Shifts in the number of pityriasis rosea diagnoses during the COVID-19 pandemic: Insights on a viral etiology?
Pityriasis rosea (PR) is an acute papulosquamous exanthem that classically begins with an enlarging, salmon-colored, scaly papule or plaque on the trunk. This “herald patch” is followed by similar smaller lesions, whose long axes are oriented along skin cleavage lines, resulting in a Christmas tree pattern.1 A viral etiology has been proposed, with much focus on human herpesvirus-6 (HHV-6), a ubiquitous beta-herpesvirus.1,2 Despite being a self-limited eruption, PR has been associated with pregnancy complications, especially when onset occurs in early gestation.2 Given the associations of PR with HHV-6B viral load and adverse events in pregnancy,2 clarifying the viral etiology of PR to assess the potential role of antivirals in vulnerable populations (i.e., pregnant patients) may be of clinical benefit.
Studying the incidence of PR during the COVID-19 pandemic may shed light on the relationship between HHV-6 and PR. Increased proinflammatory chemokines secondary to SARS-CoV-2 infection have been hypothesized to lead to HHV-6 reactivation and subsequent PR.1 In vitro, SARS-CoV-2 antigen has also been shown to up-regulate levels of OX40 (CD134),3 a CD4+ T-cell receptor that serves as the main entry receptor for HHV-6B. Clinically, a few studies have demonstrated that HHV-6 reactivation, which rarely occurs in healthy individuals, manifests in 21% to 48% of patients with acute COVID-19 infection.4–6 However, a link between SARS-CoV-2, HHV-6, and PR has only been demonstrated anecdotally.7 In light of these studies and recent data that suggest an increase in HHV-6 reactivation during the COVID-19 pandemic,4–6 an increase in PR during this time period may further support the hypothesis that HHV-6 contributes to PR pathogenesis. Therefore, we evaluated the shifts in the number of PR diagnoses before and after the onset of the COVID-19 pandemic using All of Us, a National Institutes of Health research database that aims to provide medical record data for over 1 million Americans, including those belonging to historically underrepresented populations.8
All PR cases were identified using SNOMED-CT code 77252004 or ICD-10-CM code L42. To ensure equal time representation, the dates before and after onset of the COVID-19 pandemic were set to December 1, 2017 to December 1, 2019 and January 1, 2020 to January 1, 2022, respectively. We performed a one-tailed, one-proportion Z-test, with a null hypothesis representing no difference in the number of PR diagnoses between the two timeframes. A P value ≤0.05 was considered statistically significant. This study was approved by the Baylor College of Medicine institutional review board.
Of the 327,654 participants currently enrolled in the database, 140 were diagnosed with PR within our established timeframe. Within this cohort, the percentage of people aged 18 to 31, 32 to 64, and 65+ were 28%, 60%, and 12%, respectively, with the average age being 44 (standard deviation 18). Regarding race, 43%, 25%, and 4% identified as White, Black, and Asian, respectively; 2% were of mixed race, and 26% did not provide racial data. In terms of ethnicity, 72% were non-Hispanic, 25% were Hispanic, and 4% were of unknown ethnicity. There were approximately threefold more individuals diagnosed with PR before the pandemic onset compared to after (107 vs 33, P < 0.0001) (Table 1).
Table 1.
Diagnoses of pityriasis rosea before and after onset of the COVID-19 pandemic*
| Before COVID-19 | 95% CI | After COVID-19 | 95% CI | P value | |
|---|---|---|---|---|---|
| Individuals with PR diagnosis | 107/140 (76%) | 0.69–0.84 | 33/140 (24%) | 0.16–0.31 | <0.0001 |
Before pandemic: December 1, 2017, to December 1, 2019; after pandemic, January 1, 2020, to January 1, 2022. CI indicates confidence interval.
Our results indicate that the frequency of PR decreased during the pandemic, which does not support the hypothesis that HHV-6 plays a role in the etiology of PR, assuming that there is a positive relationship between COVID-19 and HHV-6, as suggested by recent preliminary clinical studies. While Nussbaum et al also found a decrease in PR prevalence during the COVID-19 pandemic,9 other Turkish studies have reported an increase.10–12 Interestingly, studies that demonstrated an increase in PR prevalence examined disease frequency only 1 to 2 months after the onset of the pandemic,10–12 whereas studies that demonstrated a decrease in PR prevalence, including ours, examined disease frequency 1 to 2 years after the onset of the pandemic.9 The reason for this discrepancy is unclear; the authors speculate that perhaps the novelty of SARS-CoV-2 elicited a stronger OX40-related response in the early stages of the pandemic, which then led to HHV-6 reactivation and a subsequent increase in PR during the initial months of the pandemic.
Because OX40 levels are also significantly correlated with pro-inflammatory chemokines and HHV-6B viral load in drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, a severe cutaneous drug reaction,13 analyzing DRESS prevalence during the COVID-19 pandemic may further clarify the role of OX40 and preferential HHV-6 reactivation. Unfortunately, there were not enough participants with a diagnosis of DRESS (n = 8) in the All of Us database to perform any meaningful analysis.
While our sample contains an inclusive group of the US population, it is not without limitations. The All of Us database does not include adolescents under 18, a population commonly affected by PR. Additionally, an overall decrease in office visits due to lockdown, quarantine, and/or patient preference may underestimate the incidence of PR during the pandemic. It should also be noted that Black individuals in the All of Us database are overrepresented compared to the proportion reported by the US Census (21% vs 13.6%).14 However, this should not impact our results, as PR does not demonstrate a racial bias.15
In conclusion, we found a decrease in PR diagnoses in the era of COVID-19. Since there is data that suggest SARS-CoV-2 antigen stimulates HHV-6 reactivation, our results suggest that HHV-6 does not play a role in the etiology of PR. Further studies are warranted, however, as the overall literature provides mixed results regarding PR prevalence during the pandemic.
—Harrison Zhu, BSA
Baylor College of Medicine, Houston, TX
HHV-6 Foundation, Santa Barbara, CA
http://orcid.org/0000-0002-0458-044X
Harrison.zhu@bcm.edu
—Vicky Ren, MD
Department of Dermatology
Baylor College of Medicine, Houston, TX
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