Raltegravir-induced Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome – Implications for clinical practice and patient safety

Abstract

This case report describes two severe antiretroviral drug adverse reactions that occurred in the same patient. A 55-year-old HIV-positive African woman received a single epidural triamcinolone injection for pain relief of postherpetic neuralgia. Forty-one days later, she developed severe iatrogenic Cushing's syndrome due to the drug-drug interaction between triamcinolone and her boosted protease inhibitor therapy. The patient's antiretroviral regimen was thus changed to replace her protease inhibitor with the integrase inhibitor raltegravir. Shortly after commencing the drug, the patient developed a severe adverse drug reaction manifesting as Drug Reaction (or Rash) with Eosinophilia and Systemic Symptoms (DRESS) syndrome. First described in 1996, this hypersensitivity syndrome presents with severe skin reaction as well as fever, rash, lymphadenopathy and internal organ involvement with marked eosinophilia. Clinicians should be aware of raltegravir-induced DRESS syndrome as well as the potential for drug-drug interactions due to protease inhibitor-based therapy.

Extensive pulmonary involvement with raltegravir-induced DRESS syndrome in a postpartum woman with HIV

“…Although raltegravir-induced DRESS syndrome is highly uncommon, our is the third documented case,14 15 which highlights the possibility that raltegravir may be associated with DRESS syndrome more often than previously believed.…”

“…Based on the exclusion of other potential causes, as well as these new biochemical findings, a diagnosis of DRESS syndrome was made and raltegravir was identified as the most likely cause given the temporal relationship of her clinical symptoms and timing of the initiation of raltegravir. Additionally, a literature review revealed two prior cases of DRESS associated with raltegravir 14 15. Of note, the pulmonary nodules were suspected to be secondary to DRESS syndrome versus an infectious process as all cultures were unrevealing.…”

“…Although DRESS has also been documented in association with antiretroviral therapy (abacavir,1–5 nevirapine6–11 and efavirenz12 13) for HIV-1, there have only been two reported cases associated with raltegravir 14 15. Additionally, pulmonary involvement is a rare clinical characteristic of DRESS syndrome (present in only 5% of the 151 cases evaluated in a systematic review of DRESS syndrome case reports16).…”

Eosinophilia in Patients Infected with Human Immunodeficiency Virus

“…Of note, virtually all HIV antiretroviral agents can cause rash, but very few are associated with eosinophilia, such as drug reaction with eosinophilia and systemic symptoms (DRESS), which has been well-described with nevirapine and raltegravir [11–13]. …”

Antiviral Drug Allergy

“…However, many of the rash events have been confounded by use of concomitant medications associated such as NNRTIs, ABC and protease inhibitors. More recently there have been cases of raltegravir associated DRESS/DIHS and SJS/TEN with three separate case publications of raltegravir associated DRESS/DIHS syndrome all in women of African descent 60-62 . A newly approved integrase inhibitor, dolutegravir has not been associated with rash.…”