Advanced treatments for psoriasis, AD may produce paradoxical reactions

Pustular psoriasis. Photo by Roland Tanglao via Wikimedia Commons

Cutaneous paradoxical reactions to biologic therapies for psoriasis and atopic dermatitis are emerging as an important, if unpredictable, complication of these otherwise highly targeted treatments, according to Dr. Jeffrey Marcus Cohen.

In a report in the Dec. 2025 issue of The Chronicle of Skin & Allergy, Dr. Cohen noted monoclonal antibodies have transformed care by addressing the underlying immunology of chronic inflammatory skin disease. However, they can also trigger new inflammatory dermatoses or exacerbate existing conditions in unexpected ways.

Speaking at the American Academy of Dermatology annual meeting in Orlando, Fla., Dr. Cohen defined paradoxical reactions as an “exacerbation of or development of new inflammatory dermatoses” in patients treated with biologic agents, emphasizing the need for prompt recognition and management. He is an Associate Professor of Dermatology and Biomedical Informatics and Data Science and Director of the Psoriasis Treatment Program at Yale School of Medicine.

A systematic review documented these reactions across tumour necrosis factor (TNF)-alpha inhibitors, IL-17 inhibitors, IL-12/23 inhibitors, and IL-23 inhibitors, with the majority occurring in association with TNF-alpha blockade. A Canadian study of eczematous eruptions in patients on biologics similarly found paradoxical reactions to be more common with TNF-alpha inhibitors, particularly infliximab and adalimumab.

These reactions have a highly variable onset, which limits the utility of timing as a diagnostic clue, Dr. Cohen noted. Although the Canadian series reported an average of eight months on therapy before a paradoxical event, cases have appeared within days or, conversely, after many years of treatment. IL-17 inhibitors such as secukinumab, ixekizumab, bimekizumab, and brodalumab have been linked to paradoxical reactions that may involve flexural sites and the face, often with papular eczema in patients whose Th17 activity is being therapeutically dampened toward a more homeostatic state.

Paradoxical eruptions appear relatively uncommon with IL-12/23 and IL-23 inhibitors, where eczematous eruptions predominate, though psoriasiform reactions, pustular psoriasis, and even vitiligo have been reported with ustekinumab. In the atopic dermatitis setting, IL-4/IL-13 inhibitors have been associated with psoriasiform eruption, head and neck dermatitis, alopecia areata, and sarcoidosis, with more paradoxical reactions observed with dupilumab than with tralokinumab or lebrikizumab, likely reflecting broader dupilumab use.​

Dr. Cohen urged vigilance for cutaneous T-cell lymphoma (CTCL) in patients receiving dupilumab, citing reports of CTCL in this population and advising a low threshold for biopsy and additional workup when patients flare or develop concerning signs. Whether dupilumab unmasks pre-existing CTCL, contributes to its emergence, or both remains uncertain, he said.​

Management often begins with switching to a different biologic agent when a specific drug is linked to the reaction, according to Dr. Cohen. In the case of TNF-alpha inhibitors, paradoxical psoriasis or eczematous eruptions should be treated with topical therapies, systemic agents, or phototherapy, but not with a switch to another TNF-alpha inhibitor, given the likelihood of recurrence within the same class. For IL-17, IL-12/23, and IL-23 inhibitors, paradoxical eczematous eruptions may be addressed with topical agents, systemic medications, or phototherapy, while psoriasiform eruptions associated with IL-4/IL-13 inhibitors can be similarly managed, sometimes without discontinuing the atopic dermatitis biologic.

With files from correspondent Louise Gagnon