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CASE REPORT Table of Contents  
Ahead of print publication
IgA vasculitis following ChAdOx1 nCoV-19 vaccination


1 Department of General Medicine, Mazumdar Shaw Medical Centre, Bengaluru, Karnataka, India
2 Department of Dermatology, Mazumdar Shaw Medical Centre, Bengaluru, Karnataka, India

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Date of Submission30-Jan-2022
Date of Decision28-Mar-2022
Date of Acceptance20-Apr-2022
Date of Web Publication04-Aug-2022
 

  Abstract 


IgA vasculitis (IgAV), a small-vessel vasculitis, is more frequently seen in children than in adults. IgAV is triggered by various bacterial and viral infective agents. Here, we are describing a case of IgAV following ChAdOx1 nCoV-19 vaccination. A 39-year-old male presented with skin rash, joint pain, and pain abdomen. Symptoms started within 3 days of ChAdOx1 nCoV-19 vaccination. His clinical examination and investigations lead to a diagnosis of IgAV. After ruling out other possible etiologies, we concluded it as vaccine-induced IgAV. A few cases of IgAV have been reported worldwide post SARS-CoV-2 vaccination. Although rare and often self-limited, it is important to recognize the possibility of IgAV post-SARS-CoV-2 vaccination because early recognition, initiation of treatment, and timely follow-up can improve the disease outcome.

Keywords: IgA vasculitis, SARS-CoV-2 vaccine, temporal relation


How to cite this URL:
Basu M, Prathibha P M, Mohan B V. IgA vasculitis following ChAdOx1 nCoV-19 vaccination. APIK J Int Med [Epub ahead of print] [cited 2022 Sep 25]. Available from: https://www.ajim.in/preprintarticle.asp?id=353260





  Introduction Top


IgA vasculitis (IgAV) is associated with abnormally glycosylated IgA1 predominant immune complex deposition involving the skin, gastrointestinal tract (GI tract), kidney, and joints.[1] Recently, SARS-CoV-2-associated vasculitis including IgAV has been reported.[2] Vasculitis can manifest postvaccination also, reported mostly after split-virion influenza vaccination, but the causative association is still debated.[3] A few cases of post-SARS-CoV-2 vaccination vasculitis, including IgAV, or other autoimmune conditions, of new-onset or flare-up of previously existing conditions, have been reported worldwide.[4],[5]

IgAV manifests with palpable purpura mainly over the lower extremities, buttocks, and less frequently over the upper limbs and trunk. Arthralgia is common, along with gastrointestinal symptoms such as abdominal pain, GI bleeding and occasionally intestinal perforation, intussusception. Renal involvement termed IgAV nephritis, ranges from microscopic hematuria to nephrotic syndrome, is seen in adults more commonly than children and predicts poor prognosis. IgAV can also cause seizures, myocarditis, orchitis, alveolar hemorrhage or episcleritis rarely. The diagnosis is confirmed with the skin and/renal biopsy showing leukocytoclastic vasculitis or proliferative glomerulonephritis with IgA deposition.[2],[6]

Here, we are discussing a case of IgAV developed post SARS-CoV-2 adenovirus vector-mediated vaccine.


  Case Report Top


A 39-year-old male presented with complaints of a progressive rash over all four limbs. He had been diagnosed with chronic urticaria 5 years earlier and was taking Levocetirizine 2.5 mg, once a day. He was advised to increase Levocetirizine to 5 mg once a day 5 days prior to taking the ChAdOx1 nCoV-19 coronavirus vaccine (recombinant) (“Covishield”), considering the risk of flare-up of urticarial rash postvaccination. He noticed the above-mentioned skin changes along with bilateral knee and ankle joint pain 3 days after the vaccination. He was treated with levocetirizine 5 mg once daily and hydroxyzine 25 mg twice daily, but the rashes did not subside. On day 7, he developed mild diffuse abdominal pain, ultrasonography of the abdomen showed normal study and was treated with steroid in a different center. In view of the recurrence of rashes, he presented to our center on day 23. He denied a history of past COVID-19 infection, recent fever, sore-throat, diarrhea, melena, hematochezia, or hematuria. There had been no similar skin changes in the past or any significant family history.

On clinical examination, he was afebrile, normotensive (blood pressure 130/84 mmHg) with a normal pulse rate of 76/min. He had multiple palpable purpura and a few petechiae over both lower limbs till mid-thigh region and over both the forearms [Figure 1]. Systemic examination was normal.
Figure 1: Multiple purpura and few petechial lesions over lower limb till mid-thigh region and forearm

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Routine blood investigations were within the normal limits except for mildly elevated total leukocyte counts and erythrocyte sedimentation rate (ESR) [Table 1]. Skin biopsy was taken from a newly developed (within 24 h of onset) purpura which was histopathologically suggestive of vasculitis [Figure 2]. Direct immunofluorescence (DIF) of the skin biopsy sample showed IgA deposits in superficial dermal blood vessels (3+), C3 (2+) and was negative for IgG and IgM, strongly suggestive of IgAV [Figure 3].
Table 1: Bio-chemical parameters on presentation

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Figure 2: (a) Microphotograph of skin biopsy showing dense perivascular neutrophilic inflammation, infiltrating the vessel wall (haematoxylin and eosin stain; ×10). (b) Eosinophilic homogenous fibrinoid material is seen within the walls of vascular structures (haematoxylin and eosin stain; ×20)

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Figure 3: Direct immunofluorescence done on skin shows superficial dermal vessel deposits of IgA (a) and C3 (b) as marked by arrows

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He was started on tablet prednisolone 1 mg/kg and tapered off in 4 weeks. He developed new rashes 10 days after stopping prednisolone. He was started on fexofenadine 180 mg, levocetirizine 10 mg, and naproxen 500 mg per day. His skin lesions progressed over the next 4 days and developed joint and abdominal pain. He was initiated on prednisolone 0.5 mg/kg and tablet dapsone 100 mg/day. His abdominal and joint pain reduced in 1 week, purpura gradually resolved over 3 weeks. Prednisolone was tapered over 8 weeks and stopped. In view of his previous relapses, dapsone was continued for 2 months after stopping prednisolone. He is disease free on 2 months of follow-up.


  Discussion Top


IgAV, formerly called Henoch–Schönlein purpura, usually manifests with the classic clinical triad of purpura, pain abdomen, and arthralgia. It is the most common childhood vasculitis but is rarely seen in adults.[7]

IgA is an important class of antibody present in mucosal secretions and acts as the first line of defense against pathogens. The exact pathogenesis of IgAV is not known, but the proposed mechanism is the deposition of galactose-deficient IgA1 immune complexes in the tissues causing local inflammation, leading to the clinical manifestations.[6] We are currently in the middle of a pandemic caused by SARS-CoV-2. Direct endothelial injury by SARS-CoV-2, cross-reactivity, and molecular mimicry between the virus and self-antigens leads to hyperactivation of the immune system, which triggers vasculitis disorders.[8],[9] Various SARS-CoV-2 vaccines are approved for immunization which act through different mechanisms-mRNA, DNA, adenovirus vector mediated, inactivated and many more with different mechanisms are in the pipeline. Previously reported cases have shown that vasculitis can develop after the 1st or 2nd dose of SARS-CoV-2 vaccination, including with mRNA, adenovirus vector mediated, and inactivated vaccines. Our patient's symptoms developed following 1st dose of ChAdOx1 nCoV-19 vaccination (3 days postvaccination), which is similar to the other reported cases. The ChAdOx1 nCoV-19 vaccine contains a recombinant nonreplicating adenoviral vector encoding the spike protein of SARS-CoV-2, which can also trigger similar autoimmune reactions and cause vasculitis disorders like an infection by the virus itself.[4],[5],[8],[9],[10]

The management of IgAV is determined by the clinical condition of the patient, as the disease course can vary from a mild self-limiting episode to IgAV nephritis progressing to end-stage renal disease. IgAV nephritis patients may require hemodialysis or even renal transplant in future.[6],[7] Early diagnosis and proper management with regular follow-up can decrease morbidity. If the disease is mild, only symptomatic treatment is started, like non-steroidal anti-inflammatory drugs, except in cases with renal and/or, GI system involvement.[2],[7] Corticosteroids, colchicine, dapsone, ACEi, other various immunosuppressants, rituximab, and IVIg can be used for the management as per the disease course and severity.[2] Corticosteroids improve cutaneous manifestations and are used for IgA nephritis, but they do not have any prophylactic role to prevent the renal involvement.[2] Dapsone is effective for the skin involvement by reducing the generation of oxygen radicals in neutrophils and inhibiting chemotaxis of neutrophils.[7] Corticosteroids and dapsone help to reduce arthralgia and abdominal symptoms also. As our patient had a refractory course of purpura, abdominal pain, and arthralgia, we had to treat him with both corticosteroid and dapsone to achieve a complete resolution. IgAV can recur in around 25% of the cases, so follow-up monitoring is required, especially of renal function.[2],[6],[7]

Only a few cases of post-COVID-19 vaccination IgAV have been reported worldwide, and no case has been reported from India till now, to the best of our knowledge. In India, more than 165 crore doses of COVID-19 vaccine have been administered covering around 94 crores of Indians with at least one dose and 71 crores of Indians immunized with 2 doses, as of January 30, 2022, according to the Ministry of Health, India. In this context, it maybe is difficult to find a temporal correlation between these two events. The vaccination program has recently started for children; hence, awareness of vaccine-related adverse events in a population that is more prone to IgAV will help the primary health-care provider to identify and manage at the earliest.

Acknowledgment

The authors would like to thank Dr. Rajalakshmi and Dr. Saloni from the Department of Pathology, St. John's Medical College, Bengaluru, for analyzing the skin biopsy specimens histopathology and providing the HPE and DIF images.

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.
Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, et al. 2012 revised International Chapel Hill Consensus Conference nomenclature of vasculitides. Arthritis Rheum 2013;65:1-11.  Back to cited text no. 1
    
2.
Sugino H, Sawada Y, Nakamura M. IgA vasculitis: Etiology, treatment, biomarkers and epigenetic changes. Int J Mol Sci 2021;22:7538.  Back to cited text no. 2
    
3.
Bonetto C, Trotta F, Felicetti P, Alarcón GS, Santuccio C, Bachtiar NS, et al. Vasculitis as an adverse event following immunization – Systematic literature review. Vaccine 2016;34:6641-51.  Back to cited text no. 3
    
4.
Cavalli G, Colafrancesco S, De Luca G, Rizzo N, Priori R, Conti F, et al. Cutaneous vasculitis following COVID-19 vaccination. Lancet Rheumatol 2021;3:e743-4.  Back to cited text no. 4
    
5.
Berry CT, Eliliwi M, Gallagher S, Panaccione S, Klein WM, Healy AL, et al. Cutaneous small vessel vasculitis following single-dose Janssen Ad26.COV2.S vaccination. JAAD Case Rep 2021;15:11-4.  Back to cited text no. 5
    
6.
Oni L, Sampath S. Childhood IgA Vasculitis (Henoch Schonlein Purpura)—Advances and Knowledge Gaps. Front Pediatr 2019;7:257. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610473/. [Last accessed on 2021 Oct 30].  Back to cited text no. 6
    
7.
Audemard-Verger A, Pillebout E, Guillevin L, Thervet E, Terrier B. IgA vasculitis (Henoch-Shönlein purpura) in adults: Diagnostic and therapeutic aspects. Autoimmun Rev 2015;14:579-85.  Back to cited text no. 7
    
8.
Cohen SR, Prussick L, Kahn JS, Gao DX, Radfar A, Rosmarin D. Leukocytoclastic vasculitis flare following the COVID-19 vaccine. Int J Dermatol 2021;60:1032-3.  Back to cited text no. 8
    
9.
Bostan E, Gulseren D, Gokoz O. New-onset leukocytoclastic vasculitis after COVID-19 vaccine. Int J Dermatol 2021;60:1305-6. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1111/ijd. 15777. [Last accessed on 2021 Aug 16].  Back to cited text no. 9
    
10.
Dash S, Behera B, Sethy M, Mishra J, Garg S. COVID-19 vaccine-induced urticarial vasculitis. Dermatol Ther 2021;34:e15093.  Back to cited text no. 10
    

Top
Correspondence Address:
PM Prathibha,
Department of Dermatology, Mazumdar Shaw Medical Centre, Narayana Health City, Bommasandra, Anekal Taluk, Bengaluru - 560 099, Karnataka
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ajim.ajim_25_22



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    -  Prathibha P M
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