Correspondence
Treatment of Fistulas with Granulocyte Colony-Stimulating Factor in a Patient with Crohn's Disease
N Engl J Med 1999; 340:239-240January 21, 1999
- Article
To the Editor:
An adolescent boy with Crohn's disease and enterocutaneous fistulas had a response to treatment with granulocyte colony-stimulating factor (filgrastim) after all standard treatments had failed. The patient presented at the age of eight years with swollen lips. Biopsies of the tongue and oral mucosa showed a chronic inflammatory-cell infiltrate and noncaseating granulomas — findings consistent with the presence of Crohn's disease. At the age of 14 years, rectal inflammation and a perianal fistula developed. The boy had a response to treatment with prednisolone and metronidazole, but the perianal pain recurred when the prednisolone was discontinued. He was then treated with mercaptopurine, metronidazole, and prednisolone, which resulted in a decrease in pain but no healing of the fistula. After discontinuation of the prednisolone, a large abscess developed on the buttock; it was treated with antibiotics. The perianal fistula enlarged, and the boy became unable to walk. The dose of mercaptopurine was increased, and metronidazole was continued, without improvement. A diverting colostomy was performed, and a distal colocutaneous mucus fistula was created. There was no improvement, and a fistula between the abdominal wall and the sigmoid colon developed.
When the boy was 15 years old, all drugs were discontinued, and he was treated with granulocyte colony-stimulating factor (Neupogen, Amgen, Cambridge, United Kingdom) at a dose of 10 μg per kilogram of body weight administered subcutaneously daily, with parental consent. (We had previously noted that the administration of granulocyte colony-stimulating factor was associated with the healing of an enterocutaneous fistula in a three-year-old child with enterocolitis of uncertain cause who had had neutropenia with immunosuppressive treatment.)
The boy's neutrophil count rose within five days from 3500 to 30,000 per cubic millimeter. His perianal pain improved dramatically. After two weeks, his abdominal-wall fistula had healed, there was only minimal perianal tenderness, and the perianal fistula began to granulate but did not close. Over a period of 2 months, treatment with granulocyte colony-stimulating factor was discontinued three times, but on each occasion severe perianal pain and tenderness recurred within 10 days. His symptoms consistently resolved within four days after this therapy was reinstituted. He was then treated continuously for four weeks. One year after the therapy was discontinued, his abdominal-wall fistula remained healed. The perianal fistula was much smaller and was not painful. At the age of 16 years, however, inflammation developed in the colon, extending for 10 cm proximal to the colostomy and associated with lethargy and anemia.
The benefit of treatment with granulocyte colony-stimulating factor for fistulas in this boy could have been due to an antibacterial effect, an immune stimulating effect, or both. Metronidazole is effective in treating perianal disease, possibly because of its antianaerobic activity.1 Enterocolitis similar to Crohn's disease has been reported in patients with conditions of neutrophil dysfunction, including glycogen storage disease type IB, which responds to colony-stimulating factor, chronic granulomatous disease, and congenital neutropenia.2,3 Granulocyte colony-stimulating factor reduces postoperative wound breakdown and improves foot infections associated with diabetes.4,5 Its efficacy may be due to the increase in the number of neutrophils or to an effect on cytokines, including the suppression of tumor necrosis factor α.
5 ReferencesDavid Vaughan, M.D.
Brendan Drumm, M.D.
University College Dublin, Dublin 12, Ireland1
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