Refractory oral and cutaneous lichen planus successfully treated with upadacitinib

Introduction

Lichen planus (LP) is a chronic, immune-mediated inflammatory condition that can affect both the skin and mucous membranes. The disease is commonly characterized by violaceous, polygonal, flat-topped papules on the cutaneous surface, and reticular white striations (Wickham’s striae) within the oral mucosa.¹ The pathogenesis is believed to be the result of a cytotoxic CD8+ T-cell-mediated attack on basal keratinocytes with the involvement of interferon-γ at the dermoepidermal junction.²

Involvement of both mucosal and cutaneous sites adds complexity to diagnosis and management. Most cases of LP respond well to standard therapies such as topical and systemic corticosteroids and calcineurin inhibitors, and methotrexate. Some cases, however, are refractory and therapeutic options remain poorly defined in these situations.³

In this report, we present a case of refractory oral and cutaneous lichen planus successfully treated with upadacitinib. Remarkably, after years of inadequate response to conventional first and second line therapies, the patient achieved significant and sustained clinical improvement with the selective Janus kinase-1 (JAK1) inhibitor upadacitinib. This case adds to the emerging evidence that JAK inhibitors have the potential to manage refractory lichen planus.⁴ To date, there have been only isolated reports of either oral or cutaneous LP responding to JAK inhibition. No documented cases have described simultaneous refractory involvement of both sites.

Case report

The patient is a white female in her 50s who has had lichen planus for almost a decade. She presents with numerous small pink papules with overlying whitish streaks on the hands and feet, some of which coalesce (Fig 1, A, C, and D). The cutaneous lesions are intensely itchy. Whitish plaques are present on the buccal mucosa, and there is associated pain and restriction when the patient opens her mouth. A previous shave biopsy of the right lower leg showed typical features of lichen planus (Fig 2).

Fig 1.

Clinical improvement of refractory oral and cutaneous lichen planus with upadacitinib. A, C and D, Pretreatment: violaceous and coalescing papules on hands and feet, reticular white striations on the buccal mucosa. B and E, Post treatment (1 month): flattening and resolution of papules with residual hyperpigmentation.

Fig 2.

A, There is saw-toothed epidermal hyperplasia, hypergranulosis, and compact hyperorthokeratosis. There is also a lichenoid infiltrate of lymphocytes at the dermoepidermal junction in association with vacuolar alteration and necrotic keratinocytes. B, Characteristic interface changes of lichen planus are present at the dermatoepidermal junction and include Civatte bodies and retraction artifact (a Max Joseph cleft).

The patient tried and failed numerous therapies including topical triamcinolone, clobetasol, tacrolimus, ketoconazole, oral cyclosporine, methotrexate, and apremilast. Each therapy was trialed for a minimum of 3 months, with apremilast used for approximately 8 years without sustained benefit.

The patient’s repeated bloodwork has generally been unremarkable, including complete blood count and comprehensive metabolic panel. The patient does suffer from mixed hyperlipidemia, for which she had been receiving statin therapy prior to the onset of LP. Serologies for QuantiFERON Gold and Hepatitis C were negative. Past medical history includes hidradenitis suppurativa, psoriasis, and acne vulgaris, all of which developed after the onset of her lichen planus. Surgical history included an uncomplicated appendectomy, back surgery, and hysterectomy. Interestingly, the patient endorsed a strong family history of lichen planus, affecting her mother and her 2 brothers.

Due to the refractory nature of her LP, we initiated a trial of 15 mg of upadacitinib by mouth daily. Within 24 hours, the patient reported significant improvement in itch. Within 1 month, the patient noticed significant clearing of affected areas (Fig 1, B and E). On follow-up at 1 year of therapy, the patient’s LP continues to be 90% better. Repeated follow-up blood work did not show significant serologic abnormalities. Of note, the patient needed to hold upadacitinib treatment due to developing herpes zoster. However, the patient responded well to upadacitinib when it was restarted.

Discussion

Refractory LP is challenging due to its chronic nature and severe effect on the patient's quality of life. While topical and systemic corticosteroids and calcineurin inhibitors are generally effective at treating LP, a subset of patients will fail to achieve significant and sustained improvement. The pathogenesis of LP is driven by a cytotoxic T-cell-mediated response and related cytokines that promote basal layer apoptosis through the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway.⁵ This rationale supports JAK inhibitors as a potential treatment for refractory LP.

Upadacitinib, a selective JAK1 inhibitor, has had promising results in several recent reports of recalcitrant cutaneous and oral LP. Zundell et al described near-complete resolution of diffuse cutaneous LP within 8 weeks of therapy.⁶ Slater et al similarly reported improvement in erosive oral LP unresponsive to corticosteroids and immunosuppressants.⁷ Furthermore, McNamara et al demonstrated in a case series sustained remission across multiple LP variants treated with upadacitinib.⁸ Collectively, these findings suggest that JAK1 blockade may attenuate the interferon-driven inflammatory cascade central to LP pathogenesis.

To our knowledge, this is the first documented case of refractory LP with both oral and cutaneous involvement that was successfully treated with upadacitinib. The patient’s disease had proven unresponsive to multiple conventional and unconventional systemic and topical agents, yet demonstrated rapid and durable improvement following initiation of upadacitinib.

This case is noteworthy for several reasons. First, it expands the limited evidence base supporting the efficacy of JAK inhibitors in severe and multi-site LP. This would suggest that selective JAK1 blockade allows for a therapeutic effect across both mucosal and cutaneous compartments. Second, it introduces a potentially more effective and better-tolerated alternative to broader JAK inhibitors such as tofacitinib, which inhibits multiple JAK subtypes and may carry greater risks of cytopenia, hyperlipidemia, and thromboembolic events.¹ Finally, it reinforces the concept that JAK1 inhibition may interrupt the core inflammatory cascade central to LP pathogenesis, offering a rational, mechanism-driven therapeutic approach.

This report highlights the successful use of upadacitinib in a patient with both refractory oral and refractory cutaneous lichen planus. The case and treatment demonstrate the potential of selective JAK1 inhibition as novel modality for effective treatment. The patient’s development of herpes zoster highlights the potential infectious risks that are associated with JAK inhibition and emphasizes the importance of careful patient selection, counseling, and monitoring. Further studies are necessary to determine upadacitinib’s long-term safety, efficacy, and role within future LP management algorithms.

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Conflicts of interest

None disclosed.