The mpox (monkeypox) virus is a zoonotic orthopox DNA virus that results in a smallpoxlike illness.1 Vaccination against smallpox protects against other orthopox infections, including mpox; however, unlike smallpox, mpox is notable for a variety of not-yet-confirmed animal reservoirs.2 Mpox was first identified in Denmark in 1959 among nonhuman primates imported from Singapore, and the first case of human infection was diagnosed in 1970 in a 9-month-old child in the Democratic Republic of Congo.3 Endemic regions of Africa have had sporadic outbreaks with increasing frequency over time since the cessation of smallpox vaccination in 1980.2,4 Infections in nonendemic countries have occurred intermittently, including in 2003 in the Midwest United States. This outbreak was traced back to prairie dogs infected by exotic animals imported from the Republic of Ghana.5
Two genetic clades of mpox that differ in mortality rates have been identified: clade II (formerly the West African clade) generally is self-limited with an estimated mortality of 1% to 6%, whereas clade I (formerly the Congo Basin clade) is more transmissible, with a mortality of approximately 10%.2,6,7 Notably, as of May 2, 2022, all polymerase chain reaction–confirmed cases of mpox in nonendemic countries were identified as clade II.7 Following the continued international spread of mpox, the Director-General of the World Health Organization (WHO) declared the global outbreak a public health emergency of international concern on July 23, 2022.8 As of March 1, 2023, the Centers for Disease Control and Prevention (CDC) reports that there have been more than 86,000 cases of laboratory-confirmed mpox worldwide and 105 deaths, 89 of which occurred in nonendemic regions.9
Transmission of Mpox
In endemic countries, cases have been largely reported secondary to zoonotic spillover from contact with an infected animal.6 However, in nonendemic countries, mpox often results from human-to-human transmission, primarily via skin-to-skin contact with infected skin, but also may occur indirectly via contaminated fomites such as bedding or clothing, respiratory secretions, or vertical transmission.6,10 The indirect transmission of mpox via contaminated fomites is controversial, though some studies have shown the virus can survive on surfaces for up to 15 days.11 In the current outbreak, human-to-human transmission has been strongly associated with close contact during sexual activity, particularly among men who have sex with men (MSM), with notable physical concentration of initial lesions in the genital region.12 Anyone can acquire mpox—infections are not exclusive to MSM populations, and cases have been reported in all demographic groups, including women and children. It is important to avoid stigmatization of MSM to prevent the propagation of homophobia as well as a false sense of complacency in non-MSM populations.13
Clinical Presentation of Mpox
The incubation period of mpox has been reported to last up to 21 days and is posited to depend on the mode of transmission, with complex invasive exposures having a shorter duration of approximately 9 days compared to noninvasive exposures, which have a duration of approximately 13 days.14 In a recent report from the Netherlands, the average incubation time was 8.5 days in 18 men with exposure attributed to sexual encounters with men.12 Following the incubation period, mpox infection typically presents with nonspecific systemic symptoms such as fever, malaise, sore throat, cough, and headache for approximately 2 days, followed by painful generalized or localized lymphadenopathy 1 to 2 days prior to the onset of skin lesions.1,15 In a recent report from Portugal of more than 20 confirmed cases of mpox, approximately half of patients denied symptoms or had mild systemic symptoms, suggesting that many patients in the current outbreak do not endorse systemic symptoms.16
Classic cutaneous lesions are the hallmark feature of mpox.17 Over a period of 1 to 2 weeks, each lesion progresses through morphologic stages of macule, papule (Figure), vesicle, and pustule, which then crusts over, forming a scab that falls off after another 1 to 2 weeks and can result in dyspigmented or pitted scars.1,15 Lesions may be deep-seated or umbilicated; previously they were noted to typically start on the face and spread centrifugally, but recent cases have been notable for a predominance of anogenital lesions, often with the anogenital area as the sole or primary area of involvement.18 Given the high proportion of anogenital lesions in 2022, symptoms such as anogenital pain, tenesmus, and diarrhea are not uncommon.19 A recent study describing 528 international cases of mpox revealed that 95% of patients presented with a rash; nearly 75% had anogenital lesions; and 41%, 25%, and 10% had involvement of mucosae, the face, and palms/soles, respectively. More than half of patients had fewer than 10 lesions, and 10% presented with a single genital lesion.19
Mpox (monkeypox) papule.
Given the recent predilection of lesions for the anogenital area, the differential diagnosis of mpox should include other common infections localized to these areas. Unlike herpes simplex and varicella-zoster infections, mpox does not exhibit the classic herpetiform clustering of vesicles, and unlike the painless chancre of syphilis, the lesions of mpox are exquisitely painful. Similar to chancroid, mpox presents with painful genital lesions and lymphadenopathy, and the umbilicated papules of molluscum could easily be confused with mpox lesions. Proctitis caused by many sexually transmitted infections (STIs), including chlamydia and gonorrhea, may be difficult to differentiate from proctitis symptoms of mpox. Co-infection with HIV and other STIs is common among patients developing mpox in 2022, which is not surprising given that the primary mechanism of transmission of mpox at this time is through sexual contact, and cases are more common in patients with multiple recent sexual partners.19 Considering these shared risk factors and similar presentation of multiple STIs, patients suspected of having an mpox infection should be tested for other STIs, including HIV.
Complications of Mpox
Although mpox generally is characterized by a mild disease course, there is concern for adverse outcomes, particularly in more vulnerable populations, including immunocompromised, pregnant, and pediatric populations. Complications of infection can include sepsis, encephalitis, bronchopneumonia, and ophthalmic complications that can result in loss of vision.6,17 The most common complications requiring hospitalization in a recent international report of 528 mpox cases were pain management, which was primarily due to severe anogenital pain, followed by soft-tissue superinfection, with other complications including severe pharyngitis limiting oral intake and infection control practices.19 In addition to severe rectal pain, proctitis and even rectal perforation have been reported.19,20