Supportive Care Management Recommendations for Mucocutaneous Manifestations of Monkeypox Infection.

The recent monkeypox outbreak beginning in May 2022 has spread to more than 50 countries globally and has presented unique clinical, diagnostic, and therapeutic challenges.1Assistant Secretary for Public AffairsBiden-Harris Administration bolsters monkeypox response; HHS Secretary Becerra declares public health emergency. HHS.gov.https://www.hhs.gov/about/news/2022/08/04/biden-harris-administration-bolsters-monkeypox-response-hhs-secretary-becerra-declares-public-health-emergency.htmlDate accessed: August 18, 2022Google Scholar Tecovirimat, cidofovir, and brincidofovir can be used to treat monkeypox, but access is limited, and the adverse effect profile may preclude use in certain populations of patients. In parallel, specialty care including dermatology, ophthalmology, and infectious diseases may not be readily accessible. Therefore, the monkeypox outbreak has posed the risk of overwhelming already limited health care resources, still recovering from the COVID-19 pandemic.2World Health OrganizationMonkeypox.https://www.who.int/news-room/fact-sheets/detail/monkeypoxDate accessed: September 7, 2022Google Scholar,3Ranganath N. Tosh P.K. O'Horo J. Sampathkumar P. Binnicker M.J. Shah A.S. Monkeypox 2022: gearing up for another potential public health crisis.Mayo Clin Proc. 2022; 97: 1694-1699Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar Fortunately, most cases of monkeypox are self-limited and best managed with supportive care in the outpatient setting.3Ranganath N. Tosh P.K. O'Horo J. Sampathkumar P. Binnicker M.J. Shah A.S. Monkeypox 2022: gearing up for another potential public health crisis.Mayo Clin Proc. 2022; 97: 1694-1699Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar However, there is a lack of clear guidance on what “supportive care” entails, and pain management often relies on systemic administration of analgesics.4Thornhill J.P. Barkati S. Walmsley S. et al.Monkeypox virus infection in humans across 16 countries—April-June 2022.N Engl J Med. 2022; 387: 679-691Crossref PubMed Scopus (804) Google Scholar, 5Patel A. Bilinska J. Tam J.C. et al.Clinical features and novel presentations of human monkeypox in a central London centre during the 2022 outbreak: descriptive case series.BMJ. 2022; 378e072410PubMed Google Scholar, 6Reynolds M.G. McCollum A.M. Nguete B. Shongo Lushima R. Petersen B.W. Improving the care and treatment of monkeypox patients in low-resource settings: applying evidence from contemporary biomedical and smallpox biodefense research.Viruses. 2017; 9: 380Crossref PubMed Scopus (117) Google Scholar, 7Adler H. Gould S. Hine P. et al.Clinical features and management of human monkeypox: a retrospective observational study in the UK.Lancet Infect Dis. 2022; 22 (Published correction appears in Lancet Infect Dis. 2022;22(7):e177): 1153-1162Abstract Full Text Full Text PDF PubMed Scopus (584) Google Scholar In this report, we discuss the mucocutaneous manifestations of monkeypox infection during the current outbreak, draw upon management of similar mucocutaneous conditions, and propose strategies for supportive care for patients with monkeypox infection. This guidance has been designed for use among dermatologists and front-line clinicians in primary care, emergency medicine, and infectious diseases. Characteristic skin findings during monkeypox infection in endemic regions of Africa consists of a rash with lesions typically in the same stage of progression, beginning on the face and trunk, with centrifugal spread to extremities. However, in the recent outbreak in Europe and North America, atypical dermatologic features have included a high predilection for oropharyngeal and anogenital mucosal lesions at onset of infection, polymorphic cutaneous rash at different stages of evolution, and most patients with solitary or fewer than 10 skin lesions.3Ranganath N. Tosh P.K. O'Horo J. Sampathkumar P. Binnicker M.J. Shah A.S. Monkeypox 2022: gearing up for another potential public health crisis.Mayo Clin Proc. 2022; 97: 1694-1699Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar, 4Thornhill J.P. Barkati S. Walmsley S. et al.Monkeypox virus infection in humans across 16 countries—April-June 2022.N Engl J Med. 2022; 387: 679-691Crossref PubMed Scopus (804) Google Scholar, 5Patel A. Bilinska J. Tam J.C. et al.Clinical features and novel presentations of human monkeypox in a central London centre during the 2022 outbreak: descriptive case series.BMJ. 2022; 378e072410PubMed Google Scholar, 6Reynolds M.G. McCollum A.M. Nguete B. Shongo Lushima R. Petersen B.W. Improving the care and treatment of monkeypox patients in low-resource settings: applying evidence from contemporary biomedical and smallpox biodefense research.Viruses. 2017; 9: 380Crossref PubMed Scopus (117) Google Scholar, 7Adler H. Gould S. Hine P. et al.Clinical features and management of human monkeypox: a retrospective observational study in the UK.Lancet Infect Dis. 2022; 22 (Published correction appears in Lancet Infect Dis. 2022;22(7):e177): 1153-1162Abstract Full Text Full Text PDF PubMed Scopus (584) Google Scholar There is also an increased prevalence of symptoms including anorectal pain or discharge consistent with proctitis, penile edema, dysuria, and conjunctivitis.4Thornhill J.P. Barkati S. Walmsley S. et al.Monkeypox virus infection in humans across 16 countries—April-June 2022.N Engl J Med. 2022; 387: 679-691Crossref PubMed Scopus (804) Google Scholar,5Patel A. Bilinska J. Tam J.C. et al.Clinical features and novel presentations of human monkeypox in a central London centre during the 2022 outbreak: descriptive case series.BMJ. 2022; 378e072410PubMed Google Scholar The discomfort of the cutaneous lesions begins as pain initially, then progresses into localized pruritus as lesions heal.4Thornhill J.P. Barkati S. Walmsley S. et al.Monkeypox virus infection in humans across 16 countries—April-June 2022.N Engl J Med. 2022; 387: 679-691Crossref PubMed Scopus (804) Google Scholar,5Patel A. Bilinska J. Tam J.C. et al.Clinical features and novel presentations of human monkeypox in a central London centre during the 2022 outbreak: descriptive case series.BMJ. 2022; 378e072410PubMed Google Scholar In the recent report of 528 cases in 16 countries by the SHARE-net Clinical Group, 95% of the patients presented with a rash, of which 73% had anogenital lesions and 41% had mucosal lesions.4Thornhill J.P. Barkati S. Walmsley S. et al.Monkeypox virus infection in humans across 16 countries—April-June 2022.N Engl J Med. 2022; 387: 679-691Crossref PubMed Scopus (804) Google Scholar The most common reasons for admission were management of pain (30% of hospitalized cases) and infection control (19% of hospitalized cases). Overall, 41% of patients had a history of HIV infection, with 29% of patients noted to have a concomitant sexually transmitted infection.4Thornhill J.P. Barkati S. Walmsley S. et al.Monkeypox virus infection in humans across 16 countries—April-June 2022.N Engl J Med. 2022; 387: 679-691Crossref PubMed Scopus (804) Google Scholar It is therefore critical to consider a broad differential diagnosis and to manage both monkeypox and coinfections in parallel for optimal outcomes. Supportive care management of mucocutaneous lesions in monkeypox is heterogeneous and poorly described in the literature, consisting primarily of strategies in case reports and series.4Thornhill J.P. Barkati S. Walmsley S. et al.Monkeypox virus infection in humans across 16 countries—April-June 2022.N Engl J Med. 2022; 387: 679-691Crossref PubMed Scopus (804) Google Scholar, 5Patel A. Bilinska J. Tam J.C. et al.Clinical features and novel presentations of human monkeypox in a central London centre during the 2022 outbreak: descriptive case series.BMJ. 2022; 378e072410PubMed Google Scholar, 6Reynolds M.G. McCollum A.M. Nguete B. Shongo Lushima R. Petersen B.W. Improving the care and treatment of monkeypox patients in low-resource settings: applying evidence from contemporary biomedical and smallpox biodefense research.Viruses. 2017; 9: 380Crossref PubMed Scopus (117) Google Scholar, 7Adler H. Gould S. Hine P. et al.Clinical features and management of human monkeypox: a retrospective observational study in the UK.Lancet Infect Dis. 2022; 22 (Published correction appears in Lancet Infect Dis. 2022;22(7):e177): 1153-1162Abstract Full Text Full Text PDF PubMed Scopus (584) Google Scholar These management approaches for cutaneous lesions range from soap and water, moisturizing dressings, and topical antibiotics to incision and drainage of abscesses, surgical debridement, and skin grafts. For ocular involvement, topical antibiotics, antivirals, and corticosteroids have been used to prevent corneal scarring. Superimposed bacterial infections are common and may require topical and oral administration of antibiotics.4Thornhill J.P. Barkati S. Walmsley S. et al.Monkeypox virus infection in humans across 16 countries—April-June 2022.N Engl J Med. 2022; 387: 679-691Crossref PubMed Scopus (804) Google Scholar, 5Patel A. Bilinska J. Tam J.C. et al.Clinical features and novel presentations of human monkeypox in a central London centre during the 2022 outbreak: descriptive case series.BMJ. 2022; 378e072410PubMed Google Scholar, 6Reynolds M.G. McCollum A.M. Nguete B. Shongo Lushima R. Petersen B.W. Improving the care and treatment of monkeypox patients in low-resource settings: applying evidence from contemporary biomedical and smallpox biodefense research.Viruses. 2017; 9: 380Crossref PubMed Scopus (117) Google Scholar, 7Adler H. Gould S. Hine P. et al.Clinical features and management of human monkeypox: a retrospective observational study in the UK.Lancet Infect Dis. 2022; 22 (Published correction appears in Lancet Infect Dis. 2022;22(7):e177): 1153-1162Abstract Full Text Full Text PDF PubMed Scopus (584) Google Scholar Similar mucocutaneous lesions are present in an array of infectious and inflammatory conditions, for which there is greater collective experience in managing symptoms with supportive care strategies. As with monkeypox, herpetic lesions go through a painful, vesiculopustular phase distributed over both cutaneous and mucosal surfaces.8Bolognia J.L. Schaffer J.V. Cerroni L. Dermatology.4th ed. Elsevier, 2018Google Scholar Vesicles eventually crust over before the lesions are no longer infectious and can present with pruritus during this healing phase. Similarly, Mycoplasma pneumoniae–induced rash and mucositis and cutaneous chronic graft-vs-host disease can both have widespread distribution of lesions, with involvement that includes eyes, mouth, genitalia, and nongenital skin.8Bolognia J.L. Schaffer J.V. Cerroni L. Dermatology.4th ed. Elsevier, 2018Google Scholar The cutaneous lesions in these conditions can be pruritic, with ocular and oral involvement causing significant discomfort and limiting vision. Recurrent aphthous stomatitis is localized to the mouth but tends to similarly transform from papules to painful ulcers. Acute genital ulcerations consist of larger, deep ulcerations that lead to intense pain and dysuria, similar to features frequently noted during the recent monkeypox outbreak.8Bolognia J.L. Schaffer J.V. Cerroni L. Dermatology.4th ed. Elsevier, 2018Google Scholar We therefore reviewed literature surrounding supportive care management of these mucocutaneous infectious and inflammatory disorders with similar lesional morphologic features and symptoms to monkeypox. Altogether, strategies outlined are aimed at promoting healing of the affected mucosa and skin, minimizing risk of infection transmission, and addressing symptoms of pain and pruritus through a combination of topical and systemic therapies. We then developed a consensus opinion–based protocol for supportive care management of mucocutaneous lesions during monkeypox infection (Table). Behavioral, topical, and systemic strategies are outlined for ocular, oropharyngeal, anogenital, and nongenital manifestations at varying severities of symptoms (Table).TableConsiderations for Supportive Care Management of Monkeypox Based on SymptomsaNA, not applicable; NSAIDs, nonsteroidal anti-inflammatory drugs; PCR, polymerase chain reaction.bManagement strategies should incorporate clinical judgment and individualized care in selecting therapies. Systemic treatment with tecovirimat should also be considered in the appropriate clinical context for immunosuppressed patients or those with extensive disease when available per guidance from the Centers for Disease Control and Prevention.24BehavioralTopicalSystemicOcular (recommend ophthalmology consultation)6Reynolds M.G. McCollum A.M. Nguete B. Shongo Lushima R. Petersen B.W. Improving the care and treatment of monkeypox patients in low-resource settings: applying evidence from contemporary biomedical and smallpox biodefense research.Viruses. 2017; 9: 380Crossref PubMed Scopus (117) Google Scholar,9Kohanim S. Palioura S. Saeed H.N. et al.Acute and chronic ophthalmic involvement in Stevens-Johnson syndrome/toxic epidermal necrolysis—a comprehensive review and guide to therapy. II. Ophthalmic disease.Ocul Surf. 2016; 14: 168-188Crossref PubMed Scopus (139) Google ScholarAvoid contact lensMinimal pain or erythema: lubricants (such as white petrolatum–mineral oil ointment)Increasing pain, persistent erythema, or purulent discharge: in addition to above, consider adding topical antibiotics or topical antivirals such as trifluridine with guidance from ophthalmology serviceNAOropharyngeal6Reynolds M.G. McCollum A.M. Nguete B. Shongo Lushima R. Petersen B.W. 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Topical and systemic therapies for oral and perioral herpes simplex virus infections.J Calif Dent Assoc. 2013; 41: 259-262Crossref PubMed Google ScholarSoft diet to avoid further traumatizing lesionsAdequate oral hydrationOral antiseptic washes daily, plus the following up to 3 times a day as needed:■Lidocaine gel■Benzocaine gel, or■Analgesic mouth rinse, such as diphenhydramine 12.5 mg/5 mL, lidocaine 2%, aluminum hydroxide–magnesium hydroxide–simethicone (200 mg–200 mg–20 mg/5 mL), ie, “magic mouthwash”Intravenous hydration if severe odynophagiaNongenital skin7Adler H. Gould S. 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Current topical and systemic therapies for itch.Handb Exp Pharmacol. 2015; 226: 337-356Crossref PubMed Scopus (45) Google ScholarWash lesions with soapy water daily and keep dryKeep fingernails trimmed, minimize scratching to avoid spreading the virus, and wash hands promptly after accidental contact with lesionsLoose-fitting clothingPain■Small areas (<30%): 2.5% lidocaine–2.5% prilocaine cream, or amitriptyline 2%–ketamine 0.5% cream up to 3 times daily to affected areas; if refractory, can increase concentration to amitriptyline 2%–ketamine 5% cream up to 3 times daily■Large, noneroded areas (≥30%): consider systemic pain medications and lidocaine 4%-5% patches for refractory areasPruritus■For mild pruritus or small areas of involvement: cooling lotions (menthol, camphor)■For large areas or severe pruritus: tap water wet wraps with moisturizers alone or with topical corticosteroids for crusted lesionsAbscesses■Warm compresses■If deep tissue abscess, consider incision and drainage with monkeypox virus PCR swabConsider ointment-based formulations when treating open skin as creams can cause stingingFor wound care of open lesions: liberal application of petroleum jelly for moisturizing, healing, and barrier protectionPain■NSAIDs, opioids if necessary, based on clinical judgmentPruritus■Scheduled second-generation antihistamines such as cetirizine 10 mg daily■Consider double or quadruple daily dose of second generation antihistamines for symptom control, adjusted for renal function if indicatedGenital and anorectal skin6Reynolds M.G. McCollum A.M. Nguete B. Shongo Lushima R. Petersen B.W. Improving the care and treatment of monkeypox patients in low-resource settings: applying evidence from contemporary biomedical and smallpox biodefense research.Viruses. 2017; 9: 380Crossref PubMed Scopus (117) Google Scholar,10Centers for Disease Control and PreventionClinical considerations for pain management of Mpox.https://www.cdc.gov/poxvirus/monkeypox/clinicians/pain-management.htmlDate accessed: December 6, 2022Google Scholar,21Rosman I.S. Berk D.R. Bayliss S.J. White A.J. Merritt D.F. Acute genital ulcers in nonsexually active young girls: case series, review of the literature, and evaluation and management recommendations.Pediatr Dermatol. 2012; 29: 147-153Crossref PubMed Scopus (54) Google Scholar, 22Bandow G.D. Diagnosis and management of vulvar ulcers.Dermatol Clin. 2010; 28: 753-763Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar, 23Lehman J.S. Bruce A.J. Wetter D.A. Ferguson S.B. Rogers 3rd, R.S. Reactive nonsexually related acute genital ulcers: review of cases evaluated at Mayo Clinic.J Am Acad Dermatol. 2010; 63: 44-51Abstract Full Text Full Text PDF PubMed Scopus (59) Google ScholarPer abovePain■For mild pain (≤4/10): sitz bath, topical benzocaine or lidocaine gels, and topical barrier cream (zinc oxide)■For severe pain (≥5/10): amitriptyline 2%-ketamine 0.5% cream up to 3 times daily as needed to individual lesions; if refractory, can increase concentration to amitriptyline 2%-ketamine 5% cream up to 3 times daily as neededPenile edema■Cold compresses and massageConsider ointment-based formulations when treating open skin as creams can cause stingingFor wound care of open lesions: liberal application of petroleum jelly for moisturizing, healing, and barrier protectionNSAIDs, opioids, if necessary, based on clinical judgmentProctitis6Reynolds M.G. McCollum A.M. Nguete B. Shongo Lushima R. Petersen B.W. Improving the care and treatment of monkeypox patients in low-resource settings: applying evidence from contemporary biomedical and smallpox biodefense research.Viruses. 2017; 9: 380Crossref PubMed Scopus (117) Google Scholar,10Centers for Disease Control and PreventionClinical considerations for pain management of Mpox.https://www.cdc.gov/poxvirus/monkeypox/clinicians/pain-management.htmlDate accessed: December 6, 2022Google ScholarAdequate fluid and food intake to avoid hard stoolsWarm sitz bathsFor further recommendations, consider gastroenterology consultationa NA, not applicable; NSAIDs, nonsteroidal anti-inflammatory drugs; PCR, polymerase chain reaction.b Management strategies should incorporate clinical judgment and individualized care in selecting therapies. Systemic treatment with tecovirimat should also be considered in the appropriate clinical context for immunosuppressed patients or those with extensive disease when available per guidance from the Centers for Disease Control and Prevention.24Centers for Disease Control and PreventionInfection control: healthcare settings.https://www.cdc.gov/poxvirus/monkeypox/clinicians/infection-control-healthcare.htmlDate accessed: August 20, 2022Google Scholar Open table in a new tab Lastly, in addition to supportive care, there should be comprehensive evaluation, testing, and treatment of coexisting sexually transmitted infections and secondary bacterial infections. Patient education should be provided on the contagious nature of these lesions, including avoiding physical and sexual contact until the lesions have crusted over and healed, as recommended by public health infection prevention and control guidance.24Centers for Disease Control and PreventionInfection control: healthcare settings.https://www.cdc.gov/poxvirus/monkeypox/clinicians/infection-control-healthcare.htmlDate accessed: August 20, 2022Google Scholar Treatment with systemic antiviral treatment, such as tecovirimat, should be considered when available, per latest guidance from the Centers for Disease Control and Prevention.24Centers for Disease Control and PreventionInfection control: healthcare settings.https://www.cdc.gov/poxvirus/monkeypox/clinicians/infection-control-healthcare.htmlDate accessed: August 20, 2022Google Scholar Supportive care is a key component of management of all monkeypox cases, especially with the limited access to antiviral treatments. In this article, we have developed a practical guide of supportive care management stratgies for monkeypox infection by drawing upon management of similar mucocutaneous conditions.