Carbamazepine Hypersensitivity Syndrome Triggered by a Human Herpes Virus Reactivation in a Genetically Predisposed Patient

Calligaris, Lorenzo; Stocco, Gabriele; Iudicibus, Sara De; Marino, Sara; Decorti, Giuliana; Barbi, Egidio; Carrozzi, Marco; Marchetti, Federico; Bartoli, Fiora; Ventura, Alessandro

doi:10.1159/000189202

Cited by 13 publications

(10 citation statements)

References 49 publications

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“…Fever was present in all patients described in these reports. Edema, predominantly on the face, was observed with a relatively high frequency [35, 37, 39–44, 47–49, 52], as were lymphadenopathy [35, 36, 39, 41–43, 45, 46, 49–51], hypereosinophilia [35–40, 42–52], and atypical lymphocytes [35, 36, 38–40, 42, 44, 46, 47, 52]. Internal organ involvement manifested itself largely as liver dysfunction, with elevated levels of liver enzymes [35–46, 48–50, 52] and cholestatic hepatitis with hepatocellular insufficiency [51].…”

Section: Resultsmentioning

confidence: 99%

The Link between Hypersensitivity Syndrome Reaction Development and Human Herpes Virus-6 Reactivation

Pritchett

Nanau

Neuman

2012

International Journal of Hepatology

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Background. There are challenges in the clinical diagnosis of drug-induced injury and in obtaining information on the reactivation of human herpes viruses (HHV) during idiosyncratic adverse drug reactions. Objectives. (i) To develop a unified list of drugs incriminated in drug-induced hepatotoxicity and severe cutaneous reactions, in which drug hypersensitivity leads to HHV-6 reactivation and further complication of therapy and recovery and (ii) to supplement the already available data on reporting frequencies of liver- or skin-induced cases with knowledge of individual case reports, including HHV-6 reactivation and briefly introducing chromosomally integrated HHV-6. Data Sources and Extraction. Drugs identified as causes of (i) idiosyncratic reactions, (ii) drug-induced hypersensitivity, drug-induced hepatotoxicity, acute liver failure, and Stevens-Johnson syndrome, and (iii) human herpes virus reactivation in PubMed since 1997 have been collected and discussed. Results. Data presented in this paper show that HHV-6 reactivation is associated with more severe organ involvement and a prolonged course of disease. Conclusion. This analysis of HHV-6 reactivation associated with drug-induced severe cutaneous reactions and hepatotoxicity will aid in causality assessment and clinical diagnosis of possible life-threatening events and will provide a basis for further patient characterization and therapy.

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Section: Resultsmentioning

confidence: 99%

The Link between Hypersensitivity Syndrome Reaction Development and Human Herpes Virus-6 Reactivation

Pritchett

Nanau

Neuman

2012

International Journal of Hepatology

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“…[2] Drugs commonly associated with DRESS are carbamazepine, phenytoin, phenobarbitone, lamotrigine, minocycline, allopurinol, dapsone, diltiazem, abacavir, nevirapine and non-steroidal antiinflammatory drugs like ibuprofen, etc. [1,3,4] A simple drug etiology cannot explain all the features of DIHS, like its delayed onset, paradoxical worsening of clinical symptoms after stopping the causative drug and multiple organ system failures in a stepwise manner. [5] Now, it is postulated that an interplay of a virus and a drug with the immune system of the affected person leads to this clinically challenging condition.…”

Section: Discussionmentioning

confidence: 99%

Drug-induced hypersensitivity syndrome with human herpesvirus-6 reactivation

Riyaz

Sarita

Arunkumar

et al. 2012

Indian J Dermatol Venereol Leprol

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A 45-year-old man, on carbamazepine for the past 3 months, was referred as a case of atypical measles. On examination, he had high-grade fever, generalized itchy rash, cough, vomiting and jaundice. A provisional diagnosis of drug hypersensitivity syndrome to carbamazepine was made with a differential diagnosis of viral exanthema with systemic complications. Laboratory investigations revealed leukocytosis with eosnophilia and elevated liver enzymes. Real-time multiplex polymerase chain reaction (PCR) on throat swab and blood was suggestive of human herpesvirus-6 (HHV-6). Measles was ruled out by PCR and serology. The diagnosis of drug-induced hypersensitivity syndrome (DIHS) was confirmed, which could explain all the features manifested by the patient. HHV-6 infects almost all humans by age 2 years. It infects and replicates in CD4 T lymphocytes and establishes latency in human peripheral blood monocytes or macrophages and early bone marrow progenitors. In DIHS, allergic reaction to the causative drug stimulates T cells, which leads to reactivation of the herpesvirus genome. DIHS is treated by withdrawal of the culprit drug and administration of systemic steroids. Our patient responded well to steroids and HHV-6 was negative on repeat real-time multiplex PCR at the end of treatment.

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“…The patients usually develop a hypersensitivity reaction between 2 and 12 weeks after starting medicine. [6] It has been postulated that metabolites and not the parent drug are the causal agents.…”

Section: Discussionmentioning

confidence: 99%

Genetic predisposition to oxcarbazepine induced Stevens-Johnson syndrome

Wal¹,

Wal²,

Pandey³

et al. 2011

Indian Journal of Critical Care Medicine

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Stevens–Johnson syndrome (SJS) is a rare immunologic reaction that may involve skin or various mucosal surfaces. The etiology may range from multiple pharmacologic agents to viral infections. Associated findings can range from minimal skin and mucosal involvement to extensive dermal exfoliation, nephritis, lymphadenopathy, hepatitis, and multiple serologic abnormalities. We report a female patient of 38 years with a history of drug allergy who was administered oxcarbazepine for the management of right partial bronchial seizure due to left parasagittal mass lesion following which she developed papular rashes all over the body and diagnosed as SJS. Although carbamazepine (CBZ) is the most common cause of SJS, a new anticonvulsant, oxcarbazepine, which is structurally related to CBZ, has been shown to induce SJS.

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Carbamazepine Hypersensitivity Syndrome Triggered by a Human Herpes Virus Reactivation in a Genetically Predisposed Patient

Cited by 13 publications

References 49 publications

The Link between Hypersensitivity Syndrome Reaction Development and Human Herpes Virus-6 Reactivation

The Link between Hypersensitivity Syndrome Reaction Development and Human Herpes Virus-6 Reactivation

Drug-induced hypersensitivity syndrome with human herpesvirus-6 reactivation

Genetic predisposition to oxcarbazepine induced Stevens-Johnson syndrome

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