What Are Monkeypox Treatment Options for Anorectal Pain and Related Symptoms?

According to the Centers for Disease Control and Prevention (CDC), 21,504 cases of the monkeypox virus have been reported in the United States as of September 8, 2022.¹ Along with fever, myalgia, skin rash, swollen lymph nodes, sore throat, and respiratory symptoms, numerous reports have indicated a high prevalence of anorectal symptoms, including proctitis and anorectal pain and bleeding in affected patients.

In a paper published in August 2022 in the New England Journal of Medicine, clinicians from 16 countries collaborated on a large case series of patients with monkeypox.² Of the 528 cases described, 73% of patients presented with anogenital lesions. Among the 13% of patients who were hospitalized, the most common reason for hospitalization was pain management for severe anorectal pain.

In a July 2022 case series of 197 men with monkeypox, 41.6% presented with perianal lesions and 36.0% reported rectal pain.³ Additionally, a small case series of patients hospitalized with monkeypox in Berlin showed that the chief complaint in 5 of the 6 patients was intense anal pain.⁴ These individuals rated their pain level as a 9 or 10 on a 10-point numerical rating scale and described it as “unprecedented in severity… stabbing, burning, and unbearable on defecation.”

Multiple other reports have demonstrated similar findings, and nearly all reported cases were transmitted via sexual intercourse in men who have sex with men.^5-7

Gastroenterology Advisor interviewed the following physicians to discuss treatment strategies for anorectal symptoms in patients with monkeypox: Siddharth Singh, MD, assistant professor of gastroenterology at the University of San Diego School of Medicine, California; Maaza Abdi, MD, assistant professor in the division of gastroenterology and hepatology at Johns Hopkins University School of Medicine, Maryland; and Tara Palmore, MD, FACP, FIDSA, professor of medicine in the division of infectious diseases at George Washington University School of Medicine and Health Sciences and hospital epidemiologist for the George Washington University Hospital in Washington, DC.

What types of anorectal symptoms have been observed in patients with monkeypox?

Dr Siddharth: Proctitis occurs in some patients with monkeypox, particularly those who have anoreceptive intercourse. Usual symptoms are pain in the anorectal region, tenesmus, bleeding, or purulent discharge. Patients may develop a rash in the perianal region. Endoscopy or proctoscopy is not usually needed in these cases. Most patients with proctitis typically have systemic symptoms like fever, sore throat, myalgia, and skin rash prior to occurrence of proctitis. 

Dr Palmore: Monkeypox proctitis can cause excruciating pain that is substantially exacerbated by bowel movements. For some patients I have seen, the pain is so significant that they cannot sit. Imaging is not needed to make this diagnosis, but if a CT scan is done it will typically show thickening of the rectal wall. Patients may also have external vesiculopustular skin lesions in the perianal area that can be painful.

I have seen several patients identified correctly by GI and colorectal surgery colleagues as having monkeypox infection due to those specialists’ awareness of this presentation.

Dr Abdi: Monkeypox infections are characterized by prodromal fever and cutaneous lesions. However, there have been case reports of only anorectal disease. In an observational retrospective study, Ferre et al detected asymptomatic monkeypox on 6.5% of anorectal swabs collected in a sexually transmitted infections screening program.⁸

Proctitis is a clinical manifestation of the orthopoxvirus. [A patient’s medical history] commonly reveals engaging in anoreceptive intercourse. Examination can frequently reveal vesicular or pustular lesions of the perianus and skin. Regional lymphadenopathy may be present.

Digital anorectal examination may be limited by pain. Anoscopy can reveal ulceration of the anus and squamocolumnar junction. Sigmoidoscopy can demonstrate inflammation, friability, or ulceration of the rectal mucosa. Complications include pain requiring hospitalization, superimposed cellulitis, and perforation. 

The main mode of transmission is via close sexual contact (95%), close nonsexual contact (1%) and household or unknown exposure (4%).⁹ The mechanism of transmission is direct contact (skin-to-skin or sexual) with lesions and bodily fluids. Microabrasions on the skin or mucous membranes aid transmission of the virus. Other less common methods of transmission are contact via fomites, respiratory droplets, or vertical transmission. High transmission rates have been found in men who have sex with men, persons living with HIV, and concomitant sexually transmitted infection.

What treatment strategies have been found to be helpful in managing these symptoms, and how long does it typically take for symptoms to resolve? 

Dr Siddharth: For patients with mild-moderate rectal pain and with limited access to antiviral therapy, conservative therapy with NSAIDs, topical lidocaine, stool softeners, and Sitz baths may help. Symptoms usually run their course over 10 to 14 days.

Oral tecovirimat, 600 mg twice daily for 14 days, works very well for proctitis. Symptoms usually improve within 24 to 48 hours and resolve within 4 to 7 days. The most frequent side effects are headache, nausea, and abdominal pain. Tecovirimat was approved for smallpox but has been [a] very effective medication for monkeypox. It is in short supply and currently available through the CDC. Tecovirimat is [recommended] for patients with severe symptoms requiring hospitalization or high risk of complications, including immunocompromised patients and patients with monkeypox at atypical locations like the mouth, eyes, or anus.¹⁰

Dr Palmore: Multimodal treatment of monkeypox proctitis can be quite helpful. Patients need systemic pain medications. Stool softeners are essential to reduce friction on the raw mucosal surface and are doubly important if the patient is treated with opioid pain medications that reduce bowel motility. Sitz baths and topical lidocaine can provide some relief, and some patients find ice packs helpful.

The antiviral drug tecovirimat, which is available from the CDC on an expanded investigational new drug (IND) protocol to treat monkeypox infection, has anecdotally provided rapid relief to patients with monkeypox proctitis, such as the 2 we described in our recent report.⁶

Tecovirimat is recommended and being prescribed in the US for patients with monkeypox proctitis, pharyngitis, and infections in other sensitive sites, those with severe infections, as well as patients with underlying conditions predisposing them to severe infection. It is well tolerated and available in IV and oral formulations.

Dr Abdi: The majority of patients will have self-limited, mild disease and will recover without any medical interventions. Supportive treatment options include pain-relief medications, topical lidocaine, stool softeners, and sitz bath. It typically takes 2 weeks for anorectal symptoms to resolve.

The natural history of the infection includes an incubation period of 7 to 10 days, viral prodrome of 5 days, and skin lesions lasting for 2 to 3 weeks. The median time to formation of dry crust is 10 days.¹¹ The median time for skin lesions to completely resolve is 17 days.¹²

When indicated, tecovirimat is available through the Strategic National Stockpile. It halts viral maturation and release from the infected cell.¹³

What are additional recommendations for physicians regarding evaluation and treatment of these symptoms?

Dr Siddharth: Physicians should be aware of these symptoms and manifestations of monkeypox, and they should have a low threshold for suspicion in at-risk patients with suggestive symptoms. The CDC’s website is a great resource for up-to-date information.

Dr Palmore: A few points about proctitis during the monkeypox era: Some patients with monkeypox may have isolated proctitis, with few or no skin lesions at the time they are evaluated. Patients presenting with rectal pain should be tested for monkeypox as well as gonorrhea, chlamydia, and syphilis — simultaneously and regardless of a known [medical] history of monkeypox exposure. All of these, as well as herpes simplex virus, are potential causes of proctitis, and the pretest probability of monkeypox during this outbreak is very high. Many patients have coinfections.

A frequent diagnostic error that I see is patients being tested for gonorrhea, chlamydia, and syphilis, and monkeypox is not even considered until the others are negative. This stepwise approach is unnecessary and delays diagnosis and treatment, leaving patients in pain and potentially spreading a communicable infection.

Dr Abdi: CDC criteria for the clinical evaluation for monkeypox include new characteristic rash or cutaneous manifestations, along with 1 of the following: contact with a person suspected to have monkeypox within 21 days; close or intimate contact in a social group with monkeypox; travel outside the US to a country with confirmed cases of monkeypox, such as Europe; travel outside the US to a country where monkeypox virus is endemic, such as [countries within] Africa; or contact with a dead or live wild animal or an animal product from an African endemic species.¹⁴

If a patient presents with rash and suspicion for monkeypox, providers should wear full PPE or N95 mask, face shield, gown, and gloves. Patients should be examined in a room with a HEPA filter. Two swabs from each specimen should be collected in a viral medium for polymerase chain reaction (PCR) testing for orthopoxvirus DNA. Samples can be collected from skin lesions, anorectal swab, or throat swab.

Other treatment options for monkeypox include brincidofovir, an oral formulation for intravenous cidofovir.¹³ Side effects such as nephrotoxicity and elevated liver enzymes, as well as lack of evidence, limit their use.

The CDC recommends vaccination for individuals in close contact with monkeypox, those whose sexual partner was diagnosed with monkeypox, and those engaged in sex with multiple men or engaged in sex at a high-risk venue within 2 weeks. Local health departments can provide vaccination. Immunization with smallpox vaccines (JYNNEOS and ACAM2000) may protect against monkeypox virus and decrease clinical manifestations.¹⁵

References

1. Centers for Disease Control and Prevention. 2022 US Map & Case Count. Updated September 8, 2022. Accessed September 8, 2022. https://www.cdc.gov/poxvirus/monkeypox/response/2022/us-map.html
2. Thornhill JP, Barkati S, Walmsley S, et al; SHARE-net Clinical Group. Monkeypox Virus Infection in Humans across 16 Countries – April-June 2022. N Engl J Med. 2022;387(8):679-691. doi:10.1056/NEJMoa2207323
3. Patel A, Bilinska J, Tam JCH, et al. Clinical features and novel presentations of human monkeypox in a central London centre during the 2022 outbreak: descriptive case series. BMJ. 2022;378. doi:10.1136/bmj-2022-072410
4. Pfäfflin F, Wendisch D, Scherer R, et al. Monkeypox in-patients with severe anal pain. Infection. Published online August 12, 2022. doi:10.1007/s15010-022-01896-7.
5. Bragazzi NL, Kong JD, Mahroum N, et al. Epidemiological trends and clinical features of the ongoing monkeypox epidemic: a preliminary pooled data analysis and literature review. J Med Virol. Published online June 12, 2022. doi:10.1002/jmv.27931
6. Lucar J, Roberts A, Saardi KM, Yee R, Siegel MO, Palmore TN. Monkeypox virus-associated severe proctitis treated with oral tecovirimat: A report of two cases. Ann Intern Med. Published online August 18, 2022. doi:10.7326/L22-0300
7. Basgoz N, Brown CM, Smole SC, et al.  Case 24-2022: 31-year-old man with perianal and penile ulcers, rectal pain, and rash. N Engl J Med. Published online August 11, 2022. doi:10.1056/NEJMcpc2201244
8. Ferré VM, Bachelard A, Zaidi M, et al. Detection of monkeypox virus in anorectal swabs from asymptomatic men who have sex with men in a sexually transmitted infection screening program in Paris, France. Ann Intern Med. Published online August 16, 2022. doi:10.7326/M22-2183
9. Srivastava G, Srivastava G. Human monkeypox disease. Clin Dermatol. Published online August 10, 2022. doi:10.1016/j.clindermatol.2022.08.009
10. Centers for Disease Control and Prevention. Treatment Information for Healthcare Professionals. Updated July 28, 2022. Accessed September 8, 2022. https://www.cdc.gov/poxvirus/monkeypox/clinicians/treatment.html
11. Tarín-Vicente EJ, Alemany A, Agud-Dios M, et al. Clinical presentation and virological assessment of confirmed human monkeypox virus cases in Spain: a prospective observational cohort study. Lancet. 2022;400(10353):661-669. doi:10.1016/S0140-6736(22)01436-2
12. Moschese D, Pozza G, Giacomelli A, et al. Natural history of human monkeypox in individuals attending a sexual health clinic in Milan, Italy. Published online August 21, 2022. J Infect. doi:10.1016/j.jinf.2022.08.019
13. Rizk JG, Lippi G, Henry BM, Forthal DN, Rizk Y. Prevention and treatment of monkeypox. Drugs. 2022;82:957-963. doi:10.1007/s40265-022-01742-y
14. Centers for Disease Control and Prevention. Case definitions for use in the 2022 monkeypox response. Updated July 22, 2022. Accessed September 8, 2022. https://www.cdc.gov/poxvirus/monkeypox/clinicians/case-definition.html
15. Centers for Disease Control and Prevention. Monkeypox Vaccination Basics | Monkeypox | Poxvirus | CDC. Updated August 30, 2022. Accessed September 8, 2022. https://www.cdc.gov/poxvirus/monkeypox/vaccines/vaccine-basics.html

This article originally appeared on Gastroenterology Advisor