IgG4 fights viruses and bacteria. However, sometimes it targets the body itself. “This then leads to inflammation, the healing of which the body is unable to keep under control,” explained Ulf Müller-Ladner, MD, PhD, chairperson of the German Society of Internal Medicine.

At the DGIM annual press conference, Dr. Müller-Ladner, who is also director of the department of rheumatology and clinical immunology at the Kerckhoff Clinic in Bad Nauheim, Germany, explained how IgG4 inflammation is triggered throughout the body and what therapeutic options are available.
 

Many manifestations

IgG4-associated inflammation can affect one or more organs or the surrounding connective tissue and cause fibrosis. As a result of fibrosis, the organ gradually loses function and is eventually transformed completely into scarred connective tissue.

“In the case of IgG4-associated inflammation, these fibroses have a histological structure, but extracting a sample is not possible from every affected organ,” said Dr. Müller-Ladner. Liver, bile ducts, blood vessels, skin, eyes, or even the central nervous system – practically every organ system can be affected by these inflammatory reactions.

IgG4-associated diseases have likely been around for some time, but it is only in the past 10 years that awareness has grown that, despite various manifestations, “they are all one and the same disease,” said Dr. Müller-Ladner.

IgG4-associated chronic, inflammatory, fibrosing diseases were only classified together as a single entity in the past few years. In terms of pathophysiology, B lymphocytes, IgG4-positive plasma cells, follicular T-helper cells, cytotoxic CD4-positive T cells, and macrophages work together and trigger an inflammatory reaction, which then encourages fibroblasts to overproduce connective tissue.
 

Beware inexplicable inflammation

It is estimated that 1 in 100,000 people suffer from the disease, but the number of incorrectly categorized patients may be significantly higher.

The diagnostic challenge lies in the fact that IgG4-associated inflammation occurs in almost every organ. It can cause different symptoms, depending on the organ affected.

Dr. Müller-Ladner provided the following take-home message: “Every inexplicable inflammation event and every organ dysfunction, especially if associated with an increase in connective tissue, could be an IgG4-associated disease. Keeping this in mind is the key to recovery.”

With most people, the inflammation persists for many years before any symptoms of the disease develop. Highly acute courses of progression are also possible.

Classic symptoms, such as fever, are not so characteristic of the latent inflammatory reaction, and according to classification criteria published by specialist rheumatology societies, they are an exclusion criterion. This is true with respect to the differential diagnosis for vasculitis, which also occurs throughout the body.
 

Histology is key

Blood levels of IgG4 and imaging are not always enough to confirm the diagnosis. In such cases, the histology is often a crucial factor in making a definitive diagnosis. Dominant organs in IgG4-associated diseases are the pancreas, the liver, the gallbladder, the intestines, the retroperitoneum, large blood vessels, the kidneys, the heart, the brain, saliva, tear ducts, as well all of the body’s connective tissue.

The kidneys play host to inflammation in the connective tissue and space-occupying masses in particular. “If the pancreas is affected, the signs can vary from diffuse swelling to the onset of diabetes mellitus. In contrast, if the aorta is affected, then the inflammation is characterized through a thickening of the vessel walls, aneurysms, and the corresponding circulation disorders,” said Dr. Müller-Ladner.

Because of the long period before the diagnosis is made, more than 50% of patients exhibit irreversible organ damage at the time of diagnosis, he added.
 

Glucocorticoids and immunosuppressants

Despite therapeutic intervention, the disease can have a fatal outcome, even if the patient is young, said Dr. Müller-Ladner. Glucocorticoids are the current therapy of choice. The dose is more than 0.5 mg of prednisolone equivalent per kg of body weight. “This usually leads to a rapid improvement in the inflammation. Subsequently, every organ is thoroughly diagnosed to assess the severity of the disease and to plan further treatment steps.”

In the long term, proven immunosuppressants, such as azathioprine, mycophenolate, leflunomide, and methotrexate, can be used, just as for many other chronic inflammatory diseases. Cyclophosphamide or cyclosporine is used more rarely, owing to their side effect profiles.

Because of the B-cell dominance, B-cell–depleting therapy with rituximab is currently a highly effective therapeutic option but one that must be applied for, because such use is off label. “If the body responds well to the medication, organ function often recovers,” said Dr. Müller-Ladner.

This article was translated from the Medscape German edition. A version appeared on Medscape.com.

IgG4 fights viruses and bacteria. However, sometimes it targets the body itself. “This then leads to inflammation, the healing of which the body is unable to keep under control,” explained Ulf Müller-Ladner, MD, PhD, chairperson of the German Society of Internal Medicine.

At the DGIM annual press conference, Dr. Müller-Ladner, who is also director of the department of rheumatology and clinical immunology at the Kerckhoff Clinic in Bad Nauheim, Germany, explained how IgG4 inflammation is triggered throughout the body and what therapeutic options are available.
 

Many manifestations

IgG4-associated inflammation can affect one or more organs or the surrounding connective tissue and cause fibrosis. As a result of fibrosis, the organ gradually loses function and is eventually transformed completely into scarred connective tissue.

“In the case of IgG4-associated inflammation, these fibroses have a histological structure, but extracting a sample is not possible from every affected organ,” said Dr. Müller-Ladner. Liver, bile ducts, blood vessels, skin, eyes, or even the central nervous system – practically every organ system can be affected by these inflammatory reactions.

IgG4-associated diseases have likely been around for some time, but it is only in the past 10 years that awareness has grown that, despite various manifestations, “they are all one and the same disease,” said Dr. Müller-Ladner.

IgG4-associated chronic, inflammatory, fibrosing diseases were only classified together as a single entity in the past few years. In terms of pathophysiology, B lymphocytes, IgG4-positive plasma cells, follicular T-helper cells, cytotoxic CD4-positive T cells, and macrophages work together and trigger an inflammatory reaction, which then encourages fibroblasts to overproduce connective tissue.
 

Beware inexplicable inflammation

It is estimated that 1 in 100,000 people suffer from the disease, but the number of incorrectly categorized patients may be significantly higher.

The diagnostic challenge lies in the fact that IgG4-associated inflammation occurs in almost every organ. It can cause different symptoms, depending on the organ affected.

Dr. Müller-Ladner provided the following take-home message: “Every inexplicable inflammation event and every organ dysfunction, especially if associated with an increase in connective tissue, could be an IgG4-associated disease. Keeping this in mind is the key to recovery.”

With most people, the inflammation persists for many years before any symptoms of the disease develop. Highly acute courses of progression are also possible.

Classic symptoms, such as fever, are not so characteristic of the latent inflammatory reaction, and according to classification criteria published by specialist rheumatology societies, they are an exclusion criterion. This is true with respect to the differential diagnosis for vasculitis, which also occurs throughout the body.
 

Histology is key

Blood levels of IgG4 and imaging are not always enough to confirm the diagnosis. In such cases, the histology is often a crucial factor in making a definitive diagnosis. Dominant organs in IgG4-associated diseases are the pancreas, the liver, the gallbladder, the intestines, the retroperitoneum, large blood vessels, the kidneys, the heart, the brain, saliva, tear ducts, as well all of the body’s connective tissue.

The kidneys play host to inflammation in the connective tissue and space-occupying masses in particular. “If the pancreas is affected, the signs can vary from diffuse swelling to the onset of diabetes mellitus. In contrast, if the aorta is affected, then the inflammation is characterized through a thickening of the vessel walls, aneurysms, and the corresponding circulation disorders,” said Dr. Müller-Ladner.

Because of the long period before the diagnosis is made, more than 50% of patients exhibit irreversible organ damage at the time of diagnosis, he added.
 

Glucocorticoids and immunosuppressants

Despite therapeutic intervention, the disease can have a fatal outcome, even if the patient is young, said Dr. Müller-Ladner. Glucocorticoids are the current therapy of choice. The dose is more than 0.5 mg of prednisolone equivalent per kg of body weight. “This usually leads to a rapid improvement in the inflammation. Subsequently, every organ is thoroughly diagnosed to assess the severity of the disease and to plan further treatment steps.”

In the long term, proven immunosuppressants, such as azathioprine, mycophenolate, leflunomide, and methotrexate, can be used, just as for many other chronic inflammatory diseases. Cyclophosphamide or cyclosporine is used more rarely, owing to their side effect profiles.

Because of the B-cell dominance, B-cell–depleting therapy with rituximab is currently a highly effective therapeutic option but one that must be applied for, because such use is off label. “If the body responds well to the medication, organ function often recovers,” said Dr. Müller-Ladner.

This article was translated from the Medscape German edition. A version appeared on Medscape.com.

IgG4 fights viruses and bacteria. However, sometimes it targets the body itself. “This then leads to inflammation, the healing of which the body is unable to keep under control,” explained Ulf Müller-Ladner, MD, PhD, chairperson of the German Society of Internal Medicine.

At the DGIM annual press conference, Dr. Müller-Ladner, who is also director of the department of rheumatology and clinical immunology at the Kerckhoff Clinic in Bad Nauheim, Germany, explained how IgG4 inflammation is triggered throughout the body and what therapeutic options are available.
 

Many manifestations

IgG4-associated inflammation can affect one or more organs or the surrounding connective tissue and cause fibrosis. As a result of fibrosis, the organ gradually loses function and is eventually transformed completely into scarred connective tissue.

“In the case of IgG4-associated inflammation, these fibroses have a histological structure, but extracting a sample is not possible from every affected organ,” said Dr. Müller-Ladner. Liver, bile ducts, blood vessels, skin, eyes, or even the central nervous system – practically every organ system can be affected by these inflammatory reactions.

IgG4-associated diseases have likely been around for some time, but it is only in the past 10 years that awareness has grown that, despite various manifestations, “they are all one and the same disease,” said Dr. Müller-Ladner.

IgG4-associated chronic, inflammatory, fibrosing diseases were only classified together as a single entity in the past few years. In terms of pathophysiology, B lymphocytes, IgG4-positive plasma cells, follicular T-helper cells, cytotoxic CD4-positive T cells, and macrophages work together and trigger an inflammatory reaction, which then encourages fibroblasts to overproduce connective tissue.
 

Beware inexplicable inflammation

It is estimated that 1 in 100,000 people suffer from the disease, but the number of incorrectly categorized patients may be significantly higher.

The diagnostic challenge lies in the fact that IgG4-associated inflammation occurs in almost every organ. It can cause different symptoms, depending on the organ affected.

Dr. Müller-Ladner provided the following take-home message: “Every inexplicable inflammation event and every organ dysfunction, especially if associated with an increase in connective tissue, could be an IgG4-associated disease. Keeping this in mind is the key to recovery.”

With most people, the inflammation persists for many years before any symptoms of the disease develop. Highly acute courses of progression are also possible.

Classic symptoms, such as fever, are not so characteristic of the latent inflammatory reaction, and according to classification criteria published by specialist rheumatology societies, they are an exclusion criterion. This is true with respect to the differential diagnosis for vasculitis, which also occurs throughout the body.
 

Histology is key

Blood levels of IgG4 and imaging are not always enough to confirm the diagnosis. In such cases, the histology is often a crucial factor in making a definitive diagnosis. Dominant organs in IgG4-associated diseases are the pancreas, the liver, the gallbladder, the intestines, the retroperitoneum, large blood vessels, the kidneys, the heart, the brain, saliva, tear ducts, as well all of the body’s connective tissue.

The kidneys play host to inflammation in the connective tissue and space-occupying masses in particular. “If the pancreas is affected, the signs can vary from diffuse swelling to the onset of diabetes mellitus. In contrast, if the aorta is affected, then the inflammation is characterized through a thickening of the vessel walls, aneurysms, and the corresponding circulation disorders,” said Dr. Müller-Ladner.

Because of the long period before the diagnosis is made, more than 50% of patients exhibit irreversible organ damage at the time of diagnosis, he added.
 

Glucocorticoids and immunosuppressants

Despite therapeutic intervention, the disease can have a fatal outcome, even if the patient is young, said Dr. Müller-Ladner. Glucocorticoids are the current therapy of choice. The dose is more than 0.5 mg of prednisolone equivalent per kg of body weight. “This usually leads to a rapid improvement in the inflammation. Subsequently, every organ is thoroughly diagnosed to assess the severity of the disease and to plan further treatment steps.”

In the long term, proven immunosuppressants, such as azathioprine, mycophenolate, leflunomide, and methotrexate, can be used, just as for many other chronic inflammatory diseases. Cyclophosphamide or cyclosporine is used more rarely, owing to their side effect profiles.

Because of the B-cell dominance, B-cell–depleting therapy with rituximab is currently a highly effective therapeutic option but one that must be applied for, because such use is off label. “If the body responds well to the medication, organ function often recovers,” said Dr. Müller-Ladner.

This article was translated from the Medscape German edition. A version appeared on Medscape.com.

The natural immunity provided by a COVID infection protects a person against severe illness on a par with two doses of mRNA vaccine, a new study says. 

People who’ve been infected with COVID reduced their chances of hospitalization and death by 88% over 10 months compared to somebody who hasn’t been infected, according to the study, published in The Lancet. 

The natural immunity provided by infection was “at least as high, if not higher” than the immunity provided by two doses of Moderna or Pfizer mRNA vaccines against the ancestral, Alpha, Delta, and Omicron BA.1 variants, the researchers reported. 

But protection against the BA.1 subvariant of Omicron was not as high – 36% at 10 months after infection, wrote the research team from the Institute for Health Metrics and Evaluation at the University of Washington.

They examined 65 studies from 19 countries through Sept. 31, 2022. They did not study data about infection from Omicron XBB and its sub-lineages. People who had immunity from both infection and vaccination, known as hybrid immunity, were not studied. 

The findings don’t mean people should skip the vaccines and get COVID on purpose, one of the researchers told NBC News. 

“The problem of saying ‘I’m gonna get infected to get immunity’ is you might be one of those people that end up in the hospital or die,” said Christopher Murray, MD, DPhil, director of the IHME. “Why would you take the risk when you can get immunity through vaccination quite safely?”

The findings could help people figure out the most effective time to get vaccinated or boosted and guide officials in setting policies on workplace vaccine mandates and rules for high-occupancy indoor settings, the researchers concluded.

This was the largest meta-analysis of immunity following infection to date, NBC News reports.

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

The natural immunity provided by a COVID infection protects a person against severe illness on a par with two doses of mRNA vaccine, a new study says. 

People who’ve been infected with COVID reduced their chances of hospitalization and death by 88% over 10 months compared to somebody who hasn’t been infected, according to the study, published in The Lancet. 

The natural immunity provided by infection was “at least as high, if not higher” than the immunity provided by two doses of Moderna or Pfizer mRNA vaccines against the ancestral, Alpha, Delta, and Omicron BA.1 variants, the researchers reported. 

But protection against the BA.1 subvariant of Omicron was not as high – 36% at 10 months after infection, wrote the research team from the Institute for Health Metrics and Evaluation at the University of Washington.

They examined 65 studies from 19 countries through Sept. 31, 2022. They did not study data about infection from Omicron XBB and its sub-lineages. People who had immunity from both infection and vaccination, known as hybrid immunity, were not studied. 

The findings don’t mean people should skip the vaccines and get COVID on purpose, one of the researchers told NBC News. 

“The problem of saying ‘I’m gonna get infected to get immunity’ is you might be one of those people that end up in the hospital or die,” said Christopher Murray, MD, DPhil, director of the IHME. “Why would you take the risk when you can get immunity through vaccination quite safely?”

The findings could help people figure out the most effective time to get vaccinated or boosted and guide officials in setting policies on workplace vaccine mandates and rules for high-occupancy indoor settings, the researchers concluded.

This was the largest meta-analysis of immunity following infection to date, NBC News reports.

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

The natural immunity provided by a COVID infection protects a person against severe illness on a par with two doses of mRNA vaccine, a new study says. 

People who’ve been infected with COVID reduced their chances of hospitalization and death by 88% over 10 months compared to somebody who hasn’t been infected, according to the study, published in The Lancet. 

The natural immunity provided by infection was “at least as high, if not higher” than the immunity provided by two doses of Moderna or Pfizer mRNA vaccines against the ancestral, Alpha, Delta, and Omicron BA.1 variants, the researchers reported. 

But protection against the BA.1 subvariant of Omicron was not as high – 36% at 10 months after infection, wrote the research team from the Institute for Health Metrics and Evaluation at the University of Washington.

They examined 65 studies from 19 countries through Sept. 31, 2022. They did not study data about infection from Omicron XBB and its sub-lineages. People who had immunity from both infection and vaccination, known as hybrid immunity, were not studied. 

The findings don’t mean people should skip the vaccines and get COVID on purpose, one of the researchers told NBC News. 

“The problem of saying ‘I’m gonna get infected to get immunity’ is you might be one of those people that end up in the hospital or die,” said Christopher Murray, MD, DPhil, director of the IHME. “Why would you take the risk when you can get immunity through vaccination quite safely?”

The findings could help people figure out the most effective time to get vaccinated or boosted and guide officials in setting policies on workplace vaccine mandates and rules for high-occupancy indoor settings, the researchers concluded.

This was the largest meta-analysis of immunity following infection to date, NBC News reports.

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

HONOLULU – In the clinical experience of John S. Barbieri, MD, MBA, cheilitis occurs in nearly all patients taking any dose of isotretinoin.

“If they don’t have dry lips, you have to wonder if they’re even absorbing isotretinoin,” Dr. Barbieri, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, said at the Hawaii Dermatology Seminar provided by MedscapeLIVE! “Everyone is going to get dry lips.”

According to a retrospective review of 1,743 patients started on isotretinoin, other common mucocutaneous side effects include eczema, nose bleeds, and eye problems. Emerging research suggests that there may be a role for oral omega-3 in decreasing such side effects of the drug. In a case control study, 118 patients were randomized to isotretinoin alone or isotretinoin plus 1 g/day of oral omega-3 for 16 weeks. At week 16, the rate of dry lips was 26% in the isoretinoin only group compared with 14% in the combination group; similar trends were seen with dry nose (11% vs. 0 %, respectively) and dry skin (11% vs. 2%).

“Omega-3 is a simple thing that we can think about recommending for patients,” Dr. Barbieri said. “It’s very safe, inexpensive, and it may help us manage these common sides effect we run into.”

Another potential side effect of isotretinoin that he characterized as underappreciated is chronic dry eye and other ocular changes. One retrospective cohort study of 14,682 adolescents and young adults in Israel found that use of the drug resulted in reduced tear production and reduced tear quality. In another study, a review and meta-analysis of 21 publications involving 1,105 eyes of 842 patients, isotretinoin use was associated with increased conjunctival fluorescein staining, decreased corneal thickness, and worse patient-reported ocular surface disease index scores.

“These changes may be mediated by meibomian gland dysfunction and atrophy,” Dr. Barbieri said. “Fortunately, many of these tear film changes appear to resolve after treatment. Those changes in corneal thickness do seem to get better. That’s reassuring.”

In a study of 54 patients treated with isotretinoin, tear production and quality returned to baseline within 6 months of treatment completion. “But some changes in the meibomian gland may be persistent,” Dr. Barbieri said. “At 6 and 12 months after the end of treatment, you can still see changes in the meibomian glands of patients who were treated with a standard course of 120 to 150 mg/kg isotretinoin,” he said, referring to the results of a study of 88 patients .

One study investigated the effects of omega-3 fatty acids and punctal plugs on tear film and ocular surface parameters in 90 patients receiving systemic isotretinoin therapy. They were divided into three groups: Those who received a soft preloaded silicone plug that was inserted in the inferior punctum of both eyes and received oral omega-3 fatty acid capsules twice daily for a total dose of 1,040 mg/day for 6 months; those who received a soft preloaded silicone plug and oral placebo, and those who received isotretinoin alone. At 6 months’ follow-up, those who were treated with omega-3 combined with the preloaded silicone plug had better meibomian gland function than did those who received isotretinoin alone or isotretinoin with the preloaded silicone plug.

Dr. Barbieri also noted that antihistamines may play a role in enhancing the effect of isotretinoin. In one study, 20 patients were treated with isotretinoin 0.4 mg/kg per day and 20 patients were also treated with an antihistamine, desloratadine 5 mg/day for 12 weeks. At week 12, patients in the group treated with isotretinoin and the antihistamine showed a more statistically significant decrease in acne lesion counts, compared with the isotretinoin-only group (reductions of 44.8% vs. 17.8%, respectively, in noninflammatory lesions; 55.8% vs. 22.9% in inflammatory lesions, and 45.6% vs. 18.7% in total lesions (P < .05 for all associations).

A subsequent larger study yielded similar findings. There were also lower rates of initial flaring and higher rates of patient satisfaction in the antihistamine groups in both studies.

In an interview at the meeting, Lawrence F. Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego, described Dr. Barbieri as “a leader in taking a comprehensive view on what the history and latest information is on isotretinoin. His fresh approach is something everyone should consider and figure out what they can use in their practice.”

Dr. Barbieri disclosed that he receives consulting fees from Dexcel for work unrelated to his presentation. Dr. Eichenfield disclosed that he has been an investigator and/or consultant for Almirall, Cassiopea, Dermata, Galderma, and Ortho Dermatologics. Medscape and this news organization are owned by the same parent company.

HONOLULU – In the clinical experience of John S. Barbieri, MD, MBA, cheilitis occurs in nearly all patients taking any dose of isotretinoin.

“If they don’t have dry lips, you have to wonder if they’re even absorbing isotretinoin,” Dr. Barbieri, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, said at the Hawaii Dermatology Seminar provided by MedscapeLIVE! “Everyone is going to get dry lips.”

According to a retrospective review of 1,743 patients started on isotretinoin, other common mucocutaneous side effects include eczema, nose bleeds, and eye problems. Emerging research suggests that there may be a role for oral omega-3 in decreasing such side effects of the drug. In a case control study, 118 patients were randomized to isotretinoin alone or isotretinoin plus 1 g/day of oral omega-3 for 16 weeks. At week 16, the rate of dry lips was 26% in the isoretinoin only group compared with 14% in the combination group; similar trends were seen with dry nose (11% vs. 0 %, respectively) and dry skin (11% vs. 2%).

“Omega-3 is a simple thing that we can think about recommending for patients,” Dr. Barbieri said. “It’s very safe, inexpensive, and it may help us manage these common sides effect we run into.”

Another potential side effect of isotretinoin that he characterized as underappreciated is chronic dry eye and other ocular changes. One retrospective cohort study of 14,682 adolescents and young adults in Israel found that use of the drug resulted in reduced tear production and reduced tear quality. In another study, a review and meta-analysis of 21 publications involving 1,105 eyes of 842 patients, isotretinoin use was associated with increased conjunctival fluorescein staining, decreased corneal thickness, and worse patient-reported ocular surface disease index scores.

“These changes may be mediated by meibomian gland dysfunction and atrophy,” Dr. Barbieri said. “Fortunately, many of these tear film changes appear to resolve after treatment. Those changes in corneal thickness do seem to get better. That’s reassuring.”

In a study of 54 patients treated with isotretinoin, tear production and quality returned to baseline within 6 months of treatment completion. “But some changes in the meibomian gland may be persistent,” Dr. Barbieri said. “At 6 and 12 months after the end of treatment, you can still see changes in the meibomian glands of patients who were treated with a standard course of 120 to 150 mg/kg isotretinoin,” he said, referring to the results of a study of 88 patients .

One study investigated the effects of omega-3 fatty acids and punctal plugs on tear film and ocular surface parameters in 90 patients receiving systemic isotretinoin therapy. They were divided into three groups: Those who received a soft preloaded silicone plug that was inserted in the inferior punctum of both eyes and received oral omega-3 fatty acid capsules twice daily for a total dose of 1,040 mg/day for 6 months; those who received a soft preloaded silicone plug and oral placebo, and those who received isotretinoin alone. At 6 months’ follow-up, those who were treated with omega-3 combined with the preloaded silicone plug had better meibomian gland function than did those who received isotretinoin alone or isotretinoin with the preloaded silicone plug.

Dr. Barbieri also noted that antihistamines may play a role in enhancing the effect of isotretinoin. In one study, 20 patients were treated with isotretinoin 0.4 mg/kg per day and 20 patients were also treated with an antihistamine, desloratadine 5 mg/day for 12 weeks. At week 12, patients in the group treated with isotretinoin and the antihistamine showed a more statistically significant decrease in acne lesion counts, compared with the isotretinoin-only group (reductions of 44.8% vs. 17.8%, respectively, in noninflammatory lesions; 55.8% vs. 22.9% in inflammatory lesions, and 45.6% vs. 18.7% in total lesions (P < .05 for all associations).

A subsequent larger study yielded similar findings. There were also lower rates of initial flaring and higher rates of patient satisfaction in the antihistamine groups in both studies.

In an interview at the meeting, Lawrence F. Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego, described Dr. Barbieri as “a leader in taking a comprehensive view on what the history and latest information is on isotretinoin. His fresh approach is something everyone should consider and figure out what they can use in their practice.”

Dr. Barbieri disclosed that he receives consulting fees from Dexcel for work unrelated to his presentation. Dr. Eichenfield disclosed that he has been an investigator and/or consultant for Almirall, Cassiopea, Dermata, Galderma, and Ortho Dermatologics. Medscape and this news organization are owned by the same parent company.

HONOLULU – In the clinical experience of John S. Barbieri, MD, MBA, cheilitis occurs in nearly all patients taking any dose of isotretinoin.

“If they don’t have dry lips, you have to wonder if they’re even absorbing isotretinoin,” Dr. Barbieri, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, said at the Hawaii Dermatology Seminar provided by MedscapeLIVE! “Everyone is going to get dry lips.”

According to a retrospective review of 1,743 patients started on isotretinoin, other common mucocutaneous side effects include eczema, nose bleeds, and eye problems. Emerging research suggests that there may be a role for oral omega-3 in decreasing such side effects of the drug. In a case control study, 118 patients were randomized to isotretinoin alone or isotretinoin plus 1 g/day of oral omega-3 for 16 weeks. At week 16, the rate of dry lips was 26% in the isoretinoin only group compared with 14% in the combination group; similar trends were seen with dry nose (11% vs. 0 %, respectively) and dry skin (11% vs. 2%).

“Omega-3 is a simple thing that we can think about recommending for patients,” Dr. Barbieri said. “It’s very safe, inexpensive, and it may help us manage these common sides effect we run into.”

Another potential side effect of isotretinoin that he characterized as underappreciated is chronic dry eye and other ocular changes. One retrospective cohort study of 14,682 adolescents and young adults in Israel found that use of the drug resulted in reduced tear production and reduced tear quality. In another study, a review and meta-analysis of 21 publications involving 1,105 eyes of 842 patients, isotretinoin use was associated with increased conjunctival fluorescein staining, decreased corneal thickness, and worse patient-reported ocular surface disease index scores.

“These changes may be mediated by meibomian gland dysfunction and atrophy,” Dr. Barbieri said. “Fortunately, many of these tear film changes appear to resolve after treatment. Those changes in corneal thickness do seem to get better. That’s reassuring.”

In a study of 54 patients treated with isotretinoin, tear production and quality returned to baseline within 6 months of treatment completion. “But some changes in the meibomian gland may be persistent,” Dr. Barbieri said. “At 6 and 12 months after the end of treatment, you can still see changes in the meibomian glands of patients who were treated with a standard course of 120 to 150 mg/kg isotretinoin,” he said, referring to the results of a study of 88 patients .

One study investigated the effects of omega-3 fatty acids and punctal plugs on tear film and ocular surface parameters in 90 patients receiving systemic isotretinoin therapy. They were divided into three groups: Those who received a soft preloaded silicone plug that was inserted in the inferior punctum of both eyes and received oral omega-3 fatty acid capsules twice daily for a total dose of 1,040 mg/day for 6 months; those who received a soft preloaded silicone plug and oral placebo, and those who received isotretinoin alone. At 6 months’ follow-up, those who were treated with omega-3 combined with the preloaded silicone plug had better meibomian gland function than did those who received isotretinoin alone or isotretinoin with the preloaded silicone plug.

Dr. Barbieri also noted that antihistamines may play a role in enhancing the effect of isotretinoin. In one study, 20 patients were treated with isotretinoin 0.4 mg/kg per day and 20 patients were also treated with an antihistamine, desloratadine 5 mg/day for 12 weeks. At week 12, patients in the group treated with isotretinoin and the antihistamine showed a more statistically significant decrease in acne lesion counts, compared with the isotretinoin-only group (reductions of 44.8% vs. 17.8%, respectively, in noninflammatory lesions; 55.8% vs. 22.9% in inflammatory lesions, and 45.6% vs. 18.7% in total lesions (P < .05 for all associations).

A subsequent larger study yielded similar findings. There were also lower rates of initial flaring and higher rates of patient satisfaction in the antihistamine groups in both studies.

In an interview at the meeting, Lawrence F. Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego, described Dr. Barbieri as “a leader in taking a comprehensive view on what the history and latest information is on isotretinoin. His fresh approach is something everyone should consider and figure out what they can use in their practice.”

Dr. Barbieri disclosed that he receives consulting fees from Dexcel for work unrelated to his presentation. Dr. Eichenfield disclosed that he has been an investigator and/or consultant for Almirall, Cassiopea, Dermata, Galderma, and Ortho Dermatologics. Medscape and this news organization are owned by the same parent company.

Approximately one in four patients with untreated COVID-19 experience symptom relapse, while almost one in three exhibits relapse of viral load, a recent study finds.

These findings offer a natural history of COVID-19 that will inform discussions and research concerning antiviral therapy, lead author Jonathan Z. Li, MD, associate professor of infectious disease at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues reported in Annals of Internal Medicine.

“There are increasing reports that high-risk patients are avoiding nirmatrelvir-ritonavir due to concerns about post-Paxlovid rebound, but there remains a gap in our knowledge of the frequency of symptom and viral relapse during untreated natural infection,” Dr. Li said in a written comment.

To address this gap, Dr. Li and colleagues analyzed data from 563 participants from the placebo group of the Adaptive Platform Treatment Trial for Outpatients with COVID-19 (ACTIV-2/A5401).

From days 0-28, patients recorded severity of 13 symptoms, with scores ranging from absent to severe (absent = 0, mild = 1, moderate = 2, severe = 3). RNA testing was performed on samples from nasal swabs on days 0–14, 21, and 28.

“The symptom rebound definition was determined by consensus of the study team, which comprises more than 10 infectious disease, pulmonary, and critical care physicians, as likely representing a clinically meaningful change in symptoms,” Dr. Li said.

Symptom scores needed to increase by at least 4 points to reach the threshold. For instance, a patient would qualify for relapse if they had worsening of four symptoms from mild to moderate, emergence of two new moderate symptoms, or emergence of one new moderate and two new mild symptoms.

The threshold for viral relapse was defined by an increase of at least 0.5 log10 RNA copies/mL from one nasal swab to the next, while high-level viral relapse was defined by an increase of at least 5.0 log10 RNA copies/mL. The former threshold was chosen based on previous analysis of viral rebound after nirmatrelvir treatment in the EPIC-HR phase 3 trial, whereas the high-level relapse point was based on Dr. Li and colleagues’ previous work linking this cutoff with the presence of infectious virus.

Their present analysis revealed that 26% of patients had symptom relapse at a median of 11 days after first symptom onset. Viral relapse occurred in 31% of patients, while high-level viral relapse occurred in 13% of participants. In about 9 out 10 cases, these relapses were detected at only one time point, suggesting they were transient. Of note, symptom relapse and high-level viral relapse occurred simultaneously in only 3% of patients.

This lack of correlation was “surprising” and “highlights that recovery from any infection is not always a linear process,” Dr. Li said.

This finding also suggests that untreated patients with recurring symptoms probably pose a low risk of contagion, according to David Wohl, MD, coauthor of the paper and professor of medicine in the division of infectious diseases at the University of North Carolina at Chapel Hill.
 

Paxlovid may not be to blame for COVID-19 rebound

“These results provide important context for the reports of Paxlovid rebound and show that baseline rates of symptom and viral relapse should be accounted for when studying the risk of rebound after antiviral therapy,” Dr. Li said.

Dr. Wohl suggested that these data can also play a role in conversations with patients who experience rebound after taking antiviral therapy.

“Many who have a return of their symptoms after taking Paxlovid blame the drug, and that may be justified, but this study suggests it happens in untreated people too,” Dr. Wohl said in a written comment.
 

Longer antiviral therapy deserves investigation

This is a “very important study” because it offers a baseline for comparing the natural history of COVID-19 with clinical course after antiviral therapy, said Timothy Henrich, MD, associate professor in the division of experimental medicine at University of California, San Francisco.

“Unlike this natural history, where it’s kind of sputtering up and down as it goes down, [after antiviral therapy,] it goes away for several days, and then it comes back up; and when it comes up, people have symptoms again,” Dr. Henrich said in an interview.

This suggests that each type of rebound is a unique phenomenon and, from a clinical perspective, that antiviral therapy may need to be extended.

“We treat for too short a period of time,” Dr. Henrich said. “We’re able to suppress [SARS-CoV-2] to the point where we’re not detecting it in the nasal pharynx, but it’s clearly still there. And it’s clearly still in a place that can replicate without the drug.”

That said, treating for longer may not be a sure-fire solution, especially if antiviral therapy is started early in the clinical course, as this could delay SARS-CoV-2-specific immune responses that are necessary for resolution, Dr. Henrich added,

“We need further study of longer-term therapies,” he said.

An array of research questions need to be addressed, according to Aditya Shah, MBBS, an infectious disease specialist at Mayo Clinic, Rochester, Minn. In a written comment, he probed the significance of rebound in various clinical scenarios.

“What [type of] rebound matters and what doesn’t?” Dr. Shah asked. “Does symptom rebound matter? How many untreated and treated ‘symptom rebounders’ need additional treatment or health care? If rebound does not really matter, but if Paxlovid helps in certain unvaccinated and high-risk patients, then does rebound matter? Future research should also focus on Paxlovid utility in vaccinated but high-risk patients. Is it as beneficial in them as it is in unvaccinated high-risk patients?”

While potentially regimen-altering questions like these remain unanswered, Dr. Henrich advised providers to keep patients focused on what we do know about the benefits of antiviral therapy given the current 5-day course, which is that it reduces the risk of severe disease and hospitalization.

The investigators disclosed relationships with Merck, Gilead, ViiV, and others. Dr. Henrich disclosed grant support from Merck and a consulting role with Roche. Dr. Shah disclosed no conflicts of interest.

Approximately one in four patients with untreated COVID-19 experience symptom relapse, while almost one in three exhibits relapse of viral load, a recent study finds.

These findings offer a natural history of COVID-19 that will inform discussions and research concerning antiviral therapy, lead author Jonathan Z. Li, MD, associate professor of infectious disease at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues reported in Annals of Internal Medicine.

“There are increasing reports that high-risk patients are avoiding nirmatrelvir-ritonavir due to concerns about post-Paxlovid rebound, but there remains a gap in our knowledge of the frequency of symptom and viral relapse during untreated natural infection,” Dr. Li said in a written comment.

To address this gap, Dr. Li and colleagues analyzed data from 563 participants from the placebo group of the Adaptive Platform Treatment Trial for Outpatients with COVID-19 (ACTIV-2/A5401).

From days 0-28, patients recorded severity of 13 symptoms, with scores ranging from absent to severe (absent = 0, mild = 1, moderate = 2, severe = 3). RNA testing was performed on samples from nasal swabs on days 0–14, 21, and 28.

“The symptom rebound definition was determined by consensus of the study team, which comprises more than 10 infectious disease, pulmonary, and critical care physicians, as likely representing a clinically meaningful change in symptoms,” Dr. Li said.

Symptom scores needed to increase by at least 4 points to reach the threshold. For instance, a patient would qualify for relapse if they had worsening of four symptoms from mild to moderate, emergence of two new moderate symptoms, or emergence of one new moderate and two new mild symptoms.

The threshold for viral relapse was defined by an increase of at least 0.5 log10 RNA copies/mL from one nasal swab to the next, while high-level viral relapse was defined by an increase of at least 5.0 log10 RNA copies/mL. The former threshold was chosen based on previous analysis of viral rebound after nirmatrelvir treatment in the EPIC-HR phase 3 trial, whereas the high-level relapse point was based on Dr. Li and colleagues’ previous work linking this cutoff with the presence of infectious virus.

Their present analysis revealed that 26% of patients had symptom relapse at a median of 11 days after first symptom onset. Viral relapse occurred in 31% of patients, while high-level viral relapse occurred in 13% of participants. In about 9 out 10 cases, these relapses were detected at only one time point, suggesting they were transient. Of note, symptom relapse and high-level viral relapse occurred simultaneously in only 3% of patients.

This lack of correlation was “surprising” and “highlights that recovery from any infection is not always a linear process,” Dr. Li said.

This finding also suggests that untreated patients with recurring symptoms probably pose a low risk of contagion, according to David Wohl, MD, coauthor of the paper and professor of medicine in the division of infectious diseases at the University of North Carolina at Chapel Hill.
 

Paxlovid may not be to blame for COVID-19 rebound

“These results provide important context for the reports of Paxlovid rebound and show that baseline rates of symptom and viral relapse should be accounted for when studying the risk of rebound after antiviral therapy,” Dr. Li said.

Dr. Wohl suggested that these data can also play a role in conversations with patients who experience rebound after taking antiviral therapy.

“Many who have a return of their symptoms after taking Paxlovid blame the drug, and that may be justified, but this study suggests it happens in untreated people too,” Dr. Wohl said in a written comment.
 

Longer antiviral therapy deserves investigation

This is a “very important study” because it offers a baseline for comparing the natural history of COVID-19 with clinical course after antiviral therapy, said Timothy Henrich, MD, associate professor in the division of experimental medicine at University of California, San Francisco.

“Unlike this natural history, where it’s kind of sputtering up and down as it goes down, [after antiviral therapy,] it goes away for several days, and then it comes back up; and when it comes up, people have symptoms again,” Dr. Henrich said in an interview.

This suggests that each type of rebound is a unique phenomenon and, from a clinical perspective, that antiviral therapy may need to be extended.

“We treat for too short a period of time,” Dr. Henrich said. “We’re able to suppress [SARS-CoV-2] to the point where we’re not detecting it in the nasal pharynx, but it’s clearly still there. And it’s clearly still in a place that can replicate without the drug.”

That said, treating for longer may not be a sure-fire solution, especially if antiviral therapy is started early in the clinical course, as this could delay SARS-CoV-2-specific immune responses that are necessary for resolution, Dr. Henrich added,

“We need further study of longer-term therapies,” he said.

An array of research questions need to be addressed, according to Aditya Shah, MBBS, an infectious disease specialist at Mayo Clinic, Rochester, Minn. In a written comment, he probed the significance of rebound in various clinical scenarios.

“What [type of] rebound matters and what doesn’t?” Dr. Shah asked. “Does symptom rebound matter? How many untreated and treated ‘symptom rebounders’ need additional treatment or health care? If rebound does not really matter, but if Paxlovid helps in certain unvaccinated and high-risk patients, then does rebound matter? Future research should also focus on Paxlovid utility in vaccinated but high-risk patients. Is it as beneficial in them as it is in unvaccinated high-risk patients?”

While potentially regimen-altering questions like these remain unanswered, Dr. Henrich advised providers to keep patients focused on what we do know about the benefits of antiviral therapy given the current 5-day course, which is that it reduces the risk of severe disease and hospitalization.

The investigators disclosed relationships with Merck, Gilead, ViiV, and others. Dr. Henrich disclosed grant support from Merck and a consulting role with Roche. Dr. Shah disclosed no conflicts of interest.

Approximately one in four patients with untreated COVID-19 experience symptom relapse, while almost one in three exhibits relapse of viral load, a recent study finds.

These findings offer a natural history of COVID-19 that will inform discussions and research concerning antiviral therapy, lead author Jonathan Z. Li, MD, associate professor of infectious disease at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues reported in Annals of Internal Medicine.

“There are increasing reports that high-risk patients are avoiding nirmatrelvir-ritonavir due to concerns about post-Paxlovid rebound, but there remains a gap in our knowledge of the frequency of symptom and viral relapse during untreated natural infection,” Dr. Li said in a written comment.

To address this gap, Dr. Li and colleagues analyzed data from 563 participants from the placebo group of the Adaptive Platform Treatment Trial for Outpatients with COVID-19 (ACTIV-2/A5401).

From days 0-28, patients recorded severity of 13 symptoms, with scores ranging from absent to severe (absent = 0, mild = 1, moderate = 2, severe = 3). RNA testing was performed on samples from nasal swabs on days 0–14, 21, and 28.

“The symptom rebound definition was determined by consensus of the study team, which comprises more than 10 infectious disease, pulmonary, and critical care physicians, as likely representing a clinically meaningful change in symptoms,” Dr. Li said.

Symptom scores needed to increase by at least 4 points to reach the threshold. For instance, a patient would qualify for relapse if they had worsening of four symptoms from mild to moderate, emergence of two new moderate symptoms, or emergence of one new moderate and two new mild symptoms.

The threshold for viral relapse was defined by an increase of at least 0.5 log10 RNA copies/mL from one nasal swab to the next, while high-level viral relapse was defined by an increase of at least 5.0 log10 RNA copies/mL. The former threshold was chosen based on previous analysis of viral rebound after nirmatrelvir treatment in the EPIC-HR phase 3 trial, whereas the high-level relapse point was based on Dr. Li and colleagues’ previous work linking this cutoff with the presence of infectious virus.

Their present analysis revealed that 26% of patients had symptom relapse at a median of 11 days after first symptom onset. Viral relapse occurred in 31% of patients, while high-level viral relapse occurred in 13% of participants. In about 9 out 10 cases, these relapses were detected at only one time point, suggesting they were transient. Of note, symptom relapse and high-level viral relapse occurred simultaneously in only 3% of patients.

This lack of correlation was “surprising” and “highlights that recovery from any infection is not always a linear process,” Dr. Li said.

This finding also suggests that untreated patients with recurring symptoms probably pose a low risk of contagion, according to David Wohl, MD, coauthor of the paper and professor of medicine in the division of infectious diseases at the University of North Carolina at Chapel Hill.
 

Paxlovid may not be to blame for COVID-19 rebound

“These results provide important context for the reports of Paxlovid rebound and show that baseline rates of symptom and viral relapse should be accounted for when studying the risk of rebound after antiviral therapy,” Dr. Li said.

Dr. Wohl suggested that these data can also play a role in conversations with patients who experience rebound after taking antiviral therapy.

“Many who have a return of their symptoms after taking Paxlovid blame the drug, and that may be justified, but this study suggests it happens in untreated people too,” Dr. Wohl said in a written comment.
 

Longer antiviral therapy deserves investigation

This is a “very important study” because it offers a baseline for comparing the natural history of COVID-19 with clinical course after antiviral therapy, said Timothy Henrich, MD, associate professor in the division of experimental medicine at University of California, San Francisco.

“Unlike this natural history, where it’s kind of sputtering up and down as it goes down, [after antiviral therapy,] it goes away for several days, and then it comes back up; and when it comes up, people have symptoms again,” Dr. Henrich said in an interview.

This suggests that each type of rebound is a unique phenomenon and, from a clinical perspective, that antiviral therapy may need to be extended.

“We treat for too short a period of time,” Dr. Henrich said. “We’re able to suppress [SARS-CoV-2] to the point where we’re not detecting it in the nasal pharynx, but it’s clearly still there. And it’s clearly still in a place that can replicate without the drug.”

That said, treating for longer may not be a sure-fire solution, especially if antiviral therapy is started early in the clinical course, as this could delay SARS-CoV-2-specific immune responses that are necessary for resolution, Dr. Henrich added,

“We need further study of longer-term therapies,” he said.

An array of research questions need to be addressed, according to Aditya Shah, MBBS, an infectious disease specialist at Mayo Clinic, Rochester, Minn. In a written comment, he probed the significance of rebound in various clinical scenarios.

“What [type of] rebound matters and what doesn’t?” Dr. Shah asked. “Does symptom rebound matter? How many untreated and treated ‘symptom rebounders’ need additional treatment or health care? If rebound does not really matter, but if Paxlovid helps in certain unvaccinated and high-risk patients, then does rebound matter? Future research should also focus on Paxlovid utility in vaccinated but high-risk patients. Is it as beneficial in them as it is in unvaccinated high-risk patients?”

While potentially regimen-altering questions like these remain unanswered, Dr. Henrich advised providers to keep patients focused on what we do know about the benefits of antiviral therapy given the current 5-day course, which is that it reduces the risk of severe disease and hospitalization.

The investigators disclosed relationships with Merck, Gilead, ViiV, and others. Dr. Henrich disclosed grant support from Merck and a consulting role with Roche. Dr. Shah disclosed no conflicts of interest.

I’ve worn glasses since I was 8, when a routine school vision test showed I was nearsighted. Except for an ill-fated 3-month attempt at contact lenses when I was 16, glasses have been just another part of my daily routine.

The last time I got new ones was in 2018, and my vision always seemed “off” after that. I took them back to the store a few times and was told I’d adjust to them and that things would be fine, So after a few weeks of doggedly wearing them I adjusted to them. I still felt like something was slightly off, but then I was busy, and then came the pandemic, and then my eye doctor retired and I had to find a new one ... so going to get my glasses prescription rechecked kept getting pushed back.

As so many of us do over time, I’ve gotten used to taking my glasses off to read things up close, like a book, or to do a detailed jigsaw puzzle. This has gotten worse over time, and so finally I made an appointment with a new eye doctor.

I handed him my previous prescription. He did a reading off the lenses, looked at the prescription again, gave me a perplexed look, and started the usual eye exam, asking me to read different lines as he switched lenses around. This went on for 10-15 minutes.

“The right lens wasn’t made correctly,” he told me. “You’ve been working off your left eye for the last 5 years.”

He returned my glasses and I put them on. He covered my left eye and showed me how, without realizing it, I was tilting my head back to bring distant items into focus on the right – the opposite of what I should be doing – and with both eyes would adjust my position to use the left eye.

The next morning, while working at my desk, I realized for the first time that I had my head turned slightly right to bring the left eye a tad closer to the screen. In a job where we’re trained to look for such minutiae in patients I’d missed it on myself. A friend even suggested I submit my story as a case report – “An unusual cause of a head-tilt in a middle-aged male” – to a journal.

It’s an interesting commentary on how adaptable the brain is at handling vision changes. It was several hundred million years ago when the brain figured out how to invert images that were seen upside down, and it continues to find ways to compensate for field cuts, cranial nerve palsies, and other lesions. Including flawed spectacles.

When my new eyeglasses arrive, my brain will have to readjust. This time, though, I’m curious and will try to pay better attention to my own reactions. If I can.

One of the other remarkable things about the brain is how it works very hard to keep us from realizing what it’s doing in the background, so we don’t notice an issue.

Amazing stuff if you think about it.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I’ve worn glasses since I was 8, when a routine school vision test showed I was nearsighted. Except for an ill-fated 3-month attempt at contact lenses when I was 16, glasses have been just another part of my daily routine.

The last time I got new ones was in 2018, and my vision always seemed “off” after that. I took them back to the store a few times and was told I’d adjust to them and that things would be fine, So after a few weeks of doggedly wearing them I adjusted to them. I still felt like something was slightly off, but then I was busy, and then came the pandemic, and then my eye doctor retired and I had to find a new one ... so going to get my glasses prescription rechecked kept getting pushed back.

As so many of us do over time, I’ve gotten used to taking my glasses off to read things up close, like a book, or to do a detailed jigsaw puzzle. This has gotten worse over time, and so finally I made an appointment with a new eye doctor.

I handed him my previous prescription. He did a reading off the lenses, looked at the prescription again, gave me a perplexed look, and started the usual eye exam, asking me to read different lines as he switched lenses around. This went on for 10-15 minutes.

“The right lens wasn’t made correctly,” he told me. “You’ve been working off your left eye for the last 5 years.”

He returned my glasses and I put them on. He covered my left eye and showed me how, without realizing it, I was tilting my head back to bring distant items into focus on the right – the opposite of what I should be doing – and with both eyes would adjust my position to use the left eye.

The next morning, while working at my desk, I realized for the first time that I had my head turned slightly right to bring the left eye a tad closer to the screen. In a job where we’re trained to look for such minutiae in patients I’d missed it on myself. A friend even suggested I submit my story as a case report – “An unusual cause of a head-tilt in a middle-aged male” – to a journal.

It’s an interesting commentary on how adaptable the brain is at handling vision changes. It was several hundred million years ago when the brain figured out how to invert images that were seen upside down, and it continues to find ways to compensate for field cuts, cranial nerve palsies, and other lesions. Including flawed spectacles.

When my new eyeglasses arrive, my brain will have to readjust. This time, though, I’m curious and will try to pay better attention to my own reactions. If I can.

One of the other remarkable things about the brain is how it works very hard to keep us from realizing what it’s doing in the background, so we don’t notice an issue.

Amazing stuff if you think about it.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I’ve worn glasses since I was 8, when a routine school vision test showed I was nearsighted. Except for an ill-fated 3-month attempt at contact lenses when I was 16, glasses have been just another part of my daily routine.

The last time I got new ones was in 2018, and my vision always seemed “off” after that. I took them back to the store a few times and was told I’d adjust to them and that things would be fine, So after a few weeks of doggedly wearing them I adjusted to them. I still felt like something was slightly off, but then I was busy, and then came the pandemic, and then my eye doctor retired and I had to find a new one ... so going to get my glasses prescription rechecked kept getting pushed back.

As so many of us do over time, I’ve gotten used to taking my glasses off to read things up close, like a book, or to do a detailed jigsaw puzzle. This has gotten worse over time, and so finally I made an appointment with a new eye doctor.

I handed him my previous prescription. He did a reading off the lenses, looked at the prescription again, gave me a perplexed look, and started the usual eye exam, asking me to read different lines as he switched lenses around. This went on for 10-15 minutes.

“The right lens wasn’t made correctly,” he told me. “You’ve been working off your left eye for the last 5 years.”

He returned my glasses and I put them on. He covered my left eye and showed me how, without realizing it, I was tilting my head back to bring distant items into focus on the right – the opposite of what I should be doing – and with both eyes would adjust my position to use the left eye.

The next morning, while working at my desk, I realized for the first time that I had my head turned slightly right to bring the left eye a tad closer to the screen. In a job where we’re trained to look for such minutiae in patients I’d missed it on myself. A friend even suggested I submit my story as a case report – “An unusual cause of a head-tilt in a middle-aged male” – to a journal.

It’s an interesting commentary on how adaptable the brain is at handling vision changes. It was several hundred million years ago when the brain figured out how to invert images that were seen upside down, and it continues to find ways to compensate for field cuts, cranial nerve palsies, and other lesions. Including flawed spectacles.

When my new eyeglasses arrive, my brain will have to readjust. This time, though, I’m curious and will try to pay better attention to my own reactions. If I can.

One of the other remarkable things about the brain is how it works very hard to keep us from realizing what it’s doing in the background, so we don’t notice an issue.

Amazing stuff if you think about it.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

SAN DIEGO – Today’s molecular tests for managing melanoma patients are used to reclassify melanoma, identify patients at risk, as well as for diagnosis, prognosis, and treatment, but each one has its specific applications, benefits, and drawbacks, according to Gregory A. Hosler, MD, PhD.

At the annual Cutaneous Malignancy Update, Dr. Hosler, director of dermatopathology for ProPath, highlighted the following molecular tests currently used for the diagnosis of challenging melanocytic lesions:

Comparative genomic hybridization (CGH). This technique allows for the detection of chromosomal copy number changes throughout the tumor genome. “With CGH, test (tumor) DNA and normal DNA are differentially labeled and compared to a reference library. Gains and losses of portions of the tumor genome are determined by comparing the relative signals from these two groups,” said Dr. Hosler, clinical professor of pathology and dermatology at the University of Texas Southwestern Medical Center, Dallas.

“In the past, your library was a metaphase of spread of chromosomes, which introduced technical challenges and made performance of the assay labor intensive. Because of this, CGH is not routinely performed by clinical laboratories and is used more as an exploratory/research technique.”

Array CGH (also known as SNP array). Newer versions of CGH use short DNA sequences that are tiled onto a chip. “The interesting thing about these chips is that you can purchase them or design them on your own,” Dr. Hosler said. “The chips may cover the entire genome or cover specific areas of the genome at higher resolution.” One upside of array CGH, he continued, is that it allows one to detect essentially all gains or losses of chromosomal material in a single reaction. “It is not subject to the artifacts associated with cutting thin sections like with fluorescence in situ hybridization (FISH); it can detect copy number neutral loss of heterozygosity, and it is more scalable,” Dr. Hosler said at the meeting, which was hosted by Scripps MD Anderson Cancer Center.

One downside of array CGH is that does not allow one to analyze specific cells, “so if you have a tumor that’s heterogeneous, the assay is agnostic to this and spits out a result based on all the material provided,” he said. “You can’t parse out different areas of the lesion. It also does not track balanced translocations.” In addition, he said, “there are also questions about reimbursement and these are lab-developed tests, so each lab’s assay is different. Finally, it requires specialized equipment and expertise for interpretation.”

FISH. First-generation melanoma FISH assays, which became available in 2009, used six probes and four colors and had a sensitivity of about 87% and specificity of about 95%, Dr. Hosler said, but there were problems with those assays, particularly related to Spitz nevi. Spitz nevi often duplicate their chromosomes, “so instead of being diploid they’re tetraploid,” he said.

“The second-generation melanoma FISH assays addressed this by adding centromeres to the assay, and targeted probes could be compared to the centromeres on the same chromosome to determine if these were true copy number gains, due to genetic instability, or gains or losses of entire arms or whole chromosomes. This modification and the addition of new targets really improved upon the sensitivity and specificity (94% and 98%, respectively),” he said, noting that this assay is widely used.

Upsides of melanoma FISH assays are that they are a “fairly routine methodology” in large clinical laboratories, he said, and that many labs are familiar with interpretation. “I would say the biggest advantage to FISH is its ability to analyze specific cells, which is useful with small or heterogeneous tumors,” Dr. Hosler said. “Also, there is a genetic reimbursement code for it, and it yields diagnostic and potentially prognostic information.” For example, certain copy number changes have shown to portend a worse prognosis if they’re present in a melanocytic tumor, including alterations in CDKN2A, CCND1, MYC, topoisomerase, and BAP1.

Downsides of melanoma FISH assays are that they are expensive, labor-intensive, and require experts to interpret the results. “The stacking and truncation of cell nuclei innate to paraffin-embedded FISH make interpretation difficult,” he said. “Also, all colors cannot be viewed simultaneously, and each lab’s assay potentially is different, requiring validation. These are not [Food and Drug Administration]-approved tests.”

Next generation sequencing (NGS). Also known as high-throughput sequencing, this technique allows for the generation of millions of sequencing reads that are aligned to a standard human genome, and likely represents the wave of the future. “With NGS you can increase breadth, so you can sequence the entire genome if you want, but you can also increase depth, meaning increasing the number of reads over a single target of the genome,” Dr. Hosler said. “That’s useful if you’re looking for a low frequency mutation.”

For example, NGS allows one to detect alterations of BRAF and KIT and other potentially actionable alterations. It can also be used to detect mutations in benign and malignant melanocytic lesions, including historically diagnostically challenging Spitz and desmoplastic subgroups. Several different NGS technologies exist, and there are different strategies behind each assay, including whole genome sequencing, whole exome sequencing, transcriptome sequencing, and targeted panels. “I’ve seen panels of 10 and I’ve seen panels of 1,500; there’s a wide range,” Dr. Hosler said. “The biggest challenge with NGS, currently, is that it’s difficult to interpret. Trying to figure out what’s important and what’s not important can be challenging. Often you need a team of people who are experts in bioinformatics to interpret these results.”

Slow turnaround time is another downside. “It can take a month to get results, and sometimes clinicians don’t want to wait that long, especially if they think a lesion is melanoma, so that’s an area of focus for NGS laboratories,” he said. “And there are questions on reimbursement. If you run NGS on every unusual melanocytic lesion, that’s not a good use of health care dollars. Who’s paying for it? I don’t have an answer for you. It’s all over the map right now. Each lab’s test and billing practice is different.”

Dr. Hosler reported having no relevant financial disclosures. ProPath is a nationwide pathology practice.

SAN DIEGO – Today’s molecular tests for managing melanoma patients are used to reclassify melanoma, identify patients at risk, as well as for diagnosis, prognosis, and treatment, but each one has its specific applications, benefits, and drawbacks, according to Gregory A. Hosler, MD, PhD.

At the annual Cutaneous Malignancy Update, Dr. Hosler, director of dermatopathology for ProPath, highlighted the following molecular tests currently used for the diagnosis of challenging melanocytic lesions:

Comparative genomic hybridization (CGH). This technique allows for the detection of chromosomal copy number changes throughout the tumor genome. “With CGH, test (tumor) DNA and normal DNA are differentially labeled and compared to a reference library. Gains and losses of portions of the tumor genome are determined by comparing the relative signals from these two groups,” said Dr. Hosler, clinical professor of pathology and dermatology at the University of Texas Southwestern Medical Center, Dallas.

“In the past, your library was a metaphase of spread of chromosomes, which introduced technical challenges and made performance of the assay labor intensive. Because of this, CGH is not routinely performed by clinical laboratories and is used more as an exploratory/research technique.”

Array CGH (also known as SNP array). Newer versions of CGH use short DNA sequences that are tiled onto a chip. “The interesting thing about these chips is that you can purchase them or design them on your own,” Dr. Hosler said. “The chips may cover the entire genome or cover specific areas of the genome at higher resolution.” One upside of array CGH, he continued, is that it allows one to detect essentially all gains or losses of chromosomal material in a single reaction. “It is not subject to the artifacts associated with cutting thin sections like with fluorescence in situ hybridization (FISH); it can detect copy number neutral loss of heterozygosity, and it is more scalable,” Dr. Hosler said at the meeting, which was hosted by Scripps MD Anderson Cancer Center.

One downside of array CGH is that does not allow one to analyze specific cells, “so if you have a tumor that’s heterogeneous, the assay is agnostic to this and spits out a result based on all the material provided,” he said. “You can’t parse out different areas of the lesion. It also does not track balanced translocations.” In addition, he said, “there are also questions about reimbursement and these are lab-developed tests, so each lab’s assay is different. Finally, it requires specialized equipment and expertise for interpretation.”

FISH. First-generation melanoma FISH assays, which became available in 2009, used six probes and four colors and had a sensitivity of about 87% and specificity of about 95%, Dr. Hosler said, but there were problems with those assays, particularly related to Spitz nevi. Spitz nevi often duplicate their chromosomes, “so instead of being diploid they’re tetraploid,” he said.

“The second-generation melanoma FISH assays addressed this by adding centromeres to the assay, and targeted probes could be compared to the centromeres on the same chromosome to determine if these were true copy number gains, due to genetic instability, or gains or losses of entire arms or whole chromosomes. This modification and the addition of new targets really improved upon the sensitivity and specificity (94% and 98%, respectively),” he said, noting that this assay is widely used.

Upsides of melanoma FISH assays are that they are a “fairly routine methodology” in large clinical laboratories, he said, and that many labs are familiar with interpretation. “I would say the biggest advantage to FISH is its ability to analyze specific cells, which is useful with small or heterogeneous tumors,” Dr. Hosler said. “Also, there is a genetic reimbursement code for it, and it yields diagnostic and potentially prognostic information.” For example, certain copy number changes have shown to portend a worse prognosis if they’re present in a melanocytic tumor, including alterations in CDKN2A, CCND1, MYC, topoisomerase, and BAP1.

Downsides of melanoma FISH assays are that they are expensive, labor-intensive, and require experts to interpret the results. “The stacking and truncation of cell nuclei innate to paraffin-embedded FISH make interpretation difficult,” he said. “Also, all colors cannot be viewed simultaneously, and each lab’s assay potentially is different, requiring validation. These are not [Food and Drug Administration]-approved tests.”

Next generation sequencing (NGS). Also known as high-throughput sequencing, this technique allows for the generation of millions of sequencing reads that are aligned to a standard human genome, and likely represents the wave of the future. “With NGS you can increase breadth, so you can sequence the entire genome if you want, but you can also increase depth, meaning increasing the number of reads over a single target of the genome,” Dr. Hosler said. “That’s useful if you’re looking for a low frequency mutation.”

For example, NGS allows one to detect alterations of BRAF and KIT and other potentially actionable alterations. It can also be used to detect mutations in benign and malignant melanocytic lesions, including historically diagnostically challenging Spitz and desmoplastic subgroups. Several different NGS technologies exist, and there are different strategies behind each assay, including whole genome sequencing, whole exome sequencing, transcriptome sequencing, and targeted panels. “I’ve seen panels of 10 and I’ve seen panels of 1,500; there’s a wide range,” Dr. Hosler said. “The biggest challenge with NGS, currently, is that it’s difficult to interpret. Trying to figure out what’s important and what’s not important can be challenging. Often you need a team of people who are experts in bioinformatics to interpret these results.”

Slow turnaround time is another downside. “It can take a month to get results, and sometimes clinicians don’t want to wait that long, especially if they think a lesion is melanoma, so that’s an area of focus for NGS laboratories,” he said. “And there are questions on reimbursement. If you run NGS on every unusual melanocytic lesion, that’s not a good use of health care dollars. Who’s paying for it? I don’t have an answer for you. It’s all over the map right now. Each lab’s test and billing practice is different.”

Dr. Hosler reported having no relevant financial disclosures. ProPath is a nationwide pathology practice.

SAN DIEGO – Today’s molecular tests for managing melanoma patients are used to reclassify melanoma, identify patients at risk, as well as for diagnosis, prognosis, and treatment, but each one has its specific applications, benefits, and drawbacks, according to Gregory A. Hosler, MD, PhD.

At the annual Cutaneous Malignancy Update, Dr. Hosler, director of dermatopathology for ProPath, highlighted the following molecular tests currently used for the diagnosis of challenging melanocytic lesions:

Comparative genomic hybridization (CGH). This technique allows for the detection of chromosomal copy number changes throughout the tumor genome. “With CGH, test (tumor) DNA and normal DNA are differentially labeled and compared to a reference library. Gains and losses of portions of the tumor genome are determined by comparing the relative signals from these two groups,” said Dr. Hosler, clinical professor of pathology and dermatology at the University of Texas Southwestern Medical Center, Dallas.

“In the past, your library was a metaphase of spread of chromosomes, which introduced technical challenges and made performance of the assay labor intensive. Because of this, CGH is not routinely performed by clinical laboratories and is used more as an exploratory/research technique.”

Array CGH (also known as SNP array). Newer versions of CGH use short DNA sequences that are tiled onto a chip. “The interesting thing about these chips is that you can purchase them or design them on your own,” Dr. Hosler said. “The chips may cover the entire genome or cover specific areas of the genome at higher resolution.” One upside of array CGH, he continued, is that it allows one to detect essentially all gains or losses of chromosomal material in a single reaction. “It is not subject to the artifacts associated with cutting thin sections like with fluorescence in situ hybridization (FISH); it can detect copy number neutral loss of heterozygosity, and it is more scalable,” Dr. Hosler said at the meeting, which was hosted by Scripps MD Anderson Cancer Center.

One downside of array CGH is that does not allow one to analyze specific cells, “so if you have a tumor that’s heterogeneous, the assay is agnostic to this and spits out a result based on all the material provided,” he said. “You can’t parse out different areas of the lesion. It also does not track balanced translocations.” In addition, he said, “there are also questions about reimbursement and these are lab-developed tests, so each lab’s assay is different. Finally, it requires specialized equipment and expertise for interpretation.”

FISH. First-generation melanoma FISH assays, which became available in 2009, used six probes and four colors and had a sensitivity of about 87% and specificity of about 95%, Dr. Hosler said, but there were problems with those assays, particularly related to Spitz nevi. Spitz nevi often duplicate their chromosomes, “so instead of being diploid they’re tetraploid,” he said.

“The second-generation melanoma FISH assays addressed this by adding centromeres to the assay, and targeted probes could be compared to the centromeres on the same chromosome to determine if these were true copy number gains, due to genetic instability, or gains or losses of entire arms or whole chromosomes. This modification and the addition of new targets really improved upon the sensitivity and specificity (94% and 98%, respectively),” he said, noting that this assay is widely used.

Upsides of melanoma FISH assays are that they are a “fairly routine methodology” in large clinical laboratories, he said, and that many labs are familiar with interpretation. “I would say the biggest advantage to FISH is its ability to analyze specific cells, which is useful with small or heterogeneous tumors,” Dr. Hosler said. “Also, there is a genetic reimbursement code for it, and it yields diagnostic and potentially prognostic information.” For example, certain copy number changes have shown to portend a worse prognosis if they’re present in a melanocytic tumor, including alterations in CDKN2A, CCND1, MYC, topoisomerase, and BAP1.

Downsides of melanoma FISH assays are that they are expensive, labor-intensive, and require experts to interpret the results. “The stacking and truncation of cell nuclei innate to paraffin-embedded FISH make interpretation difficult,” he said. “Also, all colors cannot be viewed simultaneously, and each lab’s assay potentially is different, requiring validation. These are not [Food and Drug Administration]-approved tests.”

Next generation sequencing (NGS). Also known as high-throughput sequencing, this technique allows for the generation of millions of sequencing reads that are aligned to a standard human genome, and likely represents the wave of the future. “With NGS you can increase breadth, so you can sequence the entire genome if you want, but you can also increase depth, meaning increasing the number of reads over a single target of the genome,” Dr. Hosler said. “That’s useful if you’re looking for a low frequency mutation.”

For example, NGS allows one to detect alterations of BRAF and KIT and other potentially actionable alterations. It can also be used to detect mutations in benign and malignant melanocytic lesions, including historically diagnostically challenging Spitz and desmoplastic subgroups. Several different NGS technologies exist, and there are different strategies behind each assay, including whole genome sequencing, whole exome sequencing, transcriptome sequencing, and targeted panels. “I’ve seen panels of 10 and I’ve seen panels of 1,500; there’s a wide range,” Dr. Hosler said. “The biggest challenge with NGS, currently, is that it’s difficult to interpret. Trying to figure out what’s important and what’s not important can be challenging. Often you need a team of people who are experts in bioinformatics to interpret these results.”

Slow turnaround time is another downside. “It can take a month to get results, and sometimes clinicians don’t want to wait that long, especially if they think a lesion is melanoma, so that’s an area of focus for NGS laboratories,” he said. “And there are questions on reimbursement. If you run NGS on every unusual melanocytic lesion, that’s not a good use of health care dollars. Who’s paying for it? I don’t have an answer for you. It’s all over the map right now. Each lab’s test and billing practice is different.”

Dr. Hosler reported having no relevant financial disclosures. ProPath is a nationwide pathology practice.

Antibiotics were associated with 28% of all cases of Stevens-Johnson syndrome and toxic epidermal necrolysis, according to the first meta-analysis to examine the worldwide prevalence of SJS/TEN in connection with antibiotics.

“SJS/TEN is considered the most severe form of drug hypersensitivity reaction, and antibiotics are an important risk,” Erika Yue Lee, MD, and associates wrote in JAMA Dermatology.

Their analysis, which involved 38 studies published since 1987 with 2,917 patients from more than 20 countries, showed that 86% of all SJS/TEN cases were associated with a single drug, with the rest involving multiple drug triggers, infections, or other causes. More than a quarter (28%) of those patients had used an antibiotic, and the sulfonamides were the class most often triggering SJS/TEN, said Dr. Lee of the University of Toronto and associates.

Sulfonamides were responsible for 32% of the antibiotic-associated cases, which works out to 11% of all SJS/TEN cases included in the analysis. Penicillins were next with 22% of all antibiotic-associated cases, followed by the cephalosporins (11%), fluoroquinolones (4%), and macrolides (2%), the investigators reported.

A subgroup analysis conducted by age indicated that “there was no difference in the proportion of antibiotics associated with SJS/TEN between adult and pediatric groups,” they noted.

There were differences, however, among the various antibiotic classes. Sulfonamides represented 54% of antibiotic-triggered reactions in children, compared with 25% in adults, but adults were significantly more likely to have cephalosporin (23%) and fluoroquinolone (5%) involvement than were children (2% and 0, respectively). Macrolide-induced SJS/TEN was more common in children (18% vs. 1%), while the penicillin rate was 18% for both age groups, Dr. Lee and associates said.

A second subgroup analysis establishing the proportion of antibiotic-induced SJS/TEN by continent ranked Australia highest with 43%, but that was based on only one study of 42 patients. North America was slightly lower at 37%, but the analysis included 14 studies and 932 patients. Asia’s 16 studies and 1,298 patients were divided into three regions, with the lowest being the southeast at 16%, according to the researchers.

“Global sulfonamide antibiotic use has been decreasing since 2000 despite an ongoing upward trend of use in other antibiotic classes,” they wrote, but “antibiotics remain one of the most common culprit drugs for SJS/TEN in both adults and children worldwide.”

One of Dr. Lee’s associates has received personal fees from Janssen, AstraZeneca, UpToDate, Verve, BioCryst, Regeneron Pharmaceuticals, and Novavax and has served as codirector of IIID Pty Ltd, which holds a patent for HLA-B*57:01 testing and has a patent pending for detection of HLA-A*32:01 in connection with diagnosing drug reaction without any financial remuneration outside this study.

Antibiotics were associated with 28% of all cases of Stevens-Johnson syndrome and toxic epidermal necrolysis, according to the first meta-analysis to examine the worldwide prevalence of SJS/TEN in connection with antibiotics.

“SJS/TEN is considered the most severe form of drug hypersensitivity reaction, and antibiotics are an important risk,” Erika Yue Lee, MD, and associates wrote in JAMA Dermatology.

Their analysis, which involved 38 studies published since 1987 with 2,917 patients from more than 20 countries, showed that 86% of all SJS/TEN cases were associated with a single drug, with the rest involving multiple drug triggers, infections, or other causes. More than a quarter (28%) of those patients had used an antibiotic, and the sulfonamides were the class most often triggering SJS/TEN, said Dr. Lee of the University of Toronto and associates.

Sulfonamides were responsible for 32% of the antibiotic-associated cases, which works out to 11% of all SJS/TEN cases included in the analysis. Penicillins were next with 22% of all antibiotic-associated cases, followed by the cephalosporins (11%), fluoroquinolones (4%), and macrolides (2%), the investigators reported.

A subgroup analysis conducted by age indicated that “there was no difference in the proportion of antibiotics associated with SJS/TEN between adult and pediatric groups,” they noted.

There were differences, however, among the various antibiotic classes. Sulfonamides represented 54% of antibiotic-triggered reactions in children, compared with 25% in adults, but adults were significantly more likely to have cephalosporin (23%) and fluoroquinolone (5%) involvement than were children (2% and 0, respectively). Macrolide-induced SJS/TEN was more common in children (18% vs. 1%), while the penicillin rate was 18% for both age groups, Dr. Lee and associates said.

A second subgroup analysis establishing the proportion of antibiotic-induced SJS/TEN by continent ranked Australia highest with 43%, but that was based on only one study of 42 patients. North America was slightly lower at 37%, but the analysis included 14 studies and 932 patients. Asia’s 16 studies and 1,298 patients were divided into three regions, with the lowest being the southeast at 16%, according to the researchers.

“Global sulfonamide antibiotic use has been decreasing since 2000 despite an ongoing upward trend of use in other antibiotic classes,” they wrote, but “antibiotics remain one of the most common culprit drugs for SJS/TEN in both adults and children worldwide.”

One of Dr. Lee’s associates has received personal fees from Janssen, AstraZeneca, UpToDate, Verve, BioCryst, Regeneron Pharmaceuticals, and Novavax and has served as codirector of IIID Pty Ltd, which holds a patent for HLA-B*57:01 testing and has a patent pending for detection of HLA-A*32:01 in connection with diagnosing drug reaction without any financial remuneration outside this study.

Antibiotics were associated with 28% of all cases of Stevens-Johnson syndrome and toxic epidermal necrolysis, according to the first meta-analysis to examine the worldwide prevalence of SJS/TEN in connection with antibiotics.

“SJS/TEN is considered the most severe form of drug hypersensitivity reaction, and antibiotics are an important risk,” Erika Yue Lee, MD, and associates wrote in JAMA Dermatology.

Their analysis, which involved 38 studies published since 1987 with 2,917 patients from more than 20 countries, showed that 86% of all SJS/TEN cases were associated with a single drug, with the rest involving multiple drug triggers, infections, or other causes. More than a quarter (28%) of those patients had used an antibiotic, and the sulfonamides were the class most often triggering SJS/TEN, said Dr. Lee of the University of Toronto and associates.

Sulfonamides were responsible for 32% of the antibiotic-associated cases, which works out to 11% of all SJS/TEN cases included in the analysis. Penicillins were next with 22% of all antibiotic-associated cases, followed by the cephalosporins (11%), fluoroquinolones (4%), and macrolides (2%), the investigators reported.

A subgroup analysis conducted by age indicated that “there was no difference in the proportion of antibiotics associated with SJS/TEN between adult and pediatric groups,” they noted.

There were differences, however, among the various antibiotic classes. Sulfonamides represented 54% of antibiotic-triggered reactions in children, compared with 25% in adults, but adults were significantly more likely to have cephalosporin (23%) and fluoroquinolone (5%) involvement than were children (2% and 0, respectively). Macrolide-induced SJS/TEN was more common in children (18% vs. 1%), while the penicillin rate was 18% for both age groups, Dr. Lee and associates said.

A second subgroup analysis establishing the proportion of antibiotic-induced SJS/TEN by continent ranked Australia highest with 43%, but that was based on only one study of 42 patients. North America was slightly lower at 37%, but the analysis included 14 studies and 932 patients. Asia’s 16 studies and 1,298 patients were divided into three regions, with the lowest being the southeast at 16%, according to the researchers.

“Global sulfonamide antibiotic use has been decreasing since 2000 despite an ongoing upward trend of use in other antibiotic classes,” they wrote, but “antibiotics remain one of the most common culprit drugs for SJS/TEN in both adults and children worldwide.”

One of Dr. Lee’s associates has received personal fees from Janssen, AstraZeneca, UpToDate, Verve, BioCryst, Regeneron Pharmaceuticals, and Novavax and has served as codirector of IIID Pty Ltd, which holds a patent for HLA-B*57:01 testing and has a patent pending for detection of HLA-A*32:01 in connection with diagnosing drug reaction without any financial remuneration outside this study.

There was an explosion in the use of telemedicine during the COVID-19 pandemic, but usage has stabilized and varies between specialties. However, telemedicine use is still somewhat high among rheumatologists, according to speakers at the 2023 Rheumatology Winter Clinical Symposium.

Speaking in general about the future of rheumatology, Jack Cush, MD, a rheumatologist based in Dallas and executive editor of RheumNow.com, said it is up to rheumatologists to adapt to the changing winds in the specialty.

FatCamera/Getty Images

“The future is going to happen no matter what, so the question is, are you going to go along with it? Are you going to be a part of it? Are you going to be resistant to it?” Dr. Cush asked attendees. “Your recent experience with COVID would tell you maybe what your path is going to be if you’re dying to get back to the way it once was.”

Rheumatologists can expect changes in where they work, how they’re paid, increases in their workload, and new innovations in connecting with patients, he said.

“You’re going to be integrating a new style of medicine, you’re going to be digitally connected,” he explained. “All these networks are going to be working together to make you supposedly better at what you do, or maybe they’re working together to make you obsolete – and I think you better start protecting your space.”

One major area of change, telemedicine, already occurred as a result of the COVID-19 pandemic and will “begin to dominate” over the next decade, Dr. Cush said. An analysis conducted by consulting firm McKinsey & Company found telehealth usage increased 78-fold between February and April 2020 before leveling off at a 38-fold higher rate, compared with prepandemic levels. In the same analysis, rheumatology ranked third in terms of telehealth usage claims behind psychiatry and substance use disorder treatment, Dr. Cush observed, as other specialties have “fallen off quite a bit.”

“The common denominators are chronic care, cognitive care, nonprocedural care, pattern recognition, and monitoring, and this is what you do,” he said. “This is why, in many ways, for you to abandon telemedicine I think is a gigantic mistake.”
 

Changes to telemedicine

The most immediate change to telemedicine will come when the Biden administration officially ends the COVID-19 public health emergency in May 2023, and temporary telehealth services will be extended for approximately 5 months after the end of the public health emergency. Legislation passed by Congress will ensure some of the flexibilities in telemedicine will be extended until the end of December 2024.

Alvin Wells, MD, PhD, director of the department of rheumatology at Advocate Aurora Health in Franklin, Wisc., said he sees telemedicine as persisting even after the official COVID-19 public health emergency ends. “There’s a lot of push from the American Medical Association, from the American College of Physicians. You’re going to see people – this will not go away because [there’s] also going to be that demand.”

Despite decreased usage since April 2020, telehealth was estimated to be a $60 billion industry in 2022 and will likely increase over the next decade, Dr. Cush noted. “I question [the decline] because I think it still is a major part of your [future in] 2033.”

The number of physicians who have at least three licenses to practice in other U.S. states increased from 50,454 in 2010 to 72,752 in 2020, and that trend will continue, Dr. Wells explained. It is now becoming easier for physicians to become licensed in other states with companies like CompHealth that offer services to simplify obtaining medical licenses with states that participate in the Interstate Medical Licensure Compact.

“It’s a telemedicine easy pass,” Dr. Cush said.
 

Concerns in telemedicine

Commenting on the presentation, Allan Gibofsky, MD, JD, professor of medicine at Weill Cornell Medicine and codirector of the Clinic for Inflammatory Arthritis and Biologic Therapy at the Hospital for Special Surgery (HSS), both in New York, pointed out that because telemedicine is governed by U.S. states, rather than the federal government, a physician needs to be licensed in the state where the patient is located. While many states relaxed their restrictions during COVID-19, as states began tightening their restrictions later, “many physicians didn’t want to have three licenses,” he said.

“There’s an expense in getting three licenses. There’s an expense in obtaining it and maintaining it, and the reimbursement for the telemedicine visit did not reach that expectation,” Dr. Gibofsky explained. With the exception of the orthopedic surgeons at HSS who practice in New York and a satellite office in Florida, none of the surgeons at his center have obtained more than one license to practice telemedicine in other states.

“Our volume of telemedicine at HSS has remained about the same at 30%, but fewer physicians are doing it because they don’t want to maintain multiple licensures,” he said. “So don’t overlook the role of legal concerns in terms of who’s going to be allowed to do what where. Your talk was great in terms of an exuberance of what’s going to be available, but it’s not going to relieve the physician from the burden of being responsible for their use.”

Eric Ruderman, MD, professor of rheumatology at Northwestern University, Chicago, asked the presenters about the balance between seeing patients for virtual and in-person visits. “The question is what’s the sweet spot? Are there people you’re willing to see virtually forever?” he asked, noting that he has patients scheduling telemedicine visits that he hasn’t seen since before the COVID-19 pandemic.

“That’s not going to work for me. At some point, you have to lay hands on people,” he said.

Dr. Wells said his current practice is 40% virtual, and his staff converts potential no-shows into a telemedicine consultation over the phone. “My no-show rate has gone down to zero. Somebody’s scheduled for a visit, they don’t show up, my [medical assistants] get them on the phone, they put them on hold, tee up the refills. I turn them into a telephone call,” he said. “We don’t accept the no-show at all because we can do a telephone [consultation].”

In Dr. Cush’s practice, he alternates telemedicine visits with in-person visits. “If you come back for two videos in a row, you’re catching hell from me for that,” he said. Responding to how Dr. Wells incorporates telemedicine into his practice, Dr. Cush said many rheumatologists “don’t have the setups to support the care, and that’s why it’s hard to do and that’s why we’re not as great as we could be.”

“This is the way we were trained. We’re used to seeing these patients in the clinic that often. Not every single patient needs to be seen that frequently if they’re stable and doing fine,” Dr. Wells countered.

Dr. Cush and Dr. Wells reported having financial relationships with numerous pharmaceutical companies.

There was an explosion in the use of telemedicine during the COVID-19 pandemic, but usage has stabilized and varies between specialties. However, telemedicine use is still somewhat high among rheumatologists, according to speakers at the 2023 Rheumatology Winter Clinical Symposium.

Speaking in general about the future of rheumatology, Jack Cush, MD, a rheumatologist based in Dallas and executive editor of RheumNow.com, said it is up to rheumatologists to adapt to the changing winds in the specialty.

FatCamera/Getty Images

“The future is going to happen no matter what, so the question is, are you going to go along with it? Are you going to be a part of it? Are you going to be resistant to it?” Dr. Cush asked attendees. “Your recent experience with COVID would tell you maybe what your path is going to be if you’re dying to get back to the way it once was.”

Rheumatologists can expect changes in where they work, how they’re paid, increases in their workload, and new innovations in connecting with patients, he said.

“You’re going to be integrating a new style of medicine, you’re going to be digitally connected,” he explained. “All these networks are going to be working together to make you supposedly better at what you do, or maybe they’re working together to make you obsolete – and I think you better start protecting your space.”

One major area of change, telemedicine, already occurred as a result of the COVID-19 pandemic and will “begin to dominate” over the next decade, Dr. Cush said. An analysis conducted by consulting firm McKinsey & Company found telehealth usage increased 78-fold between February and April 2020 before leveling off at a 38-fold higher rate, compared with prepandemic levels. In the same analysis, rheumatology ranked third in terms of telehealth usage claims behind psychiatry and substance use disorder treatment, Dr. Cush observed, as other specialties have “fallen off quite a bit.”

“The common denominators are chronic care, cognitive care, nonprocedural care, pattern recognition, and monitoring, and this is what you do,” he said. “This is why, in many ways, for you to abandon telemedicine I think is a gigantic mistake.”
 

Changes to telemedicine

The most immediate change to telemedicine will come when the Biden administration officially ends the COVID-19 public health emergency in May 2023, and temporary telehealth services will be extended for approximately 5 months after the end of the public health emergency. Legislation passed by Congress will ensure some of the flexibilities in telemedicine will be extended until the end of December 2024.

Alvin Wells, MD, PhD, director of the department of rheumatology at Advocate Aurora Health in Franklin, Wisc., said he sees telemedicine as persisting even after the official COVID-19 public health emergency ends. “There’s a lot of push from the American Medical Association, from the American College of Physicians. You’re going to see people – this will not go away because [there’s] also going to be that demand.”

Despite decreased usage since April 2020, telehealth was estimated to be a $60 billion industry in 2022 and will likely increase over the next decade, Dr. Cush noted. “I question [the decline] because I think it still is a major part of your [future in] 2033.”

The number of physicians who have at least three licenses to practice in other U.S. states increased from 50,454 in 2010 to 72,752 in 2020, and that trend will continue, Dr. Wells explained. It is now becoming easier for physicians to become licensed in other states with companies like CompHealth that offer services to simplify obtaining medical licenses with states that participate in the Interstate Medical Licensure Compact.

“It’s a telemedicine easy pass,” Dr. Cush said.
 

Concerns in telemedicine

Commenting on the presentation, Allan Gibofsky, MD, JD, professor of medicine at Weill Cornell Medicine and codirector of the Clinic for Inflammatory Arthritis and Biologic Therapy at the Hospital for Special Surgery (HSS), both in New York, pointed out that because telemedicine is governed by U.S. states, rather than the federal government, a physician needs to be licensed in the state where the patient is located. While many states relaxed their restrictions during COVID-19, as states began tightening their restrictions later, “many physicians didn’t want to have three licenses,” he said.

“There’s an expense in getting three licenses. There’s an expense in obtaining it and maintaining it, and the reimbursement for the telemedicine visit did not reach that expectation,” Dr. Gibofsky explained. With the exception of the orthopedic surgeons at HSS who practice in New York and a satellite office in Florida, none of the surgeons at his center have obtained more than one license to practice telemedicine in other states.

“Our volume of telemedicine at HSS has remained about the same at 30%, but fewer physicians are doing it because they don’t want to maintain multiple licensures,” he said. “So don’t overlook the role of legal concerns in terms of who’s going to be allowed to do what where. Your talk was great in terms of an exuberance of what’s going to be available, but it’s not going to relieve the physician from the burden of being responsible for their use.”

Eric Ruderman, MD, professor of rheumatology at Northwestern University, Chicago, asked the presenters about the balance between seeing patients for virtual and in-person visits. “The question is what’s the sweet spot? Are there people you’re willing to see virtually forever?” he asked, noting that he has patients scheduling telemedicine visits that he hasn’t seen since before the COVID-19 pandemic.

“That’s not going to work for me. At some point, you have to lay hands on people,” he said.

Dr. Wells said his current practice is 40% virtual, and his staff converts potential no-shows into a telemedicine consultation over the phone. “My no-show rate has gone down to zero. Somebody’s scheduled for a visit, they don’t show up, my [medical assistants] get them on the phone, they put them on hold, tee up the refills. I turn them into a telephone call,” he said. “We don’t accept the no-show at all because we can do a telephone [consultation].”

In Dr. Cush’s practice, he alternates telemedicine visits with in-person visits. “If you come back for two videos in a row, you’re catching hell from me for that,” he said. Responding to how Dr. Wells incorporates telemedicine into his practice, Dr. Cush said many rheumatologists “don’t have the setups to support the care, and that’s why it’s hard to do and that’s why we’re not as great as we could be.”

“This is the way we were trained. We’re used to seeing these patients in the clinic that often. Not every single patient needs to be seen that frequently if they’re stable and doing fine,” Dr. Wells countered.

Dr. Cush and Dr. Wells reported having financial relationships with numerous pharmaceutical companies.

There was an explosion in the use of telemedicine during the COVID-19 pandemic, but usage has stabilized and varies between specialties. However, telemedicine use is still somewhat high among rheumatologists, according to speakers at the 2023 Rheumatology Winter Clinical Symposium.

Speaking in general about the future of rheumatology, Jack Cush, MD, a rheumatologist based in Dallas and executive editor of RheumNow.com, said it is up to rheumatologists to adapt to the changing winds in the specialty.

FatCamera/Getty Images

“The future is going to happen no matter what, so the question is, are you going to go along with it? Are you going to be a part of it? Are you going to be resistant to it?” Dr. Cush asked attendees. “Your recent experience with COVID would tell you maybe what your path is going to be if you’re dying to get back to the way it once was.”

Rheumatologists can expect changes in where they work, how they’re paid, increases in their workload, and new innovations in connecting with patients, he said.

“You’re going to be integrating a new style of medicine, you’re going to be digitally connected,” he explained. “All these networks are going to be working together to make you supposedly better at what you do, or maybe they’re working together to make you obsolete – and I think you better start protecting your space.”

One major area of change, telemedicine, already occurred as a result of the COVID-19 pandemic and will “begin to dominate” over the next decade, Dr. Cush said. An analysis conducted by consulting firm McKinsey & Company found telehealth usage increased 78-fold between February and April 2020 before leveling off at a 38-fold higher rate, compared with prepandemic levels. In the same analysis, rheumatology ranked third in terms of telehealth usage claims behind psychiatry and substance use disorder treatment, Dr. Cush observed, as other specialties have “fallen off quite a bit.”

“The common denominators are chronic care, cognitive care, nonprocedural care, pattern recognition, and monitoring, and this is what you do,” he said. “This is why, in many ways, for you to abandon telemedicine I think is a gigantic mistake.”
 

Changes to telemedicine

The most immediate change to telemedicine will come when the Biden administration officially ends the COVID-19 public health emergency in May 2023, and temporary telehealth services will be extended for approximately 5 months after the end of the public health emergency. Legislation passed by Congress will ensure some of the flexibilities in telemedicine will be extended until the end of December 2024.

Alvin Wells, MD, PhD, director of the department of rheumatology at Advocate Aurora Health in Franklin, Wisc., said he sees telemedicine as persisting even after the official COVID-19 public health emergency ends. “There’s a lot of push from the American Medical Association, from the American College of Physicians. You’re going to see people – this will not go away because [there’s] also going to be that demand.”

Despite decreased usage since April 2020, telehealth was estimated to be a $60 billion industry in 2022 and will likely increase over the next decade, Dr. Cush noted. “I question [the decline] because I think it still is a major part of your [future in] 2033.”

The number of physicians who have at least three licenses to practice in other U.S. states increased from 50,454 in 2010 to 72,752 in 2020, and that trend will continue, Dr. Wells explained. It is now becoming easier for physicians to become licensed in other states with companies like CompHealth that offer services to simplify obtaining medical licenses with states that participate in the Interstate Medical Licensure Compact.

“It’s a telemedicine easy pass,” Dr. Cush said.
 

Concerns in telemedicine

Commenting on the presentation, Allan Gibofsky, MD, JD, professor of medicine at Weill Cornell Medicine and codirector of the Clinic for Inflammatory Arthritis and Biologic Therapy at the Hospital for Special Surgery (HSS), both in New York, pointed out that because telemedicine is governed by U.S. states, rather than the federal government, a physician needs to be licensed in the state where the patient is located. While many states relaxed their restrictions during COVID-19, as states began tightening their restrictions later, “many physicians didn’t want to have three licenses,” he said.

“There’s an expense in getting three licenses. There’s an expense in obtaining it and maintaining it, and the reimbursement for the telemedicine visit did not reach that expectation,” Dr. Gibofsky explained. With the exception of the orthopedic surgeons at HSS who practice in New York and a satellite office in Florida, none of the surgeons at his center have obtained more than one license to practice telemedicine in other states.

“Our volume of telemedicine at HSS has remained about the same at 30%, but fewer physicians are doing it because they don’t want to maintain multiple licensures,” he said. “So don’t overlook the role of legal concerns in terms of who’s going to be allowed to do what where. Your talk was great in terms of an exuberance of what’s going to be available, but it’s not going to relieve the physician from the burden of being responsible for their use.”

Eric Ruderman, MD, professor of rheumatology at Northwestern University, Chicago, asked the presenters about the balance between seeing patients for virtual and in-person visits. “The question is what’s the sweet spot? Are there people you’re willing to see virtually forever?” he asked, noting that he has patients scheduling telemedicine visits that he hasn’t seen since before the COVID-19 pandemic.

“That’s not going to work for me. At some point, you have to lay hands on people,” he said.

Dr. Wells said his current practice is 40% virtual, and his staff converts potential no-shows into a telemedicine consultation over the phone. “My no-show rate has gone down to zero. Somebody’s scheduled for a visit, they don’t show up, my [medical assistants] get them on the phone, they put them on hold, tee up the refills. I turn them into a telephone call,” he said. “We don’t accept the no-show at all because we can do a telephone [consultation].”

In Dr. Cush’s practice, he alternates telemedicine visits with in-person visits. “If you come back for two videos in a row, you’re catching hell from me for that,” he said. Responding to how Dr. Wells incorporates telemedicine into his practice, Dr. Cush said many rheumatologists “don’t have the setups to support the care, and that’s why it’s hard to do and that’s why we’re not as great as we could be.”

“This is the way we were trained. We’re used to seeing these patients in the clinic that often. Not every single patient needs to be seen that frequently if they’re stable and doing fine,” Dr. Wells countered.

Dr. Cush and Dr. Wells reported having financial relationships with numerous pharmaceutical companies.