key: cord-1017148-5m7skfl0 authors: Abdelmaksoud, Ayman; Wollina, Uwe; Temiz, Selami Aykut; Hasan, Abdulkarim title: SARS‐CoV‐2 vaccination‐induced cutaneous vasculitis: Report of two new cases and literature review date: 2022-03-25 journal: Dermatol Ther DOI: 10.1111/dth.15458 sha: f01c8b96e0088a845958f1329e92a77837496b49 doc_id: 1017148 cord_uid: 5m7skfl0 Currently the most powerful tool in combating the COVID‐19 pandemic is vaccination against SARS‐CoV‐2. A growing percentage of the world's population is being vaccinated. Various vaccines are worldwide on the market. Several adverse reactions have been reported as a part of post‐marketing surveillance of COVID‐19 vaccines. Among the possible adverse events, cutaneous vasculitis has occasionally been reported. We present a narrative review on cutaneous vasculitis related to COVID‐19‐vaccination to summarize clinical findings, histopathology, treatment and outcome. We searched for “COVID vaccine”, “COVID vaccination” AND “cutaneous vasculitis” in PUBMED. Articles in English have been selected, from inception to December 2021, and analyzed for patient's characteristics, type of vaccine, time of appearance of cutaneous vasculitis and clinico‐histopathologic type. Treatment and outcome have also been considered in this narrative review. Two new unpublished cases of ours were added. Cutaneous vasculitis is a rare adverse event to COVID‐19 vaccination. It has been observed with mRNA and adenovirus‐vector vaccines. IgA vasculitis, lymphocytic and ANCA‐associated vasculitis, leukocytoclastic and urticarial vasculitis have been reported. This adverse event can occur after first or second shot. Most cases run a mild to moderate course. Cornerstone of medical treatment are systemic corticosteroids. Complete remission could be achieved in most patients. Vasculitis may not be considered as a contraindication of vaccination, being uncommonly reported and shows a favorable prognosis. The benefit of the vaccination remains high especially for immunocompromised patients. COVID‐vaccine induced vasculitis is important in the differential diagnosis of purpuric and vasculitis disorders. Vasculitis represent a heterogeneous group of disorders with blood vessels inflammation. The classification of vasculitis based upon vessels affected, dominant cells of the inflammatory infiltrate and clinical characteristics. The ideal classification has yet to be found. 1 Vascular affection is common in COVID-19 disease. Thromboembolic and inflammatory reaction patterns have been observed. 2 Vaccination against SARS-CoV2 is currently the most powerful medical approach against the pandemic. Although the various vaccines are in general well-tolerated, adverse events have occasionally been reported including the appearance or re-activation of cutaneous vasculitis. 3 In this narrative review, we analyzed the available data in the English medical literature to better characterize these adverse events and discuss the treatment options. Two new unpublished cases of ours were added ( Figure 1 ). We searched for "COVID vaccine", "COVID vaccination" AND "cutaneous vasculitis" in PUBMED. Articles in English have been selected, from inception to December 2021, and analyzed for patient's characteristics, type of vaccine, time of appearance of cutaneous vasculitis and clinico-histopathologic type. Treatment and outcome have also been considered in this narrative review. The results of our research have been classified according to the subtype of vasculitis. Of the 38 cases, including ours, 52.6% (20 cases) had received the mRNA vaccine, 31.6% (12 cases) had received ChaAdOx1 nCoV-19 vaccine (vector), and 15.8% (6 cases) had received the inactivated SARS-CoV-2 vaccine. Vasculitis developed in 63.2% (24 cases) after the first dose. The mean age of the cases was 53. 65.8% (25 cases) of the cases were female. 55.3% (20 cases) were LCV, 23.7% (9 cases) were IgA vasculitis, 7.9% (3 cases) were lymphocytic vasculitis, 5.3% (2 cases) were ANCA-associated vasculitis, 5.3% (3 cases) was urticarial vasculitis, and 2.6% (1 cases) was Immune Complex Vasculitis. The average occurrences time was 6.2 days. The lesions in the cases disappeared in an average of 2.5 weeks. The average occurrences time was 6.2 days. The lesions in the cases disappeared in an average of 2.5 weeks. The following is an overview of the reviewed cases. Summary of the data is highlighted in Table 1 . IgA vasculitis is an of small vessel vasculitis caused by perivascular deposition of IgA1 and activation of neutrophils. It may present as systemic vasculitis (Henoch-Schönlein purpura) or as a skin-limited variant. IgA-vasculitis is the most common vasculitis type in infants. 39 IgA vasculitis has been observed after Pfizer-BioNTechBNT16B2b2 mRNA vaccine and Vaxzevria (ChAdOx1 nCoV-19 AZD1222) vaccine. [4] [5] [6] [10] [11] [12] [13] [14] [15] In case of appearance after first shot, a second shot of vaccination did not cause a relapse of the vasculitis symptoms. Treatment of choice was oral corticosteroids; however, spontaneous remission was occasionally reported. Interestingly, of the reviewed cases, two had history of COVID-19 infection; two had history of IgA vasculitis. 6,10-15 A favorable risk-benefit profile of BNT162b2 in rheumatoid arthritis patients, including those on biologics, has been noted. 15 differential diagnosis from lichenoid, infectious, neoplastic to autoimmune connective tissue disorders. 41 Only three cases have been reported so far. [7] [8] [9] Kharkar et al. 8 Interestingly, in a recent study, purpura on the lower legs was mostly seen in patients with severe "Drug-induced hypersensitivity syndrome." 44 Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune vasculitis type which affects small-to medium-sized vessels. ANCA-associated vasculitis includes granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis. 45 Only 2 cases of ANCA-associated vasculitispresented with associated cutaneous findings post-COVID-19 vaccination. 16, 17 Kidney biopsy of one cases confirmed severe acute tubular injury with pauci-immune crescentic GN and interstitial nephritis. The kidney function then normalized following intravenous cyclophosphamide (initiated at 10 mg/kg). 16 Urticarial vasculitis is an uncommon clinic-pathologic entity that is characterized by chronic or recurrent episodes of urticarial lesions and LCV. 48 Vasculitis are a heterogeneous group of diseases, which share the common feature of endothelial damage secondary to inflammation. Cutaneous vasculitis is a possible adverse event associated with vaccination against SARS-CoV-2. Hypersensitivity vasculitis and antigenantibody complex deposition (type III hypersensitivity reaction) in the small vessels with potential internal organs involvement, such as the kidney and intestines, are the most common subtypes. However, as most of other post-COVID-19 vaccination cutaneous reactions, cutaneous vasculitis is not part of a multiorgan adverse hypersensitivity response triggered by the vaccine but mostlya skin-limited inflammation. The pathogenesis of vaccination-associated vasculitis is not well understood. There seems to be regional differences in frequency and presentation of vasculitis. The knowledge of (cutaneous) vasculitis adverse events is important for patient safety and in the differential diagnosis of vasculitis and purpuric skin disorders in general. We think this review will aid the dermatologists in daily practice. It also provides an overlook for international agencies to guide the manufacturers about vasculitis as one of the important reactions to COVID-19 vaccines. The authors declare that there is no conflict of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request. Ayman Abdelmaksoud https://orcid.org/0000-0003-4848-959X Uwe Wollina https://orcid.org/0000-0001-5933-2913 Selami Aykut Temiz https://orcid.org/0000-0003-4878-0045 Classification of vascular disorders in the skin and selected data on new evaluation and treatment Cutaneous signs in COVID-19 patients: a review Cutaneous and allergic reactions due to COVID-19 vaccinations: a review Henoch-Schönlein purpura presenting post COVID-19 vaccination Henoch-Schönlein purpura following the first dose of COVID-19 viral vector vaccine: a case report. Vaccines (Basel) A rare case of Henoch-Schönlein purpura following a COVID-19 vaccine-case report Cutaneous lymphocytic vasculitis after administration of COVID-19 mRNA vaccine Asymmetrical cutaneous vasculitis following COVID-19 vaccination with unusual eosinophil preponderance Cutaneous lymphocytic Vasculitis after Administration of the Second Dose of AZD1222 (Oxford-AstraZeneca) severe acute respiratory syndrome coronavirus 2 vaccination: Casuality or causality? IgA vasculitis in adult patient following vaccination by ChadOx1 nCoV-19 New-onset leukocytoclastic vasculitis after COVID-19 vaccine Reactivation of IgA vasculitis following COVID-19 vaccination Reactivation of IgA vasculitis after COVID-19 vaccination Post-COVID-19 vaccination IgA vasculitis in an adult Case of immunoglobulin a vasculitis following coronavirus disease 2019 vaccination Case report: ANCA-associated Vasculitis presenting with rhabdomyolysis and Pauci-immune crescentic glomerulonephritis after Pfizer-BioNTech COVID-19 mRNA vaccination Propylthiouracil-induced Antineutrophil cytoplasmic antibody-associated Vasculitis after COVID-19 vaccination. Vaccines (Basel) Leukocytoclastic vasculitis after exposure to COVID-19 vaccine Leukocytoclastic vasculitis flare following the COVID-19 vaccine A case of Leukocytoclastic Vasculitis following SARS-CoV-2 vaccination Small vessel vasculitis related to varicella-zoster virus after Pfizer-BioNTech COVID-19 vaccine Leukocytoclastic vasculitis as a cutaneous manifestation of ChAdOx1 nCoV-19 corona virus vaccine (recombinant) Possible case of mRNA COVID-19 vaccine-induced small-vessel vasculitis Images in vascular medicine: Leukocytoclastic vasculitis after COVID-19 vaccine booster Sinovac COVID-19 vaccineinduced cutaneous leukocytoclastic vasculitis Cutaneous small-vessel vasculitis following COVID-19 vaccine Leukocytoclastic vasculitis after coronavirus disease 2019 vaccination Cutaneous vasculitis following COVID-19 vaccination Emergence of de novo cutaneous vasculitis post coronavirus disease (COVID-19) vaccination Smallvessel vasculitis following Oxford-AstraZeneca vaccination against SARS-CoV-2 Cutaneous Leukocytoclastic Vasculitis induction following ChAdOx1 nCoV-19 vaccine Clinical images: Leukocytoclastic vasculitis after vaccination with a SARS-CoV-2 vaccine Cutaneous vasculitis after severe acute respiratory syndrome coronavirus 2 vaccine COVID-19 vaccine-induced urticarial vasculitis First description of immune complex vasculitis after COVID-19 vaccination with BNT162b2: a case report Clinical and histopathological spectrum of delayed adverse cutaneous reactions following COVID-19 vaccination Leukocytoclastic vasculitis after COVID-19 vaccination Urticarial vasculitis following mRNA anti-COVID-19 vaccine IgA vasculitis Immunogenicity and safety of anti-SARS-CoV-2 BNT162b2 vaccine in psoriasis patients treated with biologic drugs Cutaneous vasculitis update: neutrophilic muscular vessel and eosinophilic, granulomatous, and lymphocytic vasculitis syndromes Eosinophilic dermatosis after AstraZeneca COVID-19 vaccination Clinicopathological features of cutaneous reactions after mRNA-based COVID-19 vaccines Purpura as an indicator of severity in drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms: evidence from a 49-case series Immunopathogenesis of ANCA-associated Vasculitis Unraveling the Immunopathogenesis and genetic variants in Vasculitis toward development of personalized medicine Varicella zoster virus reactivation after coronavirus disease 2019 vaccination in Japanese patients: a series of 14 cases Urticarial vasculitis How to cite this article: Abdelmaksoud A, Wollina U, Temiz SA, Hasan A. SARS-CoV-2 vaccination-induced cutaneous vasculitis: Report of two new cases and literature review