A 53-year-old man who has sex with men and women presented to the emergency department with headache, fever, neck stiffness, cervical lymphadenopathy, fatigue, myalgia, rash, and a painful perianal lesion. The patient had been diagnosed previously with human immunodeficiency virus and was on antiretroviral therapy. His signs and symptoms started 5 days earlier. In the emergency department, he was febrile to 101.5°F (38.6°C) with otherwise normal vital signs.
Examination revealed a tender, ulcerated perianal lesion and scattered papules on the trunk and extremities (Figure 1). Laboratory tests showed an elevated C-reactive protein of 29.6 mg/L (reference range < 5.0) but were otherwise unremarkable. His CD4 count was 663 cells/mm3 (404–1,612) with a human immunodeficiency virus viral load of 116 copies/mL (< 20). Initial workup in the emergency department was unrevealing and included chest radiograph, urinalysis, and chlamydia and gonorrhea urine polymerase chain reaction (PCR) testing. Cerebrospinal fluid studies and blood cultures were negative.
Examination of the patient revealed a papular umbilicated rash on the trunk and an ulcerated perianal lesion.
The patient was admitted for further evaluation. A thorough sexual history was obtained and revealed that the patient engaged in unprotected, receptive anal intercourse. A wide differential for his tender perianal lesion included syphilis, herpes simplex virus, bacterial abscess, and mpox. Multiple PCR swabs and a punch biopsy of the lesion were obtained.
After 2 days, his symptoms improved, and he was discharged with empiric valacyclovir for a presumed acute herpes simplex virus infection. A herpes simplex virus PCR test was negative, but the dermatologist still felt this was the most likely diagnosis for an acute, tender, ulcerated perianal lesion acquired after high-risk sexual exposure. However, the biopsy results were suggestive of mpox virus (Figure 2). PCR testing confirmed the presence of mpox DNA, and the patient was diagnosed with mpox. He recovered fully with symptomatic treatment.
Histopathology study of a biopsy sample from the perianal lesion showed pseudoepitheliomatous hyperplasia and focal eosinophilic cytoplasmic inclusions, also known as Guarnieri bodies (arrow), features typical of mpox lesions (hematoxylin and eosin stain, magnification × 40).
MPOX
A global outbreak of mpox, an orthopoxvirus zoonotic infection, began in 2022, affecting primarily men who have sex with men. In August 2024, during this patient’s presentation, the outbreak was ongoing. It has continued into 2025, especially in Central Africa.1 Thus, clinicians should be alert to the possibility of travel-related mpox.
Skin manifestations
The prodromal phase of mpox typically includes fever, myalgia, and lymphadenopathy up to 1 week before onset of the rash.2 However, nearly 48% of patients in the 2022 outbreak had exclusively mucocutaneous manifestations or developed systemic symptoms after the skin lesions.3 The rash often starts as macules, then progresses to papules, vesicles, and finally pustules before resolution.4 Sequential progression of the rash, which occurred in this patient, differentiates mpox from varicella, in which all 4 stages appear simultaneously. Smallpox typically has a similar sequential progression but lacks the regional lymphadenopathy seen in mpox.4
Typical histopathology findings of mpox are shown in Figure 2.5 Though the pathology findings are suggestive, diagnosis is made with PCR testing.4 Notably, the papules are considered pseudopapules because they do not contain fluid and are thus not amenable to blunt unroofing. The best approach for PCR collection to minimize the risk of autoinoculation is vigorous blunt rub of at least 2 skin lesions at different sites.1
Treatment and vaccination
Although mpox is often a self-limited disease, tecovirimat is recommended and available through an expanded access investigational new drug protocol for those at high risk for progression to severe disease, including those who have invasive exposure; are younger than 18 years; have atopic dermatitis, exfoliative skin lesions, or a CD4 cell count lower than 200 cells/mm3; or are pregnant.6
The mpox vaccine is recommended for individuals at high risk of exposure, including healthcare workers, those living with a person who has mpox, men who have sex with men who have multiple partners, and sex workers and their clients.1
DISCLOSURES
The authors report no relevant financial relationships which, in the context of their contributions, could be perceived as a potential conflict of interest.
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