COVID-19 vaccines-related dermatological manifestations

Local site injection reaction

The most common adverse cutaneous manifestation reported was local injection site reactions, which are characterized by erythema, swelling, tenderness, pain, induration, and pruritus. It is usually manifested within a week of the vaccination. It is associated with mild-to-moderate pain at the injection site. There is a higher incidence of local site injection reactions in the younger population than in the elderly (60 years and older).^[2,3]

Delayed large local reactions

This type of reaction is described as the development of an erythematous and edematous patch at least 4 days or more at the injection site after the vaccine administration. It was reported in the non-trial literature.^[1] It is also known as “COVID-19 arm.” According to Moderna’s phase III trial, this was typically manifested after a week of vaccination and consisted of tenderness at the site, induration, and erythema.^[2] Most of the delayed large local reaction occurred with the Moderna vaccine (mRNA-1273), although it has also been observed with the Pfizer vaccine (BNT162b2). The etiology is not known although, a delayed hypersensitivity reaction to an excipient, polyethylene glycol in both the vaccines may be one explanation of the occurrence of the cutaneous reaction.^[4] Most of the reactions are mild and resolve spontaneously. However, few patients were treated conservatively with ice packs, antihistamines, analgesics, and topical or oral corticosteroids.^[5,6]

Morbiliform rash

This type of rash is the most commonly reported exanthem in many cases of COVID-19 infections in both pediatric and adults.^[7,8] In three observational studies, 49% of individuals received the Pfizer vaccine and 51% received the Moderna vaccine.^[9,10] The histopathological examination suggested an immunological etiopathogenesis due to direct viral effect.^[11] Therefore, it may be speculated that morbilliform rash induced by COVID-19 vaccine is a result of an immune activation.

Urticaria

Centers for Disease Control and Prevention (CDC) has defined urticaria as a part of immediate hypersensitivity reactions. It has been characterized as having an onset within or after 4 h of injection.^[10] The reaction within 4 h is a contraindication to the second dose. There have been cases reported from literature from both Pfizer and Moderna mRNA vaccines. Few of the cases had been submitted to the vaccine adverse event reporting system and labeled by the CDC as a part of anaphylaxis. However, according to the dermatology registry of COVID-19 cases, urticaria was not classified as an immediate hypersensitivity reaction.^[1]

Delayed inflammatory reactions (DIRs) to dermal fillers

Dermal fillers include hyaluronic acid fillers, which are often resistant to biodegradation. These are more durable and result in increased DIRs to the implants. Triggering factors of DIRs to fillers include viral infections, dental or surgical procedures, influenza vaccines, and the latest, COVID-19 vaccines.^[12] Of the available results from observational studies, 73% were associated with Moderna and 27% with the Pfizer vaccine.^[13,14] DIRs to dermal fillers occurred in those individuals who had been injected for more than 1–2 years in the pre-COVID-19 vaccination period.^[14] DIRs developed rapidly within a day or 2 and patients presented with swelling and inflammation in areas of fillers. The proposed hypothesis for its occurrence is due to the targeting of SARS-CoV-2 spike protein to highly expressive angiotensin-converting enzyme (ACE) 2 receptors in adipose tissue, thereby releasing a proinflammatory cascade of cytokines. ACE inhibitors promote an anti-inflammatory response.^[14] The use of short-term ACE inhibitors is useful whereas it is resistant to treatment with antihistamines, hyaluronidase, and acetaminophen.^[12,14]

Pernio and chilblains

There have been reports of pernio-like lesions since the commencement of COVID-19 pandemic.^[15] However, it has also been associated with COVID-19 vaccines.^[16] Few observational studies have revealed these manifestations with 60% with the Pfizer vaccine and the rest with the Moderna vaccine. These lesions are characterized by painless, erythematous, violaceous macules, and papules over hands and feet with cold exacerbation.^[17] The histopathological examination of vaccine-associated lesions confirmed the pernio diagnosis.^[18] Topical corticosteroids resolve the lesions in 1 week to a month.^[18]

Autoimmune-mediated reactions

The spike protein of the SARS-CoV-2 vaccine shares genetic similarities with human proteins, thereby triggering autoimmune diseases after vaccination. The term “ASIA” syndrome (autoimmune/inflammatory syndrome induced by adjuvants) is considered a phenomenon that occurs after exposure to adjuvants. Pfizer vaccine has been reported to cause subacute thyroiditis or Grave’s disease.^[19] Niebel et al.^[20] reported a patient with a flare of subacute cutaneous lupus erythematosus after the Pfizer vaccine. There are also reports of new-onset as well as a flare of re-activation of leukocytoclastic vasculitis after the Pfizer vaccine.^[21]

Reactivation of viral conditions

Vaccination may induce immune dysregulation by vaccine-specific infectious particles which result in human herpes virus reactivation leading to herpes zoster and pityriasis rosea.^[22,23]

Miscellaneous conditions

There have been reports of erythromelalgia, flare of lichen planus, varicella zoster, petechial rash, and purpura in patients with mRNA COVID-19 vaccination.^[1,24]

Thromboembolic events

There have been reports of thromboembolic events with adenoid viral vector COVID-19 vaccines.^[25] Several European nations had suspended the use of the AstraZeneca vaccine due to unusual reports of patients having blood clots with low blood platelets.^[26] However, the overall risk is quite low and the physicians should be well versed with a condition, namely vaccine-induced prothrombotic immune thrombocytopenia (VIPIT), which might be attributed as an adverse event to AstraZeneca COVID-19 vaccine.^[27] The reaction is similar to heparin-induced thrombocytopenia or drug-induced cutaneous vasculitis.^[28] VIPIT presents as erythema, petechial rash, and edema of the extremity with pallor and coldness. Systemic symptoms may include persistent headache, seizures, dyspnea, chest, and abdominal pain.^[29]

Local injection site reaction

All reported reactions were self-limiting and presented as erythema, edema, and tenderness for a few days.^[30] Viral vector vaccines including Oxford-AstraZeneca, Covishield, Sputnik, and Johnson and Johnson have shown local injection site reactions.

Urticaria

There have been reports of urticaria and dermographism in patients who received the Covishield vaccine (viral vector). The onset of reaction was within 4 days after vaccination.^[31]

Miscellaneous reactions

There have been isolated reports of morbilliform, papulovesicular, pityriasis rosea-like, and purpuric rash in patients who received viral vector vaccine.^[32] An isolated case of DIR has also been reported with the viral vector vaccine (Oxford-Astrazeneca).^[33] The acneiform eruption, allergic dermatitis, alopecia, and petechial rash have been reported in the Sputnik vaccine.^[34]

Most of the adverse events are not life-threatening except anaphylaxis, VIPIT, or thromboembolic event; however, in case of patients presenting with a petechial rash with edematous extremities and shortness of breath, the subsequent vaccine dosing should be deferred; however, physicians should weigh the risk-benefit ratio in cases where contracting COVID-19 is higher.