Introduction
Psoriasis is a Th17-driven inflammatory disease in which cytokine-targeted biologics have revolutionized treatment. However, a subset of patients develops eczematous eruptions (EE),1 with reported incidence rates of 2.2%–12.1%.2 In some cases, EE may lead to treatment discontinuation.3 Effective management of EE is therefore important to minimize disruption of otherwise effective psoriasis therapy.
The pathogenesis of IL-17A inhibitor-associated EE remains incompletely understood and is likely heterogeneous. Previous studies have suggested that IL-17A blockade may alter the balance between Th17- and Th2-associated immune responses, potentially promoting Th2-skewed inflammation or unmasking an underlying Th2-prone phenotype.3,4 The reported effectiveness of dupilumab, which targets IL-4/IL-13 signaling, in treating biologic-associated EE provides clinical support for this proposed Th2 immune shift.5
In our previous study, we identified activation of the IL-21–JAK1 axis in IL-17A inhibitor-associated EE, suggesting a potential role for JAK1 signaling in its development. This finding provides a biological rationale for exploring JAK1 inhibition (JAK1i) as a therapeutic approach for EE. Emerging evidence from retrospective studies and case reports suggests that JAK1i may be effective in EE.5,6 Nevertheless, systematic clinical evidence regarding their efficacy in IL-17A inhibitor–associated EE remains scarce.
Here, we evaluated the clinical response to selective JAK1i and subsequent treatment courses in patients with psoriasis who developed EE during IL-17A inhibitor therapy.
Material and Methods
Patients
We retrospectively reviewed 13 patients with psoriasis who developed eczematous eruptions (EE) during IL-17A inhibitor therapy and subsequently received selective Janus kinase 1 inhibitors (JAK1i) at Ruijin Hospital between January 2023 and August 2025. EE was diagnosed by two dermatologists based on characteristic eczematous clinical features, and skin biopsy was performed in selected patients when clinically indicated. Alternative diagnoses, including contact dermatitis, other drug eruptions, and fungal infections, were excluded based on clinical evaluation and additional testing when indicated.
JAK1i dosing followed the approved prescribing information. Patients were followed every 4 weeks during treatment, with routine safety monitoring, and adverse events were recorded throughout follow-up. Clinical response was assessed using the Eczema Area and Severity Index (EASI), pruritus visual analogue scale (VAS), and Psoriasis Area and Severity Index (PASI) at baseline and at weeks 4 and 8 after JAK1i initiation.
After resolution of EE, patients underwent routine clinical follow-up, during which subsequent treatment modifications and long-term clinical outcomes were recorded. For descriptive purposes, psoriasis flare was defined as an absolute increase in PASI score of ≥2 from the time of biologic discontinuation.7 Baseline patient characteristics before JAK1i initiation are summarized in Supplementary Table 1.
Histopathological Assessment
Available skin biopsy specimens from EE lesions were fixed in 10% neutral-buffered formalin, paraffin-embedded, sectioned, and stained with hematoxylin and eosin (H&E) using standard procedures. Skin biopsy specimens were histopathologically evaluated for the presence or absence of epidermal spongiosis, acanthosis, parakeratosis, and dermal inflammatory infiltrates.
Results
Initial biologic therapy was secukinumab (n=8) or ixekizumab (n=5), and the median time from IL-17A inhibitor initiation to EE onset was 22 weeks (range 3–130 weeks). Five patients (38.5%) had a personal history of atopic dermatitis (Table 1), and two (15.4%) had a family history of atopic disease. Among patients with available laboratory data, serum total IgE was elevated in four patients, whereas peripheral blood eosinophil counts were within the reference range in all patients tested (Supplementary Table 1).
Skin biopsies were performed in five patients. Histopathological findings varied among patients but commonly included spongiosis and acanthosis, with additional features including parakeratosis and perivascular inflammatory infiltrates. Eosinophilic infiltration was observed in four of the five biopsied patients (Supplementary Table 1), with representative histopathological findings shown in Figure 1A.Table 1Clinical Characteristics and Outcomes of Patients with Anti-IL-17A Therapy Induced Eczematous Eruptions Treated with JAK1 InhibitorsPatient CharacteristicsJAKi TreatmentFollow-Up OutcomesNumAgeSexExtra-Cutaneous FeaturesBiologic†Skin BiopsyEruption Onset/JAKi Initiation Interval (Weeks)JAKiPersonal History of ADPsoriasis Lesion‡‡Eczema LesionCurrent Therapy/Duration (Weeks)Follow-Up Time (Weeks)‡P153yFPsASecYes26/65UpaYesFlare, 16wCtrlSec*, Upa/4864P260yFPsAIxeNo4/1UpaNoStableCtrlUpa/100100P326yMNASecNo106/2AbroNoFlare, 8wOccas.Sec#/1220P443yFPsA, uveitisSecNo3/29UpaYesFlare, 4wOccas.Sec*, MTX/2226P547yMPsASecYes77/78UpaNoFlare, 8wOccas.Sec*/6876P654yFNASecYes8/122UpaYesStableCtrlGuse/30††102P747yFPsAIxeNo85/8UpaNoFlare, 8wCtrlGuse/6068P845yMNAIxeNo8/3UpaYesStableCtrlGuse/64§76P953yFPsASecNo22/120UpaNoStableCtrlUpa/8484P1042yMPsAIxeNo130/68UpaNoStableCtrlUpa, Ixe#/4444P1156yMPsASecYes4/15UpaNoStableCtrlUpa/6868P1235yMNAIxeNo12/26AbroNoStableCtrlTopically/1420P1340yFNASecYes130/10UpaYesStableCtrlUpa/7878Notes: †Biologic associated with EE. ‡Follow-up duration calculated from the initiation of JAK inhibitor therapy. §Psoriasis lesions stable but developed folliculitis; switched to guselkumab. ††Psoriasis and eczema remained stable throughout 60 weeks of upadacitinib treatment; psoriasis relapsed 3 months after discontinuing all treatments; switched to guselkumab. ‡‡Psoriasis status refers to that during JAK1i monotherapy before subsequent treatment adjustment. *Dose: 150 mg every 4 weeks. #dosing frequency q6w.
Flare defined as an absolute increase of PASI score ≥ 2; Patients receiving JAK inhibitors were treated with upadacitinib 15 mg once daily or abrocitinib 100 mg once daily.Abbreviations: Sec, secukinumab; Ixe, ixekizumab; Guse, guselkumab; Upa, upadacitinib; Abro, abrocitinib; Ada, adalimumab; MTX, methotrexate; Ctrl, controlled; Occas., occasional lesions requiring topical treatment.Figure 1Representative histopathological and clinical findings of eczematous eruptions following IL-17A inhibitor therapy. (A) Representative histopathological findings of eczematous eruptions. Boxed areas are shown at higher magnification: (1) eosinophilic infiltration (arrows) and (2) focal epidermal spongiosis.
(B) Representative clinical photographs of Patient 11 before and after 8 weeks of JAK1 inhibitor treatment.Composite figure of H and E skin micrographs and clinical photos comparing lesions at week 0 vs week 8.
Before JAK1i initiation, 11 patients had received antihistamines, topical corticosteroids, IL-17A inhibitor modifications, or were switched to an IL-23 inhibitor, but without satisfactory relief (Supplementary Table 1). Subsequently, biologic therapy was discontinued and JAK1i was initiated to control EE. The median interval from EE onset to JAK1i initiation was 26 weeks (range 1–122 weeks).
Representative clinical photographs demonstrated improvement in EE following JAK1i treatment (Figure 1B). After 4 weeks of JAK1i therapy, mean EASI scores decreased from 14.7 at baseline to 3.0, while mean pruritus VAS scores decreased from 9.1 to 2.2. Further improvement was observed at week 8, with mean EASI and pruritus VAS scores decreasing to 0.8 and 0.3, respectively (Figure 2A and B).
In contrast to the consistent improvement in EE and pruritus, psoriasis activity showed a more heterogeneous course. Mean PASI scores were 1.0, 1.1, and 1.4 at baseline, week 4, and week 8, respectively, with four patients showing psoriasis flare by week 8 (Figure 2C). During JAK1i treatment, one patient developed folliculitis that led to treatment discontinuation.
No adverse events were recorded in the remaining 12 patients. Detailed clinical characteristics, treatment responses, and long-term outcomes are summarized in Table 1. Figure 2Changes in EASI, pruritus VAS, and PASI scores during JAK1 inhibitor treatment.
(A) Eczema Area and Severity Index (EASI), (B) pruritus visual analog scale (VAS), and (C) Psoriasis Area and Severity Index (PASI) scores at baseline and weeks 4 and 8 of JAK1 inhibitor treatment. Lines represent individual patients.A) Line graph titled, EASI score. Horizontal axis label: Week 0, Week 4, Week 8.
Vertical axis tick labels: 0, 10, 20, 30, 40. Multiple individual patient lines. Readable Week 0 points: (Week 0, 30), (Week 0, 25), (Week 0, 20), (Week 0, 19), (Week 0, 18), (Week 0, 14), (Week 0, 13), (Week 0, 12), (Week 0, 11), (Week 0, 10), (Week 0, 9), (Week 0, 8).
Week 4 points are between 0 and 7. Week 8 points are between 0 and 4. B) Line graph titled, Pruritus VAS.
Horizontal axis label: Week 0, Week 4, Week 8. Vertical axis tick labels: 0, 5, 10, 15. Multiple individual patient lines.
Readable points: Week 0 about 10 and about 8; Week 4 about 4, about 3, about 2, about 1; Week 8 about 2, about 1, 0. C) Line graph titled, PASI score. Horizontal axis label: Week 0, Week 4, Week 8.
Vertical axis tick labels: 0, 2, 4, 6, 8. Readable line: (Week 0, 4), (Week 4, about 6.5), (Week 8, 4). Other lines stay near 0 to 1 and one rises to about 3.5 to 4 at Week 8 from about 1 to 2 at Week 0.A set of three line graphs showing EASI score, Pruritus VAS and PASI score over weeks.
During a median follow-up of 68 weeks (range 20–102 weeks), five patients experienced psoriasis flare within 16 weeks of discontinuing IL-17A inhibitors, whereas the remaining eight patients did not experience psoriasis flare during this period. JAK1i was initially introduced for the treatment of EE after discontinuation of IL-17A inhibitor therapy rather than as combination therapy with an IL-17A inhibitor.
Among those with psoriasis flare, subsequent treatment strategies included resumption of IL-17A inhibitor therapy, combination of an IL-17A inhibitor with JAK1i or methotrexate, and switching to an IL-23 inhibitor. EE occurred occasionally in patients receiving IL-17A inhibitor therapy without JAK1i, although symptoms remained manageable with topical therapy. Patients who switched to an IL-23 inhibitor or received combined JAK1i and reduced-intensity IL-17A inhibitor therapy maintained well-controlled EE and psoriasis over a median follow-up of 48 weeks (range, 30–64 weeks).
For combination therapy with JAK1i, secukinumab was reduced to 150 mg every 4 weeks when dose reduction was used; alternatively, the dosing interval was extended to every 6 weeks for either secukinumab or ixekizumab, as applicable.
Discussion
Our findings indicate that JAK1i can rapidly control IL-17A inhibitor–associated EE. Beyond the initial response, the extended follow-up provides additional insight into the subsequent course of both eczematous and psoriatic disease and the treatment adjustments required during follow-up.
The mechanisms underlying EE during IL-17A inhibition remain incompletely understood. Th2/Th22 skewing induced by IL-17A blockade is considered a potential mechanism underlying EE.1,3 In patients who experienced psoriasis flare during JAK1i therapy and resumed low-dose IL-17A inhibitor monotherapy, EE reappeared, suggesting that IL-17A inhibition may drive Th2/Th22 skewing. JAK1 inhibition can suppress signaling downstream of multiple cytokines involved in type 2 inflammation,8,9 providing a mechanistic basis for its potential efficacy against the eczematous eruption.
A previous study further demonstrated that, in addition to increased Th2-associated inflammation, EE lesions retained prominent Th1/Th17-associated inflammation compared with resolved skin after treatment.10 Together with reported clinical responses to JAK1 inhibition in patients with overlapping Th2/Th17 inflammatory features,11–13 these observations provide a rationale for JAK1 inhibition in this setting.
Building upon our previous observation of Th2/Th22 upregulation in EE lesions, the IL-21-JAK1-STAT3 axis remains a plausible candidate for driving this immune shift.10 Targeting JAK1 may therefore modulate multiple components of this inflammatory phenotype, potentially contributing to the clinical improvement observed with JAK1 inhibition. However, this pathway was not directly assessed in the present cohort, and the proposed mechanism should therefore be considered hypothesis-generating and requires further investigation.
Th17 cells are central drivers of psoriasis, and JAK-dependent cytokine signaling contributes to Th17 differentiation and maintenance. However, IL-17 receptor signaling itself is not directly mediated through the JAK–STAT pathway.14 Selective JAK1 inhibition may therefore modulate components of the Th17 inflammatory network without directly blocking IL-17A signaling. This distinction may partly explain why marked improvement in EE and pruritus was not consistently accompanied by improvement in psoriasis, with psoriasis flare occurring in some patients after biologic discontinuation.
This study has several limitations. The small sample size, uncontrolled design, and heterogeneity of subsequent treatment strategies limit the interpretation of long-term treatment outcomes. The retrospective inclusion of patients who subsequently received JAK1i may have introduced selection bias and precludes causal inference regarding treatment effects.
In addition, the clinical and histopathological heterogeneity of EE, together with the limited number of available skin biopsies, may restrict definitive characterization of the eczematous phenotype and exclusion of alternative eczematous disorders. Mechanistic interpretation is also limited by the absence of longitudinal immunological assessments. Larger prospective studies with systematic clinical, histopathological, and molecular characterization are needed to validate these observations.
Conclusion
In summary, selective JAK1 inhibitors were associated with rapid improvement in IL-17A inhibitor–associated EE, supporting their further investigation as a therapeutic option in this setting. The subsequent course of psoriasis and the heterogeneous treatment strategies observed during follow-up underscore the need for larger prospective studies to define optimal long-term management of both eczematous and psoriatic disease.