Phenotypic Switch From Atopic Dermatitis to Psoriasis During Dupilumab Therapy: A Real‐Life Experience From a Tertiary Referral Center

Atopic dermatitis (AD) and psoriasis are two chronic inflammatory skin conditions traditionally considered distinct entities, as they result from the activation of T helper (Th)-2 and Th1/Th17 pathways, respectively [1]. Growing evidence suggests a possible overlap and/or even a phenotypic transition between these conditions, particularly in the context of biologic therapies [2-4]. In this study, we report 16 patients (1.8% of 890) who exhibited a phenotypic shift from AD to psoriasis during treatment with dupilumab for moderate-to-severe AD between January 2019 and June 2025. The median baseline Eczema Area and Severity Index (EASI) score was 25.5 (interquartile range [IQR] 24–29). The mean age of the cohort (12 males and 4 females) was 57.3 years (range: 21–87), with a predominantly late-onset AD pattern observed in 11 cases (68.8%). Atopic comorbidities were observed in 11 patients (68.8%), and elevated serum immunoglobulin E (IgE) levels were detected in 13 patients (81.3%). A positive family history of psoriasis was reported in 5 cases (31.3%). The average time to onset of psoriasis following initiation of dupilumab therapy was 18.9 months (range: 1–49). A skin biopsy was performed in 7 patients (43.8%), all of whom showed histopathological confirmation of psoriasis. The most frequent clinical subtype was plaque psoriasis (14 patients, 87.5%), which was indistinguishable from classic psoriasis in appearance, with a mean Psoriasis Area and Severity Index (PASI) of 9.8. Lesions were predominantly located on the limbs (both lower and upper), followed by the trunk (Figure 1). Dupilumab was discontinued in 13 out of 16 patients (81.3%). Subsequent treatments included methotrexate (MTX), Janus kinase inhibitors (upadacitinib, abrocitinib, baricitinib), cyclosporine, narrow-band UVB phototherapy, and, in selected refractory cases, combination regimens such as dupilumab plus risankizumab or MTX plus tralokinumab. Among the three patients who continued dupilumab, two received concomitant MTX, while one reduced the dosing frequency to monthly (Table 1). Overall, 11 patients (68.8%) achieved complete clinical remission (PASI = 0), and 4 (25.0%) showed marked improvement (≥ 50% reduction in PASI from baseline). Only 1 patient (6.3%) experienced worsening. The median follow-up after psoriasis onset was 9 months (IQR 4–14), and the median time to disease control was 3 months (IQR 1–6). The mean PASI decreased from 9.8 at psoriasis' onset to 1.3 at the last follow-up. These observations align with a recent scoping review of dupilumab-associated psoriasis in adults with AD that estimated an occurrence of approximately 2%–3%, with plaque-type predominating in roughly three-quarters of cases and typical involvement of the extremities and trunk [5]. The review reported a mean time to onset of about 4 months in adults, with the vast majority arising within the first year of therapy. In our series, the mean latency was 18.9 months (range, 1–49), indicating that late-onset events can occur and supporting surveillance beyond 12 months. Despite the variability in therapeutic approaches, clinical outcomes were generally favorable, with most patients achieving substantial improvement or remission. Nevertheless, several patients required sequential or combination therapies, highlighting the complexity of management. Given the limited sample size, heterogeneity in treatment sequencing, and non-randomized design, we did not perform comparative analyses, and no firm conclusions can be drawn about a preferred regimen. Future research is warranted to clarify the immunological mechanisms underlying these paradoxical responses and to guide their prediction, prevention, and optimal management. The patients described in this paper have given their written informed consent to the publication of the case details. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.