Lichen planus following SARS‐CoV‐2 infection and vaccination? A systematic review

Dear Editor,

Lichen planus (LP) is a self‐limiting, idiopathic mucocutaneous inflammatory disease with clinical subtypes, characterized by pruritic violaceous papules favoring the extremities. ¹ , ² LP has been previously associated with viruses (e.g. Hepatitis C) and vaccinations (e.g. Hepatitis B and C, influenza, DTaP‐IPV‐MMR), ¹ , ² and specifically recently, SARS‐CoV‐2 infection/vaccination. Cases of other autoimmune dermatologic conditions following SARS‐CoV‐2 infection/vaccination have been comprehensively summarized, ³ but cases of LP have not. Thus, this study comprehensively summarizes published cases of LP following SARS‐CoV‐2 infection and vaccination.

On June 28, 2022, PubMed, Embase, and Web of Science were searched for original articles reporting new onset or exacerbation of LP associated with SARS‐CoV‐2 infection/vaccination. Following PRISMA guidelines, title/abstract screening, full‐text review, and data extractions were completed in duplicate by two researchers, and discrepancies were managed by a third (Fig. 1). Articles reporting new onset or exacerbation of LP following SARS‐CoV‐2 infection/vaccination were included. Articles reporting quantitative population data on dermatoses following SARS‐CoV‐2 infection/vaccination, which included no case specifics, were excluded.

Figure 1.

Strategy used to identify eligible articles for inclusion, following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) Guidelines.

In total, 34 articles comprising 48 cases of LP were identified. The mean age of those affected was 55.6 years, with a male‐to‐female ratio of 7:9. Mean latency period between infection/vaccination and LP presentation was 11.1 days. The majority of cases occurred after vaccination (N = 41/48, 85.4%), with five (10.4%) occurring after infection and two (4.2%) after both infection and vaccination. The most commonly implicated vaccine was Pfizer‐BioNTech (n = 18/43, 41.9%). Twelve vaccine‐induced cases (27.9%) were following the first dose, 10 (23.3%) were following the first dose with worsening after the second, and 18 (41.9%) were following the second dose.

The most commonly affected area was the limbs (N = 22/48, 45.8%). The majority of cases were biopsy‐confirmed (N = 30/48, 62.5%). The mean score on Naranjo's Adverse Drug Reaction Probability Scale ⁵ (ADRPS) was 6.3 and ranged from 5.0 to 8.0.

LP treatment was reported in 37 cases and most commonly involved a topical corticosteroid alone (n = 19/37, 51.5%) or in combination with another nonsteroidal agent (n = 30/37, 81%) with the improvement of lesions in 100% of cases commenting on disease course. Oral corticosteroids were used alone in five cases (13.5%) with an improvement of lesions in all.

Characteristics of LP following SARS‐CoV‐2 infection/vaccination are summarized in Table 1.

Table 1.

Characteristics of lichen planus following SARS‐CoV‐2 infection or vaccination

	Result	Sample size
Age (years)	Mean = 55.6; Median = 56.0; Range = 28–82	48
Sex	Male: N = 21, 43.8%; Female: N = 27, 56.3%	48
Post vaccination or infection	Vaccination N = 41, 85.4%; Infection N = 5, 10.4%; Vaccination and infection N = 2, 4.2%	48
Latency period	Mean = 11.1 days; Median = 10 days; Mode = 14 days; Range = 0 days‐1 month	48
Vaccine type		43
Pfizer‐BioNTech	N = 18, 41.9%
Moderna	N = 3, 7.0%
Pfizer‐BioNTech and Moderna	N = 1, 2.3%
Oxford‐AstraZeneca	N = 9, 20.9%
Sinopharm	N = 8, 18.6%
Johnson & Johnson	N = 1, 2.3%
CoronaVac	N = 1, 2.3%
Not reported	N = 2, 4.7%
Vaccine dose number		43
1st	N = 12, 27.9%
1st, worsening with 2nd	N = 10, 23.3%
2nd	N = 18, 41.9%
Not reported	N = 3, 7.0%
When LP occurred following the first dose, was a second dose obtained?		22
Yes	N = 11, 50.0%
2nd dose same as 1st	N = 6, 54.5%
2nd dose different than 1st	N = 1, 9.1%
2nd dose type not reported	N = 4, 36.4%
Worsening of LP	N = 10, 90.9%
No worsening of LP	N = 1, 9.1%
No	N = 1, 4.5%
Not reported	N = 10, 45.5%
Diagnosis		48
Biopsy	N = 30, 62.5%
Clinical	N = 15, 31.3%
Previously made (i.e. exacerbation)	N = 3, 6.3%
Locations of lesions		48
Face/scalp	N = 4, 8.3%
Torso/axilla/groin	N = 20, 41.7%
Proximal limbs	N = 22, 45.8%
Distal limbs & hands/feet	N = 14, 29.2%
Oral mucosa	N = 11, 22.9%
Nails	N = 1, 2.1%
Treatment; outcome		37
Topical corticosteroid	N = 19, 51.3%; 16/16 w/ improvement
Topical corticosteroid + vitamin A	N = 2, 5.4%; 2/2 w/ improvement
Topical corticosteroid + oral antihistamine	N = 3, 8.1%; 2/2 w/ improvement
Topical corticosteroid + oral antihistamine  + hydroxychloroquine	N = 1, 2.7%; 1/1 w/ improvement
Topical corticosteroid + topical calcineurin inhibitor	N = 1, 2.7%; 1/1 w/ improvement
Topical calcineurin inhibitor	N = 1, 2.7%; 1/1 w/ improvement
Topical corticosteroids + oral steroids	N = 2, 5.4%; 1/1 w/ improvement
Topical corticosteroids + oral corticosteroids + oral antihistamine	N = 1, 2.7%; 1/1 w/ improvement
Oral corticosteroids	N = 5, 13.5%; 5/5 w/ improvement
Intralesional corticosteroid + oral JAK inhibitor	N = 1, 2.7%; 1/1 w/ improvement
Oral metronidazole	N = 1, 2.7%; 1/1 w/ improvement
Naranjo's adverse drug reaction probability scale scores	Mean = 6.3; Range = 5.0–8.0

The relationship between viruses/vaccinations and LP is unknown. ² However, the proposed pathophysiology includes virus/vaccine‐induced cell‐mediated autoimmunity or molecular mimicry. ² Drug/vaccine‐induced LP and classical LP appear identical with regards to location and morphology and cannot be differentiated histologically. ⁴ The two subtypes are typically only differentiated based on whether a history of recent vaccine or drug exposure is present. ⁴

According to Naranjo's ADRPS, scores between 5.0 and 8.0 suggest “probable” causality. ⁵ Therefore, the likelihood of causality between SARS‐CoV‐2 infection/vaccination and LP may be “probable.” This is considering the number of cases, temporal association, and recurrences/worsening with subsequent vaccine doses. ⁵ Of the 11 individuals who experienced symptoms after the first dose and underwent a second dose, 10 (90.9%) experienced disease worsening. Nevertheless, given that LP is generally a self‐limiting condition, these cases should not deter individuals from receiving SARS‐CoV‐2 vaccinations. Rather, this paper aims to educate physicians so their differential diagnosis of a dermatological reaction following SARS‐CoV‐2 infection/vaccination will include LP, and their history taking for a case of LP includes inquiring about recent SARS‐CoV‐2 infection/vaccination. In addition, clinicians should be cognizant of case demographics (e.g., sex, age), commonly affected anatomical areas, and latency periods between infection/vaccination and LP presentation. Finally, physicians should note that first‐line topical corticosteroid treatment, recommended for traditional LP, ¹ appears to properly manage these infection/vaccination‐induced cases as well.

Limitations of this study include the small sample size, lack of controlled studies, and the likelihood of unreported cases because of the self‐limiting natural history of LP.