To the Editor:
The article by Nussbaum et al1 published in your journal allows us to make some observations about the pathogenesis of pityriasis rosea (PR). The authors stated that PR has inconsistent association with human herpesvirus (HHV)-6 and HHV-7.1 A large body of evidence from studies by different authors highlighted a close relationship between PR and systemic active infection with both HHV-7 and HHV-6.2,3 For a few exanthematous diseases, there is so much evidence favoring a viral etiology. Several studies have identified HHV-6 and HHV-7 DNA by polymerase chain reaction in plasma, a direct marker of viral replication, in peripheral blood mononuclear cells and in lesional skin of patients with PR; HHV-6 and HHV-7 messenger RNA expression and specific antigens have been demonstrated in PR skin lesions by in situ hybridization and immunohistochemistry, respectively. Furthermore, plasma load of HHV-6 and HHV-7 is directly associated with systemic symptoms and with low level of humoral neutralizing antibodies, further supporting that PR is associated with HHV-7 or HHV-6 active infection. Lastly, herpesvirus virions in various stages of morphogenesis were detected by electron microscopy in PR skin lesions and in the supernatant of cocultured peripheral blood mononuclear cells of patients with PR.2,3
Several clinical and laboratory observations suggest HHV-6/7 reactivation in PR rather than a primary infection: the few and sporadic familial cases, the almost absent contagiousness, the age of onset, the possibility of recurrences, the occurrence after stress or in state of altered immunity, as in pregnancy or other infections and, lastly, the presence of neutralizing antibodies against HHV-6 and HHV-7.
The credit given to the role of HHV-6/7 systemic reactivation in PR pathogenesis is easily detectable from the quotes reported by different authors in the articles about PR during COVID-19 and after COVID-19 vaccination.4 Although Nussbaum et al1 found that PR diagnoses have declined during the pandemic, other authors reported a different incidence and even a strong increase in the PR cases during the SARS-CoV-2 pandemic compared with the previous year.4,5 The authors’ hypotheses that if the etiology of PR is associated with HHV-6/7 the number of PR diagnoses during the pandemic should be reduced as the number of other viral infections,1 runs absolutely counter to the PR pathogenesis. Indeed, PR is not related to a primary infection but to an endogenous viral reactivation, as in the case of shingles and varicella-zoster virus. Therefore, the possible decrease of PR diagnoses cannot confirm an etiology associated with a viral reactivation. Considering the self-limiting disease and the pandemic closure practices, we think it is more likely that many patients have not consulted a dermatologist.
The psychologic stress linked to the pandemic and the immunosuppression associated with SARS-CoV-2 infection may act in enabling the reactivation of latent infections, such as HHV-6/7, causing, thereby indirectly, the onset of PR. Lastly, because concurrent reactivation of other HHVs was described in patients with COVID-19 and such coinfections may heavily affect the course of the disease,4 we emphasize the relevance of looking for any viral reactivation in patients infected with SARS-CoV-2.
Conflicts of interest
None declared.
Footnotes
Funding sources: None.
IRB approval status: Not applicable.
References
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