Brief reportNevirapine-induced toxic epidermal necrolysis and toxic hepatitis treated successfully with a combination of intravenous immunoglobulins and N-acetylcysteine
Introduction
For HIV-infected patients, it is common practice to continue treatment despite mild side effects, such as mild rashes, which generally regress and disappear spontaneously after a few weeks [1]. We report on an HIV-positive patient with a rapidly progressive toxic epidermal necrolysis (TEN), combined with toxic hepatitis which was caused by nevirapine (NVP). Treatment with a novel combination of intravenous immunoglobulins (IVIG) and N-acetylcysteine (NAC) resulted in an exceptionally fast recovery.
Section snippets
Case report
A 39-year-old African male with known HIV infection presented at our emergency ward with a painful mouth and sore throat. The complaints had begun 1 week earlier. He had been using chlorhexidine mouthwash for 4 days without benefit. There were no other symptoms. On physical examination, a severe stomatitis was seen with hemorrhagic crusts and white nonadherent plaques but no visible necrotic lesions. There were no other mucocutaneous lesions and vital parameters were consistent with a mild
Discussion
SJS and TEN (or Lyell's syndrome) form part of a spectrum of drug-induced, life-threatening, blistering skin conditions. The spectrum is determined by the extent of skin detachment: less than 10% is defined as SJS, more than 30% as TEN with a gray zone in-between [2], [4]. Patients generally develop flu-like prodromal symptoms, like fever, sore throat, and malaise, usually within the first 2 months of causative therapy. After a few days, fever becomes persistent and mucocutaneous lesions
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A review of toxic epidermal necrolysis management in Japan
2017, Allergology InternationalUse of etanercept to treat toxic epidermal necrolysis in a human immunodeficiency virus-positive patient
2013, Dermatologica SinicaCitation Excerpt :HIV-seropositive patients are more susceptible to cutaneous adverse drug reactions than the general population are.3,5 Furthermore, HIV-positive individuals have been shown to have a poorer prognosis5 and longer hospitalization period than those who are HIV negative.6,7 The exact mechanisms underlying this augmented reaction in HIV-positive patients are still unclear, but exposure to multiple drugs and the presence of immune disturbances may be contributing factors.5
Insights into the role of bioactivation mechanisms in the toxic events elicited by non-nucleoside reverse transcriptase inhibitors
2012, Advances in Molecular ToxicologyCitation Excerpt :Although the reasons for the adverse effects of NVP are still unclear, increasing evidence suggests that NVP bioactivation is required to initiate the toxic events induced by the parent drug. The reported fast recovery of a patient suffering from NVP-induced toxic epidermal necrolysis and toxic hepatitis, upon treatment with a continuous infusion of human immunoglobulins and a high dose (300 mg/day) of N-acetylcysteine (NAC) [61], provided relevant clinical support for both the involvement of metabolic activation in the NVP toxic response and the importance of adequate GSH levels in the detoxification of reactive NVP metabolites. Although circumstantial, this fast recovery may have stemmed from GSH replenishment in the HIV-infected patient [62], leading to decreased oxidative stress and/or induced detoxification of reactive metabolites.
Diagnosis and management of HIV drug hypersensitivity
2008, Journal of Allergy and Clinical ImmunologyCitation Excerpt :Patients with AIDS and TEN do not appear to exhibit a significantly worse outcome.44 Cases have been reported to respond to treatment with IVIG and, in 1 reported case, intravenous immunoglobulin plus N-acetylcystine was associated with rapid recovery.45,46 Hepatotoxicity associated with nevirapine has been described in at least 2 distinct patterns: an early form of liver enzyme elevation that occurs less than 6 weeks after the initiation of therapy and is associated with cutaneous hypersensitivity and/or eosinophilia, and a delayed variant that is usually devoid of extrahepatic findings and manifests after more than 2 to 3 months of exposure.
Erythema multiforme and related disorders
2007, Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and EndodontologyCitation Excerpt :However, unlike full-thickness burns, the underlying dermis in SJS and TEN is intact and epidermal regrowth usually commences within 3 to 4 days with no need of epidermal grafts.129 Overall, the following aspects should be considered in management of EMM, SJS, and TEN patients: withdrawal of causative drugs,45,61 supportive care and antibiotics,6,130 systemic corticosteroids,129,131-139 and other immunosuppressants and immunomodulating agents23,140-167 (Table VI). EM minor usually runs a mild clinical course, each episode lasting 2 to 3 weeks.
Toxic epidermal necrolysis and Stevens-Johnson syndrome: A review
2011, Critical Care MedicineCitation Excerpt :Administration of N-acetylcysteine enhances the oxidant buffering capacity of glutathione and inhibits nuclear factor kappa B, a transcription factor induced by tumor necrosis factor alpha and interleukin-6 (139). Treatment with N-acetylcysteine has been published with good results (140, 141), but numbers are small and controlled trials have not been performed. Plasmapheresis has been used in several case reports and small studies, mostly in adult patients but also in children as young as 1 yr.