Successful treatment of refractory erosive lichen planus with abrocitinib: A case report

Introduction

Lichen planus (LP) is a chronic immune-mediated inflammatory disease of the skin, adnexa, and mucous membranes. Erosive lichen planus (ELP) is a severe variant of LP that is more common in women. It primarily affects the oral and genital mucosa, with less frequent esophageal and cutaneous involvement.^1,2

ELP can cause significant morbidity, leading to pain and progressive scarring. Early management is particularly crucial in the case of esophageal involvement, as untreated or refractory esophageal disease may lead to esophageal strictures and stenosis. ¹ In addition, chronic mucosal inflammation may lead to the development of squamous cell carcinoma. Malignant transformation has also been reported in long-standing esophageal and vulvovaginal ELP.^1,2

ELP is often refractory to treatment, and spontaneous remission is rare. ³ Recently, molecularly targeted therapies, such as Janus Kinase (JAK) inhibitors, have shown promise in managing this challenging condition and may serve as effective alternatives to conventional systemic therapies.^3–8 Here, we report a case of severe, treatment-resistant ELP successfully managed with the JAK1 inhibitor Abrocitinib.

Case report

We present the case of a 62-year-old female with a 10-year history of severe ELP involving the oral and genital mucosa, new onset esophageal disease, as well as mild skin disease.

Her medical history was significant only for hypertension, for which she had been taking irbesartan. Considering that the medication had been initiated before her symptoms appeared and the possibility of drug-induced LP, it was discontinued. However, no clinical improvement ensued. A paraneoplastic etiology was ruled out through an extensive workup that included a mammography, colonoscopy, and a computed tomography scan of the chest, abdomen, and pelvis.

On examination of the oral mucosa, she exhibited erythema and desquamation of the free and the attached gingiva, along with painful erosions on the tongue, retromolar trigone, and jugal mucosa. White, reticulated patches were also present on the jugal mucosa. A gingival biopsy confirmed histopathological features consistent with ELP.

The patient also experienced dyspareunia and vaginal pain. Genital examination revealed extensive erosions and ulcerations of the vagina as well as architectural changes, including encapsulation of the clitoris, fusion of the labia majora and minora, and vaginal stenosis. She underwent vaginal dilation followed by maintenance manual dilations. Urethral strictures were also present but did not cause obstructive urinary symptoms.

Due to complaints of dysphagia and odynophagia, an upper endoscopy was performed, revealing esophageal erosions of the middle third of the esophagus. Esophageal biopsy findings were compatible with ELP. Esophageal manometry and pH monitoring were normal. Despite mild symptomatic improvement with a proton pump inhibitor, the patient required repeated esophageal dilations with bougie and balloon dilators every 4–5 weeks due to proximal esophageal stenosis.

She had previously undergone treatment with multiple agents including methotrexate (3 months, ineffective), mycophenolate mofetil (8 months, ineffective), cyclosporine (4 months, ineffective), azathioprine (2 months, discontinued due to side effects), apremilast (13 months, ineffective), dapsone (2 months, discontinued due to side effects), as well as multiple courses of oral prednisone and intramuscular triamcinolone acetonide injections. However, none of these treatments led to disease remission. She continued to use dexamethasone mouthwash three times daily and topical clobetasol on the erosive buccal and vulvovaginal lesions and required maintenance vaginal and esophageal dilations.

The patient was subsequently prescribed abrocitinib 200 mg orally once daily. After 3 months of treatment, the erosive oral and vaginal lesions resolved completely, with only mild residual reticulated white patches on the lateral tongue. Furthermore, she has not required subsequent esophageal dilations since initiating abrocitinib. Clinical improvement has been sustained for 1 year without adverse events.

Discussion

The rarity of ELP poses significant challenges, as most data regarding management and treatment efficacy are based on case reports and small case series.^3–5,7,8 Treatment goals include controlling inflammation, alleviating symptoms, and preventing long-term sequelae such as scarring and strictures. ² First-line treatments typically include high-potency topical corticosteroids for localized lesions, with immunosuppressive agents, such as systemic corticosteroids and disease-modifying anti-rheumatic drugs, reserved for extensive, refractory, or recurrent cases. Often, a combination of topical and systemic medications is required to achieve remission. ²

This case highlights the potential of JAK inhibitors as an effective treatment for recalcitrant ELP. Our patient, with a long-lasting disease who had failed multiple prior agents, achieved complete remission of ELP lesions following treatment with abrocitinib in conjunction with topical corticosteroids. Improvement was noted within 3 months and was maintained after 1 year of ongoing therapy. The treatment was well tolerated by our patient, who did not experience any side effects.

The pathogenesis of LP involves T-cell-mediated cytotoxicity, with Th1- and Th17-driven responses. Cytokines such as interferon-γ play a central role in driving and maintaining the inflammatory cascade through the JAK-signal transducer and activator of transcription pathway. Thus, JAK inhibition, particularly of JAK1 and JAK2, could reduce the chronic inflammatory process underlying LP. ⁶ Tofacitinib, a pan-JAK inhibitor that inhibits JAK1 and JAK3 and, in a dose-dependent manner, JAK2, has been effective in treating several LP variants, including ELP, lichen planopilaris, and nail LP.^5,6,8,9 Similarly, Upadacitinib, a selective JAK1 inhibitor, has shown promise in patients with ELP.^3,7 Abrocitinib, which shares a similar mechanism of action to Upadacitinib, has been used in oral LP, with favorable results. ⁹ Due to their selectivity for JAK1, Upadacitinib and Abrocitinib are believed to have a more favorable risk profile compared with pan-JAK inhibitors. ¹⁰

As opposed to traditional systemic immunosuppressants, JAK inhibitors seem to have a faster onset of action.^4,6 This is particularly relevant in ELP, where rapid symptom control is often necessary to prevent scarring and irreversible functional impairment.^5,6 The potential of JAK inhibitors to induce sustained long-term clinical remission without the need for maintenance therapy has yet to be determined.

In conclusion, our patient, with long-standing and disabling esophageal, vulvovaginal, and buccal involvement unresponsive to multiple lines of treatment, finally achieved control of her disease with Abrocitinib. Although this study is limited by its observational nature, these findings suggest that Abrocitinib may be an effective therapeutic option for refractory ELP. Larger studies are necessary to draw definitive conclusions.