key: cord-0976701-qrrvbdrm
authors: Erbaş, Gizem S.; Botsali, Aysenur; Erden, Nihan; Arı, Canan; Taşkın, Banu; Alper, Sibel; Vural, Secil
title: COVID‐19‐related oral mucosa lesions among confirmed SARS‐CoV‐2 patients: a systematic review
date: 2021-09-22
journal: Int J Dermatol
DOI: 10.1111/ijd.15889
sha: cc961617426859fd46df09e0b448ce661eda6f16
doc_id: 976701
cord_uid: qrrvbdrm

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is the virus responsible for coronavirus disease 2019 (COVID‐19), which manifests as a flu‐like respiratory infection affecting multiple organ systems, including the gastrointestinal system, central nervous system, cardiovascular system, skin, and mucosa. In this review, we investigated the literature on specific manifestations of COVID‐19 in the oral mucosa. An online literature search in PubMed, Scopus, Google Scholar, and Medline was conducted to retrieve relevant studies on confirmed COVID‐19 patients with oral mucosa findings published between December 31, 2019, and April 07, 2021. After an independent review by two authors, 39 articles considering 59 laboratory‐confirmed cases of SARS‐CoV‐2 infection were included in the final analysis. The most common finding, reported in 29 patients (43.9%), was Kawasaki‐like syndrome. In addition, oral ulcers including aphthous, hemorrhagic, and necrotic ulcers were reported in 24 patients (36.3%). Other lesions reported included pustules, macules, bullae, maculopapular enanthema, and erythema multiforme‐like lesions. Concomitant skin lesions were present in 60.6% of patients. Fever was reported in 86.2% of patients. Forty‐eight patients (76.1%) were hospitalized. Loss of taste and smell was present in 30.8% of the patients. A comprehensive understanding of the dermatologic manifestations of COVID‐19 can improve and facilitate patient management and referrals.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus that was observed initially as a cluster of cases with pneumonia in December 2019 in Wuhan, China. 1 The fatality rate is reported as between 2% and 4% in all age groups, but it increases with advanced age and the presence of comorbid conditions. 2 Erythema with vesicles or pustules (pseudo-chilblain) in acral areas, varicella-like vesicular eruptions, urticaria, maculopapular eruptions, livedo, and necrosis are among the skin manifestations seen in coronavirus disease 2019 (COVID- 19) cases. 3, 4 The pseudo-chilblain was usually associated with milder disease, whereas livedo and necrosis were associated with severe disease. 5 In children, SARS-CoV-2 infection usually has a benign course; however, Kawasaki-like multisystem inflammatory syndrome may develop, with associated skin findings, in a subset of children.

Enanthema and oral lesions are among the typical manifestations of many viral diseases. When the diagnosis is uncertain, the presence of enanthema in oral mucosa assists in distinguishing the type of viral exanthema. Recently, we observed four confirmed COVID-19 patients with oral mucosa findings: three patients with erythema multiforme and accompanying oral ulcers and cracked lips, and one patient with a swollen red tongue ( Figure 1 ). The erythema multiforme in these cases developed presumably due to a reactive response to COVID-19.

High infectivity and fatality rates restricted oral cavity exami- in addition to other related factors. 6 In this review, we searched the literature in detail for specific manifestations of COVID-19 in the oral mucosa to promote a comprehensive understanding of possible patterns and to provide up-to-date information for clinical practice.

This review was planned and conducted based on PRISMA guidelines. The inclusion criteria consisted of case reports and case series that reported the co-occurrence of COVID-19 and We searched the electronic databases for relevant articles with the keywords "oral mucosa," "oral lesions," "mucocutaneous," "gingiva," "tongue," "Kawasaki-like," AND "SARS-CoV-2" or "Covid- 19" 

The initial search yielded 5685 references (last updated on April 7, 2021). After removing duplicates, 2072 citations remained.

Following title and abstract screening, 1944 reports were considered irrelevant since they did not meet our inclusion criteria. We categorized the reported oral mucosa findings into three subgroups:

• KWL: Kawasaki-like syndrome-associated oral mucosa findings (cracked lips, dry lips, cheilitis with/without erythema of oral mucosa; Table 4 ). 17, 18, 22, 24, 26, 27, 29, 33, 40, 42, 43, 46, 49, 50 • M: Miscellaneous group (macular, papular, pustular, bullous, and overlapping cases; Table 5 ). [22] [23] [24] 31, 33, 34, 42, 43, 47, 51 Seven patients in this group had accompanying oral ulcers to other mucosal findings and are also included in Table 4 . 22, 24, 33, 40, 42, 43, 49 Kawasaki-like multisystem inflammatory disorder associated with oral mucosa symptoms was reported in 29 patients. Male patients constituted 62.1% (18/29) of this group. The reported dermatological manifestations were cracked lips, cheilitis, chapped lips, dry red lips, swollen red lips, strawberry tongue, and hemorrhagic crusts on the tongue. The median age in this group was 9 years (4 months to 45 years). Twenty-eight patients were reported to have fever (96.1%). Skin lesions were present in 92% of the patients (n = 27). Seventeen patients had respiratory system involvement (58.6%). Anosmia and dysgeusia were reported in one patient (3.4%). The age of patients in the KWL group was lower than that in both the OU and the M groups (P = 0.001).

Oral ulcers were reported in 24 patients. The median age of patients with oral ulcers was 39 years (range: 6-83). In 17 patients (70.8%), multiple lesions were reported. The majority of ulcers (58.3%, 14/24) were defined as aphthous ulcers, in which the lesion is surrounded by an erythematous halo due to dilated blood vessels and the ulcer bed is covered with a yellowish pseudomembrane. Necrotizing or ischemic ulcers were present in 12.5% (n = 3) of the patients. Shallow ulcers with irregular borders were observed in five patients (16.6%). All patients with ulcers reported pain. The tongue was the most common location for ulcers (54.1%), followed by the lips, buccal mucosa, and the palate. In the oral ulcer group, accompanying skin lesions were reported in seven patients (29.7%). Respiratory system involvement was present in 91.7% of the patients. Twelve patients reported dysgeusia and/or anosmia (50%).

The miscellaneous lesions are summarized in Table 5 . Various lesions in this group included overlapping lesions such as macular enanthema and oral ulcers. Four patients had maculopapular enanthema, and two of them had erythema multiforme, major type. Angina-bullosa-like lesions were reported in two patients (n = 2). In two patients, tongue depapillation was described.

There were more hospitalized patients and patients with systemic symptoms and fever in the KWL group versus the OU group (P = 0.004, 0.016, 0.049, respectively). Skin lesions were increased in the KWL group (P = 0.001). Dysgeusia and ageusia were reported more commonly among patients with oral ulcers (P = 0.001).

Histopathology was available for five lesions. The biopsy specimens from reddish skin areas and the ischemic ulcer, as 

In accordance with the types of studies (cases and case series) collected and publication bias, the evidence obtained is considered to be low grade.

The present systemic review was designed to collect and review reports of oral mucosa lesions in patients with COVID- 19 . Aphthous ulcers and Kawasaki-associated enanthema were reported multiple times, which enabled us to subcategorize the oral mucosa findings. Oral ulcers and cracked lips with erythema were among the most common findings in the oral mucosa.

Although symptoms and signs of infection including dysgeusia and mucosal lesions were reported, the involvement of the oral cavity in COVID- 19 has not yet been clarified. The Cases with oral ulcers accompanied by other mucosa findings, please see Tables 3 and 5 . 63 In light of safety concerns, teleconsultation or self-photography may help monitor signs and symptoms in the oral mucosa and may aid in identifying more cases.

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