Trimethoprim–sulfamethoxazole (cotrimoxazole) desensitization in an HIV‐infected 5‐yr‐old girl

To the Editor, Opportunistic infections are a major cause of morbidity and mortality in HIV-infected patients. Trimethoprim–sulfamethoxazole (TMP-SMX) (cotrimoxazole) has been shown to dramatically reduce the risk of opportunistic infections, particularly Pneumocystis carinii pneumonia, and has been used extensively in their treatment and prevention (1). Since 2006, WHO has recommended cotrimoxazole preventive therapy for all HIV-exposed infants and children born to mothers living with HIV, and continuing until cessation of risk of HIV transmission (cessation of breastfeeding) and infection can be exclude (2). In HIV-infected patients, cotrimoxazole use causes a higher rate of adverse drug reactions than in the general population (20–100% compared with 5–8% of healthy individuals) (3, 4). Hypersensitivity to cotrimoxazole is the most frequent drug reaction among HIV-infected patients, typically manifesting as a maculopapular rash, with or without fever, and usually occurring 1–2 wk after commencing treatment (5). IgE-mediated hypersensitivity is rare. The pathogenesis of TMP-SMX reactions is complex, multifactorial, and not completely understood. One or more metabolic, toxic, immunologic, or viral factors are likely to contribute, and the typical explanation is based on the variability in metabolic parameters for N-acetylation and N-oxidation (HIV-infected patients are more likely to have a slow acetylator phenotype, which results in greater oxidation and the formation of toxic intermediate SMX-derived metabolites thereby stimulating an immune response) (3, 5, 6). There are three options for the clinical management of hypersensitivity to cotrimoxazole in these patients: treating through the reaction (continuing therapy despite adverse reaction), rechallenge, or desensitization (4). Although a variety of cotrimoxazole desensitization protocols have emerged for HIV-infected patients, there is a lack of desensitization protocols for use in pediatric patients (4). A 5-yr-old Nigerian girl, with no known allergies, who was infected with HIV at birth (MTCT) was referred to the allergy department because a pruritic erythematous maculopapular rash had appeared on her face, chest, and limbs after 2 wk of treatment with cotrimoxazole, 7 ml/day, 3 times/wk (Septrim Pediatric oral suspension : 8 mg trimethoprim/40 mg sulfamethoxazole/1 ml). The reaction had occurred 15 days before she was first seen in the allergy department. She did not present fever or systemic symptoms. Hematological analysis showed a leukocyte count of 6.02 9 10/ll with 44.5% (2.68 9 10/ll) neutrophils and 43.9% (2.64 9 10/ll) lymphocytes. The CD4 T lymphocyte (CD4) count was 6% (158.4 9 10/ll). As CD4 cell count was <200 cells/mm (<200 cells/ll), prophylaxis with cotrimoxazole for at least 6 months was mandatory. After informed consent was obtained, the patient underwent a routine allergy work-up (skin tests) following the protocol of the Drug Allergy Interest Group of European Academy of Allergy and Clinical Immunology (7). Afterward, an oral desensitization protocol was carried out. The procedure was performed at the hospital, with a physician and nurse in attendance and emergency medications readily available. The results of skin prick test (SPT) with trimethoprim (10 mg/ml; Almofarma SL, Barcelona, Spain), and SPT (10 mg/ml), and intradermal test (IDT) with sulfamethoxazole (10 mg/ml; Almofarma SL) were negative. As the reaction related to cotrimoxazole use was very likely a hypersensitivity drug reaction, an oral challenge test was not performed. Instead, an oral desensitization protocol was carried out (Table 1). On the first day, gradually increasing doses of cotrimoxazole (Septrim Pediatric oral suspension ) at 15-min intervals (1 and 5 ml of dilution 1/200 and 1 and 2 ml of dilution 1/20) were tolerated. On the second day, the patient received 3 and 4 ml of 1/20 dilution at 15-min intervals with good tolerance, and on the third day, 2 undiluted doses of 0.5 and 1 ml at 45-min intervals were tolerated. On the fourth day, 30 min after the undiluted dose of 4 ml was administered (cumulative dose 6 ml), she developed a generalized pruritic erythematous maculopapular rash. The reaction immediately subsided after oral administration of dexchlorpheniramine and