|LETTER TO EDITOR
|Ahead of print publication
Herpes zoster reactivation after COVID-19 vaccination in patients with autoimmune diseases
Srinivasan Sanjay1, Deepika Ponnuru2, Sharath Kumar2, Vijay K R Rao3, Ankush Kawali1, Padmamalini Mahendradas1
1 Department of Uveitis and Ocular immunology, Narayana Nethralaya, Bangalore, India
2 Optima Arthritis and Rheumatology Clinic, Bangalore, India
3 Divisha Arthritis and Medical Center and Department of Rheumatology Manipal Hospital, Bangalore, India
|Date of Submission||26-Jun-2021|
|Date of Acceptance||02-Sep-2021|
|Date of Web Publication||26-Nov-2021|
Department of Uveitis and Ocular immunology, Narayana Nethralaya, 121/C Chord Road, Rajajinagar 1st R block Bengaluru 560010
Source of Support: None, Conflict of Interest: None
|How to cite this URL:|
Sanjay S, Ponnuru D, Kumar S, R Rao VK, Kawali A, Mahendradas P. Herpes zoster reactivation after COVID-19 vaccination in patients with autoimmune diseases. Indian J Rheumatol [Epub ahead of print] [cited 2022 Jan 16]. Available from: https://www.indianjrheumatol.com/preprintarticle.asp?id=331250
Patients with autoimmune diseases were given priority for vaccination during Phase 2 of Indian COVID-19 vaccination program (for those aged between 45 and 60 years). However, trials for COVID-19 vaccines did not include individuals with autoimmune inflammatory rheumatic diseases (AIIRDs). The efficacy and safety of these vaccines in this population are yet to be fully delineated. We report 3 Asian Indian patients, 2 females and a male with AIIRD who developed herpes zoster (HZ) shortly (3–30 days) after vaccination with COVISHIELD™.
| Case 1|| |
This case 1 was a 63-year-old male with a history of type 2 diabetes mellitus and hypertension. He had developed seropositive rheumatoid arthritis (RA) a decade earlier and presently was on treatment with oral hydroxychloroquine (HCQ) 200 mg once a day and oral methotrexate (MTX) 15 mg/week. He was diagnosed with posterior scleritis by the ophthalmologist and had 2 recurrences after cessation of oral steroids. After consultation with the rheumatologist, he received intravenous cyclophosphamide 1000 mg pulse therapy. One week after the first dose of cyclophosphamide, the patient received COVISHIELD™ vaccination and 2 weeks later, he developed herpes zoster ophthalmicus (HZO) with Sclero-uveitis with choroidal vitiligo. He was continued on systemic steroids. He was started on valacyclovir 1000 mg three times daily for 2 weeks and tapering dose of prednisolone eye drops as well as acivir eye ointment to the lids and eye. He had a relapse of kerato-uveitis in both the eyes after stopping the antiviral and steroid therapy. Cyclophosphamide was resumed after 2 weeks with maintenance of oral valacyclovir. No relapse of Herpetic uveitis was noted in 1 month follow up duplicated. He took the second dose of COVISHEILD vaccination uneventfully 6 weeks after the 1st dose.
| Case 2|| |
This case 2 was a 60-year-old female with a clinical diagnosis of polymyalgia rheumatica associated with inflammatory arthritis. She was on tofacitinib 5 mg twice per day dose after being weaned off the steroids. Soon after this, she received 1st dose of COVISHIELD™ vaccine. Thirty days postvaccination, she developed T9-10 dermatome HZ rash [Figure 1]. Tofacitinib was stopped for 30 days and she has received oral and topical (5%) acyclovir 400 mg twice daily for 10 days after which the zoster lesions have resolved. She had a flare up of arthritis 1 month after stopping tofacitinib and raised inflammatory markers, erythrocyte sedimentation rate (104 mm in 1st h) and C-reactive protein (83 mg/l) was noted. Tofacitinib was restarted 30 days after HZ infection.
| Case 3|| |
This case 3 was a 67-year-old female with a clinical diagnosis of type 2 diabetes and idiopathic pulmonary fibrosis and inflammatory polyarthritis (seropositive RA). She was on oral MTX15 mg per week and oral HCQ 200 mg daily. She received her first dose of COVISHIELD™ vaccine and developed HZ on the left T-9 dermatomal region on 3rd day after vaccination. She received oral acyclovir (800 mg three times a day) and topical acyclovir (5%) with which the lesions resolved over 3 weeks. She developed postherpetic neuralgia for which she received oral pregabalin 75 mg twice daily for 4 weeks. She received her second dose of vaccine 6 weeks after zoster uneventfully.
COVISHIELD™ vaccine which has been used extensively in India is similar to the Astra Zeneca™ vaccine. A preprint reporting on adverse events in the initial 2 weeks following vaccination in 1638 health-care workers in Haryana, India, did not report any case of HZ. The 3 cases we came across raised our suspicion whether patients with autoimmune disease were at higher risk of this complication. Only 1 study has been published till date which has attempted to determine the odds of this adverse event among AIIRD patients. HZ reactivation following vaccination with the Pfizer vaccine occurred more commonly in patients with autoimmune rheumatic diseases compared to the general population (6 out of 491 patients with AIIRD versus none of 99 healthy controls).
The details of the types of vaccine and published reports of zoster after COVID-19 vaccination have been grouped and compared in [Table 1].
|Table 1: Details of published reports of zoster reactivation post-COVID-19 vaccination|
Click here to view
HZ is a major health burden that can affect individuals of any age. It is seen more commonly among individuals aged ≥50 years, female gender, those with immunocompromised status, and those on immunosuppressant drugs (as seen in our patients too). However, some South Asian studies showed a slight male predominance.
About 1 in 3 will develop HZ in their lifetime, amounting to an estimated 1 million episodes in the United States annually. An estimated 10%–20% of people with HZ may develop HZO.
Human immunodeficiency virus (HIV), systemic lupus erythematosus, RA, cancers, inflammatory bowel disease, multiple sclerosis, and psoriasis patients are at a higher risk for HZ.
In a study from Gujarat, India, of patients with HZ, only 5.1% were HIV positive and ¾ of them were males. Cervical dermatome was most commonly involved dermatome in patients of HIV.
In a study of patients with HZO, the right side of face was commonly involved; 5.6% were immunocompromised. HIV, chemotherapy, diabetes, and postrenal transplant immune suppression were seen in this cohort.
Reports of zoster after COVID-19 infection raise the suspicion that the COVID-19 infection might be the trigger for zoster reactivation. The zoster events might be coincidentally associated with vaccination since vaccination is prioritized among those groups who are at highest risk of COVID-19. Available data (including the present case series) seems to suggest that most patients recover uneventfully without any major complications. In addition, data from small subset of rheumatic disease patients with HZ after the first dose of COVID-19 vaccination demonstrated that they could safely take the second dose of the vaccine without any recurrence. These observations could raise the question whether this adverse event is something rheumatologists really need to be concerned about. Many patients in India with zoster report to their family physician and generally recover without any specific treatment. Thus, rheumatologists and other specialists treating patients with autoimmune diseases need to be aware of a possible occurrence of zoster postvaccination. This will help them to inform their patients to report the development or occurrence of zoster.
This is the first report of zoster post-COVID-19 vaccination with COVISHIELDTM in patients with autoimmune inflammatory rheumatic disease. It is also the first report of post-COVID-19 vaccination zoster from India. Whether zoster reactivation is a direct effect of the vaccine or a co-incidental phenomenon needs to be identified by rigorous adverse event reporting and studies of larger cohorts of patients. We wish to highlight the fact that HZ may follow after COVID-19 vaccination but may not have any causal effect.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
The authors would like to thank Dr. Mahendranath, consultant rheumatologist.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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