Successful Treatment of Refractory Pityriasis Lichenoides Chronica with Upadacitinib in Two Patients

Dear Editor, Pityriasis lichenoides (PL) is a spectrum of inflammatory dermatosis with uncertain etiology, encompassing two distinct clinical variants: pityriasis lichenoides et varioliformis acuta (PLEVA) and pityriasis lichenoides chronica (PLC).[1] Despite the self-limiting nature of PLC, treatment is necessary to manage symptoms. However, current evidential options on PL management, such as phototherapy, topical corticosteroids, topical immunomodulators, and systemic antibiotics have limited outcomes. Emerging evidence suggests that janus kinase inhibitors (JAKis) may have beneficial effects on refractory inflammatory diseases. In this article, we reported two patients with refractory PLC who experienced excellent therapeutic responses to a selective JAK-1 inhibitor, Upadacitinib, suggesting an alternative treatment for refractory PLC. Clinical characteristics of both patients are presented in Table 1. Physical examination revealed erythematous-brownish papules with adherent micaceous scale. Histological examination demonstrated hyperkeratosis, parakeratosis, spongiosis, vacuolar interface dermatitis, and transepidermal elimination of erythrocytes. Moreover, mixed inflammatory cells and erythrocytes were observed surrounding the dermal blood vessels [Figure 1a and b]. The diagnosis of PLC was confirmed for each patient based on clinical manifestations with histopathological results. They had received various treatments, encompassing topical potent corticosteroids, narrowband ultraviolet B phototherapy, and methotrexate with limited response. After excluding all the contraindications of JAKis and obtaining complete informed consent, both of them switched the therapy to upadacitinib monotherapy (15 mg once daily, RINVOQ®).Table 1: Clinical data and treatment responses in two patients with PLCFigure 1: Biopsy results and clinical photographs of patient 1 during the follow-up. The biopsy results clinical photographs of patient 1 during the follow-up. (a and b) Biopsy results demonstrated hyperkeratosis, parakeratosis, spongiosis, vacuolar interface dermatitis, and transepidermal elimination of erythrocytes. Vascular dilation of the dermal papilla accompanied by lymphocytes infiltration and erythrocyte extravasation can be seen. (H and E staining, a-10× magnification, b-20× magnification). (c) Before treatment with upadacitinib; (d) After 4 weeks of treatment with upadacitinib; (e) After 24 weeks of treatment with upadacitinibExcellent responses were observed in both patients. After 2-week treatment, one patient began responding and the lesions completely resolved with mild hyperpigmentation at the 3-month follow-up. The other, with a relatively more protracted and severe condition, displayed positive changes after 4-week treatment, achieving significant remission after 6 months [Figure 1c-e]. Despite variations in response time and treatment duration, both patients exhibited excellent tolerance to upadacitinib, with no adverse events or exacerbations observed during the follow-up. Despite the unclear pathogenesis and the lack of consensus on the optimal therapy for PL, the efficacy of an oral JAK inhibitor was demonstrated in a patient with severe PLEVA.[2] It is worth noting that the increased level of diverse cytokines, such as IL-6, IL-10, and IFN-γ, was also reported in this patient.[2] Given the pivotal role of the JAK-1/STAT signaling pathway in delivering IL-6, IL-10, and IFN-γsignals,[3] JAK-1 inhibitors such as upadacitinib may represent a promising therapeutic strategy for the management of refractory PLC. To date, upadacitinib has been approved to treat various autoimmune and inflammatory disorders, owing to its capacity to modulate cytokine and chemokine production and regulate the activity of both innate and adaptive immune cells.[4,5] However, reports on the use of upadacitinib in patients with resistant PLC remain limited. Our cases provide preliminary evidence of the effective treatment in refractory PLC using the JAK-1 inhibitor, upadacitinib. The marked improvement of symptoms observed in our patients indicates that upadacitinib has broad prospects as an alternative therapy for individuals grappling with this challenging condition. Further research is needed to deepen our understanding of the core mechanisms and confirm the efficacy and safety of upadacitinib in the management of refractory PLC. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.