Abstract
Great strides have been made in the understanding of the pathogenesis and diversity of the clinical symptoms of severe cutaneous adverse drug reactions in the last decade. Among them, drug-induced hypersensitivity syndrome (DiHS) offers a unique opportunity to link between viral infections and the development of severe cutaneous adverse drug reactions, due to its strong association with human herpesvirus 6 infection. This syndrome has several unique features that cannot be solely explained by a drug antigen-driven T-cell activation: they include the delayed onset, paradoxical deterioration of clinical symptoms after withdrawal of the causative drug; unexplained crossreactivity to unrelated multiple drugs; and a variety of long-term sequelae. Dramatic expansions of Tregs observed during the acute stage of DiHS could explain the delayed onset and result in sequential occurrence of viral reactivations. A gradual loss of Treg function occurring after the resolution of DiHS could increase the risk of developing autoimmune diseases as the long-term sequelae. Thus, early recognition of clinical symptoms of DiHS and the frequent monitoring of viral reactivations are essential in improving the short-term or long-term outcomes of DiHS.
Financial & competing interests disclosure
This work was supported in part by a research grant-in-aid for scientific research from the Japanese Ministry of Education, Culture, Sports, Science and Technology (to T Shiohara) and health and labor science research grants from the Ministry of Health, Labor, and Welfare of Japan (to T Shiohara). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Notes
The diagnosis is confirmed by the presence of the seven criteria above (typical DiHS) or of five of the seven (atypical DiHS).
†This can be replaced by other organ involvement, such as renal involvement.ALT: Alanine aminotransferase; HHV-6: Human herpesvirus 6.
Data taken from Citation[14].
†Three or more required.
Data taken from Citation[16].