Day: September 2, 2024

Is this MPox?

Patient Presentation
A 16-year-old male came to clinic with a rash that he was worried was monkey pox. He had had a few lesions on his arms that he said had progressed from being papular to being vesicular over a couple of days. They were not spreading. He said they were quite pruritic and he denied any fever, chills, myalgia, headache or lymphadenopathy. He had been in the outdoors near some woods. He denied any new soaps, lotions, detergents or being around any chemicals.

The past medical history showed a healthy male who was current with all vaccination including varicella vaccine.

The pertinent physical exam showed a healthy male with normal vital signs. There were 2 lines of lesions on his right forearm. Each had about 4-6 lesions that were 1-2 mm in size that were more papular but were excoriated. A full-skin examination did not reveal other skin lesions. He also had some shotty inguinal nodes but no other lymphadenopathy.

The diagnosis of a likely contact dermatitis, possibly from a plant, was made. The pediatrician did not feel the lesions were consistent with varicella, molluscum contagiosum or flat warts. The patient was confidentially questioned about why he was concerned about monkey pox and he just related that he had been reading about it on the Internet and became very concerned. “I thought this was a pox,” he stated with some anxiety. He was counseled about what to do for the skin lesions and also about monkey pox and other pox viruses. He denied being sexually active in his lifetime, but was counseled about safe sexual health practices. He was much less anxious after all of the information.

Discussion
“A pox o’ your throat, you bawling, blasphemous, incharitable dog!”

– William Shakespeare, The Tempest, Act 1, Scene 1

Orthopoxviridae belongs to family Poxviridae which are a very diverse group of double-stranded DNA viruses. Smallpox is an ancient disease and an especially well-known cause of severe morbidity and mortality and therefore was used as a curse or epiphet.
One of Shakespeare’s other famous lines is “a plague upon both your houses,” in Romeo and Juliet (Act 3 Scene 1) which is often mis-quoted as “a pox upon both your houses.”

Smallpox is caused by variola virus (VARV). VARV causes smaller lesions than great pox or syphilis and hence the name. Smallpox has no animal reservoirs and is transmitted by direct contact with lesions or fomites or through respiratory droplets. Incubation is 7-19 days and then a prodromal period of 1-3 days occurs with high fever, malaise, headache, abdominal pain, and emesis. Characteristic lesions then appear which change from “…macule to papule, to vesicle, to pustule and to crust with approximately 48 h[ours] between stages….Crusting of all lesions is complete 2 to 3 weeks after the first lesions occur. The lesions are 7-10 mm in diameter, round, firm, deep-seated and well circumscribed….” Lesions tend to appear more on the forearms and face than rest of the body. Patients are not contagious after the crusts fall off. Complications include death, scarring, skin superinfection, sepsis, encephalitis, meningitis, febrile seizures, and premature birth. VARV in its major form (variola major, lethality up to 30%) has been described as early as the 4th century and in the 19th century a minor form (variola minor, lethality ~1%) was identified. Edward Jenner used coxpox material as the first vaccination for smallpox in 1798. Vaccination for VARV is highly effective and there are some anti-viral medications also available. The last case of smallpox occurred in 1977 in Somalia and the World Health Organization declared world-wide eradication occurred in 1980. In the US general population vaccination was discontinued in 1972. The biological smallpox materials were recommended to be destroyed in the 1990s but are still kept in secure laboratories. Vaccine stockpiles exist to try to control an outbreak if one were to occur due to a breach in laboratory security or bioweaponization.

Vaccinia virus (VACV) is also a pox virus that is not the same as variola. It causes similar disease and is one of the most studied viruses because of its linkage to vaccine development.

Horsepox is a pox virus that affects horses and not humans. It can cause lesions on the muzzle and buccal cavity of horses. It was considered extinct but in 2017 it was reconstituted in the laboratory causing controversary because of its similarity to smallpox. There is data supporting that the early 20th century smallpox vaccine was actually based on horsepox.

Coxpox is a poxvirus affecting cows and wild rodents. It has similar characteristics and natural progression of disease very similar to smallpox. There is a similar disease caused by a parapox virus which causes pseudocowpox which has fewer lesions.

Buffalopox can affect domestic buffalo, cows and humans and can be found in epidemic or sporadic outbreaks in India. Transmission is direct contact with lesions predominantly on the hands but also orally, along with fever, malaise and lymphadenopathy. There is no specific treatment but anti-viral medications are sometimes used.

Molluscum contagiosum is a self-limited pox virus infection of the skin with MCV1 being the most common genotype. Incubation is usually 2-7 weeks but can be up to 6 months, and the characteristic painless, papular, 2-3 mm sized lesions with central umbilication can resolve usually in 6-9 months but can be up to 4 years. They are transmitted by direct contact, and can spread by autoinoculation. Treatment can be watchful waiting or a variety of treatments used for other verrucous lesions like cryotherapy, chemical treatment, or methods to stimulate the immune system.

Chickenpox is caused by Varicella-Zoster virus which is not a poxvirus but is a herpes virus. It is caused by direct contact or respiratory droplet infection with incubation being 5-7 days. The viremia has fever, chills and myalgia with a characteristic pruritic rash that progresses from macules, to papules, to vesicles to crusting of the vesicles. The lesions are all in different states of progression (asynchronous) and tend to be more centrally located on the trunk and central extremities and head/neck. Complications include suprerinfection, scarring and neurological complications. Varicella vaccination is highly effective at prevention. Acyclovir can be used for treatment.

Learning Point
MPox, previously known as Monkey Pox until 2022, is caused by the monkey pox virus which is a poxvirus. Interestingly, MPox was not recognized as a distinct entity until after the eradication of smallpox as the manifestations were similar. The first case was reported in Africa in 1970. It is spread by direct contact with animals or humans. Incubation is around 7-21 days but usually around 8 days. Patients begin with high fever, and lymphadenopathy and also can have headache, myalgia, sore throat and cough. The rash begins 1-3 days after fever and lymphadenopathy. The rash has 2-5 mm lesions that progress from macular, to papular, to vesicular to pustular lesions which are monomorphic in each phase. They occur more on the face and forearms and palms. Complications can include bacterial infections, pneumonitis, encephalitis and severe (sight-threatening) keratitis. Concurrent sexually transmitted infections (29-76%) can also cause incorrect identification of MPox. Syphilis, molluscum contagiosum and lymphogranuloma vernerum should be included in the potential differential. Vaccination is preventative and should be given as soon as possible after contact. Antiviral medication may offer some help.

“In May 2022, an outbreak of [MPox] appeared suddenly and rapidly spread across Europe, the Americas and then all six WHO regions, with 110 countries reporting about 87 thousand cases and 112 deaths. The global outbreak has affected primarily (but not only) gay, bisexual, and other men who have sex with men and has spread person-to-person through sexual networks.”

“In 2022, outbreaks of [MPox] due to Clade I MPXV occurred in refugee camps in the Republic of the Sudan. A zoonotic origin has not been found.”

Questions for Further Discussion
1. What zoonotic infections are circulating in your location at this time?
2. What is the uptake of varicella vaccine in your location?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: MPox and Smallpox.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Tulman ER, Delhon G, Afonso CL, et al. Genome of Horsepox Virus. J Virol. 2006;80(18):9244-9258. doi:10.1128/JVI.00945-06

An Early American Smallpox Vaccine Based on Horsepox. New England Journal of Medicine. Accessed July 22, 2024. https://www-nejm-org.proxy.lib.uiowa.edu/doi/full/10.1056/NEJMc1707600

How Canadian researchers reconstituted an extinct poxvirus for $100,000 using mail-order DNA. Accessed July 22, 2024. https://www.science.org/content/article/how-canadian-researchers-reconstituted-extinct-poxvirus-100000-using-mail-order-dna

Meyer H, Ehmann R, Smith GL. Smallpox in the Post-Eradication Era. Viruses. 2020;12(2):138. doi:10.3390/v12020138

Zafar SJ, Shishido AA. Smallpox as a Bioagent: A Refresher and Update for the SOF Provider. J Spec Oper Med. 2022;22(3):124-128. doi:10.55460/FIIV-8Z9P

World Health Organization. Mpox (monkey pox). 18 April 2023. Accessed July 22, 2024. https://www.who.int/news-room/fact-sheets/detail/monkey pox

Mazur-Melewska K. Poxviruses in Children. Adv Exp Med Biol. 2024;1451:205-217. doi:10.1007/978-3-031-57165-7_13

OpenSourceShakespeare.org. George Mason University. 2023-24.

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa