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International medical graduates facing challenges amid COVID-19
International medical graduates (IMGs) constitute more than 24% of the total percentage of active physicians, 30% of active psychiatrists, and 33% of psychiatry residents in the United States.1 IMGs serve in various medical specialties and provide medical care to socioeconomically disadvantaged patients in underserved communities.2 Evidence suggests that patient outcomes among elderly patients admitted in U.S. hospitals for those treated by IMGs were on par with outcomes of U.S. graduates. Moreover, patients who were treated by IMGs had a lower mortality rates.3
IMGs trained in the United States make considerable contributions to psychiatry and have been very successful as educators, researchers, and leaders. Over the last 3 decades, for example, three American Psychiatric Association (APA) presidents and one past president of the American Academy of Child and Adolescent Psychiatry were IMGs. Many of them also hold department chair positions at many academic institutions.4,5
In short, IMGs are an important part of the U.S. health care system – particularly in psychiatry.
In addition to participating in psychiatry residency programs, IMG physicians are heavily represented in subspecialties, including geriatric psychiatry (45%), addiction psychiatry (42%), child and adolescent psychiatry (36%), psychosomatic medicine (32%), and forensic psychiatry (25%).6 IMG trainees face multiple challenges that begin as they transition to psychiatry residency in the United States, including understanding the American health care system, electronic medical records and documentation, and evidence-based medicine. In addition, they need to adapt to cultural changes, and work on language barriers, communication skills, and social isolation.7,8 Training programs account for these challenges and proactively take essential steps to facilitate the transition of IMGs into the U.S. system.9,10
As training programs prepare for the new academic year starting from July 2020 and continue to provide educational experiences to current trainees, the COVID-19 pandemic has brought additional challenges for the training programs. The gravity of the novel coronavirus pandemic continues to deepen, causing immense fear and uncertainty globally. An APA poll of more than 1,000 adults conducted early in the pandemic showed that about 40% of Americans were anxious about becoming seriously ill or dying with COVID-19. Nearly half of the respondents (48%) were anxious about the possibility of getting COVID-19, and even more (62%) were anxious about the possibility of their loved ones getting infected by this virus. Also, one-third of Americans reported a serious impact on their mental health.
Furthermore, the ailing economy and increasing unemployment are raising financial concerns for individuals and families. This pandemic also has had an impact on our patients’ sleep hygiene, relationships with their loved ones, and consumption of alcohol or other drugs/substances.11 Deteriorating mental health raises concerns about increased suicide risk as a secondary consequence.12
Physicians and other frontline teams who are taking care of these patients and their families continue to provide unexcelled, compassionate care in these unprecedented times. Selfless care continues despite awareness of the high probability of getting exposed to the virus and spreading it further to family members. Physicians involved in direct patient care for COVID-19 patients are at high risk for demoralization, burnout, depression, and anxiety.13
Struggles experienced by IMGs
On the personal front, IMGs often struggle with multiple stressors, such as lack of social support, ethnic-minority prejudice, and the need to understand financial structures such as mortgages in the new countries even after extended periods of residence.14 This virus has killed many health care professionals, including physicians around the world. There was a report of suicide by an emergency medicine physician who was treating patients with COVID-19 and ended up contracting the virus. That news was devastating and overwhelming for everyone, especially health care clinicians. It also adds to the stress and worries of IMGs who are still on nonimmigrant visas.
Bigger concerns exist if there is a demise of a nonimmigrant IMG and the implications of that loss for dependent families – who might face deportation. Even for those who were recently granted permanent residency status, worries about limited support systems and financial hardships to their families can be stressors.
Also, a large number of IMGs represent the geographical area where the pandemic began. Fortunately, the World Health Organization has taken a firm stance against possible discrimination by calling for global solidarity in these times. Furthermore, the WHO has emphasized the importance of referring to the disease caused by SARS-CoV-2 as “COVID-19” only – and not by the name of a particular country or city.15 Despite those official positions, people continue to express racially discriminatory opinions related to the virus, and those comments are not only disturbing to IMGs, they also are demoralizing.
Travel restrictions
In addition to the worries that IMGs might have about their own health and that of their families residing with them, the well-being of their extended families, including their aging parents back in their countries of origin, is unsettling as well. It is even more unnerving during the pandemic because the Centers for Disease Control and Prevention and the State Department advised avoiding all international travel at this time. Under these circumstances, IMGs are concerned about travel to their countries of origin in the event of a family emergency and the quarantine protocols in place, at both the country of origin and at residences.
Immigration issues
The U.S. administration temporarily suspended all immigration for 60 days, starting from April 2020. Recently, an executive order was signed suspending entry in the country on several visas, including the J-1 and the H1-B. Those are two categories that allow physicians to train and work in the United States.
IMGs in the United States reside and practice here under different types of immigrant and nonimmigrant visas (J-1, H1-B). This year, the Match results coincided with the timeline of those new immigration restrictions. Many IMGs are currently in the process of renewing their H1-B visas. They are worried because their visas will expire in the coming months. During the pandemic, U.S. Citizenship and Immigration Services suspended routine visa services and premium processing for visa renewals. This halt led to a delay in visa processing for graduating residents in June and practicing physicians seeking visa renewal. Those delays add to personal stress, and furthermore, distract these immigrant physicians from fighting this pandemic.
Another complication is that rules for J-1 visa holders have changed so that trainees must return to their countries of origin for at least 2 years after completing their training. If they decide to continue practicing medicine in the United States, they need a specific type of J-1 waiver and must gain a pathway to be a lawful permanent resident (Green Card). Many IMGs who are on waiver positions might not be able to treat patients ailing from COVID-19 to the full extent because waivers restrict them to practicing only in certain identified health systems.
IMGs who are coming from a country such India have to wait for more than 11 years after completing their accredited training to get permanent residency because of backlog for the permanent residency process.16 While waiting for a Green Card, they must continue to work on an H1-B visa, which requires periodic renewal.
Potential impact on training
Non-U.S. citizen IMGs accounted for 13% of the total of first-year positions in the 2020 Match. They will start medical training in residency programs in the United States in the coming months. The numbers for psychiatry residency matches are higher; about 16% of total first-year positions are filled by non-U.S. IMGs.17 At this time, when they should be celebrating their successful Match after many years of hard work and persistence, there is increased anxiety. They wonder whether they will be able to enter the United States to begin their training program on time. Their concerns are multifold, but the main concern is related to uncertainties around getting visas on time. With the recent executive order in place, physicians only working actively with COVID-19 patients will be able to enter the country on visas. As mental health concerns continue to rise during these times, incoming residents might not be able to start training if they are out of the country.
Furthermore, because of travel/air restrictions, there are worries about whether physicians will be able to get flights to the United States, given the lockdown in many countries around the world. Conversely, IMGs who will be graduating from residency and fellowship programs this summer and have accepted new positions also are dealing with similar uncertainty. Their new jobs will require visa processing, and the current scenario provides limited insight, so far, about whether they will be able to start their respective jobs or whether they will have to return to their home countries until their visa processing is completed.
The American Medical Association has advised the Secretary of State and acting Secretary of Homeland Security to expedite physician workforce expansion in an effort to meet the growing need for health care services during this pandemic.18 It is encouraging that, recently, the State Department declared that visa processing will continue for medical professionals and that cases would be expedited for those who meet the criteria. However, the requirement for in-person interviews remains for individuals who are seeking a U.S. visa outside the country.
As residency programs are trying their best to continue to provide educational experiences to trainees during this phase, if psychiatry residents are placed on quarantine because of either getting exposed or contracting the illness, there is a possibility that they might need to extend their training. This would bring another challenge for IMGs, requiring them to extend their visas to complete their training. Future J-1 waiver jobs could be compromised.
Investment in physician wellness critical
Psychiatrists, along with other health care workers, are front-line soldiers in the fight against COVID-19. All physicians are at high risk for demoralization, burnout, depression, anxiety, and suicide. It is of utmost importance that we invest immediately in physicians’ wellness. As noted, significant numbers of psychiatrists are IMGs who are dealing with additional challenges while responding to the pandemic. There are certain challenges for IMGs, such as the well-being of their extended families in other countries, and travel bans put in place because of the pandemic. Those issues are not easy to resolve. However, addressing visa issues and providing support to their families in the event that something happens to physicians during the pandemic would be reassuring and would help alleviate additional stress. Those kinds of actions also would allow immigrant physicians to focus on clinical work and to improve their overall well-being. Given the health risks and numerous other insecurities that go along with living amid a pandemic, IMGs should not have the additional pressure of visa uncertainty.
Public health crises such as COVID-19 are associated with increased rates of anxiety,19 depression,20 illicit substance use,21 and an increased rate of suicide.22 Patients with serious mental illness might be among the hardest hit both physically and mentally during the pandemic.23 Even in the absence of a pandemic, there is already a shortage of psychiatrists at the national level, and it is expected that this shortage will grow in the future. Rural and underserved areas are expected to experience the physician deficit more acutely.24
The pandemic is likely to resolve gradually and unpredictably – and might recur along the way over the next 1-2 years. However, the psychiatrist shortage will escalate more, as the mental health needs in the United States increase further in coming months. We need psychiatrists now more than ever, and it will be crucial that prospective residents, graduating residents, and fellows are able to come on board to join the American health care system promptly. In addition to national-level interventions, residency programs, potential employers, and communities must be aware of and do whatever they can to address the challenges faced by IMGs during these times.
Dr. Raman Baweja is affiliated with the department of psychiatry and behavioral health at Penn State University, Hershey. He has no conflicts of interest. Dr. Verma is affiliated with Rogers Behavioral Health in Kenosha County, Wis., and the department of psychiatry and behavioral health at Rosalind Franklin University of Medicine and Science in North Chicago. She has no conflicts of interest. Dr. Ritika Baweja is affiliated with the department of psychiatry and behavioral health at Penn State. Dr. Ritika Baweja is the spouse of Dr. Raman Baweja. Dr. Adam is affiliated with the department of psychiatry at the University of Missouri, Columbia.
References
1. American Psychiatric Association. Navigating psychiatry residency in the United States. A Guide for IMG Physicians.
2. Berg S. 5 IMG physicians who speak up for patients and fellow doctors. American Medical Association. 2019 Oct 22.
3. Tsugawa Y et al. BMJ. 2017 Feb 3;256. doi: 10.1136/bmj.j273.
4. Gogineni RR et al. Child Adolesc Psychiatr Clin N Am. 2010 Oct 1;19(4):833-53.
5. Majeed MH et al. Academic Psychiatry. 2017 Dec 1;41(6):849-51.
6. Brotherton SE and Etzel SI. JAMA. 2018 Sep 11;320(10):1051-70.
7. Sockalingam S et al. Acad Psychiatry. 2012 Jul 1;36(4):277-81.
8. Singareddy R et al. Acad Psychiatry. 2008 Jul-Aug;32(4):343-4.
9. Kramer MN. Acad Psychiatry. 2005 Jul-Aug;29(3):322-4.
10. Rao NR and Kotapati VP. Pathways for success in academic medicine for an international medical graduate: Challenges and opportunities. In “Roberts Academic Medicine Handbook” 2020. Springer:163-70.
11. American Psychiatric Association. New poll: COVID-19 impacting mental well-being: Americans feeling anxious, especially for loved ones; older adults are less anxious. 2020 Mar 25.
12. Reger MA et al. JAMA Psychiatry. 2020 Apr 10. doi: 10.1001/jamapsychiatry.2020.1060.
13. Lai J et al. JAMA Netw Open. 2020 Mar 23;3(3):e203976-e203976. doi: 10.1001/jamanetworkopen.2020.3976.
14. Kalra G et al. Acad Psychiatry. 2012 Jul;36(4):323-9.
15. WHO best practices for the naming of new human infectious diseases. World Health Organization. 2015.
16. U.S. Department of State. Bureau of Consular Affairs. Visa Bulletin for March 2020.
17. National Resident Matching Program® (NRMP®). Thousands of medical students and graduates celebrate NRMP Match results.
18. American Medical Association. AMA: U.S. should open visas to international physicians amid COVID-19. AMA press release. 2020 Mar 25.
19. McKay D et al. J Anxiety Disord. 2020 Jun;73:02233. doi: 10.1016/j.janxdis.2020.102233.
20. Tang W et al. J Affect Disord. 2020 May 13;274:1-7.
21. Collins F et al. NIH Director’s Blog. NIH.gov. 2020 Apr 21.
22. Reger M et al. JAMA Psychiatry. 2020 Apr 10. doi: 10.1001/jamapsychiatry.2020.1060.
23. Druss BG. JAMA Psychiatry. 2020 Apr 3. doi: 10.1001/jamapsychiatry.2020.0894.
24. American Association of Medical Colleges. “The complexities of physician supply and demand: Projections from 2018-2033.” 2020 Jun.
International medical graduates (IMGs) constitute more than 24% of the total percentage of active physicians, 30% of active psychiatrists, and 33% of psychiatry residents in the United States.1 IMGs serve in various medical specialties and provide medical care to socioeconomically disadvantaged patients in underserved communities.2 Evidence suggests that patient outcomes among elderly patients admitted in U.S. hospitals for those treated by IMGs were on par with outcomes of U.S. graduates. Moreover, patients who were treated by IMGs had a lower mortality rates.3
IMGs trained in the United States make considerable contributions to psychiatry and have been very successful as educators, researchers, and leaders. Over the last 3 decades, for example, three American Psychiatric Association (APA) presidents and one past president of the American Academy of Child and Adolescent Psychiatry were IMGs. Many of them also hold department chair positions at many academic institutions.4,5
In short, IMGs are an important part of the U.S. health care system – particularly in psychiatry.
In addition to participating in psychiatry residency programs, IMG physicians are heavily represented in subspecialties, including geriatric psychiatry (45%), addiction psychiatry (42%), child and adolescent psychiatry (36%), psychosomatic medicine (32%), and forensic psychiatry (25%).6 IMG trainees face multiple challenges that begin as they transition to psychiatry residency in the United States, including understanding the American health care system, electronic medical records and documentation, and evidence-based medicine. In addition, they need to adapt to cultural changes, and work on language barriers, communication skills, and social isolation.7,8 Training programs account for these challenges and proactively take essential steps to facilitate the transition of IMGs into the U.S. system.9,10
As training programs prepare for the new academic year starting from July 2020 and continue to provide educational experiences to current trainees, the COVID-19 pandemic has brought additional challenges for the training programs. The gravity of the novel coronavirus pandemic continues to deepen, causing immense fear and uncertainty globally. An APA poll of more than 1,000 adults conducted early in the pandemic showed that about 40% of Americans were anxious about becoming seriously ill or dying with COVID-19. Nearly half of the respondents (48%) were anxious about the possibility of getting COVID-19, and even more (62%) were anxious about the possibility of their loved ones getting infected by this virus. Also, one-third of Americans reported a serious impact on their mental health.
Furthermore, the ailing economy and increasing unemployment are raising financial concerns for individuals and families. This pandemic also has had an impact on our patients’ sleep hygiene, relationships with their loved ones, and consumption of alcohol or other drugs/substances.11 Deteriorating mental health raises concerns about increased suicide risk as a secondary consequence.12
Physicians and other frontline teams who are taking care of these patients and their families continue to provide unexcelled, compassionate care in these unprecedented times. Selfless care continues despite awareness of the high probability of getting exposed to the virus and spreading it further to family members. Physicians involved in direct patient care for COVID-19 patients are at high risk for demoralization, burnout, depression, and anxiety.13
Struggles experienced by IMGs
On the personal front, IMGs often struggle with multiple stressors, such as lack of social support, ethnic-minority prejudice, and the need to understand financial structures such as mortgages in the new countries even after extended periods of residence.14 This virus has killed many health care professionals, including physicians around the world. There was a report of suicide by an emergency medicine physician who was treating patients with COVID-19 and ended up contracting the virus. That news was devastating and overwhelming for everyone, especially health care clinicians. It also adds to the stress and worries of IMGs who are still on nonimmigrant visas.
Bigger concerns exist if there is a demise of a nonimmigrant IMG and the implications of that loss for dependent families – who might face deportation. Even for those who were recently granted permanent residency status, worries about limited support systems and financial hardships to their families can be stressors.
Also, a large number of IMGs represent the geographical area where the pandemic began. Fortunately, the World Health Organization has taken a firm stance against possible discrimination by calling for global solidarity in these times. Furthermore, the WHO has emphasized the importance of referring to the disease caused by SARS-CoV-2 as “COVID-19” only – and not by the name of a particular country or city.15 Despite those official positions, people continue to express racially discriminatory opinions related to the virus, and those comments are not only disturbing to IMGs, they also are demoralizing.
Travel restrictions
In addition to the worries that IMGs might have about their own health and that of their families residing with them, the well-being of their extended families, including their aging parents back in their countries of origin, is unsettling as well. It is even more unnerving during the pandemic because the Centers for Disease Control and Prevention and the State Department advised avoiding all international travel at this time. Under these circumstances, IMGs are concerned about travel to their countries of origin in the event of a family emergency and the quarantine protocols in place, at both the country of origin and at residences.
Immigration issues
The U.S. administration temporarily suspended all immigration for 60 days, starting from April 2020. Recently, an executive order was signed suspending entry in the country on several visas, including the J-1 and the H1-B. Those are two categories that allow physicians to train and work in the United States.
IMGs in the United States reside and practice here under different types of immigrant and nonimmigrant visas (J-1, H1-B). This year, the Match results coincided with the timeline of those new immigration restrictions. Many IMGs are currently in the process of renewing their H1-B visas. They are worried because their visas will expire in the coming months. During the pandemic, U.S. Citizenship and Immigration Services suspended routine visa services and premium processing for visa renewals. This halt led to a delay in visa processing for graduating residents in June and practicing physicians seeking visa renewal. Those delays add to personal stress, and furthermore, distract these immigrant physicians from fighting this pandemic.
Another complication is that rules for J-1 visa holders have changed so that trainees must return to their countries of origin for at least 2 years after completing their training. If they decide to continue practicing medicine in the United States, they need a specific type of J-1 waiver and must gain a pathway to be a lawful permanent resident (Green Card). Many IMGs who are on waiver positions might not be able to treat patients ailing from COVID-19 to the full extent because waivers restrict them to practicing only in certain identified health systems.
IMGs who are coming from a country such India have to wait for more than 11 years after completing their accredited training to get permanent residency because of backlog for the permanent residency process.16 While waiting for a Green Card, they must continue to work on an H1-B visa, which requires periodic renewal.
Potential impact on training
Non-U.S. citizen IMGs accounted for 13% of the total of first-year positions in the 2020 Match. They will start medical training in residency programs in the United States in the coming months. The numbers for psychiatry residency matches are higher; about 16% of total first-year positions are filled by non-U.S. IMGs.17 At this time, when they should be celebrating their successful Match after many years of hard work and persistence, there is increased anxiety. They wonder whether they will be able to enter the United States to begin their training program on time. Their concerns are multifold, but the main concern is related to uncertainties around getting visas on time. With the recent executive order in place, physicians only working actively with COVID-19 patients will be able to enter the country on visas. As mental health concerns continue to rise during these times, incoming residents might not be able to start training if they are out of the country.
Furthermore, because of travel/air restrictions, there are worries about whether physicians will be able to get flights to the United States, given the lockdown in many countries around the world. Conversely, IMGs who will be graduating from residency and fellowship programs this summer and have accepted new positions also are dealing with similar uncertainty. Their new jobs will require visa processing, and the current scenario provides limited insight, so far, about whether they will be able to start their respective jobs or whether they will have to return to their home countries until their visa processing is completed.
The American Medical Association has advised the Secretary of State and acting Secretary of Homeland Security to expedite physician workforce expansion in an effort to meet the growing need for health care services during this pandemic.18 It is encouraging that, recently, the State Department declared that visa processing will continue for medical professionals and that cases would be expedited for those who meet the criteria. However, the requirement for in-person interviews remains for individuals who are seeking a U.S. visa outside the country.
As residency programs are trying their best to continue to provide educational experiences to trainees during this phase, if psychiatry residents are placed on quarantine because of either getting exposed or contracting the illness, there is a possibility that they might need to extend their training. This would bring another challenge for IMGs, requiring them to extend their visas to complete their training. Future J-1 waiver jobs could be compromised.
Investment in physician wellness critical
Psychiatrists, along with other health care workers, are front-line soldiers in the fight against COVID-19. All physicians are at high risk for demoralization, burnout, depression, anxiety, and suicide. It is of utmost importance that we invest immediately in physicians’ wellness. As noted, significant numbers of psychiatrists are IMGs who are dealing with additional challenges while responding to the pandemic. There are certain challenges for IMGs, such as the well-being of their extended families in other countries, and travel bans put in place because of the pandemic. Those issues are not easy to resolve. However, addressing visa issues and providing support to their families in the event that something happens to physicians during the pandemic would be reassuring and would help alleviate additional stress. Those kinds of actions also would allow immigrant physicians to focus on clinical work and to improve their overall well-being. Given the health risks and numerous other insecurities that go along with living amid a pandemic, IMGs should not have the additional pressure of visa uncertainty.
Public health crises such as COVID-19 are associated with increased rates of anxiety,19 depression,20 illicit substance use,21 and an increased rate of suicide.22 Patients with serious mental illness might be among the hardest hit both physically and mentally during the pandemic.23 Even in the absence of a pandemic, there is already a shortage of psychiatrists at the national level, and it is expected that this shortage will grow in the future. Rural and underserved areas are expected to experience the physician deficit more acutely.24
The pandemic is likely to resolve gradually and unpredictably – and might recur along the way over the next 1-2 years. However, the psychiatrist shortage will escalate more, as the mental health needs in the United States increase further in coming months. We need psychiatrists now more than ever, and it will be crucial that prospective residents, graduating residents, and fellows are able to come on board to join the American health care system promptly. In addition to national-level interventions, residency programs, potential employers, and communities must be aware of and do whatever they can to address the challenges faced by IMGs during these times.
Dr. Raman Baweja is affiliated with the department of psychiatry and behavioral health at Penn State University, Hershey. He has no conflicts of interest. Dr. Verma is affiliated with Rogers Behavioral Health in Kenosha County, Wis., and the department of psychiatry and behavioral health at Rosalind Franklin University of Medicine and Science in North Chicago. She has no conflicts of interest. Dr. Ritika Baweja is affiliated with the department of psychiatry and behavioral health at Penn State. Dr. Ritika Baweja is the spouse of Dr. Raman Baweja. Dr. Adam is affiliated with the department of psychiatry at the University of Missouri, Columbia.
References
1. American Psychiatric Association. Navigating psychiatry residency in the United States. A Guide for IMG Physicians.
2. Berg S. 5 IMG physicians who speak up for patients and fellow doctors. American Medical Association. 2019 Oct 22.
3. Tsugawa Y et al. BMJ. 2017 Feb 3;256. doi: 10.1136/bmj.j273.
4. Gogineni RR et al. Child Adolesc Psychiatr Clin N Am. 2010 Oct 1;19(4):833-53.
5. Majeed MH et al. Academic Psychiatry. 2017 Dec 1;41(6):849-51.
6. Brotherton SE and Etzel SI. JAMA. 2018 Sep 11;320(10):1051-70.
7. Sockalingam S et al. Acad Psychiatry. 2012 Jul 1;36(4):277-81.
8. Singareddy R et al. Acad Psychiatry. 2008 Jul-Aug;32(4):343-4.
9. Kramer MN. Acad Psychiatry. 2005 Jul-Aug;29(3):322-4.
10. Rao NR and Kotapati VP. Pathways for success in academic medicine for an international medical graduate: Challenges and opportunities. In “Roberts Academic Medicine Handbook” 2020. Springer:163-70.
11. American Psychiatric Association. New poll: COVID-19 impacting mental well-being: Americans feeling anxious, especially for loved ones; older adults are less anxious. 2020 Mar 25.
12. Reger MA et al. JAMA Psychiatry. 2020 Apr 10. doi: 10.1001/jamapsychiatry.2020.1060.
13. Lai J et al. JAMA Netw Open. 2020 Mar 23;3(3):e203976-e203976. doi: 10.1001/jamanetworkopen.2020.3976.
14. Kalra G et al. Acad Psychiatry. 2012 Jul;36(4):323-9.
15. WHO best practices for the naming of new human infectious diseases. World Health Organization. 2015.
16. U.S. Department of State. Bureau of Consular Affairs. Visa Bulletin for March 2020.
17. National Resident Matching Program® (NRMP®). Thousands of medical students and graduates celebrate NRMP Match results.
18. American Medical Association. AMA: U.S. should open visas to international physicians amid COVID-19. AMA press release. 2020 Mar 25.
19. McKay D et al. J Anxiety Disord. 2020 Jun;73:02233. doi: 10.1016/j.janxdis.2020.102233.
20. Tang W et al. J Affect Disord. 2020 May 13;274:1-7.
21. Collins F et al. NIH Director’s Blog. NIH.gov. 2020 Apr 21.
22. Reger M et al. JAMA Psychiatry. 2020 Apr 10. doi: 10.1001/jamapsychiatry.2020.1060.
23. Druss BG. JAMA Psychiatry. 2020 Apr 3. doi: 10.1001/jamapsychiatry.2020.0894.
24. American Association of Medical Colleges. “The complexities of physician supply and demand: Projections from 2018-2033.” 2020 Jun.
International medical graduates (IMGs) constitute more than 24% of the total percentage of active physicians, 30% of active psychiatrists, and 33% of psychiatry residents in the United States.1 IMGs serve in various medical specialties and provide medical care to socioeconomically disadvantaged patients in underserved communities.2 Evidence suggests that patient outcomes among elderly patients admitted in U.S. hospitals for those treated by IMGs were on par with outcomes of U.S. graduates. Moreover, patients who were treated by IMGs had a lower mortality rates.3
IMGs trained in the United States make considerable contributions to psychiatry and have been very successful as educators, researchers, and leaders. Over the last 3 decades, for example, three American Psychiatric Association (APA) presidents and one past president of the American Academy of Child and Adolescent Psychiatry were IMGs. Many of them also hold department chair positions at many academic institutions.4,5
In short, IMGs are an important part of the U.S. health care system – particularly in psychiatry.
In addition to participating in psychiatry residency programs, IMG physicians are heavily represented in subspecialties, including geriatric psychiatry (45%), addiction psychiatry (42%), child and adolescent psychiatry (36%), psychosomatic medicine (32%), and forensic psychiatry (25%).6 IMG trainees face multiple challenges that begin as they transition to psychiatry residency in the United States, including understanding the American health care system, electronic medical records and documentation, and evidence-based medicine. In addition, they need to adapt to cultural changes, and work on language barriers, communication skills, and social isolation.7,8 Training programs account for these challenges and proactively take essential steps to facilitate the transition of IMGs into the U.S. system.9,10
As training programs prepare for the new academic year starting from July 2020 and continue to provide educational experiences to current trainees, the COVID-19 pandemic has brought additional challenges for the training programs. The gravity of the novel coronavirus pandemic continues to deepen, causing immense fear and uncertainty globally. An APA poll of more than 1,000 adults conducted early in the pandemic showed that about 40% of Americans were anxious about becoming seriously ill or dying with COVID-19. Nearly half of the respondents (48%) were anxious about the possibility of getting COVID-19, and even more (62%) were anxious about the possibility of their loved ones getting infected by this virus. Also, one-third of Americans reported a serious impact on their mental health.
Furthermore, the ailing economy and increasing unemployment are raising financial concerns for individuals and families. This pandemic also has had an impact on our patients’ sleep hygiene, relationships with their loved ones, and consumption of alcohol or other drugs/substances.11 Deteriorating mental health raises concerns about increased suicide risk as a secondary consequence.12
Physicians and other frontline teams who are taking care of these patients and their families continue to provide unexcelled, compassionate care in these unprecedented times. Selfless care continues despite awareness of the high probability of getting exposed to the virus and spreading it further to family members. Physicians involved in direct patient care for COVID-19 patients are at high risk for demoralization, burnout, depression, and anxiety.13
Struggles experienced by IMGs
On the personal front, IMGs often struggle with multiple stressors, such as lack of social support, ethnic-minority prejudice, and the need to understand financial structures such as mortgages in the new countries even after extended periods of residence.14 This virus has killed many health care professionals, including physicians around the world. There was a report of suicide by an emergency medicine physician who was treating patients with COVID-19 and ended up contracting the virus. That news was devastating and overwhelming for everyone, especially health care clinicians. It also adds to the stress and worries of IMGs who are still on nonimmigrant visas.
Bigger concerns exist if there is a demise of a nonimmigrant IMG and the implications of that loss for dependent families – who might face deportation. Even for those who were recently granted permanent residency status, worries about limited support systems and financial hardships to their families can be stressors.
Also, a large number of IMGs represent the geographical area where the pandemic began. Fortunately, the World Health Organization has taken a firm stance against possible discrimination by calling for global solidarity in these times. Furthermore, the WHO has emphasized the importance of referring to the disease caused by SARS-CoV-2 as “COVID-19” only – and not by the name of a particular country or city.15 Despite those official positions, people continue to express racially discriminatory opinions related to the virus, and those comments are not only disturbing to IMGs, they also are demoralizing.
Travel restrictions
In addition to the worries that IMGs might have about their own health and that of their families residing with them, the well-being of their extended families, including their aging parents back in their countries of origin, is unsettling as well. It is even more unnerving during the pandemic because the Centers for Disease Control and Prevention and the State Department advised avoiding all international travel at this time. Under these circumstances, IMGs are concerned about travel to their countries of origin in the event of a family emergency and the quarantine protocols in place, at both the country of origin and at residences.
Immigration issues
The U.S. administration temporarily suspended all immigration for 60 days, starting from April 2020. Recently, an executive order was signed suspending entry in the country on several visas, including the J-1 and the H1-B. Those are two categories that allow physicians to train and work in the United States.
IMGs in the United States reside and practice here under different types of immigrant and nonimmigrant visas (J-1, H1-B). This year, the Match results coincided with the timeline of those new immigration restrictions. Many IMGs are currently in the process of renewing their H1-B visas. They are worried because their visas will expire in the coming months. During the pandemic, U.S. Citizenship and Immigration Services suspended routine visa services and premium processing for visa renewals. This halt led to a delay in visa processing for graduating residents in June and practicing physicians seeking visa renewal. Those delays add to personal stress, and furthermore, distract these immigrant physicians from fighting this pandemic.
Another complication is that rules for J-1 visa holders have changed so that trainees must return to their countries of origin for at least 2 years after completing their training. If they decide to continue practicing medicine in the United States, they need a specific type of J-1 waiver and must gain a pathway to be a lawful permanent resident (Green Card). Many IMGs who are on waiver positions might not be able to treat patients ailing from COVID-19 to the full extent because waivers restrict them to practicing only in certain identified health systems.
IMGs who are coming from a country such India have to wait for more than 11 years after completing their accredited training to get permanent residency because of backlog for the permanent residency process.16 While waiting for a Green Card, they must continue to work on an H1-B visa, which requires periodic renewal.
Potential impact on training
Non-U.S. citizen IMGs accounted for 13% of the total of first-year positions in the 2020 Match. They will start medical training in residency programs in the United States in the coming months. The numbers for psychiatry residency matches are higher; about 16% of total first-year positions are filled by non-U.S. IMGs.17 At this time, when they should be celebrating their successful Match after many years of hard work and persistence, there is increased anxiety. They wonder whether they will be able to enter the United States to begin their training program on time. Their concerns are multifold, but the main concern is related to uncertainties around getting visas on time. With the recent executive order in place, physicians only working actively with COVID-19 patients will be able to enter the country on visas. As mental health concerns continue to rise during these times, incoming residents might not be able to start training if they are out of the country.
Furthermore, because of travel/air restrictions, there are worries about whether physicians will be able to get flights to the United States, given the lockdown in many countries around the world. Conversely, IMGs who will be graduating from residency and fellowship programs this summer and have accepted new positions also are dealing with similar uncertainty. Their new jobs will require visa processing, and the current scenario provides limited insight, so far, about whether they will be able to start their respective jobs or whether they will have to return to their home countries until their visa processing is completed.
The American Medical Association has advised the Secretary of State and acting Secretary of Homeland Security to expedite physician workforce expansion in an effort to meet the growing need for health care services during this pandemic.18 It is encouraging that, recently, the State Department declared that visa processing will continue for medical professionals and that cases would be expedited for those who meet the criteria. However, the requirement for in-person interviews remains for individuals who are seeking a U.S. visa outside the country.
As residency programs are trying their best to continue to provide educational experiences to trainees during this phase, if psychiatry residents are placed on quarantine because of either getting exposed or contracting the illness, there is a possibility that they might need to extend their training. This would bring another challenge for IMGs, requiring them to extend their visas to complete their training. Future J-1 waiver jobs could be compromised.
Investment in physician wellness critical
Psychiatrists, along with other health care workers, are front-line soldiers in the fight against COVID-19. All physicians are at high risk for demoralization, burnout, depression, anxiety, and suicide. It is of utmost importance that we invest immediately in physicians’ wellness. As noted, significant numbers of psychiatrists are IMGs who are dealing with additional challenges while responding to the pandemic. There are certain challenges for IMGs, such as the well-being of their extended families in other countries, and travel bans put in place because of the pandemic. Those issues are not easy to resolve. However, addressing visa issues and providing support to their families in the event that something happens to physicians during the pandemic would be reassuring and would help alleviate additional stress. Those kinds of actions also would allow immigrant physicians to focus on clinical work and to improve their overall well-being. Given the health risks and numerous other insecurities that go along with living amid a pandemic, IMGs should not have the additional pressure of visa uncertainty.
Public health crises such as COVID-19 are associated with increased rates of anxiety,19 depression,20 illicit substance use,21 and an increased rate of suicide.22 Patients with serious mental illness might be among the hardest hit both physically and mentally during the pandemic.23 Even in the absence of a pandemic, there is already a shortage of psychiatrists at the national level, and it is expected that this shortage will grow in the future. Rural and underserved areas are expected to experience the physician deficit more acutely.24
The pandemic is likely to resolve gradually and unpredictably – and might recur along the way over the next 1-2 years. However, the psychiatrist shortage will escalate more, as the mental health needs in the United States increase further in coming months. We need psychiatrists now more than ever, and it will be crucial that prospective residents, graduating residents, and fellows are able to come on board to join the American health care system promptly. In addition to national-level interventions, residency programs, potential employers, and communities must be aware of and do whatever they can to address the challenges faced by IMGs during these times.
Dr. Raman Baweja is affiliated with the department of psychiatry and behavioral health at Penn State University, Hershey. He has no conflicts of interest. Dr. Verma is affiliated with Rogers Behavioral Health in Kenosha County, Wis., and the department of psychiatry and behavioral health at Rosalind Franklin University of Medicine and Science in North Chicago. She has no conflicts of interest. Dr. Ritika Baweja is affiliated with the department of psychiatry and behavioral health at Penn State. Dr. Ritika Baweja is the spouse of Dr. Raman Baweja. Dr. Adam is affiliated with the department of psychiatry at the University of Missouri, Columbia.
References
1. American Psychiatric Association. Navigating psychiatry residency in the United States. A Guide for IMG Physicians.
2. Berg S. 5 IMG physicians who speak up for patients and fellow doctors. American Medical Association. 2019 Oct 22.
3. Tsugawa Y et al. BMJ. 2017 Feb 3;256. doi: 10.1136/bmj.j273.
4. Gogineni RR et al. Child Adolesc Psychiatr Clin N Am. 2010 Oct 1;19(4):833-53.
5. Majeed MH et al. Academic Psychiatry. 2017 Dec 1;41(6):849-51.
6. Brotherton SE and Etzel SI. JAMA. 2018 Sep 11;320(10):1051-70.
7. Sockalingam S et al. Acad Psychiatry. 2012 Jul 1;36(4):277-81.
8. Singareddy R et al. Acad Psychiatry. 2008 Jul-Aug;32(4):343-4.
9. Kramer MN. Acad Psychiatry. 2005 Jul-Aug;29(3):322-4.
10. Rao NR and Kotapati VP. Pathways for success in academic medicine for an international medical graduate: Challenges and opportunities. In “Roberts Academic Medicine Handbook” 2020. Springer:163-70.
11. American Psychiatric Association. New poll: COVID-19 impacting mental well-being: Americans feeling anxious, especially for loved ones; older adults are less anxious. 2020 Mar 25.
12. Reger MA et al. JAMA Psychiatry. 2020 Apr 10. doi: 10.1001/jamapsychiatry.2020.1060.
13. Lai J et al. JAMA Netw Open. 2020 Mar 23;3(3):e203976-e203976. doi: 10.1001/jamanetworkopen.2020.3976.
14. Kalra G et al. Acad Psychiatry. 2012 Jul;36(4):323-9.
15. WHO best practices for the naming of new human infectious diseases. World Health Organization. 2015.
16. U.S. Department of State. Bureau of Consular Affairs. Visa Bulletin for March 2020.
17. National Resident Matching Program® (NRMP®). Thousands of medical students and graduates celebrate NRMP Match results.
18. American Medical Association. AMA: U.S. should open visas to international physicians amid COVID-19. AMA press release. 2020 Mar 25.
19. McKay D et al. J Anxiety Disord. 2020 Jun;73:02233. doi: 10.1016/j.janxdis.2020.102233.
20. Tang W et al. J Affect Disord. 2020 May 13;274:1-7.
21. Collins F et al. NIH Director’s Blog. NIH.gov. 2020 Apr 21.
22. Reger M et al. JAMA Psychiatry. 2020 Apr 10. doi: 10.1001/jamapsychiatry.2020.1060.
23. Druss BG. JAMA Psychiatry. 2020 Apr 3. doi: 10.1001/jamapsychiatry.2020.0894.
24. American Association of Medical Colleges. “The complexities of physician supply and demand: Projections from 2018-2033.” 2020 Jun.
‘Doc, can I get a mask exemption?’
As more jurisdictions mandate facial coverings in public, questions have arisen about whether it’s safe for everyone – including those with lung disease – to wear masks.
To address these issues, Medscape spoke with the chief medical officer of the American Lung Association, Dr. Albert Rizzo.
The CDC recommendations on mask wearing say, “Cloth face coverings should not be placed on young children under age 2, anyone who has trouble breathing, or is unconscious, incapacitated, or otherwise unable to remove the mask without assistance.” Does this language suggest that there indeed is a subset of the adult population with lung disease who shouldn’t wear masks?
It makes sense to say that if it makes you uncomfortable to wear a mask because it affects your breathing, you should think twice about getting in a situation where you would have to wear a mask.
I’ve told many of my high-risk patients, “The best way to avoid getting COVID-19 is to stay home and stay away from sick people, especially if you feel that you are not going to be able to wear a mask or facial covering of some sort.”
The reason that some people have trouble with a mask is that they haven’t tried the right style of mask – by that I mean how tightly it fits and the material it’s made out of. Sometimes it really is just that people with lung disease don’t like to have anything covering their faces. Many of these patients feel better where there is air blowing across their faces – they will have a fan blowing even in the middle of winter because they feel more comfortable.
I won’t say it’s all in their heads, but sometimes it’s a matter of desensitizing themselves to wearing a mask. I liken it to people who have sleep apnea. We often have to desensitize them to wearing a mask for sleeping. We tell them to put it on while they are watching TV — don’t hook it up to anything yet, just get used to having something on your face.
I’ve told my patients the same thing about masks for COVID-19. Put on the mask, see how it feels. If you become uncomfortable breathing with it on, take it off, but maybe you can handle it for a half hour or 45 minutes. Find out how much time you have for a trip to the grocery store based on how comfortable you are wearing it at home.
It’s a matter of training the patient, giving them options of how to get comfortable with it, and then making them realize that they have to weigh the benefits and risks of wearing the mask and feeling out of breath versus going out in public and being potentially exposed to coronavirus. And the bottom line is, anybody who is wearing a mask and starts to feel uncomfortable, they can take the mask off.
You mentioned different types of masks. Is there a type of mask that is typically more breathable that clinicians can recommend to patients with lung disease?
First, I remind patients who think they will have trouble breathing with a mask on that they are choosing a mask not so much to protect themselves – that would take an N95 mask to filter out the virus. The mask is worn so that when they cough or drink or speak, they aren’t sending respiratory droplets out into the environment. Even when we speak, respiratory droplets can easily go out as far as 6 feet, or further with coughing or sneezing. With facial coverings, we try to keep those respiratory droplets from getting out and infecting others.
So when choosing a mask, you don’t have to worry as much about a tight-fitting mask. I recommend a loose-fitting mask that covers the nose and mouth and isn’t going to fall off but isn’t so tight around the ears and neck to make them feel uncomfortable. Even though it doesn’t really protect the wearer, it is cutting down on the ability to breathe in droplets – maybe not microscopic particles, but it’s better than nothing.
Is a face shield a reasonable alternative for someone who feels they can’t breathe with a mask on?
Yes. I’m surprised that face shields don’t get more attention. I’ve tried them out, and they are actually more comfortable than masks. They do impede the spilling out of droplets into the public, but they are not as close fitting to the face as a mask. If you want to protect others, the face shield should be adequate. It is not as good at preventing you from breathing in viral particles.
Some people have claimed that wearing a mask makes them hyperventilate and feel like they are going to pass out, or the mask causes them to become hypoxic. Are these valid concerns?
We get two questions about masks from patients who feel that they are short of breath or are worried about wearing a mask. One is whether their oxygen level is dropping. It’s usually not that. It’s usually because they feel that the mask is an impediment to getting air in. Their oxygen levels are stable.
The other question is whether the mask causes CO2 retention. For the mask to trap enough exhaled CO2 and for us to breathe enough of that CO2 back in to raise our CO2 level, it has to be a pretty tight-fitting mask. With the type of masks we are suggesting that people wear, that’s very unlikely to occur.
What can clinicians do to reassure patients with some type of lung disease that they can safely wear masks?
There are a few things they can do right in the office. Have them put the mask on for a few minutes and make sure they feel comfortable with it. With an oximeter, patients can see that their oxygen levels don’t change when they are breathing through the mask for a period of time.
You can’t really measure CO2 retention that easily, but most patients with chronic obstructive pulmonary disease or pulmonary fibrosis don’t have an elevated CO2 at baseline. A little more education is helpful in those situations. In most cases, they aren’t going to retain enough CO2 to have problems wearing a mask.
Only a small percentage of patients with lung disease are CO2 retainers, and many of those patients are being seen by pulmonary specialists. Those are the patients you might want to be more cautious with, to make sure they aren’t wearing anything that is tight fitting or that makes them work harder to breathe. It’s not that the mask is causing CO2 retention, but the increased work of breathing may make it harder to exhale the CO2.
Does a mask interfere with supplemental oxygen in any way?
Supplemental oxygen is typically supplied through a nasal cannula, so 100% oxygen is still getting to the nasal passages and entrained down into the airway, so it shouldn’t be a problem.
Some of the resistance to wearing masks has come from people with asthma. Is it safe for patients with asthma to wear masks, or should these patients be exempt from wearing masks?
In general, the breathing of people with mild asthma, both young and old, should not be impeded by the wearing of facial coverings. The concerns about oxygen and carbon dioxide among patients with more severe lung disease should not play a role in asthma.
Since younger adults with COVID-19 seem to have fewer or no symptoms and may actually be carrying the virus unknowingly, this should be the main population who should wear masks to prevent transmission to others.
Exemptions for mask wearing for mild asthma should be discouraged and dealt with on a case-by-case basis if there is a particular concern for that individual.
How do you respond if a patient asks you for a formal medical exemption to wearing a mask?
We’ve been asked to do a lot of letter writing for patients around going back to work, as well as the issue of wearing masks. The discussion usually revolves around trying to avoid going somewhere where you would have to wear a mask if it makes you feel uncomfortable.
I do not recommend automatically exempting individuals from wearing masks, even many of my pulmonary patients. There needs to be an understanding by the patient regarding the purpose of the mask and the overall advice to stay out of situations where social distancing is not being practiced. If you can take the time to discuss options as mentioned above – mask styles, desensitization, etc – the patient usually understands and will try wearing a mask.
On a case-by-case basis, some individuals may need to be exempted, but I feel this is a small number. I prefer my high-risk (older, chronic disease, etc) patients do everything they can to avoid infection – handwashing, mask wearing, and socially distancing.
They should also realize that even with a note, it is not going to help if they are in the middle of the grocery store and someone confronts them about not wearing a mask. It may help as they enter a store that says “masks required” and they can show it to someone monitoring the door. But I’m not really sure in what situations having that note is going to be helpful if confrontations occur.
Patients are also asking how safe is it for them to go back to work and be out in public. I tell them, nothing is going to be 100% safe. Until we have an effective vaccine, we are all going to have to weigh the potential risks of going to an area where social distancing isn’t maintained, people aren’t wearing face masks, and you can’t wash your hands as much as you’d like to. That’s going to be a struggle for all of us to get back out into situations where people interact socially.
Albert A. Rizzo, MD, is chief medical officer for the American Lung Association, chief of the Section of Pulmonary and Critical Care Medicine at the Christiana Care Health System in Newark, Delaware, and a member of Christiana Care Pulmonary Associates. He is board certified in internal medicine, pulmonary medicine, critical care medicine, and sleep medicine and is a clinical assistant professor of medicine at Thomas Jefferson University Medical School, Philadelphia.
This article first appeared on Medscape.com.
As more jurisdictions mandate facial coverings in public, questions have arisen about whether it’s safe for everyone – including those with lung disease – to wear masks.
To address these issues, Medscape spoke with the chief medical officer of the American Lung Association, Dr. Albert Rizzo.
The CDC recommendations on mask wearing say, “Cloth face coverings should not be placed on young children under age 2, anyone who has trouble breathing, or is unconscious, incapacitated, or otherwise unable to remove the mask without assistance.” Does this language suggest that there indeed is a subset of the adult population with lung disease who shouldn’t wear masks?
It makes sense to say that if it makes you uncomfortable to wear a mask because it affects your breathing, you should think twice about getting in a situation where you would have to wear a mask.
I’ve told many of my high-risk patients, “The best way to avoid getting COVID-19 is to stay home and stay away from sick people, especially if you feel that you are not going to be able to wear a mask or facial covering of some sort.”
The reason that some people have trouble with a mask is that they haven’t tried the right style of mask – by that I mean how tightly it fits and the material it’s made out of. Sometimes it really is just that people with lung disease don’t like to have anything covering their faces. Many of these patients feel better where there is air blowing across their faces – they will have a fan blowing even in the middle of winter because they feel more comfortable.
I won’t say it’s all in their heads, but sometimes it’s a matter of desensitizing themselves to wearing a mask. I liken it to people who have sleep apnea. We often have to desensitize them to wearing a mask for sleeping. We tell them to put it on while they are watching TV — don’t hook it up to anything yet, just get used to having something on your face.
I’ve told my patients the same thing about masks for COVID-19. Put on the mask, see how it feels. If you become uncomfortable breathing with it on, take it off, but maybe you can handle it for a half hour or 45 minutes. Find out how much time you have for a trip to the grocery store based on how comfortable you are wearing it at home.
It’s a matter of training the patient, giving them options of how to get comfortable with it, and then making them realize that they have to weigh the benefits and risks of wearing the mask and feeling out of breath versus going out in public and being potentially exposed to coronavirus. And the bottom line is, anybody who is wearing a mask and starts to feel uncomfortable, they can take the mask off.
You mentioned different types of masks. Is there a type of mask that is typically more breathable that clinicians can recommend to patients with lung disease?
First, I remind patients who think they will have trouble breathing with a mask on that they are choosing a mask not so much to protect themselves – that would take an N95 mask to filter out the virus. The mask is worn so that when they cough or drink or speak, they aren’t sending respiratory droplets out into the environment. Even when we speak, respiratory droplets can easily go out as far as 6 feet, or further with coughing or sneezing. With facial coverings, we try to keep those respiratory droplets from getting out and infecting others.
So when choosing a mask, you don’t have to worry as much about a tight-fitting mask. I recommend a loose-fitting mask that covers the nose and mouth and isn’t going to fall off but isn’t so tight around the ears and neck to make them feel uncomfortable. Even though it doesn’t really protect the wearer, it is cutting down on the ability to breathe in droplets – maybe not microscopic particles, but it’s better than nothing.
Is a face shield a reasonable alternative for someone who feels they can’t breathe with a mask on?
Yes. I’m surprised that face shields don’t get more attention. I’ve tried them out, and they are actually more comfortable than masks. They do impede the spilling out of droplets into the public, but they are not as close fitting to the face as a mask. If you want to protect others, the face shield should be adequate. It is not as good at preventing you from breathing in viral particles.
Some people have claimed that wearing a mask makes them hyperventilate and feel like they are going to pass out, or the mask causes them to become hypoxic. Are these valid concerns?
We get two questions about masks from patients who feel that they are short of breath or are worried about wearing a mask. One is whether their oxygen level is dropping. It’s usually not that. It’s usually because they feel that the mask is an impediment to getting air in. Their oxygen levels are stable.
The other question is whether the mask causes CO2 retention. For the mask to trap enough exhaled CO2 and for us to breathe enough of that CO2 back in to raise our CO2 level, it has to be a pretty tight-fitting mask. With the type of masks we are suggesting that people wear, that’s very unlikely to occur.
What can clinicians do to reassure patients with some type of lung disease that they can safely wear masks?
There are a few things they can do right in the office. Have them put the mask on for a few minutes and make sure they feel comfortable with it. With an oximeter, patients can see that their oxygen levels don’t change when they are breathing through the mask for a period of time.
You can’t really measure CO2 retention that easily, but most patients with chronic obstructive pulmonary disease or pulmonary fibrosis don’t have an elevated CO2 at baseline. A little more education is helpful in those situations. In most cases, they aren’t going to retain enough CO2 to have problems wearing a mask.
Only a small percentage of patients with lung disease are CO2 retainers, and many of those patients are being seen by pulmonary specialists. Those are the patients you might want to be more cautious with, to make sure they aren’t wearing anything that is tight fitting or that makes them work harder to breathe. It’s not that the mask is causing CO2 retention, but the increased work of breathing may make it harder to exhale the CO2.
Does a mask interfere with supplemental oxygen in any way?
Supplemental oxygen is typically supplied through a nasal cannula, so 100% oxygen is still getting to the nasal passages and entrained down into the airway, so it shouldn’t be a problem.
Some of the resistance to wearing masks has come from people with asthma. Is it safe for patients with asthma to wear masks, or should these patients be exempt from wearing masks?
In general, the breathing of people with mild asthma, both young and old, should not be impeded by the wearing of facial coverings. The concerns about oxygen and carbon dioxide among patients with more severe lung disease should not play a role in asthma.
Since younger adults with COVID-19 seem to have fewer or no symptoms and may actually be carrying the virus unknowingly, this should be the main population who should wear masks to prevent transmission to others.
Exemptions for mask wearing for mild asthma should be discouraged and dealt with on a case-by-case basis if there is a particular concern for that individual.
How do you respond if a patient asks you for a formal medical exemption to wearing a mask?
We’ve been asked to do a lot of letter writing for patients around going back to work, as well as the issue of wearing masks. The discussion usually revolves around trying to avoid going somewhere where you would have to wear a mask if it makes you feel uncomfortable.
I do not recommend automatically exempting individuals from wearing masks, even many of my pulmonary patients. There needs to be an understanding by the patient regarding the purpose of the mask and the overall advice to stay out of situations where social distancing is not being practiced. If you can take the time to discuss options as mentioned above – mask styles, desensitization, etc – the patient usually understands and will try wearing a mask.
On a case-by-case basis, some individuals may need to be exempted, but I feel this is a small number. I prefer my high-risk (older, chronic disease, etc) patients do everything they can to avoid infection – handwashing, mask wearing, and socially distancing.
They should also realize that even with a note, it is not going to help if they are in the middle of the grocery store and someone confronts them about not wearing a mask. It may help as they enter a store that says “masks required” and they can show it to someone monitoring the door. But I’m not really sure in what situations having that note is going to be helpful if confrontations occur.
Patients are also asking how safe is it for them to go back to work and be out in public. I tell them, nothing is going to be 100% safe. Until we have an effective vaccine, we are all going to have to weigh the potential risks of going to an area where social distancing isn’t maintained, people aren’t wearing face masks, and you can’t wash your hands as much as you’d like to. That’s going to be a struggle for all of us to get back out into situations where people interact socially.
Albert A. Rizzo, MD, is chief medical officer for the American Lung Association, chief of the Section of Pulmonary and Critical Care Medicine at the Christiana Care Health System in Newark, Delaware, and a member of Christiana Care Pulmonary Associates. He is board certified in internal medicine, pulmonary medicine, critical care medicine, and sleep medicine and is a clinical assistant professor of medicine at Thomas Jefferson University Medical School, Philadelphia.
This article first appeared on Medscape.com.
As more jurisdictions mandate facial coverings in public, questions have arisen about whether it’s safe for everyone – including those with lung disease – to wear masks.
To address these issues, Medscape spoke with the chief medical officer of the American Lung Association, Dr. Albert Rizzo.
The CDC recommendations on mask wearing say, “Cloth face coverings should not be placed on young children under age 2, anyone who has trouble breathing, or is unconscious, incapacitated, or otherwise unable to remove the mask without assistance.” Does this language suggest that there indeed is a subset of the adult population with lung disease who shouldn’t wear masks?
It makes sense to say that if it makes you uncomfortable to wear a mask because it affects your breathing, you should think twice about getting in a situation where you would have to wear a mask.
I’ve told many of my high-risk patients, “The best way to avoid getting COVID-19 is to stay home and stay away from sick people, especially if you feel that you are not going to be able to wear a mask or facial covering of some sort.”
The reason that some people have trouble with a mask is that they haven’t tried the right style of mask – by that I mean how tightly it fits and the material it’s made out of. Sometimes it really is just that people with lung disease don’t like to have anything covering their faces. Many of these patients feel better where there is air blowing across their faces – they will have a fan blowing even in the middle of winter because they feel more comfortable.
I won’t say it’s all in their heads, but sometimes it’s a matter of desensitizing themselves to wearing a mask. I liken it to people who have sleep apnea. We often have to desensitize them to wearing a mask for sleeping. We tell them to put it on while they are watching TV — don’t hook it up to anything yet, just get used to having something on your face.
I’ve told my patients the same thing about masks for COVID-19. Put on the mask, see how it feels. If you become uncomfortable breathing with it on, take it off, but maybe you can handle it for a half hour or 45 minutes. Find out how much time you have for a trip to the grocery store based on how comfortable you are wearing it at home.
It’s a matter of training the patient, giving them options of how to get comfortable with it, and then making them realize that they have to weigh the benefits and risks of wearing the mask and feeling out of breath versus going out in public and being potentially exposed to coronavirus. And the bottom line is, anybody who is wearing a mask and starts to feel uncomfortable, they can take the mask off.
You mentioned different types of masks. Is there a type of mask that is typically more breathable that clinicians can recommend to patients with lung disease?
First, I remind patients who think they will have trouble breathing with a mask on that they are choosing a mask not so much to protect themselves – that would take an N95 mask to filter out the virus. The mask is worn so that when they cough or drink or speak, they aren’t sending respiratory droplets out into the environment. Even when we speak, respiratory droplets can easily go out as far as 6 feet, or further with coughing or sneezing. With facial coverings, we try to keep those respiratory droplets from getting out and infecting others.
So when choosing a mask, you don’t have to worry as much about a tight-fitting mask. I recommend a loose-fitting mask that covers the nose and mouth and isn’t going to fall off but isn’t so tight around the ears and neck to make them feel uncomfortable. Even though it doesn’t really protect the wearer, it is cutting down on the ability to breathe in droplets – maybe not microscopic particles, but it’s better than nothing.
Is a face shield a reasonable alternative for someone who feels they can’t breathe with a mask on?
Yes. I’m surprised that face shields don’t get more attention. I’ve tried them out, and they are actually more comfortable than masks. They do impede the spilling out of droplets into the public, but they are not as close fitting to the face as a mask. If you want to protect others, the face shield should be adequate. It is not as good at preventing you from breathing in viral particles.
Some people have claimed that wearing a mask makes them hyperventilate and feel like they are going to pass out, or the mask causes them to become hypoxic. Are these valid concerns?
We get two questions about masks from patients who feel that they are short of breath or are worried about wearing a mask. One is whether their oxygen level is dropping. It’s usually not that. It’s usually because they feel that the mask is an impediment to getting air in. Their oxygen levels are stable.
The other question is whether the mask causes CO2 retention. For the mask to trap enough exhaled CO2 and for us to breathe enough of that CO2 back in to raise our CO2 level, it has to be a pretty tight-fitting mask. With the type of masks we are suggesting that people wear, that’s very unlikely to occur.
What can clinicians do to reassure patients with some type of lung disease that they can safely wear masks?
There are a few things they can do right in the office. Have them put the mask on for a few minutes and make sure they feel comfortable with it. With an oximeter, patients can see that their oxygen levels don’t change when they are breathing through the mask for a period of time.
You can’t really measure CO2 retention that easily, but most patients with chronic obstructive pulmonary disease or pulmonary fibrosis don’t have an elevated CO2 at baseline. A little more education is helpful in those situations. In most cases, they aren’t going to retain enough CO2 to have problems wearing a mask.
Only a small percentage of patients with lung disease are CO2 retainers, and many of those patients are being seen by pulmonary specialists. Those are the patients you might want to be more cautious with, to make sure they aren’t wearing anything that is tight fitting or that makes them work harder to breathe. It’s not that the mask is causing CO2 retention, but the increased work of breathing may make it harder to exhale the CO2.
Does a mask interfere with supplemental oxygen in any way?
Supplemental oxygen is typically supplied through a nasal cannula, so 100% oxygen is still getting to the nasal passages and entrained down into the airway, so it shouldn’t be a problem.
Some of the resistance to wearing masks has come from people with asthma. Is it safe for patients with asthma to wear masks, or should these patients be exempt from wearing masks?
In general, the breathing of people with mild asthma, both young and old, should not be impeded by the wearing of facial coverings. The concerns about oxygen and carbon dioxide among patients with more severe lung disease should not play a role in asthma.
Since younger adults with COVID-19 seem to have fewer or no symptoms and may actually be carrying the virus unknowingly, this should be the main population who should wear masks to prevent transmission to others.
Exemptions for mask wearing for mild asthma should be discouraged and dealt with on a case-by-case basis if there is a particular concern for that individual.
How do you respond if a patient asks you for a formal medical exemption to wearing a mask?
We’ve been asked to do a lot of letter writing for patients around going back to work, as well as the issue of wearing masks. The discussion usually revolves around trying to avoid going somewhere where you would have to wear a mask if it makes you feel uncomfortable.
I do not recommend automatically exempting individuals from wearing masks, even many of my pulmonary patients. There needs to be an understanding by the patient regarding the purpose of the mask and the overall advice to stay out of situations where social distancing is not being practiced. If you can take the time to discuss options as mentioned above – mask styles, desensitization, etc – the patient usually understands and will try wearing a mask.
On a case-by-case basis, some individuals may need to be exempted, but I feel this is a small number. I prefer my high-risk (older, chronic disease, etc) patients do everything they can to avoid infection – handwashing, mask wearing, and socially distancing.
They should also realize that even with a note, it is not going to help if they are in the middle of the grocery store and someone confronts them about not wearing a mask. It may help as they enter a store that says “masks required” and they can show it to someone monitoring the door. But I’m not really sure in what situations having that note is going to be helpful if confrontations occur.
Patients are also asking how safe is it for them to go back to work and be out in public. I tell them, nothing is going to be 100% safe. Until we have an effective vaccine, we are all going to have to weigh the potential risks of going to an area where social distancing isn’t maintained, people aren’t wearing face masks, and you can’t wash your hands as much as you’d like to. That’s going to be a struggle for all of us to get back out into situations where people interact socially.
Albert A. Rizzo, MD, is chief medical officer for the American Lung Association, chief of the Section of Pulmonary and Critical Care Medicine at the Christiana Care Health System in Newark, Delaware, and a member of Christiana Care Pulmonary Associates. He is board certified in internal medicine, pulmonary medicine, critical care medicine, and sleep medicine and is a clinical assistant professor of medicine at Thomas Jefferson University Medical School, Philadelphia.
This article first appeared on Medscape.com.
Eczema Herpeticum in a Patient With Hailey-Hailey Disease Confounded by Coexistent Psoriasis
To the Editor:
Hailey-Hailey disease (HHD), also known as benign familial pemphigus, is an uncommon autosomal-dominant skin disease.1 Defects in the ATPase type 2C member 1 gene, ATP2C1, result in abnormal intracellular epidermal adherence, and patients experience recurring blisters in skin folds. Longitudinal white streaks of the fingernails also may be present.1 The illness does not appear until puberty and is heightened by the second or third decade of life. Family history often suggests the presence of disease.2 Misdiagnosis of HHD occurs because of a wide spectrum of presentations. The presence of superimposed infections and carcinomas may both obscure and exacerbate this disease.2
Herpes simplex viruse types 1 and 2 (HSV-1 and HSV-2) are DNA viruses that cause common recurrent diseases. Usually, HSV-1 is associated with infection of the mouth and HSV-2 is associated with infection of the genitalia.3 Longitudinal cutaneous lesions manifest as grouped vesicles on an erythematous base. Tzanck smear of herpetic vesicles will reveal the presence of multinucleated giant cells. A direct fluorescent antibody technique also may be used to confirm the diagnosis.3
Erythrodermic HHD disease is a rare condition; moreover, there are only a few reported cases with coexistence of HHD and HSV in the literature.3-6 We report a rare presentation of erythrodermic HHD and coexistent psoriasis with HSV superinfection.
A 69-year-old man presented to an outpatient dermatology clinic for evaluation and treatment of a rash on the scalp, face, back, and lower legs. The patient confirmed a dandruff diagnosis on the scalp and face as well as psoriasis on the trunk and extremities for the last 45 years. He described a history of successful treatment with topical agents and UV light therapy. A family history revealed that the patient’s father and 1 of 2 siblings had a similar rash and “skin problems.” The patient had a medical history of thyroid cancer treated with radiation treatment and a partial thyroidectomy 35 years prior to the current presentation as well as incompletely treated chronic hepatitis C.
A search of medical records revealed a punch biopsy from the posterior neck that demonstrated an acantholytic dyskeratosis with suprabasal acantholysis. Clinicians were unable to differentiate if it was Darier disease (DAR) or HHD. Treatment of the patient’s seborrheic dermatitis and acantholytic disorder was successful at that time with ketoconazole shampoo, ketoconazole cream, desonide cream, and triamcinolone cream. The patient remained stable for 5 years before presenting again to the dermatology clinic for worsening rash despite topical therapies.
At the current presentation, physical examination at the outpatient dermatology clinic revealed few scaly, erythematous, eroded papules distributed on the mid-back; erythematous greasy scaling on the scalp, face, and chest; and pink scaly plaques with white-silvery scale on the anterior lower legs. Histopathology of a specimen from the right mid-back demonstrated acantholysis with suprabasal clefting, hyperkeratosis, and parakeratosis with no dyskeratotic cells identified. The pathologic differential diagnosis included primary acantholytic processes including Grover disease, DAR, HHD, and pemphigus. Pathology from the right shin demonstrated acanthosis, confluent parakeratosis with associated decreased granular cell layer and collections of neutrophils within the stratum corneum, spongiosis, and superficial dermal perivascular chronic inflammation with focal exocytosis and dilated blood vessels in the papillary dermis. The clinical and pathological diagnosis on the lower legs was consistent with psoriasis. Diagnoses of seborrheic dermatitis, psoriasis on the lower legs, and HHD vs DAR on the back and chest were made. The patient was instructed to continue ketoconazole shampoo, ketoconazole cream, and desonide for seborrheic dermatitis; fluocinonide ointment 0.05% to the lower legs for psoriasis; and triamcinolone cream and a bland moisturizer to the back and chest for HHD.
Over the ensuing months, the rash worsened with erythema and scaling affecting more than half of the body surface area. Topical corticosteroids and bland emollients resulted in minimal success. Biologics and acitretin were considered for the psoriasiform dermatitis but avoided due to the patient’s medical history of thyroid cancer and chronic hepatitis C infection. Because the patient described prior success with UV light therapy for psoriasis, he requested light therapy. A subsequent trial of narrowband UVB light therapy initially improved some of the psoriasiform dermatitis on the trunk and extremities; however, after 4 weeks of treatment, the patient described pain in some of the skin and felt he was burned by minimal exposure to light therapy on one particular visit, which caused him to stop light therapy.
Approximately 2 weeks later, the patient presented to the emergency department stating his psoriasis was infected; he was diagnosed with psoriasis with secondary cellulitis and received intravenous vancomycin and piperacillin-tazobactam, with bacterial cultures demonstrating Corynebacterium and methicillin-resistant Staphylococcus aureus. Some improvement was noted in the patient’s skin after antibiotics were initiated, but he continued to describe worsening “burning and pain” throughout the psoriasis lesions. The patient’s care was transferred to the Veterans Affairs hospital where a dermatology inpatient consultation was placed.
Our initial dermatologic examination revealed generalized scaly erythroderma on the neck, trunk, and extremities, sparing the face, palms, and soles (Figure 1). Multiple crusted and intact vesicles also were present overlying the erythematous plaques on the chest, back, and proximal extremities, most grouped in clusters. The patient endorsed new symptoms of pain and burning. Tzanck smear from the abdomen along with shave biopsies from the left flank and right abdomen were performed, and intravenous acyclovir was initiated immediately after these procedures.
Viral cultures were taken but were incorrectly processed by the laboratory. Tzanck smear showed severe acute inflammation with numerous neutrophils, multinucleated giant cells with viral nuclear changes, and positive immunostaining for HSV and negative immunostaining for herpes zoster. Both pathology specimens revealed an intense acute mixed, mainly neutrophilic, inflammatory infiltrate extending into the deeper dermis as well as distorted and necrotic hair follicles, some of which displayed multinucleated epithelial cells with margination of chromatin that were positive for both HSV-1 and HSV-2 and negative for herpes zoster (Figure 2). The positivity of both HSV strains might represent co-infection or could be a cross-reaction of antibodies used in immunohistochemistry to the HSV antigens. There was acantholysis surrounding the ulceration and extending through the full thickness of the epidermis with a dilapidated brick wall pattern (Figure 3) as well as negative immunohistochemical staining for HSV-1 and HSV-2 antigens. The clinical and histological picture together, along with prior clinical and pathological reports, confirmed the diagnoses of acute erythrodermic HHD with HSV superinfection.
The patient’s condition and pain improved within 24 hours on intravenous acyclovir. On the third day, his lesions were resolving and symptoms improved, so he was transitioned to oral acyclovir and discharged from the hospital. Follow-up in the dermatology outpatient clinic 1 week later revealed that all vesicles and papules had cleared, but the patient was still erythrodermic. Because HHD cannot always be distinguished histologically from other forms of pemphigus but yields a negative immunofluorescence, direct immunofluorescence and indirect immunofluorescence were obtained upon patient follow-up in the clinic and were both negative. Hepatitis C viral loads were undetectable. Consultations to gastroenterology and oncology teams were placed for consideration of systemic agents, and the patient was initiated on oral acitretin 25 mg daily, along with clobetasol as adjuvant therapy for any residual skin plaques. The laboratory results were closely monitored. Within 4 weeks after starting acitretin, the patient’s erythroderma had completely resolved. The patient has remained stable since then, except for one episode of secondary Staphylococcus infection that cleared on oral antibiotics. The patient remains stable and clear on oral acitretin 25 mg daily, with concomitant desonide cream and fluocinonide ointment as needed.
Hailey-Hailey disease is characterized by recurrent episodes of erythema, blisters, and plaques localized to intertriginous and perianal areas.1,2 Patients display a spectrum of lesions that vary in severity.8 Typical histologic examination reveals a dilapidated brick wall appearance. Pathology of well-developed lesions will show suprabasal acantholysis with minimal dyskeratosis.2
The generalized form of HHD is an extremely rare variant of the disease.10 Generalized HHD may resemble acute hypersensitivity reaction, erythema multiforme, and toxic epidermal necrolysis.1 Chronic diseases, such as psoriasis (as in this patient), also may contribute to a clinically confusing picture.8 Hailey-Hailey disease and psoriasis are thought to occasionally koebnerize (isomorphic response) to areas of trauma.16 Our patient experienced widespread erythematous papules and plaques not restricted to skin folds. His skin lesions continued to worsen over several months progressing to erythroderma. The presence of suprabasal acantholysis in a dilapidated brick wall pattern, along with the patient’s history, prior pathology reports, clinical picture, and negative direct immunofluorescence and indirect immunofluorescence studies helped to confirm the diagnosis of erythrodermic HHD.
Hailey-Hailey disease is caused by heterozygous mutations in the ATP2C1 gene on chromosome 3q21-24 coding for a Golgi ATPase called SPCA1 (secretory pathway calcium/manganese-ATPase).9 Subsequent disturbances in cytosolic-Golgi calcium concentrations interfere with epidermal keratinocyte adherence resulting in acantholytic disease. Studies of interfamilial and intrafamilial mutations fail to pinpoint a common mutation pattern among patients with generalized phenotypes,9 which further supports theories that intrinsic or extrinsic factors such as friction, heat, radiation, contact allergens, and infection affect the severity of HHD disease and not the type of mutation.3,9
Generalization of HHD is likely caused by nonspecific triggers in an already genetically disturbed epidermis.10 Interrupted epithelial function exposes skin to infections that exacerbate the underlying disease. Superimposing bacterial infections are commonly reported in HHD. Staphylococcus, Streptococcus, and Candida species colonize the skin and aggravate the disease.11 Much less commonly, HSV superinfection can complicate HHD.3-7 No data are currently available about the frequency or incidence of Herpesviridae in HHD.7 Some studies suggest that UVB light therapy can be an exacerbating factor in DAR and some but not all HHD patients,12,13 while other case reports14,15 document clinically improved responses using phototherapy for patients with HHD. Clinicians should remain suspicious and evaluate for HSV infection in refractory or sudden exacerbation of HHD.7 Furthermore, coexistent psoriasis and HHD also is a rare entity but has been described,8 which illustrates the importance of not attributing all skin manifestations to a previously diagnosed disorder but instead keeping an open mind in case new dermatologic conditions present themselves at a later time.
We present a rare case of erythrodermic HHD and coexistent psoriasis with HSV superinfection. We hope to draw awareness to this association of generalized HHD with both HSV and psoriasis to help clinicians make the correct diagnosis promptly in similar cases in the future.
- Chave TA, Milligan A. Acute generalized Hailey-Hailey disease. Clin Exp Dermatol. 2002;27:290-292.
- Mohr MR, Erdag G, Shada Al, et al. Two patients with Hailey-Hailey disease, multiple primary melanomas, and other cancers. Arch Dermatol. 2011;147:211-215.
- Lee GM, Kim YM, Lee SY, et al. A case of eczema herpeticum with Hailey-Hailey Disease. Ann Dermatol. 2009;21:311-314.
- Zaim MT, Bickers DR. Herpes simplex associated with Hailey-Hailey disease. J Am Acad Dermatol. 1987;17:701-702.
- Peppiatt T, Keefe M, White JE. Hailey-Hailey disease-exacerbation by herpes simplex virus and patch tests. Clin Exp Dermatol. 2006;17:201-202.
- Almeida L, Grossman ME. Benign familial pemphigus complicated by herpes simplex virus. Cutis. 1989;44:261-262.
- Nikkels AF, Delvenne P, Herfs M, et al. Occult herpes simplex virus colonization of bullous dermatitides. Am J Clin Dermatol. 2008;9:163-168.
- Chao SC, Lee JY, Wu MC, et al. A novel splice mutation in the ATP2C1 gene in a woman with concomitant psoriasis vulgaris and disseminated Hailey-Hailey disease. Int J Dermatol. 2012;51:947-951.
- Ikeda S, Shigihara T, Mayuzumi N, et al. Mutations of ATP2C1 in Japanese patients with Hailey-Hailey disease: intrafamilial and interfamilial phenotype variations and lack of correlation with mutation patterns. J Invest Dermatol. 2001;117:1654-1656.
- Marsch W, Stuttgen G. Generalized Hailey-Hailey disease. Br J Dermatol. 1978;99:553-559.
- Friedman-Birnbaum R, Haim S, Marcus S. Generalized familial benign chronic pemphigus. Dermatologica. 1980;161:112-115.
- Richard G, Linse R, Harth W. Hailey-Hailey disease. early detection of heterozygotes by an ultraviolet provocation tests—clinical relevance of the method. Hautarzt. 1993;44:376-379.
- Mayuzumi N, Ikeda S, Kawada H, et al. Effects of ultraviolet B irradiation, proinflammatory cytokines and raised extracellular calcium concentration on the expression of ATP2A2 and ATP2C1. Br J Dermatol. 2005;152:697-701.
- Vanderbeck KA, Giroux L, Murugan NJ, et al. Combined therapeutic use of oral alitretinoin and narrowband ultraviolet-B therapy in the treatment of Hailey-Hailey disease. Dermatol Rep. 2014;6:5604.
- Mizuno K, Hamada T, Hasimoto T, et al. Successful treatment with narrow-band UVB therapy for a case of generalized Hailey-Hailey disease with a novel splice-site mutation in ATP2C1 gene. Dermatol Ther. 2014;27:233-235.
- Thappa DM. The isomorphic phenomenon of Koebner. Indian J Dermatol Venereol Leprol. 2004;70:187-189.
To the Editor:
Hailey-Hailey disease (HHD), also known as benign familial pemphigus, is an uncommon autosomal-dominant skin disease.1 Defects in the ATPase type 2C member 1 gene, ATP2C1, result in abnormal intracellular epidermal adherence, and patients experience recurring blisters in skin folds. Longitudinal white streaks of the fingernails also may be present.1 The illness does not appear until puberty and is heightened by the second or third decade of life. Family history often suggests the presence of disease.2 Misdiagnosis of HHD occurs because of a wide spectrum of presentations. The presence of superimposed infections and carcinomas may both obscure and exacerbate this disease.2
Herpes simplex viruse types 1 and 2 (HSV-1 and HSV-2) are DNA viruses that cause common recurrent diseases. Usually, HSV-1 is associated with infection of the mouth and HSV-2 is associated with infection of the genitalia.3 Longitudinal cutaneous lesions manifest as grouped vesicles on an erythematous base. Tzanck smear of herpetic vesicles will reveal the presence of multinucleated giant cells. A direct fluorescent antibody technique also may be used to confirm the diagnosis.3
Erythrodermic HHD disease is a rare condition; moreover, there are only a few reported cases with coexistence of HHD and HSV in the literature.3-6 We report a rare presentation of erythrodermic HHD and coexistent psoriasis with HSV superinfection.
A 69-year-old man presented to an outpatient dermatology clinic for evaluation and treatment of a rash on the scalp, face, back, and lower legs. The patient confirmed a dandruff diagnosis on the scalp and face as well as psoriasis on the trunk and extremities for the last 45 years. He described a history of successful treatment with topical agents and UV light therapy. A family history revealed that the patient’s father and 1 of 2 siblings had a similar rash and “skin problems.” The patient had a medical history of thyroid cancer treated with radiation treatment and a partial thyroidectomy 35 years prior to the current presentation as well as incompletely treated chronic hepatitis C.
A search of medical records revealed a punch biopsy from the posterior neck that demonstrated an acantholytic dyskeratosis with suprabasal acantholysis. Clinicians were unable to differentiate if it was Darier disease (DAR) or HHD. Treatment of the patient’s seborrheic dermatitis and acantholytic disorder was successful at that time with ketoconazole shampoo, ketoconazole cream, desonide cream, and triamcinolone cream. The patient remained stable for 5 years before presenting again to the dermatology clinic for worsening rash despite topical therapies.
At the current presentation, physical examination at the outpatient dermatology clinic revealed few scaly, erythematous, eroded papules distributed on the mid-back; erythematous greasy scaling on the scalp, face, and chest; and pink scaly plaques with white-silvery scale on the anterior lower legs. Histopathology of a specimen from the right mid-back demonstrated acantholysis with suprabasal clefting, hyperkeratosis, and parakeratosis with no dyskeratotic cells identified. The pathologic differential diagnosis included primary acantholytic processes including Grover disease, DAR, HHD, and pemphigus. Pathology from the right shin demonstrated acanthosis, confluent parakeratosis with associated decreased granular cell layer and collections of neutrophils within the stratum corneum, spongiosis, and superficial dermal perivascular chronic inflammation with focal exocytosis and dilated blood vessels in the papillary dermis. The clinical and pathological diagnosis on the lower legs was consistent with psoriasis. Diagnoses of seborrheic dermatitis, psoriasis on the lower legs, and HHD vs DAR on the back and chest were made. The patient was instructed to continue ketoconazole shampoo, ketoconazole cream, and desonide for seborrheic dermatitis; fluocinonide ointment 0.05% to the lower legs for psoriasis; and triamcinolone cream and a bland moisturizer to the back and chest for HHD.
Over the ensuing months, the rash worsened with erythema and scaling affecting more than half of the body surface area. Topical corticosteroids and bland emollients resulted in minimal success. Biologics and acitretin were considered for the psoriasiform dermatitis but avoided due to the patient’s medical history of thyroid cancer and chronic hepatitis C infection. Because the patient described prior success with UV light therapy for psoriasis, he requested light therapy. A subsequent trial of narrowband UVB light therapy initially improved some of the psoriasiform dermatitis on the trunk and extremities; however, after 4 weeks of treatment, the patient described pain in some of the skin and felt he was burned by minimal exposure to light therapy on one particular visit, which caused him to stop light therapy.
Approximately 2 weeks later, the patient presented to the emergency department stating his psoriasis was infected; he was diagnosed with psoriasis with secondary cellulitis and received intravenous vancomycin and piperacillin-tazobactam, with bacterial cultures demonstrating Corynebacterium and methicillin-resistant Staphylococcus aureus. Some improvement was noted in the patient’s skin after antibiotics were initiated, but he continued to describe worsening “burning and pain” throughout the psoriasis lesions. The patient’s care was transferred to the Veterans Affairs hospital where a dermatology inpatient consultation was placed.
Our initial dermatologic examination revealed generalized scaly erythroderma on the neck, trunk, and extremities, sparing the face, palms, and soles (Figure 1). Multiple crusted and intact vesicles also were present overlying the erythematous plaques on the chest, back, and proximal extremities, most grouped in clusters. The patient endorsed new symptoms of pain and burning. Tzanck smear from the abdomen along with shave biopsies from the left flank and right abdomen were performed, and intravenous acyclovir was initiated immediately after these procedures.
Viral cultures were taken but were incorrectly processed by the laboratory. Tzanck smear showed severe acute inflammation with numerous neutrophils, multinucleated giant cells with viral nuclear changes, and positive immunostaining for HSV and negative immunostaining for herpes zoster. Both pathology specimens revealed an intense acute mixed, mainly neutrophilic, inflammatory infiltrate extending into the deeper dermis as well as distorted and necrotic hair follicles, some of which displayed multinucleated epithelial cells with margination of chromatin that were positive for both HSV-1 and HSV-2 and negative for herpes zoster (Figure 2). The positivity of both HSV strains might represent co-infection or could be a cross-reaction of antibodies used in immunohistochemistry to the HSV antigens. There was acantholysis surrounding the ulceration and extending through the full thickness of the epidermis with a dilapidated brick wall pattern (Figure 3) as well as negative immunohistochemical staining for HSV-1 and HSV-2 antigens. The clinical and histological picture together, along with prior clinical and pathological reports, confirmed the diagnoses of acute erythrodermic HHD with HSV superinfection.
The patient’s condition and pain improved within 24 hours on intravenous acyclovir. On the third day, his lesions were resolving and symptoms improved, so he was transitioned to oral acyclovir and discharged from the hospital. Follow-up in the dermatology outpatient clinic 1 week later revealed that all vesicles and papules had cleared, but the patient was still erythrodermic. Because HHD cannot always be distinguished histologically from other forms of pemphigus but yields a negative immunofluorescence, direct immunofluorescence and indirect immunofluorescence were obtained upon patient follow-up in the clinic and were both negative. Hepatitis C viral loads were undetectable. Consultations to gastroenterology and oncology teams were placed for consideration of systemic agents, and the patient was initiated on oral acitretin 25 mg daily, along with clobetasol as adjuvant therapy for any residual skin plaques. The laboratory results were closely monitored. Within 4 weeks after starting acitretin, the patient’s erythroderma had completely resolved. The patient has remained stable since then, except for one episode of secondary Staphylococcus infection that cleared on oral antibiotics. The patient remains stable and clear on oral acitretin 25 mg daily, with concomitant desonide cream and fluocinonide ointment as needed.
Hailey-Hailey disease is characterized by recurrent episodes of erythema, blisters, and plaques localized to intertriginous and perianal areas.1,2 Patients display a spectrum of lesions that vary in severity.8 Typical histologic examination reveals a dilapidated brick wall appearance. Pathology of well-developed lesions will show suprabasal acantholysis with minimal dyskeratosis.2
The generalized form of HHD is an extremely rare variant of the disease.10 Generalized HHD may resemble acute hypersensitivity reaction, erythema multiforme, and toxic epidermal necrolysis.1 Chronic diseases, such as psoriasis (as in this patient), also may contribute to a clinically confusing picture.8 Hailey-Hailey disease and psoriasis are thought to occasionally koebnerize (isomorphic response) to areas of trauma.16 Our patient experienced widespread erythematous papules and plaques not restricted to skin folds. His skin lesions continued to worsen over several months progressing to erythroderma. The presence of suprabasal acantholysis in a dilapidated brick wall pattern, along with the patient’s history, prior pathology reports, clinical picture, and negative direct immunofluorescence and indirect immunofluorescence studies helped to confirm the diagnosis of erythrodermic HHD.
Hailey-Hailey disease is caused by heterozygous mutations in the ATP2C1 gene on chromosome 3q21-24 coding for a Golgi ATPase called SPCA1 (secretory pathway calcium/manganese-ATPase).9 Subsequent disturbances in cytosolic-Golgi calcium concentrations interfere with epidermal keratinocyte adherence resulting in acantholytic disease. Studies of interfamilial and intrafamilial mutations fail to pinpoint a common mutation pattern among patients with generalized phenotypes,9 which further supports theories that intrinsic or extrinsic factors such as friction, heat, radiation, contact allergens, and infection affect the severity of HHD disease and not the type of mutation.3,9
Generalization of HHD is likely caused by nonspecific triggers in an already genetically disturbed epidermis.10 Interrupted epithelial function exposes skin to infections that exacerbate the underlying disease. Superimposing bacterial infections are commonly reported in HHD. Staphylococcus, Streptococcus, and Candida species colonize the skin and aggravate the disease.11 Much less commonly, HSV superinfection can complicate HHD.3-7 No data are currently available about the frequency or incidence of Herpesviridae in HHD.7 Some studies suggest that UVB light therapy can be an exacerbating factor in DAR and some but not all HHD patients,12,13 while other case reports14,15 document clinically improved responses using phototherapy for patients with HHD. Clinicians should remain suspicious and evaluate for HSV infection in refractory or sudden exacerbation of HHD.7 Furthermore, coexistent psoriasis and HHD also is a rare entity but has been described,8 which illustrates the importance of not attributing all skin manifestations to a previously diagnosed disorder but instead keeping an open mind in case new dermatologic conditions present themselves at a later time.
We present a rare case of erythrodermic HHD and coexistent psoriasis with HSV superinfection. We hope to draw awareness to this association of generalized HHD with both HSV and psoriasis to help clinicians make the correct diagnosis promptly in similar cases in the future.
To the Editor:
Hailey-Hailey disease (HHD), also known as benign familial pemphigus, is an uncommon autosomal-dominant skin disease.1 Defects in the ATPase type 2C member 1 gene, ATP2C1, result in abnormal intracellular epidermal adherence, and patients experience recurring blisters in skin folds. Longitudinal white streaks of the fingernails also may be present.1 The illness does not appear until puberty and is heightened by the second or third decade of life. Family history often suggests the presence of disease.2 Misdiagnosis of HHD occurs because of a wide spectrum of presentations. The presence of superimposed infections and carcinomas may both obscure and exacerbate this disease.2
Herpes simplex viruse types 1 and 2 (HSV-1 and HSV-2) are DNA viruses that cause common recurrent diseases. Usually, HSV-1 is associated with infection of the mouth and HSV-2 is associated with infection of the genitalia.3 Longitudinal cutaneous lesions manifest as grouped vesicles on an erythematous base. Tzanck smear of herpetic vesicles will reveal the presence of multinucleated giant cells. A direct fluorescent antibody technique also may be used to confirm the diagnosis.3
Erythrodermic HHD disease is a rare condition; moreover, there are only a few reported cases with coexistence of HHD and HSV in the literature.3-6 We report a rare presentation of erythrodermic HHD and coexistent psoriasis with HSV superinfection.
A 69-year-old man presented to an outpatient dermatology clinic for evaluation and treatment of a rash on the scalp, face, back, and lower legs. The patient confirmed a dandruff diagnosis on the scalp and face as well as psoriasis on the trunk and extremities for the last 45 years. He described a history of successful treatment with topical agents and UV light therapy. A family history revealed that the patient’s father and 1 of 2 siblings had a similar rash and “skin problems.” The patient had a medical history of thyroid cancer treated with radiation treatment and a partial thyroidectomy 35 years prior to the current presentation as well as incompletely treated chronic hepatitis C.
A search of medical records revealed a punch biopsy from the posterior neck that demonstrated an acantholytic dyskeratosis with suprabasal acantholysis. Clinicians were unable to differentiate if it was Darier disease (DAR) or HHD. Treatment of the patient’s seborrheic dermatitis and acantholytic disorder was successful at that time with ketoconazole shampoo, ketoconazole cream, desonide cream, and triamcinolone cream. The patient remained stable for 5 years before presenting again to the dermatology clinic for worsening rash despite topical therapies.
At the current presentation, physical examination at the outpatient dermatology clinic revealed few scaly, erythematous, eroded papules distributed on the mid-back; erythematous greasy scaling on the scalp, face, and chest; and pink scaly plaques with white-silvery scale on the anterior lower legs. Histopathology of a specimen from the right mid-back demonstrated acantholysis with suprabasal clefting, hyperkeratosis, and parakeratosis with no dyskeratotic cells identified. The pathologic differential diagnosis included primary acantholytic processes including Grover disease, DAR, HHD, and pemphigus. Pathology from the right shin demonstrated acanthosis, confluent parakeratosis with associated decreased granular cell layer and collections of neutrophils within the stratum corneum, spongiosis, and superficial dermal perivascular chronic inflammation with focal exocytosis and dilated blood vessels in the papillary dermis. The clinical and pathological diagnosis on the lower legs was consistent with psoriasis. Diagnoses of seborrheic dermatitis, psoriasis on the lower legs, and HHD vs DAR on the back and chest were made. The patient was instructed to continue ketoconazole shampoo, ketoconazole cream, and desonide for seborrheic dermatitis; fluocinonide ointment 0.05% to the lower legs for psoriasis; and triamcinolone cream and a bland moisturizer to the back and chest for HHD.
Over the ensuing months, the rash worsened with erythema and scaling affecting more than half of the body surface area. Topical corticosteroids and bland emollients resulted in minimal success. Biologics and acitretin were considered for the psoriasiform dermatitis but avoided due to the patient’s medical history of thyroid cancer and chronic hepatitis C infection. Because the patient described prior success with UV light therapy for psoriasis, he requested light therapy. A subsequent trial of narrowband UVB light therapy initially improved some of the psoriasiform dermatitis on the trunk and extremities; however, after 4 weeks of treatment, the patient described pain in some of the skin and felt he was burned by minimal exposure to light therapy on one particular visit, which caused him to stop light therapy.
Approximately 2 weeks later, the patient presented to the emergency department stating his psoriasis was infected; he was diagnosed with psoriasis with secondary cellulitis and received intravenous vancomycin and piperacillin-tazobactam, with bacterial cultures demonstrating Corynebacterium and methicillin-resistant Staphylococcus aureus. Some improvement was noted in the patient’s skin after antibiotics were initiated, but he continued to describe worsening “burning and pain” throughout the psoriasis lesions. The patient’s care was transferred to the Veterans Affairs hospital where a dermatology inpatient consultation was placed.
Our initial dermatologic examination revealed generalized scaly erythroderma on the neck, trunk, and extremities, sparing the face, palms, and soles (Figure 1). Multiple crusted and intact vesicles also were present overlying the erythematous plaques on the chest, back, and proximal extremities, most grouped in clusters. The patient endorsed new symptoms of pain and burning. Tzanck smear from the abdomen along with shave biopsies from the left flank and right abdomen were performed, and intravenous acyclovir was initiated immediately after these procedures.
Viral cultures were taken but were incorrectly processed by the laboratory. Tzanck smear showed severe acute inflammation with numerous neutrophils, multinucleated giant cells with viral nuclear changes, and positive immunostaining for HSV and negative immunostaining for herpes zoster. Both pathology specimens revealed an intense acute mixed, mainly neutrophilic, inflammatory infiltrate extending into the deeper dermis as well as distorted and necrotic hair follicles, some of which displayed multinucleated epithelial cells with margination of chromatin that were positive for both HSV-1 and HSV-2 and negative for herpes zoster (Figure 2). The positivity of both HSV strains might represent co-infection or could be a cross-reaction of antibodies used in immunohistochemistry to the HSV antigens. There was acantholysis surrounding the ulceration and extending through the full thickness of the epidermis with a dilapidated brick wall pattern (Figure 3) as well as negative immunohistochemical staining for HSV-1 and HSV-2 antigens. The clinical and histological picture together, along with prior clinical and pathological reports, confirmed the diagnoses of acute erythrodermic HHD with HSV superinfection.
The patient’s condition and pain improved within 24 hours on intravenous acyclovir. On the third day, his lesions were resolving and symptoms improved, so he was transitioned to oral acyclovir and discharged from the hospital. Follow-up in the dermatology outpatient clinic 1 week later revealed that all vesicles and papules had cleared, but the patient was still erythrodermic. Because HHD cannot always be distinguished histologically from other forms of pemphigus but yields a negative immunofluorescence, direct immunofluorescence and indirect immunofluorescence were obtained upon patient follow-up in the clinic and were both negative. Hepatitis C viral loads were undetectable. Consultations to gastroenterology and oncology teams were placed for consideration of systemic agents, and the patient was initiated on oral acitretin 25 mg daily, along with clobetasol as adjuvant therapy for any residual skin plaques. The laboratory results were closely monitored. Within 4 weeks after starting acitretin, the patient’s erythroderma had completely resolved. The patient has remained stable since then, except for one episode of secondary Staphylococcus infection that cleared on oral antibiotics. The patient remains stable and clear on oral acitretin 25 mg daily, with concomitant desonide cream and fluocinonide ointment as needed.
Hailey-Hailey disease is characterized by recurrent episodes of erythema, blisters, and plaques localized to intertriginous and perianal areas.1,2 Patients display a spectrum of lesions that vary in severity.8 Typical histologic examination reveals a dilapidated brick wall appearance. Pathology of well-developed lesions will show suprabasal acantholysis with minimal dyskeratosis.2
The generalized form of HHD is an extremely rare variant of the disease.10 Generalized HHD may resemble acute hypersensitivity reaction, erythema multiforme, and toxic epidermal necrolysis.1 Chronic diseases, such as psoriasis (as in this patient), also may contribute to a clinically confusing picture.8 Hailey-Hailey disease and psoriasis are thought to occasionally koebnerize (isomorphic response) to areas of trauma.16 Our patient experienced widespread erythematous papules and plaques not restricted to skin folds. His skin lesions continued to worsen over several months progressing to erythroderma. The presence of suprabasal acantholysis in a dilapidated brick wall pattern, along with the patient’s history, prior pathology reports, clinical picture, and negative direct immunofluorescence and indirect immunofluorescence studies helped to confirm the diagnosis of erythrodermic HHD.
Hailey-Hailey disease is caused by heterozygous mutations in the ATP2C1 gene on chromosome 3q21-24 coding for a Golgi ATPase called SPCA1 (secretory pathway calcium/manganese-ATPase).9 Subsequent disturbances in cytosolic-Golgi calcium concentrations interfere with epidermal keratinocyte adherence resulting in acantholytic disease. Studies of interfamilial and intrafamilial mutations fail to pinpoint a common mutation pattern among patients with generalized phenotypes,9 which further supports theories that intrinsic or extrinsic factors such as friction, heat, radiation, contact allergens, and infection affect the severity of HHD disease and not the type of mutation.3,9
Generalization of HHD is likely caused by nonspecific triggers in an already genetically disturbed epidermis.10 Interrupted epithelial function exposes skin to infections that exacerbate the underlying disease. Superimposing bacterial infections are commonly reported in HHD. Staphylococcus, Streptococcus, and Candida species colonize the skin and aggravate the disease.11 Much less commonly, HSV superinfection can complicate HHD.3-7 No data are currently available about the frequency or incidence of Herpesviridae in HHD.7 Some studies suggest that UVB light therapy can be an exacerbating factor in DAR and some but not all HHD patients,12,13 while other case reports14,15 document clinically improved responses using phototherapy for patients with HHD. Clinicians should remain suspicious and evaluate for HSV infection in refractory or sudden exacerbation of HHD.7 Furthermore, coexistent psoriasis and HHD also is a rare entity but has been described,8 which illustrates the importance of not attributing all skin manifestations to a previously diagnosed disorder but instead keeping an open mind in case new dermatologic conditions present themselves at a later time.
We present a rare case of erythrodermic HHD and coexistent psoriasis with HSV superinfection. We hope to draw awareness to this association of generalized HHD with both HSV and psoriasis to help clinicians make the correct diagnosis promptly in similar cases in the future.
- Chave TA, Milligan A. Acute generalized Hailey-Hailey disease. Clin Exp Dermatol. 2002;27:290-292.
- Mohr MR, Erdag G, Shada Al, et al. Two patients with Hailey-Hailey disease, multiple primary melanomas, and other cancers. Arch Dermatol. 2011;147:211-215.
- Lee GM, Kim YM, Lee SY, et al. A case of eczema herpeticum with Hailey-Hailey Disease. Ann Dermatol. 2009;21:311-314.
- Zaim MT, Bickers DR. Herpes simplex associated with Hailey-Hailey disease. J Am Acad Dermatol. 1987;17:701-702.
- Peppiatt T, Keefe M, White JE. Hailey-Hailey disease-exacerbation by herpes simplex virus and patch tests. Clin Exp Dermatol. 2006;17:201-202.
- Almeida L, Grossman ME. Benign familial pemphigus complicated by herpes simplex virus. Cutis. 1989;44:261-262.
- Nikkels AF, Delvenne P, Herfs M, et al. Occult herpes simplex virus colonization of bullous dermatitides. Am J Clin Dermatol. 2008;9:163-168.
- Chao SC, Lee JY, Wu MC, et al. A novel splice mutation in the ATP2C1 gene in a woman with concomitant psoriasis vulgaris and disseminated Hailey-Hailey disease. Int J Dermatol. 2012;51:947-951.
- Ikeda S, Shigihara T, Mayuzumi N, et al. Mutations of ATP2C1 in Japanese patients with Hailey-Hailey disease: intrafamilial and interfamilial phenotype variations and lack of correlation with mutation patterns. J Invest Dermatol. 2001;117:1654-1656.
- Marsch W, Stuttgen G. Generalized Hailey-Hailey disease. Br J Dermatol. 1978;99:553-559.
- Friedman-Birnbaum R, Haim S, Marcus S. Generalized familial benign chronic pemphigus. Dermatologica. 1980;161:112-115.
- Richard G, Linse R, Harth W. Hailey-Hailey disease. early detection of heterozygotes by an ultraviolet provocation tests—clinical relevance of the method. Hautarzt. 1993;44:376-379.
- Mayuzumi N, Ikeda S, Kawada H, et al. Effects of ultraviolet B irradiation, proinflammatory cytokines and raised extracellular calcium concentration on the expression of ATP2A2 and ATP2C1. Br J Dermatol. 2005;152:697-701.
- Vanderbeck KA, Giroux L, Murugan NJ, et al. Combined therapeutic use of oral alitretinoin and narrowband ultraviolet-B therapy in the treatment of Hailey-Hailey disease. Dermatol Rep. 2014;6:5604.
- Mizuno K, Hamada T, Hasimoto T, et al. Successful treatment with narrow-band UVB therapy for a case of generalized Hailey-Hailey disease with a novel splice-site mutation in ATP2C1 gene. Dermatol Ther. 2014;27:233-235.
- Thappa DM. The isomorphic phenomenon of Koebner. Indian J Dermatol Venereol Leprol. 2004;70:187-189.
- Chave TA, Milligan A. Acute generalized Hailey-Hailey disease. Clin Exp Dermatol. 2002;27:290-292.
- Mohr MR, Erdag G, Shada Al, et al. Two patients with Hailey-Hailey disease, multiple primary melanomas, and other cancers. Arch Dermatol. 2011;147:211-215.
- Lee GM, Kim YM, Lee SY, et al. A case of eczema herpeticum with Hailey-Hailey Disease. Ann Dermatol. 2009;21:311-314.
- Zaim MT, Bickers DR. Herpes simplex associated with Hailey-Hailey disease. J Am Acad Dermatol. 1987;17:701-702.
- Peppiatt T, Keefe M, White JE. Hailey-Hailey disease-exacerbation by herpes simplex virus and patch tests. Clin Exp Dermatol. 2006;17:201-202.
- Almeida L, Grossman ME. Benign familial pemphigus complicated by herpes simplex virus. Cutis. 1989;44:261-262.
- Nikkels AF, Delvenne P, Herfs M, et al. Occult herpes simplex virus colonization of bullous dermatitides. Am J Clin Dermatol. 2008;9:163-168.
- Chao SC, Lee JY, Wu MC, et al. A novel splice mutation in the ATP2C1 gene in a woman with concomitant psoriasis vulgaris and disseminated Hailey-Hailey disease. Int J Dermatol. 2012;51:947-951.
- Ikeda S, Shigihara T, Mayuzumi N, et al. Mutations of ATP2C1 in Japanese patients with Hailey-Hailey disease: intrafamilial and interfamilial phenotype variations and lack of correlation with mutation patterns. J Invest Dermatol. 2001;117:1654-1656.
- Marsch W, Stuttgen G. Generalized Hailey-Hailey disease. Br J Dermatol. 1978;99:553-559.
- Friedman-Birnbaum R, Haim S, Marcus S. Generalized familial benign chronic pemphigus. Dermatologica. 1980;161:112-115.
- Richard G, Linse R, Harth W. Hailey-Hailey disease. early detection of heterozygotes by an ultraviolet provocation tests—clinical relevance of the method. Hautarzt. 1993;44:376-379.
- Mayuzumi N, Ikeda S, Kawada H, et al. Effects of ultraviolet B irradiation, proinflammatory cytokines and raised extracellular calcium concentration on the expression of ATP2A2 and ATP2C1. Br J Dermatol. 2005;152:697-701.
- Vanderbeck KA, Giroux L, Murugan NJ, et al. Combined therapeutic use of oral alitretinoin and narrowband ultraviolet-B therapy in the treatment of Hailey-Hailey disease. Dermatol Rep. 2014;6:5604.
- Mizuno K, Hamada T, Hasimoto T, et al. Successful treatment with narrow-band UVB therapy for a case of generalized Hailey-Hailey disease with a novel splice-site mutation in ATP2C1 gene. Dermatol Ther. 2014;27:233-235.
- Thappa DM. The isomorphic phenomenon of Koebner. Indian J Dermatol Venereol Leprol. 2004;70:187-189.
Practice Points
- Misdiagnosis of Hailey-Hailey disease (HHD) occurs because of a wide spectrum of presentations.
- Hailey-Hailey disease and psoriasis are thought to occasionally koebnerize (isomorphic response) to areas of trauma.
- Clinicians should remain suspicious and evaluate for herpes simplex virus infection in refractory or sudden exacerbation of HHD.
New Insights Into the Dermatology Residency Application Process Amid the COVID-19 Pandemic
Residency application is an arduous experience for many medical students. The National Resident Matching Program reported that US medical school seniors who matched into dermatology applied to a median of 90 programs and attended 9 interviews in 2019.1 High application and interview travel costs are a disadvantage for applicants from lower socioeconomic backgrounds. We propose that the coronavirus disease 2019 (COVID-19) pandemic should serve as a call to action for dermatology to update and promote a more equitable, time-effective, and cost-efficient residency interview process.
In light of COVID-19, dermatology residency program directors have recommended a holistic application review process, taking into consideration “disparities in strength of applications due to lack of opportunity for students with smaller home programs or in areas more affected by this crisis.”2 However, in a 2018 survey of 180 dermatology faculty members, 80% stated that time spent reviewing residency applications was already excessive.3 The Association of American Medical Colleges reported that for medical student applicants with US Medical Licensing Examination Step 1 scores lower than 237 or higher than 251, the value added by submitting one additional application beyond means of 43 (95% confidence interval [CI], 34-53) and 34 (95% CI, 28-41), respectively, is reduced relative to the value added by each application before reaching the point of diminishing returns.4 Therefore, we suggest limiting the number of applications per applicant to the upper bounds of the CI for the lower US Medical Licensing Examination Step 1 score (53), facilitating a more detailed review of fewer applications by each program and limiting student expenses.
On May 7, 2020, the Association of American Medical Colleges made a statement strongly encouraging medical school and teaching hospital faculty to conduct interviews through videoconferencing.5 Videoconferencing interviews (VCIs) minimize travel-associated health risks, providing a more equitable structure for applicants and programs in areas disproportionately impacted by the pandemic. In the 2018 survey of dermatology faculty members, only 11% believed that applicants interviewing virtually received equal consideration to those interviewing in person; a solution to this problem would be to mandate that all applicants use VCIs during the COVID-19 pandemic.3 This coming year, residency programs may elect to replace in-person interviews with VCIs, or they may utilize VCIs as screening tools to narrow down the applicant pool and for students to rank their preferred programs prior to an in-person interview. By inviting fewer applicants for in-person interviews, travel-associated health risks, financial costs, and missed educational activities would be minimized. Given that many medical students have had academic activities cancelled or postponed due to COVID-19, student opportunities for live clinical experiences should be maximized.
As programs plan for future application cycles beyond COVID-19, they must work to balance competing interests. Videoconferencing interviews allow for improved access to interviewing for applicants of lower socioeconomic classes, improved geographic mobility of applicants, and increased flexibility in accommodating faculty schedules with reduced time away from patient care and research; however, with VCIs one may lose the personal element that comes from the in-person interview, including interactions among applicants, faculty, current residents, and staff on the day of interview, as well as the departmental tour. Additionally, the quality of VCIs may be diminished by technical difficulties and the possibility of distractions, making standardization of the interview experience for applicants challenging.
The COVID-19 pandemic will surely leave its mark on the residency application cycle. We must take time now to collaborate and brainstorm creative solutions to maximize the equity and efficiency of the application process for both residency programs and students. We welcome reader feedback on these ideas and other possible solutions in the form of Letters to the Editor.
- National Resident Matching Program. Results of the 2019 NRMP Applicant Survey by Preferred Specialty and Applicant Type. Washington, DC: National Resident Matching Program; 2019. https://mk0nrmp3oyqui6wqfm.kinstacdn.com/wp-content/uploads/2019/06/Applicant-Survey-Report-2019.pdf. Accessed June 22, 2020.
- Association of American Medical Colleges. Specialty response to COVID-19: dermatology residency program director consensus statement on 2020-21 application cycle. https://aamc-orange.global.ssl.fastly.net/production/media/filer_
public/0f/7b/0f7b547e-65b5-4d93-8247-951206e7f726/updated_dermatology_program_director_
statement_on_2020-21_application_cycle_.pdf. Updated June 1, 2020. Accessed June 24, 2020. - Rojek NW, Shinkai K, Fett N. Dermatology faculty and residents’ perspectives on the dermatology residency application process: a nationwide survey. J Am Acad Dermatol. 2018;79:157-159.
- Association of American Medical Colleges. Apply smart: data to consider when applying to residency. https://www.students-residents.aamc.org/applying-residency/filteredresult/apply-smart-data-consider-when-applying-residency/. Accessed June 22, 2020.
- Association of American Medical Colleges. Conducting interviews during the coronavirus pandemic. https://www.aamc.org/what-we-do/mission-areas/medical-education/conducting-interviews-during-coronavirus-pandemic/. Published May 7, 2020. Accessed June 22, 2020.
Residency application is an arduous experience for many medical students. The National Resident Matching Program reported that US medical school seniors who matched into dermatology applied to a median of 90 programs and attended 9 interviews in 2019.1 High application and interview travel costs are a disadvantage for applicants from lower socioeconomic backgrounds. We propose that the coronavirus disease 2019 (COVID-19) pandemic should serve as a call to action for dermatology to update and promote a more equitable, time-effective, and cost-efficient residency interview process.
In light of COVID-19, dermatology residency program directors have recommended a holistic application review process, taking into consideration “disparities in strength of applications due to lack of opportunity for students with smaller home programs or in areas more affected by this crisis.”2 However, in a 2018 survey of 180 dermatology faculty members, 80% stated that time spent reviewing residency applications was already excessive.3 The Association of American Medical Colleges reported that for medical student applicants with US Medical Licensing Examination Step 1 scores lower than 237 or higher than 251, the value added by submitting one additional application beyond means of 43 (95% confidence interval [CI], 34-53) and 34 (95% CI, 28-41), respectively, is reduced relative to the value added by each application before reaching the point of diminishing returns.4 Therefore, we suggest limiting the number of applications per applicant to the upper bounds of the CI for the lower US Medical Licensing Examination Step 1 score (53), facilitating a more detailed review of fewer applications by each program and limiting student expenses.
On May 7, 2020, the Association of American Medical Colleges made a statement strongly encouraging medical school and teaching hospital faculty to conduct interviews through videoconferencing.5 Videoconferencing interviews (VCIs) minimize travel-associated health risks, providing a more equitable structure for applicants and programs in areas disproportionately impacted by the pandemic. In the 2018 survey of dermatology faculty members, only 11% believed that applicants interviewing virtually received equal consideration to those interviewing in person; a solution to this problem would be to mandate that all applicants use VCIs during the COVID-19 pandemic.3 This coming year, residency programs may elect to replace in-person interviews with VCIs, or they may utilize VCIs as screening tools to narrow down the applicant pool and for students to rank their preferred programs prior to an in-person interview. By inviting fewer applicants for in-person interviews, travel-associated health risks, financial costs, and missed educational activities would be minimized. Given that many medical students have had academic activities cancelled or postponed due to COVID-19, student opportunities for live clinical experiences should be maximized.
As programs plan for future application cycles beyond COVID-19, they must work to balance competing interests. Videoconferencing interviews allow for improved access to interviewing for applicants of lower socioeconomic classes, improved geographic mobility of applicants, and increased flexibility in accommodating faculty schedules with reduced time away from patient care and research; however, with VCIs one may lose the personal element that comes from the in-person interview, including interactions among applicants, faculty, current residents, and staff on the day of interview, as well as the departmental tour. Additionally, the quality of VCIs may be diminished by technical difficulties and the possibility of distractions, making standardization of the interview experience for applicants challenging.
The COVID-19 pandemic will surely leave its mark on the residency application cycle. We must take time now to collaborate and brainstorm creative solutions to maximize the equity and efficiency of the application process for both residency programs and students. We welcome reader feedback on these ideas and other possible solutions in the form of Letters to the Editor.
Residency application is an arduous experience for many medical students. The National Resident Matching Program reported that US medical school seniors who matched into dermatology applied to a median of 90 programs and attended 9 interviews in 2019.1 High application and interview travel costs are a disadvantage for applicants from lower socioeconomic backgrounds. We propose that the coronavirus disease 2019 (COVID-19) pandemic should serve as a call to action for dermatology to update and promote a more equitable, time-effective, and cost-efficient residency interview process.
In light of COVID-19, dermatology residency program directors have recommended a holistic application review process, taking into consideration “disparities in strength of applications due to lack of opportunity for students with smaller home programs or in areas more affected by this crisis.”2 However, in a 2018 survey of 180 dermatology faculty members, 80% stated that time spent reviewing residency applications was already excessive.3 The Association of American Medical Colleges reported that for medical student applicants with US Medical Licensing Examination Step 1 scores lower than 237 or higher than 251, the value added by submitting one additional application beyond means of 43 (95% confidence interval [CI], 34-53) and 34 (95% CI, 28-41), respectively, is reduced relative to the value added by each application before reaching the point of diminishing returns.4 Therefore, we suggest limiting the number of applications per applicant to the upper bounds of the CI for the lower US Medical Licensing Examination Step 1 score (53), facilitating a more detailed review of fewer applications by each program and limiting student expenses.
On May 7, 2020, the Association of American Medical Colleges made a statement strongly encouraging medical school and teaching hospital faculty to conduct interviews through videoconferencing.5 Videoconferencing interviews (VCIs) minimize travel-associated health risks, providing a more equitable structure for applicants and programs in areas disproportionately impacted by the pandemic. In the 2018 survey of dermatology faculty members, only 11% believed that applicants interviewing virtually received equal consideration to those interviewing in person; a solution to this problem would be to mandate that all applicants use VCIs during the COVID-19 pandemic.3 This coming year, residency programs may elect to replace in-person interviews with VCIs, or they may utilize VCIs as screening tools to narrow down the applicant pool and for students to rank their preferred programs prior to an in-person interview. By inviting fewer applicants for in-person interviews, travel-associated health risks, financial costs, and missed educational activities would be minimized. Given that many medical students have had academic activities cancelled or postponed due to COVID-19, student opportunities for live clinical experiences should be maximized.
As programs plan for future application cycles beyond COVID-19, they must work to balance competing interests. Videoconferencing interviews allow for improved access to interviewing for applicants of lower socioeconomic classes, improved geographic mobility of applicants, and increased flexibility in accommodating faculty schedules with reduced time away from patient care and research; however, with VCIs one may lose the personal element that comes from the in-person interview, including interactions among applicants, faculty, current residents, and staff on the day of interview, as well as the departmental tour. Additionally, the quality of VCIs may be diminished by technical difficulties and the possibility of distractions, making standardization of the interview experience for applicants challenging.
The COVID-19 pandemic will surely leave its mark on the residency application cycle. We must take time now to collaborate and brainstorm creative solutions to maximize the equity and efficiency of the application process for both residency programs and students. We welcome reader feedback on these ideas and other possible solutions in the form of Letters to the Editor.
- National Resident Matching Program. Results of the 2019 NRMP Applicant Survey by Preferred Specialty and Applicant Type. Washington, DC: National Resident Matching Program; 2019. https://mk0nrmp3oyqui6wqfm.kinstacdn.com/wp-content/uploads/2019/06/Applicant-Survey-Report-2019.pdf. Accessed June 22, 2020.
- Association of American Medical Colleges. Specialty response to COVID-19: dermatology residency program director consensus statement on 2020-21 application cycle. https://aamc-orange.global.ssl.fastly.net/production/media/filer_
public/0f/7b/0f7b547e-65b5-4d93-8247-951206e7f726/updated_dermatology_program_director_
statement_on_2020-21_application_cycle_.pdf. Updated June 1, 2020. Accessed June 24, 2020. - Rojek NW, Shinkai K, Fett N. Dermatology faculty and residents’ perspectives on the dermatology residency application process: a nationwide survey. J Am Acad Dermatol. 2018;79:157-159.
- Association of American Medical Colleges. Apply smart: data to consider when applying to residency. https://www.students-residents.aamc.org/applying-residency/filteredresult/apply-smart-data-consider-when-applying-residency/. Accessed June 22, 2020.
- Association of American Medical Colleges. Conducting interviews during the coronavirus pandemic. https://www.aamc.org/what-we-do/mission-areas/medical-education/conducting-interviews-during-coronavirus-pandemic/. Published May 7, 2020. Accessed June 22, 2020.
- National Resident Matching Program. Results of the 2019 NRMP Applicant Survey by Preferred Specialty and Applicant Type. Washington, DC: National Resident Matching Program; 2019. https://mk0nrmp3oyqui6wqfm.kinstacdn.com/wp-content/uploads/2019/06/Applicant-Survey-Report-2019.pdf. Accessed June 22, 2020.
- Association of American Medical Colleges. Specialty response to COVID-19: dermatology residency program director consensus statement on 2020-21 application cycle. https://aamc-orange.global.ssl.fastly.net/production/media/filer_
public/0f/7b/0f7b547e-65b5-4d93-8247-951206e7f726/updated_dermatology_program_director_
statement_on_2020-21_application_cycle_.pdf. Updated June 1, 2020. Accessed June 24, 2020. - Rojek NW, Shinkai K, Fett N. Dermatology faculty and residents’ perspectives on the dermatology residency application process: a nationwide survey. J Am Acad Dermatol. 2018;79:157-159.
- Association of American Medical Colleges. Apply smart: data to consider when applying to residency. https://www.students-residents.aamc.org/applying-residency/filteredresult/apply-smart-data-consider-when-applying-residency/. Accessed June 22, 2020.
- Association of American Medical Colleges. Conducting interviews during the coronavirus pandemic. https://www.aamc.org/what-we-do/mission-areas/medical-education/conducting-interviews-during-coronavirus-pandemic/. Published May 7, 2020. Accessed June 22, 2020.
Practice Points
- We propose that the coronavirus disease 2019 pandemic should serve as a call to action for dermatology to update and promote a more equitable, time-effective, and cost-efficient residency interview process.
- A limitation on the number of applications per candidate may lower expenses and allow for a more holistic review process by residency programs.
- The benefits and challenges of videoconferencing interviews must be weighed as residency programs decide on their continued use beyond this application cycle.
Rapid Screening of Invasive Fungal Infections in the Hospital Setting Using the (1,3)-β-D-glucan Assay
Practice Gap
Invasive fungal infections are a leading cause of morbidity and mortality among neutropenic, immunocompromised, and critically ill patients. Candida species are the most common cause of fungemia, with portals of entry into the bloodstream including the gastrointestinal tract, contaminated intravascular catheters, and localized foci of infection.1 Diagnosis of invasive candidiasis remains challenging due to an absence of specific clinical signs and symptoms, varying from a mild fever that is unresponsive to antibiotics to florid sepsis. When present, clinical clues may include chorioretinitis; muscle abscesses; and skin eruptions, characteristically with Candida tropicalis. Cutaneous manifestations of disseminated Candida infections appear in only 13% of affected patients.1 The lesions typically present as 5- to 10-mm pink dermal papules or painless pustules on an erythematous base and may be singular, localized, or diffuse in distribution. Body regions normally involved are the trunk, arms, and legs, rarely the head and neck.1 Cutaneous lesions often develop at a time when patients are febrile, are not responding to antibiotics, and are clinically deteriorating.
A 15-year-old adolescent boy with pre–B-cell acute lymphoblastic leukemia was admitted with febrile neutropenia for presumed septic shock secondary to an unknown infectious etiology. The patient was started on broad-spectrum intravenous antibiotics, and blood cultures were obtained. On the second day of hospitalization, he developed approximately 10 to 15 discrete, 3- to 6-mm, pink to violaceous papules scattered on the chest and arms (Figure 1). Over several hours, the number of lesions increased to more than 50 with involvement of the legs (Figure 2). A punch biopsy of lesional skin from the left dorsal wrist demonstrated a circumscribed abscess of yeast in the papillary dermis, which was highlighted by periodic acid–Schiff staining with minimal associated inflammation (Figure 3). Blood and tissue cultures persistently grew C tropicalis. The patient was started on intravenous liposomal amphotericin B but died on day 5 of hospitalization after developing endocarditis.
Early and reliable diagnosis of Candida species fungemia is of critical importance to successful treatment, particularly with the emergence of multidrug-resistant strains such as Candida auris.2 In patients with apparent cutaneous manifestations, a lesional punch biopsy for culture and histopathologic evaluation is recommended in addition to blood culture; however, organisms may or may not be present in large numbers, and they may be difficult to identify on routine hematoxylin and eosin–stained tissue sections. To enhance the likelihood of highlighting the fungus within the sample, the pathologist must be made aware of the presumptive diagnosis of disseminated candidiasis so that special techniques can be utilized, such as periodic acid–Schiff stain.
Although positive blood culture is the gold standard for candidemia diagnosis, only 30% to 50% of patients with disseminated candidiasis had positive blood cultures at autopsy.1 Another study showed the sensitivity of blood culture for the detection of invasive fungal infection to be as low as 8.3%.3 In cases with positive blood cultures, the median time to positivity is 2 to 3 days, but it can take as long as 8 days, thus limiting its clinical utility in acutely ill patients.4 Given the low sensitivity and prolonged time required for culture growth of most fungal organisms, novel assays for rapid, non–culture-based diagnosis of systemic fungal infections hold substantial clinical promise moving forward.
The Technique
One of the more promising non–culture-based fungal diagnostic methodologies is an antigen assay based on the detection of serum (1,3)-β-D-glucan (BDG), a major cell wall constituent of most pathogenic fungi. This assay is not specific for Candida species and can be positive for Aspergillosis species, Fusarium species, Coccidioides immitis, Histoplasma capsulatum, and Pneumocystis jirovecii pneumonia, among others; therefore, it functions as a general biomarker for fungi in the bloodstream.4,5 (1,3)-β-D-glucan assay can be useful as an adjunct for blood cultures and punch biopsy, especially when cultures are negative or the results remain outstanding. The results of the BDG assay are available in less than 24 hours at minimal cost, and the test is approved by the US Food and Drug Administration for use as an aid in invasive fungal disease diagnosis. In a meta-analysis of 11 studies, BDG sensitivity was 75%.4 In a study based on autopsy cases from 6 years, BDG specificity was 98.4% with positive and negative predictive values of 86.7% and 97.1%, respectively.3 Optimal results were achieved when 2 consecutive tests were positive.4 The serum assay output is based on spectrophotometer readings, which are converted to BDG concentrations (negative, <60 pg/mL; indeterminate, 60–79 pg/mL; positive ≥80 pg/mL).5 Although we cannot be certain, utilizing the BDG assay in our patient may have led to earlier treatment and a better outcome.
A disadvantage of the BDG assay is the potential for false-positive results, which have been reported in lung transplant recipients with respiratory mold colonization and patients with other systemic bacterial infections.4 False-positive results also have been associated with use of ampicillin-clavulanate and piperacillin-tazobactam antibiotics and human blood products, hemodialysis, and severe mucositis, thus reaffirming the importance of judicious interpretation of BDG assay results by the clinician.4,6 There also is a potential for false-negative results, as the BDG assay does not detect certain fungal species such as Cryptococcus species and Blastomyces dermatitidis, which produce very low levels of BDG, or zygomycetes (Absidia, Mucor, and Rizopus species), which are not known to produce BDG.6
Practice Implications
In the setting of invasive fungal infections, a high degree of clinical suspicion is paramount due to the often subtle nature of cutaneous manifestations. A positive BDG assay can be used to identify high-risk patients for empiric antifungal therapy, prompting early intervention and improved outcomes in these acutely ill patients. The BDG assay’s excellent negative predictive value is useful in ruling out invasive Candida infections and may justify stopping unnecessary empiric antifungal therapy.4 For the dermatology hospitalist, incorporation of the BDG assay as a noninvasive screening tool may allow for more rapid initiation of appropriate antifungal therapy while awaiting confirmatory skin biopsy or culture results in disseminated candidemia and other invasive fungal infections.
- Mays SR, Bogle MA, Bodey GP. Cutaneous fungal infections in the oncology patient: recognition and management. Am J Clin Dermatol. 2006;7:31-43.
- Candida auris. Centers for Disease Control and Prevention website. https://www.cdc.gov/fungal/candida-auris/. Updated May 15, 2020. Accessed July 10, 2020.
- Obayashi T, Negishi K, Suzuki T, et al. Reappraisal of the serum (1,3)-β-D-glucan assay for the diagnosis of invasive fungal infections—a study based on autopsy cases from 6 years. Clin Infect Dis. 2008;46:1864-1870.
- Clancy CJ, Nguyen MH. Finding the “missing 50%” of invasive candidiasis: how nonculture diagnostics will improve understanding of disease spectrum and transform patient care. Clin Infect Dis. 2013;56:1284-1292.
- McCarthy MW, Petraitiene R, Walsh TJ. Translational development and application of (1→3)-β-d-glucan for diagnosis and therapeutic monitoring of invasive mycoses [published online May 24, 2017]. Int J Mol Sci. doi:10.3390/ijms18061124.
- Beta-D glucan assay. MiraVista Diagnostics website. https://miravistalabs.com/medical-fungal-infection-testing/antigen-detection/beta-d-glucan-test/. Accessed June 5, 2020.
Practice Gap
Invasive fungal infections are a leading cause of morbidity and mortality among neutropenic, immunocompromised, and critically ill patients. Candida species are the most common cause of fungemia, with portals of entry into the bloodstream including the gastrointestinal tract, contaminated intravascular catheters, and localized foci of infection.1 Diagnosis of invasive candidiasis remains challenging due to an absence of specific clinical signs and symptoms, varying from a mild fever that is unresponsive to antibiotics to florid sepsis. When present, clinical clues may include chorioretinitis; muscle abscesses; and skin eruptions, characteristically with Candida tropicalis. Cutaneous manifestations of disseminated Candida infections appear in only 13% of affected patients.1 The lesions typically present as 5- to 10-mm pink dermal papules or painless pustules on an erythematous base and may be singular, localized, or diffuse in distribution. Body regions normally involved are the trunk, arms, and legs, rarely the head and neck.1 Cutaneous lesions often develop at a time when patients are febrile, are not responding to antibiotics, and are clinically deteriorating.
A 15-year-old adolescent boy with pre–B-cell acute lymphoblastic leukemia was admitted with febrile neutropenia for presumed septic shock secondary to an unknown infectious etiology. The patient was started on broad-spectrum intravenous antibiotics, and blood cultures were obtained. On the second day of hospitalization, he developed approximately 10 to 15 discrete, 3- to 6-mm, pink to violaceous papules scattered on the chest and arms (Figure 1). Over several hours, the number of lesions increased to more than 50 with involvement of the legs (Figure 2). A punch biopsy of lesional skin from the left dorsal wrist demonstrated a circumscribed abscess of yeast in the papillary dermis, which was highlighted by periodic acid–Schiff staining with minimal associated inflammation (Figure 3). Blood and tissue cultures persistently grew C tropicalis. The patient was started on intravenous liposomal amphotericin B but died on day 5 of hospitalization after developing endocarditis.
Early and reliable diagnosis of Candida species fungemia is of critical importance to successful treatment, particularly with the emergence of multidrug-resistant strains such as Candida auris.2 In patients with apparent cutaneous manifestations, a lesional punch biopsy for culture and histopathologic evaluation is recommended in addition to blood culture; however, organisms may or may not be present in large numbers, and they may be difficult to identify on routine hematoxylin and eosin–stained tissue sections. To enhance the likelihood of highlighting the fungus within the sample, the pathologist must be made aware of the presumptive diagnosis of disseminated candidiasis so that special techniques can be utilized, such as periodic acid–Schiff stain.
Although positive blood culture is the gold standard for candidemia diagnosis, only 30% to 50% of patients with disseminated candidiasis had positive blood cultures at autopsy.1 Another study showed the sensitivity of blood culture for the detection of invasive fungal infection to be as low as 8.3%.3 In cases with positive blood cultures, the median time to positivity is 2 to 3 days, but it can take as long as 8 days, thus limiting its clinical utility in acutely ill patients.4 Given the low sensitivity and prolonged time required for culture growth of most fungal organisms, novel assays for rapid, non–culture-based diagnosis of systemic fungal infections hold substantial clinical promise moving forward.
The Technique
One of the more promising non–culture-based fungal diagnostic methodologies is an antigen assay based on the detection of serum (1,3)-β-D-glucan (BDG), a major cell wall constituent of most pathogenic fungi. This assay is not specific for Candida species and can be positive for Aspergillosis species, Fusarium species, Coccidioides immitis, Histoplasma capsulatum, and Pneumocystis jirovecii pneumonia, among others; therefore, it functions as a general biomarker for fungi in the bloodstream.4,5 (1,3)-β-D-glucan assay can be useful as an adjunct for blood cultures and punch biopsy, especially when cultures are negative or the results remain outstanding. The results of the BDG assay are available in less than 24 hours at minimal cost, and the test is approved by the US Food and Drug Administration for use as an aid in invasive fungal disease diagnosis. In a meta-analysis of 11 studies, BDG sensitivity was 75%.4 In a study based on autopsy cases from 6 years, BDG specificity was 98.4% with positive and negative predictive values of 86.7% and 97.1%, respectively.3 Optimal results were achieved when 2 consecutive tests were positive.4 The serum assay output is based on spectrophotometer readings, which are converted to BDG concentrations (negative, <60 pg/mL; indeterminate, 60–79 pg/mL; positive ≥80 pg/mL).5 Although we cannot be certain, utilizing the BDG assay in our patient may have led to earlier treatment and a better outcome.
A disadvantage of the BDG assay is the potential for false-positive results, which have been reported in lung transplant recipients with respiratory mold colonization and patients with other systemic bacterial infections.4 False-positive results also have been associated with use of ampicillin-clavulanate and piperacillin-tazobactam antibiotics and human blood products, hemodialysis, and severe mucositis, thus reaffirming the importance of judicious interpretation of BDG assay results by the clinician.4,6 There also is a potential for false-negative results, as the BDG assay does not detect certain fungal species such as Cryptococcus species and Blastomyces dermatitidis, which produce very low levels of BDG, or zygomycetes (Absidia, Mucor, and Rizopus species), which are not known to produce BDG.6
Practice Implications
In the setting of invasive fungal infections, a high degree of clinical suspicion is paramount due to the often subtle nature of cutaneous manifestations. A positive BDG assay can be used to identify high-risk patients for empiric antifungal therapy, prompting early intervention and improved outcomes in these acutely ill patients. The BDG assay’s excellent negative predictive value is useful in ruling out invasive Candida infections and may justify stopping unnecessary empiric antifungal therapy.4 For the dermatology hospitalist, incorporation of the BDG assay as a noninvasive screening tool may allow for more rapid initiation of appropriate antifungal therapy while awaiting confirmatory skin biopsy or culture results in disseminated candidemia and other invasive fungal infections.
Practice Gap
Invasive fungal infections are a leading cause of morbidity and mortality among neutropenic, immunocompromised, and critically ill patients. Candida species are the most common cause of fungemia, with portals of entry into the bloodstream including the gastrointestinal tract, contaminated intravascular catheters, and localized foci of infection.1 Diagnosis of invasive candidiasis remains challenging due to an absence of specific clinical signs and symptoms, varying from a mild fever that is unresponsive to antibiotics to florid sepsis. When present, clinical clues may include chorioretinitis; muscle abscesses; and skin eruptions, characteristically with Candida tropicalis. Cutaneous manifestations of disseminated Candida infections appear in only 13% of affected patients.1 The lesions typically present as 5- to 10-mm pink dermal papules or painless pustules on an erythematous base and may be singular, localized, or diffuse in distribution. Body regions normally involved are the trunk, arms, and legs, rarely the head and neck.1 Cutaneous lesions often develop at a time when patients are febrile, are not responding to antibiotics, and are clinically deteriorating.
A 15-year-old adolescent boy with pre–B-cell acute lymphoblastic leukemia was admitted with febrile neutropenia for presumed septic shock secondary to an unknown infectious etiology. The patient was started on broad-spectrum intravenous antibiotics, and blood cultures were obtained. On the second day of hospitalization, he developed approximately 10 to 15 discrete, 3- to 6-mm, pink to violaceous papules scattered on the chest and arms (Figure 1). Over several hours, the number of lesions increased to more than 50 with involvement of the legs (Figure 2). A punch biopsy of lesional skin from the left dorsal wrist demonstrated a circumscribed abscess of yeast in the papillary dermis, which was highlighted by periodic acid–Schiff staining with minimal associated inflammation (Figure 3). Blood and tissue cultures persistently grew C tropicalis. The patient was started on intravenous liposomal amphotericin B but died on day 5 of hospitalization after developing endocarditis.
Early and reliable diagnosis of Candida species fungemia is of critical importance to successful treatment, particularly with the emergence of multidrug-resistant strains such as Candida auris.2 In patients with apparent cutaneous manifestations, a lesional punch biopsy for culture and histopathologic evaluation is recommended in addition to blood culture; however, organisms may or may not be present in large numbers, and they may be difficult to identify on routine hematoxylin and eosin–stained tissue sections. To enhance the likelihood of highlighting the fungus within the sample, the pathologist must be made aware of the presumptive diagnosis of disseminated candidiasis so that special techniques can be utilized, such as periodic acid–Schiff stain.
Although positive blood culture is the gold standard for candidemia diagnosis, only 30% to 50% of patients with disseminated candidiasis had positive blood cultures at autopsy.1 Another study showed the sensitivity of blood culture for the detection of invasive fungal infection to be as low as 8.3%.3 In cases with positive blood cultures, the median time to positivity is 2 to 3 days, but it can take as long as 8 days, thus limiting its clinical utility in acutely ill patients.4 Given the low sensitivity and prolonged time required for culture growth of most fungal organisms, novel assays for rapid, non–culture-based diagnosis of systemic fungal infections hold substantial clinical promise moving forward.
The Technique
One of the more promising non–culture-based fungal diagnostic methodologies is an antigen assay based on the detection of serum (1,3)-β-D-glucan (BDG), a major cell wall constituent of most pathogenic fungi. This assay is not specific for Candida species and can be positive for Aspergillosis species, Fusarium species, Coccidioides immitis, Histoplasma capsulatum, and Pneumocystis jirovecii pneumonia, among others; therefore, it functions as a general biomarker for fungi in the bloodstream.4,5 (1,3)-β-D-glucan assay can be useful as an adjunct for blood cultures and punch biopsy, especially when cultures are negative or the results remain outstanding. The results of the BDG assay are available in less than 24 hours at minimal cost, and the test is approved by the US Food and Drug Administration for use as an aid in invasive fungal disease diagnosis. In a meta-analysis of 11 studies, BDG sensitivity was 75%.4 In a study based on autopsy cases from 6 years, BDG specificity was 98.4% with positive and negative predictive values of 86.7% and 97.1%, respectively.3 Optimal results were achieved when 2 consecutive tests were positive.4 The serum assay output is based on spectrophotometer readings, which are converted to BDG concentrations (negative, <60 pg/mL; indeterminate, 60–79 pg/mL; positive ≥80 pg/mL).5 Although we cannot be certain, utilizing the BDG assay in our patient may have led to earlier treatment and a better outcome.
A disadvantage of the BDG assay is the potential for false-positive results, which have been reported in lung transplant recipients with respiratory mold colonization and patients with other systemic bacterial infections.4 False-positive results also have been associated with use of ampicillin-clavulanate and piperacillin-tazobactam antibiotics and human blood products, hemodialysis, and severe mucositis, thus reaffirming the importance of judicious interpretation of BDG assay results by the clinician.4,6 There also is a potential for false-negative results, as the BDG assay does not detect certain fungal species such as Cryptococcus species and Blastomyces dermatitidis, which produce very low levels of BDG, or zygomycetes (Absidia, Mucor, and Rizopus species), which are not known to produce BDG.6
Practice Implications
In the setting of invasive fungal infections, a high degree of clinical suspicion is paramount due to the often subtle nature of cutaneous manifestations. A positive BDG assay can be used to identify high-risk patients for empiric antifungal therapy, prompting early intervention and improved outcomes in these acutely ill patients. The BDG assay’s excellent negative predictive value is useful in ruling out invasive Candida infections and may justify stopping unnecessary empiric antifungal therapy.4 For the dermatology hospitalist, incorporation of the BDG assay as a noninvasive screening tool may allow for more rapid initiation of appropriate antifungal therapy while awaiting confirmatory skin biopsy or culture results in disseminated candidemia and other invasive fungal infections.
- Mays SR, Bogle MA, Bodey GP. Cutaneous fungal infections in the oncology patient: recognition and management. Am J Clin Dermatol. 2006;7:31-43.
- Candida auris. Centers for Disease Control and Prevention website. https://www.cdc.gov/fungal/candida-auris/. Updated May 15, 2020. Accessed July 10, 2020.
- Obayashi T, Negishi K, Suzuki T, et al. Reappraisal of the serum (1,3)-β-D-glucan assay for the diagnosis of invasive fungal infections—a study based on autopsy cases from 6 years. Clin Infect Dis. 2008;46:1864-1870.
- Clancy CJ, Nguyen MH. Finding the “missing 50%” of invasive candidiasis: how nonculture diagnostics will improve understanding of disease spectrum and transform patient care. Clin Infect Dis. 2013;56:1284-1292.
- McCarthy MW, Petraitiene R, Walsh TJ. Translational development and application of (1→3)-β-d-glucan for diagnosis and therapeutic monitoring of invasive mycoses [published online May 24, 2017]. Int J Mol Sci. doi:10.3390/ijms18061124.
- Beta-D glucan assay. MiraVista Diagnostics website. https://miravistalabs.com/medical-fungal-infection-testing/antigen-detection/beta-d-glucan-test/. Accessed June 5, 2020.
- Mays SR, Bogle MA, Bodey GP. Cutaneous fungal infections in the oncology patient: recognition and management. Am J Clin Dermatol. 2006;7:31-43.
- Candida auris. Centers for Disease Control and Prevention website. https://www.cdc.gov/fungal/candida-auris/. Updated May 15, 2020. Accessed July 10, 2020.
- Obayashi T, Negishi K, Suzuki T, et al. Reappraisal of the serum (1,3)-β-D-glucan assay for the diagnosis of invasive fungal infections—a study based on autopsy cases from 6 years. Clin Infect Dis. 2008;46:1864-1870.
- Clancy CJ, Nguyen MH. Finding the “missing 50%” of invasive candidiasis: how nonculture diagnostics will improve understanding of disease spectrum and transform patient care. Clin Infect Dis. 2013;56:1284-1292.
- McCarthy MW, Petraitiene R, Walsh TJ. Translational development and application of (1→3)-β-d-glucan for diagnosis and therapeutic monitoring of invasive mycoses [published online May 24, 2017]. Int J Mol Sci. doi:10.3390/ijms18061124.
- Beta-D glucan assay. MiraVista Diagnostics website. https://miravistalabs.com/medical-fungal-infection-testing/antigen-detection/beta-d-glucan-test/. Accessed June 5, 2020.
Neural tube defect risk from dolutegravir drops as clinical experience grows
The newest data, based on 3,591 deliveries among women in Botswana infected by HIV and treated with dolutegravir at the time of conception during a little more than 5.5 years through April 2020, showed that dolutegravir use at conception linked with 7 cases of neonatal neural tube defects (NTDs), a 0.19% rate that exceeded comparator rates by about 1 in every 1,000 deliveries, far below the 0.94% rate initially found and that raised a red flag 2 years ago (New Engl J Med. 2018 Sep 6;379[10]:979-81). “The prevalence of NTDs among infants born to women on dolutegravir at conception may be stabilizing at approximately 2 per 1,000,” said Rebecca Zash, MD, during the virtual meeting of the International AIDS conference.
“This small absolute risk for neural tube defects is far outweighed by the potential benefits from dolutegravir” for better tolerability than alternative drugs and fewer drug-drug interactions. “This should allow for broader use of dolutegravir in women,” added Dr. Zash, an HIV specialist at Beth Israel Deaconess Medical Center and codirector of the Placental Scientific Working Group of the Harvard University Center for AIDS Research, both in Boston.
“What this has taught us is that women are not a niche population” of people infected with HIV, but rather constitute about half of HIV patients worldwide. “Maintaining gender equity in HIV treatment requires safety data for treatments during pregnancy,” she said during a press briefing.
The new findings mean that it’s “time to lay to rest” concerns about neural tube defects (NTDs) in infants born to women treated with dolutegravir, “given the incredible benefits of dolutegravir,” commented Monica Gandhi, MD, professor of medicine and associate chief of the division of HIV, infectious disease, and global medicine at the University of California, San Francisco. Another benefit from removing any caveats about use of dolutegravir in women who could become pregnant is that it would simplify treatment recommendations and make dolutegravir the unqualified first-line agent for treating HIV infection, Dr. Gandhi said during the briefing. “It’s super reassuring to have these data, as the incidence of NTDs goes down and down,” she added.
Following the alarm raised by initial findings from the Tsepamo study in 2018, Dr. Zash and associates first updated their data through March 2019, when they reported a revised cumulative NTD incidence rate of 0.3% (New Engl J Med. 2019 Aug 29;381[9]:827-40). The Tsepamo study began by following the pregnancy outcomes of women at eight Botswana sites during August 2014–July 2018, representing 45% of the country’s deliveries. This expanded to 18 sites and 72% of deliveries during July-September 2018, and then starting in September 2019 the scope slightly reduced to 16 Botswana sites with 70% of the nation’s deliveries.
Folate supplementation to women who might conceive is vital, but remains spotty in Botswana. “Folate supplementation is a no-brainer, but has had really slow adoption in many countries,” Dr. Zash said. “Folate supplementation, especially in food so that everyone gets it, will reduce NTDs by half.” The two most recent cases of infants born with a NTD to mothers who had been on dolutegravir at conception occurred in mothers who had received no folate supplementation, Dr. Zash reported.
The most recent HIV treatment guidelines for adults from the Department of Health & Human Services, which date from late 2019, designated dolutegravir plus lamivudine as a first-line regimen for most, but flagged it as an “alternative” antiretroviral drug when treating women who have childbearing potential and are either trying to conceive or are sexually active but not using contraception.
The study had no commercial funding. Dr. Zash has been a researcher in studies funded by CytoDyn, Fulcrum, and Gilead. Dr. Gandhi had no commercial disclosures.
The newest data, based on 3,591 deliveries among women in Botswana infected by HIV and treated with dolutegravir at the time of conception during a little more than 5.5 years through April 2020, showed that dolutegravir use at conception linked with 7 cases of neonatal neural tube defects (NTDs), a 0.19% rate that exceeded comparator rates by about 1 in every 1,000 deliveries, far below the 0.94% rate initially found and that raised a red flag 2 years ago (New Engl J Med. 2018 Sep 6;379[10]:979-81). “The prevalence of NTDs among infants born to women on dolutegravir at conception may be stabilizing at approximately 2 per 1,000,” said Rebecca Zash, MD, during the virtual meeting of the International AIDS conference.
“This small absolute risk for neural tube defects is far outweighed by the potential benefits from dolutegravir” for better tolerability than alternative drugs and fewer drug-drug interactions. “This should allow for broader use of dolutegravir in women,” added Dr. Zash, an HIV specialist at Beth Israel Deaconess Medical Center and codirector of the Placental Scientific Working Group of the Harvard University Center for AIDS Research, both in Boston.
“What this has taught us is that women are not a niche population” of people infected with HIV, but rather constitute about half of HIV patients worldwide. “Maintaining gender equity in HIV treatment requires safety data for treatments during pregnancy,” she said during a press briefing.
The new findings mean that it’s “time to lay to rest” concerns about neural tube defects (NTDs) in infants born to women treated with dolutegravir, “given the incredible benefits of dolutegravir,” commented Monica Gandhi, MD, professor of medicine and associate chief of the division of HIV, infectious disease, and global medicine at the University of California, San Francisco. Another benefit from removing any caveats about use of dolutegravir in women who could become pregnant is that it would simplify treatment recommendations and make dolutegravir the unqualified first-line agent for treating HIV infection, Dr. Gandhi said during the briefing. “It’s super reassuring to have these data, as the incidence of NTDs goes down and down,” she added.
Following the alarm raised by initial findings from the Tsepamo study in 2018, Dr. Zash and associates first updated their data through March 2019, when they reported a revised cumulative NTD incidence rate of 0.3% (New Engl J Med. 2019 Aug 29;381[9]:827-40). The Tsepamo study began by following the pregnancy outcomes of women at eight Botswana sites during August 2014–July 2018, representing 45% of the country’s deliveries. This expanded to 18 sites and 72% of deliveries during July-September 2018, and then starting in September 2019 the scope slightly reduced to 16 Botswana sites with 70% of the nation’s deliveries.
Folate supplementation to women who might conceive is vital, but remains spotty in Botswana. “Folate supplementation is a no-brainer, but has had really slow adoption in many countries,” Dr. Zash said. “Folate supplementation, especially in food so that everyone gets it, will reduce NTDs by half.” The two most recent cases of infants born with a NTD to mothers who had been on dolutegravir at conception occurred in mothers who had received no folate supplementation, Dr. Zash reported.
The most recent HIV treatment guidelines for adults from the Department of Health & Human Services, which date from late 2019, designated dolutegravir plus lamivudine as a first-line regimen for most, but flagged it as an “alternative” antiretroviral drug when treating women who have childbearing potential and are either trying to conceive or are sexually active but not using contraception.
The study had no commercial funding. Dr. Zash has been a researcher in studies funded by CytoDyn, Fulcrum, and Gilead. Dr. Gandhi had no commercial disclosures.
The newest data, based on 3,591 deliveries among women in Botswana infected by HIV and treated with dolutegravir at the time of conception during a little more than 5.5 years through April 2020, showed that dolutegravir use at conception linked with 7 cases of neonatal neural tube defects (NTDs), a 0.19% rate that exceeded comparator rates by about 1 in every 1,000 deliveries, far below the 0.94% rate initially found and that raised a red flag 2 years ago (New Engl J Med. 2018 Sep 6;379[10]:979-81). “The prevalence of NTDs among infants born to women on dolutegravir at conception may be stabilizing at approximately 2 per 1,000,” said Rebecca Zash, MD, during the virtual meeting of the International AIDS conference.
“This small absolute risk for neural tube defects is far outweighed by the potential benefits from dolutegravir” for better tolerability than alternative drugs and fewer drug-drug interactions. “This should allow for broader use of dolutegravir in women,” added Dr. Zash, an HIV specialist at Beth Israel Deaconess Medical Center and codirector of the Placental Scientific Working Group of the Harvard University Center for AIDS Research, both in Boston.
“What this has taught us is that women are not a niche population” of people infected with HIV, but rather constitute about half of HIV patients worldwide. “Maintaining gender equity in HIV treatment requires safety data for treatments during pregnancy,” she said during a press briefing.
The new findings mean that it’s “time to lay to rest” concerns about neural tube defects (NTDs) in infants born to women treated with dolutegravir, “given the incredible benefits of dolutegravir,” commented Monica Gandhi, MD, professor of medicine and associate chief of the division of HIV, infectious disease, and global medicine at the University of California, San Francisco. Another benefit from removing any caveats about use of dolutegravir in women who could become pregnant is that it would simplify treatment recommendations and make dolutegravir the unqualified first-line agent for treating HIV infection, Dr. Gandhi said during the briefing. “It’s super reassuring to have these data, as the incidence of NTDs goes down and down,” she added.
Following the alarm raised by initial findings from the Tsepamo study in 2018, Dr. Zash and associates first updated their data through March 2019, when they reported a revised cumulative NTD incidence rate of 0.3% (New Engl J Med. 2019 Aug 29;381[9]:827-40). The Tsepamo study began by following the pregnancy outcomes of women at eight Botswana sites during August 2014–July 2018, representing 45% of the country’s deliveries. This expanded to 18 sites and 72% of deliveries during July-September 2018, and then starting in September 2019 the scope slightly reduced to 16 Botswana sites with 70% of the nation’s deliveries.
Folate supplementation to women who might conceive is vital, but remains spotty in Botswana. “Folate supplementation is a no-brainer, but has had really slow adoption in many countries,” Dr. Zash said. “Folate supplementation, especially in food so that everyone gets it, will reduce NTDs by half.” The two most recent cases of infants born with a NTD to mothers who had been on dolutegravir at conception occurred in mothers who had received no folate supplementation, Dr. Zash reported.
The most recent HIV treatment guidelines for adults from the Department of Health & Human Services, which date from late 2019, designated dolutegravir plus lamivudine as a first-line regimen for most, but flagged it as an “alternative” antiretroviral drug when treating women who have childbearing potential and are either trying to conceive or are sexually active but not using contraception.
The study had no commercial funding. Dr. Zash has been a researcher in studies funded by CytoDyn, Fulcrum, and Gilead. Dr. Gandhi had no commercial disclosures.
FROM AIDS 2020
Brazilian patient in HIV remission, negative antibody test
A 35-year-old Brazilian man who participated in a trial in which he received an intensified antiretroviral regimen plus supplemental vitamin B3 for 48 weeks has joined the short list of patients who have experienced a period of remission from HIV in the absence of effective treatment.
Along with the Mississippi baby, a San Francisco man, a 24-year-old Thai man, a 9-year-old South African child, and the London and Berlin patients, the Brazilian man has an undetectable viral load and, more than a year after stopping treatment, his HIV antibody test is negative.
But as with the Berlin and London patients, it seems unlikely that – even if the man remains HIV free into the future – the circumstances of his remission will be broadly applicable to other people with HIV, said Carl Dieffenbach, PhD, director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases, National Institutes of Health.
“I don’t think it’s replicable,” Dieffenbach told Medscape Medical News. Researchers should still try to confirm the finding, but they will probably learn more by studying the man’s unique genetic characteristics and immune system “than to go out and treat another 200 people with the same protocol.”
‘Shock-and-kill strategy’
The man had been on treatment since his HIV diagnosis in 2012, and was one of 30 people to enroll in a Brazilian study – the Multi Interventional Study Exploring HIV-1 Residual Replication: A Step Toward HIV Eradication and Sterilizing Cure – in 2016. At that point, his regimen consisted of the combination of efavirenz, lamivudine, and tenofovir disoproxil fumarate (Symfi, Mylan Pharmaceuticals) and his viral load was undetectable.
He was one of five people in the study to be randomized to receive the integrase inhibitor dolutegravir (Tivicay, ViiV Healthcare), the CCR5 receptor inhibitor maraviroc (Selzentry, ViiV Healthcare), and twice-daily nicotinamide 500 mg, a form of vitamin B3, in addition to his regular regimen for 48 weeks.
Nicotinamide has been used for decades because of its anti-infective properties, particularly in tuberculosis. In vitro, it also works to reverse HIV latency, said study investigator Ricardo Diaz, MD, from the Federal University of São Paulo, who presented the data at a press conference for the International AIDS Conference (AIDS) 2020.
“This is a shock-and-kill strategy,” said Leila Giron, PhD, from the Wistar Institute in Philadelphia, who was one of the study investigators. “We did in vitro studies to make sure nicotinamide took HIV out of the cells.”
“The cell machinery changed a lot,” she told Medscape Medical News. “And because it’s a B vitamin, all five participants didn’t have any side effects.”
But the patient was the only person in his treatment group to experience viral load “blips” during treatment – at weeks 16 and 24. And viral DNA was present at low levels in his peripheral blood spots and rectal tissue at baseline and at 48 weeks, and his HIV antibodies dropped from 91.8 RLU at baseline to 58.0 RLU at week 48.
“He had a decline in cell activation, inflammation, and a very deep decline in antibody titers,” Diaz reported.
After 48 weeks of the intensified treatment, the patient returned to his usual regimen for 3 years. Then, in March 2019, he agreed to try an analytical treatment interruption and discontinued all HIV treatment.
“What’s interesting is right before the analytical treatment interruption, the HIV DNA sequences were completely negative,” said Diaz.
Every 3 weeks for the next 64.7 weeks, his viral load came back undetectable, and so did HIV DNA in blood spots. One thing did change, though: in February 2020, the man’s HIV antibody test came back negative.
The team checked that he wasn’t still taking his antiretroviral medication, which might have explained the undetectable viral load, and he wasn’t.
Surprise, skepticism, and hope
The results have prompted surprise, skepticism, and questions from clinicians and researchers.
said Anton Pozniak, MD, from Chelsea and Westminster Hospital in London, who is cochair of AIDS 2020.
“They need a bigger study to see whether or not [the participant] is one of these guys who stopped treatment and might take a year or two, or four, to rebound,” he said. But if other studies replicate the results, the control of HIV in “one in five people would still be huge.”
The rationale behind treatment intensification for HIV remission is that “the three-drug ART regimen was perhaps insufficient to completely block HIV replication” in the reservoirs, even though that replication could be happening below levels detectable with current tests, said Laura Persaud, MD, from the Johns Hopkins University School of Medicine in Baltimore, who is chair of the International Maternal Pediatric Adolescent AIDS Clinical Trial Network (IMPAACT) HIV Cure Committee and was not involved in the study.
“The idea was to see if you could accelerate the decay of the reservoir” if you added medications that targeted different parts of the HIV lifecycle. Symfi, for instance, targets just one step in the viral replication process: the point where HIV RNA reverse transcribes itself into DNA so it can integrate into immune cells. But CCR5 inhibitors block entry of HIV into the cell in the first place, and integrase inhibitors, like raltegravir (Isentress, Merck) and dolutegravir, prevent HIV DNA from integrating into the host chromosome after it has reverse transcribed itself.
Still, recent data suggest that treatment intensification might not be as effective as hypothesized, she said. And the nicotinamide study was in vitro. To what extent this is a direct result of this treatment strategy is unclear.
“It’s hard to believe, in this small study, that this agent [nicotinamide] would have such a striking effect on DNA proviral levels,” she said. “We learn from each of these cases. But this is a single case, with multiple mechanisms that may have contributed to the outcome here. To what extent this is a direct result of this treatment strategy is unclear.”
Only time will tell, and Persaud knows this first hand. Back in 2014, she presented data at another HIV conference on the Mississippi baby who, after 21 months of no treatment, still didn›t have an HIV viral load.
At the time, the baby was hailed as “functionally cured,” but just 6 months later, the virus returned.
Dieffenbach agrees. “There are 10,000 genetic variations that need to be considered, and it all adds up to a unique individual,” he said of the Brazilian patient. “This one is one person, and it’s still early days.”
Counseling patients on niacin supplementation
Some clinicians are already bracing for the flood of people with HIV now wanting to take, or who are already taking, a niacin supplement because of this case, said Laura Waters, MD, from Mortimer Market Centre in London, who is chair of the British HIV Association.
But nicotinamide is different than nicotinic acid, which is what many people mean when they talk about niacin supplementation, according to data from the Office of Dietary Supplements (ODS) at the National Institutes of Health. Nicotinic acid has been used as a supplement for people with high cholesterol for years. Most Americans get more than the recommended daily intake of both types of niacin – 16 mg for adult men and 14 mg for adult women – in their regular diet, according to the 2015/16 National Health and Nutrition Examination Survey.
The Brazilian patient received a total daily dose of nicotinamide of 1000 mg, which is not associated with any adverse effects. Doses above 3000 mg daily can lead to diarrhea and a decrease in platelet count, according to the ODS.
Although Diaz said he doesn’t think people with HIV should run out and start taking a supplement right away, Waters said she sees it as inevitable.
The good news is that if people really are taking nicotinamide – not nicotinic acid – it seems “fairly well tolerated without many side effects,” she said, but added: “I expect shortages of nicotinamide from tomorrow.”
This story first appeared on Medscape.com.
A 35-year-old Brazilian man who participated in a trial in which he received an intensified antiretroviral regimen plus supplemental vitamin B3 for 48 weeks has joined the short list of patients who have experienced a period of remission from HIV in the absence of effective treatment.
Along with the Mississippi baby, a San Francisco man, a 24-year-old Thai man, a 9-year-old South African child, and the London and Berlin patients, the Brazilian man has an undetectable viral load and, more than a year after stopping treatment, his HIV antibody test is negative.
But as with the Berlin and London patients, it seems unlikely that – even if the man remains HIV free into the future – the circumstances of his remission will be broadly applicable to other people with HIV, said Carl Dieffenbach, PhD, director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases, National Institutes of Health.
“I don’t think it’s replicable,” Dieffenbach told Medscape Medical News. Researchers should still try to confirm the finding, but they will probably learn more by studying the man’s unique genetic characteristics and immune system “than to go out and treat another 200 people with the same protocol.”
‘Shock-and-kill strategy’
The man had been on treatment since his HIV diagnosis in 2012, and was one of 30 people to enroll in a Brazilian study – the Multi Interventional Study Exploring HIV-1 Residual Replication: A Step Toward HIV Eradication and Sterilizing Cure – in 2016. At that point, his regimen consisted of the combination of efavirenz, lamivudine, and tenofovir disoproxil fumarate (Symfi, Mylan Pharmaceuticals) and his viral load was undetectable.
He was one of five people in the study to be randomized to receive the integrase inhibitor dolutegravir (Tivicay, ViiV Healthcare), the CCR5 receptor inhibitor maraviroc (Selzentry, ViiV Healthcare), and twice-daily nicotinamide 500 mg, a form of vitamin B3, in addition to his regular regimen for 48 weeks.
Nicotinamide has been used for decades because of its anti-infective properties, particularly in tuberculosis. In vitro, it also works to reverse HIV latency, said study investigator Ricardo Diaz, MD, from the Federal University of São Paulo, who presented the data at a press conference for the International AIDS Conference (AIDS) 2020.
“This is a shock-and-kill strategy,” said Leila Giron, PhD, from the Wistar Institute in Philadelphia, who was one of the study investigators. “We did in vitro studies to make sure nicotinamide took HIV out of the cells.”
“The cell machinery changed a lot,” she told Medscape Medical News. “And because it’s a B vitamin, all five participants didn’t have any side effects.”
But the patient was the only person in his treatment group to experience viral load “blips” during treatment – at weeks 16 and 24. And viral DNA was present at low levels in his peripheral blood spots and rectal tissue at baseline and at 48 weeks, and his HIV antibodies dropped from 91.8 RLU at baseline to 58.0 RLU at week 48.
“He had a decline in cell activation, inflammation, and a very deep decline in antibody titers,” Diaz reported.
After 48 weeks of the intensified treatment, the patient returned to his usual regimen for 3 years. Then, in March 2019, he agreed to try an analytical treatment interruption and discontinued all HIV treatment.
“What’s interesting is right before the analytical treatment interruption, the HIV DNA sequences were completely negative,” said Diaz.
Every 3 weeks for the next 64.7 weeks, his viral load came back undetectable, and so did HIV DNA in blood spots. One thing did change, though: in February 2020, the man’s HIV antibody test came back negative.
The team checked that he wasn’t still taking his antiretroviral medication, which might have explained the undetectable viral load, and he wasn’t.
Surprise, skepticism, and hope
The results have prompted surprise, skepticism, and questions from clinicians and researchers.
said Anton Pozniak, MD, from Chelsea and Westminster Hospital in London, who is cochair of AIDS 2020.
“They need a bigger study to see whether or not [the participant] is one of these guys who stopped treatment and might take a year or two, or four, to rebound,” he said. But if other studies replicate the results, the control of HIV in “one in five people would still be huge.”
The rationale behind treatment intensification for HIV remission is that “the three-drug ART regimen was perhaps insufficient to completely block HIV replication” in the reservoirs, even though that replication could be happening below levels detectable with current tests, said Laura Persaud, MD, from the Johns Hopkins University School of Medicine in Baltimore, who is chair of the International Maternal Pediatric Adolescent AIDS Clinical Trial Network (IMPAACT) HIV Cure Committee and was not involved in the study.
“The idea was to see if you could accelerate the decay of the reservoir” if you added medications that targeted different parts of the HIV lifecycle. Symfi, for instance, targets just one step in the viral replication process: the point where HIV RNA reverse transcribes itself into DNA so it can integrate into immune cells. But CCR5 inhibitors block entry of HIV into the cell in the first place, and integrase inhibitors, like raltegravir (Isentress, Merck) and dolutegravir, prevent HIV DNA from integrating into the host chromosome after it has reverse transcribed itself.
Still, recent data suggest that treatment intensification might not be as effective as hypothesized, she said. And the nicotinamide study was in vitro. To what extent this is a direct result of this treatment strategy is unclear.
“It’s hard to believe, in this small study, that this agent [nicotinamide] would have such a striking effect on DNA proviral levels,” she said. “We learn from each of these cases. But this is a single case, with multiple mechanisms that may have contributed to the outcome here. To what extent this is a direct result of this treatment strategy is unclear.”
Only time will tell, and Persaud knows this first hand. Back in 2014, she presented data at another HIV conference on the Mississippi baby who, after 21 months of no treatment, still didn›t have an HIV viral load.
At the time, the baby was hailed as “functionally cured,” but just 6 months later, the virus returned.
Dieffenbach agrees. “There are 10,000 genetic variations that need to be considered, and it all adds up to a unique individual,” he said of the Brazilian patient. “This one is one person, and it’s still early days.”
Counseling patients on niacin supplementation
Some clinicians are already bracing for the flood of people with HIV now wanting to take, or who are already taking, a niacin supplement because of this case, said Laura Waters, MD, from Mortimer Market Centre in London, who is chair of the British HIV Association.
But nicotinamide is different than nicotinic acid, which is what many people mean when they talk about niacin supplementation, according to data from the Office of Dietary Supplements (ODS) at the National Institutes of Health. Nicotinic acid has been used as a supplement for people with high cholesterol for years. Most Americans get more than the recommended daily intake of both types of niacin – 16 mg for adult men and 14 mg for adult women – in their regular diet, according to the 2015/16 National Health and Nutrition Examination Survey.
The Brazilian patient received a total daily dose of nicotinamide of 1000 mg, which is not associated with any adverse effects. Doses above 3000 mg daily can lead to diarrhea and a decrease in platelet count, according to the ODS.
Although Diaz said he doesn’t think people with HIV should run out and start taking a supplement right away, Waters said she sees it as inevitable.
The good news is that if people really are taking nicotinamide – not nicotinic acid – it seems “fairly well tolerated without many side effects,” she said, but added: “I expect shortages of nicotinamide from tomorrow.”
This story first appeared on Medscape.com.
A 35-year-old Brazilian man who participated in a trial in which he received an intensified antiretroviral regimen plus supplemental vitamin B3 for 48 weeks has joined the short list of patients who have experienced a period of remission from HIV in the absence of effective treatment.
Along with the Mississippi baby, a San Francisco man, a 24-year-old Thai man, a 9-year-old South African child, and the London and Berlin patients, the Brazilian man has an undetectable viral load and, more than a year after stopping treatment, his HIV antibody test is negative.
But as with the Berlin and London patients, it seems unlikely that – even if the man remains HIV free into the future – the circumstances of his remission will be broadly applicable to other people with HIV, said Carl Dieffenbach, PhD, director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases, National Institutes of Health.
“I don’t think it’s replicable,” Dieffenbach told Medscape Medical News. Researchers should still try to confirm the finding, but they will probably learn more by studying the man’s unique genetic characteristics and immune system “than to go out and treat another 200 people with the same protocol.”
‘Shock-and-kill strategy’
The man had been on treatment since his HIV diagnosis in 2012, and was one of 30 people to enroll in a Brazilian study – the Multi Interventional Study Exploring HIV-1 Residual Replication: A Step Toward HIV Eradication and Sterilizing Cure – in 2016. At that point, his regimen consisted of the combination of efavirenz, lamivudine, and tenofovir disoproxil fumarate (Symfi, Mylan Pharmaceuticals) and his viral load was undetectable.
He was one of five people in the study to be randomized to receive the integrase inhibitor dolutegravir (Tivicay, ViiV Healthcare), the CCR5 receptor inhibitor maraviroc (Selzentry, ViiV Healthcare), and twice-daily nicotinamide 500 mg, a form of vitamin B3, in addition to his regular regimen for 48 weeks.
Nicotinamide has been used for decades because of its anti-infective properties, particularly in tuberculosis. In vitro, it also works to reverse HIV latency, said study investigator Ricardo Diaz, MD, from the Federal University of São Paulo, who presented the data at a press conference for the International AIDS Conference (AIDS) 2020.
“This is a shock-and-kill strategy,” said Leila Giron, PhD, from the Wistar Institute in Philadelphia, who was one of the study investigators. “We did in vitro studies to make sure nicotinamide took HIV out of the cells.”
“The cell machinery changed a lot,” she told Medscape Medical News. “And because it’s a B vitamin, all five participants didn’t have any side effects.”
But the patient was the only person in his treatment group to experience viral load “blips” during treatment – at weeks 16 and 24. And viral DNA was present at low levels in his peripheral blood spots and rectal tissue at baseline and at 48 weeks, and his HIV antibodies dropped from 91.8 RLU at baseline to 58.0 RLU at week 48.
“He had a decline in cell activation, inflammation, and a very deep decline in antibody titers,” Diaz reported.
After 48 weeks of the intensified treatment, the patient returned to his usual regimen for 3 years. Then, in March 2019, he agreed to try an analytical treatment interruption and discontinued all HIV treatment.
“What’s interesting is right before the analytical treatment interruption, the HIV DNA sequences were completely negative,” said Diaz.
Every 3 weeks for the next 64.7 weeks, his viral load came back undetectable, and so did HIV DNA in blood spots. One thing did change, though: in February 2020, the man’s HIV antibody test came back negative.
The team checked that he wasn’t still taking his antiretroviral medication, which might have explained the undetectable viral load, and he wasn’t.
Surprise, skepticism, and hope
The results have prompted surprise, skepticism, and questions from clinicians and researchers.
said Anton Pozniak, MD, from Chelsea and Westminster Hospital in London, who is cochair of AIDS 2020.
“They need a bigger study to see whether or not [the participant] is one of these guys who stopped treatment and might take a year or two, or four, to rebound,” he said. But if other studies replicate the results, the control of HIV in “one in five people would still be huge.”
The rationale behind treatment intensification for HIV remission is that “the three-drug ART regimen was perhaps insufficient to completely block HIV replication” in the reservoirs, even though that replication could be happening below levels detectable with current tests, said Laura Persaud, MD, from the Johns Hopkins University School of Medicine in Baltimore, who is chair of the International Maternal Pediatric Adolescent AIDS Clinical Trial Network (IMPAACT) HIV Cure Committee and was not involved in the study.
“The idea was to see if you could accelerate the decay of the reservoir” if you added medications that targeted different parts of the HIV lifecycle. Symfi, for instance, targets just one step in the viral replication process: the point where HIV RNA reverse transcribes itself into DNA so it can integrate into immune cells. But CCR5 inhibitors block entry of HIV into the cell in the first place, and integrase inhibitors, like raltegravir (Isentress, Merck) and dolutegravir, prevent HIV DNA from integrating into the host chromosome after it has reverse transcribed itself.
Still, recent data suggest that treatment intensification might not be as effective as hypothesized, she said. And the nicotinamide study was in vitro. To what extent this is a direct result of this treatment strategy is unclear.
“It’s hard to believe, in this small study, that this agent [nicotinamide] would have such a striking effect on DNA proviral levels,” she said. “We learn from each of these cases. But this is a single case, with multiple mechanisms that may have contributed to the outcome here. To what extent this is a direct result of this treatment strategy is unclear.”
Only time will tell, and Persaud knows this first hand. Back in 2014, she presented data at another HIV conference on the Mississippi baby who, after 21 months of no treatment, still didn›t have an HIV viral load.
At the time, the baby was hailed as “functionally cured,” but just 6 months later, the virus returned.
Dieffenbach agrees. “There are 10,000 genetic variations that need to be considered, and it all adds up to a unique individual,” he said of the Brazilian patient. “This one is one person, and it’s still early days.”
Counseling patients on niacin supplementation
Some clinicians are already bracing for the flood of people with HIV now wanting to take, or who are already taking, a niacin supplement because of this case, said Laura Waters, MD, from Mortimer Market Centre in London, who is chair of the British HIV Association.
But nicotinamide is different than nicotinic acid, which is what many people mean when they talk about niacin supplementation, according to data from the Office of Dietary Supplements (ODS) at the National Institutes of Health. Nicotinic acid has been used as a supplement for people with high cholesterol for years. Most Americans get more than the recommended daily intake of both types of niacin – 16 mg for adult men and 14 mg for adult women – in their regular diet, according to the 2015/16 National Health and Nutrition Examination Survey.
The Brazilian patient received a total daily dose of nicotinamide of 1000 mg, which is not associated with any adverse effects. Doses above 3000 mg daily can lead to diarrhea and a decrease in platelet count, according to the ODS.
Although Diaz said he doesn’t think people with HIV should run out and start taking a supplement right away, Waters said she sees it as inevitable.
The good news is that if people really are taking nicotinamide – not nicotinic acid – it seems “fairly well tolerated without many side effects,” she said, but added: “I expect shortages of nicotinamide from tomorrow.”
This story first appeared on Medscape.com.
FDA OKs first-in-class HIV therapy for patients with few options
Fostemsavir is indicated for use in combination with other antiretroviral (ARV) agents in heavily treatment-experienced adults with multidrug-resistant HIV-1 infection who fail to achieve viral suppression on other regimens due to resistance, intolerance, or safety considerations.
“This approval marks a new class of antiretroviral medications that may benefit patients who have run out of HIV treatment options,” Jeff Murray, MD, deputy director of the Division of Antivirals in the FDA’s Center for Drug Evaluation and Research, said in a statement.
“The availability of new classes of antiretroviral drugs is critical for heavily treatment-experienced patients living with multidrug resistant HIV infection — helping people living with hard-to-treat HIV who are at greater risk for HIV-related complications to potentially live longer, healthier lives,” he said.
Fostemsavir 600 mg extended-release tablets are taken twice daily.
In the phase 3 BRIGHTE study, 60% of adults who added fostemsavir to optimized background ARV therapy achieved and maintained viral suppression through 96 weeks and saw clinically meaningful improvements in CD4+ T cells.
Most of the 371 participants in the study had been on anti-HIV therapy for more than 15 years (71%), had been exposed to five or more different HIV treatment regimens (85%), and/or had a history of AIDS (86%).
The most common adverse reactions with fostemsavir are nausea, fatigue, and diarrhea. Serious drug reactions included liver enzyme elevations in patients co-infected with hepatitis B or C virus and three cases of severe immune reconstitution inflammatory syndrome.
“Exciting” Advance
“There is a small group of heavily treatment-experienced adults living with HIV who are not able to maintain viral suppression with currently available medication and, without effective new options, are at great risk of progressing to AIDS,” Deborah Waterhouse, CEO of ViiV Healthcare, said in a news release.
“The approval of Rukobia is a culmination of incredibly complex research, development, and manufacturing efforts to ensure we leave no person living with HIV behind,” she said.
“As a novel HIV attachment inhibitor, fostemsavir targets the first step of the viral lifecycle offering a new mechanism of action to treat people living with HIV,” Jacob P. Lalezari, MD, chief executive officer and director of Quest Clinical Research, commented in the release.
Fostemsavir is an “exciting” advance for the heavily treatment-experienced population and “an advancement the HIV community has long been waiting for. As an activist as well as researcher, I am very grateful to ViiV Healthcare for their commitment to heavily-treatment experienced people living with HIV,” he added.
Fostemsavir was reviewed and approved under the FDA’s fast track and breakthrough therapy designations, which are intended to facilitate and expedite the development and review of new drugs to address unmet medical need in the treatment of a serious or life-threatening condition.
Full prescribing information is available online.
This article first appeared on Medscape.com.
Fostemsavir is indicated for use in combination with other antiretroviral (ARV) agents in heavily treatment-experienced adults with multidrug-resistant HIV-1 infection who fail to achieve viral suppression on other regimens due to resistance, intolerance, or safety considerations.
“This approval marks a new class of antiretroviral medications that may benefit patients who have run out of HIV treatment options,” Jeff Murray, MD, deputy director of the Division of Antivirals in the FDA’s Center for Drug Evaluation and Research, said in a statement.
“The availability of new classes of antiretroviral drugs is critical for heavily treatment-experienced patients living with multidrug resistant HIV infection — helping people living with hard-to-treat HIV who are at greater risk for HIV-related complications to potentially live longer, healthier lives,” he said.
Fostemsavir 600 mg extended-release tablets are taken twice daily.
In the phase 3 BRIGHTE study, 60% of adults who added fostemsavir to optimized background ARV therapy achieved and maintained viral suppression through 96 weeks and saw clinically meaningful improvements in CD4+ T cells.
Most of the 371 participants in the study had been on anti-HIV therapy for more than 15 years (71%), had been exposed to five or more different HIV treatment regimens (85%), and/or had a history of AIDS (86%).
The most common adverse reactions with fostemsavir are nausea, fatigue, and diarrhea. Serious drug reactions included liver enzyme elevations in patients co-infected with hepatitis B or C virus and three cases of severe immune reconstitution inflammatory syndrome.
“Exciting” Advance
“There is a small group of heavily treatment-experienced adults living with HIV who are not able to maintain viral suppression with currently available medication and, without effective new options, are at great risk of progressing to AIDS,” Deborah Waterhouse, CEO of ViiV Healthcare, said in a news release.
“The approval of Rukobia is a culmination of incredibly complex research, development, and manufacturing efforts to ensure we leave no person living with HIV behind,” she said.
“As a novel HIV attachment inhibitor, fostemsavir targets the first step of the viral lifecycle offering a new mechanism of action to treat people living with HIV,” Jacob P. Lalezari, MD, chief executive officer and director of Quest Clinical Research, commented in the release.
Fostemsavir is an “exciting” advance for the heavily treatment-experienced population and “an advancement the HIV community has long been waiting for. As an activist as well as researcher, I am very grateful to ViiV Healthcare for their commitment to heavily-treatment experienced people living with HIV,” he added.
Fostemsavir was reviewed and approved under the FDA’s fast track and breakthrough therapy designations, which are intended to facilitate and expedite the development and review of new drugs to address unmet medical need in the treatment of a serious or life-threatening condition.
Full prescribing information is available online.
This article first appeared on Medscape.com.
Fostemsavir is indicated for use in combination with other antiretroviral (ARV) agents in heavily treatment-experienced adults with multidrug-resistant HIV-1 infection who fail to achieve viral suppression on other regimens due to resistance, intolerance, or safety considerations.
“This approval marks a new class of antiretroviral medications that may benefit patients who have run out of HIV treatment options,” Jeff Murray, MD, deputy director of the Division of Antivirals in the FDA’s Center for Drug Evaluation and Research, said in a statement.
“The availability of new classes of antiretroviral drugs is critical for heavily treatment-experienced patients living with multidrug resistant HIV infection — helping people living with hard-to-treat HIV who are at greater risk for HIV-related complications to potentially live longer, healthier lives,” he said.
Fostemsavir 600 mg extended-release tablets are taken twice daily.
In the phase 3 BRIGHTE study, 60% of adults who added fostemsavir to optimized background ARV therapy achieved and maintained viral suppression through 96 weeks and saw clinically meaningful improvements in CD4+ T cells.
Most of the 371 participants in the study had been on anti-HIV therapy for more than 15 years (71%), had been exposed to five or more different HIV treatment regimens (85%), and/or had a history of AIDS (86%).
The most common adverse reactions with fostemsavir are nausea, fatigue, and diarrhea. Serious drug reactions included liver enzyme elevations in patients co-infected with hepatitis B or C virus and three cases of severe immune reconstitution inflammatory syndrome.
“Exciting” Advance
“There is a small group of heavily treatment-experienced adults living with HIV who are not able to maintain viral suppression with currently available medication and, without effective new options, are at great risk of progressing to AIDS,” Deborah Waterhouse, CEO of ViiV Healthcare, said in a news release.
“The approval of Rukobia is a culmination of incredibly complex research, development, and manufacturing efforts to ensure we leave no person living with HIV behind,” she said.
“As a novel HIV attachment inhibitor, fostemsavir targets the first step of the viral lifecycle offering a new mechanism of action to treat people living with HIV,” Jacob P. Lalezari, MD, chief executive officer and director of Quest Clinical Research, commented in the release.
Fostemsavir is an “exciting” advance for the heavily treatment-experienced population and “an advancement the HIV community has long been waiting for. As an activist as well as researcher, I am very grateful to ViiV Healthcare for their commitment to heavily-treatment experienced people living with HIV,” he added.
Fostemsavir was reviewed and approved under the FDA’s fast track and breakthrough therapy designations, which are intended to facilitate and expedite the development and review of new drugs to address unmet medical need in the treatment of a serious or life-threatening condition.
Full prescribing information is available online.
This article first appeared on Medscape.com.
Holistic HIV care broadens scope to noncommunicable diseases
Several HIV management efforts in African groups have developed differentiated service delivery models for people living with HIV who also have noncommunicable diseases, offering diagnostic and management strategies that can treat HIV patients holistically and address their range of health issues.
These efforts allow “countries with effective HIV programs to leverage lessons learned and best practices to enhance chronic noncommunicable disease” management, Miriam Rabkin, MD, said at the virtual meeting of the International AIDS conference. This approach aims to address the “growing prevalence of chronic noncommunicable diseases in low- and middle-income countries,” and the recognition that ”people living with HIV have the same or higher prevalence” of chronic noncommunicable diseases as that of others in the region where they live, said Dr. Rabkin, an epidemiologist at Columbia University in New York and director for health systems strengthening at ICAP, an international AIDS care program run at Columbia. The differentiated service delivery model derived from the premise that “one size does not fit all,” and that effective interventions must be “tailored” to the social and clinical circumstances of specific regions, she explained.
One program has focused on introducing more contemporary methods for diagnosing leukemias, lymphomas, and melanomas using flow cytometry at the Uganda National Health Laboratory Service in Kampala. This change in testing, which became available to patients starting in February 2019, has allowed diagnostics with fresh specimens that require minimal processing and results returned to referring physicians within 48 hours, a significant upgrade from the 1- to 4-week delay that was typical in the past, said Steven J. Kussick, MD, a hematopathologist and associate medical director of PhenoPath, a commercial pathology laboratory in Seattle.
The idea was to “leverage existing HIV laboratory capabilities to transform cancer diagnosis in sub-Saharan Africa,” he said during his talk at the conference. The flow cytometry approach allows an experienced pathologist like Dr. Kussick to diagnose clearcut cases in “5 seconds,” he said. The lab has already run specimens from more than 200 patients, and estimates an ability to handle specimens from about 250 patients per year at a total annual cost of roughly $60,000, an apparently sustainable operating model, said Dr. Kussick, who serves as a full-time consultant to the operation and was also instrumental in the 5-year process that created the diagnostic program. Future improvements planned for this program include bringing on-line a higher complexity diagnostic assay that’s closer to what is currently standard U.S. testing, digital imaging to facilitate consultation with remote experts, adding immunochemistry assays to allow diagnosis of solid tumors, and opening of a second laboratory in Kenya.
Another noncommunicable disease intervention in Africa that’s building on existing infrastructure for dealing with HIV infection is targeting hypertension, the most lethal risk factor globally for preventable deaths, said Jennifer Cohn, MD, senior vice president for cardiovascular health at the New York–based Resolve to Save Lives initiative. “We need to learn from what’s been done for HIV to rapidly incorporate and scale differentiated service models,” she said.
HIV and hypertension, along with diabetes, “are beginning to be recognized as ‘syndemics,’ ”synergistic pandemics, that need a holistic approach. A recent review of the topic reported that in the seven sub-Saharan countries with the highest HIV infection prevalence the percentage of adults with hypertension ranged from 20% to 24% (Curr Opin HIV AIDS. 2020 Jul;15[4]:356-60). Projections call for a “dramatic” increase in the prevalence of hypertension in both the general population and among people living with HIV, Dr. Cohn said.
As an example of the potential for combining HIV and antihypertensive care into a one-stop protocol, she cited a model program launched at Makarere University in Kampala, Uganda, that integrates HIV and antihypertensive treatment. Recent data from the program showed that among HIV-infected individuals 24% also had hypertension, and while the program lagged in putting only 28% of these hypertensive patients on a blood pressure-lowering regimen, more than three quarters of these patients on treatment successfully reached their goal blood pressure, proving the feasibility of the combined approach, Dr. Cohn said.
“Starting and scaling with differentiated service delivery models for noncommunicable diseases can help overcome barriers to uptake of care,” concluded Dr. Cohn. “As HIV cohorts age, we have to adapt and ensure we are providing quality, holistic care, including care for high impact noncommunicable diseases such as hypertension.”
Dr. Rabkin and Dr. Cohn had no disclosures.
Several HIV management efforts in African groups have developed differentiated service delivery models for people living with HIV who also have noncommunicable diseases, offering diagnostic and management strategies that can treat HIV patients holistically and address their range of health issues.
These efforts allow “countries with effective HIV programs to leverage lessons learned and best practices to enhance chronic noncommunicable disease” management, Miriam Rabkin, MD, said at the virtual meeting of the International AIDS conference. This approach aims to address the “growing prevalence of chronic noncommunicable diseases in low- and middle-income countries,” and the recognition that ”people living with HIV have the same or higher prevalence” of chronic noncommunicable diseases as that of others in the region where they live, said Dr. Rabkin, an epidemiologist at Columbia University in New York and director for health systems strengthening at ICAP, an international AIDS care program run at Columbia. The differentiated service delivery model derived from the premise that “one size does not fit all,” and that effective interventions must be “tailored” to the social and clinical circumstances of specific regions, she explained.
One program has focused on introducing more contemporary methods for diagnosing leukemias, lymphomas, and melanomas using flow cytometry at the Uganda National Health Laboratory Service in Kampala. This change in testing, which became available to patients starting in February 2019, has allowed diagnostics with fresh specimens that require minimal processing and results returned to referring physicians within 48 hours, a significant upgrade from the 1- to 4-week delay that was typical in the past, said Steven J. Kussick, MD, a hematopathologist and associate medical director of PhenoPath, a commercial pathology laboratory in Seattle.
The idea was to “leverage existing HIV laboratory capabilities to transform cancer diagnosis in sub-Saharan Africa,” he said during his talk at the conference. The flow cytometry approach allows an experienced pathologist like Dr. Kussick to diagnose clearcut cases in “5 seconds,” he said. The lab has already run specimens from more than 200 patients, and estimates an ability to handle specimens from about 250 patients per year at a total annual cost of roughly $60,000, an apparently sustainable operating model, said Dr. Kussick, who serves as a full-time consultant to the operation and was also instrumental in the 5-year process that created the diagnostic program. Future improvements planned for this program include bringing on-line a higher complexity diagnostic assay that’s closer to what is currently standard U.S. testing, digital imaging to facilitate consultation with remote experts, adding immunochemistry assays to allow diagnosis of solid tumors, and opening of a second laboratory in Kenya.
Another noncommunicable disease intervention in Africa that’s building on existing infrastructure for dealing with HIV infection is targeting hypertension, the most lethal risk factor globally for preventable deaths, said Jennifer Cohn, MD, senior vice president for cardiovascular health at the New York–based Resolve to Save Lives initiative. “We need to learn from what’s been done for HIV to rapidly incorporate and scale differentiated service models,” she said.
HIV and hypertension, along with diabetes, “are beginning to be recognized as ‘syndemics,’ ”synergistic pandemics, that need a holistic approach. A recent review of the topic reported that in the seven sub-Saharan countries with the highest HIV infection prevalence the percentage of adults with hypertension ranged from 20% to 24% (Curr Opin HIV AIDS. 2020 Jul;15[4]:356-60). Projections call for a “dramatic” increase in the prevalence of hypertension in both the general population and among people living with HIV, Dr. Cohn said.
As an example of the potential for combining HIV and antihypertensive care into a one-stop protocol, she cited a model program launched at Makarere University in Kampala, Uganda, that integrates HIV and antihypertensive treatment. Recent data from the program showed that among HIV-infected individuals 24% also had hypertension, and while the program lagged in putting only 28% of these hypertensive patients on a blood pressure-lowering regimen, more than three quarters of these patients on treatment successfully reached their goal blood pressure, proving the feasibility of the combined approach, Dr. Cohn said.
“Starting and scaling with differentiated service delivery models for noncommunicable diseases can help overcome barriers to uptake of care,” concluded Dr. Cohn. “As HIV cohorts age, we have to adapt and ensure we are providing quality, holistic care, including care for high impact noncommunicable diseases such as hypertension.”
Dr. Rabkin and Dr. Cohn had no disclosures.
Several HIV management efforts in African groups have developed differentiated service delivery models for people living with HIV who also have noncommunicable diseases, offering diagnostic and management strategies that can treat HIV patients holistically and address their range of health issues.
These efforts allow “countries with effective HIV programs to leverage lessons learned and best practices to enhance chronic noncommunicable disease” management, Miriam Rabkin, MD, said at the virtual meeting of the International AIDS conference. This approach aims to address the “growing prevalence of chronic noncommunicable diseases in low- and middle-income countries,” and the recognition that ”people living with HIV have the same or higher prevalence” of chronic noncommunicable diseases as that of others in the region where they live, said Dr. Rabkin, an epidemiologist at Columbia University in New York and director for health systems strengthening at ICAP, an international AIDS care program run at Columbia. The differentiated service delivery model derived from the premise that “one size does not fit all,” and that effective interventions must be “tailored” to the social and clinical circumstances of specific regions, she explained.
One program has focused on introducing more contemporary methods for diagnosing leukemias, lymphomas, and melanomas using flow cytometry at the Uganda National Health Laboratory Service in Kampala. This change in testing, which became available to patients starting in February 2019, has allowed diagnostics with fresh specimens that require minimal processing and results returned to referring physicians within 48 hours, a significant upgrade from the 1- to 4-week delay that was typical in the past, said Steven J. Kussick, MD, a hematopathologist and associate medical director of PhenoPath, a commercial pathology laboratory in Seattle.
The idea was to “leverage existing HIV laboratory capabilities to transform cancer diagnosis in sub-Saharan Africa,” he said during his talk at the conference. The flow cytometry approach allows an experienced pathologist like Dr. Kussick to diagnose clearcut cases in “5 seconds,” he said. The lab has already run specimens from more than 200 patients, and estimates an ability to handle specimens from about 250 patients per year at a total annual cost of roughly $60,000, an apparently sustainable operating model, said Dr. Kussick, who serves as a full-time consultant to the operation and was also instrumental in the 5-year process that created the diagnostic program. Future improvements planned for this program include bringing on-line a higher complexity diagnostic assay that’s closer to what is currently standard U.S. testing, digital imaging to facilitate consultation with remote experts, adding immunochemistry assays to allow diagnosis of solid tumors, and opening of a second laboratory in Kenya.
Another noncommunicable disease intervention in Africa that’s building on existing infrastructure for dealing with HIV infection is targeting hypertension, the most lethal risk factor globally for preventable deaths, said Jennifer Cohn, MD, senior vice president for cardiovascular health at the New York–based Resolve to Save Lives initiative. “We need to learn from what’s been done for HIV to rapidly incorporate and scale differentiated service models,” she said.
HIV and hypertension, along with diabetes, “are beginning to be recognized as ‘syndemics,’ ”synergistic pandemics, that need a holistic approach. A recent review of the topic reported that in the seven sub-Saharan countries with the highest HIV infection prevalence the percentage of adults with hypertension ranged from 20% to 24% (Curr Opin HIV AIDS. 2020 Jul;15[4]:356-60). Projections call for a “dramatic” increase in the prevalence of hypertension in both the general population and among people living with HIV, Dr. Cohn said.
As an example of the potential for combining HIV and antihypertensive care into a one-stop protocol, she cited a model program launched at Makarere University in Kampala, Uganda, that integrates HIV and antihypertensive treatment. Recent data from the program showed that among HIV-infected individuals 24% also had hypertension, and while the program lagged in putting only 28% of these hypertensive patients on a blood pressure-lowering regimen, more than three quarters of these patients on treatment successfully reached their goal blood pressure, proving the feasibility of the combined approach, Dr. Cohn said.
“Starting and scaling with differentiated service delivery models for noncommunicable diseases can help overcome barriers to uptake of care,” concluded Dr. Cohn. “As HIV cohorts age, we have to adapt and ensure we are providing quality, holistic care, including care for high impact noncommunicable diseases such as hypertension.”
Dr. Rabkin and Dr. Cohn had no disclosures.
FROM AIDS 2020
COVID-19 disruptions ‘life threatening’ for people with HIV
When the COVID-19 pandemic led to a blanket shelter-in-place order in California in March, it did more than shut down in-person visits at Ward 86, the HIV clinic for publicly insured patients at San Francisco General Hospital. It also led to a decrease in viral suppression among the clinic›s clients. By the end of June, the percentage of patients with an undetectable viral load had dropped by nearly one-third.
This is exactly what Monica Gandhi, MD, associate division chief of HIV, infectious diseases, and global medicine at the University of California, San Francisco, and medical director of the clinic, was afraid of.
“We’re profoundly worried about the impact of COVID-19 on actual treatment outcomes,” said Dr. Gandhi, cochair of the virtual International AIDS Conference (AIDS) 2020.
And it’s not just the clinic’s clients at risk. Of the 106 countries served by the Global Fund to Fight HIV, Tuberculosis, and Malaria, 85% saw disruptions in HIV programs, according to a report released last month.
These service disruptions are considerable and “life threatening,” affecting some of the people at greatest risk for HIV acquisition and poor outcomes – such as people engaged in transactional sex (40%), men who have sex with men (37%), and transgender people (31%) – the 2020 Global AIDS Update, released today by UNAIDS, reports.
“In sub-Saharan Africa alone, if there is a 6-month interruption in HIV treatment services, it will account for an additional 500,000 deaths. That doubles the number of deaths in sub-Saharan Africa alone and brings us back to 2008 mortality levels,” said Shannon Hader, MD, deputy executive director of UNAIDS. “We just can’t allow that to happen.”
In addition, 73 countries are at risk of running out of HIV medications, according to a World Health Organization report, also released today.
Quantifying the impact
The impact is not the same for all patients, said Anton Pozniak, MD, consulting physician in HIV medicine at the Chelsea and Westminster Hospital in London, and international cochair of AIDS 2020.
For some, COVID-19 has not changed much. Their viral loads remain undetectable and all they need is multimonth supplies of their antiretroviral therapy (ART) medications, he told Medscape Medical News. Still, he said he worries about the well-documented effects that social isolation is having on the mental health of these patients, and the increase in substance use associated with the pandemic.
Then there is a small group of patients with HIV who had put off starting ART before the pandemic, but now want to start, he reported.
And finally, there are the people for whom the fear of COVID-19 has crippled their ability to get care.
There are people who have decided they don’t want to come to the hospital or come to the clinic because they’re scared of getting COVID-19.
“It’s really very striking,” said Dr. Pozniak. “There are people who have decided they don’t want to come to the hospital or come to the clinic because they’re scared of getting COVID-19. We’ve offered to deliver treatment, but they don’t want the stigma of parcels of drugs arriving.”
In a study presented at the conference, four of 12 care and substance-use treatment facilities in Europe and North America – including Seattle and Philadelphia – reported patients taking longer to fill ART prescriptions. And four of the 12 also reported that clients who injected drugs and were at risk for or living with HIV were having trouble adhering to prescribed therapies. In addition, at 11 of the sites, HIV testing has either nearly or completely shut down.
Structural barriers to telemedicine
And then there are structural barriers to care – poverty, lack of transportation, lack of or slow internet access, and lack of insurance – which affect 10% to 20% of the people with HIV that Jodie Dionne-Odom, MD, sees at the 1917 Ryan White HIV clinic at the University of Alabama at Birmingham.
These are the patients she said she worries about most, the ones who, even before COVID-19, were barely managing to pay their rent, car payments, and cell phone bills.
“With COVID-19 and being at home or being laid off, those things could no longer be paid. They’ve lost their phone, they’ve lost their car,” said Dionne-Odom, chief of women’s health services for the clinic. “That’s a really significant impact, because that’s exactly the group you can’t reach by telemedicine.”
In March, when the 1917 Clinic began providing the majority of services online, these people fell off the radar, said Aadia Rana, MD, associate professor of infectious diseases at the University of Alabama at Birmingham, who also works at the clinic.
This is not for lack of trying, she explained. Staff called patients weekly to check in and reschedule appointments, but there were some they just couldn’t reach.
Although the data for the second quarter have not yet been analyzed, “I would expect that our typically close to 90% viral suppression rate is going to decrease,” she said.
This decrease is likely widespread, said Rana, who is principle investigator of the Long-Acting Therapy to Improve Treatment Success in Daily Life (LATITUDE) study.
Many of the 33 sites involved in LATITUDE shut down in the early months of the pandemic, but some are now coming back online. In fact, “we are getting all these pleas from sites around the country saying, ‘Hey, once LATITUDE is open for enrollment, we have so many people who would now be eligible’,” she told Medscape Medical News.
“Why are they now eligible and they weren’t eligible before? I’m assuming it’s because they now have a detectable viral load,” which is one of the requirements for enrollment in LATITUDE, she explained.
Impact on the LGBTI community
At the onset of the COVID-19 pandemic, Erik Lamontagne, senior economist at UNAIDS, wondered how the quarantine was affecting LGBTI people.
To find out, he and his colleagues launched a survey asking just that. He is also coprinciple investigator of the LGBT Happiness Survey, a multicountry survey of LGBTI people launched last year.
The 13,562 LGBTI respondents came from 138 countries or territories. Of the 1,140 respondents living with HIV, 26% had seen their HIV care disrupted or restricted in some way during the pandemic, and 55% of those had no more than a month’s worth of HIV medications on hand.
But the pandemic hasn’t just affected people already living with HIV, Mr. Lamontagne reported. Nine of 10 respondents were living under some form of stay-at-home order, 73% were not meeting their basic needs, 37% had missed meals as a result of economic hardship, and half of those who were still working expected to lose their jobs.
Many could not afford to quarantine, Mr. Lamontagne told Medscape Medical News. And financial resources were stretched so thin that about 1% of respondents reported engaging in transactional sex for the first time. Some reported that their economic circumstances were so dire that they couldn’t require clients to wear condoms, increasing their risk for both COVID-19 and HIV.
“What they can eat in the evening is what they can earn during the day,” Mr. Lamontagne explained.
Unfortunately, it is the people already in a situation of economic vulnerability – often those from the LGBTI community – who are most affected by COVID-19, he added.
PrEP use changing
The pandemic has also affected the use of pre-exposure prophylaxis (PrEP).
South African women taking PrEP to protect themselves from HIV during pregnancy were 2.36 times more likely to miss a clinic visit to refill their prescription after COVID-19 lockdowns began than before, data presented at the conference showed. The women cited fear of acquiring COVID-19 at the medical facility, fear of police, transportation barriers, and long clinic wait times to explain the missed visits.
A study on the use of PrEP at Fenway Health, a sexual health clinic in Boston, showed a 278% increase in unfilled PrEP prescriptions after stay-at-home orders and a 72.1% drop in new PrEP prescriptions.
It’s unclear what these data, which will be presented at the conference later this week, mean, said Douglas Krakower, MD, assistant professor of medicine and population medicine at Harvard Medical School in Boston.
“We don’t know whether this represents people having trouble accessing PrEP” out of concern about getting COVID “or concerns about financial implications,” he explained.
“They may have had hardships from unemployment or other financial constraints” and have lost insurance or are still having to pay copays, he told Medscape Medical News. Or it could just be that they’re not going out or having sex, so they’ve discontinued the medication.
“Anecdotally we’ve heard that some patients are sheltering in place and not having sex and so have chosen not to use PrEP,” he added.
It’s also possible that people are rationing pills or have moved themselves to the PrEP 2-1-1 protocol, which is used only when someone is having sex, said Dr. Krakower, citing a study showing that sexual behavior is continuing as usual during quarantine for about half the gay men in the United States.
Resilience and fragility
It’s not just people living with HIV whose routines have changed during the pandemic. A survey of HIV clinicians around the world conducted by the International Association of Providers of AIDS Care showed that 88% of HIV clinicians have been pulled away from their regular work to manage COVID-19 in their communities.
But the COVID-19 pandemic shows no signs of stopping, and clinicians are now having to re-engage with their HIV patients.
“What COVID-19 has represented for us is a looking glass to see the resilience, but also the fragility, in HIV responses, not just in the global south, but also in the global north,” José Zuniga, PhD, IAPAC president and chief executive officer, said during a preconference session on controlling the HIV epidemic.
For Dr. Dionne-Odom, reopening the 1917 Clinic in Alabama meant tracking down patients who could not participate in telemedicine. Fortunately (or unfortunately, depending on how you look at it), the clinic, which serves a population with a high level of economic insecurity, has worked to get as many phone numbers as possible for each patient. So when the clinic opened back up, staff was able to call family members, friends, and trusted contacts to bring their patients back into the clinic.
“No one wanted to reopen too quickly,” said Dr. Dionne-Odom. “But having people come in allowed us to do all the other things that are the key part of HIV care: getting them connected with a social worker and making sure they have enough food, helping them with their electricity bills and their housing issues, all the wrap-around services that are so crucial for these patients.”
This article first appeared on Medscape.com.
When the COVID-19 pandemic led to a blanket shelter-in-place order in California in March, it did more than shut down in-person visits at Ward 86, the HIV clinic for publicly insured patients at San Francisco General Hospital. It also led to a decrease in viral suppression among the clinic›s clients. By the end of June, the percentage of patients with an undetectable viral load had dropped by nearly one-third.
This is exactly what Monica Gandhi, MD, associate division chief of HIV, infectious diseases, and global medicine at the University of California, San Francisco, and medical director of the clinic, was afraid of.
“We’re profoundly worried about the impact of COVID-19 on actual treatment outcomes,” said Dr. Gandhi, cochair of the virtual International AIDS Conference (AIDS) 2020.
And it’s not just the clinic’s clients at risk. Of the 106 countries served by the Global Fund to Fight HIV, Tuberculosis, and Malaria, 85% saw disruptions in HIV programs, according to a report released last month.
These service disruptions are considerable and “life threatening,” affecting some of the people at greatest risk for HIV acquisition and poor outcomes – such as people engaged in transactional sex (40%), men who have sex with men (37%), and transgender people (31%) – the 2020 Global AIDS Update, released today by UNAIDS, reports.
“In sub-Saharan Africa alone, if there is a 6-month interruption in HIV treatment services, it will account for an additional 500,000 deaths. That doubles the number of deaths in sub-Saharan Africa alone and brings us back to 2008 mortality levels,” said Shannon Hader, MD, deputy executive director of UNAIDS. “We just can’t allow that to happen.”
In addition, 73 countries are at risk of running out of HIV medications, according to a World Health Organization report, also released today.
Quantifying the impact
The impact is not the same for all patients, said Anton Pozniak, MD, consulting physician in HIV medicine at the Chelsea and Westminster Hospital in London, and international cochair of AIDS 2020.
For some, COVID-19 has not changed much. Their viral loads remain undetectable and all they need is multimonth supplies of their antiretroviral therapy (ART) medications, he told Medscape Medical News. Still, he said he worries about the well-documented effects that social isolation is having on the mental health of these patients, and the increase in substance use associated with the pandemic.
Then there is a small group of patients with HIV who had put off starting ART before the pandemic, but now want to start, he reported.
And finally, there are the people for whom the fear of COVID-19 has crippled their ability to get care.
There are people who have decided they don’t want to come to the hospital or come to the clinic because they’re scared of getting COVID-19.
“It’s really very striking,” said Dr. Pozniak. “There are people who have decided they don’t want to come to the hospital or come to the clinic because they’re scared of getting COVID-19. We’ve offered to deliver treatment, but they don’t want the stigma of parcels of drugs arriving.”
In a study presented at the conference, four of 12 care and substance-use treatment facilities in Europe and North America – including Seattle and Philadelphia – reported patients taking longer to fill ART prescriptions. And four of the 12 also reported that clients who injected drugs and were at risk for or living with HIV were having trouble adhering to prescribed therapies. In addition, at 11 of the sites, HIV testing has either nearly or completely shut down.
Structural barriers to telemedicine
And then there are structural barriers to care – poverty, lack of transportation, lack of or slow internet access, and lack of insurance – which affect 10% to 20% of the people with HIV that Jodie Dionne-Odom, MD, sees at the 1917 Ryan White HIV clinic at the University of Alabama at Birmingham.
These are the patients she said she worries about most, the ones who, even before COVID-19, were barely managing to pay their rent, car payments, and cell phone bills.
“With COVID-19 and being at home or being laid off, those things could no longer be paid. They’ve lost their phone, they’ve lost their car,” said Dionne-Odom, chief of women’s health services for the clinic. “That’s a really significant impact, because that’s exactly the group you can’t reach by telemedicine.”
In March, when the 1917 Clinic began providing the majority of services online, these people fell off the radar, said Aadia Rana, MD, associate professor of infectious diseases at the University of Alabama at Birmingham, who also works at the clinic.
This is not for lack of trying, she explained. Staff called patients weekly to check in and reschedule appointments, but there were some they just couldn’t reach.
Although the data for the second quarter have not yet been analyzed, “I would expect that our typically close to 90% viral suppression rate is going to decrease,” she said.
This decrease is likely widespread, said Rana, who is principle investigator of the Long-Acting Therapy to Improve Treatment Success in Daily Life (LATITUDE) study.
Many of the 33 sites involved in LATITUDE shut down in the early months of the pandemic, but some are now coming back online. In fact, “we are getting all these pleas from sites around the country saying, ‘Hey, once LATITUDE is open for enrollment, we have so many people who would now be eligible’,” she told Medscape Medical News.
“Why are they now eligible and they weren’t eligible before? I’m assuming it’s because they now have a detectable viral load,” which is one of the requirements for enrollment in LATITUDE, she explained.
Impact on the LGBTI community
At the onset of the COVID-19 pandemic, Erik Lamontagne, senior economist at UNAIDS, wondered how the quarantine was affecting LGBTI people.
To find out, he and his colleagues launched a survey asking just that. He is also coprinciple investigator of the LGBT Happiness Survey, a multicountry survey of LGBTI people launched last year.
The 13,562 LGBTI respondents came from 138 countries or territories. Of the 1,140 respondents living with HIV, 26% had seen their HIV care disrupted or restricted in some way during the pandemic, and 55% of those had no more than a month’s worth of HIV medications on hand.
But the pandemic hasn’t just affected people already living with HIV, Mr. Lamontagne reported. Nine of 10 respondents were living under some form of stay-at-home order, 73% were not meeting their basic needs, 37% had missed meals as a result of economic hardship, and half of those who were still working expected to lose their jobs.
Many could not afford to quarantine, Mr. Lamontagne told Medscape Medical News. And financial resources were stretched so thin that about 1% of respondents reported engaging in transactional sex for the first time. Some reported that their economic circumstances were so dire that they couldn’t require clients to wear condoms, increasing their risk for both COVID-19 and HIV.
“What they can eat in the evening is what they can earn during the day,” Mr. Lamontagne explained.
Unfortunately, it is the people already in a situation of economic vulnerability – often those from the LGBTI community – who are most affected by COVID-19, he added.
PrEP use changing
The pandemic has also affected the use of pre-exposure prophylaxis (PrEP).
South African women taking PrEP to protect themselves from HIV during pregnancy were 2.36 times more likely to miss a clinic visit to refill their prescription after COVID-19 lockdowns began than before, data presented at the conference showed. The women cited fear of acquiring COVID-19 at the medical facility, fear of police, transportation barriers, and long clinic wait times to explain the missed visits.
A study on the use of PrEP at Fenway Health, a sexual health clinic in Boston, showed a 278% increase in unfilled PrEP prescriptions after stay-at-home orders and a 72.1% drop in new PrEP prescriptions.
It’s unclear what these data, which will be presented at the conference later this week, mean, said Douglas Krakower, MD, assistant professor of medicine and population medicine at Harvard Medical School in Boston.
“We don’t know whether this represents people having trouble accessing PrEP” out of concern about getting COVID “or concerns about financial implications,” he explained.
“They may have had hardships from unemployment or other financial constraints” and have lost insurance or are still having to pay copays, he told Medscape Medical News. Or it could just be that they’re not going out or having sex, so they’ve discontinued the medication.
“Anecdotally we’ve heard that some patients are sheltering in place and not having sex and so have chosen not to use PrEP,” he added.
It’s also possible that people are rationing pills or have moved themselves to the PrEP 2-1-1 protocol, which is used only when someone is having sex, said Dr. Krakower, citing a study showing that sexual behavior is continuing as usual during quarantine for about half the gay men in the United States.
Resilience and fragility
It’s not just people living with HIV whose routines have changed during the pandemic. A survey of HIV clinicians around the world conducted by the International Association of Providers of AIDS Care showed that 88% of HIV clinicians have been pulled away from their regular work to manage COVID-19 in their communities.
But the COVID-19 pandemic shows no signs of stopping, and clinicians are now having to re-engage with their HIV patients.
“What COVID-19 has represented for us is a looking glass to see the resilience, but also the fragility, in HIV responses, not just in the global south, but also in the global north,” José Zuniga, PhD, IAPAC president and chief executive officer, said during a preconference session on controlling the HIV epidemic.
For Dr. Dionne-Odom, reopening the 1917 Clinic in Alabama meant tracking down patients who could not participate in telemedicine. Fortunately (or unfortunately, depending on how you look at it), the clinic, which serves a population with a high level of economic insecurity, has worked to get as many phone numbers as possible for each patient. So when the clinic opened back up, staff was able to call family members, friends, and trusted contacts to bring their patients back into the clinic.
“No one wanted to reopen too quickly,” said Dr. Dionne-Odom. “But having people come in allowed us to do all the other things that are the key part of HIV care: getting them connected with a social worker and making sure they have enough food, helping them with their electricity bills and their housing issues, all the wrap-around services that are so crucial for these patients.”
This article first appeared on Medscape.com.
When the COVID-19 pandemic led to a blanket shelter-in-place order in California in March, it did more than shut down in-person visits at Ward 86, the HIV clinic for publicly insured patients at San Francisco General Hospital. It also led to a decrease in viral suppression among the clinic›s clients. By the end of June, the percentage of patients with an undetectable viral load had dropped by nearly one-third.
This is exactly what Monica Gandhi, MD, associate division chief of HIV, infectious diseases, and global medicine at the University of California, San Francisco, and medical director of the clinic, was afraid of.
“We’re profoundly worried about the impact of COVID-19 on actual treatment outcomes,” said Dr. Gandhi, cochair of the virtual International AIDS Conference (AIDS) 2020.
And it’s not just the clinic’s clients at risk. Of the 106 countries served by the Global Fund to Fight HIV, Tuberculosis, and Malaria, 85% saw disruptions in HIV programs, according to a report released last month.
These service disruptions are considerable and “life threatening,” affecting some of the people at greatest risk for HIV acquisition and poor outcomes – such as people engaged in transactional sex (40%), men who have sex with men (37%), and transgender people (31%) – the 2020 Global AIDS Update, released today by UNAIDS, reports.
“In sub-Saharan Africa alone, if there is a 6-month interruption in HIV treatment services, it will account for an additional 500,000 deaths. That doubles the number of deaths in sub-Saharan Africa alone and brings us back to 2008 mortality levels,” said Shannon Hader, MD, deputy executive director of UNAIDS. “We just can’t allow that to happen.”
In addition, 73 countries are at risk of running out of HIV medications, according to a World Health Organization report, also released today.
Quantifying the impact
The impact is not the same for all patients, said Anton Pozniak, MD, consulting physician in HIV medicine at the Chelsea and Westminster Hospital in London, and international cochair of AIDS 2020.
For some, COVID-19 has not changed much. Their viral loads remain undetectable and all they need is multimonth supplies of their antiretroviral therapy (ART) medications, he told Medscape Medical News. Still, he said he worries about the well-documented effects that social isolation is having on the mental health of these patients, and the increase in substance use associated with the pandemic.
Then there is a small group of patients with HIV who had put off starting ART before the pandemic, but now want to start, he reported.
And finally, there are the people for whom the fear of COVID-19 has crippled their ability to get care.
There are people who have decided they don’t want to come to the hospital or come to the clinic because they’re scared of getting COVID-19.
“It’s really very striking,” said Dr. Pozniak. “There are people who have decided they don’t want to come to the hospital or come to the clinic because they’re scared of getting COVID-19. We’ve offered to deliver treatment, but they don’t want the stigma of parcels of drugs arriving.”
In a study presented at the conference, four of 12 care and substance-use treatment facilities in Europe and North America – including Seattle and Philadelphia – reported patients taking longer to fill ART prescriptions. And four of the 12 also reported that clients who injected drugs and were at risk for or living with HIV were having trouble adhering to prescribed therapies. In addition, at 11 of the sites, HIV testing has either nearly or completely shut down.
Structural barriers to telemedicine
And then there are structural barriers to care – poverty, lack of transportation, lack of or slow internet access, and lack of insurance – which affect 10% to 20% of the people with HIV that Jodie Dionne-Odom, MD, sees at the 1917 Ryan White HIV clinic at the University of Alabama at Birmingham.
These are the patients she said she worries about most, the ones who, even before COVID-19, were barely managing to pay their rent, car payments, and cell phone bills.
“With COVID-19 and being at home or being laid off, those things could no longer be paid. They’ve lost their phone, they’ve lost their car,” said Dionne-Odom, chief of women’s health services for the clinic. “That’s a really significant impact, because that’s exactly the group you can’t reach by telemedicine.”
In March, when the 1917 Clinic began providing the majority of services online, these people fell off the radar, said Aadia Rana, MD, associate professor of infectious diseases at the University of Alabama at Birmingham, who also works at the clinic.
This is not for lack of trying, she explained. Staff called patients weekly to check in and reschedule appointments, but there were some they just couldn’t reach.
Although the data for the second quarter have not yet been analyzed, “I would expect that our typically close to 90% viral suppression rate is going to decrease,” she said.
This decrease is likely widespread, said Rana, who is principle investigator of the Long-Acting Therapy to Improve Treatment Success in Daily Life (LATITUDE) study.
Many of the 33 sites involved in LATITUDE shut down in the early months of the pandemic, but some are now coming back online. In fact, “we are getting all these pleas from sites around the country saying, ‘Hey, once LATITUDE is open for enrollment, we have so many people who would now be eligible’,” she told Medscape Medical News.
“Why are they now eligible and they weren’t eligible before? I’m assuming it’s because they now have a detectable viral load,” which is one of the requirements for enrollment in LATITUDE, she explained.
Impact on the LGBTI community
At the onset of the COVID-19 pandemic, Erik Lamontagne, senior economist at UNAIDS, wondered how the quarantine was affecting LGBTI people.
To find out, he and his colleagues launched a survey asking just that. He is also coprinciple investigator of the LGBT Happiness Survey, a multicountry survey of LGBTI people launched last year.
The 13,562 LGBTI respondents came from 138 countries or territories. Of the 1,140 respondents living with HIV, 26% had seen their HIV care disrupted or restricted in some way during the pandemic, and 55% of those had no more than a month’s worth of HIV medications on hand.
But the pandemic hasn’t just affected people already living with HIV, Mr. Lamontagne reported. Nine of 10 respondents were living under some form of stay-at-home order, 73% were not meeting their basic needs, 37% had missed meals as a result of economic hardship, and half of those who were still working expected to lose their jobs.
Many could not afford to quarantine, Mr. Lamontagne told Medscape Medical News. And financial resources were stretched so thin that about 1% of respondents reported engaging in transactional sex for the first time. Some reported that their economic circumstances were so dire that they couldn’t require clients to wear condoms, increasing their risk for both COVID-19 and HIV.
“What they can eat in the evening is what they can earn during the day,” Mr. Lamontagne explained.
Unfortunately, it is the people already in a situation of economic vulnerability – often those from the LGBTI community – who are most affected by COVID-19, he added.
PrEP use changing
The pandemic has also affected the use of pre-exposure prophylaxis (PrEP).
South African women taking PrEP to protect themselves from HIV during pregnancy were 2.36 times more likely to miss a clinic visit to refill their prescription after COVID-19 lockdowns began than before, data presented at the conference showed. The women cited fear of acquiring COVID-19 at the medical facility, fear of police, transportation barriers, and long clinic wait times to explain the missed visits.
A study on the use of PrEP at Fenway Health, a sexual health clinic in Boston, showed a 278% increase in unfilled PrEP prescriptions after stay-at-home orders and a 72.1% drop in new PrEP prescriptions.
It’s unclear what these data, which will be presented at the conference later this week, mean, said Douglas Krakower, MD, assistant professor of medicine and population medicine at Harvard Medical School in Boston.
“We don’t know whether this represents people having trouble accessing PrEP” out of concern about getting COVID “or concerns about financial implications,” he explained.
“They may have had hardships from unemployment or other financial constraints” and have lost insurance or are still having to pay copays, he told Medscape Medical News. Or it could just be that they’re not going out or having sex, so they’ve discontinued the medication.
“Anecdotally we’ve heard that some patients are sheltering in place and not having sex and so have chosen not to use PrEP,” he added.
It’s also possible that people are rationing pills or have moved themselves to the PrEP 2-1-1 protocol, which is used only when someone is having sex, said Dr. Krakower, citing a study showing that sexual behavior is continuing as usual during quarantine for about half the gay men in the United States.
Resilience and fragility
It’s not just people living with HIV whose routines have changed during the pandemic. A survey of HIV clinicians around the world conducted by the International Association of Providers of AIDS Care showed that 88% of HIV clinicians have been pulled away from their regular work to manage COVID-19 in their communities.
But the COVID-19 pandemic shows no signs of stopping, and clinicians are now having to re-engage with their HIV patients.
“What COVID-19 has represented for us is a looking glass to see the resilience, but also the fragility, in HIV responses, not just in the global south, but also in the global north,” José Zuniga, PhD, IAPAC president and chief executive officer, said during a preconference session on controlling the HIV epidemic.
For Dr. Dionne-Odom, reopening the 1917 Clinic in Alabama meant tracking down patients who could not participate in telemedicine. Fortunately (or unfortunately, depending on how you look at it), the clinic, which serves a population with a high level of economic insecurity, has worked to get as many phone numbers as possible for each patient. So when the clinic opened back up, staff was able to call family members, friends, and trusted contacts to bring their patients back into the clinic.
“No one wanted to reopen too quickly,” said Dr. Dionne-Odom. “But having people come in allowed us to do all the other things that are the key part of HIV care: getting them connected with a social worker and making sure they have enough food, helping them with their electricity bills and their housing issues, all the wrap-around services that are so crucial for these patients.”
This article first appeared on Medscape.com.