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E-IJD® - CORRESPONDENCE
Year : 2022  |  Volume : 67  |  Issue : 2  |  Page : 209
Onset of DRESS following COVID-19 vaccination: Causality or coexistence?


From the Department of Dermatology, Venereology and Leprology, Sardar Patel Medical College, Bikaner, Rajasthan, India

Date of Web Publication13-Jul-2022

Correspondence Address:
Alpana Mohta
From the Department of Dermatology, Venereology and Leprology, Sardar Patel Medical College, Bikaner, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijd.ijd_670_21

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How to cite this article:
Mohta A, Nai R, Ghiya BC, Arora A, Mehta RD. Onset of DRESS following COVID-19 vaccination: Causality or coexistence?. Indian J Dermatol 2022;67:209

How to cite this URL:
Mohta A, Nai R, Ghiya BC, Arora A, Mehta RD. Onset of DRESS following COVID-19 vaccination: Causality or coexistence?. Indian J Dermatol [serial online] 2022 [cited 2022 Aug 9];67:209. Available from: https://www.e-ijd.org/text.asp?2022/67/2/209/350842




Sir,

Amidst the global turmoil caused by the rampant spread of the novel coronavirus disease 2019 (COVID-19) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), safe vaccination is the need of the hour.[1] Fortunately, due to the resolute efforts of scientists working tirelessly to create safe vaccination, we now have a handful of vaccines capable of preventing moderate and severe COVID-19 illness in the masses. On January 16, 2021, Indian launched its nationwide vaccination program against the COVID-19 infection, and as of August 3, 2021, 105 million Indian population has been fully vaccinated.[2] The vaccine-induced hypersensitivity reactions have been reported to range from 1.5% to 9%.[3] With a rise in the proportion of population receiving vaccination, the number of atypical reactions being reported secondary to the vaccine is also gradually rising.

Severe cutaneous adverse reaction (SCAR) is an umbrella term encompassing various adverse drug reaction (ADR) syndromes, namely, drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthemous pustulosis, Steven–Johnson syndrome/toxic epidermal necrolysis, and drug-induced erythroderma. Herein, we report a case of a 24-year-old male patient who developed DRESS following his first dose of COVID-19 vaccination.

A 24-year-old man presented to us with complaint of generalized body rash, facial edema, abdominal pain, and high-grade fever for 3 days. On mucocutaneous examination, there was presence of multiple well-to-ill-defined erythematous non-follicular papules and pustules all over the body involving more than 70% of the body surface area, with the presence of purpuric targetoid lesions over bilateral legs [Figure 1]a, [Figure 1]b, [Figure 1]c. There was presence of diffused generalized urticarial rash, erythema, and edema in the background skin, predominantly involving the limbs, with bilateral cervical and inguinal lymphadenopathy. Mucosal examination revealed conjunctival erythema. Rest of the mucosa were spared. Lab investigations revealed raised liver enzymes, eosinophilia, leukocytosis, thrombocytopenia, anemia, and raised serum creatinine levels. The patient was febrile and lethargic. Serological tests for rickettsia, hepatitis B, hepatitis C, HIV, and TORCH (toxoplasmosis, rubella, cytomegalovirus, and herpes simplex) were negative. We also subjected the patient to COVID-19 and H1N1 RT-PCR tests, which turned out to be negative. However, the chemi-luminescent immunoassay done for SARS-CoV-2 S1 RBD (spike-1 receptor-binding domain) antigen revealed an IgG antibody level of <10. On the basis of strong clinical suspicion and laboratory parameters, the patient was diagnosed with DRESS and his RegiSCAR score was 5. Interestingly, while seeking a detailed drug history, the patient refused to having taken any allopathic or alternative medication within the last 3 months prior to the onset of skin rash. However, the man had been vaccinated with the first dose of COVID-19 vaccine 3 weeks back. The patient revealed that he had also undergone routine COVID-19 PCR testing before the vaccination, which was negative. The Naranjo ADR probability score was 4 (possible ADR). Histopathological analysis revealed spongiosis, basal vacuolar changes, microvesicles, and apoptotic keratinocytes in the epidermis along with perivascular infiltration [Figure 2]. He was treated with intravenous dexamethasone (4 mg) in tapering dose for 10 days and injectable fluids along with topical steroids followed by an uneventful recovery [Figure 3]a, [Figure 3]b, [Figure 3]c. The eosinophilia, hepatic, and renal function tests dropped to normal limits within the next 2 weeks.
Figure 1: (a) Multiple erythematous papules, vesicles, and morbilliform rash over urticarial base involving the trunk and (b) back, (c) with targetoid lesions and erythematous papules over bilateral lower limbs

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Figure 2: Histopathological analysis revealed spongiosis, basal vacuolar change, microvesicles, and apoptotic keratinocytes in the epidermis along with perivascular infiltration (hematoxylin and eosin, ×400)

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Figure 3: (a) Clearance of lesions with post-inflammatory exfoliation over trunk after 2 weeks of treatment with systemic steroids, (b) over back (c) clearance of lesions over lower limbs

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DRESS has a multifactorial etiology driven by the concordance of genetic, drug, and viral elements. The drugs known to cause this syndrome include anticonvulsants, antipsychotics, antiepileptics, furosemide, sulfa drugs, and antibiotics like vancomycin to name a few.[4] Nonpharmacological causes of DRESS include the human herpesvirus (Epstein–Barre virus, cytomegalovirus, HHV-6, and HHV-7). Rare cases of DRESS have also been reported following certain vaccines. DRESS syndrome differs from most of the other SCARs in having a delayed onset of 3–8 weeks following the first exposure to drug.[4] This delayed latency between drug exposure and the onset of DRESS is because of the time required for accumulation of toxic metabolites. These metabolites lead to cellular apoptosis, T-cell activation, and cytokinemia necessary to induce DRESS. There are predominantly four clinical patterns of cutaneous lesions in DRESS, namely, urticarial, morbilliform, erythrodermic, and erythema multiformae. Our patient's lesions were erythema multiformae which is known to be associated with a more severe systemic phenotype. The virally triggered DRESS has also been labeled as “VRESS” (virus reactivation with eosinophilia and systemic symptoms).[5] It is triggered by virus-mediated delayed T-cell upregulation and a drug-antigen cross-reaction leading to interleukin-5 activation and eosinophilia. This unique phenomenon of VRESS is in turn a drug-related hypersensitivity driven by viral reactivation. Negative serology/swab tests for rickettsia, hepatitis B, hepatitis C, HIV, and TORCH COVID-19 and H1N1 ruled out the possibility of other viral causes of VRESS in our case. But the low level of positive antibodies test for COVID-19 S1 RBD could be suggestive of a past subclinical COVID-19 infection which might have triggered VRESS. However, we have to keep in mind the fact that low antibody levels against spike proteins can also be seen after COVID-19 vaccination.[6] The recommended dosage of steroids in DRESS is 1 mg/kg prednisolone or 0.1 mg/kg dexamethasone, which is tapered off over 1–3 months. But since our patient had a relatively mild episode of DRESS, his dosage was tapered off within 10 days. Unfortunately, in order to avoid disease relapse, we had to advise the patient against taking the second dose.

In the past, various authors have also described the onset of DRESS following influenza vaccination.[7] Lately, a handful of reports have highlighted the onset of SCAR following COVID-19 vaccine administration.[3] However, the close temporal association of DRESS with COVID-19 vaccination hasn't been reported yet. We hypothesize that in our patient DRESS developed secondary to an immunological reaction to the viral component of the vaccine and not due to the direct effects of the virus. Nevertheless, an alternative cause of DRESS in our case due to a subclinical COVID-19 infection or an unknown drug exposure can't be ruled out.

Through this case report, we hope to elucidate a new dimension of the possible immunization-related pathomechanism at play in causing SCARs. We intend in no way to promote the already prevailing vaccine hesitancy. We must keep in mind that SCAR is an exceedingly rare squeal of COVID-19 vaccination, and the benefits of these vaccines far outweigh the risk. Physicians should explain the rarity and potentially non-fatal nature of these adverse events and counsel the patients accordingly.

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 initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Kaur SP, Gupta V. COVID-19 vaccine: A comprehensive status report. Virus Res 2020;288:198114.  Back to cited text no. 1
    
2.
National Co-Win Statistics. Total Vaccination Doses. (2021). Updated as on 3 Aug 2021. Available from: https://dashboard.cowin.gov.in/. [Last accessed on 2021 Aug 3].  Back to cited text no. 2
    
3.
Lospinoso K, Nichols CS, Malachowski SJ, Mochel MC, Nutan F. A case of severe cutaneous adverse reaction following administration of the Janssen Ad26.COV2.S COVID-19 vaccine. JAAD Case Rep 2021;13:134-7.  Back to cited text no. 3
    
4.
Choudhary S, McLeod M, Torchia D, Romanelli P. Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. J Clin Aesthet Dermatol 2013;6:31-7.  Back to cited text no. 4
    
5.
Callen JP. A possible viral cause of DRESS. NEJM Journal Watch Dermatology 2014. Available from: https://www.jwatch.org/na34650/2014/05/15/possible-viral-cause-dress. [Last accessed on 2021 Aug 3].  Back to cited text no. 5
    
6.
Jalkanen P, Kolehmainen P, Häkkinen HK, Huttunen M, Tähtinen PA, Lundberg R, et al. COVID-19 mRNA vaccine induced antibody responses against three SARS-CoV-2 variants. Nat Commun 2021;12:3991.  Back to cited text no. 6
    
7.
Girijala RL, Ramamurthi A, Wright D, Kwak Y, Goldberg LH. DRESS syndrome associated with influenza virus. Proc (Bayl Univ Med Cent) 2019;32:277-8.  Back to cited text no. 7
    


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