MDedge Dermatology

Topical ruxolitinib appears to quickly relieve itch in Black patients with atopic dermatitis (AD), an industry-sponsored analysis of pooled data from two studies suggests.

“Ruxolitinib cream monotherapy over 8 weeks was associated with rapid and considerable itch relief in Black or African American patients with AD and was well tolerated,” the study authors wrote in a poster presented at the annual meeting of the Society for Investigative Dermatology.

AD can behave differently in different racial groups and can be especially bothersome in Black patients. AD has a prevalence of about 20% in Black children and 5%-10% in Black adults. Black children are roughly twice as likely to be diagnosed with AD, and to have severe AD, than White children, according to the authors.

Lead author Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, and colleagues used pooled data from two identically designed phase 3 studies to describe the effects of the cream formulation of the Janus kinase (JAK) 1 and JAK 2 inhibitor ruxolitinib on itch in Black patients.

Topical ruxolitinib (Opzelura), 1.5%, was approved last September for treating AD in non-immunocompromised patients with mild to moderate AD, ages 12 years and older. In July 2022, it was approved for the treatment of nonsegmental vitiligo in the same age group.  

FDA approval for AD was based on the results of the TRuE-AD1 and TRuE-AD2 double-blind randomized trials, which enrolled about 1,200 patients over age 12 with AD. These patients included 292 Black teenagers and adults between aged 12-71 years who had AD for 2 years or longer, with an Investigator’s Global Assessment (IGA) score of 2 or 3, with 3%-20% affected body surface area, excluding the scalp.

Of the 292 patients, those in the two treatment groups (n = 231) applied ruxolitinib cream twice a day for 8 weeks (0.75% in 118 patients and 1.5% in 113 patients) and 61 applied the vehicle. They used electronic diaries to record the worst level of itch they had experienced each day, from 0 (no itch) to 10 (worst imaginable itch). The main results were as follows: 

• Mean itch numerical rating scale (NRS) scores at baseline were 5.3 and 5.4 for ruxolitinib cream 0.75% and 1.5%, respectively, and 5.7 for vehicle. Within about 12 hours of first application, mean itch NRS scores dropped –0.6 and –0.7 from baseline among those treated with ruxolitinib cream 0.75% and 1.5%, respectively, compared with –0.2 for those on the vehicle. At day 4, the decreases were –1.4 and –1.6 for ruxolitinib cream 0.75% and 1.5%, respectively, versus –0.6 for the vehicle (P = .026 and P = .005, respectively, vs. vehicle).
• At day 2, among the 187 patients with a baseline itch NRS score 4 or higher, more patients achieved 4-point or greater itch NRS improvement: 6.1% and 16.4% for ruxolitinib cream 0.75% and 1.5%, respectively versus 0% for vehicle. At day 7, the differences were 15.9% and 26.6% versus 3%, respectively. And by week 8, they increased to 30.1% and 43.2% versus 17.5% (P = .212 and P = .009), respectively.
• At week 2, 19% of patients in the 0.75% formulation group and 19.4% of patients in the 1.5% formulation group, compared with 5.3% in the vehicle group, reported no days of itch on question 1 of the Patient-Oriented Eczema Measure (POEM) questionnaire that evaluated various aspects of the disease over the previous week. By week 8, the differences grew to 34% and 30.8% versus 12.2%, respectively.
• Adverse events, reported by 14.4% and 22.1% of patients on 0.75% and 1.5% ruxolitinib, respectively, and by 32.8% of patients who received the vehicle, were headaches, upper respiratory tract infection, and application site pain.

Ruxolitinib may be an alternative to systemic immunosuppressives

Asked to comment on the results, Amy J. McMichael, MD, professor of dermatology at Wake Forest University School of Medicine, Winston-Salem, N.C., called itch “one of the major life disruptors in atopic dermatitis.”

Providers often assume that patients of different races respond similarly to treatment, but that is not always true, she noted in an email.

“This study proves ruxolitinib’s effectiveness in Black patients, who often have more severe atopic dermatitis signs and symptoms,” said Dr. McMichael, who was not involved in the study. “The fact that atopic dermatitis in patients of color has been singled out to examine efficacy is a great way to show that the findings are not just in those who have thinner plaques and potentially less longstanding thickening of the skin from scratching (lichenification),” she added.

Dr. McMichael welcomed the lack of systemic side effects and quick relief of itch with this treatment, noting that the effect on itch “is rare with other treatments and extremely rare with other topical medications.”

The effect of topical ruxolitinib on pruritus “was interesting and surprising because very few available topical medications can control itch,” she explained. “The strongest topical steroids can help with pruritus, but they have the risk for skin thinning (atrophy),” while topical ruxolitinib is not associated with skin atrophy.

“After topical steroids fail as first-line treatment, it is likely that more patients will be given this topical medication rather than be moved to immunosuppressive systemic medications,” she noted.

All study authors report relevant relationships with Incyte Corporation, which manufactures ruxolitinib and funded the study, and several authors report employment and shareholding interests in the company. Dr. McMichael reports no relevant relationship with the study.

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

Topical ruxolitinib appears to quickly relieve itch in Black patients with atopic dermatitis (AD), an industry-sponsored analysis of pooled data from two studies suggests.

“Ruxolitinib cream monotherapy over 8 weeks was associated with rapid and considerable itch relief in Black or African American patients with AD and was well tolerated,” the study authors wrote in a poster presented at the annual meeting of the Society for Investigative Dermatology.

AD can behave differently in different racial groups and can be especially bothersome in Black patients. AD has a prevalence of about 20% in Black children and 5%-10% in Black adults. Black children are roughly twice as likely to be diagnosed with AD, and to have severe AD, than White children, according to the authors.

Lead author Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, and colleagues used pooled data from two identically designed phase 3 studies to describe the effects of the cream formulation of the Janus kinase (JAK) 1 and JAK 2 inhibitor ruxolitinib on itch in Black patients.

Topical ruxolitinib (Opzelura), 1.5%, was approved last September for treating AD in non-immunocompromised patients with mild to moderate AD, ages 12 years and older. In July 2022, it was approved for the treatment of nonsegmental vitiligo in the same age group.  

FDA approval for AD was based on the results of the TRuE-AD1 and TRuE-AD2 double-blind randomized trials, which enrolled about 1,200 patients over age 12 with AD. These patients included 292 Black teenagers and adults between aged 12-71 years who had AD for 2 years or longer, with an Investigator’s Global Assessment (IGA) score of 2 or 3, with 3%-20% affected body surface area, excluding the scalp.

Of the 292 patients, those in the two treatment groups (n = 231) applied ruxolitinib cream twice a day for 8 weeks (0.75% in 118 patients and 1.5% in 113 patients) and 61 applied the vehicle. They used electronic diaries to record the worst level of itch they had experienced each day, from 0 (no itch) to 10 (worst imaginable itch). The main results were as follows: 

• Mean itch numerical rating scale (NRS) scores at baseline were 5.3 and 5.4 for ruxolitinib cream 0.75% and 1.5%, respectively, and 5.7 for vehicle. Within about 12 hours of first application, mean itch NRS scores dropped –0.6 and –0.7 from baseline among those treated with ruxolitinib cream 0.75% and 1.5%, respectively, compared with –0.2 for those on the vehicle. At day 4, the decreases were –1.4 and –1.6 for ruxolitinib cream 0.75% and 1.5%, respectively, versus –0.6 for the vehicle (P = .026 and P = .005, respectively, vs. vehicle).
• At day 2, among the 187 patients with a baseline itch NRS score 4 or higher, more patients achieved 4-point or greater itch NRS improvement: 6.1% and 16.4% for ruxolitinib cream 0.75% and 1.5%, respectively versus 0% for vehicle. At day 7, the differences were 15.9% and 26.6% versus 3%, respectively. And by week 8, they increased to 30.1% and 43.2% versus 17.5% (P = .212 and P = .009), respectively.
• At week 2, 19% of patients in the 0.75% formulation group and 19.4% of patients in the 1.5% formulation group, compared with 5.3% in the vehicle group, reported no days of itch on question 1 of the Patient-Oriented Eczema Measure (POEM) questionnaire that evaluated various aspects of the disease over the previous week. By week 8, the differences grew to 34% and 30.8% versus 12.2%, respectively.
• Adverse events, reported by 14.4% and 22.1% of patients on 0.75% and 1.5% ruxolitinib, respectively, and by 32.8% of patients who received the vehicle, were headaches, upper respiratory tract infection, and application site pain.

Ruxolitinib may be an alternative to systemic immunosuppressives

Asked to comment on the results, Amy J. McMichael, MD, professor of dermatology at Wake Forest University School of Medicine, Winston-Salem, N.C., called itch “one of the major life disruptors in atopic dermatitis.”

Providers often assume that patients of different races respond similarly to treatment, but that is not always true, she noted in an email.

“This study proves ruxolitinib’s effectiveness in Black patients, who often have more severe atopic dermatitis signs and symptoms,” said Dr. McMichael, who was not involved in the study. “The fact that atopic dermatitis in patients of color has been singled out to examine efficacy is a great way to show that the findings are not just in those who have thinner plaques and potentially less longstanding thickening of the skin from scratching (lichenification),” she added.

Dr. McMichael welcomed the lack of systemic side effects and quick relief of itch with this treatment, noting that the effect on itch “is rare with other treatments and extremely rare with other topical medications.”

The effect of topical ruxolitinib on pruritus “was interesting and surprising because very few available topical medications can control itch,” she explained. “The strongest topical steroids can help with pruritus, but they have the risk for skin thinning (atrophy),” while topical ruxolitinib is not associated with skin atrophy.

“After topical steroids fail as first-line treatment, it is likely that more patients will be given this topical medication rather than be moved to immunosuppressive systemic medications,” she noted.

All study authors report relevant relationships with Incyte Corporation, which manufactures ruxolitinib and funded the study, and several authors report employment and shareholding interests in the company. Dr. McMichael reports no relevant relationship with the study.

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

Topical ruxolitinib appears to quickly relieve itch in Black patients with atopic dermatitis (AD), an industry-sponsored analysis of pooled data from two studies suggests.

“Ruxolitinib cream monotherapy over 8 weeks was associated with rapid and considerable itch relief in Black or African American patients with AD and was well tolerated,” the study authors wrote in a poster presented at the annual meeting of the Society for Investigative Dermatology.

AD can behave differently in different racial groups and can be especially bothersome in Black patients. AD has a prevalence of about 20% in Black children and 5%-10% in Black adults. Black children are roughly twice as likely to be diagnosed with AD, and to have severe AD, than White children, according to the authors.

Lead author Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, and colleagues used pooled data from two identically designed phase 3 studies to describe the effects of the cream formulation of the Janus kinase (JAK) 1 and JAK 2 inhibitor ruxolitinib on itch in Black patients.

Topical ruxolitinib (Opzelura), 1.5%, was approved last September for treating AD in non-immunocompromised patients with mild to moderate AD, ages 12 years and older. In July 2022, it was approved for the treatment of nonsegmental vitiligo in the same age group.  

FDA approval for AD was based on the results of the TRuE-AD1 and TRuE-AD2 double-blind randomized trials, which enrolled about 1,200 patients over age 12 with AD. These patients included 292 Black teenagers and adults between aged 12-71 years who had AD for 2 years or longer, with an Investigator’s Global Assessment (IGA) score of 2 or 3, with 3%-20% affected body surface area, excluding the scalp.

Of the 292 patients, those in the two treatment groups (n = 231) applied ruxolitinib cream twice a day for 8 weeks (0.75% in 118 patients and 1.5% in 113 patients) and 61 applied the vehicle. They used electronic diaries to record the worst level of itch they had experienced each day, from 0 (no itch) to 10 (worst imaginable itch). The main results were as follows: 

• Mean itch numerical rating scale (NRS) scores at baseline were 5.3 and 5.4 for ruxolitinib cream 0.75% and 1.5%, respectively, and 5.7 for vehicle. Within about 12 hours of first application, mean itch NRS scores dropped –0.6 and –0.7 from baseline among those treated with ruxolitinib cream 0.75% and 1.5%, respectively, compared with –0.2 for those on the vehicle. At day 4, the decreases were –1.4 and –1.6 for ruxolitinib cream 0.75% and 1.5%, respectively, versus –0.6 for the vehicle (P = .026 and P = .005, respectively, vs. vehicle).
• At day 2, among the 187 patients with a baseline itch NRS score 4 or higher, more patients achieved 4-point or greater itch NRS improvement: 6.1% and 16.4% for ruxolitinib cream 0.75% and 1.5%, respectively versus 0% for vehicle. At day 7, the differences were 15.9% and 26.6% versus 3%, respectively. And by week 8, they increased to 30.1% and 43.2% versus 17.5% (P = .212 and P = .009), respectively.
• At week 2, 19% of patients in the 0.75% formulation group and 19.4% of patients in the 1.5% formulation group, compared with 5.3% in the vehicle group, reported no days of itch on question 1 of the Patient-Oriented Eczema Measure (POEM) questionnaire that evaluated various aspects of the disease over the previous week. By week 8, the differences grew to 34% and 30.8% versus 12.2%, respectively.
• Adverse events, reported by 14.4% and 22.1% of patients on 0.75% and 1.5% ruxolitinib, respectively, and by 32.8% of patients who received the vehicle, were headaches, upper respiratory tract infection, and application site pain.

Ruxolitinib may be an alternative to systemic immunosuppressives

Asked to comment on the results, Amy J. McMichael, MD, professor of dermatology at Wake Forest University School of Medicine, Winston-Salem, N.C., called itch “one of the major life disruptors in atopic dermatitis.”

Providers often assume that patients of different races respond similarly to treatment, but that is not always true, she noted in an email.

“This study proves ruxolitinib’s effectiveness in Black patients, who often have more severe atopic dermatitis signs and symptoms,” said Dr. McMichael, who was not involved in the study. “The fact that atopic dermatitis in patients of color has been singled out to examine efficacy is a great way to show that the findings are not just in those who have thinner plaques and potentially less longstanding thickening of the skin from scratching (lichenification),” she added.

Dr. McMichael welcomed the lack of systemic side effects and quick relief of itch with this treatment, noting that the effect on itch “is rare with other treatments and extremely rare with other topical medications.”

The effect of topical ruxolitinib on pruritus “was interesting and surprising because very few available topical medications can control itch,” she explained. “The strongest topical steroids can help with pruritus, but they have the risk for skin thinning (atrophy),” while topical ruxolitinib is not associated with skin atrophy.

“After topical steroids fail as first-line treatment, it is likely that more patients will be given this topical medication rather than be moved to immunosuppressive systemic medications,” she noted.

All study authors report relevant relationships with Incyte Corporation, which manufactures ruxolitinib and funded the study, and several authors report employment and shareholding interests in the company. Dr. McMichael reports no relevant relationship with the study.

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

Treatment with the humanized monoclonal antibody litifilimab improved scores on a validated measure of skin disease activity in an international phase 2 trial of patients with cutaneous lupus erythematosus (CLE).

Improvements in Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity (CLASI-A) scores in patients randomly assigned to receive subcutaneous litifilimab were superior to changes in patients randomly assigned to placebo over the trial period of 16 weeks. The double-blind study was published in the New England Journal of Medicine.

“This validated measure is working, and it’s very important to now go into phase 3 using the instrument that worked in phase 2 to measure improvement in the skin,” Victoria P. Werth, MD, professor of dermatology at the University of Pennsylvania, Philadelphia, and lead author of the study, said in an interview.

Research on lupus erythematosus has focused on systemic lupus erythematosus (SLE), with few randomized controlled trials addressing CLE, she said, and no Food and Drug Administration–approved treatments for CLE in the last 50 years.

Asked to comment on the results, Alisa Femia, MD, associate professor and director of autoimmune connective tissue disease in the department of dermatology at New York University, who was not involved in the research, said it is “exciting to have a trial that specifically investigates the effect of a drug on cutaneous lupus, as well-designed investigations into this potentially disfiguring disease are relatively sparse and novel treatment pathways are needed.”

The investigational drug targets blood dendritic cell antigen 2 (BDCA2) – a receptor expressed solely on the surface of plasmacytoid dendritic cells (pDCs) – and inhibits the production of type 1 interferon and other inflammatory cytokines and chemokines believed to play a major role in the pathogenesis of cutaneous and systemic lupus, the investigators said.

Rheumatologist Edward Vital, MD, who leads a lupus research group at the University of Leeds (England), said he’s most interested in how the therapy works. The “idea [has been] that pDCs are the main source of type 1 interferon. But there’s a lot of data emerging at present that suggests there are many other sources of interferons, and the drug may work in other ways,” Dr. Vital, an associate professor at the university, said in an interview. He was not involved with the study.

“Maybe pDCs have other important roles. Or maybe other cells are targeted by the therapy, too,” he said. “Understanding this will help us understand the pathogenesis of lupus and which patients will benefit the most.”
 

Improvements in CLASI-A scores

Across 54 centers, the study enrolled 132 patients with primarily moderate to severe active subacute CLE or chronic CLE (including discoid lupus erythematosus), or both subacute and chronic CLE with or without systemic manifestations. Active CLE was defined as a score of at least 8 on CLASI-A, which measures erythema and scaling or hypertrophy in 13 skin regions.

Patients were randomly assigned to receive placebo or litifilimab at doses of 50 mg, 150 mg, or 450 mg subcutaneously at weeks 0, 2, 4, 8, and 12. Mean CLASI-A scores at baseline for placebo and each of the dosage groups were 16.5, 15.2, 18.4, and 16.5, respectively.

The investigators used a test of dose-response to assess response across the four groups on the basis of the percent change in CLASI-A scores from baseline to 16 weeks, the primary endpoint. The percent changes in CLASI-A score were –38.8 ± 7.5 in the 50-mg group; –47.9 ± 7.5 in the 150-mg group; –42.5 ± 5.5 in the 450-mg group; and –14.5 ± 6.4 in the placebo group. (Negative value indicates improvement from baseline.)

When compared with placebo, the change in CLASI-A scores in each of the litifilimab groups was –24.3 percentage points for the 50-mg dose (95% confidence interval, –43.7 to –4.9); –33.4 percentage points for the 150-mg dose (95% CI, –52.7 to –14.1); and –28.0 percentage points for the 450-mg dose (95% CI, –44.6 to –11.4).

“All three dosages caused a similar skin response,” said Dr. Werth. “And importantly, the placebo response is fairly low, much lower than in SLE trials, possibly because the background therapies tend to be less overall [including with slightly lower doses of prednisone]. So we can really see the broad effect of the drug.”

Just under half of participants – 42%-48% of patients receiving litifilimab and 42% of those in the placebo group – had concomitant SLE with low to moderate disease activity as measured by the Systemic Lupus Erythematosus Disease Activity Index 2000. Patients could meet SLE criteria based on previous findings, and “didn’t have to have active SLE,” Dr. Werth noted.

The trial allowed background therapy as long as treatment had begun at least 12 weeks before randomization, with a stable dose starting at least 4 weeks before randomization and maintained throughout the trial period.

Most patients had moderate to severe CLE at baseline “despite approximately 90% having received concomitant background therapy and 80% of those participants having received antimalarial drugs, either alone or with other agents,” Dr. Werth and coinvestigators wrote.

CLASI-A has been shown to correlate to patients’ quality of life, Dr. Werth emphasized in the interview.

Most of the reported side effects in the phase 2 CLE trial were mild or moderate. The treatment was associated with three cases of hypersensitivity, three cases of oral herpes infection, and one case of herpes zoster infection. One case of herpes zoster meningitis occurred 4 months after the last dose of litifilimab.

Approximately 10% of study participants who reported race and ethnicity were Black or African American.

Phase 3 trials

The trial was one part of a two-part phase 2 study of litifilimab, named the LILAC trial, sponsored by Biogen. The other part, which will be published separately, involved patients who had SLE with active joint and skin manifestations.

Biogen is currently enrolling patients in phase 3 studies – the TOPAZ-1 and TOPAZ-2 studies – to evaluate the efficacy and safety of the drug in patients with active SLE. As secondary endpoints, both trials will measure the percentage of participants with a CLASI-A score of at least 10 at baseline who achieve improvement in the score, including a 50% improvement from baseline to week 16, Nathalie Franchimont, MD, PhD, of Biogen, a coauthor of the NEJM study, said in an email.

Biogen also has “plans to initiate a pivotal study in CLE this year,” she said.

With respect to the newly published phase 2 study, Dr. Femia said that, while “conclusions about the magnitude of efficacy are difficult to extrapolate in this trial design, there’s reason for cautious optimism.” There is “good theoretical basis to be optimistic about a drug such as litifilimab, that ultimately reduces type 1 interferon response,” she added.

Anifrolumab, a type 1 interferon receptor monoclonal antibody marketed as Saphnelo, was approved by the FDA for SLE in July 2021, but CLE subtypes were not characterized in trials and CLE was not studied independently of SLE, the authors pointed out in their NEJM article.

The study was supported by Biogen. In addition to working with Biogen, Dr. Werth serves as a consultant to Gilead Sciences and other pharmaceutical companies. Dr. Vital has research grants and has received honoraria from AstraZeneca. Dr. Femia disclosed no relevant financial relationships.

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

Treatment with the humanized monoclonal antibody litifilimab improved scores on a validated measure of skin disease activity in an international phase 2 trial of patients with cutaneous lupus erythematosus (CLE).

Improvements in Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity (CLASI-A) scores in patients randomly assigned to receive subcutaneous litifilimab were superior to changes in patients randomly assigned to placebo over the trial period of 16 weeks. The double-blind study was published in the New England Journal of Medicine.

“This validated measure is working, and it’s very important to now go into phase 3 using the instrument that worked in phase 2 to measure improvement in the skin,” Victoria P. Werth, MD, professor of dermatology at the University of Pennsylvania, Philadelphia, and lead author of the study, said in an interview.

Research on lupus erythematosus has focused on systemic lupus erythematosus (SLE), with few randomized controlled trials addressing CLE, she said, and no Food and Drug Administration–approved treatments for CLE in the last 50 years.

Asked to comment on the results, Alisa Femia, MD, associate professor and director of autoimmune connective tissue disease in the department of dermatology at New York University, who was not involved in the research, said it is “exciting to have a trial that specifically investigates the effect of a drug on cutaneous lupus, as well-designed investigations into this potentially disfiguring disease are relatively sparse and novel treatment pathways are needed.”

The investigational drug targets blood dendritic cell antigen 2 (BDCA2) – a receptor expressed solely on the surface of plasmacytoid dendritic cells (pDCs) – and inhibits the production of type 1 interferon and other inflammatory cytokines and chemokines believed to play a major role in the pathogenesis of cutaneous and systemic lupus, the investigators said.

Rheumatologist Edward Vital, MD, who leads a lupus research group at the University of Leeds (England), said he’s most interested in how the therapy works. The “idea [has been] that pDCs are the main source of type 1 interferon. But there’s a lot of data emerging at present that suggests there are many other sources of interferons, and the drug may work in other ways,” Dr. Vital, an associate professor at the university, said in an interview. He was not involved with the study.

“Maybe pDCs have other important roles. Or maybe other cells are targeted by the therapy, too,” he said. “Understanding this will help us understand the pathogenesis of lupus and which patients will benefit the most.”
 

Improvements in CLASI-A scores

Across 54 centers, the study enrolled 132 patients with primarily moderate to severe active subacute CLE or chronic CLE (including discoid lupus erythematosus), or both subacute and chronic CLE with or without systemic manifestations. Active CLE was defined as a score of at least 8 on CLASI-A, which measures erythema and scaling or hypertrophy in 13 skin regions.

Patients were randomly assigned to receive placebo or litifilimab at doses of 50 mg, 150 mg, or 450 mg subcutaneously at weeks 0, 2, 4, 8, and 12. Mean CLASI-A scores at baseline for placebo and each of the dosage groups were 16.5, 15.2, 18.4, and 16.5, respectively.

The investigators used a test of dose-response to assess response across the four groups on the basis of the percent change in CLASI-A scores from baseline to 16 weeks, the primary endpoint. The percent changes in CLASI-A score were –38.8 ± 7.5 in the 50-mg group; –47.9 ± 7.5 in the 150-mg group; –42.5 ± 5.5 in the 450-mg group; and –14.5 ± 6.4 in the placebo group. (Negative value indicates improvement from baseline.)

When compared with placebo, the change in CLASI-A scores in each of the litifilimab groups was –24.3 percentage points for the 50-mg dose (95% confidence interval, –43.7 to –4.9); –33.4 percentage points for the 150-mg dose (95% CI, –52.7 to –14.1); and –28.0 percentage points for the 450-mg dose (95% CI, –44.6 to –11.4).

“All three dosages caused a similar skin response,” said Dr. Werth. “And importantly, the placebo response is fairly low, much lower than in SLE trials, possibly because the background therapies tend to be less overall [including with slightly lower doses of prednisone]. So we can really see the broad effect of the drug.”

Just under half of participants – 42%-48% of patients receiving litifilimab and 42% of those in the placebo group – had concomitant SLE with low to moderate disease activity as measured by the Systemic Lupus Erythematosus Disease Activity Index 2000. Patients could meet SLE criteria based on previous findings, and “didn’t have to have active SLE,” Dr. Werth noted.

The trial allowed background therapy as long as treatment had begun at least 12 weeks before randomization, with a stable dose starting at least 4 weeks before randomization and maintained throughout the trial period.

Most patients had moderate to severe CLE at baseline “despite approximately 90% having received concomitant background therapy and 80% of those participants having received antimalarial drugs, either alone or with other agents,” Dr. Werth and coinvestigators wrote.

CLASI-A has been shown to correlate to patients’ quality of life, Dr. Werth emphasized in the interview.

Most of the reported side effects in the phase 2 CLE trial were mild or moderate. The treatment was associated with three cases of hypersensitivity, three cases of oral herpes infection, and one case of herpes zoster infection. One case of herpes zoster meningitis occurred 4 months after the last dose of litifilimab.

Approximately 10% of study participants who reported race and ethnicity were Black or African American.

Phase 3 trials

The trial was one part of a two-part phase 2 study of litifilimab, named the LILAC trial, sponsored by Biogen. The other part, which will be published separately, involved patients who had SLE with active joint and skin manifestations.

Biogen is currently enrolling patients in phase 3 studies – the TOPAZ-1 and TOPAZ-2 studies – to evaluate the efficacy and safety of the drug in patients with active SLE. As secondary endpoints, both trials will measure the percentage of participants with a CLASI-A score of at least 10 at baseline who achieve improvement in the score, including a 50% improvement from baseline to week 16, Nathalie Franchimont, MD, PhD, of Biogen, a coauthor of the NEJM study, said in an email.

Biogen also has “plans to initiate a pivotal study in CLE this year,” she said.

With respect to the newly published phase 2 study, Dr. Femia said that, while “conclusions about the magnitude of efficacy are difficult to extrapolate in this trial design, there’s reason for cautious optimism.” There is “good theoretical basis to be optimistic about a drug such as litifilimab, that ultimately reduces type 1 interferon response,” she added.

Anifrolumab, a type 1 interferon receptor monoclonal antibody marketed as Saphnelo, was approved by the FDA for SLE in July 2021, but CLE subtypes were not characterized in trials and CLE was not studied independently of SLE, the authors pointed out in their NEJM article.

The study was supported by Biogen. In addition to working with Biogen, Dr. Werth serves as a consultant to Gilead Sciences and other pharmaceutical companies. Dr. Vital has research grants and has received honoraria from AstraZeneca. Dr. Femia disclosed no relevant financial relationships.

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

Treatment with the humanized monoclonal antibody litifilimab improved scores on a validated measure of skin disease activity in an international phase 2 trial of patients with cutaneous lupus erythematosus (CLE).

Improvements in Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity (CLASI-A) scores in patients randomly assigned to receive subcutaneous litifilimab were superior to changes in patients randomly assigned to placebo over the trial period of 16 weeks. The double-blind study was published in the New England Journal of Medicine.

“This validated measure is working, and it’s very important to now go into phase 3 using the instrument that worked in phase 2 to measure improvement in the skin,” Victoria P. Werth, MD, professor of dermatology at the University of Pennsylvania, Philadelphia, and lead author of the study, said in an interview.

Research on lupus erythematosus has focused on systemic lupus erythematosus (SLE), with few randomized controlled trials addressing CLE, she said, and no Food and Drug Administration–approved treatments for CLE in the last 50 years.

Asked to comment on the results, Alisa Femia, MD, associate professor and director of autoimmune connective tissue disease in the department of dermatology at New York University, who was not involved in the research, said it is “exciting to have a trial that specifically investigates the effect of a drug on cutaneous lupus, as well-designed investigations into this potentially disfiguring disease are relatively sparse and novel treatment pathways are needed.”

The investigational drug targets blood dendritic cell antigen 2 (BDCA2) – a receptor expressed solely on the surface of plasmacytoid dendritic cells (pDCs) – and inhibits the production of type 1 interferon and other inflammatory cytokines and chemokines believed to play a major role in the pathogenesis of cutaneous and systemic lupus, the investigators said.

Rheumatologist Edward Vital, MD, who leads a lupus research group at the University of Leeds (England), said he’s most interested in how the therapy works. The “idea [has been] that pDCs are the main source of type 1 interferon. But there’s a lot of data emerging at present that suggests there are many other sources of interferons, and the drug may work in other ways,” Dr. Vital, an associate professor at the university, said in an interview. He was not involved with the study.

“Maybe pDCs have other important roles. Or maybe other cells are targeted by the therapy, too,” he said. “Understanding this will help us understand the pathogenesis of lupus and which patients will benefit the most.”
 

Improvements in CLASI-A scores

Across 54 centers, the study enrolled 132 patients with primarily moderate to severe active subacute CLE or chronic CLE (including discoid lupus erythematosus), or both subacute and chronic CLE with or without systemic manifestations. Active CLE was defined as a score of at least 8 on CLASI-A, which measures erythema and scaling or hypertrophy in 13 skin regions.

Patients were randomly assigned to receive placebo or litifilimab at doses of 50 mg, 150 mg, or 450 mg subcutaneously at weeks 0, 2, 4, 8, and 12. Mean CLASI-A scores at baseline for placebo and each of the dosage groups were 16.5, 15.2, 18.4, and 16.5, respectively.

The investigators used a test of dose-response to assess response across the four groups on the basis of the percent change in CLASI-A scores from baseline to 16 weeks, the primary endpoint. The percent changes in CLASI-A score were –38.8 ± 7.5 in the 50-mg group; –47.9 ± 7.5 in the 150-mg group; –42.5 ± 5.5 in the 450-mg group; and –14.5 ± 6.4 in the placebo group. (Negative value indicates improvement from baseline.)

When compared with placebo, the change in CLASI-A scores in each of the litifilimab groups was –24.3 percentage points for the 50-mg dose (95% confidence interval, –43.7 to –4.9); –33.4 percentage points for the 150-mg dose (95% CI, –52.7 to –14.1); and –28.0 percentage points for the 450-mg dose (95% CI, –44.6 to –11.4).

“All three dosages caused a similar skin response,” said Dr. Werth. “And importantly, the placebo response is fairly low, much lower than in SLE trials, possibly because the background therapies tend to be less overall [including with slightly lower doses of prednisone]. So we can really see the broad effect of the drug.”

Just under half of participants – 42%-48% of patients receiving litifilimab and 42% of those in the placebo group – had concomitant SLE with low to moderate disease activity as measured by the Systemic Lupus Erythematosus Disease Activity Index 2000. Patients could meet SLE criteria based on previous findings, and “didn’t have to have active SLE,” Dr. Werth noted.

The trial allowed background therapy as long as treatment had begun at least 12 weeks before randomization, with a stable dose starting at least 4 weeks before randomization and maintained throughout the trial period.

Most patients had moderate to severe CLE at baseline “despite approximately 90% having received concomitant background therapy and 80% of those participants having received antimalarial drugs, either alone or with other agents,” Dr. Werth and coinvestigators wrote.

CLASI-A has been shown to correlate to patients’ quality of life, Dr. Werth emphasized in the interview.

Most of the reported side effects in the phase 2 CLE trial were mild or moderate. The treatment was associated with three cases of hypersensitivity, three cases of oral herpes infection, and one case of herpes zoster infection. One case of herpes zoster meningitis occurred 4 months after the last dose of litifilimab.

Approximately 10% of study participants who reported race and ethnicity were Black or African American.

Phase 3 trials

The trial was one part of a two-part phase 2 study of litifilimab, named the LILAC trial, sponsored by Biogen. The other part, which will be published separately, involved patients who had SLE with active joint and skin manifestations.

Biogen is currently enrolling patients in phase 3 studies – the TOPAZ-1 and TOPAZ-2 studies – to evaluate the efficacy and safety of the drug in patients with active SLE. As secondary endpoints, both trials will measure the percentage of participants with a CLASI-A score of at least 10 at baseline who achieve improvement in the score, including a 50% improvement from baseline to week 16, Nathalie Franchimont, MD, PhD, of Biogen, a coauthor of the NEJM study, said in an email.

Biogen also has “plans to initiate a pivotal study in CLE this year,” she said.

With respect to the newly published phase 2 study, Dr. Femia said that, while “conclusions about the magnitude of efficacy are difficult to extrapolate in this trial design, there’s reason for cautious optimism.” There is “good theoretical basis to be optimistic about a drug such as litifilimab, that ultimately reduces type 1 interferon response,” she added.

Anifrolumab, a type 1 interferon receptor monoclonal antibody marketed as Saphnelo, was approved by the FDA for SLE in July 2021, but CLE subtypes were not characterized in trials and CLE was not studied independently of SLE, the authors pointed out in their NEJM article.

The study was supported by Biogen. In addition to working with Biogen, Dr. Werth serves as a consultant to Gilead Sciences and other pharmaceutical companies. Dr. Vital has research grants and has received honoraria from AstraZeneca. Dr. Femia disclosed no relevant financial relationships.

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

The White House declared monkeypox a public health emergency Aug. 4. There have been more than 6,600 reported cases of the disease in the United States, up from less than 5,000 cases reported last week.

“This public health emergency will allow us to explore additional strategies to get vaccines and treatments more quickly out in the affected communities. And it will allow us to get more data from jurisdictions so we can effectively track and attack this outbreak,” Robert Fenton, who was named as the national monkeypox response coordinator this week, said at a news briefing Aug. 4.

Those who catch the virus usually have fever-like symptoms, followed by red lesions on the body that can raise and develop pus. Those at highest risk of monkeypox are gay and bisexual men, as well as men who have sex with other men. There are between 1.6 million and 1.7 million Americans in this high-risk group, Health and Human Services Secretary Xavier Becerra said at the briefing.

The Jynneos vaccine is being distributed to protect against monkeypox and can prevent severe symptoms. It’s mostly going to those with the greatest risk of catching the virus.

Last week, the Biden administration made over 1.1 million doses of the Jynneos vaccine available – of which over 600,000 doses have already been distributed across the country – and have secured over 6.9 million Jynneos doses altogether.

Around 786,000 vaccines have already been allocated, and the first doses were shipped this week. States will be able to order more doses beginning Aug. 15. If a state has used 90% or more of its vaccine supply, it will be eligible to order more doses before Aug. 15, according to Dawn O’Connell, JD, assistant secretary for preparedness and response at the U.S. Department of Health and Human Services.

An additional 150,000 doses will be added to the national stockpile in September, with more doses to come later this year, Ms. O’Connell says.

The administration is also stressing the importance of monkeypox testing and says it can now distribute 80,000 monkeypox tests per week.

An antiviral drug – known as TPOXX – is also available to treat severe cases of monkeypox. Around 1,700,000 doses are available in the Strategic National Stockpile, public health officials say.

“We are prepared to take our response to the next level, and we urge every American to take this seriously and to take responsibility to help us tackle this virus,” Secretary Becerra told reporters.

The White House says it will continue reaching out to doctors, public health partners, LGBTQ advocates, and other impacted communities.

“The public health emergency further raises awareness about monkeypox, which will encourage clinicians to test for it,” Rochelle Walensky, MD, director of the Centers for Disease Control and Prevention, said at the briefing.

This week, President Joe Biden appointed a new White House monkeypox response team. Besides Mr. Fenton as the response coordinator, Demetre Daskalakis, MD, will serve as the White House national monkeypox response deputy coordinator. He is the director of the CDC’s Division of HIV Prevention.

“This virus is moving fast. This is a unique outbreak that is spreading faster than previous outbreaks,” Mr. Fenton told reporters Aug. 4. “That’s why the president asked me to explore everything we can do to combat monkeypox and protect communities at risk.”

This article was updated 8/4/22.

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

The White House declared monkeypox a public health emergency Aug. 4. There have been more than 6,600 reported cases of the disease in the United States, up from less than 5,000 cases reported last week.

“This public health emergency will allow us to explore additional strategies to get vaccines and treatments more quickly out in the affected communities. And it will allow us to get more data from jurisdictions so we can effectively track and attack this outbreak,” Robert Fenton, who was named as the national monkeypox response coordinator this week, said at a news briefing Aug. 4.

Those who catch the virus usually have fever-like symptoms, followed by red lesions on the body that can raise and develop pus. Those at highest risk of monkeypox are gay and bisexual men, as well as men who have sex with other men. There are between 1.6 million and 1.7 million Americans in this high-risk group, Health and Human Services Secretary Xavier Becerra said at the briefing.

The Jynneos vaccine is being distributed to protect against monkeypox and can prevent severe symptoms. It’s mostly going to those with the greatest risk of catching the virus.

Last week, the Biden administration made over 1.1 million doses of the Jynneos vaccine available – of which over 600,000 doses have already been distributed across the country – and have secured over 6.9 million Jynneos doses altogether.

Around 786,000 vaccines have already been allocated, and the first doses were shipped this week. States will be able to order more doses beginning Aug. 15. If a state has used 90% or more of its vaccine supply, it will be eligible to order more doses before Aug. 15, according to Dawn O’Connell, JD, assistant secretary for preparedness and response at the U.S. Department of Health and Human Services.

An additional 150,000 doses will be added to the national stockpile in September, with more doses to come later this year, Ms. O’Connell says.

The administration is also stressing the importance of monkeypox testing and says it can now distribute 80,000 monkeypox tests per week.

An antiviral drug – known as TPOXX – is also available to treat severe cases of monkeypox. Around 1,700,000 doses are available in the Strategic National Stockpile, public health officials say.

“We are prepared to take our response to the next level, and we urge every American to take this seriously and to take responsibility to help us tackle this virus,” Secretary Becerra told reporters.

The White House says it will continue reaching out to doctors, public health partners, LGBTQ advocates, and other impacted communities.

“The public health emergency further raises awareness about monkeypox, which will encourage clinicians to test for it,” Rochelle Walensky, MD, director of the Centers for Disease Control and Prevention, said at the briefing.

This week, President Joe Biden appointed a new White House monkeypox response team. Besides Mr. Fenton as the response coordinator, Demetre Daskalakis, MD, will serve as the White House national monkeypox response deputy coordinator. He is the director of the CDC’s Division of HIV Prevention.

“This virus is moving fast. This is a unique outbreak that is spreading faster than previous outbreaks,” Mr. Fenton told reporters Aug. 4. “That’s why the president asked me to explore everything we can do to combat monkeypox and protect communities at risk.”

This article was updated 8/4/22.

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

The White House declared monkeypox a public health emergency Aug. 4. There have been more than 6,600 reported cases of the disease in the United States, up from less than 5,000 cases reported last week.

“This public health emergency will allow us to explore additional strategies to get vaccines and treatments more quickly out in the affected communities. And it will allow us to get more data from jurisdictions so we can effectively track and attack this outbreak,” Robert Fenton, who was named as the national monkeypox response coordinator this week, said at a news briefing Aug. 4.

Those who catch the virus usually have fever-like symptoms, followed by red lesions on the body that can raise and develop pus. Those at highest risk of monkeypox are gay and bisexual men, as well as men who have sex with other men. There are between 1.6 million and 1.7 million Americans in this high-risk group, Health and Human Services Secretary Xavier Becerra said at the briefing.

The Jynneos vaccine is being distributed to protect against monkeypox and can prevent severe symptoms. It’s mostly going to those with the greatest risk of catching the virus.

Last week, the Biden administration made over 1.1 million doses of the Jynneos vaccine available – of which over 600,000 doses have already been distributed across the country – and have secured over 6.9 million Jynneos doses altogether.

Around 786,000 vaccines have already been allocated, and the first doses were shipped this week. States will be able to order more doses beginning Aug. 15. If a state has used 90% or more of its vaccine supply, it will be eligible to order more doses before Aug. 15, according to Dawn O’Connell, JD, assistant secretary for preparedness and response at the U.S. Department of Health and Human Services.

An additional 150,000 doses will be added to the national stockpile in September, with more doses to come later this year, Ms. O’Connell says.

The administration is also stressing the importance of monkeypox testing and says it can now distribute 80,000 monkeypox tests per week.

An antiviral drug – known as TPOXX – is also available to treat severe cases of monkeypox. Around 1,700,000 doses are available in the Strategic National Stockpile, public health officials say.

“We are prepared to take our response to the next level, and we urge every American to take this seriously and to take responsibility to help us tackle this virus,” Secretary Becerra told reporters.

The White House says it will continue reaching out to doctors, public health partners, LGBTQ advocates, and other impacted communities.

“The public health emergency further raises awareness about monkeypox, which will encourage clinicians to test for it,” Rochelle Walensky, MD, director of the Centers for Disease Control and Prevention, said at the briefing.

This week, President Joe Biden appointed a new White House monkeypox response team. Besides Mr. Fenton as the response coordinator, Demetre Daskalakis, MD, will serve as the White House national monkeypox response deputy coordinator. He is the director of the CDC’s Division of HIV Prevention.

“This virus is moving fast. This is a unique outbreak that is spreading faster than previous outbreaks,” Mr. Fenton told reporters Aug. 4. “That’s why the president asked me to explore everything we can do to combat monkeypox and protect communities at risk.”

This article was updated 8/4/22.

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

The major classifications of thyroid disease include hyperthyroidism, which is seen in Graves disease, and hypothyroidism due to iodine deficiency and Hashimoto thyroiditis, which have potentially devastating health consequences. The prevalence of hyperthyroidism ranges from 0.2% to 1.3% in iodine-sufficient parts of the world, and the prevalence of hypothyroidism in the general population is 5.3% in Europe and 3.7% in the United States.¹ Thyroid hormones physiologically potentiate α- and β-adrenergic receptors by increasing their sensitivity to catecholamines. Excess thyroid hormones manifest as tachycardia, increased cardiac output, increased body temperature, hyperhidrosis, and warm moist skin. Reduced sensitivity of adrenergic receptors to catecholamines from insufficient thyroid hormones results in a lower metabolic rate and decreases response to the sympathetic nervous system.² Nail changes in thyroid patients have not been well studied.³ Our objectives were to characterize nail findings in patients with thyroid disease. Early diagnosis of thyroid disease and prompt referral for treatment may be instrumental in preventing serious morbidities and permanent sequelae.

Methods

PubMed, Scopus, Web of Science, and Google Scholar were searched for the terms nail + thyroid, nail + hyperthyroid, nail + hypothyroid, nail + Graves, and nail + Hashimoto on June 10, 2020, and then updated on November 18, 2020. All English-language articles were included. Non–English-language articles and those that did not describe clinical trials of nail changes in patients with thyroid disease were excluded. One study that utilized survey-based data for nail changes without corroboration with physical examination findings was excluded. Hypothyroidism/hyperthyroidism was defined by all authors as measurement of serum thyroid hormones triiodothyronine, thyroxine, and thyroid-stimulating hormone outside of the normal range. Eight studies were included in the final analysis. Patient demographics, thyroid disease type, physical examination findings, nail clinical findings, age at diagnosis, age at onset of nail changes, treatments/medications, and comorbidities were recorded and analyzed.

Results

Nail changes in patients with thyroid disease were reported in 8 studies (7 cross-sectional, 1 retrospective cohort) and are summarized in the Table.^4-11 The mean age was 41.2 years (range, 5–80 years), with a higher representation of females (range, 70%–94% female). The most common nail changes in thyroid patients were koilonychia, clubbing, and nail brittleness. Other changes included onycholysis, thin nails, dryness, and changes in nail growth rate. Frequent physical findings were xerosis, pruritus, and alopecia.

Both koilonychia and clubbing were reported in patients with hyperthyroidism. In a study of 32 patients with koilonychia, 22 (68.8%) were diagnosed with hyperthyroidism.¹⁰ Nail clubbing affected 7.3% of Graves disease patients (n=150)⁶ and 5.0% of hyperthyroid patients (n=120).⁷ Dermopathy presented more than 1 year after diagnosis of Graves disease in 99 (66%) of 150 patients as a late manifestation of thyrotoxicosis.⁶ Additional physical features in patients with Graves disease (n=150) were pretibial myxedema (100%), ophthalmopathy (99.0%), and proptosis (88.0%). Non–Graves hyperthyroid patients showed physical features of soft hair (83.3%) and soft skin (66.0%).⁷

Nail brittleness was a frequently reported nail change in thyroid patients (4/8 studies, 50%), most often seen in 22% of autoimmune patients, 19.6% of nonautoimmune patients, 13.9% of hypothyroid patients, and 9.2% of hyperthyroid patients.^5,8 For comparison, brittle nails presented in 10.8% of participants in a control group.⁵ Brittle nails in thyroid patients often are accompanied by other nail findings such as thinning, onycholysis, and pitting.

Among hypothyroid patients, nail changes included fragility (70%; n=50), slow growth (48%; n=50), thinning (40%; n=50), onycholysis (38%; n=50),⁷ and brittleness (13.9%; n=173).⁵ Less common nail changes in hypothyroid patients were leukonychia (9.4%; n=32), striped nails (6%; n=50), and pitting (1.2%; n=173).^5,7,11 Among hyperthyroid patients, the most common nail changes were koilonychia (100%; n=22), softening (83%; n=120), onycholysis (29%; n=14), and brittleness (9.2%; n=173).^5,7,9,10 Less common nail changes in hyperthyroid patients were clubbing (5%; n=120), thinning (4.6%; n=173), and leukonychia (3%; n=120).^5,7

Additional cutaneous findings of thyroid disorder included xerosis, alopecia, pruritus, and weight change. Xerosis was most common in hypothyroid disease (57.2%; n=460).⁴ In 2 studies,^8,9 alopecia affected approximately 70% of autoimmune, nonautoimmune, and hyperthyroid patients. Hair loss was reported in 42.6% (n=460)⁴ and 33.0% (n=36)⁹ of hypothyroid patients. Additionally, pruritus affected up to 28% (n=32)¹¹ of hypothyroid and 16.0% (n=120)⁷ of hyperthyroid patients and was more common in autoimmune (41%) vs nonautoimmune (32%) thyroid patients.⁸ Weight gain was seen in 72% of hypothyroid patients (n=32),¹¹ and soft hair and skin were reported in 83.3% and 66% of hyperthyroid patients (n=120), respectively.⁷ Flushing was a less common physical finding in thyroid patients (usually affecting <10%); however, it also was reported in 17.1% of autoimmune and 57.1% of hyperthyroid patients from 2 separate studies.^8,9

 

 

Comment

There are limited data describing nail changes with thyroid disease. Singal and Arora³ reported in their clinical review of nail changes in systemic disease that koilonychia, onycholysis, and melanonychia are associated with thyroid disorders. We similarly found that koilonychia and onycholysis are associated with thyroid disorders without an association with melanonychia.

In his clinical review of thyroid hormone action on the skin, Safer¹² described hypothyroid patients having coarse, dull, thin, and brittle nails, whereas in thyrotoxicosis, patients had shiny, soft, and concave nails with onycholysis; however, the author commented that there were limited data on the clinical findings in thyroid disorders. These nail findings are consistent with our results, but onycholysis was more common in hypothyroid patients than in hyperthyroid patients in our review. Fox¹³ reported on 30 cases of onycholysis, stating that it affected patients with hypothyroidism and improved with thyroid treatment. In a clinical review of 8 commonly seen nail abnormalities, Fowler et al¹⁴ reported that hyperthyroidism was associated with nail findings in 5% of cases and may result in onycholysis of the fourth and fifth nails or all nails. They also reported that onychorrhexis may be seen in patients with hypothyroidism, a finding that differed from our results.¹⁴

The mechanism of nail changes in thyroid disease has not been well studied. A protein/amino acid–deficiency state may contribute to the development of koilonychia. Hyperthyroid patients, who have high metabolic activity, may have hypoalbuminemia, leading to koilonychia.¹⁵ Hypothyroidism causes hypothermia from decreased metabolic rate and secondary compensatory vasoconstriction. Vasoconstriction decreases blood flow of nutrients and oxygen to cutaneous structures and may cause slow-growing, brittle nails. In hyperthyroidism, vasodilation alternatively may contribute to the fast-growing nails. Anti–thyroid-stimulating hormone receptor antibodies in Graves disease may increase the synthesis of hyaluronic acid and glycosaminoglycans from fibroblasts, keratinocytes, adipocytes, or endothelial cells in the dermis and may contribute to development of clubbing.¹⁶

Our review is subject to several limitations. We recorded nail findings as they were described in the original studies; however, we could not confirm the accuracy of these descriptions. In addition, some specific nail changes were not described in sufficient detail. In all but 1 study, dermatologists performed the physical examination. In the study by Al-Dabbagh and Al-Abachi,¹⁰ the physical examinations were performed by general medicine physicians, but they selected only for patients with koilonychia and did not assess for other skin findings. Fragile nails and brittle nails were described in hypothyroid and hyperthyroid patients, but these nail changes were not described in detail. There also were studies describing nail changes in thyroid patients; some studies had small numbers of patients, and many did not have a control group.

Conclusion

Nail changes may be early clinical presenting signs of thyroid disorders and may be the clue to prompt diagnosis of thyroid disease. Dermatologists should be mindful that fragile, slow-growing, thin nails and onycholysis are associated with hypothyroidism and that koilonychia, softening, onycholysis, and brittle nail changes may be seen in hyperthyroidism. Our review aimed to describe nail changes associated with thyroid disease to guide dermatologists on diagnosis and promote future research on dermatologic manifestations of thyroid disease. Future research is necessary to explore the association between koilonychia and hyperthyroidism as well as the association of nail changes with thyroid disease duration and severity.

The major classifications of thyroid disease include hyperthyroidism, which is seen in Graves disease, and hypothyroidism due to iodine deficiency and Hashimoto thyroiditis, which have potentially devastating health consequences. The prevalence of hyperthyroidism ranges from 0.2% to 1.3% in iodine-sufficient parts of the world, and the prevalence of hypothyroidism in the general population is 5.3% in Europe and 3.7% in the United States.¹ Thyroid hormones physiologically potentiate α- and β-adrenergic receptors by increasing their sensitivity to catecholamines. Excess thyroid hormones manifest as tachycardia, increased cardiac output, increased body temperature, hyperhidrosis, and warm moist skin. Reduced sensitivity of adrenergic receptors to catecholamines from insufficient thyroid hormones results in a lower metabolic rate and decreases response to the sympathetic nervous system.² Nail changes in thyroid patients have not been well studied.³ Our objectives were to characterize nail findings in patients with thyroid disease. Early diagnosis of thyroid disease and prompt referral for treatment may be instrumental in preventing serious morbidities and permanent sequelae.

Methods

PubMed, Scopus, Web of Science, and Google Scholar were searched for the terms nail + thyroid, nail + hyperthyroid, nail + hypothyroid, nail + Graves, and nail + Hashimoto on June 10, 2020, and then updated on November 18, 2020. All English-language articles were included. Non–English-language articles and those that did not describe clinical trials of nail changes in patients with thyroid disease were excluded. One study that utilized survey-based data for nail changes without corroboration with physical examination findings was excluded. Hypothyroidism/hyperthyroidism was defined by all authors as measurement of serum thyroid hormones triiodothyronine, thyroxine, and thyroid-stimulating hormone outside of the normal range. Eight studies were included in the final analysis. Patient demographics, thyroid disease type, physical examination findings, nail clinical findings, age at diagnosis, age at onset of nail changes, treatments/medications, and comorbidities were recorded and analyzed.

Results

Nail changes in patients with thyroid disease were reported in 8 studies (7 cross-sectional, 1 retrospective cohort) and are summarized in the Table.^4-11 The mean age was 41.2 years (range, 5–80 years), with a higher representation of females (range, 70%–94% female). The most common nail changes in thyroid patients were koilonychia, clubbing, and nail brittleness. Other changes included onycholysis, thin nails, dryness, and changes in nail growth rate. Frequent physical findings were xerosis, pruritus, and alopecia.

Both koilonychia and clubbing were reported in patients with hyperthyroidism. In a study of 32 patients with koilonychia, 22 (68.8%) were diagnosed with hyperthyroidism.¹⁰ Nail clubbing affected 7.3% of Graves disease patients (n=150)⁶ and 5.0% of hyperthyroid patients (n=120).⁷ Dermopathy presented more than 1 year after diagnosis of Graves disease in 99 (66%) of 150 patients as a late manifestation of thyrotoxicosis.⁶ Additional physical features in patients with Graves disease (n=150) were pretibial myxedema (100%), ophthalmopathy (99.0%), and proptosis (88.0%). Non–Graves hyperthyroid patients showed physical features of soft hair (83.3%) and soft skin (66.0%).⁷

Nail brittleness was a frequently reported nail change in thyroid patients (4/8 studies, 50%), most often seen in 22% of autoimmune patients, 19.6% of nonautoimmune patients, 13.9% of hypothyroid patients, and 9.2% of hyperthyroid patients.^5,8 For comparison, brittle nails presented in 10.8% of participants in a control group.⁵ Brittle nails in thyroid patients often are accompanied by other nail findings such as thinning, onycholysis, and pitting.

Among hypothyroid patients, nail changes included fragility (70%; n=50), slow growth (48%; n=50), thinning (40%; n=50), onycholysis (38%; n=50),⁷ and brittleness (13.9%; n=173).⁵ Less common nail changes in hypothyroid patients were leukonychia (9.4%; n=32), striped nails (6%; n=50), and pitting (1.2%; n=173).^5,7,11 Among hyperthyroid patients, the most common nail changes were koilonychia (100%; n=22), softening (83%; n=120), onycholysis (29%; n=14), and brittleness (9.2%; n=173).^5,7,9,10 Less common nail changes in hyperthyroid patients were clubbing (5%; n=120), thinning (4.6%; n=173), and leukonychia (3%; n=120).^5,7

Additional cutaneous findings of thyroid disorder included xerosis, alopecia, pruritus, and weight change. Xerosis was most common in hypothyroid disease (57.2%; n=460).⁴ In 2 studies,^8,9 alopecia affected approximately 70% of autoimmune, nonautoimmune, and hyperthyroid patients. Hair loss was reported in 42.6% (n=460)⁴ and 33.0% (n=36)⁹ of hypothyroid patients. Additionally, pruritus affected up to 28% (n=32)¹¹ of hypothyroid and 16.0% (n=120)⁷ of hyperthyroid patients and was more common in autoimmune (41%) vs nonautoimmune (32%) thyroid patients.⁸ Weight gain was seen in 72% of hypothyroid patients (n=32),¹¹ and soft hair and skin were reported in 83.3% and 66% of hyperthyroid patients (n=120), respectively.⁷ Flushing was a less common physical finding in thyroid patients (usually affecting <10%); however, it also was reported in 17.1% of autoimmune and 57.1% of hyperthyroid patients from 2 separate studies.^8,9

 

 

Comment

There are limited data describing nail changes with thyroid disease. Singal and Arora³ reported in their clinical review of nail changes in systemic disease that koilonychia, onycholysis, and melanonychia are associated with thyroid disorders. We similarly found that koilonychia and onycholysis are associated with thyroid disorders without an association with melanonychia.

In his clinical review of thyroid hormone action on the skin, Safer¹² described hypothyroid patients having coarse, dull, thin, and brittle nails, whereas in thyrotoxicosis, patients had shiny, soft, and concave nails with onycholysis; however, the author commented that there were limited data on the clinical findings in thyroid disorders. These nail findings are consistent with our results, but onycholysis was more common in hypothyroid patients than in hyperthyroid patients in our review. Fox¹³ reported on 30 cases of onycholysis, stating that it affected patients with hypothyroidism and improved with thyroid treatment. In a clinical review of 8 commonly seen nail abnormalities, Fowler et al¹⁴ reported that hyperthyroidism was associated with nail findings in 5% of cases and may result in onycholysis of the fourth and fifth nails or all nails. They also reported that onychorrhexis may be seen in patients with hypothyroidism, a finding that differed from our results.¹⁴

The mechanism of nail changes in thyroid disease has not been well studied. A protein/amino acid–deficiency state may contribute to the development of koilonychia. Hyperthyroid patients, who have high metabolic activity, may have hypoalbuminemia, leading to koilonychia.¹⁵ Hypothyroidism causes hypothermia from decreased metabolic rate and secondary compensatory vasoconstriction. Vasoconstriction decreases blood flow of nutrients and oxygen to cutaneous structures and may cause slow-growing, brittle nails. In hyperthyroidism, vasodilation alternatively may contribute to the fast-growing nails. Anti–thyroid-stimulating hormone receptor antibodies in Graves disease may increase the synthesis of hyaluronic acid and glycosaminoglycans from fibroblasts, keratinocytes, adipocytes, or endothelial cells in the dermis and may contribute to development of clubbing.¹⁶

Our review is subject to several limitations. We recorded nail findings as they were described in the original studies; however, we could not confirm the accuracy of these descriptions. In addition, some specific nail changes were not described in sufficient detail. In all but 1 study, dermatologists performed the physical examination. In the study by Al-Dabbagh and Al-Abachi,¹⁰ the physical examinations were performed by general medicine physicians, but they selected only for patients with koilonychia and did not assess for other skin findings. Fragile nails and brittle nails were described in hypothyroid and hyperthyroid patients, but these nail changes were not described in detail. There also were studies describing nail changes in thyroid patients; some studies had small numbers of patients, and many did not have a control group.

Conclusion

Nail changes may be early clinical presenting signs of thyroid disorders and may be the clue to prompt diagnosis of thyroid disease. Dermatologists should be mindful that fragile, slow-growing, thin nails and onycholysis are associated with hypothyroidism and that koilonychia, softening, onycholysis, and brittle nail changes may be seen in hyperthyroidism. Our review aimed to describe nail changes associated with thyroid disease to guide dermatologists on diagnosis and promote future research on dermatologic manifestations of thyroid disease. Future research is necessary to explore the association between koilonychia and hyperthyroidism as well as the association of nail changes with thyroid disease duration and severity.

The major classifications of thyroid disease include hyperthyroidism, which is seen in Graves disease, and hypothyroidism due to iodine deficiency and Hashimoto thyroiditis, which have potentially devastating health consequences. The prevalence of hyperthyroidism ranges from 0.2% to 1.3% in iodine-sufficient parts of the world, and the prevalence of hypothyroidism in the general population is 5.3% in Europe and 3.7% in the United States.¹ Thyroid hormones physiologically potentiate α- and β-adrenergic receptors by increasing their sensitivity to catecholamines. Excess thyroid hormones manifest as tachycardia, increased cardiac output, increased body temperature, hyperhidrosis, and warm moist skin. Reduced sensitivity of adrenergic receptors to catecholamines from insufficient thyroid hormones results in a lower metabolic rate and decreases response to the sympathetic nervous system.² Nail changes in thyroid patients have not been well studied.³ Our objectives were to characterize nail findings in patients with thyroid disease. Early diagnosis of thyroid disease and prompt referral for treatment may be instrumental in preventing serious morbidities and permanent sequelae.

Methods

PubMed, Scopus, Web of Science, and Google Scholar were searched for the terms nail + thyroid, nail + hyperthyroid, nail + hypothyroid, nail + Graves, and nail + Hashimoto on June 10, 2020, and then updated on November 18, 2020. All English-language articles were included. Non–English-language articles and those that did not describe clinical trials of nail changes in patients with thyroid disease were excluded. One study that utilized survey-based data for nail changes without corroboration with physical examination findings was excluded. Hypothyroidism/hyperthyroidism was defined by all authors as measurement of serum thyroid hormones triiodothyronine, thyroxine, and thyroid-stimulating hormone outside of the normal range. Eight studies were included in the final analysis. Patient demographics, thyroid disease type, physical examination findings, nail clinical findings, age at diagnosis, age at onset of nail changes, treatments/medications, and comorbidities were recorded and analyzed.

Results

Nail changes in patients with thyroid disease were reported in 8 studies (7 cross-sectional, 1 retrospective cohort) and are summarized in the Table.^4-11 The mean age was 41.2 years (range, 5–80 years), with a higher representation of females (range, 70%–94% female). The most common nail changes in thyroid patients were koilonychia, clubbing, and nail brittleness. Other changes included onycholysis, thin nails, dryness, and changes in nail growth rate. Frequent physical findings were xerosis, pruritus, and alopecia.

Both koilonychia and clubbing were reported in patients with hyperthyroidism. In a study of 32 patients with koilonychia, 22 (68.8%) were diagnosed with hyperthyroidism.¹⁰ Nail clubbing affected 7.3% of Graves disease patients (n=150)⁶ and 5.0% of hyperthyroid patients (n=120).⁷ Dermopathy presented more than 1 year after diagnosis of Graves disease in 99 (66%) of 150 patients as a late manifestation of thyrotoxicosis.⁶ Additional physical features in patients with Graves disease (n=150) were pretibial myxedema (100%), ophthalmopathy (99.0%), and proptosis (88.0%). Non–Graves hyperthyroid patients showed physical features of soft hair (83.3%) and soft skin (66.0%).⁷

Nail brittleness was a frequently reported nail change in thyroid patients (4/8 studies, 50%), most often seen in 22% of autoimmune patients, 19.6% of nonautoimmune patients, 13.9% of hypothyroid patients, and 9.2% of hyperthyroid patients.^5,8 For comparison, brittle nails presented in 10.8% of participants in a control group.⁵ Brittle nails in thyroid patients often are accompanied by other nail findings such as thinning, onycholysis, and pitting.

Among hypothyroid patients, nail changes included fragility (70%; n=50), slow growth (48%; n=50), thinning (40%; n=50), onycholysis (38%; n=50),⁷ and brittleness (13.9%; n=173).⁵ Less common nail changes in hypothyroid patients were leukonychia (9.4%; n=32), striped nails (6%; n=50), and pitting (1.2%; n=173).^5,7,11 Among hyperthyroid patients, the most common nail changes were koilonychia (100%; n=22), softening (83%; n=120), onycholysis (29%; n=14), and brittleness (9.2%; n=173).^5,7,9,10 Less common nail changes in hyperthyroid patients were clubbing (5%; n=120), thinning (4.6%; n=173), and leukonychia (3%; n=120).^5,7

Additional cutaneous findings of thyroid disorder included xerosis, alopecia, pruritus, and weight change. Xerosis was most common in hypothyroid disease (57.2%; n=460).⁴ In 2 studies,^8,9 alopecia affected approximately 70% of autoimmune, nonautoimmune, and hyperthyroid patients. Hair loss was reported in 42.6% (n=460)⁴ and 33.0% (n=36)⁹ of hypothyroid patients. Additionally, pruritus affected up to 28% (n=32)¹¹ of hypothyroid and 16.0% (n=120)⁷ of hyperthyroid patients and was more common in autoimmune (41%) vs nonautoimmune (32%) thyroid patients.⁸ Weight gain was seen in 72% of hypothyroid patients (n=32),¹¹ and soft hair and skin were reported in 83.3% and 66% of hyperthyroid patients (n=120), respectively.⁷ Flushing was a less common physical finding in thyroid patients (usually affecting <10%); however, it also was reported in 17.1% of autoimmune and 57.1% of hyperthyroid patients from 2 separate studies.^8,9

 

 

Comment

There are limited data describing nail changes with thyroid disease. Singal and Arora³ reported in their clinical review of nail changes in systemic disease that koilonychia, onycholysis, and melanonychia are associated with thyroid disorders. We similarly found that koilonychia and onycholysis are associated with thyroid disorders without an association with melanonychia.

In his clinical review of thyroid hormone action on the skin, Safer¹² described hypothyroid patients having coarse, dull, thin, and brittle nails, whereas in thyrotoxicosis, patients had shiny, soft, and concave nails with onycholysis; however, the author commented that there were limited data on the clinical findings in thyroid disorders. These nail findings are consistent with our results, but onycholysis was more common in hypothyroid patients than in hyperthyroid patients in our review. Fox¹³ reported on 30 cases of onycholysis, stating that it affected patients with hypothyroidism and improved with thyroid treatment. In a clinical review of 8 commonly seen nail abnormalities, Fowler et al¹⁴ reported that hyperthyroidism was associated with nail findings in 5% of cases and may result in onycholysis of the fourth and fifth nails or all nails. They also reported that onychorrhexis may be seen in patients with hypothyroidism, a finding that differed from our results.¹⁴

The mechanism of nail changes in thyroid disease has not been well studied. A protein/amino acid–deficiency state may contribute to the development of koilonychia. Hyperthyroid patients, who have high metabolic activity, may have hypoalbuminemia, leading to koilonychia.¹⁵ Hypothyroidism causes hypothermia from decreased metabolic rate and secondary compensatory vasoconstriction. Vasoconstriction decreases blood flow of nutrients and oxygen to cutaneous structures and may cause slow-growing, brittle nails. In hyperthyroidism, vasodilation alternatively may contribute to the fast-growing nails. Anti–thyroid-stimulating hormone receptor antibodies in Graves disease may increase the synthesis of hyaluronic acid and glycosaminoglycans from fibroblasts, keratinocytes, adipocytes, or endothelial cells in the dermis and may contribute to development of clubbing.¹⁶

Our review is subject to several limitations. We recorded nail findings as they were described in the original studies; however, we could not confirm the accuracy of these descriptions. In addition, some specific nail changes were not described in sufficient detail. In all but 1 study, dermatologists performed the physical examination. In the study by Al-Dabbagh and Al-Abachi,¹⁰ the physical examinations were performed by general medicine physicians, but they selected only for patients with koilonychia and did not assess for other skin findings. Fragile nails and brittle nails were described in hypothyroid and hyperthyroid patients, but these nail changes were not described in detail. There also were studies describing nail changes in thyroid patients; some studies had small numbers of patients, and many did not have a control group.

Conclusion

Nail changes may be early clinical presenting signs of thyroid disorders and may be the clue to prompt diagnosis of thyroid disease. Dermatologists should be mindful that fragile, slow-growing, thin nails and onycholysis are associated with hypothyroidism and that koilonychia, softening, onycholysis, and brittle nail changes may be seen in hyperthyroidism. Our review aimed to describe nail changes associated with thyroid disease to guide dermatologists on diagnosis and promote future research on dermatologic manifestations of thyroid disease. Future research is necessary to explore the association between koilonychia and hyperthyroidism as well as the association of nail changes with thyroid disease duration and severity.

The Cutis Editorial Board is now accepting applications for the 2023 Resident Corner column. The Editorial Board will select 2 to 3 residents to serve as the Resident Corner columnists for 1 year. Articles are posted online only at www.mdedge.com/dermatology but will be referenced in Index Medicus. All applicants must be current residents and will be in residency throughout 2023.

For consideration, send your curriculum vitae along with a brief (not to exceed 500 words) statement of why you enjoy Cutis and what you can offer your fellow residents in contributing a monthly column.

A signed letter of recommendation from the Director of the dermatology residency program also should be supplied.

All materials should be submitted via email to Melissa Sears ([email protected]) by October 28. The residents who are selected to write the column for the upcoming year will be notified by November 4.

We look forward to continuing to educate dermatology residents on topics that are most important to them!

The Cutis Editorial Board is now accepting applications for the 2023 Resident Corner column. The Editorial Board will select 2 to 3 residents to serve as the Resident Corner columnists for 1 year. Articles are posted online only at www.mdedge.com/dermatology but will be referenced in Index Medicus. All applicants must be current residents and will be in residency throughout 2023.

For consideration, send your curriculum vitae along with a brief (not to exceed 500 words) statement of why you enjoy Cutis and what you can offer your fellow residents in contributing a monthly column.

A signed letter of recommendation from the Director of the dermatology residency program also should be supplied.

All materials should be submitted via email to Melissa Sears ([email protected]) by October 28. The residents who are selected to write the column for the upcoming year will be notified by November 4.

We look forward to continuing to educate dermatology residents on topics that are most important to them!

The Cutis Editorial Board is now accepting applications for the 2023 Resident Corner column. The Editorial Board will select 2 to 3 residents to serve as the Resident Corner columnists for 1 year. Articles are posted online only at www.mdedge.com/dermatology but will be referenced in Index Medicus. All applicants must be current residents and will be in residency throughout 2023.

For consideration, send your curriculum vitae along with a brief (not to exceed 500 words) statement of why you enjoy Cutis and what you can offer your fellow residents in contributing a monthly column.

A signed letter of recommendation from the Director of the dermatology residency program also should be supplied.

All materials should be submitted via email to Melissa Sears ([email protected]) by October 28. The residents who are selected to write the column for the upcoming year will be notified by November 4.

We look forward to continuing to educate dermatology residents on topics that are most important to them!

Finding a fiber of good moral fiber

If you’ve ever wandered into the supplement aisle at your local grocery store, you’ve probably noticed an overabundance of fiber supplements that claim to do this for you and benefit that. Since there’s no Food and Drug Administration regulation on fiber supplements, manufacturers are free to (and do) make whatever wild claims they like. And much like choosing which of 500 shows to watch on Netflix, when you’re spoiled for choice, it can be difficult to pick.

Duke University Photo

Enter a team of molecular geneticists and microbiologists from Duke University. They can’t tell you what show to watch next, but they can tell you which fiber to choose, thanks to their new study. And the answer? Yes.

Well that’s not very helpful, but let us explain. For their study, a group of 28 received three of the main fiber supplements (inulin, dextrin, and galactooligosaccharides) for a week each, followed by a week off of fibers for their gut to return to baseline until they’d received all three. Those who consumed the least fiber at baseline saw the greatest benefit from fiber supplementation, with no appreciable difference between the three types. It was the same story for study participants who already consumed enough fiber; because their guts already hosted a more-optimal microbiome, the type of supplement didn’t matter. The benefits were the same across the board.

In an additional study, the Duke researchers found that gut microbiomes reacted to new fiber within a day, being primed to consume fiber on the first dose and digesting it more quickly on the second fiber dose.

The results, the researchers pointed out, make sense, since the average American only consumes 20%-40% of their daily recommended supply of fiber. Our digestive systems aren’t picky; they just want more, so go out there and choose whatever fiber you’d like. Do that, and then feel free to eat as many double bacon cheeseburgers as you’d like. That is the pinnacle of diet right there. Dietitians literally could not complain about it.
 

Jarlsberg vs. Camembert: This time it’s skeletal

Fiber is fabulous, of course, but the road to dietary health and wellness fulfillment takes us to many other, equally wondrous places. Hey, look! This next exit is covered with cheese.

PxHere

All the cheeses are here, from Abbaye de Belloc to Zwitser, and there, right between the jalapeno cheddar and the Jermi tortes you’ll find Jarlsberg, a mild, semisoft, nutty-flavored cheese that comes from Jarlsberg in eastern Norway. A recent study also suggests that Jarlsberg may help to prevent osteopenia and osteoporosis.

A group of Norwegian investigators gathered together 66 healthy women and gave them a daily portion of either Jarlsberg or Camembert for 6 weeks, at which point the Camembert group was switched to Jarlsberg for another 6 weeks.

The research team choose Camembert because of its similarity to Jarlsberg in fat and protein content. Jarlsberg, however, also is rich in vitamin K_{2, which is important for bone health,} and a substance known as DHNA, which “might combat bone thinning and increase bone tissue formation,” they said in a Eurekalert release.

After the first 6 weeks, blood levels of osteocalcin; vitamin K_{2; and} PINP, a peptide involved in bone turnover, were significantly higher in the Jarlsberg group only. All those measures rose significantly after the switch from Camembert to Jarlsberg, while levels of total and LDL cholesterol “fell significantly in the Camembert group after they switched to Jarlsberg,” the team added.

But wait! There’s more! HbA1c fell significantly among those initially eating the Jarlsberg but rose sharply in those eating Camembert. Do you see where this is going? After the Camembert group made the switch to Jarlsberg, their HbA1c levels fell significantly as well.

So it’s not just a cheese thing: The effects are specific to Jarlsberg. Can you guess what we’re having for lunch? Double bacon and fiber Jarlsbergers. Mmm, Jarlsburgers.
 

Luck be a lady: The mother of twins

It’s widely believed that women who have twins must be more fertile, giving birth to more than one child at a time. Some studies have supported the idea, but more recent work is refuting that claim. In actuality, it might just be more statistics and luck than fertility after all.

Michael Blackburn/istockphoto

Those earlier studies supporting fertility didn’t specify whether the chances of twin births were based on the ability to produce more than one egg at a time or on the number of births that women had overall. Looking at 100,000 preindustrial European births, before contraception was available, researchers from Norway, Germany, France, and the United Kingdom found that the number of total births, twins included, makes all the difference.

“When a woman gives birth several times, the chances increase that at least one of these births will be a twin birth,” investigator Gine Roll Skjærvø of the Norwegian University of Science and Technology said in a written statement.

Since twins occur in 1%-3% of all births, the more births that a woman has, the better her chances of giving birth to twins. The researchers compared it to playing the lottery. You buy enough tickets, eventually your numbers are going to come up. Despite that, however, they found that women who give birth to twins give birth less often than those who don’t have twins. Which raises the idea of sheer luck.

The researchers said that there’s still a lot to uncover in twin births, noting that “uncritically comparing groups of women with and without twins can trick us into believing the opposite of what is really true. These groupings may either hide the effects of twinning and fertility genes where they exist, or vice versa, create the illusion of these if they do not exist.”

For now, this new research claims that it’s basically a lottery. And women who give birth to twins hit the jackpot.
 

Those with low wages may be earning future memory loss

Not only are low wages detrimental to our souls, hopes, and dreams, but a new study shows that low wages also are linked to quicker memory decline later in life. Sustained low wages not only cause stress and food insecurity in the lives of many, but they also can cause diseases such as depression, obesity, and high blood pressure, which are risk factors for cognitive aging.

Nicola Barts/Pexels

The study was conducted using records from the Health and Retirement Study for the years 1992-2016 and focused on 2,879 adults born between 1936 and 1941. The participants were divided into three groups: those who never earned low wages, those who sometimes did, and those who always did.

The investigators found that workers who earned sustained low wages – defined as an hourly wage lower than two-thirds of the federal median wage for the corresponding year – “experienced significantly faster memory decline in older age” than did those who never earned low wages.

There are signs of inflation everywhere we look these days, but many people are not earning higher wages to compensate for the extra expenses. “Increasing the federal minimum wage, for example to $15 per hour, remains a gridlock issue in Congress,” lead author Katrina Kezios of the Columbia University Mailman School of Public Health, said in a statement released by the university.

If only salaries would rise instead of prices for once.

Finding a fiber of good moral fiber

If you’ve ever wandered into the supplement aisle at your local grocery store, you’ve probably noticed an overabundance of fiber supplements that claim to do this for you and benefit that. Since there’s no Food and Drug Administration regulation on fiber supplements, manufacturers are free to (and do) make whatever wild claims they like. And much like choosing which of 500 shows to watch on Netflix, when you’re spoiled for choice, it can be difficult to pick.

Duke University Photo

Enter a team of molecular geneticists and microbiologists from Duke University. They can’t tell you what show to watch next, but they can tell you which fiber to choose, thanks to their new study. And the answer? Yes.

Well that’s not very helpful, but let us explain. For their study, a group of 28 received three of the main fiber supplements (inulin, dextrin, and galactooligosaccharides) for a week each, followed by a week off of fibers for their gut to return to baseline until they’d received all three. Those who consumed the least fiber at baseline saw the greatest benefit from fiber supplementation, with no appreciable difference between the three types. It was the same story for study participants who already consumed enough fiber; because their guts already hosted a more-optimal microbiome, the type of supplement didn’t matter. The benefits were the same across the board.

In an additional study, the Duke researchers found that gut microbiomes reacted to new fiber within a day, being primed to consume fiber on the first dose and digesting it more quickly on the second fiber dose.

The results, the researchers pointed out, make sense, since the average American only consumes 20%-40% of their daily recommended supply of fiber. Our digestive systems aren’t picky; they just want more, so go out there and choose whatever fiber you’d like. Do that, and then feel free to eat as many double bacon cheeseburgers as you’d like. That is the pinnacle of diet right there. Dietitians literally could not complain about it.
 

Jarlsberg vs. Camembert: This time it’s skeletal

Fiber is fabulous, of course, but the road to dietary health and wellness fulfillment takes us to many other, equally wondrous places. Hey, look! This next exit is covered with cheese.

PxHere

All the cheeses are here, from Abbaye de Belloc to Zwitser, and there, right between the jalapeno cheddar and the Jermi tortes you’ll find Jarlsberg, a mild, semisoft, nutty-flavored cheese that comes from Jarlsberg in eastern Norway. A recent study also suggests that Jarlsberg may help to prevent osteopenia and osteoporosis.

A group of Norwegian investigators gathered together 66 healthy women and gave them a daily portion of either Jarlsberg or Camembert for 6 weeks, at which point the Camembert group was switched to Jarlsberg for another 6 weeks.

The research team choose Camembert because of its similarity to Jarlsberg in fat and protein content. Jarlsberg, however, also is rich in vitamin K_{2, which is important for bone health,} and a substance known as DHNA, which “might combat bone thinning and increase bone tissue formation,” they said in a Eurekalert release.

After the first 6 weeks, blood levels of osteocalcin; vitamin K_{2; and} PINP, a peptide involved in bone turnover, were significantly higher in the Jarlsberg group only. All those measures rose significantly after the switch from Camembert to Jarlsberg, while levels of total and LDL cholesterol “fell significantly in the Camembert group after they switched to Jarlsberg,” the team added.

But wait! There’s more! HbA1c fell significantly among those initially eating the Jarlsberg but rose sharply in those eating Camembert. Do you see where this is going? After the Camembert group made the switch to Jarlsberg, their HbA1c levels fell significantly as well.

So it’s not just a cheese thing: The effects are specific to Jarlsberg. Can you guess what we’re having for lunch? Double bacon and fiber Jarlsbergers. Mmm, Jarlsburgers.
 

Luck be a lady: The mother of twins

It’s widely believed that women who have twins must be more fertile, giving birth to more than one child at a time. Some studies have supported the idea, but more recent work is refuting that claim. In actuality, it might just be more statistics and luck than fertility after all.

Michael Blackburn/istockphoto

Those earlier studies supporting fertility didn’t specify whether the chances of twin births were based on the ability to produce more than one egg at a time or on the number of births that women had overall. Looking at 100,000 preindustrial European births, before contraception was available, researchers from Norway, Germany, France, and the United Kingdom found that the number of total births, twins included, makes all the difference.

“When a woman gives birth several times, the chances increase that at least one of these births will be a twin birth,” investigator Gine Roll Skjærvø of the Norwegian University of Science and Technology said in a written statement.

Since twins occur in 1%-3% of all births, the more births that a woman has, the better her chances of giving birth to twins. The researchers compared it to playing the lottery. You buy enough tickets, eventually your numbers are going to come up. Despite that, however, they found that women who give birth to twins give birth less often than those who don’t have twins. Which raises the idea of sheer luck.

The researchers said that there’s still a lot to uncover in twin births, noting that “uncritically comparing groups of women with and without twins can trick us into believing the opposite of what is really true. These groupings may either hide the effects of twinning and fertility genes where they exist, or vice versa, create the illusion of these if they do not exist.”

For now, this new research claims that it’s basically a lottery. And women who give birth to twins hit the jackpot.
 

Those with low wages may be earning future memory loss

Not only are low wages detrimental to our souls, hopes, and dreams, but a new study shows that low wages also are linked to quicker memory decline later in life. Sustained low wages not only cause stress and food insecurity in the lives of many, but they also can cause diseases such as depression, obesity, and high blood pressure, which are risk factors for cognitive aging.

Nicola Barts/Pexels

The study was conducted using records from the Health and Retirement Study for the years 1992-2016 and focused on 2,879 adults born between 1936 and 1941. The participants were divided into three groups: those who never earned low wages, those who sometimes did, and those who always did.

The investigators found that workers who earned sustained low wages – defined as an hourly wage lower than two-thirds of the federal median wage for the corresponding year – “experienced significantly faster memory decline in older age” than did those who never earned low wages.

There are signs of inflation everywhere we look these days, but many people are not earning higher wages to compensate for the extra expenses. “Increasing the federal minimum wage, for example to $15 per hour, remains a gridlock issue in Congress,” lead author Katrina Kezios of the Columbia University Mailman School of Public Health, said in a statement released by the university.

If only salaries would rise instead of prices for once.

Finding a fiber of good moral fiber

If you’ve ever wandered into the supplement aisle at your local grocery store, you’ve probably noticed an overabundance of fiber supplements that claim to do this for you and benefit that. Since there’s no Food and Drug Administration regulation on fiber supplements, manufacturers are free to (and do) make whatever wild claims they like. And much like choosing which of 500 shows to watch on Netflix, when you’re spoiled for choice, it can be difficult to pick.

Duke University Photo

Enter a team of molecular geneticists and microbiologists from Duke University. They can’t tell you what show to watch next, but they can tell you which fiber to choose, thanks to their new study. And the answer? Yes.

Well that’s not very helpful, but let us explain. For their study, a group of 28 received three of the main fiber supplements (inulin, dextrin, and galactooligosaccharides) for a week each, followed by a week off of fibers for their gut to return to baseline until they’d received all three. Those who consumed the least fiber at baseline saw the greatest benefit from fiber supplementation, with no appreciable difference between the three types. It was the same story for study participants who already consumed enough fiber; because their guts already hosted a more-optimal microbiome, the type of supplement didn’t matter. The benefits were the same across the board.

In an additional study, the Duke researchers found that gut microbiomes reacted to new fiber within a day, being primed to consume fiber on the first dose and digesting it more quickly on the second fiber dose.

The results, the researchers pointed out, make sense, since the average American only consumes 20%-40% of their daily recommended supply of fiber. Our digestive systems aren’t picky; they just want more, so go out there and choose whatever fiber you’d like. Do that, and then feel free to eat as many double bacon cheeseburgers as you’d like. That is the pinnacle of diet right there. Dietitians literally could not complain about it.
 

Jarlsberg vs. Camembert: This time it’s skeletal

Fiber is fabulous, of course, but the road to dietary health and wellness fulfillment takes us to many other, equally wondrous places. Hey, look! This next exit is covered with cheese.

PxHere

All the cheeses are here, from Abbaye de Belloc to Zwitser, and there, right between the jalapeno cheddar and the Jermi tortes you’ll find Jarlsberg, a mild, semisoft, nutty-flavored cheese that comes from Jarlsberg in eastern Norway. A recent study also suggests that Jarlsberg may help to prevent osteopenia and osteoporosis.

A group of Norwegian investigators gathered together 66 healthy women and gave them a daily portion of either Jarlsberg or Camembert for 6 weeks, at which point the Camembert group was switched to Jarlsberg for another 6 weeks.

The research team choose Camembert because of its similarity to Jarlsberg in fat and protein content. Jarlsberg, however, also is rich in vitamin K_{2, which is important for bone health,} and a substance known as DHNA, which “might combat bone thinning and increase bone tissue formation,” they said in a Eurekalert release.

After the first 6 weeks, blood levels of osteocalcin; vitamin K_{2; and} PINP, a peptide involved in bone turnover, were significantly higher in the Jarlsberg group only. All those measures rose significantly after the switch from Camembert to Jarlsberg, while levels of total and LDL cholesterol “fell significantly in the Camembert group after they switched to Jarlsberg,” the team added.

But wait! There’s more! HbA1c fell significantly among those initially eating the Jarlsberg but rose sharply in those eating Camembert. Do you see where this is going? After the Camembert group made the switch to Jarlsberg, their HbA1c levels fell significantly as well.

So it’s not just a cheese thing: The effects are specific to Jarlsberg. Can you guess what we’re having for lunch? Double bacon and fiber Jarlsbergers. Mmm, Jarlsburgers.
 

Luck be a lady: The mother of twins

It’s widely believed that women who have twins must be more fertile, giving birth to more than one child at a time. Some studies have supported the idea, but more recent work is refuting that claim. In actuality, it might just be more statistics and luck than fertility after all.

Michael Blackburn/istockphoto

Those earlier studies supporting fertility didn’t specify whether the chances of twin births were based on the ability to produce more than one egg at a time or on the number of births that women had overall. Looking at 100,000 preindustrial European births, before contraception was available, researchers from Norway, Germany, France, and the United Kingdom found that the number of total births, twins included, makes all the difference.

“When a woman gives birth several times, the chances increase that at least one of these births will be a twin birth,” investigator Gine Roll Skjærvø of the Norwegian University of Science and Technology said in a written statement.

Since twins occur in 1%-3% of all births, the more births that a woman has, the better her chances of giving birth to twins. The researchers compared it to playing the lottery. You buy enough tickets, eventually your numbers are going to come up. Despite that, however, they found that women who give birth to twins give birth less often than those who don’t have twins. Which raises the idea of sheer luck.

The researchers said that there’s still a lot to uncover in twin births, noting that “uncritically comparing groups of women with and without twins can trick us into believing the opposite of what is really true. These groupings may either hide the effects of twinning and fertility genes where they exist, or vice versa, create the illusion of these if they do not exist.”

For now, this new research claims that it’s basically a lottery. And women who give birth to twins hit the jackpot.
 

Those with low wages may be earning future memory loss

Not only are low wages detrimental to our souls, hopes, and dreams, but a new study shows that low wages also are linked to quicker memory decline later in life. Sustained low wages not only cause stress and food insecurity in the lives of many, but they also can cause diseases such as depression, obesity, and high blood pressure, which are risk factors for cognitive aging.

Nicola Barts/Pexels

The study was conducted using records from the Health and Retirement Study for the years 1992-2016 and focused on 2,879 adults born between 1936 and 1941. The participants were divided into three groups: those who never earned low wages, those who sometimes did, and those who always did.

The investigators found that workers who earned sustained low wages – defined as an hourly wage lower than two-thirds of the federal median wage for the corresponding year – “experienced significantly faster memory decline in older age” than did those who never earned low wages.

There are signs of inflation everywhere we look these days, but many people are not earning higher wages to compensate for the extra expenses. “Increasing the federal minimum wage, for example to $15 per hour, remains a gridlock issue in Congress,” lead author Katrina Kezios of the Columbia University Mailman School of Public Health, said in a statement released by the university.

If only salaries would rise instead of prices for once.

Community service (CS) or service learning in dermatology (eg, free skin cancer screenings, providing care through free clinics, free teledermatology consultations) is instrumental in mitigating disparities and improving access to equitable dermatologic care. With the rate of underinsured and uninsured patients on the rise, free and federally qualified clinics frequently are the sole means by which patients access specialty care such as dermatology.¹ Contributing to the economic gap in access, the geographic disparity of dermatologists in the United States continues to climb, and many marginalized communities remain without dermatologists.² Nearly 30% of the total US population resides in geographic areas that are underserved by dermatologists, while there appears to be an oversupply of dermatologists in urban areas.³ Dermatologists practicing in rural areas make up only 10% of the dermatology workforce,⁴ whereas 40% of all dermatologists practice in the most densely populated US cities.⁵ Consequently, patients in these underserved communities face longer wait times⁶ and are less likely to utilize dermatology services than patients in dermatologist-dense geographic areas.⁷

Service opportunities have become increasingly integrated into graduate medical education.⁸ These service activities help bridge the health care access gap while fulfilling Accreditation Council of Graduate Medical Education (ACGME) requirements. Our study assessed the importance of CS to dermatology residency program directors (PDs), dermatology residents, and recent dermatology residency graduates. Herein, we describe the perceptions of CS within dermatology residency training among PDs and residents.

Methods

In this study, CS is defined as participation in activities to increase dermatologic access, education, and resources to underserved communities. Using the approved Association of Professors of Dermatology listserve and direct email communication, we surveyed 142 PDs of ACGME-accredited dermatology residency training programs. The deidentified respondents voluntarily completed a 17-question Qualtrics survey with a 5-point Likert scale (extremely, very, moderately, slightly, or not at all), yes/no/undecided, and qualitative responses.

We also surveyed current dermatology residents and recent graduates of ACGME-accredited dermatology residency programs via PDs nationwide. The deidentified respondents voluntarily completed a 19-question Qualtrics survey with a 5-point Likert scale (extremely, very, moderately, slightly, or not at all), yes/no/undecided, and qualitative responses.

Descriptive statistics were used for data analysis for both Qualtrics surveys. The University of Pittsburgh institutional review board deemed this study exempt.

Results

Feedback From PDs—Of the 142 PDs, we received 78 responses (54.9%). For selection of dermatology residents, CS was moderately to extremely important to 64 (82.1%) PDs, and 63 (80.8%) PDs stated CS was moderately to extremely important to their dermatology residency program at large. For dermatology residency training, 66 (84.6%) PDs believed CS is important, whereas 3 (3.8%) believed it is not important, and 9 (11.5%) remained undecided (Figure 1). Notably, 17 (21.8%) programs required CS as part of the dermatology educational curriculum, with most of these programs requiring 10 hours or less during the 3 years of residency training. Of the programs with required CS, 15 (88.2%) had dermatology-specific CS requirements, with 10 (58.8%) programs involved in CS at free and/or underserved clinics and some programs participating in other CS activities, such as advocacy, mentorship, educational outreach, or sports (Figure 2A).

Community service opportunities were offered to dermatology residents by 69 (88.5%) programs, including the 17 programs that required CS as part of the dermatology educational curriculum. Among these programs with optional CS, 43 (82.7%) PDs reported CS opportunities at free and/or underserved clinics, and 30 (57.7%) reported CS opportunities through global health initiatives (Figure 2B). Other CS opportunities offered included partnerships with community outreach organizations and mentoring underprivileged students. Patient populations that benefit from CS offered by these dermatology residency programs included 55 (79.7%) underserved, 33 (47.8%) minority, 31 (44.9%) immigrant, 14 (20.3%) pediatric, 14 (20.3%) elderly, and 10 (14.5%) rural populations (Figure 2C). At dermatology residency programs with optional CS opportunities, 22 (42.3%) PDs endorsed at least 50% of their residents participating in these activities.

Qualitative responses revealed that some PDs view CS as “a way for residents to stay connected to what drew them to medicine” and “essential to improving perceptions by physicians and patients about dermatology.” Program directors perceived lack of available time, initiative, and resources as well as minimal resident interest, malpractice coverage, and lack of educational opportunities as potential barriers to CS involvement by residents (Table). Forty-six (59.0%) PDs believed that CS should not be an ACGME requirement for dermatology training, 23 (29.5%) believed it should be required, and 9 (11.5%) were undecided.

Feedback From Residents—We received responses from 92 current dermatology residents and recent dermatology residency graduates; 86 (93.5%) respondents were trainees or recent graduates from academic dermatology residency training programs, and 6 (6.5%) were from community-based training programs. Community service was perceived to be an important part of dermatology training by 68 (73.9%) respondents, and dermatology-specific CS opportunities were available to 65 (70.7%) respondents (Figure 1). Although CS was required of only 7 (7.6%) respondents, 36 (39.1%) respondents volunteered at a free dermatology clinic during residency training. Among respondents who were not provided CS opportunities through their residency program, 23 (85.2%) stated they would have participated if given the opportunity.

Dermatology residents listed increased access to care for marginalized populations, increased sense of purpose, increased competence, and decreased burnout as perceived benefits of participation in CS. Of the dermatology residents who volunteered at a free dermatology clinic during training, 27 (75.0%) regarded the experience as a “high-yield learning opportunity.” Additionally, 29 (80.6%) residents stated their participation in a free dermatology clinic increased their awareness of health disparities and societal factors affecting dermatologic care in underserved patient populations. These respondents affirmed that their participation motivated them to become more involved in outreach targeting underserved populations throughout the duration of their careers.

Comment

The results of this nationwide survey have several important implications for dermatology residency programs, with a focus on programs in well-resourced and high socioeconomic status areas. Although most PDs believe that CS is important for dermatology resident training, few programs have CS requirements, and the majority are opposed to ACGME-mandated CS. Dermatology residents and recent graduates overwhelmingly conveyed that participation in a free dermatology clinic during residency training increased their knowledge base surrounding socioeconomic determinants of health and practicing in resource-limited settings. Furthermore, most trainees expressed that CS participation as a resident motivated them to continue to partake in CS for the underserved as an attending physician. The discordance between perceived value of CS by residents and the lack of CS requirements and opportunities by residency programs represents a realistic opportunity for residency training programs to integrate CS into the curriculum.

Residency programs that integrate service for the underserved into their program goals are 3 times more successful in graduating dermatology residents who practice in underserved communities.⁹ Patients in marginalized communities and those from lower socioeconomic backgrounds face many barriers to accessing dermatologic care including longer wait times and higher practice rejection rates than patients with private insurance.⁶ Through increased CS opportunities, dermatology residency programs can strengthen the local health care infrastructure and bridge the gap in access to dermatologic care.

By establishing a formal CS rotation in dermatology residency programs, residents will experience invaluable first-hand educational opportunities, provide comprehensive care for patients in resource-limited settings, and hopefully continue to serve in marginalized communities. Incorporating service for the underserved into the dermatology residency curriculum not only enhances the cultural competency of trainees but also mandates that skin health equity be made a priority. By exposing dermatology residents to the diverse patient populations often served by free clinics, residents will increase their knowledge of skin disease presentation in patients with darker skin tones, which has historically been deficient in medical education.^10,11

The limitations of this survey study included recall bias, the response rate of PDs (54.9%), and the inability to determine response rate of residents, as we were unable to establish the total number of residents who received our survey. Based on geographic location, some dermatology residency programs may treat a high percentage of medically underserved patients, which already improves access to dermatology. For this reason, follow-up studies correlating PD and resident responses with region, program size, and university/community affiliation will increase our understanding of CS participation and perceptions.

Conclusion

Dermatology residency program participation in CS helps reduce barriers to access for patients in marginalized communities. Incorporating CS into the dermatology residency program curriculum creates a rewarding training environment that increases skin health equity, fosters an interest in health disparities, and enhances the cultural competency of its trainees.

Community service (CS) or service learning in dermatology (eg, free skin cancer screenings, providing care through free clinics, free teledermatology consultations) is instrumental in mitigating disparities and improving access to equitable dermatologic care. With the rate of underinsured and uninsured patients on the rise, free and federally qualified clinics frequently are the sole means by which patients access specialty care such as dermatology.¹ Contributing to the economic gap in access, the geographic disparity of dermatologists in the United States continues to climb, and many marginalized communities remain without dermatologists.² Nearly 30% of the total US population resides in geographic areas that are underserved by dermatologists, while there appears to be an oversupply of dermatologists in urban areas.³ Dermatologists practicing in rural areas make up only 10% of the dermatology workforce,⁴ whereas 40% of all dermatologists practice in the most densely populated US cities.⁵ Consequently, patients in these underserved communities face longer wait times⁶ and are less likely to utilize dermatology services than patients in dermatologist-dense geographic areas.⁷

Service opportunities have become increasingly integrated into graduate medical education.⁸ These service activities help bridge the health care access gap while fulfilling Accreditation Council of Graduate Medical Education (ACGME) requirements. Our study assessed the importance of CS to dermatology residency program directors (PDs), dermatology residents, and recent dermatology residency graduates. Herein, we describe the perceptions of CS within dermatology residency training among PDs and residents.

Methods

In this study, CS is defined as participation in activities to increase dermatologic access, education, and resources to underserved communities. Using the approved Association of Professors of Dermatology listserve and direct email communication, we surveyed 142 PDs of ACGME-accredited dermatology residency training programs. The deidentified respondents voluntarily completed a 17-question Qualtrics survey with a 5-point Likert scale (extremely, very, moderately, slightly, or not at all), yes/no/undecided, and qualitative responses.

We also surveyed current dermatology residents and recent graduates of ACGME-accredited dermatology residency programs via PDs nationwide. The deidentified respondents voluntarily completed a 19-question Qualtrics survey with a 5-point Likert scale (extremely, very, moderately, slightly, or not at all), yes/no/undecided, and qualitative responses.

Descriptive statistics were used for data analysis for both Qualtrics surveys. The University of Pittsburgh institutional review board deemed this study exempt.

Results

Feedback From PDs—Of the 142 PDs, we received 78 responses (54.9%). For selection of dermatology residents, CS was moderately to extremely important to 64 (82.1%) PDs, and 63 (80.8%) PDs stated CS was moderately to extremely important to their dermatology residency program at large. For dermatology residency training, 66 (84.6%) PDs believed CS is important, whereas 3 (3.8%) believed it is not important, and 9 (11.5%) remained undecided (Figure 1). Notably, 17 (21.8%) programs required CS as part of the dermatology educational curriculum, with most of these programs requiring 10 hours or less during the 3 years of residency training. Of the programs with required CS, 15 (88.2%) had dermatology-specific CS requirements, with 10 (58.8%) programs involved in CS at free and/or underserved clinics and some programs participating in other CS activities, such as advocacy, mentorship, educational outreach, or sports (Figure 2A).

Community service opportunities were offered to dermatology residents by 69 (88.5%) programs, including the 17 programs that required CS as part of the dermatology educational curriculum. Among these programs with optional CS, 43 (82.7%) PDs reported CS opportunities at free and/or underserved clinics, and 30 (57.7%) reported CS opportunities through global health initiatives (Figure 2B). Other CS opportunities offered included partnerships with community outreach organizations and mentoring underprivileged students. Patient populations that benefit from CS offered by these dermatology residency programs included 55 (79.7%) underserved, 33 (47.8%) minority, 31 (44.9%) immigrant, 14 (20.3%) pediatric, 14 (20.3%) elderly, and 10 (14.5%) rural populations (Figure 2C). At dermatology residency programs with optional CS opportunities, 22 (42.3%) PDs endorsed at least 50% of their residents participating in these activities.

Qualitative responses revealed that some PDs view CS as “a way for residents to stay connected to what drew them to medicine” and “essential to improving perceptions by physicians and patients about dermatology.” Program directors perceived lack of available time, initiative, and resources as well as minimal resident interest, malpractice coverage, and lack of educational opportunities as potential barriers to CS involvement by residents (Table). Forty-six (59.0%) PDs believed that CS should not be an ACGME requirement for dermatology training, 23 (29.5%) believed it should be required, and 9 (11.5%) were undecided.

Feedback From Residents—We received responses from 92 current dermatology residents and recent dermatology residency graduates; 86 (93.5%) respondents were trainees or recent graduates from academic dermatology residency training programs, and 6 (6.5%) were from community-based training programs. Community service was perceived to be an important part of dermatology training by 68 (73.9%) respondents, and dermatology-specific CS opportunities were available to 65 (70.7%) respondents (Figure 1). Although CS was required of only 7 (7.6%) respondents, 36 (39.1%) respondents volunteered at a free dermatology clinic during residency training. Among respondents who were not provided CS opportunities through their residency program, 23 (85.2%) stated they would have participated if given the opportunity.

Dermatology residents listed increased access to care for marginalized populations, increased sense of purpose, increased competence, and decreased burnout as perceived benefits of participation in CS. Of the dermatology residents who volunteered at a free dermatology clinic during training, 27 (75.0%) regarded the experience as a “high-yield learning opportunity.” Additionally, 29 (80.6%) residents stated their participation in a free dermatology clinic increased their awareness of health disparities and societal factors affecting dermatologic care in underserved patient populations. These respondents affirmed that their participation motivated them to become more involved in outreach targeting underserved populations throughout the duration of their careers.

Comment

The results of this nationwide survey have several important implications for dermatology residency programs, with a focus on programs in well-resourced and high socioeconomic status areas. Although most PDs believe that CS is important for dermatology resident training, few programs have CS requirements, and the majority are opposed to ACGME-mandated CS. Dermatology residents and recent graduates overwhelmingly conveyed that participation in a free dermatology clinic during residency training increased their knowledge base surrounding socioeconomic determinants of health and practicing in resource-limited settings. Furthermore, most trainees expressed that CS participation as a resident motivated them to continue to partake in CS for the underserved as an attending physician. The discordance between perceived value of CS by residents and the lack of CS requirements and opportunities by residency programs represents a realistic opportunity for residency training programs to integrate CS into the curriculum.

Residency programs that integrate service for the underserved into their program goals are 3 times more successful in graduating dermatology residents who practice in underserved communities.⁹ Patients in marginalized communities and those from lower socioeconomic backgrounds face many barriers to accessing dermatologic care including longer wait times and higher practice rejection rates than patients with private insurance.⁶ Through increased CS opportunities, dermatology residency programs can strengthen the local health care infrastructure and bridge the gap in access to dermatologic care.

By establishing a formal CS rotation in dermatology residency programs, residents will experience invaluable first-hand educational opportunities, provide comprehensive care for patients in resource-limited settings, and hopefully continue to serve in marginalized communities. Incorporating service for the underserved into the dermatology residency curriculum not only enhances the cultural competency of trainees but also mandates that skin health equity be made a priority. By exposing dermatology residents to the diverse patient populations often served by free clinics, residents will increase their knowledge of skin disease presentation in patients with darker skin tones, which has historically been deficient in medical education.^10,11

The limitations of this survey study included recall bias, the response rate of PDs (54.9%), and the inability to determine response rate of residents, as we were unable to establish the total number of residents who received our survey. Based on geographic location, some dermatology residency programs may treat a high percentage of medically underserved patients, which already improves access to dermatology. For this reason, follow-up studies correlating PD and resident responses with region, program size, and university/community affiliation will increase our understanding of CS participation and perceptions.

Conclusion

Dermatology residency program participation in CS helps reduce barriers to access for patients in marginalized communities. Incorporating CS into the dermatology residency program curriculum creates a rewarding training environment that increases skin health equity, fosters an interest in health disparities, and enhances the cultural competency of its trainees.

Community service (CS) or service learning in dermatology (eg, free skin cancer screenings, providing care through free clinics, free teledermatology consultations) is instrumental in mitigating disparities and improving access to equitable dermatologic care. With the rate of underinsured and uninsured patients on the rise, free and federally qualified clinics frequently are the sole means by which patients access specialty care such as dermatology.¹ Contributing to the economic gap in access, the geographic disparity of dermatologists in the United States continues to climb, and many marginalized communities remain without dermatologists.² Nearly 30% of the total US population resides in geographic areas that are underserved by dermatologists, while there appears to be an oversupply of dermatologists in urban areas.³ Dermatologists practicing in rural areas make up only 10% of the dermatology workforce,⁴ whereas 40% of all dermatologists practice in the most densely populated US cities.⁵ Consequently, patients in these underserved communities face longer wait times⁶ and are less likely to utilize dermatology services than patients in dermatologist-dense geographic areas.⁷

Service opportunities have become increasingly integrated into graduate medical education.⁸ These service activities help bridge the health care access gap while fulfilling Accreditation Council of Graduate Medical Education (ACGME) requirements. Our study assessed the importance of CS to dermatology residency program directors (PDs), dermatology residents, and recent dermatology residency graduates. Herein, we describe the perceptions of CS within dermatology residency training among PDs and residents.

Methods

In this study, CS is defined as participation in activities to increase dermatologic access, education, and resources to underserved communities. Using the approved Association of Professors of Dermatology listserve and direct email communication, we surveyed 142 PDs of ACGME-accredited dermatology residency training programs. The deidentified respondents voluntarily completed a 17-question Qualtrics survey with a 5-point Likert scale (extremely, very, moderately, slightly, or not at all), yes/no/undecided, and qualitative responses.

We also surveyed current dermatology residents and recent graduates of ACGME-accredited dermatology residency programs via PDs nationwide. The deidentified respondents voluntarily completed a 19-question Qualtrics survey with a 5-point Likert scale (extremely, very, moderately, slightly, or not at all), yes/no/undecided, and qualitative responses.

Descriptive statistics were used for data analysis for both Qualtrics surveys. The University of Pittsburgh institutional review board deemed this study exempt.

Results

Feedback From PDs—Of the 142 PDs, we received 78 responses (54.9%). For selection of dermatology residents, CS was moderately to extremely important to 64 (82.1%) PDs, and 63 (80.8%) PDs stated CS was moderately to extremely important to their dermatology residency program at large. For dermatology residency training, 66 (84.6%) PDs believed CS is important, whereas 3 (3.8%) believed it is not important, and 9 (11.5%) remained undecided (Figure 1). Notably, 17 (21.8%) programs required CS as part of the dermatology educational curriculum, with most of these programs requiring 10 hours or less during the 3 years of residency training. Of the programs with required CS, 15 (88.2%) had dermatology-specific CS requirements, with 10 (58.8%) programs involved in CS at free and/or underserved clinics and some programs participating in other CS activities, such as advocacy, mentorship, educational outreach, or sports (Figure 2A).

Community service opportunities were offered to dermatology residents by 69 (88.5%) programs, including the 17 programs that required CS as part of the dermatology educational curriculum. Among these programs with optional CS, 43 (82.7%) PDs reported CS opportunities at free and/or underserved clinics, and 30 (57.7%) reported CS opportunities through global health initiatives (Figure 2B). Other CS opportunities offered included partnerships with community outreach organizations and mentoring underprivileged students. Patient populations that benefit from CS offered by these dermatology residency programs included 55 (79.7%) underserved, 33 (47.8%) minority, 31 (44.9%) immigrant, 14 (20.3%) pediatric, 14 (20.3%) elderly, and 10 (14.5%) rural populations (Figure 2C). At dermatology residency programs with optional CS opportunities, 22 (42.3%) PDs endorsed at least 50% of their residents participating in these activities.

Qualitative responses revealed that some PDs view CS as “a way for residents to stay connected to what drew them to medicine” and “essential to improving perceptions by physicians and patients about dermatology.” Program directors perceived lack of available time, initiative, and resources as well as minimal resident interest, malpractice coverage, and lack of educational opportunities as potential barriers to CS involvement by residents (Table). Forty-six (59.0%) PDs believed that CS should not be an ACGME requirement for dermatology training, 23 (29.5%) believed it should be required, and 9 (11.5%) were undecided.

Feedback From Residents—We received responses from 92 current dermatology residents and recent dermatology residency graduates; 86 (93.5%) respondents were trainees or recent graduates from academic dermatology residency training programs, and 6 (6.5%) were from community-based training programs. Community service was perceived to be an important part of dermatology training by 68 (73.9%) respondents, and dermatology-specific CS opportunities were available to 65 (70.7%) respondents (Figure 1). Although CS was required of only 7 (7.6%) respondents, 36 (39.1%) respondents volunteered at a free dermatology clinic during residency training. Among respondents who were not provided CS opportunities through their residency program, 23 (85.2%) stated they would have participated if given the opportunity.

Dermatology residents listed increased access to care for marginalized populations, increased sense of purpose, increased competence, and decreased burnout as perceived benefits of participation in CS. Of the dermatology residents who volunteered at a free dermatology clinic during training, 27 (75.0%) regarded the experience as a “high-yield learning opportunity.” Additionally, 29 (80.6%) residents stated their participation in a free dermatology clinic increased their awareness of health disparities and societal factors affecting dermatologic care in underserved patient populations. These respondents affirmed that their participation motivated them to become more involved in outreach targeting underserved populations throughout the duration of their careers.

Comment

The results of this nationwide survey have several important implications for dermatology residency programs, with a focus on programs in well-resourced and high socioeconomic status areas. Although most PDs believe that CS is important for dermatology resident training, few programs have CS requirements, and the majority are opposed to ACGME-mandated CS. Dermatology residents and recent graduates overwhelmingly conveyed that participation in a free dermatology clinic during residency training increased their knowledge base surrounding socioeconomic determinants of health and practicing in resource-limited settings. Furthermore, most trainees expressed that CS participation as a resident motivated them to continue to partake in CS for the underserved as an attending physician. The discordance between perceived value of CS by residents and the lack of CS requirements and opportunities by residency programs represents a realistic opportunity for residency training programs to integrate CS into the curriculum.

Residency programs that integrate service for the underserved into their program goals are 3 times more successful in graduating dermatology residents who practice in underserved communities.⁹ Patients in marginalized communities and those from lower socioeconomic backgrounds face many barriers to accessing dermatologic care including longer wait times and higher practice rejection rates than patients with private insurance.⁶ Through increased CS opportunities, dermatology residency programs can strengthen the local health care infrastructure and bridge the gap in access to dermatologic care.

By establishing a formal CS rotation in dermatology residency programs, residents will experience invaluable first-hand educational opportunities, provide comprehensive care for patients in resource-limited settings, and hopefully continue to serve in marginalized communities. Incorporating service for the underserved into the dermatology residency curriculum not only enhances the cultural competency of trainees but also mandates that skin health equity be made a priority. By exposing dermatology residents to the diverse patient populations often served by free clinics, residents will increase their knowledge of skin disease presentation in patients with darker skin tones, which has historically been deficient in medical education.^10,11

The limitations of this survey study included recall bias, the response rate of PDs (54.9%), and the inability to determine response rate of residents, as we were unable to establish the total number of residents who received our survey. Based on geographic location, some dermatology residency programs may treat a high percentage of medically underserved patients, which already improves access to dermatology. For this reason, follow-up studies correlating PD and resident responses with region, program size, and university/community affiliation will increase our understanding of CS participation and perceptions.

Conclusion

Dermatology residency program participation in CS helps reduce barriers to access for patients in marginalized communities. Incorporating CS into the dermatology residency program curriculum creates a rewarding training environment that increases skin health equity, fosters an interest in health disparities, and enhances the cultural competency of its trainees.

As residents, it is important to understand the steps of the manicuring process and be able to inform patients on how to maintain optimal nail health while continuing to go to nail salons. Most patients are not aware of the possible allergic, traumatic, and/or infectious complications of manicuring their nails. There are practical steps that can be taken to prevent nail issues, such as avoiding cutting one’s cuticles or using allergen-free nail polishes. These simple fixes can make a big difference in long-term nail health in our patients.

Nail Polish Application Process

The nails are first soaked in a warm soapy solution to soften the nail plate and cuticles.¹ Then the nail tips and plates are filed and occasionally are smoothed with a drill. The cuticles are cut with a cuticle cutter. Nail polish—base coat, color enamel, and top coat—is then applied to the nail. Acrylic or sculptured nails and gel and dip manicures are composed of chemical monomers and polymers that harden either at room temperature or through UV or light-emitting diode (LED) exposure. The chemicals in these products can damage nails and cause allergic reactions.

Contact Dermatitis

Approximately 2% of individuals have been found to have allergic or irritant contact dermatitis to nail care products. The top 5 allergens implicated in nail products are (1) 2-hydroxyethyl methacrylate, (2) methyl methacrylate, (3) ethyl acrylate, (4) ethyl-2-cyanoacrylate, and (5) tosylamide.² Methyl methacrylate was banned in 1974 by the US Food and Drug Administration due to reports of severe contact dermatitis, paronychia, and nail dystrophy.³ Due to their potent sensitizing effects, acrylates were named the contact allergen of the year in 2012 by the American Contact Dermatitis Society.³

Acrylates are plastic products formed by polymerization of acrylic or methacrylic acid.⁴ Artificial sculptured nails are created by mixing powdered polymethyl methacrylate polymers and liquid ethyl or isobutyl methacrylate monomers and then applying this mixture to the nail plate.⁵ Gel and powder nails employ a mixture that is similar to acrylic powders, which require UV or LED radiation to polymerize and harden on the nail plate.

Tosylamide, or tosylamide formaldehyde resin, is another potent allergen that promotes adhesion of the enamel to the nail.⁶ It is important to note that sensitization may develop months to years after using artificial nails.

Clinical features of contact allergy secondary to nail polish can vary. Some patients experience severe periungual dermatitis. Others can present with facial or eyelid dermatitis due to exposure to airborne particles of acrylates or from contact with fingertips bearing acrylic nails.^6,7 If inhaled, acrylates also can cause wheezing asthma or allergic rhinoconjunctivitis.

Common Onychodystrophies

Damage to the natural nail plate is inevitable with continued wear of sculptured nails. With 2 to 4 months of consecutive wear, the natural nails turn yellow, brittle, and weak.⁵ One study noted that the thickness of an individual’s left thumb nail plate thinned from 0.059 cm to 0.03 cm after a gel manicure was removed from the nail.⁸ Nail injuries due to manicuring include keratin granulations, onycholysis, pincer nail deformities, pseudopsoriatic nails, lamellar onychoschizia, transverse leukonychia, and ingrown nails.⁶ One interesting nail dystrophy reported secondary to gel manicures is pterygium inversum unguis or a ventral pterygium that causes an abnormal painful adherence of the hyponychium to the ventral surface of the nail plate. Patients prone to developing pterygium inversum unguis can experience sensitivity, pain, or burning sensations during LED or UVA light exposure.⁹

Infections

In addition to contact allergies and nail dystrophies, each step of the manicuring process, such as cutting cuticles, presents opportunities for infectious agents to enter the nail fold. Acute or chronic paronychia, or inflammation of the nail fold, most commonly is caused by bacterial infections with Staphylococcus aureus. Green nail syndrome caused by Pseudomonas aeruginosa also is common.¹ Onychomycosis due to Trichophyton rubrum is one of the most frequent fungal infections contracted at nail salons. Mycobacteria such as Mycobacterium fortuitum also have been implicated in infections from salons, as they can be found in the jets of pedicure spas, which are not sanitized regularly.¹⁰

Final Thoughts

Nail cosmetics are an integral part of many patients’ lives. Being able to educate yourself and your patients on the hazards of nail salons can help them avoid painful infections, contact allergies, and acute to chronic nail deformities. It is important for residents to be aware of the different dermatoses that can arise in men and women who frequent nail salons as the popularity of the nail beauty industry continues to rise.

As residents, it is important to understand the steps of the manicuring process and be able to inform patients on how to maintain optimal nail health while continuing to go to nail salons. Most patients are not aware of the possible allergic, traumatic, and/or infectious complications of manicuring their nails. There are practical steps that can be taken to prevent nail issues, such as avoiding cutting one’s cuticles or using allergen-free nail polishes. These simple fixes can make a big difference in long-term nail health in our patients.

Nail Polish Application Process

The nails are first soaked in a warm soapy solution to soften the nail plate and cuticles.¹ Then the nail tips and plates are filed and occasionally are smoothed with a drill. The cuticles are cut with a cuticle cutter. Nail polish—base coat, color enamel, and top coat—is then applied to the nail. Acrylic or sculptured nails and gel and dip manicures are composed of chemical monomers and polymers that harden either at room temperature or through UV or light-emitting diode (LED) exposure. The chemicals in these products can damage nails and cause allergic reactions.

Contact Dermatitis

Approximately 2% of individuals have been found to have allergic or irritant contact dermatitis to nail care products. The top 5 allergens implicated in nail products are (1) 2-hydroxyethyl methacrylate, (2) methyl methacrylate, (3) ethyl acrylate, (4) ethyl-2-cyanoacrylate, and (5) tosylamide.² Methyl methacrylate was banned in 1974 by the US Food and Drug Administration due to reports of severe contact dermatitis, paronychia, and nail dystrophy.³ Due to their potent sensitizing effects, acrylates were named the contact allergen of the year in 2012 by the American Contact Dermatitis Society.³

Acrylates are plastic products formed by polymerization of acrylic or methacrylic acid.⁴ Artificial sculptured nails are created by mixing powdered polymethyl methacrylate polymers and liquid ethyl or isobutyl methacrylate monomers and then applying this mixture to the nail plate.⁵ Gel and powder nails employ a mixture that is similar to acrylic powders, which require UV or LED radiation to polymerize and harden on the nail plate.

Tosylamide, or tosylamide formaldehyde resin, is another potent allergen that promotes adhesion of the enamel to the nail.⁶ It is important to note that sensitization may develop months to years after using artificial nails.

Clinical features of contact allergy secondary to nail polish can vary. Some patients experience severe periungual dermatitis. Others can present with facial or eyelid dermatitis due to exposure to airborne particles of acrylates or from contact with fingertips bearing acrylic nails.^6,7 If inhaled, acrylates also can cause wheezing asthma or allergic rhinoconjunctivitis.

Common Onychodystrophies

Damage to the natural nail plate is inevitable with continued wear of sculptured nails. With 2 to 4 months of consecutive wear, the natural nails turn yellow, brittle, and weak.⁵ One study noted that the thickness of an individual’s left thumb nail plate thinned from 0.059 cm to 0.03 cm after a gel manicure was removed from the nail.⁸ Nail injuries due to manicuring include keratin granulations, onycholysis, pincer nail deformities, pseudopsoriatic nails, lamellar onychoschizia, transverse leukonychia, and ingrown nails.⁶ One interesting nail dystrophy reported secondary to gel manicures is pterygium inversum unguis or a ventral pterygium that causes an abnormal painful adherence of the hyponychium to the ventral surface of the nail plate. Patients prone to developing pterygium inversum unguis can experience sensitivity, pain, or burning sensations during LED or UVA light exposure.⁹

Infections

In addition to contact allergies and nail dystrophies, each step of the manicuring process, such as cutting cuticles, presents opportunities for infectious agents to enter the nail fold. Acute or chronic paronychia, or inflammation of the nail fold, most commonly is caused by bacterial infections with Staphylococcus aureus. Green nail syndrome caused by Pseudomonas aeruginosa also is common.¹ Onychomycosis due to Trichophyton rubrum is one of the most frequent fungal infections contracted at nail salons. Mycobacteria such as Mycobacterium fortuitum also have been implicated in infections from salons, as they can be found in the jets of pedicure spas, which are not sanitized regularly.¹⁰

Final Thoughts

Nail cosmetics are an integral part of many patients’ lives. Being able to educate yourself and your patients on the hazards of nail salons can help them avoid painful infections, contact allergies, and acute to chronic nail deformities. It is important for residents to be aware of the different dermatoses that can arise in men and women who frequent nail salons as the popularity of the nail beauty industry continues to rise.

As residents, it is important to understand the steps of the manicuring process and be able to inform patients on how to maintain optimal nail health while continuing to go to nail salons. Most patients are not aware of the possible allergic, traumatic, and/or infectious complications of manicuring their nails. There are practical steps that can be taken to prevent nail issues, such as avoiding cutting one’s cuticles or using allergen-free nail polishes. These simple fixes can make a big difference in long-term nail health in our patients.

Nail Polish Application Process

The nails are first soaked in a warm soapy solution to soften the nail plate and cuticles.¹ Then the nail tips and plates are filed and occasionally are smoothed with a drill. The cuticles are cut with a cuticle cutter. Nail polish—base coat, color enamel, and top coat—is then applied to the nail. Acrylic or sculptured nails and gel and dip manicures are composed of chemical monomers and polymers that harden either at room temperature or through UV or light-emitting diode (LED) exposure. The chemicals in these products can damage nails and cause allergic reactions.

Contact Dermatitis

Approximately 2% of individuals have been found to have allergic or irritant contact dermatitis to nail care products. The top 5 allergens implicated in nail products are (1) 2-hydroxyethyl methacrylate, (2) methyl methacrylate, (3) ethyl acrylate, (4) ethyl-2-cyanoacrylate, and (5) tosylamide.² Methyl methacrylate was banned in 1974 by the US Food and Drug Administration due to reports of severe contact dermatitis, paronychia, and nail dystrophy.³ Due to their potent sensitizing effects, acrylates were named the contact allergen of the year in 2012 by the American Contact Dermatitis Society.³

Acrylates are plastic products formed by polymerization of acrylic or methacrylic acid.⁴ Artificial sculptured nails are created by mixing powdered polymethyl methacrylate polymers and liquid ethyl or isobutyl methacrylate monomers and then applying this mixture to the nail plate.⁵ Gel and powder nails employ a mixture that is similar to acrylic powders, which require UV or LED radiation to polymerize and harden on the nail plate.

Tosylamide, or tosylamide formaldehyde resin, is another potent allergen that promotes adhesion of the enamel to the nail.⁶ It is important to note that sensitization may develop months to years after using artificial nails.

Clinical features of contact allergy secondary to nail polish can vary. Some patients experience severe periungual dermatitis. Others can present with facial or eyelid dermatitis due to exposure to airborne particles of acrylates or from contact with fingertips bearing acrylic nails.^6,7 If inhaled, acrylates also can cause wheezing asthma or allergic rhinoconjunctivitis.

Common Onychodystrophies

Damage to the natural nail plate is inevitable with continued wear of sculptured nails. With 2 to 4 months of consecutive wear, the natural nails turn yellow, brittle, and weak.⁵ One study noted that the thickness of an individual’s left thumb nail plate thinned from 0.059 cm to 0.03 cm after a gel manicure was removed from the nail.⁸ Nail injuries due to manicuring include keratin granulations, onycholysis, pincer nail deformities, pseudopsoriatic nails, lamellar onychoschizia, transverse leukonychia, and ingrown nails.⁶ One interesting nail dystrophy reported secondary to gel manicures is pterygium inversum unguis or a ventral pterygium that causes an abnormal painful adherence of the hyponychium to the ventral surface of the nail plate. Patients prone to developing pterygium inversum unguis can experience sensitivity, pain, or burning sensations during LED or UVA light exposure.⁹

Infections

In addition to contact allergies and nail dystrophies, each step of the manicuring process, such as cutting cuticles, presents opportunities for infectious agents to enter the nail fold. Acute or chronic paronychia, or inflammation of the nail fold, most commonly is caused by bacterial infections with Staphylococcus aureus. Green nail syndrome caused by Pseudomonas aeruginosa also is common.¹ Onychomycosis due to Trichophyton rubrum is one of the most frequent fungal infections contracted at nail salons. Mycobacteria such as Mycobacterium fortuitum also have been implicated in infections from salons, as they can be found in the jets of pedicure spas, which are not sanitized regularly.¹⁰

Final Thoughts

Nail cosmetics are an integral part of many patients’ lives. Being able to educate yourself and your patients on the hazards of nail salons can help them avoid painful infections, contact allergies, and acute to chronic nail deformities. It is important for residents to be aware of the different dermatoses that can arise in men and women who frequent nail salons as the popularity of the nail beauty industry continues to rise.

We all have friends or relatives who, somehow, have managed to avoid catching COVID-19, which has infected more than 91.5 million Americans. You may even be one of the lucky ones yourself.

But health experts are saying: Not so fast. A mounting pile of scientific evidence suggests millions of Americans have been infected with the virus without ever even knowing it because they didn’t have symptoms or had mild cases they mistook for a cold or allergies.

The upshot: These silent COVID-19 cases reflect a hidden side of the pandemic that may be helping to drive new surges and viral variants.

Still, infectious disease experts say there is little doubt that some people have indeed managed to avoid COVID-19 infection altogether, and they are trying to understand why.

Several recent studies have suggested certain genetic and immune system traits may better protect this group of people against the coronavirus, making them less likely than others to be infected or seriously sickened. Researchers around the world are now studying these seemingly super-immune people for clues to what makes them so special, with an eye toward better vaccines, treatments, and prevention strategies.

Infectious disease specialists say both types of cases – those unknowingly infected by COVID-19 and people who’ve avoided the virus altogether – matter greatly to public health, more than 2 years into the pandemic.

“It’s definitely true that some people have had COVID and don’t realize it,” says Stephen Kissler, PhD, an infectious disease researcher with the Harvard T.H. Chan School of Public Health, Boston. “It is potentially good news if there’s more immunity in the population than we realize.”

But he says that being able to identify genetic and other factors that may offer some people protection against COVID-19 is an “exciting prospect” that could help find out who’s most at risk and improve efforts to get the pandemic under control.

Some studies have found a person’s genetic profile, past exposure to other COVID-like viruses, allergies, and even drugs they take for other conditions may all provide some defense – even for people who have not been vaccinated, don’t use masks, or don’t practice social distancing.

A person’s medical history and genetics may help decide their risk from new diseases, meaning “we may be able to help identify people who are at especially high risk from infection,” Dr. Kissler says. “That knowledge could help those people better shield themselves from infection and get quicker access to treatment and vaccines, if necessary. … We don’t yet know, but studies are ongoing for these things.”

Amesh Adalja, MD, an infectious disease specialist with the Johns Hopkins Center for Health Security, Baltimore, agrees that emerging research on people who’ve avoided infection offers the chance of new public health strategies to combat COVID-19.

“I’m sure there is some subset of people who are [COVID] negative,” he says. “So what explains that phenomenon, especially if that person was out there getting significant exposures?”
 

Have you had COVID without knowing it?

In a media briefing late last month, White House COVID-19 Response Coordinator Ashish Jha, MD, said more than 70% of the U.S. population has had the virus, according to the latest CDC data. That’s up from 33.5% in December.

But the actual number of people in the U.S. who have been infected with SARS-CoV-2, the scientific name for the virus that causes COVID-19, is likely to be much higher due to cases without symptoms that are unreported, experts say.

Since the early days of the pandemic, researchers have tried to put a number on these hidden cases, but that figure has been evolving and a clear consensus has not emerged.

In September 2020, a study published in the Annals of Internal Medicine said “approximately 40% to 45% of those infected with SARS-CoV-2 will remain asymptomatic.”

A follow-up analysis of 95 studies, published last December, reached similar findings, estimating that more than 40% of COVID-19 infections didn’t come with symptoms.

To get a better handle on the issue, CDC officials have been working with the American Red Cross and other blood banks to track COVID-19 antibodies – proteins your body makes after exposure to the virus to fight off an infection – in donors who said they have never had COVID-19.

While that joint effort is still ongoing, early findings say the number of donors with antibodies from COVID-19 infection increased in blood donors from 3.5% in July 2020 to at least 20.2% in May 2021. Since then, those percentages have soared, in part due to the introduction of vaccines, which also make the body produce COVID-19 antibodies.

The most current findings show that 83.3% of donors have combined COVID infection– and vaccine-induced antibodies in their blood. Those findings are based on 1.4 million blood donations.

Health experts say all of these studies are strong evidence that many COVID-19 cases continue to go undetected. In fact, the University of Washington Institute for Health Metrics and Evaluation estimates that only 7% of positive COVID-19 cases in the U.S. are being detected. That means case rates are actually 14.5 times higher than the official count of 131,000 new COVID infections each day, according to the Centers for Disease Control and Prevention, which reports the virus is still killing about 440 Americans daily.

So, why is all this important, in terms of public health?

Experts say people are more likely to be cautious if they know COVID-19 cases are high where they live, work, and play. On the other hand, if they believe case rates in their communities are lower than they actually are, they may be less likely to get vaccinated and boosted, wear masks indoors, avoid crowded indoor spaces, and take other precautions to fend off infection.
 

How do some avoid infection altogether?

In addition to tracking cases that go unreported and don’t have symptoms, infectious disease experts have also been trying to figure out why some people have managed to avoid getting the highly contagious virus.

Several leading lines of research have produced promising early results – suggesting that a person’s genetic makeup, past exposure to less-lethal coronaviruses, allergies, and even certain drugs they take for other conditions may all provide at least some protection against COVID.

“Our study showed that there are many human genes – hundreds of genes – that can impact SARS-CoV-2 infection,” says Neville Sanjana, PhD, a geneticist at New York University and the New York Genome Center who co-led the study. “With a better understanding of host genetic factors, we can find new kinds of therapies that target these host factors to block infection.”

In addition, he says several studies show some drugs that regulate genes, such as the breast cancer drug tamoxifen, also appear to knock down COVID-19 risk. He suggests such drugs, already approved by the Food and Drug Administration, might be “repurposed” to target the virus.

Studies in other countries show that patients taking tamoxifen before the pandemic were protected against severe COVID-19, Dr. Sanjana says. “That was a really cool thing, highlighting the power of harnessing host genetics. The virus critically depends on our genes to complete key parts of its life cycle.”

The NYU research findings echo other studies that have been published in recent months.

In July, a team of researchers led by the National Cancer Institute identified a genetic factor that appears to determine how severe an infection will be. In a study involving 3,000 people, they found that two gene changes, or mutations, that decrease the expression of a gene called OAS1 boosted the risk of hospitalization from COVID-19. OAS1 is part of the immune system’s response to viral infections.

As a result, developing a genetic therapy designed to increase the OAS1 gene’s expression might reduce the risk of severe disease.

“It’s very natural to get infected once you are exposed. There’s no magic bullet for that. But after you get infected, how you’re going to respond to this infection, that’s what is going to be affected by your genetic variants,” said Ludmila Prokunina-Olsson, PhD, the study’s lead researcher and chief of the National Cancer Institute’s Laboratory of Translational Genomics, Bethesda, Md., in an interview with NBC News.

Benjamin tenOever, PhD, a New York University virologist who co-authored the 2020 research, says the new genetic research is promising, but he believes it’s unlikely scientists will be able to identify a single gene responsible for actually preventing a COVID-19 infection.

“On the flip side, we have identified many genes that makes the disease worse,” he says.
 

T cells ‘remember’ past viral infections

As Dr. tenOever and Dr. Sanjana suggest, another intriguing line of research has found that prior viral infections may prime the body’s immune system to fight COVID-19.

Four other common coronaviruses – aside from SARS-CoV-2 – infect people worldwide, typically causing mild to moderate upper respiratory illnesses like the common cold, says Alessandro Sette, PhD, an infectious disease expert and vaccine researcher with the La Jolla (Calif.) Institute for Immunology.

In a recent study published in Science, he and his team found past infection with these other coronaviruses may give some protection against SARS-CoV-2.

T cells – white blood cells that act like immunological ninjas to ferret out and fight infections – appear to maintain a kind of “biological memory” of coronaviruses they have seen before and can mount an attack on similar pathogens, such SARS-CoV-2, Dr. Sette says.

The new work builds on a prior research he helped lead that found 40%-60% of people never exposed to SARS-CoV-2 had T cells that reacted to the virus – with their immune systems recognizing fragments of a virus they had never seen before.

Dr. Sette says his research shows that people whose T cells have this “preexisting memory” of past coronavirus exposures also tend to respond better to vaccination for reasons not yet well understood.

“The question is, at which point will there be enough immunity from vaccination, repeated infections from other coronaviruses, but also some of the variants of the SARS-CoV-2 … where infections become less frequent? We’re not there yet,” he says.

In addition to these exciting genetic and T-cell findings, other research has suggested low-grade inflammation from allergies – a key part of the body’s immune response to foreign substances – may also give some people an extra leg up, in terms of avoiding COVID infection.

Last May, a study of 1,400 households published in The Journal of Allergy and Clinical Immunology found that having a food allergy cut the risk of COVID-19 infection in half.

The researchers said it’s unclear why allergies may reduce the risk of infection, but they noted that people with food allergies express fewer ACE2 receptors on the surface of their airway cells, making it harder for the virus to enter cells.
 

The big picture: Prevention still your best bet

So, what’s the takeaway from all of this emerging research?

New York University’s Dr. tenOever says that while genes, T cells and allergies may offer some protection against COVID, tried-and-true precautions – vaccination, wearing masks, avoiding crowded indoor spaces, and social distancing – are likely to provide a greater defense.

He believes these precautions are likely why he and his family have never contracted COVID-19.

“I was tested weekly, as were my kids at school,” he says. “We definitely never got COVID, despite the fact that we live in New York City and I worked in a hospital every single day of the pandemic.”

Ziyad Al-Aly, MD, an infectious disease specialist and director of clinical epidemiology at Washington University in St. Louis, agrees that the new research on COVID-19 is intriguing but won’t likely result in practical changes in the approach to fighting the virus in the near term.

“Getting a deeper understanding of potential genetic factors or other characteristics – that could really help us understand why the virus just comes and goes without any ill effects in some people, and in other people it produces really serious disease,” he says. “That will really help us eventually to design better vaccines to prevent it or reduce severity or even [treat] people who get severe disease.”

In the meantime, Dr. Al-Aly says, “it’s still best to do everything you can to avoid infection in the first place – even if you’re vaccinated or previously infected, you should really try to avoid reinfection.”

That means sit outside if you can when visiting a restaurant. Wear a mask on a plane, even though it’s not required. And get vaccinated and boosted.

“In the future, there may be more tools to address this pandemic, but that’s really the best advice for now,” Dr. Al-Aly says.

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

We all have friends or relatives who, somehow, have managed to avoid catching COVID-19, which has infected more than 91.5 million Americans. You may even be one of the lucky ones yourself.

But health experts are saying: Not so fast. A mounting pile of scientific evidence suggests millions of Americans have been infected with the virus without ever even knowing it because they didn’t have symptoms or had mild cases they mistook for a cold or allergies.

The upshot: These silent COVID-19 cases reflect a hidden side of the pandemic that may be helping to drive new surges and viral variants.

Still, infectious disease experts say there is little doubt that some people have indeed managed to avoid COVID-19 infection altogether, and they are trying to understand why.

Several recent studies have suggested certain genetic and immune system traits may better protect this group of people against the coronavirus, making them less likely than others to be infected or seriously sickened. Researchers around the world are now studying these seemingly super-immune people for clues to what makes them so special, with an eye toward better vaccines, treatments, and prevention strategies.

Infectious disease specialists say both types of cases – those unknowingly infected by COVID-19 and people who’ve avoided the virus altogether – matter greatly to public health, more than 2 years into the pandemic.

“It’s definitely true that some people have had COVID and don’t realize it,” says Stephen Kissler, PhD, an infectious disease researcher with the Harvard T.H. Chan School of Public Health, Boston. “It is potentially good news if there’s more immunity in the population than we realize.”

But he says that being able to identify genetic and other factors that may offer some people protection against COVID-19 is an “exciting prospect” that could help find out who’s most at risk and improve efforts to get the pandemic under control.

Some studies have found a person’s genetic profile, past exposure to other COVID-like viruses, allergies, and even drugs they take for other conditions may all provide some defense – even for people who have not been vaccinated, don’t use masks, or don’t practice social distancing.

A person’s medical history and genetics may help decide their risk from new diseases, meaning “we may be able to help identify people who are at especially high risk from infection,” Dr. Kissler says. “That knowledge could help those people better shield themselves from infection and get quicker access to treatment and vaccines, if necessary. … We don’t yet know, but studies are ongoing for these things.”

Amesh Adalja, MD, an infectious disease specialist with the Johns Hopkins Center for Health Security, Baltimore, agrees that emerging research on people who’ve avoided infection offers the chance of new public health strategies to combat COVID-19.

“I’m sure there is some subset of people who are [COVID] negative,” he says. “So what explains that phenomenon, especially if that person was out there getting significant exposures?”
 

Have you had COVID without knowing it?

In a media briefing late last month, White House COVID-19 Response Coordinator Ashish Jha, MD, said more than 70% of the U.S. population has had the virus, according to the latest CDC data. That’s up from 33.5% in December.

But the actual number of people in the U.S. who have been infected with SARS-CoV-2, the scientific name for the virus that causes COVID-19, is likely to be much higher due to cases without symptoms that are unreported, experts say.

Since the early days of the pandemic, researchers have tried to put a number on these hidden cases, but that figure has been evolving and a clear consensus has not emerged.

In September 2020, a study published in the Annals of Internal Medicine said “approximately 40% to 45% of those infected with SARS-CoV-2 will remain asymptomatic.”

A follow-up analysis of 95 studies, published last December, reached similar findings, estimating that more than 40% of COVID-19 infections didn’t come with symptoms.

To get a better handle on the issue, CDC officials have been working with the American Red Cross and other blood banks to track COVID-19 antibodies – proteins your body makes after exposure to the virus to fight off an infection – in donors who said they have never had COVID-19.

While that joint effort is still ongoing, early findings say the number of donors with antibodies from COVID-19 infection increased in blood donors from 3.5% in July 2020 to at least 20.2% in May 2021. Since then, those percentages have soared, in part due to the introduction of vaccines, which also make the body produce COVID-19 antibodies.

The most current findings show that 83.3% of donors have combined COVID infection– and vaccine-induced antibodies in their blood. Those findings are based on 1.4 million blood donations.

Health experts say all of these studies are strong evidence that many COVID-19 cases continue to go undetected. In fact, the University of Washington Institute for Health Metrics and Evaluation estimates that only 7% of positive COVID-19 cases in the U.S. are being detected. That means case rates are actually 14.5 times higher than the official count of 131,000 new COVID infections each day, according to the Centers for Disease Control and Prevention, which reports the virus is still killing about 440 Americans daily.

So, why is all this important, in terms of public health?

Experts say people are more likely to be cautious if they know COVID-19 cases are high where they live, work, and play. On the other hand, if they believe case rates in their communities are lower than they actually are, they may be less likely to get vaccinated and boosted, wear masks indoors, avoid crowded indoor spaces, and take other precautions to fend off infection.
 

How do some avoid infection altogether?

In addition to tracking cases that go unreported and don’t have symptoms, infectious disease experts have also been trying to figure out why some people have managed to avoid getting the highly contagious virus.

Several leading lines of research have produced promising early results – suggesting that a person’s genetic makeup, past exposure to less-lethal coronaviruses, allergies, and even certain drugs they take for other conditions may all provide at least some protection against COVID.

“Our study showed that there are many human genes – hundreds of genes – that can impact SARS-CoV-2 infection,” says Neville Sanjana, PhD, a geneticist at New York University and the New York Genome Center who co-led the study. “With a better understanding of host genetic factors, we can find new kinds of therapies that target these host factors to block infection.”

In addition, he says several studies show some drugs that regulate genes, such as the breast cancer drug tamoxifen, also appear to knock down COVID-19 risk. He suggests such drugs, already approved by the Food and Drug Administration, might be “repurposed” to target the virus.

Studies in other countries show that patients taking tamoxifen before the pandemic were protected against severe COVID-19, Dr. Sanjana says. “That was a really cool thing, highlighting the power of harnessing host genetics. The virus critically depends on our genes to complete key parts of its life cycle.”

The NYU research findings echo other studies that have been published in recent months.

In July, a team of researchers led by the National Cancer Institute identified a genetic factor that appears to determine how severe an infection will be. In a study involving 3,000 people, they found that two gene changes, or mutations, that decrease the expression of a gene called OAS1 boosted the risk of hospitalization from COVID-19. OAS1 is part of the immune system’s response to viral infections.

As a result, developing a genetic therapy designed to increase the OAS1 gene’s expression might reduce the risk of severe disease.

“It’s very natural to get infected once you are exposed. There’s no magic bullet for that. But after you get infected, how you’re going to respond to this infection, that’s what is going to be affected by your genetic variants,” said Ludmila Prokunina-Olsson, PhD, the study’s lead researcher and chief of the National Cancer Institute’s Laboratory of Translational Genomics, Bethesda, Md., in an interview with NBC News.

Benjamin tenOever, PhD, a New York University virologist who co-authored the 2020 research, says the new genetic research is promising, but he believes it’s unlikely scientists will be able to identify a single gene responsible for actually preventing a COVID-19 infection.

“On the flip side, we have identified many genes that makes the disease worse,” he says.
 

T cells ‘remember’ past viral infections

As Dr. tenOever and Dr. Sanjana suggest, another intriguing line of research has found that prior viral infections may prime the body’s immune system to fight COVID-19.

Four other common coronaviruses – aside from SARS-CoV-2 – infect people worldwide, typically causing mild to moderate upper respiratory illnesses like the common cold, says Alessandro Sette, PhD, an infectious disease expert and vaccine researcher with the La Jolla (Calif.) Institute for Immunology.

In a recent study published in Science, he and his team found past infection with these other coronaviruses may give some protection against SARS-CoV-2.

T cells – white blood cells that act like immunological ninjas to ferret out and fight infections – appear to maintain a kind of “biological memory” of coronaviruses they have seen before and can mount an attack on similar pathogens, such SARS-CoV-2, Dr. Sette says.

The new work builds on a prior research he helped lead that found 40%-60% of people never exposed to SARS-CoV-2 had T cells that reacted to the virus – with their immune systems recognizing fragments of a virus they had never seen before.

Dr. Sette says his research shows that people whose T cells have this “preexisting memory” of past coronavirus exposures also tend to respond better to vaccination for reasons not yet well understood.

“The question is, at which point will there be enough immunity from vaccination, repeated infections from other coronaviruses, but also some of the variants of the SARS-CoV-2 … where infections become less frequent? We’re not there yet,” he says.

In addition to these exciting genetic and T-cell findings, other research has suggested low-grade inflammation from allergies – a key part of the body’s immune response to foreign substances – may also give some people an extra leg up, in terms of avoiding COVID infection.

Last May, a study of 1,400 households published in The Journal of Allergy and Clinical Immunology found that having a food allergy cut the risk of COVID-19 infection in half.

The researchers said it’s unclear why allergies may reduce the risk of infection, but they noted that people with food allergies express fewer ACE2 receptors on the surface of their airway cells, making it harder for the virus to enter cells.
 

The big picture: Prevention still your best bet

So, what’s the takeaway from all of this emerging research?

New York University’s Dr. tenOever says that while genes, T cells and allergies may offer some protection against COVID, tried-and-true precautions – vaccination, wearing masks, avoiding crowded indoor spaces, and social distancing – are likely to provide a greater defense.

He believes these precautions are likely why he and his family have never contracted COVID-19.

“I was tested weekly, as were my kids at school,” he says. “We definitely never got COVID, despite the fact that we live in New York City and I worked in a hospital every single day of the pandemic.”

Ziyad Al-Aly, MD, an infectious disease specialist and director of clinical epidemiology at Washington University in St. Louis, agrees that the new research on COVID-19 is intriguing but won’t likely result in practical changes in the approach to fighting the virus in the near term.

“Getting a deeper understanding of potential genetic factors or other characteristics – that could really help us understand why the virus just comes and goes without any ill effects in some people, and in other people it produces really serious disease,” he says. “That will really help us eventually to design better vaccines to prevent it or reduce severity or even [treat] people who get severe disease.”

In the meantime, Dr. Al-Aly says, “it’s still best to do everything you can to avoid infection in the first place – even if you’re vaccinated or previously infected, you should really try to avoid reinfection.”

That means sit outside if you can when visiting a restaurant. Wear a mask on a plane, even though it’s not required. And get vaccinated and boosted.

“In the future, there may be more tools to address this pandemic, but that’s really the best advice for now,” Dr. Al-Aly says.

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

We all have friends or relatives who, somehow, have managed to avoid catching COVID-19, which has infected more than 91.5 million Americans. You may even be one of the lucky ones yourself.

But health experts are saying: Not so fast. A mounting pile of scientific evidence suggests millions of Americans have been infected with the virus without ever even knowing it because they didn’t have symptoms or had mild cases they mistook for a cold or allergies.

The upshot: These silent COVID-19 cases reflect a hidden side of the pandemic that may be helping to drive new surges and viral variants.

Still, infectious disease experts say there is little doubt that some people have indeed managed to avoid COVID-19 infection altogether, and they are trying to understand why.

Several recent studies have suggested certain genetic and immune system traits may better protect this group of people against the coronavirus, making them less likely than others to be infected or seriously sickened. Researchers around the world are now studying these seemingly super-immune people for clues to what makes them so special, with an eye toward better vaccines, treatments, and prevention strategies.

Infectious disease specialists say both types of cases – those unknowingly infected by COVID-19 and people who’ve avoided the virus altogether – matter greatly to public health, more than 2 years into the pandemic.

“It’s definitely true that some people have had COVID and don’t realize it,” says Stephen Kissler, PhD, an infectious disease researcher with the Harvard T.H. Chan School of Public Health, Boston. “It is potentially good news if there’s more immunity in the population than we realize.”

But he says that being able to identify genetic and other factors that may offer some people protection against COVID-19 is an “exciting prospect” that could help find out who’s most at risk and improve efforts to get the pandemic under control.

Some studies have found a person’s genetic profile, past exposure to other COVID-like viruses, allergies, and even drugs they take for other conditions may all provide some defense – even for people who have not been vaccinated, don’t use masks, or don’t practice social distancing.

A person’s medical history and genetics may help decide their risk from new diseases, meaning “we may be able to help identify people who are at especially high risk from infection,” Dr. Kissler says. “That knowledge could help those people better shield themselves from infection and get quicker access to treatment and vaccines, if necessary. … We don’t yet know, but studies are ongoing for these things.”

Amesh Adalja, MD, an infectious disease specialist with the Johns Hopkins Center for Health Security, Baltimore, agrees that emerging research on people who’ve avoided infection offers the chance of new public health strategies to combat COVID-19.

“I’m sure there is some subset of people who are [COVID] negative,” he says. “So what explains that phenomenon, especially if that person was out there getting significant exposures?”
 

Have you had COVID without knowing it?

In a media briefing late last month, White House COVID-19 Response Coordinator Ashish Jha, MD, said more than 70% of the U.S. population has had the virus, according to the latest CDC data. That’s up from 33.5% in December.

But the actual number of people in the U.S. who have been infected with SARS-CoV-2, the scientific name for the virus that causes COVID-19, is likely to be much higher due to cases without symptoms that are unreported, experts say.

Since the early days of the pandemic, researchers have tried to put a number on these hidden cases, but that figure has been evolving and a clear consensus has not emerged.

In September 2020, a study published in the Annals of Internal Medicine said “approximately 40% to 45% of those infected with SARS-CoV-2 will remain asymptomatic.”

A follow-up analysis of 95 studies, published last December, reached similar findings, estimating that more than 40% of COVID-19 infections didn’t come with symptoms.

To get a better handle on the issue, CDC officials have been working with the American Red Cross and other blood banks to track COVID-19 antibodies – proteins your body makes after exposure to the virus to fight off an infection – in donors who said they have never had COVID-19.

While that joint effort is still ongoing, early findings say the number of donors with antibodies from COVID-19 infection increased in blood donors from 3.5% in July 2020 to at least 20.2% in May 2021. Since then, those percentages have soared, in part due to the introduction of vaccines, which also make the body produce COVID-19 antibodies.

The most current findings show that 83.3% of donors have combined COVID infection– and vaccine-induced antibodies in their blood. Those findings are based on 1.4 million blood donations.

Health experts say all of these studies are strong evidence that many COVID-19 cases continue to go undetected. In fact, the University of Washington Institute for Health Metrics and Evaluation estimates that only 7% of positive COVID-19 cases in the U.S. are being detected. That means case rates are actually 14.5 times higher than the official count of 131,000 new COVID infections each day, according to the Centers for Disease Control and Prevention, which reports the virus is still killing about 440 Americans daily.

So, why is all this important, in terms of public health?

Experts say people are more likely to be cautious if they know COVID-19 cases are high where they live, work, and play. On the other hand, if they believe case rates in their communities are lower than they actually are, they may be less likely to get vaccinated and boosted, wear masks indoors, avoid crowded indoor spaces, and take other precautions to fend off infection.
 

How do some avoid infection altogether?

In addition to tracking cases that go unreported and don’t have symptoms, infectious disease experts have also been trying to figure out why some people have managed to avoid getting the highly contagious virus.

Several leading lines of research have produced promising early results – suggesting that a person’s genetic makeup, past exposure to less-lethal coronaviruses, allergies, and even certain drugs they take for other conditions may all provide at least some protection against COVID.

“Our study showed that there are many human genes – hundreds of genes – that can impact SARS-CoV-2 infection,” says Neville Sanjana, PhD, a geneticist at New York University and the New York Genome Center who co-led the study. “With a better understanding of host genetic factors, we can find new kinds of therapies that target these host factors to block infection.”

In addition, he says several studies show some drugs that regulate genes, such as the breast cancer drug tamoxifen, also appear to knock down COVID-19 risk. He suggests such drugs, already approved by the Food and Drug Administration, might be “repurposed” to target the virus.

Studies in other countries show that patients taking tamoxifen before the pandemic were protected against severe COVID-19, Dr. Sanjana says. “That was a really cool thing, highlighting the power of harnessing host genetics. The virus critically depends on our genes to complete key parts of its life cycle.”

The NYU research findings echo other studies that have been published in recent months.

In July, a team of researchers led by the National Cancer Institute identified a genetic factor that appears to determine how severe an infection will be. In a study involving 3,000 people, they found that two gene changes, or mutations, that decrease the expression of a gene called OAS1 boosted the risk of hospitalization from COVID-19. OAS1 is part of the immune system’s response to viral infections.

As a result, developing a genetic therapy designed to increase the OAS1 gene’s expression might reduce the risk of severe disease.

“It’s very natural to get infected once you are exposed. There’s no magic bullet for that. But after you get infected, how you’re going to respond to this infection, that’s what is going to be affected by your genetic variants,” said Ludmila Prokunina-Olsson, PhD, the study’s lead researcher and chief of the National Cancer Institute’s Laboratory of Translational Genomics, Bethesda, Md., in an interview with NBC News.

Benjamin tenOever, PhD, a New York University virologist who co-authored the 2020 research, says the new genetic research is promising, but he believes it’s unlikely scientists will be able to identify a single gene responsible for actually preventing a COVID-19 infection.

“On the flip side, we have identified many genes that makes the disease worse,” he says.
 

T cells ‘remember’ past viral infections

As Dr. tenOever and Dr. Sanjana suggest, another intriguing line of research has found that prior viral infections may prime the body’s immune system to fight COVID-19.

Four other common coronaviruses – aside from SARS-CoV-2 – infect people worldwide, typically causing mild to moderate upper respiratory illnesses like the common cold, says Alessandro Sette, PhD, an infectious disease expert and vaccine researcher with the La Jolla (Calif.) Institute for Immunology.

In a recent study published in Science, he and his team found past infection with these other coronaviruses may give some protection against SARS-CoV-2.

T cells – white blood cells that act like immunological ninjas to ferret out and fight infections – appear to maintain a kind of “biological memory” of coronaviruses they have seen before and can mount an attack on similar pathogens, such SARS-CoV-2, Dr. Sette says.

The new work builds on a prior research he helped lead that found 40%-60% of people never exposed to SARS-CoV-2 had T cells that reacted to the virus – with their immune systems recognizing fragments of a virus they had never seen before.

Dr. Sette says his research shows that people whose T cells have this “preexisting memory” of past coronavirus exposures also tend to respond better to vaccination for reasons not yet well understood.

“The question is, at which point will there be enough immunity from vaccination, repeated infections from other coronaviruses, but also some of the variants of the SARS-CoV-2 … where infections become less frequent? We’re not there yet,” he says.

In addition to these exciting genetic and T-cell findings, other research has suggested low-grade inflammation from allergies – a key part of the body’s immune response to foreign substances – may also give some people an extra leg up, in terms of avoiding COVID infection.

Last May, a study of 1,400 households published in The Journal of Allergy and Clinical Immunology found that having a food allergy cut the risk of COVID-19 infection in half.

The researchers said it’s unclear why allergies may reduce the risk of infection, but they noted that people with food allergies express fewer ACE2 receptors on the surface of their airway cells, making it harder for the virus to enter cells.
 

The big picture: Prevention still your best bet

So, what’s the takeaway from all of this emerging research?

New York University’s Dr. tenOever says that while genes, T cells and allergies may offer some protection against COVID, tried-and-true precautions – vaccination, wearing masks, avoiding crowded indoor spaces, and social distancing – are likely to provide a greater defense.

He believes these precautions are likely why he and his family have never contracted COVID-19.

“I was tested weekly, as were my kids at school,” he says. “We definitely never got COVID, despite the fact that we live in New York City and I worked in a hospital every single day of the pandemic.”

Ziyad Al-Aly, MD, an infectious disease specialist and director of clinical epidemiology at Washington University in St. Louis, agrees that the new research on COVID-19 is intriguing but won’t likely result in practical changes in the approach to fighting the virus in the near term.

“Getting a deeper understanding of potential genetic factors or other characteristics – that could really help us understand why the virus just comes and goes without any ill effects in some people, and in other people it produces really serious disease,” he says. “That will really help us eventually to design better vaccines to prevent it or reduce severity or even [treat] people who get severe disease.”

In the meantime, Dr. Al-Aly says, “it’s still best to do everything you can to avoid infection in the first place – even if you’re vaccinated or previously infected, you should really try to avoid reinfection.”

That means sit outside if you can when visiting a restaurant. Wear a mask on a plane, even though it’s not required. And get vaccinated and boosted.

“In the future, there may be more tools to address this pandemic, but that’s really the best advice for now,” Dr. Al-Aly says.

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

Scientists have found three types of long COVID, which have their own symptoms and seem to appear across several coronavirus variants, according to a new preprint study published on MedRxiv that hasn’t yet been peer-reviewed.

Long COVID has been hard to define due to its large number of symptoms, but researchers at King’s College London have identified three distinct profiles – with long-term symptoms focused on neurological, respiratory, or physical conditions. So far, they also found patterns among people infected with the original coronavirus strain, the Alpha variant, and the Delta variant.

“These data show clearly that post-COVID syndrome is not just one condition but appears to have several subtypes,” Claire Steves, PhD, one of the study authors and a senior clinical lecturer in King’s College London’s School of Life Course & Population Sciences, said in a statement.

“Understanding the root causes of these subtypes may help in finding treatment strategies,” she said. “Moreover, these data emphasize the need for long-COVID services to incorporate a personalized approach sensitive to the issues of each individual.”

The research team analyzed ZOE COVID app data for 1,459 people who have had symptoms for more than 84 days, or 12 weeks, according to their definition of long COVID or post-COVID syndrome.

They found that the largest group had a cluster of symptoms in the nervous system, such as fatigue, brain fog, and headaches. It was the most common subtype among the Alpha variant, which was dominant in winter 2020-2021, and the Delta variant, which was dominant in 2021.

The second group had respiratory symptoms, such as chest pain and severe shortness of breath, which could suggest lung damage, the researchers wrote. It was the largest cluster for the original coronavirus strain in spring 2020, when people were unvaccinated.

The third group included people who reported a diverse range of physical symptoms, including heart palpitations, muscle aches and pain, and changes to their skin and hair. This group had some of the “most severe and debilitating multi-organ symptoms,” the researchers wrote.

The researchers found that the subtypes were similar in vaccinated and unvaccinated people based on the variants investigated so far. But the data showed that the risk of long COVID was reduced by vaccination.

In addition, although the three subtypes were present in all the variants, other symptom clusters had subtle differences among the variants, such as symptoms in the stomach and intestines. The differences could be due to other things that changed during the pandemic, such as the time of year, social behaviors, and treatments, the researchers said.

“Machine learning approaches, such as clustering analysis, have made it possible to start exploring and identifying different profiles of post-COVID syndrome,” Marc Modat, PhD, who led the analysis and is a senior lecturer at King’s College London’s School of Biomedical Engineering & Imaging Sciences, said in the statement.

“This opens new avenues of research to better understand COVID-19 and to motivate clinical research that might mitigate the long-term effects of the disease,” he said.

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

Scientists have found three types of long COVID, which have their own symptoms and seem to appear across several coronavirus variants, according to a new preprint study published on MedRxiv that hasn’t yet been peer-reviewed.

Long COVID has been hard to define due to its large number of symptoms, but researchers at King’s College London have identified three distinct profiles – with long-term symptoms focused on neurological, respiratory, or physical conditions. So far, they also found patterns among people infected with the original coronavirus strain, the Alpha variant, and the Delta variant.

“These data show clearly that post-COVID syndrome is not just one condition but appears to have several subtypes,” Claire Steves, PhD, one of the study authors and a senior clinical lecturer in King’s College London’s School of Life Course & Population Sciences, said in a statement.

“Understanding the root causes of these subtypes may help in finding treatment strategies,” she said. “Moreover, these data emphasize the need for long-COVID services to incorporate a personalized approach sensitive to the issues of each individual.”

The research team analyzed ZOE COVID app data for 1,459 people who have had symptoms for more than 84 days, or 12 weeks, according to their definition of long COVID or post-COVID syndrome.

They found that the largest group had a cluster of symptoms in the nervous system, such as fatigue, brain fog, and headaches. It was the most common subtype among the Alpha variant, which was dominant in winter 2020-2021, and the Delta variant, which was dominant in 2021.

The second group had respiratory symptoms, such as chest pain and severe shortness of breath, which could suggest lung damage, the researchers wrote. It was the largest cluster for the original coronavirus strain in spring 2020, when people were unvaccinated.

The third group included people who reported a diverse range of physical symptoms, including heart palpitations, muscle aches and pain, and changes to their skin and hair. This group had some of the “most severe and debilitating multi-organ symptoms,” the researchers wrote.

The researchers found that the subtypes were similar in vaccinated and unvaccinated people based on the variants investigated so far. But the data showed that the risk of long COVID was reduced by vaccination.

In addition, although the three subtypes were present in all the variants, other symptom clusters had subtle differences among the variants, such as symptoms in the stomach and intestines. The differences could be due to other things that changed during the pandemic, such as the time of year, social behaviors, and treatments, the researchers said.

“Machine learning approaches, such as clustering analysis, have made it possible to start exploring and identifying different profiles of post-COVID syndrome,” Marc Modat, PhD, who led the analysis and is a senior lecturer at King’s College London’s School of Biomedical Engineering & Imaging Sciences, said in the statement.

“This opens new avenues of research to better understand COVID-19 and to motivate clinical research that might mitigate the long-term effects of the disease,” he said.

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

Scientists have found three types of long COVID, which have their own symptoms and seem to appear across several coronavirus variants, according to a new preprint study published on MedRxiv that hasn’t yet been peer-reviewed.

Long COVID has been hard to define due to its large number of symptoms, but researchers at King’s College London have identified three distinct profiles – with long-term symptoms focused on neurological, respiratory, or physical conditions. So far, they also found patterns among people infected with the original coronavirus strain, the Alpha variant, and the Delta variant.

“These data show clearly that post-COVID syndrome is not just one condition but appears to have several subtypes,” Claire Steves, PhD, one of the study authors and a senior clinical lecturer in King’s College London’s School of Life Course & Population Sciences, said in a statement.

“Understanding the root causes of these subtypes may help in finding treatment strategies,” she said. “Moreover, these data emphasize the need for long-COVID services to incorporate a personalized approach sensitive to the issues of each individual.”

The research team analyzed ZOE COVID app data for 1,459 people who have had symptoms for more than 84 days, or 12 weeks, according to their definition of long COVID or post-COVID syndrome.

They found that the largest group had a cluster of symptoms in the nervous system, such as fatigue, brain fog, and headaches. It was the most common subtype among the Alpha variant, which was dominant in winter 2020-2021, and the Delta variant, which was dominant in 2021.

The second group had respiratory symptoms, such as chest pain and severe shortness of breath, which could suggest lung damage, the researchers wrote. It was the largest cluster for the original coronavirus strain in spring 2020, when people were unvaccinated.

The third group included people who reported a diverse range of physical symptoms, including heart palpitations, muscle aches and pain, and changes to their skin and hair. This group had some of the “most severe and debilitating multi-organ symptoms,” the researchers wrote.

The researchers found that the subtypes were similar in vaccinated and unvaccinated people based on the variants investigated so far. But the data showed that the risk of long COVID was reduced by vaccination.

In addition, although the three subtypes were present in all the variants, other symptom clusters had subtle differences among the variants, such as symptoms in the stomach and intestines. The differences could be due to other things that changed during the pandemic, such as the time of year, social behaviors, and treatments, the researchers said.

“Machine learning approaches, such as clustering analysis, have made it possible to start exploring and identifying different profiles of post-COVID syndrome,” Marc Modat, PhD, who led the analysis and is a senior lecturer at King’s College London’s School of Biomedical Engineering & Imaging Sciences, said in the statement.

“This opens new avenues of research to better understand COVID-19 and to motivate clinical research that might mitigate the long-term effects of the disease,” he said.

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