Wolf's isotopic response: A case of dermatomal granuloma annulare after COVID‐19 vaccination

Abstract

The SARS‐CoV‐2 pandemic was announced in March 2020, with the first vaccines becoming available later that year. Although generally well tolerated, there have been reports of skin reactions occurring after receiving COVID‐19 vaccines, with a rare occurrence of granuloma annulare. Granuloma annulare can occur secondarily to herpes zoster infection in a phenomenon known as Wolf's isotopic response (WIR). WIR has been described to often occur after herpes zoster virus infection, at the location of the healed shingles rash, termed ‘post‐herpetic isotopic response' (PHIR). We present the first reported case of PHIR with granuloma annulare after the Moderna COVID‐19 vaccination series. This reported reaction should not limit receipt of the COVID‐19 vaccine, but awareness of this association can minimise additional work‐up and treatment.

INTRODUCTION

In response to the COVID‐19 pandemic, the first vaccines against SARS‐CoV‐2 became available in December 2020 and over 500,000,000 vaccine doses have been administered in the United States. Although generally well tolerated, there have been reports of skin reactions occurring after receiving COVID‐19 vaccines, including local site reactions, urticaria, erythromelalgia, and very rarely, granuloma annulare. ¹ Granuloma annulare is a benign and self‐limited cutaneous condition presenting with erythematous, granulomatous plaques and papules in an annular configuration, often on the hands and feet. ² Granuloma annulare can occur secondarily to herpes zoster infection in a phenomenon known as Wolf's isotopic response (WIR). ² , ³

WIR is a dermatological condition where a skin condition develops at the same location of a previous, morphologically distinct, and healed rash; it is a relatively rare condition. ⁴ WIR has been described to often occur after herpes zoster virus (HZV) infection, at the location of the healed shingles rash, termed ‘postherpetic isotopic response’ (PHIR). ⁴ , ⁵ We present the first reported case of PHIR with granuloma annulare after the Moderna COVID‐19 vaccination series.

CASE REPORT

A 63‐year‐old female patient presented with a dermatomal rash on her right flank that erupted 5 days after receiving the first dose of the Moderna COVID‐19 vaccine. While the rash faded, it recurred after the administration of the second dose of the vaccine. The rash was at its worst after the booster dose, at which time a punch biopsy was obtained. Her past medical history was notable for HZV infection, and hypercholesterolaemia treated by Simvastatin; she took no other medications regularly.

Multiple clusters of 1 cm × 1 cm annular pink plaques and papules with central clearing were on the patient's upper right abdomen and flank in a T6–T7 dermatomal distribution at the same location of an HZV rash 2 years prior (Figure 1). The pathology report of a punch biopsy demonstrated palisading granulomatous dermatitis with increased dermal mucin (shown by Alcian Blue Stain), consistent with granuloma annulare (Figure 2). Periodic Acid‐Schiff stain was unremarkable. Given that granuloma annulare occurred in the same location as the patient's previous HZV rash, this is consistent with WIR. After the biopsy results were explained, the patient elected against medical treatment of her granuloma annulare as it was asymptomatic.

Figure 1.

Granuloma annulare on the patient's right upper abdomen (a) and flank (b)

Figure 2.

Palisading granulomatous dermatitis with increased dermal mucin (a) Alcian blue, ×10 and (b) Alcian blue, ×40

DISCUSSION

There are many proposed theories for the pathogenesis behind WIR. The immunologic hypothesis proposes that during the healing process, memory T cells are recruited to the primary skin lesion; these memory T cells can be reactivated by future insults, causing secondary skin disease at the same location. ⁴ Alternatively, the neural hypothesis states that the primary skin lesion, caused by the HZV rash, leads to neuronal damage and neuropeptide release, which subsequently causes secondary skin disease. ⁴ A combination of factors likely plays a role in the development of WIR following HZV infection.

Numerous secondary skin lesions have been reported to occur in WIR, including lichen planus, leukaemia cutis, Majocchi's Granuloma, squamous cell carcinoma, and granuloma annulare. ⁴ , ⁵ Granuloma annulare is more likely to occur in women and can be triggered by infections, malignancy, trauma, and rarely, by vaccinations. ² , ³ García‐Gill et al., describe 14 cases of granuloma annulare occurring after vaccination. ³ Most cases occurred after the Bacillus Calmette‐Guerin vaccine, with others occurring after the Hepatitis B, Tetanus, Diphtheria‐Tetanus toxoid, Influenza, and pneumococcal vaccines. ³ According to the Centers for Disease Control and Prevention, of the 362,000 side effects reported from the mRNA COVID‐19 vaccinations, three cases of granuloma annulare were reported after Pfizer‐BioNTech and 13 cases were reported after Moderna, all in women. ⁶

In conclusion, we present the first reported case of PHIR with granuloma annulare after Moderna COVID‐19 vaccination. This reaction should not limit receipt of the vaccine, but awareness of this association can minimise additional work‐up and treatment.

AUTHOR CONTRIBUTION

All authors contributed to the preparation of this manuscript.

CONFLICT OF INTEREST

The authors declare no conflict of interest.

ETHICS STATEMENT

The patient in this manuscript has given informed consent to the publication of their case details. The University of Vermont Medical Center does not require IRB approval for case reports.

Esfandiari N, Benson P, Morley K. Wolf's isotopic response: A case of dermatomal granuloma annulare after COVID‐19 vaccination. JEADV Clin Pract. 2022;1–3. 10.1002/jvc2.90

DATA AVAILABILITY STATEMENT

Not applicable.