Oral Manifestations of Monkeypox: A Report of 2 Cases

Abstract

Monkeypox is a zoonotic infection caused by the monkeypox virus. It is a double-stranded DNA virus belonging to the Orthopoxvirus genus and the poxvirus family.1Brown K. Leggat P.A. Human monkeypox: Current state of knowledge and implications for the future.Trop Med Infect Dis. 2016; 1: 8-20Crossref PubMed Scopus (81) Google Scholar In the past, the clinical relevance of monkeypox was limited to Western and Central Africa, with transient outbreaks in the Western Hemisphere linked to either international travel or trade of exotic pets.2Khodakevich L. Jezek Z. Messenger D. Monkeypox virus: Ecology and public health significance.Bull World Health Organ. 1988; 66: 747-752PubMed Google Scholar,3Jezek Z. Grab B. Szczeniowski M. et al.Clinico-epidemiological features of monkeypox patients with an animal or human source of infection.Bull World Health Organ. 1988; 66: 459-464PubMed Google Scholar Currently, the Centers for Disease Control and Prevention and World Health Organization are tracking an outbreak of monkeypox cases, which began in May 2022. At the time of writing, approximately 15,000 cases have been reported in nearly 70 countries. Of these cases, more than 98% have occurred in locations where monkeypox has not traditionally been reported.4Kumar S. Subramaniam G. Karuppanan K. Human monkeypox outbreak in 2022.J Med Virol. 2022; (https://doi.org/10.1002/jmv.27894): 1-7Google Scholar, 5The Centers for Disease Control and Prevention2022 Monkeypox Outbreak Global Map.https://www.cdc.gov/poxvirus/monkeypox/response/2022/world-map.htmlDate accessed: July 15, 2022Google Scholar, 6World Health OrganizationClinical management and infection prevention and control for monkeypox. Emergency Response, WHO Headquarters (HQ), World Health Organization, 2022Google Scholar In the majority of these cases, international travel to endemic regions was not documented, suggesting community spread. There have been more than 2,000 cases reported in the United States during this outbreak, with many of these cases occurring in patients who identify as either homosexual or bisexual.5The Centers for Disease Control and Prevention2022 Monkeypox Outbreak Global Map.https://www.cdc.gov/poxvirus/monkeypox/response/2022/world-map.htmlDate accessed: July 15, 2022Google Scholar,7The Centers for Disease Control and Prevention2022 U.S. Map and Case Count.https://www.cdc.gov/poxvirus/monkeypox/response/2022/us-map.htmlDate accessed: July 15, 2022Google Scholar Patients with monkeypox infection will often report fever, fatigue, and influenza-like symptoms such as headaches, muscle aches, and swollen, painful lymph nodes. Most notably, patients will develop a pustular rash involving the skin.1Brown K. Leggat P.A. Human monkeypox: Current state of knowledge and implications for the future.Trop Med Infect Dis. 2016; 1: 8-20Crossref PubMed Scopus (81) Google Scholar,8Jezek Z. Szczeniowski M. Paluku K.M. et al.Human monkeypox: Clinical features of 282 patients.J Infect Dis. 1987; 156: 293-298Crossref PubMed Scopus (197) Google Scholar Monkeypox infection can spread from person to person via close contact with an infected individual. Transmission may occur via direct contact with the rash, respiratory secretions, or through fomites that have previously come in contact with an infected individual. Vertical transmission from infected mother to fetus through the placenta has also been documented.9Kumar N. Acharya A. Gendelman H.E. et al.The 2022 outbreak and the pathobiology of the monkeypox virus.J Autoimmun. 2022; 131: 102855Crossref PubMed Scopus (42) Google Scholar Although the cutaneous rash of monkeypox infection has been well documented, oral monkeypox lesions have only been infrequently described. Herein, we report 2 cases of oral manifestations of monkeypox infection. In both cases, the diagnosis of monkeypox was confirmed via laboratory testing shortly after the onset of the oral lesions. A 38-year-old male presented to an oral and maxillofacial surgeon for the evaluation of a recent onset anterior tongue lesion. The patient reported that the area was tender to palpation and endorsed worsening sensitivity in association with hot and spicy foods and beverages. He could not recall any clear history of trauma to his tongue. He reported that the lesion had been present for a few days before his appointment. The patient denied any underlying medical conditions, although he did endorse that he uses emtricitabine-tenofovir (Truvada) for the prevention of HIV. He also stated that he took Valacyclovir for a few days following the onset of his tongue lesion. At the time of presentation, the patient mentioned that he had a fever and fatigue but denied the presence of any additional oral or skin lesions. Clinical examination revealed an approximately 1 cm tan-gray, well-defined ulcerated lesion involving the tip of the tongue along the midline. In addition, smaller, clustered tan-gray vesiculo-ulcerative lesions were seen along the anterior ventral aspect of the tongue (Fig 1). A swab of the tongue lesions was performed and was positive for the monkeypox virus. Subsequently, the patient reported the development of approximately 20 skin lesions involving his arms, legs, and torso (Fig 2). He was prescribed tecovirimat and is currently recovering, although he is still symptomatic at this time.Figure 2(A and B) Pustular skin rash (marked by arrows), which manifested several days after the oral lesions.View Large Image Figure ViewerDownload Hi-res image Download (PPT) A 30-year-old male presented to the emergency department of Columbia University Irving Medical Center for the evaluation of a painful oral lesion involving the anterior dorsal aspect of his tongue. The patient also endorsed a 3-day history of fever, sore throat, and neck soreness. With regard to the oral lesion, he described a painful, “pimple-like” tender nodule of the tip of his tongue, which increased in size before his presentation to the emergency department. At the time of evaluation, a well-defined, tan-gray ulceration of the anterior tongue measuring approximately 1.0 cm in size was identified (Fig 3). No other oral lesions were observed, and no cutaneous lesions were identified on initial presentation. The patient's past medical history was significant for HIV, which was first diagnosed in 2016. At present, he reported that his viral load was undetectable, although he was unsure of his CD4 cell count. His past medical history was also significant for a prior diagnosis of syphilis. With regard to his social history, the patient reported that he was sexually promiscuous with multiple male partners over the past 6 months. Given the patient's clinical symptoms and reported social and medical history, the initial differential diagnosis included a wide range of infectious pathologies, including syphilis, a deep fungal ulcer, an atypical herpetic lesion, and tuberculosis. A traumatic ulcer was also considered, given the tip of tongue location. During his hospital stay, the patient subsequently developed a pustular, rash-like process involving the skin of his groin region, finger, back, and shoulders (Fig 4). Swabs from the cutaneous lesions and the tongue lesion were performed and were positive for monkeypox virus deoxyribonucleic acid (DNA) by nucleic acid amplification test with probe detection. Human monkeypox is a viral zoonosis belonging to the Orthopoxvirus genus. This genus also includes variola virus (the etiologic agent of smallpox), vaccinia virus, and cowpox virus.1Brown K. Leggat P.A. Human monkeypox: Current state of knowledge and implications for the future.Trop Med Infect Dis. 2016; 1: 8-20Crossref PubMed Scopus (81) Google Scholar The first documented case of monkeypox in humans occurred in 1970 in a 9-month-old male in the Democratic Republic of the Congo.10Ladnyj I.D. Ziegler P. Kima E. A human infection caused by monkeypox virus in Basankusu Territory, Democratic Republic of the Congo.Bull World Health Organ. 1972; 46: 593-597PubMed Google Scholar Monkeypox is known to be endemic to Western and Central Africa, and sporadic cases of monkeypox infection have been reported in multiple countries, including Cameroon, the Central African Republic, Congo Brazzaville, Ivory Coast, Gabon, Liberia, Nigeria, Sierra Leone, and South Sudan.11Breman J.G. Kalisa-Ruti Steniowski M.V. et al.Human monkeypox 1970-79.Bull World Health Organ. 1980; 58: 165-182PubMed Google Scholar,12Foster S.O. Brink E.W. Hutchins D.L. et al.Human monkeypox.Bull World Health Organ. 1972; 46: 569-576PubMed Google Scholar In addition, a single outbreak of 122 cases occurring in Nigeria was documented during 2017 to 2018.13Yinka-Ogunleye A. Aruna O. Dalhat M. et al.Outbreak of human monkeypox in Nigeria in 2017-18: A clinical and epidemiological report.Lancet Infect Dis. 2019; 19: 872-879Abstract Full Text Full Text PDF PubMed Scopus (170) Google Scholar The first reported cases of monkeypox infection in the United States occurred in 2003 and were due to exposure to infected African wildlife.14McCollum A.M. Damon I.K. Human monkeypox.Clin Infect Dis. 2014; 58: 260-267Crossref PubMed Scopus (219) Google Scholar Monkeypox infection has traditionally been of limited clinical concern in Europe and North America, with infrequent cases being linked to a history of travel to an endemic area. In May 2022, multiple countries in Europe, North America, South America, and Asia began to report a rising number of monkeypox infections. More than 98% of these cases were from locations not considered endemic for monkeypox infection.5The Centers for Disease Control and Prevention2022 Monkeypox Outbreak Global Map.https://www.cdc.gov/poxvirus/monkeypox/response/2022/world-map.htmlDate accessed: July 15, 2022Google Scholar Furthermore, a history of travel to endemic areas or exposure to infected wildlife was not reported, suggesting that this current outbreak is growing via community spread. Trends in the current outbreak include a higher frequency of cases in individuals who are homosexual or bisexual or are males who have sexual intercourse with other males. Other higher risk groups include individuals who are immunosuppressed, pregnant women, and health care or laboratory workers.15Kozlov M. Monkeypox goes global: Why scientists are on alert.Nature. 2022; 606: 15-16Crossref PubMed Scopus (66) Google Scholar Monkeypox is spread via close contact with an infected individual. It can be transmitted via direct exposure to the pustular rash, from respiratory droplets, or by touching surfaces that have come in contact with an infected individual. It can also be spread via direct contact with an infected animal or by consuming or using infected animal meat or products.15Kozlov M. Monkeypox goes global: Why scientists are on alert.Nature. 2022; 606: 15-16Crossref PubMed Scopus (66) Google Scholar,16Cohen J. Monkeypox outbreak questions intensify as cases soar.Science. 2022; 376: 902-903Crossref PubMed Scopus (14) Google Scholar Symptoms of monkeypox infection include fever, fatigue, chills, cervical lymphadenopathy, and muscle soreness. The most characteristic feature of Monkeypox infection is the development of a vesicular or pustular rash, which often involves the skin of the face, upper and lower extremities, torso and abdomen, and anogenital region. The development of the rash may occur before or after the onset of constitutional symptoms.1Brown K. Leggat P.A. Human monkeypox: Current state of knowledge and implications for the future.Trop Med Infect Dis. 2016; 1: 8-20Crossref PubMed Scopus (81) Google Scholar Monkeypox infection is a self-limiting illness, which resolves in most patients over a course of 2 to 4 weeks.1Brown K. Leggat P.A. Human monkeypox: Current state of knowledge and implications for the future.Trop Med Infect Dis. 2016; 1: 8-20Crossref PubMed Scopus (81) Google Scholar,17Petersen E. Kantele A. Koopmans M. Human monkeypox: Epidemiologic and clinical characteristics, diagnosis, and prevention.Infect Dis Clin North Am. 2019; 33: 1027-1043Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar Although the monkeypox rash has been reported to involve the oral mucosa, documentation of oral manifestations of monkeypox infection to date has been poor.18Sookaromdee P. Wiwanitkit V. Mouth sores and monkeypox: A consideration.J Stomatol Oral Maxillofac Surg. 2022; (pii: S2468-7855(22)00180-X)https://doi.org/10.1016/j.jormas.2022.06.020Crossref PubMed Scopus (12) Google Scholar This report describes 2 cases of oral lesions in patients with confirmed monkeypox infection. Although it is not possible to make sweeping generalizations based on such a limited number of cases, there were some findings in both that merit further discussion. In both patients, the oral lesions preceded the development of the skin rash by 1 or more days. In addition, the oral lesions appeared to have a somewhat midline distribution along the anterior aspect of the tongue. Both patients reported constitutional symptoms of fever, fatigue, and soreness before the onset of the oral lesions. Because of the limited clinical relevance of monkeypox before the May 2022 outbreak, it is often not initially considered in differential diagnosis. The differential diagnosis may include other infectious pathologies. Syphilis should be ruled out, given the presence of a papular rash. Other viral infections, including chickenpox, smallpox, and molluscum contagiosum, should also be excluded. Herpetiform drug eruptions may also be considered.1Brown K. Leggat P.A. Human monkeypox: Current state of knowledge and implications for the future.Trop Med Infect Dis. 2016; 1: 8-20Crossref PubMed Scopus (81) Google Scholar,19Bunge E.M. Hoet B. Chen L. et al.The changing epidemiology of human monkeypox-A potential threat? A systematic review.Plos Negl Trop Dis. 2022; 16: e0010141Crossref PubMed Scopus (305) Google Scholar With regard to the oral findings in particular, the differential diagnosis will often include more commonly encountered inflammatory and infectious processes. Traumatic ulcerations from biting may be considered in cases where the lesion presents as a tan-gray ulceration involving the anterior tongue. In the presence of constitutional symptoms such as fever, fatigue, and malaise, consideration may be given to primary herpetic gingivostomatitis, although this condition occurs more frequently in children. In patients with a history of immunosuppression, atypical manifestations of recurrent herpes simplex virus, as well as Epstein Barr Virus mucocutaneous ulcers, and ulcers caused by cytomegalovirus should be excluded. Syphilis may also present intraorally, and the oral lesions of monkeypox may resemble mucous patches of secondary syphilis infection. Oral manifestations of tuberculosis, although rare, may also present as ulcerated lesions of the oral mucosa. Diagnosis of monkeypox infection is confirmed via tissue swab of an active lesion.20The Centers for Disease Control and PreventionGuidance for tecovirimat Use Under Expanded Access Investigational New Drug Protocol during 2022 U.S. Monkeypox Cases.https://www.cdc.gov/poxvirus/monkeypox/clinicians/Tecovirimat.htmlDate accessed: July 15, 2022Google Scholar Testing of skin lesions is typically performed. If the oral lesions of monkeypox precede the development of the skin rash, then analysis of these lesions may help expedite diagnosis. Monkeypox infection is a self-limiting disease but rarely can be fatal in those who are very young or immunosuppressed. For individuals at higher risk for serious illness, antipoxviral drugs such as tecovirimat may be used. Tecovirimat is a medication used in the treatment of smallpox; however, its use for monkeypox infection has not been approved by the Food and Drug Administration. It is currently being used based on nonresearch expanded access investigational new drug protocol authorized by the Centers for Disease Control and Prevention. Based on these guidelines, it is recommended that tecovirimat be administered to patients who are immunocompromised, pediatric patients below the age of 8 years, individuals who are pregnant or breastfeeding, patients with atopic dermatitis or other exfoliative skin conditions, or in those with disease course complications, such as secondary bacterial infection or lesions involving high-risk anatomical sites such as the eyes or mouth.20The Centers for Disease Control and PreventionGuidance for tecovirimat Use Under Expanded Access Investigational New Drug Protocol during 2022 U.S. Monkeypox Cases.https://www.cdc.gov/poxvirus/monkeypox/clinicians/Tecovirimat.htmlDate accessed: July 15, 2022Google Scholar It can be administered either orally or intravenously. Vaccination for monkeypox does exist, although its use is currently limited to those who are considered high risk for developing monkeypox infection or who have been exposed to an individual with monkeypox.21Adler H. Gould S. Hine P. et al.Clinical features and management of human monkeypox: a retrospective observational study in the UK [published correction appears in Lancet Infect Dis. 2022 Jul;22(7):e177] [published correction appears in Lancet Infect Dis. 2022 Jul;22(7):e177].Lancet Infect Dis. 2022; 22: 1153-1162Abstract Full Text Full Text PDF PubMed Scopus (252) Google Scholar Human monkeypox infection is a rare viral zoonosis with increasing clinical relevance due to a recent global outbreak of cases. Oral manifestations of monkeypox infection are infrequently reported but may play a role in the diagnosis and management of this condition. Monkeypox should be considered in the differential diagnosis of acute onset oral ulcerations, especially in patients who are at higher risk for developing this condition. RE: Oral Manifestations of Monkeypox: A Report of Two CasesJournal of Oral and Maxillofacial SurgeryVol. 80Issue 12PreviewWe would like to share ideas on the publication “Oral manifestations of monkeypox: A report of two cases”.1 Two unusual instances of monkeypox that presented to the doctor with the first symptom of mouth lesions were documented by Peters et al.1 Currently, monkeypox is becoming a new public health concern. There is little doubt that the recent outbreak's nature means that there are not many data at this time. The distinct clinical appearance of monkeypox must be considered. No fever and an odd skin rash can be atypical clinical symptoms of the sickness. Full-Text PDF