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Drug-induced hypersensitivity syndrome after initiation of darunavir and raltegravir

Walter de Araujo Eyer-Silva1 Maria Alessandra Leite Freire2 Guilherme Almeida Rosa da Silva1

1Centro de Ciências Biológicas e da Saúde, Hospital Universitário Gaffrée e Guinle, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. 2Programa Municipal de HIV/Aids de Miracema, Miracema, RJ, Brasil.

DOI: 10.1590/0037-8682-0373-2016

She appeared ill and icteric (Figures A/C), which she attributed to Zika virus infection.

A 38-year-old HIV-infected African-Brazilian woman on virologic treatment failure presented with a 5-day history of fever, malaise, and a cutaneous eruption that started on the face. She appeared ill and icteric (Figures A/C), which she attributed to Zika virus infection. Five weeks previously, a novel genotype-guided antiretroviral combination (raltegravir and ritonavir-boosted darunavir) was initiated. Previous episodes of cryptococcosis left visual and auditory deficits. She had experienced multiple antiretroviral agents, and her CD4 count was 521/mm3.

The rash was characteristic of drug-induced hypersensitivity syndrome (DIHS): facial edema, mainly periorbital, with follicular accentuation (Figures A/F). Caudal progression (Figure B ), scaling (Figure G-H), cheilitis (Figure E), and Terry’s nails (Figure I) followed. An ocular secretion gave the face a yellowish-crusted appearance (Figure J). There was leukocytosis without eosinophilia, elevated liver transaminases, and conjugated hyperbilirubinemia. She died of respiratory failure in the intensive care unit 9 days later.

Also known as a drug reaction with eosinophilia and systemic symptoms (DRESS), DIHS is a severe, idiosyncratic, multiorgan disorder that arises weeks after initiation of a drug. Eosinophilia is absent in approximately 40% of cases. Aromatic anticonvulsants are prominent culprits. Diverse antiretroviral and other antimicrobial agents may induce DIHS/DRESS1,2. Raltegravir, the first HIV integrase inhibitor, is considered to have few adverse effects. Five previous cases of raltegravir-associated DIHS/DRESS were reported3. Notably, 5 out of 6 and 5 out of 5 cases occurred in women and patients of African ancestry, respectively (ethnicity unknown in one). The most important treatment intervention is early withdrawal of the offending drug.

Figure 1 


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2. Miller Quidley A, Bookstaver PB, Gainey AB, Gainey MD. Fatal clindamycin-induced drug rash with eosinophilia and systemic symptoms (DRESS) syndrome. Pharmacotherapy. 2012;32(12):e387-92. [ Links ]

3. Ripamonti D, Benatti SV, Filippo E, Ravasio V, Rizzi M. Drug reaction with eosinophilia and systemic symptoms associated with raltegravir use: case report and review of the literature. AIDS. 2014;28(7):1077-9. [ Links ]

2Informed consent: Informed consent of the patient was obtained for publication of the case and images.

3Notice: The present case was published in abstract form at the “Global HIV Clinical Forum – Integrase Inhibitors”, an international meeting held in Durban, South Africa, on July 16th, 2016 (Abstract O_06).

Received: September 11, 2016; Accepted: October 21, 2016

Corresponding author: Dr. Walter de Araujo Eyer-Silva. e-mail:walter.eyer@ig.com.br

Conflict of interest: The authors declare that there is no conflict of interest.