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Monkeypox (MPX) disease poses a threat to the frontline health workers, including dental practitioners; however, there is limited literature on its dental implications. The objective of this scoping review was to map the oral manifestations of MPX and its management based on existing information.
Materials and Methods
Articles published up to July 31, 2022 were searched to select relevant observational and experimental studies in humans who reported oral lesions in MPX disease, including case reports. The findings of this review are based on the pooled data of 1,136 patients (age range: 2-52 years) reported from different parts of the world.
Results
Oral lesions included mouth sores, oral mucosal lesions, ulcers on the tongue, tongue swelling, pustular lesions on the gingiva, perioral erosive lesions, oral candidiasis, and oropharyngeal lesions. Oral lesions of MPX infection and their management strategies are relevant to dentists. Dental practitioners may be the first to detect the initial symptoms of MPX disease.
Conclusion
Oral lesions may present as initial lesions of MPX suggesting that dentists and dental personnel should be aware of the nature of the disease. Clinicians must be alert to rashes resembling MPX lesions and distinguish MPX from herpetic and similar vesicular-bullous lesions for differential diagnosis. Symptomatic and supportive care for oral lesions is important.
Statement of Clinical Relevance
The oral lesions of monkeypox infection and their management are pertinent for clinicians. Dental practitioners may be the first to identify monkeypox lesions and should be more cautious while examining patients with fever and lymphadenopathy
The emergence of monkeypox (MPX) in humans is a global concern during the current COVID-19 crisis. Human MPX is a viral disease of animal origin (zoonosis) caused by a virus of the orthopox family and is closely associated with smallpox viruses. Although the first case was reported in the mid-1900s in Africa, it is now spreading to different parts of the world, which has led the World Health Organization (WHO) to declare it as a “global emergency.” Monkeypox virus (MPXV) infections have been reported in African countries, high-income settings (i.e., USA, Canada, Australia, Singapore) and several European countries (i.e., UK, Sweden, Spain, Portugal, Netherlands, Italy, Germany, Belgium, and France).
One of the hypotheses regarding the current outbreak is the general decline in the population's immunity to smallpox and similar orthopox virus diseases, as the smallpox vaccination program was discontinued 30 years ago.
Although there is no conclusive evidence of how the infection spreads, a primary animal-to-human infection by direct or indirect contact with the body fluid of an MPXV-infected animal
Monkeypox - enhancing public health preparedness for an emerging lethal human zoonotic epidemic threat in the wake of the smallpox post-eradication era.
Monkeypox - enhancing public health preparedness for an emerging lethal human zoonotic epidemic threat in the wake of the smallpox post-eradication era.
This transmission mode has been considered a significant threat to community health after the 2018 Nigerian outbreak. Diagnosis is made based on viremia, samples from upper respiratory tract swabs, and the presence of MPXV DNA by multiple molecular assays, especially polymerase chain reaction of the samples collected from the lesions.
In July 2022, the WHO declared MPX infection a public health emergency of international concern. This should alert the frontline health workers, including dental practitioners, to the high risk of developing MPX disease if they come in contact with infected patients and their body fluids. We have witnessed the catastrophic impact of the COVID-19 pandemic on dentists and dental practices. In this context, it is necessary to discuss the implications of MPXV infections on dental practice. Therefore, the objective of this scoping review was to map the oral manifestations of MPX disease and its management based on existing information.
MATERIALS AND METHODS
This scoping review aimed to map the oral manifestations of MPX disease and its management, based on existing information. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist was used. The protocol was prepared after a preliminary search of existing literature.
Eligibility criteria
Articles published up to August 15, 2022 were searched to select appropriate studies using the following Population/Concept/Context framework: Population: Human patients (all ages); Concept: Case reports, observational, and experimental studies; Context: MPX disease in humans. Case reports and observational and experimental studies conducted in English were included in this review. However, in vitro and in vivo studies, editorials, commentaries, letters to the editor, conference papers, and consensus papers were excluded.
Search strategy
Prominent literature databases, such as MEDLINE/PubMed, Scopus, Google Scholar, and Web of Science, were extensively searched on August 15, 2022. The search was conducted based on “Monkeypox” and “Oral lesions,” which are the key concepts in the research question. Literature that contained the MeSH terms, keywords, and other free terms related to “monkeypox,” “monkeypox,” “monkeypox virus,” “monkeypox virus,” “MPX,” “MPXV,” “oral lesions,” “oral ulcers,” “mouth,” “perioral,” “pharynx,” “oropharynx,” and “nasopharynx” were searched with Boolean operators and included in the initial screening. In addition, preprints (medrxiv and biorxiv) were searched. The full text of the selected articles was read in detail, and the evidence was corroborated in this review.
A preliminary search identified 45 eligible studies, of which 12 were excluded during the screening of title and abstract based on the eligibility criteria. Duplicates were removed using the reference manager (Endnote), and 2 reviewers examined the remaining 33 articles in full length based on the eligibility criteria. In cases of disagreement, a third reviewer resolved the differences through a discussion. Finally, 21 studies were excluded where oral manifestations were not described, and the remaining 12 studies were included where oral lesions in human MPX disease were reported (Figure 1).
Fig. 1Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart.
The relevant data were selected and recorded by 2 reviewers. The author's name, year of publication, country, mean age, sample size, study design, oral lesions, management of oral lesions, remarks assessed, results, and conclusions were charted for all the included studies.
RESULTS
The findings of this review were based on the pooled data of 1136 patients (age range: 2-52 years) reported in case reports, retrospective observational studies, and prospective cohort studies from different parts of the world (i.e., USA, UK, Nigeria, Spain, and Korea; Table I). Only 1 study included epidemiologic reports from multiple (16) countries.
Lesions with prodrome occurred in 17/30 cases. Isolated oral lesions in 13/30 cases. Within 7 d, ulcers on the tongue, corner of the mouth, and perioral umbilicated and vesicular lesions appeared. Pharyngitis, odynophagia, epiglottitis, and tonsillar lesions.
43.33%
Not mentioned specifically. Antiviral treatment, hospitalization for management of severe anorectal pain, and tissue superinfection.
Oropharyngeal symptoms were reported as the initial symptoms in 26/528 cases. Transmission is suspected through sexual activity in 95% of the infected persons. Generalized lymphadenopathy.
All 197 participants were men. 196 were gay or bisexual. Tonsillar signs were seen in 9/197 cases, and sore throat in 33/197 cases. Lymphadenopathy in most cases.
Demographic and clinical characteristics of confirmed human monkeypox virus cases in individuals attending a sexual health centre in London, UK: an observational analysis.
No specific management for oral lesions. Admission to hospital, mainly due to pain or localized bacterial cellulitis requiring antibiotic intervention or analgesia.
Most cases were in MSM. High proportion of concomitant STIs. Local inoculation occurs during close skin-to-skin or mucosal contact.
Young adult MSM with a previous history of STIs. MPX DNA was detected in saliva samples collected between 4 and 16 d after the onset of symptoms.
MPX, monkeypox; MSM, men who have sex with men; STI, sexually transmitted infection; IM, intramuscular; IV, intravenous; IM, intramuscular; PrEP, pre-exposure prophylaxis.
Demographic and clinical characteristics of confirmed human monkeypox virus cases in individuals attending a sexual health centre in London, UK: an observational analysis.
Demographic and clinical characteristics of confirmed human monkeypox virus cases in individuals attending a sexual health centre in London, UK: an observational analysis.
Demographic and clinical characteristics of confirmed human monkeypox virus cases in individuals attending a sexual health centre in London, UK: an observational analysis.
Demographic and clinical characteristics of confirmed human monkeypox virus cases in individuals attending a sexual health centre in London, UK: an observational analysis.
The specific management of these lesions has not been mentioned in most reports. Tonsillar edema and odynophagia improved slowly after initiation of tecovirimat for systemic lesions, and the patient recovered after 5 days.
The Magic mouthwash, intravenous fluconazole for oral candidiasis, and an intramuscular dose of penicillin were administered along with supportive care.
Various presentations of oral lesions have been reported in several cases of human MPX infections (Figures 2A and 2B). The oral mucosa may present with lesions that transform from vesicles to pustules, including umbilication and crusting, within 1 to 4 weeks.
These lesions may appear in the oral cavity and then follow the skin around the extremities in a centrifugal pattern, along with fever and lymphadenopathy.
Mahmoud A, Nchasi G. Monkeypox virus: a zoonosis of concern [e-pub ahead of print]. J Med Virol.https://doi.org/10.1002/jmv.27968, accessed September 14, 2022.
The oral lesions (enanthem) have detectable viral DNA particles in the oral and pharyngeal passages, even in the absence of skin lesions in the prodromal stage.
irrespective of the route of infection (intradermally or intranasally).
Fig. 2(A) Perioral lesions in a 26-year-old male who tested positive for monkeypox polymerase chain reaction test. Arrow depicts umbilicated pox-like lesions of monkeypox disease. (B) Oral candidiasis and umbilicated lesions on the tongue in the same 26-year-old male patient. PCR, polymerase chain reaction. Photo credit: Ajmera KM, Goyal L, Pandit T, Pandit R. Monkeypox - an emerging pandemic. IDCases. 2022;29:e01587.
The oral lesions on the oral epithelium, tongue, and labial mucosa have shown epithelial hyperplasia, intracellular edema (ballooning degeneration), necrosis, ulceration, and scattered and poorly defined eosinophilic intracytoplasmic inclusion bodies.
The exact mode of MPXV transmission to humans has not yet been confirmed. It can either be transmitted from animals to humans through direct or indirect contact with MPX-infected animals or their body fluids
Monkeypox - enhancing public health preparedness for an emerging lethal human zoonotic epidemic threat in the wake of the smallpox post-eradication era.
The virus enters the body via damaged skin, the respiratory tract, or the mucous membranes of the eyes, nose, or oral cavity; large respiratory droplets; or direct or indirect contact with body fluids, lesion material, and contaminated surfaces, clothing, or linens. Local inoculation occurs during close skin-to-skin or mucosal contact.
Demographic and clinical characteristics of confirmed human monkeypox virus cases in individuals attending a sexual health centre in London, UK: an observational analysis.
Dentists should be vigilant when examining a suspected case of MPX because the primary lesions often originate in the oropharynx before manifesting on the skin.
which could be of particular significance in children and patients with comorbidities such as diabetes mellitus.
A possible sex predilection may be suggested based on the findings of the marmoset model of MPX. This experiment found more lesions and a lower viral burden (viremia and oral shedding) in women than in men.
Demographic and clinical characteristics of confirmed human monkeypox virus cases in individuals attending a sexual health centre in London, UK: an observational analysis.
in non-endemic regions such as the UK and Spain. A noteworthy finding was that most infected persons were gay or bisexual men; hence, transmission was suspected to occur through sexual activity.
Demographic and clinical characteristics of confirmed human monkeypox virus cases in individuals attending a sexual health centre in London, UK: an observational analysis.
Demographic and clinical characteristics of confirmed human monkeypox virus cases in individuals attending a sexual health centre in London, UK: an observational analysis.
However, these well-controlled patients with HIV were on antiretroviral therapy (ART), and a very low HIV viral load (<50 copies per mL) was seen in most patients.
have also been reported in patients with MPX disease.
Management of oral lesions of MPX disease
Most reports included in this review did not mention the specific management of oral lesions. Although it is self-limiting, prompt management is essential. Symptomatic treatment is the mainstay of therapy, especially during the prodromal phase.
Afshar ZM, Rostami HN, Hosseinzadeh R, et al. The reemergence of monkeypox as a new potential health challenge: a critical review [e-pub ahead of print]. Authorea.https://doi.org/10.22541/au.165446104.43472483/v1, accessed September 14, 2022.
The interim rapid response guidance released on June 10, 2022 by the WHO recommends rinsing the mouth with saltwater at least 4 times a day in case of oral lesions. Oral lesions can cause secondary infections and facilitate person-to-person viral transmissions. A clean, moist microenvironment can mitigate transmission potential by covering infectious sores and promoting re-epithelialization of damaged exanthem. Using an oral antiseptic solution, such as chlorhexidine mouthwash, can keep the lesions clean. Alternatively, cleansing the ulcers with a dilute povidone-iodine solution will help maintain a hygienic microenvironment.
Oral and topical analgesics or acetaminophen can be administered to control the pain in oral mucosal lesions. Patients with secondary bacterial infections should be treated with appropriate antibiotics.
The use of non-steroidal anti-inflammatory drugs for pain relief should be limited owing to the concern of developing hemorrhagic lesions. Mucosal lesions of the mouth can be painful and warrant the use of appropriate analgesics.
“Magic mouthwash” along with intravenous fluconazole for oral candidiasis and an intramuscular dose of penicillin demonstrated symptomatic relief in a patient.
Co-administration of tecovirimat and ACAM2000 in non-human primates: effect of tecovirimat treatment on ACAM2000 immunogenicity and efficacy versus lethal monkeypox virus challenge.
in controlling the outbreak since the MPX and smallpox viruses are related. Cidofovir, brincidofovir, and tecovirimat are antivirals suggested to defend against MPX
Siegrist EA, Sassine J. Antivirals with activity against monkeypox: a clinically oriented review [e-pub ahead of print]. Clin Infect Dis.https://doi.org/10.1093/cid/ciac622, accessed September 14, 2022.
infection and as a post-exposure prophylactic agent in exposed immunocompromised individuals who are contraindicated to receive the smallpox vaccine as a post-exposure prophylactic measure.
Patients with oral lesions should be monitored for dehydration and malnutrition and should maintain good nutrition and hydration. Complications of illness include low mood and emotional lability, which may expose patients to poor oral health practices.
Elective surgery should be deferred as long as the patient is infectious. Linens, hospital gowns, towels, and other fabrics should be carefully handled.
Precautions in dental clinics
Transmission can be prevented in dental care settings by taking standard, contact, and droplet infection control precautions when treating patients with MPX symptoms.
Tsagkaris C, Eleftheriades A, Laubscher L, Vladyckuk V, Papadakis M. Viruses monkeying around with surgical safety: monkeypox preparedness in surgical settings [e-pub ahead of print]. J Med Virol.https://doi.org/10.1002/jmv.27915, accessed September 14, 2022.
The patient should be managed in isolation, and precautions should be taken to minimize the exposure to surrounding individuals, such as covering any exposed skin lesions and placing a surgical mask over the patient's nose and mouth. In patients with probable or confirmed MPX infection, elective dental treatment should be deferred until the patient is no longer infectious.
Ulcers in the oral cavity or oropharynx can be the primary lesions compared with skin lesions in MPX cases. Oral ulcers have been recorded in almost one-quarter of patients with MPX infection. The lesions initially appear as pink macules or papules. Oral ulcers make it difficult for patients to consume food. Perioral blistered and ulcerated lesions have also been reported in several recent cases. The management of oral ulcerations includes symptomatic and supportive care, including the use of mouthwashes. Antiviral treatment and the use of antibiotics are recommended in severe cases and in cases with multiple lesions elsewhere in the body. Dental practitioners may be the first to detect the initial symptoms of MPX infection. Therefore, caution should be exercised, particularly when examining patients with fever and lymphadenopathy.
FUNDING
Funding for open access publishing has been received from Qatar national library.
Declaration of interest
none.
REFERENCES
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Emergence of monkeypox: another concern amidst COVID-19 crisis.
Monkeypox - enhancing public health preparedness for an emerging lethal human zoonotic epidemic threat in the wake of the smallpox post-eradication era.
Demographic and clinical characteristics of confirmed human monkeypox virus cases in individuals attending a sexual health centre in London, UK: an observational analysis.
Mahmoud A, Nchasi G. Monkeypox virus: a zoonosis of concern [e-pub ahead of print]. J Med Virol.https://doi.org/10.1002/jmv.27968, accessed September 14, 2022.
Afshar ZM, Rostami HN, Hosseinzadeh R, et al. The reemergence of monkeypox as a new potential health challenge: a critical review [e-pub ahead of print]. Authorea.https://doi.org/10.22541/au.165446104.43472483/v1, accessed September 14, 2022.
Co-administration of tecovirimat and ACAM2000 in non-human primates: effect of tecovirimat treatment on ACAM2000 immunogenicity and efficacy versus lethal monkeypox virus challenge.
Siegrist EA, Sassine J. Antivirals with activity against monkeypox: a clinically oriented review [e-pub ahead of print]. Clin Infect Dis.https://doi.org/10.1093/cid/ciac622, accessed September 14, 2022.
Tsagkaris C, Eleftheriades A, Laubscher L, Vladyckuk V, Papadakis M. Viruses monkeying around with surgical safety: monkeypox preparedness in surgical settings [e-pub ahead of print]. J Med Virol.https://doi.org/10.1002/jmv.27915, accessed September 14, 2022.
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