1152 CORRESPONDENCE
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Advances in dermatology and venereology Acta Dermato-Venereologica
Human Herpesvirus-7 Papular Rash : A Comment to Brazzelli et al .
Francesco DRAGO , Giulia CICCARESE * and Aurora PARODI DISSAL Department of Dermatology . IRCCS A . O . U . San Martino-IST , Largo Rosanna Benzi , 10 , IT-16132 Genoa , Italy . * E-mail : giuliaciccarese @ libero . it
We read with interest the paper by Brazzelli et al . ( 1 ), and would like to make some observations . The case of erythemato-papular exanthem described has been related to human herpesvirus ( HHV ) -7 infection . However , despite suspecting an infectious aetiology , the authors did not examine the palpable lymph nodes or the oral mucosa ( 1 ). In fact , infectious exanthems , both classic and atypical ( 2 , 3 ), are frequently associated with regional / diffuse lymph node enlargement and lesions of the oral mucosa ( enanthems ). The latter may have a different morphology ( macular , maculopapular , erythemato-vesicular , petechial ) that may help to distinguish the causative infectious agent ( 2 , 3 ). Furthermore , Brazzelli et al . ( 1 ) did not specify whether the patient had exanthematous diseases during childhood or if he was vaccinated against them . Finally , his history of recent travel to and from epidemic areas for tropical viruses , such as arbovirus ( Central / South America , sub-Saharan Africa , Asia ), was not investigated ( 3 ).
Regarding the laboratory examinations , it is unclear for which of the many infectious agents listed in the paper ( 1 ) the authors performed serology , and for which they eventually performed counts of DNA copies in blood samples . Incidentally , some of the infectious agents mentioned in the paper are RNA viruses ( HIV and hepatitis C virus ( HCV )) and not DNA viruses . In addition , the authors did not mention the method used for detecting viral DNA / RNA in the blood . The presence and copy number of cytomegalovirus ( CMV ), Epstein Barr virus ( EBV ), human herpesvirus ( HHV ) -6 , HHV-7 , Parvovirus B19 ( B19V ), Coxsackievirus , Echovirus DNA and of HCV and HIV RNA in serum samples can be properly evaluated by calibrated quantitative real-time PCR ( cQPCR ) ( 4 ).
Despite the initial diagnosis of insect bites , serology for Rickettsia conorii was not carried out , although it is responsible for the most frequent rickettsiosis in Europe ( Mediterranean spotted fever ) and is transmitted by the brown dog tick ( 3 ). Furthermore , other common infectious agents that might be responsible for atypical exanthems with erythemato-papular morphology were not checked , such as Streptococcus pyogenes and Staphylococcus aureus among the bacteria , and HHV-8 among the viruses ( 3 ).
We agree with the authors that the detection of circulating HHV-7 DNA in the blood is a marker of active infection ( 1 ), but without the results of HHV-7 serology this finding is incomplete ( 1 ). In fact , HHV-7 antibody titres in the acute phase and after resolution of the exanthem would have allowed the authors to distinguish between primary infection and systemic reactivation ( 5 ). Distinguishing between primary and recurrent infection requires observation of the response of specific IgG subclasses by using an antibody avidity test . Since the change in antibody avidity correlates with time after infection , the presence in the serum of low-avidity antibodies suggests a recent primary infection , whereas the presence of high avidity antibodies indicates a past or recurrent infection ( 6 ).
Finally , not only exanthema subitum , as stated by Brazzelli et al . ( 1 ), but also pityriasis rosea ( PR ), is associated with HHV-7 infection , perhaps with even greater evidence . Indeed , the association of PR with HHV-7 infection is based on several and consistent observations and not on occasional findings . Several studies have identified HHV-6 and HHV-7 DNA by PCR and real-time cq-PCR in plasma , peripheral blood mononuclear cells ( PBMCs ) and skin samples of patients with PR . In addition , cytopathic effects specific for herpesviruses and considered marker of viral replication , were observed in co-cultured mononuclear PBMCs from patients with PR . High levels of interferon α and γ were detected in their sera , and virions resembling herpesviruses were shown in the cellfree supernatants of their co-cultured PBMCs by electron microscopy . Furthermore , HHV-6 viral messenger RNA ( mRNA ) expression by in situ hybridization and HHV-6 and HHV-7 antigens were observed in PR skin lesions ( 7 ). The expression in PR skin lesions of the specific HHV-7 and HHV-6 antigens involved in the late stages of the infection as well as mRNA expressions indicate a productive viral infection and emphasize the role of both viruses in the pathogenesis of the disease ( 8 , 9 ). Regarding indirect diagnosis , significant neutralizing antibodies against HHV-6 and HHV-7 have been observed in patients with PR , indicating an endogenous reactivation ( 8 ). The inverse correlation between titres of anti-HHV-7 neutralizing antibodies and detection of HHV-7 DNA in plasma of patients with PR may imply that humoral responses contribute to limit the systemic reactivation and dissemination of the virus ( 5 , 8 ). In addition , some clinical findings in patients with PR suggest HHV-6 and HHV-7 reactivation rather than primary infections : few familiar cases , poor / absent contagiousness , age of onset , possibility of relapsing ( 10 ) and / or persistent ( 11 ) presentations , and occurrence after or during stressful events ( 5 ) or in patients with altered immune response , such as pregnant women ( 12 ). doi : 10.2340 / 00015555-2768 Acta Derm Venereol 2017 ; 97 : 1152 – 1154
This is an open access article under the CC BY-NC license . www . medicaljournals . se / acta Journal Compilation © 2017 Acta Dermato-Venereologica .