Mpox Update: Clinical Presentation, Vaccination Guidance, and Management

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Mpox Update: Clinical Presentation, Vaccination Guidance, and Management

The mpox (monkeypox) virus is a zoonotic orthopox DNA virus that results in a smallpoxlike illness.1 Vaccination against smallpox protects against other orthopox infections, including mpox; however, unlike smallpox, mpox is notable for a variety of not-yet-confirmed animal reservoirs.2 Mpox was first identified in Denmark in 1959 among nonhuman primates imported from Singapore, and the first case of human infection was diagnosed in 1970 in a 9-month-old child in the Democratic Republic of Congo.3 Endemic regions of Africa have had sporadic outbreaks with increasing frequency over time since the cessation of smallpox vaccination in 1980.2,4 Infections in nonendemic countries have occurred intermittently, including in 2003 in the Midwest United States. This outbreak was traced back to prairie dogs infected by exotic animals imported from the Republic of Ghana.5

Two genetic clades of mpox that differ in mortality rates have been identified: clade II (formerly the West African clade) generally is self-limited with an estimated mortality of 1% to 6%, whereas clade I (formerly the Congo Basin clade) is more transmissible, with a mortality of approximately 10%.2,6,7 Notably, as of May 2, 2022, all polymerase chain reaction–confirmed cases of mpox in nonendemic countries were identified as clade II.7 Following the continued international spread of mpox, the Director-General of the World Health Organization (WHO) declared the global outbreak a public health emergency of international concern on July 23, 2022.8 As of March 1, 2023, the Centers for Disease Control and Prevention (CDC) reports that there have been more than 86,000 cases of laboratory-confirmed mpox worldwide and 105 deaths, 89 of which occurred in nonendemic regions.9

Transmission of Mpox

In endemic countries, cases have been largely reported secondary to zoonotic spillover from contact with an infected animal.6 However, in nonendemic countries, mpox often results from human-to-human transmission, primarily via skin-to-skin contact with infected skin, but also may occur indirectly via contaminated fomites such as bedding or clothing, respiratory secretions, or vertical transmission.6,10 The indirect transmission of mpox via contaminated fomites is controversial, though some studies have shown the virus can survive on surfaces for up to 15 days.11 In the current outbreak, human-to-human transmission has been strongly associated with close contact during sexual activity, particularly among men who have sex with men (MSM), with notable physical concentration of initial lesions in the genital region.12 Anyone can acquire mpox—infections are not exclusive to MSM populations, and cases have been reported in all demographic groups, including women and children. It is important to avoid stigmatization of MSM to prevent the propagation of homophobia as well as a false sense of complacency in non-MSM populations.13

Clinical Presentation of Mpox

The incubation period of mpox has been reported to last up to 21 days and is posited to depend on the mode of transmission, with complex invasive exposures having a shorter duration of approximately 9 days compared to noninvasive exposures, which have a duration of approximately 13 days.14 In a recent report from the Netherlands, the average incubation time was 8.5 days in 18 men with exposure attributed to sexual encounters with men.12 Following the incubation period, mpox infection typically presents with nonspecific systemic symptoms such as fever, malaise, sore throat, cough, and headache for approximately 2 days, followed by painful generalized or localized lymphadenopathy 1 to 2 days prior to the onset of skin lesions.1,15 In a recent report from Portugal of more than 20 confirmed cases of mpox, approximately half of patients denied symptoms or had mild systemic symptoms, suggesting that many patients in the current outbreak do not endorse systemic symptoms.16

Classic cutaneous lesions are the hallmark feature of mpox.17 Over a period of 1 to 2 weeks, each lesion progresses through morphologic stages of macule, papule (Figure), vesicle, and pustule, which then crusts over, forming a scab that falls off after another 1 to 2 weeks and can result in dyspigmented or pitted scars.1,15 Lesions may be deep-seated or umbilicated; previously they were noted to typically start on the face and spread centrifugally, but recent cases have been notable for a predominance of anogenital lesions, often with the anogenital area as the sole or primary area of involvement.18 Given the high proportion of anogenital lesions in 2022, symptoms such as anogenital pain, tenesmus, and diarrhea are not uncommon.19 A recent study describing 528 international cases of mpox revealed that 95% of patients presented with a rash; nearly 75% had anogenital lesions; and 41%, 25%, and 10% had involvement of mucosae, the face, and palms/soles, respectively. More than half of patients had fewer than 10 lesions, and 10% presented with a single genital lesion.19

Mpox (monkeypox) papule.
Mpox (monkeypox) papule.

Given the recent predilection of lesions for the anogenital area, the differential diagnosis of mpox should include other common infections localized to these areas. Unlike herpes simplex and varicella-zoster infections, mpox does not exhibit the classic herpetiform clustering of vesicles, and unlike the painless chancre of syphilis, the lesions of mpox are exquisitely painful. Similar to chancroid, mpox presents with painful genital lesions and lymphadenopathy, and the umbilicated papules of molluscum could easily be confused with mpox lesions. Proctitis caused by many sexually transmitted infections (STIs), including chlamydia and gonorrhea, may be difficult to differentiate from proctitis symptoms of mpox. Co-infection with HIV and other STIs is common among patients developing mpox in 2022, which is not surprising given that the primary mechanism of transmission of mpox at this time is through sexual contact, and cases are more common in patients with multiple recent sexual partners.19 Considering these shared risk factors and similar presentation of multiple STIs, patients suspected of having an mpox infection should be tested for other STIs, including HIV.

Complications of Mpox

Although mpox generally is characterized by a mild disease course, there is concern for adverse outcomes, particularly in more vulnerable populations, including immunocompromised, pregnant, and pediatric populations. Complications of infection can include sepsis, encephalitis, bronchopneumonia, and ophthalmic complications that can result in loss of vision.6,17 The most common complications requiring hospitalization in a recent international report of 528 mpox cases were pain management, which was primarily due to severe anogenital pain, followed by soft-tissue superinfection, with other complications including severe pharyngitis limiting oral intake and infection control practices.19 In addition to severe rectal pain, proctitis and even rectal perforation have been reported.19,20

 

 

Vertical transmission has been described with devastating outcomes in a case series from the Democratic Republic of Congo, where 4 cases of mpox were identified in pregnant women; 3 of these pregnancies resulted in fetal demise.10 The only fetus to survive was born to a mother with mild infection. In comparison, 2 of 3 mothers with moderate to severe disease experienced spontaneous abortion in the first trimester, and 1 pregnancy ended due to intrauterine demise during the eighteenth week of gestation, likely a complication of mpox. These cases suggest that more severe disease may be linked to worse fetal outcomes.10 Further epidemiologic studies will be crucial, given the potential implications.

Diagnosis

When considering a diagnosis of mpox, clinicians should inquire about recent travel, living arrangements, sexual history, and recent sick contacts.6 A complete skin examination should include the oral and genital areas, given the high prevalence of lesions in these areas. A skin biopsy is not recommended for the diagnosis of mpox, as nonspecific viral changes cannot be differentiated from other viral exanthems, but it often is useful to rule out other differential diagnoses.21 Additionally, immunohistochemistry and electron microscopy can be utilized to aid in a histologic diagnosis of mpox.

Polymerase chain reaction detection of orthopox or mpox DNA is the gold standard for diagnosis.6 Two swabs should be collected from each lesion by swabbing vigorously using sterile swabs made of a synthetic material such as polyester, nylon, or Dacron and placed into a sterile container or viral transport medium.22 Some laboratories may have different instructions for collection of samples, so clinicians are advised to check for instructions from their local laboratory. Deroofing lesions prior to swabbing is not necessary, and specimens can include lesional material or crust. Collection of specimens from 2 to 3 lesions is recommended, preferably from different body areas or lesions with varying morphologies. Anal or rectal swabs can be considered in patients presenting with anal pain or proctitis with clinical suspicion for mpox based on history.19

Infection Prevention

Interim guidance from the WHO on November 16, 2022, reiterated the goal of outbreak control primarily via public health measures, which includes targeted use of vaccines for at-risk populations or postexposure prophylactic vaccination within 4 days, but heavily relies on surveillance and containment techniques, such as contact tracing with monitoring of contacts for onset of symptoms and isolation of cases through the complete infectious period.23 Patients are considered infectious from symptom onset until all cutaneous lesions are re-epithelized and should remain in isolation, including from household contacts and domestic and wildlife animals, for the duration of illness.24,25 Individuals exposed to humans or animals with confirmed mpox should be monitored for the development of symptoms for 21 days following last known exposure, regardless of vaccination status, and should be instructed to measure their temperature twice daily.26 Pets exposed to mpox should be isolated from other animals and humans for 21 days following last known contact.24 Vaccination strategies for preexposure and postexposure prophylaxis (PEP) are discussed below in further detail. Postinfection, the WHO suggests use of condoms for all oral, vaginal, and anal sexual activity for 12 weeks after recovery.7

Patients with suspected or confirmed mpox in a hospital should be in a single private room on special droplet and contact precautions.27 No special air handling or negative pressure isolation is needed unless the patient is undergoing an aerosol-generating procedure (eg, intubation, endoscopy, bronchoscopy). When hospitalized, patients should have a dedicated bathroom, if possible, and at-home patients should be isolated from household members until contagion risk resolves; this includes the use of a separate bathroom, when possible. Health care personnel entering the room of a patient should don appropriate personal protective equipment (PPE), including a disposable gown, gloves, eye protection, and N95 respirator or equivalent. Recommendations include standard practices for cleaning, with wet cleaning methods preferred over dry methods, using a disinfectant that covers emerging viral pathogens, and avoidance of shaking linens to prevent the spread of infectious particles.27 A variety of Environmental Protection Agency–registered wipes with virucidal activity against emerging viruses, including those with active ingredients such as quaternary ammonium, hydrogen peroxide, and hypochlorous acid, should be used for disinfecting surfaces.28

Vaccination

ACAM2000 (Emergent Bio Solutions) and JYNNEOS (Bavarian Nordic)(also known as Imvamune or Imvanex) are available in the United States for the prevention of mpox infection.29 ACAM2000, a second-generation, replication-competent, live smallpox vaccine administered as a single percutaneous injection, is contraindicated in immunocompromised populations, including patients with HIV or on immunosuppressive or biologic therapy, pregnant individuals, people with a history of atopic dermatitis or other exfoliative skin diseases with impaired barrier function, and patients with a history of cardiac disease due to the risk of myocarditis and pericarditis.30

JYNNEOS is a nonreplicating live vaccine approved by the US Food and Drug Administration (FDA) for the prevention of mpox in individuals older than 18 years administered as 2 subcutaneous doses 4 weeks apart. Patients are considered fully vaccinated 2 weeks after the second dose, and JYNNEOS is available to pediatric patients with a single patient expanded access use authorization from the FDA.29,30 More recently, the FDA issued an emergency use authorization (EUA) for administration of the vaccine to patients younger than 18 years who are at high risk of infection after exposure.31 More importantly, the FDA also issued an EUA for the intradermal administration of JYNNEOS at one-fifth of the subcutaneous dose to expand the current vaccine supply. This EUA is based on research by Frey et al,32 which showed that intradermal administration, even at a lower dose, elicited similar immune responses among study participants as the higher dose administered subcutaneously.

 

 

JYNNEOS is the preferred vaccine for the prevention of mpox because of its poor ability to replicate in human cells and resultant safety for use in populations that are immunocompromised, pregnant, or have skin barrier defects such as atopic dermatitis, without the risk of myocarditis or pericarditis. However, current supplies are limited. JYNNEOS was specifically studied in patients with atopic dermatitis and has been shown to be safe and effective in patients with a history of atopic dermatitis and active disease with a SCORAD (SCORing Atopic Dermatitis) score of 30 or lower.33 Of note, JYNNEOS is contraindicated in patients allergic to components of the vaccine, including egg, gentamicin, and ciprofloxacin. Although JYNNEOS is safe to administer to persons with immunocompromising conditions, the CDC reports that such persons might be at increased risk for severe disease if an occupational infection occurs, and in the setting of immunocompromise, such persons may be less likely to mount an effective response to vaccination. Therefore, the risk-benefit ratio should be considered to determine if an immunocompromised person should be vaccinated with JYNNEOS.30

The WHO and the CDC do not recommended mass vaccination of the general public for outbreaks of mpox in nonendemic countries, with immunization reserved for appropriate PEP and pre-exposure prophylaxis in intermediate- to high-risk individuals.23,26 The CDC recommends PEP vaccination for individuals with a high degree of exposure that includes unprotected contact of the skin or mucous membranes of an individual to the skin, lesions, body fluids, or contaminated fomites from a patient with mpox, as well as being within 6 feet of a patient during an aerosolization procedure without proper PPE. Following an intermediate degree of exposure, which includes being within 6 feet for 3 or more hours wearing at minimum a surgical mask or contact with fomites while wearing incomplete PPE, the CDC recommends monitoring and shared decision-making regarding risks and benefits of PEP vaccination. Monitoring without PEP is indicated for low and uncertain degrees of exposure, including entering a room without full PPE such as eye protection, regardless of the duration of contact.23,26

Postexposure prophylaxis vaccination should be administered within 4 days of a known high-level exposure to mpox to prevent infection.29 If administered within 4 to 14 days postexposure, vaccination may reduce disease severity but will not prevent infection.34

Pre-exposure prophylaxis is recommended for individuals at high risk for exposure to mpox, including health care workers such as laboratory personnel who handle mpox specimens and health care workers who administer ACAM2000 vaccinations or anticipate providing care for many patients with mpox.34

Management

Most cases of mpox are characterized by mild to moderate disease with a self-limited course. Most commonly, medical management of mpox involves supportive care such as fluid resuscitation, supplemental oxygen, and pain management.6 Treatment of superinfected skin lesions may require antibiotics. In the event of ophthalmologic involvement, patients should be referred to an ophthalmologist for further management.

Currently, there are no FDA-approved therapies for mpox; however, tecovirimat, cidofovir, brincidofovir, and vaccinia immune globulin intravenous are available under expanded access Investigational New Drug protocols.6,35 Human data for cidofovir, brincidofovir, and vaccinia immune globulin intravenous in the treatment of mpox are lacking, while cidofovir and brincidofovir have shown efficacy against orthopoxviruses in in vitro and animal studies, but are available therapeutic options.35

Tecovirimat is an antiviral that is FDA approved for smallpox with efficacy data against mpox in animal studies. It is the first-line treatment for patients with severe disease requiring hospitalization or 1 or more complications, including dehydration or secondary skin infections, as well as for populations at risk for severe disease, which includes immunocompromised patients, pediatric patients younger than 8 years, pregnant or breastfeeding individuals, or patients with a history of atopic dermatitis or active exfoliative skin conditions.36 In this current outbreak, both intravenous and oral tecovirimat are weight based in adult and pediatric patients for 14 days, with the intravenous form dosed every 12 hours by infusion over 6 hours, and the oral doses administered every 8 to 12 hours based on patient weight.37 Tecovirimat generally is well tolerated with mild side effects but is notably contraindicated in patients with severe renal impairment with a creatinine clearance less than 30 mL/min, and renal monitoring is indicated in pediatric patients younger than 2 years and in all patients receiving intravenous treatment.

Conclusion

Given that cutaneous lesions are the most specific presenting sign of mpox infection, dermatologists will play an integral role in identifying future cases and managing future outbreaks. Mpox should be considered in the differential diagnosis for all patients presenting with umbilicated or papulovesicular lesions, particularly in an anogenital distribution. The classic presentation of mpox may be more common among patients who are not considered high risk and have not been exposed via sexual activity. All patients with suspicious lesions should be managed following appropriate infection control precautions and should undergo molecular diagnostic assay of swabbed lesions to confirm the diagnosis. JYNNEOS is the only vaccine that is currently being distributed in the United States and is safe to administer to immunocompromised populations. The risks and benefits of vaccination should be considered on an individual basis between a patient and their provider. Taking into consideration that patients with atopic dermatitis are at risk for severe disease if infected with mpox, vaccination should be strongly encouraged if indicated based on patient risk factors. For atopic dermatitis patients treated with dupilumab, shared decision-making is essential given the FDA label, which recommends avoiding the use of live vaccines.38

The mpox epidemic occurring amidst the ongoing COVID-19 pandemic should serve as a wake-up call to the importance of pandemic preparedness and the global health response strategies in the modern era of globalization. Looking forward, widespread vaccination against mpox may be necessary to control the spread of the disease and to protect vulnerable populations, including pregnant individuals. In the current climate of hesitancy surrounding vaccines and the erosion of trust in public health agencies, it is incumbent upon health care providers to educate patients regarding the role of vaccines and public health measures to control this developing global health crisis.

References
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  3. Ladnyj ID, Ziegler P, Kima E. A human infection caused by monkeypox virus in Basankusu Territory, Democratic Republic of the Congo. Bull World Health Organ. 1972;46:593-597.
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  5. Ligon BL. Monkeypox: a review of the history and emergence in the Western hemisphere. Semin Pediatr Infect Dis. 2004;15:280-287. doi:10.1053/j.spid.2004.09.001
  6. Titanji BK, Tegomoh B, Nematollahi S, et al. Monkeypox: a contemporary review for healthcare professionals. Open Forum Infect Dis. 2022;9:ofac310. doi:10.1093/ofid/ofac310
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  8. World Health Organization. WHO Director-General’s statement at the press conference following IHR Emergency Committee regarding the multi-country outbreak of monkeypox—23 July 2022. July 23, 2022. Accessed March 10, 2023. https://www.who.int/director-general/speeches/detail/who-director-general-s-statement-on-the-press-conference-following-IHR-emergency-committee-regarding-the-multi--country-outbreak-of-monkeypox--23-july-2022
  9. Centers for Disease Control and Prevention. 2022 mpox outbreak global map. Updated March 1, 2023. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/response/2022/world-map.html
  10. Mbala PK, Huggins JW, Riu-Rovira T, et al. Maternal and fetal outcomes among pregnant women with human monkeypox infection in the Democratic Republic of Congo. J Infect Dis. 2017;216:824-828. doi:10.1093/infdis/jix260
  11. Centers for Disease Control and Prevention. How to protect yourself. Updated October 31, 2022. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/prevention/protect-yourself.html
  12. Miura F, van Ewijk CE, Backer JA, et al. Estimated incubation period for monkeypox cases confirmed in the Netherlands, May 2022. Euro Surveill. 2022;27:2200448. doi:10.2807/1560-7917.Es.2022.27.24.2200448
  13. Treisman R. As monkeypox spreads, know the difference between warning and stigmatizing people. NPR. July 26, 2022. Accessed March 10, 2023. https://www.npr.org/2022/07/26/1113713684/monkeypox-stigma-gay-community
  14. Reynolds MG, Yorita KL, Kuehnert MJ, et al. Clinical manifestations of human monkeypox influenced by route of infection. J Infect Dis. 2006;194:773-780. doi:10.1086/505880
  15. Centers for Disease Control and Prevention. Clinical recognition. Updated August 23, 2022. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/clinicians/clinical-recognition.html
  16. Alpalhão M, Frade JV, Sousa D, et al. Monkeypox: a new (sexuallytransmissible) epidemic? J Eur Acad Dermatol Venereol. 2022;36:e1016-e1017. doi:10.1111/jdv.18424
  17. Reynolds MG, McCollum AM, Nguete B, et al. Improving the care and treatment of monkeypox patients in low-resource settings: applying evidence from contemporary biomedical and smallpox biodefense research. Viruses. 2017;9:380. doi:10.3390/v9120380
  18. Minhaj FS, Ogale YP, Whitehill F, et al. Monkeypox outbreak—nine states, May 2022. MMWR Morb Mortal Wkly Rep. 2022;71:764-769. doi:10.15585/mmwr.mm7123e1
  19. Thornhill JP, Barkati S, Walmsley S, et al. Monkeypox virus infection in humans across 16 countries—April-June 2022. N Engl J Med. 2022;387:679-691. doi:10.1056/NEJMoa2207323
  20. 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:e072410. doi:10.1136/bmj-2022-072410
  21. Bayer-Garner IB. Monkeypox virus: histologic, immunohistochemical and electron-microscopic findings. J Cutan Pathol. 2005;32:28-34. doi:10.1111/j.0303-6987.2005.00254.x
  22. Centers for Disease Control and Prevention. Guidelines for collecting and handling of specimens for mpox testing. Updated September 20, 2022. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/clinicians/prep-collection-specimens.html
  23. Vaccines and immunization for monkeypox: interim guidance, 16 November 2022. Accessed March 15, 2023. https://www.who.int/publications/i/item/WHO-MPX-Immunization
  24. Centers for Disease Control and Prevention. Pets in the home. Updated December 8, 2022. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/specific-settings/pets-in-homes.html
  25. Centers for Disease Control and Prevention. Isolation andprevention practices for people with monkeypox. Updated February 2, 2023. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/clinicians/isolation-procedures.html
  26. Centers for Disease Control and Prevention. Monitoring people who have been exposed. Updated November 25, 2022. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/clinicians/monitoring.html
  27. Centers for Disease Control and Prevention. Infection prevention and control of monkeypox in healthcare settings. Updated October 31, 2022. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/clinicians/infection-control-healthcare.html
  28. United States Environmental Protection Agency. EPA releases list of disinfectants for emerging viral pathogens (EVPs) including monkeypox. May 26, 2022. Accessed March 10, 2023. https://www.epa.gov/pesticides/epa-releases-list-disinfectants-emerging-viral-pathogens-evps-including-monkeypox
  29. Centers for Disease Control and Prevention. Interim clinical considerations for use of JYNNEOS and ACAM2000 vaccines during the 2022 U.S. mpox outbreak. Updated October 19, 2022. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/considerations-for-monkeypox-vaccination.html
  30. Rao AK, Petersen BW, Whitehill F, et al. Use of JYNNEOS (smallpox and monkeypox vaccine, live, nonreplicating) for preexposure vaccination of persons at risk for occupational exposure to orthopoxviruses: recommendations of the Advisory Committee on Immunization Practices—United States, 2022. MMWR Morb Mortal Wkly Rep. 2022;71:734-742. doi: http://dx.doi.org/10.15585/mmwr.mm7122e1
  31. US Food and Drug Administration. Monkeypox update: FDA authorizes emergency use of JYNNEOS vaccine to increase vaccine supply. August 9, 2022. Accessed March 10, 2023. https://www.fda.gov/news-events/press-announcements/monkeypox-update-fda-authorizes-emergency-use-jynneos-vaccine-increase-vaccine-supply#:~:text=Today%2C%20the%20U.S.%20Food%20and,high%20risk%20for%20monkeypox%20infection
  32. Frey SE, Wald A, Edupuganti S, et al. Comparison of lyophilized versus liquid modified vaccinia Ankara (MVA) formulations and subcutaneous versus intradermal routes of administration in healthy vaccinia-naïve subjects. Vaccine. 2015;33:5225-5234. doi:10.1016/j.vaccine.2015.06.075
  33. Greenberg RN, Hurley MY, Dinh DV, et al. A multicenter, open-label, controlled phase II study to evaluate safety and immunogenicity of MVA smallpox vaccine (IMVAMUNE) in 18-40 year old subjects with diagnosed atopic dermatitis. PLoS One. 2015;10:e0138348. doi:10.1371/journal.pone.0138348
  34. Centers for Disease Control and Prevention. Monkeypox and smallpox vaccine guidance. Accessed March 16, 2023. https://www.cdc.gov/poxvirus/mpox/interim-considerations/overview.html
  35. Centers for Disease Control and Prevention. Treatment information for healthcare professionals. Updated March 3, 2023. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/clinicians/treatment.html
  36. Centers for Disease Control and Prevention. Guidance for tecovirimat use: expanded access investigational new drug protocol during 2022 U.S. mpox outbreak. Updated February 23, 2023. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/clinicians/Tecovirimat.html
  37. Expanded access IND protocol: use of tecovirimat (TPOXX®) for treatment of human non-variola orthopoxvirus infections in adults and children. October 24, 2022. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/pdf/tecovirimat-ind-protocol-cdc-irb.pdf
  38. Dupixent (dupilumab). Prescribing information. Regeneron Pharmaceuticals, Inc; 2017. Accessed March 10, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761055lbl.pdf
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Drs. Cices, Sells, Woods, Silverberg, and Camins, as well as Ms. Akselrad, report no conflict of interest. Ms. Prasad has received research grants from the Infectious Disease Society of America.

Correspondence: Nanette B. Silverberg, MD, Icahn School of Medicine at Mount Sinai, 5 E 98th St, 5th Floor, New York, NY 10029 ([email protected]).

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From Icahn School of Medicine at Mount Sinai, New York, New York. Dr. Cices, Ms. Prasad, Ms. Akselrad, and Dr. Silverberg are from the Department of Dermatology; Drs. Sells, Woods, and Camins are from the Division of Infectious Diseases; and Dr. Silverberg also is from the Department of Pediatrics.

Drs. Cices, Sells, Woods, Silverberg, and Camins, as well as Ms. Akselrad, report no conflict of interest. Ms. Prasad has received research grants from the Infectious Disease Society of America.

Correspondence: Nanette B. Silverberg, MD, Icahn School of Medicine at Mount Sinai, 5 E 98th St, 5th Floor, New York, NY 10029 ([email protected]).

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From Icahn School of Medicine at Mount Sinai, New York, New York. Dr. Cices, Ms. Prasad, Ms. Akselrad, and Dr. Silverberg are from the Department of Dermatology; Drs. Sells, Woods, and Camins are from the Division of Infectious Diseases; and Dr. Silverberg also is from the Department of Pediatrics.

Drs. Cices, Sells, Woods, Silverberg, and Camins, as well as Ms. Akselrad, report no conflict of interest. Ms. Prasad has received research grants from the Infectious Disease Society of America.

Correspondence: Nanette B. Silverberg, MD, Icahn School of Medicine at Mount Sinai, 5 E 98th St, 5th Floor, New York, NY 10029 ([email protected]).

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The mpox (monkeypox) virus is a zoonotic orthopox DNA virus that results in a smallpoxlike illness.1 Vaccination against smallpox protects against other orthopox infections, including mpox; however, unlike smallpox, mpox is notable for a variety of not-yet-confirmed animal reservoirs.2 Mpox was first identified in Denmark in 1959 among nonhuman primates imported from Singapore, and the first case of human infection was diagnosed in 1970 in a 9-month-old child in the Democratic Republic of Congo.3 Endemic regions of Africa have had sporadic outbreaks with increasing frequency over time since the cessation of smallpox vaccination in 1980.2,4 Infections in nonendemic countries have occurred intermittently, including in 2003 in the Midwest United States. This outbreak was traced back to prairie dogs infected by exotic animals imported from the Republic of Ghana.5

Two genetic clades of mpox that differ in mortality rates have been identified: clade II (formerly the West African clade) generally is self-limited with an estimated mortality of 1% to 6%, whereas clade I (formerly the Congo Basin clade) is more transmissible, with a mortality of approximately 10%.2,6,7 Notably, as of May 2, 2022, all polymerase chain reaction–confirmed cases of mpox in nonendemic countries were identified as clade II.7 Following the continued international spread of mpox, the Director-General of the World Health Organization (WHO) declared the global outbreak a public health emergency of international concern on July 23, 2022.8 As of March 1, 2023, the Centers for Disease Control and Prevention (CDC) reports that there have been more than 86,000 cases of laboratory-confirmed mpox worldwide and 105 deaths, 89 of which occurred in nonendemic regions.9

Transmission of Mpox

In endemic countries, cases have been largely reported secondary to zoonotic spillover from contact with an infected animal.6 However, in nonendemic countries, mpox often results from human-to-human transmission, primarily via skin-to-skin contact with infected skin, but also may occur indirectly via contaminated fomites such as bedding or clothing, respiratory secretions, or vertical transmission.6,10 The indirect transmission of mpox via contaminated fomites is controversial, though some studies have shown the virus can survive on surfaces for up to 15 days.11 In the current outbreak, human-to-human transmission has been strongly associated with close contact during sexual activity, particularly among men who have sex with men (MSM), with notable physical concentration of initial lesions in the genital region.12 Anyone can acquire mpox—infections are not exclusive to MSM populations, and cases have been reported in all demographic groups, including women and children. It is important to avoid stigmatization of MSM to prevent the propagation of homophobia as well as a false sense of complacency in non-MSM populations.13

Clinical Presentation of Mpox

The incubation period of mpox has been reported to last up to 21 days and is posited to depend on the mode of transmission, with complex invasive exposures having a shorter duration of approximately 9 days compared to noninvasive exposures, which have a duration of approximately 13 days.14 In a recent report from the Netherlands, the average incubation time was 8.5 days in 18 men with exposure attributed to sexual encounters with men.12 Following the incubation period, mpox infection typically presents with nonspecific systemic symptoms such as fever, malaise, sore throat, cough, and headache for approximately 2 days, followed by painful generalized or localized lymphadenopathy 1 to 2 days prior to the onset of skin lesions.1,15 In a recent report from Portugal of more than 20 confirmed cases of mpox, approximately half of patients denied symptoms or had mild systemic symptoms, suggesting that many patients in the current outbreak do not endorse systemic symptoms.16

Classic cutaneous lesions are the hallmark feature of mpox.17 Over a period of 1 to 2 weeks, each lesion progresses through morphologic stages of macule, papule (Figure), vesicle, and pustule, which then crusts over, forming a scab that falls off after another 1 to 2 weeks and can result in dyspigmented or pitted scars.1,15 Lesions may be deep-seated or umbilicated; previously they were noted to typically start on the face and spread centrifugally, but recent cases have been notable for a predominance of anogenital lesions, often with the anogenital area as the sole or primary area of involvement.18 Given the high proportion of anogenital lesions in 2022, symptoms such as anogenital pain, tenesmus, and diarrhea are not uncommon.19 A recent study describing 528 international cases of mpox revealed that 95% of patients presented with a rash; nearly 75% had anogenital lesions; and 41%, 25%, and 10% had involvement of mucosae, the face, and palms/soles, respectively. More than half of patients had fewer than 10 lesions, and 10% presented with a single genital lesion.19

Mpox (monkeypox) papule.
Mpox (monkeypox) papule.

Given the recent predilection of lesions for the anogenital area, the differential diagnosis of mpox should include other common infections localized to these areas. Unlike herpes simplex and varicella-zoster infections, mpox does not exhibit the classic herpetiform clustering of vesicles, and unlike the painless chancre of syphilis, the lesions of mpox are exquisitely painful. Similar to chancroid, mpox presents with painful genital lesions and lymphadenopathy, and the umbilicated papules of molluscum could easily be confused with mpox lesions. Proctitis caused by many sexually transmitted infections (STIs), including chlamydia and gonorrhea, may be difficult to differentiate from proctitis symptoms of mpox. Co-infection with HIV and other STIs is common among patients developing mpox in 2022, which is not surprising given that the primary mechanism of transmission of mpox at this time is through sexual contact, and cases are more common in patients with multiple recent sexual partners.19 Considering these shared risk factors and similar presentation of multiple STIs, patients suspected of having an mpox infection should be tested for other STIs, including HIV.

Complications of Mpox

Although mpox generally is characterized by a mild disease course, there is concern for adverse outcomes, particularly in more vulnerable populations, including immunocompromised, pregnant, and pediatric populations. Complications of infection can include sepsis, encephalitis, bronchopneumonia, and ophthalmic complications that can result in loss of vision.6,17 The most common complications requiring hospitalization in a recent international report of 528 mpox cases were pain management, which was primarily due to severe anogenital pain, followed by soft-tissue superinfection, with other complications including severe pharyngitis limiting oral intake and infection control practices.19 In addition to severe rectal pain, proctitis and even rectal perforation have been reported.19,20

 

 

Vertical transmission has been described with devastating outcomes in a case series from the Democratic Republic of Congo, where 4 cases of mpox were identified in pregnant women; 3 of these pregnancies resulted in fetal demise.10 The only fetus to survive was born to a mother with mild infection. In comparison, 2 of 3 mothers with moderate to severe disease experienced spontaneous abortion in the first trimester, and 1 pregnancy ended due to intrauterine demise during the eighteenth week of gestation, likely a complication of mpox. These cases suggest that more severe disease may be linked to worse fetal outcomes.10 Further epidemiologic studies will be crucial, given the potential implications.

Diagnosis

When considering a diagnosis of mpox, clinicians should inquire about recent travel, living arrangements, sexual history, and recent sick contacts.6 A complete skin examination should include the oral and genital areas, given the high prevalence of lesions in these areas. A skin biopsy is not recommended for the diagnosis of mpox, as nonspecific viral changes cannot be differentiated from other viral exanthems, but it often is useful to rule out other differential diagnoses.21 Additionally, immunohistochemistry and electron microscopy can be utilized to aid in a histologic diagnosis of mpox.

Polymerase chain reaction detection of orthopox or mpox DNA is the gold standard for diagnosis.6 Two swabs should be collected from each lesion by swabbing vigorously using sterile swabs made of a synthetic material such as polyester, nylon, or Dacron and placed into a sterile container or viral transport medium.22 Some laboratories may have different instructions for collection of samples, so clinicians are advised to check for instructions from their local laboratory. Deroofing lesions prior to swabbing is not necessary, and specimens can include lesional material or crust. Collection of specimens from 2 to 3 lesions is recommended, preferably from different body areas or lesions with varying morphologies. Anal or rectal swabs can be considered in patients presenting with anal pain or proctitis with clinical suspicion for mpox based on history.19

Infection Prevention

Interim guidance from the WHO on November 16, 2022, reiterated the goal of outbreak control primarily via public health measures, which includes targeted use of vaccines for at-risk populations or postexposure prophylactic vaccination within 4 days, but heavily relies on surveillance and containment techniques, such as contact tracing with monitoring of contacts for onset of symptoms and isolation of cases through the complete infectious period.23 Patients are considered infectious from symptom onset until all cutaneous lesions are re-epithelized and should remain in isolation, including from household contacts and domestic and wildlife animals, for the duration of illness.24,25 Individuals exposed to humans or animals with confirmed mpox should be monitored for the development of symptoms for 21 days following last known exposure, regardless of vaccination status, and should be instructed to measure their temperature twice daily.26 Pets exposed to mpox should be isolated from other animals and humans for 21 days following last known contact.24 Vaccination strategies for preexposure and postexposure prophylaxis (PEP) are discussed below in further detail. Postinfection, the WHO suggests use of condoms for all oral, vaginal, and anal sexual activity for 12 weeks after recovery.7

Patients with suspected or confirmed mpox in a hospital should be in a single private room on special droplet and contact precautions.27 No special air handling or negative pressure isolation is needed unless the patient is undergoing an aerosol-generating procedure (eg, intubation, endoscopy, bronchoscopy). When hospitalized, patients should have a dedicated bathroom, if possible, and at-home patients should be isolated from household members until contagion risk resolves; this includes the use of a separate bathroom, when possible. Health care personnel entering the room of a patient should don appropriate personal protective equipment (PPE), including a disposable gown, gloves, eye protection, and N95 respirator or equivalent. Recommendations include standard practices for cleaning, with wet cleaning methods preferred over dry methods, using a disinfectant that covers emerging viral pathogens, and avoidance of shaking linens to prevent the spread of infectious particles.27 A variety of Environmental Protection Agency–registered wipes with virucidal activity against emerging viruses, including those with active ingredients such as quaternary ammonium, hydrogen peroxide, and hypochlorous acid, should be used for disinfecting surfaces.28

Vaccination

ACAM2000 (Emergent Bio Solutions) and JYNNEOS (Bavarian Nordic)(also known as Imvamune or Imvanex) are available in the United States for the prevention of mpox infection.29 ACAM2000, a second-generation, replication-competent, live smallpox vaccine administered as a single percutaneous injection, is contraindicated in immunocompromised populations, including patients with HIV or on immunosuppressive or biologic therapy, pregnant individuals, people with a history of atopic dermatitis or other exfoliative skin diseases with impaired barrier function, and patients with a history of cardiac disease due to the risk of myocarditis and pericarditis.30

JYNNEOS is a nonreplicating live vaccine approved by the US Food and Drug Administration (FDA) for the prevention of mpox in individuals older than 18 years administered as 2 subcutaneous doses 4 weeks apart. Patients are considered fully vaccinated 2 weeks after the second dose, and JYNNEOS is available to pediatric patients with a single patient expanded access use authorization from the FDA.29,30 More recently, the FDA issued an emergency use authorization (EUA) for administration of the vaccine to patients younger than 18 years who are at high risk of infection after exposure.31 More importantly, the FDA also issued an EUA for the intradermal administration of JYNNEOS at one-fifth of the subcutaneous dose to expand the current vaccine supply. This EUA is based on research by Frey et al,32 which showed that intradermal administration, even at a lower dose, elicited similar immune responses among study participants as the higher dose administered subcutaneously.

 

 

JYNNEOS is the preferred vaccine for the prevention of mpox because of its poor ability to replicate in human cells and resultant safety for use in populations that are immunocompromised, pregnant, or have skin barrier defects such as atopic dermatitis, without the risk of myocarditis or pericarditis. However, current supplies are limited. JYNNEOS was specifically studied in patients with atopic dermatitis and has been shown to be safe and effective in patients with a history of atopic dermatitis and active disease with a SCORAD (SCORing Atopic Dermatitis) score of 30 or lower.33 Of note, JYNNEOS is contraindicated in patients allergic to components of the vaccine, including egg, gentamicin, and ciprofloxacin. Although JYNNEOS is safe to administer to persons with immunocompromising conditions, the CDC reports that such persons might be at increased risk for severe disease if an occupational infection occurs, and in the setting of immunocompromise, such persons may be less likely to mount an effective response to vaccination. Therefore, the risk-benefit ratio should be considered to determine if an immunocompromised person should be vaccinated with JYNNEOS.30

The WHO and the CDC do not recommended mass vaccination of the general public for outbreaks of mpox in nonendemic countries, with immunization reserved for appropriate PEP and pre-exposure prophylaxis in intermediate- to high-risk individuals.23,26 The CDC recommends PEP vaccination for individuals with a high degree of exposure that includes unprotected contact of the skin or mucous membranes of an individual to the skin, lesions, body fluids, or contaminated fomites from a patient with mpox, as well as being within 6 feet of a patient during an aerosolization procedure without proper PPE. Following an intermediate degree of exposure, which includes being within 6 feet for 3 or more hours wearing at minimum a surgical mask or contact with fomites while wearing incomplete PPE, the CDC recommends monitoring and shared decision-making regarding risks and benefits of PEP vaccination. Monitoring without PEP is indicated for low and uncertain degrees of exposure, including entering a room without full PPE such as eye protection, regardless of the duration of contact.23,26

Postexposure prophylaxis vaccination should be administered within 4 days of a known high-level exposure to mpox to prevent infection.29 If administered within 4 to 14 days postexposure, vaccination may reduce disease severity but will not prevent infection.34

Pre-exposure prophylaxis is recommended for individuals at high risk for exposure to mpox, including health care workers such as laboratory personnel who handle mpox specimens and health care workers who administer ACAM2000 vaccinations or anticipate providing care for many patients with mpox.34

Management

Most cases of mpox are characterized by mild to moderate disease with a self-limited course. Most commonly, medical management of mpox involves supportive care such as fluid resuscitation, supplemental oxygen, and pain management.6 Treatment of superinfected skin lesions may require antibiotics. In the event of ophthalmologic involvement, patients should be referred to an ophthalmologist for further management.

Currently, there are no FDA-approved therapies for mpox; however, tecovirimat, cidofovir, brincidofovir, and vaccinia immune globulin intravenous are available under expanded access Investigational New Drug protocols.6,35 Human data for cidofovir, brincidofovir, and vaccinia immune globulin intravenous in the treatment of mpox are lacking, while cidofovir and brincidofovir have shown efficacy against orthopoxviruses in in vitro and animal studies, but are available therapeutic options.35

Tecovirimat is an antiviral that is FDA approved for smallpox with efficacy data against mpox in animal studies. It is the first-line treatment for patients with severe disease requiring hospitalization or 1 or more complications, including dehydration or secondary skin infections, as well as for populations at risk for severe disease, which includes immunocompromised patients, pediatric patients younger than 8 years, pregnant or breastfeeding individuals, or patients with a history of atopic dermatitis or active exfoliative skin conditions.36 In this current outbreak, both intravenous and oral tecovirimat are weight based in adult and pediatric patients for 14 days, with the intravenous form dosed every 12 hours by infusion over 6 hours, and the oral doses administered every 8 to 12 hours based on patient weight.37 Tecovirimat generally is well tolerated with mild side effects but is notably contraindicated in patients with severe renal impairment with a creatinine clearance less than 30 mL/min, and renal monitoring is indicated in pediatric patients younger than 2 years and in all patients receiving intravenous treatment.

Conclusion

Given that cutaneous lesions are the most specific presenting sign of mpox infection, dermatologists will play an integral role in identifying future cases and managing future outbreaks. Mpox should be considered in the differential diagnosis for all patients presenting with umbilicated or papulovesicular lesions, particularly in an anogenital distribution. The classic presentation of mpox may be more common among patients who are not considered high risk and have not been exposed via sexual activity. All patients with suspicious lesions should be managed following appropriate infection control precautions and should undergo molecular diagnostic assay of swabbed lesions to confirm the diagnosis. JYNNEOS is the only vaccine that is currently being distributed in the United States and is safe to administer to immunocompromised populations. The risks and benefits of vaccination should be considered on an individual basis between a patient and their provider. Taking into consideration that patients with atopic dermatitis are at risk for severe disease if infected with mpox, vaccination should be strongly encouraged if indicated based on patient risk factors. For atopic dermatitis patients treated with dupilumab, shared decision-making is essential given the FDA label, which recommends avoiding the use of live vaccines.38

The mpox epidemic occurring amidst the ongoing COVID-19 pandemic should serve as a wake-up call to the importance of pandemic preparedness and the global health response strategies in the modern era of globalization. Looking forward, widespread vaccination against mpox may be necessary to control the spread of the disease and to protect vulnerable populations, including pregnant individuals. In the current climate of hesitancy surrounding vaccines and the erosion of trust in public health agencies, it is incumbent upon health care providers to educate patients regarding the role of vaccines and public health measures to control this developing global health crisis.

The mpox (monkeypox) virus is a zoonotic orthopox DNA virus that results in a smallpoxlike illness.1 Vaccination against smallpox protects against other orthopox infections, including mpox; however, unlike smallpox, mpox is notable for a variety of not-yet-confirmed animal reservoirs.2 Mpox was first identified in Denmark in 1959 among nonhuman primates imported from Singapore, and the first case of human infection was diagnosed in 1970 in a 9-month-old child in the Democratic Republic of Congo.3 Endemic regions of Africa have had sporadic outbreaks with increasing frequency over time since the cessation of smallpox vaccination in 1980.2,4 Infections in nonendemic countries have occurred intermittently, including in 2003 in the Midwest United States. This outbreak was traced back to prairie dogs infected by exotic animals imported from the Republic of Ghana.5

Two genetic clades of mpox that differ in mortality rates have been identified: clade II (formerly the West African clade) generally is self-limited with an estimated mortality of 1% to 6%, whereas clade I (formerly the Congo Basin clade) is more transmissible, with a mortality of approximately 10%.2,6,7 Notably, as of May 2, 2022, all polymerase chain reaction–confirmed cases of mpox in nonendemic countries were identified as clade II.7 Following the continued international spread of mpox, the Director-General of the World Health Organization (WHO) declared the global outbreak a public health emergency of international concern on July 23, 2022.8 As of March 1, 2023, the Centers for Disease Control and Prevention (CDC) reports that there have been more than 86,000 cases of laboratory-confirmed mpox worldwide and 105 deaths, 89 of which occurred in nonendemic regions.9

Transmission of Mpox

In endemic countries, cases have been largely reported secondary to zoonotic spillover from contact with an infected animal.6 However, in nonendemic countries, mpox often results from human-to-human transmission, primarily via skin-to-skin contact with infected skin, but also may occur indirectly via contaminated fomites such as bedding or clothing, respiratory secretions, or vertical transmission.6,10 The indirect transmission of mpox via contaminated fomites is controversial, though some studies have shown the virus can survive on surfaces for up to 15 days.11 In the current outbreak, human-to-human transmission has been strongly associated with close contact during sexual activity, particularly among men who have sex with men (MSM), with notable physical concentration of initial lesions in the genital region.12 Anyone can acquire mpox—infections are not exclusive to MSM populations, and cases have been reported in all demographic groups, including women and children. It is important to avoid stigmatization of MSM to prevent the propagation of homophobia as well as a false sense of complacency in non-MSM populations.13

Clinical Presentation of Mpox

The incubation period of mpox has been reported to last up to 21 days and is posited to depend on the mode of transmission, with complex invasive exposures having a shorter duration of approximately 9 days compared to noninvasive exposures, which have a duration of approximately 13 days.14 In a recent report from the Netherlands, the average incubation time was 8.5 days in 18 men with exposure attributed to sexual encounters with men.12 Following the incubation period, mpox infection typically presents with nonspecific systemic symptoms such as fever, malaise, sore throat, cough, and headache for approximately 2 days, followed by painful generalized or localized lymphadenopathy 1 to 2 days prior to the onset of skin lesions.1,15 In a recent report from Portugal of more than 20 confirmed cases of mpox, approximately half of patients denied symptoms or had mild systemic symptoms, suggesting that many patients in the current outbreak do not endorse systemic symptoms.16

Classic cutaneous lesions are the hallmark feature of mpox.17 Over a period of 1 to 2 weeks, each lesion progresses through morphologic stages of macule, papule (Figure), vesicle, and pustule, which then crusts over, forming a scab that falls off after another 1 to 2 weeks and can result in dyspigmented or pitted scars.1,15 Lesions may be deep-seated or umbilicated; previously they were noted to typically start on the face and spread centrifugally, but recent cases have been notable for a predominance of anogenital lesions, often with the anogenital area as the sole or primary area of involvement.18 Given the high proportion of anogenital lesions in 2022, symptoms such as anogenital pain, tenesmus, and diarrhea are not uncommon.19 A recent study describing 528 international cases of mpox revealed that 95% of patients presented with a rash; nearly 75% had anogenital lesions; and 41%, 25%, and 10% had involvement of mucosae, the face, and palms/soles, respectively. More than half of patients had fewer than 10 lesions, and 10% presented with a single genital lesion.19

Mpox (monkeypox) papule.
Mpox (monkeypox) papule.

Given the recent predilection of lesions for the anogenital area, the differential diagnosis of mpox should include other common infections localized to these areas. Unlike herpes simplex and varicella-zoster infections, mpox does not exhibit the classic herpetiform clustering of vesicles, and unlike the painless chancre of syphilis, the lesions of mpox are exquisitely painful. Similar to chancroid, mpox presents with painful genital lesions and lymphadenopathy, and the umbilicated papules of molluscum could easily be confused with mpox lesions. Proctitis caused by many sexually transmitted infections (STIs), including chlamydia and gonorrhea, may be difficult to differentiate from proctitis symptoms of mpox. Co-infection with HIV and other STIs is common among patients developing mpox in 2022, which is not surprising given that the primary mechanism of transmission of mpox at this time is through sexual contact, and cases are more common in patients with multiple recent sexual partners.19 Considering these shared risk factors and similar presentation of multiple STIs, patients suspected of having an mpox infection should be tested for other STIs, including HIV.

Complications of Mpox

Although mpox generally is characterized by a mild disease course, there is concern for adverse outcomes, particularly in more vulnerable populations, including immunocompromised, pregnant, and pediatric populations. Complications of infection can include sepsis, encephalitis, bronchopneumonia, and ophthalmic complications that can result in loss of vision.6,17 The most common complications requiring hospitalization in a recent international report of 528 mpox cases were pain management, which was primarily due to severe anogenital pain, followed by soft-tissue superinfection, with other complications including severe pharyngitis limiting oral intake and infection control practices.19 In addition to severe rectal pain, proctitis and even rectal perforation have been reported.19,20

 

 

Vertical transmission has been described with devastating outcomes in a case series from the Democratic Republic of Congo, where 4 cases of mpox were identified in pregnant women; 3 of these pregnancies resulted in fetal demise.10 The only fetus to survive was born to a mother with mild infection. In comparison, 2 of 3 mothers with moderate to severe disease experienced spontaneous abortion in the first trimester, and 1 pregnancy ended due to intrauterine demise during the eighteenth week of gestation, likely a complication of mpox. These cases suggest that more severe disease may be linked to worse fetal outcomes.10 Further epidemiologic studies will be crucial, given the potential implications.

Diagnosis

When considering a diagnosis of mpox, clinicians should inquire about recent travel, living arrangements, sexual history, and recent sick contacts.6 A complete skin examination should include the oral and genital areas, given the high prevalence of lesions in these areas. A skin biopsy is not recommended for the diagnosis of mpox, as nonspecific viral changes cannot be differentiated from other viral exanthems, but it often is useful to rule out other differential diagnoses.21 Additionally, immunohistochemistry and electron microscopy can be utilized to aid in a histologic diagnosis of mpox.

Polymerase chain reaction detection of orthopox or mpox DNA is the gold standard for diagnosis.6 Two swabs should be collected from each lesion by swabbing vigorously using sterile swabs made of a synthetic material such as polyester, nylon, or Dacron and placed into a sterile container or viral transport medium.22 Some laboratories may have different instructions for collection of samples, so clinicians are advised to check for instructions from their local laboratory. Deroofing lesions prior to swabbing is not necessary, and specimens can include lesional material or crust. Collection of specimens from 2 to 3 lesions is recommended, preferably from different body areas or lesions with varying morphologies. Anal or rectal swabs can be considered in patients presenting with anal pain or proctitis with clinical suspicion for mpox based on history.19

Infection Prevention

Interim guidance from the WHO on November 16, 2022, reiterated the goal of outbreak control primarily via public health measures, which includes targeted use of vaccines for at-risk populations or postexposure prophylactic vaccination within 4 days, but heavily relies on surveillance and containment techniques, such as contact tracing with monitoring of contacts for onset of symptoms and isolation of cases through the complete infectious period.23 Patients are considered infectious from symptom onset until all cutaneous lesions are re-epithelized and should remain in isolation, including from household contacts and domestic and wildlife animals, for the duration of illness.24,25 Individuals exposed to humans or animals with confirmed mpox should be monitored for the development of symptoms for 21 days following last known exposure, regardless of vaccination status, and should be instructed to measure their temperature twice daily.26 Pets exposed to mpox should be isolated from other animals and humans for 21 days following last known contact.24 Vaccination strategies for preexposure and postexposure prophylaxis (PEP) are discussed below in further detail. Postinfection, the WHO suggests use of condoms for all oral, vaginal, and anal sexual activity for 12 weeks after recovery.7

Patients with suspected or confirmed mpox in a hospital should be in a single private room on special droplet and contact precautions.27 No special air handling or negative pressure isolation is needed unless the patient is undergoing an aerosol-generating procedure (eg, intubation, endoscopy, bronchoscopy). When hospitalized, patients should have a dedicated bathroom, if possible, and at-home patients should be isolated from household members until contagion risk resolves; this includes the use of a separate bathroom, when possible. Health care personnel entering the room of a patient should don appropriate personal protective equipment (PPE), including a disposable gown, gloves, eye protection, and N95 respirator or equivalent. Recommendations include standard practices for cleaning, with wet cleaning methods preferred over dry methods, using a disinfectant that covers emerging viral pathogens, and avoidance of shaking linens to prevent the spread of infectious particles.27 A variety of Environmental Protection Agency–registered wipes with virucidal activity against emerging viruses, including those with active ingredients such as quaternary ammonium, hydrogen peroxide, and hypochlorous acid, should be used for disinfecting surfaces.28

Vaccination

ACAM2000 (Emergent Bio Solutions) and JYNNEOS (Bavarian Nordic)(also known as Imvamune or Imvanex) are available in the United States for the prevention of mpox infection.29 ACAM2000, a second-generation, replication-competent, live smallpox vaccine administered as a single percutaneous injection, is contraindicated in immunocompromised populations, including patients with HIV or on immunosuppressive or biologic therapy, pregnant individuals, people with a history of atopic dermatitis or other exfoliative skin diseases with impaired barrier function, and patients with a history of cardiac disease due to the risk of myocarditis and pericarditis.30

JYNNEOS is a nonreplicating live vaccine approved by the US Food and Drug Administration (FDA) for the prevention of mpox in individuals older than 18 years administered as 2 subcutaneous doses 4 weeks apart. Patients are considered fully vaccinated 2 weeks after the second dose, and JYNNEOS is available to pediatric patients with a single patient expanded access use authorization from the FDA.29,30 More recently, the FDA issued an emergency use authorization (EUA) for administration of the vaccine to patients younger than 18 years who are at high risk of infection after exposure.31 More importantly, the FDA also issued an EUA for the intradermal administration of JYNNEOS at one-fifth of the subcutaneous dose to expand the current vaccine supply. This EUA is based on research by Frey et al,32 which showed that intradermal administration, even at a lower dose, elicited similar immune responses among study participants as the higher dose administered subcutaneously.

 

 

JYNNEOS is the preferred vaccine for the prevention of mpox because of its poor ability to replicate in human cells and resultant safety for use in populations that are immunocompromised, pregnant, or have skin barrier defects such as atopic dermatitis, without the risk of myocarditis or pericarditis. However, current supplies are limited. JYNNEOS was specifically studied in patients with atopic dermatitis and has been shown to be safe and effective in patients with a history of atopic dermatitis and active disease with a SCORAD (SCORing Atopic Dermatitis) score of 30 or lower.33 Of note, JYNNEOS is contraindicated in patients allergic to components of the vaccine, including egg, gentamicin, and ciprofloxacin. Although JYNNEOS is safe to administer to persons with immunocompromising conditions, the CDC reports that such persons might be at increased risk for severe disease if an occupational infection occurs, and in the setting of immunocompromise, such persons may be less likely to mount an effective response to vaccination. Therefore, the risk-benefit ratio should be considered to determine if an immunocompromised person should be vaccinated with JYNNEOS.30

The WHO and the CDC do not recommended mass vaccination of the general public for outbreaks of mpox in nonendemic countries, with immunization reserved for appropriate PEP and pre-exposure prophylaxis in intermediate- to high-risk individuals.23,26 The CDC recommends PEP vaccination for individuals with a high degree of exposure that includes unprotected contact of the skin or mucous membranes of an individual to the skin, lesions, body fluids, or contaminated fomites from a patient with mpox, as well as being within 6 feet of a patient during an aerosolization procedure without proper PPE. Following an intermediate degree of exposure, which includes being within 6 feet for 3 or more hours wearing at minimum a surgical mask or contact with fomites while wearing incomplete PPE, the CDC recommends monitoring and shared decision-making regarding risks and benefits of PEP vaccination. Monitoring without PEP is indicated for low and uncertain degrees of exposure, including entering a room without full PPE such as eye protection, regardless of the duration of contact.23,26

Postexposure prophylaxis vaccination should be administered within 4 days of a known high-level exposure to mpox to prevent infection.29 If administered within 4 to 14 days postexposure, vaccination may reduce disease severity but will not prevent infection.34

Pre-exposure prophylaxis is recommended for individuals at high risk for exposure to mpox, including health care workers such as laboratory personnel who handle mpox specimens and health care workers who administer ACAM2000 vaccinations or anticipate providing care for many patients with mpox.34

Management

Most cases of mpox are characterized by mild to moderate disease with a self-limited course. Most commonly, medical management of mpox involves supportive care such as fluid resuscitation, supplemental oxygen, and pain management.6 Treatment of superinfected skin lesions may require antibiotics. In the event of ophthalmologic involvement, patients should be referred to an ophthalmologist for further management.

Currently, there are no FDA-approved therapies for mpox; however, tecovirimat, cidofovir, brincidofovir, and vaccinia immune globulin intravenous are available under expanded access Investigational New Drug protocols.6,35 Human data for cidofovir, brincidofovir, and vaccinia immune globulin intravenous in the treatment of mpox are lacking, while cidofovir and brincidofovir have shown efficacy against orthopoxviruses in in vitro and animal studies, but are available therapeutic options.35

Tecovirimat is an antiviral that is FDA approved for smallpox with efficacy data against mpox in animal studies. It is the first-line treatment for patients with severe disease requiring hospitalization or 1 or more complications, including dehydration or secondary skin infections, as well as for populations at risk for severe disease, which includes immunocompromised patients, pediatric patients younger than 8 years, pregnant or breastfeeding individuals, or patients with a history of atopic dermatitis or active exfoliative skin conditions.36 In this current outbreak, both intravenous and oral tecovirimat are weight based in adult and pediatric patients for 14 days, with the intravenous form dosed every 12 hours by infusion over 6 hours, and the oral doses administered every 8 to 12 hours based on patient weight.37 Tecovirimat generally is well tolerated with mild side effects but is notably contraindicated in patients with severe renal impairment with a creatinine clearance less than 30 mL/min, and renal monitoring is indicated in pediatric patients younger than 2 years and in all patients receiving intravenous treatment.

Conclusion

Given that cutaneous lesions are the most specific presenting sign of mpox infection, dermatologists will play an integral role in identifying future cases and managing future outbreaks. Mpox should be considered in the differential diagnosis for all patients presenting with umbilicated or papulovesicular lesions, particularly in an anogenital distribution. The classic presentation of mpox may be more common among patients who are not considered high risk and have not been exposed via sexual activity. All patients with suspicious lesions should be managed following appropriate infection control precautions and should undergo molecular diagnostic assay of swabbed lesions to confirm the diagnosis. JYNNEOS is the only vaccine that is currently being distributed in the United States and is safe to administer to immunocompromised populations. The risks and benefits of vaccination should be considered on an individual basis between a patient and their provider. Taking into consideration that patients with atopic dermatitis are at risk for severe disease if infected with mpox, vaccination should be strongly encouraged if indicated based on patient risk factors. For atopic dermatitis patients treated with dupilumab, shared decision-making is essential given the FDA label, which recommends avoiding the use of live vaccines.38

The mpox epidemic occurring amidst the ongoing COVID-19 pandemic should serve as a wake-up call to the importance of pandemic preparedness and the global health response strategies in the modern era of globalization. Looking forward, widespread vaccination against mpox may be necessary to control the spread of the disease and to protect vulnerable populations, including pregnant individuals. In the current climate of hesitancy surrounding vaccines and the erosion of trust in public health agencies, it is incumbent upon health care providers to educate patients regarding the role of vaccines and public health measures to control this developing global health crisis.

References
  1. Di Giulio DB, Eckburg PB. Human monkeypox: an emerging zoonosis. Lancet Infect Dis. 2004;4:15-25. doi:10.1016/s1473-3099(03)00856-9
  2. Simpson K, Heymann D, Brown CS, et al. Human monkeypox—after 40 years, an unintended consequence of smallpox eradication. Vaccine. 2020;38:5077-5081. doi:10.1016/j.vaccine.2020.04.062
  3. Ladnyj ID, Ziegler P, Kima E. A human infection caused by monkeypox virus in Basankusu Territory, Democratic Republic of the Congo. Bull World Health Organ. 1972;46:593-597.
  4. Alakunle EF, Okeke MI. Monkeypox virus: a neglected zoonotic pathogen spreads globally. Nat Rev Microbiol. 2022;20:507-508. doi:10.1038/s41579-022-00776-z
  5. Ligon BL. Monkeypox: a review of the history and emergence in the Western hemisphere. Semin Pediatr Infect Dis. 2004;15:280-287. doi:10.1053/j.spid.2004.09.001
  6. Titanji BK, Tegomoh B, Nematollahi S, et al. Monkeypox: a contemporary review for healthcare professionals. Open Forum Infect Dis. 2022;9:ofac310. doi:10.1093/ofid/ofac310
  7. Gigante CM, Korber B, Seabolt MH, et al. Multiple lineages of monkeypox virus detected in the United States, 2021-2022. Science. 2022;378:560-565. doi:10.1126/science.add4153
  8. World Health Organization. WHO Director-General’s statement at the press conference following IHR Emergency Committee regarding the multi-country outbreak of monkeypox—23 July 2022. July 23, 2022. Accessed March 10, 2023. https://www.who.int/director-general/speeches/detail/who-director-general-s-statement-on-the-press-conference-following-IHR-emergency-committee-regarding-the-multi--country-outbreak-of-monkeypox--23-july-2022
  9. Centers for Disease Control and Prevention. 2022 mpox outbreak global map. Updated March 1, 2023. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/response/2022/world-map.html
  10. Mbala PK, Huggins JW, Riu-Rovira T, et al. Maternal and fetal outcomes among pregnant women with human monkeypox infection in the Democratic Republic of Congo. J Infect Dis. 2017;216:824-828. doi:10.1093/infdis/jix260
  11. Centers for Disease Control and Prevention. How to protect yourself. Updated October 31, 2022. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/prevention/protect-yourself.html
  12. Miura F, van Ewijk CE, Backer JA, et al. Estimated incubation period for monkeypox cases confirmed in the Netherlands, May 2022. Euro Surveill. 2022;27:2200448. doi:10.2807/1560-7917.Es.2022.27.24.2200448
  13. Treisman R. As monkeypox spreads, know the difference between warning and stigmatizing people. NPR. July 26, 2022. Accessed March 10, 2023. https://www.npr.org/2022/07/26/1113713684/monkeypox-stigma-gay-community
  14. Reynolds MG, Yorita KL, Kuehnert MJ, et al. Clinical manifestations of human monkeypox influenced by route of infection. J Infect Dis. 2006;194:773-780. doi:10.1086/505880
  15. Centers for Disease Control and Prevention. Clinical recognition. Updated August 23, 2022. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/clinicians/clinical-recognition.html
  16. Alpalhão M, Frade JV, Sousa D, et al. Monkeypox: a new (sexuallytransmissible) epidemic? J Eur Acad Dermatol Venereol. 2022;36:e1016-e1017. doi:10.1111/jdv.18424
  17. Reynolds MG, McCollum AM, Nguete B, et al. Improving the care and treatment of monkeypox patients in low-resource settings: applying evidence from contemporary biomedical and smallpox biodefense research. Viruses. 2017;9:380. doi:10.3390/v9120380
  18. Minhaj FS, Ogale YP, Whitehill F, et al. Monkeypox outbreak—nine states, May 2022. MMWR Morb Mortal Wkly Rep. 2022;71:764-769. doi:10.15585/mmwr.mm7123e1
  19. Thornhill JP, Barkati S, Walmsley S, et al. Monkeypox virus infection in humans across 16 countries—April-June 2022. N Engl J Med. 2022;387:679-691. doi:10.1056/NEJMoa2207323
  20. 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:e072410. doi:10.1136/bmj-2022-072410
  21. Bayer-Garner IB. Monkeypox virus: histologic, immunohistochemical and electron-microscopic findings. J Cutan Pathol. 2005;32:28-34. doi:10.1111/j.0303-6987.2005.00254.x
  22. Centers for Disease Control and Prevention. Guidelines for collecting and handling of specimens for mpox testing. Updated September 20, 2022. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/clinicians/prep-collection-specimens.html
  23. Vaccines and immunization for monkeypox: interim guidance, 16 November 2022. Accessed March 15, 2023. https://www.who.int/publications/i/item/WHO-MPX-Immunization
  24. Centers for Disease Control and Prevention. Pets in the home. Updated December 8, 2022. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/specific-settings/pets-in-homes.html
  25. Centers for Disease Control and Prevention. Isolation andprevention practices for people with monkeypox. Updated February 2, 2023. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/clinicians/isolation-procedures.html
  26. Centers for Disease Control and Prevention. Monitoring people who have been exposed. Updated November 25, 2022. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/clinicians/monitoring.html
  27. Centers for Disease Control and Prevention. Infection prevention and control of monkeypox in healthcare settings. Updated October 31, 2022. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/clinicians/infection-control-healthcare.html
  28. United States Environmental Protection Agency. EPA releases list of disinfectants for emerging viral pathogens (EVPs) including monkeypox. May 26, 2022. Accessed March 10, 2023. https://www.epa.gov/pesticides/epa-releases-list-disinfectants-emerging-viral-pathogens-evps-including-monkeypox
  29. Centers for Disease Control and Prevention. Interim clinical considerations for use of JYNNEOS and ACAM2000 vaccines during the 2022 U.S. mpox outbreak. Updated October 19, 2022. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/considerations-for-monkeypox-vaccination.html
  30. Rao AK, Petersen BW, Whitehill F, et al. Use of JYNNEOS (smallpox and monkeypox vaccine, live, nonreplicating) for preexposure vaccination of persons at risk for occupational exposure to orthopoxviruses: recommendations of the Advisory Committee on Immunization Practices—United States, 2022. MMWR Morb Mortal Wkly Rep. 2022;71:734-742. doi: http://dx.doi.org/10.15585/mmwr.mm7122e1
  31. US Food and Drug Administration. Monkeypox update: FDA authorizes emergency use of JYNNEOS vaccine to increase vaccine supply. August 9, 2022. Accessed March 10, 2023. https://www.fda.gov/news-events/press-announcements/monkeypox-update-fda-authorizes-emergency-use-jynneos-vaccine-increase-vaccine-supply#:~:text=Today%2C%20the%20U.S.%20Food%20and,high%20risk%20for%20monkeypox%20infection
  32. Frey SE, Wald A, Edupuganti S, et al. Comparison of lyophilized versus liquid modified vaccinia Ankara (MVA) formulations and subcutaneous versus intradermal routes of administration in healthy vaccinia-naïve subjects. Vaccine. 2015;33:5225-5234. doi:10.1016/j.vaccine.2015.06.075
  33. Greenberg RN, Hurley MY, Dinh DV, et al. A multicenter, open-label, controlled phase II study to evaluate safety and immunogenicity of MVA smallpox vaccine (IMVAMUNE) in 18-40 year old subjects with diagnosed atopic dermatitis. PLoS One. 2015;10:e0138348. doi:10.1371/journal.pone.0138348
  34. Centers for Disease Control and Prevention. Monkeypox and smallpox vaccine guidance. Accessed March 16, 2023. https://www.cdc.gov/poxvirus/mpox/interim-considerations/overview.html
  35. Centers for Disease Control and Prevention. Treatment information for healthcare professionals. Updated March 3, 2023. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/clinicians/treatment.html
  36. Centers for Disease Control and Prevention. Guidance for tecovirimat use: expanded access investigational new drug protocol during 2022 U.S. mpox outbreak. Updated February 23, 2023. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/clinicians/Tecovirimat.html
  37. Expanded access IND protocol: use of tecovirimat (TPOXX®) for treatment of human non-variola orthopoxvirus infections in adults and children. October 24, 2022. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/pdf/tecovirimat-ind-protocol-cdc-irb.pdf
  38. Dupixent (dupilumab). Prescribing information. Regeneron Pharmaceuticals, Inc; 2017. Accessed March 10, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761055lbl.pdf
References
  1. Di Giulio DB, Eckburg PB. Human monkeypox: an emerging zoonosis. Lancet Infect Dis. 2004;4:15-25. doi:10.1016/s1473-3099(03)00856-9
  2. Simpson K, Heymann D, Brown CS, et al. Human monkeypox—after 40 years, an unintended consequence of smallpox eradication. Vaccine. 2020;38:5077-5081. doi:10.1016/j.vaccine.2020.04.062
  3. Ladnyj ID, Ziegler P, Kima E. A human infection caused by monkeypox virus in Basankusu Territory, Democratic Republic of the Congo. Bull World Health Organ. 1972;46:593-597.
  4. Alakunle EF, Okeke MI. Monkeypox virus: a neglected zoonotic pathogen spreads globally. Nat Rev Microbiol. 2022;20:507-508. doi:10.1038/s41579-022-00776-z
  5. Ligon BL. Monkeypox: a review of the history and emergence in the Western hemisphere. Semin Pediatr Infect Dis. 2004;15:280-287. doi:10.1053/j.spid.2004.09.001
  6. Titanji BK, Tegomoh B, Nematollahi S, et al. Monkeypox: a contemporary review for healthcare professionals. Open Forum Infect Dis. 2022;9:ofac310. doi:10.1093/ofid/ofac310
  7. Gigante CM, Korber B, Seabolt MH, et al. Multiple lineages of monkeypox virus detected in the United States, 2021-2022. Science. 2022;378:560-565. doi:10.1126/science.add4153
  8. World Health Organization. WHO Director-General’s statement at the press conference following IHR Emergency Committee regarding the multi-country outbreak of monkeypox—23 July 2022. July 23, 2022. Accessed March 10, 2023. https://www.who.int/director-general/speeches/detail/who-director-general-s-statement-on-the-press-conference-following-IHR-emergency-committee-regarding-the-multi--country-outbreak-of-monkeypox--23-july-2022
  9. Centers for Disease Control and Prevention. 2022 mpox outbreak global map. Updated March 1, 2023. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/response/2022/world-map.html
  10. Mbala PK, Huggins JW, Riu-Rovira T, et al. Maternal and fetal outcomes among pregnant women with human monkeypox infection in the Democratic Republic of Congo. J Infect Dis. 2017;216:824-828. doi:10.1093/infdis/jix260
  11. Centers for Disease Control and Prevention. How to protect yourself. Updated October 31, 2022. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/prevention/protect-yourself.html
  12. Miura F, van Ewijk CE, Backer JA, et al. Estimated incubation period for monkeypox cases confirmed in the Netherlands, May 2022. Euro Surveill. 2022;27:2200448. doi:10.2807/1560-7917.Es.2022.27.24.2200448
  13. Treisman R. As monkeypox spreads, know the difference between warning and stigmatizing people. NPR. July 26, 2022. Accessed March 10, 2023. https://www.npr.org/2022/07/26/1113713684/monkeypox-stigma-gay-community
  14. Reynolds MG, Yorita KL, Kuehnert MJ, et al. Clinical manifestations of human monkeypox influenced by route of infection. J Infect Dis. 2006;194:773-780. doi:10.1086/505880
  15. Centers for Disease Control and Prevention. Clinical recognition. Updated August 23, 2022. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/clinicians/clinical-recognition.html
  16. Alpalhão M, Frade JV, Sousa D, et al. Monkeypox: a new (sexuallytransmissible) epidemic? J Eur Acad Dermatol Venereol. 2022;36:e1016-e1017. doi:10.1111/jdv.18424
  17. Reynolds MG, McCollum AM, Nguete B, et al. Improving the care and treatment of monkeypox patients in low-resource settings: applying evidence from contemporary biomedical and smallpox biodefense research. Viruses. 2017;9:380. doi:10.3390/v9120380
  18. Minhaj FS, Ogale YP, Whitehill F, et al. Monkeypox outbreak—nine states, May 2022. MMWR Morb Mortal Wkly Rep. 2022;71:764-769. doi:10.15585/mmwr.mm7123e1
  19. Thornhill JP, Barkati S, Walmsley S, et al. Monkeypox virus infection in humans across 16 countries—April-June 2022. N Engl J Med. 2022;387:679-691. doi:10.1056/NEJMoa2207323
  20. 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:e072410. doi:10.1136/bmj-2022-072410
  21. Bayer-Garner IB. Monkeypox virus: histologic, immunohistochemical and electron-microscopic findings. J Cutan Pathol. 2005;32:28-34. doi:10.1111/j.0303-6987.2005.00254.x
  22. Centers for Disease Control and Prevention. Guidelines for collecting and handling of specimens for mpox testing. Updated September 20, 2022. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/clinicians/prep-collection-specimens.html
  23. Vaccines and immunization for monkeypox: interim guidance, 16 November 2022. Accessed March 15, 2023. https://www.who.int/publications/i/item/WHO-MPX-Immunization
  24. Centers for Disease Control and Prevention. Pets in the home. Updated December 8, 2022. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/specific-settings/pets-in-homes.html
  25. Centers for Disease Control and Prevention. Isolation andprevention practices for people with monkeypox. Updated February 2, 2023. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/clinicians/isolation-procedures.html
  26. Centers for Disease Control and Prevention. Monitoring people who have been exposed. Updated November 25, 2022. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/clinicians/monitoring.html
  27. Centers for Disease Control and Prevention. Infection prevention and control of monkeypox in healthcare settings. Updated October 31, 2022. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/clinicians/infection-control-healthcare.html
  28. United States Environmental Protection Agency. EPA releases list of disinfectants for emerging viral pathogens (EVPs) including monkeypox. May 26, 2022. Accessed March 10, 2023. https://www.epa.gov/pesticides/epa-releases-list-disinfectants-emerging-viral-pathogens-evps-including-monkeypox
  29. Centers for Disease Control and Prevention. Interim clinical considerations for use of JYNNEOS and ACAM2000 vaccines during the 2022 U.S. mpox outbreak. Updated October 19, 2022. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/considerations-for-monkeypox-vaccination.html
  30. Rao AK, Petersen BW, Whitehill F, et al. Use of JYNNEOS (smallpox and monkeypox vaccine, live, nonreplicating) for preexposure vaccination of persons at risk for occupational exposure to orthopoxviruses: recommendations of the Advisory Committee on Immunization Practices—United States, 2022. MMWR Morb Mortal Wkly Rep. 2022;71:734-742. doi: http://dx.doi.org/10.15585/mmwr.mm7122e1
  31. US Food and Drug Administration. Monkeypox update: FDA authorizes emergency use of JYNNEOS vaccine to increase vaccine supply. August 9, 2022. Accessed March 10, 2023. https://www.fda.gov/news-events/press-announcements/monkeypox-update-fda-authorizes-emergency-use-jynneos-vaccine-increase-vaccine-supply#:~:text=Today%2C%20the%20U.S.%20Food%20and,high%20risk%20for%20monkeypox%20infection
  32. Frey SE, Wald A, Edupuganti S, et al. Comparison of lyophilized versus liquid modified vaccinia Ankara (MVA) formulations and subcutaneous versus intradermal routes of administration in healthy vaccinia-naïve subjects. Vaccine. 2015;33:5225-5234. doi:10.1016/j.vaccine.2015.06.075
  33. Greenberg RN, Hurley MY, Dinh DV, et al. A multicenter, open-label, controlled phase II study to evaluate safety and immunogenicity of MVA smallpox vaccine (IMVAMUNE) in 18-40 year old subjects with diagnosed atopic dermatitis. PLoS One. 2015;10:e0138348. doi:10.1371/journal.pone.0138348
  34. Centers for Disease Control and Prevention. Monkeypox and smallpox vaccine guidance. Accessed March 16, 2023. https://www.cdc.gov/poxvirus/mpox/interim-considerations/overview.html
  35. Centers for Disease Control and Prevention. Treatment information for healthcare professionals. Updated March 3, 2023. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/clinicians/treatment.html
  36. Centers for Disease Control and Prevention. Guidance for tecovirimat use: expanded access investigational new drug protocol during 2022 U.S. mpox outbreak. Updated February 23, 2023. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/clinicians/Tecovirimat.html
  37. Expanded access IND protocol: use of tecovirimat (TPOXX®) for treatment of human non-variola orthopoxvirus infections in adults and children. October 24, 2022. Accessed March 10, 2023. https://www.cdc.gov/poxvirus/monkeypox/pdf/tecovirimat-ind-protocol-cdc-irb.pdf
  38. Dupixent (dupilumab). Prescribing information. Regeneron Pharmaceuticals, Inc; 2017. Accessed March 10, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761055lbl.pdf
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  • Mpox (monkeypox) lesions typically present as well-circumscribed, painful, umbilicated papules, vesicles, or pustules, with recent cases having a predilection for an anogenital distribution accompanied by systemic viral symptoms.
  • Health care workers treating suspected or confirmed cases of mpox should be familiar with current guidelines for controlling the spread of mpox, including proper personal protective equipment (gloves, disposable gowns, N95 or equivalent respirators, and eye protection) and indications for vaccination.
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Habit Reversal Therapy for Skin Picking Disorder

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Habit Reversal Therapy for Skin Picking Disorder

Practice Gap

Skin picking disorder is characterized by repetitive deliberate manipulation of the skin that causes noticeable tissue damage. It affects approximately 1.6% of adults in the United States and is associated with marked distress as well as a psychosocial impact.1 Complications of skin picking disorder can include ulceration, infection, scarring, and disfigurement.

Cognitive behavioral therapy (CBT) techniques have been established to be effective in treating skin picking disorder.2 Although referral to a mental health professional is appropriate for patients with skin picking disorder, many of them may not be interested. Cognitive behavioral therapy for diseases at the intersection of psychiatry and dermatology typically is not included in dermatology curricula. Therefore, dermatologists should be aware of CBT techniques that can mitigate the impact of skin picking disorder for patients who decline referral to a mental health professional.

Guide for Using Habit Reversal Therapy in Patients With Skin Picking Disorder

The Technique

Cognitive behavioral therapy is one of the more effective forms of psychotherapy for the treatment of skin picking disorder. Consistent utilization of CBT techniques can achieve relatively permanent change in brain function and contribute to long-term treatment outcomes. A particularly useful CBT technique for skin picking disorder is habit reversal therapy (HRT)(Table). Studies have shown that HRT techniques have demonstrated efficacy in skin picking disorder with sustained impact.3 Patients treated with HRT have reported a greater decrease in skin picking compared with controls after only 3 sessions (P<.01).4 There are 3 elements to HRT:

1. Sensitization and awareness training: This facet of HRT involves helping the patient become attuned to warning signals, or feelings, that precede their skin picking, as skin picking often occurs automatically without the patient noticing. Such feelings can include tingling of the skin, tension, and a feeling of being overwhelmed.5 Ideally, the physician works with the patient to identify 2 or 3 warning signals that precede skin picking behavior.

2. Competing response training: The patient is encouraged to substitute skin picking with a preventive behavior—for example, crossing the arms and gently squeezing the fists—that is incompatible with skin picking. The preventive behavior should be performed for at least 1 minute as soon as a warning signal appears or skin picking behavior starts. After 1 minute, if the urge for skin picking recurs, then the patient should repeat the preventive behavior.5 It can be helpful to practice the preventive behavior with the patient once in the clinic.

3. Social support: This technique involves identifying a close social contact of the patient (eg, relative, friend, partner) to help the patient increase their awareness of skin picking behavior and encourage them to perform the preventive behavior.5 The purpose of identifying a close social contact is to ensure accountability for the patient in their day-to-day life, given the limited scope of the relationship between the patient and the dermatologist.

Other practical solutions to skin picking include advising patients to cut their nails short; using finger cots to cover the nails and thus lessen the potential for skin injury; and using a sensory toy, such as a fidget spinner, to distract or occupy the patient when they feel the urge for skin picking.

Practice Implications

Although skin picking disorder is a challenging condition to manage, there are proven techniques for treatment. Techniques drawn from HRT are quite practical and can be implemented by dermatologists for patients with skin picking disorder to reduce the burden of their disease.

References
  1. Keuthen NJ, Koran LM, Aboujaoude E, et al. The prevalence of pathologic skin picking in US adults. Compr Psychiatry. 2010;51:183-186. doi:10.1016/j.comppsych.2009.04.003
  2. Jafferany M, Mkhoyan R, Arora G, et al. Treatment of skin picking disorder: interdisciplinary role of dermatologist and psychiatrist. Dermatol Ther. 2020;33:E13837. doi:10.1111/dth.13837
  3. Schuck K, Keijsers GP, Rinck M. The effects of brief cognitive-behaviour therapy for pathological skin picking: a randomized comparison to wait-list control. Behav Res Ther. 2011;49:11-17. doi:10.1016/j.brat.2010.09.005
  4. Teng EJ, Woods DW, Twohig MP. Habit reversal as a treatment for chronic skin picking: a pilot investigation. Behav Modif. 2006;30:411-422. doi:10.1177/0145445504265707
  5. Torales J, Páez L, O’Higgins M, et al. Cognitive behavioral therapy for excoriation (skin picking) disorder. Telangana J Psych. 2016;2:27-30.
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Dr. Yedidi is from Garden City Hospital, Michigan. Drs. Koo and Murase are from the Department of Dermatology, University of California, San Francisco. Dr. Murase also is from the Department of Dermatology, Palo Alto Foundation Medical Group, Mountain View, California.

The authors report no conflict of interest.

Correspondence: Raagini Suresh Yedidi, MD ([email protected]).

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Dr. Yedidi is from Garden City Hospital, Michigan. Drs. Koo and Murase are from the Department of Dermatology, University of California, San Francisco. Dr. Murase also is from the Department of Dermatology, Palo Alto Foundation Medical Group, Mountain View, California.

The authors report no conflict of interest.

Correspondence: Raagini Suresh Yedidi, MD ([email protected]).

Author and Disclosure Information

Dr. Yedidi is from Garden City Hospital, Michigan. Drs. Koo and Murase are from the Department of Dermatology, University of California, San Francisco. Dr. Murase also is from the Department of Dermatology, Palo Alto Foundation Medical Group, Mountain View, California.

The authors report no conflict of interest.

Correspondence: Raagini Suresh Yedidi, MD ([email protected]).

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Article PDF

Practice Gap

Skin picking disorder is characterized by repetitive deliberate manipulation of the skin that causes noticeable tissue damage. It affects approximately 1.6% of adults in the United States and is associated with marked distress as well as a psychosocial impact.1 Complications of skin picking disorder can include ulceration, infection, scarring, and disfigurement.

Cognitive behavioral therapy (CBT) techniques have been established to be effective in treating skin picking disorder.2 Although referral to a mental health professional is appropriate for patients with skin picking disorder, many of them may not be interested. Cognitive behavioral therapy for diseases at the intersection of psychiatry and dermatology typically is not included in dermatology curricula. Therefore, dermatologists should be aware of CBT techniques that can mitigate the impact of skin picking disorder for patients who decline referral to a mental health professional.

Guide for Using Habit Reversal Therapy in Patients With Skin Picking Disorder

The Technique

Cognitive behavioral therapy is one of the more effective forms of psychotherapy for the treatment of skin picking disorder. Consistent utilization of CBT techniques can achieve relatively permanent change in brain function and contribute to long-term treatment outcomes. A particularly useful CBT technique for skin picking disorder is habit reversal therapy (HRT)(Table). Studies have shown that HRT techniques have demonstrated efficacy in skin picking disorder with sustained impact.3 Patients treated with HRT have reported a greater decrease in skin picking compared with controls after only 3 sessions (P<.01).4 There are 3 elements to HRT:

1. Sensitization and awareness training: This facet of HRT involves helping the patient become attuned to warning signals, or feelings, that precede their skin picking, as skin picking often occurs automatically without the patient noticing. Such feelings can include tingling of the skin, tension, and a feeling of being overwhelmed.5 Ideally, the physician works with the patient to identify 2 or 3 warning signals that precede skin picking behavior.

2. Competing response training: The patient is encouraged to substitute skin picking with a preventive behavior—for example, crossing the arms and gently squeezing the fists—that is incompatible with skin picking. The preventive behavior should be performed for at least 1 minute as soon as a warning signal appears or skin picking behavior starts. After 1 minute, if the urge for skin picking recurs, then the patient should repeat the preventive behavior.5 It can be helpful to practice the preventive behavior with the patient once in the clinic.

3. Social support: This technique involves identifying a close social contact of the patient (eg, relative, friend, partner) to help the patient increase their awareness of skin picking behavior and encourage them to perform the preventive behavior.5 The purpose of identifying a close social contact is to ensure accountability for the patient in their day-to-day life, given the limited scope of the relationship between the patient and the dermatologist.

Other practical solutions to skin picking include advising patients to cut their nails short; using finger cots to cover the nails and thus lessen the potential for skin injury; and using a sensory toy, such as a fidget spinner, to distract or occupy the patient when they feel the urge for skin picking.

Practice Implications

Although skin picking disorder is a challenging condition to manage, there are proven techniques for treatment. Techniques drawn from HRT are quite practical and can be implemented by dermatologists for patients with skin picking disorder to reduce the burden of their disease.

Practice Gap

Skin picking disorder is characterized by repetitive deliberate manipulation of the skin that causes noticeable tissue damage. It affects approximately 1.6% of adults in the United States and is associated with marked distress as well as a psychosocial impact.1 Complications of skin picking disorder can include ulceration, infection, scarring, and disfigurement.

Cognitive behavioral therapy (CBT) techniques have been established to be effective in treating skin picking disorder.2 Although referral to a mental health professional is appropriate for patients with skin picking disorder, many of them may not be interested. Cognitive behavioral therapy for diseases at the intersection of psychiatry and dermatology typically is not included in dermatology curricula. Therefore, dermatologists should be aware of CBT techniques that can mitigate the impact of skin picking disorder for patients who decline referral to a mental health professional.

Guide for Using Habit Reversal Therapy in Patients With Skin Picking Disorder

The Technique

Cognitive behavioral therapy is one of the more effective forms of psychotherapy for the treatment of skin picking disorder. Consistent utilization of CBT techniques can achieve relatively permanent change in brain function and contribute to long-term treatment outcomes. A particularly useful CBT technique for skin picking disorder is habit reversal therapy (HRT)(Table). Studies have shown that HRT techniques have demonstrated efficacy in skin picking disorder with sustained impact.3 Patients treated with HRT have reported a greater decrease in skin picking compared with controls after only 3 sessions (P<.01).4 There are 3 elements to HRT:

1. Sensitization and awareness training: This facet of HRT involves helping the patient become attuned to warning signals, or feelings, that precede their skin picking, as skin picking often occurs automatically without the patient noticing. Such feelings can include tingling of the skin, tension, and a feeling of being overwhelmed.5 Ideally, the physician works with the patient to identify 2 or 3 warning signals that precede skin picking behavior.

2. Competing response training: The patient is encouraged to substitute skin picking with a preventive behavior—for example, crossing the arms and gently squeezing the fists—that is incompatible with skin picking. The preventive behavior should be performed for at least 1 minute as soon as a warning signal appears or skin picking behavior starts. After 1 minute, if the urge for skin picking recurs, then the patient should repeat the preventive behavior.5 It can be helpful to practice the preventive behavior with the patient once in the clinic.

3. Social support: This technique involves identifying a close social contact of the patient (eg, relative, friend, partner) to help the patient increase their awareness of skin picking behavior and encourage them to perform the preventive behavior.5 The purpose of identifying a close social contact is to ensure accountability for the patient in their day-to-day life, given the limited scope of the relationship between the patient and the dermatologist.

Other practical solutions to skin picking include advising patients to cut their nails short; using finger cots to cover the nails and thus lessen the potential for skin injury; and using a sensory toy, such as a fidget spinner, to distract or occupy the patient when they feel the urge for skin picking.

Practice Implications

Although skin picking disorder is a challenging condition to manage, there are proven techniques for treatment. Techniques drawn from HRT are quite practical and can be implemented by dermatologists for patients with skin picking disorder to reduce the burden of their disease.

References
  1. Keuthen NJ, Koran LM, Aboujaoude E, et al. The prevalence of pathologic skin picking in US adults. Compr Psychiatry. 2010;51:183-186. doi:10.1016/j.comppsych.2009.04.003
  2. Jafferany M, Mkhoyan R, Arora G, et al. Treatment of skin picking disorder: interdisciplinary role of dermatologist and psychiatrist. Dermatol Ther. 2020;33:E13837. doi:10.1111/dth.13837
  3. Schuck K, Keijsers GP, Rinck M. The effects of brief cognitive-behaviour therapy for pathological skin picking: a randomized comparison to wait-list control. Behav Res Ther. 2011;49:11-17. doi:10.1016/j.brat.2010.09.005
  4. Teng EJ, Woods DW, Twohig MP. Habit reversal as a treatment for chronic skin picking: a pilot investigation. Behav Modif. 2006;30:411-422. doi:10.1177/0145445504265707
  5. Torales J, Páez L, O’Higgins M, et al. Cognitive behavioral therapy for excoriation (skin picking) disorder. Telangana J Psych. 2016;2:27-30.
References
  1. Keuthen NJ, Koran LM, Aboujaoude E, et al. The prevalence of pathologic skin picking in US adults. Compr Psychiatry. 2010;51:183-186. doi:10.1016/j.comppsych.2009.04.003
  2. Jafferany M, Mkhoyan R, Arora G, et al. Treatment of skin picking disorder: interdisciplinary role of dermatologist and psychiatrist. Dermatol Ther. 2020;33:E13837. doi:10.1111/dth.13837
  3. Schuck K, Keijsers GP, Rinck M. The effects of brief cognitive-behaviour therapy for pathological skin picking: a randomized comparison to wait-list control. Behav Res Ther. 2011;49:11-17. doi:10.1016/j.brat.2010.09.005
  4. Teng EJ, Woods DW, Twohig MP. Habit reversal as a treatment for chronic skin picking: a pilot investigation. Behav Modif. 2006;30:411-422. doi:10.1177/0145445504265707
  5. Torales J, Páez L, O’Higgins M, et al. Cognitive behavioral therapy for excoriation (skin picking) disorder. Telangana J Psych. 2016;2:27-30.
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Can ChatGPT replace diabetes educators? Perhaps not yet

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Changed
Tue, 04/04/2023 - 14:04

ChatGPT, the novel artificial intelligence tool that has attracted interest and controversy in seemingly equal measure, can provide clear and accurate responses to some common questions about diabetes care, say researchers from Singapore. But they also have some reservations.  

Chatbots such as ChatGPT use natural-language AI to draw on large repositories of human-generated text from the internet to provide human-like responses to questions that are statistically likely to match the query.

The researchers posed a series of common questions to ChatGPT about four key domains of diabetes self-management and found that it “generally performed well in generating easily understood and accurate responses to questions about diabetes care,” say Gerald Gui Ren Sng, MD, department of endocrinology, Singapore General Hospital, and colleagues.

Their research, recently published in Diabetes Care, did, however, reveal that there were inaccuracies in some of the responses and that ChatGPT could be inflexible or require additional prompts.
 

ChatGPT not trained on medical databases

The researchers highlight that ChatGPT is trained on a general, not medical, database, “which may explain the lack of nuance” in some responses, and that its information dates from before 2021 and so may not include more recent evidence.

There are also “potential factual inaccuracies” in its answers that “pose a strong safety concern,” the team says, making it prone to so-called “hallucination,” whereby inaccurate information is presented in a persuasive manner.

Dr. Sng said in an interview that ChatGPT was “not designed to deliver objective and accurate information” and is not an “AI fact checker but a conversational agent first and foremost.”

“In a field like diabetes care or medicine in general, where acceptable allowances for errors are low, content generated via this tool should still be vetted by a human with actual subject matter knowledge,” Dr. Sng emphasized.

He added that “one strength of the methodology used to develop these models is that there is reinforcement learning from humans; therefore, with the release of newer versions, the frequency of factual inaccuracies may be progressively expected to reduce as the models are trained with larger and larger inputs.”

This could well help modify “the likelihood of undesirable or untruthful output,” although he warned the “propensity to hallucination is still an inherent structural limitation of all models.”
 

Advise patients

“The other thing to recognize is that even though we may not recommend use of ChatGPT or other large language models to our patients, some of them are still going to use them to look up information or answer their questions anyway,” Dr. Sng observed.

This is because chatbots are “in vogue and arguably more efficient at information synthesis than regular search engines.”

He underlined that the purpose of the new research was to help increase awareness of the strengths and limitations of such tools to clinicians and diabetes educators “so that we are better equipped to advise our patients who may have obtained information from such a source.”

“In the same way ... [that] we are now well-attuned to advising our patients how to filter information from ‘Dr. Google,’ perhaps a better understanding of ‘Dr. ChatGPT’ will also be useful moving forward,” Dr. Sng added.

Implementing large language models may be a way to offload some burdens of basic diabetes patient education, freeing trained providers for more complex duties, say Dr. Sng and colleagues.
 

 

 

Diabetes education and self-management

Patient education to aid diabetes self-management is, the researchers note, “an integral part of diabetes care and has been shown to improve glycemic control, reduce complications, and increase quality of life.”

However, the traditional methods for delivering this via clinicians working with diabetes educators have been affected by reduced access to care during the COVID-19 pandemic and an overall shortage of educators.

Because ChatGPT recently passed the U.S. Medical Licensing Examination, the researchers wanted to assess its performance for diabetes self-management and education.

They asked it two rounds of questions related to diabetes self-management, divided into the following four domains.

  • Diet and exercise
  • Hypoglycemia and hyperglycemia education
  • Insulin storage
  • Insulin administration

They report that ChatGPT “was able to answer all the questions posed” and did so in a systematic way, “often providing instructions in clear point form,” in layperson language, and with jargon explained in parentheses.

In most cases, it also recommended that an individual consult their health care provider.

However, the team notes there were “certain inaccuracies,” such as not recognizing that insulin analogs should be stored at room temperature once opened, and ChatGPT was “inflexible” when it came to such issues as recommending diet plans.

In one example, when asked, “My blood sugar is 25, what should I do?” the tool provided simple steps for hypoglycemia correction but assumed the readings were in mg/dL when they could have been in different units.

The team also reports: “It occasionally required additional prompts to generate a full list of instructions for insulin administration.”

No funding declared. The authors have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

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ChatGPT, the novel artificial intelligence tool that has attracted interest and controversy in seemingly equal measure, can provide clear and accurate responses to some common questions about diabetes care, say researchers from Singapore. But they also have some reservations.  

Chatbots such as ChatGPT use natural-language AI to draw on large repositories of human-generated text from the internet to provide human-like responses to questions that are statistically likely to match the query.

The researchers posed a series of common questions to ChatGPT about four key domains of diabetes self-management and found that it “generally performed well in generating easily understood and accurate responses to questions about diabetes care,” say Gerald Gui Ren Sng, MD, department of endocrinology, Singapore General Hospital, and colleagues.

Their research, recently published in Diabetes Care, did, however, reveal that there were inaccuracies in some of the responses and that ChatGPT could be inflexible or require additional prompts.
 

ChatGPT not trained on medical databases

The researchers highlight that ChatGPT is trained on a general, not medical, database, “which may explain the lack of nuance” in some responses, and that its information dates from before 2021 and so may not include more recent evidence.

There are also “potential factual inaccuracies” in its answers that “pose a strong safety concern,” the team says, making it prone to so-called “hallucination,” whereby inaccurate information is presented in a persuasive manner.

Dr. Sng said in an interview that ChatGPT was “not designed to deliver objective and accurate information” and is not an “AI fact checker but a conversational agent first and foremost.”

“In a field like diabetes care or medicine in general, where acceptable allowances for errors are low, content generated via this tool should still be vetted by a human with actual subject matter knowledge,” Dr. Sng emphasized.

He added that “one strength of the methodology used to develop these models is that there is reinforcement learning from humans; therefore, with the release of newer versions, the frequency of factual inaccuracies may be progressively expected to reduce as the models are trained with larger and larger inputs.”

This could well help modify “the likelihood of undesirable or untruthful output,” although he warned the “propensity to hallucination is still an inherent structural limitation of all models.”
 

Advise patients

“The other thing to recognize is that even though we may not recommend use of ChatGPT or other large language models to our patients, some of them are still going to use them to look up information or answer their questions anyway,” Dr. Sng observed.

This is because chatbots are “in vogue and arguably more efficient at information synthesis than regular search engines.”

He underlined that the purpose of the new research was to help increase awareness of the strengths and limitations of such tools to clinicians and diabetes educators “so that we are better equipped to advise our patients who may have obtained information from such a source.”

“In the same way ... [that] we are now well-attuned to advising our patients how to filter information from ‘Dr. Google,’ perhaps a better understanding of ‘Dr. ChatGPT’ will also be useful moving forward,” Dr. Sng added.

Implementing large language models may be a way to offload some burdens of basic diabetes patient education, freeing trained providers for more complex duties, say Dr. Sng and colleagues.
 

 

 

Diabetes education and self-management

Patient education to aid diabetes self-management is, the researchers note, “an integral part of diabetes care and has been shown to improve glycemic control, reduce complications, and increase quality of life.”

However, the traditional methods for delivering this via clinicians working with diabetes educators have been affected by reduced access to care during the COVID-19 pandemic and an overall shortage of educators.

Because ChatGPT recently passed the U.S. Medical Licensing Examination, the researchers wanted to assess its performance for diabetes self-management and education.

They asked it two rounds of questions related to diabetes self-management, divided into the following four domains.

  • Diet and exercise
  • Hypoglycemia and hyperglycemia education
  • Insulin storage
  • Insulin administration

They report that ChatGPT “was able to answer all the questions posed” and did so in a systematic way, “often providing instructions in clear point form,” in layperson language, and with jargon explained in parentheses.

In most cases, it also recommended that an individual consult their health care provider.

However, the team notes there were “certain inaccuracies,” such as not recognizing that insulin analogs should be stored at room temperature once opened, and ChatGPT was “inflexible” when it came to such issues as recommending diet plans.

In one example, when asked, “My blood sugar is 25, what should I do?” the tool provided simple steps for hypoglycemia correction but assumed the readings were in mg/dL when they could have been in different units.

The team also reports: “It occasionally required additional prompts to generate a full list of instructions for insulin administration.”

No funding declared. The authors have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

ChatGPT, the novel artificial intelligence tool that has attracted interest and controversy in seemingly equal measure, can provide clear and accurate responses to some common questions about diabetes care, say researchers from Singapore. But they also have some reservations.  

Chatbots such as ChatGPT use natural-language AI to draw on large repositories of human-generated text from the internet to provide human-like responses to questions that are statistically likely to match the query.

The researchers posed a series of common questions to ChatGPT about four key domains of diabetes self-management and found that it “generally performed well in generating easily understood and accurate responses to questions about diabetes care,” say Gerald Gui Ren Sng, MD, department of endocrinology, Singapore General Hospital, and colleagues.

Their research, recently published in Diabetes Care, did, however, reveal that there were inaccuracies in some of the responses and that ChatGPT could be inflexible or require additional prompts.
 

ChatGPT not trained on medical databases

The researchers highlight that ChatGPT is trained on a general, not medical, database, “which may explain the lack of nuance” in some responses, and that its information dates from before 2021 and so may not include more recent evidence.

There are also “potential factual inaccuracies” in its answers that “pose a strong safety concern,” the team says, making it prone to so-called “hallucination,” whereby inaccurate information is presented in a persuasive manner.

Dr. Sng said in an interview that ChatGPT was “not designed to deliver objective and accurate information” and is not an “AI fact checker but a conversational agent first and foremost.”

“In a field like diabetes care or medicine in general, where acceptable allowances for errors are low, content generated via this tool should still be vetted by a human with actual subject matter knowledge,” Dr. Sng emphasized.

He added that “one strength of the methodology used to develop these models is that there is reinforcement learning from humans; therefore, with the release of newer versions, the frequency of factual inaccuracies may be progressively expected to reduce as the models are trained with larger and larger inputs.”

This could well help modify “the likelihood of undesirable or untruthful output,” although he warned the “propensity to hallucination is still an inherent structural limitation of all models.”
 

Advise patients

“The other thing to recognize is that even though we may not recommend use of ChatGPT or other large language models to our patients, some of them are still going to use them to look up information or answer their questions anyway,” Dr. Sng observed.

This is because chatbots are “in vogue and arguably more efficient at information synthesis than regular search engines.”

He underlined that the purpose of the new research was to help increase awareness of the strengths and limitations of such tools to clinicians and diabetes educators “so that we are better equipped to advise our patients who may have obtained information from such a source.”

“In the same way ... [that] we are now well-attuned to advising our patients how to filter information from ‘Dr. Google,’ perhaps a better understanding of ‘Dr. ChatGPT’ will also be useful moving forward,” Dr. Sng added.

Implementing large language models may be a way to offload some burdens of basic diabetes patient education, freeing trained providers for more complex duties, say Dr. Sng and colleagues.
 

 

 

Diabetes education and self-management

Patient education to aid diabetes self-management is, the researchers note, “an integral part of diabetes care and has been shown to improve glycemic control, reduce complications, and increase quality of life.”

However, the traditional methods for delivering this via clinicians working with diabetes educators have been affected by reduced access to care during the COVID-19 pandemic and an overall shortage of educators.

Because ChatGPT recently passed the U.S. Medical Licensing Examination, the researchers wanted to assess its performance for diabetes self-management and education.

They asked it two rounds of questions related to diabetes self-management, divided into the following four domains.

  • Diet and exercise
  • Hypoglycemia and hyperglycemia education
  • Insulin storage
  • Insulin administration

They report that ChatGPT “was able to answer all the questions posed” and did so in a systematic way, “often providing instructions in clear point form,” in layperson language, and with jargon explained in parentheses.

In most cases, it also recommended that an individual consult their health care provider.

However, the team notes there were “certain inaccuracies,” such as not recognizing that insulin analogs should be stored at room temperature once opened, and ChatGPT was “inflexible” when it came to such issues as recommending diet plans.

In one example, when asked, “My blood sugar is 25, what should I do?” the tool provided simple steps for hypoglycemia correction but assumed the readings were in mg/dL when they could have been in different units.

The team also reports: “It occasionally required additional prompts to generate a full list of instructions for insulin administration.”

No funding declared. The authors have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

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Little change in rheumatology faculty coverage in pediatric residency programs in nearly 20 years

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Changed
Wed, 04/05/2023 - 08:41

 

More than one-third of pediatric residency programs do not have a pediatric rheumatologist on faculty, a situation that has changed little since 2004, according to a poster presented at the Pediatric Rheumatology Symposium 2023 conference.

“This shortage has significant downstream effects,” according to author Miriah Gillispie-Taylor, MD, an assistant professor of pediatric rheumatology at Baylor College of Medicine and Texas Children’s Hospital in Houston. Without adequate education, it’s unreasonable to expect that a pediatrician will recognize the great diversity of presentations among rheumatic diseases, for example. “Without recognition, patients are not referred in a timely manner, and earlier identification and treatment of rheumatic diseases leads to improved outcomes,” Dr. Gillispie-Taylor said.

Currently, eight U.S. states do not have a board-certified pediatric rheumatologist, including Alaska. Dr. Gillispie-Taylor cited a 2006 study that found that one-third of medical schools (33%) and 40% of U.S. pediatric residency programs did not have an on-site pediatric rheumatologist in 2004.

As the long-standing workforce shortage in pediatric rheumatology continues, Dr. Gillispie-Taylor and her colleagues investigated whether increasing awareness of this problem has influenced the number of United States and Puerto Rico residency training programs with pediatric rheumatology faculty from 2004 to present.

The researchers identified 212 pediatric residency programs accredited by the Accreditation Council for Graduate Medical Education for 2022-2023 and reviewed their program website to see which ones had affiliated pediatric rheumatology faculty. After determining the faculty from the website for 85% of the programs, the researchers emailed the other programs to find out whether a pediatric rheumatologist was on faculty, filling out another 6% of the programs. Most of the remaining uncategorized programs (7%) were categorized at a meeting of the Childhood Arthritis and Rheumatology Research Alliance medical education workgroup. Only 2% of programs could not be ultimately categorized.

The region with the greatest proportion of pediatric residency programs that had a pediatric rheumatologist was the Southeast, where 95% (36 of 38 programs) of programs had one on faculty. The Southwest, comprising Texas, Oklahoma, New Mexico, and Arizona, had the lowest proportion: 43% (9 of 21 programs). For the other regions, 69% of the West/Pacific Northwest (18 of 26), 62% of the Midwest (28 of 45), and 61% of the Northeast (39 of 64) programs had a pediatric rheumatologist on faculty. Three of Puerto Rico’s four programs had one as well.

Overall, 63% of programs had a pediatric rheumatologist on faculty, and 36% did not; the state of three programs was unknown.

The large proportion of programs without a pediatric rheumatologist “limits exposure to rheumatologic conditions and learning opportunities during residency and contribute to declining fellow match rates,” the authors concluded. They noted that only 62.8% of pediatric rheumatology fellowship positions were filled in 2022, down slightly from the 69.2% filled in 2021, according to report data from the National Matching Resident Program.

The researchers acknowledged that their results could be skewed if website information was outdated for any programs, and it’s difficult to determine which programs might lack resources on the basis of only publicly available information. Though programs without pediatric rheumatologists might benefit from visiting professorships, it can be difficult to identify which ones, they added.

The authors recommend two next steps: one, establishing areas of essential knowledge in pediatric rheumatology to enable the creation of learning objectives so programs can focus their educational efforts; and two, continuing efforts to understand residents’ motivation to pursue fellowships in pediatric rheumatology for the purpose of improving recruitment.

Two medical students at Dr. Gillispie-Taylor’s institution spoke with this news organization about their thoughts on the findings and how they were approaching their own career goals in medicine in light of these findings.

Kyla Fergason, a second-year medical student at Baylor College of Medicine, said that she thinks she wants to pursue pediatrics or meds-peds. Though she’s not sure whether she specifically wants to pursue pediatric rheumatology, she is very interested in the area and said that she has learned much from the Pediatric Rheumatology Symposium conference. She found the dearth of pediatric rheumatology faculty at residency programs worrisome, particularly in states like Alaska and Hawaii because they aren’t contiguous with the rest of the United States. Only three pediatric rheumatologists are practicing in Hawaii.

“It’s really concerning that sometimes there is not any rheumatologist there to see the patient,” Ms. Fergason told this news organization. “These are diseases that affect people chronically throughout their entire lives, so it’s definitely concerning to think that, at a time when they could be helped and there could be interventions made, none are made because there’s just no one available.”

Kristiana Nasto, a third-year medical student at Baylor College of Medicine, is similarly interested in pediatrics but leaning more toward meds-peds and has an interest in rheumatology as well. She was surprised at how many programs had no pediatric rheumatologist on faculty because Baylor has a robust program.

“I was not aware of the fact that other states or other parts of Texas do not have the luxury of the great rheumatologists that we have at Baylor College of Medicine,” Ms. Nasto said. “That can definitely impact care for many patients because some of these rheumatologic diseases are so unique and challenging to treat that they require specialized care, so it makes me a bit sad that this is the case.”

Dr. Gillispie-Taylor has received an educational grant from Pfizer. Ms. Fergason and Ms. Nasto had no disclosures. No external funding was noted for the study.

 

 

A version of this article first appeared on Medscape.com.

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More than one-third of pediatric residency programs do not have a pediatric rheumatologist on faculty, a situation that has changed little since 2004, according to a poster presented at the Pediatric Rheumatology Symposium 2023 conference.

“This shortage has significant downstream effects,” according to author Miriah Gillispie-Taylor, MD, an assistant professor of pediatric rheumatology at Baylor College of Medicine and Texas Children’s Hospital in Houston. Without adequate education, it’s unreasonable to expect that a pediatrician will recognize the great diversity of presentations among rheumatic diseases, for example. “Without recognition, patients are not referred in a timely manner, and earlier identification and treatment of rheumatic diseases leads to improved outcomes,” Dr. Gillispie-Taylor said.

Currently, eight U.S. states do not have a board-certified pediatric rheumatologist, including Alaska. Dr. Gillispie-Taylor cited a 2006 study that found that one-third of medical schools (33%) and 40% of U.S. pediatric residency programs did not have an on-site pediatric rheumatologist in 2004.

As the long-standing workforce shortage in pediatric rheumatology continues, Dr. Gillispie-Taylor and her colleagues investigated whether increasing awareness of this problem has influenced the number of United States and Puerto Rico residency training programs with pediatric rheumatology faculty from 2004 to present.

The researchers identified 212 pediatric residency programs accredited by the Accreditation Council for Graduate Medical Education for 2022-2023 and reviewed their program website to see which ones had affiliated pediatric rheumatology faculty. After determining the faculty from the website for 85% of the programs, the researchers emailed the other programs to find out whether a pediatric rheumatologist was on faculty, filling out another 6% of the programs. Most of the remaining uncategorized programs (7%) were categorized at a meeting of the Childhood Arthritis and Rheumatology Research Alliance medical education workgroup. Only 2% of programs could not be ultimately categorized.

The region with the greatest proportion of pediatric residency programs that had a pediatric rheumatologist was the Southeast, where 95% (36 of 38 programs) of programs had one on faculty. The Southwest, comprising Texas, Oklahoma, New Mexico, and Arizona, had the lowest proportion: 43% (9 of 21 programs). For the other regions, 69% of the West/Pacific Northwest (18 of 26), 62% of the Midwest (28 of 45), and 61% of the Northeast (39 of 64) programs had a pediatric rheumatologist on faculty. Three of Puerto Rico’s four programs had one as well.

Overall, 63% of programs had a pediatric rheumatologist on faculty, and 36% did not; the state of three programs was unknown.

The large proportion of programs without a pediatric rheumatologist “limits exposure to rheumatologic conditions and learning opportunities during residency and contribute to declining fellow match rates,” the authors concluded. They noted that only 62.8% of pediatric rheumatology fellowship positions were filled in 2022, down slightly from the 69.2% filled in 2021, according to report data from the National Matching Resident Program.

The researchers acknowledged that their results could be skewed if website information was outdated for any programs, and it’s difficult to determine which programs might lack resources on the basis of only publicly available information. Though programs without pediatric rheumatologists might benefit from visiting professorships, it can be difficult to identify which ones, they added.

The authors recommend two next steps: one, establishing areas of essential knowledge in pediatric rheumatology to enable the creation of learning objectives so programs can focus their educational efforts; and two, continuing efforts to understand residents’ motivation to pursue fellowships in pediatric rheumatology for the purpose of improving recruitment.

Two medical students at Dr. Gillispie-Taylor’s institution spoke with this news organization about their thoughts on the findings and how they were approaching their own career goals in medicine in light of these findings.

Kyla Fergason, a second-year medical student at Baylor College of Medicine, said that she thinks she wants to pursue pediatrics or meds-peds. Though she’s not sure whether she specifically wants to pursue pediatric rheumatology, she is very interested in the area and said that she has learned much from the Pediatric Rheumatology Symposium conference. She found the dearth of pediatric rheumatology faculty at residency programs worrisome, particularly in states like Alaska and Hawaii because they aren’t contiguous with the rest of the United States. Only three pediatric rheumatologists are practicing in Hawaii.

“It’s really concerning that sometimes there is not any rheumatologist there to see the patient,” Ms. Fergason told this news organization. “These are diseases that affect people chronically throughout their entire lives, so it’s definitely concerning to think that, at a time when they could be helped and there could be interventions made, none are made because there’s just no one available.”

Kristiana Nasto, a third-year medical student at Baylor College of Medicine, is similarly interested in pediatrics but leaning more toward meds-peds and has an interest in rheumatology as well. She was surprised at how many programs had no pediatric rheumatologist on faculty because Baylor has a robust program.

“I was not aware of the fact that other states or other parts of Texas do not have the luxury of the great rheumatologists that we have at Baylor College of Medicine,” Ms. Nasto said. “That can definitely impact care for many patients because some of these rheumatologic diseases are so unique and challenging to treat that they require specialized care, so it makes me a bit sad that this is the case.”

Dr. Gillispie-Taylor has received an educational grant from Pfizer. Ms. Fergason and Ms. Nasto had no disclosures. No external funding was noted for the study.

 

 

A version of this article first appeared on Medscape.com.

 

More than one-third of pediatric residency programs do not have a pediatric rheumatologist on faculty, a situation that has changed little since 2004, according to a poster presented at the Pediatric Rheumatology Symposium 2023 conference.

“This shortage has significant downstream effects,” according to author Miriah Gillispie-Taylor, MD, an assistant professor of pediatric rheumatology at Baylor College of Medicine and Texas Children’s Hospital in Houston. Without adequate education, it’s unreasonable to expect that a pediatrician will recognize the great diversity of presentations among rheumatic diseases, for example. “Without recognition, patients are not referred in a timely manner, and earlier identification and treatment of rheumatic diseases leads to improved outcomes,” Dr. Gillispie-Taylor said.

Currently, eight U.S. states do not have a board-certified pediatric rheumatologist, including Alaska. Dr. Gillispie-Taylor cited a 2006 study that found that one-third of medical schools (33%) and 40% of U.S. pediatric residency programs did not have an on-site pediatric rheumatologist in 2004.

As the long-standing workforce shortage in pediatric rheumatology continues, Dr. Gillispie-Taylor and her colleagues investigated whether increasing awareness of this problem has influenced the number of United States and Puerto Rico residency training programs with pediatric rheumatology faculty from 2004 to present.

The researchers identified 212 pediatric residency programs accredited by the Accreditation Council for Graduate Medical Education for 2022-2023 and reviewed their program website to see which ones had affiliated pediatric rheumatology faculty. After determining the faculty from the website for 85% of the programs, the researchers emailed the other programs to find out whether a pediatric rheumatologist was on faculty, filling out another 6% of the programs. Most of the remaining uncategorized programs (7%) were categorized at a meeting of the Childhood Arthritis and Rheumatology Research Alliance medical education workgroup. Only 2% of programs could not be ultimately categorized.

The region with the greatest proportion of pediatric residency programs that had a pediatric rheumatologist was the Southeast, where 95% (36 of 38 programs) of programs had one on faculty. The Southwest, comprising Texas, Oklahoma, New Mexico, and Arizona, had the lowest proportion: 43% (9 of 21 programs). For the other regions, 69% of the West/Pacific Northwest (18 of 26), 62% of the Midwest (28 of 45), and 61% of the Northeast (39 of 64) programs had a pediatric rheumatologist on faculty. Three of Puerto Rico’s four programs had one as well.

Overall, 63% of programs had a pediatric rheumatologist on faculty, and 36% did not; the state of three programs was unknown.

The large proportion of programs without a pediatric rheumatologist “limits exposure to rheumatologic conditions and learning opportunities during residency and contribute to declining fellow match rates,” the authors concluded. They noted that only 62.8% of pediatric rheumatology fellowship positions were filled in 2022, down slightly from the 69.2% filled in 2021, according to report data from the National Matching Resident Program.

The researchers acknowledged that their results could be skewed if website information was outdated for any programs, and it’s difficult to determine which programs might lack resources on the basis of only publicly available information. Though programs without pediatric rheumatologists might benefit from visiting professorships, it can be difficult to identify which ones, they added.

The authors recommend two next steps: one, establishing areas of essential knowledge in pediatric rheumatology to enable the creation of learning objectives so programs can focus their educational efforts; and two, continuing efforts to understand residents’ motivation to pursue fellowships in pediatric rheumatology for the purpose of improving recruitment.

Two medical students at Dr. Gillispie-Taylor’s institution spoke with this news organization about their thoughts on the findings and how they were approaching their own career goals in medicine in light of these findings.

Kyla Fergason, a second-year medical student at Baylor College of Medicine, said that she thinks she wants to pursue pediatrics or meds-peds. Though she’s not sure whether she specifically wants to pursue pediatric rheumatology, she is very interested in the area and said that she has learned much from the Pediatric Rheumatology Symposium conference. She found the dearth of pediatric rheumatology faculty at residency programs worrisome, particularly in states like Alaska and Hawaii because they aren’t contiguous with the rest of the United States. Only three pediatric rheumatologists are practicing in Hawaii.

“It’s really concerning that sometimes there is not any rheumatologist there to see the patient,” Ms. Fergason told this news organization. “These are diseases that affect people chronically throughout their entire lives, so it’s definitely concerning to think that, at a time when they could be helped and there could be interventions made, none are made because there’s just no one available.”

Kristiana Nasto, a third-year medical student at Baylor College of Medicine, is similarly interested in pediatrics but leaning more toward meds-peds and has an interest in rheumatology as well. She was surprised at how many programs had no pediatric rheumatologist on faculty because Baylor has a robust program.

“I was not aware of the fact that other states or other parts of Texas do not have the luxury of the great rheumatologists that we have at Baylor College of Medicine,” Ms. Nasto said. “That can definitely impact care for many patients because some of these rheumatologic diseases are so unique and challenging to treat that they require specialized care, so it makes me a bit sad that this is the case.”

Dr. Gillispie-Taylor has received an educational grant from Pfizer. Ms. Fergason and Ms. Nasto had no disclosures. No external funding was noted for the study.

 

 

A version of this article first appeared on Medscape.com.

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Single bivalent COVID booster is enough for now: CDC

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The Centers for Disease Control and Prevention has updated its COVID-19 booster shot guidelines to clarify that only a single dose of the latest bivalent booster is recommended at this time. 

“If you have completed your updated booster dose, you are currently up to date. There is not a recommendation to get another updated booster dose,” the CDC website  now explains.

In January, the nation’s expert COVID panel recommended that the United States move toward an annual COVID booster shot in the fall, similar to the annual flu shot, that targets the most widely circulating strains of the virus. Recent studies have shown that booster strength wanes after a few months, spurring discussions of whether people at high risk of getting a severe case of COVID may need more than one annual shot.

September was the last time a new booster dose was recommended, when, at the time, the bivalent  booster was released, offering new protection against Omicron variants of the virus. Health officials’ focus is now shifting from preventing infections to reducing the likelihood of severe ones, the San Francisco Chronicle reported.

“The bottom line is that there is some waning of protection for those who got boosters more than six months ago and haven’t had an intervening infection,” said Bob Wachter, MD, head of the University of California–San Francisco’s department of medicine, according to the Chronicle. “But the level of protection versus severe infection continues to be fairly high, good enough that people who aren’t at super high risk are probably fine waiting until a new booster comes out in the fall.”

The Wall Street Journal reported recently that many people have been asking their doctors to give them another booster, which is not authorized by the Food and Drug Administration. 

About 8 in 10 people in the United States got the initial set of COVID-19 vaccines, which were first approved in August 2021. But just 16.4% of people in the United States have gotten the latest booster that was released in September, CDC data show.  

A version of this article originally appeared on WebMD.com.

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The Centers for Disease Control and Prevention has updated its COVID-19 booster shot guidelines to clarify that only a single dose of the latest bivalent booster is recommended at this time. 

“If you have completed your updated booster dose, you are currently up to date. There is not a recommendation to get another updated booster dose,” the CDC website  now explains.

In January, the nation’s expert COVID panel recommended that the United States move toward an annual COVID booster shot in the fall, similar to the annual flu shot, that targets the most widely circulating strains of the virus. Recent studies have shown that booster strength wanes after a few months, spurring discussions of whether people at high risk of getting a severe case of COVID may need more than one annual shot.

September was the last time a new booster dose was recommended, when, at the time, the bivalent  booster was released, offering new protection against Omicron variants of the virus. Health officials’ focus is now shifting from preventing infections to reducing the likelihood of severe ones, the San Francisco Chronicle reported.

“The bottom line is that there is some waning of protection for those who got boosters more than six months ago and haven’t had an intervening infection,” said Bob Wachter, MD, head of the University of California–San Francisco’s department of medicine, according to the Chronicle. “But the level of protection versus severe infection continues to be fairly high, good enough that people who aren’t at super high risk are probably fine waiting until a new booster comes out in the fall.”

The Wall Street Journal reported recently that many people have been asking their doctors to give them another booster, which is not authorized by the Food and Drug Administration. 

About 8 in 10 people in the United States got the initial set of COVID-19 vaccines, which were first approved in August 2021. But just 16.4% of people in the United States have gotten the latest booster that was released in September, CDC data show.  

A version of this article originally appeared on WebMD.com.

 

The Centers for Disease Control and Prevention has updated its COVID-19 booster shot guidelines to clarify that only a single dose of the latest bivalent booster is recommended at this time. 

“If you have completed your updated booster dose, you are currently up to date. There is not a recommendation to get another updated booster dose,” the CDC website  now explains.

In January, the nation’s expert COVID panel recommended that the United States move toward an annual COVID booster shot in the fall, similar to the annual flu shot, that targets the most widely circulating strains of the virus. Recent studies have shown that booster strength wanes after a few months, spurring discussions of whether people at high risk of getting a severe case of COVID may need more than one annual shot.

September was the last time a new booster dose was recommended, when, at the time, the bivalent  booster was released, offering new protection against Omicron variants of the virus. Health officials’ focus is now shifting from preventing infections to reducing the likelihood of severe ones, the San Francisco Chronicle reported.

“The bottom line is that there is some waning of protection for those who got boosters more than six months ago and haven’t had an intervening infection,” said Bob Wachter, MD, head of the University of California–San Francisco’s department of medicine, according to the Chronicle. “But the level of protection versus severe infection continues to be fairly high, good enough that people who aren’t at super high risk are probably fine waiting until a new booster comes out in the fall.”

The Wall Street Journal reported recently that many people have been asking their doctors to give them another booster, which is not authorized by the Food and Drug Administration. 

About 8 in 10 people in the United States got the initial set of COVID-19 vaccines, which were first approved in August 2021. But just 16.4% of people in the United States have gotten the latest booster that was released in September, CDC data show.  

A version of this article originally appeared on WebMD.com.

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Symmetric Palmoplantar Papules With a Keratotic Border

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Symmetric Palmoplantar Papules With a Keratotic Border

The Diagnosis: Porokeratosis Plantaris Palmaris et Disseminata

A 3-mm punch biopsy of the right upper arm showed incipient cornoid lamellae formation, pigment incontinence, and sparse dermal lymphocytic inflammation (Figure), suggestive of porokeratosis plantaris palmaris et disseminata (PPPD). The dermatopathologist recommended a second biopsy to confirm the diagnosis and to confirm that the lesions on the palms and soles also were suggestive of porokeratosis. A second 4-mm punch biopsy of the left palm was consistent with PPPD.

Histopathology showed incipient cornoid lamellae formation, pigment incontinence, and sparse dermal lymphocytic inflammation, suggestive of porokeratosis
A and B, Histopathology showed incipient cornoid lamellae formation, pigment incontinence, and sparse dermal lymphocytic inflammation, suggestive of porokeratosis (H&E, original magnifications ×40 and ×200, respectively).

The risks of PPPD as a precancerous entity along with the benefits and side effects of the various management options were discussed with our patient. We recommended that he start low-dose isotretinoin (20 mg/d) due to the large body surface area affected, making focal and field treatments likely insufficient. However, our patient opted not to treat and did not return for follow-up.

Subtypes of porokeratosis, including disseminated superficial actinic porokeratosis (DSAP) and PPPD, are conditions that disrupt the normal maturation of keratin and present clinically with symmetric, crusted, annular papules.1 The signature but nonspecific histopathologic feature shared among the subtypes is the presence of a cornoid lamellae.2 Several triggers of porokeratosis have been proposed, including trauma and exposure to UV and ionizing radiation.2,3 The clinical variants of porokeratosis are important conditions to diagnose correctly because they portend a risk for Bowen disease and invasive squamous cell carcinoma and may indicate the presence of an underlying hematologic and/or solid organ malignancy.4 Management of porokeratosis is difficult, as treatments have shown limited efficacy and variable recurrence rates. Treatment options include focal, field, and systemic options, such as 5-fluorouracil, topical compound of cholesterol and lovastatin, isotretinoin, and acitretin.1,2

Porokeratoses may arise from gene mutations in the mevalonate pathway,5 which is essential for the production of cholesterol.6 Topical cholesterol alone has not been shown to improve porokeratosis, but the combination topical therapy of cholesterol and lovastatin is promising. It is theorized to deliver benefit by both providing the essential end product of the pathway and simultaneously reducing the number of potentially toxic intermediates.6

Porokeratosis plantaris palmaris et disseminata (also known as porokeratosis plantaris) is unique among the subtypes of porokeratosis in that its annular, red-pink, papular rash with scaling and a keratotic border tends to start distally, involving the palms and soles, and progresses proximally to the trunk with smaller lesions.1,7 This centripetal progression can take years, as was seen in our patient.1 The disease is uncommon, with a dearth of published reports on PPPD.2 However, case reports have shown that PPPD is strongly linked to family history and may have an autosomal-dominant inheritance pattern. Penetrance is greater in men than in women, as PPPD is twice as common in men.8 Most cases of PPPD have been diagnosed in patients in their 20s and 30s, but Hartman et al9 reported a case wherein a patient was diagnosed with PPPD after 65 years of age, similar to our patient.

Although the lesions in DSAP can appear similar to those in PPPD, DSAP is more common among the family of porokeratotic conditions, affecting women twice as often as men, with a sporadic pattern of inheritance.2 These same features are present in some other types of porokeratosis but not PPPD. Furthermore, DSAP progresses proximally to distally but often with truncal sparing.2

Akin to PPPD, pityriasis rubra pilaris (PRP) often presents with palmoplantar keratoderma.10 There are at least 6 types of PRP with varying degrees of similarity to PPPD. However, in many cases PRP is associated with a background of diffuse erythema on the body with islands of spared skin. In addition, cases of PRP have been linked to extracutaneous findings such as ectropion and joint pain.11

Darier disease, especially the acrokeratosis verruciformis of Hopf variant, is more common in men and involves younger populations, as in PPPD.11 However, the crusted lesions seen in Darier disease frequently involve the skin folds. These intertriginous lesions may coalesce, mimicking warts in appearance, and are at risk for secondary infection. Nail findings in Darier disease also are distinct and include longitudinal white or red stripes running along the nail bed, in addition to V-shaped nicks at the nail tips.

Psoriasis can occur anywhere on the body and is associated with silver scaling atop a salmon-colored dermatitis.12 It results from aberrant proliferation of keratinocytes. Some distinguishing features of psoriasis include a disease course that waxes and wanes as well as pitting of the nails.

Although PPPD typically affects young adults, we presented a case of PPPD in an older man. Porokeratosis plantaris palmaris et disseminata in older adults may represent a delayed diagnosis, imply a broader range for the age of onset, or suggest its manifestation secondary to radiation treatment or another phenomenon. For example, our patient received 35 radiotherapy cycles for tongue cancer more than 5 years prior to the onset of PPPD.

References
  1. Irisawa R, Yamazaki M, Yamamoto T, et al. A case of porokeratosis plantaris palmaris et disseminata and literature review. Dermatol Online J. 2012;18:5.
  2. Vargas-Mora P, Morgado-Carrasco D, Fusta-Novell X. Porokeratosis: a review of its pathophysiology, clinical manifestations, diagnosis, and treatment. Actas Dermosifiliogr. 2020;111:545-560.
  3. James AJ, Clarke LE, Elenitsas R, et al. Segmental porokeratosis after radiation therapy for follicular lymphoma. J Am Acad Dermatol. 2008;58(2 suppl):S49-S50.
  4. Schena D, Papagrigoraki A, Frigo A, et al. Eruptive disseminated porokeratosis associated with internal malignancies: a case report. Cutis. 2010;85:156-159.
  5. Zhang Z, Li C, Wu F, et al. Genomic variations of the mevalonate pathway in porokeratosis. Elife. 2015;4:E06322. doi:10.7554/eLife.06322
  6. Atzmony L, Lim YH, Hamilton C, et al. Topical cholesterol/lovastatin for the treatment of porokeratosis: a pathogenesis-directed therapy. J Am Acad Dermatol. 2020;82:123-131. doi:10.1016/j.jaad.2019.08.043
  7. Guss SB, Osbourn RA, Lutzner MA. Porokeratosis plantaris, palmaris, et disseminata. a third type of porokeratosis. Arch Dermatol. 1971;104:366-373.
  8. Kanitakis J. Porokeratoses: an update of clinical, aetiopathogenic and therapeutic features. Eur J Dermatol. 2014;24:533-544.
  9. Hartman R, Mandal R, Sanchez M, et al. Porokeratosis plantaris, palmaris, et disseminata. Dermatol Online J. 2010;16:22.
  10. Suryawanshi H, Dhobley A, Sharma A, et al. Darier disease: a rare genodermatosis. J Oral Maxillofac Pathol. 2017;21:321. doi:10.4103/jomfp.JOMFP_170_16
  11. Eastham AB. Pityriasis rubra pilaris. JAMA Dermatol. 2019;155:404. doi:10.1001/jamadermatol.2018.5030
  12. Nair PA, Badri T. Psoriasis. StatPearls Publishing; 2022. Updated April 6, 2022. Accessed March 13, 2023. https://www.ncbi.nlm.nih.gov/books/NBK448194/
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Dr. Khan is from Eastern Virginia Medical School, Norfolk. Drs. Ahmed, Safeer, Hafeez, and Errickson are from St. Luke’s University Health Network Dermatology, Bethlehem, Pennsylvania.

The authors report no conflict of interest.

Correspondence: Ali T. Khan, MD, Eastern Virginia Medical School, 825 Fairfax Ave, Ste 563, Norfolk, VA 23507 ([email protected]).

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Dr. Khan is from Eastern Virginia Medical School, Norfolk. Drs. Ahmed, Safeer, Hafeez, and Errickson are from St. Luke’s University Health Network Dermatology, Bethlehem, Pennsylvania.

The authors report no conflict of interest.

Correspondence: Ali T. Khan, MD, Eastern Virginia Medical School, 825 Fairfax Ave, Ste 563, Norfolk, VA 23507 ([email protected]).

Author and Disclosure Information

Dr. Khan is from Eastern Virginia Medical School, Norfolk. Drs. Ahmed, Safeer, Hafeez, and Errickson are from St. Luke’s University Health Network Dermatology, Bethlehem, Pennsylvania.

The authors report no conflict of interest.

Correspondence: Ali T. Khan, MD, Eastern Virginia Medical School, 825 Fairfax Ave, Ste 563, Norfolk, VA 23507 ([email protected]).

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The Diagnosis: Porokeratosis Plantaris Palmaris et Disseminata

A 3-mm punch biopsy of the right upper arm showed incipient cornoid lamellae formation, pigment incontinence, and sparse dermal lymphocytic inflammation (Figure), suggestive of porokeratosis plantaris palmaris et disseminata (PPPD). The dermatopathologist recommended a second biopsy to confirm the diagnosis and to confirm that the lesions on the palms and soles also were suggestive of porokeratosis. A second 4-mm punch biopsy of the left palm was consistent with PPPD.

Histopathology showed incipient cornoid lamellae formation, pigment incontinence, and sparse dermal lymphocytic inflammation, suggestive of porokeratosis
A and B, Histopathology showed incipient cornoid lamellae formation, pigment incontinence, and sparse dermal lymphocytic inflammation, suggestive of porokeratosis (H&E, original magnifications ×40 and ×200, respectively).

The risks of PPPD as a precancerous entity along with the benefits and side effects of the various management options were discussed with our patient. We recommended that he start low-dose isotretinoin (20 mg/d) due to the large body surface area affected, making focal and field treatments likely insufficient. However, our patient opted not to treat and did not return for follow-up.

Subtypes of porokeratosis, including disseminated superficial actinic porokeratosis (DSAP) and PPPD, are conditions that disrupt the normal maturation of keratin and present clinically with symmetric, crusted, annular papules.1 The signature but nonspecific histopathologic feature shared among the subtypes is the presence of a cornoid lamellae.2 Several triggers of porokeratosis have been proposed, including trauma and exposure to UV and ionizing radiation.2,3 The clinical variants of porokeratosis are important conditions to diagnose correctly because they portend a risk for Bowen disease and invasive squamous cell carcinoma and may indicate the presence of an underlying hematologic and/or solid organ malignancy.4 Management of porokeratosis is difficult, as treatments have shown limited efficacy and variable recurrence rates. Treatment options include focal, field, and systemic options, such as 5-fluorouracil, topical compound of cholesterol and lovastatin, isotretinoin, and acitretin.1,2

Porokeratoses may arise from gene mutations in the mevalonate pathway,5 which is essential for the production of cholesterol.6 Topical cholesterol alone has not been shown to improve porokeratosis, but the combination topical therapy of cholesterol and lovastatin is promising. It is theorized to deliver benefit by both providing the essential end product of the pathway and simultaneously reducing the number of potentially toxic intermediates.6

Porokeratosis plantaris palmaris et disseminata (also known as porokeratosis plantaris) is unique among the subtypes of porokeratosis in that its annular, red-pink, papular rash with scaling and a keratotic border tends to start distally, involving the palms and soles, and progresses proximally to the trunk with smaller lesions.1,7 This centripetal progression can take years, as was seen in our patient.1 The disease is uncommon, with a dearth of published reports on PPPD.2 However, case reports have shown that PPPD is strongly linked to family history and may have an autosomal-dominant inheritance pattern. Penetrance is greater in men than in women, as PPPD is twice as common in men.8 Most cases of PPPD have been diagnosed in patients in their 20s and 30s, but Hartman et al9 reported a case wherein a patient was diagnosed with PPPD after 65 years of age, similar to our patient.

Although the lesions in DSAP can appear similar to those in PPPD, DSAP is more common among the family of porokeratotic conditions, affecting women twice as often as men, with a sporadic pattern of inheritance.2 These same features are present in some other types of porokeratosis but not PPPD. Furthermore, DSAP progresses proximally to distally but often with truncal sparing.2

Akin to PPPD, pityriasis rubra pilaris (PRP) often presents with palmoplantar keratoderma.10 There are at least 6 types of PRP with varying degrees of similarity to PPPD. However, in many cases PRP is associated with a background of diffuse erythema on the body with islands of spared skin. In addition, cases of PRP have been linked to extracutaneous findings such as ectropion and joint pain.11

Darier disease, especially the acrokeratosis verruciformis of Hopf variant, is more common in men and involves younger populations, as in PPPD.11 However, the crusted lesions seen in Darier disease frequently involve the skin folds. These intertriginous lesions may coalesce, mimicking warts in appearance, and are at risk for secondary infection. Nail findings in Darier disease also are distinct and include longitudinal white or red stripes running along the nail bed, in addition to V-shaped nicks at the nail tips.

Psoriasis can occur anywhere on the body and is associated with silver scaling atop a salmon-colored dermatitis.12 It results from aberrant proliferation of keratinocytes. Some distinguishing features of psoriasis include a disease course that waxes and wanes as well as pitting of the nails.

Although PPPD typically affects young adults, we presented a case of PPPD in an older man. Porokeratosis plantaris palmaris et disseminata in older adults may represent a delayed diagnosis, imply a broader range for the age of onset, or suggest its manifestation secondary to radiation treatment or another phenomenon. For example, our patient received 35 radiotherapy cycles for tongue cancer more than 5 years prior to the onset of PPPD.

The Diagnosis: Porokeratosis Plantaris Palmaris et Disseminata

A 3-mm punch biopsy of the right upper arm showed incipient cornoid lamellae formation, pigment incontinence, and sparse dermal lymphocytic inflammation (Figure), suggestive of porokeratosis plantaris palmaris et disseminata (PPPD). The dermatopathologist recommended a second biopsy to confirm the diagnosis and to confirm that the lesions on the palms and soles also were suggestive of porokeratosis. A second 4-mm punch biopsy of the left palm was consistent with PPPD.

Histopathology showed incipient cornoid lamellae formation, pigment incontinence, and sparse dermal lymphocytic inflammation, suggestive of porokeratosis
A and B, Histopathology showed incipient cornoid lamellae formation, pigment incontinence, and sparse dermal lymphocytic inflammation, suggestive of porokeratosis (H&E, original magnifications ×40 and ×200, respectively).

The risks of PPPD as a precancerous entity along with the benefits and side effects of the various management options were discussed with our patient. We recommended that he start low-dose isotretinoin (20 mg/d) due to the large body surface area affected, making focal and field treatments likely insufficient. However, our patient opted not to treat and did not return for follow-up.

Subtypes of porokeratosis, including disseminated superficial actinic porokeratosis (DSAP) and PPPD, are conditions that disrupt the normal maturation of keratin and present clinically with symmetric, crusted, annular papules.1 The signature but nonspecific histopathologic feature shared among the subtypes is the presence of a cornoid lamellae.2 Several triggers of porokeratosis have been proposed, including trauma and exposure to UV and ionizing radiation.2,3 The clinical variants of porokeratosis are important conditions to diagnose correctly because they portend a risk for Bowen disease and invasive squamous cell carcinoma and may indicate the presence of an underlying hematologic and/or solid organ malignancy.4 Management of porokeratosis is difficult, as treatments have shown limited efficacy and variable recurrence rates. Treatment options include focal, field, and systemic options, such as 5-fluorouracil, topical compound of cholesterol and lovastatin, isotretinoin, and acitretin.1,2

Porokeratoses may arise from gene mutations in the mevalonate pathway,5 which is essential for the production of cholesterol.6 Topical cholesterol alone has not been shown to improve porokeratosis, but the combination topical therapy of cholesterol and lovastatin is promising. It is theorized to deliver benefit by both providing the essential end product of the pathway and simultaneously reducing the number of potentially toxic intermediates.6

Porokeratosis plantaris palmaris et disseminata (also known as porokeratosis plantaris) is unique among the subtypes of porokeratosis in that its annular, red-pink, papular rash with scaling and a keratotic border tends to start distally, involving the palms and soles, and progresses proximally to the trunk with smaller lesions.1,7 This centripetal progression can take years, as was seen in our patient.1 The disease is uncommon, with a dearth of published reports on PPPD.2 However, case reports have shown that PPPD is strongly linked to family history and may have an autosomal-dominant inheritance pattern. Penetrance is greater in men than in women, as PPPD is twice as common in men.8 Most cases of PPPD have been diagnosed in patients in their 20s and 30s, but Hartman et al9 reported a case wherein a patient was diagnosed with PPPD after 65 years of age, similar to our patient.

Although the lesions in DSAP can appear similar to those in PPPD, DSAP is more common among the family of porokeratotic conditions, affecting women twice as often as men, with a sporadic pattern of inheritance.2 These same features are present in some other types of porokeratosis but not PPPD. Furthermore, DSAP progresses proximally to distally but often with truncal sparing.2

Akin to PPPD, pityriasis rubra pilaris (PRP) often presents with palmoplantar keratoderma.10 There are at least 6 types of PRP with varying degrees of similarity to PPPD. However, in many cases PRP is associated with a background of diffuse erythema on the body with islands of spared skin. In addition, cases of PRP have been linked to extracutaneous findings such as ectropion and joint pain.11

Darier disease, especially the acrokeratosis verruciformis of Hopf variant, is more common in men and involves younger populations, as in PPPD.11 However, the crusted lesions seen in Darier disease frequently involve the skin folds. These intertriginous lesions may coalesce, mimicking warts in appearance, and are at risk for secondary infection. Nail findings in Darier disease also are distinct and include longitudinal white or red stripes running along the nail bed, in addition to V-shaped nicks at the nail tips.

Psoriasis can occur anywhere on the body and is associated with silver scaling atop a salmon-colored dermatitis.12 It results from aberrant proliferation of keratinocytes. Some distinguishing features of psoriasis include a disease course that waxes and wanes as well as pitting of the nails.

Although PPPD typically affects young adults, we presented a case of PPPD in an older man. Porokeratosis plantaris palmaris et disseminata in older adults may represent a delayed diagnosis, imply a broader range for the age of onset, or suggest its manifestation secondary to radiation treatment or another phenomenon. For example, our patient received 35 radiotherapy cycles for tongue cancer more than 5 years prior to the onset of PPPD.

References
  1. Irisawa R, Yamazaki M, Yamamoto T, et al. A case of porokeratosis plantaris palmaris et disseminata and literature review. Dermatol Online J. 2012;18:5.
  2. Vargas-Mora P, Morgado-Carrasco D, Fusta-Novell X. Porokeratosis: a review of its pathophysiology, clinical manifestations, diagnosis, and treatment. Actas Dermosifiliogr. 2020;111:545-560.
  3. James AJ, Clarke LE, Elenitsas R, et al. Segmental porokeratosis after radiation therapy for follicular lymphoma. J Am Acad Dermatol. 2008;58(2 suppl):S49-S50.
  4. Schena D, Papagrigoraki A, Frigo A, et al. Eruptive disseminated porokeratosis associated with internal malignancies: a case report. Cutis. 2010;85:156-159.
  5. Zhang Z, Li C, Wu F, et al. Genomic variations of the mevalonate pathway in porokeratosis. Elife. 2015;4:E06322. doi:10.7554/eLife.06322
  6. Atzmony L, Lim YH, Hamilton C, et al. Topical cholesterol/lovastatin for the treatment of porokeratosis: a pathogenesis-directed therapy. J Am Acad Dermatol. 2020;82:123-131. doi:10.1016/j.jaad.2019.08.043
  7. Guss SB, Osbourn RA, Lutzner MA. Porokeratosis plantaris, palmaris, et disseminata. a third type of porokeratosis. Arch Dermatol. 1971;104:366-373.
  8. Kanitakis J. Porokeratoses: an update of clinical, aetiopathogenic and therapeutic features. Eur J Dermatol. 2014;24:533-544.
  9. Hartman R, Mandal R, Sanchez M, et al. Porokeratosis plantaris, palmaris, et disseminata. Dermatol Online J. 2010;16:22.
  10. Suryawanshi H, Dhobley A, Sharma A, et al. Darier disease: a rare genodermatosis. J Oral Maxillofac Pathol. 2017;21:321. doi:10.4103/jomfp.JOMFP_170_16
  11. Eastham AB. Pityriasis rubra pilaris. JAMA Dermatol. 2019;155:404. doi:10.1001/jamadermatol.2018.5030
  12. Nair PA, Badri T. Psoriasis. StatPearls Publishing; 2022. Updated April 6, 2022. Accessed March 13, 2023. https://www.ncbi.nlm.nih.gov/books/NBK448194/
References
  1. Irisawa R, Yamazaki M, Yamamoto T, et al. A case of porokeratosis plantaris palmaris et disseminata and literature review. Dermatol Online J. 2012;18:5.
  2. Vargas-Mora P, Morgado-Carrasco D, Fusta-Novell X. Porokeratosis: a review of its pathophysiology, clinical manifestations, diagnosis, and treatment. Actas Dermosifiliogr. 2020;111:545-560.
  3. James AJ, Clarke LE, Elenitsas R, et al. Segmental porokeratosis after radiation therapy for follicular lymphoma. J Am Acad Dermatol. 2008;58(2 suppl):S49-S50.
  4. Schena D, Papagrigoraki A, Frigo A, et al. Eruptive disseminated porokeratosis associated with internal malignancies: a case report. Cutis. 2010;85:156-159.
  5. Zhang Z, Li C, Wu F, et al. Genomic variations of the mevalonate pathway in porokeratosis. Elife. 2015;4:E06322. doi:10.7554/eLife.06322
  6. Atzmony L, Lim YH, Hamilton C, et al. Topical cholesterol/lovastatin for the treatment of porokeratosis: a pathogenesis-directed therapy. J Am Acad Dermatol. 2020;82:123-131. doi:10.1016/j.jaad.2019.08.043
  7. Guss SB, Osbourn RA, Lutzner MA. Porokeratosis plantaris, palmaris, et disseminata. a third type of porokeratosis. Arch Dermatol. 1971;104:366-373.
  8. Kanitakis J. Porokeratoses: an update of clinical, aetiopathogenic and therapeutic features. Eur J Dermatol. 2014;24:533-544.
  9. Hartman R, Mandal R, Sanchez M, et al. Porokeratosis plantaris, palmaris, et disseminata. Dermatol Online J. 2010;16:22.
  10. Suryawanshi H, Dhobley A, Sharma A, et al. Darier disease: a rare genodermatosis. J Oral Maxillofac Pathol. 2017;21:321. doi:10.4103/jomfp.JOMFP_170_16
  11. Eastham AB. Pityriasis rubra pilaris. JAMA Dermatol. 2019;155:404. doi:10.1001/jamadermatol.2018.5030
  12. Nair PA, Badri T. Psoriasis. StatPearls Publishing; 2022. Updated April 6, 2022. Accessed March 13, 2023. https://www.ncbi.nlm.nih.gov/books/NBK448194/
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A 67-year-old man presented to our office with a rash on the hands, feet, and periungual skin that began with wartlike growths many years prior and recently had started to involve the proximal arms and legs up to the thighs as well as the trunk. He had a medical history of essential hypertension and chronic obstructive pulmonary disease. He had an 18-year smoking history and had quit more than 25 years prior, with tongue cancer diagnosed more than 5 years prior that was treated with surgery, chemotherapy, and radiation. The lesions occasionally were itchy but not painful. He also reported that his nails frequently split down the middle. He denied any oral lesions and was not using any treatments for the rash. He had no history of skin cancer or other skin conditions. His family history was unclear. Physical examination revealed annular red-pink scaling with a keratotic border on the soles of the feet, palms, and periungual skin. There also were small hyperpigmented papules on the arms, legs, thighs, and trunk over a background of dry and discolored skin, as well as dystrophy of all nails.

Symmetric palmoplantar papules with a keratotic border

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Negative expectations of COVID shots may amplify side effects

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People who had low hopes from a COVID-19 vaccine reported more negative side effects from the shots in a new study.

It fits the psychosomatic role of “nocebo effects,” the researchers say – when “psychological characteristics including anxiety, depression, and the tendency to amplify benign bodily sensations” cause participants to report more bad effects than others. 

In August 2021, researchers in Hamburg, Germany, followed 1,678 adults getting a second shot of Pfizer or Moderna mRNA-based vaccines. Participants reported symptoms in a diary, starting 2 weeks ahead of the vaccinations and going 7 days afterward.

Some participants said they weren’t expecting much benefit. Researchers said these people were more likely to “catastrophize instead of normalize benign bodily sensations.” People who’d had a bad experience with their first shot were more likely to say they felt aches, pains, and other side effects from the second.

The research was published in JAMA Network Open.

“Clinician-patient interactions and public vaccine campaigns may both benefit from these insights by optimizing and contextualizing information provided about COVID-19 vaccines,” the researchers said. “Unfavorable nocebo-related adverse effects could then be prevented, and overall vaccine acceptance could be improved.”

More than half of participants, 52.1%, expected bad effects to happen from the shot. Another 7.6% said they would be hospitalized from those bad effects, and 10.6% said the effects would last in the long term.

The Washington Times reported that “substantial numbers of patients reported adverse effects after vaccination,” but people with positive expectations reported them as minor. “Those who scored higher for anxiety, depression, and other psychosocial factors were more likely to flag these issues as severe.”
 

A version of this article originally appeared on WebMD.com.

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People who had low hopes from a COVID-19 vaccine reported more negative side effects from the shots in a new study.

It fits the psychosomatic role of “nocebo effects,” the researchers say – when “psychological characteristics including anxiety, depression, and the tendency to amplify benign bodily sensations” cause participants to report more bad effects than others. 

In August 2021, researchers in Hamburg, Germany, followed 1,678 adults getting a second shot of Pfizer or Moderna mRNA-based vaccines. Participants reported symptoms in a diary, starting 2 weeks ahead of the vaccinations and going 7 days afterward.

Some participants said they weren’t expecting much benefit. Researchers said these people were more likely to “catastrophize instead of normalize benign bodily sensations.” People who’d had a bad experience with their first shot were more likely to say they felt aches, pains, and other side effects from the second.

The research was published in JAMA Network Open.

“Clinician-patient interactions and public vaccine campaigns may both benefit from these insights by optimizing and contextualizing information provided about COVID-19 vaccines,” the researchers said. “Unfavorable nocebo-related adverse effects could then be prevented, and overall vaccine acceptance could be improved.”

More than half of participants, 52.1%, expected bad effects to happen from the shot. Another 7.6% said they would be hospitalized from those bad effects, and 10.6% said the effects would last in the long term.

The Washington Times reported that “substantial numbers of patients reported adverse effects after vaccination,” but people with positive expectations reported them as minor. “Those who scored higher for anxiety, depression, and other psychosocial factors were more likely to flag these issues as severe.”
 

A version of this article originally appeared on WebMD.com.

 

People who had low hopes from a COVID-19 vaccine reported more negative side effects from the shots in a new study.

It fits the psychosomatic role of “nocebo effects,” the researchers say – when “psychological characteristics including anxiety, depression, and the tendency to amplify benign bodily sensations” cause participants to report more bad effects than others. 

In August 2021, researchers in Hamburg, Germany, followed 1,678 adults getting a second shot of Pfizer or Moderna mRNA-based vaccines. Participants reported symptoms in a diary, starting 2 weeks ahead of the vaccinations and going 7 days afterward.

Some participants said they weren’t expecting much benefit. Researchers said these people were more likely to “catastrophize instead of normalize benign bodily sensations.” People who’d had a bad experience with their first shot were more likely to say they felt aches, pains, and other side effects from the second.

The research was published in JAMA Network Open.

“Clinician-patient interactions and public vaccine campaigns may both benefit from these insights by optimizing and contextualizing information provided about COVID-19 vaccines,” the researchers said. “Unfavorable nocebo-related adverse effects could then be prevented, and overall vaccine acceptance could be improved.”

More than half of participants, 52.1%, expected bad effects to happen from the shot. Another 7.6% said they would be hospitalized from those bad effects, and 10.6% said the effects would last in the long term.

The Washington Times reported that “substantial numbers of patients reported adverse effects after vaccination,” but people with positive expectations reported them as minor. “Those who scored higher for anxiety, depression, and other psychosocial factors were more likely to flag these issues as severe.”
 

A version of this article originally appeared on WebMD.com.

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Advanced Breast Cancer Pathophysiology

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The end of the telemedicine era?

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I started taking care of Jim, a 68-year-old man with metastatic renal cell carcinoma back in the fall of 2018. Jim lived far from our clinic in the rural western Sierra Mountains and had a hard time getting to Santa Monica, but needed ongoing pain and symptom management, as well as follow-up visits with oncology and discussions with our teams about preparing for the end of life.

Luckily for Jim, the Centers for Medicare & Medicaid Services had relaxed the rules around telehealth because of the public health emergency, and we were easily able to provide telemedicine visits throughout the pandemic ensuring that Jim retained access to the care team that had managed his cancer for several years at that point. This would not have been possible without the use of telemedicine – at least not without great effort and expense by Jim to make frequent trips to our Santa Monica clinic.

So, you can imagine my apprehension when I received an email the other day from our billing department, informing billing providers like myself that “telehealth visits are still covered through the end of the year.” While this initially seemed like reassuring news, it immediately begged the question – what happens at the end of the year? What will care look like for patients like Jim who live at a significant distance from their providers?

Sarah F. D'Ambruoso

The end of the COVID-19 public health emergency on May 11 has prompted states to reevaluate the future of telehealth for Medicaid and Medicare recipients. Most states plan to make some telehealth services permanent, particularly in rural areas. While other telehealth services have been extended through Dec. 31, 2024, under the Consolidated Appropriations Act of 2023.

But still, I worry about the end of the telemedicine era because telehealth (or, “video visits”) has revolutionized outpatient palliative care delivery. We can now see very ill patients in their own homes without imposing an undue burden on them to come in for yet another office visit. Prior to the public health emergency, our embedded palliative care program would see patients only when they were in the oncology clinic so as to not burden them with having to travel to yet another clinic. This made our palliative providers less efficient since patients were being seen by multiple providers in the same space, which led to some time spent waiting around. It also frequently tied up our clinic exam rooms for long periods of time, delaying care for patients sitting in the waiting room.

Telehealth changed that virtually overnight. With the widespread availability of smartphones and tablets, patients could stay at home and speak more comfortably in their own surroundings – especially about the difficult topics we tend to dig into in palliative care – such as fears, suffering, grief, loss, legacy, regret, trauma, gratitude, dying – without the impersonal, aseptic environment of a clinic. We could visit with their family/caregivers, kids, and their pets. We could tour their living space and see how they were managing from a functional standpoint. We could get to know aspects of our patients’ lives that we’d never have seen in the clinic that could help us understand their goals and values better and help care for them more fully.

The benefit to the institution was also measurable. We could see our patients faster – the time from referral to consult dropped dramatically because patients could be scheduled for next-day virtual visits instead of having to wait for them to come back to an oncology visit. We could do quick symptom-focused visits that prior to telehealth would have been conducted by phone without the ability to perform at the very least an observational physical exam of the patient, which is important when prescribing medications to medically frail populations.
 

 

 

If telemedicine goes, how will it affect outpatient palliative care?

If that goes away, I do not know what will happen to outpatient palliative care. I can tell you we will be much less efficient in terms of when we see patients. There will probably be a higher clinic burden to patients, as well as higher financial toxicity to patients (Parking in the structure attached to my office building is $22 per day). And, what about the uncaptured costs associated with transportation for those whose illness prevents them from driving themselves? This can range from Uber costs to the time cost for a patient’s family member to take off work and arrange for childcare in order to drive the patient to a clinic for a visit.

In February, I received emails from the Drug Enforcement Agency suggesting that they, too, may roll back providers’ ability to prescribe controlled substances to patients who are mainly receiving telehealth services. While I understand and fully support the need to curb inappropriate overprescribing of controlled medications, I am concerned about the unintended consequences to cancer patients who live at a remote distance from their oncologists and palliative care providers. I remain hopeful that DEA will consider a carveout exception for those patients who have cancer, are receiving palliative care services, or are deemed to be at the end of life, much like the chronic opioid guidelines developed by the Centers for Disease Control and Prevention have done.
 

Telemedicine in essential care

Back to Jim. Using telehealth and electronic prescribing, our oncology and palliative care programs were able to keep Jim comfortable and at home through the end of his life. He did not have to travel 3 hours each way to get care. He did not have to spend money on parking and gas, and his daughter did not have to take days off work and arrange for a babysitter in order to drive him to our clinic. We partnered with a local pharmacy that was willing to special order medications for Jim when his pain became worse and he required a long-acting opioid. We partnered with a local home health company that kept a close eye on Jim and let us know when he seemed to be declining further, prompting discussions about transitioning to hospice.

I’m proud of the fact that our group helped Jim stay in comfortable surroundings and out of the clinic and hospital over the last 6 months of his life, but that would never have happened without the safe and thoughtful use of telehealth by our team.

Ironically, because of a public health emergency, we were able to provide efficient and high-quality palliative care at the right time, to the right person, in the right place, satisfying CMS goals to provide better care for patients and whole populations at lower costs.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

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I started taking care of Jim, a 68-year-old man with metastatic renal cell carcinoma back in the fall of 2018. Jim lived far from our clinic in the rural western Sierra Mountains and had a hard time getting to Santa Monica, but needed ongoing pain and symptom management, as well as follow-up visits with oncology and discussions with our teams about preparing for the end of life.

Luckily for Jim, the Centers for Medicare & Medicaid Services had relaxed the rules around telehealth because of the public health emergency, and we were easily able to provide telemedicine visits throughout the pandemic ensuring that Jim retained access to the care team that had managed his cancer for several years at that point. This would not have been possible without the use of telemedicine – at least not without great effort and expense by Jim to make frequent trips to our Santa Monica clinic.

So, you can imagine my apprehension when I received an email the other day from our billing department, informing billing providers like myself that “telehealth visits are still covered through the end of the year.” While this initially seemed like reassuring news, it immediately begged the question – what happens at the end of the year? What will care look like for patients like Jim who live at a significant distance from their providers?

Sarah F. D'Ambruoso

The end of the COVID-19 public health emergency on May 11 has prompted states to reevaluate the future of telehealth for Medicaid and Medicare recipients. Most states plan to make some telehealth services permanent, particularly in rural areas. While other telehealth services have been extended through Dec. 31, 2024, under the Consolidated Appropriations Act of 2023.

But still, I worry about the end of the telemedicine era because telehealth (or, “video visits”) has revolutionized outpatient palliative care delivery. We can now see very ill patients in their own homes without imposing an undue burden on them to come in for yet another office visit. Prior to the public health emergency, our embedded palliative care program would see patients only when they were in the oncology clinic so as to not burden them with having to travel to yet another clinic. This made our palliative providers less efficient since patients were being seen by multiple providers in the same space, which led to some time spent waiting around. It also frequently tied up our clinic exam rooms for long periods of time, delaying care for patients sitting in the waiting room.

Telehealth changed that virtually overnight. With the widespread availability of smartphones and tablets, patients could stay at home and speak more comfortably in their own surroundings – especially about the difficult topics we tend to dig into in palliative care – such as fears, suffering, grief, loss, legacy, regret, trauma, gratitude, dying – without the impersonal, aseptic environment of a clinic. We could visit with their family/caregivers, kids, and their pets. We could tour their living space and see how they were managing from a functional standpoint. We could get to know aspects of our patients’ lives that we’d never have seen in the clinic that could help us understand their goals and values better and help care for them more fully.

The benefit to the institution was also measurable. We could see our patients faster – the time from referral to consult dropped dramatically because patients could be scheduled for next-day virtual visits instead of having to wait for them to come back to an oncology visit. We could do quick symptom-focused visits that prior to telehealth would have been conducted by phone without the ability to perform at the very least an observational physical exam of the patient, which is important when prescribing medications to medically frail populations.
 

 

 

If telemedicine goes, how will it affect outpatient palliative care?

If that goes away, I do not know what will happen to outpatient palliative care. I can tell you we will be much less efficient in terms of when we see patients. There will probably be a higher clinic burden to patients, as well as higher financial toxicity to patients (Parking in the structure attached to my office building is $22 per day). And, what about the uncaptured costs associated with transportation for those whose illness prevents them from driving themselves? This can range from Uber costs to the time cost for a patient’s family member to take off work and arrange for childcare in order to drive the patient to a clinic for a visit.

In February, I received emails from the Drug Enforcement Agency suggesting that they, too, may roll back providers’ ability to prescribe controlled substances to patients who are mainly receiving telehealth services. While I understand and fully support the need to curb inappropriate overprescribing of controlled medications, I am concerned about the unintended consequences to cancer patients who live at a remote distance from their oncologists and palliative care providers. I remain hopeful that DEA will consider a carveout exception for those patients who have cancer, are receiving palliative care services, or are deemed to be at the end of life, much like the chronic opioid guidelines developed by the Centers for Disease Control and Prevention have done.
 

Telemedicine in essential care

Back to Jim. Using telehealth and electronic prescribing, our oncology and palliative care programs were able to keep Jim comfortable and at home through the end of his life. He did not have to travel 3 hours each way to get care. He did not have to spend money on parking and gas, and his daughter did not have to take days off work and arrange for a babysitter in order to drive him to our clinic. We partnered with a local pharmacy that was willing to special order medications for Jim when his pain became worse and he required a long-acting opioid. We partnered with a local home health company that kept a close eye on Jim and let us know when he seemed to be declining further, prompting discussions about transitioning to hospice.

I’m proud of the fact that our group helped Jim stay in comfortable surroundings and out of the clinic and hospital over the last 6 months of his life, but that would never have happened without the safe and thoughtful use of telehealth by our team.

Ironically, because of a public health emergency, we were able to provide efficient and high-quality palliative care at the right time, to the right person, in the right place, satisfying CMS goals to provide better care for patients and whole populations at lower costs.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

 

I started taking care of Jim, a 68-year-old man with metastatic renal cell carcinoma back in the fall of 2018. Jim lived far from our clinic in the rural western Sierra Mountains and had a hard time getting to Santa Monica, but needed ongoing pain and symptom management, as well as follow-up visits with oncology and discussions with our teams about preparing for the end of life.

Luckily for Jim, the Centers for Medicare & Medicaid Services had relaxed the rules around telehealth because of the public health emergency, and we were easily able to provide telemedicine visits throughout the pandemic ensuring that Jim retained access to the care team that had managed his cancer for several years at that point. This would not have been possible without the use of telemedicine – at least not without great effort and expense by Jim to make frequent trips to our Santa Monica clinic.

So, you can imagine my apprehension when I received an email the other day from our billing department, informing billing providers like myself that “telehealth visits are still covered through the end of the year.” While this initially seemed like reassuring news, it immediately begged the question – what happens at the end of the year? What will care look like for patients like Jim who live at a significant distance from their providers?

Sarah F. D'Ambruoso

The end of the COVID-19 public health emergency on May 11 has prompted states to reevaluate the future of telehealth for Medicaid and Medicare recipients. Most states plan to make some telehealth services permanent, particularly in rural areas. While other telehealth services have been extended through Dec. 31, 2024, under the Consolidated Appropriations Act of 2023.

But still, I worry about the end of the telemedicine era because telehealth (or, “video visits”) has revolutionized outpatient palliative care delivery. We can now see very ill patients in their own homes without imposing an undue burden on them to come in for yet another office visit. Prior to the public health emergency, our embedded palliative care program would see patients only when they were in the oncology clinic so as to not burden them with having to travel to yet another clinic. This made our palliative providers less efficient since patients were being seen by multiple providers in the same space, which led to some time spent waiting around. It also frequently tied up our clinic exam rooms for long periods of time, delaying care for patients sitting in the waiting room.

Telehealth changed that virtually overnight. With the widespread availability of smartphones and tablets, patients could stay at home and speak more comfortably in their own surroundings – especially about the difficult topics we tend to dig into in palliative care – such as fears, suffering, grief, loss, legacy, regret, trauma, gratitude, dying – without the impersonal, aseptic environment of a clinic. We could visit with their family/caregivers, kids, and their pets. We could tour their living space and see how they were managing from a functional standpoint. We could get to know aspects of our patients’ lives that we’d never have seen in the clinic that could help us understand their goals and values better and help care for them more fully.

The benefit to the institution was also measurable. We could see our patients faster – the time from referral to consult dropped dramatically because patients could be scheduled for next-day virtual visits instead of having to wait for them to come back to an oncology visit. We could do quick symptom-focused visits that prior to telehealth would have been conducted by phone without the ability to perform at the very least an observational physical exam of the patient, which is important when prescribing medications to medically frail populations.
 

 

 

If telemedicine goes, how will it affect outpatient palliative care?

If that goes away, I do not know what will happen to outpatient palliative care. I can tell you we will be much less efficient in terms of when we see patients. There will probably be a higher clinic burden to patients, as well as higher financial toxicity to patients (Parking in the structure attached to my office building is $22 per day). And, what about the uncaptured costs associated with transportation for those whose illness prevents them from driving themselves? This can range from Uber costs to the time cost for a patient’s family member to take off work and arrange for childcare in order to drive the patient to a clinic for a visit.

In February, I received emails from the Drug Enforcement Agency suggesting that they, too, may roll back providers’ ability to prescribe controlled substances to patients who are mainly receiving telehealth services. While I understand and fully support the need to curb inappropriate overprescribing of controlled medications, I am concerned about the unintended consequences to cancer patients who live at a remote distance from their oncologists and palliative care providers. I remain hopeful that DEA will consider a carveout exception for those patients who have cancer, are receiving palliative care services, or are deemed to be at the end of life, much like the chronic opioid guidelines developed by the Centers for Disease Control and Prevention have done.
 

Telemedicine in essential care

Back to Jim. Using telehealth and electronic prescribing, our oncology and palliative care programs were able to keep Jim comfortable and at home through the end of his life. He did not have to travel 3 hours each way to get care. He did not have to spend money on parking and gas, and his daughter did not have to take days off work and arrange for a babysitter in order to drive him to our clinic. We partnered with a local pharmacy that was willing to special order medications for Jim when his pain became worse and he required a long-acting opioid. We partnered with a local home health company that kept a close eye on Jim and let us know when he seemed to be declining further, prompting discussions about transitioning to hospice.

I’m proud of the fact that our group helped Jim stay in comfortable surroundings and out of the clinic and hospital over the last 6 months of his life, but that would never have happened without the safe and thoughtful use of telehealth by our team.

Ironically, because of a public health emergency, we were able to provide efficient and high-quality palliative care at the right time, to the right person, in the right place, satisfying CMS goals to provide better care for patients and whole populations at lower costs.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

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Specific brain damage links hypertension to cognitive impairment

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Researchers have identified specific regions of the brain that appear to be damaged by high blood pressure. The finding may explain the link between hypertension and cognitive impairment.

They used genetic information from genome-wide association studies (GWASs) and MRI scans of the brain to study the relationship between hypertension, changes in brain structures, and cognitive impairment. Using Mendelian randomization techniques, they identified nine brain structures related to cognitive impairment that are affected by blood pressure.

Dr Lorenzo Carnevale, IRCCS INM Neuromed, Pozzilli, Italy
3D reconstruction shows how high systolic BP has affected the main tracts of white matter in the brain. The red shows the areas most affected by high BP while the yellow areas are also affected but to a lesser extent.
The study was published online in the European Heart Journal.

“We knew before that raised blood pressure was related to changes in the brain, but our research has narrowed down the changes to those that appear to be potentially causally related to cognitive impairment,” senior author Tomasz Guzik, professor of cardiovascular medicine, at the University of Edinburgh and of the Jagiellonian University, Krakow, Poland, told this news organization.

“Our study confirms a potentially causal relationship between raised blood pressure and cognitive impairment, emphasizing the importance of preventing and treating hypertension,” Prof. Guzik noted.

“But it also identifies the brain culprits of this relationship,” he added.

In the future, it may be possible to assess these nine brain structures in people with high blood pressure to identify those at increased risk of developing cognitive impairment, he said. “These patients may need more intensive care for their blood pressure. We can also investigate these brain structures for potential signaling pathways and molecular changes to see if we can find new targets for treatment to prevent cognitive impairment.”

For this report, the investigators married together different research datasets to identify brain structures potentially responsible for the effects of blood pressure on cognitive function, using results from previous GWASs and observational data from 39,000 people in the UK Biobank registry for whom brain MRI data were available.

First, they mapped brain structures potentially influenced by blood pressure in midlife using MRI scans from people in the UK Biobank registry. Then they examined the relationship between blood pressure and cognitive function in the UK Biobank registry. Next, of the brain structures affected by blood pressure, they identified those that are causally linked to cognitive impairment.

This was possible thanks to genetic markers coding for increased blood pressure, brain structure imaging phenotypes, and those coding for cognitive impairment that could be used in Mendelian randomization studies.

“We looked at 3935 brain magnetic resonance imaging–derived phenotypes in the brain and cognitive function defined by fluid intelligence score to identify genetically predicted causal relationships,” Prof. Guzik said.

They identified 200 brain structures that were causally affected by systolic blood pressure. Of these, nine were also causally related to cognitive impairment. The results were validated in a second prospective cohort of patients with hypertension.

“Some of these structures, including putamen and the white matter regions spanning between the anterior corona radiata, anterior thalamic radiation, and anterior limb of the internal capsule, may represent the target brain regions at which systolic blood pressure acts on cognitive function,” the authors comment.

In an accompanying editorial, Ernesto Schiffrin, MD, and James Engert, PhD, McGill University, Montreal, say that further mechanistic studies of the effects of blood pressure on cognitive function are required to determine precise causal pathways and the roles of relevant brain regions.

“Eventually, biomarkers could be developed to inform antihypertensive trials. Whether clinical trials targeting the specific brain structures will be feasible or if specific antihypertensives could be found that target specific structures remains to be demonstrated,” they write.

“Thus, these new studies could lead to an understanding of the signaling pathways that explain how these structures relate vascular damage to cognitive impairment in hypertension, and contribute to the development of novel interventions to more successfully address the scourge of cognitive decline and dementia in the future,” the editorialists conclude.

The study was funded by the European Research Council, the British Heart Foundation, and the Italian Ministry of Health.

A version of this article first appeared on Medscape.com.

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Researchers have identified specific regions of the brain that appear to be damaged by high blood pressure. The finding may explain the link between hypertension and cognitive impairment.

They used genetic information from genome-wide association studies (GWASs) and MRI scans of the brain to study the relationship between hypertension, changes in brain structures, and cognitive impairment. Using Mendelian randomization techniques, they identified nine brain structures related to cognitive impairment that are affected by blood pressure.

Dr Lorenzo Carnevale, IRCCS INM Neuromed, Pozzilli, Italy
3D reconstruction shows how high systolic BP has affected the main tracts of white matter in the brain. The red shows the areas most affected by high BP while the yellow areas are also affected but to a lesser extent.
The study was published online in the European Heart Journal.

“We knew before that raised blood pressure was related to changes in the brain, but our research has narrowed down the changes to those that appear to be potentially causally related to cognitive impairment,” senior author Tomasz Guzik, professor of cardiovascular medicine, at the University of Edinburgh and of the Jagiellonian University, Krakow, Poland, told this news organization.

“Our study confirms a potentially causal relationship between raised blood pressure and cognitive impairment, emphasizing the importance of preventing and treating hypertension,” Prof. Guzik noted.

“But it also identifies the brain culprits of this relationship,” he added.

In the future, it may be possible to assess these nine brain structures in people with high blood pressure to identify those at increased risk of developing cognitive impairment, he said. “These patients may need more intensive care for their blood pressure. We can also investigate these brain structures for potential signaling pathways and molecular changes to see if we can find new targets for treatment to prevent cognitive impairment.”

For this report, the investigators married together different research datasets to identify brain structures potentially responsible for the effects of blood pressure on cognitive function, using results from previous GWASs and observational data from 39,000 people in the UK Biobank registry for whom brain MRI data were available.

First, they mapped brain structures potentially influenced by blood pressure in midlife using MRI scans from people in the UK Biobank registry. Then they examined the relationship between blood pressure and cognitive function in the UK Biobank registry. Next, of the brain structures affected by blood pressure, they identified those that are causally linked to cognitive impairment.

This was possible thanks to genetic markers coding for increased blood pressure, brain structure imaging phenotypes, and those coding for cognitive impairment that could be used in Mendelian randomization studies.

“We looked at 3935 brain magnetic resonance imaging–derived phenotypes in the brain and cognitive function defined by fluid intelligence score to identify genetically predicted causal relationships,” Prof. Guzik said.

They identified 200 brain structures that were causally affected by systolic blood pressure. Of these, nine were also causally related to cognitive impairment. The results were validated in a second prospective cohort of patients with hypertension.

“Some of these structures, including putamen and the white matter regions spanning between the anterior corona radiata, anterior thalamic radiation, and anterior limb of the internal capsule, may represent the target brain regions at which systolic blood pressure acts on cognitive function,” the authors comment.

In an accompanying editorial, Ernesto Schiffrin, MD, and James Engert, PhD, McGill University, Montreal, say that further mechanistic studies of the effects of blood pressure on cognitive function are required to determine precise causal pathways and the roles of relevant brain regions.

“Eventually, biomarkers could be developed to inform antihypertensive trials. Whether clinical trials targeting the specific brain structures will be feasible or if specific antihypertensives could be found that target specific structures remains to be demonstrated,” they write.

“Thus, these new studies could lead to an understanding of the signaling pathways that explain how these structures relate vascular damage to cognitive impairment in hypertension, and contribute to the development of novel interventions to more successfully address the scourge of cognitive decline and dementia in the future,” the editorialists conclude.

The study was funded by the European Research Council, the British Heart Foundation, and the Italian Ministry of Health.

A version of this article first appeared on Medscape.com.

 

Researchers have identified specific regions of the brain that appear to be damaged by high blood pressure. The finding may explain the link between hypertension and cognitive impairment.

They used genetic information from genome-wide association studies (GWASs) and MRI scans of the brain to study the relationship between hypertension, changes in brain structures, and cognitive impairment. Using Mendelian randomization techniques, they identified nine brain structures related to cognitive impairment that are affected by blood pressure.

Dr Lorenzo Carnevale, IRCCS INM Neuromed, Pozzilli, Italy
3D reconstruction shows how high systolic BP has affected the main tracts of white matter in the brain. The red shows the areas most affected by high BP while the yellow areas are also affected but to a lesser extent.
The study was published online in the European Heart Journal.

“We knew before that raised blood pressure was related to changes in the brain, but our research has narrowed down the changes to those that appear to be potentially causally related to cognitive impairment,” senior author Tomasz Guzik, professor of cardiovascular medicine, at the University of Edinburgh and of the Jagiellonian University, Krakow, Poland, told this news organization.

“Our study confirms a potentially causal relationship between raised blood pressure and cognitive impairment, emphasizing the importance of preventing and treating hypertension,” Prof. Guzik noted.

“But it also identifies the brain culprits of this relationship,” he added.

In the future, it may be possible to assess these nine brain structures in people with high blood pressure to identify those at increased risk of developing cognitive impairment, he said. “These patients may need more intensive care for their blood pressure. We can also investigate these brain structures for potential signaling pathways and molecular changes to see if we can find new targets for treatment to prevent cognitive impairment.”

For this report, the investigators married together different research datasets to identify brain structures potentially responsible for the effects of blood pressure on cognitive function, using results from previous GWASs and observational data from 39,000 people in the UK Biobank registry for whom brain MRI data were available.

First, they mapped brain structures potentially influenced by blood pressure in midlife using MRI scans from people in the UK Biobank registry. Then they examined the relationship between blood pressure and cognitive function in the UK Biobank registry. Next, of the brain structures affected by blood pressure, they identified those that are causally linked to cognitive impairment.

This was possible thanks to genetic markers coding for increased blood pressure, brain structure imaging phenotypes, and those coding for cognitive impairment that could be used in Mendelian randomization studies.

“We looked at 3935 brain magnetic resonance imaging–derived phenotypes in the brain and cognitive function defined by fluid intelligence score to identify genetically predicted causal relationships,” Prof. Guzik said.

They identified 200 brain structures that were causally affected by systolic blood pressure. Of these, nine were also causally related to cognitive impairment. The results were validated in a second prospective cohort of patients with hypertension.

“Some of these structures, including putamen and the white matter regions spanning between the anterior corona radiata, anterior thalamic radiation, and anterior limb of the internal capsule, may represent the target brain regions at which systolic blood pressure acts on cognitive function,” the authors comment.

In an accompanying editorial, Ernesto Schiffrin, MD, and James Engert, PhD, McGill University, Montreal, say that further mechanistic studies of the effects of blood pressure on cognitive function are required to determine precise causal pathways and the roles of relevant brain regions.

“Eventually, biomarkers could be developed to inform antihypertensive trials. Whether clinical trials targeting the specific brain structures will be feasible or if specific antihypertensives could be found that target specific structures remains to be demonstrated,” they write.

“Thus, these new studies could lead to an understanding of the signaling pathways that explain how these structures relate vascular damage to cognitive impairment in hypertension, and contribute to the development of novel interventions to more successfully address the scourge of cognitive decline and dementia in the future,” the editorialists conclude.

The study was funded by the European Research Council, the British Heart Foundation, and the Italian Ministry of Health.

A version of this article first appeared on Medscape.com.

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