Symptoms of monkeypox differ from previous outbreaks

Even as the coronavirus disease 2019 (COVID-19) pandemic persists, an outbreak of the monkeypox virus is reaching unprecedented numbers of cases in non-endemic countries. A new BMJ The study describes the clinical features of monkeypox infections during the current epidemic from a large number of cases in central London.

Study: Clinical features and new presentations of human monkeypox in a central London center during the 2022 outbreak: a descriptive case series. Image Credit: Lightspring /


Monkeypox is a zoonotic disease caused by an orthopoxvirus similar to the smallpox virus. Monkeypox virus has long been endemic in parts of Africa since 1970, when it was first identified in the Democratic Republic of Congo.

Recently, the world has witnessed a sudden increase in monkeypox cases which have been almost exclusively diagnosed in men who have sex with men (MSM). This has led researchers to explore the altered clinical features of monkeypox infection during the current outbreak.

In the UK, the first case of monkeypox during the current outbreak was reported when the UK’s High Consequence Infectious Diseases (HCID) Network was made aware of a man who had just returned from West Africa in early May 2022. This was followed by a total of over 1,700 cases reported in the second week of July.

Similar waves of infection have been reported in several other non-endemic countries in Europe and the Americas. Spain and Germany have reported the highest number of cases.

Early outbreaks of monkeypox were limited to fewer than 100 people, with most cases linked to zoonotic transmission through wild game and close contacts being responsible for human-to-human transmission. This occurs mainly through respiratory droplets and skin lesions.

In the United States, previous outbreaks were reported in 11 people in 2003, which was the first time a Western country was affected by monkeypox. Sporadic infections have since been reported.

In the UK, four people have been diagnosed with monkeypox infection linked to travel to endemic countries since 2018. These four people had transmitted the virus to three others.

In the classic clinical presentation, monkeypox has a prodromal phase of fever, malaise, and enlarged lymph nodes, often with headache and sweating. The rash appears over two to four days, beginning as macules and progressing to papules, vesicles, and pustules. These lesions eventually scab over and fall off.

The lesions occur at the same time, mainly on the face; however, in about 75% of individuals, lesions will also appear on the palms, soles, and mucous membranes. Genital lesions were rare. Taken together, the episode resolves in two to four weeks.

Complications occur in some people, some of which may include encephalitis, pneumonia, secondary bacterial skin infection, and loss of vision due to eye damage. Newborns and children, as well as those with weakened immune systems, are at greater risk of complicated monkeypox.

Colorized transmission electron micrograph of monkeypox virus particles (blue) cultured and purified from cell culture.  Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland.  Credit: NIAIDColorized transmission electron micrograph of monkeypox virus particles (blue) cultured and purified from cell culture. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

Differences in the current epidemic

Patient characteristics

While children were primarily affected in previous outbreaks in endemic countries, adult males and children have predominated in more recent outbreaks in these regions. In contrast, the current epidemic has primarily included men and almost exclusively affected MSM.


Almost all patients in the current outbreak had a median of five skin or mucosal lesions in varying stages of healing. Of the approximately 200 cases, eight had more than 100 lesions, while 22 had only one. The most common site was the external genitalia or the perianal region, or both, in approximately 90% of patients.

Nearly 40% of cases presented with a mucocutaneous rash without a distinct prodromal phase. That is, systemic symptoms were delayed or sometimes absent.

This contrasts with current UK Health Safety Agency guidance for probable monkeypox which outlines typical systemic symptoms as required. This is in addition to a rash and epidemiological risk factors, such as a history of contact with an infected person or travel to an endemic region.

Most cases presented with lesions in the genital or perianal region or in the oral or peritonsillar regions. When combined with a history of recent sexual contact in almost all patients, this indicates the formation of lesions at the site of virus entry, with later systemic features and the appearance of more extensive lesions.

Tonsil lesions were not typical of monkeypox infection before this time. A subset of patients had only one lesion at presentation and thereafter. These lesions could be mistaken for other conditions.

For example, a single lesion could be misdiagnosed as an ingrown hair follicle or a syphilitic chancre. Comparatively, tonsillar lesions could be mistaken for bacterial tonsillitis, especially given the accompanying secondary bacterial infection, nasopharyngeal abscess, ulceration, and pain.

More than a third of patients have lesions at various stages of development, possibly due to repeated inoculations of the virus by the patient. Some patients presented with maculopapular rashes that did not ulcerate or pustulate.

Lack of travel history

Only one patient in the current outbreak has reported a travel history related to an endemic region, adding to the evidence that the current outbreak of monkeypox is spreading in the community. More than 25% of patients had a history of travel to Western Europe or close contact with someone infected with monkeypox.


One in three patients has also been diagnosed with a sexually transmitted infection (STI), primarily gonorrhea and Chlamydia trachomatis, as well as monkeypox. Not only could this explain the severity of rectal pain, but it also highlights the urgent need to screen all patients for STIs.

A third of the patients were also diagnosed with the human immunodeficiency virus (HIV), most of whom were on antiretroviral therapy (ART) and had an undetectable HIV viral load.

Overall, there is an altered clinical presentation in the current outbreak. Single throat sores or rashes can also go unnoticed, contributing to the rapid community spread at present. The disease appears to be self resolving and mostly mild in severity.


The study results indicate that monkeypox is primarily sexually transmitted and diagnosed in a large number of MSM worldwide. The clinical course of the disease also appears to have changed in the current outbreak, with rectal pain and penile edema being new features of the disease.

The study provides information on common symptoms that are not considered warning signs of monkeypox in public health messages and guidelines issued today. In fact, if the current UK Health Security Agency criteria were applied, one in seven of these patients would likely go undiagnosed.

Some previously rare but now commonly reported symptoms include single lesions, tonsillar lesions, and maculopapular or polymorphic lesions, as well as rectal pain and penile swelling, which were the two most common reasons for hospitalization.

There were five patients who also reported abscesses, all of whom had a relatively low number of atypical lesions or rashes. These patients were not considered probable monkeypox patients when initially admitted to the surgical department.

These presentations should be included in public health messages to facilitate early diagnosis and reduce onward transmission.”

Journal reference:

  • Patel, A., Bilinska, J., Tam, JCH, et al. (2022). Clinical features and new presentations of human monkeypox in a central London center during the 2022 outbreak: a descriptive case series. BMJ. doi: 10.1136/bmj-2022-072410.

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