When treatment is not working for adults with atopic dermatitis (AD), first-time guidelines from the American Academy of Dermatology (AAD) suggest considering other factors in the differential diagnosis, such as comorbid conditions with overlapping skin symptoms, issues with treatment availability, and patient tolerability to therapy.

Increasing awareness of how these factors can contribute to treatment-refractory AD and highlighting ways to diagnose these patients are the primary aims of the “Guidelines for Diagnostic Testing in Adults With Presumed Atopic Dermatitis Refractory to Treatment,” published online on August 31 in the Journal of the American Academy of Dermatology.

“If something looks like eczema and you’ve tried traditional therapy, and it appears not to be working, perhaps it’s not atopic dermatitis, or it’s not solely atopic dermatitis. You need to think about other conditions,” Dawn Davis, MD, senior author and co-chair of the AAD working group for the guidelines, told Medscape Medical News. Allergic or irritant contact dermatitis, food allergies, asthma, allergic rhinitis, psoriasis, urticaria, and cutaneous T-cell lymphoma are among the possibilities.

Someone might have an undiagnosed food allergy, food intolerance, or uncontrolled hay fever that could drive the immune system into overdrive, and their eczema does not respond to treatment. “It’s common, for example, in my practice for my atopic dermatitis patients to be doing well,” said Davis, who is also a dermatologist at Mayo Clinic in Rochester, Minnesota. “Then they have allergic rhinoconjunctivitis symptoms, and they’ll tell me that their eczema flares, or they’ll develop gluten sensitivity, and they’ll have eczema flares.” 

The guidelines include a review of confounding dermatoses, timing of assessments and follow-up, as well as clinical and diagnostic testing to consider in the workup of adults with presumed treatment-resistant AD, such as patch testing, skin biopsy, bacterial skin culture, skin scraping, and other tests.

Think Beyond Upping Therapy

“I think the most important message is deceptively simple: When presumed AD is not responding appropriately to optimized treatment, we should not automatically assume that it is simply ‘refractory AD’ and keep escalating therapy,” Peter Lio, MD, clinical assistant professor of dermatology and pediatrics at Northwestern University Feinberg School of Medicine in Chicago, and a scientific advisor to the National Eczema Association, said when asked to comment on the guidelines.

“For patients, I think the message is a hopeful one,” added Lio, who was not an author of the guidelines. In a patient with AD who is not improving despite appropriate treatment, he said, “It is worth asking why. Sometimes there is another condition masquerading as AD or occurring alongside it. Sometimes the issue is treatment access, complexity, tolerability, or another barrier that makes an otherwise good treatment plan difficult to follow.”

By Popular Demand

So why are these guidelines needed and why now? “In clinical practice, we noted that clinicians struggled at times with differentiating atopic dermatitis from other skin diseases, particularly in adults, and particularly if patients had adult-onset atopic dermatitis,” Davis said. About 1 in 4 cases of AD among adults starts in adulthood, and approximately 2% of adults worldwide have AD, the guidelines noted. The proportion of adults with presumed AD who are treatment-refractory is unknown.

Davis and coauthors acted on feedback from dermatologists to create the guidelines, which are part of a series, including previous guidance on care and management of adults with AD using topical therapies published in 2023 and guidelines on management with phototherapy and systemic therapies in 2024.

A Challenging Diagnosis

Diagnosis of adult-onset AD can be complex, the guideline authors noted. Symptoms overlap with other skin conditions. A personal or family history of atopy is less common in adult-onset cases compared with childhood AD. That leaves physicians to rely on history, physical exam, and diagnostic criteria (essential, important, and associated features are outlined in the guidelines).

“We are often asked, particularly by nondermatologists and by patients, what is the one test I can do to confirm atopic dermatitis?” Davis said. However, there is no standard diagnostic assay. The guideline authors also noted that in resource-limited settings, testing and specialists may not be readily available. 

“I like that this guideline gives clinicians a practical framework: Confirm the diagnosis and treatment optimization, then let the clinical presentation guide the next diagnostic step,” Lio said.

The guidelines address the risks for over-testing and under-testing. “Over-testing may increase health care costs, cause unnecessary patient burden, and result in diagnostic confusion, while under-testing may delay appropriate treatment and worsen outcomes,” the authors concluded.

“This may be the most important nuance in the guideline,” Lio said. “The goal is not to order every possible test in every patient with difficult AD.” Instead, testing should be targeted to the morphology, distribution, history, exposures, associated symptoms, and response to treatment, and “clinical judgment remains essential and at the center,” he said.

“One way I think about this is: Treatment failure is information,” Lio said. “A patient who does not respond as expected is telling us something.” That information could be about the diagnosis, a concomitant disease, adherence or access, or simply that the chosen therapy is not effective for that individual. He added, “With so many effective treatments now available for AD, persistent refractory disease should prompt curiosity and reassessment rather than automatic escalation.”

A goal of these guidelines is to “hopefully encourage clinicians to pause and consider the diagnosis to either rule in eczema or rule it out,” Davis said. “In addition, [the aim is] to practice whole-person care because the eczema is not going to respond appropriately if there are other active comorbidities or systemic concerns.”

Davis reported having no relevant financial disclosures. Lio reported being on the speaker’s bureau for AbbVie, Arcutis Biotherapeutics, Eli Lilly, Galderma, Incyte, La Roche-Posay/L'Oréal, Pfizer, Pierre Fabre Dermatology, Regeneron/Sanofi Genzyme, Verrica, and ZenZema; and serving as a consultant or advisory board member for Alphyn Biologics, AbbVie, Almirall, Amyris, Apogee, Arcutis Biotherapeutics, Astria Therapeutics, Castle Biosciences, Codex Labs, Concerto Biosciences, Dermavant Sciences, Eli Lilly, Galderma, Kenvue, LEO Pharma, Lipidor, L'Oréal, Merck, Nektar Therapeutics, Nia Health, Pelthos Therapeutics, Novartis, Phyla, Regeneron/Sanofi Genzyme, Sibel Health, Skinesa, Skinfix, Soteri Skin, Stratum Biosciences, Sun Pharma, Theraplex, Thimble Health, Topaz Biosciences, Unilever, Verdant Scientific, Verrica, and Yobee Care. He reported having stock options with Alphyn Biologics, Codex Labs, Concerto Biosciences, Thimble, Topaz Biosciences, and Yobee Care. In addition, Lio reported receiving royalties for a Theraplex product and being a Scientific Advisory Committee Member Emeritus of the National Eczema Association.