History and exam
Key diagnostic factors
common
rash/lesion(s)
Traditionally, patients develop a characteristic rash that generally starts on the face and body and spreads centrifugally to the palms and soles (it may be preceded by a rash affecting the oropharynx and tongue in the 24 hours prior). Lesions simultaneously progress through four stages - macular, papular, vesicular, and pustular - before scabbing over and resolving. Lesions are typically 5 to 10 mm in diameter, may be discrete or confluent, and may be few in number or several thousand. Vesicles are well-circumscribed and located deep in the dermis. The rash usually resolves over a period of 2 to 4 weeks.[1][11][96][178][198]
[Figure caption and citation for the preceding image starts]: Characteristic maculopapular cutaneous rashWorld Health Organization (WHO)/Brian W.J. Mahy, BSc, MA, PhD, ScD, DSc [Citation ends].
In more recent outbreaks, the presentation has been atypical, with the rash presenting primarily in the anogenital region.[58] Lesions tend to be localized to the genital, perineal/perianal, or perioral areas and often do not spread further.[74][198][209][210][211][212][213] Other atypical presentations include: presentation of only a few lesions (or even just a single lesion) and may not be disseminated; absence of skin lesions with anal pain and bleeding; lesions appearing at different stages of development (asynchronous); rash does not always appear on palms and soles; and appearance of lesions before the prodrome.[74][198][200][214] Localized vulvar, intravaginal, and cervical lesions have been reported in women.[219][220][221][222] Rash/lesions have been reported in 95.2% of patients.[16]
[Figure caption and citation for the preceding image starts]: Images of individual lesions (2022 global outbreak)UKHSA [Citation ends].
Erythematous maculopapular, generalized purpuric, and morbilliform rashes have been reported in some patients.[200][223][225]
Skin lesion severity can be determined by the number of lesions: mild (<25 lesions); moderate (25-99 lesions); severe (100-250 lesions); very severe (>250 lesions).[1] Most patients (64%) had <10 lesions, with approximately 10% having only a single genital lesion in the 2022 global clade II mpox outbreak.[106]
Lesions may be painful initially, and become itchy during the healing phase. Lesions on the external genitalia may cause severe swelling and pain. Oral lesions may cause difficulties with eating and drinking, which may lead to dehydration and malnutrition. See Complications.
The World Health Organization and Centers for Disease Control and Prevention have published photos that show examples of lesions. WHO: atlas of mpox lesions - a tool for clinical researchers Opens in new window CDC: mpox rash photos Opens in new window
anorectal symptoms
Anorectal symptoms have been unique to more recent outbreaks, and were not described previously.[34][59]
Some patients may present with severe/intense anorectal pain (including severe pain on defecation), tenesmus, rectal bleeding, or purulent or bloody stools, associated with perianal/rectal lesions and proctitis. Patients may have no signs of a rash.[198][199][200][202][203] Other anal symptoms may include pruritus, dyschezia, burning, swelling, and mucus discharge.[204]
Data from the 2022 global clade II mpox outbreak indicate that 65.7% of patients had anogenital lesions and 18.5% had proctitis or anorectal pain.[16]
Men who engaged in anal-receptive sex presented with proctitis more frequently than men who did not engage in anal-receptive sex.[205]
The presentation may easily be confused with some STIs or other etiologies of proctitis.[192]
fever
Typically a symptom of the prodromal period (usually preceding the appearance of the rash), but may present after the rash or not at all.
Historically, fever has been reported in 85% of cases, and chills in 71% of cases.[49]
Reported in 58.4% of patients in the 2022 global clade II mpox outbreak (chills in 23.8%).[16]
lymphadenopathy
May be generalized or localized to several areas. Typically occurs with onset of fever preceding the rash or, rarely, with rash onset. May be submandibular and cervical, axillary, or inguinal, and occur on both sides of the body or just one side.[198] Inguinal lymphadenopathy has been the most common presentation in the 2022 global clade II mpox outbreak (47%).[16]
Enlarged lymph nodes are approximately 1 to 4 cm in diameter, firm, tender, and sometimes painful.
Lymphadenopathy is a common distinguishing feature, but is rare in smallpox and other diseases in the differential diagnosis.[1][49][96][178]
Reported in 53% of patients in the 2022 global clade II mpox outbreak.[16]
Painful cervical lymphadenopathy causing dysphagia may be a sign of severe or complicated disease.[1] Severe lymphadenopathy that can be obstructing (e.g., in airways) or necrotizing has been reported.[197]
Other diagnostic factors
common
fatigue/asthenia/malaise
Typically a symptom of the prodromal period (usually preceding the appearance of the rash), but may present after the rash or not at all.
Reported in 38.7% of patients in the 2022 global clade II mpox outbreak.[16]
myalgia
headache
sore throat
Typically a symptom of the prodromal period (usually preceding the appearance of the rash), but may present after the rash or not at all.
Oropharyngeal symptoms may cause severe pain or difficulty swallowing (odynophagia).
Historically, pharyngitis has been reported in 60% of cases.[49]
Sore throat/odynophagia have been reported in 23.4% of patients in the 2022 global clade II mpox outbreak. Dysphagia has been reported in 11.8%.[16]
backache
cough
Typically a symptom of the prodromal period (usually preceding the appearance of the rash), but may present after the rash or not at all.
Reported in 7.3% of patients in the 2022 global clade II mpox outbreak.[16]
nausea/vomiting
uncommon
diarrhea
Typically a symptom of the prodromal period (usually preceding the appearance of the rash), but may present after the rash or not at all.
Historically, diarrhea has been reported in 6% of cases.[49]
May contribute to severe dehydration.
delirium/confusion
seizures
Typically a symptom of the prodromal period (usually preceding the appearance of the rash), but may present after the rash or not at all.
Historically, seizures have been reported in 3% of cases.[49]
Risk factors
strong
recent travel to/living in endemic country or country with outbreak
Patients may report recent travel to (or living in) previously endemic countries (Central or West Africa) or a country with a current outbreak in the 21 days prior to symptom onset.
There are currently ongoing global outbreaks across several countries. Consult public health authorities for more information about currently affected locations.
contact with suspected, probable, or confirmed case
Human-to-human transmission occurs rarely, but serial transmission events have been reported and there are currently ongoing global outbreaks across several countries involving human-to-human transmission.[4][110] People who are younger than 40 to 50 years of age (depending on the country) may be more susceptible as a result of the termination of routine smallpox vaccination worldwide after the eradication of smallpox.[1]
The risk for the general population in countries newly affected by outbreaks is considered to be moderate, while the risk for the general population in countries with historic transmission (and their neighboring countries) is considered to be moderate, with the exception of the eastern Democratic Republic of the Congo (and its neighboring countries) and areas of the DRC where mpox is endemic where the risk is considered to be high.[12]
The World Health Organization defines a contact as a person who has been exposed to a suspected, probable, or confirmed case during the infectious period (i.e., the period beginning with the onset of the index case’s first symptoms, or if relevant up to 2 days before the onset, and ending when their skin lesions have crusted, the scabs have fallen off, and a fresh layer of skin has formed underneath) and has had one or more of the following exposures (including health workers potentially exposed in the absence of proper use of appropriate protective personal equipment): direct skin-to-skin and skin-to-mucosal or mouth-to-mucosal physical contact; contact with contaminated materials; prolonged face-to-face respiratory exposure in close proximity; or respiratory exposure or eye mucosal exposure to lesion material from an infected person.[116]
Case definitions vary between regions. Consult your local public health authority for more information and guidance. See Criteria.
occupational exposure
Healthcare workers have a low overall risk for infection (with or without proper personal protective equipment). The risk is considered to be moderate in healthcare workers performing aerosol-generating procedures without proper personal protective equipment.[79]
A small number of cases have been reported among health workers in the 2022 global clade II mpox outbreak, with most cases being infected in the community rather than via occupational exposure.[12]
In practice, the risk for healthcare workers appears to be very low even with incomplete adherence to recommended personal protective equipment.[117] However, there have been reports of transmission via needlestick injuries, and likely fomite transmission.[118]
Dentists (and dental assistants) may be the first to detect symptoms due to the presence of oropharyngeal lesions, and are at risk from the production of droplets and aerosols during dental procedures.[119]
The risk among staff and students after exposure to a confirmed case in educational settings appears to be low.[120]
random one-time sexual encounters or multiple sexual partners
The vast majority of cases in the 2022 global clade II mpox outbreak were in men who have sex with men reporting multiple sexual partners (often 5 or more within the last 3 months).[62] Condomless receptive anal sex and oral sex was associated with approximately five times the risk of infection among men who have sex with men and transgender people.[121]
recent tattoo or piercing
Outbreaks related to piercing and tattoo establishments (including microblading, a semi-permanent tattooing technique for eyebrow pigmentation) have been reported in the 2022 global clade II mpox outbreak. In one outbreak, 37% of contacts developed the infection, and most cases developed a rash at the tattoo/piercing site.[122][123][124][125]
contact with infected animal
An animal reservoir may be the initial source of human infection, particularly in endemic areas. There may be a history of contact with nonhuman primates or rodents (e.g., squirrels, rats, dormice) originating from Africa.[1] It is difficult to eradicate the disease because of the presence of animal reservoirs in West and Central Africa.
Animals that can be infected with mpox include prairie dogs, squirrels, marmots and groundhogs, chinchillas, giant-pouched rats, hedgehogs, shrews, monkeys, and apes. Mice, rats, and domestic rabbits can possibly be infected, although this may vary by species. It is currently unknown whether other animals (e.g., dogs, cats, gerbils, guinea pigs, hamsters, domestic and farm animals, wildlife) can be infected.[126]
The risk of establishment of an enzootic cycle and spill-over events to humans is considered to be low.[79]
children (severe disease)
Children may be at increased risk of severe disease.[1][5][96] Previous outbreaks mainly affected children.[34] However, available evidence from the 2022 global clade II mpox outbreak indicate that cases in children are rare and the clinical presentation is typically not more severe than that of adults. Very few neonates and infants developed mpox, so it is unclear whether the youngest children (particularly those ages <6 months) could have a more severe illness.[36]
Infection in children is usually acquired in the household setting or following close contact with an infected animal.[127] However, the secondary attack rate among pediatric household contacts appears to be low (4.7%).[128]
pregnant women (severe disease)
Pregnant women may be at increased risk of severe disease.[1][5][96] Data in pregnancy are limited. It is unknown if pregnant women are more susceptible to infection or if disease is more severe in pregnancy. However, adverse pregnancy outcomes including spontaneous pregnancy loss and stillbirth, preterm delivery, and neonatal infection have been reported. Perinatal transmission is possible.[5][129][130] Infection in pregnancy may be associated with a high risk of perinatal loss and vertical transmission, depending on the virus clade.[131]
A number of cases of infection occurring in pregnant women have been reported during the 2022 global clade II mpox outbreak, with no cases of adverse perinatal outcomes (including stillbirth) reported.[132] However, a systematic review identified 32 pregnant women with clade II mpox between 6 and 31 weeks’ gestation, and of the 12 pregnancies with reported outcomes, half resulted in intrauterine fetal death.[133]
A study of eight pregnant women with clade I mpox in the Democratic Republic of Congo (DRC) reported a 50% fetal mortality rate.[134]
immunocompromised (severe disease)
Immunocompromised people may be at increased risk of severe disease.[1][5][96] Data in immunocompromised people (i.e., people who are immunocompromised from a condition or immunosuppressant treatment) are limited. Although severely immunocompromised people may be at higher risk of more severe disease, hospitalization, and disseminated disease, severe outcomes are not universally seen.[37] Disseminated infection has been reported in solid organ transplant recipients.[135][136]
HIV infection (severe disease)
There is no evidence that people with well-controlled HIV are at increased risk of severe disease.[137] However, people with HIV-associated immunosuppression (i.e., <200 cells/microliter, and especially <50 cells/microliter) may be at increased risk of severe disease, hospitalization, and disseminated disease. It is currently unknown whether HIV status increases the risk of infection.[37]
Limited data indicate that people with advanced and uncontrolled HIV can be at a higher risk of severe or prolonged disease. In one retrospective review of cases in Nigeria, people with HIV infection experienced more prolonged illness, larger lesions, and higher rates of secondary bacterial skin infections and ulcers.[138]
Data from the 2022 global clade II mpox outbreak indicate HIV infection has not been linked to disease severity.[106][139] However, data from the US indicate that people with HIV may have a higher rate of hospitalization compared with those without HIV, particularly those with low CD4 counts or without viral suppression.[140][141]
Patients with advanced HIV or AIDS are at increased risk of severe complications, intensive care unit admission, and death.[142][143] Severe complications were more common in patients with CD4 counts <100 cells/microliter compared with patients with CD4 counts <300 cells/microliter, and included necrotizing skin lesions, lung dysfunction, secondary infections, and sepsis. All deaths were among patients with CD4 counts <200 cells/microliter, and most occurred in those with a high HIV viral load.[144]
People living with HIV who are on antiretroviral therapy (ART) with suppressed viral load are not considered to be immunocompromised.[1] A suppressed/undetectable viral load may protect against a more severe disease course.[145]
Observational evidence suggests that the immune response to childhood smallpox vaccination declined faster among people who subsequently became infected with HIV, and that antigen-specific CD4+ T-cell memory to vaccinations or infections prior to HIV infection did not recover after immune reconstitution in patients on ART.[146]
acute or chronic skin conditions (severe disease)
People with a history or presence of a condition affecting skin integrity (e.g., eczema, burns, impetigo, shingles, herpes simplex infection, severe acne, severe diaper rash, psoriasis, keratosis follicularis) may be at increased risk for severe disease or complications (e.g., secondary bacterial infection).[1] People with atopic dermatitis may be more susceptible to infection, and may develop eczema monkeypoxicum.[147][148]
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