Pityriasis rosea: An update with a critical appraisal of its possible herpesviral etiology Francesco Drago, MD, a Francesco Broccolo, MD, b and Alfredo Rebora, MD a Genoa and Monza, Italy Pityriasis rosea is an acute, self-healing exanthem characterized by oval erythematous-squamous lesions of the trunk and limbs, that usually spares face, scalp, palms, and soles. Constitutional symptoms, which have the character of true prodromes; clinical features, which resemble those of the known exanthems; and many epidemiologic data all suggest an infectious origin. A host of infectious agents have been incriminated, but, recently, human herpesvirus 6 and 7 have been extensively studied. The goal of this review is to outline the epidemiologic, clinical, histologic, and ultrastructural features of pityriasis rosea, but mainly to stress its possible human herpesvirus nature. In addition, clues have been added to help the reader to go through the complex subtleties of the virologic investigation. ( J Am Acad Dermatol 2009;61:303-18.) DEFINITION Described by Gibert 1 in 1860, but recognized as early as in 1798 by Willan, 2 pityriasis rosea (PR) is an acute, self-healing exanthem characterized by oval erythematous-squamous lesions of the trunk and limbs, usually sparing face, scalp, palms, and soles. Epidemiology Numerous studies have tried to establish PR prevalence. 3 Bjo ¨rnberg and Hellgren 4 estimated it at 1.31%, but, taking into account the atypical forms and the forms that nondermatologists fail to diag- nose, this figure is possibly underestimated. Most epidemiologic studies have been done in Asia or in Africa. In fact, PR seems to be more frequent in Africa, representing about 2% of all patients seen, although wide variations have been observed rang- ing from 0.5% in Kenya to 2.6% in South Africa. 5 According to Truhan 6 and Chuang et al, 7 the age of maximum incidence is between 10 and 35 years or 10 and 29 years for others 8,9 (youngest patient aged 3 months, 10 oldest 83 years 4 ). The female:male ratio is 1.5:1, 7 but Bjo ¨rnberg and Hellgren 4 did not find any statistically significant variation between sexes. A higher prevalence in cold seasons has been claimed, 7,8 but controversial opinions remain, 3 mainly related to the occurrence in clusters, a phe- nomenon well known to the practicing dermatolo- gist. In fact, Messenger et al 11 found that clustering occurs only in women, whereas Chuh et al, 12 who examined 1379 patients from 3 different geographic areas (Minnesota, Kuwait, and Turkey), found sig- nificant clustering in both sexes, although in differ- ent seasons. In our experience on 430 patients, PR occurs uniformly all during the year. Rarely is PR reported to occur within the family or any circum- scribed environment. Bjo ¨rnberg and Hellgren, 4 how- ever, found 5% prevalence and maintain that the phenomenon is more common than generally as- sumed. In our series, only in two cases were family episodes observed (father/daughter and fiance ´e). CLINICAL MANIFESTATIONS Prodromal symptoms Often disregarded by textbooks, constitutional symptoms are more frequent than generally thought. Malaise, nausea, loss of appetite, headache, difficulty in concentration, irritability, gastrointestinal and Abbreviations used: CQ: calibrated quantitative HA: high avidity HHV: human herpesvirus mRNA: messenger RNA PBMC: peripheral blood mononuclear cell PCR: polymerase chain reaction PR: pityriasis rosea RT: real time From the Department of Endocrinological and Metabolic Sciences, Section of Dermatology, University of Genoa a ; and the De- partment of Clinical Medicine and Prevention, University of Milano-Bicocca, Monza. b Funding sources: None. Conflicts of interest: None declared. Reprints not available from the authors. Correspondence to: Francesco Drago, MD, Clinica Dermatologica dell’Universita `, Viale Benedetto XV 7, 16132, Genova, Italy. 0190-9622/$36.00 ª 2008 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2008.07.045 303