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Severe Manifestations of Monkeypox among People who are Immunocompromised Due to HIV or Other Conditions
  Distributed via the CDC Health Alert Network
September 29, 2022 02:15 PM ET
The purpose of this Centers for Disease Control and Prevention (CDC) Health Alert Network (HAN) Health Advisory is to inform healthcare providers that
1. Severe manifestations of monkeypox have been observed in the United States in the current outbreak.
2. People who are immunocompromised due to HIV or other conditions are at higher risk for severe manifestations of monkeypox than people who are immunocompetent.
3. Because people with HIV-associated immunocompromise are at risk for severe manifestations of monkeypox, the HIV status of all sexually active adults and adolescents with suspected or confirmed monkeypox should be determined.
4. There are diagnostic and clinical management strategies that may help address severe manifestations of monkeypox.
Since May 2022, more than 25,000 monkeypox cases have been identified in the United States. During the current outbreak in the United States, 38 percent of people diagnosed with monkeypox were coinfected with HIV1 and most reported cases of monkeypox with severe manifestations have been among people living with untreated HIV.
Some patients with monkeypox in the United States have experienced prolonged hospitalizations or substantial morbidity; deaths have occurred. As the monkeypox outbreak has progressed, an increasing proportion of cases have been identified among Black and Hispanic/Latino people. Black and Hispanic/Latino people are disproportionately affected by HIV.
Severe manifestations of monkeypox can occur in both immunocompetent and immunocompromised people; however, most people diagnosed with monkeypox have had mild-to-moderate clinical courses. Of the people with severe manifestations of monkeypox for whom CDC has been consulted, the majority have had HIV with CD4 counts <200 cells/ml, indicating substantial immunosuppression. Healthcare providers should recognize underlying risk factors for severe disease, optimize immune function, and when appropriate, initiate medical countermeasures (such as tecovirimat and vaccinia immunoglobulin) early to prevent or mitigate severe disease.
During the current outbreak, CDC has received reports of people with monkeypox who have severe manifestations of disease, including but not limited to
• Atypical or persistent rash with coalescing or necrotic lesions, or both, some which have required extensive surgical debridement or amputation of an affected extremity.
• Lesions on a significant proportion of the total body surface area, which may be associated with edema and secondary bacterial or fungal infections among other complications.
• Lesions in sensitive areas (including mucosal surfaces such as, oropharynx, urethra, rectum, vagina) resulting in severe pain that interferes with activities of daily living.
• Bowel lesions that are exudative or cause significant tissue edema, leading to obstruction.
• Severe lymphadenopathy that can be necrotizing or obstructing (such as in airways).
• Lesions leading to stricture and scar formation resulting in significant morbidity such as urethral and bowel strictures, phimosis, and facial scarring.
• Involvement of multiple organ systems and associated comorbidities, including:
• Oropharyngeal lesions inhibiting oral intake
• Pulmonary involvement with nodular lesions
• Neurologic conditions including encephalitis and transverse myelitis
• Cardiac complications including myocarditis and pericardial disease
• Ocular conditions including severe conjunctivitis and sight-threatening corneal ulcerations
• Urologic involvement including urethritis and penile necrosis
Healthcare providers should be aware of risk factors for severe manifestations of monkeypox and should conduct HIV testing for people with confirmed or suspected monkeypox. In prior monkeypox outbreaks in Nigeria, co-infection with HIV was associated with worse clinical outcomes, including severe manifestations of monkeypox, hospitalization, and death.2 Providers should also consider other immunocompromising conditions* and medications that may increase risk of severe manifestation of monkeypox.
In immunocompromised people, monkeypox treatment should include optimizing immune function by limiting the use of immunosuppressive medications if not otherwise clinically indicated, and, for those with HIV, providing antiretroviral therapy. In addition, there are medical countermeasures that may have a role in treating severe illness, including oral and intravenous tecovirimat (TPOXX), cidofovir or brincidofovir, and vaccinia immune globulin intravenous (VIGIV), although there are no data on effectiveness in treating human monkeypox with these medical countermeasures. Decisions on whether and when to use these medical countermeasures must be made individually for each person and can depend on a variety of clinical and other parameters.
Healthcare providers of people with monkeypox who are at risk for or who have severe manifestations of disease should reach out to their local public health jurisdictions or CDC for guidance about appropriate treatment. People with severe manifestations of monkeypox may benefit from multidisciplinary consultation with specialists such as infectious disease, ophthalmology, dermatology, urology, or critical care medicine. CDC offers a clinical consultation service (email eocevent482"at"cdc.gov or healthcare providers may contact the CDC Emergency Operations Center [EOC] at (770) 488-7100) and can provide additional guidance to clinicians with patient management questions. Clinicians seeking treatments should work with their local or state public health jurisdictions and CDC to access appropriate treatments as soon as potential need becomes apparent.
Worsening, non-healing, recurrent, and new skin lesions while receiving antiviral treatment have been observed among immunocompromised people with severe manifestations of monkeypox. Clinicians are encouraged to obtain repeat lesion swabs to assess for persistent monkeypox DNA. In such people, clinicians may consider continuing tecovirimat beyond 14 days, until there is clinical improvement (no more than 90 days).3 In certain clinical situations, modifications to the dose, frequency, and duration may be necessary depending on the individual patient’s clinical condition, disease progression, therapeutic response, and/or clinical judgement in consultation with CDC and U.S. Food and Drug Administration (FDA) as appropriate. To request clinical consultation regarding dosing adjustments, contact the CDC EOC at (770) 488-7100 or send an email to eocevent482@cdc.gov.3
Currently, CDC is conducting surveillance to monitor for the development of resistance to tecovirimat primarily from specimens that were sent to CDC for monkeypox confirmatory testing; however, resistance testing results are not CLIA-waived (approved) for use in clinical decision making. For the purposes of public health surveillance, CDC encourages clinicians to submit specimens for further monkeypox virus characterization through genetic sequencing to identify mutations that could potentially result in resistance to antiviral therapy. At this time, after evaluating more than 600 samples, there have been no specimens with mutations associated with tecovirimat resistance; however, it is not clear how many of those samples were collected from people with disease progression while on tecovirimat.
* Severe immunocompromise due to leukemia, lymphoma, generalized malignancy, solid organ transplantation, therapy with alkylating agents, antimetabolites, radiation, tumor necrosis factor inhibitors, or high-dose corticosteroids, being a recipient of a hematopoietic stem cell transplant <24 months post-transplant or ≥24 months but with graft-versus-host disease or disease relapse, or having autoimmune disease with immunodeficiency as a clinical component

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