The June issue of CGH was the final column under my management. I have enjoyed the opportunity to provide you with information about practice management and health care reform. I also have enjoyed working with the Clinical Gastroenterology and Hepatology board of editors, and Erin Landis and Brook Simpson from AGA headquarters. Beginning in July 2017, this section will become the responsibility of Ziad Gellad, MD, MPH, AGAF, from Duke University. I have worked with Ziad for many years, and he serves on my board of editors for GI & Hepatology News. I have great confidence in his knowledge and ability.

During the last 5 years, we have published 58 columns beginning with an article where I made several broad predictions. I have tried to present important concepts and management tools related to private and academic clinical practice, health care reform, and health economics. This article was written in early January 2017 just before the inauguration of Donald Trump. As I wrote, we did not know the full extent or the pace of “Repeal and Replace,” as Obamacare becomes Trumpcare (www.healthaffairs.org/obamacare-to-trumpcare).

The extent of current Republican control of federal and state governments is unprecedented in modern political history. Per Newt Gingrich (The Economist, Jan. 7, 2017, p. 25), this will be the third attempt, after Ronald Reagan’s election in 1980 and Gingrich’s “Contract with America” in 1994, to break free from a “Big Government” mindset initiated by Franklin Roosevelt’s New Deal. In this article, I will speculate how a right-leaning shift in American health care policy might impact the business model of gastroenterology. No matter how government regulations or funds flow change, we (physicians) will ultimately be responsible for digestive care provided to our patients. In the words of Martin Luther King Jr. (as he paraphrased Theodore Parker), “The arc of the moral universe is long, but it bends toward justice.” What is remembered by fewer people, however, are words he then added during his speeches: “but only if we march.”

John I. Allen, MD, MBA, AGAF

Editor in Chief

The first column was published in July 2012.¹ I wrote about five dominant themes that would alter our gastroenterology practices in the ensuing years. They were 1) an increasing requirement for us to demonstrate value, 2) the need to think about population management in addition to individual patient care, 3) consolidation that would occur at all levels of health care delivery, 4) increasing cost pressure, and 5) how medical decisions would be linked to reimbursement (now called value-based payment). I fully expected the Patient Protection and Affordable Care Act (ACA) would shape the health care landscape for the rest of our careers. After the article’s publication, I was invited to speak about health care reform at many academic centers and private practices. My last talk before the election was in Pasadena, Calif. (Oct. 28, 2016) where I confidently spoke about the implications of President Clinton’s cementing ACA into the fabric of U.S. medicine.

Repeal and replace

Destruction of the ACA is a top priority of President Trump and Republican leaders of both houses of Congress. The ACA was a Democratic bill (passed with no Republican support), although it had many similarities to previous Republican legislative ideas dating from 1993.³

Although outright repeal could be blocked by a Democratic filibuster, the law could be drastically modified through budget reconciliation whose passage takes only a simple Senate majority. Thus, a simple budget-related bill could serve as a vehicle to defund many parts of ACA, including money for Medicaid expansion, insurance risk corridors, money to offset out-of-pocket expenses and individual premium subsidies, for example.^4,5

There would be substantial problems if ACA were repealed even with a 2- or 3-year delay, a scenario proposed to provide time for a replacement bill. On Jan. 4, 2017, the House Republican Study Committee introduced the American Health Care Reform Act (AHCRA) as a replacement proposal, with the stipulation that ACA would be repealed as of Jan. 1, 2018. This initial bill hinted at Republican intent and was detailed in a Health Affairs blog.⁶ Importantly, there were distinct similarities between this and prior Republican proposals put forward by Representative Tom Price (nominated to head the Department of Health & Human Services under President Trump) and Speaker of the House Paul Ryan.^7,8

Consistently, Republicans have advocated for expansion of health savings accounts, altering the tax code to allow individuals to deduct health insurance premiums, establishment of association risk pools, imposition of malpractice limits, protections for people with preexisting conditions, and further restrictions on abortion coverage. The AHCRA changes financial subsidies for purchasing insurance from a tax credit (which can be paid to people even if they do not pay taxes) to a tax deduction (only applicable to people who pay taxes). Analysis of a similar proposal made by President Trump during the campaign found that this plan would increase the number of uninsured people by more than 15 million.

If ACA is repealed, effects would be broader than just factors related to insurance coverage.⁹ ACA provides for preventive care (including colonoscopy) without copays, education of additional medical personnel, closing the donut hole for Medicare Part D (medications), approval of generic biologics, and Medicaid expansions, among other initiatives. If ACA were defunded without restoring pre-ACA support for Disproportion Share Hospital charity care, research, and graduate medical education, then safety-net hospitals and many academic medical centers (AMCs) could face enormous funding cuts.¹⁰ Defunding Medicaid expansion would adversely affect states in many ways, as pointed out by Ayanian et al.¹¹ Medicaid expansion had broad economic impact in states that accepted federal money to expand. In Michigan for example, 30,900 jobs were added to the state in 2016 because of Medicaid expansion, with two-thirds outside of the health care industry. President Obama defined his view about the effects of ACA repeal in the New England Journal of Medicine.¹²

Lessons learned

Economic principles and unique characteristics of United States health care help explain why solutions to its high cost and uneven coverage are so difficult to achieve. These include higher prices for goods in the United States compared with other countries, variation in price (unrelated to quality), restraints on government price negotiations, inefficiencies due to variation in size of delivery systems, and “moral hazard” related to rich insurance coverage, which are some of the factors that doom any simple solutions. These are reviewed by Victor Fuchs¹³ in an excellent article in Annals of Internal Medicine. Payment methods for health care services also distort resource use and efficiencies. Understanding the eight basic payment methodologies in health care and current predictions about future health care spending will be important in shaping reimbursement policies.^14,15

Disruptions in health care are unpopular and, as Uve Reinardt stated: “Our health care financing system will always remain a horrendous mess and a fountain for such dismay among the providers of health care as well as among patients.”⁴ Lessons to inform the next iteration of health care policy, learned from the 2009-2010 experience, might be as follows:

1. If a bill is to be passed, the president must personally lead in explaining the bill to the public in simple terms.

2. Even the threat of repeal may disrupt the current market and force insurance companies to exit quickly.

3. Coverage must be affordable to individuals, state budgets, and health care providers. Because expansion states saw positive impacts to state budgets⁸ and mental health and substance abuse services became part of Medicaid benefits, how will a replacement bill maintain coverage and compensate for new state moneys used now for other imperatives such as education and infrastructure?

4. Health care is like a massive cargo ship, not a sports car, so a bill to replace the ACA may take a long time (and might never be passed).

5. Health care is intensely personal, so it will always be politically charged.

Ultimately, physicians will need to make strategic guesses and rapid adjustments to sustain financial viability and provide high-value care. Strategies differ depending on your practice situation. Keep in mind the five principles listed in the opening paragraph of this article. It is likely that the most important principle to factor into your practice strategy is continuing reduction in reimbursements. No matter what model is adopted to reform the ACA, the financial pot (Medicare, Medicaid, commercial insurance, bundled payments, fee-for-service payments) will be reduced, and the number of uninsured patients will increase. How would you change your practice if Medicare was your best payer (“manage to Medicare”)?

Independent practices

Physicians in small- to medium-size independent practices continue to struggle with reducing reimbursements, reporting burdens, increasing overhead expenses, crushing regulatory requirements, and provider burnout. Trumpcare will favor small practices more than Obamacare from a policy (not necessarily a financial) perspective. Regulations on small business and reporting burdens may ease, but the move toward value-based reimbursement as outlined in the MACRA (passed with overwhelming bipartisan support) will not end.¹⁶ Practices in small communities continue to thrive because they give excellent care with limited competition and low overhead. Some practices in suburban and urban centers struggle because payers tend to favor (with enhanced managed care rates) larger practices and health systems. Large, horizontally integrated, efficient gastroenterology practices will continue to thrive because they can develop a “must-have” position with payers. Building remote patient monitoring, teleconsulting, and capabilities around value demonstration will be strategically advantageous.

Options for independent physicians include 1) maintaining status quo, 2) retiring, or 3) exiting the independent business model through a practice sale. Traditionally, physicians who wanted to sell their practices turned to hospitals or health systems. Recently, a physician-run model funded by venture capital has emerged where reduced overhead (through centralization of services) is combined with enhanced power during payer negotiations (because of scale). This model has allowed practices to merge into a physician organization and remain free from health system employment.¹⁷

Large health systems

Physicians employed by large health systems, whether they are nonprofit, for-profit, or AMCs, will see their future tied directly to health system success. If bundled payment, alternative payment, and capitation models of health care financing continue to grow in popularity, then success will be determined by a health system’s market share and its ability to form true clinical integration. In a capitated environment, expansion of market share (especially of relatively healthy patients) will help support margins. However, financial success will come from a system’s ability to manage high-cost patients, those 5% of patients who consume 50% of health care resources.¹⁸

Hospitals with a financially challenged patient base (safety-net hospitals) will have enormous financial pressures going forward. Repeal of ACA without restoration of pre-ACA funding will affect directly the financial health of systems including AMCs. AMCs and other health systems will be forced to reduce fixed overhead, enhance productivity of faculty, and restrict nonfunded activities (teaching for example). Although most AMCs are now in an active acquisition mode, this strategy is naturally limited by the number of remaining acquisition targets. Traditional high managed care rates enjoyed by AMCs will shrink, as will federal research funding (which typically comes with high indirect financial support). Health systems and GI societies will need to dedicate much more attention to state policy makers as Trumpcare progresses.

Finally, all providers will need to manage the business implications of retail health. As people assume higher deductibles and copays and health savings accounts grow, patients will change their patterns of purchasing services. Reputation counts for less when people are facing large price differences, so attention to patient-centric amenities, price, patient engagement, and patient satisfaction will become even more important.

Conclusion

The United States has undergone a massive and rapid political transformation. The mandate felt by conservative politicians, perhaps not supported by numbers, will carry a conservative platform forward. In areas where progressive Democrats emphasized federal power and socialized regulation (religion, education, civil rights, income security, and health policy), conservatives will transfer decision power as much as possible to states, local communities, and individuals. Maintaining the concept of “health as a right” will test the conscience of all of us.

References

1. Allen, J.I. The road ahead. Clin Gastroenterol Hepatol. 2012;10:692-6.

2. Gill KE. Visual guide: the balance of power between Congress and the Presidency (1901-2016). Wired Pen. November 2016. Available from http://wiredpen.com/resources/political-commentary-and-analysis/a-visual-guide-balance-of-power-congress-presidency/. Accessed Dec. 30, 2016.

3. Mertens M. Chart: comparing health reform bills – Democrats and Republicans 2009, Republics 1993. Kaiser Health News. Feb. 24, 2010. Available from http://khn.org/022310-bill-comparison/. Accessed Jan. 8, 2017.

4. Hotchkiss M. Q&A: what a Trump presidency means for the Affordable Care Act. Nov. 16, 2016 News at Princeton. Princeton University. Available from https://www.princeton.edu/main/news/archive/S47/93/09C11/index.xml?section=topstories. Accessed Dec. 30, 2016.

5. Jost T. Taking stock of health reform: where we’ve been, where we’re going. Health Affairs Blog. Available from http://healthaffairs.org/blog/2016/12/06/taking-stock-of-health-reform-where-weve-been-where-were-going/. Accessed Dec. 30, 2016.

6. Jost T. The Republican Study Committee’s ACA replacement proposal (updated). Health Affairs Blog. Available from http://healthaffairs.org/blog/2017/01/05/the-republican-study-committees-aca-replacement-proposal/. Accessed Jan. 10, 2017.

7. Price T. Empowering patients first. Available from http://tomprice.house.gov/sites/tomprice.house.gov/files/HR%202300%20Empowering%20Patients%20First%20Act%202015.pdf. Accessed Dec. 30, 2016.

8. Ryan P. A better way. Available from https://abetterway.speaker.gov/_assets/pdf/ABetterWay-HealthCare-PolicyPaper.pdf. Accessed Dec. 30, 2016.

9. Oberlander, J. The end of Obamacare. N Engl J Med. 2017;376:1-3.

10. Goodnough A. Hospitals in safety net brace for health care law’s repeal. New York Times. Dec. 28, 2016. Available from http://www.nytimes.com/2016/12/28/health/hospitals-medicaid-obamacare-trump.html?smprod=nytcore-iphone&smid=nytcore-iphone-share&_r=0. Accessed Jan. 10, 2017.

11. Ayanian, J.Z., Ehrlich, G.M., Grimes, D.R., et al. Economic effects of Medicaid expansion in Michigan. N Engl J Med. 2017;376:407-10.

12. Obama, B.H. Repealing the ACA without a replacement: the risks to American health care. N Engl J Med. 2017;376:297-9.

13. Fuchs, V.R. Major concepts of health economics. Ann Intern Med. 2015;162:380-3.

14. Quinn, K. The 8 basic payment methods in health care. Ann Intern Med. 2015;163:300-6.

15. Schoenman JA. A detailed look at US health care spending: a presentation from the National Institute for Health Care Management (NIHCM). Oct. 25, 2012. Available from http://www.nihcm.org/images/stories/Health_care_spending_slides_-_MILI_-_Schoenman.pdf. Accessed Dec. 30, 2016.

16. Allen, J.I., Allen, C.C., Brill, J.V. Gastroenterology 2020: no time for WIMPs. Gastroenterology. 2016;150:295-9.

17. Sciacca R. Weekly Byte: GI roundtable and navigating uncharted waters in health care. The PMD Blog. Available from https://www.pmd.com/blog/post/weekly-byte-gi-roundtable-and-navigating-uncharted-waters-in-health-care. Accessed Jan. 10, 2017.

18. Powers, B.W., Chaguturu, S.K. ACOs and high-cost patients. N Engl J Med. 2016;374:203-5.

Dr. Allen is professor of medicine, University of Michigan School of Medicine, Institute for Health Care Policy and Innovations, and associate medical director of Network Strategy and Business Development – Michigan Medicine, Ann Arbor. He discloses no conflicts.

The June issue of CGH was the final column under my management. I have enjoyed the opportunity to provide you with information about practice management and health care reform. I also have enjoyed working with the Clinical Gastroenterology and Hepatology board of editors, and Erin Landis and Brook Simpson from AGA headquarters. Beginning in July 2017, this section will become the responsibility of Ziad Gellad, MD, MPH, AGAF, from Duke University. I have worked with Ziad for many years, and he serves on my board of editors for GI & Hepatology News. I have great confidence in his knowledge and ability.

During the last 5 years, we have published 58 columns beginning with an article where I made several broad predictions. I have tried to present important concepts and management tools related to private and academic clinical practice, health care reform, and health economics. This article was written in early January 2017 just before the inauguration of Donald Trump. As I wrote, we did not know the full extent or the pace of “Repeal and Replace,” as Obamacare becomes Trumpcare (www.healthaffairs.org/obamacare-to-trumpcare).

The extent of current Republican control of federal and state governments is unprecedented in modern political history. Per Newt Gingrich (The Economist, Jan. 7, 2017, p. 25), this will be the third attempt, after Ronald Reagan’s election in 1980 and Gingrich’s “Contract with America” in 1994, to break free from a “Big Government” mindset initiated by Franklin Roosevelt’s New Deal. In this article, I will speculate how a right-leaning shift in American health care policy might impact the business model of gastroenterology. No matter how government regulations or funds flow change, we (physicians) will ultimately be responsible for digestive care provided to our patients. In the words of Martin Luther King Jr. (as he paraphrased Theodore Parker), “The arc of the moral universe is long, but it bends toward justice.” What is remembered by fewer people, however, are words he then added during his speeches: “but only if we march.”

John I. Allen, MD, MBA, AGAF

Editor in Chief

The first column was published in July 2012.¹ I wrote about five dominant themes that would alter our gastroenterology practices in the ensuing years. They were 1) an increasing requirement for us to demonstrate value, 2) the need to think about population management in addition to individual patient care, 3) consolidation that would occur at all levels of health care delivery, 4) increasing cost pressure, and 5) how medical decisions would be linked to reimbursement (now called value-based payment). I fully expected the Patient Protection and Affordable Care Act (ACA) would shape the health care landscape for the rest of our careers. After the article’s publication, I was invited to speak about health care reform at many academic centers and private practices. My last talk before the election was in Pasadena, Calif. (Oct. 28, 2016) where I confidently spoke about the implications of President Clinton’s cementing ACA into the fabric of U.S. medicine.

Repeal and replace

Destruction of the ACA is a top priority of President Trump and Republican leaders of both houses of Congress. The ACA was a Democratic bill (passed with no Republican support), although it had many similarities to previous Republican legislative ideas dating from 1993.³

Although outright repeal could be blocked by a Democratic filibuster, the law could be drastically modified through budget reconciliation whose passage takes only a simple Senate majority. Thus, a simple budget-related bill could serve as a vehicle to defund many parts of ACA, including money for Medicaid expansion, insurance risk corridors, money to offset out-of-pocket expenses and individual premium subsidies, for example.^4,5

There would be substantial problems if ACA were repealed even with a 2- or 3-year delay, a scenario proposed to provide time for a replacement bill. On Jan. 4, 2017, the House Republican Study Committee introduced the American Health Care Reform Act (AHCRA) as a replacement proposal, with the stipulation that ACA would be repealed as of Jan. 1, 2018. This initial bill hinted at Republican intent and was detailed in a Health Affairs blog.⁶ Importantly, there were distinct similarities between this and prior Republican proposals put forward by Representative Tom Price (nominated to head the Department of Health & Human Services under President Trump) and Speaker of the House Paul Ryan.^7,8

Consistently, Republicans have advocated for expansion of health savings accounts, altering the tax code to allow individuals to deduct health insurance premiums, establishment of association risk pools, imposition of malpractice limits, protections for people with preexisting conditions, and further restrictions on abortion coverage. The AHCRA changes financial subsidies for purchasing insurance from a tax credit (which can be paid to people even if they do not pay taxes) to a tax deduction (only applicable to people who pay taxes). Analysis of a similar proposal made by President Trump during the campaign found that this plan would increase the number of uninsured people by more than 15 million.

If ACA is repealed, effects would be broader than just factors related to insurance coverage.⁹ ACA provides for preventive care (including colonoscopy) without copays, education of additional medical personnel, closing the donut hole for Medicare Part D (medications), approval of generic biologics, and Medicaid expansions, among other initiatives. If ACA were defunded without restoring pre-ACA support for Disproportion Share Hospital charity care, research, and graduate medical education, then safety-net hospitals and many academic medical centers (AMCs) could face enormous funding cuts.¹⁰ Defunding Medicaid expansion would adversely affect states in many ways, as pointed out by Ayanian et al.¹¹ Medicaid expansion had broad economic impact in states that accepted federal money to expand. In Michigan for example, 30,900 jobs were added to the state in 2016 because of Medicaid expansion, with two-thirds outside of the health care industry. President Obama defined his view about the effects of ACA repeal in the New England Journal of Medicine.¹²

Lessons learned

Economic principles and unique characteristics of United States health care help explain why solutions to its high cost and uneven coverage are so difficult to achieve. These include higher prices for goods in the United States compared with other countries, variation in price (unrelated to quality), restraints on government price negotiations, inefficiencies due to variation in size of delivery systems, and “moral hazard” related to rich insurance coverage, which are some of the factors that doom any simple solutions. These are reviewed by Victor Fuchs¹³ in an excellent article in Annals of Internal Medicine. Payment methods for health care services also distort resource use and efficiencies. Understanding the eight basic payment methodologies in health care and current predictions about future health care spending will be important in shaping reimbursement policies.^14,15

Disruptions in health care are unpopular and, as Uve Reinardt stated: “Our health care financing system will always remain a horrendous mess and a fountain for such dismay among the providers of health care as well as among patients.”⁴ Lessons to inform the next iteration of health care policy, learned from the 2009-2010 experience, might be as follows:

1. If a bill is to be passed, the president must personally lead in explaining the bill to the public in simple terms.

2. Even the threat of repeal may disrupt the current market and force insurance companies to exit quickly.

3. Coverage must be affordable to individuals, state budgets, and health care providers. Because expansion states saw positive impacts to state budgets⁸ and mental health and substance abuse services became part of Medicaid benefits, how will a replacement bill maintain coverage and compensate for new state moneys used now for other imperatives such as education and infrastructure?

4. Health care is like a massive cargo ship, not a sports car, so a bill to replace the ACA may take a long time (and might never be passed).

5. Health care is intensely personal, so it will always be politically charged.

Ultimately, physicians will need to make strategic guesses and rapid adjustments to sustain financial viability and provide high-value care. Strategies differ depending on your practice situation. Keep in mind the five principles listed in the opening paragraph of this article. It is likely that the most important principle to factor into your practice strategy is continuing reduction in reimbursements. No matter what model is adopted to reform the ACA, the financial pot (Medicare, Medicaid, commercial insurance, bundled payments, fee-for-service payments) will be reduced, and the number of uninsured patients will increase. How would you change your practice if Medicare was your best payer (“manage to Medicare”)?

Independent practices

Physicians in small- to medium-size independent practices continue to struggle with reducing reimbursements, reporting burdens, increasing overhead expenses, crushing regulatory requirements, and provider burnout. Trumpcare will favor small practices more than Obamacare from a policy (not necessarily a financial) perspective. Regulations on small business and reporting burdens may ease, but the move toward value-based reimbursement as outlined in the MACRA (passed with overwhelming bipartisan support) will not end.¹⁶ Practices in small communities continue to thrive because they give excellent care with limited competition and low overhead. Some practices in suburban and urban centers struggle because payers tend to favor (with enhanced managed care rates) larger practices and health systems. Large, horizontally integrated, efficient gastroenterology practices will continue to thrive because they can develop a “must-have” position with payers. Building remote patient monitoring, teleconsulting, and capabilities around value demonstration will be strategically advantageous.

Options for independent physicians include 1) maintaining status quo, 2) retiring, or 3) exiting the independent business model through a practice sale. Traditionally, physicians who wanted to sell their practices turned to hospitals or health systems. Recently, a physician-run model funded by venture capital has emerged where reduced overhead (through centralization of services) is combined with enhanced power during payer negotiations (because of scale). This model has allowed practices to merge into a physician organization and remain free from health system employment.¹⁷

Large health systems

Physicians employed by large health systems, whether they are nonprofit, for-profit, or AMCs, will see their future tied directly to health system success. If bundled payment, alternative payment, and capitation models of health care financing continue to grow in popularity, then success will be determined by a health system’s market share and its ability to form true clinical integration. In a capitated environment, expansion of market share (especially of relatively healthy patients) will help support margins. However, financial success will come from a system’s ability to manage high-cost patients, those 5% of patients who consume 50% of health care resources.¹⁸

Hospitals with a financially challenged patient base (safety-net hospitals) will have enormous financial pressures going forward. Repeal of ACA without restoration of pre-ACA funding will affect directly the financial health of systems including AMCs. AMCs and other health systems will be forced to reduce fixed overhead, enhance productivity of faculty, and restrict nonfunded activities (teaching for example). Although most AMCs are now in an active acquisition mode, this strategy is naturally limited by the number of remaining acquisition targets. Traditional high managed care rates enjoyed by AMCs will shrink, as will federal research funding (which typically comes with high indirect financial support). Health systems and GI societies will need to dedicate much more attention to state policy makers as Trumpcare progresses.

Finally, all providers will need to manage the business implications of retail health. As people assume higher deductibles and copays and health savings accounts grow, patients will change their patterns of purchasing services. Reputation counts for less when people are facing large price differences, so attention to patient-centric amenities, price, patient engagement, and patient satisfaction will become even more important.

Conclusion

The United States has undergone a massive and rapid political transformation. The mandate felt by conservative politicians, perhaps not supported by numbers, will carry a conservative platform forward. In areas where progressive Democrats emphasized federal power and socialized regulation (religion, education, civil rights, income security, and health policy), conservatives will transfer decision power as much as possible to states, local communities, and individuals. Maintaining the concept of “health as a right” will test the conscience of all of us.

References

1. Allen, J.I. The road ahead. Clin Gastroenterol Hepatol. 2012;10:692-6.

2. Gill KE. Visual guide: the balance of power between Congress and the Presidency (1901-2016). Wired Pen. November 2016. Available from http://wiredpen.com/resources/political-commentary-and-analysis/a-visual-guide-balance-of-power-congress-presidency/. Accessed Dec. 30, 2016.

3. Mertens M. Chart: comparing health reform bills – Democrats and Republicans 2009, Republics 1993. Kaiser Health News. Feb. 24, 2010. Available from http://khn.org/022310-bill-comparison/. Accessed Jan. 8, 2017.

4. Hotchkiss M. Q&A: what a Trump presidency means for the Affordable Care Act. Nov. 16, 2016 News at Princeton. Princeton University. Available from https://www.princeton.edu/main/news/archive/S47/93/09C11/index.xml?section=topstories. Accessed Dec. 30, 2016.

5. Jost T. Taking stock of health reform: where we’ve been, where we’re going. Health Affairs Blog. Available from http://healthaffairs.org/blog/2016/12/06/taking-stock-of-health-reform-where-weve-been-where-were-going/. Accessed Dec. 30, 2016.

6. Jost T. The Republican Study Committee’s ACA replacement proposal (updated). Health Affairs Blog. Available from http://healthaffairs.org/blog/2017/01/05/the-republican-study-committees-aca-replacement-proposal/. Accessed Jan. 10, 2017.

7. Price T. Empowering patients first. Available from http://tomprice.house.gov/sites/tomprice.house.gov/files/HR%202300%20Empowering%20Patients%20First%20Act%202015.pdf. Accessed Dec. 30, 2016.

8. Ryan P. A better way. Available from https://abetterway.speaker.gov/_assets/pdf/ABetterWay-HealthCare-PolicyPaper.pdf. Accessed Dec. 30, 2016.

9. Oberlander, J. The end of Obamacare. N Engl J Med. 2017;376:1-3.

10. Goodnough A. Hospitals in safety net brace for health care law’s repeal. New York Times. Dec. 28, 2016. Available from http://www.nytimes.com/2016/12/28/health/hospitals-medicaid-obamacare-trump.html?smprod=nytcore-iphone&smid=nytcore-iphone-share&_r=0. Accessed Jan. 10, 2017.

11. Ayanian, J.Z., Ehrlich, G.M., Grimes, D.R., et al. Economic effects of Medicaid expansion in Michigan. N Engl J Med. 2017;376:407-10.

12. Obama, B.H. Repealing the ACA without a replacement: the risks to American health care. N Engl J Med. 2017;376:297-9.

13. Fuchs, V.R. Major concepts of health economics. Ann Intern Med. 2015;162:380-3.

14. Quinn, K. The 8 basic payment methods in health care. Ann Intern Med. 2015;163:300-6.

15. Schoenman JA. A detailed look at US health care spending: a presentation from the National Institute for Health Care Management (NIHCM). Oct. 25, 2012. Available from http://www.nihcm.org/images/stories/Health_care_spending_slides_-_MILI_-_Schoenman.pdf. Accessed Dec. 30, 2016.

16. Allen, J.I., Allen, C.C., Brill, J.V. Gastroenterology 2020: no time for WIMPs. Gastroenterology. 2016;150:295-9.

17. Sciacca R. Weekly Byte: GI roundtable and navigating uncharted waters in health care. The PMD Blog. Available from https://www.pmd.com/blog/post/weekly-byte-gi-roundtable-and-navigating-uncharted-waters-in-health-care. Accessed Jan. 10, 2017.

18. Powers, B.W., Chaguturu, S.K. ACOs and high-cost patients. N Engl J Med. 2016;374:203-5.

Dr. Allen is professor of medicine, University of Michigan School of Medicine, Institute for Health Care Policy and Innovations, and associate medical director of Network Strategy and Business Development – Michigan Medicine, Ann Arbor. He discloses no conflicts.

The June issue of CGH was the final column under my management. I have enjoyed the opportunity to provide you with information about practice management and health care reform. I also have enjoyed working with the Clinical Gastroenterology and Hepatology board of editors, and Erin Landis and Brook Simpson from AGA headquarters. Beginning in July 2017, this section will become the responsibility of Ziad Gellad, MD, MPH, AGAF, from Duke University. I have worked with Ziad for many years, and he serves on my board of editors for GI & Hepatology News. I have great confidence in his knowledge and ability.

During the last 5 years, we have published 58 columns beginning with an article where I made several broad predictions. I have tried to present important concepts and management tools related to private and academic clinical practice, health care reform, and health economics. This article was written in early January 2017 just before the inauguration of Donald Trump. As I wrote, we did not know the full extent or the pace of “Repeal and Replace,” as Obamacare becomes Trumpcare (www.healthaffairs.org/obamacare-to-trumpcare).

The extent of current Republican control of federal and state governments is unprecedented in modern political history. Per Newt Gingrich (The Economist, Jan. 7, 2017, p. 25), this will be the third attempt, after Ronald Reagan’s election in 1980 and Gingrich’s “Contract with America” in 1994, to break free from a “Big Government” mindset initiated by Franklin Roosevelt’s New Deal. In this article, I will speculate how a right-leaning shift in American health care policy might impact the business model of gastroenterology. No matter how government regulations or funds flow change, we (physicians) will ultimately be responsible for digestive care provided to our patients. In the words of Martin Luther King Jr. (as he paraphrased Theodore Parker), “The arc of the moral universe is long, but it bends toward justice.” What is remembered by fewer people, however, are words he then added during his speeches: “but only if we march.”

John I. Allen, MD, MBA, AGAF

Editor in Chief

The first column was published in July 2012.¹ I wrote about five dominant themes that would alter our gastroenterology practices in the ensuing years. They were 1) an increasing requirement for us to demonstrate value, 2) the need to think about population management in addition to individual patient care, 3) consolidation that would occur at all levels of health care delivery, 4) increasing cost pressure, and 5) how medical decisions would be linked to reimbursement (now called value-based payment). I fully expected the Patient Protection and Affordable Care Act (ACA) would shape the health care landscape for the rest of our careers. After the article’s publication, I was invited to speak about health care reform at many academic centers and private practices. My last talk before the election was in Pasadena, Calif. (Oct. 28, 2016) where I confidently spoke about the implications of President Clinton’s cementing ACA into the fabric of U.S. medicine.

Repeal and replace

Destruction of the ACA is a top priority of President Trump and Republican leaders of both houses of Congress. The ACA was a Democratic bill (passed with no Republican support), although it had many similarities to previous Republican legislative ideas dating from 1993.³

Although outright repeal could be blocked by a Democratic filibuster, the law could be drastically modified through budget reconciliation whose passage takes only a simple Senate majority. Thus, a simple budget-related bill could serve as a vehicle to defund many parts of ACA, including money for Medicaid expansion, insurance risk corridors, money to offset out-of-pocket expenses and individual premium subsidies, for example.^4,5

There would be substantial problems if ACA were repealed even with a 2- or 3-year delay, a scenario proposed to provide time for a replacement bill. On Jan. 4, 2017, the House Republican Study Committee introduced the American Health Care Reform Act (AHCRA) as a replacement proposal, with the stipulation that ACA would be repealed as of Jan. 1, 2018. This initial bill hinted at Republican intent and was detailed in a Health Affairs blog.⁶ Importantly, there were distinct similarities between this and prior Republican proposals put forward by Representative Tom Price (nominated to head the Department of Health & Human Services under President Trump) and Speaker of the House Paul Ryan.^7,8

Consistently, Republicans have advocated for expansion of health savings accounts, altering the tax code to allow individuals to deduct health insurance premiums, establishment of association risk pools, imposition of malpractice limits, protections for people with preexisting conditions, and further restrictions on abortion coverage. The AHCRA changes financial subsidies for purchasing insurance from a tax credit (which can be paid to people even if they do not pay taxes) to a tax deduction (only applicable to people who pay taxes). Analysis of a similar proposal made by President Trump during the campaign found that this plan would increase the number of uninsured people by more than 15 million.

If ACA is repealed, effects would be broader than just factors related to insurance coverage.⁹ ACA provides for preventive care (including colonoscopy) without copays, education of additional medical personnel, closing the donut hole for Medicare Part D (medications), approval of generic biologics, and Medicaid expansions, among other initiatives. If ACA were defunded without restoring pre-ACA support for Disproportion Share Hospital charity care, research, and graduate medical education, then safety-net hospitals and many academic medical centers (AMCs) could face enormous funding cuts.¹⁰ Defunding Medicaid expansion would adversely affect states in many ways, as pointed out by Ayanian et al.¹¹ Medicaid expansion had broad economic impact in states that accepted federal money to expand. In Michigan for example, 30,900 jobs were added to the state in 2016 because of Medicaid expansion, with two-thirds outside of the health care industry. President Obama defined his view about the effects of ACA repeal in the New England Journal of Medicine.¹²

Lessons learned

Economic principles and unique characteristics of United States health care help explain why solutions to its high cost and uneven coverage are so difficult to achieve. These include higher prices for goods in the United States compared with other countries, variation in price (unrelated to quality), restraints on government price negotiations, inefficiencies due to variation in size of delivery systems, and “moral hazard” related to rich insurance coverage, which are some of the factors that doom any simple solutions. These are reviewed by Victor Fuchs¹³ in an excellent article in Annals of Internal Medicine. Payment methods for health care services also distort resource use and efficiencies. Understanding the eight basic payment methodologies in health care and current predictions about future health care spending will be important in shaping reimbursement policies.^14,15

Disruptions in health care are unpopular and, as Uve Reinardt stated: “Our health care financing system will always remain a horrendous mess and a fountain for such dismay among the providers of health care as well as among patients.”⁴ Lessons to inform the next iteration of health care policy, learned from the 2009-2010 experience, might be as follows:

1. If a bill is to be passed, the president must personally lead in explaining the bill to the public in simple terms.

2. Even the threat of repeal may disrupt the current market and force insurance companies to exit quickly.

3. Coverage must be affordable to individuals, state budgets, and health care providers. Because expansion states saw positive impacts to state budgets⁸ and mental health and substance abuse services became part of Medicaid benefits, how will a replacement bill maintain coverage and compensate for new state moneys used now for other imperatives such as education and infrastructure?

4. Health care is like a massive cargo ship, not a sports car, so a bill to replace the ACA may take a long time (and might never be passed).

5. Health care is intensely personal, so it will always be politically charged.

Ultimately, physicians will need to make strategic guesses and rapid adjustments to sustain financial viability and provide high-value care. Strategies differ depending on your practice situation. Keep in mind the five principles listed in the opening paragraph of this article. It is likely that the most important principle to factor into your practice strategy is continuing reduction in reimbursements. No matter what model is adopted to reform the ACA, the financial pot (Medicare, Medicaid, commercial insurance, bundled payments, fee-for-service payments) will be reduced, and the number of uninsured patients will increase. How would you change your practice if Medicare was your best payer (“manage to Medicare”)?

Independent practices

Physicians in small- to medium-size independent practices continue to struggle with reducing reimbursements, reporting burdens, increasing overhead expenses, crushing regulatory requirements, and provider burnout. Trumpcare will favor small practices more than Obamacare from a policy (not necessarily a financial) perspective. Regulations on small business and reporting burdens may ease, but the move toward value-based reimbursement as outlined in the MACRA (passed with overwhelming bipartisan support) will not end.¹⁶ Practices in small communities continue to thrive because they give excellent care with limited competition and low overhead. Some practices in suburban and urban centers struggle because payers tend to favor (with enhanced managed care rates) larger practices and health systems. Large, horizontally integrated, efficient gastroenterology practices will continue to thrive because they can develop a “must-have” position with payers. Building remote patient monitoring, teleconsulting, and capabilities around value demonstration will be strategically advantageous.

Options for independent physicians include 1) maintaining status quo, 2) retiring, or 3) exiting the independent business model through a practice sale. Traditionally, physicians who wanted to sell their practices turned to hospitals or health systems. Recently, a physician-run model funded by venture capital has emerged where reduced overhead (through centralization of services) is combined with enhanced power during payer negotiations (because of scale). This model has allowed practices to merge into a physician organization and remain free from health system employment.¹⁷

Large health systems

Physicians employed by large health systems, whether they are nonprofit, for-profit, or AMCs, will see their future tied directly to health system success. If bundled payment, alternative payment, and capitation models of health care financing continue to grow in popularity, then success will be determined by a health system’s market share and its ability to form true clinical integration. In a capitated environment, expansion of market share (especially of relatively healthy patients) will help support margins. However, financial success will come from a system’s ability to manage high-cost patients, those 5% of patients who consume 50% of health care resources.¹⁸

Hospitals with a financially challenged patient base (safety-net hospitals) will have enormous financial pressures going forward. Repeal of ACA without restoration of pre-ACA funding will affect directly the financial health of systems including AMCs. AMCs and other health systems will be forced to reduce fixed overhead, enhance productivity of faculty, and restrict nonfunded activities (teaching for example). Although most AMCs are now in an active acquisition mode, this strategy is naturally limited by the number of remaining acquisition targets. Traditional high managed care rates enjoyed by AMCs will shrink, as will federal research funding (which typically comes with high indirect financial support). Health systems and GI societies will need to dedicate much more attention to state policy makers as Trumpcare progresses.

Finally, all providers will need to manage the business implications of retail health. As people assume higher deductibles and copays and health savings accounts grow, patients will change their patterns of purchasing services. Reputation counts for less when people are facing large price differences, so attention to patient-centric amenities, price, patient engagement, and patient satisfaction will become even more important.

Conclusion

The United States has undergone a massive and rapid political transformation. The mandate felt by conservative politicians, perhaps not supported by numbers, will carry a conservative platform forward. In areas where progressive Democrats emphasized federal power and socialized regulation (religion, education, civil rights, income security, and health policy), conservatives will transfer decision power as much as possible to states, local communities, and individuals. Maintaining the concept of “health as a right” will test the conscience of all of us.

References

1. Allen, J.I. The road ahead. Clin Gastroenterol Hepatol. 2012;10:692-6.

2. Gill KE. Visual guide: the balance of power between Congress and the Presidency (1901-2016). Wired Pen. November 2016. Available from http://wiredpen.com/resources/political-commentary-and-analysis/a-visual-guide-balance-of-power-congress-presidency/. Accessed Dec. 30, 2016.

3. Mertens M. Chart: comparing health reform bills – Democrats and Republicans 2009, Republics 1993. Kaiser Health News. Feb. 24, 2010. Available from http://khn.org/022310-bill-comparison/. Accessed Jan. 8, 2017.

4. Hotchkiss M. Q&A: what a Trump presidency means for the Affordable Care Act. Nov. 16, 2016 News at Princeton. Princeton University. Available from https://www.princeton.edu/main/news/archive/S47/93/09C11/index.xml?section=topstories. Accessed Dec. 30, 2016.

5. Jost T. Taking stock of health reform: where we’ve been, where we’re going. Health Affairs Blog. Available from http://healthaffairs.org/blog/2016/12/06/taking-stock-of-health-reform-where-weve-been-where-were-going/. Accessed Dec. 30, 2016.

6. Jost T. The Republican Study Committee’s ACA replacement proposal (updated). Health Affairs Blog. Available from http://healthaffairs.org/blog/2017/01/05/the-republican-study-committees-aca-replacement-proposal/. Accessed Jan. 10, 2017.

7. Price T. Empowering patients first. Available from http://tomprice.house.gov/sites/tomprice.house.gov/files/HR%202300%20Empowering%20Patients%20First%20Act%202015.pdf. Accessed Dec. 30, 2016.

8. Ryan P. A better way. Available from https://abetterway.speaker.gov/_assets/pdf/ABetterWay-HealthCare-PolicyPaper.pdf. Accessed Dec. 30, 2016.

9. Oberlander, J. The end of Obamacare. N Engl J Med. 2017;376:1-3.

10. Goodnough A. Hospitals in safety net brace for health care law’s repeal. New York Times. Dec. 28, 2016. Available from http://www.nytimes.com/2016/12/28/health/hospitals-medicaid-obamacare-trump.html?smprod=nytcore-iphone&smid=nytcore-iphone-share&_r=0. Accessed Jan. 10, 2017.

11. Ayanian, J.Z., Ehrlich, G.M., Grimes, D.R., et al. Economic effects of Medicaid expansion in Michigan. N Engl J Med. 2017;376:407-10.

12. Obama, B.H. Repealing the ACA without a replacement: the risks to American health care. N Engl J Med. 2017;376:297-9.

13. Fuchs, V.R. Major concepts of health economics. Ann Intern Med. 2015;162:380-3.

14. Quinn, K. The 8 basic payment methods in health care. Ann Intern Med. 2015;163:300-6.

15. Schoenman JA. A detailed look at US health care spending: a presentation from the National Institute for Health Care Management (NIHCM). Oct. 25, 2012. Available from http://www.nihcm.org/images/stories/Health_care_spending_slides_-_MILI_-_Schoenman.pdf. Accessed Dec. 30, 2016.

16. Allen, J.I., Allen, C.C., Brill, J.V. Gastroenterology 2020: no time for WIMPs. Gastroenterology. 2016;150:295-9.

17. Sciacca R. Weekly Byte: GI roundtable and navigating uncharted waters in health care. The PMD Blog. Available from https://www.pmd.com/blog/post/weekly-byte-gi-roundtable-and-navigating-uncharted-waters-in-health-care. Accessed Jan. 10, 2017.

18. Powers, B.W., Chaguturu, S.K. ACOs and high-cost patients. N Engl J Med. 2016;374:203-5.

Dr. Allen is professor of medicine, University of Michigan School of Medicine, Institute for Health Care Policy and Innovations, and associate medical director of Network Strategy and Business Development – Michigan Medicine, Ann Arbor. He discloses no conflicts.

For the first time, endoscopists have used focal cryoballoon ablation to eradicate early esophageal squamous cell neoplasias, including high-grade lesions in treatment-experienced patients.

A single session of treatment with the novel, portable nitrous oxide system (C2 Therapeutics, Redwood City, Calif.) produced complete pathologic and endoscopic responses at 3 months in 8 of 10 patients, reported Marcia Irene Canto, MD, of Johns Hopkins University in Baltimore, with her associates. Two to five sessions produced complete responses in the other two patients, and all patients were disease-free at their last visit (median follow-up, 10.7 months; interquartile range, 4-14 months). The study was published online July 15 in Gastrointestinal Endoscopy (2017. doi: 10.1016/j.gie.2017.07.013).

©Nephron/Wikimedia Commons/CC BY-SA 3.0/No changes

For the first time, endoscopists have used focal cryoballoon ablation to eradicate early esophageal squamous cell neoplasias, including high-grade lesions in treatment-experienced patients.

A single session of treatment with the novel, portable nitrous oxide system (C2 Therapeutics, Redwood City, Calif.) produced complete pathologic and endoscopic responses at 3 months in 8 of 10 patients, reported Marcia Irene Canto, MD, of Johns Hopkins University in Baltimore, with her associates. Two to five sessions produced complete responses in the other two patients, and all patients were disease-free at their last visit (median follow-up, 10.7 months; interquartile range, 4-14 months). The study was published online July 15 in Gastrointestinal Endoscopy (2017. doi: 10.1016/j.gie.2017.07.013).

©Nephron/Wikimedia Commons/CC BY-SA 3.0/No changes

For the first time, endoscopists have used focal cryoballoon ablation to eradicate early esophageal squamous cell neoplasias, including high-grade lesions in treatment-experienced patients.

A single session of treatment with the novel, portable nitrous oxide system (C2 Therapeutics, Redwood City, Calif.) produced complete pathologic and endoscopic responses at 3 months in 8 of 10 patients, reported Marcia Irene Canto, MD, of Johns Hopkins University in Baltimore, with her associates. Two to five sessions produced complete responses in the other two patients, and all patients were disease-free at their last visit (median follow-up, 10.7 months; interquartile range, 4-14 months). The study was published online July 15 in Gastrointestinal Endoscopy (2017. doi: 10.1016/j.gie.2017.07.013).

©Nephron/Wikimedia Commons/CC BY-SA 3.0/No changes

Patients who received antiretroviral treatment (ART) on the day they underwent HIV testing were more likely to continue treatment and have a lower mortality rate, a study conducted in Port-au-Prince, Haiti, showed.

According to the World Health Organization, ART treatment is essential in stopping the spread of HIV; however, one-quarter to one-third of patients do not continue the treatment process after starting ART, the investigators reported.

Starting ART treatment the same day as HIV testing showed the potential to reduce this problem. “Our findings suggest that ART initiation as soon as possible after HIV testing may be beneficial for clinically stable patients,” wrote Serena Koenig, MD, of the department of infectious diseases at Brigham and Women’s Hospital, Boston, and her coinvestigators. “In resource-poor settings with fragile delivery systems, such as Haiti, the provision of immediate support by care providers at the time of HIV diagnosis can have both structural and individual impact.”

In a randomized, controlled study of 703 patients, 277 of 347 same-day ART patients (80%) retained care, and 10 (3%) died, compared with 256 of 356 patients (72%) in the standard care group, 20 (6%) of whom died (PLoS Med. 2017 Jul 25. doi: 10.1371/journal.pmed.1002357).

Retention of care was defined as attending one clinic visit between 12 months and 15 months after testing, the investigators reported.

The median age of participating patients was 37 years; the median CD4 count was 247 cells/mm³ in the standard care group and 249 cells/mm³ in the same-day group.

At the end of the study, the adjusted mortality risk among patients in the same-day ART group was less than half that of the standard care group (risk ratio, 0.43; P = .033).

Care retention might be related to a more positive mindset among those who start ART immediately after diagnosis, the investigators said.

“Making treatment initiation logistically easier for patients, we believe that same-day counseling and ART initiation increase the sense of hope, optimism, and overall connectedness to the health care system for patients, which have been shown to be important for retention,” Dr. Koenig and her colleagues wrote.

The findings update the 2016 World Health Organization standard guidelines for ART treatment, which report that there is not enough information to recommend same-day treatment. The study was limited by the single-center patient population. Patients also had lower than usual CD4 counts, which may have exaggerated successful results.

The National Institute of Allergy and Infectious Diseases funded the study. The investigators reported they had no relevant financial disclosures.

[email protected]On Twitter @eaztweets

Patients who received antiretroviral treatment (ART) on the day they underwent HIV testing were more likely to continue treatment and have a lower mortality rate, a study conducted in Port-au-Prince, Haiti, showed.

According to the World Health Organization, ART treatment is essential in stopping the spread of HIV; however, one-quarter to one-third of patients do not continue the treatment process after starting ART, the investigators reported.

Starting ART treatment the same day as HIV testing showed the potential to reduce this problem. “Our findings suggest that ART initiation as soon as possible after HIV testing may be beneficial for clinically stable patients,” wrote Serena Koenig, MD, of the department of infectious diseases at Brigham and Women’s Hospital, Boston, and her coinvestigators. “In resource-poor settings with fragile delivery systems, such as Haiti, the provision of immediate support by care providers at the time of HIV diagnosis can have both structural and individual impact.”

In a randomized, controlled study of 703 patients, 277 of 347 same-day ART patients (80%) retained care, and 10 (3%) died, compared with 256 of 356 patients (72%) in the standard care group, 20 (6%) of whom died (PLoS Med. 2017 Jul 25. doi: 10.1371/journal.pmed.1002357).

Retention of care was defined as attending one clinic visit between 12 months and 15 months after testing, the investigators reported.

The median age of participating patients was 37 years; the median CD4 count was 247 cells/mm³ in the standard care group and 249 cells/mm³ in the same-day group.

At the end of the study, the adjusted mortality risk among patients in the same-day ART group was less than half that of the standard care group (risk ratio, 0.43; P = .033).

Care retention might be related to a more positive mindset among those who start ART immediately after diagnosis, the investigators said.

“Making treatment initiation logistically easier for patients, we believe that same-day counseling and ART initiation increase the sense of hope, optimism, and overall connectedness to the health care system for patients, which have been shown to be important for retention,” Dr. Koenig and her colleagues wrote.

The findings update the 2016 World Health Organization standard guidelines for ART treatment, which report that there is not enough information to recommend same-day treatment. The study was limited by the single-center patient population. Patients also had lower than usual CD4 counts, which may have exaggerated successful results.

The National Institute of Allergy and Infectious Diseases funded the study. The investigators reported they had no relevant financial disclosures.

[email protected]On Twitter @eaztweets

Patients who received antiretroviral treatment (ART) on the day they underwent HIV testing were more likely to continue treatment and have a lower mortality rate, a study conducted in Port-au-Prince, Haiti, showed.

According to the World Health Organization, ART treatment is essential in stopping the spread of HIV; however, one-quarter to one-third of patients do not continue the treatment process after starting ART, the investigators reported.

Starting ART treatment the same day as HIV testing showed the potential to reduce this problem. “Our findings suggest that ART initiation as soon as possible after HIV testing may be beneficial for clinically stable patients,” wrote Serena Koenig, MD, of the department of infectious diseases at Brigham and Women’s Hospital, Boston, and her coinvestigators. “In resource-poor settings with fragile delivery systems, such as Haiti, the provision of immediate support by care providers at the time of HIV diagnosis can have both structural and individual impact.”

In a randomized, controlled study of 703 patients, 277 of 347 same-day ART patients (80%) retained care, and 10 (3%) died, compared with 256 of 356 patients (72%) in the standard care group, 20 (6%) of whom died (PLoS Med. 2017 Jul 25. doi: 10.1371/journal.pmed.1002357).

Retention of care was defined as attending one clinic visit between 12 months and 15 months after testing, the investigators reported.

The median age of participating patients was 37 years; the median CD4 count was 247 cells/mm³ in the standard care group and 249 cells/mm³ in the same-day group.

At the end of the study, the adjusted mortality risk among patients in the same-day ART group was less than half that of the standard care group (risk ratio, 0.43; P = .033).

Care retention might be related to a more positive mindset among those who start ART immediately after diagnosis, the investigators said.

“Making treatment initiation logistically easier for patients, we believe that same-day counseling and ART initiation increase the sense of hope, optimism, and overall connectedness to the health care system for patients, which have been shown to be important for retention,” Dr. Koenig and her colleagues wrote.

The findings update the 2016 World Health Organization standard guidelines for ART treatment, which report that there is not enough information to recommend same-day treatment. The study was limited by the single-center patient population. Patients also had lower than usual CD4 counts, which may have exaggerated successful results.

The National Institute of Allergy and Infectious Diseases funded the study. The investigators reported they had no relevant financial disclosures.

[email protected]On Twitter @eaztweets

Granuloma faciale (GF) is a chronic benign leukocytoclastic vasculitis that can be difficult to treat. It is characterized by single or multiple, soft, well-circumscribed papules, plaques, or nodules ranging in color from red, violet, or yellow to brown that may darken with sun exposure.¹ Lesions usually are smooth with follicular orifices that are accentuated, thus producing a peau d’orange appearance. Lesions generally are slow to develop and asymptomatic, though some patients report pruritus or burning.^2,3 Diagnosis of GF is based on the presence of distinct histologic features. The epidermis usually is spared, with a prominent grenz zone of normal collagen separating the epidermis from a dense infiltrate of neutrophils, lymphocytes, and eosinophils. This mixed inflammatory infiltrate is seen mainly in the superficial dermis but occasionally spreads to the lower dermis and subcutaneous tissues.⁴

As the name implies, GF usually is confined to the face but occasionally involves extrafacial sites.^5-15 The clinical characteristics of these rare extrafacial lesions are not well understood. The purpose of this study was to identify the clinical and demographic features of extrafacial GF in patients treated at Mayo Clinic (Rochester, Minnesota) during a 54-year period.

Methods

This study was approved by the Mayo institutional review board. We searched the Mayo Clinic Rochester dermatology database for all patients with a diagnosis of GF from 1959 through 2013. All histopathology slides were reviewed by a board-certified dermatologist (A.G.B.) and dermatopathologist (A.G.B.) before inclusion in this study. Histologic criteria for diagnosis of GF included the presence of a mixed inflammatory infiltrate of neutrophils, eosinophils, lymphocytes, and histiocytes in the superficial or deep dermis; a prominent grenz zone separating the uninvolved epidermis; and the presence of vascular damage, as seen by fibrin deposition in dermal blood vessels.

Medical records were reviewed for patient demographics and for history pertinent to the diagnosis of GF, including sites involved, appearance, histopathology reports, symptoms, treatments, and outcomes.

Literature Search Strategy
A computerized Ovid MEDLINE database search was undertaken to identify English-language articles concerning GF in humans using the search terms granuloma faciale with extrafacial or disseminated. To ensure that no articles were overlooked, we conducted another search for English-language articles in the Embase database (1946-2013) using the terms granuloma faciale and extrafacial or disseminated.

Statistical Analysis
Descriptive clinical and histopathologic data were summarized using means, medians, and ranges or proportions as appropriate; statistical analysis was performed using SAS software (JMP package).

Results

Ninety-six patients with a diagnosis of GF were identified, and 12 (13%) had a diagnosis of extrafacial GF. Of them, 2 patients had a diagnosis of extrafacial GF supported only by histopathology slides without accompanying clinical records and therefore were excluded from the study. Thus, 10 cases of extrafacial GF were identified from our search and were included in the study group. Clinical data for these patients are summarized in Table 1. The mean age was 58.7 years (range, 26–87 years). Six (60%) patients were male, and all patients were white. Seven patients (70%) had facial GF in addition to extrafacial GF. Six patients reported no symptoms (60%), and 4 (40%) reported pruritus, discomfort, or both associated with their GF lesions.

Extrafacial GF was diagnosed in the following anatomic locations: scalp (n=3 [30%]), posterior auricular area (n=3 [30%]), mid upper back (n=1 [10%]), right shoulder (n=1 [10%]), both ears (n=1 [10%]), right elbow (n=1 [10%]), and left infra-auricular area (n=1 [10%]). Only 1 (10%) patient had multiple extrafacial sites identified.

The lesions were characterized clinically as violet, red, and yellow to brown smooth papules, plaques, and nodules (Figure 1). Biopsies from these lesions showed a subepidermal and adnexal grenz zone; a polymorphous perivascular and periadnexal dermal infiltrate composed of neutrophils, eosinophils, lymphocytes, histiocytes, and plasma cells; and a mild subtle leukocytoclastic vasculitis with subtle mild vascular necrosis (Figure 2).

For the 9 patients who elected to undergo GF treatment, the average number of treatments attempted was 2.8 (range, 1–5). The most common method of treatment was a combination of intralesional and topical corticosteroids (n=5 [50%]). Other methods included surgery (n=3 [30%]), dapsone (n=2 [20%]), radiation therapy (n=2 [20%]), cryosurgery (n=1 [10%]), nitrogen mustard (n=1 [10%]), liquid nitrogen (n=1 [10%]), and tar shampoo and fluocinolone acetonide solution 0.01% (n=1 [10%]).

Treatment outcomes were available for 8 of 9 treated patients. Three patients (patients 7, 8, and 10) had long-term successful resolution of their lesions. Patient 7 had an extrafacial lesion that was successfully treated with intralesional and topical corticosteroids, but the facial lesions recurred. The extrafacial GF lesion in patient 8 was found adjacent to a squamous cell carcinoma and was removed with a wide surgical excision that included both lesions. Patient 10 was successfully treated with a combination of liquid nitrogen and topical corticosteroid. Patients 2 and 4 were well controlled while on dapsone; however, once the treatment was discontinued, primarily due to adverse effects, the lesions returned.

Literature Search
Our search of the English-language literature identified 20 patients with extrafacial GF (Table 2). Fifteen (75%) patients were male, which was similar to our study (6/10 [60%]). Our patient population was slightly older with a mean age of 58.7 years compared to a median age of 54 years among those identified in the literature. Additionally, 3 (30%) patients in our study had no facial lesions, as seen in classic GF, which is comparable to 8 (40%) patients identified in the literature.

Comment

Extrafacial GF primarily affects white individuals and is more prevalent in men, as demonstrated in our study. Extrafacial GF was most often found in association with facial lesions, with only 3 patients having exclusively extrafacial sites.

Data from the current study indicate that diverse modalities were used to treat extrafacial GF with variable outcomes (chronic recurrence to complete resolution). The most common first-line treatment, intralesional corticosteroid injection, was used in 5 (50%) patients but resulted in only 1 (10%) successful resolution. Other methods frequently used in our study and prior studies were surgical excision, cryotherapy, electrosurgery, and dermabrasion.^1,20 These treatments do not appear to be uniformly definitive, and the ablative methods may result in scarring.¹ Different laser treatments are emerging for the management of GF lesions. Prior reports of treating facial GF with argon and CO₂ lasers have indicated minimized residual scarring and pigmentation.^21-23 The use of pulsed dye lasers has resulted in complete clearance of facial GF lesions, without recurrence on long-term follow-up.^20,24-26

The latest investigations of immunomodulatory drugs indicate these agents are promising for the management of facial GF. Eetam et al²⁷ reported the successful use of topical tacrolimus to treat facial GF. The relatively low cost and ease of use make these topical medications a competitive alternative to currently available surgical and laser methods. The appearance of all of these novel therapeutic modalities creates the necessity for a randomized trial to establish their efficacy on extrafacial GF lesions.

The wide array of treatments reflects the recalcitrant nature of extrafacial GF lesions. Further insight into the etiology of these lesions is needed to understand their tendency to recur. The important contribution of our study is the observed predilection of extrafacial GF for sun-exposed areas such as the scalp, upper trunk, and arms and legs. This pattern of extrafacial distribution along with the lack of mucosal involvement suggests a possible connection with UV light exposure. Furthermore, one of the extrafacial GF lesions in our study occurred in association with a squamous cell carcinoma, which may be an additional indication that these sites have been subjected to sun damage. This finding strengthens the importance of obtaining an adequate skin biopsy of any well-demarcated plaque or nodule found on the trunk, arms, and legs. The observed GF prevalence on sun-exposed areas and association with photoexacerbation have been speculated in prior studies, but no clear connection has been established.^1,28

Conclusion

The findings from this study and the cases reviewed in the literature provide a unique contribution to the understanding of the clinical and demographic characteristics of extrafacial GF. The rarity of this condition is the single most important constraint of our study, reflected in the emblematic limitations of a retrospective analysis in a select group of patients. The results of analysis of data from our patients were similar to the findings reported in the English-language medical literature. Serious consideration should be given to the development of a national registry for patients with GF. A database containing the clinicopathologic features, treatments, and outcomes for patients with both facial and extrafacial manifestations of GF may be invaluable in evaluating various treatment options and increasing understanding of the etiology and epidemiology of the disease.

Granuloma faciale (GF) is a chronic benign leukocytoclastic vasculitis that can be difficult to treat. It is characterized by single or multiple, soft, well-circumscribed papules, plaques, or nodules ranging in color from red, violet, or yellow to brown that may darken with sun exposure.¹ Lesions usually are smooth with follicular orifices that are accentuated, thus producing a peau d’orange appearance. Lesions generally are slow to develop and asymptomatic, though some patients report pruritus or burning.^2,3 Diagnosis of GF is based on the presence of distinct histologic features. The epidermis usually is spared, with a prominent grenz zone of normal collagen separating the epidermis from a dense infiltrate of neutrophils, lymphocytes, and eosinophils. This mixed inflammatory infiltrate is seen mainly in the superficial dermis but occasionally spreads to the lower dermis and subcutaneous tissues.⁴

As the name implies, GF usually is confined to the face but occasionally involves extrafacial sites.^5-15 The clinical characteristics of these rare extrafacial lesions are not well understood. The purpose of this study was to identify the clinical and demographic features of extrafacial GF in patients treated at Mayo Clinic (Rochester, Minnesota) during a 54-year period.

Methods

This study was approved by the Mayo institutional review board. We searched the Mayo Clinic Rochester dermatology database for all patients with a diagnosis of GF from 1959 through 2013. All histopathology slides were reviewed by a board-certified dermatologist (A.G.B.) and dermatopathologist (A.G.B.) before inclusion in this study. Histologic criteria for diagnosis of GF included the presence of a mixed inflammatory infiltrate of neutrophils, eosinophils, lymphocytes, and histiocytes in the superficial or deep dermis; a prominent grenz zone separating the uninvolved epidermis; and the presence of vascular damage, as seen by fibrin deposition in dermal blood vessels.

Medical records were reviewed for patient demographics and for history pertinent to the diagnosis of GF, including sites involved, appearance, histopathology reports, symptoms, treatments, and outcomes.

Literature Search Strategy
A computerized Ovid MEDLINE database search was undertaken to identify English-language articles concerning GF in humans using the search terms granuloma faciale with extrafacial or disseminated. To ensure that no articles were overlooked, we conducted another search for English-language articles in the Embase database (1946-2013) using the terms granuloma faciale and extrafacial or disseminated.

Statistical Analysis
Descriptive clinical and histopathologic data were summarized using means, medians, and ranges or proportions as appropriate; statistical analysis was performed using SAS software (JMP package).

Results

Ninety-six patients with a diagnosis of GF were identified, and 12 (13%) had a diagnosis of extrafacial GF. Of them, 2 patients had a diagnosis of extrafacial GF supported only by histopathology slides without accompanying clinical records and therefore were excluded from the study. Thus, 10 cases of extrafacial GF were identified from our search and were included in the study group. Clinical data for these patients are summarized in Table 1. The mean age was 58.7 years (range, 26–87 years). Six (60%) patients were male, and all patients were white. Seven patients (70%) had facial GF in addition to extrafacial GF. Six patients reported no symptoms (60%), and 4 (40%) reported pruritus, discomfort, or both associated with their GF lesions.

Extrafacial GF was diagnosed in the following anatomic locations: scalp (n=3 [30%]), posterior auricular area (n=3 [30%]), mid upper back (n=1 [10%]), right shoulder (n=1 [10%]), both ears (n=1 [10%]), right elbow (n=1 [10%]), and left infra-auricular area (n=1 [10%]). Only 1 (10%) patient had multiple extrafacial sites identified.

The lesions were characterized clinically as violet, red, and yellow to brown smooth papules, plaques, and nodules (Figure 1). Biopsies from these lesions showed a subepidermal and adnexal grenz zone; a polymorphous perivascular and periadnexal dermal infiltrate composed of neutrophils, eosinophils, lymphocytes, histiocytes, and plasma cells; and a mild subtle leukocytoclastic vasculitis with subtle mild vascular necrosis (Figure 2).

For the 9 patients who elected to undergo GF treatment, the average number of treatments attempted was 2.8 (range, 1–5). The most common method of treatment was a combination of intralesional and topical corticosteroids (n=5 [50%]). Other methods included surgery (n=3 [30%]), dapsone (n=2 [20%]), radiation therapy (n=2 [20%]), cryosurgery (n=1 [10%]), nitrogen mustard (n=1 [10%]), liquid nitrogen (n=1 [10%]), and tar shampoo and fluocinolone acetonide solution 0.01% (n=1 [10%]).

Treatment outcomes were available for 8 of 9 treated patients. Three patients (patients 7, 8, and 10) had long-term successful resolution of their lesions. Patient 7 had an extrafacial lesion that was successfully treated with intralesional and topical corticosteroids, but the facial lesions recurred. The extrafacial GF lesion in patient 8 was found adjacent to a squamous cell carcinoma and was removed with a wide surgical excision that included both lesions. Patient 10 was successfully treated with a combination of liquid nitrogen and topical corticosteroid. Patients 2 and 4 were well controlled while on dapsone; however, once the treatment was discontinued, primarily due to adverse effects, the lesions returned.

Literature Search
Our search of the English-language literature identified 20 patients with extrafacial GF (Table 2). Fifteen (75%) patients were male, which was similar to our study (6/10 [60%]). Our patient population was slightly older with a mean age of 58.7 years compared to a median age of 54 years among those identified in the literature. Additionally, 3 (30%) patients in our study had no facial lesions, as seen in classic GF, which is comparable to 8 (40%) patients identified in the literature.

Comment

Extrafacial GF primarily affects white individuals and is more prevalent in men, as demonstrated in our study. Extrafacial GF was most often found in association with facial lesions, with only 3 patients having exclusively extrafacial sites.

Data from the current study indicate that diverse modalities were used to treat extrafacial GF with variable outcomes (chronic recurrence to complete resolution). The most common first-line treatment, intralesional corticosteroid injection, was used in 5 (50%) patients but resulted in only 1 (10%) successful resolution. Other methods frequently used in our study and prior studies were surgical excision, cryotherapy, electrosurgery, and dermabrasion.^1,20 These treatments do not appear to be uniformly definitive, and the ablative methods may result in scarring.¹ Different laser treatments are emerging for the management of GF lesions. Prior reports of treating facial GF with argon and CO₂ lasers have indicated minimized residual scarring and pigmentation.^21-23 The use of pulsed dye lasers has resulted in complete clearance of facial GF lesions, without recurrence on long-term follow-up.^20,24-26

The latest investigations of immunomodulatory drugs indicate these agents are promising for the management of facial GF. Eetam et al²⁷ reported the successful use of topical tacrolimus to treat facial GF. The relatively low cost and ease of use make these topical medications a competitive alternative to currently available surgical and laser methods. The appearance of all of these novel therapeutic modalities creates the necessity for a randomized trial to establish their efficacy on extrafacial GF lesions.

The wide array of treatments reflects the recalcitrant nature of extrafacial GF lesions. Further insight into the etiology of these lesions is needed to understand their tendency to recur. The important contribution of our study is the observed predilection of extrafacial GF for sun-exposed areas such as the scalp, upper trunk, and arms and legs. This pattern of extrafacial distribution along with the lack of mucosal involvement suggests a possible connection with UV light exposure. Furthermore, one of the extrafacial GF lesions in our study occurred in association with a squamous cell carcinoma, which may be an additional indication that these sites have been subjected to sun damage. This finding strengthens the importance of obtaining an adequate skin biopsy of any well-demarcated plaque or nodule found on the trunk, arms, and legs. The observed GF prevalence on sun-exposed areas and association with photoexacerbation have been speculated in prior studies, but no clear connection has been established.^1,28

Conclusion

The findings from this study and the cases reviewed in the literature provide a unique contribution to the understanding of the clinical and demographic characteristics of extrafacial GF. The rarity of this condition is the single most important constraint of our study, reflected in the emblematic limitations of a retrospective analysis in a select group of patients. The results of analysis of data from our patients were similar to the findings reported in the English-language medical literature. Serious consideration should be given to the development of a national registry for patients with GF. A database containing the clinicopathologic features, treatments, and outcomes for patients with both facial and extrafacial manifestations of GF may be invaluable in evaluating various treatment options and increasing understanding of the etiology and epidemiology of the disease.

Granuloma faciale (GF) is a chronic benign leukocytoclastic vasculitis that can be difficult to treat. It is characterized by single or multiple, soft, well-circumscribed papules, plaques, or nodules ranging in color from red, violet, or yellow to brown that may darken with sun exposure.¹ Lesions usually are smooth with follicular orifices that are accentuated, thus producing a peau d’orange appearance. Lesions generally are slow to develop and asymptomatic, though some patients report pruritus or burning.^2,3 Diagnosis of GF is based on the presence of distinct histologic features. The epidermis usually is spared, with a prominent grenz zone of normal collagen separating the epidermis from a dense infiltrate of neutrophils, lymphocytes, and eosinophils. This mixed inflammatory infiltrate is seen mainly in the superficial dermis but occasionally spreads to the lower dermis and subcutaneous tissues.⁴

As the name implies, GF usually is confined to the face but occasionally involves extrafacial sites.^5-15 The clinical characteristics of these rare extrafacial lesions are not well understood. The purpose of this study was to identify the clinical and demographic features of extrafacial GF in patients treated at Mayo Clinic (Rochester, Minnesota) during a 54-year period.

Methods

This study was approved by the Mayo institutional review board. We searched the Mayo Clinic Rochester dermatology database for all patients with a diagnosis of GF from 1959 through 2013. All histopathology slides were reviewed by a board-certified dermatologist (A.G.B.) and dermatopathologist (A.G.B.) before inclusion in this study. Histologic criteria for diagnosis of GF included the presence of a mixed inflammatory infiltrate of neutrophils, eosinophils, lymphocytes, and histiocytes in the superficial or deep dermis; a prominent grenz zone separating the uninvolved epidermis; and the presence of vascular damage, as seen by fibrin deposition in dermal blood vessels.

Medical records were reviewed for patient demographics and for history pertinent to the diagnosis of GF, including sites involved, appearance, histopathology reports, symptoms, treatments, and outcomes.

Literature Search Strategy
A computerized Ovid MEDLINE database search was undertaken to identify English-language articles concerning GF in humans using the search terms granuloma faciale with extrafacial or disseminated. To ensure that no articles were overlooked, we conducted another search for English-language articles in the Embase database (1946-2013) using the terms granuloma faciale and extrafacial or disseminated.

Statistical Analysis
Descriptive clinical and histopathologic data were summarized using means, medians, and ranges or proportions as appropriate; statistical analysis was performed using SAS software (JMP package).

Results

Ninety-six patients with a diagnosis of GF were identified, and 12 (13%) had a diagnosis of extrafacial GF. Of them, 2 patients had a diagnosis of extrafacial GF supported only by histopathology slides without accompanying clinical records and therefore were excluded from the study. Thus, 10 cases of extrafacial GF were identified from our search and were included in the study group. Clinical data for these patients are summarized in Table 1. The mean age was 58.7 years (range, 26–87 years). Six (60%) patients were male, and all patients were white. Seven patients (70%) had facial GF in addition to extrafacial GF. Six patients reported no symptoms (60%), and 4 (40%) reported pruritus, discomfort, or both associated with their GF lesions.

Extrafacial GF was diagnosed in the following anatomic locations: scalp (n=3 [30%]), posterior auricular area (n=3 [30%]), mid upper back (n=1 [10%]), right shoulder (n=1 [10%]), both ears (n=1 [10%]), right elbow (n=1 [10%]), and left infra-auricular area (n=1 [10%]). Only 1 (10%) patient had multiple extrafacial sites identified.

The lesions were characterized clinically as violet, red, and yellow to brown smooth papules, plaques, and nodules (Figure 1). Biopsies from these lesions showed a subepidermal and adnexal grenz zone; a polymorphous perivascular and periadnexal dermal infiltrate composed of neutrophils, eosinophils, lymphocytes, histiocytes, and plasma cells; and a mild subtle leukocytoclastic vasculitis with subtle mild vascular necrosis (Figure 2).

For the 9 patients who elected to undergo GF treatment, the average number of treatments attempted was 2.8 (range, 1–5). The most common method of treatment was a combination of intralesional and topical corticosteroids (n=5 [50%]). Other methods included surgery (n=3 [30%]), dapsone (n=2 [20%]), radiation therapy (n=2 [20%]), cryosurgery (n=1 [10%]), nitrogen mustard (n=1 [10%]), liquid nitrogen (n=1 [10%]), and tar shampoo and fluocinolone acetonide solution 0.01% (n=1 [10%]).

Treatment outcomes were available for 8 of 9 treated patients. Three patients (patients 7, 8, and 10) had long-term successful resolution of their lesions. Patient 7 had an extrafacial lesion that was successfully treated with intralesional and topical corticosteroids, but the facial lesions recurred. The extrafacial GF lesion in patient 8 was found adjacent to a squamous cell carcinoma and was removed with a wide surgical excision that included both lesions. Patient 10 was successfully treated with a combination of liquid nitrogen and topical corticosteroid. Patients 2 and 4 were well controlled while on dapsone; however, once the treatment was discontinued, primarily due to adverse effects, the lesions returned.

Literature Search
Our search of the English-language literature identified 20 patients with extrafacial GF (Table 2). Fifteen (75%) patients were male, which was similar to our study (6/10 [60%]). Our patient population was slightly older with a mean age of 58.7 years compared to a median age of 54 years among those identified in the literature. Additionally, 3 (30%) patients in our study had no facial lesions, as seen in classic GF, which is comparable to 8 (40%) patients identified in the literature.

Comment

Extrafacial GF primarily affects white individuals and is more prevalent in men, as demonstrated in our study. Extrafacial GF was most often found in association with facial lesions, with only 3 patients having exclusively extrafacial sites.

Data from the current study indicate that diverse modalities were used to treat extrafacial GF with variable outcomes (chronic recurrence to complete resolution). The most common first-line treatment, intralesional corticosteroid injection, was used in 5 (50%) patients but resulted in only 1 (10%) successful resolution. Other methods frequently used in our study and prior studies were surgical excision, cryotherapy, electrosurgery, and dermabrasion.^1,20 These treatments do not appear to be uniformly definitive, and the ablative methods may result in scarring.¹ Different laser treatments are emerging for the management of GF lesions. Prior reports of treating facial GF with argon and CO₂ lasers have indicated minimized residual scarring and pigmentation.^21-23 The use of pulsed dye lasers has resulted in complete clearance of facial GF lesions, without recurrence on long-term follow-up.^20,24-26

The latest investigations of immunomodulatory drugs indicate these agents are promising for the management of facial GF. Eetam et al²⁷ reported the successful use of topical tacrolimus to treat facial GF. The relatively low cost and ease of use make these topical medications a competitive alternative to currently available surgical and laser methods. The appearance of all of these novel therapeutic modalities creates the necessity for a randomized trial to establish their efficacy on extrafacial GF lesions.

The wide array of treatments reflects the recalcitrant nature of extrafacial GF lesions. Further insight into the etiology of these lesions is needed to understand their tendency to recur. The important contribution of our study is the observed predilection of extrafacial GF for sun-exposed areas such as the scalp, upper trunk, and arms and legs. This pattern of extrafacial distribution along with the lack of mucosal involvement suggests a possible connection with UV light exposure. Furthermore, one of the extrafacial GF lesions in our study occurred in association with a squamous cell carcinoma, which may be an additional indication that these sites have been subjected to sun damage. This finding strengthens the importance of obtaining an adequate skin biopsy of any well-demarcated plaque or nodule found on the trunk, arms, and legs. The observed GF prevalence on sun-exposed areas and association with photoexacerbation have been speculated in prior studies, but no clear connection has been established.^1,28

Conclusion

The findings from this study and the cases reviewed in the literature provide a unique contribution to the understanding of the clinical and demographic characteristics of extrafacial GF. The rarity of this condition is the single most important constraint of our study, reflected in the emblematic limitations of a retrospective analysis in a select group of patients. The results of analysis of data from our patients were similar to the findings reported in the English-language medical literature. Serious consideration should be given to the development of a national registry for patients with GF. A database containing the clinicopathologic features, treatments, and outcomes for patients with both facial and extrafacial manifestations of GF may be invaluable in evaluating various treatment options and increasing understanding of the etiology and epidemiology of the disease.

Evidence of a correlation between chronic traumatic encephalopathy (CTE) and playing American football was strengthened in the largest retrospective study cohort to date.

The progressive neurodegenerative disease associated with recurrent head trauma has been linked to football over the past decade. However, this new study took steps to solidify the connection by studying 202 deceased brains, more than double the size of a previous 2013 report.

First author Jesse Mez, MD, of Boston University, and his colleagues examined the brains donated to a brain bank jointly run by the VA Boston Healthcare System, Boston University, and the Concussion Legacy Foundation. They correlated their findings with interviews and questionnaires filled out in 2014 by those close to the donors (JAMA. 2017 Jul 25. doi: 10.1001/jama.2017.8334).

The donors were male, and a majority (79%) were white. The average age at death was 67 years. In the mild cases, there was an average of 13 years of play; in severe cases, the average was 15.8 years.

The researchers found evidence of CTE in 177 (88%) of the 202 brains of football players, with cases found in 3 (21%) who played only in high school, 48 (91%) who played in college, 9 (64%) semiprofessional players, 7 (88%) Canadian Football League players, and 110 (99%) NFL players, according to investigators.

“Nearly all of the former NFL players in this study had CTE pathology, and this pathology was frequently severe,” noted Dr. Mez and his coinvestigators. ”These findings suggest that CTE may be related to prior participation in football and that a high level of play may be related to substantial disease burden.”

Severity of CTE positively correlated with longer playing history and more competitive levels of play. According to the investigators, severe cases of CTE were found in none of the high school players, 27 college players (56%), 5 semiprofessional players (56%), 6 Canadian professional players (86%), and 95 NFL players (86%).

All participants with CTE commonly displayed certain symptoms regardless of severity level.

Impulsiveness occurred in 23 mild cases (89%) and 65 severe cases (80%). Depression was seen in 18 mild cases (67%) and 46 severe cases (56%). A total of 13 players (50%) with mild symptoms showed apathy, compared with 43 with severe symptoms (52%). Anxiety was reported for 14 mild cases (52%) and 41 severe cases (50%). Cognitive symptoms such as problems with memory and attention were also common at both levels of severity, with 19 cases (73%) and 18 cases (69%), respectively, among donors with mild CTE, and 76 (92%) and 67 (81%) among donors with severe CTE.

Those interviewed who were close to the donors also reported other behavior or mood symptoms that the investigators inferred to be related to CTE.

“Many of these participants had a substance use disorder, demonstrated suicidality, or had a family history of psychiatric illness,” the investigators wrote. “Behavior or mood symptoms may be the initial presentation for a subset of individuals with CTE, or alternatively, CTE [phosphorylated tau] pathology may lower the threshold for psychiatric manifestations in susceptible individuals.”

The investigators asserted that the correlation of CTE diagnosis and severity may be more nuanced than just how many times a player is hit.

“Several other football-related factors may influence CTE risk and disease severity, including but not limited to age at first exposure to football, duration of play, player position, cumulative hits, and linear and rotational acceleration of hits,” Dr. Mez and his associates wrote. “Recent work in living former football players has shown that age at first exposure may be related to impaired cognitive performance and altered corpus callosum white matter and that cumulative hits may be related to impairment on self-report and objective measures of cognition, mood, and behavior, although it is unclear if any of these outcomes are related to CTE pathology.”

This study was limited by the potential bias of donors who participated in the program. Researchers acknowledge that public awareness of the issue of CTE and head trauma may have influenced players with symptoms to donate their brains, thereby increasing the CTE frequency in the sample.

In addition, the brain bank where the sample was taken is not representative of the entire population of American football players, as most donors played at the college, semi-professional, and professional level, as opposed to only high school or youth leagues.

The senior author of the study, Ann C. McKee, MD, discussed the study further in a related video interview.

The National Institute of Neurological Disorders and Stroke, the National Institute of Aging, the U.S. Department of Defense, the U.S. Department of Veterans Affairs, the National Operating Committee on Standards for Athletic Equipment, the Alzheimer’s Association, the Concussion Legacy Foundation, the Andlinger Family Foundation, the WWE, and the NFL supported the study. Five authors reported receiving support from relevant sources, including the NFL.

[email protected]

On Twitter @eaztweets

Evidence of a correlation between chronic traumatic encephalopathy (CTE) and playing American football was strengthened in the largest retrospective study cohort to date.

The progressive neurodegenerative disease associated with recurrent head trauma has been linked to football over the past decade. However, this new study took steps to solidify the connection by studying 202 deceased brains, more than double the size of a previous 2013 report.

First author Jesse Mez, MD, of Boston University, and his colleagues examined the brains donated to a brain bank jointly run by the VA Boston Healthcare System, Boston University, and the Concussion Legacy Foundation. They correlated their findings with interviews and questionnaires filled out in 2014 by those close to the donors (JAMA. 2017 Jul 25. doi: 10.1001/jama.2017.8334).

The donors were male, and a majority (79%) were white. The average age at death was 67 years. In the mild cases, there was an average of 13 years of play; in severe cases, the average was 15.8 years.

The researchers found evidence of CTE in 177 (88%) of the 202 brains of football players, with cases found in 3 (21%) who played only in high school, 48 (91%) who played in college, 9 (64%) semiprofessional players, 7 (88%) Canadian Football League players, and 110 (99%) NFL players, according to investigators.

“Nearly all of the former NFL players in this study had CTE pathology, and this pathology was frequently severe,” noted Dr. Mez and his coinvestigators. ”These findings suggest that CTE may be related to prior participation in football and that a high level of play may be related to substantial disease burden.”

Severity of CTE positively correlated with longer playing history and more competitive levels of play. According to the investigators, severe cases of CTE were found in none of the high school players, 27 college players (56%), 5 semiprofessional players (56%), 6 Canadian professional players (86%), and 95 NFL players (86%).

All participants with CTE commonly displayed certain symptoms regardless of severity level.

Impulsiveness occurred in 23 mild cases (89%) and 65 severe cases (80%). Depression was seen in 18 mild cases (67%) and 46 severe cases (56%). A total of 13 players (50%) with mild symptoms showed apathy, compared with 43 with severe symptoms (52%). Anxiety was reported for 14 mild cases (52%) and 41 severe cases (50%). Cognitive symptoms such as problems with memory and attention were also common at both levels of severity, with 19 cases (73%) and 18 cases (69%), respectively, among donors with mild CTE, and 76 (92%) and 67 (81%) among donors with severe CTE.

Those interviewed who were close to the donors also reported other behavior or mood symptoms that the investigators inferred to be related to CTE.

“Many of these participants had a substance use disorder, demonstrated suicidality, or had a family history of psychiatric illness,” the investigators wrote. “Behavior or mood symptoms may be the initial presentation for a subset of individuals with CTE, or alternatively, CTE [phosphorylated tau] pathology may lower the threshold for psychiatric manifestations in susceptible individuals.”

The investigators asserted that the correlation of CTE diagnosis and severity may be more nuanced than just how many times a player is hit.

“Several other football-related factors may influence CTE risk and disease severity, including but not limited to age at first exposure to football, duration of play, player position, cumulative hits, and linear and rotational acceleration of hits,” Dr. Mez and his associates wrote. “Recent work in living former football players has shown that age at first exposure may be related to impaired cognitive performance and altered corpus callosum white matter and that cumulative hits may be related to impairment on self-report and objective measures of cognition, mood, and behavior, although it is unclear if any of these outcomes are related to CTE pathology.”

This study was limited by the potential bias of donors who participated in the program. Researchers acknowledge that public awareness of the issue of CTE and head trauma may have influenced players with symptoms to donate their brains, thereby increasing the CTE frequency in the sample.

In addition, the brain bank where the sample was taken is not representative of the entire population of American football players, as most donors played at the college, semi-professional, and professional level, as opposed to only high school or youth leagues.

The senior author of the study, Ann C. McKee, MD, discussed the study further in a related video interview.

The National Institute of Neurological Disorders and Stroke, the National Institute of Aging, the U.S. Department of Defense, the U.S. Department of Veterans Affairs, the National Operating Committee on Standards for Athletic Equipment, the Alzheimer’s Association, the Concussion Legacy Foundation, the Andlinger Family Foundation, the WWE, and the NFL supported the study. Five authors reported receiving support from relevant sources, including the NFL.

[email protected]

On Twitter @eaztweets

Evidence of a correlation between chronic traumatic encephalopathy (CTE) and playing American football was strengthened in the largest retrospective study cohort to date.

The progressive neurodegenerative disease associated with recurrent head trauma has been linked to football over the past decade. However, this new study took steps to solidify the connection by studying 202 deceased brains, more than double the size of a previous 2013 report.

First author Jesse Mez, MD, of Boston University, and his colleagues examined the brains donated to a brain bank jointly run by the VA Boston Healthcare System, Boston University, and the Concussion Legacy Foundation. They correlated their findings with interviews and questionnaires filled out in 2014 by those close to the donors (JAMA. 2017 Jul 25. doi: 10.1001/jama.2017.8334).

The donors were male, and a majority (79%) were white. The average age at death was 67 years. In the mild cases, there was an average of 13 years of play; in severe cases, the average was 15.8 years.

The researchers found evidence of CTE in 177 (88%) of the 202 brains of football players, with cases found in 3 (21%) who played only in high school, 48 (91%) who played in college, 9 (64%) semiprofessional players, 7 (88%) Canadian Football League players, and 110 (99%) NFL players, according to investigators.

“Nearly all of the former NFL players in this study had CTE pathology, and this pathology was frequently severe,” noted Dr. Mez and his coinvestigators. ”These findings suggest that CTE may be related to prior participation in football and that a high level of play may be related to substantial disease burden.”

Severity of CTE positively correlated with longer playing history and more competitive levels of play. According to the investigators, severe cases of CTE were found in none of the high school players, 27 college players (56%), 5 semiprofessional players (56%), 6 Canadian professional players (86%), and 95 NFL players (86%).

All participants with CTE commonly displayed certain symptoms regardless of severity level.

Impulsiveness occurred in 23 mild cases (89%) and 65 severe cases (80%). Depression was seen in 18 mild cases (67%) and 46 severe cases (56%). A total of 13 players (50%) with mild symptoms showed apathy, compared with 43 with severe symptoms (52%). Anxiety was reported for 14 mild cases (52%) and 41 severe cases (50%). Cognitive symptoms such as problems with memory and attention were also common at both levels of severity, with 19 cases (73%) and 18 cases (69%), respectively, among donors with mild CTE, and 76 (92%) and 67 (81%) among donors with severe CTE.

Those interviewed who were close to the donors also reported other behavior or mood symptoms that the investigators inferred to be related to CTE.

“Many of these participants had a substance use disorder, demonstrated suicidality, or had a family history of psychiatric illness,” the investigators wrote. “Behavior or mood symptoms may be the initial presentation for a subset of individuals with CTE, or alternatively, CTE [phosphorylated tau] pathology may lower the threshold for psychiatric manifestations in susceptible individuals.”

The investigators asserted that the correlation of CTE diagnosis and severity may be more nuanced than just how many times a player is hit.

“Several other football-related factors may influence CTE risk and disease severity, including but not limited to age at first exposure to football, duration of play, player position, cumulative hits, and linear and rotational acceleration of hits,” Dr. Mez and his associates wrote. “Recent work in living former football players has shown that age at first exposure may be related to impaired cognitive performance and altered corpus callosum white matter and that cumulative hits may be related to impairment on self-report and objective measures of cognition, mood, and behavior, although it is unclear if any of these outcomes are related to CTE pathology.”

This study was limited by the potential bias of donors who participated in the program. Researchers acknowledge that public awareness of the issue of CTE and head trauma may have influenced players with symptoms to donate their brains, thereby increasing the CTE frequency in the sample.

In addition, the brain bank where the sample was taken is not representative of the entire population of American football players, as most donors played at the college, semi-professional, and professional level, as opposed to only high school or youth leagues.

The senior author of the study, Ann C. McKee, MD, discussed the study further in a related video interview.

The National Institute of Neurological Disorders and Stroke, the National Institute of Aging, the U.S. Department of Defense, the U.S. Department of Veterans Affairs, the National Operating Committee on Standards for Athletic Equipment, the Alzheimer’s Association, the Concussion Legacy Foundation, the Andlinger Family Foundation, the WWE, and the NFL supported the study. Five authors reported receiving support from relevant sources, including the NFL.

[email protected]

On Twitter @eaztweets

Mobile health interventions targeting mothers of healthy newborns significantly improved safe sleep practices, compared with controls, in a randomized trial of 1,600 mothers published online July 25 in JAMA.

Despite the success of the Back to Sleep campaign in reducing rates of sudden infant death syndrome, approximately 3,500 infant deaths due to SIDS, accidental suffocation, or strangulation in bed occurred in 2014, wrote Rachel Y. Moon, MD, of the University of Virginia, Charlottesville, and her colleagues (JAMA. 2017;318:351-9).

Halfpoint/thinkstock

Mobile health interventions targeting mothers of healthy newborns significantly improved safe sleep practices, compared with controls, in a randomized trial of 1,600 mothers published online July 25 in JAMA.

Despite the success of the Back to Sleep campaign in reducing rates of sudden infant death syndrome, approximately 3,500 infant deaths due to SIDS, accidental suffocation, or strangulation in bed occurred in 2014, wrote Rachel Y. Moon, MD, of the University of Virginia, Charlottesville, and her colleagues (JAMA. 2017;318:351-9).

Halfpoint/thinkstock

Mobile health interventions targeting mothers of healthy newborns significantly improved safe sleep practices, compared with controls, in a randomized trial of 1,600 mothers published online July 25 in JAMA.

Despite the success of the Back to Sleep campaign in reducing rates of sudden infant death syndrome, approximately 3,500 infant deaths due to SIDS, accidental suffocation, or strangulation in bed occurred in 2014, wrote Rachel Y. Moon, MD, of the University of Virginia, Charlottesville, and her colleagues (JAMA. 2017;318:351-9).

Halfpoint/thinkstock

SAN FRANCISCO – Very brief, outside-the-box therapeutic interventions are racking up respectable efficacy scores in randomized, controlled trials addressing a variety of common psychiatric problems in youths, Jessica L. Schleider observed at the annual conference of the Anxiety and Depression Association of America.

The impetus for developing very brief interventions – or VBIs, as they are known in psychotherapy research parlance – is mounting recognition that conventional treatment approaches have by and large failed children and adolescents who have mental health problems, explained Ms. Schleider, a doctoral candidate in clinical psychology at Harvard University in Cambridge, Mass.

Bruce Jancin/Frontline Medical News

[email protected]

SAN FRANCISCO – Very brief, outside-the-box therapeutic interventions are racking up respectable efficacy scores in randomized, controlled trials addressing a variety of common psychiatric problems in youths, Jessica L. Schleider observed at the annual conference of the Anxiety and Depression Association of America.

The impetus for developing very brief interventions – or VBIs, as they are known in psychotherapy research parlance – is mounting recognition that conventional treatment approaches have by and large failed children and adolescents who have mental health problems, explained Ms. Schleider, a doctoral candidate in clinical psychology at Harvard University in Cambridge, Mass.

Bruce Jancin/Frontline Medical News

[email protected]

SAN FRANCISCO – Very brief, outside-the-box therapeutic interventions are racking up respectable efficacy scores in randomized, controlled trials addressing a variety of common psychiatric problems in youths, Jessica L. Schleider observed at the annual conference of the Anxiety and Depression Association of America.

The impetus for developing very brief interventions – or VBIs, as they are known in psychotherapy research parlance – is mounting recognition that conventional treatment approaches have by and large failed children and adolescents who have mental health problems, explained Ms. Schleider, a doctoral candidate in clinical psychology at Harvard University in Cambridge, Mass.

Bruce Jancin/Frontline Medical News

[email protected]

CHICAGO – Ask patients with recessive dystrophic epidermolysis bullosa (EB) to name their most bothersome symptom, and they’re likely to say itch, followed closely by pain, according to Jemima Mellerio, MD.

“We don’t really understand a lot about the mechanism of itch in patients with this disease, which is one of the reasons why we don’t have good treatments,” Prof. Mellerio said at the World Congress of Pediatric Dermatology.

[email protected]

CHICAGO – Ask patients with recessive dystrophic epidermolysis bullosa (EB) to name their most bothersome symptom, and they’re likely to say itch, followed closely by pain, according to Jemima Mellerio, MD.

“We don’t really understand a lot about the mechanism of itch in patients with this disease, which is one of the reasons why we don’t have good treatments,” Prof. Mellerio said at the World Congress of Pediatric Dermatology.

[email protected]

CHICAGO – Ask patients with recessive dystrophic epidermolysis bullosa (EB) to name their most bothersome symptom, and they’re likely to say itch, followed closely by pain, according to Jemima Mellerio, MD.

“We don’t really understand a lot about the mechanism of itch in patients with this disease, which is one of the reasons why we don’t have good treatments,” Prof. Mellerio said at the World Congress of Pediatric Dermatology.

[email protected]

Case Report

A 37-year-old woman was admitted to the intensive care unit secondary to the acute development of an erythematous rash with tissue sloughing that involved acral sites and mucosal surfaces. Her medical history was notable for anti-Ro/Sjögren syndrome antigen A (SS-A)–positive lupus erythematosus (LE) with a morphologic semblance to subacute cutaneous LE (SCLE). Prior treatment had included oral corticosteroids. In addition, she reported a concurrent history of acral and mucosal lesions that appeared to flare with her lupus. The nature of these lesions was not clear to the patient or her physicians. Before this particular episode, her primary care physician had attempted to wean her off of the corticosteroids. As she dropped below 20 mg of prednisone daily, new lesions developed. The patient stated that her social situation was poor and that these lesions did seem to develop more frequently during times of physical and emotional stress. She recounted her first episode developing during her second pregnancy. Oral prednisone and over-the-counter calcium with vitamin D were her only reported medications. She denied the use of any other medications, including nonsteroidal anti-inflammatory drugs, acetaminophen, and recent antibiotic therapy.

Dermatology was called in for consultation, and physical examination revealed areas of epidermal sloughing on the hands and feet. Complete clinical exposure of the underlying dermis was noted with remarkable tenderness. These lesions were noted to be in various stages of healing (Figure 1). Figure 2 displays a lesion in early development. The mucosal surfaces of the lips and eyes demonstrated hemorrhagic crusting, and some tissue sloughing was noted on the ears. A widespread erythematous exanthema with fine scaling was noted on the face, neck, chest, back, abdomen, arms, and legs (Figure 3).

Laboratory evaluation revealed positive antinuclear antibodies (ANAs), anti-Ro/SS-A antibodies, anti-La/Sjögren syndrome antigen B (SS-B) antibodies, and anti–double-stranded DNA. The hemoglobin level was 9.4 g/dL (reference range, 12–15 g/dL) and hematocrit was 28.8% (reference range, 36%–47%). The mean corpuscular hemoglobin level was 32 pg/cell (reference range, 27–31 pg/cell), and the mean corpuscular hemoglobin concentration was 32.5 g/dL (reference range, 30–35 g/dL). Rheumatoid factor (RF) and herpes simplex virus types 1 and 2 IgM were all found to be negative.

A deep shave biopsy obtained from the patient’s right knee revealed an atrophic interface dermatitis associated with a lymphocytic eccrine hidradenitis accompanied by abundant mesenchymal mucin deposition (Figure 4). Direct immunofluorescence (DIF) from the same area demonstrated IgG and IgM along the dermoepidermal junction with some granular deposition. Frozen sections performed on acral lesions demonstrated epidermal necrosis (Figure 5). Direct immunofluorescence of acral lesions was negative. In light of these findings, a diagnosis of Rowell syndrome (RS) was suspected to be the most likely explanation for the presentation.

Intravenous corticosteroids and antibiotics were administered, and over a 2-week hospitalization, the lesions on the feet and hands slowly reepithelialized. Physical therapy was required to aid in ambulation. The patient was discharged on a tapering course of oral prednisone and hydroxychloroquine. After 6 months of therapy with hydroxychloroquine 200 mg twice daily, the patient continued to experience recurrent bouts of acral lesions, and pulse doses of oral prednisone were required. The lesions currently are controlled with azathioprine 50 mg twice daily and prednisone 10 mg by mouth daily.

Comment

The 4 prototypical patients identified by Rowell et al¹ in 1963 in the first account of the eponymous syndrome were all females with discoid lupus erythematosus (DLE) and perniosis. In addition, they all displayed positive RF and saline extract of human tissue antibodies (analogous to anti-Ro/SS-A and anti-La/SS-B).² Since then, at least 132 patients with clinical symptoms suspicious of RS have been identified with variations on these original criteria.³ The reported permutations of the lupus component of the disease include cutaneous LE (CLE), bullous systemic LE, necrotic lesions associated with antiphospholipid syndrome, annular/polycyclic SCLE, systemic LE (SLE) without CLE, SLE with lupus nephritis, SLE with pericarditis, SLE with systemic vasculitis, Sjögren syndrome, rheumatoid arthritis, and necrotizing lymphadenitis.² In addition, variations of the erythema multiforme (EM)–like lesions found in reported cases include changes to their gross appearance (flat vs raised), location (acral or mucosal involvement), and resemblance to other conditions (Stevens-Johnson syndrome or toxic epidermal necrolysis).^2,3 From this information alone, it is clear that, as further cases have been chronicled, defining exact criteria for the disease has been challenging.

The essential question concerning the existence of RS hinges on the strength of its distinctiveness: Is it a unique disorder or merely another variant of lupus? Antiga et al² concluded that it should be characterized as a variant of SCLE. Lee at al⁴ agreed, stating that “[i]n view of the lack of specific features that distinguish RS from LE, Kuhn et al⁵ suggested that [RS] is probably not a distinct entity and is now widely considered to be a variant of SCLE.” One of the primary contributors to this conclusion is that the laboratory findings of reported patients with SCLE have more closely mirrored the original cases from Rowell et al’s¹ report than those of typical LE. Patients with SCLE have demonstrated positive ANA antibodies in 60% to 80% of cases, positive anti-Ro/SS-A antibodies in 40% to 100% of cases, positive anti-La/SS-B antibodies in 12% to 42% of cases, positive anti–double-stranded DNA in 1.2% to 10% of cases, and positive RF antibodies in 33% of cases.² An argument could certainly be made to ascribe our patient’s condition to an SCLE variant, as 4 of 5 preceding laboratory findings were found to be positive; however, the majority of reported cases of SCLE have been linked to drugs (ie, hydrochlorothiazide, angiotensin-converting enzyme inhibitors, calcium channel blockers, terbinafine),² which has not commonly been the attributable etiology of other cases of RS, including the 4 cases reported by Rowell et al.¹

In a review of the literature on RS since 2010 in addition to their report of 132 new cases, Torchia et al³ outlined a set of diagnostic standards for the condition consisting of major and minor criteria. According to the authors, if all 4 major and 1 minor criteria are met, the patient meets the standards for true RS. The major criteria include the following: (1) presence of chronic CLE [DLE and/or chilblain]; (2) presence of EM-like lesions [typical or atypical targets]; (3) at least 1 positivity among speckled ANA, anti-Ro/SS-A, and anti-La/SS-B antibodies; and (4) negative DIF on lesional EM-like targetoid lesions. The minor criteria include the following: (1) absence of infectious or pharmacologic triggers; (2) absence of typical EM location (acral and mucosal); and (3) presence of at least 1 additional American College of Rheumatology criterion for diagnosis of SLE⁸ besides discoid rash and positive ANA antibodies and excluding photosensitivity, malar rash, and oral ulcers. Using these criteria, the patient in our case met the standards for diagnosis of RS.

One area of disagreement that has been encountered in the literature is the exact histologic determination of true RS, specifically related to the microscopic findings of the EM-like lesions. Two cases presented by Modi et al⁶ were interpreted under the stipulation that true RS must contain histologic LE and histologic EM. Because the EM-appearing lesions revealed LE histology, the cases were concluded to be variants of LE. These cases are similar to our case in that the EM-like lesions in our patient demonstrated LE pathology. Torchia et al,³ as demonstrated in the above criteria, seemed to be less concerned about the histology of the EM-like lesions, only requiring them to show negative DIF.

Conclusion

In the search for answers concerning RS, many unanswered questions remain: Where should the line be drawn in the inclusion of so many variations of both the LE and EM components of the condition? Also, should these elements even be approached as distinct components in the first place? Viewing the majority of RS cases as simply simultaneous LE and EM, Shteyngarts et al⁷ concluded that “the concomitant occurrence of EM with LE did not change the course, therapy, or prognosis of either disease. SLE and DLE can coexist with EM, but the coexistence does not impart any unusual characteristic to either illness. Rowell’s syndrome is not reproducible, and the immunologic disturbances in such patients are probably coincidental.”

If the condition is a genuine pathological individuality, should we not view the seemingly separate LE and EM as the product of a single underlying biochemical process? These questions and others in the search for a true definition of the disease should continue to be debated. It is clear that further investigation is warranted in the understanding of the underlying mechanism of the pathology.

Case Report

A 37-year-old woman was admitted to the intensive care unit secondary to the acute development of an erythematous rash with tissue sloughing that involved acral sites and mucosal surfaces. Her medical history was notable for anti-Ro/Sjögren syndrome antigen A (SS-A)–positive lupus erythematosus (LE) with a morphologic semblance to subacute cutaneous LE (SCLE). Prior treatment had included oral corticosteroids. In addition, she reported a concurrent history of acral and mucosal lesions that appeared to flare with her lupus. The nature of these lesions was not clear to the patient or her physicians. Before this particular episode, her primary care physician had attempted to wean her off of the corticosteroids. As she dropped below 20 mg of prednisone daily, new lesions developed. The patient stated that her social situation was poor and that these lesions did seem to develop more frequently during times of physical and emotional stress. She recounted her first episode developing during her second pregnancy. Oral prednisone and over-the-counter calcium with vitamin D were her only reported medications. She denied the use of any other medications, including nonsteroidal anti-inflammatory drugs, acetaminophen, and recent antibiotic therapy.

Dermatology was called in for consultation, and physical examination revealed areas of epidermal sloughing on the hands and feet. Complete clinical exposure of the underlying dermis was noted with remarkable tenderness. These lesions were noted to be in various stages of healing (Figure 1). Figure 2 displays a lesion in early development. The mucosal surfaces of the lips and eyes demonstrated hemorrhagic crusting, and some tissue sloughing was noted on the ears. A widespread erythematous exanthema with fine scaling was noted on the face, neck, chest, back, abdomen, arms, and legs (Figure 3).

Laboratory evaluation revealed positive antinuclear antibodies (ANAs), anti-Ro/SS-A antibodies, anti-La/Sjögren syndrome antigen B (SS-B) antibodies, and anti–double-stranded DNA. The hemoglobin level was 9.4 g/dL (reference range, 12–15 g/dL) and hematocrit was 28.8% (reference range, 36%–47%). The mean corpuscular hemoglobin level was 32 pg/cell (reference range, 27–31 pg/cell), and the mean corpuscular hemoglobin concentration was 32.5 g/dL (reference range, 30–35 g/dL). Rheumatoid factor (RF) and herpes simplex virus types 1 and 2 IgM were all found to be negative.

A deep shave biopsy obtained from the patient’s right knee revealed an atrophic interface dermatitis associated with a lymphocytic eccrine hidradenitis accompanied by abundant mesenchymal mucin deposition (Figure 4). Direct immunofluorescence (DIF) from the same area demonstrated IgG and IgM along the dermoepidermal junction with some granular deposition. Frozen sections performed on acral lesions demonstrated epidermal necrosis (Figure 5). Direct immunofluorescence of acral lesions was negative. In light of these findings, a diagnosis of Rowell syndrome (RS) was suspected to be the most likely explanation for the presentation.

Intravenous corticosteroids and antibiotics were administered, and over a 2-week hospitalization, the lesions on the feet and hands slowly reepithelialized. Physical therapy was required to aid in ambulation. The patient was discharged on a tapering course of oral prednisone and hydroxychloroquine. After 6 months of therapy with hydroxychloroquine 200 mg twice daily, the patient continued to experience recurrent bouts of acral lesions, and pulse doses of oral prednisone were required. The lesions currently are controlled with azathioprine 50 mg twice daily and prednisone 10 mg by mouth daily.

Comment

The 4 prototypical patients identified by Rowell et al¹ in 1963 in the first account of the eponymous syndrome were all females with discoid lupus erythematosus (DLE) and perniosis. In addition, they all displayed positive RF and saline extract of human tissue antibodies (analogous to anti-Ro/SS-A and anti-La/SS-B).² Since then, at least 132 patients with clinical symptoms suspicious of RS have been identified with variations on these original criteria.³ The reported permutations of the lupus component of the disease include cutaneous LE (CLE), bullous systemic LE, necrotic lesions associated with antiphospholipid syndrome, annular/polycyclic SCLE, systemic LE (SLE) without CLE, SLE with lupus nephritis, SLE with pericarditis, SLE with systemic vasculitis, Sjögren syndrome, rheumatoid arthritis, and necrotizing lymphadenitis.² In addition, variations of the erythema multiforme (EM)–like lesions found in reported cases include changes to their gross appearance (flat vs raised), location (acral or mucosal involvement), and resemblance to other conditions (Stevens-Johnson syndrome or toxic epidermal necrolysis).^2,3 From this information alone, it is clear that, as further cases have been chronicled, defining exact criteria for the disease has been challenging.

The essential question concerning the existence of RS hinges on the strength of its distinctiveness: Is it a unique disorder or merely another variant of lupus? Antiga et al² concluded that it should be characterized as a variant of SCLE. Lee at al⁴ agreed, stating that “[i]n view of the lack of specific features that distinguish RS from LE, Kuhn et al⁵ suggested that [RS] is probably not a distinct entity and is now widely considered to be a variant of SCLE.” One of the primary contributors to this conclusion is that the laboratory findings of reported patients with SCLE have more closely mirrored the original cases from Rowell et al’s¹ report than those of typical LE. Patients with SCLE have demonstrated positive ANA antibodies in 60% to 80% of cases, positive anti-Ro/SS-A antibodies in 40% to 100% of cases, positive anti-La/SS-B antibodies in 12% to 42% of cases, positive anti–double-stranded DNA in 1.2% to 10% of cases, and positive RF antibodies in 33% of cases.² An argument could certainly be made to ascribe our patient’s condition to an SCLE variant, as 4 of 5 preceding laboratory findings were found to be positive; however, the majority of reported cases of SCLE have been linked to drugs (ie, hydrochlorothiazide, angiotensin-converting enzyme inhibitors, calcium channel blockers, terbinafine),² which has not commonly been the attributable etiology of other cases of RS, including the 4 cases reported by Rowell et al.¹

In a review of the literature on RS since 2010 in addition to their report of 132 new cases, Torchia et al³ outlined a set of diagnostic standards for the condition consisting of major and minor criteria. According to the authors, if all 4 major and 1 minor criteria are met, the patient meets the standards for true RS. The major criteria include the following: (1) presence of chronic CLE [DLE and/or chilblain]; (2) presence of EM-like lesions [typical or atypical targets]; (3) at least 1 positivity among speckled ANA, anti-Ro/SS-A, and anti-La/SS-B antibodies; and (4) negative DIF on lesional EM-like targetoid lesions. The minor criteria include the following: (1) absence of infectious or pharmacologic triggers; (2) absence of typical EM location (acral and mucosal); and (3) presence of at least 1 additional American College of Rheumatology criterion for diagnosis of SLE⁸ besides discoid rash and positive ANA antibodies and excluding photosensitivity, malar rash, and oral ulcers. Using these criteria, the patient in our case met the standards for diagnosis of RS.

One area of disagreement that has been encountered in the literature is the exact histologic determination of true RS, specifically related to the microscopic findings of the EM-like lesions. Two cases presented by Modi et al⁶ were interpreted under the stipulation that true RS must contain histologic LE and histologic EM. Because the EM-appearing lesions revealed LE histology, the cases were concluded to be variants of LE. These cases are similar to our case in that the EM-like lesions in our patient demonstrated LE pathology. Torchia et al,³ as demonstrated in the above criteria, seemed to be less concerned about the histology of the EM-like lesions, only requiring them to show negative DIF.

Conclusion

In the search for answers concerning RS, many unanswered questions remain: Where should the line be drawn in the inclusion of so many variations of both the LE and EM components of the condition? Also, should these elements even be approached as distinct components in the first place? Viewing the majority of RS cases as simply simultaneous LE and EM, Shteyngarts et al⁷ concluded that “the concomitant occurrence of EM with LE did not change the course, therapy, or prognosis of either disease. SLE and DLE can coexist with EM, but the coexistence does not impart any unusual characteristic to either illness. Rowell’s syndrome is not reproducible, and the immunologic disturbances in such patients are probably coincidental.”

If the condition is a genuine pathological individuality, should we not view the seemingly separate LE and EM as the product of a single underlying biochemical process? These questions and others in the search for a true definition of the disease should continue to be debated. It is clear that further investigation is warranted in the understanding of the underlying mechanism of the pathology.

Case Report

A 37-year-old woman was admitted to the intensive care unit secondary to the acute development of an erythematous rash with tissue sloughing that involved acral sites and mucosal surfaces. Her medical history was notable for anti-Ro/Sjögren syndrome antigen A (SS-A)–positive lupus erythematosus (LE) with a morphologic semblance to subacute cutaneous LE (SCLE). Prior treatment had included oral corticosteroids. In addition, she reported a concurrent history of acral and mucosal lesions that appeared to flare with her lupus. The nature of these lesions was not clear to the patient or her physicians. Before this particular episode, her primary care physician had attempted to wean her off of the corticosteroids. As she dropped below 20 mg of prednisone daily, new lesions developed. The patient stated that her social situation was poor and that these lesions did seem to develop more frequently during times of physical and emotional stress. She recounted her first episode developing during her second pregnancy. Oral prednisone and over-the-counter calcium with vitamin D were her only reported medications. She denied the use of any other medications, including nonsteroidal anti-inflammatory drugs, acetaminophen, and recent antibiotic therapy.

Dermatology was called in for consultation, and physical examination revealed areas of epidermal sloughing on the hands and feet. Complete clinical exposure of the underlying dermis was noted with remarkable tenderness. These lesions were noted to be in various stages of healing (Figure 1). Figure 2 displays a lesion in early development. The mucosal surfaces of the lips and eyes demonstrated hemorrhagic crusting, and some tissue sloughing was noted on the ears. A widespread erythematous exanthema with fine scaling was noted on the face, neck, chest, back, abdomen, arms, and legs (Figure 3).

Laboratory evaluation revealed positive antinuclear antibodies (ANAs), anti-Ro/SS-A antibodies, anti-La/Sjögren syndrome antigen B (SS-B) antibodies, and anti–double-stranded DNA. The hemoglobin level was 9.4 g/dL (reference range, 12–15 g/dL) and hematocrit was 28.8% (reference range, 36%–47%). The mean corpuscular hemoglobin level was 32 pg/cell (reference range, 27–31 pg/cell), and the mean corpuscular hemoglobin concentration was 32.5 g/dL (reference range, 30–35 g/dL). Rheumatoid factor (RF) and herpes simplex virus types 1 and 2 IgM were all found to be negative.

A deep shave biopsy obtained from the patient’s right knee revealed an atrophic interface dermatitis associated with a lymphocytic eccrine hidradenitis accompanied by abundant mesenchymal mucin deposition (Figure 4). Direct immunofluorescence (DIF) from the same area demonstrated IgG and IgM along the dermoepidermal junction with some granular deposition. Frozen sections performed on acral lesions demonstrated epidermal necrosis (Figure 5). Direct immunofluorescence of acral lesions was negative. In light of these findings, a diagnosis of Rowell syndrome (RS) was suspected to be the most likely explanation for the presentation.

Intravenous corticosteroids and antibiotics were administered, and over a 2-week hospitalization, the lesions on the feet and hands slowly reepithelialized. Physical therapy was required to aid in ambulation. The patient was discharged on a tapering course of oral prednisone and hydroxychloroquine. After 6 months of therapy with hydroxychloroquine 200 mg twice daily, the patient continued to experience recurrent bouts of acral lesions, and pulse doses of oral prednisone were required. The lesions currently are controlled with azathioprine 50 mg twice daily and prednisone 10 mg by mouth daily.

Comment

The 4 prototypical patients identified by Rowell et al¹ in 1963 in the first account of the eponymous syndrome were all females with discoid lupus erythematosus (DLE) and perniosis. In addition, they all displayed positive RF and saline extract of human tissue antibodies (analogous to anti-Ro/SS-A and anti-La/SS-B).² Since then, at least 132 patients with clinical symptoms suspicious of RS have been identified with variations on these original criteria.³ The reported permutations of the lupus component of the disease include cutaneous LE (CLE), bullous systemic LE, necrotic lesions associated with antiphospholipid syndrome, annular/polycyclic SCLE, systemic LE (SLE) without CLE, SLE with lupus nephritis, SLE with pericarditis, SLE with systemic vasculitis, Sjögren syndrome, rheumatoid arthritis, and necrotizing lymphadenitis.² In addition, variations of the erythema multiforme (EM)–like lesions found in reported cases include changes to their gross appearance (flat vs raised), location (acral or mucosal involvement), and resemblance to other conditions (Stevens-Johnson syndrome or toxic epidermal necrolysis).^2,3 From this information alone, it is clear that, as further cases have been chronicled, defining exact criteria for the disease has been challenging.

The essential question concerning the existence of RS hinges on the strength of its distinctiveness: Is it a unique disorder or merely another variant of lupus? Antiga et al² concluded that it should be characterized as a variant of SCLE. Lee at al⁴ agreed, stating that “[i]n view of the lack of specific features that distinguish RS from LE, Kuhn et al⁵ suggested that [RS] is probably not a distinct entity and is now widely considered to be a variant of SCLE.” One of the primary contributors to this conclusion is that the laboratory findings of reported patients with SCLE have more closely mirrored the original cases from Rowell et al’s¹ report than those of typical LE. Patients with SCLE have demonstrated positive ANA antibodies in 60% to 80% of cases, positive anti-Ro/SS-A antibodies in 40% to 100% of cases, positive anti-La/SS-B antibodies in 12% to 42% of cases, positive anti–double-stranded DNA in 1.2% to 10% of cases, and positive RF antibodies in 33% of cases.² An argument could certainly be made to ascribe our patient’s condition to an SCLE variant, as 4 of 5 preceding laboratory findings were found to be positive; however, the majority of reported cases of SCLE have been linked to drugs (ie, hydrochlorothiazide, angiotensin-converting enzyme inhibitors, calcium channel blockers, terbinafine),² which has not commonly been the attributable etiology of other cases of RS, including the 4 cases reported by Rowell et al.¹

In a review of the literature on RS since 2010 in addition to their report of 132 new cases, Torchia et al³ outlined a set of diagnostic standards for the condition consisting of major and minor criteria. According to the authors, if all 4 major and 1 minor criteria are met, the patient meets the standards for true RS. The major criteria include the following: (1) presence of chronic CLE [DLE and/or chilblain]; (2) presence of EM-like lesions [typical or atypical targets]; (3) at least 1 positivity among speckled ANA, anti-Ro/SS-A, and anti-La/SS-B antibodies; and (4) negative DIF on lesional EM-like targetoid lesions. The minor criteria include the following: (1) absence of infectious or pharmacologic triggers; (2) absence of typical EM location (acral and mucosal); and (3) presence of at least 1 additional American College of Rheumatology criterion for diagnosis of SLE⁸ besides discoid rash and positive ANA antibodies and excluding photosensitivity, malar rash, and oral ulcers. Using these criteria, the patient in our case met the standards for diagnosis of RS.

One area of disagreement that has been encountered in the literature is the exact histologic determination of true RS, specifically related to the microscopic findings of the EM-like lesions. Two cases presented by Modi et al⁶ were interpreted under the stipulation that true RS must contain histologic LE and histologic EM. Because the EM-appearing lesions revealed LE histology, the cases were concluded to be variants of LE. These cases are similar to our case in that the EM-like lesions in our patient demonstrated LE pathology. Torchia et al,³ as demonstrated in the above criteria, seemed to be less concerned about the histology of the EM-like lesions, only requiring them to show negative DIF.

Conclusion

In the search for answers concerning RS, many unanswered questions remain: Where should the line be drawn in the inclusion of so many variations of both the LE and EM components of the condition? Also, should these elements even be approached as distinct components in the first place? Viewing the majority of RS cases as simply simultaneous LE and EM, Shteyngarts et al⁷ concluded that “the concomitant occurrence of EM with LE did not change the course, therapy, or prognosis of either disease. SLE and DLE can coexist with EM, but the coexistence does not impart any unusual characteristic to either illness. Rowell’s syndrome is not reproducible, and the immunologic disturbances in such patients are probably coincidental.”

If the condition is a genuine pathological individuality, should we not view the seemingly separate LE and EM as the product of a single underlying biochemical process? These questions and others in the search for a true definition of the disease should continue to be debated. It is clear that further investigation is warranted in the understanding of the underlying mechanism of the pathology.

The Diagnosis: Lymphomatoid Papulosis

A shave biopsy of an established lesion on the volar aspect of the left wrist was performed (Figure 1). The biopsy showed an ulcerated nodular lesion characterized by a dense mixed inflammatory cell infiltrate in the dermis composed of lymphocytes, histiocytes, scattered neutrophils, and numerous eosinophils (Figure 2). Notably there was a minor population of large atypical cells with immunoblastic and anaplastic morphology present individually and in small clusters most prominently within the upper dermis (Figures 3 and 4). Immunohistochemistry of the anaplastic cells revealed a CD30⁺, CD3⁻, CD4⁺, CD5⁻, CD8⁻, CD2⁻, CD7⁻, CD56⁻, ALK1⁻ (anaplastic lymphoma kinase-1), PAX5⁻ (paired box protein-5), CD20⁻, and CD15⁻ phenotype. These morphologic and immunohistochemical features suggested a CD30⁺ cutaneous lymphoproliferative disorder. The clinical history of recurrent self-healing papulonodules in an otherwise-healthy patient established the diagnosis of lymphomatoid papulosis (LyP).

Lymphomatoid papulosis is a lymphoproliferative disorder characterized by recurrent crops of self-resolving eruptive papulonodular skin lesions that may show a variety of histologic features including a CD30⁺ malignant T-cell lymphoma.¹ Lymphomatoid papulosis was first described in 1968¹ but debate continues whether the condition should be considered malignant or benign.² Although the prognosis is excellent, LyP is characterized by a protracted course, often lasting many years. Additionally, these patients have a lifelong increased risk for development of a second cutaneous or systemic lymphoma such as mycosis fungoides (MF), cutaneous or nodal anaplastic large cell lymphoma (ALCL), or Hodgkin lymphoma, among others.

Lymphomatoid papulosis is a rare disease occurring in all ethnic groups and at any age, though most commonly presenting in the fifth decade of life. Finding large atypical T cells expressing CD30 in recurring skin lesions is highly suggestive of LyP; however, large CD30⁺ cells also can be seen in numerous benign reactive processes such as arthropod assault, drug eruption, viral skin infections, and other dermatoses, thus clinical correlation is always paramount. The cause of LyP is largely unknown; however, spontaneous regression may be explained by CD30-CD30 ligand interaction³ as well as an increased proapoptotic milieu.⁴ Specific translocations such as interferon regulatory factor-4 have been hypothesized as a risk factor for malignant progression.^5-7 Additionally, an inactivating gene mutation resulting in loss of transforming growth factor β1 receptor expression and subsequent unresponsiveness to the growth inhibitory effect of transforming growth factor β may play a role in progression of LyP to ALCL.⁸

Clinically, LyP consists of red-brown papules and nodules generally smaller than 2 cm, often with central hemorrhage, necrosis, and crusting. Lesions are at different stages of eruption and resolution. They are often grouped but may be disseminated. Spontaneous regression typically occurs within 3 to 8 weeks. Pruritus or mild tenderness may occur as well as residual hyperpigmentation or scarring. Systemic symptoms are notably absent.

The histologic features of LyP vary according to the age of the lesion and subtype.² Early lesions may only show a few inflammatory cells, but as lesions evolve, larger immunoblastlike CD30⁺ atypical cells accumulate that may resemble the Reed-Sternberg cells of Hodgkin lymphoma. Of the 5 subtypes, the most common is type A. It is characterized by a wedge-shaped infiltrate with a mixed population of scattered or clustered, large, atypical CD30⁺ cells, lymphocytes, neutrophils, eosinophils, and histiocytes.⁹ Frequent mitoses often are seen. Type B appears similar to MF due to a predominantly epidermotropic infiltrate of CD3⁺ and often CD30⁻ atypical cells. Spontaneously regressing papules favor LyP, whereas persistent patches or plaques favor MF. Type C appears identical to ALCL with diffuse sheets of large atypical CD30⁺ cells and relatively few inflammatory cells, but spontaneously regressing lesions again favor LyP, whereas persistent tumors favor ALCL. Type D appears similar to primary cutaneous aggressive epidermotropic CD8⁺ cytotoxic T cell lymphoma due to a markedly epidermotropic infiltrate of small atypical CD8⁺ and CD30⁺ lymphocytes, often TIA-1⁺ (T-cell intracytoplasmic antigen-1) or granzyme B⁺, but CD30 positivity and self-resolving lesions favor LyP. Type E mimics extranodal natural killer/T cell lymphoma (nasal type) due to angioinvasive CD30⁺ and beta F1⁺ T lymphocytes, often CD8⁺ and/or TIA-1⁺, but self-resolving lesions again favor LyP, as well as absence of Epstein-Barr virus and CD56⁻.⁹

The most common therapeutic approaches to LyP include topical steroids, phototherapy, and low-dose methotrexate.¹⁰ However, treatment does not change overall disease course or reduce the future risk for developing an associated lymphoma. Accordingly, abstaining from active therapeutic intervention is reasonable, especially in patients with only a few asymptomatic lesions.

The Diagnosis: Lymphomatoid Papulosis

A shave biopsy of an established lesion on the volar aspect of the left wrist was performed (Figure 1). The biopsy showed an ulcerated nodular lesion characterized by a dense mixed inflammatory cell infiltrate in the dermis composed of lymphocytes, histiocytes, scattered neutrophils, and numerous eosinophils (Figure 2). Notably there was a minor population of large atypical cells with immunoblastic and anaplastic morphology present individually and in small clusters most prominently within the upper dermis (Figures 3 and 4). Immunohistochemistry of the anaplastic cells revealed a CD30⁺, CD3⁻, CD4⁺, CD5⁻, CD8⁻, CD2⁻, CD7⁻, CD56⁻, ALK1⁻ (anaplastic lymphoma kinase-1), PAX5⁻ (paired box protein-5), CD20⁻, and CD15⁻ phenotype. These morphologic and immunohistochemical features suggested a CD30⁺ cutaneous lymphoproliferative disorder. The clinical history of recurrent self-healing papulonodules in an otherwise-healthy patient established the diagnosis of lymphomatoid papulosis (LyP).

Lymphomatoid papulosis is a lymphoproliferative disorder characterized by recurrent crops of self-resolving eruptive papulonodular skin lesions that may show a variety of histologic features including a CD30⁺ malignant T-cell lymphoma.¹ Lymphomatoid papulosis was first described in 1968¹ but debate continues whether the condition should be considered malignant or benign.² Although the prognosis is excellent, LyP is characterized by a protracted course, often lasting many years. Additionally, these patients have a lifelong increased risk for development of a second cutaneous or systemic lymphoma such as mycosis fungoides (MF), cutaneous or nodal anaplastic large cell lymphoma (ALCL), or Hodgkin lymphoma, among others.

Lymphomatoid papulosis is a rare disease occurring in all ethnic groups and at any age, though most commonly presenting in the fifth decade of life. Finding large atypical T cells expressing CD30 in recurring skin lesions is highly suggestive of LyP; however, large CD30⁺ cells also can be seen in numerous benign reactive processes such as arthropod assault, drug eruption, viral skin infections, and other dermatoses, thus clinical correlation is always paramount. The cause of LyP is largely unknown; however, spontaneous regression may be explained by CD30-CD30 ligand interaction³ as well as an increased proapoptotic milieu.⁴ Specific translocations such as interferon regulatory factor-4 have been hypothesized as a risk factor for malignant progression.^5-7 Additionally, an inactivating gene mutation resulting in loss of transforming growth factor β1 receptor expression and subsequent unresponsiveness to the growth inhibitory effect of transforming growth factor β may play a role in progression of LyP to ALCL.⁸

Clinically, LyP consists of red-brown papules and nodules generally smaller than 2 cm, often with central hemorrhage, necrosis, and crusting. Lesions are at different stages of eruption and resolution. They are often grouped but may be disseminated. Spontaneous regression typically occurs within 3 to 8 weeks. Pruritus or mild tenderness may occur as well as residual hyperpigmentation or scarring. Systemic symptoms are notably absent.

The histologic features of LyP vary according to the age of the lesion and subtype.² Early lesions may only show a few inflammatory cells, but as lesions evolve, larger immunoblastlike CD30⁺ atypical cells accumulate that may resemble the Reed-Sternberg cells of Hodgkin lymphoma. Of the 5 subtypes, the most common is type A. It is characterized by a wedge-shaped infiltrate with a mixed population of scattered or clustered, large, atypical CD30⁺ cells, lymphocytes, neutrophils, eosinophils, and histiocytes.⁹ Frequent mitoses often are seen. Type B appears similar to MF due to a predominantly epidermotropic infiltrate of CD3⁺ and often CD30⁻ atypical cells. Spontaneously regressing papules favor LyP, whereas persistent patches or plaques favor MF. Type C appears identical to ALCL with diffuse sheets of large atypical CD30⁺ cells and relatively few inflammatory cells, but spontaneously regressing lesions again favor LyP, whereas persistent tumors favor ALCL. Type D appears similar to primary cutaneous aggressive epidermotropic CD8⁺ cytotoxic T cell lymphoma due to a markedly epidermotropic infiltrate of small atypical CD8⁺ and CD30⁺ lymphocytes, often TIA-1⁺ (T-cell intracytoplasmic antigen-1) or granzyme B⁺, but CD30 positivity and self-resolving lesions favor LyP. Type E mimics extranodal natural killer/T cell lymphoma (nasal type) due to angioinvasive CD30⁺ and beta F1⁺ T lymphocytes, often CD8⁺ and/or TIA-1⁺, but self-resolving lesions again favor LyP, as well as absence of Epstein-Barr virus and CD56⁻.⁹

The most common therapeutic approaches to LyP include topical steroids, phototherapy, and low-dose methotrexate.¹⁰ However, treatment does not change overall disease course or reduce the future risk for developing an associated lymphoma. Accordingly, abstaining from active therapeutic intervention is reasonable, especially in patients with only a few asymptomatic lesions.

The Diagnosis: Lymphomatoid Papulosis

A shave biopsy of an established lesion on the volar aspect of the left wrist was performed (Figure 1). The biopsy showed an ulcerated nodular lesion characterized by a dense mixed inflammatory cell infiltrate in the dermis composed of lymphocytes, histiocytes, scattered neutrophils, and numerous eosinophils (Figure 2). Notably there was a minor population of large atypical cells with immunoblastic and anaplastic morphology present individually and in small clusters most prominently within the upper dermis (Figures 3 and 4). Immunohistochemistry of the anaplastic cells revealed a CD30⁺, CD3⁻, CD4⁺, CD5⁻, CD8⁻, CD2⁻, CD7⁻, CD56⁻, ALK1⁻ (anaplastic lymphoma kinase-1), PAX5⁻ (paired box protein-5), CD20⁻, and CD15⁻ phenotype. These morphologic and immunohistochemical features suggested a CD30⁺ cutaneous lymphoproliferative disorder. The clinical history of recurrent self-healing papulonodules in an otherwise-healthy patient established the diagnosis of lymphomatoid papulosis (LyP).

Lymphomatoid papulosis is a lymphoproliferative disorder characterized by recurrent crops of self-resolving eruptive papulonodular skin lesions that may show a variety of histologic features including a CD30⁺ malignant T-cell lymphoma.¹ Lymphomatoid papulosis was first described in 1968¹ but debate continues whether the condition should be considered malignant or benign.² Although the prognosis is excellent, LyP is characterized by a protracted course, often lasting many years. Additionally, these patients have a lifelong increased risk for development of a second cutaneous or systemic lymphoma such as mycosis fungoides (MF), cutaneous or nodal anaplastic large cell lymphoma (ALCL), or Hodgkin lymphoma, among others.

Lymphomatoid papulosis is a rare disease occurring in all ethnic groups and at any age, though most commonly presenting in the fifth decade of life. Finding large atypical T cells expressing CD30 in recurring skin lesions is highly suggestive of LyP; however, large CD30⁺ cells also can be seen in numerous benign reactive processes such as arthropod assault, drug eruption, viral skin infections, and other dermatoses, thus clinical correlation is always paramount. The cause of LyP is largely unknown; however, spontaneous regression may be explained by CD30-CD30 ligand interaction³ as well as an increased proapoptotic milieu.⁴ Specific translocations such as interferon regulatory factor-4 have been hypothesized as a risk factor for malignant progression.^5-7 Additionally, an inactivating gene mutation resulting in loss of transforming growth factor β1 receptor expression and subsequent unresponsiveness to the growth inhibitory effect of transforming growth factor β may play a role in progression of LyP to ALCL.⁸

Clinically, LyP consists of red-brown papules and nodules generally smaller than 2 cm, often with central hemorrhage, necrosis, and crusting. Lesions are at different stages of eruption and resolution. They are often grouped but may be disseminated. Spontaneous regression typically occurs within 3 to 8 weeks. Pruritus or mild tenderness may occur as well as residual hyperpigmentation or scarring. Systemic symptoms are notably absent.

The histologic features of LyP vary according to the age of the lesion and subtype.² Early lesions may only show a few inflammatory cells, but as lesions evolve, larger immunoblastlike CD30⁺ atypical cells accumulate that may resemble the Reed-Sternberg cells of Hodgkin lymphoma. Of the 5 subtypes, the most common is type A. It is characterized by a wedge-shaped infiltrate with a mixed population of scattered or clustered, large, atypical CD30⁺ cells, lymphocytes, neutrophils, eosinophils, and histiocytes.⁹ Frequent mitoses often are seen. Type B appears similar to MF due to a predominantly epidermotropic infiltrate of CD3⁺ and often CD30⁻ atypical cells. Spontaneously regressing papules favor LyP, whereas persistent patches or plaques favor MF. Type C appears identical to ALCL with diffuse sheets of large atypical CD30⁺ cells and relatively few inflammatory cells, but spontaneously regressing lesions again favor LyP, whereas persistent tumors favor ALCL. Type D appears similar to primary cutaneous aggressive epidermotropic CD8⁺ cytotoxic T cell lymphoma due to a markedly epidermotropic infiltrate of small atypical CD8⁺ and CD30⁺ lymphocytes, often TIA-1⁺ (T-cell intracytoplasmic antigen-1) or granzyme B⁺, but CD30 positivity and self-resolving lesions favor LyP. Type E mimics extranodal natural killer/T cell lymphoma (nasal type) due to angioinvasive CD30⁺ and beta F1⁺ T lymphocytes, often CD8⁺ and/or TIA-1⁺, but self-resolving lesions again favor LyP, as well as absence of Epstein-Barr virus and CD56⁻.⁹

The most common therapeutic approaches to LyP include topical steroids, phototherapy, and low-dose methotrexate.¹⁰ However, treatment does not change overall disease course or reduce the future risk for developing an associated lymphoma. Accordingly, abstaining from active therapeutic intervention is reasonable, especially in patients with only a few asymptomatic lesions.