A case of cutaneous small vessel vasculitis after the seventh dose of COVID‐19 vaccination

Abstract

A 77‐year‐old woman on regular hemodialysis was admitted due to purpura on her extremities, elevated C‐reactive protein (CRP), D‐dimer, and syncope attack. Despite hospitalization and treatment, her purpura got worse, and a skin biopsy revealed cutaneous small vessel vasculitis (CSVV). No apparent cause could be pointed out for CSVV. Her purpura had deteriorated until we started treatment with prednisolone (PSL). We later confirmed that she had received her seventh COVID‐19 vaccination before the onset of purpura on her extremities. In this case, the highlight is that even the seventh dose of the COVID‐19 vaccination could potentially induce CSVV.

The COVID‐19 vaccine, even after the seventh dose, could elicit CSVV, and it is mandatory to take the vaccination history when encountering a patient with CSVV.

1. INTRODUCTION

Vaccinations are generally safe and crucial for infectious disease prevention. Although adverse events to vaccinations are usually mild and well tolerated, they can elicit cutaneous reactions. ¹ Cutaneous adverse events related to the COVID‐19 vaccines have been commonly reported ² , ³ with more and more use. One of them is CSVV, which may be idiopathic or secondary to defined causes, such as infection, medications, autoimmune connective tissue diseases, or malignancy. ⁴ We report a case of CSVV that the seventh dose of COVID‐19 vaccination could have induced.

2. CASE PRESENTATION

A 77‐year‐old Japanese woman on regular hemodialysis treatment at Izumo Tokushukai Hospital noticed purpura on her extremities from the previous day (Figure 1A,B). Therefore, blood tests were performed at the time of hemodialysis, which revealed elevated CRP (4.06 mg/dL) and D‐dimer (41.2 μg/mL) levels. After the completion of hemodialysis, she was referred to an outpatient clinic.

FIGURE 1.

(A) Symmetrically distributed purpuric macules and papules were located on the hands. (B) Symmetrically distributed purpuric macules and papules were located on the legs.

Anamnesis showed no personal or family history of autoimmunity, no smoking, and no drug allergies. She was introduced to hemodialysis 2 years ago due to end‐stage renal failure caused by type 2 diabetes. She regularly took ursodeoxycholic acid, precipitated calcium carbonate, atorvastatin, calcium hydrate, lansoprazole, aspirin, alogliptin benzoate, evocarset, alfacalcidol, and nifedipine. No new medication episodes were identified, even though over‐the‐counter medications and supplements were checked 3 months before the purpura appeared.

During clinical examination, her vital signs were stable, with a blood pressure of 124/78 mmHg and a pulse rate of 78 beats/minute. She had no subjective symptoms other than purpura and was aware of only a mild itching sensation in the lower extremities. At the end of the examination, as she was leaving the examination room, she suddenly lost consciousness, and her systolic blood pressure dropped to 80 mmHg. She recovered to the 100 mmHg range after bed rest and intravenous infusion. Since sepsis was also considered from the course of her illness, she was admitted to our hospital.

First, antimicrobial therapy was started under the tentative diagnosis of infection. After a while, blood culture on admission showed only one set of coagulase‐negative staphylococci, which appeared to be contaminants. Moreover, no significant bacteria in subsequent cultures were detected. During hospitalization, she had no physical symptoms other than purpura with a mild itching sensation and was negative for cryoglobulin, anti‐CL‐β2GP1, and antineutrophil cytoplasmic antibodies.

However, on day 5 of hospitalization, an exacerbation of her purpura was noted. After discontinuation of all medications from Day 6, a skin biopsy from the outer left thigh with newly appearing lesions was performed. Histopathological examination from the biopsy of a purpuric lesion revealed an inflammatory infiltrate composed predominantly of neutrophils with their fragments, mainly around small blood vessels in the slightly edematous dermis. There was no fibrin deposition or thrombus formation in the vessels (Figure 2). She was diagnosed with CSVV based on the clinical course confined to the skin and histopathological character referring to vascular damage caused by the infiltration of neutrophils. ⁵

FIGURE 2.

Histopathological examination (H&E stain). Sections showed a perivascular inflammatory infiltrate predominantly composed of neutrophils.

Next, we discontinued medications that she usually took regularly, in addition to the antimicrobial used on admission. However, she had another exacerbation of purpura from Day 13, so we prescribed prednisolone (PSL) at 20 mg/day on day 14. Computed tomography (CT) examination, gastroscopy and colonoscopy performed during hospitalization showed no malignancy. Since the purpura, as well as elevated CRP and D‐dimer, improved with the start of PSL, and no further deterioration was observed after the resumption of regular oral medications. So, she was discharged home on Day 23 after the tapering of PSL.

After discharge, a comprehensive interview revealed that she had received the seventh dose of the COVID‐19 vaccine 11 days prior to the onset of purpura on the skin. Therefore, it was ultimately determined that the seventh dose of the COVID‐19 vaccine was the inciting factor in her CSVV.

3. DISCUSSION

In previous reports, 45%–55% of CSVV cases are idiopathic. ⁶ They were reported to be caused by infections (15%–20%), autoimmune connective tissue disease or inflammatory conditions (10%–15%), hypersensitivity drug reactions (10%–15%), or lymphoproliferative disorders or malignancies (5%). ⁶ , ⁷ In our case, on admission, antibiotic treatment was initiated, considering the purpura of the extremities, elevated CRP and D‐dimer, and syncope due to hypotension. Based on the course of treatment and the results of the blood culture, the cause of syncope was presumed to be orthostatic hypotension after hemodialysis, not infection. Other than infection, possible causes of CSVV were considered to be drug reactions. However, despite the discontinuation of medications, the purpura got worse. There were no subjective symptoms other than purpura, and no malignant tumors were found on thoracoabdominal CT, gastroscopy, or colonoscopy. There also were no significant physical or laboratory findings suggestive of autoimmune diseases.

Some vaccines, such as influenza, hepatitis B, and hepatitis A, have also been associated with vasculitis ⁸ in the case reports of CSVV. The frequency of CSVV due to vaccination is difficult to ascertain precisely because it is uncommon, and the reported cases are sporadic. Upon reconfirmation with the patient, we got to know that she had taken the seventh COVID‐19 vaccine 11 days before the onset of her purpura. In previous reports ⁹ , ¹⁰ CSVV occurred 1 to 20 days after COVID‐19 vaccination. Since she had not received any vaccine other than COVID‐19 for the past 3 months, we ultimately concluded that her seventh COVID‐19 vaccine most likely induced CSVV.

We experienced a case of CSVV associated with the seventh dose of COVID‐19 vaccine. She had no adverse reactions to the previous six COVID‐19 vaccines. Most adverse cutaneous reactions following COVID‐19 vaccination have been reported to occur in the first or second dose. ¹¹ , ¹² To our knowledge, this is the first case report of CSVV associated with the seventh dose of COVID‐19 vaccine. A review of her vaccination history revealed that her fifth and sixth COVID‐19 vaccines were bivalent original/Omicron‐BA.4/BA.5‐adapted BNT162b2. The seventh COVID‐19 vaccine given 11 days before the appearance of purpura was monovalent Omicron XBB.1.5‐adapted BNT162b2. Her adverse skin reaction could be because the seventh vaccine was the first type of omicron reactant. If so, we must bear in mind that differences in vaccine composition may elicit CSVV; therefore, taking the vaccination history is mandatory for a patient with CSVV.

CONFLICT OF INTEREST STATEMENT

We have no conflicts of interest to declare.

ETHICS STATEMENT

Ethical approval statement: None.

Patient consent statement: We have obtained all appropriate patient consent forms for her photographs and data received.

Clinical trial registration: None.

Sato H, Maruyama R, Kishi H, Higashi K, Yuki M, Nagami H, et al. A case of cutaneous small vessel vasculitis after the seventh dose of COVID‐19 vaccination. J Gen Fam Med. 2025;26:163–165. 10.1002/jgf2.762