Clinical Pearls & Morning Reports

Posted by Carla Rothaus

Published November 9, 2022


Do the clinical manifestations of the 2022 monkeypox outbreak differ from those classically seen in cases in African countries?

Monkeypox is a zoonotic disease, but its animal reservoir remains unknown. Read the NEJM Review Article here.

Clinical Pearls

Q: What are the three phases of monkeypox?

A: Monkeypox affects both children and adults and typically has three phases: incubation, prodrome, and the eruptive stage. After primary infection, which may be difficult to date precisely, especially in the context of a zoonotic origin, the mean incubation period is 13 days (range, 3 to 34). The prodromal phase lasts for 1 to 4 days and is characterized by a high temperature, headache, fatigue, and often, lymphadenopathy, especially in the cervical and maxillary regions. The lymphadenopathy distinguishes monkeypox from chickenpox, the main infection in the differential diagnosis.

Q: How do the skin lesions of monkeypox typically manifest in cases that occur in African countries?

A: A patient may have from a few to several thousand lesions, located principally on the face, trunk, arms, and legs. Lesions frequently occur on the palms and soles, a feature that distinguishes monkeypox from chickenpox. More rarely, skin lesions affect other areas, such as the genitals, or are associated with oral ulcers and conjunctival damage. Usually, all lesions are at the same stage of development, another feature that differentiates monkeypox from other illnesses with skin manifestations, such as chickenpox. Monkeypox usually follows a self-limiting course, but clinical sequelae, including pitted facial scars, are common.

Morning Report Questions 

Q: Do the clinical manifestations of the 2022 monkeypox outbreak differ from those classically seen in cases in African countries?

A: By October 7, 2022, a total of 71,096 cases of monkeypox infection had been reported in 107 locations worldwide, with 70,377 of the cases in countries that have not historically reported monkeypox. As of this writing, the current monkeypox outbreak appears to be mainly transmitted in defined gay, bisexual, or men who have sex with men sexual networks, although there is some evidence of transmission beyond these groups. It is probably too early to provide a precise description of the clinical aspects of this monkeypox outbreak. However, they seem to match the classic presentation described above, except for some differences in clinical manifestations. In the current outbreak, lesions are being observed without a prodromal phase in a large proportion of patients. The number of skin lesions is highly variable, with some patients presenting with only a few painless lesions. The skin lesions also appear to be asynchronous, ranging from single or clustered spots to umbilicated papules with progressive central ulceration and, finally, scabs, in contrast to the previously described pattern of simultaneous progression. In addition, the pattern of skin lesions is unusual, often in genital, anal, and perianal areas, without the typical centrifugal distribution.

Q: What treatments are currently authorized for monkeypox in the United States?

A: The treatments currently authorized for monkeypox are tecovirimat in the United States and Europe and brincidofovir in the United States alone. Tecovirimat inhibits the orthopoxvirus protein p37, blocking cell-to-cell viral transmission. Although tecovirimat is approved for the treatment of smallpox in the United States, its use for monkeypox is based on an investigational new drug application, and the agent has not received full regulatory approval. The efficacy of tecovirimat has been shown in preclinical studies, including four pivotal studies in nonhuman primates showing that the drug provided 95% protection from death, as compared with placebo. Phase 1 and 2 clinical trials have assessed the safety and side-effect profile of tecovirimat in humans. A recent observational study involving a very small number of patients with monkeypox suggested that tecovirimat may reduce the duration of viral shedding and illness.

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