Drug-induced Hypersensitivity Syndrome(DIHS): A Reaction Induced by a Complex Interplay among Herpesviruses and Antiviral and Antidrug Immune Responses

Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan.
Allergology International 04/2006; 55(1):1-8. DOI: 10.2332/allergolint.55.1
Source: PubMed

ABSTRACT A relationship between viral infections and the simultaneous or subsequent development of allergic inflammation has often been observed in various clinical situations. Recent studies suggest an intimate relationship between reactivations of herpesviruses including human herpesvirus 6 (HHV-6) and the development of a severe systemic hypersensitivity reaction referred to as drug-induced hypersensitivity syndrome (DIHS). This syndrome has several important clinical features that cannot be solely explained by drug antigen-driven oligoclonal expansion of T cells: they include paradoxical worsening of clinical symptoms after discontinuation of the causative drug. In view of the similarity to GVHD or immune reconstitution syndrome (IRS) in clinical manifestations and emergence of viral infections, the clinical symptoms observed during the course of DIHS and GVHD are likely to be mediated by antiviral T cells that can cross-react with the drug and alloantigens, respectively. In considering common intrinsic properties of the causative drugs to potentially induce immunosuppression, reconstitution of a valid immune response to these viruses, which is typically observed in IRS, may be the most crucial process that takes place after withdrawal of the causative drug in patients with DIHS. Thus, this syndrome should be regarded as a reaction induced by a complex interplay among several herpesviruses (EB virus, HHV-6, HHV-7, and cytomegalovirus), antiviral immune responses, and drug-specific immune responses. This review includes discussion of the pathomechanism, the clinical symptoms, laboratory findings, pathological findings and therapy.

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    • "The skin covers a surface area of approximately 1.7 m 2 in an average adult body and receives about one third of the circulating blood. Although the skin is the primary tissue that protects our body from ultraviolet irradiation, infection, microorganisms, and exogenous toxic compounds, it is also one of the tissues where severe adverse reactions caused by administered drugs, such as Stevens–Johnson syndrome (Fritsch and Sidoroff 2000), psoriasis (Tsankov et al. 2000), allergy (Kaplan 1984), drug-induced hypersensitivity syndrome (Shiohara et al. 2006), Lyell syndrome (Saiag et al. 1992), and druginduced photosensitivity (Harber and Baer 1972) are seen. "
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    ABSTRACT: ATP-binding cassette (ABC) transporters transport a variety of substrates across cellular membranes coupled with hydrolysis of ATP. Currently 49 ABC transporters consisting of seven subfamilies, ABCA, ABCB, ABCC, ABCD, ABCE, ABCF, and ABCG, have been identified in humans and they are extensively expressed in various tissues. Skin can develop a number of drug-induced toxicities' such as Stevens–Johnson syndrome and psoriasis. Concentration of drugs in the skin cells is associated with the development of adverse drug reactions. ABC transporters play important roles in absorption and disposition of drugs in the cells; however, the expression pattern of human ABC transporters in the skin has not been determined. In this study, the expression patterns of 48 human ABC transporters were determined in the human skin as well as in the liver and small intestine. Most of the ABCA, ABCB, ABCC, ABCD, ABCE, and ABCF family members were highly or moderately expressed in the skin, while ABCG family members were slightly expressed in the skin. Significant interindividual variability was also observed in the expression levels of those ATP transporters in the skin, except for ABCA5 and ABCF1, which were found to be expressed in all of the human skin samples tested in this study. In conclusion, this is the first study to identify the expression pattern of the whole human ABC family of transporters in the skin. The interindividual variability in the expression levels of ABC transporters in the human skin might be associated with drug-induced skin diseases.
    10/2013; 1(1). DOI:10.1002/prp2.5
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    • "It is possible, however, that immunosuppressive therapy may worsen the infectious complications of DIHS. Some small series have reported the efficacy of intravenous immunoglobulin and plasmapheresis in patients with DIHS (Shiohara et al., 2006). Because of the viral contribution in DIHS, we may need to address the viral infections rather than administering immunosuppressive therapy. "
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    ABSTRACT: Drug-induced hypersensitivity syndrome (DIHS) is a life-threatening idiosyncratic drug reaction, and an early accurate diagnosis is essential for its treatment. We describe a 14-year-old boy with localization-related epilepsy, who developed severe adverse cutaneous and systemic reactions after 3 weeks of carbamazepine administration. During the course of the clinical symptoms, reactivation of human herpesvirus 6 (HHV-6) was proven by detection of the HHV-6 genome in serum and elevation of HHV-6 immunoglobulin G (IgG). He fulfilled the newly established criteria for DIHS. Among eight identified medications that can precipitate DIHS, four are antiepileptic drugs. Establishing a treatment strategy for DIHS is warranted to improve its outcome. Therefore, it is important to raise awareness of DIHS among epileptologists.
    Epilepsia 10/2008; 49(12):2118-21. DOI:10.1111/j.1528-1167.2008.01785.x · 4.58 Impact Factor
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    ABSTRACT: The DRESS (drug rash, eosinophilia and systemic symptoms) syndrome, also known as DIHS (drug-induced hypersensitivity syndrome), is a severe idiosyncratic reaction to several drugs, mainly antiepileptics and antibiotics, which can occasionally produce acute liver failure. In this article we present two cases of the DRESS syndrome presenting with severe acute hepatitis, including the first case of DRESS associated with levetiracetam. Although both cases finally resolved with good outcomes, DRESS can lead to acute liver failure and has a bad prognosis when liver damage is present. Rapid diagnosis is crucial since withdrawal of the offending drug is the key of treatment, while the potential role of corticosteroids is discussed.
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