Medication overuse headache, previously known as rebound headache or medication-induced headache, may be caused by the frequent or excessive use of various acute care medications. When these medications are used too frequently, they can cause headaches rather than relieving them. (Some headache specialists feel that MOH is the result of recurring severe headaches, and the patients’ overuse of medications to relieve them.) These medications, some of which are painkillers or analgesics, include over-the-counter products such as acetaminophen, aspirin, and anti-inflammatories, as well as prescription medications such as triptans, ergots opioids, opioids, and barbiturates. The one category of acute care medication that does not seem to cause MOH is the gepants, such as rimegepant and ubrogepant.

MOH is the fourth most common headache disorder. It is defined by the International Classification of Headache Disorders (ICHD-3) as a headache present 15 days per month, evolving from regular use of strong acute medication (10 or more days of triptans, ergotamines, butalbital medications, opioids, or combination medications or 15 or more days per month of simple analgesics such as aspirin, acetaminophen, or nonsteroidal anti-inflammatories) for 3 months. 

Patients are usually not aware they have MOH, and this is the most problematic aspect of the condition. Patients do not realize that the medicine they are taking is making their headaches worse. It can be difficult to explain to the patient exactly what is going on with MOH, and why they are doing the wrong thing by taking the very medication that was prescribed by their doctor to stop a migraine attack. Many doctors do not fully understand MOH either, which can make it difficult to treat patients with this type of headache; therefore, it is imperative to educate both doctors and patients on the causes and treatments of MOH.

One of the most important facets of treating MOH traditionally has been the process of detoxifying patients from their overused medication by gradually or precipitously withdrawing the offending medication. There is variability in how detoxification can be accomplished. Some of my patients stopped medications abruptly and experienced very bad headaches. Others tried reducing dosages on their own and reported experiencing the worst headaches of their lives—some of which lasted for a few weeks. I have found that if patients can endure 2 to 3 weeks of detox, they start to feel better. But because the headaches can worsen before they get better, patients understandably try to avoid the detoxification process. 

I start patients on preventive medicine, then slowly increase it to an effective dose, and have them come back in a month for an evaluation. I then have them gradually reduce, but not completely stop, the pain medication before they return. Once I feel their preventive medication is at a therapeutic level, I have them begin a slow detox. After a month of preventive medication, there is a reasonable chance that headaches will start to decrease and be less severe. I tell them that if their headache is less severe try to avoid taking the medicine that they were overusing to prevent perpetuating the MOH.

One plausible physiologic mechanism behind MOH is that chronic exposure to acute care migraine treatment leads to suppression of the serotonergic/norepinephrinergic  endogenous antinociceptive system in the upper brain stem, with facilitation of the trigeminal nociceptive process via up-regulation of calcitonin gene-related peptide (CGRP).This increase in CGRP at the end of peripheral nerve terminals in the trigeminovascular system may facilitate pain transmission. An increase in cortical CGRP may cause cortical spreading depression: a wave of excitement traveling through the cortex, followed by a wave of electrical depression seems to cause headache.  

Good, effective prevention often helps avoid MOH; medications such as topiramate, nortriptyline, gabapentin, onabotulinumtoxinA, and CGRP monoclonal antibodies or some type of local nerve block have improved MOH in patients, but detoxification is usually necessary is some patients. 

Monoclonal antibodies targeting CGRP or its receptor (CGRP-R), given by subcutaneous or intravenous injection or small molecule CGRP receptor antagonists given orally (gepants), seem to be able to treat MOH in some patients without a detoxification. This has been best demonstrated in the monoclonal antibody group, but there is some evidence showing that it may also occur with gepants. These treatments seem to work even when patients are overusing acute care medications; this helps some patients to self-detoxify at their own pace, which is easier for both the patient and the doctor.

Currently, there are 4 monoclonal antibodies against CGRP or the CGRP-R. Erenumab is the only completely human one and the only antibody that blocks the CGRP receptor to prevent the CGRP ligand from docking and exerting its effect. The other 3 (fremanezumab, galcanezumab, and eptinezumab) are humanized monoclonal antibodies that selectively bind to the CGRP ligand, preventing it from docking on its receptor.  Patients started on the monoclonal antibodies against CGRP or its receptor usually have fewer headaches in the first week or two of therapy, and this helps make the self-detox easier for the patient. 

Further, substantial data have shown that onabotulinumtoxinA reduces the number/frequency of headaches and reduces the need for patients to take acute medication. OnabotulinumtoxinA is currently the only medication approved for preventive treatment of chronic migraine; it has long-term safety data available and has reported efficacy lasting for up to 3 years when given in multiple injection sites every 3 months. Interestingly, although topiramate is used as a preventive medication, a recent study comparing erenumab vs topiramate for reducing monthly migraine days (MMD) showed that erenumab outperformed topiramate with a 50% reduction in MMD, and with fewer reported adverse events.

We are just starting to learn about some other potential cellular mechanisms that could be causing MOH in patients; these data could help create new and improved therapies for treating and possibly preventing MOH in the future. Patient outcomes could also be improved by encouraging the inclusion of MOH as part of a continuing education program for physicians who could potentially be treating new patients presenting with MOH. 

Medication overuse headache, previously known as rebound headache or medication-induced headache, may be caused by the frequent or excessive use of various acute care medications. When these medications are used too frequently, they can cause headaches rather than relieving them. (Some headache specialists feel that MOH is the result of recurring severe headaches, and the patients’ overuse of medications to relieve them.) These medications, some of which are painkillers or analgesics, include over-the-counter products such as acetaminophen, aspirin, and anti-inflammatories, as well as prescription medications such as triptans, ergots opioids, opioids, and barbiturates. The one category of acute care medication that does not seem to cause MOH is the gepants, such as rimegepant and ubrogepant.

MOH is the fourth most common headache disorder. It is defined by the International Classification of Headache Disorders (ICHD-3) as a headache present 15 days per month, evolving from regular use of strong acute medication (10 or more days of triptans, ergotamines, butalbital medications, opioids, or combination medications or 15 or more days per month of simple analgesics such as aspirin, acetaminophen, or nonsteroidal anti-inflammatories) for 3 months. 

Patients are usually not aware they have MOH, and this is the most problematic aspect of the condition. Patients do not realize that the medicine they are taking is making their headaches worse. It can be difficult to explain to the patient exactly what is going on with MOH, and why they are doing the wrong thing by taking the very medication that was prescribed by their doctor to stop a migraine attack. Many doctors do not fully understand MOH either, which can make it difficult to treat patients with this type of headache; therefore, it is imperative to educate both doctors and patients on the causes and treatments of MOH.

One of the most important facets of treating MOH traditionally has been the process of detoxifying patients from their overused medication by gradually or precipitously withdrawing the offending medication. There is variability in how detoxification can be accomplished. Some of my patients stopped medications abruptly and experienced very bad headaches. Others tried reducing dosages on their own and reported experiencing the worst headaches of their lives—some of which lasted for a few weeks. I have found that if patients can endure 2 to 3 weeks of detox, they start to feel better. But because the headaches can worsen before they get better, patients understandably try to avoid the detoxification process. 

I start patients on preventive medicine, then slowly increase it to an effective dose, and have them come back in a month for an evaluation. I then have them gradually reduce, but not completely stop, the pain medication before they return. Once I feel their preventive medication is at a therapeutic level, I have them begin a slow detox. After a month of preventive medication, there is a reasonable chance that headaches will start to decrease and be less severe. I tell them that if their headache is less severe try to avoid taking the medicine that they were overusing to prevent perpetuating the MOH.

One plausible physiologic mechanism behind MOH is that chronic exposure to acute care migraine treatment leads to suppression of the serotonergic/norepinephrinergic  endogenous antinociceptive system in the upper brain stem, with facilitation of the trigeminal nociceptive process via up-regulation of calcitonin gene-related peptide (CGRP).This increase in CGRP at the end of peripheral nerve terminals in the trigeminovascular system may facilitate pain transmission. An increase in cortical CGRP may cause cortical spreading depression: a wave of excitement traveling through the cortex, followed by a wave of electrical depression seems to cause headache.  

Good, effective prevention often helps avoid MOH; medications such as topiramate, nortriptyline, gabapentin, onabotulinumtoxinA, and CGRP monoclonal antibodies or some type of local nerve block have improved MOH in patients, but detoxification is usually necessary is some patients. 

Monoclonal antibodies targeting CGRP or its receptor (CGRP-R), given by subcutaneous or intravenous injection or small molecule CGRP receptor antagonists given orally (gepants), seem to be able to treat MOH in some patients without a detoxification. This has been best demonstrated in the monoclonal antibody group, but there is some evidence showing that it may also occur with gepants. These treatments seem to work even when patients are overusing acute care medications; this helps some patients to self-detoxify at their own pace, which is easier for both the patient and the doctor.

Currently, there are 4 monoclonal antibodies against CGRP or the CGRP-R. Erenumab is the only completely human one and the only antibody that blocks the CGRP receptor to prevent the CGRP ligand from docking and exerting its effect. The other 3 (fremanezumab, galcanezumab, and eptinezumab) are humanized monoclonal antibodies that selectively bind to the CGRP ligand, preventing it from docking on its receptor.  Patients started on the monoclonal antibodies against CGRP or its receptor usually have fewer headaches in the first week or two of therapy, and this helps make the self-detox easier for the patient. 

Further, substantial data have shown that onabotulinumtoxinA reduces the number/frequency of headaches and reduces the need for patients to take acute medication. OnabotulinumtoxinA is currently the only medication approved for preventive treatment of chronic migraine; it has long-term safety data available and has reported efficacy lasting for up to 3 years when given in multiple injection sites every 3 months. Interestingly, although topiramate is used as a preventive medication, a recent study comparing erenumab vs topiramate for reducing monthly migraine days (MMD) showed that erenumab outperformed topiramate with a 50% reduction in MMD, and with fewer reported adverse events.

We are just starting to learn about some other potential cellular mechanisms that could be causing MOH in patients; these data could help create new and improved therapies for treating and possibly preventing MOH in the future. Patient outcomes could also be improved by encouraging the inclusion of MOH as part of a continuing education program for physicians who could potentially be treating new patients presenting with MOH. 

Medication overuse headache, previously known as rebound headache or medication-induced headache, may be caused by the frequent or excessive use of various acute care medications. When these medications are used too frequently, they can cause headaches rather than relieving them. (Some headache specialists feel that MOH is the result of recurring severe headaches, and the patients’ overuse of medications to relieve them.) These medications, some of which are painkillers or analgesics, include over-the-counter products such as acetaminophen, aspirin, and anti-inflammatories, as well as prescription medications such as triptans, ergots opioids, opioids, and barbiturates. The one category of acute care medication that does not seem to cause MOH is the gepants, such as rimegepant and ubrogepant.

MOH is the fourth most common headache disorder. It is defined by the International Classification of Headache Disorders (ICHD-3) as a headache present 15 days per month, evolving from regular use of strong acute medication (10 or more days of triptans, ergotamines, butalbital medications, opioids, or combination medications or 15 or more days per month of simple analgesics such as aspirin, acetaminophen, or nonsteroidal anti-inflammatories) for 3 months. 

Patients are usually not aware they have MOH, and this is the most problematic aspect of the condition. Patients do not realize that the medicine they are taking is making their headaches worse. It can be difficult to explain to the patient exactly what is going on with MOH, and why they are doing the wrong thing by taking the very medication that was prescribed by their doctor to stop a migraine attack. Many doctors do not fully understand MOH either, which can make it difficult to treat patients with this type of headache; therefore, it is imperative to educate both doctors and patients on the causes and treatments of MOH.

One of the most important facets of treating MOH traditionally has been the process of detoxifying patients from their overused medication by gradually or precipitously withdrawing the offending medication. There is variability in how detoxification can be accomplished. Some of my patients stopped medications abruptly and experienced very bad headaches. Others tried reducing dosages on their own and reported experiencing the worst headaches of their lives—some of which lasted for a few weeks. I have found that if patients can endure 2 to 3 weeks of detox, they start to feel better. But because the headaches can worsen before they get better, patients understandably try to avoid the detoxification process. 

I start patients on preventive medicine, then slowly increase it to an effective dose, and have them come back in a month for an evaluation. I then have them gradually reduce, but not completely stop, the pain medication before they return. Once I feel their preventive medication is at a therapeutic level, I have them begin a slow detox. After a month of preventive medication, there is a reasonable chance that headaches will start to decrease and be less severe. I tell them that if their headache is less severe try to avoid taking the medicine that they were overusing to prevent perpetuating the MOH.

One plausible physiologic mechanism behind MOH is that chronic exposure to acute care migraine treatment leads to suppression of the serotonergic/norepinephrinergic  endogenous antinociceptive system in the upper brain stem, with facilitation of the trigeminal nociceptive process via up-regulation of calcitonin gene-related peptide (CGRP).This increase in CGRP at the end of peripheral nerve terminals in the trigeminovascular system may facilitate pain transmission. An increase in cortical CGRP may cause cortical spreading depression: a wave of excitement traveling through the cortex, followed by a wave of electrical depression seems to cause headache.  

Good, effective prevention often helps avoid MOH; medications such as topiramate, nortriptyline, gabapentin, onabotulinumtoxinA, and CGRP monoclonal antibodies or some type of local nerve block have improved MOH in patients, but detoxification is usually necessary is some patients. 

Monoclonal antibodies targeting CGRP or its receptor (CGRP-R), given by subcutaneous or intravenous injection or small molecule CGRP receptor antagonists given orally (gepants), seem to be able to treat MOH in some patients without a detoxification. This has been best demonstrated in the monoclonal antibody group, but there is some evidence showing that it may also occur with gepants. These treatments seem to work even when patients are overusing acute care medications; this helps some patients to self-detoxify at their own pace, which is easier for both the patient and the doctor.

Currently, there are 4 monoclonal antibodies against CGRP or the CGRP-R. Erenumab is the only completely human one and the only antibody that blocks the CGRP receptor to prevent the CGRP ligand from docking and exerting its effect. The other 3 (fremanezumab, galcanezumab, and eptinezumab) are humanized monoclonal antibodies that selectively bind to the CGRP ligand, preventing it from docking on its receptor.  Patients started on the monoclonal antibodies against CGRP or its receptor usually have fewer headaches in the first week or two of therapy, and this helps make the self-detox easier for the patient. 

Further, substantial data have shown that onabotulinumtoxinA reduces the number/frequency of headaches and reduces the need for patients to take acute medication. OnabotulinumtoxinA is currently the only medication approved for preventive treatment of chronic migraine; it has long-term safety data available and has reported efficacy lasting for up to 3 years when given in multiple injection sites every 3 months. Interestingly, although topiramate is used as a preventive medication, a recent study comparing erenumab vs topiramate for reducing monthly migraine days (MMD) showed that erenumab outperformed topiramate with a 50% reduction in MMD, and with fewer reported adverse events.

We are just starting to learn about some other potential cellular mechanisms that could be causing MOH in patients; these data could help create new and improved therapies for treating and possibly preventing MOH in the future. Patient outcomes could also be improved by encouraging the inclusion of MOH as part of a continuing education program for physicians who could potentially be treating new patients presenting with MOH. 

Adult and adolescent patients with moderate to severe atopic dermatitis (AD) showed significant improvements with the addition of lebrikizumab to topical corticosteroid (TCS) therapy, compared with TCS plus placebo, according to results of the 16-week phase 3 ADhere trial.

“Lebrikizumab, a monoclonal antibody inhibiting interleukin-13, combined with TCS was associated with reduced overall disease severity of moderate to severe AD in adolescents and adults, and had a safety profile consistent with previous lebrikizumab AD studies,” noted lead author Eric L. Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland, and coauthors in their article on the study, which was published in JAMA Dermatology.

The double-blind trial, conducted at 54 sites across Germany, Poland, Canada, and the United States, included 211 patients, mean age 37.2 years, of whom 48.8% were female and roughly 22% were adolescents. Almost 15% were Asian, and about 13% were Black.

At baseline, participants had a score of 16 or higher on the Eczema Area and Severity Index (EASI), a score of 3 or higher on the Investigator’s Global Assessment (IGA) scale, AD covering a body surface area of 10% or greater, and a history of inadequate response to treatment with topical medications.

After a minimum 1-week washout period from topical and systemic therapy, participants were randomized in a 2:1 ratio to receive lebrikizumab plus TCS (n = 145) or placebo plus TCS (n = 66) for 16 weeks.

Lebrikizumab or placebo was administered by subcutaneous injection every 2 weeks; the loading and week-2 doses of lebrikizumab were 500 mg, followed by 250 mg thereafter. All patients were instructed to use low- to mid-potency TCS at their own discretion. Study sites provided a mid-potency TCS (triamcinolone acetonide 0.1% cream) and a low-potency TCS (hydrocortisone 1% cream), with topical calcineurin inhibitors permitted for sensitive skin areas.

Primary outcomes at 16 weeks included a 2-point or more reduction in IGA score from baseline and EASI-75 response. Patients in the lebrikizumab arm had superior responses on both of these outcomes, with statistical significance achieved as early as week 8 and week 4, respectively, and maintained through week 16. Specifically, 41.2% of those treated with lebrikizumab had an IGA reduction of 2 points or more, compared with 22.1% of those receiving placebo plus TCS (P = .01), and the proportion of patients achieving EASI-75 responses was 69.5% vs. 42.2%, respectively (P < .001).

Patients treated with lebrikizumab also showed statistically significant improvements, compared with TCS alone in all key secondary endpoints, “including skin clearance, improvement in itch, itch interference on sleep, and enhanced QoL [quality of life],” noted the authors. “This study captured the clinical benefit of lebrikizumab through the combined end point of physician-assessed clinical sign of skin clearance (EASI-75) and patient-reported outcome of improvement in itch (Pruritus NRS).”

The percentage of patients who achieved the combined endpoint was more than double for the lebrikizumab plus TCS group vs. the group on TCS alone, indicating that patients treated with lebrikizumab plus TCS “were more likely to experience improvement in skin symptoms and itch,” the investigators added.

The authors noted that most treatment-emergent adverse events “were nonserious, mild, or moderate in severity, and did not lead to study discontinuation.” These included conjunctivitis (4.8%), headache (4.8%), hypertension (2.8%), injection-site reactions (2.8%), and herpes infection (3.4%) – all of which occurred in 1.5% or less of patients in the placebo group.

“The higher incidence of conjunctivitis has also been reported in other biologics inhibiting IL [interleukin]–13 and/or IL-4 signaling, as well as lebrikizumab monotherapy studies,” they noted. The 4.8% rate of conjunctivitis reported in the combination study, they added, is “compared with 7.5% frequency in 16-week data from the lebrikizumab monotherapy studies. Although the mechanism remains unclear, it has been reported that conjunctival goblet cell scarcity due to IL-13 and IL-4 inhibition, and subsequent effects on the homeostasis of the conjunctival mucosal surface, results in ocular AEs [adverse events].”

“This truly is a time of great hope and promise for our patients with AD,” commented Zelma Chiesa Fuxench, MD, who was not involved in the study. “The advent of newer, targeted therapeutic agents for AD continues to revolutionize the treatment experience for our patients, offering the possibility of greater AD disease control with a favorable risk profile and less need for blood work monitoring compared to traditional systemic agents.”

On the basis of the study results, Dr. Chiesa Fuxench, of the department of dermatology at the University of Pennsylvania, Philadelphia, said in an interview that “lebrikizumab represents an additional option in the treatment armamentarium for providers who care for patients with AD.” She added that, “while head-to-head trials comparing lebrikizumab to dupilumab, the first FDA-approved biologic for AD, would be beneficial, to the best of my knowledge this data is currently lacking. However, based on the results of this study, we would expect lebrikizumab to work at least similarly to dupilumab, based on the reported improvements in IGA and EASI score.”

Additionally, lebrikizumab showed a favorable safety profile, “with most treatment-emergent adverse effects reported as nonserious and not leading to drug discontinuation,” she said. “Of interest to clinicians may be the reported rates of conjunctivitis in this study. Rates of conjunctivitis for lebrikizumab appear to be lower than those reported in the LIBERTY AD CHRONOS study for dupilumab – a finding that merits further scrutiny in my opinion, as this one of the most frequent treatment-emergent adverse events that I encounter in my clinical practice.”

The study was funded by Dermira, a subsidiary of Eli Lilly. Dr. Simpson reported personal fees and grants from multiple sources, including Dermira and Eli Lilly, the companies developing lebrikizumab. Several authors were employees of Eli Lilly. Dr. Fuxench disclosed serving as a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, Pfizer, AbbVie, and Incyte, for which she has received honoraria for AD-related work. She is the recipient of research grants through Regeneron, Sanofi, Tioga, Vanda, Menlo Therapeutics, Leo Pharma, and Eli Lilly for work related to AD as well as honoraria for continuing medical education work related to AD sponsored through educational grants from Regeneron/Sanofi and Pfizer.

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

Adult and adolescent patients with moderate to severe atopic dermatitis (AD) showed significant improvements with the addition of lebrikizumab to topical corticosteroid (TCS) therapy, compared with TCS plus placebo, according to results of the 16-week phase 3 ADhere trial.

“Lebrikizumab, a monoclonal antibody inhibiting interleukin-13, combined with TCS was associated with reduced overall disease severity of moderate to severe AD in adolescents and adults, and had a safety profile consistent with previous lebrikizumab AD studies,” noted lead author Eric L. Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland, and coauthors in their article on the study, which was published in JAMA Dermatology.

The double-blind trial, conducted at 54 sites across Germany, Poland, Canada, and the United States, included 211 patients, mean age 37.2 years, of whom 48.8% were female and roughly 22% were adolescents. Almost 15% were Asian, and about 13% were Black.

At baseline, participants had a score of 16 or higher on the Eczema Area and Severity Index (EASI), a score of 3 or higher on the Investigator’s Global Assessment (IGA) scale, AD covering a body surface area of 10% or greater, and a history of inadequate response to treatment with topical medications.

After a minimum 1-week washout period from topical and systemic therapy, participants were randomized in a 2:1 ratio to receive lebrikizumab plus TCS (n = 145) or placebo plus TCS (n = 66) for 16 weeks.

Lebrikizumab or placebo was administered by subcutaneous injection every 2 weeks; the loading and week-2 doses of lebrikizumab were 500 mg, followed by 250 mg thereafter. All patients were instructed to use low- to mid-potency TCS at their own discretion. Study sites provided a mid-potency TCS (triamcinolone acetonide 0.1% cream) and a low-potency TCS (hydrocortisone 1% cream), with topical calcineurin inhibitors permitted for sensitive skin areas.

Primary outcomes at 16 weeks included a 2-point or more reduction in IGA score from baseline and EASI-75 response. Patients in the lebrikizumab arm had superior responses on both of these outcomes, with statistical significance achieved as early as week 8 and week 4, respectively, and maintained through week 16. Specifically, 41.2% of those treated with lebrikizumab had an IGA reduction of 2 points or more, compared with 22.1% of those receiving placebo plus TCS (P = .01), and the proportion of patients achieving EASI-75 responses was 69.5% vs. 42.2%, respectively (P < .001).

Patients treated with lebrikizumab also showed statistically significant improvements, compared with TCS alone in all key secondary endpoints, “including skin clearance, improvement in itch, itch interference on sleep, and enhanced QoL [quality of life],” noted the authors. “This study captured the clinical benefit of lebrikizumab through the combined end point of physician-assessed clinical sign of skin clearance (EASI-75) and patient-reported outcome of improvement in itch (Pruritus NRS).”

The percentage of patients who achieved the combined endpoint was more than double for the lebrikizumab plus TCS group vs. the group on TCS alone, indicating that patients treated with lebrikizumab plus TCS “were more likely to experience improvement in skin symptoms and itch,” the investigators added.

The authors noted that most treatment-emergent adverse events “were nonserious, mild, or moderate in severity, and did not lead to study discontinuation.” These included conjunctivitis (4.8%), headache (4.8%), hypertension (2.8%), injection-site reactions (2.8%), and herpes infection (3.4%) – all of which occurred in 1.5% or less of patients in the placebo group.

“The higher incidence of conjunctivitis has also been reported in other biologics inhibiting IL [interleukin]–13 and/or IL-4 signaling, as well as lebrikizumab monotherapy studies,” they noted. The 4.8% rate of conjunctivitis reported in the combination study, they added, is “compared with 7.5% frequency in 16-week data from the lebrikizumab monotherapy studies. Although the mechanism remains unclear, it has been reported that conjunctival goblet cell scarcity due to IL-13 and IL-4 inhibition, and subsequent effects on the homeostasis of the conjunctival mucosal surface, results in ocular AEs [adverse events].”

“This truly is a time of great hope and promise for our patients with AD,” commented Zelma Chiesa Fuxench, MD, who was not involved in the study. “The advent of newer, targeted therapeutic agents for AD continues to revolutionize the treatment experience for our patients, offering the possibility of greater AD disease control with a favorable risk profile and less need for blood work monitoring compared to traditional systemic agents.”

On the basis of the study results, Dr. Chiesa Fuxench, of the department of dermatology at the University of Pennsylvania, Philadelphia, said in an interview that “lebrikizumab represents an additional option in the treatment armamentarium for providers who care for patients with AD.” She added that, “while head-to-head trials comparing lebrikizumab to dupilumab, the first FDA-approved biologic for AD, would be beneficial, to the best of my knowledge this data is currently lacking. However, based on the results of this study, we would expect lebrikizumab to work at least similarly to dupilumab, based on the reported improvements in IGA and EASI score.”

Additionally, lebrikizumab showed a favorable safety profile, “with most treatment-emergent adverse effects reported as nonserious and not leading to drug discontinuation,” she said. “Of interest to clinicians may be the reported rates of conjunctivitis in this study. Rates of conjunctivitis for lebrikizumab appear to be lower than those reported in the LIBERTY AD CHRONOS study for dupilumab – a finding that merits further scrutiny in my opinion, as this one of the most frequent treatment-emergent adverse events that I encounter in my clinical practice.”

The study was funded by Dermira, a subsidiary of Eli Lilly. Dr. Simpson reported personal fees and grants from multiple sources, including Dermira and Eli Lilly, the companies developing lebrikizumab. Several authors were employees of Eli Lilly. Dr. Fuxench disclosed serving as a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, Pfizer, AbbVie, and Incyte, for which she has received honoraria for AD-related work. She is the recipient of research grants through Regeneron, Sanofi, Tioga, Vanda, Menlo Therapeutics, Leo Pharma, and Eli Lilly for work related to AD as well as honoraria for continuing medical education work related to AD sponsored through educational grants from Regeneron/Sanofi and Pfizer.

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

Adult and adolescent patients with moderate to severe atopic dermatitis (AD) showed significant improvements with the addition of lebrikizumab to topical corticosteroid (TCS) therapy, compared with TCS plus placebo, according to results of the 16-week phase 3 ADhere trial.

“Lebrikizumab, a monoclonal antibody inhibiting interleukin-13, combined with TCS was associated with reduced overall disease severity of moderate to severe AD in adolescents and adults, and had a safety profile consistent with previous lebrikizumab AD studies,” noted lead author Eric L. Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland, and coauthors in their article on the study, which was published in JAMA Dermatology.

The double-blind trial, conducted at 54 sites across Germany, Poland, Canada, and the United States, included 211 patients, mean age 37.2 years, of whom 48.8% were female and roughly 22% were adolescents. Almost 15% were Asian, and about 13% were Black.

At baseline, participants had a score of 16 or higher on the Eczema Area and Severity Index (EASI), a score of 3 or higher on the Investigator’s Global Assessment (IGA) scale, AD covering a body surface area of 10% or greater, and a history of inadequate response to treatment with topical medications.

After a minimum 1-week washout period from topical and systemic therapy, participants were randomized in a 2:1 ratio to receive lebrikizumab plus TCS (n = 145) or placebo plus TCS (n = 66) for 16 weeks.

Lebrikizumab or placebo was administered by subcutaneous injection every 2 weeks; the loading and week-2 doses of lebrikizumab were 500 mg, followed by 250 mg thereafter. All patients were instructed to use low- to mid-potency TCS at their own discretion. Study sites provided a mid-potency TCS (triamcinolone acetonide 0.1% cream) and a low-potency TCS (hydrocortisone 1% cream), with topical calcineurin inhibitors permitted for sensitive skin areas.

Primary outcomes at 16 weeks included a 2-point or more reduction in IGA score from baseline and EASI-75 response. Patients in the lebrikizumab arm had superior responses on both of these outcomes, with statistical significance achieved as early as week 8 and week 4, respectively, and maintained through week 16. Specifically, 41.2% of those treated with lebrikizumab had an IGA reduction of 2 points or more, compared with 22.1% of those receiving placebo plus TCS (P = .01), and the proportion of patients achieving EASI-75 responses was 69.5% vs. 42.2%, respectively (P < .001).

Patients treated with lebrikizumab also showed statistically significant improvements, compared with TCS alone in all key secondary endpoints, “including skin clearance, improvement in itch, itch interference on sleep, and enhanced QoL [quality of life],” noted the authors. “This study captured the clinical benefit of lebrikizumab through the combined end point of physician-assessed clinical sign of skin clearance (EASI-75) and patient-reported outcome of improvement in itch (Pruritus NRS).”

The percentage of patients who achieved the combined endpoint was more than double for the lebrikizumab plus TCS group vs. the group on TCS alone, indicating that patients treated with lebrikizumab plus TCS “were more likely to experience improvement in skin symptoms and itch,” the investigators added.

The authors noted that most treatment-emergent adverse events “were nonserious, mild, or moderate in severity, and did not lead to study discontinuation.” These included conjunctivitis (4.8%), headache (4.8%), hypertension (2.8%), injection-site reactions (2.8%), and herpes infection (3.4%) – all of which occurred in 1.5% or less of patients in the placebo group.

“The higher incidence of conjunctivitis has also been reported in other biologics inhibiting IL [interleukin]–13 and/or IL-4 signaling, as well as lebrikizumab monotherapy studies,” they noted. The 4.8% rate of conjunctivitis reported in the combination study, they added, is “compared with 7.5% frequency in 16-week data from the lebrikizumab monotherapy studies. Although the mechanism remains unclear, it has been reported that conjunctival goblet cell scarcity due to IL-13 and IL-4 inhibition, and subsequent effects on the homeostasis of the conjunctival mucosal surface, results in ocular AEs [adverse events].”

“This truly is a time of great hope and promise for our patients with AD,” commented Zelma Chiesa Fuxench, MD, who was not involved in the study. “The advent of newer, targeted therapeutic agents for AD continues to revolutionize the treatment experience for our patients, offering the possibility of greater AD disease control with a favorable risk profile and less need for blood work monitoring compared to traditional systemic agents.”

On the basis of the study results, Dr. Chiesa Fuxench, of the department of dermatology at the University of Pennsylvania, Philadelphia, said in an interview that “lebrikizumab represents an additional option in the treatment armamentarium for providers who care for patients with AD.” She added that, “while head-to-head trials comparing lebrikizumab to dupilumab, the first FDA-approved biologic for AD, would be beneficial, to the best of my knowledge this data is currently lacking. However, based on the results of this study, we would expect lebrikizumab to work at least similarly to dupilumab, based on the reported improvements in IGA and EASI score.”

Additionally, lebrikizumab showed a favorable safety profile, “with most treatment-emergent adverse effects reported as nonserious and not leading to drug discontinuation,” she said. “Of interest to clinicians may be the reported rates of conjunctivitis in this study. Rates of conjunctivitis for lebrikizumab appear to be lower than those reported in the LIBERTY AD CHRONOS study for dupilumab – a finding that merits further scrutiny in my opinion, as this one of the most frequent treatment-emergent adverse events that I encounter in my clinical practice.”

The study was funded by Dermira, a subsidiary of Eli Lilly. Dr. Simpson reported personal fees and grants from multiple sources, including Dermira and Eli Lilly, the companies developing lebrikizumab. Several authors were employees of Eli Lilly. Dr. Fuxench disclosed serving as a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, Pfizer, AbbVie, and Incyte, for which she has received honoraria for AD-related work. She is the recipient of research grants through Regeneron, Sanofi, Tioga, Vanda, Menlo Therapeutics, Leo Pharma, and Eli Lilly for work related to AD as well as honoraria for continuing medical education work related to AD sponsored through educational grants from Regeneron/Sanofi and Pfizer.

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

Emergency department visits and hospitalizations for COVID-19 in children appear to be following the declining trend set by weekly cases since early December, based on data from the Centers for Disease Control and Prevention.

Rates of ED visits involving diagnosed COVID-19 in children had been rising since mid-November, 2022, but are now declining in early January, 2023. New cases took a different path that had the weekly total falling through November before taking a big jump during the week of Nov. 27 to Dec. 3 – the count doubled from 30,000 the previous week to 63,000 – and then decreased again, the CDC reported.

The proportion of ED visits with COVID, which was down to 1.0% of all ED visits (7-day average) for children aged 0-4 years on Nov. 4, was up to 3.2% on Jan. 3 but slipped to 2.5% as of Jan. 10. The patterns for older children are similar, with some differences in timing and lower peaks (1.7% for 12- to 15-year-olds and 1.9% for those aged 16-17), according to the CDC’s COVID Data Tracker.

The trend for new hospital admissions of children with confirmed COVID showed a similar rise through December, and the latest data for the very beginning of January suggest an even faster drop, although there is more of a reporting lag with hospitalization data, compared with ED visits, the CDC noted.

The most current data (Dec. 30 to Jan. 5) available from the American Academy of Pediatrics and the Children’s Hospital Association show less volatility in the number of weekly cases through November and December, with the peak being about 48,000 in mid-December. The AAP/CHA totals for the last 2 weeks, however, were both higher than the CDC’s corresponding counts, which are more preliminary and subject to revision.

The CDC puts the total number of COVID cases in children at 16.7 million – about 17.2% of all cases – as of Jan. 11, with 1,981 deaths reported so far. The AAP and CHA are not tracking deaths, but their case total as of Jan. 5 was 15.2 million, which represents 18.1% of cases in all ages. The AAP/CHA report is based on data reported publicly by an ever-decreasing number of states and territories.

Emergency department visits and hospitalizations for COVID-19 in children appear to be following the declining trend set by weekly cases since early December, based on data from the Centers for Disease Control and Prevention.

Rates of ED visits involving diagnosed COVID-19 in children had been rising since mid-November, 2022, but are now declining in early January, 2023. New cases took a different path that had the weekly total falling through November before taking a big jump during the week of Nov. 27 to Dec. 3 – the count doubled from 30,000 the previous week to 63,000 – and then decreased again, the CDC reported.

The proportion of ED visits with COVID, which was down to 1.0% of all ED visits (7-day average) for children aged 0-4 years on Nov. 4, was up to 3.2% on Jan. 3 but slipped to 2.5% as of Jan. 10. The patterns for older children are similar, with some differences in timing and lower peaks (1.7% for 12- to 15-year-olds and 1.9% for those aged 16-17), according to the CDC’s COVID Data Tracker.

The trend for new hospital admissions of children with confirmed COVID showed a similar rise through December, and the latest data for the very beginning of January suggest an even faster drop, although there is more of a reporting lag with hospitalization data, compared with ED visits, the CDC noted.

The most current data (Dec. 30 to Jan. 5) available from the American Academy of Pediatrics and the Children’s Hospital Association show less volatility in the number of weekly cases through November and December, with the peak being about 48,000 in mid-December. The AAP/CHA totals for the last 2 weeks, however, were both higher than the CDC’s corresponding counts, which are more preliminary and subject to revision.

The CDC puts the total number of COVID cases in children at 16.7 million – about 17.2% of all cases – as of Jan. 11, with 1,981 deaths reported so far. The AAP and CHA are not tracking deaths, but their case total as of Jan. 5 was 15.2 million, which represents 18.1% of cases in all ages. The AAP/CHA report is based on data reported publicly by an ever-decreasing number of states and territories.

Emergency department visits and hospitalizations for COVID-19 in children appear to be following the declining trend set by weekly cases since early December, based on data from the Centers for Disease Control and Prevention.

Rates of ED visits involving diagnosed COVID-19 in children had been rising since mid-November, 2022, but are now declining in early January, 2023. New cases took a different path that had the weekly total falling through November before taking a big jump during the week of Nov. 27 to Dec. 3 – the count doubled from 30,000 the previous week to 63,000 – and then decreased again, the CDC reported.

The proportion of ED visits with COVID, which was down to 1.0% of all ED visits (7-day average) for children aged 0-4 years on Nov. 4, was up to 3.2% on Jan. 3 but slipped to 2.5% as of Jan. 10. The patterns for older children are similar, with some differences in timing and lower peaks (1.7% for 12- to 15-year-olds and 1.9% for those aged 16-17), according to the CDC’s COVID Data Tracker.

The trend for new hospital admissions of children with confirmed COVID showed a similar rise through December, and the latest data for the very beginning of January suggest an even faster drop, although there is more of a reporting lag with hospitalization data, compared with ED visits, the CDC noted.

The most current data (Dec. 30 to Jan. 5) available from the American Academy of Pediatrics and the Children’s Hospital Association show less volatility in the number of weekly cases through November and December, with the peak being about 48,000 in mid-December. The AAP/CHA totals for the last 2 weeks, however, were both higher than the CDC’s corresponding counts, which are more preliminary and subject to revision.

The CDC puts the total number of COVID cases in children at 16.7 million – about 17.2% of all cases – as of Jan. 11, with 1,981 deaths reported so far. The AAP and CHA are not tracking deaths, but their case total as of Jan. 5 was 15.2 million, which represents 18.1% of cases in all ages. The AAP/CHA report is based on data reported publicly by an ever-decreasing number of states and territories.

A California woman developed skin cancer after getting a cut during a manicure. Now, she and her doctor are spreading the word about her ordeal as a lesson that speed and persistence in seeking treatment are the keys that make her type of cancer – squamous cell carcinoma – completely curable.

“She cut me, and the cut wasn’t just a regular cuticle cut. She cut me deep, and that was one of the first times that happened to me,” Grace Garcia, 50, told TODAY.com, recalling the November 2021 incident.

Ms. Garcia had been getting her nails done regularly for 20 years, she said, but happened to go to a different salon than her usual spot because she couldn’t get an appointment during the busy pre-Thanksgiving season. She doesn’t recall whether the technician opened packaging that signals unused tools.

She put antibiotic ointment on the cut, but it didn’t heal after a few days. Eventually, the skin closed and a darkened bump formed. It was painful. She went to her doctor, who said it was a “callus from writing,” she told TODAY.com. But it was on her ring finger, which didn’t seem connected to writing. Her doctor said to keep an eye on it. 

Five months after the cut occurred, she mentioned it during a gynecology appointment and was referred to a dermatologist, who also advised keeping an eye on it. A wart developed. She went back to her primary care physician and then to another dermatologist. The spot was biopsied.

Squamous cell carcinoma is a common type of skin cancer, according to the American Academy of Dermatology. It can have many causes, but the cause in Ms. Garcia’s case was both very common and very rare: human papillomavirus, or HPV. HPV is a virus that infects millions of people every year, but it’s not a typical cause of skin cancer.

“It’s pretty rare for several reasons. Generally speaking, the strains that cause cancer from an HPV standpoint tend to be more sexually transmitted,” dermatologist Teo Soleymani told TODAY.com. “In Grace’s case, she had an injury, which became the portal of entry. So that thick skin that we have on our hands and feet that acts as a natural barrier against infections and things like that was no longer the case, and the virus was able to infect her skin.”

Dr. Soleymani said Ms. Garcia’s persistence to get answers likely saved her from losing a finger.

“Your outcomes are entirely dictated by how early you catch them, and very often they’re completely curable,” he said. “Her persistence – not only was she able to have a great outcome, she probably saved herself from having her finger amputated.”

A California woman developed skin cancer after getting a cut during a manicure. Now, she and her doctor are spreading the word about her ordeal as a lesson that speed and persistence in seeking treatment are the keys that make her type of cancer – squamous cell carcinoma – completely curable.

“She cut me, and the cut wasn’t just a regular cuticle cut. She cut me deep, and that was one of the first times that happened to me,” Grace Garcia, 50, told TODAY.com, recalling the November 2021 incident.

Ms. Garcia had been getting her nails done regularly for 20 years, she said, but happened to go to a different salon than her usual spot because she couldn’t get an appointment during the busy pre-Thanksgiving season. She doesn’t recall whether the technician opened packaging that signals unused tools.

She put antibiotic ointment on the cut, but it didn’t heal after a few days. Eventually, the skin closed and a darkened bump formed. It was painful. She went to her doctor, who said it was a “callus from writing,” she told TODAY.com. But it was on her ring finger, which didn’t seem connected to writing. Her doctor said to keep an eye on it. 

Five months after the cut occurred, she mentioned it during a gynecology appointment and was referred to a dermatologist, who also advised keeping an eye on it. A wart developed. She went back to her primary care physician and then to another dermatologist. The spot was biopsied.

Squamous cell carcinoma is a common type of skin cancer, according to the American Academy of Dermatology. It can have many causes, but the cause in Ms. Garcia’s case was both very common and very rare: human papillomavirus, or HPV. HPV is a virus that infects millions of people every year, but it’s not a typical cause of skin cancer.

“It’s pretty rare for several reasons. Generally speaking, the strains that cause cancer from an HPV standpoint tend to be more sexually transmitted,” dermatologist Teo Soleymani told TODAY.com. “In Grace’s case, she had an injury, which became the portal of entry. So that thick skin that we have on our hands and feet that acts as a natural barrier against infections and things like that was no longer the case, and the virus was able to infect her skin.”

Dr. Soleymani said Ms. Garcia’s persistence to get answers likely saved her from losing a finger.

“Your outcomes are entirely dictated by how early you catch them, and very often they’re completely curable,” he said. “Her persistence – not only was she able to have a great outcome, she probably saved herself from having her finger amputated.”

A California woman developed skin cancer after getting a cut during a manicure. Now, she and her doctor are spreading the word about her ordeal as a lesson that speed and persistence in seeking treatment are the keys that make her type of cancer – squamous cell carcinoma – completely curable.

“She cut me, and the cut wasn’t just a regular cuticle cut. She cut me deep, and that was one of the first times that happened to me,” Grace Garcia, 50, told TODAY.com, recalling the November 2021 incident.

Ms. Garcia had been getting her nails done regularly for 20 years, she said, but happened to go to a different salon than her usual spot because she couldn’t get an appointment during the busy pre-Thanksgiving season. She doesn’t recall whether the technician opened packaging that signals unused tools.

She put antibiotic ointment on the cut, but it didn’t heal after a few days. Eventually, the skin closed and a darkened bump formed. It was painful. She went to her doctor, who said it was a “callus from writing,” she told TODAY.com. But it was on her ring finger, which didn’t seem connected to writing. Her doctor said to keep an eye on it. 

Five months after the cut occurred, she mentioned it during a gynecology appointment and was referred to a dermatologist, who also advised keeping an eye on it. A wart developed. She went back to her primary care physician and then to another dermatologist. The spot was biopsied.

Squamous cell carcinoma is a common type of skin cancer, according to the American Academy of Dermatology. It can have many causes, but the cause in Ms. Garcia’s case was both very common and very rare: human papillomavirus, or HPV. HPV is a virus that infects millions of people every year, but it’s not a typical cause of skin cancer.

“It’s pretty rare for several reasons. Generally speaking, the strains that cause cancer from an HPV standpoint tend to be more sexually transmitted,” dermatologist Teo Soleymani told TODAY.com. “In Grace’s case, she had an injury, which became the portal of entry. So that thick skin that we have on our hands and feet that acts as a natural barrier against infections and things like that was no longer the case, and the virus was able to infect her skin.”

Dr. Soleymani said Ms. Garcia’s persistence to get answers likely saved her from losing a finger.

“Your outcomes are entirely dictated by how early you catch them, and very often they’re completely curable,” he said. “Her persistence – not only was she able to have a great outcome, she probably saved herself from having her finger amputated.”

Ecopipam, in development for Tourette syndrome in children and adolescents, has shown in a randomized, controlled trial that, compared with placebo, it reduced tics and reduced the risk for some of the common side effects of other treatments, including weight gain.

Findings of the multicenter, double-blind, trial funded by the drug maker, Emalex Biosciences, were published online in Pediatrics. The trial was conducted at 68 sites in the United States, Canada, Germany, France, and Poland between May 2019 and September 2021.

Donald L. Gilbert, MD, MS, with the division of neurology at Cincinnati Children’s Hospital, and colleagues noted that all Food and Drug Administration–approved medications for Tourette syndrome are antipsychotics. The medications carry a risk of weight gain, electrocardiogram abnormalities, metabolic changes, and drug-induced movement disorders.

First-in-class medication ecopipam, targets the D1 dopamine receptor, while currently approved medications block the D2 receptor. It “may be a safe and effective treatment of Tourette syndrome with advantages over other currently approved therapeutic agents,” the authors wrote.

The study included 153 individuals at least 6 years old up to age 18 with a baseline Yale Global Tic Severity Score Total Tic Score of at least 20.

They were randomly assigned 1:1 to ecopipam or placebo.
 

Significant reduction in tic severity

Researchers saw a 30% reduction in the tic severity score from baseline to week 12 for the ecopipam group compared with the placebo group.

The data showed a least-squares mean difference of 3.44 (95% confidence interval [CI], 6.09-0.79, P = .01). Researchers also saw improvement in Clinical Global Impression of Tourette Syndrome Severity in the ecopipam group (P = .03).

Sara Pawlowski, MD, division chief for primary care mental health integration at University of Vermont Health Network and assistant professor of psychiatry, University of Vermont, Burlington, said in an interview that several things should be considered with this research.

One is that, though the results show a reduction in tics, the study lasted only 12 weeks and “tics can last a lifetime,” she noted.

“They also can ebb and flow with major life events, stressors, and various other variables. So, I wonder how the effects of improvement can be teased out from the natural ebb and flow of the condition in a 3-month window, which is a snapshot into the course of a known relapsing, remitting, lifetime, and chronically variable condition,” she said.
 

Headaches, insomnia among side effects

Weight gain was larger in the placebo group than in the ecopipam group: 17.1% in the ecopipam group and 20.3% of those who got a placebo had a weight gain of more than 7% over the study period.

The most common side effects of the study drug were headache (15.8%), insomnia (14.5%), fatigue (7.9%), and somnolence (7.9%).

A limitation of the study was lack of racial and ethnic diversity, as 93.5% of those in the placebo group and 86.8% in the ecopipam group were White.

Guidelines in North America and Europe agree that behavioral treatments should be the first-line therapy.

Dr. Pawlowski said that although effective medications are needed, she urges focusing on better access to nonmedication treatments “that work for children and adolescents” as children who start taking the medications early may take them for the rest of their lives.

Also, while the research didn’t find weight gain in the ecopipam group, the side effects they did find in the group, including headache and insomnia, “do impact a child’s life,” she noted.

“We also can’t be reassured that over the course of chronic treatment there wouldn’t be movement disorders or metabolic disorders that emerge. Those are side effects or disorders that can emerge surreptitiously over time, and more time than 12 weeks,” she said.

The study was funded by Emalex Biosciences. Dr. Gilbert has received consulting fees from Biogen and PTC therapeutics. Study coauthors disclosed ties with Emalex, Alkermes, and Paragon Biosciences. Dr. Pawlowski reports no relevant financial relationships.

Ecopipam, in development for Tourette syndrome in children and adolescents, has shown in a randomized, controlled trial that, compared with placebo, it reduced tics and reduced the risk for some of the common side effects of other treatments, including weight gain.

Findings of the multicenter, double-blind, trial funded by the drug maker, Emalex Biosciences, were published online in Pediatrics. The trial was conducted at 68 sites in the United States, Canada, Germany, France, and Poland between May 2019 and September 2021.

Donald L. Gilbert, MD, MS, with the division of neurology at Cincinnati Children’s Hospital, and colleagues noted that all Food and Drug Administration–approved medications for Tourette syndrome are antipsychotics. The medications carry a risk of weight gain, electrocardiogram abnormalities, metabolic changes, and drug-induced movement disorders.

First-in-class medication ecopipam, targets the D1 dopamine receptor, while currently approved medications block the D2 receptor. It “may be a safe and effective treatment of Tourette syndrome with advantages over other currently approved therapeutic agents,” the authors wrote.

The study included 153 individuals at least 6 years old up to age 18 with a baseline Yale Global Tic Severity Score Total Tic Score of at least 20.

They were randomly assigned 1:1 to ecopipam or placebo.
 

Significant reduction in tic severity

Researchers saw a 30% reduction in the tic severity score from baseline to week 12 for the ecopipam group compared with the placebo group.

The data showed a least-squares mean difference of 3.44 (95% confidence interval [CI], 6.09-0.79, P = .01). Researchers also saw improvement in Clinical Global Impression of Tourette Syndrome Severity in the ecopipam group (P = .03).

Sara Pawlowski, MD, division chief for primary care mental health integration at University of Vermont Health Network and assistant professor of psychiatry, University of Vermont, Burlington, said in an interview that several things should be considered with this research.

One is that, though the results show a reduction in tics, the study lasted only 12 weeks and “tics can last a lifetime,” she noted.

“They also can ebb and flow with major life events, stressors, and various other variables. So, I wonder how the effects of improvement can be teased out from the natural ebb and flow of the condition in a 3-month window, which is a snapshot into the course of a known relapsing, remitting, lifetime, and chronically variable condition,” she said.
 

Headaches, insomnia among side effects

Weight gain was larger in the placebo group than in the ecopipam group: 17.1% in the ecopipam group and 20.3% of those who got a placebo had a weight gain of more than 7% over the study period.

The most common side effects of the study drug were headache (15.8%), insomnia (14.5%), fatigue (7.9%), and somnolence (7.9%).

A limitation of the study was lack of racial and ethnic diversity, as 93.5% of those in the placebo group and 86.8% in the ecopipam group were White.

Guidelines in North America and Europe agree that behavioral treatments should be the first-line therapy.

Dr. Pawlowski said that although effective medications are needed, she urges focusing on better access to nonmedication treatments “that work for children and adolescents” as children who start taking the medications early may take them for the rest of their lives.

Also, while the research didn’t find weight gain in the ecopipam group, the side effects they did find in the group, including headache and insomnia, “do impact a child’s life,” she noted.

“We also can’t be reassured that over the course of chronic treatment there wouldn’t be movement disorders or metabolic disorders that emerge. Those are side effects or disorders that can emerge surreptitiously over time, and more time than 12 weeks,” she said.

The study was funded by Emalex Biosciences. Dr. Gilbert has received consulting fees from Biogen and PTC therapeutics. Study coauthors disclosed ties with Emalex, Alkermes, and Paragon Biosciences. Dr. Pawlowski reports no relevant financial relationships.

Ecopipam, in development for Tourette syndrome in children and adolescents, has shown in a randomized, controlled trial that, compared with placebo, it reduced tics and reduced the risk for some of the common side effects of other treatments, including weight gain.

Findings of the multicenter, double-blind, trial funded by the drug maker, Emalex Biosciences, were published online in Pediatrics. The trial was conducted at 68 sites in the United States, Canada, Germany, France, and Poland between May 2019 and September 2021.

Donald L. Gilbert, MD, MS, with the division of neurology at Cincinnati Children’s Hospital, and colleagues noted that all Food and Drug Administration–approved medications for Tourette syndrome are antipsychotics. The medications carry a risk of weight gain, electrocardiogram abnormalities, metabolic changes, and drug-induced movement disorders.

First-in-class medication ecopipam, targets the D1 dopamine receptor, while currently approved medications block the D2 receptor. It “may be a safe and effective treatment of Tourette syndrome with advantages over other currently approved therapeutic agents,” the authors wrote.

The study included 153 individuals at least 6 years old up to age 18 with a baseline Yale Global Tic Severity Score Total Tic Score of at least 20.

They were randomly assigned 1:1 to ecopipam or placebo.
 

Significant reduction in tic severity

Researchers saw a 30% reduction in the tic severity score from baseline to week 12 for the ecopipam group compared with the placebo group.

The data showed a least-squares mean difference of 3.44 (95% confidence interval [CI], 6.09-0.79, P = .01). Researchers also saw improvement in Clinical Global Impression of Tourette Syndrome Severity in the ecopipam group (P = .03).

Sara Pawlowski, MD, division chief for primary care mental health integration at University of Vermont Health Network and assistant professor of psychiatry, University of Vermont, Burlington, said in an interview that several things should be considered with this research.

One is that, though the results show a reduction in tics, the study lasted only 12 weeks and “tics can last a lifetime,” she noted.

“They also can ebb and flow with major life events, stressors, and various other variables. So, I wonder how the effects of improvement can be teased out from the natural ebb and flow of the condition in a 3-month window, which is a snapshot into the course of a known relapsing, remitting, lifetime, and chronically variable condition,” she said.
 

Headaches, insomnia among side effects

Weight gain was larger in the placebo group than in the ecopipam group: 17.1% in the ecopipam group and 20.3% of those who got a placebo had a weight gain of more than 7% over the study period.

The most common side effects of the study drug were headache (15.8%), insomnia (14.5%), fatigue (7.9%), and somnolence (7.9%).

A limitation of the study was lack of racial and ethnic diversity, as 93.5% of those in the placebo group and 86.8% in the ecopipam group were White.

Guidelines in North America and Europe agree that behavioral treatments should be the first-line therapy.

Dr. Pawlowski said that although effective medications are needed, she urges focusing on better access to nonmedication treatments “that work for children and adolescents” as children who start taking the medications early may take them for the rest of their lives.

Also, while the research didn’t find weight gain in the ecopipam group, the side effects they did find in the group, including headache and insomnia, “do impact a child’s life,” she noted.

“We also can’t be reassured that over the course of chronic treatment there wouldn’t be movement disorders or metabolic disorders that emerge. Those are side effects or disorders that can emerge surreptitiously over time, and more time than 12 weeks,” she said.

The study was funded by Emalex Biosciences. Dr. Gilbert has received consulting fees from Biogen and PTC therapeutics. Study coauthors disclosed ties with Emalex, Alkermes, and Paragon Biosciences. Dr. Pawlowski reports no relevant financial relationships.

Vaccinations have substantially reduced morbidity and mortality from many infectious diseases. Despite the clear value of vaccinations in public health, efforts to better understand adverse events (AEs) following immunization are important to sustain public trust and vaccine confidence. Noninfectious inflammation of the heart may manifest as myocarditis or pericarditis, or occasionally, with shared signs and symptoms of each, as myopericarditis. This is a rare AE following some immunizations. Vaccine-associated myocarditis, pericarditis, or myopericarditis (VAMP) has been most clearly associated with smallpox vaccines and mRNA COVID-19 vaccines.^1-6 Although extremely rare, VAMP also has been associated with other vaccines.^7,8 Limited information exists to guide shared clinical decision making on COVID-19 vaccination in persons with a history of VAMP. It is unknown whether individuals with a history of VAMP are at higher risk for developing a recurrence or experiencing a more severe outcome following COVID-19 vaccination.

Methods

As part of the collaborative public health mission with the Centers for Disease Control and Prevention (CDC) for enhanced vaccine AE surveillance, the Defense Health Agency Immunization Healthcare Division (IHD) maintains a clinical database of service members and beneficiaries referred for suspected AEs following immunizations. A review of all AEs following immunization cases in this database from January 1, 2003, through February 28, 2022, identified individuals meeting the following criteria: (a) VAMP prior to receipt of COVID-19 vaccine; (b) receipt of COVID-19 vaccine in 2021; and (c) medical documentation in available electronic health records sufficient to describe health status at least 30 days following COVID-19 vaccination.⁹ If medical entries suggested cardiac symptoms following a COVID-19 vaccine, additional information was sought to verify VAMP based on current published criteria.^10,11 Both the initial VAMP cases and the suspected COVID-19 VAMP cases were adjudicated by a team of vaccine experts and specialists in immunology, cardiology, and preventive medicine.

This retrospective review was approved and conducted in accordance with the Walter Reed National Military Medical Center Institutional Review Board protocol #20664. All individuals with recurrent VAMP consented to share their health records and clinical details.

Results

Among 9260 cases in the IHD database, 431 met the case definition for VAMP.

Among the 179 patients included in this analysis, 171 (96%) were male. Their median age was 39 years at the time of COVID-19 vaccination.

Within 1 month of receipt of any COVID-19 vaccine, 11 individuals had documented symptoms suggesting cardiac involvement, specifically, chest pain, palpitations, or dyspnea. After cardiac evaluation, 4 patients met the criteria for VAMP after COVID-19 vaccination.^10,11 Seven patients either did not meet the criteria for VAMP or had alternative causes for their symptoms.

Two men aged 49 and 50 years with a history of vaccine-associated myocarditis following smallpox vaccination (Dryvax and ACAM2000) developed myocarditis 3 days after their second dose of the Moderna vaccine. One of these patients received a Pfizer-BioNTech booster 10 months later with no recurrence of symptoms. A 55-year-old man with a history of vaccine-associated myocarditis following Dryvax vaccination developed myocarditis 2 days after his Pfizer-BioNTech booster. None of the patients who developed post-COVID-19 VAMP reported residual symptoms from their initial VAMP episode, which occurred 12 to 18 years earlier. All were hospitalized briefly for observation and had complete symptom resolution within 6 weeks.

A 25-year-old man developed pericarditis 4 days after his second Pfizer-BioNTech vaccination. His previous ACAM2000 vaccine-associated myocarditis occurred 3 years earlier, with no residual symptoms. Of note, he had a mild COVID-19 infection 78 days before the onset of his pericarditis. After the onset of his COVID-19 vaccine-associated pericarditis, he continued to experience transient bouts of chest pressure and exertional dyspnea that resolved within 7 months of onset.

The median interval between COVID-19 vaccine doses in those who developed post-COVID-19 VAMP was within the recommended mRNA vaccine dosing intervals of 3 to 4 weeks and was consistent with the median mRNA vaccine dosing intervals among the entire cohort.

Due to the small cohort size and other limitations of this study, the suggested rate of cardiac injury in this review (4 cases in 179 persons, or 2.2%) is an imprecise estimate of risk in a small population (95% CI, 0.1%-4.4%). While this rate may seem higher than expected within the general population after COVID-19 vaccination, it is lower than the estimated lifetime risk of recurrent myocarditis from any cause.^6,12

Discussion

To our knowledge, this is the first report describing cardiac outcomes after COVID-19 vaccination among a cohort of individuals with prior history of VAMP. Four cases of COVID-19 VAMP were identified among 179 patients with previous VAMP. All cases had experienced VAMP after the smallpox vaccine several years earlier, with complete resolution of symptoms. Three cases presented with recurrent VAMP after their second dose of an mRNA COVID-19 vaccine, and one after an mRNA booster dose. All fully recovered over the course of several months.

Myocarditis is a heterogeneous inflammatory injury with diverse, sometimes idiopathic, etiologies.¹³ In contrast to infection-related cardiac injury, prior reports of vaccine-associated myocarditis have suggested a hypersensitivity reaction characterized by patchy eosinophilic infiltrates, a benign clinical course, and good prognosis.^2,3

There are several common features between VAMP after smallpox and COVID-19 vaccination. Cases occur predominantly in young men. The onset of symptoms after smallpox vaccine (mean, 10 days) and after mRNA COVID-19 vaccine (mean, 3 days) appears to correspond to the timing of peak postvaccination pro-inflammatory cytokine elevation.¹⁴ While all VAMP cases are serious events, the majority of patients appear to have a relatively benign clinical course with rapid and full recovery.¹³

Patients who have experienced an inflammatory cardiac injury may be at higher risk for recurrence, but quantifying risk of this rare phenomenon is challenging. Cases of VAMP after the COVID-19 vaccine have occasionally been reported in patients with previous cardiac injury unrelated to vaccination.^15-17 The cases presented here represent the first report of recurrent VAMP following prior non-COVID-19 vaccinations.

Most patients with prior VAMP in this cohort did not experience cardiac-suggestive symptoms following COVID-19 vaccination. Among 11 patients who developed symptoms, 3 had confirmed myocarditis and 1 had confirmed pericarditis. The clinical course for these patients with recurrent VAMP was observed to be no different in severity or duration from those who experience new-onset VAMP.⁴ All other patients not meeting criteria for VAMP or having alternative explanations for their symptoms also had a benign clinical course. Nonetheless, of the study cohort of 179, recurrent VAMP was diagnosed in 4 of the 11 who developed cardiac-suggestive symptoms following COVID-19 vaccination. The importance of cardiac evaluation should be emphasized for any patient presenting with chest pain, dyspnea, or other cardiac-suggestive symptoms following vaccination.

Strengths and Limitations

The strength of this review of VAMP recurrence associated with COVID-19 vaccination derives from our large and unique longitudinal database of VAMP among current and prior service members. Additionally, the IHD’s ongoing enhanced vaccine AEs surveillance provides the opportunity to contact patients and review their electronic health records over an extended interval of time.

When interpreting this report’s implications, limitations inherent to any retrospective case review should be considered. The cohort of cases of prior VAMP included primarily healthy, fit, young service members; this population is not representative of the general population. The cohort included prior VAMP cases that generally occurred after smallpox vaccination. Experiences after smallpox vaccine may not apply to cardiac injury from other vaccines or etiologies. By the nature of this review, the population studied at the time of COVID-19 vaccination was somewhat older than those most likely to develop an initial bout of VAMP.² This review was limited by information available in the electronic health records of a small number of patients. Subclinical cases of VAMP and cases without adequate clinical evaluation also could not be included.

Conclusions

Noninfectious inflammation of the heart (myocarditis, pericarditis, or myopericarditis) is a rare AE following certain vaccines, especially live replicating smallpox vaccine and mRNA COVID-19 vaccines. In this observational analysis, the majority of patients with previous VAMP successfully received a COVID-19 vaccine without recurrence. The 4 patients who were identified with recurrent VAMP following COVID-19 vaccination all recovered with supportive care. While the CDC endorses that individuals with a history of infectious myocarditis may receive COVID-19 vaccine after symptoms have resolved, there is currently insufficient safety data regarding COVID-19 vaccination of those with prior non-COVID-19 VAMP or following subsequent COVID-19 vaccination in those with prior VAMP related to COVID-19.¹⁰ For these individuals, COVID-19 vaccination is a precaution.¹⁰ Although insufficient to determine a precise level of risk, this report does provide data on which to base the CDC-recommended shared decision-making counseling of these patients. More research is needed to better define factors that increase risk for, or protection from, immune-mediated AEs following immunization, including VAMP. While benefits of vaccination have clearly outweighed risks during the COVID-19 pandemic, such research may optimize future vaccine recommendations.¹⁸

Vaccinations have substantially reduced morbidity and mortality from many infectious diseases. Despite the clear value of vaccinations in public health, efforts to better understand adverse events (AEs) following immunization are important to sustain public trust and vaccine confidence. Noninfectious inflammation of the heart may manifest as myocarditis or pericarditis, or occasionally, with shared signs and symptoms of each, as myopericarditis. This is a rare AE following some immunizations. Vaccine-associated myocarditis, pericarditis, or myopericarditis (VAMP) has been most clearly associated with smallpox vaccines and mRNA COVID-19 vaccines.^1-6 Although extremely rare, VAMP also has been associated with other vaccines.^7,8 Limited information exists to guide shared clinical decision making on COVID-19 vaccination in persons with a history of VAMP. It is unknown whether individuals with a history of VAMP are at higher risk for developing a recurrence or experiencing a more severe outcome following COVID-19 vaccination.

Methods

As part of the collaborative public health mission with the Centers for Disease Control and Prevention (CDC) for enhanced vaccine AE surveillance, the Defense Health Agency Immunization Healthcare Division (IHD) maintains a clinical database of service members and beneficiaries referred for suspected AEs following immunizations. A review of all AEs following immunization cases in this database from January 1, 2003, through February 28, 2022, identified individuals meeting the following criteria: (a) VAMP prior to receipt of COVID-19 vaccine; (b) receipt of COVID-19 vaccine in 2021; and (c) medical documentation in available electronic health records sufficient to describe health status at least 30 days following COVID-19 vaccination.⁹ If medical entries suggested cardiac symptoms following a COVID-19 vaccine, additional information was sought to verify VAMP based on current published criteria.^10,11 Both the initial VAMP cases and the suspected COVID-19 VAMP cases were adjudicated by a team of vaccine experts and specialists in immunology, cardiology, and preventive medicine.

This retrospective review was approved and conducted in accordance with the Walter Reed National Military Medical Center Institutional Review Board protocol #20664. All individuals with recurrent VAMP consented to share their health records and clinical details.

Results

Among 9260 cases in the IHD database, 431 met the case definition for VAMP.

Among the 179 patients included in this analysis, 171 (96%) were male. Their median age was 39 years at the time of COVID-19 vaccination.

Within 1 month of receipt of any COVID-19 vaccine, 11 individuals had documented symptoms suggesting cardiac involvement, specifically, chest pain, palpitations, or dyspnea. After cardiac evaluation, 4 patients met the criteria for VAMP after COVID-19 vaccination.^10,11 Seven patients either did not meet the criteria for VAMP or had alternative causes for their symptoms.

Two men aged 49 and 50 years with a history of vaccine-associated myocarditis following smallpox vaccination (Dryvax and ACAM2000) developed myocarditis 3 days after their second dose of the Moderna vaccine. One of these patients received a Pfizer-BioNTech booster 10 months later with no recurrence of symptoms. A 55-year-old man with a history of vaccine-associated myocarditis following Dryvax vaccination developed myocarditis 2 days after his Pfizer-BioNTech booster. None of the patients who developed post-COVID-19 VAMP reported residual symptoms from their initial VAMP episode, which occurred 12 to 18 years earlier. All were hospitalized briefly for observation and had complete symptom resolution within 6 weeks.

A 25-year-old man developed pericarditis 4 days after his second Pfizer-BioNTech vaccination. His previous ACAM2000 vaccine-associated myocarditis occurred 3 years earlier, with no residual symptoms. Of note, he had a mild COVID-19 infection 78 days before the onset of his pericarditis. After the onset of his COVID-19 vaccine-associated pericarditis, he continued to experience transient bouts of chest pressure and exertional dyspnea that resolved within 7 months of onset.

The median interval between COVID-19 vaccine doses in those who developed post-COVID-19 VAMP was within the recommended mRNA vaccine dosing intervals of 3 to 4 weeks and was consistent with the median mRNA vaccine dosing intervals among the entire cohort.

Due to the small cohort size and other limitations of this study, the suggested rate of cardiac injury in this review (4 cases in 179 persons, or 2.2%) is an imprecise estimate of risk in a small population (95% CI, 0.1%-4.4%). While this rate may seem higher than expected within the general population after COVID-19 vaccination, it is lower than the estimated lifetime risk of recurrent myocarditis from any cause.^6,12

Discussion

To our knowledge, this is the first report describing cardiac outcomes after COVID-19 vaccination among a cohort of individuals with prior history of VAMP. Four cases of COVID-19 VAMP were identified among 179 patients with previous VAMP. All cases had experienced VAMP after the smallpox vaccine several years earlier, with complete resolution of symptoms. Three cases presented with recurrent VAMP after their second dose of an mRNA COVID-19 vaccine, and one after an mRNA booster dose. All fully recovered over the course of several months.

Myocarditis is a heterogeneous inflammatory injury with diverse, sometimes idiopathic, etiologies.¹³ In contrast to infection-related cardiac injury, prior reports of vaccine-associated myocarditis have suggested a hypersensitivity reaction characterized by patchy eosinophilic infiltrates, a benign clinical course, and good prognosis.^2,3

There are several common features between VAMP after smallpox and COVID-19 vaccination. Cases occur predominantly in young men. The onset of symptoms after smallpox vaccine (mean, 10 days) and after mRNA COVID-19 vaccine (mean, 3 days) appears to correspond to the timing of peak postvaccination pro-inflammatory cytokine elevation.¹⁴ While all VAMP cases are serious events, the majority of patients appear to have a relatively benign clinical course with rapid and full recovery.¹³

Patients who have experienced an inflammatory cardiac injury may be at higher risk for recurrence, but quantifying risk of this rare phenomenon is challenging. Cases of VAMP after the COVID-19 vaccine have occasionally been reported in patients with previous cardiac injury unrelated to vaccination.^15-17 The cases presented here represent the first report of recurrent VAMP following prior non-COVID-19 vaccinations.

Most patients with prior VAMP in this cohort did not experience cardiac-suggestive symptoms following COVID-19 vaccination. Among 11 patients who developed symptoms, 3 had confirmed myocarditis and 1 had confirmed pericarditis. The clinical course for these patients with recurrent VAMP was observed to be no different in severity or duration from those who experience new-onset VAMP.⁴ All other patients not meeting criteria for VAMP or having alternative explanations for their symptoms also had a benign clinical course. Nonetheless, of the study cohort of 179, recurrent VAMP was diagnosed in 4 of the 11 who developed cardiac-suggestive symptoms following COVID-19 vaccination. The importance of cardiac evaluation should be emphasized for any patient presenting with chest pain, dyspnea, or other cardiac-suggestive symptoms following vaccination.

Strengths and Limitations

The strength of this review of VAMP recurrence associated with COVID-19 vaccination derives from our large and unique longitudinal database of VAMP among current and prior service members. Additionally, the IHD’s ongoing enhanced vaccine AEs surveillance provides the opportunity to contact patients and review their electronic health records over an extended interval of time.

When interpreting this report’s implications, limitations inherent to any retrospective case review should be considered. The cohort of cases of prior VAMP included primarily healthy, fit, young service members; this population is not representative of the general population. The cohort included prior VAMP cases that generally occurred after smallpox vaccination. Experiences after smallpox vaccine may not apply to cardiac injury from other vaccines or etiologies. By the nature of this review, the population studied at the time of COVID-19 vaccination was somewhat older than those most likely to develop an initial bout of VAMP.² This review was limited by information available in the electronic health records of a small number of patients. Subclinical cases of VAMP and cases without adequate clinical evaluation also could not be included.

Conclusions

Noninfectious inflammation of the heart (myocarditis, pericarditis, or myopericarditis) is a rare AE following certain vaccines, especially live replicating smallpox vaccine and mRNA COVID-19 vaccines. In this observational analysis, the majority of patients with previous VAMP successfully received a COVID-19 vaccine without recurrence. The 4 patients who were identified with recurrent VAMP following COVID-19 vaccination all recovered with supportive care. While the CDC endorses that individuals with a history of infectious myocarditis may receive COVID-19 vaccine after symptoms have resolved, there is currently insufficient safety data regarding COVID-19 vaccination of those with prior non-COVID-19 VAMP or following subsequent COVID-19 vaccination in those with prior VAMP related to COVID-19.¹⁰ For these individuals, COVID-19 vaccination is a precaution.¹⁰ Although insufficient to determine a precise level of risk, this report does provide data on which to base the CDC-recommended shared decision-making counseling of these patients. More research is needed to better define factors that increase risk for, or protection from, immune-mediated AEs following immunization, including VAMP. While benefits of vaccination have clearly outweighed risks during the COVID-19 pandemic, such research may optimize future vaccine recommendations.¹⁸

Vaccinations have substantially reduced morbidity and mortality from many infectious diseases. Despite the clear value of vaccinations in public health, efforts to better understand adverse events (AEs) following immunization are important to sustain public trust and vaccine confidence. Noninfectious inflammation of the heart may manifest as myocarditis or pericarditis, or occasionally, with shared signs and symptoms of each, as myopericarditis. This is a rare AE following some immunizations. Vaccine-associated myocarditis, pericarditis, or myopericarditis (VAMP) has been most clearly associated with smallpox vaccines and mRNA COVID-19 vaccines.^1-6 Although extremely rare, VAMP also has been associated with other vaccines.^7,8 Limited information exists to guide shared clinical decision making on COVID-19 vaccination in persons with a history of VAMP. It is unknown whether individuals with a history of VAMP are at higher risk for developing a recurrence or experiencing a more severe outcome following COVID-19 vaccination.

Methods

As part of the collaborative public health mission with the Centers for Disease Control and Prevention (CDC) for enhanced vaccine AE surveillance, the Defense Health Agency Immunization Healthcare Division (IHD) maintains a clinical database of service members and beneficiaries referred for suspected AEs following immunizations. A review of all AEs following immunization cases in this database from January 1, 2003, through February 28, 2022, identified individuals meeting the following criteria: (a) VAMP prior to receipt of COVID-19 vaccine; (b) receipt of COVID-19 vaccine in 2021; and (c) medical documentation in available electronic health records sufficient to describe health status at least 30 days following COVID-19 vaccination.⁹ If medical entries suggested cardiac symptoms following a COVID-19 vaccine, additional information was sought to verify VAMP based on current published criteria.^10,11 Both the initial VAMP cases and the suspected COVID-19 VAMP cases were adjudicated by a team of vaccine experts and specialists in immunology, cardiology, and preventive medicine.

This retrospective review was approved and conducted in accordance with the Walter Reed National Military Medical Center Institutional Review Board protocol #20664. All individuals with recurrent VAMP consented to share their health records and clinical details.

Results

Among 9260 cases in the IHD database, 431 met the case definition for VAMP.

Among the 179 patients included in this analysis, 171 (96%) were male. Their median age was 39 years at the time of COVID-19 vaccination.

Within 1 month of receipt of any COVID-19 vaccine, 11 individuals had documented symptoms suggesting cardiac involvement, specifically, chest pain, palpitations, or dyspnea. After cardiac evaluation, 4 patients met the criteria for VAMP after COVID-19 vaccination.^10,11 Seven patients either did not meet the criteria for VAMP or had alternative causes for their symptoms.

Two men aged 49 and 50 years with a history of vaccine-associated myocarditis following smallpox vaccination (Dryvax and ACAM2000) developed myocarditis 3 days after their second dose of the Moderna vaccine. One of these patients received a Pfizer-BioNTech booster 10 months later with no recurrence of symptoms. A 55-year-old man with a history of vaccine-associated myocarditis following Dryvax vaccination developed myocarditis 2 days after his Pfizer-BioNTech booster. None of the patients who developed post-COVID-19 VAMP reported residual symptoms from their initial VAMP episode, which occurred 12 to 18 years earlier. All were hospitalized briefly for observation and had complete symptom resolution within 6 weeks.

A 25-year-old man developed pericarditis 4 days after his second Pfizer-BioNTech vaccination. His previous ACAM2000 vaccine-associated myocarditis occurred 3 years earlier, with no residual symptoms. Of note, he had a mild COVID-19 infection 78 days before the onset of his pericarditis. After the onset of his COVID-19 vaccine-associated pericarditis, he continued to experience transient bouts of chest pressure and exertional dyspnea that resolved within 7 months of onset.

The median interval between COVID-19 vaccine doses in those who developed post-COVID-19 VAMP was within the recommended mRNA vaccine dosing intervals of 3 to 4 weeks and was consistent with the median mRNA vaccine dosing intervals among the entire cohort.

Due to the small cohort size and other limitations of this study, the suggested rate of cardiac injury in this review (4 cases in 179 persons, or 2.2%) is an imprecise estimate of risk in a small population (95% CI, 0.1%-4.4%). While this rate may seem higher than expected within the general population after COVID-19 vaccination, it is lower than the estimated lifetime risk of recurrent myocarditis from any cause.^6,12

Discussion

To our knowledge, this is the first report describing cardiac outcomes after COVID-19 vaccination among a cohort of individuals with prior history of VAMP. Four cases of COVID-19 VAMP were identified among 179 patients with previous VAMP. All cases had experienced VAMP after the smallpox vaccine several years earlier, with complete resolution of symptoms. Three cases presented with recurrent VAMP after their second dose of an mRNA COVID-19 vaccine, and one after an mRNA booster dose. All fully recovered over the course of several months.

Myocarditis is a heterogeneous inflammatory injury with diverse, sometimes idiopathic, etiologies.¹³ In contrast to infection-related cardiac injury, prior reports of vaccine-associated myocarditis have suggested a hypersensitivity reaction characterized by patchy eosinophilic infiltrates, a benign clinical course, and good prognosis.^2,3

There are several common features between VAMP after smallpox and COVID-19 vaccination. Cases occur predominantly in young men. The onset of symptoms after smallpox vaccine (mean, 10 days) and after mRNA COVID-19 vaccine (mean, 3 days) appears to correspond to the timing of peak postvaccination pro-inflammatory cytokine elevation.¹⁴ While all VAMP cases are serious events, the majority of patients appear to have a relatively benign clinical course with rapid and full recovery.¹³

Patients who have experienced an inflammatory cardiac injury may be at higher risk for recurrence, but quantifying risk of this rare phenomenon is challenging. Cases of VAMP after the COVID-19 vaccine have occasionally been reported in patients with previous cardiac injury unrelated to vaccination.^15-17 The cases presented here represent the first report of recurrent VAMP following prior non-COVID-19 vaccinations.

Most patients with prior VAMP in this cohort did not experience cardiac-suggestive symptoms following COVID-19 vaccination. Among 11 patients who developed symptoms, 3 had confirmed myocarditis and 1 had confirmed pericarditis. The clinical course for these patients with recurrent VAMP was observed to be no different in severity or duration from those who experience new-onset VAMP.⁴ All other patients not meeting criteria for VAMP or having alternative explanations for their symptoms also had a benign clinical course. Nonetheless, of the study cohort of 179, recurrent VAMP was diagnosed in 4 of the 11 who developed cardiac-suggestive symptoms following COVID-19 vaccination. The importance of cardiac evaluation should be emphasized for any patient presenting with chest pain, dyspnea, or other cardiac-suggestive symptoms following vaccination.

Strengths and Limitations

The strength of this review of VAMP recurrence associated with COVID-19 vaccination derives from our large and unique longitudinal database of VAMP among current and prior service members. Additionally, the IHD’s ongoing enhanced vaccine AEs surveillance provides the opportunity to contact patients and review their electronic health records over an extended interval of time.

When interpreting this report’s implications, limitations inherent to any retrospective case review should be considered. The cohort of cases of prior VAMP included primarily healthy, fit, young service members; this population is not representative of the general population. The cohort included prior VAMP cases that generally occurred after smallpox vaccination. Experiences after smallpox vaccine may not apply to cardiac injury from other vaccines or etiologies. By the nature of this review, the population studied at the time of COVID-19 vaccination was somewhat older than those most likely to develop an initial bout of VAMP.² This review was limited by information available in the electronic health records of a small number of patients. Subclinical cases of VAMP and cases without adequate clinical evaluation also could not be included.

Conclusions

Noninfectious inflammation of the heart (myocarditis, pericarditis, or myopericarditis) is a rare AE following certain vaccines, especially live replicating smallpox vaccine and mRNA COVID-19 vaccines. In this observational analysis, the majority of patients with previous VAMP successfully received a COVID-19 vaccine without recurrence. The 4 patients who were identified with recurrent VAMP following COVID-19 vaccination all recovered with supportive care. While the CDC endorses that individuals with a history of infectious myocarditis may receive COVID-19 vaccine after symptoms have resolved, there is currently insufficient safety data regarding COVID-19 vaccination of those with prior non-COVID-19 VAMP or following subsequent COVID-19 vaccination in those with prior VAMP related to COVID-19.¹⁰ For these individuals, COVID-19 vaccination is a precaution.¹⁰ Although insufficient to determine a precise level of risk, this report does provide data on which to base the CDC-recommended shared decision-making counseling of these patients. More research is needed to better define factors that increase risk for, or protection from, immune-mediated AEs following immunization, including VAMP. While benefits of vaccination have clearly outweighed risks during the COVID-19 pandemic, such research may optimize future vaccine recommendations.¹⁸

Dementia prevalence is 61% higher among older people with moderate to severe hearing loss compared with those with normal hearing, new national data show. Investigators also found that even mild hearing loss was associated with increased dementia risk, although it was not statistically significant, and that hearing aid use was tied to a 32% decrease in dementia prevalence.

“Every 10-decibel increase in hearing loss was associated with 16% greater prevalence of dementia, such that prevalence of dementia in older adults with moderate or greater hearing loss was 61% higher than prevalence in those with normal hearing,” said lead investigator Alison Huang, PhD, senior research associate in epidemiology at Johns Hopkins Bloomberg School of Public Health and core faculty in the Cochlear Center for Hearing and Public Health, Baltimore.

The findings were published online in JAMA.
 

Dose dependent effect

For their study, researchers analyzed data on 2,413 community-dwelling participants in the National Health and Aging Trends Study, a nationally representative, continuous panel study of U.S. Medicare beneficiaries aged 65 and older.

Data from the study was collected during in-home interviews, setting it apart from previous work that relied on data collected in a clinical setting, Dr. Huang said.

“This study was able to capture more vulnerable populations, such as the oldest old and older adults with disabilities, typically excluded from prior epidemiologic studies of the hearing loss–dementia association that use clinic-based data collection, which only captures people who have the ability and means to get to clinics,” Dr. Huang said.

Weighted hearing loss prevalence was 36.7% for mild and 29.8% for moderate to severe hearing loss, and weighted prevalence of dementia was 10.3%.

Those with moderate to severe hearing loss were 61% more likely to have dementia than were those with normal hearing (prevalence ratio, 1.61; 95% confidence interval [CI], 1.09-2.38).

Dementia prevalence increased with increasing severity of hearing loss: Normal hearing: 6.19% (95% CI, 4.31-8.80); mild hearing loss: 8.93% (95% CI, 6.99-11.34); moderate to severe hearing loss: 16.52% (95% CI, 13.81-19.64). But only moderate to severe hearing loss showed a statistically significant association with dementia (P = .02).

Dementia prevalence increased 16% per 10-decibel increase in hearing loss (prevalence ratio 1.16; P < .001).

Among the 853 individuals in the study with moderate to severe hearing loss, those who used hearing aids (n = 414) had a 32% lower risk of dementia compared with those who didn’t use assisted devices (prevalence ratio, 0.68; 95% CI, 0.47-1.00). Similar data were published in JAMA Neurology, suggesting that hearing aids reduce dementia risk.

“With this study, we were able to refine our understanding of the strength of the hearing loss–dementia association in a study more representative of older adults in the United States,” said Dr. Huang.
 

Robust association

Commenting on the findings, Justin S. Golub, MD, associate professor in the department of otolaryngology–head and neck surgery at Columbia University, New York, said the study supports earlier research and suggests a “robust” association between hearing loss and dementia.

“The particular advantage of this study was that it was high quality and nationally representative,” Dr. Golub said. “It is also among a smaller set of studies that have shown hearing aid use to be associated with lower risk of dementia.”

Although not statistically significant, researchers did find increasing prevalence of dementia among people with only mild hearing loss, and clinicians should take note, said Dr. Golub, who was not involved with this study.

“We would expect the relationship between mild hearing loss and dementia to be weaker than severe hearing loss and dementia and, as a result, it might take more participants to show an association among the mild group,” Dr. Golub said.

“Even though this particular study did not specifically find a relationship between mild hearing loss and dementia, I would still recommend people to start treating their hearing loss when it is early,” Dr. Golub added.

The study was funded by the National Institute on Aging. Dr. Golub reports no relevant financial relationships. Full disclosures for study authors are included in the original article.

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

Dementia prevalence is 61% higher among older people with moderate to severe hearing loss compared with those with normal hearing, new national data show. Investigators also found that even mild hearing loss was associated with increased dementia risk, although it was not statistically significant, and that hearing aid use was tied to a 32% decrease in dementia prevalence.

“Every 10-decibel increase in hearing loss was associated with 16% greater prevalence of dementia, such that prevalence of dementia in older adults with moderate or greater hearing loss was 61% higher than prevalence in those with normal hearing,” said lead investigator Alison Huang, PhD, senior research associate in epidemiology at Johns Hopkins Bloomberg School of Public Health and core faculty in the Cochlear Center for Hearing and Public Health, Baltimore.

The findings were published online in JAMA.
 

Dose dependent effect

For their study, researchers analyzed data on 2,413 community-dwelling participants in the National Health and Aging Trends Study, a nationally representative, continuous panel study of U.S. Medicare beneficiaries aged 65 and older.

Data from the study was collected during in-home interviews, setting it apart from previous work that relied on data collected in a clinical setting, Dr. Huang said.

“This study was able to capture more vulnerable populations, such as the oldest old and older adults with disabilities, typically excluded from prior epidemiologic studies of the hearing loss–dementia association that use clinic-based data collection, which only captures people who have the ability and means to get to clinics,” Dr. Huang said.

Weighted hearing loss prevalence was 36.7% for mild and 29.8% for moderate to severe hearing loss, and weighted prevalence of dementia was 10.3%.

Those with moderate to severe hearing loss were 61% more likely to have dementia than were those with normal hearing (prevalence ratio, 1.61; 95% confidence interval [CI], 1.09-2.38).

Dementia prevalence increased with increasing severity of hearing loss: Normal hearing: 6.19% (95% CI, 4.31-8.80); mild hearing loss: 8.93% (95% CI, 6.99-11.34); moderate to severe hearing loss: 16.52% (95% CI, 13.81-19.64). But only moderate to severe hearing loss showed a statistically significant association with dementia (P = .02).

Dementia prevalence increased 16% per 10-decibel increase in hearing loss (prevalence ratio 1.16; P < .001).

Among the 853 individuals in the study with moderate to severe hearing loss, those who used hearing aids (n = 414) had a 32% lower risk of dementia compared with those who didn’t use assisted devices (prevalence ratio, 0.68; 95% CI, 0.47-1.00). Similar data were published in JAMA Neurology, suggesting that hearing aids reduce dementia risk.

“With this study, we were able to refine our understanding of the strength of the hearing loss–dementia association in a study more representative of older adults in the United States,” said Dr. Huang.
 

Robust association

Commenting on the findings, Justin S. Golub, MD, associate professor in the department of otolaryngology–head and neck surgery at Columbia University, New York, said the study supports earlier research and suggests a “robust” association between hearing loss and dementia.

“The particular advantage of this study was that it was high quality and nationally representative,” Dr. Golub said. “It is also among a smaller set of studies that have shown hearing aid use to be associated with lower risk of dementia.”

Although not statistically significant, researchers did find increasing prevalence of dementia among people with only mild hearing loss, and clinicians should take note, said Dr. Golub, who was not involved with this study.

“We would expect the relationship between mild hearing loss and dementia to be weaker than severe hearing loss and dementia and, as a result, it might take more participants to show an association among the mild group,” Dr. Golub said.

“Even though this particular study did not specifically find a relationship between mild hearing loss and dementia, I would still recommend people to start treating their hearing loss when it is early,” Dr. Golub added.

The study was funded by the National Institute on Aging. Dr. Golub reports no relevant financial relationships. Full disclosures for study authors are included in the original article.

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

Dementia prevalence is 61% higher among older people with moderate to severe hearing loss compared with those with normal hearing, new national data show. Investigators also found that even mild hearing loss was associated with increased dementia risk, although it was not statistically significant, and that hearing aid use was tied to a 32% decrease in dementia prevalence.

“Every 10-decibel increase in hearing loss was associated with 16% greater prevalence of dementia, such that prevalence of dementia in older adults with moderate or greater hearing loss was 61% higher than prevalence in those with normal hearing,” said lead investigator Alison Huang, PhD, senior research associate in epidemiology at Johns Hopkins Bloomberg School of Public Health and core faculty in the Cochlear Center for Hearing and Public Health, Baltimore.

The findings were published online in JAMA.
 

Dose dependent effect

For their study, researchers analyzed data on 2,413 community-dwelling participants in the National Health and Aging Trends Study, a nationally representative, continuous panel study of U.S. Medicare beneficiaries aged 65 and older.

Data from the study was collected during in-home interviews, setting it apart from previous work that relied on data collected in a clinical setting, Dr. Huang said.

“This study was able to capture more vulnerable populations, such as the oldest old and older adults with disabilities, typically excluded from prior epidemiologic studies of the hearing loss–dementia association that use clinic-based data collection, which only captures people who have the ability and means to get to clinics,” Dr. Huang said.

Weighted hearing loss prevalence was 36.7% for mild and 29.8% for moderate to severe hearing loss, and weighted prevalence of dementia was 10.3%.

Those with moderate to severe hearing loss were 61% more likely to have dementia than were those with normal hearing (prevalence ratio, 1.61; 95% confidence interval [CI], 1.09-2.38).

Dementia prevalence increased with increasing severity of hearing loss: Normal hearing: 6.19% (95% CI, 4.31-8.80); mild hearing loss: 8.93% (95% CI, 6.99-11.34); moderate to severe hearing loss: 16.52% (95% CI, 13.81-19.64). But only moderate to severe hearing loss showed a statistically significant association with dementia (P = .02).

Dementia prevalence increased 16% per 10-decibel increase in hearing loss (prevalence ratio 1.16; P < .001).

Among the 853 individuals in the study with moderate to severe hearing loss, those who used hearing aids (n = 414) had a 32% lower risk of dementia compared with those who didn’t use assisted devices (prevalence ratio, 0.68; 95% CI, 0.47-1.00). Similar data were published in JAMA Neurology, suggesting that hearing aids reduce dementia risk.

“With this study, we were able to refine our understanding of the strength of the hearing loss–dementia association in a study more representative of older adults in the United States,” said Dr. Huang.
 

Robust association

Commenting on the findings, Justin S. Golub, MD, associate professor in the department of otolaryngology–head and neck surgery at Columbia University, New York, said the study supports earlier research and suggests a “robust” association between hearing loss and dementia.

“The particular advantage of this study was that it was high quality and nationally representative,” Dr. Golub said. “It is also among a smaller set of studies that have shown hearing aid use to be associated with lower risk of dementia.”

Although not statistically significant, researchers did find increasing prevalence of dementia among people with only mild hearing loss, and clinicians should take note, said Dr. Golub, who was not involved with this study.

“We would expect the relationship between mild hearing loss and dementia to be weaker than severe hearing loss and dementia and, as a result, it might take more participants to show an association among the mild group,” Dr. Golub said.

“Even though this particular study did not specifically find a relationship between mild hearing loss and dementia, I would still recommend people to start treating their hearing loss when it is early,” Dr. Golub added.

The study was funded by the National Institute on Aging. Dr. Golub reports no relevant financial relationships. Full disclosures for study authors are included in the original article.

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

This patient was experiencing a flare of his psoriasis. Three factors contributed to the flare: noncompliance with his treatment regimen, decreased sunlight in the winter, and his lithium therapy. Though carcinogenic, certain wavelengths of UV light are beneficial for psoriasis, and the shorter days of winter can cause flaring of psoriasis (or relative flaring). In addition, lithium—the most effective therapy for this patient’s bipolar disorder—can worsen psoriasis.

Psoriasis is a chronic multisystem inflammatory disorder with characteristic skin findings that include well-demarcated micaceous plaques, nail pitting, and sometimes tendon pain and inflammatory arthritis. Severity can range from small, thin plaques that are intermittently noticeable on the elbows or knees to widespread ash-like plaques covering most of the body.

Good topical choices for facial skin include hydrocortisone 2.5% cream or desonide 0.05%. Nonsteroidal topical therapies that are safe for facial skin include tacrolimus 0.1% ointment or pimecrolimus 1% cream.¹ These options may be used twice daily until the disease is controlled.

In many cases (as in this one), the patient’s previous psoriasis outbreaks could not be controlled with topical therapy alone. The patient had not responded to a previous methotrexate regimen, and more recently had been clear for several years on systemic ustekinumab, a monoclonal antibody. Dosed every 12 weeks, or sometimes every 8 weeks, ustekinumab is given by subcutaneous injection, usually in the abdomen, through normal skin. Ustekinumab was recently approved for home use with just 4 injections per year for maintenance therapy. However, the infrequency of the injections sometimes leads to noncompliance, as occurred with this patient. He had missed 2 doses since taking over his own dosing regimen.

Ultimately, the patient’s flare resolved when he was transitioned back to in-office treatment with ustekinumab.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

This patient was experiencing a flare of his psoriasis. Three factors contributed to the flare: noncompliance with his treatment regimen, decreased sunlight in the winter, and his lithium therapy. Though carcinogenic, certain wavelengths of UV light are beneficial for psoriasis, and the shorter days of winter can cause flaring of psoriasis (or relative flaring). In addition, lithium—the most effective therapy for this patient’s bipolar disorder—can worsen psoriasis.

Psoriasis is a chronic multisystem inflammatory disorder with characteristic skin findings that include well-demarcated micaceous plaques, nail pitting, and sometimes tendon pain and inflammatory arthritis. Severity can range from small, thin plaques that are intermittently noticeable on the elbows or knees to widespread ash-like plaques covering most of the body.

Good topical choices for facial skin include hydrocortisone 2.5% cream or desonide 0.05%. Nonsteroidal topical therapies that are safe for facial skin include tacrolimus 0.1% ointment or pimecrolimus 1% cream.¹ These options may be used twice daily until the disease is controlled.

In many cases (as in this one), the patient’s previous psoriasis outbreaks could not be controlled with topical therapy alone. The patient had not responded to a previous methotrexate regimen, and more recently had been clear for several years on systemic ustekinumab, a monoclonal antibody. Dosed every 12 weeks, or sometimes every 8 weeks, ustekinumab is given by subcutaneous injection, usually in the abdomen, through normal skin. Ustekinumab was recently approved for home use with just 4 injections per year for maintenance therapy. However, the infrequency of the injections sometimes leads to noncompliance, as occurred with this patient. He had missed 2 doses since taking over his own dosing regimen.

Ultimately, the patient’s flare resolved when he was transitioned back to in-office treatment with ustekinumab.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

This patient was experiencing a flare of his psoriasis. Three factors contributed to the flare: noncompliance with his treatment regimen, decreased sunlight in the winter, and his lithium therapy. Though carcinogenic, certain wavelengths of UV light are beneficial for psoriasis, and the shorter days of winter can cause flaring of psoriasis (or relative flaring). In addition, lithium—the most effective therapy for this patient’s bipolar disorder—can worsen psoriasis.

Psoriasis is a chronic multisystem inflammatory disorder with characteristic skin findings that include well-demarcated micaceous plaques, nail pitting, and sometimes tendon pain and inflammatory arthritis. Severity can range from small, thin plaques that are intermittently noticeable on the elbows or knees to widespread ash-like plaques covering most of the body.

Good topical choices for facial skin include hydrocortisone 2.5% cream or desonide 0.05%. Nonsteroidal topical therapies that are safe for facial skin include tacrolimus 0.1% ointment or pimecrolimus 1% cream.¹ These options may be used twice daily until the disease is controlled.

In many cases (as in this one), the patient’s previous psoriasis outbreaks could not be controlled with topical therapy alone. The patient had not responded to a previous methotrexate regimen, and more recently had been clear for several years on systemic ustekinumab, a monoclonal antibody. Dosed every 12 weeks, or sometimes every 8 weeks, ustekinumab is given by subcutaneous injection, usually in the abdomen, through normal skin. Ustekinumab was recently approved for home use with just 4 injections per year for maintenance therapy. However, the infrequency of the injections sometimes leads to noncompliance, as occurred with this patient. He had missed 2 doses since taking over his own dosing regimen.

Ultimately, the patient’s flare resolved when he was transitioned back to in-office treatment with ustekinumab.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

People with long COVID may have dizziness, headaches, sleep problems, sluggish thinking, and many other problems. But they can also face another problem – stigma.

Most people with long COVID find they’re facing stigma due to their condition, according to a new report from researchers in the United Kingdom. In short: Relatives and friends may not believe they’re truly sick.

The U.K. team found that more than three-quarters of people studied had experienced stigma often or always. 

In fact, 95% of people with long COVID faced at least one type of stigma at least sometimes, according to the study, published in November in the journal PLOS One.

Those conclusions had surprised the study’s lead researcher, Marija Pantelic, PhD, a public health lecturer at Brighton and Sussex Medical School, England.

“After years of working on HIV-related stigma, I was shocked to see how many people were turning a blind eye to and dismissing the difficulties experienced by people with long COVID,” Dr. Pantelic says. “It has also been clear to me from the start that this stigma is detrimental not just for people’s dignity, but also public health.”

Even some doctors argue that the growing attention paid to long COVID is excessive.

“It’s often normal to experience mild fatigue or weaknesses for weeks after being sick and inactive and not eating well. Calling these cases long COVID is the medicalization of modern life,” Marty Makary, MD, a surgeon and public policy researcher at Johns Hopkins University, Baltimore, wrote in a commentary in the Wall Street Journal.

Other doctors strongly disagree, including Alba Azola, MD, codirector of the Johns Hopkins Post-Acute COVID-19 Team and an expert in the stigma surrounding long COVID.

“Putting that spin on things, it’s just hurting people,” she says.

One example is people who cannot return to work.

“A lot of their family members tell me that they’re being lazy,” Dr. Azola says. “That’s part of the public stigma, that these are people just trying to get out of work.”

Some experts say the U.K. study represents a landmark.

“When you have data like this on long COVID stigma, it becomes more difficult to deny its existence or address it,” says Naomi Torres-Mackie, PhD, a clinical psychologist at Lenox Hill Hospital in New York. She also is head of research at the New York–based Mental Health Coalition, a group of experts working to end the stigma surrounding mental health.

She recalls her first patient with long COVID.

“She experienced the discomfort and pain itself, and then she had this crushing feeling that it wasn’t valid, or real. She felt very alone in it,” Dr. Torres-Mackie says.

Another one of her patients is working at her job from home but facing doubt about her condition from her employers.

“Every month, her medical doctor has to produce a letter confirming her medical condition,” Dr. Torres-Mackie says.

Taking part in the British stigma survey were 1,166 people, including 966 residents of the United Kingdom, with the average age of 48. Nearly 85% were female, and more than three-quarters were educated at the university level or higher.

Half of them said they had a clinical diagnosis of long COVID.

More than 60% of them said that at least some of the time, they were cautious about who they talked to about their condition. And fully 34% of those who did disclose their diagnosis said that they regretted having done so.

That’s a difficult experience for those with long COVID, says Leonard Jason, PhD, a professor of psychology at DePaul University in Chicago.

“It’s like they’re traumatized by the initial experience of being sick, and retraumatized by the response of others to them,” he says.

Unexplained illnesses are not well-regarded by the general public, Dr. Jason says.

He gave the example of multiple sclerosis. Before the 1980s, those with MS were considered to have a psychological illness, he says. “Then, in the 1980s, there were biomarkers that said, ‘Here’s the evidence.’ ”

The British study described three types of stigma stemming from the long COVID diagnosis of those questioned:

• Enacted stigma: People were directly treated unfairly because of their condition.
• Internalized stigma: People felt embarrassed by that condition.
• Anticipated stigma: People expected they would be treated poorly because of their diagnosis.

Dr. Azola calls the medical community a major problem when it comes to dealing with long COVID.

“What I see with my patients is medical trauma,” she says. They may have symptoms that send them to the emergency room, and then the tests come back negative. “Instead of tracking the patients’ symptoms, patients get told, ‘Everything looks good, you can go home, this is a panic attack,’ ” she says.

Some people go online to search for treatments, sometimes launching GoFundMe campaigns to raise money for unreliable treatments.

Long COVID patients may have gone through 5 to 10 doctors before they arrive for treatment with the Johns Hopkins Post-Acute COVID-19 Team. The clinic began in April 2020 remotely and in August of that year in person.

Today, the clinic staff spends an hour with a first-time long COVID patient, hearing their stories and helping relieve anxiety, Dr. Azola says.

The phenomenon of long COVID is similar to what patients have had with chronic fatigue syndrome, lupus, or fibromyalgia, where people have symptoms that are hard to explain, says Jennifer Chevinsky, MD, deputy public health officer for Riverside County, Calif.

“Stigma within medicine or health care is nothing new,” she says.

In Chicago, Dr. Jason notes that the federal government’s decision to invest hundreds of millions of dollars in long COVID research “shows the government is helping destigmatize it.”

Dr. Pantelic says she and her colleagues are continuing their research.

“We are interested in understanding the impacts of this stigma, and how to mitigate any adverse outcomes for patients and services,” she says.

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

People with long COVID may have dizziness, headaches, sleep problems, sluggish thinking, and many other problems. But they can also face another problem – stigma.

Most people with long COVID find they’re facing stigma due to their condition, according to a new report from researchers in the United Kingdom. In short: Relatives and friends may not believe they’re truly sick.

The U.K. team found that more than three-quarters of people studied had experienced stigma often or always. 

In fact, 95% of people with long COVID faced at least one type of stigma at least sometimes, according to the study, published in November in the journal PLOS One.

Those conclusions had surprised the study’s lead researcher, Marija Pantelic, PhD, a public health lecturer at Brighton and Sussex Medical School, England.

“After years of working on HIV-related stigma, I was shocked to see how many people were turning a blind eye to and dismissing the difficulties experienced by people with long COVID,” Dr. Pantelic says. “It has also been clear to me from the start that this stigma is detrimental not just for people’s dignity, but also public health.”

Even some doctors argue that the growing attention paid to long COVID is excessive.

“It’s often normal to experience mild fatigue or weaknesses for weeks after being sick and inactive and not eating well. Calling these cases long COVID is the medicalization of modern life,” Marty Makary, MD, a surgeon and public policy researcher at Johns Hopkins University, Baltimore, wrote in a commentary in the Wall Street Journal.

Other doctors strongly disagree, including Alba Azola, MD, codirector of the Johns Hopkins Post-Acute COVID-19 Team and an expert in the stigma surrounding long COVID.

“Putting that spin on things, it’s just hurting people,” she says.

One example is people who cannot return to work.

“A lot of their family members tell me that they’re being lazy,” Dr. Azola says. “That’s part of the public stigma, that these are people just trying to get out of work.”

Some experts say the U.K. study represents a landmark.

“When you have data like this on long COVID stigma, it becomes more difficult to deny its existence or address it,” says Naomi Torres-Mackie, PhD, a clinical psychologist at Lenox Hill Hospital in New York. She also is head of research at the New York–based Mental Health Coalition, a group of experts working to end the stigma surrounding mental health.

She recalls her first patient with long COVID.

“She experienced the discomfort and pain itself, and then she had this crushing feeling that it wasn’t valid, or real. She felt very alone in it,” Dr. Torres-Mackie says.

Another one of her patients is working at her job from home but facing doubt about her condition from her employers.

“Every month, her medical doctor has to produce a letter confirming her medical condition,” Dr. Torres-Mackie says.

Taking part in the British stigma survey were 1,166 people, including 966 residents of the United Kingdom, with the average age of 48. Nearly 85% were female, and more than three-quarters were educated at the university level or higher.

Half of them said they had a clinical diagnosis of long COVID.

More than 60% of them said that at least some of the time, they were cautious about who they talked to about their condition. And fully 34% of those who did disclose their diagnosis said that they regretted having done so.

That’s a difficult experience for those with long COVID, says Leonard Jason, PhD, a professor of psychology at DePaul University in Chicago.

“It’s like they’re traumatized by the initial experience of being sick, and retraumatized by the response of others to them,” he says.

Unexplained illnesses are not well-regarded by the general public, Dr. Jason says.

He gave the example of multiple sclerosis. Before the 1980s, those with MS were considered to have a psychological illness, he says. “Then, in the 1980s, there were biomarkers that said, ‘Here’s the evidence.’ ”

The British study described three types of stigma stemming from the long COVID diagnosis of those questioned:

• Enacted stigma: People were directly treated unfairly because of their condition.
• Internalized stigma: People felt embarrassed by that condition.
• Anticipated stigma: People expected they would be treated poorly because of their diagnosis.

Dr. Azola calls the medical community a major problem when it comes to dealing with long COVID.

“What I see with my patients is medical trauma,” she says. They may have symptoms that send them to the emergency room, and then the tests come back negative. “Instead of tracking the patients’ symptoms, patients get told, ‘Everything looks good, you can go home, this is a panic attack,’ ” she says.

Some people go online to search for treatments, sometimes launching GoFundMe campaigns to raise money for unreliable treatments.

Long COVID patients may have gone through 5 to 10 doctors before they arrive for treatment with the Johns Hopkins Post-Acute COVID-19 Team. The clinic began in April 2020 remotely and in August of that year in person.

Today, the clinic staff spends an hour with a first-time long COVID patient, hearing their stories and helping relieve anxiety, Dr. Azola says.

The phenomenon of long COVID is similar to what patients have had with chronic fatigue syndrome, lupus, or fibromyalgia, where people have symptoms that are hard to explain, says Jennifer Chevinsky, MD, deputy public health officer for Riverside County, Calif.

“Stigma within medicine or health care is nothing new,” she says.

In Chicago, Dr. Jason notes that the federal government’s decision to invest hundreds of millions of dollars in long COVID research “shows the government is helping destigmatize it.”

Dr. Pantelic says she and her colleagues are continuing their research.

“We are interested in understanding the impacts of this stigma, and how to mitigate any adverse outcomes for patients and services,” she says.

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

People with long COVID may have dizziness, headaches, sleep problems, sluggish thinking, and many other problems. But they can also face another problem – stigma.

Most people with long COVID find they’re facing stigma due to their condition, according to a new report from researchers in the United Kingdom. In short: Relatives and friends may not believe they’re truly sick.

The U.K. team found that more than three-quarters of people studied had experienced stigma often or always. 

In fact, 95% of people with long COVID faced at least one type of stigma at least sometimes, according to the study, published in November in the journal PLOS One.

Those conclusions had surprised the study’s lead researcher, Marija Pantelic, PhD, a public health lecturer at Brighton and Sussex Medical School, England.

“After years of working on HIV-related stigma, I was shocked to see how many people were turning a blind eye to and dismissing the difficulties experienced by people with long COVID,” Dr. Pantelic says. “It has also been clear to me from the start that this stigma is detrimental not just for people’s dignity, but also public health.”

Even some doctors argue that the growing attention paid to long COVID is excessive.

“It’s often normal to experience mild fatigue or weaknesses for weeks after being sick and inactive and not eating well. Calling these cases long COVID is the medicalization of modern life,” Marty Makary, MD, a surgeon and public policy researcher at Johns Hopkins University, Baltimore, wrote in a commentary in the Wall Street Journal.

Other doctors strongly disagree, including Alba Azola, MD, codirector of the Johns Hopkins Post-Acute COVID-19 Team and an expert in the stigma surrounding long COVID.

“Putting that spin on things, it’s just hurting people,” she says.

One example is people who cannot return to work.

“A lot of their family members tell me that they’re being lazy,” Dr. Azola says. “That’s part of the public stigma, that these are people just trying to get out of work.”

Some experts say the U.K. study represents a landmark.

“When you have data like this on long COVID stigma, it becomes more difficult to deny its existence or address it,” says Naomi Torres-Mackie, PhD, a clinical psychologist at Lenox Hill Hospital in New York. She also is head of research at the New York–based Mental Health Coalition, a group of experts working to end the stigma surrounding mental health.

She recalls her first patient with long COVID.

“She experienced the discomfort and pain itself, and then she had this crushing feeling that it wasn’t valid, or real. She felt very alone in it,” Dr. Torres-Mackie says.

Another one of her patients is working at her job from home but facing doubt about her condition from her employers.

“Every month, her medical doctor has to produce a letter confirming her medical condition,” Dr. Torres-Mackie says.

Taking part in the British stigma survey were 1,166 people, including 966 residents of the United Kingdom, with the average age of 48. Nearly 85% were female, and more than three-quarters were educated at the university level or higher.

Half of them said they had a clinical diagnosis of long COVID.

More than 60% of them said that at least some of the time, they were cautious about who they talked to about their condition. And fully 34% of those who did disclose their diagnosis said that they regretted having done so.

That’s a difficult experience for those with long COVID, says Leonard Jason, PhD, a professor of psychology at DePaul University in Chicago.

“It’s like they’re traumatized by the initial experience of being sick, and retraumatized by the response of others to them,” he says.

Unexplained illnesses are not well-regarded by the general public, Dr. Jason says.

He gave the example of multiple sclerosis. Before the 1980s, those with MS were considered to have a psychological illness, he says. “Then, in the 1980s, there were biomarkers that said, ‘Here’s the evidence.’ ”

The British study described three types of stigma stemming from the long COVID diagnosis of those questioned:

• Enacted stigma: People were directly treated unfairly because of their condition.
• Internalized stigma: People felt embarrassed by that condition.
• Anticipated stigma: People expected they would be treated poorly because of their diagnosis.

Dr. Azola calls the medical community a major problem when it comes to dealing with long COVID.

“What I see with my patients is medical trauma,” she says. They may have symptoms that send them to the emergency room, and then the tests come back negative. “Instead of tracking the patients’ symptoms, patients get told, ‘Everything looks good, you can go home, this is a panic attack,’ ” she says.

Some people go online to search for treatments, sometimes launching GoFundMe campaigns to raise money for unreliable treatments.

Long COVID patients may have gone through 5 to 10 doctors before they arrive for treatment with the Johns Hopkins Post-Acute COVID-19 Team. The clinic began in April 2020 remotely and in August of that year in person.

Today, the clinic staff spends an hour with a first-time long COVID patient, hearing their stories and helping relieve anxiety, Dr. Azola says.

The phenomenon of long COVID is similar to what patients have had with chronic fatigue syndrome, lupus, or fibromyalgia, where people have symptoms that are hard to explain, says Jennifer Chevinsky, MD, deputy public health officer for Riverside County, Calif.

“Stigma within medicine or health care is nothing new,” she says.

In Chicago, Dr. Jason notes that the federal government’s decision to invest hundreds of millions of dollars in long COVID research “shows the government is helping destigmatize it.”

Dr. Pantelic says she and her colleagues are continuing their research.

“We are interested in understanding the impacts of this stigma, and how to mitigate any adverse outcomes for patients and services,” she says.

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