Monkeypox in a Non-endemic Setting: Challenges in the Diagnosis and Management of an Atypical Case

Monkeypox is a zoonotic viral disease caused by the monkeypox virus, an Orthopoxvirus closely related to smallpox. While historically confined to endemic regions in Africa, recent outbreaks have demonstrated its capacity to spread globally, posing significant diagnostic and therapeutic challenges. We present the case of a 28-year-old previously healthy Caucasian male who repeatedly sought care in the emergency department (ED) for nonspecific flu-like symptoms, including fever, lymphadenopathy, dysphagia, and a progressive vesiculopustular rash. The initial lack of a clear clinical picture led to multiple misdiagnoses and treatments for presumed bacterial infections. Despite multiple evaluations and initial misdiagnoses, the persistence and progression of symptoms - including worsening lymphadenopathy, dysphagia, and a vesiculopustular rash with umbilicated lesions - raised concern for an Orthopoxvirus infection. Given the patient's history of intimate contact with a male partner who had recently traveled internationally, monkeypox became a key diagnostic consideration. Other possible differential diagnoses included bacterial tonsillitis, peritonsillar abscess, syphilis, varicella, and other sexually transmitted infections. This evolving clinical picture prompted expedited non-variola Orthopoxvirus DNA polymerase chain reaction (PCR) testing, which ultimately confirmed the diagnosis. This report highlights the diagnostic challenges posed by monkeypox in non-endemic settings, where healthcare providers may have limited familiarity with the disease. It demonstrates the need for heightened clinical suspicion in patients with compatible symptoms, especially during outbreak periods. The patient's subsequent treatment with tecovirimat demonstrated its potential effectiveness in mitigating symptoms and improving outcomes when initiated promptly. Additionally, this report emphasizes the crucial role of public health measures, including robust surveillance systems such as enhanced case reporting, rapid diagnostic testing networks, and contact tracing programs, alongside healthcare provider education and vaccination strategies, in combating the spread of this reemerging infectious disease.