangrenosum is an idiopathic, inflammatory, and ulcerative condition of the skin associated with IBD. It occurs more frequently in the lower extremities, but also has been reported in peristomal areas (6). Treatment for peristomal pyoderma gangrenosum includes oral and intralesional steroids, immunomodulators, antibiotics, 5-aminosalicylate compounds, and surgery (7).
Infliximab is an antitumor necrosis factor α chimeric monoclonal antibody that has been used recently to treat Crohn disease (8,9). Gastrointestinal indications for using infliximab include active Crohn disease unresponsive to conventional therapies and fistulizing disease (10,11). Infliximab therapy has been demonstrated to be safe and effective in children (12,13). This report describes a patient with dramatic improvement of severe peristomal pyoderma gangrenosum after treatment with infliximab.
Our patient is 13-year-old girl with a longstanding history of Crohn disease complicated by peristomal pyoderma gangrenosum. The diagnosis of Crohn disease was made at 15 months of age, when she experienced failure to thrive, intermittent episodes of bloody diarrhea, rectovaginal fistula, and perianal skin tags. Her initial evaluation included a flexible sigmoidoscopy that showed colitis with a single multinucleated giant cell in the lamina propria of the rectal mucosa, suggestive of Crohn disease. Results of an upper gastrointestinal series with small bowel follow-through were normal. An immunologic evaluation did not show B-cell or immunoglobulin disorders. Sulfasalazine, folic acid, metronidazole, azathioprine, and prednisone were administered, with good clinical response. Corticosteroid therapy was used intermittently for increased disease activity.
At 8 years of age, while on corticosteroid therapy, the patient was admitted for a severe exacerbation of her disease and treated with intravenous cyclosporine. During this hospitalization, toxic megacolon with colonic perforations developed, which required an emergency subtotal colectomy with ileostomy placement. After this event, all immunosuppression therapies, including prednisone, were discontinued. She continued to receive maintenance 5-aminosalycilate (mesalamine) therapy. Two months after the surgery, a gastrocutaneous fistula and prolapse of the ileostomy developed.
The first revision of her ileostomy, because of ileostomy prolapse and peristomal skin ulcerations, was performed 11 months after the colectomy. This revised ileostomy was placed on the left side of the abdomen with the creation of a Hartmann pouch. Abdominal wound excision biopsy specimens taken during her revision showed dermal ulceration and subcutaneous inflammation with focal necrosis consistent with peristomal pyoderma gangrenosum. Dehiscence of the wound and recurrence of peristomal pyoderma gangrenosum around the new ileostomy site complicated the procedure. The ileostomy continued to prolapse, and recurrent peristomal pyoderma gangrenosum significantly complicated ostomy care. Approximately 7 months later, a second ileostomy revision was performed. The ileostomy was placed in the right lower quadrant. The ileostomy prolapsed 1 year after the second revision, and the peristomal pyoderma gangrenosum continued to recur, resulting in a third revision of her ileostomy.
Because of incomplete healing around the ostomy site and significant ulceration on the abdominal wall while receiving mesalamine and metronidazole therapy, the patient received an infusion of 5 mg/kg infliximab (at 12.5 years of age). Her abdominal wall wound healed almost completely within 2 weeks of the first infusion (Fig. 1). Three infusions (5 mg/kg each) were administered (at 0, 2, and 10 weeks). She had received no immunomodulatory therapies in the 4 years before the first infusion and did not experience any infusion reactions. Her Crohn disease has been in remission, and peristomal pyoderma gangrenosum has not recurred in 4 months of follow-up since the first infusion. She tolerates a regular diet without supplementation and remains on mesalamine without immunomodulatory therapy.
Pyoderma gangrenosum is an uncommon, chronic disorder characterized by ulcerative cutaneous lesions. It is an extraintestinal manifestation of IBD. Pyoderma gangrenosum also can be evident in hematologic disorders, seronegative arthritides, and paraproteinemias. In 50% of the cases, it is an isolated condition (14).
The pathogenesis of pyoderma gangrenosum is yet to be established. Defects in both the humoral and cellular immune systems have been described (14). Pyoderma gangrenosum associated with IBD can present as either ulcerations or pustules. The histopathologic features of pyoderma gangrenosum include neutrophilic infiltrations of the dermis associated with areas of necrotic ulceration and lymphocytic infiltrations of the blood vessels. Treatment for pyoderma gangrenosum is both topical and systemic. Most therapies for IBD have been used to treat pyoderma gangrenosum. No randomized, controlled studies have been conducted for any of the treatment modalities for this disease (14). Tan et al. (15) reported the effective use of infliximab to treat two patients with pyoderma gangrenosum.
One of the clinical variants of pyoderma gangrenosum is peristomal pyoderma gangrenosum (14), previously reported in patients with IBD (6,16). Peristomal pyoderma gangrenosum is frequently misdiagnosed as skin trauma from feces, infection, or metastatic disease (17). Peristomal pyoderma gangrenosum is more common in patients with Crohn disease, although pyoderma gangrenosum of the extremities is more common in ulcerative colitis. Most of the reports document a female predominance (6,7).
In Crohn disease, peristomal pyoderma gangrenosum is associated with active disease elsewhere and is typically harder to treat than in ulcerative colitis (7). The average age of presentation in the largest series published was 48 years (range, 21–77 years) (7). Medical treatment can be classified as inflammatory, antimicrobial, or immunosuppressant. Some cases resolve spontaneously (7). Sheldon et al. (7) reported no healing of peristomal pyoderma gangrenosum with the use of prednisone alone and reported healing with metronidazole in 5 of 13 subjects with Crohn disease. Two of their subjects who did not respond to prednisone and metronidazole were successfully treated with cyclosporine (an intravenous followed by an oral course). The authors reported the recurrence of peristomal pyoderma gangrenosum after stoma revision in two patients with Crohn disease (7), which was evident in our case as well.
Ours is the first report of peristomal pyoderma gangrenosum in a pediatric patient with Crohn disease. Klein et al. (18) described a 16-year-old female with ulcerative colitis who had pyoderma gangrenosum at multiple incision sites (including line placement sites and abdominal incisions) after colectomy. In that patient, the peristomal region was not involved and she responded to intravenous corticosteroids.
Our patient responded dramatically to the first infusion of infliximab (Fig. 1). In their series of seven patients with peristomal pyoderma gangrenosum, Hughes et al. (17) described one patient (a 72-year-old female) with Crohn disease who was treated with infliximab. Her intestinal Crohn disease improved and the peristomal pyoderma gangrenosum almost completely resolved after the third infusion, but recurred within 4 weeks. Sheldon et al. (7) reported, in their series of 20 patients with peristomal pyoderma gangrenosum, two patients treated with infliximab. The peristomal pyoderma gangrenosum in one patient resolved with three infusions, and the other patient did not respond to infliximab.
We speculate that tumor necrosis factor α played an important role in the pathogenesis of peristomal pyoderma gangrenosum in our patient. Therapy with infliximab should be considered in children with Crohn disease complicated by peristomal pyoderma gangrenosum.
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