Herpes zoster involving trigeminal nerve: An early cutaneous predictor of COVID‐19—a case series and review of the literature

To the Editor, Over the past year, clinicians have reported a diverse range of cutaneous manifestations in association with coronavirus disease 2019 (COVID-19) like pernio-like lesions, morbilliform, urticarial, varicelliform, papulo-squamous, purpuric eruptions, and livedo reticularis-like rashes. Although occurrence of herpes zoster in COVID-19 patients has been adequately documented, only a few cases have reported HZ infection as the initial clinical clue to an underlying asymptomatic COVID-19.1 We hereby report a series of six Indian patients where HZ involving the trigeminal nerve branches was the initial cutaneous presentation in the latent pre-symptomatic stage of COVID-19. We came across six patients, four males and two females (M:F = 2:1), with mean age of 58.2 ± 14.2 years (age range 34–76 years) who presented with painful facial vesicles associated with burning sensation during the course of the current COVID-19 pandemic. Only one patient (16.7%) had diabetes, controlled on oral drugs. Examination revealed herpes zoster involving trigeminal nerve branches—ophthalmic (2), maxillary (2), and mandibular (2). (Figure 1) Ocular involvement was noted in four (66.7%), while oral mucosa was involved in two patients. All patients received the standard 7-day oral course of tablet acyclovir (800 mg given five times per day). HZ lesions resolved within 10 days without any further mucocutaneous or ocular complication. After 2–6 days (mean = 4 days) from initial HZ presentation, they experienced fever (100%), malaise (100%), arthralgia (83.3%), anosmia (66.7%), sore throat (66.7%), dry cough (50%), and diarrhea (33.3%). Complete blood count revealed lymphopenia in all patients (mean value: 0.985 × 103/µl; reference range: 1.5–4 × 103/µl). Serology for human immunodeficiency virus, venereal disease research laboratory, and viral hepatitis markers test were negative. RT-PCR test for SARS-CoV-2 from naso- and oro-pharyngeal swab came out positive in all of them. Subsequently, two patients developed severe respiratory distress, requiring hospitalization. Rest of the patients recovered with symptomatic treatment at home. Written informed consent was obtained from all patients included in this study. Tartari et al.2 reported three hospitalized COVID-19 patients, on mechanical ventilation, who developed HZ affecting the maxillary segment. One patient being treated with tocilizumab developed necrotic lesions. Nofal et al. described four cases of HZ involving maxillary division of trigeminal nerve after mean duration of 4.5 days following COVID-19 infection.3 Similar observations were also noted by Shors AR and Bhargava et al.4, 5 Interestingly, a much longer latency period (26 days post-COVID) was highlighted in another study.6 Table 1 summarizes reported cases of HZ (involving the trigeminal nerve branches) associated with COVID-19. Based on current evidence, which is limited to case reports and case series, it is not possible to determine whether COVID-19 increases the risk of HZ. In our study, HZ preceded the diagnosis of COVID-19 by a mean duration of 4 days. None of these patients complained of any symptom suggestive of SARS-CoV-2 infection during initial consultation. Similar to these previous findings, post-herpetic neuralgia and debilitating ocular complications were not encountered in the present study. Lymphocyte count (×103/µl) Reference value: 1.5–4 × 103/µl 42/M 7/F 28/M 9/M V1a a Side not mentioned. V1a a Side not mentioned. V1a a Side not mentioned. V1 (right) 4 days following COVID 5 days following COVID 5 days following COVID 4 days following COVID 0.85 0.95 0.92 0.88 68/F 74/F 71/F V2a a Side not mentioned. V2a a Side not mentioned. V2a a Side not mentioned. 6 days following COVID 5 days following COVID 7 days following COVIDb b Necrotic lesions of HZ were observed. 0.53 0.61 0.47 63/F 56/F Hypertension Dyslipidemia V1a a Side not mentioned. V1a a Side not mentioned. Uncomplicated in both patients 72/M 55/F 76/F 34/M 63/M 49/M Nil Nil Nil Nil Nil Diabetes V1 (left) V1 (right) V2 (left) V2 (left) V3 (right) V3 (left) 3 days preceding COVID 6 days preceding COVID 2 days preceding COVID 4 days preceding COVID 5 days preceding COVID 4 days preceding COVID 0.887 1.2 0.855 0.876 1.1 0.995 The relationship between COVID-19 and the HZ remains poorly understood. Lymphopenia occurs as a result of direct infection of lymphocytes with SARS-CoV-2, activation-induced cell death, and impairment to antiviral responses.4 Ultimately, suppressed T-cell immunity facilitates HZV reactivation. Furthermore, COVID-19 infection-associated physical and emotional stress might also be a triggering factor for VZV reactivation. SARS-CoV-2 led to reactivation of VZV, ascending in a retrograde manner from the nasal cavity where the trigeminal branches are located and provides a plausible explanation to our findings.7 Our study, although limited by a small sample, highlights that HZ associated with low lymphocyte count could be a cutaneous indicator of latent SARS-CoV-2 infection even in patients without any overt COVID-19–related symptom. As we battle the ongoing surge of cases, it would be prudent for dermatologists to be vigilant regarding thorough follow-up of patients presenting with HZ along trigeminal nerve branches and exclude the possibility of COVID-19 to contain the spread of infection. None. The study did not require approval by the local ethics committee considering this is a systematic review.