SUBMITTED 28 FEB 23 1

ACCEPTED 28 MAR 23 2

ONLINE-FIRST: MARCH 2023 3

DOI: https://doi.org/10.18295/squmj.3.2023.017 4

Re: Leukocytoclastic Vasculitis 6

A peculiar presentation of scrub typhus 7

Dear Editor, 9

We read with interest the recent report of Vasireddy A et al. about 10

leukocytoclastic vasculitis (LV) associated with a Scrub typhus infection affecting a 28-11

year-old male, who presented with multiple, palpable purpuric eruptions mainly on the 12

lower extremities.1 The routine laboratory determinations were unremarkable, and blood 13

specific tests for autoimmune disorders, as well as malaria and bacterial and viral 14

infections were negative; except for the Weil Felix test that was positive with a titer over 15

than 1:640 against OXK. Biopsy study of skin lesion showed the dermis with vasculo-16

centric infiltrate, and vessel walls with fibrinoid necrosis and dense infiltration by 17

neutrophils, and leukocytoclasis. The final confirmed diagnosis was of LV, an 18

uncommon manifestation of the Orientia tsutsugamushi infection, which is a zoonosis 19

naturally transmitted by mite bites. Undergoing antimicrobial schedule of doxycycline, 20

the patient improved in three weeks.1 In fact, the authors emphasized the major 21

infectious causes of leukocytoclastic vasculitis; but in the current global scenario one 22

could include COVID-19 among the etiologies.2-5 23

Capoferri G et al.2 described a 93-year-old man who had COVID-19 infection 25

and 8 days later presented LV evolving with extensive skin necrosis in the lower 26

extremities. The lesions were erythematous and purpuric macules, hemorrhagic papules, 27

and blisters. Skin biopsy study revealed the classic features of LV that was treated with 28

corticosteroids. He evolved with dry gangrene of both legs and feet and declined the 29

amputations; being discharged one month later, he died seven weeks after the initial 30

diagnosis of COVID-19. The unfavorable evolution at least in part was due risk factors 31

including older age, arterial hypertension, peripheral artery disease, and a heterozygous 32

Factor V Leiden mutation2 Corrà A et al.3 reviewed 19 cases with histological 33

confirmation of LV, 68.4% males, median age of 48.4 (13-93) years; 3 patients had 34

diagnosis of IgA vasculitis, 5 had diagnosis of urticarial vasculitis, and the 11 others 35

were considered as LV. Palpable purpura (with or without necrosis and hemorrhagic 36

blistering) was the predominant manifestation; and the commonest affected areas were 37

the lower limbs and the trunk.3 The span of time from the COVID-19 infection to the 38

appearance of the skin rash ranged from concomitant until more than 30 days after the 39

first positive nasopharyngeal swab. Worthy of note, the SARS-CoV-2 was found in the 40

vessel wall in 3 cases by PCR technique, supporting the direct virus role in the 41

pathogenesis of cutaneous vasculitis.3 After vaccination, 39 cases had vasculitis, 61.5% 42

women, mean age of 53.2 (22-94) years; the predominant manifestation was purpuric 43

papules or maculae in the lower extremities. Direct immunofluorescence was not cited 44

in 21 cases, and in 5 was negative; among the remaining 13 cases, 5 cases were of IgA 45

vasculitis and 3 of vasculitis with C3 deposition.3 Kutlu Ö et al.4 compared 198 people 46

(111 patients with COVID-19 and 87 age and sex-matched patients with other diseases) 47

regarding the common dermatologic comorbidities. In COVID-19 group, the most 48

common entities were pruritus (8.1%), eczema (6.3%), infections (3.6%), LV (1.8%), 49

and urticaria (0.9%); while in control group were infections (9.2%), eczema (3.4%), 50

pruritus (2.3%), urticaria (1.1%), and none of patients had LV; the findings showed that 51

pruritus and LV are more common in severe COVID-19 cases.4 The authors also 52

emphasized the pathogenic mechanism of Th1 cells hyperactivation to produce IL 6, IL 53

2, and TNF‐α is a major cause of death in severe COVID‐19 cases.4 Wong K et al.5 54

reviewed 9 cases of vasculitis secondary to COVID-19, with mean age of 29.17 ± 28.2 55

years, age range from 6 months to 83 years, and male to female ratio of 4:5. Most 56

common lesions were maculopapular, violaceous, popular, and erythematous rash. The 57

patients utilized heparin (n = 2), methylprednisolone (n = 6), and intravenous 58

immunoglobulin (n = 4); and significant improvement was obtained in 89% of patients. 59

A 7-year-old patient who died due to hypoxia was the unique death in the studied group. 60

The high-quality report of Vasireddy A et al. is really very useful, including for 62

physicians out of the “tsutsugamushi triangle” who can have diagnostic challenges to 63

care of infected travelers. Nevertheless, the current pandemic may be also included in 64

the roll of the LV differential diagnosis, because an earliest diagnosis will allow better 65

outcomes. We strongly believe that descriptions of case studies may enhance the 66

suspicion index about uncommon conditions, which favors prompt diagnosis and 67

adequate management. 68

Authors’ Contribution 70

VMS and TAMS drafted the manuscript. VMS and TAMS reviewed the literature and 71

performed the critical revision of the manuscript. All authors approved the final version 72

of the manuscript. 73

*Vitorino M. dos Santos1 and Taciana A.M. Sugai2 75

1Department of Internal Medicine, Armed Forces Hospital, and Catholic University of 76

Brasília, Brasília, Brazil; 2Department of Neurophysiology, American Society of 77

Neurophysiology, Brasília, Brazil 78

*Corresponding Author’s E-mail: vitorinomodesto@gmail.com 79

References 81

1. Vasireddy A, Pai K, Shetty VM, Acharya RV, Kusugodlu R, Doddamani A, et al. 82

Leukocytoclastic vasculitis: a peculiar presentation of scrub typhus. Sultan Qaboos 83

Univ Med J. 2023; 23(1):109-12. doi: 10.18295/squmj.1.2022.011. 84

2. Capoferri G, Daikeler T, Mühleisen B, Trendelenburg M, Müller S. Cutaneous 85

leukocytoclastic vasculitis secondary to COVID-19 infection leading to extensive skin 86

necrosis. Clin Dermatol. 2022; 40(4):397-401. doi: 10.1016/j.clindermatol.2022.02.013. 87

3. Corrà A, Verdelli A, Mariotti EB, Ruffo di Calabria V, Quintarelli L, Aimo C, et al. 88

Cutaneous vasculitis: Lessons from COVID-19 and COVID-19 vaccination. Front Med 89

(Lausanne). 2022 Dec 9;9:1013846. doi: 10.3389/fmed.2022.1013846. 90

4. Kutlu Ö, Öğüt ND, Erbağcı E, Metin A. Dermatologic comorbidities of the patients 91

with severe COVID-19: A case-control study. Dermatol Ther. 2021; 34(1):e14731. doi: 92

10.1111/dth.14731. 93

5. Wong K, Farooq Alam Shah MU, Khurshid M, Ullah I, Tahir MJ, Yousaf Z. COVID-94

19 associated vasculitis: A systematic review of case reports and case series. Ann Med 95

Surg (Lon 96

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