Atopic Dermatitis

Key clinical point: Majority of patients with atopic dermatitis (AD) who tested positive for COVID-19 experienced subclinical infection; however, extended treatment with systemic corticosteroids during the pandemic increased chances of COVID-19-associated hospitalization.

Major finding: Most (93.1%) of the COVID-19 infections in patients with AD were subclinical. COVID-19-related complications resulted in 6% hospitalizations, 0.3% mechanical ventilations, and 1.1% deaths. Intake of systemic corticosteroids for 2 or more months during the pandemic was associated with hospitalizations related to COVID-19 (adjusted odds ratio, 1.96; P = .005). However, mortality associated with COVID-19 was not predicted by AD-related variables.

Study details: Findings are from a nested case-control study including 3618 patients with AD who tested positive for COVID-19.

Disclosures: No funding source was identified. Dr. Cohen declared serving as an advisor, investigator, or speaker for various sources. The other authors had no disclosures.

Source: Kridin K et al. Dermatitis. 2021 Jun 15. doi: 10.1097/DER.0000000000000772.

Key clinical point: Majority of patients with atopic dermatitis (AD) who tested positive for COVID-19 experienced subclinical infection; however, extended treatment with systemic corticosteroids during the pandemic increased chances of COVID-19-associated hospitalization.

Major finding: Most (93.1%) of the COVID-19 infections in patients with AD were subclinical. COVID-19-related complications resulted in 6% hospitalizations, 0.3% mechanical ventilations, and 1.1% deaths. Intake of systemic corticosteroids for 2 or more months during the pandemic was associated with hospitalizations related to COVID-19 (adjusted odds ratio, 1.96; P = .005). However, mortality associated with COVID-19 was not predicted by AD-related variables.

Study details: Findings are from a nested case-control study including 3618 patients with AD who tested positive for COVID-19.

Disclosures: No funding source was identified. Dr. Cohen declared serving as an advisor, investigator, or speaker for various sources. The other authors had no disclosures.

Source: Kridin K et al. Dermatitis. 2021 Jun 15. doi: 10.1097/DER.0000000000000772.

Key clinical point: Majority of patients with atopic dermatitis (AD) who tested positive for COVID-19 experienced subclinical infection; however, extended treatment with systemic corticosteroids during the pandemic increased chances of COVID-19-associated hospitalization.

Major finding: Most (93.1%) of the COVID-19 infections in patients with AD were subclinical. COVID-19-related complications resulted in 6% hospitalizations, 0.3% mechanical ventilations, and 1.1% deaths. Intake of systemic corticosteroids for 2 or more months during the pandemic was associated with hospitalizations related to COVID-19 (adjusted odds ratio, 1.96; P = .005). However, mortality associated with COVID-19 was not predicted by AD-related variables.

Study details: Findings are from a nested case-control study including 3618 patients with AD who tested positive for COVID-19.

Disclosures: No funding source was identified. Dr. Cohen declared serving as an advisor, investigator, or speaker for various sources. The other authors had no disclosures.

Source: Kridin K et al. Dermatitis. 2021 Jun 15. doi: 10.1097/DER.0000000000000772.

Key clinical point: Delgocitinib ointment was effective and safe for up to 56 weeks in pediatric patients with atopic dermatitis (AD).

Major finding: By the end of initial 4-week treatment, least-squares mean percentage change from baseline in the modified Eczema Area and Severity Index (mEASI) score was significantly greater for delgocitinib vs vehicle (−39.3% vs +10.9%; P less than .001) groups. Improvement in mEASI score continued through the 52-week extension phase. Treatment-related mild adverse events were reported by only 9.7% of patients.

Study details: Findings are from a phase 3 study including 137 Japanese patients aged 2-15 years with mild/moderate/severe AD randomly allocated to either delgocitinib (0.25%) or vehicle ointment for 4 weeks. Eligible patients entered the 52-week extension study phase to receive 0.25% or 0.5% delgocitinib ointment.

Disclosures: This study was funded by Japan Tobacco Inc. and Torii Pharmaceutical Co, Ltd. Some of the authors declared receiving consulting fees, research grants, speaker honoraria, and/or advisory board honoraria from various sources including Japan Tobacco Inc. Two authors declared being employees of Japan Tobacco Inc.

Source: Nakagawa H et al. J Am Acad Dermatol. 2021 Jun 9. doi: 10.1016/j.jaad.2021.06.014.

Key clinical point: Delgocitinib ointment was effective and safe for up to 56 weeks in pediatric patients with atopic dermatitis (AD).

Major finding: By the end of initial 4-week treatment, least-squares mean percentage change from baseline in the modified Eczema Area and Severity Index (mEASI) score was significantly greater for delgocitinib vs vehicle (−39.3% vs +10.9%; P less than .001) groups. Improvement in mEASI score continued through the 52-week extension phase. Treatment-related mild adverse events were reported by only 9.7% of patients.

Study details: Findings are from a phase 3 study including 137 Japanese patients aged 2-15 years with mild/moderate/severe AD randomly allocated to either delgocitinib (0.25%) or vehicle ointment for 4 weeks. Eligible patients entered the 52-week extension study phase to receive 0.25% or 0.5% delgocitinib ointment.

Disclosures: This study was funded by Japan Tobacco Inc. and Torii Pharmaceutical Co, Ltd. Some of the authors declared receiving consulting fees, research grants, speaker honoraria, and/or advisory board honoraria from various sources including Japan Tobacco Inc. Two authors declared being employees of Japan Tobacco Inc.

Source: Nakagawa H et al. J Am Acad Dermatol. 2021 Jun 9. doi: 10.1016/j.jaad.2021.06.014.

Key clinical point: Delgocitinib ointment was effective and safe for up to 56 weeks in pediatric patients with atopic dermatitis (AD).

Major finding: By the end of initial 4-week treatment, least-squares mean percentage change from baseline in the modified Eczema Area and Severity Index (mEASI) score was significantly greater for delgocitinib vs vehicle (−39.3% vs +10.9%; P less than .001) groups. Improvement in mEASI score continued through the 52-week extension phase. Treatment-related mild adverse events were reported by only 9.7% of patients.

Study details: Findings are from a phase 3 study including 137 Japanese patients aged 2-15 years with mild/moderate/severe AD randomly allocated to either delgocitinib (0.25%) or vehicle ointment for 4 weeks. Eligible patients entered the 52-week extension study phase to receive 0.25% or 0.5% delgocitinib ointment.

Disclosures: This study was funded by Japan Tobacco Inc. and Torii Pharmaceutical Co, Ltd. Some of the authors declared receiving consulting fees, research grants, speaker honoraria, and/or advisory board honoraria from various sources including Japan Tobacco Inc. Two authors declared being employees of Japan Tobacco Inc.

Source: Nakagawa H et al. J Am Acad Dermatol. 2021 Jun 9. doi: 10.1016/j.jaad.2021.06.014.

Key clinical point: A topical cream containing cultured autologous antimicrobial-producing coagulase-negative strain of Staphylococcus (CoNS-AM+) safely decreased Staphylococcus aureus colonization and improved disease severity in patients with atopic dermatitis (AD).

Major finding: At the end of treatment, CoNS-AM+ reduced S. aureus colonization on lesioned skin by 99.2% compared with the vehicle (mean of log10 ratio to baseline, −1.702 vs 0.671; P = .01), which persisted even 4 days after treatment (P = .03). On day 11, Eczema Area and Severity Index scores improved significantly in patients receiving CoNS-AM+ vs vehicle (P = .04). No serious adverse events were recorded in either group.

Study details: This was a double-blind, vehicle-controlled randomized clinical trial of 11 adult patients with moderate-to-severe AD randomly assigned to either CoNS-AM+ (n=5) or the vehicle (n=6).

Disclosures: This work was supported by grants from the National Institute of Health. Dr. Nakatsuji, Dr. Gallo, and Dr. Shafiq reported receiving grants and/or consulting fees from and holding patent/pending patent, and/or holding equity in various sources.

Source: Nakatsuji T et al. JAMA Dermatol. 2021 Jun 16. doi: 10.1001/jamadermatol.2021.1311.

Key clinical point: A topical cream containing cultured autologous antimicrobial-producing coagulase-negative strain of Staphylococcus (CoNS-AM+) safely decreased Staphylococcus aureus colonization and improved disease severity in patients with atopic dermatitis (AD).

Major finding: At the end of treatment, CoNS-AM+ reduced S. aureus colonization on lesioned skin by 99.2% compared with the vehicle (mean of log10 ratio to baseline, −1.702 vs 0.671; P = .01), which persisted even 4 days after treatment (P = .03). On day 11, Eczema Area and Severity Index scores improved significantly in patients receiving CoNS-AM+ vs vehicle (P = .04). No serious adverse events were recorded in either group.

Study details: This was a double-blind, vehicle-controlled randomized clinical trial of 11 adult patients with moderate-to-severe AD randomly assigned to either CoNS-AM+ (n=5) or the vehicle (n=6).

Disclosures: This work was supported by grants from the National Institute of Health. Dr. Nakatsuji, Dr. Gallo, and Dr. Shafiq reported receiving grants and/or consulting fees from and holding patent/pending patent, and/or holding equity in various sources.

Source: Nakatsuji T et al. JAMA Dermatol. 2021 Jun 16. doi: 10.1001/jamadermatol.2021.1311.

Key clinical point: A topical cream containing cultured autologous antimicrobial-producing coagulase-negative strain of Staphylococcus (CoNS-AM+) safely decreased Staphylococcus aureus colonization and improved disease severity in patients with atopic dermatitis (AD).

Major finding: At the end of treatment, CoNS-AM+ reduced S. aureus colonization on lesioned skin by 99.2% compared with the vehicle (mean of log10 ratio to baseline, −1.702 vs 0.671; P = .01), which persisted even 4 days after treatment (P = .03). On day 11, Eczema Area and Severity Index scores improved significantly in patients receiving CoNS-AM+ vs vehicle (P = .04). No serious adverse events were recorded in either group.

Study details: This was a double-blind, vehicle-controlled randomized clinical trial of 11 adult patients with moderate-to-severe AD randomly assigned to either CoNS-AM+ (n=5) or the vehicle (n=6).

Disclosures: This work was supported by grants from the National Institute of Health. Dr. Nakatsuji, Dr. Gallo, and Dr. Shafiq reported receiving grants and/or consulting fees from and holding patent/pending patent, and/or holding equity in various sources.

Source: Nakatsuji T et al. JAMA Dermatol. 2021 Jun 16. doi: 10.1001/jamadermatol.2021.1311.

Many validation studies of clinician- and patient-reported outcome measures for atopic dermatitis (AD) lack adequate reporting of race, ethnicity, and skin tone, according to results from a systematic review.

“AD is associated with considerable heterogeneity across different races and skin tones,” presenting study author Trisha Kaundinya said at the Revolutionizing Atopic Dermatitis symposium. “Compared with lighter skin tones, darker skin tones more commonly have diffuse xerosis, Dennis-Morgan lines, hyperlinearity of the palms, periorbital dark circles, lichenification, and prurigo nodularis. This heterogeneity can be challenging to assess in clinical trials and in practice.”

The Harmonizing Outcome Measures for Eczema (HOME) group has selected several scales by international consensus. For clinical trials, the group recommends the Patient-Oriented Eczema Measure (POEM), Eczema Area and Severity Index (EASI), and Dermatology Life Quality Index (DLQI). In clinical practice, the HOME group recommends the POEM, Patient-Oriented Scoring Atopic Dermatitis (PO-SCORAD), and the Numeric Rating Scale (NRS)-itch measures. “The psychometric validity and reliability of these outcome measures have undergone robust investigation before, but the validity and reliability of these outcome measures remains uncertain across different races, ethnicities, and skin tones,” Ms. Kaundinya said.

Jonathan Silverberg, MD, PhD, associate professor of dermatology at George Washington University, Washington, in collaboration with Andrew F. Alexis, MD, MPH, vice-chair for diversity and inclusion for the department of dermatology at Weill-Cornell Medicine, New York, and Jacob P. Thyssen, MD, PhD, at the University of Copenhagen, Denmark, sought to examine reporting of race, ethnicity, and skin tone, and to compare results across these groups from studies of psychometric properties for outcome measures in AD. Under the mentorship of Dr. Silverberg, Ms. Kaundinya, a medical student at Northwestern University, Chicago, and her research associates conducted a systematic review that searched PubMed and Embase and identified 165 relevant published studies of 41,146 individuals.

Of the individuals participating in these 165 studies, 73% had an unspecified racial background, 18% were White, 4% were Asian, 2% were Black, 2% were Hispanic, 1% were multiracial/other, and the remainder were American Indian/Alaskan Native. Only 55 of the studies (33%) reported the distribution of race or ethnicity, 5 (3%) reported the distribution of skin tone, and 16 (10%) reported psychometric differences in patients with different races, ethnicities, or skin tones. In addition, only 5 of 113 (4%) studies that did not report race, ethnicity, or skin tone–based differences acknowledged absence of stratification as a limitation.

Of note, significant differential item functioning was found between race subgroups for one or more items of the PO-SCORAD, the Patient-Reported Outcomes Measurement Information System (PROMIS) Itch Questionnaire (PIQ) Short Forms, POEM, DLQI, Hospital Anxiety and Depression Scale (HADS), Itchy Quality of Life (ItchyQOL) scale, 5-dimensions (5D) itch scale, Short Form (SF)-12, and NRS-itch. “Correlations of the POEM with the Investigator’s Global Assessment (IGA) differed the most between skin of color and lighter skin,” Ms. Kaundinya said.

“The POEM did seem to correlate similarly with the DLQI and the EASI in both white and nonwhite participants, which may indicate why this trifecta of instruments is recommended by the HOME group. One study found that substituting the erythema component of the EASI scale with greyness for darker skin, in which erythema is more challenging to assess, did not significantly improve the reliability of EASI. This indicates that further research is needed to investigate how EASI can be modified to perform better in darker skin tones.”

She pointed out that some studies of clinician-reported outcome measures were underpowered to detect meaningful differences between patient subgroups. “There were also insufficient data to perform meta-regression of differences between patient subgroups,” she said. “Overall, future studies are needed to determine whether outcome measures recommended by the HOME and other tools perform equally well across diverse patient populations. This systematic review indicates significant reporting and knowledge gaps for psychometric properties of outcome measures by race, ethnicity, or skin tone in AD.”

Ms. Kaundinya reported having no relevant financial disclosures. Dr. Silverberg, the study’s senior author, is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.

dbrunk@mdedge.com

Many validation studies of clinician- and patient-reported outcome measures for atopic dermatitis (AD) lack adequate reporting of race, ethnicity, and skin tone, according to results from a systematic review.

“AD is associated with considerable heterogeneity across different races and skin tones,” presenting study author Trisha Kaundinya said at the Revolutionizing Atopic Dermatitis symposium. “Compared with lighter skin tones, darker skin tones more commonly have diffuse xerosis, Dennis-Morgan lines, hyperlinearity of the palms, periorbital dark circles, lichenification, and prurigo nodularis. This heterogeneity can be challenging to assess in clinical trials and in practice.”

The Harmonizing Outcome Measures for Eczema (HOME) group has selected several scales by international consensus. For clinical trials, the group recommends the Patient-Oriented Eczema Measure (POEM), Eczema Area and Severity Index (EASI), and Dermatology Life Quality Index (DLQI). In clinical practice, the HOME group recommends the POEM, Patient-Oriented Scoring Atopic Dermatitis (PO-SCORAD), and the Numeric Rating Scale (NRS)-itch measures. “The psychometric validity and reliability of these outcome measures have undergone robust investigation before, but the validity and reliability of these outcome measures remains uncertain across different races, ethnicities, and skin tones,” Ms. Kaundinya said.

Jonathan Silverberg, MD, PhD, associate professor of dermatology at George Washington University, Washington, in collaboration with Andrew F. Alexis, MD, MPH, vice-chair for diversity and inclusion for the department of dermatology at Weill-Cornell Medicine, New York, and Jacob P. Thyssen, MD, PhD, at the University of Copenhagen, Denmark, sought to examine reporting of race, ethnicity, and skin tone, and to compare results across these groups from studies of psychometric properties for outcome measures in AD. Under the mentorship of Dr. Silverberg, Ms. Kaundinya, a medical student at Northwestern University, Chicago, and her research associates conducted a systematic review that searched PubMed and Embase and identified 165 relevant published studies of 41,146 individuals.

Of the individuals participating in these 165 studies, 73% had an unspecified racial background, 18% were White, 4% were Asian, 2% were Black, 2% were Hispanic, 1% were multiracial/other, and the remainder were American Indian/Alaskan Native. Only 55 of the studies (33%) reported the distribution of race or ethnicity, 5 (3%) reported the distribution of skin tone, and 16 (10%) reported psychometric differences in patients with different races, ethnicities, or skin tones. In addition, only 5 of 113 (4%) studies that did not report race, ethnicity, or skin tone–based differences acknowledged absence of stratification as a limitation.

Of note, significant differential item functioning was found between race subgroups for one or more items of the PO-SCORAD, the Patient-Reported Outcomes Measurement Information System (PROMIS) Itch Questionnaire (PIQ) Short Forms, POEM, DLQI, Hospital Anxiety and Depression Scale (HADS), Itchy Quality of Life (ItchyQOL) scale, 5-dimensions (5D) itch scale, Short Form (SF)-12, and NRS-itch. “Correlations of the POEM with the Investigator’s Global Assessment (IGA) differed the most between skin of color and lighter skin,” Ms. Kaundinya said.

“The POEM did seem to correlate similarly with the DLQI and the EASI in both white and nonwhite participants, which may indicate why this trifecta of instruments is recommended by the HOME group. One study found that substituting the erythema component of the EASI scale with greyness for darker skin, in which erythema is more challenging to assess, did not significantly improve the reliability of EASI. This indicates that further research is needed to investigate how EASI can be modified to perform better in darker skin tones.”

She pointed out that some studies of clinician-reported outcome measures were underpowered to detect meaningful differences between patient subgroups. “There were also insufficient data to perform meta-regression of differences between patient subgroups,” she said. “Overall, future studies are needed to determine whether outcome measures recommended by the HOME and other tools perform equally well across diverse patient populations. This systematic review indicates significant reporting and knowledge gaps for psychometric properties of outcome measures by race, ethnicity, or skin tone in AD.”

Ms. Kaundinya reported having no relevant financial disclosures. Dr. Silverberg, the study’s senior author, is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.

dbrunk@mdedge.com

Many validation studies of clinician- and patient-reported outcome measures for atopic dermatitis (AD) lack adequate reporting of race, ethnicity, and skin tone, according to results from a systematic review.

“AD is associated with considerable heterogeneity across different races and skin tones,” presenting study author Trisha Kaundinya said at the Revolutionizing Atopic Dermatitis symposium. “Compared with lighter skin tones, darker skin tones more commonly have diffuse xerosis, Dennis-Morgan lines, hyperlinearity of the palms, periorbital dark circles, lichenification, and prurigo nodularis. This heterogeneity can be challenging to assess in clinical trials and in practice.”

The Harmonizing Outcome Measures for Eczema (HOME) group has selected several scales by international consensus. For clinical trials, the group recommends the Patient-Oriented Eczema Measure (POEM), Eczema Area and Severity Index (EASI), and Dermatology Life Quality Index (DLQI). In clinical practice, the HOME group recommends the POEM, Patient-Oriented Scoring Atopic Dermatitis (PO-SCORAD), and the Numeric Rating Scale (NRS)-itch measures. “The psychometric validity and reliability of these outcome measures have undergone robust investigation before, but the validity and reliability of these outcome measures remains uncertain across different races, ethnicities, and skin tones,” Ms. Kaundinya said.

Jonathan Silverberg, MD, PhD, associate professor of dermatology at George Washington University, Washington, in collaboration with Andrew F. Alexis, MD, MPH, vice-chair for diversity and inclusion for the department of dermatology at Weill-Cornell Medicine, New York, and Jacob P. Thyssen, MD, PhD, at the University of Copenhagen, Denmark, sought to examine reporting of race, ethnicity, and skin tone, and to compare results across these groups from studies of psychometric properties for outcome measures in AD. Under the mentorship of Dr. Silverberg, Ms. Kaundinya, a medical student at Northwestern University, Chicago, and her research associates conducted a systematic review that searched PubMed and Embase and identified 165 relevant published studies of 41,146 individuals.

Of the individuals participating in these 165 studies, 73% had an unspecified racial background, 18% were White, 4% were Asian, 2% were Black, 2% were Hispanic, 1% were multiracial/other, and the remainder were American Indian/Alaskan Native. Only 55 of the studies (33%) reported the distribution of race or ethnicity, 5 (3%) reported the distribution of skin tone, and 16 (10%) reported psychometric differences in patients with different races, ethnicities, or skin tones. In addition, only 5 of 113 (4%) studies that did not report race, ethnicity, or skin tone–based differences acknowledged absence of stratification as a limitation.

Of note, significant differential item functioning was found between race subgroups for one or more items of the PO-SCORAD, the Patient-Reported Outcomes Measurement Information System (PROMIS) Itch Questionnaire (PIQ) Short Forms, POEM, DLQI, Hospital Anxiety and Depression Scale (HADS), Itchy Quality of Life (ItchyQOL) scale, 5-dimensions (5D) itch scale, Short Form (SF)-12, and NRS-itch. “Correlations of the POEM with the Investigator’s Global Assessment (IGA) differed the most between skin of color and lighter skin,” Ms. Kaundinya said.

“The POEM did seem to correlate similarly with the DLQI and the EASI in both white and nonwhite participants, which may indicate why this trifecta of instruments is recommended by the HOME group. One study found that substituting the erythema component of the EASI scale with greyness for darker skin, in which erythema is more challenging to assess, did not significantly improve the reliability of EASI. This indicates that further research is needed to investigate how EASI can be modified to perform better in darker skin tones.”

She pointed out that some studies of clinician-reported outcome measures were underpowered to detect meaningful differences between patient subgroups. “There were also insufficient data to perform meta-regression of differences between patient subgroups,” she said. “Overall, future studies are needed to determine whether outcome measures recommended by the HOME and other tools perform equally well across diverse patient populations. This systematic review indicates significant reporting and knowledge gaps for psychometric properties of outcome measures by race, ethnicity, or skin tone in AD.”

Ms. Kaundinya reported having no relevant financial disclosures. Dr. Silverberg, the study’s senior author, is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.

dbrunk@mdedge.com

A meta-analysis by Australian researchers found no link between childhood vaccinations and an increase in allergies and asthma. In fact, children who received the BCG vaccine actually had a lesser incidence of eczema than other children, but there was no difference shown in any of the allergies or asthma.

The researchers, in a report published in the journal Allergy, write, “We found no evidence that childhood vaccination with commonly administered vaccines was associated with increased risk of later allergic disease.”

“Allergies have increased worldwide in the last 50 years, and in developed countries, earlier,” said study author Caroline J. Lodge, PhD, principal research fellow at the University of Melbourne, in an interview. “In developing countries, it is still a crisis.” No one knows why, she said. That was the reason for the recent study.

Allergic diseases such as allergic rhinitis (hay fever) and food allergies have a serious influence on quality of life, and the incidence is growing. According to the Global Asthma Network, there are 334 million people living with asthma. Between 2%-10% of adults have atopic eczema, and more than a 250,000 people have food allergies. This coincides temporally with an increase in mass vaccination of children.

Unlike the controversy surrounding vaccinations and autism, which has long been debunked as baseless, a hygiene hypothesis postulates that when children acquire immunity from many diseases, they become vulnerable to allergic reactions. Thanks to vaccinations, children in the developed world now are routinely immune to dozens of diseases.

That immunity leads to suppression of a major antibody response, increasing sensitivity to allergens and allergic disease. Suspicion of a link with childhood vaccinations has been used by opponents of vaccines in lobbying campaigns jeopardizing the sustainability of vaccine programs. In recent days, for example, the state of Tennessee has halted a program to encourage vaccination for COVID-19 as well as all other vaccinations, the result of pressure on the state by anti-vaccination lobbying.

But the Melbourne researchers reported that the meta-analysis of 42 published research studies doesn’t support the vaccine–allergy hypothesis. Using PubMed and EMBASE records between January 1946 and January 2018, researchers selected studies to be included in the analysis, looking for allergic outcomes in children given BCG or vaccines for measles or pertussis. Thirty-five publications reported cohort studies, and seven were based on randomized controlled trials.

The Australian study is not the only one showing the same lack of linkage between vaccination and allergy. The International Study of Asthma and Allergies in Childhood (ISAAC) found no association between mass vaccination and atopic disease. A 1998 Swedish study of 669 children found no differences in the incidence of allergic diseases between those who received pertussis vaccine and those who did not.

“The bottom line is that vaccines prevent infectious diseases,” said Matthew B. Laurens, associate professor of pediatrics at the University of Maryland, Baltimore, in an interview. Dr. Laurens was not part of the Australian study.

“Large-scale epidemiological studies do not support the theory that vaccines are associated with an increased risk of allergy or asthma,” he stressed. “Parents should not be deterred from vaccinating their children because of fears that this would increase risks of allergy and/or asthma.”

Dr. Lodge and Dr. Laurens have disclosed no relevant financial relationships.

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

A meta-analysis by Australian researchers found no link between childhood vaccinations and an increase in allergies and asthma. In fact, children who received the BCG vaccine actually had a lesser incidence of eczema than other children, but there was no difference shown in any of the allergies or asthma.

The researchers, in a report published in the journal Allergy, write, “We found no evidence that childhood vaccination with commonly administered vaccines was associated with increased risk of later allergic disease.”

“Allergies have increased worldwide in the last 50 years, and in developed countries, earlier,” said study author Caroline J. Lodge, PhD, principal research fellow at the University of Melbourne, in an interview. “In developing countries, it is still a crisis.” No one knows why, she said. That was the reason for the recent study.

Allergic diseases such as allergic rhinitis (hay fever) and food allergies have a serious influence on quality of life, and the incidence is growing. According to the Global Asthma Network, there are 334 million people living with asthma. Between 2%-10% of adults have atopic eczema, and more than a 250,000 people have food allergies. This coincides temporally with an increase in mass vaccination of children.

Unlike the controversy surrounding vaccinations and autism, which has long been debunked as baseless, a hygiene hypothesis postulates that when children acquire immunity from many diseases, they become vulnerable to allergic reactions. Thanks to vaccinations, children in the developed world now are routinely immune to dozens of diseases.

That immunity leads to suppression of a major antibody response, increasing sensitivity to allergens and allergic disease. Suspicion of a link with childhood vaccinations has been used by opponents of vaccines in lobbying campaigns jeopardizing the sustainability of vaccine programs. In recent days, for example, the state of Tennessee has halted a program to encourage vaccination for COVID-19 as well as all other vaccinations, the result of pressure on the state by anti-vaccination lobbying.

But the Melbourne researchers reported that the meta-analysis of 42 published research studies doesn’t support the vaccine–allergy hypothesis. Using PubMed and EMBASE records between January 1946 and January 2018, researchers selected studies to be included in the analysis, looking for allergic outcomes in children given BCG or vaccines for measles or pertussis. Thirty-five publications reported cohort studies, and seven were based on randomized controlled trials.

The Australian study is not the only one showing the same lack of linkage between vaccination and allergy. The International Study of Asthma and Allergies in Childhood (ISAAC) found no association between mass vaccination and atopic disease. A 1998 Swedish study of 669 children found no differences in the incidence of allergic diseases between those who received pertussis vaccine and those who did not.

“The bottom line is that vaccines prevent infectious diseases,” said Matthew B. Laurens, associate professor of pediatrics at the University of Maryland, Baltimore, in an interview. Dr. Laurens was not part of the Australian study.

“Large-scale epidemiological studies do not support the theory that vaccines are associated with an increased risk of allergy or asthma,” he stressed. “Parents should not be deterred from vaccinating their children because of fears that this would increase risks of allergy and/or asthma.”

Dr. Lodge and Dr. Laurens have disclosed no relevant financial relationships.

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

A meta-analysis by Australian researchers found no link between childhood vaccinations and an increase in allergies and asthma. In fact, children who received the BCG vaccine actually had a lesser incidence of eczema than other children, but there was no difference shown in any of the allergies or asthma.

The researchers, in a report published in the journal Allergy, write, “We found no evidence that childhood vaccination with commonly administered vaccines was associated with increased risk of later allergic disease.”

“Allergies have increased worldwide in the last 50 years, and in developed countries, earlier,” said study author Caroline J. Lodge, PhD, principal research fellow at the University of Melbourne, in an interview. “In developing countries, it is still a crisis.” No one knows why, she said. That was the reason for the recent study.

Allergic diseases such as allergic rhinitis (hay fever) and food allergies have a serious influence on quality of life, and the incidence is growing. According to the Global Asthma Network, there are 334 million people living with asthma. Between 2%-10% of adults have atopic eczema, and more than a 250,000 people have food allergies. This coincides temporally with an increase in mass vaccination of children.

Unlike the controversy surrounding vaccinations and autism, which has long been debunked as baseless, a hygiene hypothesis postulates that when children acquire immunity from many diseases, they become vulnerable to allergic reactions. Thanks to vaccinations, children in the developed world now are routinely immune to dozens of diseases.

That immunity leads to suppression of a major antibody response, increasing sensitivity to allergens and allergic disease. Suspicion of a link with childhood vaccinations has been used by opponents of vaccines in lobbying campaigns jeopardizing the sustainability of vaccine programs. In recent days, for example, the state of Tennessee has halted a program to encourage vaccination for COVID-19 as well as all other vaccinations, the result of pressure on the state by anti-vaccination lobbying.

But the Melbourne researchers reported that the meta-analysis of 42 published research studies doesn’t support the vaccine–allergy hypothesis. Using PubMed and EMBASE records between January 1946 and January 2018, researchers selected studies to be included in the analysis, looking for allergic outcomes in children given BCG or vaccines for measles or pertussis. Thirty-five publications reported cohort studies, and seven were based on randomized controlled trials.

The Australian study is not the only one showing the same lack of linkage between vaccination and allergy. The International Study of Asthma and Allergies in Childhood (ISAAC) found no association between mass vaccination and atopic disease. A 1998 Swedish study of 669 children found no differences in the incidence of allergic diseases between those who received pertussis vaccine and those who did not.

“The bottom line is that vaccines prevent infectious diseases,” said Matthew B. Laurens, associate professor of pediatrics at the University of Maryland, Baltimore, in an interview. Dr. Laurens was not part of the Australian study.

“Large-scale epidemiological studies do not support the theory that vaccines are associated with an increased risk of allergy or asthma,” he stressed. “Parents should not be deterred from vaccinating their children because of fears that this would increase risks of allergy and/or asthma.”

Dr. Lodge and Dr. Laurens have disclosed no relevant financial relationships.

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

In what could be a model for other states, Texas has become the first state to exempt physicians from prior authorizations for meeting insurer benchmarks.

The law was passed in June and will take effect in September. It excuses physicians from having to obtain prior authorization if, during the previous 6 months, 90% of their treatments met medical necessity criteria by the health insurer. Through this law, doctors in the state will spend less time getting approvals for treatments for their patients.

Automatic approval of authorizations for treatments – or what the Texas Medical Association (TMA) calls a “gold card” – “allows patients to get the care they need in a more timely fashion,” says Debra Patt, MD, an Austin, Tex.–based oncologist and former chair of the council on legislation for the TMA.

Eighty-seven percent of Texas physicians reported a “drastic increase over the past five years in the burden of prior authorization on their patients and their practices,” per a 2020 survey by the TMA. Nearly half (48%) of Texas physicians have hired staff whose work focuses on processing requests for prior authorization, according to the survey.

Jack Resneck Jr., MD, a San Francisco–based dermatologist and president-elect of the American Medical Association (AMA), said other states have investigated ways to ease the impact of prior authorizations on physicians, but no other state has passed such a law.

Administrative burdens plague physicians around the country. The Medscape Physician Compensation Report 2021 found that physicians spend on average 15.6 hours per week on paperwork and administrative duties.
 

Better outcomes, less anxiety for patients

Dr. Patt, who testified in support of the law’s passage in the Texas legislature, says automatic approval of authorizations “is better for patients because it reduces their anxiety about whether they’re able to get the treatments they need now, and they will have better outcomes if they’re able to receive more timely care.”

Recently, a chemotherapy treatment Dr. Patt prescribed for one of her patients was not authorized by an insurer. The result is “a lot of anxiety and potentially health problems” for the patient, said Dr. Patt.

She expects that automatic approval for treatments will be based on prescribing patterns during the preceding 6 months. “It means that when I order a test today, the [health insurer] looks back at my record 6 months previously,” she said. Still, Dr. Patt awaits guidance from the Texas Department of Insurance, which regulates health insurers in the state, regarding the law.

Dr. Resneck said the pharmacy counter is where most patients encounter prior authorization delays. “That’s when the pharmacist looks at them and says, ‘Actually, this isn’t covered by your health insurer’s formulary,’ or it isn’t covered fully on their formulary.”

One of Dr. Resneck’s patients had a life-altering case of eczema that lasted many years. Because of the condition, the patient couldn’t work or maintain meaningful bonds with family members. A biologic treatment transformed his patient’s life. The patient was able to return to work and to re-engage with family, said Dr. Resneck. But a year after his patient started the treatment, the health insurer wouldn’t authorize the treatment because the patient wasn’t experiencing the same symptoms.

The patient didn’t have the same symptoms because the biologic treatment worked, said Dr. Resneck.

Kristine Grow, a spokesperson for America’s Health Insurance Plans, a national association for health insurers, said, “The use of prior authorization is relatively small – typically, less than 15% – and can help ensure safer opioid prescribing, help prevent dangerous drug interactions, and help protect patients from unnecessary exposure to potentially harmful radiation for inappropriate diagnostic imaging. Numerous studies show that Americans frequently receive inappropriate care, and 25% of unnecessary treatments are associated with complications or adverse events.”

Medical management tools, such as prior authorization, are an “an important way” to deliver “safe, high-quality care” to patients, she added.
 

State and federal efforts to curb prior authorization

In addition to efforts to curb prior authorization in other states, the AMA supports the Improving Seniors’ Timely Access to Care Act (HR 3173). The act includes a provision related to “gold-carding,” said Robert Mills, an AMA spokesperson.

The bill establishes requirements and standards for prior authorization processes related to Medicare Advantage (MA) plans. The requirements and standards for MA plans include the following:

• Establishing an electronic prior authorization program that meets specific standards, such as the ability to provide real-time decisions in response to requests for items and services that are routinely approved.
• Publishing on an annual basis specific prior authorization information, including the percentage of requests approved and the average response time.
• Meeting standards set by the Centers for Medicare & Medicaid Services related to the quality and timeliness of prior authorization determinations.

The act was introduced to the U.S. House of Representatives in May, after which it was referred to two committees for consideration.

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

In what could be a model for other states, Texas has become the first state to exempt physicians from prior authorizations for meeting insurer benchmarks.

The law was passed in June and will take effect in September. It excuses physicians from having to obtain prior authorization if, during the previous 6 months, 90% of their treatments met medical necessity criteria by the health insurer. Through this law, doctors in the state will spend less time getting approvals for treatments for their patients.

Automatic approval of authorizations for treatments – or what the Texas Medical Association (TMA) calls a “gold card” – “allows patients to get the care they need in a more timely fashion,” says Debra Patt, MD, an Austin, Tex.–based oncologist and former chair of the council on legislation for the TMA.

Eighty-seven percent of Texas physicians reported a “drastic increase over the past five years in the burden of prior authorization on their patients and their practices,” per a 2020 survey by the TMA. Nearly half (48%) of Texas physicians have hired staff whose work focuses on processing requests for prior authorization, according to the survey.

Jack Resneck Jr., MD, a San Francisco–based dermatologist and president-elect of the American Medical Association (AMA), said other states have investigated ways to ease the impact of prior authorizations on physicians, but no other state has passed such a law.

Administrative burdens plague physicians around the country. The Medscape Physician Compensation Report 2021 found that physicians spend on average 15.6 hours per week on paperwork and administrative duties.
 

Better outcomes, less anxiety for patients

Dr. Patt, who testified in support of the law’s passage in the Texas legislature, says automatic approval of authorizations “is better for patients because it reduces their anxiety about whether they’re able to get the treatments they need now, and they will have better outcomes if they’re able to receive more timely care.”

Recently, a chemotherapy treatment Dr. Patt prescribed for one of her patients was not authorized by an insurer. The result is “a lot of anxiety and potentially health problems” for the patient, said Dr. Patt.

She expects that automatic approval for treatments will be based on prescribing patterns during the preceding 6 months. “It means that when I order a test today, the [health insurer] looks back at my record 6 months previously,” she said. Still, Dr. Patt awaits guidance from the Texas Department of Insurance, which regulates health insurers in the state, regarding the law.

Dr. Resneck said the pharmacy counter is where most patients encounter prior authorization delays. “That’s when the pharmacist looks at them and says, ‘Actually, this isn’t covered by your health insurer’s formulary,’ or it isn’t covered fully on their formulary.”

One of Dr. Resneck’s patients had a life-altering case of eczema that lasted many years. Because of the condition, the patient couldn’t work or maintain meaningful bonds with family members. A biologic treatment transformed his patient’s life. The patient was able to return to work and to re-engage with family, said Dr. Resneck. But a year after his patient started the treatment, the health insurer wouldn’t authorize the treatment because the patient wasn’t experiencing the same symptoms.

The patient didn’t have the same symptoms because the biologic treatment worked, said Dr. Resneck.

Kristine Grow, a spokesperson for America’s Health Insurance Plans, a national association for health insurers, said, “The use of prior authorization is relatively small – typically, less than 15% – and can help ensure safer opioid prescribing, help prevent dangerous drug interactions, and help protect patients from unnecessary exposure to potentially harmful radiation for inappropriate diagnostic imaging. Numerous studies show that Americans frequently receive inappropriate care, and 25% of unnecessary treatments are associated with complications or adverse events.”

Medical management tools, such as prior authorization, are an “an important way” to deliver “safe, high-quality care” to patients, she added.
 

State and federal efforts to curb prior authorization

In addition to efforts to curb prior authorization in other states, the AMA supports the Improving Seniors’ Timely Access to Care Act (HR 3173). The act includes a provision related to “gold-carding,” said Robert Mills, an AMA spokesperson.

The bill establishes requirements and standards for prior authorization processes related to Medicare Advantage (MA) plans. The requirements and standards for MA plans include the following:

• Establishing an electronic prior authorization program that meets specific standards, such as the ability to provide real-time decisions in response to requests for items and services that are routinely approved.
• Publishing on an annual basis specific prior authorization information, including the percentage of requests approved and the average response time.
• Meeting standards set by the Centers for Medicare & Medicaid Services related to the quality and timeliness of prior authorization determinations.

The act was introduced to the U.S. House of Representatives in May, after which it was referred to two committees for consideration.

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

In what could be a model for other states, Texas has become the first state to exempt physicians from prior authorizations for meeting insurer benchmarks.

The law was passed in June and will take effect in September. It excuses physicians from having to obtain prior authorization if, during the previous 6 months, 90% of their treatments met medical necessity criteria by the health insurer. Through this law, doctors in the state will spend less time getting approvals for treatments for their patients.

Automatic approval of authorizations for treatments – or what the Texas Medical Association (TMA) calls a “gold card” – “allows patients to get the care they need in a more timely fashion,” says Debra Patt, MD, an Austin, Tex.–based oncologist and former chair of the council on legislation for the TMA.

Eighty-seven percent of Texas physicians reported a “drastic increase over the past five years in the burden of prior authorization on their patients and their practices,” per a 2020 survey by the TMA. Nearly half (48%) of Texas physicians have hired staff whose work focuses on processing requests for prior authorization, according to the survey.

Jack Resneck Jr., MD, a San Francisco–based dermatologist and president-elect of the American Medical Association (AMA), said other states have investigated ways to ease the impact of prior authorizations on physicians, but no other state has passed such a law.

Administrative burdens plague physicians around the country. The Medscape Physician Compensation Report 2021 found that physicians spend on average 15.6 hours per week on paperwork and administrative duties.
 

Better outcomes, less anxiety for patients

Dr. Patt, who testified in support of the law’s passage in the Texas legislature, says automatic approval of authorizations “is better for patients because it reduces their anxiety about whether they’re able to get the treatments they need now, and they will have better outcomes if they’re able to receive more timely care.”

Recently, a chemotherapy treatment Dr. Patt prescribed for one of her patients was not authorized by an insurer. The result is “a lot of anxiety and potentially health problems” for the patient, said Dr. Patt.

She expects that automatic approval for treatments will be based on prescribing patterns during the preceding 6 months. “It means that when I order a test today, the [health insurer] looks back at my record 6 months previously,” she said. Still, Dr. Patt awaits guidance from the Texas Department of Insurance, which regulates health insurers in the state, regarding the law.

Dr. Resneck said the pharmacy counter is where most patients encounter prior authorization delays. “That’s when the pharmacist looks at them and says, ‘Actually, this isn’t covered by your health insurer’s formulary,’ or it isn’t covered fully on their formulary.”

One of Dr. Resneck’s patients had a life-altering case of eczema that lasted many years. Because of the condition, the patient couldn’t work or maintain meaningful bonds with family members. A biologic treatment transformed his patient’s life. The patient was able to return to work and to re-engage with family, said Dr. Resneck. But a year after his patient started the treatment, the health insurer wouldn’t authorize the treatment because the patient wasn’t experiencing the same symptoms.

The patient didn’t have the same symptoms because the biologic treatment worked, said Dr. Resneck.

Kristine Grow, a spokesperson for America’s Health Insurance Plans, a national association for health insurers, said, “The use of prior authorization is relatively small – typically, less than 15% – and can help ensure safer opioid prescribing, help prevent dangerous drug interactions, and help protect patients from unnecessary exposure to potentially harmful radiation for inappropriate diagnostic imaging. Numerous studies show that Americans frequently receive inappropriate care, and 25% of unnecessary treatments are associated with complications or adverse events.”

Medical management tools, such as prior authorization, are an “an important way” to deliver “safe, high-quality care” to patients, she added.
 

State and federal efforts to curb prior authorization

In addition to efforts to curb prior authorization in other states, the AMA supports the Improving Seniors’ Timely Access to Care Act (HR 3173). The act includes a provision related to “gold-carding,” said Robert Mills, an AMA spokesperson.

The bill establishes requirements and standards for prior authorization processes related to Medicare Advantage (MA) plans. The requirements and standards for MA plans include the following:

• Establishing an electronic prior authorization program that meets specific standards, such as the ability to provide real-time decisions in response to requests for items and services that are routinely approved.
• Publishing on an annual basis specific prior authorization information, including the percentage of requests approved and the average response time.
• Meeting standards set by the Centers for Medicare & Medicaid Services related to the quality and timeliness of prior authorization determinations.

The act was introduced to the U.S. House of Representatives in May, after which it was referred to two committees for consideration.

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

Higher direct ultraviolet light exposure in the first 3 months of life was linked to lower incidence of proinflammatory immune markers and lower incidence of eczema in an early-stage double-blind, randomized controlled trial.  

Kristina Rueter, MD, with the University of Western Australia, Perth, who presented her team’s findings on Sunday at the European Academy of Allergy and Clinical Immunology (EAACI) Hybrid Congress 2021, said their study is the first to demonstrate the association.

“There has been a significant rise in allergic diseases, particularly within the last 20-30 years,” Dr. Rueter noted.  

“Changes to the genetic pool take thousands of years to have an impact,” she said, “so the question is why do we have the significant, very recent rise of allergic diseases?”

Suboptimal vitamin D levels during infancy, lifestyle changes, nutritional changes, and living at higher latitudes have emerged as explanations.

In this study, 195 high-risk newborns were randomized to receive oral vitamin D supplements (400 IU/day) or placebo until 6 months of age.

Researchers found that UV light exposure appears more beneficial than vitamin D supplements as an allergy prevention strategy in the critical early years of immune system development.

The researchers used a novel approach of attaching a personal UV dosimeter to the infants’ clothing to measure direct UV light exposure (290-380 nm). Vitamin D levels were measured at 3, 6, 12, and 30 months of age. Immune function was assessed at 6 months of age, and food allergy, eczema, and wheeze were assessed at 6, 12, and 30 months of age.

At 3 (P < .01) and 6 (P = .02) months of age, vitamin D levels were greater in the children who received vitamin D supplements than those who received placebo, but there was no difference in eczema incidence between groups. The finding matched those of previous studies that compared the supplements with placebo, Dr. Rueter said.

However, infants with eczema were found to have had less UV light exposure compared to those without eczema (median interquartile range [IQR], 555 J/m² vs. 998 J/m²; P = .023).

“We also found an inverse correlation between total UV light exposure and toll-like receptor cytokine production,” Dr. Rueter said.

“The more direct UV light exposure a child got, the less the chance to develop eczema,” she said.

Researchers then extended their analysis to see whether the effect of direct UV light exposure on reduced eczema would be maintained in the first 2.5 years of life, “and we could see again a significant difference, that the children who received higher UV light exposure had less eczema,” Dr. Rueter said.

Barbara Rogala, MD, PhD, professor at the Medical University of Silesia, Katowice, Poland, told this news organization that, just as in studies on vitamin D in adult populations, there must be a balance in infant studies between potential benefit of a therapeutic strategy of vitamin D and sunlight and risk of side effects. (Dr. Rogala was not involved in Dr. Rueter’s study.)

Although vitamin D supplements are a standard part of infant care, exposure to sunlight can come with cancer risk, she noted.

Dr. Rueter agreed caution is necessary.

“You have to follow the cancer guidelines,” she said. “Sunlight may play a role in causing skin cancer, and lots of research needs to be done to find the right balance between what is a good amount which may influence the immune system in a positive way and what, on the other hand, might be too much.”

As for vitamin D supplements, Dr. Rueter said, toxic levels require “extremely high doses,” so with 400 IU/day used in the study, children are likely not being overtreated by combining sunlight and vitamin D supplements.

The study was supported by grants from Telethon–New Children’s Hospital Research Fund, Australia; Asthma Foundation of Western Australia; and the Princess Margaret Hospital Foundation, Australia. Dr. Rueter and Dr. Rogala have reported no relevant financial relationships.

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

Higher direct ultraviolet light exposure in the first 3 months of life was linked to lower incidence of proinflammatory immune markers and lower incidence of eczema in an early-stage double-blind, randomized controlled trial.  

Kristina Rueter, MD, with the University of Western Australia, Perth, who presented her team’s findings on Sunday at the European Academy of Allergy and Clinical Immunology (EAACI) Hybrid Congress 2021, said their study is the first to demonstrate the association.

“There has been a significant rise in allergic diseases, particularly within the last 20-30 years,” Dr. Rueter noted.  

“Changes to the genetic pool take thousands of years to have an impact,” she said, “so the question is why do we have the significant, very recent rise of allergic diseases?”

Suboptimal vitamin D levels during infancy, lifestyle changes, nutritional changes, and living at higher latitudes have emerged as explanations.

In this study, 195 high-risk newborns were randomized to receive oral vitamin D supplements (400 IU/day) or placebo until 6 months of age.

Researchers found that UV light exposure appears more beneficial than vitamin D supplements as an allergy prevention strategy in the critical early years of immune system development.

The researchers used a novel approach of attaching a personal UV dosimeter to the infants’ clothing to measure direct UV light exposure (290-380 nm). Vitamin D levels were measured at 3, 6, 12, and 30 months of age. Immune function was assessed at 6 months of age, and food allergy, eczema, and wheeze were assessed at 6, 12, and 30 months of age.

At 3 (P < .01) and 6 (P = .02) months of age, vitamin D levels were greater in the children who received vitamin D supplements than those who received placebo, but there was no difference in eczema incidence between groups. The finding matched those of previous studies that compared the supplements with placebo, Dr. Rueter said.

However, infants with eczema were found to have had less UV light exposure compared to those without eczema (median interquartile range [IQR], 555 J/m² vs. 998 J/m²; P = .023).

“We also found an inverse correlation between total UV light exposure and toll-like receptor cytokine production,” Dr. Rueter said.

“The more direct UV light exposure a child got, the less the chance to develop eczema,” she said.

Researchers then extended their analysis to see whether the effect of direct UV light exposure on reduced eczema would be maintained in the first 2.5 years of life, “and we could see again a significant difference, that the children who received higher UV light exposure had less eczema,” Dr. Rueter said.

Barbara Rogala, MD, PhD, professor at the Medical University of Silesia, Katowice, Poland, told this news organization that, just as in studies on vitamin D in adult populations, there must be a balance in infant studies between potential benefit of a therapeutic strategy of vitamin D and sunlight and risk of side effects. (Dr. Rogala was not involved in Dr. Rueter’s study.)

Although vitamin D supplements are a standard part of infant care, exposure to sunlight can come with cancer risk, she noted.

Dr. Rueter agreed caution is necessary.

“You have to follow the cancer guidelines,” she said. “Sunlight may play a role in causing skin cancer, and lots of research needs to be done to find the right balance between what is a good amount which may influence the immune system in a positive way and what, on the other hand, might be too much.”

As for vitamin D supplements, Dr. Rueter said, toxic levels require “extremely high doses,” so with 400 IU/day used in the study, children are likely not being overtreated by combining sunlight and vitamin D supplements.

The study was supported by grants from Telethon–New Children’s Hospital Research Fund, Australia; Asthma Foundation of Western Australia; and the Princess Margaret Hospital Foundation, Australia. Dr. Rueter and Dr. Rogala have reported no relevant financial relationships.

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

Higher direct ultraviolet light exposure in the first 3 months of life was linked to lower incidence of proinflammatory immune markers and lower incidence of eczema in an early-stage double-blind, randomized controlled trial.  

Kristina Rueter, MD, with the University of Western Australia, Perth, who presented her team’s findings on Sunday at the European Academy of Allergy and Clinical Immunology (EAACI) Hybrid Congress 2021, said their study is the first to demonstrate the association.

“There has been a significant rise in allergic diseases, particularly within the last 20-30 years,” Dr. Rueter noted.  

“Changes to the genetic pool take thousands of years to have an impact,” she said, “so the question is why do we have the significant, very recent rise of allergic diseases?”

Suboptimal vitamin D levels during infancy, lifestyle changes, nutritional changes, and living at higher latitudes have emerged as explanations.

In this study, 195 high-risk newborns were randomized to receive oral vitamin D supplements (400 IU/day) or placebo until 6 months of age.

Researchers found that UV light exposure appears more beneficial than vitamin D supplements as an allergy prevention strategy in the critical early years of immune system development.

The researchers used a novel approach of attaching a personal UV dosimeter to the infants’ clothing to measure direct UV light exposure (290-380 nm). Vitamin D levels were measured at 3, 6, 12, and 30 months of age. Immune function was assessed at 6 months of age, and food allergy, eczema, and wheeze were assessed at 6, 12, and 30 months of age.

At 3 (P < .01) and 6 (P = .02) months of age, vitamin D levels were greater in the children who received vitamin D supplements than those who received placebo, but there was no difference in eczema incidence between groups. The finding matched those of previous studies that compared the supplements with placebo, Dr. Rueter said.

However, infants with eczema were found to have had less UV light exposure compared to those without eczema (median interquartile range [IQR], 555 J/m² vs. 998 J/m²; P = .023).

“We also found an inverse correlation between total UV light exposure and toll-like receptor cytokine production,” Dr. Rueter said.

“The more direct UV light exposure a child got, the less the chance to develop eczema,” she said.

Researchers then extended their analysis to see whether the effect of direct UV light exposure on reduced eczema would be maintained in the first 2.5 years of life, “and we could see again a significant difference, that the children who received higher UV light exposure had less eczema,” Dr. Rueter said.

Barbara Rogala, MD, PhD, professor at the Medical University of Silesia, Katowice, Poland, told this news organization that, just as in studies on vitamin D in adult populations, there must be a balance in infant studies between potential benefit of a therapeutic strategy of vitamin D and sunlight and risk of side effects. (Dr. Rogala was not involved in Dr. Rueter’s study.)

Although vitamin D supplements are a standard part of infant care, exposure to sunlight can come with cancer risk, she noted.

Dr. Rueter agreed caution is necessary.

“You have to follow the cancer guidelines,” she said. “Sunlight may play a role in causing skin cancer, and lots of research needs to be done to find the right balance between what is a good amount which may influence the immune system in a positive way and what, on the other hand, might be too much.”

As for vitamin D supplements, Dr. Rueter said, toxic levels require “extremely high doses,” so with 400 IU/day used in the study, children are likely not being overtreated by combining sunlight and vitamin D supplements.

The study was supported by grants from Telethon–New Children’s Hospital Research Fund, Australia; Asthma Foundation of Western Australia; and the Princess Margaret Hospital Foundation, Australia. Dr. Rueter and Dr. Rogala have reported no relevant financial relationships.

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

The heterogeneous clinical course of atopic dermatitis (AD) and its differing signs, symptoms, burden, and response to treatment can pose a quandary for physicians.

This is behind a new classification framework called DESCRIBE-AD, proposed by Jonathan I. Silverberg, MD, PhD, MPH, not only as a way to standardize the assessment of AD in clinical practice – but also to improve the classification of AD in clinical practice and clinical trials, facilitate tailoring of therapy to individual patient characteristics, and better identify therapeutically relevant disease subsets.

Dr. Silverberg, director of clinical research in the department of dermatology at George Washington University, Washington, debuted DESCRIBE-AD during the Revolutionizing Atopic Dermatitis symposium. The “D” in the mnemonic stands for dermatitis morphology and phenotype, the “E” for evolution of disease, the “S” for symptom severity, the “C” for comorbid health disorders, the “R” for response to therapy, the “I” for intensity of lesions, the “B” for burden of disease, and the “E” for extent of lesions.

At the meeting, he discussed the concepts behind each letter of the mnemonic.
 

Dermatitis morphology and phenotype

In the dermatitis morphology and phenotype component of DESCRIBE-AD, “there’s a lot to consider,” he said. “There are chronic signs like lichenification and prurigo nodules, which have treatment ramifications,” such as the length of time patients may need to be treated, and possibly “the use of more potent, targeted options to go after some of these lesions.”

Recent studies suggest that nummular lesions have a different underlying pathogenesis suggesting an overlap between Th2 and Th17 cell–mediated lesions. “How does that impact response to targeted therapies?” he asked. “We have no idea. We need to learn that.” He noted that psoriasiform lesions are not limited to Asian patients, but also appear in elderly patients with AD. “They look different [in elderly patients] and they may respond differently; they have more psoriasiform lesions and it’s not exactly clear why.”

Other morphologic variants of AD to be aware of include follicular eczema, xerosis, and the itch-dominant form, which Dr. Silverberg and colleagues addressed in a recently published study. “There are some patients who have milder-looking lesions, but their itch is just out of control,” he said. “This is a pattern that we need to recognize.”

Evolution of disease, symptom severity

Factors to consider for the evolution of disease component of the proposed classification include age of AD onset or disease recurrence, frequency and duration of flares, disease activity between flares, periods of disease clearance, and the overall disease trajectory. “We do get patients who say that every year their disease seems to get worse over time, for reasons that are not always clear,” Dr. Silverberg said.

Assessment tools he recommends for the symptom severity component of DESCRIBE-AD include the patient-reported global AD severity, numerical rating scale (NRS) worst or average itch in the past 7 days, the Skin Pain NRS, and the Sleep Quality NRS, which each take fewer than 30 seconds to complete. “You can have your nurses do this or can you have the patients fill out the form in the waiting area before they see you,” Dr. Silverberg said.

He also advises asking patients about the number of nights they experience sleep disturbance and if they have difficulty falling asleep or have nighttime awakenings because of their AD. Symptoms of anxiety and depression can be assessed with the Hospital Anxiety and Depression Scale and the Patient-Health Questionnaire–9, which each take 2-3 minutes to complete.

Recommended assessment tools for other symptoms – such as bleeding, oozing, and xerosis – include the Patient-Oriented Eczema Measure, which takes 2-3 minutes to complete, and the Atopic Dermatitis Control Tool or the Recap of Atopic Eczema, which each take 2-3 minutes to complete.
 

Comorbid health disorders

Comorbid health disorders linked to AD are varied and include atopic comorbidities such as asthma or wheeze, hay fever or oculonasal symptoms, food allergy, recurrent infections such as herpes simplex virus, mental health disorders, alopecia areata, Th1-mediated comorbidities, and adverse events to medication such as venous thromboembolism, hypertension, and impaired renal or liver function. “All of these are important because if the patients have these at baseline, they may not be good candidates for some therapies that cause these types of side effects,” Dr. Silverberg said.

Response to therapy, intensity of lesions

As for response to therapy, clinicians can ask patients, “How do you feel you’re improving?” But it’s also important to assess the signs, symptoms, frequency of flares, and comorbidities as part of that response to therapy, “and of course the adverse events and treatment burden,” he said.

For the intensity of lesions component of DESCRIBE-AD, Dr. Silverberg said that the Investigator’s Global Assessment–AD is an effective tool for clinical use. “You can also use tools like the Eczema Area and Severity Index or the Scoring AD, but recognize these are challenging,” and can be difficult to use if not well trained to use them, he said. “At the very least, do an Investigator’s Global Assessment and do a body surface area measurement.”

In his opinion, four key signs that should be assessed in clinical trials are erythema, edema/papulation, excoriation, and lichenification/prurigo nodules.
 

Burden of disease

In terms of assessing AD disease burden, guidelines from the American Academy of Dermatology don’t give a specific tool to use, but recommend asking open-ended questions, Dr. Silverberg said. “I would not recommend that, because when you ask an open-ended question, the flood gates open up because most patients are suffering miserably with this disease when it’s uncontrolled.

“That’s why it’s valuable to use structured, validated tools like the Dermatology Life Quality Index and the Patient Reported Outcome Measurement Information System. They don’t take a lot of time to complete, and you can look at the score and determine how burdensome their disease is, even in a busy clinical practice. They’re not going to slow you down; they’re going to speed you up and make you better at your therapeutic decision-making. I can guarantee you that most patients will love you for it. Sometimes patients say to me, ‘you’re the first doctor to ask these questions.’ ”
 

Extent of disease

Finally, for the extent of disease component of DESCRIBE-AD, he emphasized the importance of doing a full-body exam to appreciate the affected body surface area, flexural versus extensor distribution, and involvement and severity of disease on special sites such as the face, hands, feet, genitals, and scalp.

Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.

dbrunk@mdedge.com

The heterogeneous clinical course of atopic dermatitis (AD) and its differing signs, symptoms, burden, and response to treatment can pose a quandary for physicians.

This is behind a new classification framework called DESCRIBE-AD, proposed by Jonathan I. Silverberg, MD, PhD, MPH, not only as a way to standardize the assessment of AD in clinical practice – but also to improve the classification of AD in clinical practice and clinical trials, facilitate tailoring of therapy to individual patient characteristics, and better identify therapeutically relevant disease subsets.

Dr. Silverberg, director of clinical research in the department of dermatology at George Washington University, Washington, debuted DESCRIBE-AD during the Revolutionizing Atopic Dermatitis symposium. The “D” in the mnemonic stands for dermatitis morphology and phenotype, the “E” for evolution of disease, the “S” for symptom severity, the “C” for comorbid health disorders, the “R” for response to therapy, the “I” for intensity of lesions, the “B” for burden of disease, and the “E” for extent of lesions.

At the meeting, he discussed the concepts behind each letter of the mnemonic.
 

Dermatitis morphology and phenotype

In the dermatitis morphology and phenotype component of DESCRIBE-AD, “there’s a lot to consider,” he said. “There are chronic signs like lichenification and prurigo nodules, which have treatment ramifications,” such as the length of time patients may need to be treated, and possibly “the use of more potent, targeted options to go after some of these lesions.”

Recent studies suggest that nummular lesions have a different underlying pathogenesis suggesting an overlap between Th2 and Th17 cell–mediated lesions. “How does that impact response to targeted therapies?” he asked. “We have no idea. We need to learn that.” He noted that psoriasiform lesions are not limited to Asian patients, but also appear in elderly patients with AD. “They look different [in elderly patients] and they may respond differently; they have more psoriasiform lesions and it’s not exactly clear why.”

Other morphologic variants of AD to be aware of include follicular eczema, xerosis, and the itch-dominant form, which Dr. Silverberg and colleagues addressed in a recently published study. “There are some patients who have milder-looking lesions, but their itch is just out of control,” he said. “This is a pattern that we need to recognize.”

Evolution of disease, symptom severity

Factors to consider for the evolution of disease component of the proposed classification include age of AD onset or disease recurrence, frequency and duration of flares, disease activity between flares, periods of disease clearance, and the overall disease trajectory. “We do get patients who say that every year their disease seems to get worse over time, for reasons that are not always clear,” Dr. Silverberg said.

Assessment tools he recommends for the symptom severity component of DESCRIBE-AD include the patient-reported global AD severity, numerical rating scale (NRS) worst or average itch in the past 7 days, the Skin Pain NRS, and the Sleep Quality NRS, which each take fewer than 30 seconds to complete. “You can have your nurses do this or can you have the patients fill out the form in the waiting area before they see you,” Dr. Silverberg said.

He also advises asking patients about the number of nights they experience sleep disturbance and if they have difficulty falling asleep or have nighttime awakenings because of their AD. Symptoms of anxiety and depression can be assessed with the Hospital Anxiety and Depression Scale and the Patient-Health Questionnaire–9, which each take 2-3 minutes to complete.

Recommended assessment tools for other symptoms – such as bleeding, oozing, and xerosis – include the Patient-Oriented Eczema Measure, which takes 2-3 minutes to complete, and the Atopic Dermatitis Control Tool or the Recap of Atopic Eczema, which each take 2-3 minutes to complete.
 

Comorbid health disorders

Comorbid health disorders linked to AD are varied and include atopic comorbidities such as asthma or wheeze, hay fever or oculonasal symptoms, food allergy, recurrent infections such as herpes simplex virus, mental health disorders, alopecia areata, Th1-mediated comorbidities, and adverse events to medication such as venous thromboembolism, hypertension, and impaired renal or liver function. “All of these are important because if the patients have these at baseline, they may not be good candidates for some therapies that cause these types of side effects,” Dr. Silverberg said.

Response to therapy, intensity of lesions

As for response to therapy, clinicians can ask patients, “How do you feel you’re improving?” But it’s also important to assess the signs, symptoms, frequency of flares, and comorbidities as part of that response to therapy, “and of course the adverse events and treatment burden,” he said.

For the intensity of lesions component of DESCRIBE-AD, Dr. Silverberg said that the Investigator’s Global Assessment–AD is an effective tool for clinical use. “You can also use tools like the Eczema Area and Severity Index or the Scoring AD, but recognize these are challenging,” and can be difficult to use if not well trained to use them, he said. “At the very least, do an Investigator’s Global Assessment and do a body surface area measurement.”

In his opinion, four key signs that should be assessed in clinical trials are erythema, edema/papulation, excoriation, and lichenification/prurigo nodules.
 

Burden of disease

In terms of assessing AD disease burden, guidelines from the American Academy of Dermatology don’t give a specific tool to use, but recommend asking open-ended questions, Dr. Silverberg said. “I would not recommend that, because when you ask an open-ended question, the flood gates open up because most patients are suffering miserably with this disease when it’s uncontrolled.

“That’s why it’s valuable to use structured, validated tools like the Dermatology Life Quality Index and the Patient Reported Outcome Measurement Information System. They don’t take a lot of time to complete, and you can look at the score and determine how burdensome their disease is, even in a busy clinical practice. They’re not going to slow you down; they’re going to speed you up and make you better at your therapeutic decision-making. I can guarantee you that most patients will love you for it. Sometimes patients say to me, ‘you’re the first doctor to ask these questions.’ ”
 

Extent of disease

Finally, for the extent of disease component of DESCRIBE-AD, he emphasized the importance of doing a full-body exam to appreciate the affected body surface area, flexural versus extensor distribution, and involvement and severity of disease on special sites such as the face, hands, feet, genitals, and scalp.

Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.

dbrunk@mdedge.com

The heterogeneous clinical course of atopic dermatitis (AD) and its differing signs, symptoms, burden, and response to treatment can pose a quandary for physicians.

This is behind a new classification framework called DESCRIBE-AD, proposed by Jonathan I. Silverberg, MD, PhD, MPH, not only as a way to standardize the assessment of AD in clinical practice – but also to improve the classification of AD in clinical practice and clinical trials, facilitate tailoring of therapy to individual patient characteristics, and better identify therapeutically relevant disease subsets.

Dr. Silverberg, director of clinical research in the department of dermatology at George Washington University, Washington, debuted DESCRIBE-AD during the Revolutionizing Atopic Dermatitis symposium. The “D” in the mnemonic stands for dermatitis morphology and phenotype, the “E” for evolution of disease, the “S” for symptom severity, the “C” for comorbid health disorders, the “R” for response to therapy, the “I” for intensity of lesions, the “B” for burden of disease, and the “E” for extent of lesions.

At the meeting, he discussed the concepts behind each letter of the mnemonic.
 

Dermatitis morphology and phenotype

In the dermatitis morphology and phenotype component of DESCRIBE-AD, “there’s a lot to consider,” he said. “There are chronic signs like lichenification and prurigo nodules, which have treatment ramifications,” such as the length of time patients may need to be treated, and possibly “the use of more potent, targeted options to go after some of these lesions.”

Recent studies suggest that nummular lesions have a different underlying pathogenesis suggesting an overlap between Th2 and Th17 cell–mediated lesions. “How does that impact response to targeted therapies?” he asked. “We have no idea. We need to learn that.” He noted that psoriasiform lesions are not limited to Asian patients, but also appear in elderly patients with AD. “They look different [in elderly patients] and they may respond differently; they have more psoriasiform lesions and it’s not exactly clear why.”

Other morphologic variants of AD to be aware of include follicular eczema, xerosis, and the itch-dominant form, which Dr. Silverberg and colleagues addressed in a recently published study. “There are some patients who have milder-looking lesions, but their itch is just out of control,” he said. “This is a pattern that we need to recognize.”

Evolution of disease, symptom severity

Factors to consider for the evolution of disease component of the proposed classification include age of AD onset or disease recurrence, frequency and duration of flares, disease activity between flares, periods of disease clearance, and the overall disease trajectory. “We do get patients who say that every year their disease seems to get worse over time, for reasons that are not always clear,” Dr. Silverberg said.

Assessment tools he recommends for the symptom severity component of DESCRIBE-AD include the patient-reported global AD severity, numerical rating scale (NRS) worst or average itch in the past 7 days, the Skin Pain NRS, and the Sleep Quality NRS, which each take fewer than 30 seconds to complete. “You can have your nurses do this or can you have the patients fill out the form in the waiting area before they see you,” Dr. Silverberg said.

He also advises asking patients about the number of nights they experience sleep disturbance and if they have difficulty falling asleep or have nighttime awakenings because of their AD. Symptoms of anxiety and depression can be assessed with the Hospital Anxiety and Depression Scale and the Patient-Health Questionnaire–9, which each take 2-3 minutes to complete.

Recommended assessment tools for other symptoms – such as bleeding, oozing, and xerosis – include the Patient-Oriented Eczema Measure, which takes 2-3 minutes to complete, and the Atopic Dermatitis Control Tool or the Recap of Atopic Eczema, which each take 2-3 minutes to complete.
 

Comorbid health disorders

Comorbid health disorders linked to AD are varied and include atopic comorbidities such as asthma or wheeze, hay fever or oculonasal symptoms, food allergy, recurrent infections such as herpes simplex virus, mental health disorders, alopecia areata, Th1-mediated comorbidities, and adverse events to medication such as venous thromboembolism, hypertension, and impaired renal or liver function. “All of these are important because if the patients have these at baseline, they may not be good candidates for some therapies that cause these types of side effects,” Dr. Silverberg said.

Response to therapy, intensity of lesions

As for response to therapy, clinicians can ask patients, “How do you feel you’re improving?” But it’s also important to assess the signs, symptoms, frequency of flares, and comorbidities as part of that response to therapy, “and of course the adverse events and treatment burden,” he said.

For the intensity of lesions component of DESCRIBE-AD, Dr. Silverberg said that the Investigator’s Global Assessment–AD is an effective tool for clinical use. “You can also use tools like the Eczema Area and Severity Index or the Scoring AD, but recognize these are challenging,” and can be difficult to use if not well trained to use them, he said. “At the very least, do an Investigator’s Global Assessment and do a body surface area measurement.”

In his opinion, four key signs that should be assessed in clinical trials are erythema, edema/papulation, excoriation, and lichenification/prurigo nodules.
 

Burden of disease

In terms of assessing AD disease burden, guidelines from the American Academy of Dermatology don’t give a specific tool to use, but recommend asking open-ended questions, Dr. Silverberg said. “I would not recommend that, because when you ask an open-ended question, the flood gates open up because most patients are suffering miserably with this disease when it’s uncontrolled.

“That’s why it’s valuable to use structured, validated tools like the Dermatology Life Quality Index and the Patient Reported Outcome Measurement Information System. They don’t take a lot of time to complete, and you can look at the score and determine how burdensome their disease is, even in a busy clinical practice. They’re not going to slow you down; they’re going to speed you up and make you better at your therapeutic decision-making. I can guarantee you that most patients will love you for it. Sometimes patients say to me, ‘you’re the first doctor to ask these questions.’ ”
 

Extent of disease

Finally, for the extent of disease component of DESCRIBE-AD, he emphasized the importance of doing a full-body exam to appreciate the affected body surface area, flexural versus extensor distribution, and involvement and severity of disease on special sites such as the face, hands, feet, genitals, and scalp.

Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.

dbrunk@mdedge.com

Sublingual immunotherapy (SLIT) emerged over a century ago as a gentler alternative to allergy shots. It uses the same antigens found in allergy shots, delivering them through tablets or drops under the tongue rather than by injecting them into the skin.

Yet injection immunotherapy has been the mainstay of allergy treatment in the United States. Allergy shots are “the bread and butter, keeping the lights on at allergy practices,” said allergist Sakina Bajowala, MD, of Kaneland Allergy and Asthma Center, in the Chicago area. So even “when environmental SLIT showed quite clearly that it had efficacy, people were so slow to adapt.”

SLIT – a daily treatment that builds protection from allergens gradually over years with few side effects – is popular around the globe, particularly for environmental allergies. But only a handful of clinics offer food SLIT. Even though recent trials in peanut-allergic children show that SLIT is far safer than oral immunotherapy and about as effective as the Food and Drug Administration–approved peanut-allergy product and has lasting benefits for toddlers, many allergists lack experience with customized immunotherapies and hesitate to offer an unregulated treatment for which the evidence base is still emerging.
 

Why hasn’t food allergy SLIT caught on?

One issue is that there is scant evidence from randomized, controlled trials. The treatments that clinics offer often hinge on insurance coverage, and increasingly, insurers only cover FDA-approved products. FDA approval requires thousands of patients being enrolled in long, expensive studies to prove the treatment’s merit. In a similar vein, doctors are trained to question methods that lack a strong publication base, for good reason.

Yet SLIT caught the attention of pioneering physicians who were intrigued by this “low-and-slow” immune-modifying approach, despite limited published evidence, and they sought real-world experience.

The late physician David Morris, MD, came across SLIT in the 1960s while searching for alternative ways to help mold-allergic farmers who were suffering terrible side effects from allergy shots. Dr. Morris attended conferences, learned more about sublingual techniques, got board certified in allergy, and opened Allergy Associates of La Crosse (Wis.), in 1970 to offer SLIT as a treatment for food and environmental allergies.

Dr. Morris and colleagues developed a protocol to create custom SLIT drops tailored to individual patients’ clinical histories and allergy test results. The method has been used to treat more than 200,000 patients. It has been used by allergist Nikhila Schroeder, MD, MEng, who learned SLIT methods while treating nearly 1,000 patients at Allergy Associates. In 2018, she opened her own direct-care SLIT practice, Allergenuity Health, in the Charlotte metropolitan area of North Carolina (see part 2 of this series).

Dr. Bajowala’s clinic offers SLIT in addition to oral immunotherapy (OIT). She was encouraged by the recent toddler SLIT data but wondered whether it would translate to a real-world setting. According to her calculations, the published protocol – according to which participants receive up to 4 mg/d over 6 months and continue receiving a daily maintenance dose of 4 mg for 3 years – would cost $10,000 per patient.

With this dosing regimen, the intervention is unaffordable, Dr. Bajowala said. And “there’s no way to make it cheaper because that’s the raw materials cost. It does not include labor or bottles or profit at all. That’s just $10,000 in peanut extract.”

Owing to cost, Dr. Bajowala’s clinic generally uses SLIT as a bridge to OIT. Her food allergy patients receive up to 1 mg/d and remain at that dose for a month or so before transitioning to OIT, “for which the supplies are orders of magnitude cheaper,” she said.

Dr. Schroeder said there is evidence for efficacy at microgram and even nanogram dosing – much lower than used in the recent food SLIT trials. Maintenance doses range from 50 ng/d to 25 mcg/d for environmental SLIT and 4-37 mcg/d for food SLIT, she said. The La Crosse method uses even lower dose ranges.

However, dosing information is not readily available, Dr. Schroeder noted. She has spent years scrutinizing articles and compiling information from allergen extract suppliers – all the while treating hundreds of SLIT patients. “I have had to expend a lot of time and effort,” said Dr. Schroeder. “It’s really hard to explain quickly.”

In the published literature, SLIT dosing recommendations vary widely. According to a 2007 analysis, environmental allergy symptoms improved with doses over a 1,000-fold range. What’s more, success did not scale with increased dosing and seemed to depend more on frequency and duration of treatment.

There are fewer studies regarding food SLIT. The most promising data come from recent trials of peanut-allergic children led by Edwin Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill. Still, “I am nervous to tell people to go do this based on 150 kids at one site,” Dr. Kim said. “We need to have a gigantic study across multiple sites that actually confirms what we have found in our single center.”

Because there are few published trials of food SLIT, confusion about which doses are optimal, how early to start, and how long the benefits last will be a barrier for many clinicians, said Douglas Mack, MD, FRCPC, assistant clinical professor in pediatrics at McMaster University, Hamilton, Ont.

Much could be learned from Allergy Associates of La Crosse, Allergenuity Health, and other clinics with SLIT experience involving thousands of patients. But that real-world data are messy and difficult to publish. Plus, it is hard for private allergists to find time to review charts, analyze data, and draft papers alongside seeing patients and running a clinic – especially without students and interns, who typically assist with academic research, Dr. Schroeder said.

Ruchi Gupta, MD, MPH, professor of pediatrics and medicine at Northwestern University, Chicago, and colleagues worked with a La Crosse team 6 or 7 years ago to try to analyze and publish SLIT outcomes for 121 peanut-allergic children who were treated for food and environmental allergies at the Wisconsin clinic. The researchers had hoped to publish an article describing caregiver-reported and clinical outcomes.

Among 73 caregivers who responded to a survey, more than half reported improved eczema, asthma, and environmental allergy symptoms, and virtually all families said SLIT calmed anxieties and minimized fear of allergic reactions. However, the clinical outcomes – skinprick test results, immune changes, and oral food challenges – were not as robust. And the data were incomplete. Some patients had traveled to La Crosse for SLIT drops but underwent skin and blood testing with their local allergist. Compiling records is “so much harder when you’re not doing a prospective clinical trial,” Dr. Gupta said.

The caregiver-reported outcomes were presented as a poster at the 2015 annual meeting of the American College of Allergy, Asthma, and Immunology and the 2016 annual meeting of the Pediatric Academic Society, said Jeff Kessler, MBA, FACHE, who is practice executive at La Crosse. However, with only self-reported data and no convincing lab metrics, the findings were never submitted for publication.

Others are eager to see clearer proof that SLIT works at doses lower than those published in the most recent trials. “If we can get efficacy with lower doses, that means we can increase accessibility, because we can lower the cost,” Dr. Bajowala said.

Robert Wood, MD, professor of pediatrics and director of pediatric allergy and immunology at Johns Hopkins University, Baltimore, has a pending grant proposal for a multifood trial of SLIT. “It’s a big missing piece,” he said.

Dr. Mack said that in Canada there was “almost an instant change in group think” when the Canadian Society of Allergy and Clinical Immunology published guidelines in support of OIT. With the new guidelines, “people are less concerned about liability. Once they start getting into OIT, I think you’re going to see SLIT coming right along for the ride.”

The shift will be slower in the United States, which has 20 times as many practicing allergists as Canada. Nevertheless, “I totally think SLIT has a place at the table,” Dr. Mack said. “I hope we start to see more high-quality data and people start to use it and experiment with it a bit and see how it works.”

A version of this article first appeared on Medscape.com. This is part three of a three-part series. Part one is here. Part two is here.

Sublingual immunotherapy (SLIT) emerged over a century ago as a gentler alternative to allergy shots. It uses the same antigens found in allergy shots, delivering them through tablets or drops under the tongue rather than by injecting them into the skin.

Yet injection immunotherapy has been the mainstay of allergy treatment in the United States. Allergy shots are “the bread and butter, keeping the lights on at allergy practices,” said allergist Sakina Bajowala, MD, of Kaneland Allergy and Asthma Center, in the Chicago area. So even “when environmental SLIT showed quite clearly that it had efficacy, people were so slow to adapt.”

SLIT – a daily treatment that builds protection from allergens gradually over years with few side effects – is popular around the globe, particularly for environmental allergies. But only a handful of clinics offer food SLIT. Even though recent trials in peanut-allergic children show that SLIT is far safer than oral immunotherapy and about as effective as the Food and Drug Administration–approved peanut-allergy product and has lasting benefits for toddlers, many allergists lack experience with customized immunotherapies and hesitate to offer an unregulated treatment for which the evidence base is still emerging.
 

Why hasn’t food allergy SLIT caught on?

One issue is that there is scant evidence from randomized, controlled trials. The treatments that clinics offer often hinge on insurance coverage, and increasingly, insurers only cover FDA-approved products. FDA approval requires thousands of patients being enrolled in long, expensive studies to prove the treatment’s merit. In a similar vein, doctors are trained to question methods that lack a strong publication base, for good reason.

Yet SLIT caught the attention of pioneering physicians who were intrigued by this “low-and-slow” immune-modifying approach, despite limited published evidence, and they sought real-world experience.

The late physician David Morris, MD, came across SLIT in the 1960s while searching for alternative ways to help mold-allergic farmers who were suffering terrible side effects from allergy shots. Dr. Morris attended conferences, learned more about sublingual techniques, got board certified in allergy, and opened Allergy Associates of La Crosse (Wis.), in 1970 to offer SLIT as a treatment for food and environmental allergies.

Dr. Morris and colleagues developed a protocol to create custom SLIT drops tailored to individual patients’ clinical histories and allergy test results. The method has been used to treat more than 200,000 patients. It has been used by allergist Nikhila Schroeder, MD, MEng, who learned SLIT methods while treating nearly 1,000 patients at Allergy Associates. In 2018, she opened her own direct-care SLIT practice, Allergenuity Health, in the Charlotte metropolitan area of North Carolina (see part 2 of this series).

Dr. Bajowala’s clinic offers SLIT in addition to oral immunotherapy (OIT). She was encouraged by the recent toddler SLIT data but wondered whether it would translate to a real-world setting. According to her calculations, the published protocol – according to which participants receive up to 4 mg/d over 6 months and continue receiving a daily maintenance dose of 4 mg for 3 years – would cost $10,000 per patient.

With this dosing regimen, the intervention is unaffordable, Dr. Bajowala said. And “there’s no way to make it cheaper because that’s the raw materials cost. It does not include labor or bottles or profit at all. That’s just $10,000 in peanut extract.”

Owing to cost, Dr. Bajowala’s clinic generally uses SLIT as a bridge to OIT. Her food allergy patients receive up to 1 mg/d and remain at that dose for a month or so before transitioning to OIT, “for which the supplies are orders of magnitude cheaper,” she said.

Dr. Schroeder said there is evidence for efficacy at microgram and even nanogram dosing – much lower than used in the recent food SLIT trials. Maintenance doses range from 50 ng/d to 25 mcg/d for environmental SLIT and 4-37 mcg/d for food SLIT, she said. The La Crosse method uses even lower dose ranges.

However, dosing information is not readily available, Dr. Schroeder noted. She has spent years scrutinizing articles and compiling information from allergen extract suppliers – all the while treating hundreds of SLIT patients. “I have had to expend a lot of time and effort,” said Dr. Schroeder. “It’s really hard to explain quickly.”

In the published literature, SLIT dosing recommendations vary widely. According to a 2007 analysis, environmental allergy symptoms improved with doses over a 1,000-fold range. What’s more, success did not scale with increased dosing and seemed to depend more on frequency and duration of treatment.

There are fewer studies regarding food SLIT. The most promising data come from recent trials of peanut-allergic children led by Edwin Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill. Still, “I am nervous to tell people to go do this based on 150 kids at one site,” Dr. Kim said. “We need to have a gigantic study across multiple sites that actually confirms what we have found in our single center.”

Because there are few published trials of food SLIT, confusion about which doses are optimal, how early to start, and how long the benefits last will be a barrier for many clinicians, said Douglas Mack, MD, FRCPC, assistant clinical professor in pediatrics at McMaster University, Hamilton, Ont.

Much could be learned from Allergy Associates of La Crosse, Allergenuity Health, and other clinics with SLIT experience involving thousands of patients. But that real-world data are messy and difficult to publish. Plus, it is hard for private allergists to find time to review charts, analyze data, and draft papers alongside seeing patients and running a clinic – especially without students and interns, who typically assist with academic research, Dr. Schroeder said.

Ruchi Gupta, MD, MPH, professor of pediatrics and medicine at Northwestern University, Chicago, and colleagues worked with a La Crosse team 6 or 7 years ago to try to analyze and publish SLIT outcomes for 121 peanut-allergic children who were treated for food and environmental allergies at the Wisconsin clinic. The researchers had hoped to publish an article describing caregiver-reported and clinical outcomes.

Among 73 caregivers who responded to a survey, more than half reported improved eczema, asthma, and environmental allergy symptoms, and virtually all families said SLIT calmed anxieties and minimized fear of allergic reactions. However, the clinical outcomes – skinprick test results, immune changes, and oral food challenges – were not as robust. And the data were incomplete. Some patients had traveled to La Crosse for SLIT drops but underwent skin and blood testing with their local allergist. Compiling records is “so much harder when you’re not doing a prospective clinical trial,” Dr. Gupta said.

The caregiver-reported outcomes were presented as a poster at the 2015 annual meeting of the American College of Allergy, Asthma, and Immunology and the 2016 annual meeting of the Pediatric Academic Society, said Jeff Kessler, MBA, FACHE, who is practice executive at La Crosse. However, with only self-reported data and no convincing lab metrics, the findings were never submitted for publication.

Others are eager to see clearer proof that SLIT works at doses lower than those published in the most recent trials. “If we can get efficacy with lower doses, that means we can increase accessibility, because we can lower the cost,” Dr. Bajowala said.

Robert Wood, MD, professor of pediatrics and director of pediatric allergy and immunology at Johns Hopkins University, Baltimore, has a pending grant proposal for a multifood trial of SLIT. “It’s a big missing piece,” he said.

Dr. Mack said that in Canada there was “almost an instant change in group think” when the Canadian Society of Allergy and Clinical Immunology published guidelines in support of OIT. With the new guidelines, “people are less concerned about liability. Once they start getting into OIT, I think you’re going to see SLIT coming right along for the ride.”

The shift will be slower in the United States, which has 20 times as many practicing allergists as Canada. Nevertheless, “I totally think SLIT has a place at the table,” Dr. Mack said. “I hope we start to see more high-quality data and people start to use it and experiment with it a bit and see how it works.”

A version of this article first appeared on Medscape.com. This is part three of a three-part series. Part one is here. Part two is here.

Sublingual immunotherapy (SLIT) emerged over a century ago as a gentler alternative to allergy shots. It uses the same antigens found in allergy shots, delivering them through tablets or drops under the tongue rather than by injecting them into the skin.

Yet injection immunotherapy has been the mainstay of allergy treatment in the United States. Allergy shots are “the bread and butter, keeping the lights on at allergy practices,” said allergist Sakina Bajowala, MD, of Kaneland Allergy and Asthma Center, in the Chicago area. So even “when environmental SLIT showed quite clearly that it had efficacy, people were so slow to adapt.”

SLIT – a daily treatment that builds protection from allergens gradually over years with few side effects – is popular around the globe, particularly for environmental allergies. But only a handful of clinics offer food SLIT. Even though recent trials in peanut-allergic children show that SLIT is far safer than oral immunotherapy and about as effective as the Food and Drug Administration–approved peanut-allergy product and has lasting benefits for toddlers, many allergists lack experience with customized immunotherapies and hesitate to offer an unregulated treatment for which the evidence base is still emerging.
 

Why hasn’t food allergy SLIT caught on?

One issue is that there is scant evidence from randomized, controlled trials. The treatments that clinics offer often hinge on insurance coverage, and increasingly, insurers only cover FDA-approved products. FDA approval requires thousands of patients being enrolled in long, expensive studies to prove the treatment’s merit. In a similar vein, doctors are trained to question methods that lack a strong publication base, for good reason.

Yet SLIT caught the attention of pioneering physicians who were intrigued by this “low-and-slow” immune-modifying approach, despite limited published evidence, and they sought real-world experience.

The late physician David Morris, MD, came across SLIT in the 1960s while searching for alternative ways to help mold-allergic farmers who were suffering terrible side effects from allergy shots. Dr. Morris attended conferences, learned more about sublingual techniques, got board certified in allergy, and opened Allergy Associates of La Crosse (Wis.), in 1970 to offer SLIT as a treatment for food and environmental allergies.

Dr. Morris and colleagues developed a protocol to create custom SLIT drops tailored to individual patients’ clinical histories and allergy test results. The method has been used to treat more than 200,000 patients. It has been used by allergist Nikhila Schroeder, MD, MEng, who learned SLIT methods while treating nearly 1,000 patients at Allergy Associates. In 2018, she opened her own direct-care SLIT practice, Allergenuity Health, in the Charlotte metropolitan area of North Carolina (see part 2 of this series).

Dr. Bajowala’s clinic offers SLIT in addition to oral immunotherapy (OIT). She was encouraged by the recent toddler SLIT data but wondered whether it would translate to a real-world setting. According to her calculations, the published protocol – according to which participants receive up to 4 mg/d over 6 months and continue receiving a daily maintenance dose of 4 mg for 3 years – would cost $10,000 per patient.

With this dosing regimen, the intervention is unaffordable, Dr. Bajowala said. And “there’s no way to make it cheaper because that’s the raw materials cost. It does not include labor or bottles or profit at all. That’s just $10,000 in peanut extract.”

Owing to cost, Dr. Bajowala’s clinic generally uses SLIT as a bridge to OIT. Her food allergy patients receive up to 1 mg/d and remain at that dose for a month or so before transitioning to OIT, “for which the supplies are orders of magnitude cheaper,” she said.

Dr. Schroeder said there is evidence for efficacy at microgram and even nanogram dosing – much lower than used in the recent food SLIT trials. Maintenance doses range from 50 ng/d to 25 mcg/d for environmental SLIT and 4-37 mcg/d for food SLIT, she said. The La Crosse method uses even lower dose ranges.

However, dosing information is not readily available, Dr. Schroeder noted. She has spent years scrutinizing articles and compiling information from allergen extract suppliers – all the while treating hundreds of SLIT patients. “I have had to expend a lot of time and effort,” said Dr. Schroeder. “It’s really hard to explain quickly.”

In the published literature, SLIT dosing recommendations vary widely. According to a 2007 analysis, environmental allergy symptoms improved with doses over a 1,000-fold range. What’s more, success did not scale with increased dosing and seemed to depend more on frequency and duration of treatment.

There are fewer studies regarding food SLIT. The most promising data come from recent trials of peanut-allergic children led by Edwin Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill. Still, “I am nervous to tell people to go do this based on 150 kids at one site,” Dr. Kim said. “We need to have a gigantic study across multiple sites that actually confirms what we have found in our single center.”

Because there are few published trials of food SLIT, confusion about which doses are optimal, how early to start, and how long the benefits last will be a barrier for many clinicians, said Douglas Mack, MD, FRCPC, assistant clinical professor in pediatrics at McMaster University, Hamilton, Ont.

Much could be learned from Allergy Associates of La Crosse, Allergenuity Health, and other clinics with SLIT experience involving thousands of patients. But that real-world data are messy and difficult to publish. Plus, it is hard for private allergists to find time to review charts, analyze data, and draft papers alongside seeing patients and running a clinic – especially without students and interns, who typically assist with academic research, Dr. Schroeder said.

Ruchi Gupta, MD, MPH, professor of pediatrics and medicine at Northwestern University, Chicago, and colleagues worked with a La Crosse team 6 or 7 years ago to try to analyze and publish SLIT outcomes for 121 peanut-allergic children who were treated for food and environmental allergies at the Wisconsin clinic. The researchers had hoped to publish an article describing caregiver-reported and clinical outcomes.

Among 73 caregivers who responded to a survey, more than half reported improved eczema, asthma, and environmental allergy symptoms, and virtually all families said SLIT calmed anxieties and minimized fear of allergic reactions. However, the clinical outcomes – skinprick test results, immune changes, and oral food challenges – were not as robust. And the data were incomplete. Some patients had traveled to La Crosse for SLIT drops but underwent skin and blood testing with their local allergist. Compiling records is “so much harder when you’re not doing a prospective clinical trial,” Dr. Gupta said.

The caregiver-reported outcomes were presented as a poster at the 2015 annual meeting of the American College of Allergy, Asthma, and Immunology and the 2016 annual meeting of the Pediatric Academic Society, said Jeff Kessler, MBA, FACHE, who is practice executive at La Crosse. However, with only self-reported data and no convincing lab metrics, the findings were never submitted for publication.

Others are eager to see clearer proof that SLIT works at doses lower than those published in the most recent trials. “If we can get efficacy with lower doses, that means we can increase accessibility, because we can lower the cost,” Dr. Bajowala said.

Robert Wood, MD, professor of pediatrics and director of pediatric allergy and immunology at Johns Hopkins University, Baltimore, has a pending grant proposal for a multifood trial of SLIT. “It’s a big missing piece,” he said.

Dr. Mack said that in Canada there was “almost an instant change in group think” when the Canadian Society of Allergy and Clinical Immunology published guidelines in support of OIT. With the new guidelines, “people are less concerned about liability. Once they start getting into OIT, I think you’re going to see SLIT coming right along for the ride.”

The shift will be slower in the United States, which has 20 times as many practicing allergists as Canada. Nevertheless, “I totally think SLIT has a place at the table,” Dr. Mack said. “I hope we start to see more high-quality data and people start to use it and experiment with it a bit and see how it works.”

A version of this article first appeared on Medscape.com. This is part three of a three-part series. Part one is here. Part two is here.