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. 2026 Apr 9;16(6):3263–3274. doi: 10.1007/s13555-026-01742-w

Targeting TYK2 in Cutaneous Autoimmunity: Deucravacitinib-Induced Remission of Discoid Lupus and Psoriasis with Supportive Confocal Microscopy Findings

Francesco D’Oria 1,2, Francesco Piscazzi 1, Paola Facheris 1, Giulio Foggi 1,2, Marco Ardigò 1,2, Antonio Costanzo 1,2, Mario Valenti 1,2,✉
PMCID: PMC13237309  PMID: 41957317

Abstract

Introduction

Cutaneous lupus erythematosus (CLE), particularly discoid lupus erythematosus (DLE), is a chronic autoimmune condition driven in part by type I interferon signaling. No systemic therapies are specifically approved for CLE, and management is often extrapolated from systemic lupus erythematosus. Deucravacitinib, a selective oral tyrosine kinase 2 (TYK2) inhibitor targeting the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway, has shown efficacy in psoriasis and emerging promise in lupus.

Case Report

We describe a 29-year-old woman with biopsy-proven DLE refractory to prednisone and hydroxychloroquine who subsequently developed moderate-to-severe plaque psoriasis (Psoriasis Area and Severity Index [PASI] 16). Initial treatment with ixekizumab improved psoriasis but failed to control DLE, and psoriatic lesions later relapsed. Therapy was switched to deucravacitinib 6 mg daily. After 9 weeks, marked improvement of both conditions was observed (PASI 0.2) with progressive regression of DLE lesions. By week 27, complete clinical remission of psoriasis (PASI 0) and full resolution of DLE lesions were achieved, confirmed by reflectance confocal microscopy.

Conclusion

This case highlights the potential of deucravacitinib as an effective therapeutic option for refractory DLE, particularly in patients with concomitant psoriasis, supporting TYK2 inhibition as a promising targeted strategy in cutaneous autoimmunity.

Keywords: Discoid lupus erythematosus, Cutaneous lupus erythematosus, Deucravacitinib, TYK2 inhibition, Plaque psoriasis

Key Summary Points

Deucravacitinib achieved complete remission of both discoid lupus erythematosus and plaque psoriasis in a treatment-refractory patient.
Tyrosine kinase 2 inhibition targets type I interferon-mediated pathways central to the pathogenesis of cutaneous lupus erythematosus.
Reflectance confocal microscopy supported non-invasive monitoring, confirming resolution of active inflammatory and interface changes.
This case supports deucravacitinib as a promising targeted therapy for refractory cutaneous lupus erythematosus, especially with comorbid psoriasis.
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Introduction

Cutaneous lupus erythematosus (CLE) is an autoimmune condition that may present as a skin-limited disease or as part of the broader clinical spectrum of systemic lupus erythematosus (SLE) [1, 2]. The pathogenesis of CLE is multifactorial and incompletely understood, although type I interferons are recognized as key mediators in the local immune response within lesional skin [3]. Currently, there are no systemic therapies specifically approved for CLE, and management is often extrapolated from treatment paradigms used in SLE [1, 2].

Deucravacitinib is an oral, selective allosteric inhibitor of tyrosine kinase 2 (TYK2), a key signaling molecule in the JAK–STAT pathway involved in type I interferon signaling [3, 4]. It is currently approved for the treatment of moderate-to-severe plaque psoriasis and has shown efficacy in psoriatic arthritis and inflammatory bowel disease. In Japan, its indications also extend to pustular and erythrodermic psoriasis [5–7].

Promising off-label use of deucravacitinib has also been reported in lupus, where its inhibition of TYK2-dependent type I interferon and interleukin (IL)-12/IL-23 signaling has led to clinical improvements in both discoid and systemic forms. These findings highlight its potential as a future therapeutic option in lupus beyond its current approved indications [8].

We describe a case of a patient affected by both DLE and plaque psoriasis, refractory to standard treatments, in which clinical remission was achieved with deucravacitinib.

Case Report

A 29-year-old female patient with no personal or family history of deep vein thrombosis or pulmonary embolism presented to our center with a previously established diagnosis of DLE. She had occasionally reported joint pain; however, rheumatologic investigations ruled out systemic lupus erythematosus and inflammatory arthropathy and did not reveal features suggestive of spondyloarthritis, including arthritis, dactylitis, inflammatory low back pain, or uveitis.

A complete autoimmune serologic panel was negative, including antinuclear antibodies (ANA), anti-dsDNA, and the extractable nuclear antigen (ENA) profile (Sm, U1RNP, SSA, SSB, JO1, and SCL70), with all values within normal limits or below positivity thresholds.

A previous histopathological examination, performed on a small nasal biopsy, confirmed the diagnosis of DLE. Hematoxylin–eosin–saffron staining revealed an orthokeratotic stratum corneum overlying a flattened basal layer with focal vacuolization. A moderate lymphocytic infiltrate was present in the superficial to deep dermis, predominantly perifollicular, with occasional disruption of follicular walls and rare perivascular extension. Lymphocytes focally obscured the basal layer. Immunohistochemistry with CD123 highlighted scattered plasmacytoid dendritic cells, sometimes clustered near sebaceous glands. Direct immunofluorescence to assess the lupus band test was not performed.

Previous treatments, including prednisone and hydroxychloroquine, resulted in little to no cutaneous improvement.

Differential Diagnosis and Treatment

During her initial dermatological assessment at our institution, she presented with erythematous, atrophic plaques on the left eyebrow and nasal dorsum, consistent with her known DLE diagnosis (Fig. 1). On this occasion, the nasal lesions were also evaluated using reflectance confocal microscopy (RCM) (Fig. 2).

Fig. 1.

Fig. 1

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a Clinical image showing a well-demarcated erythematous plaque on the nasal bridge with slightly elevated borders, a centrally hyperkeratotic and hypopigmented area, and a smooth, shiny surface with fine adherent scaling. A similar lesion is noted over the left eyebrow, with erythematous active margins and a central cicatricial zone. b Dermoscopic image of the nasal lesion reveals multiple yellowish keratotic plugs within dilated follicular ostia, primarily in the central and inferior regions. The background is pink to light erythematous with white, structureless areas suggestive of dermal fibrosis. Subtle linear and arborizing telangiectatic vessels are observed, especially peripherally. Perifollicular white halos and the absence of a pigment network further support the diagnosis of DLE

Fig. 2.

Fig. 2

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Reflectance confocal microscopy findings from three representative areas of the nasal lesion (500 × 500 µm2). a Irregular honeycomb pattern is seen in the upper and right-central portion; in the left-central part, exocytosis is seen as hyperreflective dots in the stratum spinosus. b Multiple dilated hyporeflective follicular openings with hyperreflective roundish, amorphous keratin plugs are shown. In the dermis, thickened and hyperreflective collagen bundles consistent with peri-adnexal dermal fibrosis were observed, hyperrefractive round and polygonal cells corresponding to leukocytes and melanophages (white circles), indicative of interface damage and pigment incontinence. c Epidermal architecture appears markedly disorganized, with loss of the regular honeycomb pattern. Bright dendritic cells are scattered in the upper epidermis with clusters of granular hyperreflective dots corresponding to leukocyte exocytosis

Additionally, the patient exhibited new-onset symmetrically distributed erythematous and scaly patches with well-defined borders on the trunk and extremities. The clinical presentation of this new skin finding favored a diagnosis of psoriasis over other cutaneous manifestations of lupus.

A punch biopsy of a representative lesion on the right flank revealed mild epidermal hyperplasia, ortho-parakeratosis with superficial neutrophilic microabscesses, and a superficial perivascular mixed infiltrate with minimal eosinophils, findings consistent with plaque psoriasis.

Given the histological confirmation and the extensive cutaneous involvement (Psoriasis Area and Severity Index [PASI] 16), treatment with ixekizumab 80 mg was initiated as per approved schedule.

After 8 weeks, psoriatic lesions had significantly regressed; however, DLE activity remained evident, with persistent plaques on the nasal dorsum, left eyebrow, and temporal region.

By week 34, psoriatic lesions worsened, with new erythematous plaques appearing on the external auditory canals, clavicular areas, and anterior chest. Ixekizumab was therefore discontinued, and deucravacitinib was started at 6 mg once daily.

At week 9 of deucravacitinib treatment, the patient had minimal residual psoriatic activity (PASI 0.2), reported a transient episode of stomatitis, and showed initial regression of facial DLE lesions. By week 27, she achieved complete clinical remission, with PASI 0 and full resolution of DLE lesions, including those on the nasal dorsum and eyebrow, as confirmed by confocal microscopy (Figs. 3 and 4).

Fig. 3.

Fig. 3

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a By week 27, the previously active lesions have fully resolved clinically, leaving behind subtle skin changes. Mild central depression and slight hypopigmentation are visible over the nasal bridge and left eyebrow region, consistent with post-inflammatory remodeling in the context of discoid lupus erythematosus remission. b Dermoscopy of the nasal area at follow-up reveals regular follicular openings, pink–white structureless areas, and absence of keratotic plugs, perifollicular halos, or prominent telangiectatic vessels—findings consistent with significant clinical and dermoscopic improvement of the previous lesion

Fig. 4.

Fig. 4

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Reflectance confocal microscopy findings from two representative areas of the nasal lesion (500 × 500 µm2) at week 27. a Spinous layer demonstrates restoration of a regular honeycomb pattern with well-preserved keratinocytes; in contrast to baseline alterations, only rare inflammatory cells persist, indicating significant resolution. b Normal-appearing dermis with regularly arranged collagen bundles and preserved adnexal structures. Compared with baseline, dilated follicular openings, keratin plugs, peri-adnexal fibrosis, and inflammatory or pigmented cells are absent, consistent with significant recovery

Discussion

DLE is among the most frequent subtypes of CLE. DLE is characterized by chronic, relapsing erythematous plaques with variable scaling, often annular in morphology that affect both sun-exposed and protected regions [3, 9]. Over time, lesions may heal with residual scarring, pigmentary changes and visible disfigurement, causing a profound negative impact on patients’ quality of life [5, 10].

Currently, there are no systemic therapies specifically approved for CLE, and management is often extrapolated from treatment paradigms used in SLE [1, 2]. Antimalarials, especially hydroxychloroquine sulfate (typically 200 mg once or twice daily [3]), remain the cornerstone of therapy [1, 2]. In cases unresponsive to antimalarials, systemic corticosteroids, immunosuppressive agents such as methotrexate or mycophenolate mofetil, and oral retinoids may be employed, though response rates are variable and often unpredictable [5, 10]. In more refractory cases, second- and third-line agents such as thalidomide or lenalidomide have been utilized [5]. More recently, anifrolumab, a type I interferon receptor antagonist, has shown promise in managing resistant forms of DLE, offering a potential targeted option for patients with inadequate response to conventional treatments [10].

Recent evidence has highlighted the therapeutic potential of Janus kinase (JAK) inhibitors, including deucravacitinib, in systemic lupus erythematosus (SLE) [11, 12], with emerging data supporting their role in modulating disease activity. Isolated case reports have described clinical improvement in patients with tumid and subacute cutaneous lupus erythematosus treated with these agents [1, 3, 5, 13, 14]. Although data on the use of JAK inhibitors in DLE remain limited, reports involving ruxolitinib [15, 16] and tofacitinib [17–23] have shown encouraging responses. Furthermore, two phase II clinical trials investigating topical formulations, delgocitinib [24] and R333 [25], for DLE yielded preliminary signals of activity but failed to meet their primary endpoints [5, 26].

Deucravacitinib, an oral TYK2 inhibitor, has emerged as a promising therapeutic option in this setting. Our patient experienced a rapid and complete resolution of active disease following the initiation of deucravacitinib, with only mild post-inflammatory atrophy and hypopigmentation remaining by week 27. This clinical trajectory mirrors that observed in other recently published cases, where patients with longstanding and treatment-resistant DLE or subacute cutaneous lupus erythematosus (SCLE) showed substantial improvement within four months of starting deucravacitinib [1, 3, 5, 11–13].

In this case, treatment selection was guided by the presence of comorbid plaque psoriasis, creating the opportunity to address two immune-mediated skin diseases with a single therapeutic agent. The use of deucravacitinib allowed for simultaneous control of both conditions, reducing the need for multiple systemic drugs and minimizing the risk of polypharmacy, a significant consideration in chronic dermatologic care.

TYK2 is essential for mediating cytokine signaling, particularly type I interferons (IFN-I), interleukin IL-6, IL-10, IL-12, and IL-23 [1, 27] (Fig. 5). IFN-I is a signaling pathway strongly implicated in the pathogenesis of lupus. Genetic polymorphisms in the TYK2 gene have been associated with an increased risk of systemic lupus erythematosus (SLE), and elevated interferon signatures in the peripheral blood have been documented in both SCLE and DLE [28]. Notably, higher IFN-I activity has been shown to correlate with greater severity of cutaneous manifestations, reinforcing the biological rationale for targeting this pathway in therapy [1, 29].

Fig. 5.

Fig. 5

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Deucravacitinib selectively targets TYK2, a central signaling hub in the JAK–STAT pathway. On the left, IFN-I receptor engagement highlights the interferon-driven axis implicated in lupus erythematosus. On the right, IL-12 and IL-23 receptor signaling illustrates the psoriatic pathway. Both converge downstream on TYK2, whose inhibition disrupts pathogenic signaling in systemic and cutaneous lupus as well as psoriasis, thereby providing a unifying therapeutic mechanism

Recent evidence from Wasserer et al. [30] further shows that TYK2 expression correlates tightly with the severity of interface dermatitis, reinforcing its central role in cutaneous lupus pathogenesis [31–34]. Immunohistochemistry confirms that TYK2 protein is highly abundant across CLE subtypes, particularly within keratinocytes, compared with other type I inflammatory dermatoses [34].

Functionally, TYK2 inhibition with deucravacitinib strongly suppresses IFN-α-driven inflammation, leading to marked reductions in CXCL9 and CXCL10 expression and attenuating downstream STAT1/2-mediated signaling [35–38]. Deucravacitinib also reduces IFN-γ secretion from lesional T cells in a dose-dependent manner, highlighting its ability to modulate both IFN-I- and T-cell-mediated pathways [39].

At the molecular level, TYK2 blockade downregulates key type I interferon response genes—including IRF7, IFI44L, MX1, and others—while normalizing keratinocyte differentiation programs altered in CLE [40–42]. Ex vivo studies further show decreased expression of CXCL9, CXCL10, CCL8, as well as TLR7, a known high-risk locus for SLE, together with a reduction of necroptosis mediators MLKL and RIPK3 [39, 43].

Deucravacitinib is currently being investigated for the treatment of active DLE and/or SCLE in a randomized, double-blind, placebo-controlled phase 2 trial (NCT04857034) [44]. The study evaluates two different doses of deucravacitinib compared with placebo, with the primary endpoint being the percentage change from baseline in the Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) score at week 16. At that time point, CLASI-A scores were reduced by −48.56% with deucravacitinib 3 mg, −48.93% with deucravacitinib 6 mg, and −27.31% with placebo, demonstrating an almost twofold greater improvement with active treatment compared with placebo. The magnitude of benefit was comparable between the two deucravacitinib doses, indicating no clear incremental advantage of the higher dose within the study timeframe.

In addition, a phase 4 extension study [45] is currently recruiting. This study aims to continue deucravacitinib treatment in patients with systemic lupus erythematosus (SLE), including those with DLE and SCLE, who have previously completed participation in related studies IM011074 (NCT03920267) [46] or IM011132 (NCT04857034) [44]. The extension will further assess the long-term safety and tolerability of deucravacitinib. The main ongoing clinical trials investigating deucravacitinib in cutaneous lupus erythematosus are summarized in Table 1.

Table 1.

List of clinical trials of deucravacitinib in patients with DLE/SCLE

Candidate drug Trial identifier Trial phase, status Target population Arms and interventions Primary endpoint or purpose Outcome
Deucravacitinib NCT04857034 2, active not recruiting DLE/SCLE

(A) Experimental active treatment: deucravacitinib 3 mg

(B) Experimental active treatment: deucravacitinib 6 mg in placebo controlled period and deucravacitinib 6 mg in active treatment period

(C) Placebo comparator: placebo

 Percentage change from baseline in CLASI-A score at week 16

(A) Experimental active treatment: −48.56%

(B) Experimental active treatment: −48.93%

(C) Placebo comparator: −27.31%
NCT06875960 4, recruiting

SLE

DLE/SCLE

 (A) Experimental administration of BMS-986165: n = 35 (estimated) Extension study to continue deucravacitinib in patients completing IM011074 or IM011132 Results not yet available
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In this context, TYK2 inhibition represents a promising and innovative therapeutic strategy for cutaneous lupus, warranting further investigation. The present case further contributes to the emerging body of evidence supporting TYK2 inhibition in cutaneous lupus erythematosus. In particular, it highlights the potential role of deucravacitinib in patients with overlapping immune-mediated conditions such as psoriasis and discoid lupus erythematosus, where a single targeted therapy may effectively control both diseases.

Moreover, our case underscores the utility of noninvasive imaging, particularly RCM, in both diagnosis and monitoring. In our patient, RCM enabled high-resolution visualization of characteristic features, including follicular hyperkeratosis, dermal fibrosis, and pigment incontinence, without the need for repeated biopsies [47, 48]. When used in conjunction with clinical examination and dermoscopy, RCM strengthens diagnostic accuracy and allows for real-time assessment of disease evolution and therapeutic response, especially in esthetically sensitive areas where biopsy may be impractical.

Conclusions

Our case supports the potential of deucravacitinib as a treatment for chronic cutaneous lupus, particularly DLE, a subtype that is often resistant to conventional therapies and associated with a substantial cosmetic and psychosocial burden. Targeted therapies, guided by biomarker studies and mechanism-of-action insights, have revolutionized the treatment of other cutaneous diseases such as psoriasis and atopic dermatitis but are still lacking in the management of cutaneous lupus. While ongoing clinical trials are expected to clarify the long-term efficacy of TYK2 inhibition, individual case reports remain essential for expanding real-world clinical experience and guiding therapeutic strategies in the interim.

Finally, the integration of noninvasive imaging techniques, particularly RCM, is emphasized as a powerful adjunct for diagnosis and follow-up, enabling in vivo visualization of key pathological features such as follicular hyperkeratosis, dermal fibrosis, and interface changes, while reducing the need for invasive biopsy procedures.

Acknowledgements

We thank the participant of the study.

Author Contributions

Francesco D’Oria, Francesco Piscazzi, and Giulio Foggi contributed to data collection and drafting of the manuscript. Paola Facheris, Marco Ardigò, Antonio Costanzo, and Mario Valenti contributed to clinical management, manuscript revision, and supervision. All authors read and approved the final version of the manuscript.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Data Availability

All data generated or analyzed during this study are included in this published article.

Declarations

Conflict of Interest

Paola Facheris has served as a consultant for Eli Lilly and as a speaker for UCB, AbbVie, and Pfizer. Marco Ardigò has received consulting fees from Pierre Fabre and has participated in lectures, presentations, and advisory boards for Almirall, Kyowa Kirin, Pierre Fabre, Recordati Rare Diseases, and Cantabria Labs. Antonio Costanzo has served as an advisory board member and consultant and has received fees and speaker’s honoraria or has participated in clinical trials for AbbVie, Almirall, Biogen, LEO Pharma, Lilly, Janssen, Novartis, Pfizer, Sanofi Genzyme, and UCB. Mario Valenti has served as a consultant and/or speaker for Sanofi, Leo Pharma, Eli Lilly, Novartis, Janssen, AbbVie, Boehringer Ingelheim, Almirall, UCB, and Difa Cooper. Mario Valenti is a member of the Editorial Board of Dermatology and Therapy. Mario Valenti was not involved in the selection of peer reviewers for the manuscript nor in any of the subsequent editorial decisions. Francesco D’Oria, Francesco Piscazzi, and Giulio Foggi declare no conflicts of interest.

Ethical Approval

Written informed consent was obtained from the patient for publication of clinical information and images.

Footnotes

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Associated Data

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Data Availability Statement

All data generated or analyzed during this study are included in this published article.

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