Severe Cutaneous Reactions Associated with the Use of Human Immunodeficiency Virus Medications

Abstract

Patients infected with human immunodeficiency virus are highly susceptible to adverse dermatological reactions to specific medications. Severe cutaneous conditions such as Stevens-Johnson syndrome and toxic epidermal necrolysis are associated with high morbidity and, notably for toxic epidermal necrolysis, high mortality. Although overall mortality from human immunodeficiency virus has dramatically declined owing to highly active antiretroviral therapy, these antiretroviral regimens have been associated with a wide spectrum of severe cutaneous reactions. We reviewed case reports and clinical trials in the English literature on Medline (1966 to 2001) and Aidsline (1980 to 2000) to determine the prevalence of Stevens-Johnson syndrome and toxic epidermal necrolysis attributable to the current FDA approved antiretroviral medications. We identified a total of approximately 50 patients who had Stevens-Johnson syndrome and/or toxic epidermal necrolysis associated with the use of 5 antiretroviral medications: 2 nucleoside reverse transcriptase inhibitors, zidovudine (2 patients) and didanosine (1 patient); 1 non-nucleoside reverse transcriptase inhibitor, nevirapine (42 patients); and 2 protease inhibitors, indinavir (1 patient) and amprenavir (an unspecified number within the 1% of over 1400 patients experiencing severe life-threatening reactions). Of the reports that specified the onset time of adverse reaction after initiation of treatment, 86% (19/22) of patients experienced reactions within 4 weeks. Ten of the approximately 50 patients were diagnosed with Stevens-Johnson syndrome or toxic epidermal necrolysis, due to specific antiretroviral medication, or a combination of medications identified by either resolution upon withdrawal, consistent biopsy findings or a positive rechallenge. The remainder of the identified patients were reported in articles lacking data regarding drug administration, reaction history or other details.

Lyell Syndrome with Fatal Outcome in Two Pregnant Women Receiving Antiretroviral Therapy in Guinea Conakry

“…The frequency of serious toxidermia due to nevirapine varies according to the authors. Indeed, if in the majority of cases toxidermia induced by nevirapine are benign and are largely dominated by maculopapular exanthema, the frequency of severe toxidermia is not egligible [7,23,24]. The risk of SJS/TEN patients treated with nevirapine is 0.3 percent [7].…”

Tiapride Associated Toxic Epidermal Necrolysis in an HIV-Infected Patient

“…Genetic predisposition seems to play an important role in adverse drug reactions, as is the case in the association between abacavir hypersensitivity and the presence of class I major histocompatibility complex (MHC) allele HLA-B5701 [12]. Other possible explanations include viral infection and reactivation, increased use of certain drugs, immune reconstitution, elevated serum IgE levels, a Th2 type of cytokine pattern, slow acetylation and decreased anti-oxidant levels [13][14][15][16]. Our case report seems to contradict some of these hypotheses.…”

Risk of nevirapine-associated Stevens-Johnson syndrome among HIV-infected pregnant women: The Medunsa National Pharmacovigilance Centre, 2007 - 2012

“…[13,14] In addition, the greater likelihood of such patients using the drugs at higher dosages than the general population, further predisposes them to SJS. [7,15] Although the first ARV agent was licensed in 1987, South Africa (SA) only began antiretroviral therapy (ART) in 2003. At that time, ARV use was guided by the National Department of Health's Operational Plan for Comprehensive HIV and AIDS Care, Management, and Treatment; this plan was revised in 2010.…”

“…aminopenicillins, sulphonamides, quinolones, cycline antibiotics) [7,12] and antiretroviral (ARV) medications (e.g. nevirapine (NVP), zidovudine (AZT), stavudine (d4T), indinavir, didanosine) [7] being some of the most frequent offending agents.…”

“…[4,5] Typically, the drug reaction develops within the first 6 weeks after the causative drug initiation. [1,[6][7][8][9] Initial symptoms are cough, fever, sore throat and facial swelling. If not detected early, and the offending drug discontinued, skin rash may develop that leads to skin ulcers and skin sloughing.…”