Dermatology Online Journal

Refractory pyoderma gangrenosum associated with ulcerative colitis successfully treated with infliximab
Miho Ueda, Mayumi Katoh, Hideaki Tanizaki, Miki Tanioka, Yumi Matsumura, Yoshiki Miyachi
Dermatology Online Journal 18 (1): 12

Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Abstract

Pyoderma gangrenosum (PG) is a rare, immune-mediated ulcerating skin disease. In up to 50 percent of the cases, PG is associated with underlying systemic disorders, most commonly inflammatory bowel diseases, connective tissue diseases, or hematological disorders. Herein, we present a case of refractory PG associated with ulcerative colitis (UC), successfully treated with infliximab.

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Pyoderma gangrenosum (PG) is a rare, immune-mediated ulcerating skin disease. In up to 50 percent of the cases, PG is associated with underlying systemic disorders, most commonly inflammatory bowel diseases, connective tissue diseases, or hematological disorders [1]. Herein, we present a case of refractory PG associated with ulcerative colitis (UC) ,successfully treated with infliximab.

Figure 1a	Figure 1b
Figure 1a. A cutaneous ulcer on the right neck Figure 1b. Her neck ulcer healed 6 weeks after the first infusion of infliximab.

A 54-year-old woman, who was diagnosed with UC 9 years prior to presentation. Over the 9 years she had been treated with prednisolone (0.5 mg/kg/day), as well as repeated granulocytapheresis therapy. She was referred to our department with ulcers on the gingival mucosa and right neck, accompanied by a subcutaneous abscess on her left buttock. Three months before her visit to our clinic, an ulcer on the right neck developed and rapidly deteriorated. Her UC had also worsened; the number of bloody stools also increased in the past 3 months.

On physical examination, she had a painful, necrotic ulcer on the gingiva, a 70 mm x 50 mm ulcer on the right neck with exposed muscles, and a subcutaneous abscess on the left buttock (Figure 1a).

Abnormal laboratory findings showed an elevated white blood cell count of 10.0 x 10⁹/L and increased C-reactive protein (CRP) of 10.9 mg/dL. Repeated bacterial and fungal cultures were all negative. Histopathology of a skin biopsy taken from the neck ulcer showed a dense, mature neutrophilic infiltration in the dermis and subcutaneous fat. Pathological Grocott, PAS, Ziehl-Neelsen stains were all negative. Taking these data into consideration, the diagnosis of PG was made. The dose of prednisolone was increased to 1 mg/kg/day. However, her bloody diarrhea still persisted, which required several blood transfusions, and the skin ulcers showed no improvement. For the purpose of the UC treatment, she commenced infliximab therapy at 5 mg/kg at weeks 0, 2, and 6 and every 8 weeks after that. Both the skin lesions and bowel complaints regressed significantly 7 days after the first infusion and completely resolved at week 6 after 3 infusions (Figure 1b). The symptoms of PG and UC have been suppressed for 2 years after initiation of infliximab therapy. Prednisolone was tapered to 5 mg/day/body in two years.

In the present case, both UC and PG, which were refractory to systemic steroid therapy and repeated granulocytapheresis therapy, responded dramatically to infliximab administration. The cause of PG remains unknown, but 50 percent of the cases develop in association with other conditions. Inflammatory bowel disease (IBD) is the most relevant condition and 30 percent of PG cases occur in association with IBD. Conversely, PG is seen only in 1 percent of Crohn disease (CD) and 3 percent to 5 percent of UC [1]. The pathogenesis of PG is not fully understood. However, previous reports of immune-cell-mediated, humoral abnormalities as well as an association of PG with other immunological disorders suggest that immunological aberrancies are related to the disease pathogenesis [1].

There is currently no gold standard of treatment or published algorithm for the treatment of choice for PG [2]. Therapy will depend on multiple factors including size and depth of the lesion, the speed of lesion growth, the appearance of new lesions, the associated systemic diseases (e.g., inflammatory bowel disease, arthritis), and the general medical status of the patient. Other factors determining treatment include the associated toxicities of the medications because up to 50 percent of the patients with classic PG require long-term therapy to maintain remission [2]. Among biologics, infliximab is the only one demonstrated to be efficacious in classic PG in a randomized, double-blind, placebo-controlled trial [3].

The efficacy of infliximab as a treatment for PG has been demonstrated by molecular, biochemical, and clinical studies. Neutrophils are the main cells involved in PG and TNF-α seems to play a major role. It induces NF-κB activation, augments neutrophil activation and adhesion molecule up-regulation, resulting in reactive oxygen species synthesis and lipid peroxidation. In addition, apoptosis of monocytes and activated T lymphocytes via the caspase pathway may be an important mechanism that could explain the powerful and sustained anti-inflammatory effect of infliximab in patients with chronic active CD [2].

In conclusion, treatment options for PG have greatly expanded with the introduction of TNF-α blocking agents. Our case report supports the use of infliximab as an alternative therapy for PG associated with UC when conventional treatment is ineffective.

References

1. Growson AN, Mihm MC, Magro C. Pyoderma gangrenous: a review. J Cutan Pathol 2003; 30: 97-107. [PubMed]

2. Miller J, Yentzer B, Clark A, et al. Pyoderma gangrenosum: A review and update on new therapies. J Am Acad Dermatol 2010; 62: 646-654. [PubMed]

3. Brooklyn TN, Dunnill MG, Shetty A, et al. Infliximab for the treatment of pyoderma gangrenosum: a randomized, double blind, placebo controlled trial. Gut 2006; 55: 505-9. [PubMed]

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