Human Herpesvirus 6 Reactivation in Drug-induced Hypersensitivity Syndrome and DRESS Validation Score

Abstract

We read with great interest the article entitled, “The DRESS Syndrome: A Literature Review” by Cacoub et al.1Cacoub P. Musette P. Descamps V. et al.The DRESS syndrome: a literature review.Am J Med. 2011; 124: 588-597Abstract Full Text Full Text PDF PubMed Scopus (642) Google Scholar The authors classified 172 cases reported as drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome in the literature by using the RegiSCAR scoring system.2Kardraun S.H. Sidoroff A. Valeyrie-Allanore L. et al.Variability in the clinical pattern of cutaneous side-effects of drugs with systemic symptoms: does a DRESS syndrome really exist?.Br J Dermatol. 2007; 156: 609-611Crossref PubMed Scopus (713) Google Scholar They concluded that the vast majority of cases could be defined as “probable/definite” DRESS cases. Among various terms to refer to this syndrome, the criteria for drug-induced hypersensitivity syndrome (DIHS) proposed by a Japanese severe cutaneous adverse reaction group includes human herpesvirus 6 (HHV-6) reactivation,3Shiohara T. Iijima M. Ikezawa Z. Hashimoto K. The diagnosis of a DRESS syndrome has been sufficiently established on the basis of typical clinical features and viral reactivations.Br J Dermatol. 2007; 156: 1083-1084Crossref PubMed Scopus (376) Google Scholar different from that for DRESS reported by Bocquet et al.4Bocquet H. Martine B. Roujeau J.C. Drug-induced pseudolymphoma and drug hypersensitivity syndrome (drug rash with eosinophilia and systemic symptoms: DRESS).Semin Cutan Med Surg. 1996; 15: 250-257Crossref PubMed Scopus (769) Google Scholar Considering that HHV-6 reactivation is rarely detected in patients who develop a milder form of the syndrome, the detection of HHV-6 reactivation is an important marker for the diagnosis of DIHS.Although the authors noted the detection of HHV-6 in this review, the measurement of HHV-6 reactivation was performed in less than half of the cases. Based upon these results, the association between probable/definite DRESS and HHV-6 reactivation remains uncertain. Because the results of this study are dependent on the literature review and are thus subjected to interpretation, this analysis of HHV-6 has considerable limitations.To clarify the association between DRESS validation score and HHV-6 DNA loads in DIHS, we analyzed 30 definite DIHS patients (16 male, 14 female, age range 24-81 years, mean age 55.5±17.4 years) who were treated in our hospital between 1998 and 2010. In these patients, HHV-6 DNA loads in leukocytes were measured every 2-3 weeks after admission. In addition, cytomegalovirus reactivations also were evaluated because fatal complications often resulted from cytomegalovirus infection in this setting.5Asano Y. Kagawa H. Kano Y. et al.Cytomegalovirus disease during severe drug eruptions: report of 2 cases and retrospective study of 18 patients with drug-induced hypersensitivity syndrome.Arch Dermatol. 2009; 145: 1030-1036Crossref PubMed Scopus (58) Google Scholar Our results showed that definite DIHS was consistent with probable/definite DRESS; there was no significant correlation between HHV-6 DNA load and DRESS validation score; cytomegalovirus reactivation was observed markedly in the definite DRESS patients (Figure 1).In conclusion, the DRESS validation score is a useful tool for diagnosis of DIHS/DRESS when the evaluation of HHV-6 is unavailable in clinical practice. We read with great interest the article entitled, “The DRESS Syndrome: A Literature Review” by Cacoub et al.1Cacoub P. Musette P. Descamps V. et al.The DRESS syndrome: a literature review.Am J Med. 2011; 124: 588-597Abstract Full Text Full Text PDF PubMed Scopus (642) Google Scholar The authors classified 172 cases reported as drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome in the literature by using the RegiSCAR scoring system.2Kardraun S.H. Sidoroff A. Valeyrie-Allanore L. et al.Variability in the clinical pattern of cutaneous side-effects of drugs with systemic symptoms: does a DRESS syndrome really exist?.Br J Dermatol. 2007; 156: 609-611Crossref PubMed Scopus (713) Google Scholar They concluded that the vast majority of cases could be defined as “probable/definite” DRESS cases. Among various terms to refer to this syndrome, the criteria for drug-induced hypersensitivity syndrome (DIHS) proposed by a Japanese severe cutaneous adverse reaction group includes human herpesvirus 6 (HHV-6) reactivation,3Shiohara T. Iijima M. Ikezawa Z. Hashimoto K. The diagnosis of a DRESS syndrome has been sufficiently established on the basis of typical clinical features and viral reactivations.Br J Dermatol. 2007; 156: 1083-1084Crossref PubMed Scopus (376) Google Scholar different from that for DRESS reported by Bocquet et al.4Bocquet H. Martine B. Roujeau J.C. Drug-induced pseudolymphoma and drug hypersensitivity syndrome (drug rash with eosinophilia and systemic symptoms: DRESS).Semin Cutan Med Surg. 1996; 15: 250-257Crossref PubMed Scopus (769) Google Scholar Considering that HHV-6 reactivation is rarely detected in patients who develop a milder form of the syndrome, the detection of HHV-6 reactivation is an important marker for the diagnosis of DIHS. Although the authors noted the detection of HHV-6 in this review, the measurement of HHV-6 reactivation was performed in less than half of the cases. Based upon these results, the association between probable/definite DRESS and HHV-6 reactivation remains uncertain. Because the results of this study are dependent on the literature review and are thus subjected to interpretation, this analysis of HHV-6 has considerable limitations. To clarify the association between DRESS validation score and HHV-6 DNA loads in DIHS, we analyzed 30 definite DIHS patients (16 male, 14 female, age range 24-81 years, mean age 55.5±17.4 years) who were treated in our hospital between 1998 and 2010. In these patients, HHV-6 DNA loads in leukocytes were measured every 2-3 weeks after admission. In addition, cytomegalovirus reactivations also were evaluated because fatal complications often resulted from cytomegalovirus infection in this setting.5Asano Y. Kagawa H. Kano Y. et al.Cytomegalovirus disease during severe drug eruptions: report of 2 cases and retrospective study of 18 patients with drug-induced hypersensitivity syndrome.Arch Dermatol. 2009; 145: 1030-1036Crossref PubMed Scopus (58) Google Scholar Our results showed that definite DIHS was consistent with probable/definite DRESS; there was no significant correlation between HHV-6 DNA load and DRESS validation score; cytomegalovirus reactivation was observed markedly in the definite DRESS patients (Figure 1). In conclusion, the DRESS validation score is a useful tool for diagnosis of DIHS/DRESS when the evaluation of HHV-6 is unavailable in clinical practice. This work was partly supported by grants from the Ministry of Education, Culture, Sports, Science and Technology (TS, YK) and the Ministry of Health, Labour and Welfare of Japan (TS) and the Japanese Research Commitee on Severe Cutaneous Adverse Reaction (J-SCAR). The DRESS Syndrome: A Literature ReviewThe American Journal of MedicineVol. 124Issue 7PreviewThe Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) is a severe adverse drug-induced reaction. Diagnosing DRESS is challenging due to the diversity of cutaneous eruption and organs involved. We used the RegiSCAR scoring system that grades DRESS cases as “no,” “possible,” “probable,” or “definite” to classify cases reported in the literature. We also analyzed the clinical course and treatments of the cases. A total of 44 drugs were associated with the 172 cases reported between January 1997 and May 2009 in PubMed and MEDLINE. Full-Text PDF