Pictures of monkeypox and disease information have been excerpted from the VisualDx® clinical decision support system as a public health service. Additional information, including symptoms, diagnostic pearls, differential diagnosis, best tests, and management pearls, is available in VisualDx.

Full Clinical Write-up


Updated November 4, 2022. Refer to US Centers for Disease Control and Prevention (CDC) (Information for Clinicians) for the most current information. See Diagnostic Pearls section for the CDC case definitions.

The World Health Organization (WHO) declared monkeypox (MPX) to be a public health emergency of international concern on July 23, 2022. MPX was declared a public health emergency in the United States on August 4, 2022.

As of November 4, 2022, the CDC reports 78 000 confirmed cases of MPX globally in over 100 locations, the vast majority of which (> 90%) have not historically reported MPX infections, and more than 28 600 confirmed cases across the United States, including 8 deaths. However, the 7-day daily average of new cases has been falling since a peak in August 2022, with cases hitting the lowest level since June.

Transmission continues to occur primarily among men who have sex with men (MSM), but any individual who has been in close, personal contact with someone who has monkeypox – regardless of age, sexual orientation, or gender identity – is at risk for contracting MPX.

Per a CDC report spanning May 17 through September 24, 2022, MPX virus infections in children and adolescents younger than 18 years of age were rare, representing 0.3% of all US cases; none of the cases resulted in critical illness or death. Children aged 0-12 years typically acquired MPX after skin-to-skin contact with an infected household member during caregiving activities, and adolescents aged 13–17 years were most frequently exposed through male-to-male sexual contact.

Domestic animals, pets, and wildlife in close contact with an infected individual may also be at risk for contracting illness.

Immunocompromised patient considerations: Immunocompromised individuals, particularly people with advanced or inadequately treated HIV, are at risk for severe and prolonged illness and even death. An increasing proportion of cases have been identified among Black and Hispanic / Latino individuals, who are disproportionately affected by HIV.

The 2022 outbreak of MPX is unique in several ways.

  • Many cases have no clear connection to the larger clusters of cases and no clear history of associated travel.
  • In the 2022 outbreak, it appears MPX is spreading through specific social and sexual networks, particularly among persons who identify as gay, bisexual, or MSM, although it is in no way limited to any specific population.

Community transmission seems to be occurring through close contact, ie, direct contact with skin lesions or bodily fluids, or indirect contact via contaminated clothing or linens, or exposure to large respiratory droplets.

Anyone who has had close physical contact with someone with MPX is at risk of contracting the virus.

Clinical features:
The incubation period of MPX is approximately 12 days (7-14 day range usually, but can be 5-21 days).

The clinical presentation is distinct from prior descriptions of the illness. Notably, anogenital lesions (in some cases painful, in others painless), often without a prodrome, are being observed.

  • Many patients have had no associated or preceding febrile illness, fatigue, or other systemic symptoms.
  • The eruption that many of these patients develop does not begin on the face, hands, and legs and may not be widespread, nor are the lesions initially numerous. Many patients have presented with a small number of lesions (in some cases 1 or 2) involving the genital or perianal region before the rash spreads to the extremities. These lesions can be, but are not always, quite painful and/or pruritic and may leave scarring.
  • The classically described lymphadenopathy associated with MPX does not seem to be a requisite aspect of cases in this outbreak, with some patients having only a single swollen lymph node and some having no lymphadenopathy.
  • Some patients present with proctitis or anorectal pain.
  • Oropharyngeal symptoms have been reported (including pharyngitis, oral / tonsillar lesions, odynophagia, and epiglottitis) as have conjunctival mucosa lesions.

In the 2022 outbreak, MPX may present in a form that can be very subtle and easily mistaken for many other conditions such as primary and secondary syphilisgenital herpes simplex virus (HSV), and chancroid, among others. This presentation has been described across many parts of Europe, the United Kingdom, Canada, and the United States.

Human-to-human transmission occurs through close contact, ie, large respiratory droplets, direct contact with skin lesions or bodily fluids, or indirect contact via contaminated clothing or linens. The WHO notes that anyone who has had close physical contact with someone with MPX is at risk of contracting the virus, and there is a high likelihood that further cases with unidentified chains of transmission will be identified. MSM may be at higher risk for infection.

All skin lesions may be infectious. Persons are thought to be infectious starting at the onset of symptoms. Patients should be considered to be infectious until crusts have fallen off and the underlying skin re-epithelialized.

Of note, a UK study of more than 2700 people with confirmed MPX virus between May 6 and August 1, 2022, suggests that presymptomatic transmission (1-4 days before symptoms appear) occurred in around half of all cases (53%).

About MPX
MPX is a rare zoonotic Orthopoxvirus infection that is clinically similar to smallpox.

There are 2 clades of MPX, with differing mortality rates. The Central Africa (Congo Basin) clade is both more contagious and more severe with a reported mortality rate of around 10.6%. The West African clade is thought to be less severe with a mortality rate of about 3.6%.

Historically, MPX begins with a prodrome of fever, headache, malaise, backache, lymphadenopathy, chills, nonproductive cough, and arthralgias followed 1-10 days later (usually by day 3) by the development of a papular, vesicular, then pustular eruption on the face, trunk, and extremities. Some patients also experience myalgias, nausea and vomiting, lethargy, sore throat, dyspnea, and sweats. The clinical presentation is similar to but milder than that of smallpox, with the primary difference being that individuals with MPX develop lymphadenopathy, whereas those with smallpox do not. Illness typically lasts 2-4 weeks. Individuals who received smallpox vaccination were reported to develop milder cases.

Before the 2022 outbreak, cases in the United States were primarily limited to laboratory workers, pet shop workers, and veterinarians. There were 2 US cases in 2021 (July and November), both from travelers returning from Nigeria.

In Africa, the disease affects people who have hunted or eaten squirrels and other infected mammals. Animal species susceptible to Monkeypox virus (MPXV) may include nonhuman primates, lagomorphs (rabbits), and some rodents. Predominant person-to-person transmission and prolonged chains of transmission were suspected in 1996 when 71 cases emerged in Katako-Kombe Health Zone, Kasai-Oriental, and Democratic Republic of the Congo, and again in 2003 in the Likouala region of Republic of the Congo. In order to sustain the disease in the human population, it was believed that repeated animal reintroduction of MPXV was needed.

The first documented outbreak of MPX in the Western Hemisphere was attributed to a shipment of small mammals from Ghana to the United States in 2003. An infected Gambian giant rat from this shipment infected prairie dogs, which in turn transmitted the disease to humans. The prairie dogs were sold by a Milwaukee animal distributor to 2 pet shops in the Milwaukee area and during a pet “swap meet” (pets for sale or exchange) in northern Wisconsin. Patients from this outbreak reported direct or close contact with prairie dogs, most of which were sick. Illness in the prairie dogs was frequently reported as beginning with a blepharoconjunctivitis that was followed by the appearance of nodular lesions in some cases. Some prairie dogs died from the illness while others reportedly recovered. Lesions in the 2003 US outbreak differed from smallpox lesions in that they were not in the same stage of evolution at the same time. In some patients seen in the United States in 2003, early lesions became ulcerated, especially those at animal bite / scratch sites.

Look For

Some cases from the 2022 outbreak seem to lack or have mild prodromal symptoms. Look for one or a few papular, vesicular, pustular, or ulcerative lesions involving the genitals or perianal region. Some patients may present with proctitis or pharyngitis. Individuals with advanced or inadequately treated HIV are at risk of life-threatening disease.

In a case series of over 500 patients with MPX infection diagnosed between April 27 and June 24, 2022, at over 40 locations and 16 countries, the most common body locations for lesions were the anogenital area (73%); the trunk, arms, and legs (55%); the face (25%); and the palms and soles (10%). Lesion types included macules, pustules, vesicles, and crusted lesions. Lesions in different stages of development were seen. Mucosal lesions were present in around 40% of patients. Systemic manifestations included fever, lethargy, myalgia, headache, and lymphadenopathy; these symptoms often preceded a generalized rash.

Impact of skin color on clinical presentation: In darker skin colors, erythema can be difficult to discern, and may appear pink, violaceous, dark brown, or any shade of gray. In lighter skin colors, they may appear any shade of pink or red.

Immunocompromised patient considerations: Per the CDC, severe manifestations have included the following.

  • Atypical or persistent rash with coalescing or necrotic lesions, or both, some which have required extensive surgical debridement or amputation of an affected extremity.
  • Lesions on a significant proportion of the total body surface area, which may be associated with edema and secondary bacterial or fungal infections, among other complications.
  • Lesions in sensitive areas (including mucosal surfaces such as, oropharynx, urethra, rectum, vagina) resulting in severe pain that interferes with activities of daily living.
  • Bowel lesions that are exudative or cause significant tissue edema, leading to obstruction.
  • Severe lymphadenopathy that can be necrotizing or obstructing (such as in airways).
  • Lesions leading to stricture and scar formation resulting in significant morbidity such as urethral and bowel strictures, phimosis, and facial scarring.
  • Involvement of multiple organ systems and associated comorbidities, including:
    • Oropharyngeal lesions inhibiting oral intake
    • Pulmonary involvement with nodular lesions
    • Neurologic conditions including encephalitis and transverse myelitis
    • Cardiac complications including myocarditis and pericardial disease
    • Ocular conditions including severe conjunctivitis and sight-threatening corneal ulcerations
    • Urologic involvement including urethritis and penile necrosis

In classic MPX (that is commonly seen in Africa), skin lesions develop 1-3 days after onset of fever. Skin lesions evolve from macules (that are present for 1-2 days) to papules (1-2 days), then to vesicles (1-2 days) and pustules (that last for 5-7 days) and, ultimately, crusts (that may last for up to 14 days). Umbilication of vesicles and pustules may be seen. Crusts may be hemorrhagic. While the majority of lesions are at the same stage of development, lesions at differing stages may be seen.

In classic MPX, the rash usually starts on the face and distal extremities with centripetal spread to involve the more proximal extremities and trunk. Lesions commonly involve the face (95%), palms and soles (75%), and oral mucous membranes (70%) and, less commonly, the genitalia (30%; although among 2022 cases this seems higher) and conjunctiva (20%; can be sight-threatening). Lesion number can vary from 1 to more than 1000. In addition to lesions on the head, trunk, and extremities, patients can have initial and satellite lesions on the palms, soles, and extremities. Rashes can generalize in some patients.

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Monkeypox Emergency Medicine Project