Successful Treatment of Localized Scleroderma in Intertriginous Areas with Tofacitinib: A Case Report

Abstract

Localized scleroderma (LS) is a chronic skin disorder marked by excessive collagen deposition. We report a 61-year-old woman with LS predominantly affecting intertriginous areas, refractory to conventional therapies, who was treated with the Janus kinase 1/3 (JAK1/3) inhibitor tofacitinib at 5 mg twice daily, later reduced to 5 mg once daily for maintenance. Within two months, she experienced rapid relief of pruritus and marked softening of skin induration, with Localized Scleroderma Cutaneous Assessment Tool (LoSCAT) scores improving from 5 to 1 on the LoSAI and from 3 to 2 on the LoSDI. No adverse effects were observed, and the patient reported high satisfaction. This case suggests that tofacitinib may represent a potential therapeutic option for patients with refractory LS, warranting further studies to clarify its long-term efficacy and safety.

Introduction

Localized scleroderma (LS), or morphea, is a chronic skin disorder characterized by excessive collagen deposition, resulting in discoloration, thickening, scarring, and functional impairment.^1,2

LS that specifically affects intertriginous areas is rare.³ The limited literature consists mainly of sporadic case reports describing multiple pigmented patches or mildly indurated plaques predominantly involving intertriginous sites, often in a symmetric distribution.^4,5 Conventional treatments for LS, including topical therapies, phototherapy, corticosteroids, methotrexate, and mycophenolate mofetil, have limited effectiveness and substantial side effects.^6,7 Emerging evidence suggests that profibrotic cytokines such as transforming growth factor‑β (TGF‑β) can signal through the JAK/STAT pathway to promote fibroblast activation and collagen deposition, providing a mechanistic rationale for Janus kinase (JAK) inhibition in fibrosing disorders such as LS. Oral JAK inhibitors like tofacitinib show promise in treating immune-mediated dermatologic diseases and may also be effective for LS.⁸ Here, we report a case of a 61-year-old woman with LS, predominantly affecting the intertriginous areas, who achieved significant clinical improvement with tofacitinib without experiencing any adverse effects.

Case Presentation

A 61-year-old woman presented with a 3-year history of progressive skin lesions involving the neck, axillae, and inframammary folds, which developed spontaneously. The skin lesions initially presented as round or oval edematous erythema with a shiny surface, gradually enlarging over time. As the disease progressed, the affected skin became hardened in texture and developed hyperpigmentation, along with features resembling focal scarring (Figure 1a–e). At disease onset, she was sequentially treated with topical corticosteroid ointment, mucopolysaccharide polysulfate cream, and asiaticoside cream. However, no clinical improvement was observed. In August 2025, she presented to the hospital with worsening skin induration and severe pruritus. Laboratory investigations showed negative antinuclear antibodies (ANA) and extractable nuclear antigen (ENA), normal C‑reactive protein (CRP), and no abnormalities in the complete blood count, D‑dimer, erythrocyte sedimentation rate (ESR), or liver and renal function tests. High‑resolution chest computed tomography revealed no obvious abnormalities. The patient reported no history of Raynaud phenomenon, and physical examination revealed neither sclerodactyly nor nailfold capillary abnormalities. Collectively, these findings supported the exclusion of systemic sclerosis.

Figure 1.

Localized scleroderma involving intertriginous areas. Clinical photographs show thickened, indurated, hyperpigmented plaques: (a and b) cervical region; (c) right axilla with notable scar-like lesions; (d) inframammary fold; and (e) left axilla with similar scar-like lesions.

We subsequently performed a biopsy and histopathologic examination revealed dermal superficial small blood vessels exhibiting congestion, with perivascular lymphocytic infiltration. In addition, thickened, densely packed collagen bundles were observed throughout the dermis, consistent with localized scleroderma (Figure 2a and b). Given the flexural distribution and hyperpigmented indurated plaques in this 61‑year‑old woman, the differential diagnosis included lichen sclerosus, scleredema, scleromyxedema, and post‑inflammatory fibrosis. However, the absence of typical features such as non‑pitting edema or mucin deposition, together with dense dermal collagen thickening and negative serology, favored localized scleroderma. Accordingly, the patient was diagnosed with LS. Disease severity was assessed using the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT), comprising the Skin Activity Index (LoSAI) and Skin Damage Index (LoSDI). At baseline, LoSAI and LoSDI scores were 5 and 3, respectively. The patient refused treatment with methotrexate due to concerns about its side effects. Given the progression of the condition, the unsatisfactory effects of conventional medications, and the patient’s preferences, we decided to initiate oral tofacitinib therapy after confirming the absence of severe infections and coagulopathy. Tofacitinib is a novel JAK inhibitor. The initial dosing regimen consisted of 5 mg administered orally twice daily. After two weeks of treatment, the patient exhibited a significant reduction in pruritus, and cutaneous lesions ceased to progress or expand. At the two-month follow-up, marked clinical improvement was observed, characterized by softening of the rash, improved skin elasticity, enhanced mobility, reduced hyperpigmentation in affected areas, and complete resolution of pruritus (Figure 3a–e). The LoSAI and LoSDI scores improved from 5 to 1 and from 3 to 2, respectively. By week 12, disease remained in stable remission without new or expanding lesions. Given her age and the dose‑dependent safety profile of JAK inhibitors, the dose was reduced to 5 mg once daily as the lowest effective maintenance regimen. Over the subsequent two months, clinical remission and LoSCAT scores remained stable Comprehensive laboratory re‑evaluation—including hepatic and renal function tests—showed all results within normal reference ranges, and no clinically significant adverse effects were observed. The patient reported high treatment satisfaction and had resumed full participation in daily activities.

Figure 2.

Pathological examination of localized scleroderma in intertriginous areas: Skin biopsy shows superficial dermal small vessels with congestion and perivascular lymphocytic infiltration. Collagen fiber hyperplasia is present in the dermis. (a) Low‑power view of the lesion (H&E; scale bar=250 µm). (b) Higher‑power view highlighting the perivascular lymphocytic infiltrate in the superficial dermis (H&E; scale bar=100 µm).

Figure 3.

Response to tofacitinib treatment. Clinical photographs show marked improvement after two months: rash softening, improved skin elasticity and mobility, and lightened pigmentation in affected areas. Notably, scar-like lesions in the axillary region showed modest improvement. (a–e). Clinical photographs were taken under routine conditions without fully standardized lighting, which may affect the visual impression of pigmentation.

Discussion

LS can affect the entire body, with reports of involvement in the trunk, limbs, face, and scalp.⁹ However, there have been exceedingly rare reports of LS primarily involving intertriginous areas. LS has an incompletely understood etiology, with several potential triggers identified, including trauma, radiation therapy for breast cancer, and chronic venous insufficiency leading to localized tissue hypoxia.^10,11 Herein, we report a case of LS in a 61-year-old woman, characterized by predominant involvement of intertriginous areas-including the neck, inframammary folds, and axillae-with clinical manifestations of skin induration, dyspigmentation, and pruritus, all of which significantly impaired her quality of life. We speculate that anatomical areas such as the axilla and inframammary folds, which may be more exposed to mechanical stress and local circulatory impairment,¹² could contribute to the intertriginous localization in this patient. However, this remains a hypothesis and warrants further investigation.

Extensive studies have demonstrated that in the pathogenesis of LS, TGF-β drives fibrosis by promoting fibroblast proliferation and collagen deposition, and this fibrotic signaling process involves the JAK/STAT pathway.^13,14 Tofacitinib, a JAK1/3 inhibitor that targets the kinase component of JAK proteins to prevent STAT phosphorylation, has been shown to effectively block the downstream signaling of pro-fibrotic cytokines such as TGF-β, thereby reducing collagen production and the expression of genes associated with inflammation and fibrosis.^15,16 Tofacitinib has been reported in several cases to show encouraging efficacy and an acceptable safety profile in fibrotic tissue diseases, notably systemic sclerosis and localized scleroderma.^17,18 However, previous reports have rarely focused on intertriginous involvement or on the antipruritic effect of tofacitinib in LS. In our patient, tofacitinib led to marked clinical improvement, including reduced skin thickness, lesion softening, and relief of pruritus. These changes are consistent with its proposed anti-fibrotic mechanism and are likely attributable to attenuated collagen deposition and fibrotic tissue remodeling. Quantitatively, the patient’s LoSAI score decreased from 5 to 1, while the LoSDI score decreased from 3 to 2. Consistent with previous case reports of tofacitinib in localized scleroderma, which have used a higher induction dose for about 2 months followed by a lower maintenance dose with sustained benefit,¹⁹ we considered dose reduction after disease control was achieved. Given her older age, the dose‑dependent risks of infection, herpes zoster, thrombosis, and cardiovascular events, and her marked clinical and LoSCAT improvement at 12 weeks with stable, skin‑limited disease, we reduced the dose to 5 mg once daily as an exploratory maintenance regimen, with close clinical and laboratory monitoring and a plan to re‑escalate the dose in case of relapse.

Compared with previously reported cases of LS treated with tofacitinib, our case provides additional information in several aspects. First, this case describes a rare intertriginous variant of LS (neck, axillae, inframammary folds) and, to our knowledge, the first reported case showing significant improvement with tofacitinib in this distribution. Second, prior reports on tofacitinib in LS have provided limited information on patients’ subjective symptoms, especially pruritus, even though itching, pain, burning, and stinging can markedly affect health-related quality of life (HRQoL).²⁰ In our patient, severe pruritus was rapidly and sustainably controlled by tofacitinib. JAK inhibitors may alleviate itch by blocking cytokine-mediated signaling (eg, IL‑31) through the JAK/STAT pathway and by inhibiting mast cell and basophil activation and degranulation, thereby reducing the release of pruritogenic mediators. Taken together, these findings suggest that tofacitinib may be particularly advantageous in LS patients with prominent pruritus.^21,22 Third, in our patient, clinical improvement and itch control were maintained even after dose reduction, highlighting that tofacitinib may allow effective disease control with a lower maintenance dose in some patients with milder disease. However, this remains an exploratory observation based on limited case-level evidence.

In this case, tofacitinib was associated with a relatively rapid onset of action and good tolerability, which, together with previous reports, suggests that JAK inhibition may have the potential to improve patient adherence and reduce treatment‑related adverse effects in the long‑term management of localized scleroderma. Recently, Su et al reported favorable outcomes with the highly JAK1‑selective inhibitor upadacitinib in juvenile localized scleroderma.²³ Taken together with our adult case treated with tofacitinib, these findings suggest that different JAK inhibitors may benefit distinct age groups and clinical subsets of LS, and that JAK1‑selective agents such as upadacitinib, which may offer a more favorable safety profile, are promising therapeutic options warranting further study.

This report has several important limitations. First, in this case, tapering to 5 mg once daily after 12 weeks was guided by the patient’s skin‑limited disease, long‑term safety concerns, and our institutional experience rather than LS‑specific evidence. As maintenance dosing in LS lacks established standards or prospective data, this dose‑reduction strategy should be regarded as hypothesis‑generating and requires confirmation in larger, controlled studies. Second, the observation period was relatively short and the patient remains on maintenance therapy, so the post‑treatment course, true relapse risk, and optimal treatment duration remain uncertain, underscoring the need for longer follow‑up. Third, although clinical assessment was based on direct in‑person examination, treatment response was illustrated mainly using clinical photographs that were not fully standardized. Finally, although tofacitinib was effective in this patient, this does not guarantee efficacy in all individuals, and randomized, multicenter, large‑scale clinical trials are needed to establish its therapeutic benefit.

Conclusion

In summary, this case illustrates that the JAK1/3 inhibitor tofacitinib can be effective in a rare intertriginous variant of localized scleroderma, with particularly rapid relief of severe pruritus and reduction of skin induration, and with no observed adverse effects during short‑term follow‑up. Our findings also suggest that, in selected patients with skin‑limited disease, disease control may be maintained on a reduced maintenance dose. These observations support further investigation of JAK inhibitors across different clinical subsets of localized scleroderma.

Funding Statement

This work was supported by the Zhejiang Traditional Chinese Medicine Science and Technology Project [2026ZL0013] and Medical and Health Science Program of Zhejiang Province [2025HY0073].

Ethics Approval and Consent to Participate

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Institutional approval for the publication of anonymized case details was granted by Zhejiang Provincial People’s Hospital. This study was performed in accordance with the Declaration of Helsinki.

Disclosure

The authors declare no competing interests in this work.