Atopic Dermatitis

Key clinical point: A longer dupilumab dosing interval might be a good treatment option for patients with atopic dermatitis (AD) who have achieved good clinical response (GCR) or report treatment-related conjunctivitis with a previous dupilumab treatment (600 mg followed by 300 mg every 2 weeks).

Major finding: In the GCR group, the mean Eczema Area and Severity Index (EASI) score was 28.22, which reduced significantly to 0.44 among patients receiving dupilumab once every 3 weeks (Q3W) and to 0.19 among patients receiving dupilumab once every 4 weeks (Q4W) after >60 weeks (both P < .0001). EASI improved after 18 weeks in the treatment-resistant conjunctivitis group (P < .0001).

Study details: Findings are retrospectively collected data of 59 adult patients with AD who implemented Q3W (84.75%) or Q4W (15.25%) dupilumab dosing interval due to GCR or conjunctivitis.

Disclosures: This study did not receive any funding. Some authors declared serving as speakers, investigators, consultants, or advisory board members, or receiving personal fees from several sources.

Source: Patruno C et al. Dupilumab dose spacing after initial successful treatment or adverse events in adult patients with atopic dermatitis: A retrospective analysis. Dermatol Ther. 2022 (Oct 13). Doi: 10.1111/dth.15933

Key clinical point: A longer dupilumab dosing interval might be a good treatment option for patients with atopic dermatitis (AD) who have achieved good clinical response (GCR) or report treatment-related conjunctivitis with a previous dupilumab treatment (600 mg followed by 300 mg every 2 weeks).

Major finding: In the GCR group, the mean Eczema Area and Severity Index (EASI) score was 28.22, which reduced significantly to 0.44 among patients receiving dupilumab once every 3 weeks (Q3W) and to 0.19 among patients receiving dupilumab once every 4 weeks (Q4W) after >60 weeks (both P < .0001). EASI improved after 18 weeks in the treatment-resistant conjunctivitis group (P < .0001).

Study details: Findings are retrospectively collected data of 59 adult patients with AD who implemented Q3W (84.75%) or Q4W (15.25%) dupilumab dosing interval due to GCR or conjunctivitis.

Disclosures: This study did not receive any funding. Some authors declared serving as speakers, investigators, consultants, or advisory board members, or receiving personal fees from several sources.

Source: Patruno C et al. Dupilumab dose spacing after initial successful treatment or adverse events in adult patients with atopic dermatitis: A retrospective analysis. Dermatol Ther. 2022 (Oct 13). Doi: 10.1111/dth.15933

Key clinical point: A longer dupilumab dosing interval might be a good treatment option for patients with atopic dermatitis (AD) who have achieved good clinical response (GCR) or report treatment-related conjunctivitis with a previous dupilumab treatment (600 mg followed by 300 mg every 2 weeks).

Major finding: In the GCR group, the mean Eczema Area and Severity Index (EASI) score was 28.22, which reduced significantly to 0.44 among patients receiving dupilumab once every 3 weeks (Q3W) and to 0.19 among patients receiving dupilumab once every 4 weeks (Q4W) after >60 weeks (both P < .0001). EASI improved after 18 weeks in the treatment-resistant conjunctivitis group (P < .0001).

Study details: Findings are retrospectively collected data of 59 adult patients with AD who implemented Q3W (84.75%) or Q4W (15.25%) dupilumab dosing interval due to GCR or conjunctivitis.

Disclosures: This study did not receive any funding. Some authors declared serving as speakers, investigators, consultants, or advisory board members, or receiving personal fees from several sources.

Source: Patruno C et al. Dupilumab dose spacing after initial successful treatment or adverse events in adult patients with atopic dermatitis: A retrospective analysis. Dermatol Ther. 2022 (Oct 13). Doi: 10.1111/dth.15933

Key clinical point: Baricitinib demonstrated long-term (52 weeks) efficacy in reducing disease severity in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: At week 52, >45% of patients achieved ≥75% improvement in the Eczema Area and Severity Index (EASI), with a mean improvement of 56.8 points in the total EASI score.

Study details: Findings are from the phase 3, BREEZE-AD5 study including 146 patients with moderate-to-severe AD who were assigned to receive 2 mg baricitinib, of which 98 patients participated in the open-label extension, BREEZE-AD6 study.

Disclosures: This study was funded by Eli Lilly and Company, under license from Incyte Corporation. Five authors declared being employees and shareholders of Eli Lilly, and the other authors reported ties with several sources, including Eli Lily.

Source: Simpson E et al. Baricitinib 2 mg for the treatment of atopic dermatitis in North America: Long-term efficacy and patient-reported outcomes. Dermatol Ther. 2022 (Oct 21). Doi: 10.1111/dth.15954

Key clinical point: Baricitinib demonstrated long-term (52 weeks) efficacy in reducing disease severity in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: At week 52, >45% of patients achieved ≥75% improvement in the Eczema Area and Severity Index (EASI), with a mean improvement of 56.8 points in the total EASI score.

Study details: Findings are from the phase 3, BREEZE-AD5 study including 146 patients with moderate-to-severe AD who were assigned to receive 2 mg baricitinib, of which 98 patients participated in the open-label extension, BREEZE-AD6 study.

Disclosures: This study was funded by Eli Lilly and Company, under license from Incyte Corporation. Five authors declared being employees and shareholders of Eli Lilly, and the other authors reported ties with several sources, including Eli Lily.

Source: Simpson E et al. Baricitinib 2 mg for the treatment of atopic dermatitis in North America: Long-term efficacy and patient-reported outcomes. Dermatol Ther. 2022 (Oct 21). Doi: 10.1111/dth.15954

Key clinical point: Baricitinib demonstrated long-term (52 weeks) efficacy in reducing disease severity in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: At week 52, >45% of patients achieved ≥75% improvement in the Eczema Area and Severity Index (EASI), with a mean improvement of 56.8 points in the total EASI score.

Study details: Findings are from the phase 3, BREEZE-AD5 study including 146 patients with moderate-to-severe AD who were assigned to receive 2 mg baricitinib, of which 98 patients participated in the open-label extension, BREEZE-AD6 study.

Disclosures: This study was funded by Eli Lilly and Company, under license from Incyte Corporation. Five authors declared being employees and shareholders of Eli Lilly, and the other authors reported ties with several sources, including Eli Lily.

Source: Simpson E et al. Baricitinib 2 mg for the treatment of atopic dermatitis in North America: Long-term efficacy and patient-reported outcomes. Dermatol Ther. 2022 (Oct 21). Doi: 10.1111/dth.15954

Key clinical point: Baricitinib demonstrated long-term (52 weeks) efficacy in reducing disease severity in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: At week 52, >45% of patients achieved ≥75% improvement in the Eczema Area and Severity Index (EASI), with a mean improvement of 56.8 points in the total EASI score.

Study details: Findings are from the phase 3, BREEZE-AD5 study including 146 patients with moderate-to-severe AD who were assigned to receive 2 mg baricitinib, of which 98 patients participated in the open-label extension, BREEZE-AD6 study.

Disclosures: This study was funded by Eli Lilly and Company, under license from Incyte Corporation. Five authors declared being employees and shareholders of Eli Lilly, and the other authors reported ties with several sources, including Eli Lily.

Source: Simpson E et al. Baricitinib 2 mg for the treatment of atopic dermatitis in North America: Long-term efficacy and patient-reported outcomes. Dermatol Ther. 2022 (Oct 21). Doi: 10.1111/dth.15954

Key clinical point: Baricitinib demonstrated long-term (52 weeks) efficacy in reducing disease severity in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: At week 52, >45% of patients achieved ≥75% improvement in the Eczema Area and Severity Index (EASI), with a mean improvement of 56.8 points in the total EASI score.

Study details: Findings are from the phase 3, BREEZE-AD5 study including 146 patients with moderate-to-severe AD who were assigned to receive 2 mg baricitinib, of which 98 patients participated in the open-label extension, BREEZE-AD6 study.

Disclosures: This study was funded by Eli Lilly and Company, under license from Incyte Corporation. Five authors declared being employees and shareholders of Eli Lilly, and the other authors reported ties with several sources, including Eli Lily.

Source: Simpson E et al. Baricitinib 2 mg for the treatment of atopic dermatitis in North America: Long-term efficacy and patient-reported outcomes. Dermatol Ther. 2022 (Oct 21). Doi: 10.1111/dth.15954

Key clinical point: Baricitinib demonstrated long-term (52 weeks) efficacy in reducing disease severity in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: At week 52, >45% of patients achieved ≥75% improvement in the Eczema Area and Severity Index (EASI), with a mean improvement of 56.8 points in the total EASI score.

Study details: Findings are from the phase 3, BREEZE-AD5 study including 146 patients with moderate-to-severe AD who were assigned to receive 2 mg baricitinib, of which 98 patients participated in the open-label extension, BREEZE-AD6 study.

Disclosures: This study was funded by Eli Lilly and Company, under license from Incyte Corporation. Five authors declared being employees and shareholders of Eli Lilly, and the other authors reported ties with several sources, including Eli Lily.

Source: Simpson E et al. Baricitinib 2 mg for the treatment of atopic dermatitis in North America: Long-term efficacy and patient-reported outcomes. Dermatol Ther. 2022 (Oct 21). Doi: 10.1111/dth.15954

Key clinical point: In patients with moderate-to-severe atopic dermatitis (AD), continuous long-term dupilumab treatment was not associated with an increased risk for overall systemic/cutaneous infections.

Major finding: At 4 years, the overall infection rate was 71.27 number of patients with ≥1 event per 100 patient-years (nP/100 PY), with most infections being mild to moderate in severity, and only a very small number of infections resulted in treatment discontinuation (0.34 nP/100 PY). The rate of total skin infections decreased from 28.10 to 11.48 nP/100 PY from week 16 to year 4.

Study details: Findings are from the analysis of the LIBERTY AD OLE study including 2677 patients with moderate-to-severe AD who received dupilumab, of which 13.1% completed treatment up to week 204.

Disclosures: This research was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Four authors declared being employees and shareholders of Regeneron Pharmaceuticals. Three authors declared being employees or holding stock options in Sanofi. The other authors reported ties with several sources, including Regeneron and Sanofi.

Source: Blauvelt A et al. No increased risk of overall infection in adults with moderate-to-severe atopic dermatitis treated for up to 4 years with dupilumab. Adv Ther. 2022 (Nov 1). Doi: 10.1007/s12325-022-02322-y

Key clinical point: In patients with moderate-to-severe atopic dermatitis (AD), continuous long-term dupilumab treatment was not associated with an increased risk for overall systemic/cutaneous infections.

Major finding: At 4 years, the overall infection rate was 71.27 number of patients with ≥1 event per 100 patient-years (nP/100 PY), with most infections being mild to moderate in severity, and only a very small number of infections resulted in treatment discontinuation (0.34 nP/100 PY). The rate of total skin infections decreased from 28.10 to 11.48 nP/100 PY from week 16 to year 4.

Study details: Findings are from the analysis of the LIBERTY AD OLE study including 2677 patients with moderate-to-severe AD who received dupilumab, of which 13.1% completed treatment up to week 204.

Disclosures: This research was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Four authors declared being employees and shareholders of Regeneron Pharmaceuticals. Three authors declared being employees or holding stock options in Sanofi. The other authors reported ties with several sources, including Regeneron and Sanofi.

Source: Blauvelt A et al. No increased risk of overall infection in adults with moderate-to-severe atopic dermatitis treated for up to 4 years with dupilumab. Adv Ther. 2022 (Nov 1). Doi: 10.1007/s12325-022-02322-y

Key clinical point: In patients with moderate-to-severe atopic dermatitis (AD), continuous long-term dupilumab treatment was not associated with an increased risk for overall systemic/cutaneous infections.

Major finding: At 4 years, the overall infection rate was 71.27 number of patients with ≥1 event per 100 patient-years (nP/100 PY), with most infections being mild to moderate in severity, and only a very small number of infections resulted in treatment discontinuation (0.34 nP/100 PY). The rate of total skin infections decreased from 28.10 to 11.48 nP/100 PY from week 16 to year 4.

Study details: Findings are from the analysis of the LIBERTY AD OLE study including 2677 patients with moderate-to-severe AD who received dupilumab, of which 13.1% completed treatment up to week 204.

Disclosures: This research was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Four authors declared being employees and shareholders of Regeneron Pharmaceuticals. Three authors declared being employees or holding stock options in Sanofi. The other authors reported ties with several sources, including Regeneron and Sanofi.

Source: Blauvelt A et al. No increased risk of overall infection in adults with moderate-to-severe atopic dermatitis treated for up to 4 years with dupilumab. Adv Ther. 2022 (Nov 1). Doi: 10.1007/s12325-022-02322-y

Key clinical point: Air pollution due to a wildfire increased the rate of clinic visits for atopic dermatitis (AD), especially at a 0-week lag, in adults aged ≥65 years.

Major finding: In adults aged ≥65 years, the adjusted rate of clinic visits for AD during a week with a wildfire was 1.4 (95% CI 1.1-1.9) times the rate during weeks without wildfire and every 1-unit increase in the mean weekly smoke plume density score increased the rate of clinic visits for AD by 1.3 (95% CI 1.1-1.6) times.

Study details: This study analyzed the data of outpatient dermatology visits for AD (5529 visits) and itch (1319 visits).

Disclosures: This study did not report the source of funding. Dr. Grimes declared receiving grants from the University of California, San Francisco.

Source: Fadadu RP et al. Association of exposure to wildfire air pollution with exacerbations of atopic dermatitis and itch among older adults. JAMA Netw Open. 2022;5(10):e2238594 (Oct 26). Doi: 10.1001/jamanetworkopen.2022.38594

Key clinical point: Air pollution due to a wildfire increased the rate of clinic visits for atopic dermatitis (AD), especially at a 0-week lag, in adults aged ≥65 years.

Major finding: In adults aged ≥65 years, the adjusted rate of clinic visits for AD during a week with a wildfire was 1.4 (95% CI 1.1-1.9) times the rate during weeks without wildfire and every 1-unit increase in the mean weekly smoke plume density score increased the rate of clinic visits for AD by 1.3 (95% CI 1.1-1.6) times.

Study details: This study analyzed the data of outpatient dermatology visits for AD (5529 visits) and itch (1319 visits).

Disclosures: This study did not report the source of funding. Dr. Grimes declared receiving grants from the University of California, San Francisco.

Source: Fadadu RP et al. Association of exposure to wildfire air pollution with exacerbations of atopic dermatitis and itch among older adults. JAMA Netw Open. 2022;5(10):e2238594 (Oct 26). Doi: 10.1001/jamanetworkopen.2022.38594

Key clinical point: Air pollution due to a wildfire increased the rate of clinic visits for atopic dermatitis (AD), especially at a 0-week lag, in adults aged ≥65 years.

Major finding: In adults aged ≥65 years, the adjusted rate of clinic visits for AD during a week with a wildfire was 1.4 (95% CI 1.1-1.9) times the rate during weeks without wildfire and every 1-unit increase in the mean weekly smoke plume density score increased the rate of clinic visits for AD by 1.3 (95% CI 1.1-1.6) times.

Study details: This study analyzed the data of outpatient dermatology visits for AD (5529 visits) and itch (1319 visits).

Disclosures: This study did not report the source of funding. Dr. Grimes declared receiving grants from the University of California, San Francisco.

Source: Fadadu RP et al. Association of exposure to wildfire air pollution with exacerbations of atopic dermatitis and itch among older adults. JAMA Netw Open. 2022;5(10):e2238594 (Oct 26). Doi: 10.1001/jamanetworkopen.2022.38594

Key clinical point: In patients with atopic dermatitis (AD), serum dupilumab levels at week 16 were not associated with treatment response or adverse effects due to dupilumab during the first year of treatment.

Major finding: Serum dupilumab levels at 16 weeks were not associated with the prediction of treatment response at 52 weeks (≥90% improvement in the Eczema Area and Severity Index; odds ratio [OR] 0.96; P = .34) or adverse events during the first year of treatment (OR 1.01; P = .83).

Study details: Findings are from a prospective clinical cohort study including 295 patients with AD who started dupilumab and had treatment week 16 serum samples available.

Disclosures: This study was funded by AbbVie, Eli Lilly, and other sources. The authors declared receiving consulting fees, speaking fees, investigator fees, or research funding from several sources.

Source: Spekhorst LS et al. Association of serum dupilumab levels at 16 weeks with treatment response and adverse effects in patients with atopic dermatitis: A prospective clinical cohort study from the BioDay registry. JAMA Dermatol. 2022 (Nov 2). Doi: 10.1001/jamadermatol.2022.4639

Key clinical point: In patients with atopic dermatitis (AD), serum dupilumab levels at week 16 were not associated with treatment response or adverse effects due to dupilumab during the first year of treatment.

Major finding: Serum dupilumab levels at 16 weeks were not associated with the prediction of treatment response at 52 weeks (≥90% improvement in the Eczema Area and Severity Index; odds ratio [OR] 0.96; P = .34) or adverse events during the first year of treatment (OR 1.01; P = .83).

Study details: Findings are from a prospective clinical cohort study including 295 patients with AD who started dupilumab and had treatment week 16 serum samples available.

Disclosures: This study was funded by AbbVie, Eli Lilly, and other sources. The authors declared receiving consulting fees, speaking fees, investigator fees, or research funding from several sources.

Source: Spekhorst LS et al. Association of serum dupilumab levels at 16 weeks with treatment response and adverse effects in patients with atopic dermatitis: A prospective clinical cohort study from the BioDay registry. JAMA Dermatol. 2022 (Nov 2). Doi: 10.1001/jamadermatol.2022.4639

Key clinical point: In patients with atopic dermatitis (AD), serum dupilumab levels at week 16 were not associated with treatment response or adverse effects due to dupilumab during the first year of treatment.

Major finding: Serum dupilumab levels at 16 weeks were not associated with the prediction of treatment response at 52 weeks (≥90% improvement in the Eczema Area and Severity Index; odds ratio [OR] 0.96; P = .34) or adverse events during the first year of treatment (OR 1.01; P = .83).

Study details: Findings are from a prospective clinical cohort study including 295 patients with AD who started dupilumab and had treatment week 16 serum samples available.

Disclosures: This study was funded by AbbVie, Eli Lilly, and other sources. The authors declared receiving consulting fees, speaking fees, investigator fees, or research funding from several sources.

Source: Spekhorst LS et al. Association of serum dupilumab levels at 16 weeks with treatment response and adverse effects in patients with atopic dermatitis: A prospective clinical cohort study from the BioDay registry. JAMA Dermatol. 2022 (Nov 2). Doi: 10.1001/jamadermatol.2022.4639

This patient's symptoms are consistent with a diagnosis of blepharitis.

Blepharitis is an inflammatory disorder of the eyelids that is frequently associated with bacterial colonization of the eyelid. Anatomically, it can be categorized as anterior blepharitis or posterior blepharitis. Anterior blepharitis refers to inflammation primarily positioned around the skin, eyelashes, and lash follicles and is usually further divided into staphylococcal and seborrheic variants. Posterior blepharitis involves the meibomian gland orifices, meibomian glands, tarsal plate, and blepharo-conjunctival junction. 

Blepharitis can be acute or chronic. It is frequently associated with systemic diseases, such as rosacea, atopy, and seborrheic dermatitis, as well as ocular diseases, such as dry eye syndromes, chalazion, trichiasis, ectropion and entropion, infectious or other inflammatory conjunctivitis, and keratitis. Moreover, high rates of blepharitis have been reported in patients treated with dupilumab for atopic dermatitis. 

Eye irritation, itching, erythema of the lids, flaking of the lid margins, and/or changes in the eyelashes are common presenting symptoms in patients with blepharitis. Other symptoms may include:
•    Burning
•    Watering
•    Foreign-body sensation
•    Crusting and mattering of the lashes and medial canthus
•    Red lids
•    Red eyes
•    Photophobia
•    Pain
•    Decreased vision
•    Visual fluctuations
•    Heat, cold, alcohol, and spicy-food intolerance

The differential diagnosis for blepharitis includes bacterial keratitis, which is a serious ocular disorder that can lead to vision loss if not properly treated. Bacterial keratitis progresses rapidly and can result in corneal destruction within 24-48 hours with some particularly virulent bacteria. Patients with bacterial keratitis typically report rapid onset of pain, photophobia, and decreased vision.

Ocular rosacea should also be considered in the differential diagnosis of blepharitis, and the two conditions can co-occur. Patients with ocular rosacea may experience facial symptoms (eg, recurrent flushing episodes, persistent and/or recurrent midfacial erythema, papular and pustular lesions) in addition to ocular symptoms, which can range from minor irritation, foreign-body sensation, and blurry vision to severe ocular surface disruption and inflammatory keratitis.

Bacterial conjunctivitis involves inflammation of the bulbar and/or palpebral conjunctiva, whereas blepharitis involves inflammation of the eyelids only. Other conditions to consider in the diagnosis of blepharitis can be found here. 

Given the unprecedented efficacy seen in clinical trials, dupilumab is emerging as a first-line therapeutic for moderate to severe atopic dermatitis. However, clinicians should be alert to ocular complications among their patients with atopic dermatitis who are being treated with dupilumab. In some patients, this may be because of preexisting meibomian gland disease and ocular surface disease. After a diagnosis of ocular complications, the continued use of dupilumab should be jointly evaluated by the ophthalmologist and dermatologist or allergist on the basis of the ocular risk vs systemic benefit. Treatment for blepharitis typically includes strict eyelid hygiene and topical antibiotic ointment; oral antibiotics can be beneficial for refractory disease.

William D. James, MD, Professor, Department of Dermatology, University of Pennsylvania, Philadelphia.

Disclosure: William D. James, MD, has disclosed the following relevant financial relationships:
Received income in an amount equal to or greater than $250 from: Elsevier.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

This patient's symptoms are consistent with a diagnosis of blepharitis.

Blepharitis is an inflammatory disorder of the eyelids that is frequently associated with bacterial colonization of the eyelid. Anatomically, it can be categorized as anterior blepharitis or posterior blepharitis. Anterior blepharitis refers to inflammation primarily positioned around the skin, eyelashes, and lash follicles and is usually further divided into staphylococcal and seborrheic variants. Posterior blepharitis involves the meibomian gland orifices, meibomian glands, tarsal plate, and blepharo-conjunctival junction. 

Blepharitis can be acute or chronic. It is frequently associated with systemic diseases, such as rosacea, atopy, and seborrheic dermatitis, as well as ocular diseases, such as dry eye syndromes, chalazion, trichiasis, ectropion and entropion, infectious or other inflammatory conjunctivitis, and keratitis. Moreover, high rates of blepharitis have been reported in patients treated with dupilumab for atopic dermatitis. 

Eye irritation, itching, erythema of the lids, flaking of the lid margins, and/or changes in the eyelashes are common presenting symptoms in patients with blepharitis. Other symptoms may include:
•    Burning
•    Watering
•    Foreign-body sensation
•    Crusting and mattering of the lashes and medial canthus
•    Red lids
•    Red eyes
•    Photophobia
•    Pain
•    Decreased vision
•    Visual fluctuations
•    Heat, cold, alcohol, and spicy-food intolerance

The differential diagnosis for blepharitis includes bacterial keratitis, which is a serious ocular disorder that can lead to vision loss if not properly treated. Bacterial keratitis progresses rapidly and can result in corneal destruction within 24-48 hours with some particularly virulent bacteria. Patients with bacterial keratitis typically report rapid onset of pain, photophobia, and decreased vision.

Ocular rosacea should also be considered in the differential diagnosis of blepharitis, and the two conditions can co-occur. Patients with ocular rosacea may experience facial symptoms (eg, recurrent flushing episodes, persistent and/or recurrent midfacial erythema, papular and pustular lesions) in addition to ocular symptoms, which can range from minor irritation, foreign-body sensation, and blurry vision to severe ocular surface disruption and inflammatory keratitis.

Bacterial conjunctivitis involves inflammation of the bulbar and/or palpebral conjunctiva, whereas blepharitis involves inflammation of the eyelids only. Other conditions to consider in the diagnosis of blepharitis can be found here. 

Given the unprecedented efficacy seen in clinical trials, dupilumab is emerging as a first-line therapeutic for moderate to severe atopic dermatitis. However, clinicians should be alert to ocular complications among their patients with atopic dermatitis who are being treated with dupilumab. In some patients, this may be because of preexisting meibomian gland disease and ocular surface disease. After a diagnosis of ocular complications, the continued use of dupilumab should be jointly evaluated by the ophthalmologist and dermatologist or allergist on the basis of the ocular risk vs systemic benefit. Treatment for blepharitis typically includes strict eyelid hygiene and topical antibiotic ointment; oral antibiotics can be beneficial for refractory disease.

William D. James, MD, Professor, Department of Dermatology, University of Pennsylvania, Philadelphia.

Disclosure: William D. James, MD, has disclosed the following relevant financial relationships:
Received income in an amount equal to or greater than $250 from: Elsevier.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

This patient's symptoms are consistent with a diagnosis of blepharitis.

Blepharitis is an inflammatory disorder of the eyelids that is frequently associated with bacterial colonization of the eyelid. Anatomically, it can be categorized as anterior blepharitis or posterior blepharitis. Anterior blepharitis refers to inflammation primarily positioned around the skin, eyelashes, and lash follicles and is usually further divided into staphylococcal and seborrheic variants. Posterior blepharitis involves the meibomian gland orifices, meibomian glands, tarsal plate, and blepharo-conjunctival junction. 

Blepharitis can be acute or chronic. It is frequently associated with systemic diseases, such as rosacea, atopy, and seborrheic dermatitis, as well as ocular diseases, such as dry eye syndromes, chalazion, trichiasis, ectropion and entropion, infectious or other inflammatory conjunctivitis, and keratitis. Moreover, high rates of blepharitis have been reported in patients treated with dupilumab for atopic dermatitis. 

Eye irritation, itching, erythema of the lids, flaking of the lid margins, and/or changes in the eyelashes are common presenting symptoms in patients with blepharitis. Other symptoms may include:
•    Burning
•    Watering
•    Foreign-body sensation
•    Crusting and mattering of the lashes and medial canthus
•    Red lids
•    Red eyes
•    Photophobia
•    Pain
•    Decreased vision
•    Visual fluctuations
•    Heat, cold, alcohol, and spicy-food intolerance

The differential diagnosis for blepharitis includes bacterial keratitis, which is a serious ocular disorder that can lead to vision loss if not properly treated. Bacterial keratitis progresses rapidly and can result in corneal destruction within 24-48 hours with some particularly virulent bacteria. Patients with bacterial keratitis typically report rapid onset of pain, photophobia, and decreased vision.

Ocular rosacea should also be considered in the differential diagnosis of blepharitis, and the two conditions can co-occur. Patients with ocular rosacea may experience facial symptoms (eg, recurrent flushing episodes, persistent and/or recurrent midfacial erythema, papular and pustular lesions) in addition to ocular symptoms, which can range from minor irritation, foreign-body sensation, and blurry vision to severe ocular surface disruption and inflammatory keratitis.

Bacterial conjunctivitis involves inflammation of the bulbar and/or palpebral conjunctiva, whereas blepharitis involves inflammation of the eyelids only. Other conditions to consider in the diagnosis of blepharitis can be found here. 

Given the unprecedented efficacy seen in clinical trials, dupilumab is emerging as a first-line therapeutic for moderate to severe atopic dermatitis. However, clinicians should be alert to ocular complications among their patients with atopic dermatitis who are being treated with dupilumab. In some patients, this may be because of preexisting meibomian gland disease and ocular surface disease. After a diagnosis of ocular complications, the continued use of dupilumab should be jointly evaluated by the ophthalmologist and dermatologist or allergist on the basis of the ocular risk vs systemic benefit. Treatment for blepharitis typically includes strict eyelid hygiene and topical antibiotic ointment; oral antibiotics can be beneficial for refractory disease.

William D. James, MD, Professor, Department of Dermatology, University of Pennsylvania, Philadelphia.

Disclosure: William D. James, MD, has disclosed the following relevant financial relationships:
Received income in an amount equal to or greater than $250 from: Elsevier.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The finding that serum dupilumab levels in patients with atopic dermatitis (AD) do not predict long-term response levels or adverse events (AEs) suggests that factors beyond interpatient variability of the interleukin-4 receptor subunit-alpha (IL-4R-alpha) may drive response levels, according to a study published in JAMA Dermatology.

The study results mean that researchers should continue exploring potential AD drugs with novel mechanisms to help patients who fail type 2 inflammatory inhibition, experts told this news organization. The search for accurate augurs of clinical performance also must continue.

Addressing inadequate response

Quantifying nonresponse and incomplete response levels with dupilumab is difficult, said Jonathan I. Silverberg, MD, PhD, MPH, offering perspective on the study. “True nonresponse is probably less than 20%, but many other patients are inadequate responders even if they are having partial response.” Dr. Silverberg, professor of dermatology and director of clinical research, at George Washington University, Washington, was not an investigator.

Robert Sidbury, MD, MPH, added, “When a patient doesn’t respond to a medication that you expect they should, we always ask ourselves why.” Dermatologists have long assumed that, as with biologics for psoriasis, low blood levels were to blame for dupilumab nonresponse, said Dr. Sidbury, who is division chief of dermatology at Seattle Children’s Hospital and was not involved with the study. “This study showed that there was no correlation between response and blood levels.”

In the study, Lotte S. Spekhorst, MD, of National Expertise Center for Atopic Dermatitis, department of dermatology and allergology, University Medical Center Utrecht (the Netherlands) and coinvestigators prospectively followed 295 consecutive adult patients with moderate AD who were treated with dupilumab for 1 year. All patients received the same loading (600 mg) and biweekly (300 mg) doses.

The median dupilumab level at 16 weeks was 86.6 mcg/mL, which is higher than serum levels observed with other monoclonal antibodies used for other indications, such as psoriasis and inflammatory bowel disease, the authors noted. More importantly, researchers found no significant relationship between median week 16 dupilumab levels and 1-year clinical responses measured either discretely (Eczema Area and Severity Index [EASI] < 50, 50, 75, or 90; P = .18) or as quartiles (P = .06).

“It may be that response is dependent on target availability of the IL-4R-alpha, with an interpatient variability producing heterogeneity in response,” the authors wrote. But because serum dupilumab levels were relatively high, they said, all patients’ IL-4R-alpha “was likely fully saturated” at 16 weeks.

“This would explain why serum dupilumab levels were not related to effectiveness,” they noted, “although we cannot rule out differential effects in the tissue associated with heterogeneity in serum dupilumab levels.”

The study helps explain why some patients do not fully respond to dupilumab, said Eric L. Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, who was not involved with the study.

“One hypothesis would be that drug serum levels differ due to metabolism or absorption reasons,” Dr. Simpson said in an interview. Results also suggest that heterogeneity in disease biology, such as other uninhibited cytokine pathways, might explain differences in clinical results. “Thus, more therapeutics that target different inflammatory pathways are needed to capture responses in patients not adequately responding to type 2 inflammatory blockade,” he said.
 

Assessing AEs

As with response levels, serum dupilumab levels at week 16 did not predict AEs including dupilumab-associated ocular surface disease (DAOSD), which impacted 46.4% of 216 patients who reported AEs. These findings also contradict what happens with biologics in other diseases such as psoriasis and inflammatory bowel disease, said Dr. Sidbury, wherein serum drug levels may predict both clinical response and side-effect risks.

A previous study showed that lowering dupilumab levels led to improvement in DAOSD. Authors of the current study therefore surmised that DAOSD development might be more associated with interpatient variability in IL-4R-alpha expression than with serum drug levels. “More research is necessary to confirm the hypothesis of interpatient variability of the IL-4Ra and the pharmacokinetics of dupilumab,” they concluded.

For now, said Dr. Sidbury, the study helps clinicians look beyond serum drug levels when patients respond inadequately to dupilumab. Moreover, added Dr. Silverberg, study results mean that physicians must find other ways to predict dupilumab response levels. “We need better predictors of clinical response – theranostic markers that we could test the patient to and understand how well they’re going to do,” he said.

Be it dupilumab or any other medication, he said, physicians lack even confirmatory biomarkers to reflect when a drug is working well. “Right now, we go with clinical assessments. But if it’s not drug levels, we have to figure out why some patients do markedly better than others.”

It was not unreasonable, Dr. Silverberg said, for the investigators to seek a biomarker in blood rather than tissue. “But in this disease, we believe that the more important place to look for biomarkers and drug levels would be in the skin itself. So we are still left with the issue” that drug levels in tissue might reflect response when serum levels do not.

The study was supported by grants from AbbVie, Eli Lilly, Leo Pharma, Pfizer, and Sanofi. Study patients participated in the BioDay Registry, which is sponsored by Sanofi, Regeneron, AbbVie, Eli Lilly, LEO Pharma, and Pfizer; the sponsors had no role in the study design and conduct. Dr. Spekhorst discloses receiving speaking fees from Abbvie outside the work; disclosures of other authors included receiving advisory, speaking consulting, and/or investigator fees from Sanofi Genzyme during the study. Several authors had no disclosures.

Dr. Simpson has been an investigator and consultant for Regeneron and Sanofi, makers of dupilumab. Dr. Silverberg has been an investigator, consultant, and speaker for Regeneron and Sanofi. Dr. Sidbury has been a clinical investigator for all dupilumab pediatric trials. (His institution has a contract with Regeneron and Sanofi, but he receives no money from the arrangement.)

The finding that serum dupilumab levels in patients with atopic dermatitis (AD) do not predict long-term response levels or adverse events (AEs) suggests that factors beyond interpatient variability of the interleukin-4 receptor subunit-alpha (IL-4R-alpha) may drive response levels, according to a study published in JAMA Dermatology.

The study results mean that researchers should continue exploring potential AD drugs with novel mechanisms to help patients who fail type 2 inflammatory inhibition, experts told this news organization. The search for accurate augurs of clinical performance also must continue.

Addressing inadequate response

Quantifying nonresponse and incomplete response levels with dupilumab is difficult, said Jonathan I. Silverberg, MD, PhD, MPH, offering perspective on the study. “True nonresponse is probably less than 20%, but many other patients are inadequate responders even if they are having partial response.” Dr. Silverberg, professor of dermatology and director of clinical research, at George Washington University, Washington, was not an investigator.

Robert Sidbury, MD, MPH, added, “When a patient doesn’t respond to a medication that you expect they should, we always ask ourselves why.” Dermatologists have long assumed that, as with biologics for psoriasis, low blood levels were to blame for dupilumab nonresponse, said Dr. Sidbury, who is division chief of dermatology at Seattle Children’s Hospital and was not involved with the study. “This study showed that there was no correlation between response and blood levels.”

In the study, Lotte S. Spekhorst, MD, of National Expertise Center for Atopic Dermatitis, department of dermatology and allergology, University Medical Center Utrecht (the Netherlands) and coinvestigators prospectively followed 295 consecutive adult patients with moderate AD who were treated with dupilumab for 1 year. All patients received the same loading (600 mg) and biweekly (300 mg) doses.

The median dupilumab level at 16 weeks was 86.6 mcg/mL, which is higher than serum levels observed with other monoclonal antibodies used for other indications, such as psoriasis and inflammatory bowel disease, the authors noted. More importantly, researchers found no significant relationship between median week 16 dupilumab levels and 1-year clinical responses measured either discretely (Eczema Area and Severity Index [EASI] < 50, 50, 75, or 90; P = .18) or as quartiles (P = .06).

“It may be that response is dependent on target availability of the IL-4R-alpha, with an interpatient variability producing heterogeneity in response,” the authors wrote. But because serum dupilumab levels were relatively high, they said, all patients’ IL-4R-alpha “was likely fully saturated” at 16 weeks.

“This would explain why serum dupilumab levels were not related to effectiveness,” they noted, “although we cannot rule out differential effects in the tissue associated with heterogeneity in serum dupilumab levels.”

The study helps explain why some patients do not fully respond to dupilumab, said Eric L. Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, who was not involved with the study.

“One hypothesis would be that drug serum levels differ due to metabolism or absorption reasons,” Dr. Simpson said in an interview. Results also suggest that heterogeneity in disease biology, such as other uninhibited cytokine pathways, might explain differences in clinical results. “Thus, more therapeutics that target different inflammatory pathways are needed to capture responses in patients not adequately responding to type 2 inflammatory blockade,” he said.
 

Assessing AEs

As with response levels, serum dupilumab levels at week 16 did not predict AEs including dupilumab-associated ocular surface disease (DAOSD), which impacted 46.4% of 216 patients who reported AEs. These findings also contradict what happens with biologics in other diseases such as psoriasis and inflammatory bowel disease, said Dr. Sidbury, wherein serum drug levels may predict both clinical response and side-effect risks.

A previous study showed that lowering dupilumab levels led to improvement in DAOSD. Authors of the current study therefore surmised that DAOSD development might be more associated with interpatient variability in IL-4R-alpha expression than with serum drug levels. “More research is necessary to confirm the hypothesis of interpatient variability of the IL-4Ra and the pharmacokinetics of dupilumab,” they concluded.

For now, said Dr. Sidbury, the study helps clinicians look beyond serum drug levels when patients respond inadequately to dupilumab. Moreover, added Dr. Silverberg, study results mean that physicians must find other ways to predict dupilumab response levels. “We need better predictors of clinical response – theranostic markers that we could test the patient to and understand how well they’re going to do,” he said.

Be it dupilumab or any other medication, he said, physicians lack even confirmatory biomarkers to reflect when a drug is working well. “Right now, we go with clinical assessments. But if it’s not drug levels, we have to figure out why some patients do markedly better than others.”

It was not unreasonable, Dr. Silverberg said, for the investigators to seek a biomarker in blood rather than tissue. “But in this disease, we believe that the more important place to look for biomarkers and drug levels would be in the skin itself. So we are still left with the issue” that drug levels in tissue might reflect response when serum levels do not.

The study was supported by grants from AbbVie, Eli Lilly, Leo Pharma, Pfizer, and Sanofi. Study patients participated in the BioDay Registry, which is sponsored by Sanofi, Regeneron, AbbVie, Eli Lilly, LEO Pharma, and Pfizer; the sponsors had no role in the study design and conduct. Dr. Spekhorst discloses receiving speaking fees from Abbvie outside the work; disclosures of other authors included receiving advisory, speaking consulting, and/or investigator fees from Sanofi Genzyme during the study. Several authors had no disclosures.

Dr. Simpson has been an investigator and consultant for Regeneron and Sanofi, makers of dupilumab. Dr. Silverberg has been an investigator, consultant, and speaker for Regeneron and Sanofi. Dr. Sidbury has been a clinical investigator for all dupilumab pediatric trials. (His institution has a contract with Regeneron and Sanofi, but he receives no money from the arrangement.)

The finding that serum dupilumab levels in patients with atopic dermatitis (AD) do not predict long-term response levels or adverse events (AEs) suggests that factors beyond interpatient variability of the interleukin-4 receptor subunit-alpha (IL-4R-alpha) may drive response levels, according to a study published in JAMA Dermatology.

The study results mean that researchers should continue exploring potential AD drugs with novel mechanisms to help patients who fail type 2 inflammatory inhibition, experts told this news organization. The search for accurate augurs of clinical performance also must continue.

Addressing inadequate response

Quantifying nonresponse and incomplete response levels with dupilumab is difficult, said Jonathan I. Silverberg, MD, PhD, MPH, offering perspective on the study. “True nonresponse is probably less than 20%, but many other patients are inadequate responders even if they are having partial response.” Dr. Silverberg, professor of dermatology and director of clinical research, at George Washington University, Washington, was not an investigator.

Robert Sidbury, MD, MPH, added, “When a patient doesn’t respond to a medication that you expect they should, we always ask ourselves why.” Dermatologists have long assumed that, as with biologics for psoriasis, low blood levels were to blame for dupilumab nonresponse, said Dr. Sidbury, who is division chief of dermatology at Seattle Children’s Hospital and was not involved with the study. “This study showed that there was no correlation between response and blood levels.”

In the study, Lotte S. Spekhorst, MD, of National Expertise Center for Atopic Dermatitis, department of dermatology and allergology, University Medical Center Utrecht (the Netherlands) and coinvestigators prospectively followed 295 consecutive adult patients with moderate AD who were treated with dupilumab for 1 year. All patients received the same loading (600 mg) and biweekly (300 mg) doses.

The median dupilumab level at 16 weeks was 86.6 mcg/mL, which is higher than serum levels observed with other monoclonal antibodies used for other indications, such as psoriasis and inflammatory bowel disease, the authors noted. More importantly, researchers found no significant relationship between median week 16 dupilumab levels and 1-year clinical responses measured either discretely (Eczema Area and Severity Index [EASI] < 50, 50, 75, or 90; P = .18) or as quartiles (P = .06).

“It may be that response is dependent on target availability of the IL-4R-alpha, with an interpatient variability producing heterogeneity in response,” the authors wrote. But because serum dupilumab levels were relatively high, they said, all patients’ IL-4R-alpha “was likely fully saturated” at 16 weeks.

“This would explain why serum dupilumab levels were not related to effectiveness,” they noted, “although we cannot rule out differential effects in the tissue associated with heterogeneity in serum dupilumab levels.”

The study helps explain why some patients do not fully respond to dupilumab, said Eric L. Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, who was not involved with the study.

“One hypothesis would be that drug serum levels differ due to metabolism or absorption reasons,” Dr. Simpson said in an interview. Results also suggest that heterogeneity in disease biology, such as other uninhibited cytokine pathways, might explain differences in clinical results. “Thus, more therapeutics that target different inflammatory pathways are needed to capture responses in patients not adequately responding to type 2 inflammatory blockade,” he said.
 

Assessing AEs

As with response levels, serum dupilumab levels at week 16 did not predict AEs including dupilumab-associated ocular surface disease (DAOSD), which impacted 46.4% of 216 patients who reported AEs. These findings also contradict what happens with biologics in other diseases such as psoriasis and inflammatory bowel disease, said Dr. Sidbury, wherein serum drug levels may predict both clinical response and side-effect risks.

A previous study showed that lowering dupilumab levels led to improvement in DAOSD. Authors of the current study therefore surmised that DAOSD development might be more associated with interpatient variability in IL-4R-alpha expression than with serum drug levels. “More research is necessary to confirm the hypothesis of interpatient variability of the IL-4Ra and the pharmacokinetics of dupilumab,” they concluded.

For now, said Dr. Sidbury, the study helps clinicians look beyond serum drug levels when patients respond inadequately to dupilumab. Moreover, added Dr. Silverberg, study results mean that physicians must find other ways to predict dupilumab response levels. “We need better predictors of clinical response – theranostic markers that we could test the patient to and understand how well they’re going to do,” he said.

Be it dupilumab or any other medication, he said, physicians lack even confirmatory biomarkers to reflect when a drug is working well. “Right now, we go with clinical assessments. But if it’s not drug levels, we have to figure out why some patients do markedly better than others.”

It was not unreasonable, Dr. Silverberg said, for the investigators to seek a biomarker in blood rather than tissue. “But in this disease, we believe that the more important place to look for biomarkers and drug levels would be in the skin itself. So we are still left with the issue” that drug levels in tissue might reflect response when serum levels do not.

The study was supported by grants from AbbVie, Eli Lilly, Leo Pharma, Pfizer, and Sanofi. Study patients participated in the BioDay Registry, which is sponsored by Sanofi, Regeneron, AbbVie, Eli Lilly, LEO Pharma, and Pfizer; the sponsors had no role in the study design and conduct. Dr. Spekhorst discloses receiving speaking fees from Abbvie outside the work; disclosures of other authors included receiving advisory, speaking consulting, and/or investigator fees from Sanofi Genzyme during the study. Several authors had no disclosures.

Dr. Simpson has been an investigator and consultant for Regeneron and Sanofi, makers of dupilumab. Dr. Silverberg has been an investigator, consultant, and speaker for Regeneron and Sanofi. Dr. Sidbury has been a clinical investigator for all dupilumab pediatric trials. (His institution has a contract with Regeneron and Sanofi, but he receives no money from the arrangement.)

Apple A. Bodemer, MD, a dermatologist at the University of Wisconsin, Madison, teaches patients how to breathe mindfully. So does Kathy Farah, MD, an integrative family physician who practices in Roberts, Wis.

Mindful breathing is the most basic mind-body skill and one that can help interrupt the itch-scratch cycle and relieve pain, stress, and distress often experienced by children, teens, and adults with dermatologic conditions, they said at the annual Integrative Dermatology Symposium.

“As with any integrative modality, if it’s safe and effective, then let’s use it,” Dr. Farah said in a presentation on the mind-body approach to pain and itch.

“A breathwork session can literally take 1 minute,” said Dr. Bodemer, associate professor of dermatology at the University of Wisconsin and director of an integrative dermatology clinic. Dr. Bodemer, who completed a fellowship in integrative medicine at the Andrew Weil Center for Integrative Medicine at the University of Arizona and sits on the American Board of Integrative Medicine, spoke on a mindfulness panel at the meeting.

Her favorite breathing practice is the “4-7-8” breath taught by Andrew Weil, MD, founder and director of the center. This involves inhaling through the nose for a count of 4, holding for 7, and exhaling through the mouth for a count of 8. “It doesn’t matter how slow or fast, it’s the tempo that matters ... On exhale, squeeze your abs in to engage your core and get air out of your lungs as much as you can,” she said, advising a cycle of three at a time.

A technique known as “square breathing” (breath in 4, hold for 4, breath out for 4, hold for 4) is another helpful technique to “reset the nervous system” said Dr. Farah, who worked for many years in a children’s hospital. With children, she said, “I often do five finger breathing.”

For five finger breathing, the children spread their fingers apart in front of them or on the ground and use the pointer finger of the opposite hand to trace each finger, inhaling while tracing upward, and exhaling while tracing down.

Dr. Farah, associate clinical director of The Center for Mind-Body Medicine in Washington, DC, said her commitment to mindfulness was influenced by a “seminal” study published over 20 years ago showing that patients with moderate to severe psoriasis who used a meditation-based, audiotape-guided stress reduction intervention during phototherapy sessions had more rapid resolution of psoriatic lesions than did patients who didn’t use the mindfulness exercise.

Among more recent findings: A cross-sectional study of 120 adult dermatology patients, published in the British Journal of Dermatology in 2016, assessed skin shame, social anxiety, anxiety, depression, dermatological quality of life, and levels of mindfulness, and found that higher levels of mindfulness were associated with lower levels of psychosocial distress.

Another cross-sectional questionnaire study looked at mindfulness and “itch catastrophizing” in 155 adult patients with atopic dermatitis. Higher levels of a specific facet of mindfulness termed “acting with awareness” were associated with lower levels of itch catastrophizing, the researchers found. “Catastrophizing is a negative way of thinking, this itching will never stop,” Dr. Farah explained. The study shows that “mindfulness can actually help reduce some of the automatic scratching and response to itch. So it’s a great adjunct to pharmaceuticals.”

Affirmations – phrases and statements that are repeated to oneself to help challenge negative thoughts – can also help reverse itch catastrophizing. Statements such as “I can breathe through this feeling of itching,” or “I can move to feel comfortable and relaxed” encourage positive change, she said.

“I teach [mindfulness skills like breathing] a lot, without any expectations. I’ll say ‘give it a try and see what you think.’ If patients feel even a micron better, then they’re invested” and can then find numerous tools online, Dr. Farah said. “Can I do this [in a busy schedule] with every patient? Absolutely not. But can I do it with every 10th patient? Maybe.”

Dr. Bodemer’s experience has shown her that “breathing with your patient builds rapport,” she said. “There’s something very powerful in that in terms of building trust. ... I’ll just do it [during a visit, to show them] and almost always, patients start breathing with me, with an invitation or without.”

For her own health, 4-7-8 breathing has “been a gateway to meditation and deeper practices,” she said. “But even without going very deep, it has a long history of being able to modulate the stress response. It’s the parasympathetic-sympathetic rebalancing I’m interested in.”

Mindful breathing and other mind-body practices also can be helpful for parents of children with eczema, she and Dr. Farah said.

Dr. Bodemer and Dr. Farah reported no financial relationships to disclose.

Apple A. Bodemer, MD, a dermatologist at the University of Wisconsin, Madison, teaches patients how to breathe mindfully. So does Kathy Farah, MD, an integrative family physician who practices in Roberts, Wis.

Mindful breathing is the most basic mind-body skill and one that can help interrupt the itch-scratch cycle and relieve pain, stress, and distress often experienced by children, teens, and adults with dermatologic conditions, they said at the annual Integrative Dermatology Symposium.

“As with any integrative modality, if it’s safe and effective, then let’s use it,” Dr. Farah said in a presentation on the mind-body approach to pain and itch.

“A breathwork session can literally take 1 minute,” said Dr. Bodemer, associate professor of dermatology at the University of Wisconsin and director of an integrative dermatology clinic. Dr. Bodemer, who completed a fellowship in integrative medicine at the Andrew Weil Center for Integrative Medicine at the University of Arizona and sits on the American Board of Integrative Medicine, spoke on a mindfulness panel at the meeting.

Her favorite breathing practice is the “4-7-8” breath taught by Andrew Weil, MD, founder and director of the center. This involves inhaling through the nose for a count of 4, holding for 7, and exhaling through the mouth for a count of 8. “It doesn’t matter how slow or fast, it’s the tempo that matters ... On exhale, squeeze your abs in to engage your core and get air out of your lungs as much as you can,” she said, advising a cycle of three at a time.

A technique known as “square breathing” (breath in 4, hold for 4, breath out for 4, hold for 4) is another helpful technique to “reset the nervous system” said Dr. Farah, who worked for many years in a children’s hospital. With children, she said, “I often do five finger breathing.”

For five finger breathing, the children spread their fingers apart in front of them or on the ground and use the pointer finger of the opposite hand to trace each finger, inhaling while tracing upward, and exhaling while tracing down.

Dr. Farah, associate clinical director of The Center for Mind-Body Medicine in Washington, DC, said her commitment to mindfulness was influenced by a “seminal” study published over 20 years ago showing that patients with moderate to severe psoriasis who used a meditation-based, audiotape-guided stress reduction intervention during phototherapy sessions had more rapid resolution of psoriatic lesions than did patients who didn’t use the mindfulness exercise.

Among more recent findings: A cross-sectional study of 120 adult dermatology patients, published in the British Journal of Dermatology in 2016, assessed skin shame, social anxiety, anxiety, depression, dermatological quality of life, and levels of mindfulness, and found that higher levels of mindfulness were associated with lower levels of psychosocial distress.

Another cross-sectional questionnaire study looked at mindfulness and “itch catastrophizing” in 155 adult patients with atopic dermatitis. Higher levels of a specific facet of mindfulness termed “acting with awareness” were associated with lower levels of itch catastrophizing, the researchers found. “Catastrophizing is a negative way of thinking, this itching will never stop,” Dr. Farah explained. The study shows that “mindfulness can actually help reduce some of the automatic scratching and response to itch. So it’s a great adjunct to pharmaceuticals.”

Affirmations – phrases and statements that are repeated to oneself to help challenge negative thoughts – can also help reverse itch catastrophizing. Statements such as “I can breathe through this feeling of itching,” or “I can move to feel comfortable and relaxed” encourage positive change, she said.

“I teach [mindfulness skills like breathing] a lot, without any expectations. I’ll say ‘give it a try and see what you think.’ If patients feel even a micron better, then they’re invested” and can then find numerous tools online, Dr. Farah said. “Can I do this [in a busy schedule] with every patient? Absolutely not. But can I do it with every 10th patient? Maybe.”

Dr. Bodemer’s experience has shown her that “breathing with your patient builds rapport,” she said. “There’s something very powerful in that in terms of building trust. ... I’ll just do it [during a visit, to show them] and almost always, patients start breathing with me, with an invitation or without.”

For her own health, 4-7-8 breathing has “been a gateway to meditation and deeper practices,” she said. “But even without going very deep, it has a long history of being able to modulate the stress response. It’s the parasympathetic-sympathetic rebalancing I’m interested in.”

Mindful breathing and other mind-body practices also can be helpful for parents of children with eczema, she and Dr. Farah said.

Dr. Bodemer and Dr. Farah reported no financial relationships to disclose.

Apple A. Bodemer, MD, a dermatologist at the University of Wisconsin, Madison, teaches patients how to breathe mindfully. So does Kathy Farah, MD, an integrative family physician who practices in Roberts, Wis.

Mindful breathing is the most basic mind-body skill and one that can help interrupt the itch-scratch cycle and relieve pain, stress, and distress often experienced by children, teens, and adults with dermatologic conditions, they said at the annual Integrative Dermatology Symposium.

“As with any integrative modality, if it’s safe and effective, then let’s use it,” Dr. Farah said in a presentation on the mind-body approach to pain and itch.

“A breathwork session can literally take 1 minute,” said Dr. Bodemer, associate professor of dermatology at the University of Wisconsin and director of an integrative dermatology clinic. Dr. Bodemer, who completed a fellowship in integrative medicine at the Andrew Weil Center for Integrative Medicine at the University of Arizona and sits on the American Board of Integrative Medicine, spoke on a mindfulness panel at the meeting.

Her favorite breathing practice is the “4-7-8” breath taught by Andrew Weil, MD, founder and director of the center. This involves inhaling through the nose for a count of 4, holding for 7, and exhaling through the mouth for a count of 8. “It doesn’t matter how slow or fast, it’s the tempo that matters ... On exhale, squeeze your abs in to engage your core and get air out of your lungs as much as you can,” she said, advising a cycle of three at a time.

A technique known as “square breathing” (breath in 4, hold for 4, breath out for 4, hold for 4) is another helpful technique to “reset the nervous system” said Dr. Farah, who worked for many years in a children’s hospital. With children, she said, “I often do five finger breathing.”

For five finger breathing, the children spread their fingers apart in front of them or on the ground and use the pointer finger of the opposite hand to trace each finger, inhaling while tracing upward, and exhaling while tracing down.

Dr. Farah, associate clinical director of The Center for Mind-Body Medicine in Washington, DC, said her commitment to mindfulness was influenced by a “seminal” study published over 20 years ago showing that patients with moderate to severe psoriasis who used a meditation-based, audiotape-guided stress reduction intervention during phototherapy sessions had more rapid resolution of psoriatic lesions than did patients who didn’t use the mindfulness exercise.

Among more recent findings: A cross-sectional study of 120 adult dermatology patients, published in the British Journal of Dermatology in 2016, assessed skin shame, social anxiety, anxiety, depression, dermatological quality of life, and levels of mindfulness, and found that higher levels of mindfulness were associated with lower levels of psychosocial distress.

Another cross-sectional questionnaire study looked at mindfulness and “itch catastrophizing” in 155 adult patients with atopic dermatitis. Higher levels of a specific facet of mindfulness termed “acting with awareness” were associated with lower levels of itch catastrophizing, the researchers found. “Catastrophizing is a negative way of thinking, this itching will never stop,” Dr. Farah explained. The study shows that “mindfulness can actually help reduce some of the automatic scratching and response to itch. So it’s a great adjunct to pharmaceuticals.”

Affirmations – phrases and statements that are repeated to oneself to help challenge negative thoughts – can also help reverse itch catastrophizing. Statements such as “I can breathe through this feeling of itching,” or “I can move to feel comfortable and relaxed” encourage positive change, she said.

“I teach [mindfulness skills like breathing] a lot, without any expectations. I’ll say ‘give it a try and see what you think.’ If patients feel even a micron better, then they’re invested” and can then find numerous tools online, Dr. Farah said. “Can I do this [in a busy schedule] with every patient? Absolutely not. But can I do it with every 10th patient? Maybe.”

Dr. Bodemer’s experience has shown her that “breathing with your patient builds rapport,” she said. “There’s something very powerful in that in terms of building trust. ... I’ll just do it [during a visit, to show them] and almost always, patients start breathing with me, with an invitation or without.”

For her own health, 4-7-8 breathing has “been a gateway to meditation and deeper practices,” she said. “But even without going very deep, it has a long history of being able to modulate the stress response. It’s the parasympathetic-sympathetic rebalancing I’m interested in.”

Mindful breathing and other mind-body practices also can be helpful for parents of children with eczema, she and Dr. Farah said.

Dr. Bodemer and Dr. Farah reported no financial relationships to disclose.

It is unsurprising that food frequently is thought to be the culprit behind an eczema flare, especially in infants. Indeed, it often is said that infants do only 3 things: eat, sleep, and poop.¹ For those unfortunate enough to develop the signs and symptoms of atopic dermatitis (AD), food quickly emerges as a potential culprit from the tiny pool of suspects, which is against a cultural backdrop of unprecedented focus on foods and food reactions.² The prevalence of food allergies in children, though admittedly fraught with methodological difficulties, is estimated to have more than doubled from 3.4% in 1999 to 7.6% in 2018.³ As expected, prevalence rates were higher among children with other atopic comorbidities including AD, with up to 50% of children with AD demonstrating convincing food allergy.⁴ It is easy to imagine a patient conflating these 2 entities and mistaking their correlation for causation. Thus, it follows that more than 90% of parents/guardians have reported that their children have had food-induced AD, and understandably—at least according to one study—75% of parents/guardians were found to have manipulated the diet in an attempt to manage the disease.^5,6

Patients and parents/guardians are not the only ones who have suspected food as a driving force in AD. An article in the British Medical Journal from the 1800s beautifully encapsulated the depth and duration of this quandary: “There is probably no subject in which more deeply rooted convictions have been held, not only in the profession but by the laity, than the connection between diet and disease, both as regards the causation and treatment of the latter.”⁷ Herein, a wide range of food reactions is examined to highlight evidence for the role of diet in AD, which may contradict what patients—and even some clinicians—believe.

No Easy Answers

A definitive statement that food allergy is not the root cause of AD would put this issue to rest, but such simplicity does not reflect the complex reality. First, we must agree on definitions for certain terms. What do we mean by food allergy? A broader category—adverse food reactions—covers a wide range of entities, some immune mediated and some not, including lactose intolerance, irritant contact dermatitis around the mouth, and even dermatitis herpetiformis (the cutaneous manifestation of celiac disease).⁸ Although the term food allergy often is used synonymously with adverse food reactions, the exact definition of a food allergy is specific: “adverse immune responses to food proteins that result in typical clinical symptoms.”⁸ The fact that many patients and even health care practitioners seem to frequently misapply this term makes it even more confusing. 

The current focus is on foods that could trigger a flare of AD, which clearly is a broader question than food allergy sensu stricto. It seems self-evident, for example, that if an infant with AD were to (messily) eat an acidic food such as an orange, a flare-up of AD around the mouth and on the cheeks and hands would be a forgone conclusion. Similar nonimmunologic scenarios unambiguously can occur with many foods, including citrus; corn; radish; mustard; garlic; onion; pineapple; and many spices, food additives, and preservatives.⁹ Clearly there are some scenarios whereby food could trigger an AD flare, and yet this more limited vignette generally is not what patients are referring to when suggesting that food is the root cause of their AD.

The Labyrinth of Testing for Food Allergies

Although there is no reliable method for testing for irritant dermatitis, understanding the other types of tests may help guide our thinking. Testing for IgE-mediated food allergies generally is done via an immunoenzymatic serum assay that can document sensitization to a food protein; however, this testing by itself is not sufficient to diagnose a clinical food allergy.¹⁰ Similarly, skin prick testing allows for intradermal administration of a food extract to evaluate for an urticarial reaction within 10 to 15 minutes. Although the sensitivity and specificity vary by age, population, and the specific allergen being tested, these are limited to immediate-type reactions and do not reflect the potential to drive an eczematous flare.

The gold standard, if there is one, is likely the double-blind, placebo-controlled food challenge (DBPCFC), ideally with a long enough observation period to capture later-occurring reactions such as an AD flare. However, given the nature of the test—having patients eat the foods of concern and then carefully following them for reactions—it remains time consuming, expensive, and labor intensive.¹¹ 

To further complicate matters, several unvalidated tests exist such as IgG testing, atopy patch testing, kinesiology, and hair and gastric juice analysis, which remain investigational but continue to be used and may further confuse patients and clinicians.¹²

It is useful to first separate out the classic IgE-mediated food allergy reactions that are common. In these immediate-type reactions, a person sensitized to a food protein will develop characteristic cutaneous and/or extracutaneous reactions such as urticaria, angioedema, and even anaphylaxis, usually within minutes of exposure. Although it is possible that an IgE-mediated reaction could trigger an AD flare—perhaps simply by causing pruritus, which could initiate the itch-scratch cycle—because of the near simultaneity with ingestion of the offending food and the often dramatic clinical presentations, such foods clearly do not represent “hidden” triggers for AD flares.³ The concept of food-triggered AD (FTAD) is crucial for thinking about foods that could result in true eczematous flares, which historically have been classified as early-type (<2 hours after food challenge) and late-type (≥2 hours after food challenge) reactions.^13,14 

A study of more than 1000 DBPCFCs performed in patients with AD was illustrative.¹⁵ Immediate reactions other than AD were fairly common and were observed in 40% of the food challenges compared to only 9% in the placebo group. These reactions included urticaria, angioedema, and gastrointestinal and respiratory tract symptoms. Immediate reactions of AD alone were exceedingly rare at only 0.7% and not significantly elevated compared to placebo. Just over 4% experienced both an immediate AD exacerbation along with other non-AD findings, which was significantly greater than placebo (P<.01). Although intermediate and late reactions manifesting as AD exacerbations did occur after food ingestion, they were rare (2.2% or less) and not significantly different from placebo. The authors concluded that an exacerbation of AD in the absence of other allergic symptoms in children was unlikely to be due to food,¹⁵ which is an important finding.

A recent retrospective review of 372 children with AD reported similar results.⁴ The authors defined FTAD in a different way; instead of showing a flare after a DBPCFC, they looked for “physician-noted sustained improvement in AD upon removal of a food (typically after 2–6-wk follow-up), to which the child was sensitized without any other changes in skin care.” Despite this fundamentally different approach, they similarly concluded that while food allergies were common, FTAD was relatively uncommon—found in 2% of those with mild AD, 6% of those with moderate AD, and 4% of those with severe AD.⁴ 

There are other ways that foods could contribute to disease flares, however, and one of the most compelling is that there may be broader concepts at play; perhaps some diets are not specifically driving the AD but rather are affecting inflammation in the body at large. Although somewhat speculative, there is evidence that some foods may simply be proinflammatory, working to exacerbate the disease outside of a specific mechanism, which has been seen in a variety of other conditions such as acne or rheumatoid arthritis.^16,17 To speculate further, it is possible that there may be a threshold effect such that when the AD is poorly controlled, certain factors such as inflammatory foods could lead to a flare, while when under better control, these same factors may not cause an effect.

Finally, it is important to also consider the emotional and/or psychological aspects related to food and diet. The power of the placebo in dietary change has been documented in several diseases, though this certainly is not to be dismissive of the patient’s symptoms; it seems reasonable that the very act of changing such a fundamental aspect of daily life could result in a placebo effect.^18,19 In the context of relapsing and remitting conditions such as AD, this effect may be magnified. A landmark study by Thompson and Hanifin²⁰ illustrates this possibility. The authors found that in 80% of cases in which patients were convinced that food was a major contributing factor to their AD, such concerns diminished markedly once better control of the eczema was achieved.²⁰

This brings us to what to do with an individual patient in the examination room. Because there is such widespread concern and discussion around this topic, it is important to at least briefly address it. If there are known food allergens that are being avoided, it is important to underscore the importance of continuing to avoid those foods, especially when there is actual evidence of true food allergy rather than sensitization alone. Historically, elimination diets often were recommended empirically, though more recent studies, meta-analyses, and guidance documents increasingly have recommended against them.³ In particular, there are major concerns for iatrogenic harm. 

First, heavily restricted diets may result in nutritional and/or caloric deficiencies that can be dangerous and lead to poor growth.²¹ Practices such as drinking unpasteurized milk can expose children to dangerous infections, while feeding them exclusively rice milk can lead to severe malnutrition.²² 

Second, there is a dawning realization that children with AD placed on elimination diets may actually develop true IgE-mediated allergies, including fatal anaphylaxis, to the excluded foods. In fact, one retrospective review of 298 patients with a history of AD and no prior immediate reactions found that 19% of patients developed new immediate-type hypersensitivity reactions after starting an elimination diet, presumably due to the loss of tolerance to these foods. A striking one-third of these reactions were classified as anaphylaxis, with cow’s milk and egg being the most common offenders.²³

It also is crucial to acknowledge that recommending sweeping lifestyle changes is not easy for patients, especially pediatric patients. Onerous dietary restrictions may add considerable stress, ironically a known trigger for AD itself. 

Finally, dietary modifications can be a distraction from conventional therapy and may result in treatment delays while the patient continues to experience uncontrolled symptoms of AD. 

Final Thoughts

Diet is intimately related to AD. Although the narrative continues to unfold in fascinating domains, such as the skin barrier and the microbiome, it is increasingly clear that these are intertwined and always have been. Despite the rarity of true food-triggered AD, the perception of dietary triggers is so widespread and addressing the topic is important and may help avoid unnecessary harm from unfounded extreme dietary changes. A recent multispecialty workgroup report on AD and food allergy succinctly summarized this as: “AD has many triggers and comorbidities, and food allergy is only one of the potential triggers and comorbid conditions. With regard to AD management, education and skin care are most important.”³ With proper testing, guidance, and both topical and systemic therapies, most AD can be brought under control, and for at least some patients, this may allay concerns about foods triggering their AD. 

It is unsurprising that food frequently is thought to be the culprit behind an eczema flare, especially in infants. Indeed, it often is said that infants do only 3 things: eat, sleep, and poop.¹ For those unfortunate enough to develop the signs and symptoms of atopic dermatitis (AD), food quickly emerges as a potential culprit from the tiny pool of suspects, which is against a cultural backdrop of unprecedented focus on foods and food reactions.² The prevalence of food allergies in children, though admittedly fraught with methodological difficulties, is estimated to have more than doubled from 3.4% in 1999 to 7.6% in 2018.³ As expected, prevalence rates were higher among children with other atopic comorbidities including AD, with up to 50% of children with AD demonstrating convincing food allergy.⁴ It is easy to imagine a patient conflating these 2 entities and mistaking their correlation for causation. Thus, it follows that more than 90% of parents/guardians have reported that their children have had food-induced AD, and understandably—at least according to one study—75% of parents/guardians were found to have manipulated the diet in an attempt to manage the disease.^5,6

Patients and parents/guardians are not the only ones who have suspected food as a driving force in AD. An article in the British Medical Journal from the 1800s beautifully encapsulated the depth and duration of this quandary: “There is probably no subject in which more deeply rooted convictions have been held, not only in the profession but by the laity, than the connection between diet and disease, both as regards the causation and treatment of the latter.”⁷ Herein, a wide range of food reactions is examined to highlight evidence for the role of diet in AD, which may contradict what patients—and even some clinicians—believe.

No Easy Answers

A definitive statement that food allergy is not the root cause of AD would put this issue to rest, but such simplicity does not reflect the complex reality. First, we must agree on definitions for certain terms. What do we mean by food allergy? A broader category—adverse food reactions—covers a wide range of entities, some immune mediated and some not, including lactose intolerance, irritant contact dermatitis around the mouth, and even dermatitis herpetiformis (the cutaneous manifestation of celiac disease).⁸ Although the term food allergy often is used synonymously with adverse food reactions, the exact definition of a food allergy is specific: “adverse immune responses to food proteins that result in typical clinical symptoms.”⁸ The fact that many patients and even health care practitioners seem to frequently misapply this term makes it even more confusing. 

The current focus is on foods that could trigger a flare of AD, which clearly is a broader question than food allergy sensu stricto. It seems self-evident, for example, that if an infant with AD were to (messily) eat an acidic food such as an orange, a flare-up of AD around the mouth and on the cheeks and hands would be a forgone conclusion. Similar nonimmunologic scenarios unambiguously can occur with many foods, including citrus; corn; radish; mustard; garlic; onion; pineapple; and many spices, food additives, and preservatives.⁹ Clearly there are some scenarios whereby food could trigger an AD flare, and yet this more limited vignette generally is not what patients are referring to when suggesting that food is the root cause of their AD.

The Labyrinth of Testing for Food Allergies

Although there is no reliable method for testing for irritant dermatitis, understanding the other types of tests may help guide our thinking. Testing for IgE-mediated food allergies generally is done via an immunoenzymatic serum assay that can document sensitization to a food protein; however, this testing by itself is not sufficient to diagnose a clinical food allergy.¹⁰ Similarly, skin prick testing allows for intradermal administration of a food extract to evaluate for an urticarial reaction within 10 to 15 minutes. Although the sensitivity and specificity vary by age, population, and the specific allergen being tested, these are limited to immediate-type reactions and do not reflect the potential to drive an eczematous flare.

The gold standard, if there is one, is likely the double-blind, placebo-controlled food challenge (DBPCFC), ideally with a long enough observation period to capture later-occurring reactions such as an AD flare. However, given the nature of the test—having patients eat the foods of concern and then carefully following them for reactions—it remains time consuming, expensive, and labor intensive.¹¹ 

To further complicate matters, several unvalidated tests exist such as IgG testing, atopy patch testing, kinesiology, and hair and gastric juice analysis, which remain investigational but continue to be used and may further confuse patients and clinicians.¹²

It is useful to first separate out the classic IgE-mediated food allergy reactions that are common. In these immediate-type reactions, a person sensitized to a food protein will develop characteristic cutaneous and/or extracutaneous reactions such as urticaria, angioedema, and even anaphylaxis, usually within minutes of exposure. Although it is possible that an IgE-mediated reaction could trigger an AD flare—perhaps simply by causing pruritus, which could initiate the itch-scratch cycle—because of the near simultaneity with ingestion of the offending food and the often dramatic clinical presentations, such foods clearly do not represent “hidden” triggers for AD flares.³ The concept of food-triggered AD (FTAD) is crucial for thinking about foods that could result in true eczematous flares, which historically have been classified as early-type (<2 hours after food challenge) and late-type (≥2 hours after food challenge) reactions.^13,14 

A study of more than 1000 DBPCFCs performed in patients with AD was illustrative.¹⁵ Immediate reactions other than AD were fairly common and were observed in 40% of the food challenges compared to only 9% in the placebo group. These reactions included urticaria, angioedema, and gastrointestinal and respiratory tract symptoms. Immediate reactions of AD alone were exceedingly rare at only 0.7% and not significantly elevated compared to placebo. Just over 4% experienced both an immediate AD exacerbation along with other non-AD findings, which was significantly greater than placebo (P<.01). Although intermediate and late reactions manifesting as AD exacerbations did occur after food ingestion, they were rare (2.2% or less) and not significantly different from placebo. The authors concluded that an exacerbation of AD in the absence of other allergic symptoms in children was unlikely to be due to food,¹⁵ which is an important finding.

A recent retrospective review of 372 children with AD reported similar results.⁴ The authors defined FTAD in a different way; instead of showing a flare after a DBPCFC, they looked for “physician-noted sustained improvement in AD upon removal of a food (typically after 2–6-wk follow-up), to which the child was sensitized without any other changes in skin care.” Despite this fundamentally different approach, they similarly concluded that while food allergies were common, FTAD was relatively uncommon—found in 2% of those with mild AD, 6% of those with moderate AD, and 4% of those with severe AD.⁴ 

There are other ways that foods could contribute to disease flares, however, and one of the most compelling is that there may be broader concepts at play; perhaps some diets are not specifically driving the AD but rather are affecting inflammation in the body at large. Although somewhat speculative, there is evidence that some foods may simply be proinflammatory, working to exacerbate the disease outside of a specific mechanism, which has been seen in a variety of other conditions such as acne or rheumatoid arthritis.^16,17 To speculate further, it is possible that there may be a threshold effect such that when the AD is poorly controlled, certain factors such as inflammatory foods could lead to a flare, while when under better control, these same factors may not cause an effect.

Finally, it is important to also consider the emotional and/or psychological aspects related to food and diet. The power of the placebo in dietary change has been documented in several diseases, though this certainly is not to be dismissive of the patient’s symptoms; it seems reasonable that the very act of changing such a fundamental aspect of daily life could result in a placebo effect.^18,19 In the context of relapsing and remitting conditions such as AD, this effect may be magnified. A landmark study by Thompson and Hanifin²⁰ illustrates this possibility. The authors found that in 80% of cases in which patients were convinced that food was a major contributing factor to their AD, such concerns diminished markedly once better control of the eczema was achieved.²⁰

This brings us to what to do with an individual patient in the examination room. Because there is such widespread concern and discussion around this topic, it is important to at least briefly address it. If there are known food allergens that are being avoided, it is important to underscore the importance of continuing to avoid those foods, especially when there is actual evidence of true food allergy rather than sensitization alone. Historically, elimination diets often were recommended empirically, though more recent studies, meta-analyses, and guidance documents increasingly have recommended against them.³ In particular, there are major concerns for iatrogenic harm. 

First, heavily restricted diets may result in nutritional and/or caloric deficiencies that can be dangerous and lead to poor growth.²¹ Practices such as drinking unpasteurized milk can expose children to dangerous infections, while feeding them exclusively rice milk can lead to severe malnutrition.²² 

Second, there is a dawning realization that children with AD placed on elimination diets may actually develop true IgE-mediated allergies, including fatal anaphylaxis, to the excluded foods. In fact, one retrospective review of 298 patients with a history of AD and no prior immediate reactions found that 19% of patients developed new immediate-type hypersensitivity reactions after starting an elimination diet, presumably due to the loss of tolerance to these foods. A striking one-third of these reactions were classified as anaphylaxis, with cow’s milk and egg being the most common offenders.²³

It also is crucial to acknowledge that recommending sweeping lifestyle changes is not easy for patients, especially pediatric patients. Onerous dietary restrictions may add considerable stress, ironically a known trigger for AD itself. 

Finally, dietary modifications can be a distraction from conventional therapy and may result in treatment delays while the patient continues to experience uncontrolled symptoms of AD. 

Final Thoughts

Diet is intimately related to AD. Although the narrative continues to unfold in fascinating domains, such as the skin barrier and the microbiome, it is increasingly clear that these are intertwined and always have been. Despite the rarity of true food-triggered AD, the perception of dietary triggers is so widespread and addressing the topic is important and may help avoid unnecessary harm from unfounded extreme dietary changes. A recent multispecialty workgroup report on AD and food allergy succinctly summarized this as: “AD has many triggers and comorbidities, and food allergy is only one of the potential triggers and comorbid conditions. With regard to AD management, education and skin care are most important.”³ With proper testing, guidance, and both topical and systemic therapies, most AD can be brought under control, and for at least some patients, this may allay concerns about foods triggering their AD. 

It is unsurprising that food frequently is thought to be the culprit behind an eczema flare, especially in infants. Indeed, it often is said that infants do only 3 things: eat, sleep, and poop.¹ For those unfortunate enough to develop the signs and symptoms of atopic dermatitis (AD), food quickly emerges as a potential culprit from the tiny pool of suspects, which is against a cultural backdrop of unprecedented focus on foods and food reactions.² The prevalence of food allergies in children, though admittedly fraught with methodological difficulties, is estimated to have more than doubled from 3.4% in 1999 to 7.6% in 2018.³ As expected, prevalence rates were higher among children with other atopic comorbidities including AD, with up to 50% of children with AD demonstrating convincing food allergy.⁴ It is easy to imagine a patient conflating these 2 entities and mistaking their correlation for causation. Thus, it follows that more than 90% of parents/guardians have reported that their children have had food-induced AD, and understandably—at least according to one study—75% of parents/guardians were found to have manipulated the diet in an attempt to manage the disease.^5,6

Patients and parents/guardians are not the only ones who have suspected food as a driving force in AD. An article in the British Medical Journal from the 1800s beautifully encapsulated the depth and duration of this quandary: “There is probably no subject in which more deeply rooted convictions have been held, not only in the profession but by the laity, than the connection between diet and disease, both as regards the causation and treatment of the latter.”⁷ Herein, a wide range of food reactions is examined to highlight evidence for the role of diet in AD, which may contradict what patients—and even some clinicians—believe.

No Easy Answers

A definitive statement that food allergy is not the root cause of AD would put this issue to rest, but such simplicity does not reflect the complex reality. First, we must agree on definitions for certain terms. What do we mean by food allergy? A broader category—adverse food reactions—covers a wide range of entities, some immune mediated and some not, including lactose intolerance, irritant contact dermatitis around the mouth, and even dermatitis herpetiformis (the cutaneous manifestation of celiac disease).⁸ Although the term food allergy often is used synonymously with adverse food reactions, the exact definition of a food allergy is specific: “adverse immune responses to food proteins that result in typical clinical symptoms.”⁸ The fact that many patients and even health care practitioners seem to frequently misapply this term makes it even more confusing. 

The current focus is on foods that could trigger a flare of AD, which clearly is a broader question than food allergy sensu stricto. It seems self-evident, for example, that if an infant with AD were to (messily) eat an acidic food such as an orange, a flare-up of AD around the mouth and on the cheeks and hands would be a forgone conclusion. Similar nonimmunologic scenarios unambiguously can occur with many foods, including citrus; corn; radish; mustard; garlic; onion; pineapple; and many spices, food additives, and preservatives.⁹ Clearly there are some scenarios whereby food could trigger an AD flare, and yet this more limited vignette generally is not what patients are referring to when suggesting that food is the root cause of their AD.

The Labyrinth of Testing for Food Allergies

Although there is no reliable method for testing for irritant dermatitis, understanding the other types of tests may help guide our thinking. Testing for IgE-mediated food allergies generally is done via an immunoenzymatic serum assay that can document sensitization to a food protein; however, this testing by itself is not sufficient to diagnose a clinical food allergy.¹⁰ Similarly, skin prick testing allows for intradermal administration of a food extract to evaluate for an urticarial reaction within 10 to 15 minutes. Although the sensitivity and specificity vary by age, population, and the specific allergen being tested, these are limited to immediate-type reactions and do not reflect the potential to drive an eczematous flare.

The gold standard, if there is one, is likely the double-blind, placebo-controlled food challenge (DBPCFC), ideally with a long enough observation period to capture later-occurring reactions such as an AD flare. However, given the nature of the test—having patients eat the foods of concern and then carefully following them for reactions—it remains time consuming, expensive, and labor intensive.¹¹ 

To further complicate matters, several unvalidated tests exist such as IgG testing, atopy patch testing, kinesiology, and hair and gastric juice analysis, which remain investigational but continue to be used and may further confuse patients and clinicians.¹²

It is useful to first separate out the classic IgE-mediated food allergy reactions that are common. In these immediate-type reactions, a person sensitized to a food protein will develop characteristic cutaneous and/or extracutaneous reactions such as urticaria, angioedema, and even anaphylaxis, usually within minutes of exposure. Although it is possible that an IgE-mediated reaction could trigger an AD flare—perhaps simply by causing pruritus, which could initiate the itch-scratch cycle—because of the near simultaneity with ingestion of the offending food and the often dramatic clinical presentations, such foods clearly do not represent “hidden” triggers for AD flares.³ The concept of food-triggered AD (FTAD) is crucial for thinking about foods that could result in true eczematous flares, which historically have been classified as early-type (<2 hours after food challenge) and late-type (≥2 hours after food challenge) reactions.^13,14 

A study of more than 1000 DBPCFCs performed in patients with AD was illustrative.¹⁵ Immediate reactions other than AD were fairly common and were observed in 40% of the food challenges compared to only 9% in the placebo group. These reactions included urticaria, angioedema, and gastrointestinal and respiratory tract symptoms. Immediate reactions of AD alone were exceedingly rare at only 0.7% and not significantly elevated compared to placebo. Just over 4% experienced both an immediate AD exacerbation along with other non-AD findings, which was significantly greater than placebo (P<.01). Although intermediate and late reactions manifesting as AD exacerbations did occur after food ingestion, they were rare (2.2% or less) and not significantly different from placebo. The authors concluded that an exacerbation of AD in the absence of other allergic symptoms in children was unlikely to be due to food,¹⁵ which is an important finding.

A recent retrospective review of 372 children with AD reported similar results.⁴ The authors defined FTAD in a different way; instead of showing a flare after a DBPCFC, they looked for “physician-noted sustained improvement in AD upon removal of a food (typically after 2–6-wk follow-up), to which the child was sensitized without any other changes in skin care.” Despite this fundamentally different approach, they similarly concluded that while food allergies were common, FTAD was relatively uncommon—found in 2% of those with mild AD, 6% of those with moderate AD, and 4% of those with severe AD.⁴ 

There are other ways that foods could contribute to disease flares, however, and one of the most compelling is that there may be broader concepts at play; perhaps some diets are not specifically driving the AD but rather are affecting inflammation in the body at large. Although somewhat speculative, there is evidence that some foods may simply be proinflammatory, working to exacerbate the disease outside of a specific mechanism, which has been seen in a variety of other conditions such as acne or rheumatoid arthritis.^16,17 To speculate further, it is possible that there may be a threshold effect such that when the AD is poorly controlled, certain factors such as inflammatory foods could lead to a flare, while when under better control, these same factors may not cause an effect.

Finally, it is important to also consider the emotional and/or psychological aspects related to food and diet. The power of the placebo in dietary change has been documented in several diseases, though this certainly is not to be dismissive of the patient’s symptoms; it seems reasonable that the very act of changing such a fundamental aspect of daily life could result in a placebo effect.^18,19 In the context of relapsing and remitting conditions such as AD, this effect may be magnified. A landmark study by Thompson and Hanifin²⁰ illustrates this possibility. The authors found that in 80% of cases in which patients were convinced that food was a major contributing factor to their AD, such concerns diminished markedly once better control of the eczema was achieved.²⁰

This brings us to what to do with an individual patient in the examination room. Because there is such widespread concern and discussion around this topic, it is important to at least briefly address it. If there are known food allergens that are being avoided, it is important to underscore the importance of continuing to avoid those foods, especially when there is actual evidence of true food allergy rather than sensitization alone. Historically, elimination diets often were recommended empirically, though more recent studies, meta-analyses, and guidance documents increasingly have recommended against them.³ In particular, there are major concerns for iatrogenic harm. 

First, heavily restricted diets may result in nutritional and/or caloric deficiencies that can be dangerous and lead to poor growth.²¹ Practices such as drinking unpasteurized milk can expose children to dangerous infections, while feeding them exclusively rice milk can lead to severe malnutrition.²² 

Second, there is a dawning realization that children with AD placed on elimination diets may actually develop true IgE-mediated allergies, including fatal anaphylaxis, to the excluded foods. In fact, one retrospective review of 298 patients with a history of AD and no prior immediate reactions found that 19% of patients developed new immediate-type hypersensitivity reactions after starting an elimination diet, presumably due to the loss of tolerance to these foods. A striking one-third of these reactions were classified as anaphylaxis, with cow’s milk and egg being the most common offenders.²³

It also is crucial to acknowledge that recommending sweeping lifestyle changes is not easy for patients, especially pediatric patients. Onerous dietary restrictions may add considerable stress, ironically a known trigger for AD itself. 

Finally, dietary modifications can be a distraction from conventional therapy and may result in treatment delays while the patient continues to experience uncontrolled symptoms of AD. 

Final Thoughts

Diet is intimately related to AD. Although the narrative continues to unfold in fascinating domains, such as the skin barrier and the microbiome, it is increasingly clear that these are intertwined and always have been. Despite the rarity of true food-triggered AD, the perception of dietary triggers is so widespread and addressing the topic is important and may help avoid unnecessary harm from unfounded extreme dietary changes. A recent multispecialty workgroup report on AD and food allergy succinctly summarized this as: “AD has many triggers and comorbidities, and food allergy is only one of the potential triggers and comorbid conditions. With regard to AD management, education and skin care are most important.”³ With proper testing, guidance, and both topical and systemic therapies, most AD can be brought under control, and for at least some patients, this may allay concerns about foods triggering their AD.