Abstract

A 25-year-old HIV-infected woman participating in a study of the effects of hormonal contraception on HIV disease progression was started on antiretroviral therapy-Combivir & Nevirapine (NVP) on May 27, 2004. NVP was 200mg daily initially for two weeks to be increased to 200mg bid thereafter. On day twelve, she presented with a mild skin rash on the trunk, purulent conjunctivitis, pharyngitis and fever. She was treated symptomatically and sent home. The following day she returned with a generalized erythematous eruption. She was admitted to JCRC (Joint Clinical and Research Centre) on June 14 and was diagnosed with Stevens - Johnson syndrome (SJS). Antiretroviral therapy was stopped. By July 05, 2004, she had improved and was discharged .After recovery she was restarted on Combivir and Efavirenz and is subsequently doing well on this regimen.

Key words: Stevens - Johnson syndrome, antiretroviral therapy, generalized erythematous eruption, nevirapine

Introduction

First described in 1922 by Stevens and Johnson, Stevens -Johnson syndrome (SJS) is an immune complex hypersensitivity reaction that can be caused by many factors such as infections, drugs and malignancies. Recent reports have linked SJS to the use of drugs rather than other etiologic factors. Antibiotics e.g. sulphonamides are the most common cause of SJS, followed by analgesics, cough and cold medication, nonsteroidal antiinflammatory drug (NSAID), psycho-epileptics, and antigout drugs¹. Nevirapine has also been implicated in the pathogenesis of SJS^{2, 3}. There may be a genetic predisposition to developing SJS³. We hereby report a case of severe SJS.

Case history and examination findings

A 25 yr old female participant in the Genital Shedding study (GS) is presented. This study is under the Makerere University-Case Western Reserve University (MU-CWRU) research collaboration. She was initially in the Hormonal Contraception and risk of HIV acquisition (HC-HIV) study. This was a longitudinal multi-centre multi-site study which followed women who were HIV negative. The women were followed every three months for a period of 15 –24 months or until HIV sero conversion. Women who became HIV-infected were invited to join the GS Study; informed consent was sought and provided prior to enrollment in the study

The client was enrolled in the HC-HIV study on February 2, 2000 and tested HIV-negative at that time. At her visit on March 27, 2001 she first tested HIV-positive. She enrolled in the GS study on June 6, 2001 with a CD4 count of 843cells/mm³. She had vaginal candidiasis and was treated with clotrimazole vaginal pessaries. In January 2003 she developed otitis media, which improved on treatment with Erythromycin 500mg q.i.d for one week. She developed genital herpes in March 2003 and her CD4 cell count dropped to 324 cells/mm³. In September 2003 she presented with a generalized pruritic papular rash. Her weight had dropped from 58 kg to 53 kg (8.6% weight loss). On December 1, 2003 she had vaginal candidiasis which was treated with Ketoconazole 200mg o.d. for seven days and she improved. In February 2004 she had a pruritic papular eruption (PPE) again, oral hairy leukoplakia, and vaginal candidiasis. In May 2004 she presented with vaginal candidiasis, PPE and 10% weight loss (WHO stage III disease). The candidiasis was now poorly responsive to anti-fungal therapy (Fluconazole, Ketoconazole). Her CD4 count had dropped to 220cells/mm³and her viral load was 68,073copies/ml.

The study HIV consultant recommended that she starts Anti-Retroviral Therapy (ART) based on WHO stage III disease coupled with the client’s willingness and commitment to take ART. She started Nevirapine 200mg once daily and Combivir 450mg twice daily on May 27, 2004. Twelve days later she came in with a mild skin rash on the trunk, purulent conjunctivitis, pharyngitis and fever. She was treated as a mild grade 1 Nevirapine rash and went home to continue with ART and was advised to come back if symptoms worsened. She returned the following day with a diffuse erythematous rash on the face, trunk and upper limbs. The oral mucosal erythema and ulceration was progressive and caused difficulty in swallowing. Nevirapine was discontinued and Combivir continued for 3 days then withdrawn. The initial intention was to overlap the Nevirapine with Combivir for seven days but this was not possible because of esophageal pain on swallowing. A pus swab was taken from the eyes and throat. The eye swab cultured staphylococcus aureus and throat swab cultured a non-significant growth of streptococcus viridans.

She was hospitalized at the JCRC and treated symptomatically with oral morphine, cloxacillin, tetracycline eye ointment, nursing care, nasogastric tube for feeding, and I.V fluids for rehydration. While on the ward she developed oral ulceration and generalized bullous lesions. Some of which ruptured leaving a denuded skin (figure I).

(Figure II)

Investigations during hospitalization

Blood slide showed plasmodium falciparum + and she was treated with metakelfin. ALT and AST were normal at 33.7 iu/l and 36.0 iu/l, respectively. Serum creatinine was 1.01mg/dl and serum amylase was 75.8 iu/l. Complete blood count was wbc-4500/cubic mm. Red blood cells were 4.65 million/cubic mm and lymphocytes were 24.7%. Haemoglobin level was 12.5g%, haematocrit was 36.2% and platelets were 139,000/cubic mm.