Clinical features and novel presentations of human monkeypox in a central London centre during the 2022 outbreak: descriptive case series - The BMJ

Introduction

On 6 May 2022, the UK High Consequence Infectious Diseases (HCID) network was alerted to an individual with monkeypox who had recently returned from West Africa. Six further infected individuals were identified the following week, without epidemiological linkage to West Africa. As of 12 July, 1735 people had been identified with monkeypox in the UK, most (96%) occurring in gay, bisexual, or other men who have sex with men, and 79% occurring in London.12 People with monkeypox infection have also been reported in several other non-endemic countries in Europe and the Americas, with the highest reported case loads outside of the UK in Spain and Germany.3

Monkeypox is due to an orthopoxvirus, which rarely causes disease in humans. Although the exact reservoir of the virus is still unknown, rodents are suspected to play a part in transmission. The virus was first identified in 1958, among primates in captivity for research purposes.4 Two genetically distinct viral clades are described: Central African (Congo Basin) and West African.5 The first reports of humans becoming infected were recorded in 1970, when a smallpox-like illness was investigated in areas of the Democratic Republic of Congo thought to be free of variola.67 Monkeypox is endemic in the Congo Basin and West Africa, where outbreaks involving 23 to 88 people have been described.89 Several animal species are susceptible to the infection, and animal to human transmission through handling and ingesting wild game animals has been identified as the primary route of infection in African outbreaks, followed by human to human transmission through close contact with infected individuals.10 Spread of respiratory droplets and direct contact with skin lesions and scabs have been described as the predominant routes of transmission between humans, but transmission can also occur via fomites.11 In 2003, the first monkeypox outbreak in the Western hemisphere was reported in 11 people in the United States who had been in close contact with infected prairie dogs. These animals had been transported alongside a Giant Gambian rat, presumed to be the primary source of the infection.12 Since 2018, travel associated monkeypox infection has been diagnosed in four people in the UK, with onward transmission to three further people.13 Sporadic cases of imported infections have also been reported in the US, Singapore, and Israel.14

The incubation period of monkeypox is currently understood to be about 12 days (range 5-24 days).1112 Classic descriptions of monkeypox infection depict biphasic clinical features, with a prodromal phase characterised by fever, malaise, sweats, lymphadenopathy, and headache, followed by skin eruption 2-4 days later.11 Skin lesions follow a typical pattern of evolution, starting as macules and progressing into papules, vesicles, and pustules, which subsequently crust over and then desquamate.1315 Historically, lesions have appeared simultaneously and progressed sequentially.16 Lesions have predominantly affected the face (95% of infected people), palms and soles (75%), mucous membranes (70%), and, less commonly, genitals.5 Most infections are self-limiting and relatively mild, with symptoms lasting 2-4 weeks. Severe manifestations of infection include encephalitis, secondary skin infection, pneumonia, and ocular disease leading to loss of vision. Higher risk populations include neonates, children, and those with immunodeficiency.17

Monkeypox is designated as a high consequence infectious disease in the UK.18 In the 2022 outbreak, the rapid community spread meant that most infected individuals were managed at home after risk assessment.19 The box shows the current UK Health Security Agency case definition of possible and probable monkeypox infection.20

UK Health Security Agency case definition of possible and probable monkeypox infection as of 16 July 2022

Possible infection

• A person with a febrile prodrome* compatible with monkeypox infection where there is known prior contact with a confirmed case in the 21 days before symptom onset.

• Or

• A person with an illness where the clinician has a high suspicion of monkeypox (for example, this may include prodrome or atypical presentations with exposure histories deemed high risk by the clinician, or classical rash without risk factors).

Probable infection

• has an epidemiological link to a confirmed or probable case of monkeypox in the 21 days before symptom onset

• reported a travel history to West or Central Africa in the 21 days before symptom onset

• is a gay or bisexual man or man who has sex with men

• *Consists of fever ≥38°C, chills, headache, exhaustion, muscle aches (myalgia), joint pain (arthralgia), backache, and swollen lymph nodes (lymphadenopathy).

• †Acute illness with fever (>38.5°C), intense headaches, myalgia, arthralgia, back pain, lymphadenopathy.

The observed clinical features of monkeypox infection in the 2022 UK outbreak differ from those in historical reports. We describe the characteristics and clinical features of monkeypox infection in people managed through a single south London centre and present a series of novel presentations.

Methods

Setting

We conducted a retrospective observational analysis of people with polymerase chain reaction (PCR) confirmed monkeypox virus, who were tested and managed through a south London HCID centre. The centre is one of five HCID centres in the UK and serves an inner city central and south London population. Swabs for diagnostic sampling were taken from the lesions at affiliated community sexual health and HIV medicine services, on admission to hospital (inpatient ward or emergency department) or on transfer of patients with suspected monkeypox from neighbouring NHS trusts (see supplementary figure 1). Samples were processed at the Rare and Imported Pathogens Laboratory at Porton Down, UK.21 People with suspected and confirmed monkeypox infection were risk stratified according to disease severity, immune status, and their ability to self-isolate, and managed accordingly. As part of routine clinical care, individuals were clinically assessed before testing. All people with a positive PCR test result for monkeypox virus took part in a telephone consultation to be counselled about their result and to conduct a risk assessment.

Inclusion criteria and data collection

All people tested for monkeypox virus between 13 May and 1 July 2022 were identified through routine tracking of samples sent from the centre's virology laboratory to the Rare and Imported Pathogens Laboratory. Those who tested positive were included for further study.

Clinical data were collected through one of three electronic healthcare systems: Electronic Patient Record iSOFT Clinical Manager 1.6 (iSOFT Group, Falls Church, VA), eNoting Client (an in-house patient records system), and preView (IMS MAXIMS, Milton Keynes, UK). Data were collected on personal characteristics, signs and symptoms reported at presentation, mucocutaneous manifestations (description, number, characteristics, and locations), risk factors as defined by the UK Health Security Agency (travel, contacts, and sexual history), HIV status, and sexual health screen results. Typical lesions were defined as macules, papules, vesicles, pustules, umbilication, crust, or scab.

Statistical analysis

We calculated means and medians for continuous data, and percentages for nominal data. The Clopper-Pearson exact method was used to calculate confidence intervals for symptom prevalence. Kaplan Meier for length of stay analysis was calculated using Graphpad Prism version 9.3.1. All other analysis was calculated using Microsoft Excel version 16.62.

Patient and public involvement

The research question for this study was formed through discussions with patients. Although there was no further direct patient or public involvement in this paper owing to limited resources, we have asked members of the public to read our manuscript after submission and also plan to disseminate key messages through social media and conferences.

Novel presentations

We describe presentations of monkeypox infection in the participants that are not commonly reported. Some symptoms were severe and required hospital admission. Images represent both a range of presentations and a series of progression, giving an insight into the clinical course of the disease in an outbreak largely centred on gay, bisexual, and other men and men who have sex with men.

Penile oedema

Of the 31 participants who reported penile oedema, five had documented paraphimosis or phimosis.

One participant, a 34-year-old circumcised man, presented with multiple penile lesions with clinically significant associated oedema. He had a history of Crohn's disease and was receiving adalimumab. He initially described multiple small, vesicular lesions on the penile shaft, coronal sulcus, and scrotum, which enlarged over the next two days, becoming umbilicated, flesh coloured papules (fig 1). The lesions then became more indurated, and the patient developed fever and cervical lymphadenopathy. On day 5 of symptoms, he developed erythema and swelling that extended from the mid-penile shaft to the glans. Overnight the swelling progressed rapidly, and the patient was admitted to hospital for assessment.

Fig 1

Progression of penile lesions and penile oedema

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Fig 1

Progression of penile lesions and penile oedema

On examination, 14 large, umbilicated lesions were identified along the penile shaft, coronal sulcus, and scrotum. There was associated subcutaneous oedema with no evidence of necrosis, and the skin was not tense or painful. Single pustular lesions on the participant's arm, back, and hip were also noted, along with inguinal lymphadenopathy. He was able to urinate. Results of a Treponema pallidum particle assay and rectal swab for N gonorrhoeae and C trachomatis nucleic acid amplification tests were negative, respectively. The urology team advised conservative management with cold compression and massage, and analgesia including topical lidocaine gel, ibuprofen, and oral morphine sulphate. Over the next 48 hours the swelling remained unchanged, with bruising extending from the glans towards the penile base. The swelling subsequently subsided gradually, and the patient was discharged on day 13. By day 16 the swelling had largely resolved, and the penile lesions had crusted over.

Secondary bacterial infection

One participant, a 47-year-old man with a history of HIV (viral load <200 copies/mL on antiretroviral therapy, CD4 count 755 cells/μL), was referred for review with extensive genital lesions, penile swelling, and purulent penile discharge.

He attended the emergency department when he first noticed spreading vesicles on his scrotum. A swab taken from the lesion confirmed monkeypox virus. The patient re-presented to the emergency department with progressive scrotal swelling, pain, and worsening penile ulceration and was subsequently admitted to hospital. On examination, extensive purulent lesions were identified on the penis and scrotum, with surrounding oedema (fig 2, also see supplementary figure 4). Vesicles were also noted on the arms and torso. No pain was elicited during digital rectal examination. Although there was no urinary retention or dysuria, the patient was catheterised because of concerns about increasing swelling of the penis. He was treated with co-amoxiclav to cover for a superadded bacterial infection but was switched to meropenem and clindamycin because of clinical suspicion of Fournier's gangrene. A swab sample taken from the penis grew Staphylococcus aureus and Streptococcus dysgalactiae. Lesions were negative for herpes simplex virus. A computed tomography scan showed extensive penile ulceration, a large hydrocele, and fluid within the scrotum. There was no collection or gas within soft tissue. The participant remains an inpatient at the time of writing.

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Fig 2

Secondary bacterial infection of penis due to Staphylococcus aureus and Streptococcus dysgalactiae. Also see supplementary figure 4