Atopic Dermatitis

ETIOLOGIES

Diet

Broadly speaking, diet and food allergies as a cause of atopic dermatitis are uncommon and essentially never the sole cause of atopic dermatitis. There are a couple of very good review articles and commentaries on this topic that I have come across.
- One is by Dr. Peter Lio who a is a pediatric dermatologist at Northwestern and proponent of alternative medicine, originally published in Cutis and then reprinted in Practical Dermatology. (36638380) He does a good job providing a balanced paradigm for how diet relates to atopic dermatitis. First, he acknowledges that there is a significant focus on diet as cause of disease which leads to 90% of parents believing their child's AD is caused by foods. He is careful to point out that foods can contribute to AD, however, even trigger a flare, but that this is different than being causative. For example, there are a number of foods that can cause nonimmunologic skin irritation due to their acidity or other properties, precipitating a flare of AD when contacting the skin. Foods that may have that potential include:
  - citrus, corn, radish, mustard, garlic, onion, pineapple, many spices, food additives and preservatives
- Dr. Lio points out the two main diagnostic modalities for identifying IgE-mediated food allergies which manifest with urticaria, angioedema, and potentially anaphylaxis. Immunoenzymatic serum assay for IgE antibodies and intradermal skin prick testing are used to identify the potential for these allergies. Allergies identified by this method, if accompanied by signs and symptoms of pruritus and histamine release after food ingestion, may contribute to AD flares by initiating scratching and leading to the itch-scratch-AD flare cycle.
- He describes the gold standard for identifying food-induced AD which is the double-blind placebo-controlled food challenged (DBPCFC). In trials using this method, <1% of participants had immediate AD flares alone when ingesting foods, and the rates were no different from placebo. However, 4% of participants developed AD flares along with other non-AD skin findings, which was greater than placebo. This demonstrates that AD alone is an uncommon immediate manifestation of food allergy, but that if accompanied by other non-AD signs and symptoms it could contribute to a flare. Delayed onset manifestations of AD occurred in 2.2% of participants and was no different than placebo. Conclusion: exacerbation of AD in the absence of other signs of food allergy is unlikely to be related to food intake.
Another review article written primarily by allergists (mitigating potential specialty bias in favor of one's specialty being the more integral to the disease process), "Are avoidance diets still warranted in children with atopic dermatitis?" published in Pediatric Allergy and Immunology, advocates for limited testing for food allergens as a cause of atopic dermatitis. The abstract provides a nice summary (31273833), but main points included:
- 40% of children with moderate-severe AD have clinically significant food allergies. Many children will demonstrate positive reactions on tests but have no clinically significant reaction.
- Postulates that IgE sensitization of oral food allergies may occur via the skin and not ingestion (i.e., skin contact with peanuts primes immune system, then peanut allergy is observed on first challenge with peanuts).
- They advocate the following plan:
  - First, good skin care routine. Emollients, topical steroids, anti-itch plan. Role of food often becomes minor if skin is addressed
  - Next, food history. Tomato, eggplant, and parmesan cheese among many others may provoke just perioral erythema and does not warrant food allergy testing.
  - If allergy testing warranted, restrict it to a subset of suspected foods based on history, often egg, milk, wheat, and rarely soy. Tests have good negative predictive value but like patch testing positive results must be clinically correlated. Testing for other foods that could be a cause of severe anaphylactic reactions like peanuts, although not likely a cause of AD, may be warranted given the association between AD, food allergies that may contribute to AD, and anaphylactic food allergies.
  - If foods are identified via history and testing, a 2-3 week elimination trial can be attempted while continuing skin care. Elimination may improve symptoms, but also may lead to progression of the allergy towards an anaphylactic response. If no response is seen, food allergy is not proven. If improvement is seen, rechallenge to establish the cause.
  - Avoidance diets do not need to be complete. Small amounts of a food like eggs or milk cooked in a baked good may be tolerable, prevent worsening of the allergy, and complete elimination will not likely lead to any additional improvement.

Environmental Factors

A study in Taiwan established that air quality seems to have a dose-response relationship with the incidence of atopic dermatitis. 38311242

Contact Dermatitis

The prevalence of contact dermatitis in children with atopic dermatitis appears to be higher, with ~50% greater odds of having more than 1 positive reaction. Reaction to cocamidopropyl betaine was 3.7x more likely in AD patients than those without AD. 37768237

Staph Aureus

Although staph is not causal, it an complicate or perpetuate eczema flares.

Antibiotic susceptibility

"Global Antimicrobial Susceptibility Patterns of Staphylococcus aureus in Atopic Dermatitis" (39320869)
- Clindamycin: 0.79
- Daptomycin: 0.98
- Doxycycline: 0.94
- Erythromycin: 0.73
- Fusidic acid: 0.80
- Linezolid: 1.00
- Methicillin, oxacillin, and cefoxitin: 0.85
- Minocycline: 1.00
- Mupirocin: 0.98
- Trimethoprim and sulfamethoxazole: 0.97
- Vancomycin: 1.00

Scoring/Grading

Multiple grading systems have been reviewed here. (Tables)

TREATMENTS

Comparative Efficacy/Safety

EASI scores Compared to dupilumab: upadacitinib 30mg > abrocitinib 200mg > upadadcitinib 15mg ~ dupilumab > lebrikizumab ~ abrocitinib 100mg > baricitinib 4mg > tralokinumab > baricitinib 2mg. 39018058

Pediatric

Real-world treatment outcomes of systemic treatments for moderate-to-severe atopic dermatitis in children aged less than 12 years: 2-year results from PEDIatric STudy in Atopic Dermatitis. J Am Acad Dermatol. 2025. PMID: 39389429.

Study Design: A real-world, prospective, observational, 10-year study named PEDIatric STudy in Atopic Dermatitis (PEDISTAD) analyzed systemic treatments in children under 12 years old with moderate-to-severe atopic dermatitis (AD) who had inadequate control with topical therapies.
Participants: 1,329 children enrolled between September 2018 – May 2021, receiving either dupilumab (n = 144), methotrexate (n = 114), or cyclosporine (n = 121); remaining patients received other systemic drugs or topical medications only.
Results:
- Median duration: Methotrexate (13.0 months) > Cyclosporine (10.7 months) > Dupilumab (8.1 months)
  - Dupilumab had fewer discontinuations (8.3%) compared to methotrexate (28.9%) and cyclosporine (43.0%).
  - The seemingly contradictory finding—that dupilumab had the lowest discontinuation rates but the shortest median duration of treatment—can be explained by a few key factors including enrollment timelines, how long patients had access to the drug (dupilumab was a newer drug) and differences in how the medications are used (CsA and MTX we typically try to get patients off more readily).
- Efficacy: Dupilumab showed the most improvement: EASI Score: -12.4 (vs. -5.7 for methotrexate, -3.3 for cyclosporine) - similar findings across most treatment endpoints
- Safety & Adverse Events (AEs):
  - Dupilumab had the lowest rate of adverse events (18.1%) compared to methotrexate (29.8%) and cyclosporine (31.4%).
  - Most common AEs:
    - Dupilumab: Allergic conjunctivitis (2.1%)
    - Methotrexate: Atopic dermatitis flare (7.0%)
    - Cyclosporine: Impetigo (9.9%)
  - Lower infection rates with dupilumab compared to the other two drugs.
- Treatment Discontinuation: Dupilumab had the highest treatment adherence (91.7% continued treatment), compared to 71.1% for methotrexate and 57.0% for cyclosporine. Fewer discontinuations due to lack of efficacy (1.4% for dupilumab vs. 5.3% for methotrexate and 9.1% for cyclosporine).

Dupilumab (Dupixent)

Safety

IN a 5-year open-label extension study, nasopharyngitis occurred in 28.9%, URI in 13.6%, conjunctivitis 10.3%, allergic conjunctivitis 9%, herpes infections 12.8%. 38985486
- On conjunctivitis: "A total of 536 of 2677 patients (20.0%) reported 894 conjunctivitis events (reported events under the narrow Custom MedDRA Query comprising the following PTs: conjunctivitis, conjunctivitis allergic, conjunctivitis bacterial, conjunctivitis viral, and atopic keratoconjunctivitis). A total of 27 patients patients (1.0%) experienced 1 or more instances of treatment-emergent severe conjunctivitis over the course of the 5-year study. Most conjunctivitis cases were reported recovered or resolved during the study (784 of 894 [87.7%])."

Effect of Treatment on Cognitive Issues

In patients with a diagnosis of atopic dermatitis and ADHD, dupilumab was associated with a lower relative risk of psychostimulant or nootropic (natural or synthetic "cognitive enhancers") use compared to those not on dupilumab: RR 0.85, 0.75 for males, 0.99 for females. Relative risk of psychostimulant or nootropic use after starting dupilumab compared to before was 0.72 (0.67 for males, 0.77 for females). 36736623

Other IL-13 Inhibitors

Cendakimab

IL-13 inhibitor (receptor alpha 1 and alpha 2 antagonist) owned by Bristol Meyers Squib. 39018038

Lebrikizumab (Ebglyss)

JAK inhibitors

Safety and Efficacy

Effectiveness and tolerance of Janus kinase inhibitors for the treatment of recalcitrant atopic dermatitis in a real-life French multicenter adult cohort. J Am Acad Dermatol. 2023. PMID: 36280001.

MY SUMMARY: 100 patients treated with upadacitinib or baricitinib (approved in Europe, not in US). 60% experienced at least 1 AE: 23% elevated cholesterol, 18% elevated triglycerides, 13% facial papular eruption, 11% increased ALT or AST, 6% HSV eruption. No TEs. 6 patients discontinued due to adverse events: one each for papular facial eruption, cytolysis, increased total or LDL-cholesterol, dyspnea, facial edema, and asthenia (supplementary table II).

Pediatric Safety and Efficacy

Efficacy and Safety of Upadacitinib Treatment in Adolescents With Moderate-to-Severe Atopic Dermatitis: Analysis of the Measure Up 1, Measure Up 2, and AD Up Randomized Clinical Trials. JAMA Dermatol. 2023. PMID: 37043227.

MY SUMMARY: This is a summary of 3 RCTs for 12-17 year olds, Measure 1, Measure 2, and AD Up, with 16 week efficacy and safety data. Efficacy was excellent. Most common treatment-emergent adverse events were acne, HA, URTI, CPK elevation, and nasopharyngitis. Acne was more common compared to placebo, and occurred a median of ~50 days after starting medication, with range ~1-100 days (certainly some challenge determining which cases were complicated by the drug or were part of natural history of adolescence). CPK elevations occurred in about 1 in 20-25 patients compared to 1 in 100 for placebo.

Upadacitinib

In adolescents (12-17yo) through 76 weeks of treatment (~1.5 years), better than 4 in 5 achieved EASI-75. Main AEs observed were herpes zoster and CK elevation. 39441580

Baricitinib

Approved for AD in Europe but not the US. BREEZE-AD7 trial showed safety and efficacy in non-US patients when used in combination with topical steroids. 33001140

Roflumilast 0.15% (Zoryve)

At week 4, ~29-32% using roflumilast achieved an IGA of 0 or 1 (and at least a 2 point improvement from baseline) compared to ~12-15% in the placebo group. ~42-43% achieved a EASI 75 compared to ~20-22% of placebo. (39292443)