Commentary

In the field of lung cancer, and more broadly in oncology, many of our biggest advances in 2021 have come as clinically meaningful improvements in surrogate endpoints – disease-free survival, progression-free survival, and sometimes even pathologic complete response rate.

I have historically been most compelled to consider new findings to be practice-changing when they improve overall survival or quality of life – the endpoints that translate to direct benefits for patients. However, I also feel it is appropriate to call surrogate endpoints practice-changing when they can predict improvements in overall survival or quality of life.

Take the PACIFIC trial, which assessed maintenance durvalumab after concurrent chemoradiation for unresectable stage III non–small cell lung cancer (NSCLC).

Back in 2017, I was initially unconvinced by the interim phase 3 data that were presented in a press release that highlighted the disease-free survival benefit. However, after examining additional data more closely, I saw the dramatic improvement in time to distant relapse or death was overwhelmingly likely to predict an improvement in overall survival – a benefit that the data subsequently bore out.

More recently, the disease-free survival results for adjuvant osimertinib in resected endothelial growth factor receptor mutation–positive NSCLC and adjuvant atezolizumab in resected programmed death-ligand 1–positive stage II-IIIA NSCLC have led to excitement about Food and Drug Administration approvals for these therapies. Although there is reason to be cautious about the likelihood of an overall survival benefit with either therapy – particularly for patients with low programmed death-ligand 1 who receive atezolizumab – I think that the results are promising enough to discuss these treatment options with appropriate patients.

Some argue, however, that overall survival is not necessarily a critical goal and that certain surrogate endpoints are inherently beneficial. Patients and oncologists may, for instance, view delaying disease progression as a win, even if overall survival remains the same.

I appreciate the view that favorable scan results are an achievement, even without a survival benefit. Patients appreciate the good news, and it is gratifying for us to deliver it. However, what remains unspoken is whether the benefit can be provided at a reasonable value given the financial costs associated with the new treatment.

In the United States, we consider the physician-patient relationship to be autonomous and even revered, but we conveniently ignore the fact that both are deciding on treatments that are funded by people who are not represented in the room. And in a health care system that fails to cover basic cancer care needs as well as other critical, high-value interventions for both the uninsured and underinsured, we should acknowledge that our decisions redirect limited resources from others.

Is it the best use of $10,000 per month for a new drug that improves disease-free survival but not overall survival? Given the cost of so many of these newer treatments, we should expect more than indirect, inferred benefits for patients.

At the same time, we also have to remain vigilant and reflect on whether we are echoing the marketing messages of the companies selling these treatments. Having recently watched the excellent Hulu series Dopesick, which realistically portrays the medical community’s egregious overuse of Oxycontin at the behest of Purdue Pharmaceuticals, it is striking to see how effectively the pharmaceutical industry can co-opt stakeholders. Very few physicians or patients have expertise in health care policy with broad societal perspective, yet subspecialists offer edicts as if society should dedicate unlimited resources first and foremost to our career focus or personal cause.

I certainly appreciate the appeal of surrogate endpoints in a world in which we hope to offer novel therapies to patients in a timely fashion. In the next few years, some of our most promising data in oncology will demand that we consider whether surrogate endpoints are practice-changing. We are facing a fundamental question: Are we using these surrogate endpoints to predict overall survival or quality of life or do these endpoints stand on their own as practice-changing metrics?

We need to acknowledge that our primary clinical focus is not the only one that deserves our attention, particularly when our treatment decisions are, in fact, spending other people’s money. We should be asking not whether we prefer to deliver good news after a scan, but whether that alone is enough to justify the high cost of a new treatment without an overall survival benefit.

Dr. West disclosed serving as a director, officer, partner, employee, adviser, consultant, or trustee for Ariad/Takeda, Bristol-Myers Squibb, Boehringer Ingelheim, Spectrum, AstraZeneca, Celgene, Genentech/Roche, Pfizer, and Merck; serving as a speaker or a member of a speakers bureau for Ariad/Takeda, AstraZeneca, and Genentech/Roche; and receiving income from Eli Lilly. A version of this article first appeared on Medscape.com.

In the field of lung cancer, and more broadly in oncology, many of our biggest advances in 2021 have come as clinically meaningful improvements in surrogate endpoints – disease-free survival, progression-free survival, and sometimes even pathologic complete response rate.

I have historically been most compelled to consider new findings to be practice-changing when they improve overall survival or quality of life – the endpoints that translate to direct benefits for patients. However, I also feel it is appropriate to call surrogate endpoints practice-changing when they can predict improvements in overall survival or quality of life.

Take the PACIFIC trial, which assessed maintenance durvalumab after concurrent chemoradiation for unresectable stage III non–small cell lung cancer (NSCLC).

Back in 2017, I was initially unconvinced by the interim phase 3 data that were presented in a press release that highlighted the disease-free survival benefit. However, after examining additional data more closely, I saw the dramatic improvement in time to distant relapse or death was overwhelmingly likely to predict an improvement in overall survival – a benefit that the data subsequently bore out.

More recently, the disease-free survival results for adjuvant osimertinib in resected endothelial growth factor receptor mutation–positive NSCLC and adjuvant atezolizumab in resected programmed death-ligand 1–positive stage II-IIIA NSCLC have led to excitement about Food and Drug Administration approvals for these therapies. Although there is reason to be cautious about the likelihood of an overall survival benefit with either therapy – particularly for patients with low programmed death-ligand 1 who receive atezolizumab – I think that the results are promising enough to discuss these treatment options with appropriate patients.

Some argue, however, that overall survival is not necessarily a critical goal and that certain surrogate endpoints are inherently beneficial. Patients and oncologists may, for instance, view delaying disease progression as a win, even if overall survival remains the same.

I appreciate the view that favorable scan results are an achievement, even without a survival benefit. Patients appreciate the good news, and it is gratifying for us to deliver it. However, what remains unspoken is whether the benefit can be provided at a reasonable value given the financial costs associated with the new treatment.

In the United States, we consider the physician-patient relationship to be autonomous and even revered, but we conveniently ignore the fact that both are deciding on treatments that are funded by people who are not represented in the room. And in a health care system that fails to cover basic cancer care needs as well as other critical, high-value interventions for both the uninsured and underinsured, we should acknowledge that our decisions redirect limited resources from others.

Is it the best use of $10,000 per month for a new drug that improves disease-free survival but not overall survival? Given the cost of so many of these newer treatments, we should expect more than indirect, inferred benefits for patients.

At the same time, we also have to remain vigilant and reflect on whether we are echoing the marketing messages of the companies selling these treatments. Having recently watched the excellent Hulu series Dopesick, which realistically portrays the medical community’s egregious overuse of Oxycontin at the behest of Purdue Pharmaceuticals, it is striking to see how effectively the pharmaceutical industry can co-opt stakeholders. Very few physicians or patients have expertise in health care policy with broad societal perspective, yet subspecialists offer edicts as if society should dedicate unlimited resources first and foremost to our career focus or personal cause.

I certainly appreciate the appeal of surrogate endpoints in a world in which we hope to offer novel therapies to patients in a timely fashion. In the next few years, some of our most promising data in oncology will demand that we consider whether surrogate endpoints are practice-changing. We are facing a fundamental question: Are we using these surrogate endpoints to predict overall survival or quality of life or do these endpoints stand on their own as practice-changing metrics?

We need to acknowledge that our primary clinical focus is not the only one that deserves our attention, particularly when our treatment decisions are, in fact, spending other people’s money. We should be asking not whether we prefer to deliver good news after a scan, but whether that alone is enough to justify the high cost of a new treatment without an overall survival benefit.

Dr. West disclosed serving as a director, officer, partner, employee, adviser, consultant, or trustee for Ariad/Takeda, Bristol-Myers Squibb, Boehringer Ingelheim, Spectrum, AstraZeneca, Celgene, Genentech/Roche, Pfizer, and Merck; serving as a speaker or a member of a speakers bureau for Ariad/Takeda, AstraZeneca, and Genentech/Roche; and receiving income from Eli Lilly. A version of this article first appeared on Medscape.com.

In the field of lung cancer, and more broadly in oncology, many of our biggest advances in 2021 have come as clinically meaningful improvements in surrogate endpoints – disease-free survival, progression-free survival, and sometimes even pathologic complete response rate.

I have historically been most compelled to consider new findings to be practice-changing when they improve overall survival or quality of life – the endpoints that translate to direct benefits for patients. However, I also feel it is appropriate to call surrogate endpoints practice-changing when they can predict improvements in overall survival or quality of life.

Take the PACIFIC trial, which assessed maintenance durvalumab after concurrent chemoradiation for unresectable stage III non–small cell lung cancer (NSCLC).

Back in 2017, I was initially unconvinced by the interim phase 3 data that were presented in a press release that highlighted the disease-free survival benefit. However, after examining additional data more closely, I saw the dramatic improvement in time to distant relapse or death was overwhelmingly likely to predict an improvement in overall survival – a benefit that the data subsequently bore out.

More recently, the disease-free survival results for adjuvant osimertinib in resected endothelial growth factor receptor mutation–positive NSCLC and adjuvant atezolizumab in resected programmed death-ligand 1–positive stage II-IIIA NSCLC have led to excitement about Food and Drug Administration approvals for these therapies. Although there is reason to be cautious about the likelihood of an overall survival benefit with either therapy – particularly for patients with low programmed death-ligand 1 who receive atezolizumab – I think that the results are promising enough to discuss these treatment options with appropriate patients.

Some argue, however, that overall survival is not necessarily a critical goal and that certain surrogate endpoints are inherently beneficial. Patients and oncologists may, for instance, view delaying disease progression as a win, even if overall survival remains the same.

I appreciate the view that favorable scan results are an achievement, even without a survival benefit. Patients appreciate the good news, and it is gratifying for us to deliver it. However, what remains unspoken is whether the benefit can be provided at a reasonable value given the financial costs associated with the new treatment.

In the United States, we consider the physician-patient relationship to be autonomous and even revered, but we conveniently ignore the fact that both are deciding on treatments that are funded by people who are not represented in the room. And in a health care system that fails to cover basic cancer care needs as well as other critical, high-value interventions for both the uninsured and underinsured, we should acknowledge that our decisions redirect limited resources from others.

Is it the best use of $10,000 per month for a new drug that improves disease-free survival but not overall survival? Given the cost of so many of these newer treatments, we should expect more than indirect, inferred benefits for patients.

At the same time, we also have to remain vigilant and reflect on whether we are echoing the marketing messages of the companies selling these treatments. Having recently watched the excellent Hulu series Dopesick, which realistically portrays the medical community’s egregious overuse of Oxycontin at the behest of Purdue Pharmaceuticals, it is striking to see how effectively the pharmaceutical industry can co-opt stakeholders. Very few physicians or patients have expertise in health care policy with broad societal perspective, yet subspecialists offer edicts as if society should dedicate unlimited resources first and foremost to our career focus or personal cause.

I certainly appreciate the appeal of surrogate endpoints in a world in which we hope to offer novel therapies to patients in a timely fashion. In the next few years, some of our most promising data in oncology will demand that we consider whether surrogate endpoints are practice-changing. We are facing a fundamental question: Are we using these surrogate endpoints to predict overall survival or quality of life or do these endpoints stand on their own as practice-changing metrics?

We need to acknowledge that our primary clinical focus is not the only one that deserves our attention, particularly when our treatment decisions are, in fact, spending other people’s money. We should be asking not whether we prefer to deliver good news after a scan, but whether that alone is enough to justify the high cost of a new treatment without an overall survival benefit.

Dr. West disclosed serving as a director, officer, partner, employee, adviser, consultant, or trustee for Ariad/Takeda, Bristol-Myers Squibb, Boehringer Ingelheim, Spectrum, AstraZeneca, Celgene, Genentech/Roche, Pfizer, and Merck; serving as a speaker or a member of a speakers bureau for Ariad/Takeda, AstraZeneca, and Genentech/Roche; and receiving income from Eli Lilly. A version of this article first appeared on Medscape.com.

A 64-year-old woman is evaluated for fever, diarrhea, and abdominal pain. She was diagnosed with Clostridioides difficile 2 months ago and completed a 10-day course of vancomycin. Her stool toxin test is positive for Clostridioides difficile (C. diff). Based on the most recent Infectious Diseases Society of America (IDSA) guidelines, what would be the preferred therapy?

A) Metronidazole

B) Fidaxomicin + bezlotoxumab

C) Vancomycin

D) Fecal microbiota transplant

The recommendations from the 2021 guidelines would be to treat with fidaxomicin and add bezlotoxumab.¹ The guidelines highlight the following changes:

• In patients with an initial Clostridioides difficile infections (CDI) fidaxomicin is preferred over vancomycin.
• In patients with a recurrent CDI episode, fidaxomicin is favored over vancomycin. For patients with multiple recurrences, vancomycin in a tapered and pulsed regimen, vancomycin followed by rifaximin, and fecal microbiota transplantation are options in addition to fidaxomicin.
• Addition of bezlotoxumab to standard of care antibiotics is recommended for recurrence of CDI within the first 6 months over standard of care antibiotics alone

The feasibility of these recommendations is up for debate. The cost of a course of fidaxomicin is $2,800, and the cost of bezlotoxumab is about $4,500. Cost effectiveness studies that helped drive the recommendations show a savings by reducing future hospitalizations for C. diff.² Unfortunately, this enthusiasm is not shared by many insurance companies for outpatient treatment.

Knee osteoarthritis

I will save you the excitement of the new acromegaly guidelines and focus on something we see all the time: knee osteoarthritis. The American Academy of Orthopedic Surgeons has released guidelines for this condition.³ The useful points I found were as follows:

• Topical application of nonsteroidal anti-inflammatory drugs (e.g., diclofenac) should be used to improve function and quality of life in patients with knee osteoarthritis.
• Exercise routines (i.e, supervised, unsupervised, and/or aquatic) are recommended versus no exercise for improving pain and function in patients with knee osteoarthritis.
• Not recommended is the use of oral narcotics (including tramadol), as they are not effective at improving pain or function, and their use results in a significant increased risk of adverse events.
• Not recommended for routine use in symptomatic knee osteoarthritis is intra-articular injection of hyaluronic acid.

I was happy to see topical NSAIDS recommended, as they are a much safer option in older patients than oral NSAIDS (which were also recommended). The recommendation against narcotics, including tramadol, is a shift from the recommendation of tramadol in the 2013 guidelines.⁴ Acetaminophen was enthusiastically recommended, and is still worth a try.

Sexually transmitted infections

• The dosing for the treatment of gonorrhea has increased to 500 mg of ceftriaxone (was 250 mg in 2015 guidelines), with a dose of 1 gram for patients who weigh more than 150 kg.
• Chlamydia infections should be treated with a 7-day course of doxycycline as the preferred antibiotic, except in pregnant women (where azithromycin is recommended).
• Herpes simplex virus 2 recurrences can be treated with twice-daily dosing of 800 mg of acyclovir for 5 days, or acyclovir 800 mg three times a day for 2 days. The shortest course for recurrence is famciclovir 1 gram twice a day for 1 day.
• The Centers for Disease Control and Prevention has removed the recommendation for avoidance of alcohol when taking metronidazole.

I hope these highlights of guidelines for common issues we see are helpful!

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Johnson S et al. Clinical practice guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused update guidelines on management of Clostridioides difficile Infection in adults. Clin Infect Dis. 2021 Sep 7;73(5):e1029-e1044.

2. Pabhu VS et al. Cost-effectiveness of bezlotoxumab compared with placebo for the prevention of recurrent Clostridium difficile infection. Clin Infect Dis. 2018 Feb 1;66(3):355-62.

3. American Academy of Orthopaedic Surgeons: Management of osteoarthritis of the knee (non-arthroplasty) – Evidence-based clinical practice guideline (2021 Aug 31. https://www.aaos.org/oak3cpg).

4. Jevsevar DS. Treatment of osteoarthritis of the knee: Evidence-based guideline, 2nd edition. J Am Acad Orthop Surg. 2013: Sep;21(9):571-6.

5. Sexually transmitted infections treatment guidelines, 2021 recommendations and reports. MMWR 2021 Jul 23;70(4):1-187.

A 64-year-old woman is evaluated for fever, diarrhea, and abdominal pain. She was diagnosed with Clostridioides difficile 2 months ago and completed a 10-day course of vancomycin. Her stool toxin test is positive for Clostridioides difficile (C. diff). Based on the most recent Infectious Diseases Society of America (IDSA) guidelines, what would be the preferred therapy?

A) Metronidazole

B) Fidaxomicin + bezlotoxumab

C) Vancomycin

D) Fecal microbiota transplant

The recommendations from the 2021 guidelines would be to treat with fidaxomicin and add bezlotoxumab.¹ The guidelines highlight the following changes:

• In patients with an initial Clostridioides difficile infections (CDI) fidaxomicin is preferred over vancomycin.
• In patients with a recurrent CDI episode, fidaxomicin is favored over vancomycin. For patients with multiple recurrences, vancomycin in a tapered and pulsed regimen, vancomycin followed by rifaximin, and fecal microbiota transplantation are options in addition to fidaxomicin.
• Addition of bezlotoxumab to standard of care antibiotics is recommended for recurrence of CDI within the first 6 months over standard of care antibiotics alone

The feasibility of these recommendations is up for debate. The cost of a course of fidaxomicin is $2,800, and the cost of bezlotoxumab is about $4,500. Cost effectiveness studies that helped drive the recommendations show a savings by reducing future hospitalizations for C. diff.² Unfortunately, this enthusiasm is not shared by many insurance companies for outpatient treatment.

Knee osteoarthritis

I will save you the excitement of the new acromegaly guidelines and focus on something we see all the time: knee osteoarthritis. The American Academy of Orthopedic Surgeons has released guidelines for this condition.³ The useful points I found were as follows:

• Topical application of nonsteroidal anti-inflammatory drugs (e.g., diclofenac) should be used to improve function and quality of life in patients with knee osteoarthritis.
• Exercise routines (i.e, supervised, unsupervised, and/or aquatic) are recommended versus no exercise for improving pain and function in patients with knee osteoarthritis.
• Not recommended is the use of oral narcotics (including tramadol), as they are not effective at improving pain or function, and their use results in a significant increased risk of adverse events.
• Not recommended for routine use in symptomatic knee osteoarthritis is intra-articular injection of hyaluronic acid.

I was happy to see topical NSAIDS recommended, as they are a much safer option in older patients than oral NSAIDS (which were also recommended). The recommendation against narcotics, including tramadol, is a shift from the recommendation of tramadol in the 2013 guidelines.⁴ Acetaminophen was enthusiastically recommended, and is still worth a try.

Sexually transmitted infections

• The dosing for the treatment of gonorrhea has increased to 500 mg of ceftriaxone (was 250 mg in 2015 guidelines), with a dose of 1 gram for patients who weigh more than 150 kg.
• Chlamydia infections should be treated with a 7-day course of doxycycline as the preferred antibiotic, except in pregnant women (where azithromycin is recommended).
• Herpes simplex virus 2 recurrences can be treated with twice-daily dosing of 800 mg of acyclovir for 5 days, or acyclovir 800 mg three times a day for 2 days. The shortest course for recurrence is famciclovir 1 gram twice a day for 1 day.
• The Centers for Disease Control and Prevention has removed the recommendation for avoidance of alcohol when taking metronidazole.

I hope these highlights of guidelines for common issues we see are helpful!

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Johnson S et al. Clinical practice guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused update guidelines on management of Clostridioides difficile Infection in adults. Clin Infect Dis. 2021 Sep 7;73(5):e1029-e1044.

2. Pabhu VS et al. Cost-effectiveness of bezlotoxumab compared with placebo for the prevention of recurrent Clostridium difficile infection. Clin Infect Dis. 2018 Feb 1;66(3):355-62.

3. American Academy of Orthopaedic Surgeons: Management of osteoarthritis of the knee (non-arthroplasty) – Evidence-based clinical practice guideline (2021 Aug 31. https://www.aaos.org/oak3cpg).

4. Jevsevar DS. Treatment of osteoarthritis of the knee: Evidence-based guideline, 2nd edition. J Am Acad Orthop Surg. 2013: Sep;21(9):571-6.

5. Sexually transmitted infections treatment guidelines, 2021 recommendations and reports. MMWR 2021 Jul 23;70(4):1-187.

A 64-year-old woman is evaluated for fever, diarrhea, and abdominal pain. She was diagnosed with Clostridioides difficile 2 months ago and completed a 10-day course of vancomycin. Her stool toxin test is positive for Clostridioides difficile (C. diff). Based on the most recent Infectious Diseases Society of America (IDSA) guidelines, what would be the preferred therapy?

A) Metronidazole

B) Fidaxomicin + bezlotoxumab

C) Vancomycin

D) Fecal microbiota transplant

The recommendations from the 2021 guidelines would be to treat with fidaxomicin and add bezlotoxumab.¹ The guidelines highlight the following changes:

• In patients with an initial Clostridioides difficile infections (CDI) fidaxomicin is preferred over vancomycin.
• In patients with a recurrent CDI episode, fidaxomicin is favored over vancomycin. For patients with multiple recurrences, vancomycin in a tapered and pulsed regimen, vancomycin followed by rifaximin, and fecal microbiota transplantation are options in addition to fidaxomicin.
• Addition of bezlotoxumab to standard of care antibiotics is recommended for recurrence of CDI within the first 6 months over standard of care antibiotics alone

The feasibility of these recommendations is up for debate. The cost of a course of fidaxomicin is $2,800, and the cost of bezlotoxumab is about $4,500. Cost effectiveness studies that helped drive the recommendations show a savings by reducing future hospitalizations for C. diff.² Unfortunately, this enthusiasm is not shared by many insurance companies for outpatient treatment.

Knee osteoarthritis

I will save you the excitement of the new acromegaly guidelines and focus on something we see all the time: knee osteoarthritis. The American Academy of Orthopedic Surgeons has released guidelines for this condition.³ The useful points I found were as follows:

• Topical application of nonsteroidal anti-inflammatory drugs (e.g., diclofenac) should be used to improve function and quality of life in patients with knee osteoarthritis.
• Exercise routines (i.e, supervised, unsupervised, and/or aquatic) are recommended versus no exercise for improving pain and function in patients with knee osteoarthritis.
• Not recommended is the use of oral narcotics (including tramadol), as they are not effective at improving pain or function, and their use results in a significant increased risk of adverse events.
• Not recommended for routine use in symptomatic knee osteoarthritis is intra-articular injection of hyaluronic acid.

I was happy to see topical NSAIDS recommended, as they are a much safer option in older patients than oral NSAIDS (which were also recommended). The recommendation against narcotics, including tramadol, is a shift from the recommendation of tramadol in the 2013 guidelines.⁴ Acetaminophen was enthusiastically recommended, and is still worth a try.

Sexually transmitted infections

• The dosing for the treatment of gonorrhea has increased to 500 mg of ceftriaxone (was 250 mg in 2015 guidelines), with a dose of 1 gram for patients who weigh more than 150 kg.
• Chlamydia infections should be treated with a 7-day course of doxycycline as the preferred antibiotic, except in pregnant women (where azithromycin is recommended).
• Herpes simplex virus 2 recurrences can be treated with twice-daily dosing of 800 mg of acyclovir for 5 days, or acyclovir 800 mg three times a day for 2 days. The shortest course for recurrence is famciclovir 1 gram twice a day for 1 day.
• The Centers for Disease Control and Prevention has removed the recommendation for avoidance of alcohol when taking metronidazole.

I hope these highlights of guidelines for common issues we see are helpful!

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Johnson S et al. Clinical practice guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused update guidelines on management of Clostridioides difficile Infection in adults. Clin Infect Dis. 2021 Sep 7;73(5):e1029-e1044.

2. Pabhu VS et al. Cost-effectiveness of bezlotoxumab compared with placebo for the prevention of recurrent Clostridium difficile infection. Clin Infect Dis. 2018 Feb 1;66(3):355-62.

3. American Academy of Orthopaedic Surgeons: Management of osteoarthritis of the knee (non-arthroplasty) – Evidence-based clinical practice guideline (2021 Aug 31. https://www.aaos.org/oak3cpg).

4. Jevsevar DS. Treatment of osteoarthritis of the knee: Evidence-based guideline, 2nd edition. J Am Acad Orthop Surg. 2013: Sep;21(9):571-6.

5. Sexually transmitted infections treatment guidelines, 2021 recommendations and reports. MMWR 2021 Jul 23;70(4):1-187.

Physician clients will find themselves in difficult legal situations from time to time. Sometimes it’s an investigation for Medicare fraud or other illegal conduct. Other times it’s a review related to Drug Enforcement Administration or licensure compliance. More commonly, physicians are involved in employer inquiries into workplace misconduct.

The common element among these very different legal issues is that physicians typically have no idea what to do when they find themselves potentially in trouble, but how they choose to deal with the issue can have significant consequences.

In my opinion, physicians should have a relationship with a health care lawyer or firm in place before any investigation occurs. Whether they are being investigated for a license or medical staff issue, Medicare fraud, or contract issue, it’s important to know where to go for help quickly. Even if the physician does not retain a lawyer in advance, having the name of a qualified person who can be called for a variety of health care issues is already a step in the right direction.

More important than having a knowledgeable lawyer is actually contacting that lawyer. Some physicians will sit and chat with the Federal Bureau of Investigation or other investigators for hours, only to call me after the visitors leave. I have other clients who handle important medical staff hearings, discipline meetings, and license investigations on their own without consulting counsel first. In all of these situations, it can be too late to help a physician once their case has progressed too far down the road.

Employment issues arising in the workplace setting are the most common and troubling. Physicians will – without a second thought – attend a human resources–called or other meeting without thinking through the reason for the meeting, whether they are prepared or not, and without considering whether counsel could be helpful. Sometimes in the moment, there may be no choice, but most meetings are scheduled in advance with ample time for consultation and planning.

Many issues that arise in the workplace setting are troubling because they can be easily avoided. The No. 1 piece of advice which I offer to young physician clients as they enter the workplace is: Remember that nobody in the workplace is your friend. Every word that is said, text that is sent, gesture that is made, can put you at risk. You must assume that all conversations and messages will be shared with others. Joking around in the operating room about sexual escapades, sending texts with flirtatious comments, making comments that can be construed as racist or homophobic, or raising your voice in a moment of frustration are all real examples of situations where physicians ended up disciplined and terminated. Are these innocent comments or ones the doctor thought they could get away with among “friends?” From a human resources perspective, there is little tolerance for such conduct, regardless of the doctor’s intent.

There are also situations in the workplace that are more troubling. Many times a physician is accused of noncompliance with a contract or a policy, when in fact the accuser is retaliating or engaging in efforts to discredit a doctor. I have seen this happen where minority physicians complain about how they are treated and are suddenly investigated for a performance issue. I have had female physicians criticize a business decision at a committee meeting, only to receive a formal notice that their “negative attitude” violated a policy.

In these situations, talking with counsel before a meeting with the employer representative is recommended and can impact the trajectory of a physician’s career. Physicians cannot and should not handle such events on their own.

If a physician is forced or chooses to attend a meeting with an investigator or other party without counsel, there are some steps to consider (subject to the type of meeting and the specific circumstances).

• Listen more than you talk. Make sure you know the name of everyone who is present and their role within the organization.
• If you have previously provided any written or oral statements, or have written correspondence related to the issues at hand, review all materials in advance. If there is anything you think needs to be corrected or added, let the interviewer know that at the outset.
• Be familiar with your own employment agreement/policies and the terms that may be relevant to the discussion or meeting.
• Be calm, honest, and forthcoming in response to the questions, and don’t embellish or exaggerate.
• Avoid personal attacks on anyone. This generally serves to weaken an argument and credibility.
• Be prepared to explain your allegations or defense, and when you do so, keep in mind that the interviewer may not know the history, background, or details of any of the issues.
• If the reason for the situation relates to race or national origin, age, gender, sexual orientation, disability, or other protected category, don’t hesitate to say so.
• Answer the question you’re asked, but if you feel that the interviewer needs more information or is not understanding what you’ve said, feel free to explain. Be forthcoming, but don’t dominate the conversation.
• If they ask whether you have counsel, be honest, but decline to provide them any information about what you discussed with counsel, as those conversations are privileged.
• If the interviewer asks to record the conversation, you can agree, but ask to be provided a copy of the recording.
• Know your rights in advance. If the subject of the meeting is governed by bylaws or policies, for example, you may have the right to bring an attorney or adviser to the meeting, receive advance notice of who will be attending the meeting and the subject matter, and avail yourself of specific procedures or appeal rights of any discipline or decisions decided during the meeting.

There are many circumstances that can lead to a physician being under investigation or interrogation. In every single circumstance, it is ideal to seek legal counsel immediately. Whether the physician has actually engaged in wrongful conduct or not, without proper handling a physician’s career can be permanently, and sometimes irrevocably, affected.

Ms. Adler is a shareholder and health law practice group manager for Chicago-based law firm Roetzel, a member of the Illinois Association of Healthcare Attorneys, and a current advisory board member at DePaul College of Law Health Law Institute. She disclosed no relevant financial relationships.

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

Physician clients will find themselves in difficult legal situations from time to time. Sometimes it’s an investigation for Medicare fraud or other illegal conduct. Other times it’s a review related to Drug Enforcement Administration or licensure compliance. More commonly, physicians are involved in employer inquiries into workplace misconduct.

The common element among these very different legal issues is that physicians typically have no idea what to do when they find themselves potentially in trouble, but how they choose to deal with the issue can have significant consequences.

In my opinion, physicians should have a relationship with a health care lawyer or firm in place before any investigation occurs. Whether they are being investigated for a license or medical staff issue, Medicare fraud, or contract issue, it’s important to know where to go for help quickly. Even if the physician does not retain a lawyer in advance, having the name of a qualified person who can be called for a variety of health care issues is already a step in the right direction.

More important than having a knowledgeable lawyer is actually contacting that lawyer. Some physicians will sit and chat with the Federal Bureau of Investigation or other investigators for hours, only to call me after the visitors leave. I have other clients who handle important medical staff hearings, discipline meetings, and license investigations on their own without consulting counsel first. In all of these situations, it can be too late to help a physician once their case has progressed too far down the road.

Employment issues arising in the workplace setting are the most common and troubling. Physicians will – without a second thought – attend a human resources–called or other meeting without thinking through the reason for the meeting, whether they are prepared or not, and without considering whether counsel could be helpful. Sometimes in the moment, there may be no choice, but most meetings are scheduled in advance with ample time for consultation and planning.

Many issues that arise in the workplace setting are troubling because they can be easily avoided. The No. 1 piece of advice which I offer to young physician clients as they enter the workplace is: Remember that nobody in the workplace is your friend. Every word that is said, text that is sent, gesture that is made, can put you at risk. You must assume that all conversations and messages will be shared with others. Joking around in the operating room about sexual escapades, sending texts with flirtatious comments, making comments that can be construed as racist or homophobic, or raising your voice in a moment of frustration are all real examples of situations where physicians ended up disciplined and terminated. Are these innocent comments or ones the doctor thought they could get away with among “friends?” From a human resources perspective, there is little tolerance for such conduct, regardless of the doctor’s intent.

There are also situations in the workplace that are more troubling. Many times a physician is accused of noncompliance with a contract or a policy, when in fact the accuser is retaliating or engaging in efforts to discredit a doctor. I have seen this happen where minority physicians complain about how they are treated and are suddenly investigated for a performance issue. I have had female physicians criticize a business decision at a committee meeting, only to receive a formal notice that their “negative attitude” violated a policy.

In these situations, talking with counsel before a meeting with the employer representative is recommended and can impact the trajectory of a physician’s career. Physicians cannot and should not handle such events on their own.

If a physician is forced or chooses to attend a meeting with an investigator or other party without counsel, there are some steps to consider (subject to the type of meeting and the specific circumstances).

• Listen more than you talk. Make sure you know the name of everyone who is present and their role within the organization.
• If you have previously provided any written or oral statements, or have written correspondence related to the issues at hand, review all materials in advance. If there is anything you think needs to be corrected or added, let the interviewer know that at the outset.
• Be familiar with your own employment agreement/policies and the terms that may be relevant to the discussion or meeting.
• Be calm, honest, and forthcoming in response to the questions, and don’t embellish or exaggerate.
• Avoid personal attacks on anyone. This generally serves to weaken an argument and credibility.
• Be prepared to explain your allegations or defense, and when you do so, keep in mind that the interviewer may not know the history, background, or details of any of the issues.
• If the reason for the situation relates to race or national origin, age, gender, sexual orientation, disability, or other protected category, don’t hesitate to say so.
• Answer the question you’re asked, but if you feel that the interviewer needs more information or is not understanding what you’ve said, feel free to explain. Be forthcoming, but don’t dominate the conversation.
• If they ask whether you have counsel, be honest, but decline to provide them any information about what you discussed with counsel, as those conversations are privileged.
• If the interviewer asks to record the conversation, you can agree, but ask to be provided a copy of the recording.
• Know your rights in advance. If the subject of the meeting is governed by bylaws or policies, for example, you may have the right to bring an attorney or adviser to the meeting, receive advance notice of who will be attending the meeting and the subject matter, and avail yourself of specific procedures or appeal rights of any discipline or decisions decided during the meeting.

There are many circumstances that can lead to a physician being under investigation or interrogation. In every single circumstance, it is ideal to seek legal counsel immediately. Whether the physician has actually engaged in wrongful conduct or not, without proper handling a physician’s career can be permanently, and sometimes irrevocably, affected.

Ms. Adler is a shareholder and health law practice group manager for Chicago-based law firm Roetzel, a member of the Illinois Association of Healthcare Attorneys, and a current advisory board member at DePaul College of Law Health Law Institute. She disclosed no relevant financial relationships.

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

Physician clients will find themselves in difficult legal situations from time to time. Sometimes it’s an investigation for Medicare fraud or other illegal conduct. Other times it’s a review related to Drug Enforcement Administration or licensure compliance. More commonly, physicians are involved in employer inquiries into workplace misconduct.

The common element among these very different legal issues is that physicians typically have no idea what to do when they find themselves potentially in trouble, but how they choose to deal with the issue can have significant consequences.

In my opinion, physicians should have a relationship with a health care lawyer or firm in place before any investigation occurs. Whether they are being investigated for a license or medical staff issue, Medicare fraud, or contract issue, it’s important to know where to go for help quickly. Even if the physician does not retain a lawyer in advance, having the name of a qualified person who can be called for a variety of health care issues is already a step in the right direction.

More important than having a knowledgeable lawyer is actually contacting that lawyer. Some physicians will sit and chat with the Federal Bureau of Investigation or other investigators for hours, only to call me after the visitors leave. I have other clients who handle important medical staff hearings, discipline meetings, and license investigations on their own without consulting counsel first. In all of these situations, it can be too late to help a physician once their case has progressed too far down the road.

Employment issues arising in the workplace setting are the most common and troubling. Physicians will – without a second thought – attend a human resources–called or other meeting without thinking through the reason for the meeting, whether they are prepared or not, and without considering whether counsel could be helpful. Sometimes in the moment, there may be no choice, but most meetings are scheduled in advance with ample time for consultation and planning.

Many issues that arise in the workplace setting are troubling because they can be easily avoided. The No. 1 piece of advice which I offer to young physician clients as they enter the workplace is: Remember that nobody in the workplace is your friend. Every word that is said, text that is sent, gesture that is made, can put you at risk. You must assume that all conversations and messages will be shared with others. Joking around in the operating room about sexual escapades, sending texts with flirtatious comments, making comments that can be construed as racist or homophobic, or raising your voice in a moment of frustration are all real examples of situations where physicians ended up disciplined and terminated. Are these innocent comments or ones the doctor thought they could get away with among “friends?” From a human resources perspective, there is little tolerance for such conduct, regardless of the doctor’s intent.

There are also situations in the workplace that are more troubling. Many times a physician is accused of noncompliance with a contract or a policy, when in fact the accuser is retaliating or engaging in efforts to discredit a doctor. I have seen this happen where minority physicians complain about how they are treated and are suddenly investigated for a performance issue. I have had female physicians criticize a business decision at a committee meeting, only to receive a formal notice that their “negative attitude” violated a policy.

In these situations, talking with counsel before a meeting with the employer representative is recommended and can impact the trajectory of a physician’s career. Physicians cannot and should not handle such events on their own.

If a physician is forced or chooses to attend a meeting with an investigator or other party without counsel, there are some steps to consider (subject to the type of meeting and the specific circumstances).

• Listen more than you talk. Make sure you know the name of everyone who is present and their role within the organization.
• If you have previously provided any written or oral statements, or have written correspondence related to the issues at hand, review all materials in advance. If there is anything you think needs to be corrected or added, let the interviewer know that at the outset.
• Be familiar with your own employment agreement/policies and the terms that may be relevant to the discussion or meeting.
• Be calm, honest, and forthcoming in response to the questions, and don’t embellish or exaggerate.
• Avoid personal attacks on anyone. This generally serves to weaken an argument and credibility.
• Be prepared to explain your allegations or defense, and when you do so, keep in mind that the interviewer may not know the history, background, or details of any of the issues.
• If the reason for the situation relates to race or national origin, age, gender, sexual orientation, disability, or other protected category, don’t hesitate to say so.
• Answer the question you’re asked, but if you feel that the interviewer needs more information or is not understanding what you’ve said, feel free to explain. Be forthcoming, but don’t dominate the conversation.
• If they ask whether you have counsel, be honest, but decline to provide them any information about what you discussed with counsel, as those conversations are privileged.
• If the interviewer asks to record the conversation, you can agree, but ask to be provided a copy of the recording.
• Know your rights in advance. If the subject of the meeting is governed by bylaws or policies, for example, you may have the right to bring an attorney or adviser to the meeting, receive advance notice of who will be attending the meeting and the subject matter, and avail yourself of specific procedures or appeal rights of any discipline or decisions decided during the meeting.

There are many circumstances that can lead to a physician being under investigation or interrogation. In every single circumstance, it is ideal to seek legal counsel immediately. Whether the physician has actually engaged in wrongful conduct or not, without proper handling a physician’s career can be permanently, and sometimes irrevocably, affected.

Ms. Adler is a shareholder and health law practice group manager for Chicago-based law firm Roetzel, a member of the Illinois Association of Healthcare Attorneys, and a current advisory board member at DePaul College of Law Health Law Institute. She disclosed no relevant financial relationships.

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

In patients with persistent atopic dermatitis (AD) who are taking dupilumab, is there benefit of patch testing to determine if allergic contact dermatitis (ACD) also is contributing to their disease? Results of patch testing are likely be influenced by the immunomodulatory effects of dupilumab. Similar to the recommendation for patients to refrain from using topical or systemic corticosteroids for 1 week or more prior to patch testing to eliminate false negatives, we reviewed the literature to create practice guidelines for dermatologists regarding patch testing while a patient is taking dupilumab.

Pathophysiology and Pathomechanism

Dupilumab functions through the blockade of T helper 2 (T_H2) cells; ACD is propagated through the T helper 1 (T_H1) cellular pathway. However, patients with ACD that is unresponsive to allergen avoidance and traditional therapies, such as topical and oral corticosteroids, have responded to dupilumab. The more common reports of this responsiveness are with fragrances; multiple case series described patients with ACD to fragrance mix I¹ and balsam of Peru^1,2 who improved on dupilumab when other treatments failed. There also are reports of response when ACD was secondary to nickel,^2,3p-phenylenediamine,¹ Compositae,⁴ and non–formaldehyde-releasing preservatives (non-FRPs).⁵ Therefore, not all ACD is propagated through the T_H1 cellular pathway.

As noted in these cases, ACD can be a response to an allergen whose pathogenesis involves the T_H2 pathway or when patient characteristics favor a T_H2 response. It has been suggested that AD patients are more susceptible to T_H2-mediated contact sensitization to less-potent allergens, such as fragrances.⁶

Patch Test Results

Positive patch test results for allergens have been reported while patients are on dupilumab therapy, including a few studies in which results prior to starting dupilumab were compared with those while patients were on dupilumab therapy. In a retrospective chart review of 48 patients on dupilumab for AD with persistent disease, 23 patients were patch tested before and during dupilumab therapy. In these patients, the majority of contact allergies were persistent and only 10% (13/125) of patch test–positive results resolved on dupilumab therapy.⁷ Contact allergies that resolved included those to emulsifiers (propylene glycol, Amerchol L101 [lanolin-containing products found in cosmetics and other goods], dimethylaminopropylamine), fragrances (fragrance mix I, balsam of Peru), sunscreens (sulisobenzone, phenylbenzimidazole-5-sulfonic acid), and metals (vanadium chloride, phenylmercuric acetate).⁷ The following results observed in individual cases demonstrated conflicting findings: persistence of allergy to non-FRPs (methylisothiazolinone [MI]) but resolution of allergy to formaldehyde⁸; persistence of allergy to corticosteroids (budesonide and alclometasone)⁹; persistence of allergy to an antibiotic (neomycin sulfate) but resolution of allergies to a different antibiotic (bacitracin), glues (ethyl acrylate), bleach, and glutaraldehyde⁹; persistence of nickel allergy but resolution of allergies to fragrances (cinnamic aldehyde, balsam of Peru) and non-FRPs (methylchloroisothiazolinone or MI)¹⁰; and persistence of allergies to non-FRPs (MI) and FRPs (bronopol) but resolution of allergies to nickel, fragrances (hydroperoxides of linalool), and Compositae.¹¹ Additional case reports of positive patch test results while on dupilumab but with no pretreatment results for comparison include allergies to rubber additives,^12-14 nickel,¹⁴ textile dyes,¹⁴ cosmetic and hair care additives,^12,14,15 corticosteroids,¹⁵ FRPs,¹⁵ fragrances,^15,16 emulsifiers,¹⁶ and non-FRPs.¹⁷

An evident theme in the dupilumab patch-testing literature has been that results are variable and case specific: a given patient with ACD to an allergen will respond to dupilumab treatment and have subsequent negative patch testing, while another patient will not respond to dupilumab treatment and have persistent positive patch testing. This is likely because, in certain individuals, the allergen-immune system combination shifts ACD pathogenesis from a purely T_H1 response to at least a partial T_H2 response, thus allowing for benefit from dupilumab therapy. T helper 1 cell–mediated ACD should not be affected by dupilumab; therefore, reliable results can be elucidated from patch testing despite the drug.

Final Thoughts

We propose that AD patients with residual disease after taking dupilumab undergo patch testing. Positive results indicate allergens that are not inhibited by the drug. Patients will need to follow strict allergen avoidance to resolve this component of their disease; failure to improve might suggest the result was a nonrelevant positive.

If patch testing is negative, an alternative cause for residual disease must be sought. We do not recommend stopping dupilumab prior to patch testing to avoid a disease flare from AD or possible T_H2-mediated ACD.

In patients with persistent atopic dermatitis (AD) who are taking dupilumab, is there benefit of patch testing to determine if allergic contact dermatitis (ACD) also is contributing to their disease? Results of patch testing are likely be influenced by the immunomodulatory effects of dupilumab. Similar to the recommendation for patients to refrain from using topical or systemic corticosteroids for 1 week or more prior to patch testing to eliminate false negatives, we reviewed the literature to create practice guidelines for dermatologists regarding patch testing while a patient is taking dupilumab.

Pathophysiology and Pathomechanism

Dupilumab functions through the blockade of T helper 2 (T_H2) cells; ACD is propagated through the T helper 1 (T_H1) cellular pathway. However, patients with ACD that is unresponsive to allergen avoidance and traditional therapies, such as topical and oral corticosteroids, have responded to dupilumab. The more common reports of this responsiveness are with fragrances; multiple case series described patients with ACD to fragrance mix I¹ and balsam of Peru^1,2 who improved on dupilumab when other treatments failed. There also are reports of response when ACD was secondary to nickel,^2,3p-phenylenediamine,¹ Compositae,⁴ and non–formaldehyde-releasing preservatives (non-FRPs).⁵ Therefore, not all ACD is propagated through the T_H1 cellular pathway.

As noted in these cases, ACD can be a response to an allergen whose pathogenesis involves the T_H2 pathway or when patient characteristics favor a T_H2 response. It has been suggested that AD patients are more susceptible to T_H2-mediated contact sensitization to less-potent allergens, such as fragrances.⁶

Patch Test Results

Positive patch test results for allergens have been reported while patients are on dupilumab therapy, including a few studies in which results prior to starting dupilumab were compared with those while patients were on dupilumab therapy. In a retrospective chart review of 48 patients on dupilumab for AD with persistent disease, 23 patients were patch tested before and during dupilumab therapy. In these patients, the majority of contact allergies were persistent and only 10% (13/125) of patch test–positive results resolved on dupilumab therapy.⁷ Contact allergies that resolved included those to emulsifiers (propylene glycol, Amerchol L101 [lanolin-containing products found in cosmetics and other goods], dimethylaminopropylamine), fragrances (fragrance mix I, balsam of Peru), sunscreens (sulisobenzone, phenylbenzimidazole-5-sulfonic acid), and metals (vanadium chloride, phenylmercuric acetate).⁷ The following results observed in individual cases demonstrated conflicting findings: persistence of allergy to non-FRPs (methylisothiazolinone [MI]) but resolution of allergy to formaldehyde⁸; persistence of allergy to corticosteroids (budesonide and alclometasone)⁹; persistence of allergy to an antibiotic (neomycin sulfate) but resolution of allergies to a different antibiotic (bacitracin), glues (ethyl acrylate), bleach, and glutaraldehyde⁹; persistence of nickel allergy but resolution of allergies to fragrances (cinnamic aldehyde, balsam of Peru) and non-FRPs (methylchloroisothiazolinone or MI)¹⁰; and persistence of allergies to non-FRPs (MI) and FRPs (bronopol) but resolution of allergies to nickel, fragrances (hydroperoxides of linalool), and Compositae.¹¹ Additional case reports of positive patch test results while on dupilumab but with no pretreatment results for comparison include allergies to rubber additives,^12-14 nickel,¹⁴ textile dyes,¹⁴ cosmetic and hair care additives,^12,14,15 corticosteroids,¹⁵ FRPs,¹⁵ fragrances,^15,16 emulsifiers,¹⁶ and non-FRPs.¹⁷

An evident theme in the dupilumab patch-testing literature has been that results are variable and case specific: a given patient with ACD to an allergen will respond to dupilumab treatment and have subsequent negative patch testing, while another patient will not respond to dupilumab treatment and have persistent positive patch testing. This is likely because, in certain individuals, the allergen-immune system combination shifts ACD pathogenesis from a purely T_H1 response to at least a partial T_H2 response, thus allowing for benefit from dupilumab therapy. T helper 1 cell–mediated ACD should not be affected by dupilumab; therefore, reliable results can be elucidated from patch testing despite the drug.

Final Thoughts

We propose that AD patients with residual disease after taking dupilumab undergo patch testing. Positive results indicate allergens that are not inhibited by the drug. Patients will need to follow strict allergen avoidance to resolve this component of their disease; failure to improve might suggest the result was a nonrelevant positive.

If patch testing is negative, an alternative cause for residual disease must be sought. We do not recommend stopping dupilumab prior to patch testing to avoid a disease flare from AD or possible T_H2-mediated ACD.

In patients with persistent atopic dermatitis (AD) who are taking dupilumab, is there benefit of patch testing to determine if allergic contact dermatitis (ACD) also is contributing to their disease? Results of patch testing are likely be influenced by the immunomodulatory effects of dupilumab. Similar to the recommendation for patients to refrain from using topical or systemic corticosteroids for 1 week or more prior to patch testing to eliminate false negatives, we reviewed the literature to create practice guidelines for dermatologists regarding patch testing while a patient is taking dupilumab.

Pathophysiology and Pathomechanism

Dupilumab functions through the blockade of T helper 2 (T_H2) cells; ACD is propagated through the T helper 1 (T_H1) cellular pathway. However, patients with ACD that is unresponsive to allergen avoidance and traditional therapies, such as topical and oral corticosteroids, have responded to dupilumab. The more common reports of this responsiveness are with fragrances; multiple case series described patients with ACD to fragrance mix I¹ and balsam of Peru^1,2 who improved on dupilumab when other treatments failed. There also are reports of response when ACD was secondary to nickel,^2,3p-phenylenediamine,¹ Compositae,⁴ and non–formaldehyde-releasing preservatives (non-FRPs).⁵ Therefore, not all ACD is propagated through the T_H1 cellular pathway.

As noted in these cases, ACD can be a response to an allergen whose pathogenesis involves the T_H2 pathway or when patient characteristics favor a T_H2 response. It has been suggested that AD patients are more susceptible to T_H2-mediated contact sensitization to less-potent allergens, such as fragrances.⁶

Patch Test Results

Positive patch test results for allergens have been reported while patients are on dupilumab therapy, including a few studies in which results prior to starting dupilumab were compared with those while patients were on dupilumab therapy. In a retrospective chart review of 48 patients on dupilumab for AD with persistent disease, 23 patients were patch tested before and during dupilumab therapy. In these patients, the majority of contact allergies were persistent and only 10% (13/125) of patch test–positive results resolved on dupilumab therapy.⁷ Contact allergies that resolved included those to emulsifiers (propylene glycol, Amerchol L101 [lanolin-containing products found in cosmetics and other goods], dimethylaminopropylamine), fragrances (fragrance mix I, balsam of Peru), sunscreens (sulisobenzone, phenylbenzimidazole-5-sulfonic acid), and metals (vanadium chloride, phenylmercuric acetate).⁷ The following results observed in individual cases demonstrated conflicting findings: persistence of allergy to non-FRPs (methylisothiazolinone [MI]) but resolution of allergy to formaldehyde⁸; persistence of allergy to corticosteroids (budesonide and alclometasone)⁹; persistence of allergy to an antibiotic (neomycin sulfate) but resolution of allergies to a different antibiotic (bacitracin), glues (ethyl acrylate), bleach, and glutaraldehyde⁹; persistence of nickel allergy but resolution of allergies to fragrances (cinnamic aldehyde, balsam of Peru) and non-FRPs (methylchloroisothiazolinone or MI)¹⁰; and persistence of allergies to non-FRPs (MI) and FRPs (bronopol) but resolution of allergies to nickel, fragrances (hydroperoxides of linalool), and Compositae.¹¹ Additional case reports of positive patch test results while on dupilumab but with no pretreatment results for comparison include allergies to rubber additives,^12-14 nickel,¹⁴ textile dyes,¹⁴ cosmetic and hair care additives,^12,14,15 corticosteroids,¹⁵ FRPs,¹⁵ fragrances,^15,16 emulsifiers,¹⁶ and non-FRPs.¹⁷

An evident theme in the dupilumab patch-testing literature has been that results are variable and case specific: a given patient with ACD to an allergen will respond to dupilumab treatment and have subsequent negative patch testing, while another patient will not respond to dupilumab treatment and have persistent positive patch testing. This is likely because, in certain individuals, the allergen-immune system combination shifts ACD pathogenesis from a purely T_H1 response to at least a partial T_H2 response, thus allowing for benefit from dupilumab therapy. T helper 1 cell–mediated ACD should not be affected by dupilumab; therefore, reliable results can be elucidated from patch testing despite the drug.

Final Thoughts

We propose that AD patients with residual disease after taking dupilumab undergo patch testing. Positive results indicate allergens that are not inhibited by the drug. Patients will need to follow strict allergen avoidance to resolve this component of their disease; failure to improve might suggest the result was a nonrelevant positive.

If patch testing is negative, an alternative cause for residual disease must be sought. We do not recommend stopping dupilumab prior to patch testing to avoid a disease flare from AD or possible T_H2-mediated ACD.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder affecting 7% of adults and 13% of children in the United States.^1,2 Atopic dermatitis is characterized by pruritus, dry skin, and pain, all of which can negatively impact quality of life and put patients at higher risk for psychiatric comorbidities such as anxiety and depression.³ The pathogenesis of AD is multifactorial, involving genetics, epidermal barrier dysfunction, and immune dysregulation. Overactivation of helper T cell (T_H2) pathway cytokines, including IL-4, IL-13, and IL-31, is thought to propagate both inflammation and pruritus, which are central to AD. The JAK-STAT signaling pathway plays a pivotal role in the immune system dysregulation and exaggeration of T_H2 cell response, making JAK-STAT inhibitors (or JAK inhibitors) strong theoretical candidates for the treatment of AD.⁴ In humans, the Janus kinases are composed of 4 different members—JAK1, JAK2, JAK3, and tyrosine kinase 2—all of which can be targeted by JAK inhibitors.⁵

JAK inhibitors such as tofacitinib have already been approved by the US Food and Drug Administration (FDA) to treat various inflammatory conditions, including rheumatoid arthritis, ulcerative colitis, and psoriatic arthritis; other JAK inhibitors such as baricitinib are only approved for patients with rheumatoid arthritis.^6,7 The success of these small molecule inhibitors in these immune-mediated conditions make them attractive candidates for the treatment of AD. Several JAK inhibitors are in phase 2 and phase 3 clinical trials as oral therapies (moderate to severe AD) or as topical treatments (mild to moderate AD). Currently, ruxolitinib (RUX) is the only topical JAK inhibitor that is FDA approved for the treatment of AD in the United States.⁸ In this editorial, we focus on recent trials of JAK inhibitors tested in patients with AD, including topical RUX, as well as oral abrocitinib, upadacitinib, and baricitinib.

Topical RUX in AD

Ruxolitinib is a topical JAK1/2 small molecule inhibitor approved by the FDA for the treatment of AD in 2021. In a randomized trial by Kim et al⁹ in 2020, all tested regimens of RUX demonstrated significant improvement in eczema area and severity index (EASI) scores vs vehicle; notably, RUX cream 1.5% applied twice daily achieved the greatest mean percentage change in baseline EASI score vs vehicle at 4 weeks (76.1% vs 15.5%; P<.0001). Ruxolitinib cream was well tolerated through week 8 of the trial, and all adverse events (AEs) were mild to moderate in severity and comparable to those in the vehicle group.⁹

Topical JAK inhibitors appear to be effective for mild to moderate AD and have had an acceptable safety profile in clinical trials thus far. Although topical corticosteroids and calcineurin inhibitors can have great clinical benefit in AD, they are recommended for short-term use given side effects such as thinning of the skin, burning, or telangiectasia formation.^10,11 The hope is that topical JAK inhibitors may be an alternative to standard topical treatments for AD, as they can be used for longer periods due to a safer side-effect profile.

Oral JAK Inhibitors in AD

Several oral JAK inhibitors are undergoing investigation for the systemic treatment of moderate to severe AD. Abrocitinib is an oral JAK1 inhibitor that has demonstrated efficacy in several phase 3 trials in patients with moderate to severe AD. In a 2021 trial, patients were randomized in a 2:2:2:1 ratio to receive abrocitinib 200 mg daily, abrocitinib 100 mg daily, subcutaneous dupilumab 300 mg every other week, or placebo, respectively.¹² Patients in both abrocitinib groups showed significant improvement in AD vs placebo, and EASI-75 response was achieved in 70.3%, 58.7%, 58.1%, and 27.1% of patients, respectively (P<.001 for both abrocitinib doses vs placebo). Adverse events occurred more frequently in the abrocitinib 200-mg group vs placebo. Nausea, acne, nasopharyngitis, and headache were the most frequently reported AEs with abrocitinib.¹² Another phase 3 trial by Silverberg et al¹³ (N=391) had similar treatment results, with 38.1% of participants receiving abrocitinib 200 mg and 28.4% of participants receiving abrocitinib 100 mg achieving investigator global assessment scores of 0 (clear) or 1 (almost clear) vs 9.1% of participants receiving placebo (P<.001). Abrocitinib was well tolerated in this trial with few serious AEs (ie, herpangina [0.6%], pneumonia [0.6%]).¹³ In both trials, there were rare instances of laboratory values indicating thrombocytopenia with the 200-mg dose (0.9%¹² and 3.2%¹³) without any clinical manifestations. Although a decrease in platelets was observed, no thrombocytopenia occurred in the abrocitinib 100-mg group in the latter trial.¹³

Baricitinib is another oral inhibitor of JAK1 and JAK2 with potential for the treatment of AD. One randomized trial (N=329) demonstrated its efficacy in combination with a topical corticosteroid (TCS). At 16 weeks, a higher number of participants treated with baricitinib and TCS achieved investigator global assessment scores of 0 (clear) or 1 (almost clear) compared to those who received placebo and TCS (31% with baricitinib 4 mg + TCS, 24% with baricitinib 2 mg + TCS, and 15% with placebo + TCS).¹⁴ Similarly, in BREEZE-AD5,another phase 3 trial (N=440), baricitinib monotherapy demonstrated a higher rate of treatment success vs placebo.¹⁵ Specifically, 13% of patients treated with baricitinib 1 mg and 30% of those treated with baricitinib 2 mg achieved 75% or greater reduction in EASI scores compared to 8% in the placebo group. The most common AEs associated with baricitinib were nasopharyngitis and headache. Adverse events occurred with similar frequency across both experimental and control groups.¹⁵ Reich et al¹⁴ demonstrated a higher overall rate of AEs—most commonly nasopharyngitis, upper respiratory tract infections, and folliculitis—in baricitinib-treated patients; however, serious AEs occurred with similar frequency across all groups, including the control group.

The selective JAK1 inhibitor upadacitinib also is undergoing testing in treating moderate to severe AD. In one trial, 167 patients were randomized to once daily oral upadacitinib 7.5 mg, 15 mg, or 30 mg or placebo.¹⁶ All doses of upadacitinib demonstrated considerably higher percentage improvements from baseline in EASI scores compared to placebo at 16 weeks with a clear dose-response relationship (39%, 62%, and 74% vs 23%, respectively). In this trial, there were no dose-limiting safety events. Serious AEs were infrequent, occurring in 4.8%, 2.4%, and 0% of upadacitinib groups vs 2.5% for placebo. The serious AEs observed with upadacitinib were 1 case of appendicitis, lower jaw pericoronitis in a patient with a history of repeated tooth infections, and an exacerbation of AD.¹⁶

Tofacitinib, another JAK inhibitor, has been shown to increase the risk for blood clots and death in a large trial in the treatment of rheumatoid arthritis. Following this study, the FDA is requiring black box warnings for tofacitinib and also for the 2 JAK inhibitors baricitinib and upadacitinib regarding the risks for heart-related events, cancer, blood clots, and death. Given that these medications share a similar mechanism of action to tofacitinib, they may have similar risks, though they have not yet been fully evaluated in large safety trials.¹⁷

With more recent investigation into novel therapeutics for AD, oral JAK inhibitors may play an important role in the future to treat patients with moderate to severe AD with inadequate response or contraindications to other systemic therapies. In trials thus far, oral JAK inhibitors have exhibited acceptable safety profiles and have demonstrated treatment success in AD. More randomized, controlled, phase 3 studies with larger patient populations are required to confirm their potential as effective treatments and elucidate their long-term safety.

Deucravacitinib in Psoriasis

Deucravacitinib is a first-in-class, oral, selective TYK2 inhibitor currently undergoing testing for the treatment of psoriasis. A randomized phase 2 trial (N=267) found that deucravacitinib was more effective than placebo in treating chronic plaque psoriasis at doses of 3 to 12 mg daily.¹⁸ The percentage of participants with a 75% or greater reduction from baseline in the psoriasis area and severity index score was 7% with placebo, 9% with deucravacitinib 3 mg every other day (P=.49 vs placebo), 39% with 3 mg once daily (P<.001 vs placebo), 69% with 3 mg twice daily (P<.001 vs placebo), 67% with 6 mg twice daily (P<.001 vs placebo), and 75% with 12 mg once daily (P<.001 vs placebo). The most commonly reported AEs were nasopharyngitis, headache, diarrhea, nausea, and upper respiratory tract infection. Adverse events occurred in 51% of participants in the control group and in 55% to 80% of those in the experimental groups. Additionally, there was 1 reported case of melanoma (stage 0) 96 days after the start of treatment in a patient in the 3-mg once-daily group. Serious AEs occurred in only 0% to 2% of participants who received deucravacitinib.¹⁸

Two phase 3 trials—POETYK PSO-1 and POETYK PSO-2 (N=1686)—found deucravacitinib to be notably more effective than both placebo and apremilast in treating psoriasis.¹⁹ Among participants receiving deucravacitinib 6 mg daily, 58.7% and 53.6% in the 2 respective trials achieved psoriasis area and severity index 75 response vs 12.7% and 9.4% receiving placebo and 35.1% and 40.2% receiving apremilast. Overall, the treatment was well tolerated, with a low rate of discontinuation of deucravacitinib due to AEs (2.4% of patients on deucravacitinib compared to 3.8% on placebo and 5.2% on apremilast). The most frequently observed AEs with deucravacitinib were nasopharyngitis and upper respiratory tract infection. The full results of these trials are expected to be published soon.^19,20

Final Thoughts

Overall, JAK inhibitors are a novel class of therapeutics that may have further success in the treatment of other dermatologic conditions that negatively affect patients’ quality of life and productivity. We should look forward to additional successful trials with these promising medications.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder affecting 7% of adults and 13% of children in the United States.^1,2 Atopic dermatitis is characterized by pruritus, dry skin, and pain, all of which can negatively impact quality of life and put patients at higher risk for psychiatric comorbidities such as anxiety and depression.³ The pathogenesis of AD is multifactorial, involving genetics, epidermal barrier dysfunction, and immune dysregulation. Overactivation of helper T cell (T_H2) pathway cytokines, including IL-4, IL-13, and IL-31, is thought to propagate both inflammation and pruritus, which are central to AD. The JAK-STAT signaling pathway plays a pivotal role in the immune system dysregulation and exaggeration of T_H2 cell response, making JAK-STAT inhibitors (or JAK inhibitors) strong theoretical candidates for the treatment of AD.⁴ In humans, the Janus kinases are composed of 4 different members—JAK1, JAK2, JAK3, and tyrosine kinase 2—all of which can be targeted by JAK inhibitors.⁵

JAK inhibitors such as tofacitinib have already been approved by the US Food and Drug Administration (FDA) to treat various inflammatory conditions, including rheumatoid arthritis, ulcerative colitis, and psoriatic arthritis; other JAK inhibitors such as baricitinib are only approved for patients with rheumatoid arthritis.^6,7 The success of these small molecule inhibitors in these immune-mediated conditions make them attractive candidates for the treatment of AD. Several JAK inhibitors are in phase 2 and phase 3 clinical trials as oral therapies (moderate to severe AD) or as topical treatments (mild to moderate AD). Currently, ruxolitinib (RUX) is the only topical JAK inhibitor that is FDA approved for the treatment of AD in the United States.⁸ In this editorial, we focus on recent trials of JAK inhibitors tested in patients with AD, including topical RUX, as well as oral abrocitinib, upadacitinib, and baricitinib.

Topical RUX in AD

Ruxolitinib is a topical JAK1/2 small molecule inhibitor approved by the FDA for the treatment of AD in 2021. In a randomized trial by Kim et al⁹ in 2020, all tested regimens of RUX demonstrated significant improvement in eczema area and severity index (EASI) scores vs vehicle; notably, RUX cream 1.5% applied twice daily achieved the greatest mean percentage change in baseline EASI score vs vehicle at 4 weeks (76.1% vs 15.5%; P<.0001). Ruxolitinib cream was well tolerated through week 8 of the trial, and all adverse events (AEs) were mild to moderate in severity and comparable to those in the vehicle group.⁹

Topical JAK inhibitors appear to be effective for mild to moderate AD and have had an acceptable safety profile in clinical trials thus far. Although topical corticosteroids and calcineurin inhibitors can have great clinical benefit in AD, they are recommended for short-term use given side effects such as thinning of the skin, burning, or telangiectasia formation.^10,11 The hope is that topical JAK inhibitors may be an alternative to standard topical treatments for AD, as they can be used for longer periods due to a safer side-effect profile.

Oral JAK Inhibitors in AD

Several oral JAK inhibitors are undergoing investigation for the systemic treatment of moderate to severe AD. Abrocitinib is an oral JAK1 inhibitor that has demonstrated efficacy in several phase 3 trials in patients with moderate to severe AD. In a 2021 trial, patients were randomized in a 2:2:2:1 ratio to receive abrocitinib 200 mg daily, abrocitinib 100 mg daily, subcutaneous dupilumab 300 mg every other week, or placebo, respectively.¹² Patients in both abrocitinib groups showed significant improvement in AD vs placebo, and EASI-75 response was achieved in 70.3%, 58.7%, 58.1%, and 27.1% of patients, respectively (P<.001 for both abrocitinib doses vs placebo). Adverse events occurred more frequently in the abrocitinib 200-mg group vs placebo. Nausea, acne, nasopharyngitis, and headache were the most frequently reported AEs with abrocitinib.¹² Another phase 3 trial by Silverberg et al¹³ (N=391) had similar treatment results, with 38.1% of participants receiving abrocitinib 200 mg and 28.4% of participants receiving abrocitinib 100 mg achieving investigator global assessment scores of 0 (clear) or 1 (almost clear) vs 9.1% of participants receiving placebo (P<.001). Abrocitinib was well tolerated in this trial with few serious AEs (ie, herpangina [0.6%], pneumonia [0.6%]).¹³ In both trials, there were rare instances of laboratory values indicating thrombocytopenia with the 200-mg dose (0.9%¹² and 3.2%¹³) without any clinical manifestations. Although a decrease in platelets was observed, no thrombocytopenia occurred in the abrocitinib 100-mg group in the latter trial.¹³

Baricitinib is another oral inhibitor of JAK1 and JAK2 with potential for the treatment of AD. One randomized trial (N=329) demonstrated its efficacy in combination with a topical corticosteroid (TCS). At 16 weeks, a higher number of participants treated with baricitinib and TCS achieved investigator global assessment scores of 0 (clear) or 1 (almost clear) compared to those who received placebo and TCS (31% with baricitinib 4 mg + TCS, 24% with baricitinib 2 mg + TCS, and 15% with placebo + TCS).¹⁴ Similarly, in BREEZE-AD5,another phase 3 trial (N=440), baricitinib monotherapy demonstrated a higher rate of treatment success vs placebo.¹⁵ Specifically, 13% of patients treated with baricitinib 1 mg and 30% of those treated with baricitinib 2 mg achieved 75% or greater reduction in EASI scores compared to 8% in the placebo group. The most common AEs associated with baricitinib were nasopharyngitis and headache. Adverse events occurred with similar frequency across both experimental and control groups.¹⁵ Reich et al¹⁴ demonstrated a higher overall rate of AEs—most commonly nasopharyngitis, upper respiratory tract infections, and folliculitis—in baricitinib-treated patients; however, serious AEs occurred with similar frequency across all groups, including the control group.

The selective JAK1 inhibitor upadacitinib also is undergoing testing in treating moderate to severe AD. In one trial, 167 patients were randomized to once daily oral upadacitinib 7.5 mg, 15 mg, or 30 mg or placebo.¹⁶ All doses of upadacitinib demonstrated considerably higher percentage improvements from baseline in EASI scores compared to placebo at 16 weeks with a clear dose-response relationship (39%, 62%, and 74% vs 23%, respectively). In this trial, there were no dose-limiting safety events. Serious AEs were infrequent, occurring in 4.8%, 2.4%, and 0% of upadacitinib groups vs 2.5% for placebo. The serious AEs observed with upadacitinib were 1 case of appendicitis, lower jaw pericoronitis in a patient with a history of repeated tooth infections, and an exacerbation of AD.¹⁶

Tofacitinib, another JAK inhibitor, has been shown to increase the risk for blood clots and death in a large trial in the treatment of rheumatoid arthritis. Following this study, the FDA is requiring black box warnings for tofacitinib and also for the 2 JAK inhibitors baricitinib and upadacitinib regarding the risks for heart-related events, cancer, blood clots, and death. Given that these medications share a similar mechanism of action to tofacitinib, they may have similar risks, though they have not yet been fully evaluated in large safety trials.¹⁷

With more recent investigation into novel therapeutics for AD, oral JAK inhibitors may play an important role in the future to treat patients with moderate to severe AD with inadequate response or contraindications to other systemic therapies. In trials thus far, oral JAK inhibitors have exhibited acceptable safety profiles and have demonstrated treatment success in AD. More randomized, controlled, phase 3 studies with larger patient populations are required to confirm their potential as effective treatments and elucidate their long-term safety.

Deucravacitinib in Psoriasis

Deucravacitinib is a first-in-class, oral, selective TYK2 inhibitor currently undergoing testing for the treatment of psoriasis. A randomized phase 2 trial (N=267) found that deucravacitinib was more effective than placebo in treating chronic plaque psoriasis at doses of 3 to 12 mg daily.¹⁸ The percentage of participants with a 75% or greater reduction from baseline in the psoriasis area and severity index score was 7% with placebo, 9% with deucravacitinib 3 mg every other day (P=.49 vs placebo), 39% with 3 mg once daily (P<.001 vs placebo), 69% with 3 mg twice daily (P<.001 vs placebo), 67% with 6 mg twice daily (P<.001 vs placebo), and 75% with 12 mg once daily (P<.001 vs placebo). The most commonly reported AEs were nasopharyngitis, headache, diarrhea, nausea, and upper respiratory tract infection. Adverse events occurred in 51% of participants in the control group and in 55% to 80% of those in the experimental groups. Additionally, there was 1 reported case of melanoma (stage 0) 96 days after the start of treatment in a patient in the 3-mg once-daily group. Serious AEs occurred in only 0% to 2% of participants who received deucravacitinib.¹⁸

Two phase 3 trials—POETYK PSO-1 and POETYK PSO-2 (N=1686)—found deucravacitinib to be notably more effective than both placebo and apremilast in treating psoriasis.¹⁹ Among participants receiving deucravacitinib 6 mg daily, 58.7% and 53.6% in the 2 respective trials achieved psoriasis area and severity index 75 response vs 12.7% and 9.4% receiving placebo and 35.1% and 40.2% receiving apremilast. Overall, the treatment was well tolerated, with a low rate of discontinuation of deucravacitinib due to AEs (2.4% of patients on deucravacitinib compared to 3.8% on placebo and 5.2% on apremilast). The most frequently observed AEs with deucravacitinib were nasopharyngitis and upper respiratory tract infection. The full results of these trials are expected to be published soon.^19,20

Final Thoughts

Overall, JAK inhibitors are a novel class of therapeutics that may have further success in the treatment of other dermatologic conditions that negatively affect patients’ quality of life and productivity. We should look forward to additional successful trials with these promising medications.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder affecting 7% of adults and 13% of children in the United States.^1,2 Atopic dermatitis is characterized by pruritus, dry skin, and pain, all of which can negatively impact quality of life and put patients at higher risk for psychiatric comorbidities such as anxiety and depression.³ The pathogenesis of AD is multifactorial, involving genetics, epidermal barrier dysfunction, and immune dysregulation. Overactivation of helper T cell (T_H2) pathway cytokines, including IL-4, IL-13, and IL-31, is thought to propagate both inflammation and pruritus, which are central to AD. The JAK-STAT signaling pathway plays a pivotal role in the immune system dysregulation and exaggeration of T_H2 cell response, making JAK-STAT inhibitors (or JAK inhibitors) strong theoretical candidates for the treatment of AD.⁴ In humans, the Janus kinases are composed of 4 different members—JAK1, JAK2, JAK3, and tyrosine kinase 2—all of which can be targeted by JAK inhibitors.⁵

JAK inhibitors such as tofacitinib have already been approved by the US Food and Drug Administration (FDA) to treat various inflammatory conditions, including rheumatoid arthritis, ulcerative colitis, and psoriatic arthritis; other JAK inhibitors such as baricitinib are only approved for patients with rheumatoid arthritis.^6,7 The success of these small molecule inhibitors in these immune-mediated conditions make them attractive candidates for the treatment of AD. Several JAK inhibitors are in phase 2 and phase 3 clinical trials as oral therapies (moderate to severe AD) or as topical treatments (mild to moderate AD). Currently, ruxolitinib (RUX) is the only topical JAK inhibitor that is FDA approved for the treatment of AD in the United States.⁸ In this editorial, we focus on recent trials of JAK inhibitors tested in patients with AD, including topical RUX, as well as oral abrocitinib, upadacitinib, and baricitinib.

Topical RUX in AD

Ruxolitinib is a topical JAK1/2 small molecule inhibitor approved by the FDA for the treatment of AD in 2021. In a randomized trial by Kim et al⁹ in 2020, all tested regimens of RUX demonstrated significant improvement in eczema area and severity index (EASI) scores vs vehicle; notably, RUX cream 1.5% applied twice daily achieved the greatest mean percentage change in baseline EASI score vs vehicle at 4 weeks (76.1% vs 15.5%; P<.0001). Ruxolitinib cream was well tolerated through week 8 of the trial, and all adverse events (AEs) were mild to moderate in severity and comparable to those in the vehicle group.⁹

Topical JAK inhibitors appear to be effective for mild to moderate AD and have had an acceptable safety profile in clinical trials thus far. Although topical corticosteroids and calcineurin inhibitors can have great clinical benefit in AD, they are recommended for short-term use given side effects such as thinning of the skin, burning, or telangiectasia formation.^10,11 The hope is that topical JAK inhibitors may be an alternative to standard topical treatments for AD, as they can be used for longer periods due to a safer side-effect profile.

Oral JAK Inhibitors in AD

Several oral JAK inhibitors are undergoing investigation for the systemic treatment of moderate to severe AD. Abrocitinib is an oral JAK1 inhibitor that has demonstrated efficacy in several phase 3 trials in patients with moderate to severe AD. In a 2021 trial, patients were randomized in a 2:2:2:1 ratio to receive abrocitinib 200 mg daily, abrocitinib 100 mg daily, subcutaneous dupilumab 300 mg every other week, or placebo, respectively.¹² Patients in both abrocitinib groups showed significant improvement in AD vs placebo, and EASI-75 response was achieved in 70.3%, 58.7%, 58.1%, and 27.1% of patients, respectively (P<.001 for both abrocitinib doses vs placebo). Adverse events occurred more frequently in the abrocitinib 200-mg group vs placebo. Nausea, acne, nasopharyngitis, and headache were the most frequently reported AEs with abrocitinib.¹² Another phase 3 trial by Silverberg et al¹³ (N=391) had similar treatment results, with 38.1% of participants receiving abrocitinib 200 mg and 28.4% of participants receiving abrocitinib 100 mg achieving investigator global assessment scores of 0 (clear) or 1 (almost clear) vs 9.1% of participants receiving placebo (P<.001). Abrocitinib was well tolerated in this trial with few serious AEs (ie, herpangina [0.6%], pneumonia [0.6%]).¹³ In both trials, there were rare instances of laboratory values indicating thrombocytopenia with the 200-mg dose (0.9%¹² and 3.2%¹³) without any clinical manifestations. Although a decrease in platelets was observed, no thrombocytopenia occurred in the abrocitinib 100-mg group in the latter trial.¹³

Baricitinib is another oral inhibitor of JAK1 and JAK2 with potential for the treatment of AD. One randomized trial (N=329) demonstrated its efficacy in combination with a topical corticosteroid (TCS). At 16 weeks, a higher number of participants treated with baricitinib and TCS achieved investigator global assessment scores of 0 (clear) or 1 (almost clear) compared to those who received placebo and TCS (31% with baricitinib 4 mg + TCS, 24% with baricitinib 2 mg + TCS, and 15% with placebo + TCS).¹⁴ Similarly, in BREEZE-AD5,another phase 3 trial (N=440), baricitinib monotherapy demonstrated a higher rate of treatment success vs placebo.¹⁵ Specifically, 13% of patients treated with baricitinib 1 mg and 30% of those treated with baricitinib 2 mg achieved 75% or greater reduction in EASI scores compared to 8% in the placebo group. The most common AEs associated with baricitinib were nasopharyngitis and headache. Adverse events occurred with similar frequency across both experimental and control groups.¹⁵ Reich et al¹⁴ demonstrated a higher overall rate of AEs—most commonly nasopharyngitis, upper respiratory tract infections, and folliculitis—in baricitinib-treated patients; however, serious AEs occurred with similar frequency across all groups, including the control group.

The selective JAK1 inhibitor upadacitinib also is undergoing testing in treating moderate to severe AD. In one trial, 167 patients were randomized to once daily oral upadacitinib 7.5 mg, 15 mg, or 30 mg or placebo.¹⁶ All doses of upadacitinib demonstrated considerably higher percentage improvements from baseline in EASI scores compared to placebo at 16 weeks with a clear dose-response relationship (39%, 62%, and 74% vs 23%, respectively). In this trial, there were no dose-limiting safety events. Serious AEs were infrequent, occurring in 4.8%, 2.4%, and 0% of upadacitinib groups vs 2.5% for placebo. The serious AEs observed with upadacitinib were 1 case of appendicitis, lower jaw pericoronitis in a patient with a history of repeated tooth infections, and an exacerbation of AD.¹⁶

Tofacitinib, another JAK inhibitor, has been shown to increase the risk for blood clots and death in a large trial in the treatment of rheumatoid arthritis. Following this study, the FDA is requiring black box warnings for tofacitinib and also for the 2 JAK inhibitors baricitinib and upadacitinib regarding the risks for heart-related events, cancer, blood clots, and death. Given that these medications share a similar mechanism of action to tofacitinib, they may have similar risks, though they have not yet been fully evaluated in large safety trials.¹⁷

With more recent investigation into novel therapeutics for AD, oral JAK inhibitors may play an important role in the future to treat patients with moderate to severe AD with inadequate response or contraindications to other systemic therapies. In trials thus far, oral JAK inhibitors have exhibited acceptable safety profiles and have demonstrated treatment success in AD. More randomized, controlled, phase 3 studies with larger patient populations are required to confirm their potential as effective treatments and elucidate their long-term safety.

Deucravacitinib in Psoriasis

Deucravacitinib is a first-in-class, oral, selective TYK2 inhibitor currently undergoing testing for the treatment of psoriasis. A randomized phase 2 trial (N=267) found that deucravacitinib was more effective than placebo in treating chronic plaque psoriasis at doses of 3 to 12 mg daily.¹⁸ The percentage of participants with a 75% or greater reduction from baseline in the psoriasis area and severity index score was 7% with placebo, 9% with deucravacitinib 3 mg every other day (P=.49 vs placebo), 39% with 3 mg once daily (P<.001 vs placebo), 69% with 3 mg twice daily (P<.001 vs placebo), 67% with 6 mg twice daily (P<.001 vs placebo), and 75% with 12 mg once daily (P<.001 vs placebo). The most commonly reported AEs were nasopharyngitis, headache, diarrhea, nausea, and upper respiratory tract infection. Adverse events occurred in 51% of participants in the control group and in 55% to 80% of those in the experimental groups. Additionally, there was 1 reported case of melanoma (stage 0) 96 days after the start of treatment in a patient in the 3-mg once-daily group. Serious AEs occurred in only 0% to 2% of participants who received deucravacitinib.¹⁸

Two phase 3 trials—POETYK PSO-1 and POETYK PSO-2 (N=1686)—found deucravacitinib to be notably more effective than both placebo and apremilast in treating psoriasis.¹⁹ Among participants receiving deucravacitinib 6 mg daily, 58.7% and 53.6% in the 2 respective trials achieved psoriasis area and severity index 75 response vs 12.7% and 9.4% receiving placebo and 35.1% and 40.2% receiving apremilast. Overall, the treatment was well tolerated, with a low rate of discontinuation of deucravacitinib due to AEs (2.4% of patients on deucravacitinib compared to 3.8% on placebo and 5.2% on apremilast). The most frequently observed AEs with deucravacitinib were nasopharyngitis and upper respiratory tract infection. The full results of these trials are expected to be published soon.^19,20

Final Thoughts

Overall, JAK inhibitors are a novel class of therapeutics that may have further success in the treatment of other dermatologic conditions that negatively affect patients’ quality of life and productivity. We should look forward to additional successful trials with these promising medications.

I was taught to think clinically first and legally second. There are moments when following every regulation is clearly detrimental to the well-being of both the patient and the medical community at large, and these challenges have been highlighted by issues with telemental health during the pandemic.

A friend emailed me with a problem: He has a son who is a traveling nurse and is currently in psychotherapy. The therapist has, in accordance with licensing requirements, told his son that she can not see him when assignments take him to any state where she is not licensed. The patient needs to physically be in the same state where the clinician holds a license, technically for every appointment. The nursing assignments last for 3 months and he will be going to a variety of states. Does he really need to get a new therapist every 90 days?

The logistics seem mind-boggling in a time when there is a shortage of mental health professionals, and there are often long wait lists to get care. And even if it was all easy, I’ll point out that working with a therapist is a bit different then going to an urgent care center to have sutures removed or to obtain antibiotics for strep throat: The relationship is not easily interchangeable, and I know of no one who would think it clinically optimal for anyone to change psychotherapists every 3 months. The traveling nurse does not just need to find a “provider” in each state, he needs to find one he is comfortable with and he will have to spend several sessions relaying his history and forming a new therapeutic alliance. And given the ambiguities of psychotherapy, he would optimally see therapists who do not make conflicting interpretations or recommendations. Mind-boggling. And while none of us are irreplaceable, it feels heartless to tell someone who is traveling to provide medical care to others during a pandemic that they can’t have mental health care when our technology would allow for it.

In the “old days” it was simpler: Patients came to the office and both the patient and the clinician were physically located in the same state, even if the patient resided in another state and commuted hours to the appointment. Telemental health was done in select rural areas or in military settings, and most physicians did not consider the option for video visits, much less full video treatment. For the average practitioner, issues of location were not relevant. The exception was for college students who might reside in one state and see a psychiatrist or therapist in another, but typically everyone was comfortable taking a break from therapy when the patient could not meet with the therapist in person. If psychiatrists were having phone or video sessions with out-of-state patients on an occasional basis, it may have been because there was less scrutiny and it was less obvious that this was not permitted.

When the pandemic forced treatment to go online, the issues changed. At the beginning, issues related to state licensing were waived. Now each state has a different requirement with regard to out-of-state physicians; some allow their residents to be seen, while others require the physician to get licensed in their state and the process may or may not be costly or arduous for the provider. The regulations change frequently, and can be quite confusing to follow. Since psychiatry is a shortage field, many psychiatrists are not looking to have more patients from other states and are not motivated to apply for extra licenses.

Life as a practicing psychiatrist has been a moving target: I reopened my practice for some in-person visits for vaccinated patients in June 2021, then closed it when the Omicron surge seemed too risky, and I’ll be reopening soon. Patients, too, have had unpredictable lives.

For the practitioner who is following the rules precisely, the issues can be sticky. It may be fine to have Zoom visits with a patient who lives across the street, but not with the elderly patient who has to drive 90 minutes across a state line, and it’s always fine to have a video session with a patient in Guam. If a patient signs on for a video visit with a doctor licensed in Maine and announces there will be a visit to a brother in Michigan, does the clinician abruptly end the session? Does he charge for the then missed appointment, and don’t we feel this is a waste of the psychiatrist’s time when appointments are limited?

If college students started with therapists in their home states when universities shut down in the spring of 2020, must they now try to get treatment in the states where their college campuses are located? What if the university has a long wait for services, there are no local psychiatrists taking on new patients, or the student feels he is making good progress with the doctor he is working with? And how do we even know for sure where our patients are located? Are we obligated to ask for a precise location at the beginning of each session? What if patients do not offer their locations, or lie about where they are?

Oddly, the issue is with the location of the patient; the doctor can be anywhere as long as the patient’s body is in a state where he or she is licensed. And it has never been a problem to send prescriptions to pharmacies in other states, though this seems to me the essence of practicing across state lines.

In the State of the Union Address on March 1, President Biden had a hefty agenda: The Russian invasion of Ukraine, a global pandemic, spiraling inflation, and for the first time in a SOTU address, our president discussed a strategy to address our National Mental Health Crisis. The fact sheet released by the White House details many long-awaited changes to increase the mental health workforce to address shortages, instituting a “988” crisis line to initiate “someone to call, someone to respond, and somewhere for every American in crisis to go.” The proposals call for a sweeping reform in providing access to services, strengthening parity, and improving community, veterans, and university services – and the Biden administration specifically addresses telemental health. “To maintain continuity of access, the Administration will work with Congress to ensure coverage of tele-behavioral health across health plans, and support appropriate delivery of telemedicine across state lines.”

This is good news, as it’s time we concentrated on allowing for access to care in a consumer-oriented way. It may let us focus on offering good clinical care and not focus on following outdated regulations. Hopefully, those who want help will be able to access it, and perhaps soon a traveling nurse will be permitted to get mental health care with continuity of treatment.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins in Baltimore. Dr. Miller has no conflicts of interest.

I was taught to think clinically first and legally second. There are moments when following every regulation is clearly detrimental to the well-being of both the patient and the medical community at large, and these challenges have been highlighted by issues with telemental health during the pandemic.

A friend emailed me with a problem: He has a son who is a traveling nurse and is currently in psychotherapy. The therapist has, in accordance with licensing requirements, told his son that she can not see him when assignments take him to any state where she is not licensed. The patient needs to physically be in the same state where the clinician holds a license, technically for every appointment. The nursing assignments last for 3 months and he will be going to a variety of states. Does he really need to get a new therapist every 90 days?

The logistics seem mind-boggling in a time when there is a shortage of mental health professionals, and there are often long wait lists to get care. And even if it was all easy, I’ll point out that working with a therapist is a bit different then going to an urgent care center to have sutures removed or to obtain antibiotics for strep throat: The relationship is not easily interchangeable, and I know of no one who would think it clinically optimal for anyone to change psychotherapists every 3 months. The traveling nurse does not just need to find a “provider” in each state, he needs to find one he is comfortable with and he will have to spend several sessions relaying his history and forming a new therapeutic alliance. And given the ambiguities of psychotherapy, he would optimally see therapists who do not make conflicting interpretations or recommendations. Mind-boggling. And while none of us are irreplaceable, it feels heartless to tell someone who is traveling to provide medical care to others during a pandemic that they can’t have mental health care when our technology would allow for it.

In the “old days” it was simpler: Patients came to the office and both the patient and the clinician were physically located in the same state, even if the patient resided in another state and commuted hours to the appointment. Telemental health was done in select rural areas or in military settings, and most physicians did not consider the option for video visits, much less full video treatment. For the average practitioner, issues of location were not relevant. The exception was for college students who might reside in one state and see a psychiatrist or therapist in another, but typically everyone was comfortable taking a break from therapy when the patient could not meet with the therapist in person. If psychiatrists were having phone or video sessions with out-of-state patients on an occasional basis, it may have been because there was less scrutiny and it was less obvious that this was not permitted.

When the pandemic forced treatment to go online, the issues changed. At the beginning, issues related to state licensing were waived. Now each state has a different requirement with regard to out-of-state physicians; some allow their residents to be seen, while others require the physician to get licensed in their state and the process may or may not be costly or arduous for the provider. The regulations change frequently, and can be quite confusing to follow. Since psychiatry is a shortage field, many psychiatrists are not looking to have more patients from other states and are not motivated to apply for extra licenses.

Life as a practicing psychiatrist has been a moving target: I reopened my practice for some in-person visits for vaccinated patients in June 2021, then closed it when the Omicron surge seemed too risky, and I’ll be reopening soon. Patients, too, have had unpredictable lives.

For the practitioner who is following the rules precisely, the issues can be sticky. It may be fine to have Zoom visits with a patient who lives across the street, but not with the elderly patient who has to drive 90 minutes across a state line, and it’s always fine to have a video session with a patient in Guam. If a patient signs on for a video visit with a doctor licensed in Maine and announces there will be a visit to a brother in Michigan, does the clinician abruptly end the session? Does he charge for the then missed appointment, and don’t we feel this is a waste of the psychiatrist’s time when appointments are limited?

If college students started with therapists in their home states when universities shut down in the spring of 2020, must they now try to get treatment in the states where their college campuses are located? What if the university has a long wait for services, there are no local psychiatrists taking on new patients, or the student feels he is making good progress with the doctor he is working with? And how do we even know for sure where our patients are located? Are we obligated to ask for a precise location at the beginning of each session? What if patients do not offer their locations, or lie about where they are?

Oddly, the issue is with the location of the patient; the doctor can be anywhere as long as the patient’s body is in a state where he or she is licensed. And it has never been a problem to send prescriptions to pharmacies in other states, though this seems to me the essence of practicing across state lines.

In the State of the Union Address on March 1, President Biden had a hefty agenda: The Russian invasion of Ukraine, a global pandemic, spiraling inflation, and for the first time in a SOTU address, our president discussed a strategy to address our National Mental Health Crisis. The fact sheet released by the White House details many long-awaited changes to increase the mental health workforce to address shortages, instituting a “988” crisis line to initiate “someone to call, someone to respond, and somewhere for every American in crisis to go.” The proposals call for a sweeping reform in providing access to services, strengthening parity, and improving community, veterans, and university services – and the Biden administration specifically addresses telemental health. “To maintain continuity of access, the Administration will work with Congress to ensure coverage of tele-behavioral health across health plans, and support appropriate delivery of telemedicine across state lines.”

This is good news, as it’s time we concentrated on allowing for access to care in a consumer-oriented way. It may let us focus on offering good clinical care and not focus on following outdated regulations. Hopefully, those who want help will be able to access it, and perhaps soon a traveling nurse will be permitted to get mental health care with continuity of treatment.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins in Baltimore. Dr. Miller has no conflicts of interest.

I was taught to think clinically first and legally second. There are moments when following every regulation is clearly detrimental to the well-being of both the patient and the medical community at large, and these challenges have been highlighted by issues with telemental health during the pandemic.

A friend emailed me with a problem: He has a son who is a traveling nurse and is currently in psychotherapy. The therapist has, in accordance with licensing requirements, told his son that she can not see him when assignments take him to any state where she is not licensed. The patient needs to physically be in the same state where the clinician holds a license, technically for every appointment. The nursing assignments last for 3 months and he will be going to a variety of states. Does he really need to get a new therapist every 90 days?

The logistics seem mind-boggling in a time when there is a shortage of mental health professionals, and there are often long wait lists to get care. And even if it was all easy, I’ll point out that working with a therapist is a bit different then going to an urgent care center to have sutures removed or to obtain antibiotics for strep throat: The relationship is not easily interchangeable, and I know of no one who would think it clinically optimal for anyone to change psychotherapists every 3 months. The traveling nurse does not just need to find a “provider” in each state, he needs to find one he is comfortable with and he will have to spend several sessions relaying his history and forming a new therapeutic alliance. And given the ambiguities of psychotherapy, he would optimally see therapists who do not make conflicting interpretations or recommendations. Mind-boggling. And while none of us are irreplaceable, it feels heartless to tell someone who is traveling to provide medical care to others during a pandemic that they can’t have mental health care when our technology would allow for it.

In the “old days” it was simpler: Patients came to the office and both the patient and the clinician were physically located in the same state, even if the patient resided in another state and commuted hours to the appointment. Telemental health was done in select rural areas or in military settings, and most physicians did not consider the option for video visits, much less full video treatment. For the average practitioner, issues of location were not relevant. The exception was for college students who might reside in one state and see a psychiatrist or therapist in another, but typically everyone was comfortable taking a break from therapy when the patient could not meet with the therapist in person. If psychiatrists were having phone or video sessions with out-of-state patients on an occasional basis, it may have been because there was less scrutiny and it was less obvious that this was not permitted.

When the pandemic forced treatment to go online, the issues changed. At the beginning, issues related to state licensing were waived. Now each state has a different requirement with regard to out-of-state physicians; some allow their residents to be seen, while others require the physician to get licensed in their state and the process may or may not be costly or arduous for the provider. The regulations change frequently, and can be quite confusing to follow. Since psychiatry is a shortage field, many psychiatrists are not looking to have more patients from other states and are not motivated to apply for extra licenses.

Life as a practicing psychiatrist has been a moving target: I reopened my practice for some in-person visits for vaccinated patients in June 2021, then closed it when the Omicron surge seemed too risky, and I’ll be reopening soon. Patients, too, have had unpredictable lives.

For the practitioner who is following the rules precisely, the issues can be sticky. It may be fine to have Zoom visits with a patient who lives across the street, but not with the elderly patient who has to drive 90 minutes across a state line, and it’s always fine to have a video session with a patient in Guam. If a patient signs on for a video visit with a doctor licensed in Maine and announces there will be a visit to a brother in Michigan, does the clinician abruptly end the session? Does he charge for the then missed appointment, and don’t we feel this is a waste of the psychiatrist’s time when appointments are limited?

If college students started with therapists in their home states when universities shut down in the spring of 2020, must they now try to get treatment in the states where their college campuses are located? What if the university has a long wait for services, there are no local psychiatrists taking on new patients, or the student feels he is making good progress with the doctor he is working with? And how do we even know for sure where our patients are located? Are we obligated to ask for a precise location at the beginning of each session? What if patients do not offer their locations, or lie about where they are?

Oddly, the issue is with the location of the patient; the doctor can be anywhere as long as the patient’s body is in a state where he or she is licensed. And it has never been a problem to send prescriptions to pharmacies in other states, though this seems to me the essence of practicing across state lines.

In the State of the Union Address on March 1, President Biden had a hefty agenda: The Russian invasion of Ukraine, a global pandemic, spiraling inflation, and for the first time in a SOTU address, our president discussed a strategy to address our National Mental Health Crisis. The fact sheet released by the White House details many long-awaited changes to increase the mental health workforce to address shortages, instituting a “988” crisis line to initiate “someone to call, someone to respond, and somewhere for every American in crisis to go.” The proposals call for a sweeping reform in providing access to services, strengthening parity, and improving community, veterans, and university services – and the Biden administration specifically addresses telemental health. “To maintain continuity of access, the Administration will work with Congress to ensure coverage of tele-behavioral health across health plans, and support appropriate delivery of telemedicine across state lines.”

This is good news, as it’s time we concentrated on allowing for access to care in a consumer-oriented way. It may let us focus on offering good clinical care and not focus on following outdated regulations. Hopefully, those who want help will be able to access it, and perhaps soon a traveling nurse will be permitted to get mental health care with continuity of treatment.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins in Baltimore. Dr. Miller has no conflicts of interest.

Four years ago, I was fully employed in a “traditional” rheumatology clinic. I met Alan, a 42-year-old gentleman who was a high school math teacher in my town. He was the first patient on my panel that day. Once I entered the examining room, Alan greeted me with: “You are the third rheumatologist who I have consulted for what everybody believes is fibromyalgia. I am paying out of pocket to see you as you are not on my insurance panel. I have researched your background, and I have high expectations of you.” He was cutting to the chase.

Alan had struggled with pain for about 1½ years. He insisted that he was very healthy before his symptoms started abruptly. In the past 2 years, his personal life had been under much stress as he was caring for a disabled child and facing an imminent divorce. While his symptoms were suggestive of an inflammatory arthritis, his workup was not. Unfortunately, the allocated time with Alan was 15 minutes – too short to cover both medical and personal struggles. Meanwhile, my nurses had to room in another two patients. I felt rushed and responsible for not letting the others wait. I asked Alan to keep a diary of his symptoms and come back in 2 weeks. A few minutes after discharging Alan, my nurse followed and asked me: “Where would you like me to add this patient, as you have no openings for 4 months ?”

“Overbook him!” I said.

This was happening almost every day. Scheduled patients, overbooked patients, tens of emails, calls to patients, and fights with insurance companies to approve tests and medications. Nearly every day I was getting home, preparing dinner, feeding my family, and going back to writing notes, as I would be financially penalized if my notes were not submitted in 24-48 hours. I had no time for my family and didn’t even think about any hobbies.

In 2 weeks, Alan came back for his visit. That day, I paid someone to take my kids to school and came to my office earlier. We had 1 hour to talk about his history. At the end of the visit, Alan said: “What kind of doctor are you? You looked into my eyes while I was talking, and you didn’t touch the computer keyboard?!” His remark was not uncommon for me. Most patients complain that physicians spend more time typing than looking at them. Maybe patients do not realize, but this is the only way that physicians get paid: writing the “proper notes” and placing the correct billing code.

Alan was diagnosed and treated successfully for seronegative rheumatoid arthritis. In 1 year, paying out of pocket to see me, he ended up spending many, many thousands of dollars. As you can imagine, I was not in control of those bills.

After 4 years in the traditional system, I decided to change something for my patients and for myself as their physician, and as a mother of three kids, a wife, a daughter, and a sister.

I decided to create a clinic where I am comfortable practicing “uncomplicated” medicine, as a friend of mine said. Today, insurance companies are restricting patients to limited panels of specialists. They dictate patients’ care, giving the false impression that they will save money. Insurance companies interfere with the physician’s medical judgment. They make algorithms to approve tests and have preferred lists of medication. They decide whether a test or a medication is appropriate for you. In addition, they don’t disclose how much they pay for your consultation, tests, and medication, and they ban the contracted parties from disclosing this information. They force patients to use their testing facilities and mailing pharmacies. Although patients and employers are the payers, they do not have access to their insurance companies’ “real” prices.

I decided that it was time to take control of my time spent with patients to make my services available when patients need me, without becoming a financial burden. I created a clinic where patients do not have copayments and will never receive a “surprise bill.” All costs are transparent to patients, including laboratory and imaging tests. Patients can talk to me on the phone, send a text, or email. A clinic where patients can talk to the physician on the phone or send a text or email? This is direct specialty care.

Is direct care a new concept? No, not at all. Is direct care the same as concierge medicine? I think it is a type of concierge service, but without the price tag.

Why?

Physicians practicing the traditional concierge medicine model here in the United States still bill patients’ insurance. In addition, to make their practice profitable, they charge a retainer fee that will allow them to keep a small patient panel. In contrast, direct care specialists do not have a contract with insurance companies.

I believe that both concierge medicine and direct care specialists offer exceptional care and better access to physicians. The difference is in costs: One is more expensive than the other. Traditional concierge medicine practices usually ask for high retainer fees in addition to copayments for visits. They do not offer any access to discounted pricing for laboratory or imaging tests. Patients continue to receive surprise bills from their insurance company.

Why don’t direct specialty care practices contract with insurance companies? Contracting with insurance companies increases a practice’s overhead costs (as more money is spent on coding and billing services and more office staff). When practice overhead is lower, the cost of patient care can be significantly lower. Patients pay a monthly membership to become a direct specialty care practice member. The membership covers the cost of visits and access to the benefits of the practice. In addition, direct care specialists do not charge copayments or send surprise bills. They can contract directly with laboratory and imaging centers and offer discounted prices. Patients with insurance are welcome to use it to cover tests, imaging, and medication. The patient has the power to choose between paying a cash price versus a “covered” service.

Most young patients, like Alan, have a high-deductible plan. A few regular blood tests might cost a patient hundreds of dollars before meeting a deductible. One MRI scan costs $4,000-$6,000. Patients who join a direct specialty care practice pay $30-$40 for regular labs and $400-$500 for an MRI.

I am now 2 years into practicing medicine as a direct care specialist. It is not a dream anymore. Yes, you may call it “concierge medicine without the price tag.” I call it “direct specialty care.” My patients and I are both accountable to one another. Together, we make a plan, and we have the time to implement it.

I am not alone. Other specialists are embracing this model. That is why we created the Direct Specialty Care Alliance, a place where physicians are welcome to network and share with others what they have learned along their journeys.

After I started my company, Alan was one of the first patients to join. He embraced my practice model and became one of the ambassadors of the direct specialty care movement. He is back to a normal life of taking care of his family, getting his wife back, and teaching math to high school kids.

Dr Girnita is the CEO and founder of RheumatologistOnCall, actively seeing patients via telemedicine in 10 U.S. states. She is an advocate for digital health and telemedicine that will empower physicians and patients to take charge of their medical care. She is a cofounder of the Direct Specialty Care Alliance. She disclosed no relevant financial relationships.

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

Four years ago, I was fully employed in a “traditional” rheumatology clinic. I met Alan, a 42-year-old gentleman who was a high school math teacher in my town. He was the first patient on my panel that day. Once I entered the examining room, Alan greeted me with: “You are the third rheumatologist who I have consulted for what everybody believes is fibromyalgia. I am paying out of pocket to see you as you are not on my insurance panel. I have researched your background, and I have high expectations of you.” He was cutting to the chase.

Alan had struggled with pain for about 1½ years. He insisted that he was very healthy before his symptoms started abruptly. In the past 2 years, his personal life had been under much stress as he was caring for a disabled child and facing an imminent divorce. While his symptoms were suggestive of an inflammatory arthritis, his workup was not. Unfortunately, the allocated time with Alan was 15 minutes – too short to cover both medical and personal struggles. Meanwhile, my nurses had to room in another two patients. I felt rushed and responsible for not letting the others wait. I asked Alan to keep a diary of his symptoms and come back in 2 weeks. A few minutes after discharging Alan, my nurse followed and asked me: “Where would you like me to add this patient, as you have no openings for 4 months ?”

“Overbook him!” I said.

This was happening almost every day. Scheduled patients, overbooked patients, tens of emails, calls to patients, and fights with insurance companies to approve tests and medications. Nearly every day I was getting home, preparing dinner, feeding my family, and going back to writing notes, as I would be financially penalized if my notes were not submitted in 24-48 hours. I had no time for my family and didn’t even think about any hobbies.

In 2 weeks, Alan came back for his visit. That day, I paid someone to take my kids to school and came to my office earlier. We had 1 hour to talk about his history. At the end of the visit, Alan said: “What kind of doctor are you? You looked into my eyes while I was talking, and you didn’t touch the computer keyboard?!” His remark was not uncommon for me. Most patients complain that physicians spend more time typing than looking at them. Maybe patients do not realize, but this is the only way that physicians get paid: writing the “proper notes” and placing the correct billing code.

Alan was diagnosed and treated successfully for seronegative rheumatoid arthritis. In 1 year, paying out of pocket to see me, he ended up spending many, many thousands of dollars. As you can imagine, I was not in control of those bills.

After 4 years in the traditional system, I decided to change something for my patients and for myself as their physician, and as a mother of three kids, a wife, a daughter, and a sister.

I decided to create a clinic where I am comfortable practicing “uncomplicated” medicine, as a friend of mine said. Today, insurance companies are restricting patients to limited panels of specialists. They dictate patients’ care, giving the false impression that they will save money. Insurance companies interfere with the physician’s medical judgment. They make algorithms to approve tests and have preferred lists of medication. They decide whether a test or a medication is appropriate for you. In addition, they don’t disclose how much they pay for your consultation, tests, and medication, and they ban the contracted parties from disclosing this information. They force patients to use their testing facilities and mailing pharmacies. Although patients and employers are the payers, they do not have access to their insurance companies’ “real” prices.

I decided that it was time to take control of my time spent with patients to make my services available when patients need me, without becoming a financial burden. I created a clinic where patients do not have copayments and will never receive a “surprise bill.” All costs are transparent to patients, including laboratory and imaging tests. Patients can talk to me on the phone, send a text, or email. A clinic where patients can talk to the physician on the phone or send a text or email? This is direct specialty care.

Is direct care a new concept? No, not at all. Is direct care the same as concierge medicine? I think it is a type of concierge service, but without the price tag.

Why?

Physicians practicing the traditional concierge medicine model here in the United States still bill patients’ insurance. In addition, to make their practice profitable, they charge a retainer fee that will allow them to keep a small patient panel. In contrast, direct care specialists do not have a contract with insurance companies.

I believe that both concierge medicine and direct care specialists offer exceptional care and better access to physicians. The difference is in costs: One is more expensive than the other. Traditional concierge medicine practices usually ask for high retainer fees in addition to copayments for visits. They do not offer any access to discounted pricing for laboratory or imaging tests. Patients continue to receive surprise bills from their insurance company.

Why don’t direct specialty care practices contract with insurance companies? Contracting with insurance companies increases a practice’s overhead costs (as more money is spent on coding and billing services and more office staff). When practice overhead is lower, the cost of patient care can be significantly lower. Patients pay a monthly membership to become a direct specialty care practice member. The membership covers the cost of visits and access to the benefits of the practice. In addition, direct care specialists do not charge copayments or send surprise bills. They can contract directly with laboratory and imaging centers and offer discounted prices. Patients with insurance are welcome to use it to cover tests, imaging, and medication. The patient has the power to choose between paying a cash price versus a “covered” service.

Most young patients, like Alan, have a high-deductible plan. A few regular blood tests might cost a patient hundreds of dollars before meeting a deductible. One MRI scan costs $4,000-$6,000. Patients who join a direct specialty care practice pay $30-$40 for regular labs and $400-$500 for an MRI.

I am now 2 years into practicing medicine as a direct care specialist. It is not a dream anymore. Yes, you may call it “concierge medicine without the price tag.” I call it “direct specialty care.” My patients and I are both accountable to one another. Together, we make a plan, and we have the time to implement it.

I am not alone. Other specialists are embracing this model. That is why we created the Direct Specialty Care Alliance, a place where physicians are welcome to network and share with others what they have learned along their journeys.

After I started my company, Alan was one of the first patients to join. He embraced my practice model and became one of the ambassadors of the direct specialty care movement. He is back to a normal life of taking care of his family, getting his wife back, and teaching math to high school kids.

Dr Girnita is the CEO and founder of RheumatologistOnCall, actively seeing patients via telemedicine in 10 U.S. states. She is an advocate for digital health and telemedicine that will empower physicians and patients to take charge of their medical care. She is a cofounder of the Direct Specialty Care Alliance. She disclosed no relevant financial relationships.

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

Four years ago, I was fully employed in a “traditional” rheumatology clinic. I met Alan, a 42-year-old gentleman who was a high school math teacher in my town. He was the first patient on my panel that day. Once I entered the examining room, Alan greeted me with: “You are the third rheumatologist who I have consulted for what everybody believes is fibromyalgia. I am paying out of pocket to see you as you are not on my insurance panel. I have researched your background, and I have high expectations of you.” He was cutting to the chase.

Alan had struggled with pain for about 1½ years. He insisted that he was very healthy before his symptoms started abruptly. In the past 2 years, his personal life had been under much stress as he was caring for a disabled child and facing an imminent divorce. While his symptoms were suggestive of an inflammatory arthritis, his workup was not. Unfortunately, the allocated time with Alan was 15 minutes – too short to cover both medical and personal struggles. Meanwhile, my nurses had to room in another two patients. I felt rushed and responsible for not letting the others wait. I asked Alan to keep a diary of his symptoms and come back in 2 weeks. A few minutes after discharging Alan, my nurse followed and asked me: “Where would you like me to add this patient, as you have no openings for 4 months ?”

“Overbook him!” I said.

This was happening almost every day. Scheduled patients, overbooked patients, tens of emails, calls to patients, and fights with insurance companies to approve tests and medications. Nearly every day I was getting home, preparing dinner, feeding my family, and going back to writing notes, as I would be financially penalized if my notes were not submitted in 24-48 hours. I had no time for my family and didn’t even think about any hobbies.

In 2 weeks, Alan came back for his visit. That day, I paid someone to take my kids to school and came to my office earlier. We had 1 hour to talk about his history. At the end of the visit, Alan said: “What kind of doctor are you? You looked into my eyes while I was talking, and you didn’t touch the computer keyboard?!” His remark was not uncommon for me. Most patients complain that physicians spend more time typing than looking at them. Maybe patients do not realize, but this is the only way that physicians get paid: writing the “proper notes” and placing the correct billing code.

Alan was diagnosed and treated successfully for seronegative rheumatoid arthritis. In 1 year, paying out of pocket to see me, he ended up spending many, many thousands of dollars. As you can imagine, I was not in control of those bills.

After 4 years in the traditional system, I decided to change something for my patients and for myself as their physician, and as a mother of three kids, a wife, a daughter, and a sister.

I decided to create a clinic where I am comfortable practicing “uncomplicated” medicine, as a friend of mine said. Today, insurance companies are restricting patients to limited panels of specialists. They dictate patients’ care, giving the false impression that they will save money. Insurance companies interfere with the physician’s medical judgment. They make algorithms to approve tests and have preferred lists of medication. They decide whether a test or a medication is appropriate for you. In addition, they don’t disclose how much they pay for your consultation, tests, and medication, and they ban the contracted parties from disclosing this information. They force patients to use their testing facilities and mailing pharmacies. Although patients and employers are the payers, they do not have access to their insurance companies’ “real” prices.

I decided that it was time to take control of my time spent with patients to make my services available when patients need me, without becoming a financial burden. I created a clinic where patients do not have copayments and will never receive a “surprise bill.” All costs are transparent to patients, including laboratory and imaging tests. Patients can talk to me on the phone, send a text, or email. A clinic where patients can talk to the physician on the phone or send a text or email? This is direct specialty care.

Is direct care a new concept? No, not at all. Is direct care the same as concierge medicine? I think it is a type of concierge service, but without the price tag.

Why?

Physicians practicing the traditional concierge medicine model here in the United States still bill patients’ insurance. In addition, to make their practice profitable, they charge a retainer fee that will allow them to keep a small patient panel. In contrast, direct care specialists do not have a contract with insurance companies.

I believe that both concierge medicine and direct care specialists offer exceptional care and better access to physicians. The difference is in costs: One is more expensive than the other. Traditional concierge medicine practices usually ask for high retainer fees in addition to copayments for visits. They do not offer any access to discounted pricing for laboratory or imaging tests. Patients continue to receive surprise bills from their insurance company.

Why don’t direct specialty care practices contract with insurance companies? Contracting with insurance companies increases a practice’s overhead costs (as more money is spent on coding and billing services and more office staff). When practice overhead is lower, the cost of patient care can be significantly lower. Patients pay a monthly membership to become a direct specialty care practice member. The membership covers the cost of visits and access to the benefits of the practice. In addition, direct care specialists do not charge copayments or send surprise bills. They can contract directly with laboratory and imaging centers and offer discounted prices. Patients with insurance are welcome to use it to cover tests, imaging, and medication. The patient has the power to choose between paying a cash price versus a “covered” service.

Most young patients, like Alan, have a high-deductible plan. A few regular blood tests might cost a patient hundreds of dollars before meeting a deductible. One MRI scan costs $4,000-$6,000. Patients who join a direct specialty care practice pay $30-$40 for regular labs and $400-$500 for an MRI.

I am now 2 years into practicing medicine as a direct care specialist. It is not a dream anymore. Yes, you may call it “concierge medicine without the price tag.” I call it “direct specialty care.” My patients and I are both accountable to one another. Together, we make a plan, and we have the time to implement it.

I am not alone. Other specialists are embracing this model. That is why we created the Direct Specialty Care Alliance, a place where physicians are welcome to network and share with others what they have learned along their journeys.

After I started my company, Alan was one of the first patients to join. He embraced my practice model and became one of the ambassadors of the direct specialty care movement. He is back to a normal life of taking care of his family, getting his wife back, and teaching math to high school kids.

Dr Girnita is the CEO and founder of RheumatologistOnCall, actively seeing patients via telemedicine in 10 U.S. states. She is an advocate for digital health and telemedicine that will empower physicians and patients to take charge of their medical care. She is a cofounder of the Direct Specialty Care Alliance. She disclosed no relevant financial relationships.

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

It would be overused and trite to say that the pandemic has drastically altered all of our lives and will cause lasting impact on how we function in society and medicine for years to come. While it seems that the current trend of the latest Omicron variant is on the downslope, the path to get to this point has been fraught with challenges that have struck at the very core of our society. As a primary care physician on the front lines seeing COVID patients, I have had to deal with not only the disease but the politics around it. As critical and life saving as the vaccines have been, many physicians have not been able to get access to these vaccines and give them to their patients. I am one of those physicians. I practice in Florida, and I still cannot give COVID vaccines in my office. 

I am a firm believer in the ability for physicians to be able to give all the necessary adult vaccines and provide them for their patients. The COVID vaccine exacerbated a majorly flawed system that further increased the health care disparities in the country. The current vaccine system for the majority of adult vaccines involves the physician’s being able to directly purchase supplies from the vaccine manufacturer, administer them to the patients, and be reimbursed.
 

Third parties can purchase vaccines at lower rates than those for physicians

The Affordable Care Act mandates that all vaccines approved by the Advisory Committee on Immunization Practices (ACIP) at the Centers for Disease Control and Prevention must be covered. This allows for better access to care as physicians will be able to purchase, store, and deliver vaccines to their patients. The fallacy in this system is that third parties get involved and rebates or incentives are given to these groups to purchase vaccines at a rate lower than those for physicians.

In addition, many organizations can get access to vaccines before physicians and at a lower cost. That system was flawed to begin with and created a deterrent for access to care and physician involvement in the vaccination process. This was worsened by different states being given the ability to decide how vaccines would be distributed for COVID.

Many pharmacies were able to give out COVID vaccines while many physician offices still have not received access to any of the vaccines. One of the major safety issues with this is that no physicians were involved in the administration of the vaccine, and it is unclear what training was given to the individuals injecting that vaccine. Finally, different places were interpreting the recommendations from ACIP on their own and not necessarily following the appropriate guidelines. All of these factors have further widened the health care disparity gap and made it difficult to provide the COVID vaccines in doctors’ offices.
 

Recommended next steps, solutions to problem

The question is what to do about this. The most important thing is to get the vaccines in arms so they can save lives. In addition, doctors need to be able to get the vaccines in their offices.

Many patients trust their physicians to advise them on what to do regarding health care. The majority of patients want to know if they should get the vaccine and ask for counseling. Physicians answering patients’ questions about vaccines is an important step in overcoming vaccine hesitancy.

Also, doctors need to be informed and supportive of the vaccine process.

The next step is the governmental aspect with those in power making sure that vaccines are accessible to all. Even if the vaccine cannot be given in the office, doctors should still be recommending that patients receive them. Plus, doctors should take every opportunity to ask about what vaccines their patients have received and encourage their patients to get vaccinated.

The COVID-19 vaccines are safe and effective and have been monitored for safety more than any other vaccine. There are multiple systems in place to look for any signals that could indicate an issue was caused by a COVID-19 vaccine. These vaccines can be administered with other vaccines, and there is a great opportunity for physicians to encourage patients to receive these life-saving vaccines.

While it may seem that the COVID-19 case counts are on the downslope, the importance of continuing to vaccinate is predicated on the very real concern that the disease is still circulating and the unvaccinated are still at risk for severe infection.

Dr. Goldman is immediate past governor of the Florida chapter of the American College of Physicians, a regent for the American College of Physicians, vice-president of the Florida Medical Association, and president of the Florida Medical Association Political Action Committee. You can reach Dr. Goldman at [email protected].

It would be overused and trite to say that the pandemic has drastically altered all of our lives and will cause lasting impact on how we function in society and medicine for years to come. While it seems that the current trend of the latest Omicron variant is on the downslope, the path to get to this point has been fraught with challenges that have struck at the very core of our society. As a primary care physician on the front lines seeing COVID patients, I have had to deal with not only the disease but the politics around it. As critical and life saving as the vaccines have been, many physicians have not been able to get access to these vaccines and give them to their patients. I am one of those physicians. I practice in Florida, and I still cannot give COVID vaccines in my office. 

I am a firm believer in the ability for physicians to be able to give all the necessary adult vaccines and provide them for their patients. The COVID vaccine exacerbated a majorly flawed system that further increased the health care disparities in the country. The current vaccine system for the majority of adult vaccines involves the physician’s being able to directly purchase supplies from the vaccine manufacturer, administer them to the patients, and be reimbursed.
 

Third parties can purchase vaccines at lower rates than those for physicians

The Affordable Care Act mandates that all vaccines approved by the Advisory Committee on Immunization Practices (ACIP) at the Centers for Disease Control and Prevention must be covered. This allows for better access to care as physicians will be able to purchase, store, and deliver vaccines to their patients. The fallacy in this system is that third parties get involved and rebates or incentives are given to these groups to purchase vaccines at a rate lower than those for physicians.

In addition, many organizations can get access to vaccines before physicians and at a lower cost. That system was flawed to begin with and created a deterrent for access to care and physician involvement in the vaccination process. This was worsened by different states being given the ability to decide how vaccines would be distributed for COVID.

Many pharmacies were able to give out COVID vaccines while many physician offices still have not received access to any of the vaccines. One of the major safety issues with this is that no physicians were involved in the administration of the vaccine, and it is unclear what training was given to the individuals injecting that vaccine. Finally, different places were interpreting the recommendations from ACIP on their own and not necessarily following the appropriate guidelines. All of these factors have further widened the health care disparity gap and made it difficult to provide the COVID vaccines in doctors’ offices.
 

Recommended next steps, solutions to problem

The question is what to do about this. The most important thing is to get the vaccines in arms so they can save lives. In addition, doctors need to be able to get the vaccines in their offices.

Many patients trust their physicians to advise them on what to do regarding health care. The majority of patients want to know if they should get the vaccine and ask for counseling. Physicians answering patients’ questions about vaccines is an important step in overcoming vaccine hesitancy.

Also, doctors need to be informed and supportive of the vaccine process.

The next step is the governmental aspect with those in power making sure that vaccines are accessible to all. Even if the vaccine cannot be given in the office, doctors should still be recommending that patients receive them. Plus, doctors should take every opportunity to ask about what vaccines their patients have received and encourage their patients to get vaccinated.

The COVID-19 vaccines are safe and effective and have been monitored for safety more than any other vaccine. There are multiple systems in place to look for any signals that could indicate an issue was caused by a COVID-19 vaccine. These vaccines can be administered with other vaccines, and there is a great opportunity for physicians to encourage patients to receive these life-saving vaccines.

While it may seem that the COVID-19 case counts are on the downslope, the importance of continuing to vaccinate is predicated on the very real concern that the disease is still circulating and the unvaccinated are still at risk for severe infection.

Dr. Goldman is immediate past governor of the Florida chapter of the American College of Physicians, a regent for the American College of Physicians, vice-president of the Florida Medical Association, and president of the Florida Medical Association Political Action Committee. You can reach Dr. Goldman at [email protected].

It would be overused and trite to say that the pandemic has drastically altered all of our lives and will cause lasting impact on how we function in society and medicine for years to come. While it seems that the current trend of the latest Omicron variant is on the downslope, the path to get to this point has been fraught with challenges that have struck at the very core of our society. As a primary care physician on the front lines seeing COVID patients, I have had to deal with not only the disease but the politics around it. As critical and life saving as the vaccines have been, many physicians have not been able to get access to these vaccines and give them to their patients. I am one of those physicians. I practice in Florida, and I still cannot give COVID vaccines in my office. 

I am a firm believer in the ability for physicians to be able to give all the necessary adult vaccines and provide them for their patients. The COVID vaccine exacerbated a majorly flawed system that further increased the health care disparities in the country. The current vaccine system for the majority of adult vaccines involves the physician’s being able to directly purchase supplies from the vaccine manufacturer, administer them to the patients, and be reimbursed.
 

Third parties can purchase vaccines at lower rates than those for physicians

The Affordable Care Act mandates that all vaccines approved by the Advisory Committee on Immunization Practices (ACIP) at the Centers for Disease Control and Prevention must be covered. This allows for better access to care as physicians will be able to purchase, store, and deliver vaccines to their patients. The fallacy in this system is that third parties get involved and rebates or incentives are given to these groups to purchase vaccines at a rate lower than those for physicians.

In addition, many organizations can get access to vaccines before physicians and at a lower cost. That system was flawed to begin with and created a deterrent for access to care and physician involvement in the vaccination process. This was worsened by different states being given the ability to decide how vaccines would be distributed for COVID.

Many pharmacies were able to give out COVID vaccines while many physician offices still have not received access to any of the vaccines. One of the major safety issues with this is that no physicians were involved in the administration of the vaccine, and it is unclear what training was given to the individuals injecting that vaccine. Finally, different places were interpreting the recommendations from ACIP on their own and not necessarily following the appropriate guidelines. All of these factors have further widened the health care disparity gap and made it difficult to provide the COVID vaccines in doctors’ offices.
 

Recommended next steps, solutions to problem

The question is what to do about this. The most important thing is to get the vaccines in arms so they can save lives. In addition, doctors need to be able to get the vaccines in their offices.

Many patients trust their physicians to advise them on what to do regarding health care. The majority of patients want to know if they should get the vaccine and ask for counseling. Physicians answering patients’ questions about vaccines is an important step in overcoming vaccine hesitancy.

Also, doctors need to be informed and supportive of the vaccine process.

The next step is the governmental aspect with those in power making sure that vaccines are accessible to all. Even if the vaccine cannot be given in the office, doctors should still be recommending that patients receive them. Plus, doctors should take every opportunity to ask about what vaccines their patients have received and encourage their patients to get vaccinated.

The COVID-19 vaccines are safe and effective and have been monitored for safety more than any other vaccine. There are multiple systems in place to look for any signals that could indicate an issue was caused by a COVID-19 vaccine. These vaccines can be administered with other vaccines, and there is a great opportunity for physicians to encourage patients to receive these life-saving vaccines.

While it may seem that the COVID-19 case counts are on the downslope, the importance of continuing to vaccinate is predicated on the very real concern that the disease is still circulating and the unvaccinated are still at risk for severe infection.

Dr. Goldman is immediate past governor of the Florida chapter of the American College of Physicians, a regent for the American College of Physicians, vice-president of the Florida Medical Association, and president of the Florida Medical Association Political Action Committee. You can reach Dr. Goldman at [email protected].

While evaluating an adolescent who had endured a several-day history of vomiting and diarrhea, I mentioned the likelihood of a viral causation, including SARS-CoV-2 infection. His well-informed mother responded, “He has no respiratory symptoms. Does COVID cause GI disease?”

Indeed, not only is the gastrointestinal tract a potential portal of entry of the virus but it may well be the site of mediation of both local and remote injury and thus a harbinger of more severe clinical phenotypes.

As we learn more about the clinical spectrum of COVID, it is becoming increasingly clear that certain features of GI tract involvement may allow us to establish a timeline of the clinical course and perhaps predict the outcome.
 

The GI tract’s involvement isn’t surprising

The ways in which the GI tract serves as a target organ of SARS-CoV-2 have been postulated in the literature. In part, this is related to the presence of abundant receptors for SARS-CoV-2 cell binding and internalization. The virus uses angiotensin-converting enzyme 2 receptors to enter various cells. These receptors are highly expressed on not only lung cells but also enterocytes. Binding of SARS-CoV-2 to ACE2 receptors allows GI involvement, leading to microscopic mucosal inflammation, increased permeability, and altered intestinal absorption.

The clinical GI manifestations of this include anorexia, nausea, vomiting, diarrhea, and abdominal pain, which may be the earliest, or sole, symptoms of COVID-19, often noted before the onset of fever or respiratory symptoms. In fact, John Ong, MBBS, and colleagues, in a discussion about patients with primary GI SARS-CoV-2 infection and symptoms, use the term “GI-COVID.”
 

Clinical course of GI manifestations

After SARS-CoV-2 exposure, adults most commonly present with respiratory symptoms, with GI symptoms reported in 10%-15% of cases. However, the overall incidence of GI involvement during SARS-CoV-2 infection varies according to age, with children more likely than adults to manifest intestinal symptoms.

There are also differences in incidence reported when comparing hospitalized with nonhospitalized individuals. In early reports from the onset of the COVID-19 pandemic, 11%-43% of hospitalized adult patients manifested GI symptoms. Of note, the presence of GI symptoms was associated with more severe disease and thus predictive of outcomes in those admitted to hospitals.

In a multicenter study that assessed pediatric inpatients with COVID-19, GI manifestations were present in 57% of patients and were the first manifestation in 14%. Adjusted by confounding factors, those with GI symptoms had a higher risk for pediatric intensive care unit admission. Patients admitted to the PICU also had higher serum C-reactive protein and aspartate aminotransferase values.
 

Emerging data on MIS-C

In previously healthy children and adolescents, the severe, life-threatening complication of multisystem inflammatory syndrome in children (MIS-C) may present 2-6 weeks after acute infection with SARS-CoV-2. MIS-C appears to be an immune activation syndrome and is presumed to be the delayed immunologic sequelae of mild/asymptomatic SARS-CoV-2 infection. This response manifests as hyperinflammation in conjunction with a peak in antibody production a few weeks later.

One report of 186 children with MIS-C in the United States noted that the involved organ system included the GI tract in 92%, followed by cardiovascular in 80%, hematologic in 76%, mucocutaneous in 74%, and respiratory in 70%. Affected children were hospitalized for a median of 7 days, with 80% requiring intensive care, 20% receiving mechanical ventilation, and 48% receiving vasoactive support; 2% died. In a similar study of patients hospitalized in New York, 88% had GI symptoms (abdominal pain, vomiting, and/or diarrhea). A retrospective chart review of patients with MIS-C found that the majority had GI symptoms with any portion of the GI tract potentially involved, but ileal and colonic inflammation predominated.

Elizabeth Whittaker, MD, and colleagues described the clinical characteristics of children in eight hospitals in England who met criteria for MIS-C that were temporally associated with SARS-CoV-2. At presentation, all of the patients manifested fever and nonspecific GI symptoms, including vomiting (45%), abdominal pain (53%), and diarrhea (52%). During hospitalization, 50% developed shock with evidence of myocardial dysfunction.

Ermias D. Belay, MD, and colleagues described the clinical characteristics of a large cohort of patients with MIS-C that were reported to the U.S. Centers for Disease Control and Prevention. Of 1,733 patients identified, GI symptoms were reported in 53%-67%. Over half developed hypotension or shock and were admitted for intensive care. Younger children more frequently presented with abdominal pain in contrast with adolescents, who more frequently manifest respiratory symptoms.

In a multicenter retrospective study of Italian children with COVID-19 that was conducted from the onset of the pandemic to early 2021, GI symptoms were noted in 38%. These manifestations were mild and self-limiting, comparable to other viral intestinal infections. However, a subset of children (9.5%) had severe GI manifestations of MIS-C, defined as a medical and/or radiologic diagnosis of acute abdomen, appendicitis, intussusception, pancreatitis, abdominal fluid collection, or diffuse adenomesenteritis requiring surgical consultation. Overall, 42% of this group underwent surgery. The authors noted that the clinical presentation of abdominal pain, lymphopenia, and increased C-reactive protein and ferritin levels were associated with a 9- to 30-fold increased probability of these severe sequelae. In addition, the severity of the GI manifestations was correlated with age (5-10 years: overall response, 8.33; >10 years: OR, 6.37). Again, the presence of GI symptoms was a harbinger of hospitalization and PICU admission.

Given that GI symptoms are a common presentation of MIS-C, its diagnosis may be delayed as clinicians first consider other GI/viral infections, inflammatory bowel disease, or Kawasaki disease. Prompt identification of GI involvement and awareness of the potential outcomes may guide the management and improve the outcome.

These studies provide a clear picture of the differential presenting features of COVID-19 and MIS-C. Although there may be other environmental/genetic factors that govern the incidence, impact, and manifestations, COVID’s status as an ongoing pandemic gives these observations worldwide relevance. This is evident in a recent report documenting pronounced GI symptoms in African children with COVID-19.

It should be noted, however, that the published data cited here reflect the impact of the initial variants of SARS-CoV-2. The GI binding, effects, and aftermath of infection with the Delta and Omicron variants is not yet known.
 

Cause and effect, or simply coincidental?

Some insight into MIS-C pathogenesis was provided by Lael M. Yonker, MD, and colleagues in their analysis of biospecimens from 100 children: 19 with MIS-C, 26 with acute COVID-19, and 55 controls. They demonstrated that in children with MIS-C the prolonged presence of SARS-CoV-2 in the GI tract led to the release of zonulin, a biomarker of intestinal permeability, with subsequent trafficking of SARS-CoV-2 antigens into the bloodstream, leading to hyperinflammation. They were then able to decrease plasma SARS-CoV-2 spike antigen levels and inflammatory markers, with resulting clinical improvement after administration of larazotide, a zonulin antagonist.

These observations regarding the potential mechanism and triggers of MIS-C may offer biomarkers for early detection and/or strategies for prevention and treatment of MIS-C.
 

Bottom line

The GI tract is the target of an immune-mediated inflammatory response that is triggered by SARS-CoV-2, with MIS-C being the major manifestation of the resultant high degree of inflammation. These observations will allow an increased awareness of nonrespiratory symptoms of SARS-CoV-2 infection by clinicians working in emergency departments and primary care settings.

Clues that may enhance the ability of pediatric clinicians to recognize the potential for severe GI involvement include the occurrence of abdominal pain, leukopenia, and elevated inflammatory markers. Their presence should raise suspicion of MIS-C and lead to early evaluation.

Of note, COVID-19 mRNA vaccination is associated with a lower incidence of MIS-C in adolescents. This underscores the importance of COVID vaccination for all eligible children. Yet, we clearly have our work cut out for us. Of 107 children with MIS-C who were hospitalized in France, 31% were adolescents eligible for vaccination; however, none had been fully vaccinated. At the end of 2021, CDC data noted that less than 1% of vaccine-eligible children (12-17 years) were fully vaccinated.

The Pfizer-BioNTech vaccine is now authorized for receipt by children aged 5-11 years, the age group that is at highest risk for MIS-C. However, despite the approval of vaccines for these younger children, there is limited access in some parts of the United States at a time of rising incidence.

We look forward to broad availability of pediatric vaccination strategies. In addition, with the intense focus on safe and effective therapeutics for SARS-CoV-2 infection, we hope to soon have strategies to prevent and/or treat the life-threatening manifestations and long-term consequences of MIS-C. For example, the recently reported central role of the gut microbiota in immunity against SARS-CoV-2 infection offer the possibility that “microbiota modulation” may both reduce GI injury and enhance vaccine efficacy.

Dr. Balistreri has disclosed no relevant financial relationships.

William F. Balistreri, MD, is the Dorothy M.M. Kersten Professor of Pediatrics; director emeritus, Pediatric Liver Care Center; medical director emeritus, liver transplantation; and professor, University of Cincinnati College of Medicine, department of pediatrics, Cincinnati Children’s Hospital Medical Center. He has served as director of the division of gastroenterology, hepatology, and nutrition at Cincinnati Children’s for 25 years and frequently covers gastroenterology, liver, and nutrition-related topics for this news organization. Dr Balistreri is currently editor-in-chief of the Journal of Pediatrics, having previously served as editor-in-chief of several journals and textbooks. He also became the first pediatrician to act as president of the American Association for the Study of Liver Diseases. In his spare time, he coaches youth lacrosse.

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

While evaluating an adolescent who had endured a several-day history of vomiting and diarrhea, I mentioned the likelihood of a viral causation, including SARS-CoV-2 infection. His well-informed mother responded, “He has no respiratory symptoms. Does COVID cause GI disease?”

Indeed, not only is the gastrointestinal tract a potential portal of entry of the virus but it may well be the site of mediation of both local and remote injury and thus a harbinger of more severe clinical phenotypes.

As we learn more about the clinical spectrum of COVID, it is becoming increasingly clear that certain features of GI tract involvement may allow us to establish a timeline of the clinical course and perhaps predict the outcome.
 

The GI tract’s involvement isn’t surprising

The ways in which the GI tract serves as a target organ of SARS-CoV-2 have been postulated in the literature. In part, this is related to the presence of abundant receptors for SARS-CoV-2 cell binding and internalization. The virus uses angiotensin-converting enzyme 2 receptors to enter various cells. These receptors are highly expressed on not only lung cells but also enterocytes. Binding of SARS-CoV-2 to ACE2 receptors allows GI involvement, leading to microscopic mucosal inflammation, increased permeability, and altered intestinal absorption.

The clinical GI manifestations of this include anorexia, nausea, vomiting, diarrhea, and abdominal pain, which may be the earliest, or sole, symptoms of COVID-19, often noted before the onset of fever or respiratory symptoms. In fact, John Ong, MBBS, and colleagues, in a discussion about patients with primary GI SARS-CoV-2 infection and symptoms, use the term “GI-COVID.”
 

Clinical course of GI manifestations

After SARS-CoV-2 exposure, adults most commonly present with respiratory symptoms, with GI symptoms reported in 10%-15% of cases. However, the overall incidence of GI involvement during SARS-CoV-2 infection varies according to age, with children more likely than adults to manifest intestinal symptoms.

There are also differences in incidence reported when comparing hospitalized with nonhospitalized individuals. In early reports from the onset of the COVID-19 pandemic, 11%-43% of hospitalized adult patients manifested GI symptoms. Of note, the presence of GI symptoms was associated with more severe disease and thus predictive of outcomes in those admitted to hospitals.

In a multicenter study that assessed pediatric inpatients with COVID-19, GI manifestations were present in 57% of patients and were the first manifestation in 14%. Adjusted by confounding factors, those with GI symptoms had a higher risk for pediatric intensive care unit admission. Patients admitted to the PICU also had higher serum C-reactive protein and aspartate aminotransferase values.
 

Emerging data on MIS-C

In previously healthy children and adolescents, the severe, life-threatening complication of multisystem inflammatory syndrome in children (MIS-C) may present 2-6 weeks after acute infection with SARS-CoV-2. MIS-C appears to be an immune activation syndrome and is presumed to be the delayed immunologic sequelae of mild/asymptomatic SARS-CoV-2 infection. This response manifests as hyperinflammation in conjunction with a peak in antibody production a few weeks later.

One report of 186 children with MIS-C in the United States noted that the involved organ system included the GI tract in 92%, followed by cardiovascular in 80%, hematologic in 76%, mucocutaneous in 74%, and respiratory in 70%. Affected children were hospitalized for a median of 7 days, with 80% requiring intensive care, 20% receiving mechanical ventilation, and 48% receiving vasoactive support; 2% died. In a similar study of patients hospitalized in New York, 88% had GI symptoms (abdominal pain, vomiting, and/or diarrhea). A retrospective chart review of patients with MIS-C found that the majority had GI symptoms with any portion of the GI tract potentially involved, but ileal and colonic inflammation predominated.

Elizabeth Whittaker, MD, and colleagues described the clinical characteristics of children in eight hospitals in England who met criteria for MIS-C that were temporally associated with SARS-CoV-2. At presentation, all of the patients manifested fever and nonspecific GI symptoms, including vomiting (45%), abdominal pain (53%), and diarrhea (52%). During hospitalization, 50% developed shock with evidence of myocardial dysfunction.

Ermias D. Belay, MD, and colleagues described the clinical characteristics of a large cohort of patients with MIS-C that were reported to the U.S. Centers for Disease Control and Prevention. Of 1,733 patients identified, GI symptoms were reported in 53%-67%. Over half developed hypotension or shock and were admitted for intensive care. Younger children more frequently presented with abdominal pain in contrast with adolescents, who more frequently manifest respiratory symptoms.

In a multicenter retrospective study of Italian children with COVID-19 that was conducted from the onset of the pandemic to early 2021, GI symptoms were noted in 38%. These manifestations were mild and self-limiting, comparable to other viral intestinal infections. However, a subset of children (9.5%) had severe GI manifestations of MIS-C, defined as a medical and/or radiologic diagnosis of acute abdomen, appendicitis, intussusception, pancreatitis, abdominal fluid collection, or diffuse adenomesenteritis requiring surgical consultation. Overall, 42% of this group underwent surgery. The authors noted that the clinical presentation of abdominal pain, lymphopenia, and increased C-reactive protein and ferritin levels were associated with a 9- to 30-fold increased probability of these severe sequelae. In addition, the severity of the GI manifestations was correlated with age (5-10 years: overall response, 8.33; >10 years: OR, 6.37). Again, the presence of GI symptoms was a harbinger of hospitalization and PICU admission.

Given that GI symptoms are a common presentation of MIS-C, its diagnosis may be delayed as clinicians first consider other GI/viral infections, inflammatory bowel disease, or Kawasaki disease. Prompt identification of GI involvement and awareness of the potential outcomes may guide the management and improve the outcome.

These studies provide a clear picture of the differential presenting features of COVID-19 and MIS-C. Although there may be other environmental/genetic factors that govern the incidence, impact, and manifestations, COVID’s status as an ongoing pandemic gives these observations worldwide relevance. This is evident in a recent report documenting pronounced GI symptoms in African children with COVID-19.

It should be noted, however, that the published data cited here reflect the impact of the initial variants of SARS-CoV-2. The GI binding, effects, and aftermath of infection with the Delta and Omicron variants is not yet known.
 

Cause and effect, or simply coincidental?

Some insight into MIS-C pathogenesis was provided by Lael M. Yonker, MD, and colleagues in their analysis of biospecimens from 100 children: 19 with MIS-C, 26 with acute COVID-19, and 55 controls. They demonstrated that in children with MIS-C the prolonged presence of SARS-CoV-2 in the GI tract led to the release of zonulin, a biomarker of intestinal permeability, with subsequent trafficking of SARS-CoV-2 antigens into the bloodstream, leading to hyperinflammation. They were then able to decrease plasma SARS-CoV-2 spike antigen levels and inflammatory markers, with resulting clinical improvement after administration of larazotide, a zonulin antagonist.

These observations regarding the potential mechanism and triggers of MIS-C may offer biomarkers for early detection and/or strategies for prevention and treatment of MIS-C.
 

Bottom line

The GI tract is the target of an immune-mediated inflammatory response that is triggered by SARS-CoV-2, with MIS-C being the major manifestation of the resultant high degree of inflammation. These observations will allow an increased awareness of nonrespiratory symptoms of SARS-CoV-2 infection by clinicians working in emergency departments and primary care settings.

Clues that may enhance the ability of pediatric clinicians to recognize the potential for severe GI involvement include the occurrence of abdominal pain, leukopenia, and elevated inflammatory markers. Their presence should raise suspicion of MIS-C and lead to early evaluation.

Of note, COVID-19 mRNA vaccination is associated with a lower incidence of MIS-C in adolescents. This underscores the importance of COVID vaccination for all eligible children. Yet, we clearly have our work cut out for us. Of 107 children with MIS-C who were hospitalized in France, 31% were adolescents eligible for vaccination; however, none had been fully vaccinated. At the end of 2021, CDC data noted that less than 1% of vaccine-eligible children (12-17 years) were fully vaccinated.

The Pfizer-BioNTech vaccine is now authorized for receipt by children aged 5-11 years, the age group that is at highest risk for MIS-C. However, despite the approval of vaccines for these younger children, there is limited access in some parts of the United States at a time of rising incidence.

We look forward to broad availability of pediatric vaccination strategies. In addition, with the intense focus on safe and effective therapeutics for SARS-CoV-2 infection, we hope to soon have strategies to prevent and/or treat the life-threatening manifestations and long-term consequences of MIS-C. For example, the recently reported central role of the gut microbiota in immunity against SARS-CoV-2 infection offer the possibility that “microbiota modulation” may both reduce GI injury and enhance vaccine efficacy.

Dr. Balistreri has disclosed no relevant financial relationships.

William F. Balistreri, MD, is the Dorothy M.M. Kersten Professor of Pediatrics; director emeritus, Pediatric Liver Care Center; medical director emeritus, liver transplantation; and professor, University of Cincinnati College of Medicine, department of pediatrics, Cincinnati Children’s Hospital Medical Center. He has served as director of the division of gastroenterology, hepatology, and nutrition at Cincinnati Children’s for 25 years and frequently covers gastroenterology, liver, and nutrition-related topics for this news organization. Dr Balistreri is currently editor-in-chief of the Journal of Pediatrics, having previously served as editor-in-chief of several journals and textbooks. He also became the first pediatrician to act as president of the American Association for the Study of Liver Diseases. In his spare time, he coaches youth lacrosse.

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

While evaluating an adolescent who had endured a several-day history of vomiting and diarrhea, I mentioned the likelihood of a viral causation, including SARS-CoV-2 infection. His well-informed mother responded, “He has no respiratory symptoms. Does COVID cause GI disease?”

Indeed, not only is the gastrointestinal tract a potential portal of entry of the virus but it may well be the site of mediation of both local and remote injury and thus a harbinger of more severe clinical phenotypes.

As we learn more about the clinical spectrum of COVID, it is becoming increasingly clear that certain features of GI tract involvement may allow us to establish a timeline of the clinical course and perhaps predict the outcome.
 

The GI tract’s involvement isn’t surprising

The ways in which the GI tract serves as a target organ of SARS-CoV-2 have been postulated in the literature. In part, this is related to the presence of abundant receptors for SARS-CoV-2 cell binding and internalization. The virus uses angiotensin-converting enzyme 2 receptors to enter various cells. These receptors are highly expressed on not only lung cells but also enterocytes. Binding of SARS-CoV-2 to ACE2 receptors allows GI involvement, leading to microscopic mucosal inflammation, increased permeability, and altered intestinal absorption.

The clinical GI manifestations of this include anorexia, nausea, vomiting, diarrhea, and abdominal pain, which may be the earliest, or sole, symptoms of COVID-19, often noted before the onset of fever or respiratory symptoms. In fact, John Ong, MBBS, and colleagues, in a discussion about patients with primary GI SARS-CoV-2 infection and symptoms, use the term “GI-COVID.”
 

Clinical course of GI manifestations

After SARS-CoV-2 exposure, adults most commonly present with respiratory symptoms, with GI symptoms reported in 10%-15% of cases. However, the overall incidence of GI involvement during SARS-CoV-2 infection varies according to age, with children more likely than adults to manifest intestinal symptoms.

There are also differences in incidence reported when comparing hospitalized with nonhospitalized individuals. In early reports from the onset of the COVID-19 pandemic, 11%-43% of hospitalized adult patients manifested GI symptoms. Of note, the presence of GI symptoms was associated with more severe disease and thus predictive of outcomes in those admitted to hospitals.

In a multicenter study that assessed pediatric inpatients with COVID-19, GI manifestations were present in 57% of patients and were the first manifestation in 14%. Adjusted by confounding factors, those with GI symptoms had a higher risk for pediatric intensive care unit admission. Patients admitted to the PICU also had higher serum C-reactive protein and aspartate aminotransferase values.
 

Emerging data on MIS-C

In previously healthy children and adolescents, the severe, life-threatening complication of multisystem inflammatory syndrome in children (MIS-C) may present 2-6 weeks after acute infection with SARS-CoV-2. MIS-C appears to be an immune activation syndrome and is presumed to be the delayed immunologic sequelae of mild/asymptomatic SARS-CoV-2 infection. This response manifests as hyperinflammation in conjunction with a peak in antibody production a few weeks later.

One report of 186 children with MIS-C in the United States noted that the involved organ system included the GI tract in 92%, followed by cardiovascular in 80%, hematologic in 76%, mucocutaneous in 74%, and respiratory in 70%. Affected children were hospitalized for a median of 7 days, with 80% requiring intensive care, 20% receiving mechanical ventilation, and 48% receiving vasoactive support; 2% died. In a similar study of patients hospitalized in New York, 88% had GI symptoms (abdominal pain, vomiting, and/or diarrhea). A retrospective chart review of patients with MIS-C found that the majority had GI symptoms with any portion of the GI tract potentially involved, but ileal and colonic inflammation predominated.

Elizabeth Whittaker, MD, and colleagues described the clinical characteristics of children in eight hospitals in England who met criteria for MIS-C that were temporally associated with SARS-CoV-2. At presentation, all of the patients manifested fever and nonspecific GI symptoms, including vomiting (45%), abdominal pain (53%), and diarrhea (52%). During hospitalization, 50% developed shock with evidence of myocardial dysfunction.

Ermias D. Belay, MD, and colleagues described the clinical characteristics of a large cohort of patients with MIS-C that were reported to the U.S. Centers for Disease Control and Prevention. Of 1,733 patients identified, GI symptoms were reported in 53%-67%. Over half developed hypotension or shock and were admitted for intensive care. Younger children more frequently presented with abdominal pain in contrast with adolescents, who more frequently manifest respiratory symptoms.

In a multicenter retrospective study of Italian children with COVID-19 that was conducted from the onset of the pandemic to early 2021, GI symptoms were noted in 38%. These manifestations were mild and self-limiting, comparable to other viral intestinal infections. However, a subset of children (9.5%) had severe GI manifestations of MIS-C, defined as a medical and/or radiologic diagnosis of acute abdomen, appendicitis, intussusception, pancreatitis, abdominal fluid collection, or diffuse adenomesenteritis requiring surgical consultation. Overall, 42% of this group underwent surgery. The authors noted that the clinical presentation of abdominal pain, lymphopenia, and increased C-reactive protein and ferritin levels were associated with a 9- to 30-fold increased probability of these severe sequelae. In addition, the severity of the GI manifestations was correlated with age (5-10 years: overall response, 8.33; >10 years: OR, 6.37). Again, the presence of GI symptoms was a harbinger of hospitalization and PICU admission.

Given that GI symptoms are a common presentation of MIS-C, its diagnosis may be delayed as clinicians first consider other GI/viral infections, inflammatory bowel disease, or Kawasaki disease. Prompt identification of GI involvement and awareness of the potential outcomes may guide the management and improve the outcome.

These studies provide a clear picture of the differential presenting features of COVID-19 and MIS-C. Although there may be other environmental/genetic factors that govern the incidence, impact, and manifestations, COVID’s status as an ongoing pandemic gives these observations worldwide relevance. This is evident in a recent report documenting pronounced GI symptoms in African children with COVID-19.

It should be noted, however, that the published data cited here reflect the impact of the initial variants of SARS-CoV-2. The GI binding, effects, and aftermath of infection with the Delta and Omicron variants is not yet known.
 

Cause and effect, or simply coincidental?

Some insight into MIS-C pathogenesis was provided by Lael M. Yonker, MD, and colleagues in their analysis of biospecimens from 100 children: 19 with MIS-C, 26 with acute COVID-19, and 55 controls. They demonstrated that in children with MIS-C the prolonged presence of SARS-CoV-2 in the GI tract led to the release of zonulin, a biomarker of intestinal permeability, with subsequent trafficking of SARS-CoV-2 antigens into the bloodstream, leading to hyperinflammation. They were then able to decrease plasma SARS-CoV-2 spike antigen levels and inflammatory markers, with resulting clinical improvement after administration of larazotide, a zonulin antagonist.

These observations regarding the potential mechanism and triggers of MIS-C may offer biomarkers for early detection and/or strategies for prevention and treatment of MIS-C.
 

Bottom line

The GI tract is the target of an immune-mediated inflammatory response that is triggered by SARS-CoV-2, with MIS-C being the major manifestation of the resultant high degree of inflammation. These observations will allow an increased awareness of nonrespiratory symptoms of SARS-CoV-2 infection by clinicians working in emergency departments and primary care settings.

Clues that may enhance the ability of pediatric clinicians to recognize the potential for severe GI involvement include the occurrence of abdominal pain, leukopenia, and elevated inflammatory markers. Their presence should raise suspicion of MIS-C and lead to early evaluation.

Of note, COVID-19 mRNA vaccination is associated with a lower incidence of MIS-C in adolescents. This underscores the importance of COVID vaccination for all eligible children. Yet, we clearly have our work cut out for us. Of 107 children with MIS-C who were hospitalized in France, 31% were adolescents eligible for vaccination; however, none had been fully vaccinated. At the end of 2021, CDC data noted that less than 1% of vaccine-eligible children (12-17 years) were fully vaccinated.

The Pfizer-BioNTech vaccine is now authorized for receipt by children aged 5-11 years, the age group that is at highest risk for MIS-C. However, despite the approval of vaccines for these younger children, there is limited access in some parts of the United States at a time of rising incidence.

We look forward to broad availability of pediatric vaccination strategies. In addition, with the intense focus on safe and effective therapeutics for SARS-CoV-2 infection, we hope to soon have strategies to prevent and/or treat the life-threatening manifestations and long-term consequences of MIS-C. For example, the recently reported central role of the gut microbiota in immunity against SARS-CoV-2 infection offer the possibility that “microbiota modulation” may both reduce GI injury and enhance vaccine efficacy.

Dr. Balistreri has disclosed no relevant financial relationships.

William F. Balistreri, MD, is the Dorothy M.M. Kersten Professor of Pediatrics; director emeritus, Pediatric Liver Care Center; medical director emeritus, liver transplantation; and professor, University of Cincinnati College of Medicine, department of pediatrics, Cincinnati Children’s Hospital Medical Center. He has served as director of the division of gastroenterology, hepatology, and nutrition at Cincinnati Children’s for 25 years and frequently covers gastroenterology, liver, and nutrition-related topics for this news organization. Dr Balistreri is currently editor-in-chief of the Journal of Pediatrics, having previously served as editor-in-chief of several journals and textbooks. He also became the first pediatrician to act as president of the American Association for the Study of Liver Diseases. In his spare time, he coaches youth lacrosse.

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

On the first Friday in March, it has become an annual tradition to dress in blue to promote colorectal cancer awareness. Twitter feeds are filled with photos of members of our gastroenterology community (sometimes entire endoscopy units!) swathed in various shades of blue. This tradition was started in the mid-2000’s by a patient diagnosed with early-onset colorectal cancer who planned a fund raiser at her daughter’s elementary school where students were encouraged to wear a blue outfit and make a $1 donation to support awareness of this deadly but preventable cancer. What was once a local effort has now grown into a national phenomenon, and a powerful opportunity for the medical community to educate patients, friends, and family regarding risk factors for colorectal cancer and the importance of timely and effective screening. But while raising awareness is vital, it is only an initial step in the complex process of optimizing delivery of screening services and improving cancer outcomes through prevention and early detection.

In this month’s issue of GIHN, we report on a study from Cancer demonstrating the effectiveness of Spanish-speaking patient navigators in boosting colorectal cancer screening rates among Hispanic patients. We also highlight a quality improvement initiative at a large academic medical center demonstrating the impact of an electronic “primer” message delivered through the patient portal on screening completion rates in a mailed fecal immunochemical test outreach program. Finally, in this month’s Practice Management Toolbox column, Dr. Brill and Dr. Lieberman advise us on how to prepare for upcoming coverage changes impacting screening colonoscopy – a result of AGA’s tireless efforts to eliminate financial barriers impeding access to colorectal cancer screening.

As always, thank you for being a dedicated reader and please stay safe out there. Better days are ahead.

Megan A. Adams, MD, JD, MSc
Editor in Chief

On the first Friday in March, it has become an annual tradition to dress in blue to promote colorectal cancer awareness. Twitter feeds are filled with photos of members of our gastroenterology community (sometimes entire endoscopy units!) swathed in various shades of blue. This tradition was started in the mid-2000’s by a patient diagnosed with early-onset colorectal cancer who planned a fund raiser at her daughter’s elementary school where students were encouraged to wear a blue outfit and make a $1 donation to support awareness of this deadly but preventable cancer. What was once a local effort has now grown into a national phenomenon, and a powerful opportunity for the medical community to educate patients, friends, and family regarding risk factors for colorectal cancer and the importance of timely and effective screening. But while raising awareness is vital, it is only an initial step in the complex process of optimizing delivery of screening services and improving cancer outcomes through prevention and early detection.

In this month’s issue of GIHN, we report on a study from Cancer demonstrating the effectiveness of Spanish-speaking patient navigators in boosting colorectal cancer screening rates among Hispanic patients. We also highlight a quality improvement initiative at a large academic medical center demonstrating the impact of an electronic “primer” message delivered through the patient portal on screening completion rates in a mailed fecal immunochemical test outreach program. Finally, in this month’s Practice Management Toolbox column, Dr. Brill and Dr. Lieberman advise us on how to prepare for upcoming coverage changes impacting screening colonoscopy – a result of AGA’s tireless efforts to eliminate financial barriers impeding access to colorectal cancer screening.

As always, thank you for being a dedicated reader and please stay safe out there. Better days are ahead.

Megan A. Adams, MD, JD, MSc
Editor in Chief

On the first Friday in March, it has become an annual tradition to dress in blue to promote colorectal cancer awareness. Twitter feeds are filled with photos of members of our gastroenterology community (sometimes entire endoscopy units!) swathed in various shades of blue. This tradition was started in the mid-2000’s by a patient diagnosed with early-onset colorectal cancer who planned a fund raiser at her daughter’s elementary school where students were encouraged to wear a blue outfit and make a $1 donation to support awareness of this deadly but preventable cancer. What was once a local effort has now grown into a national phenomenon, and a powerful opportunity for the medical community to educate patients, friends, and family regarding risk factors for colorectal cancer and the importance of timely and effective screening. But while raising awareness is vital, it is only an initial step in the complex process of optimizing delivery of screening services and improving cancer outcomes through prevention and early detection.

In this month’s issue of GIHN, we report on a study from Cancer demonstrating the effectiveness of Spanish-speaking patient navigators in boosting colorectal cancer screening rates among Hispanic patients. We also highlight a quality improvement initiative at a large academic medical center demonstrating the impact of an electronic “primer” message delivered through the patient portal on screening completion rates in a mailed fecal immunochemical test outreach program. Finally, in this month’s Practice Management Toolbox column, Dr. Brill and Dr. Lieberman advise us on how to prepare for upcoming coverage changes impacting screening colonoscopy – a result of AGA’s tireless efforts to eliminate financial barriers impeding access to colorectal cancer screening.

As always, thank you for being a dedicated reader and please stay safe out there. Better days are ahead.

Megan A. Adams, MD, JD, MSc
Editor in Chief