People with congenital ichthyoses have a higher rate of atopic disease than the general population, which researchers say could be due to epidermal barrier impairment associated with these conditions, according to the results of a recent cross-sectional survey.

Congenital ichthyoses are associated with rough and painful erythroderma, scaling, and palmoplantar keratoderma. While it was suspected that patients with these rare skin disorders are at a greater risk for atopy, congenital ichthyoses — also called epidermal differentiation disorders — have been difficult to study.

“Over the last decade, we’ve learned that these ichthyoses that we thought were just skin problems have evidence of systemic immune activation, and that made us start thinking about comorbidities,” Amy S. Paller, MD, study author and professor dermatology and pediatrics and chair of dermatology at Northwestern University in Chicago, told Medscape Dermatology.

Congenital ichthyoses are characterized by a poor epidermal barrier, something they have in common with atopic dermatitis, which carries a greater risk for allergic disorders, Paller said.

Results from the survey of patients and their parents have found patients with congenital ichthyoses have a greater degree of barrier dysfunction — as measured by transepidermal water loss — that is “at the level of atopic dermatitis or higher,” Paller said. Most of these patients also have at least one atopic disorder such as allergic rhinitis, food allergy, and allergic asthma compared with the general population.

The study was published online in The Journal of Allergy and Clinical Immunology.

High Rates of Atopic Disorder

The researchers surveyed 115 patients with congenital ichthyosis and their parents from Ann & Robert H. Lurie Children’s Hospital of Chicago in Chicago and the Foundation for Ichthyosis and Related Skin Types family conference.

The survey asked patients about their ichthyosis subtype, any allergic conditions they had, and whether they took allergy medication or had a family history of allergic disease. Researchers compared the answers with atopy data obtained from an age-matched population of participants in the 2021 National Health Interview Survey.

Overall, 59 children aged between 6 and 17 years and 56 adults were enrolled, with most patients having lamellar ichthyosis (N = 27), congenital ichthyosiform erythroderma (N = 26), and X-linked ichthyosis (N = 21).

The results showed that 68.2% of patients reported at least one allergic condition diagnosed by a physician, which included 64.3% vs 72.5% of children vs adults.

Across all congenital ichthyosis subtypes, patients reported significantly higher rates of atopic disorder, including allergic rhinitis, food allergy, and allergic asthma than the age-matched population. However, only allergic rhinitis was significant for adults with congenital ichthyosis.

Patients most likely to have allergic conditions included erythrodermic ichthyosis subtypes such as Netherton syndrome (100%), ichthyosis with confetti (100%), and harlequin ichthyosis (83.3%), as well as X-linked ichthyosis (85.7%), which the study authors noted has a level of barrier impairment similar to atopic dermatitis.

There also tended to be a family history of allergic disease, with 54.2% of survey respondents noting that allergic disease runs in their family. A majority of survey respondents also reported previously using allergy medications (57.9%), and more than one quarter of respondents reported having a positive allergen test (28.0%).

Taking a Holistic Approach

Prior to this study, Netherton syndrome was the sole congenital ichthyosis subtype associated with allergies. Paller said the results of the study are an opportunity to identify potentially undiagnosed allergies in patients with congenital ichthyosis.

“We shouldn’t just be thinking about Netherton syndrome as a form of congenital ichthyosis that’s associated with allergies but rather should be asking our patients as we try to have a holistic approach about allergic disorders,” she said.

Patients who see a dermatologist for skin disease may not think to disclose symptoms they see as unrelated to care, such as a chronic cough, runny nose, and food allergies — all signs that potentially point to asthma or allergic rhinitis, Paller explained. If patients don’t currently have allergies, bringing it up during a visit can keep it top of mind and help to broach the topic in the future.

“We may be the ones who may be able to get them to an allergist and get them the relief that they need from allergies that they don’t even know exist,” she said.

Paller said that one future area of research could examine the potential of early use of agents such as dupilumab in reducing the risk for the atopic march in patients with congenital ichthyosis.

“We’ve been finding many patients with ichthyosis whose itch is improved by dupilumab, so it may lower the threshold in this patient population for trying to treat [off-label] with an agent that also reduces the risk, potentially, of allergies,” she said.

Paller reported being an investigator for AbbVie; BioMendics; Dermavant Sciences; Eli Lilly and Company; Incyte; Johnson & Johnson Innovative Medicine; MoonLake Immunotherapeutics; Quoin; Regeneron; TWi Pharmaceuticals, Inc.; and UCB; a consultant for Abeona Therapeutics, Almirall, Apogee, APR Applied Pharma Research SA, Arcutis Biotherapeutics, BioCryst Pharmaceuticals, Boehringer Ingelheim, Chiesi Farmaceutici S.p.A., Gedeon Richter Plc., Johnson & Johnson Innovative Medicine, Kamari Pharma Ltd., Eli Lilly and Company, L’Oreal, MoonLake, Novartis, Palvella Therapeutics, Pelthos Therapeutics, Pfizer, Quoin, Sanofi, and Takeda; and a data safety monitoring board member for AbbVie, Abeona, BioCryst, and Galderma. The other authors reported having no disclosures.

Jeff Craven is an independent journalist living in Wilmington, Delaware.