EM@3AM: Monkeypox

Author: Petrus Malherbe, MBChB (EM Resident Physician, Ochsner Hospital Foundation, New Orleans, LA) and Daniel J Sessions, MD (@Danosaurus, EM and Medical Toxicology Attending Physician, Ochsner Hospital Foundation, New Orleans, LA) // Reviewed by: Sophia Görgens, MD (EM Resident Physician, Zucker-Northwell NS/LIJ, NY) and Cassandra Mackey, MD (Assistant Professor of Emergency Medicine, UMass Chan Medical School) 

Welcome to EM@3AM, an emDOCs series designed to foster your working knowledge by providing an expedited review of clinical basics. We’ll keep it short, while you keep that EM brain sharp.

A 26-year-old female patient comes to the ED with an 8-day history of progressive weakness, fevers, and body aches. She reports that 4 days ago she noticed “bug bites” on her face, neck, arm, and hands. Sixteen days ago, she returned from a trip to Los Angeles where she shared a bed with her friend who was ill and had a rash at the time. The patient’s medical history is unremarkable, and she takes no medications. She is in a monogamous relationship with her long-term boyfriend and uses condoms consistently. Her temperature is 38.1º C (100.6ºF). Examination shows bilateral anterior cervical lymphadenopathy, and the lesion pictured below is noted, which resembles other lesions on her face, neck, right upper arm, and other hand.   

What is the most likely cause of this patient’s rash? 

Answer: Monkeypox



  • Orthopoxvirus 
    • Large, enveloped DNA virus 2, 3
  • Zoonotic disease 
    • Spread from rodents 2, 3
    • Endemic to West and Central Africa 2, 3
    • First identified in monkeys in 1958 2, 3
  • 2 Clades
    • West African Clade: responsible for current public health emergency (mortality <1%)4
    • Congo Basin Clade: 11% mortality rate 4
  • Timeline:
    • 1970: first confirmed case in humans (Democratic Republic of Congo) 2-4
    • 2003-2020: various small clusters identified in travelers from Africa 4
    • May 7, 2022: UK confirms case in man with travel history from Nigeria 5
    • May 12, 2022: UK confirms 2 new cases in unrelated persons 5
    • May 18, 2022: USA identifies first case 6
    • June 16, 2022: USA confirms 100th case 6
    • July 13, 2022: USA confirms 1000th case 6
    • July 23, 2022: WHO declares Public Health Emergency of International Concern 7
    • August 18, 2022: 39,400 total global cases/ 13,500 total USA cases 6, 7


Disease Course 

  • Transmission: droplet and contact spread 2, 6
  • Majority of cases spread through sexual and close contact. Current outbreak seen predominately in men who have sex with men. 1, 6
  • Stages of infection: 
    • Incubation stage: 5-21 days 6, 8
    • Febrile stage: 1-4 days 6, 8
      • Fever, malaise, lymphadenopathy, sore throat 
  • Rash stage: 2-4 weeks 6, 8
    • Starts on head and spreads to trunk and extremities
    • All lesions in same stage and may be present on palms and soles, or as a single genital or anal lesion and may be extremely painful. 1, 6, 8, 9
      • Macules (1-2 days)
      • Papules (1-2 days)
      • Vesicles (1-2 days)
      • Pustules (5-7 days) 
      • Crusts (7-14 days): remain infectious until all crusts resolve. 
  • Resolution: crusts fall off (2-4 weeks) 6, 8
  • Complications: Pain, corneal infection and vision loss, secondary bacterial infections and sepsis, encephalitis, pneumonia (bacterial/ viral), miscarriage, and death (due to secondary infection) 6, 8


Differential Diagnosis 

  • Chickenpox (VZV), molluscum contagiosum, measles, bacterial skin infections, scabies, secondary syphilis, allergic skin conditions, smallpox 11



  • PCR test: skin lesion testing should be performed as soon as Monkeypox is suspected
    • CDC recommends 2 dry swabs (vigorously rubbed on skin lesions) from 3 different sites (6 total). 6, 8
    • Freezing of samples is strongly recommended 6, 8
    • Local laboratories may differ



  • Patient encounter: PPE for contact and droplet precaution (gown, gloves, N-95 mask, and eye protection) 8
  • Vaccine: Pre-exposure only recommended in healthcare workers with high exposure (personnel administering ACAM2000 vaccines, frequent care for patients with monkeypox, laboratory workers).
    Post-exposure prophylaxis reserved for individuals with sexual contact with a person infected with monkeypox within the last 14 days.  

    • JYNNEOS: two dose non-replicating live virus vaccine. 6, 8
    • ACAM2000: single dose live Vaccinia virus that causes lesion on arm and individuals must be cautioned against infecting others after vaccination. 6, 8
      • There is a low risk of cutaneous vaccinia, generalized vaccinia, myopericarditis, and encephalitis, especially in immunodeficient patients 12
  • Isolation: CDC recommendations are to isolate for entire duration of rash, as patients are no longer infectious 2-4 weeks after rash and lesions have scabbed over and fallen off. Avoid close contact and sexual encounters with 6
  • Treatment: No specific treatment
    • Supportive: analgesia for pain, antibiotics for secondary bacterial infections, oral rinses, and eye drops for corneal infections. 6, 8
    • Tecovirimat (TPOXX): Antiviral against orthopoxviruses. Typically reserved for patients with severe disease 6, 8, 13, 14
      • 40 kg to <120 kg: 600 mg PO BID for 14 days
        ≥120 kg: 600 mg PO TID for 14 days  



  • Long incubation period (5-21 days) and disease course (1-4 weeks)
  • Differential includes VZV, measles, bacterial skin infections, scabies, secondary syphilis, and smallpox
  • Not a sexually transmitted disease but high transmission rates through sexual contact
  • Low mortality, but significant morbidity
  • If monkeypox is suspected: practice contact and droplet precautions (gown, gloves,
    N-95 mask, and eye protection), 2 swabs from 3 different lesions, recommend isolation. 
  • Antivirals utilized for patients with severe disease, otherwise supportive care is the current recommended treatment

Further Reading:







  1. Basgoz N, Brown CM, Smole SC, Madoff LC, Biddinger PD, Baugh JJ, Shenoy ES. Case 24-2022: A 31-Year-Old Man with Perianal and Penile Ulcers, Rectal Pain, and Rash. New England Journal of Medicine. 2022 Jun 15.
  2. Bunge EM, Hoet B, Chen L, Lienert F, Weidenthaler H, Baer LR, Steffen R. The changing epidemiology of human monkeypox—A potential threat? A systematic review. PLoS neglected tropical diseases. 2022 Feb 11;16(2):e0010141.
  3. Girometti N, Byrne R, Bracchi M, Heskin J, McOwan A, Tittle V, Gedela K, Scott C, Patel S, Gohil J, Nugent D. Demographic and clinical characteristics of confirmed human monkeypox virus cases in individuals attending a sexual health centre in London, UK: an observational analysis. The Lancet Infectious Diseases. 2022 Jul 1.
  4. Sklenovská N, Van Ranst M. Emergence of monkeypox as the most important orthopoxvirus infection in humans. Front Public Health. 2018; 6: 241.
  5. Monkeypox: Two more confirmed cases of viral infection. BBC News. 2022. Available from: https://www.bbc.com/news/uk-england-london-61449214
  6. 2022 U.S. Monkeypox Outbreak [Internet]. Centers for Disease Control and Prevention. 2022. Available from: https://www.cdc.gov/poxvirus/monkeypox/response/2022/index.html
  7. Second meeting of the International Health Regulations (2005) (IHR) Emergency Committee regarding the multi-country outbreak of monkeypox. 2022. Available from: https://www.who.int/news/item/23-07-2022-second-meeting-of-the-international-health-regulations-(2005)-(ihr)-emergency-committee-regarding-the-multi-country-outbreak-of-monkeypox
  8. ACEP Monkeypox Field Guide [Internet]. ACEP; 2022 [cited 12 August 2022]. Available from: https://www.acep.org/monkeypox-field-guide/us-monkeypox-2022/
  9. Patrocinio-Jesus R, Peruzzu F. Monkeypox genital lesions. New England Journal of 2022 Jul 7;387(1):66-. 
  10. OpenWHO- Monkeypox: Introductory course for African outbreak contexts. 2022.
  11. Monkeypox Key Facts. World Health Organization; 2022.
  12. Nalca A, Zumbrun EE. ACAM2000: the new smallpox vaccine for United States Strategic National Stockpile. Drug Des Devel Ther. 2010;4:71-79. Published 2010 May 25. doi:10.2147/dddt.s3687
  13. Merchlinsky M, Albright A, Olson V, Schiltz H, Merkeley T, Hughes C, Petersen B, Challberg M. The development and approval of tecovirimat (TPOXX®), the first antiviral against smallpox. Antiviral research. 2019 Aug 1;168:168-74.
  14. Sherwat A, Brooks JT, Birnkrant D, Kim P. Tecovirimat and the Treatment of Monkeypox—Past, Present, and Future Considerations. New England Journal of Medicine. 2022 Aug 3.

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