Pityriasis rubra pilaris (type I) following administration of the BNT162b2 mRNA COVID‐19 vaccine: Successful treatment with ustekinumab and acitretin

Dear Editor,

Pityriasis rubra pilaris (PRP) is a rare erythematous papulosquamous disorder, clinically and pathologically similar to psoriasis. ¹

Since the approval of the mRNA vaccines for SARS‐CoV‐2, multiple cutaneous adverse events were associated with the administration of the vaccine. ² , ³

We report a case of recalcitrant PRP following administration of the BNT162b2 COVID‐19 vaccine (Pfizer‐BioNTech).

A 47‐year‐old Caucasian man presented us with fast development of scaly reddish plaques on scalp, back, chest, and limbs that appeared 15 days after he received the booster with the BNT162b2 vaccine in October 2021 (Figure 1A). He was vaccinated with two doses of CoronaVac (Sinovac Biotech) in March 2021, without intercurrences. He did not have any evidence of previous comorbidities or active infection and was not using other drugs. The patient also reported no personal or family history of psoriasis, PRP, or other autoimmune disease.

FIGURE 1.

(A) Clinical image of the patient demonstrating erythematous scaly plaques on limbs. (B) Psoriasiform hyperplasia and lymphocytic infiltrate in superficial dermis. Hematoxylin and eosin, original magnification × 10. (C) Decreased of granular layer with confluent parakeratosis and vascular ectasia. Hematoxylin and eosin, original magnification × 40. (D) Islands of sparing on neck 12 weeks after the use of secukinumab. (E) Islands of sparing on calves 12 weeks after the use of secukinumab. (F) Onychodystrophy 12 weeks after the use of secukinumab

Laboratory investigations showed a raised C‐reactive‐protein level and liver and kidney function altered. Serological testing for viruses and SARS‐CoV‐2 were negative. The chest x‐ray was normal and there were no signs of occult malignancy.

The skin biopsy performed on the chest showed psoriasiform hyperplasia with confluent parakeratosis, decreased granular layer, and lymphohistiocytic perivascular and perianexyal infiltrate in the papillary dermis (Figure 1B,C). The diagnosis of psoriasis was favored, with a differential diagnosis with adult PRP.

When the biopsy was performed, the patient had already used prednisolone 40 mg/day for about 15 days. Initially, the hypothesis of psoriasis was raised, despite the absence of neutrophils and microabscesses. However, the biopsy showed perifollicular infiltrate that could be related to PRP. The presence of orthokeratosis alternating with parakeratosis was not visualized, probably due to the previous use of prednisolone.

The evolution, the clinical presentation was more suggestive of PRP, with areas of healthy skin, extensive involvement of the palmoplantar regions and nails.

Secukinumab, a monoclonal anti‐interleukin (IL‐17A), was initiated due to the severity of the lesions. The patient did not have a good response to Secukinumab, and, within 12 weeks, his rash progressed with associated pruritus. Dermatological examination revealed a rash involving 90% of the body surface area with islands of sparing on neck and legs along with palmar‐plantar hyperkeratosis, onychodystrophy, and ectropion (Figure 1D–F). In this context, the patient was erythrodermic and had scalp involvement with scales, as well as erythema in the genital region. The nail involvement was posterior with palmoplantar keratoderma. Liver and kidney function tests were normal. These clinical features were consistent with the diagnosis of PRP.

Given the severity of the persistent eruption and unresponsiveness to the anti‐IL17, the treatment was switched to ustekinumab according to psoriasis protocol administration (90 mg at week 0, week 4, and then every 12 weeks) and acitretin (25 mg/day). Ustekinumab, a human monoclonal antibody that inhibits IL‐12 and IL‐23, was chosen as biologic agent since the patient used anti‐IL17 (secukinumab) and did not respond after 8 to 10 weeks. The use of anti‐IL23/IL‐12 monoclonal antibodies has been authorized just for psoriasis by our public health service, particularly in moderate and severe presentations. In our case, the use of ustekinumab was off‐label, based on studies that showed sustained effectiveness when compared to secukinumab. ⁴ , ⁵ , ⁶ , ⁷ , ⁸ There was a gradual improvement after the second dose of ustekinumab.

The etiology and pathogenesis of PRP remains unclear. It is best explained as an immune disorder, with an exacerbated immune response to antigenic triggers. ¹ , ⁹ , ¹⁰ Activation of the Th1 response with inflammatory cytokines alter the signaling of retinoid receptors, leading to epidermal changes found in PRP. ¹

In our case, a diagnosis of PRP Type I of Griffiths' classification 1 was made and the probable trigger considered was the Pfizer‐BioNTech vaccine. These association has been reported in two articles (Table 1). ⁹ , ¹⁰

TABLE 1.

Comparison among similar cases described in the literature about Pityriasis rubra pilaris (PRP) following COVID‐19 vaccination

Author, country, date	Dose/vaccine	Age/sex	Time to onset after vaccination	Treatment
Gamonal et al., Brazil, 2022	First and second dose sinovac, third dose BNT162b2	47 years/M	2 weeks after First dose BNT162b2	Ustekinumab and acitretin 25 mg/day
Hunjan et al., UK, 2022 4	First and second dose BNT162b2	51 years/M	Few days after second dose BNT162b2	Acitretin 20 mg and topical corticosteroid
Sechi et al., Italy, 2022 5	First dose BNT162b2	82 years/F	7 days after 1st dose BNT162b2	Subcutaneous methotrexate 15 mg/weekly

The causal relationship between mRNA vaccines and cutaneous immunological reactions is still under debate, but triggers include an abundance of type I interferons as a direct effect of the immunogenicity of vaccines (Th1 response), activation of tissue‐resident memory T cells in susceptible individuals (Th17/Th22 response), and vaccine‐derived damage to the extracellular matrix (imbalance of regulatory T cells). ² , ³ We are just starting to understand more about the efficacy and toxicity of the novel COVID‐19 vaccines.

Current therapeutic recommendations for PRP are based on the use of retinoids and methotrexate. The increase of Th1 cytokines was related to the success of tumor necrosis factor‐a inhibitors in the management of PRP, as well as secukinumab and ustekinumab. ¹ Recent studies have shown the efficacy of ustekinumab in the treatment of PRP. ⁴ , ⁵ , ⁶ , ⁷ , ⁸ Our patient was refractory to secukinumab, but the clinical response with ustekinumab was rapid and safe.

Although the association between COVID‐19 vaccination and PRP could be entirely casual, Dermatologists should be aware of these reactions and they can play an important role in appropriate identification and management of the condition, as well as in patient counseling.

The patient gave written consent for the use of his photographs and his clinical history.

AUTHOR CONTRIBUTIONS

Shirley Braga Lima Gamonal: Conceptualization and design of the study; Article draft and revision; final approval of the version to be submitted. Nathália Couri Vieira Marques: Conceptualization and design of the study; Article draft and revision; final approval of the version to be submitted. Heitor Motta Bini Pereira: Conceptualization and design of the study; Article draft and revision; final approval of the version to be submitted. Aloisio Carlos Couri Gamonal: Conceptualization and design of the study; Article draft and revision; final approval of the version to be submitted.

CONFLICT OF INTEREST

The authors declare no conflicts of interest.

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.