Last revised by Dr William Tanguay on 03 Jun 2022

Monkeypox is a rare zoonosis caused by an orthopoxvirus and in general, produces a mild flu-like illness and rash in humans. Virologically and clinically the condition is similar to smallpox, the first viral disease to be eradicated by humans. In 2022, a new outbreak of monkeypox was identified in the UK, with spread to Europe and the United States.

Since the diagnosis of the first human case of monkeypox in August 1970 in the Democratic Republic of the Congo, the disease has become endemic in several mainly Central and West African states. In 2003, an outbreak of 72 cases in the United States, transmitted by pet prairie dogs, were the first reported cases outside Africa, but no human-human transmission occurred in this outbreak 1,8.

In 2022, a new outbreak of cases, all infections of the West African clade, first in the United Kingdom and then elsewhere in Europe and the US, occurred. This is the first time that any chains of transmission have been demonstrated in Europe without evidence of an epidemiological connection to known endemic areas in Africa 2.

The majority of cases have been found in men, and it seems to be more common in adults now, although historically (the 1970s-1990s) was more common in children 1. Fortunately, mortality rates are low, with almost all children under the age of 10 years 6,7.

It is interesting to consider why monkeypox appears to be on the rise in the 2000s; prevailing wisdom suggests that it is the combination of two main factors, firstly the decline of population-wide immunity against smallpox. Secondly, the continual encroachment of humans into previously wild areas following environmental degradation 3.

In most cases, the presentation starts with a typical febrile prodrome:

  • fever
  • chills
  • headache
  • exhaustion
  • myalgia and/or arthralgia
  • backache
  • lymphadenopathy

A classic rash develops a few days after the prodrome. Initially, macules appear, which evolve to papules, then vesicles, and finally pustules, which then crust over. By four weeks the scabs fall off. Each stage of the rash lasts 1-2 days. These lesions develop in a synchronous fashion, i.e. all the lesions change in lockstep. 

Rash distribution is usually centrifugal, i.e. it predominates on the face and extremities, with relative sparing of the torso (cf. centripetal rash of VZV). In the 2022 outbreak, many patients have had genital rashes 2,12

The World Health Organization (WHO) reports involvement of the oral mucous membranes in 70% of cases, and conjunctival involvement in 20% of cases, with corneal involvement also possible 12

Rarely monkeypox cases may develop encephalitis, and this has been seen both in Africa and in the United States; in some cases, it is fatal 4,6,8,9

A concurrent HIV infection seems to lead to more severe disease than in HIV-negative monkeypox cases, in particular 4:

  • skin
    • larger lesions
    • more likely genital involvement
  • longer disease course
  • more superadded bacterial infections

Some observational studies report the formation of deep tissue abscesses, which are not necessarily adjacent to superficial mucocutaneous lesions 11. At least one case of retropharyngeal abscess has been reported, causing tracheal airway compromise 13. It is unclear if abscess formation requires superimposed bacterial infection.

A significant proportion of monkeypox cases develop ophtalmological symptoms related to the disease, including conjunctivitis and corneal scarring secondary to corneal lesions 10

Monkeypox virus (MPXV) is a member of the Orthopoxvirus genus, from the Poxviridae family. Smallpox virus (variola virus) is a close relative. Genetically, there are two clear-cut clades of monkeypox, the Central African (or Congo Basin) clade and the West African clade. The virus is a double-stranded DNA virus with a protein envelope 1,5,7.

It is primarily a direct zoonosis i.e. most cases are from direct contact with animals, person-to-person transmission is rare. 

  • airborne droplets
  • close contact
  • eating bushmeat

Although the current outbreak in the UK was clustered in men having sex with men, it is not thought to be a sexually-transmitted infection, and rather is due to close human contact and associated transmission 2.

Lymphadenopathy can be a prominent feature detected on CT, albeit nonspecific. In some cases, cutaneous lesions may also be visible on CT.

The appearance of monkeypox encephalitis has been reported on MRI of the brain, the reported features - in a single case in a 6 year old girl - were diffuse edema, increased FLAIR signal in the thalamus and parietal cortex and meningeal enhancement  8.

Supportive care is the only treatment currently advised for monkeypox. Some experimental antivirals have shown activity in animals and have been tried with some success in sicker cases 2.

Fortunately, the existing vaccine against smallpox has been found to be up to 85% effective against monkeypox in retrospective data analyzes 1.

Fortunately, in most cases, monkeypox is not serious, and no deaths have ever been reported outside Africa. In a large series of 282 cases published in 1987, the only deaths were reported in children under 10 years old 7.

Monkeypox was first isolated in 1958 in macaque monkeys in a Danish laboratory. However, monkeypox is a misnomer as the main hosts in the wild are thought to be rodents. The first documented human patient was a 9-month old infant in the Democratic Republic of the Congo in August 1970, which was called Zaire at the time 1,7

In 2003, there was an outbreak of 72 cases, 34 confirmed, and a further 38 probable, in the United States which were transmitted by pet prairie dogs which acted as the vector; these were the first reported cases outside Africa. The origin of the outbreak was sourced to a batch of imported infected rodents from Ghana which entered the US in April 2003. These small mammals included Gambian giant pouched rats, rope squirrels, and dormice 1,8.

The pouched rats were transported with prairie dogs as they traveled to an animal distribution center in Illinois; during transit, the prairie dogs caught the monkeypox from the giant pouched rats. From Illinois, the prairie dogs were passaged to a further distributor in Wisconsin, and then onto pet stores where consumers purchased the infected animals 1,8.

The main clinical differential diagnoses are other orthopoxviruses as well as common causes of vesiculopustular rashes:

  • varicella zoster virus (VZV)
    • centripetal rash: a centrifugal rash is very rare in chickenpox
    • lymphadenopathy is unusual in chickenpox
  • herpes simplex virus (HSV)
  • HIV
  • secondary syphilis
  • rickettsial infections

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