Successful treatment of Cronkhite-Canada syndrome using anti-tumor necrosis factor antibody therapy.

Abstract

Cronkhite–Canada syndrome (CCS) is a rare nonhereditary syndrome characterized by gastrointestinal polyposis and ectodermal changes [1]. Although several treatments, such as steroids, are available, the prognosis is poor, with a 5-year mortality rate of 55% [2]. A 57-year-old man, who suffered from alopecia, anorexia, severe diarrhea, dystrophic nail changes, and pigmentation on the hands, presented to our hospital. Colonoscopy revealed numerous polyps throughout the colon (● Fig.1a). Gastroscopy and small-bowel series also showed severe gastric and small-bowel polyposis, and histology showed juvenile-like polyps with mild inflammation. On the basis of these findings, the patient was diagnosed with CCS. He was treated with medications including corticosteroids, antiplasmin agents, and azathioprine; however, the symptoms persisted. He developed intussusception 7 years after diagnosis (● Fig.1b) and underwent ileocecal resection. As he continued to suffer from frequent relapses, with diarrhea and malnutrition with severe hypoalbuminemia, a different therapeutic strategy was needed to control the disease progression. Supported by a single report finding of high levels of tumor necrosis factor alpha (TNF-α) in tissue affected by CCS [3], implying that antiTNF-α therapy could be useful for CCS patients, the patient was administered infliximab at 200mg every 2 weeks. His general condition improved, and colonoscopy performed 20 months after induction of anti-TNF therapy showed complete remission with the disappearance of polyposis (● Fig.1c). He now receives 200mg of infliximab every 8 weeks, and has been symptom free for 3 years since the initial administration. There is one report that described strong TNF-α expression in intestinal mucosa affected by CCS, implicating the potential usefulness of anti-TNF-α antibody for patients with CCS. However, to the best of our knowledge, this treatment has not been tested until now [3]. Although we could not detect TNF-α expression in the polyps of this patient by immunohistochemistry (● Fig.2), given the patient’s dramatic response to therapy, it can be assumed that TNF plays an important role in disease development, perhaps upstream of polyp formation. This case indicates that further basic and clinical research is warranted, and that anti-TNF therapy could be an important new strategy for treatment of CCS.