Madhavi Bhatia,NIPER Guwahati
SARS-covid-19 is now well-known as a severe acute respiratory syndrome that has affected all parts of the world. It has caused almost 3.9 million deaths worldwide resulting in a global pandemic. To curb the disease, various drugs are approved and used worldwide.
Today, immunization is considered a safe and effective tool to fight against infectious diseases. In the USA, 2 messenger mRNA vaccines (Pfizer-BioNtech COVID-19 vaccine and Moderna COVID-19) were authorized for emergency use by the regulatory authority of the USA, United States Food and Drug Administration (US FDA). These vaccines contain mRNA which encodes the SARS-CoV-2 spike protein enveloped in lipid nanoparticles, thereby penetrating the cell membrane into the cell and producing spike protein for subsequent antigen presentation and immune activation. The mRNA present stimulates innate immunity through endosolic and cytoplasmic nucleic receptors. Eg. Toll-like receptors (TLRs) 3,7,8 and 9 and components of the inflammasome (Retinoic acid-inducible gene-1 and melanoma differentiation-associated gene-5).
After administration of the vaccine, an array of innate and adaptive immune responses, including molecular mimicry, occurs. Adjuvants, a group of substances that drive the innate immune system pattern recognition receptor (PRR) activation, are commonly used in vaccines to boost immune reactivity towards target antigen. Within 24 hours of administration of the vaccine, most of the population experience common side effects like mild subjective fevers, headache, and injection site soreness. However, there is a case found in which 42-year-old –women with hypertension and severe obesity develop rashes on the lower limb, which had first appeared 4 days after vaccination with the BIONTECH/Pfizer SARS-Cov2 vaccine. The rash had a typical appearance of cutaneous small-vessel vasculitis (CSVV), which has spread from the lower limbs to the gluteal area over a few days. Pathological findings have shown a slightly elevated inflammation marker. IgG and TSH levels were slightly raised (20.3 g/l and 8.3 mU/l). A skin biopsy from the left ankle revealed leukocytoclastic vasculitis. Immunostaining was tried but could not be evaluated.
LCV has been reported secondary to multiple vaccines such as influenza, hepatitis B (HBV), Bacille Calmette-Guerin (BCG), and HPV vaccine. Vessel damage can likely be a secondary response to abnormal immunological activation with vaccine-related antigens promoting antibody development and immune complex deposition. The COVID-19 virus may induce hyperactivation of the immune system secondary to cross-reactivity and molecular mimicry between virus and self-antigens, consequently triggering autoimmune disorders such as vasculitis, immune-mediated myositis.
What is LCV?
LCV is a histopathologic term. It is a small vessel vasculitis that presents palpable purp, most often on the lower extremities. The inflammatory infiltrate is composed of neutrophils. After degranulation, neutrophils undergo death and breakdown known as leukocytoclastia, releasing nuclear debris. The vessels affected by LCV show fibrinoid necrosis (fibrin deposition within and around the vessel walls), signs of damage (extravasated red blood cells, damaged endothelial cells) of the vessel wall in the surrounding tissue.
What are the causes of LCV?
LCV may be a primary disorder without any identifiable cause, isolated to the skin, or involves other organs in the body, it may be secondary to other autoimmune diseases, various types of infection, drugs, or malignancies.
Treatment of LCV varies according to the etiology and extent of disease and consists mostly of a combination of steroids and other immunosuppressive drugs. Nowadays, rituximab is used and drugs targeting various cytokines IL-6 and IL-5 might be used in the future. In the case of LCV due to COVID-19 infection prednisolone is used.
Although the significance of such leukocytoclastic vasculitis is yet unclear, post-marketing surveillance will be necessary and further studies and investigations may be required to understand the reason behind such adverse effects.
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References:
1. Jedlowski PM, Jedlowski MF. Morbilliform rash after administration of Pfizer-BioNTech COVID-19 mRNA vaccine. Dermatology online journal. 2021;27(1).
2. Erler, Anne, et al. “A Case of Leukocytoclastic Vasculitis after Vaccination with a SARS-CoV2-Vaccine – a Case Report.” Arthritis & Rheumatology, vol. n/a, no. n/a. Wiley Online Library, doi:http://10.1002/art.41910. Accessed 3 July 2021.
Image source: https://www.researchgate.net/figure/Skin-biopsy-showing-leukocytoclastic-vasculitis-with-thromboses-full-arrows_fig3_305346369
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