Portal de Periódicos da CAPES

Cyclosporine for Rectoperineal Fistula in a Human Immunodeficiency Virus-Infected Child

1999; Lippincott Williams & Wilkins; Volume: 28; Issue: 3 Linguagem: Inglês

10.1097/00005176-199903000-00024

1536-4801

Desirée Caselli, Anna Maccabruni, Giampiero Beluffi, L. Minoli,

Inflammatory Bowel Disease

Inflammatory conditions of the anal-rectal area were reported in a significant proportion of human immunodeficiency virus (HIV)-positive adults from a surgical survey (1). Two simultaneous reports independently suggest that acquired rectovaginal fistula may be an unexpected complication in HIV-infected infant girls (2,3). Of note, both reports came from African countries, but at least one European case is reported (4). Acquired rectoperineal fistulas may also complicate the course of chronic inflammatory bowel disease in HIV-negative patients. Surgery and immunosuppression therapy have been used for its treatment with nonuniform results (5). Cyclosporine has been successfully used in children with Crohn's disease, ulcerative colitis, or chronic granulomatous disease (6-12) and for Crohn's-associated fistulas (13). We report the successful treatment with cyclosporine of a rectoperineal fistula in an HIV-infected male child. CASE REPORT The patient, a boy born to an HIV-infected mother, underwent transverse and descendent colon resection due to necrotizing enterocolitis soon after birth. The small bowel was entirely preserved, and no malabsorption or malnutrition developed during follow-up. Although identified as HIV-infected, he had an uneventful clinical course until the age of 5.5 years, when Burkitt's lymphoma was diagnosed and successfully treated with chemotherapy. Four years later, at the age of 9.3 years, a rectoperineal fistula developed. It was responsible for massive water loss (about 3000 ml/day) resulting in severe hypocalcemia (calcium, 5.9 mg/dl) and hypokalemia (potassium, 2.3 mEq/l) with seizures. Careful evaluation of the discharged fluid excluded a urinary origin (also based on creatinine concentration) and the presence of mycobacteria (excluded by negative culture and Ziehl-Neelsen staining) or viral (excluded by culture) infection; staining for Cryptosporidium parvum was also negative. Cytologic examination showed only granulocytes, bacterial colonies, and amorphous substance. Bacterial cultures yielded growth of Enterobacter cloacae, Staphylococcus aureus, and Escherichia coli strains. After injection of nonionic contrast medium into the fistula, radiographic and computed tomographic imaging demonstrated a connection between the rectal ampulla and the perineal surface through the fistula (Fig. 1). Antibiotic therapy did not affect the discharge; continuous infusion of 100 mEq/m2 sodium, 75 mEq/m2 potassium, and 5 g/day calcium daily, provided an adequate control of salt loss, whereas transient shift to oral administration (potassium 96 mEq/day, calcium 9 g/day) was ineffective. Surgical excision of the fistula was considered but the risk-benefit balance of such invasive surgery in an immunocompromised patient was not favorable. In October 1995, 1 year after the onset of fistula discharge, when the child was clinically stable, with HIV-infection Centers for Disease Control 1994 stage IC3 (i.e., infected, symptomatic due to previous opportunistic neoplasm, with severe immune depression: CD4 lymphocyte count 0/mm3), cyclosporine therapy was initiated at a 2 mg/kg per day by continuous infusion over 7 days. The dose was adjusted to maintain the plasma level of approximately 300 ng/ml (determined by the polyclonal immunoenzymatic assay: TDX, Abbott FPA, Chicago, IL). Treatment was well tolerated with no side effect. On day 3 fistula discharge had reduced to 500 ml/day, with need of salt reduced by one half; by day 7 fistula discharge was less than 10 ml/day with no salt loss. Cyclosporine therapy was withdrawn.FIG. 1: Fistulography: Nonionic contrast medium injection through a catheter shows a long, winding fistula with irregular margins and content. The fistula connects the perineal surface with a walled off cavity (i.e., the rectum).At the time of this writing 36 months later, the boy, now 13 years old, remains completely respondent to therapy. The perineal orifice of the fistula is still visible but without discharge or salt loss; he is asymptomatic having been maintained with antiretroviral therapy since 1996, initially with azidothymidine (AZT), and dideoxynosine (DDI), then with nelfinavir, lamivudina (3TC), and stavudina (d4T). DISCUSSION Acquired rectovaginal (or rectoperineal) fistula is uncommon in children. Its observation in 27 HIV-infected African girls from Malawi and Zimbabwe, at an age usually younger than 12 months (3), suggests a strong association with HIV infection. In one study of surgical pathology of HIV infection in African adults, 8 of 48 seropositive patients had inflammatory conditions of the anorectal area (1). It is notable that because none of these patients practiced anal intercourse, either homosexual or heterosexual, local microtrauma could not be responsible for this otherwise unusual event. Report of preceding perineal infection in HIV-positive patients (2,4) and the observation of an increased frequency of fistulas in children with congenital immunodeficiency (9) seem to point toward an association between perineal fistula and immunodeficiency, either congenital or acquired. Fistula is likely to develop through an increased frequency of local infection, in keeping with previous suggestion of a role for Pseudomonas infection (4). Furthermore, its occurrence in patients with chronic inflammatory bowel diseases is also intriguing (5). Although its pathogenesis remains controversial (14), it is common opinion that immune-mediated mechanisms, particularly T lymphocytes, play a major role in such disease. On that basis, the use of immunosuppressive agents including 6-mercaptopurine and azathioprine is well established in children with Crohn's disease (15,16). Recently the role of cyclosporine as an alternative to surgery in children with extended inflammatory bowel disease has been questioned (7,11), in particular, in some cases in which rapid clinical response was followed by disease reactivation during follow-up (8). The use of immunosuppression in patients with HIV could raise some question concerning a possible increase in the patient's immune depression. Recent reports suggest that cyclosporine may be safely used in adults with HIV, and there has been a favorable effect on HIV replication in vitro (17-19). In the present case, the use of short-term infusion of cyclosporine provided excellent control of rectoperineal fistula, leading to abolition of discharge and of salt loss. It is interesting to note that the patient developed rectoperineal fistula during HIV-induced complete depletion of blood CD4 lymphocytes. This suggests that CD4 cells are not the only effectors of such immune-mediated inflammatory diseases. Acknowledgement: The authors thank Dr. Maurizio Aricò and Prof. Alessandro Ventura for support.