Phenotype Switching Between Psoriasis and AD Gains Clinical Ground in Biologic-Treated Patients

A multicenter real-world study provides some of the strongest evidence to date that psoriasis and atopic dermatitis (AD) can shift clinical phenotypes during systemic and biologic therapy. This so-called “flip-flop” phenomenon is increasingly relevant in day-to-day dermatology practice, particularly for clinicians managing patients on targeted immunomodulators.^1,2

“Recognition of this entity is essential to avoid misclassification as treatment failure and to guide appropriate therapeutic adaptation,” study investigators wrote. “In real-world practice, JAK inhibitors emerged as a frequently used therapeutic option following phenotype switching and were associated with favourable clinical outcomes.”

The study included 148 patients from 17 dermatology centers across Europe and Canada who developed a treatment-associated switch between psoriasis and AD. Most cases (68.2%) involved patients with psoriasis who subsequently developed eczematous dermatitis while on systemic therapy, while 31.8% involved patients with AD who developed psoriasiform disease during treatment.

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Patient Characteristics and Comorbidity Patterns

Patients who shifted from psoriasis to AD tended to be older and had higher rates of cardiometabolic comorbidities such as hypertension, diabetes, and dyslipidemia. In contrast, patients who transitioned from AD to psoriasis more commonly had a personal history of atopic disease, including asthma, allergic rhinitis, or food allergy. Despite these trends, overlap was frequent, with a substantial proportion of patients demonstrating mixed atopic and psoriatic backgrounds, reinforcing the idea that these conditions may coexist along a shared inflammatory spectrum in certain individuals.

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Treatment Associations and Triggering Agents

Clear treatment associations emerged across both directions of switching. In patients treated for psoriasis, phenotype switching toward eczematous disease was most often observed with IL-17 inhibitors, followed by IL-23 inhibitors and, less commonly, TNF inhibitors. In contrast, nearly all cases of psoriasis-like eruptions in patients with AD occurred during treatment with biologics targeting type 2 inflammation, most notably dupilumab, with a smaller number occurring on IL-13 inhibitors such as tralokinumab or lebrikizumab.

Mechanistic Interpretation: Immune Rebalancing

From a mechanistic standpoint, these findings support the concept of immune rebalancing. Suppressing one inflammatory pathway, such as Th17/Th1 in psoriasis or Th2 in AD, may allow a previously subclinical opposing pathway to emerge clinically in susceptible patients. Importantly, this differs from classic paradoxical reactions in that the resulting phenotype is often sustained and requires a true change in long-term disease management strategy rather than temporary interruption of therapy.

Clinical Recognition: Why It Matters in Practice

Clinically, recognition of this pattern is essential. In real-world practice, a new eczematous eruption in a patient with psoriasis on biologic therapy may be misinterpreted as drug failure or hypersensitivity rather than a phenotype shift. Similarly, the development of psoriasiform plaques in a patient with well-controlled AD on dupilumab or an IL-13 inhibitor may lead to unnecessary discontinuation of effective therapy if the underlying process is not recognized.

Management Strategies in Real-World Practice

Management strategies in this cohort were variable but followed several consistent themes. In patients with psoriasis who developed eczematous disease, switching to a Janus kinase (JAK) inhibitor was the most common approach, used in approximately 60% of cases. Upadacitinib accounted for the majority of JAK use in this group, reflecting its broad anti-inflammatory activity across both type 2 and type 1 pathways. Some patients were instead managed by switching biologic classes or by discontinuing the triggering agent and using topical or conventional systemic therapies, although these approaches were less frequent.

In the opposite scenario, patients with AD who developed psoriasiform disease were managed more heterogeneously. Many clinicians continued the original AD-directed biologic while adding topical corticosteroids, systemic agents, or in some cases psoriasis-directed biologics. A substantial subset, however, was transitioned to JAK inhibitor therapy, again most commonly upadacitinib, reflecting a similar preference for broader immunomodulation when disease phenotype becomes mixed or unstable.

Clinical Outcomes After Treatment Adjustment

Outcomes were generally favorable following treatment modification. Both psoriasis and eczema severity scores improved significantly over follow-up, with reductions in PASI and EASI values indicating that disease control can be regained despite phenotype switching. This reinforces an important practical point: switching does not necessarily represent treatment failure, but rather a signal to reassess the dominant inflammatory pathway.

Clinical Implications

From a clinical decision-making standpoint, the study supports a more flexible interpretation of evolving skin morphology during biologic therapy. Rather than immediately discontinuing effective systemic treatment, clinicians may benefit from considering phenotype switching as part of the differential diagnosis, particularly in patients with mixed atopic or psoriatic risk factors.

Limitations and Generalizability

Several limitations should be considered. The study was retrospective and observational, and phenotype switching was defined clinically without standardized histopathologic or molecular confirmation. There is also potential interobserver variability across participating centers. In addition, the population was predominantly Caucasian, which may limit generalizability to more diverse patient groups.

Bottom Line for Clinical Practice

Despite these limitations, the consistency of findings across multiple international centers strengthens the clinical relevance of the results. For dermatology clinicians, the key takeaway is that psoriasis and AD are not always rigidly distinct entities in the context of modern targeted therapy. Instead, they may behave as dynamic, interrelated inflammatory states that can shift under selective immune pressure. Recognizing this pattern can help avoid premature discontinuation of effective therapies and support more appropriate transitions to broader agents, particularly JAK inhibitors, when clinically indicated.

References

1. Torres T, Valenti M, Balato A, et al. Treatment-associated phenotype switching between psoriasis and atopic dermatitis. J Eur Acad Dermatol Venereol. Published online May 14, 2026. doi:10.1111/jdv.70503
2. Müller S, Welchowski T, Schmid M, et al. Development of a clinical algorithm to predict phenotypic switches between atopic dermatitis and psoriasis (the "Flip-Flop" phenomenon). Allergy. 2024;79(1):164-173. doi:10.1111/all.15921