EFAVIRENZ ASSOCIATED STEVENS-JOHNSON SYNDROME To the Editor: Persons with human immunodeficiency virus (HIV) infection are highly susceptible to adverse dermatological reactions to specific medications (1,2). Stevens- Johnson syndrome has been observed in HIV-infected individuals treated with sulfphonamides (3), sulfones (4), thiacetazone (5), and antiretrovirals (6,7). Among the antiretrovirals it is particularly nevirapine that has been associated with this syndrome (6,7). Nevirapine-induced rash has been reported to occur in 32-48% of patients, and Stevens-Johnson syndrome in 1%. Stevens-Johnson syndrome has occasionally been associated with the use of other antiretrovirals such as zidovudine, didanosine, indinavir and amprenavir (2). Its association with the use of efavirenz has been reported in less than 0.14% patients treated with this antiretroviral (2). Case report In August 2003 a 19-year-old Ghanaian woman with HIV infection was admitted with very painful oral lesions. In April 2003 she had been hospitalized for pulmonary tuberculosis. Anti-tuberculosis treatment, including isoniazid, myambutol, pyrazinamide and rifampicin was started, together with cotrimoxazole. Because her CD4+ lymphocyte count was very low (42/µl) highly active antiretroviral treatment (HAART) was added two weeks after the start of the anti-tuberculosis treatment. The HAART regimen included zidovudine, lamivudine and efavirenz. One week later these antiretrovirals were stopped because of fever, increasing dyspnoea, cough and pulmonary infiltrates, probably due to an immune reactivation syndrome. During corticosteroid therapy her clinical condition improved rapidly. Four months later HAART was reintroduced: stavudine 30 mg twice daily, lamivudine 150 mg twice daily and 1
efavirenz 600 mg once daily. One week after restarting HAART she developed very painful lesions in her mouth and on the lips. She was admitted because there was trismus; furthermore, she was unable to eat, drink or speak. On admission she had lost 4 kg, and weighed 42 kg. There was a purulent vaginal discharge and urination was very painful. Hemorrhagic ulcerations were present on her lips and in the anal region, she also presented with acute conjunctivitis. Target-like lesions were not observed on her skin, but some erythema was present on the soles of her feet. There was no fever. Laboratory evaluations showed: CD4+ lymphocyte count 12/µl, haemoglobin 12.3 mg/dl, total lymphocytes 880/ml, AST 87 units/l (normal 5-40 U/L), ALT 44 units/l (normal 7-56 U/L). A rapid plasma reagine test for syphilis was negative. A PCR test for Herpes simplex and Mycoplasma pneumoniae performed on a swab from the labial lesions was negative. Further viral, bacterial and fungal cultures of conjunctival and vaginal swabs remained sterile. Based on the presumptive diagnosis of Stevens-Johnson syndrome, efavirenz was discontinued immediately, and stavudine/lamivudine two days later. She received supportive care with intravenous hydration, nasal tube feeding, and corticosteroids. As soon as the efavirenz was discontinued her clinical condition improved and she regained her normal weight. In October 2003 she was re-hospitalized because of a new episode of Stevens-Johnson syndrome with mouth and conjunctiva lesions 7 days after starting dapsone prophylaxis. After stopping the dapsone all lesions disappeared. This patient experienced 2 episodes of Stevens-Johnson syndrome, characterized by mucositis but without characteristic skin lesions. In the first episode the lesions appeared one week after starting antiretroviral treatment and we suspect efavirenz was the cause of this episode. Four months earlier, when an antiretroviral regimen containing efavirenz was started for the first time, she had developed fever, but at that time without mucosal or skin lesions. 2
The second episode of Stevens-Johnson syndrome was probably caused by dapsone (a sulfone antimicrobial agent) (4). Stevens-Johnson syndrome is a well-known complication of the other nonnucleoside reverse transcriptase inhibitor, nevirapine. A case control study performed in Europe and Israel identified 18 patients with HIV infection and Stevens-Johnson syndrome, and 15 (83%) of these were considered to be caused by nevirapine (2). One of the 3 other patients had received efavirenz. In this study the nevirapineassociated Stevens-Johnson syndrome began 10 to 240 days after the introduction of nevirapine (median 12 days). The reason why HIV-infected persons are at increased risk of severe cutaneous reactions, including Stevens-Johnson syndrome, remains unclear. The unusual factor in our patient was that despite severe mucositis there was almost no skin involvement. This case suggests that physicians treating persons with HIV infection should also consider a diagnosis of Stevens-Johnson syndrome in patients not on a nevirapinecontaining treatment regimen and presenting only with mucositis. Robert Colebunders 1,2 Thomas Vanwolleghem 1,2 Peter Meurrens 1,2 Filip Moerman 1,2 1. Institute of Tropical Medicine, Nationalestraat 155, B 2000 Antwerp, Belgium 2. University Hospital Antwerp, Wilrijkstraat 10, B - 2650, Belgium 3
Correspondence : R. Colebunders Institute of Tropical Medicine Nationalestraat 155 B - 2000 Antwerpen Belgium + 32 3 247 64 26 + 32 3 247 64 32 E-mail : bcoleb@itg.be 4
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