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Case Letter
Open Access
Available online 24 November 2021
Leukocytoclastic vasculitis after exposure to COVID-19 vaccine
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Matheus Fritzena,
Corresponding author
matheusfritzen2@gmail.com

Corresponding author.
, Gabriella Di Giunta Funchalb, Mariana Oliveira Luizc, Giovanna Steffenello Durigond
a Faculty of Medicine, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
b Department of Dermatopathology, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
c Department of Dermatology, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
d Department of Hematology, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
Received 09 August 2021. Accepted 28 September 2021
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Table 1. Laboratory tests.a
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Dear Editor,

A 60-year-old female patient with a history of chronic liver disease, portal hypertension, polycythemia vera, hypothyroidism, and type 2 diabetes mellitus, presented to the Emergency Section of a University Hospital reporting the appearance of painful purpuric lesions in the lower limbs three days before. She denied fever, chills, arthralgia, or trauma. She denied the use of new medications. She reported receiving the second dose of the COVID-19 vaccine (Oxford-AstraZeneca) approximately eleven days before. She denied a similar previous clinical picture. On physical examination, she had purpuric lesions and palpable papules, which did not disappear on digital pressure (Figs. 1 and 2).

Figure 1.

Purpuric lesions on the lower limbs on the first day of hospitalization.

(0.3MB).
Figure 2.

Multiple petechiae and palpable purpura.

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She reported daily use of propranolol, metformin and levothyroxine. She described stability of the polycythemia vera since December 2015. She was submitted to two lower-limb skin punch biopsies for histopathological analysis and immunofluorescence (IF). Prednisone (1 mg/kg/day) was started once a day. The histopathological examination showed a mixed inflammatory infiltrate with predominantly perivascular fragmented neutrophils associated with extravasated red blood cells (Fig. 3a–c). IF showed deposits of IgA and IgM on the walls of postcapillary vessels (Fig. 3d). The histological picture was compatible with leukocytoclastic vasculitis. The patient denied symptoms or a previous clinical picture of COVID-19. The possibility of cryoglobulinemia was suggested, and serum cryoglobulins were measured, which were negative. She had elevated C-reactive protein levels and leukocytosis with a leftward shift. The remaining blood count results, liver function, coagulogram, and partial urine tests were within the normal limits or compatible with the comorbidities (Table 1). After three days of hospitalization, she showed improvement of the lower limb lesions and painful symptoms. After a seven-day treatment with 60 mg prednisone, a progressive reduction was started, and she was discharged from the hospital on 40 mg/day of prednisone.

Figure 3.

(A and B), Histopathology of the skin showing diffuse inflammatory infiltrate in the dermis (Hematoxylin & eosin, ×10). (C), Postcapillary dermal vessels permeated by neutrophils with leukocytoclasia. Presence of signs of endothelial damage with mural and interstitial fibrin deposits, in addition to extravasated red blood cells. (Hematoxylin & eosin, ×40). (D), Direct immunofluorescence showing granular deposits of IgA and IgM on the postcapillary vessel wall.

(2.15MB).
Table 1.

Laboratory tests.a

Variables  Reference values (adults)  Admission 
Blood     
Hematocrit (%)  11.5–16.5  13.6 
Hemoglobin (g/dL)  36–48  43.2 
Leukocytes (per μL)  3,000–11,000  31,610 
Differential (mm3   
Neutrophils  1,700–7,500  19,914 
Lymphocytes  1,000–2,500  1,896 
Monocytes  200–920  632 
Eosinophils  20–670  632 
Band cells  –  4,741 
Metamyelocytes  –  2,528 
Myelocytes  –  948 
Promyelocytes  –  316 
Platelets (per μL)  150,000–440,000  138,000 
Prothrombin time (s)  12.1  16.8 
INR  <1.2  1.42 
Activated partial prothrombin time (s)  27.3  41.3 
C-Reactive Protein (mg/L)  < 3  4.8 
Erythrocyte sedimentation rate (mm/h)  Up to 15 
Aspartate aminotransferase (U/L)  10–40  51 
Alanine aminotransferase (U/L)  14–59  12 
Lactic dehydrogenase (U/L)  81–234  1,304 
Creatinine (mg/dL)  0.7–1.2  1.04 
Urine     
Color  Citrine yellow  Citrine yellow 
Aspect  Slightly cloudy  Slightly cloudy 
Density  1,010–1,030  1,025 
pH  5.0–7.0  5.0 
Proteins  Negative  Negative 
Reducing substances  Negative  Negative 
Ketone bodies  Negative  Negative 
Hemoglobin  Negative  Negative 
Bilirubin  Negative  Negative 
Urobilinogen  Negative  Negative 
Epithelial cells  Rare  Rare 
Leukocytes  <20,000/mL  56,000 
Red blood cells  <20,000/mL  17,000 
Bacterial flora  Absent  Discrete 
Hyaline cylinders  <400/mL  2,000 
a

Reference values are affected by many variables, including the patient population and the laboratory methods used. The ranges used are for adult females who are not pregnant and have no medical conditions that could affect results. Therefore, they may not be adequate for all patients.

Immunization is a highly important resource in the fight against pandemics, especially the current one caused by COVID-19. However, possible side effects have not yet been fully described. As portrayed by Cohen et al. (2021) and Bostan et al. (2021), there are reports in the literature that point to leukocytoclastic vasculitis following the application of the COVID-19 messenger ribonucleic acid (mRNA) vaccine, such as the vaccine produced by Moderna and Pfizer.1,2 However, there are few reports in the literature on these findings in cases of viral vector vaccines, such as the one produced by Oxford-AstraZeneca. Due to the patient’s multiple comorbidities, the investigation started with the main hypothesis of exacerbation of some of the previous diseases. Hence, the importance of considering possible reactions to the vaccine in the differential diagnosis.

It is unclear whether the COVID-19 vaccine can reactivate or trigger autoimmune diseases.1–4 Leukocytoclastic vasculitis has been described in a range of infections and after administration of some vaccines, such as pneumococcal, influenza, rotavirus, hepatitis A and B, HPV.3,4 We already know that SARS-CoV-2 can cause immune system hyperactivation through cross-reactivity and molecular mimicry,5 and it is possible that after the administration of the second dose of the vaccine, immune complexes comprising vaccine antigens and native antibodies initiated the vasculitis.4 The temporal association between the COVID-19 vaccine and the development of the skin condition is significant. This report suggests the possibility that the COVID-19 vaccine has the potential to induce leukocytoclastic vasculitis.

Financial support

None declared.

Authors' contributions

Matheus Fritzen: Statistical analysis; approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.

Gabriella Di Giunta Funchal: Statistical analysis; approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.

Mariana Oliveira Luiz: Statistical analysis; approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.

Giovanna Steffenello Durigon: Statistical analysis; approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.

Conflicts of interest

None declared.

References
[1]
S.R. Cohen, L. Prussick, J.S. Kahn, D.X. Gao, A. Radfar, D. Rosmarin.
Leukocytoclastic vasculitis flare following the COVID-19 vaccine.
Int J Dermatol, (2021), pp. 1032-1033
[2]
S. Jariwala, N. Vernon, J. Shliozberg.
Henoch-Schönlein purpura after hepatitis A vaccination.
Ann Allergy Asthma Immunol, 107 (2011), pp. 180-181
[3]
C. Bonetto, F. Trotta, P. Felicetti, G.S. Alarcón, C. Santuccio, N.S. Bachtiar, et al.
Vasculitis as an adverse event following immunization – Systematic literature review.
Vaccine, 34 (2016), pp. 6641-6651
[4]
E. Bostan, D. Gulseren, O. Gokoz.
New-onset leukocytoclastic vasculitis after COVID-19 vaccine.
Int J Dermatol, 60 (2021), pp. 1305-1306
[5]
A. Vojdani, E. Vojdani, D. Kharrazian.
Reaction of Human Monoclonal Antibodies to SARS-CoV-2 Proteins with Tissue Antigens: Implications for Autoimmune Diseases.
Front in Immunol, 11 (2021), pp. 1-16

Study conducted at the Hospital Universitário Polydoro Ernani de São Thiago – Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.

Copyright © 2021. Sociedade Brasileira de Dermatologia
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