The Variable Clinical Picture of Drug-Induced Hypersensitivity Syndrome/Drug Rash with Eosinophilia and Systemic Symptoms in Relation to the Eliciting Drug

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Drug-induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS) is a life-threatening adverse reaction characterized by skin rashes, fever, leukocytosis with eosinophilia or atypical lymphocytosis, lymph node enlargement, and liver or renal dysfunction. The syndrome develops 2 to 6 weeks after initiation of administration of a specific drug. It has been demonstrated that various herpesvirus reactivations, in addition to human herpesvirus 6, contribute to internal organ involvement and the relapse of symptoms observed long after discontinuation of the causative drugs. A better understanding of the interplay in the development of DIHS/DRESS has implications for safer and more efficient treatment of this syndrome.

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Diagnosis of drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms

The criteria for the diagnosis of DRESS proposed by Bocquet and colleagues4 are as follows: (1) cutaneous drug eruption; (2) hematologic abnormalities, including eosinophilia greater than 1.5 × 109 eosinophils/L or the presence of atypical lymphocytes; and (3) systemic involvement, including adenopathies greater than 2 cm in diameter, hepatitis (liver transaminases values >2 N), interstitial nephritis, interstitial pneumonia, or carditis. The criteria emphasize two important characteristics:

Characteristics of the causative drugs

DIHS/DRESS is caused by a limited number of specific drugs, such as anticonvulsants, allopurinol, and sulfonamides. Box 3 lists drugs that reportedly cause DIHS/DRESS. It remains unknown, however, why a limited number of drugs can cause the development of DIHS/DRESS because they do not have any pharmacologic actions or structural similarities in common.

Various factors may contribute to the development of DIHS/DRESS. The authors have demonstrated that there is a decrease in serum immunoglobulin

Aromatic Anticonvulsants

Anticonvulsant hypersensitivity syndrome is a life-threatening syndrome that occurs after exposure to aromatic anticonvulsants, including CBZ, phenytoin, and phenobarbital. The incidence of this syndrome induced by these anticonvulsants is thought to be in the range of 1 per 1000 to 10,000 exposures.2 Cross-reactivity between CBZ, phenytoin, and phenobarbital may be as high as 70% to 80%;25 this may explain why symptoms persist or recur after switching to another aromatic anticonvulsant. In

Summary

DIHS/DRESS exhibits a broad range of clinical manifestations and laboratory abnormalities that are a result of the interplay of host immune status, the extent of sensitization to the drug, immunologic and pharmacokinetic properties of the drug, and the sites and types of viral reactions associated with this syndrome. They could also induce reactions with a different time sequence. Despite a variable clinical appearance, however, DIHS/DRESS is a distinct clinical entity with highly reproducible

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      Citation Excerpt :

      After 3 days of his admission, the patient recovered his renal function with a good clinico-biological evolution, and a complete weaning of the drugs, and then the patient is transferred in service of rheumatology for adjustment of his hypourecemiant treatment. The term DRESS (drug rush with eosinophilia and systemic symptoms) was initially introduced by bocquet [1], later we realized that it was a systemic reaction so it changed to DRESS (drug reaction with eosinophilia and systemic symptoms) [2], in fact the first symptoms were described in cases induced by anticonvulsant such us carbamazepine and dress syndrome was called at that time AHS (anticonvulsant hypersensivity syndrome) [3] The incidence of DRESS syndrome varies between 1/1000 and 1/10000 [4] with a mortality of 10–20% [5]. The clinical presentation of dress is predominantly cutaneous, with or without visceral involvement, with fever, adenopathy, elevated white blood count, and abnormal liver function.

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    This work was supported in part by grants from the Ministry of Education, Sports, Science, and Culture of Japan (to Y.K. and T.S.) and Health and Labo Sciences Research grants from the Ministry of Health, Labor, and Welfare of Japan (to T.S.).

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