Dear Editor, Twenty-nail dystrophy (TND), a subtype of trachyonychia, is manifested by the presence of longitudinal striations, ridges, fissures, and/or depressions on all 20 nails.1 TND can either be idiopathic or associated with systemic or dermatological conditions, such as alopecia areata, lichen planus, psoriasis, or atopic dermatitis.2 TND is a severe disfiguring disorder that can impose substantial social stigma on patients and even lead to social and life impairments. Unfortunately, the management of TND presents significant challenges due to the lack of a standardized treatment regimen. Herein, we have successfully cured a patient with TND with second-generation selective JAK1 inhibitor, Upadacitinib, for the first time. A 48-year-old woman complained of a 1-year history of nail alterations without any subjective symptoms. All her nails manifested several longitudinal ridges and a sandpaper-like appearance, along with individual subungual hemorrhage, onychorrhexis, and brownish discoloration persisting Figure 1. On physical examination, no primary or secondary skin lesions were found elsewhere except on the affected nails. The patient denied a history of infection, allergies, chemical corrosion, other potential triggers as well as relevant family medical history. The patient refused further biopsy. Based on the medical history and clinical signs, an idiopathic TND was clinically diagnosed. Subsequently, the patient commenced local injection therapy with compound betamethasone. However, the treatment was discontinued after just one attempt due to severe pain. Subsequently, after accomplishing baseline investigations, including complete blood count, liver and renal function tests, lipid profile, creatine kinase, and screenings for tuberculosis, HIV, and hepatitis B and C viruses, Upadacitinib was administered to the patient at 15 mg daily for 6 months. After the completion of the treatment course, the patient’s nails showed remarkable improvement: longitudinal ridges decreased, smoothness and luster recovered, affected nails grew out, and nail color lightened Figure 2. No adverse reactions or abnormalities were detected in routine laboratory tests.Figure 1: All twenty nails of the patient exhibited longitudinal ridging and a sandpaper-like textureFigure 2: After 6 months of oral Upadacitinib treatment, dramatic improvements were observed in the patient’s twenty nails: Longitudinal ridging was reduced, and the nails’ smoothness and luster were restored. Furthermore, the previously damaged nails exhibited healthier growth, and the nail color became lighterThe precise cause of nail unit inflammation in patients with TND persists remains unclear. Nevertheless, the utilization of JAK-STAT inhibitors has offers new therapeutic options for the management of these patients. The hypothesized mechanism involves the nail matrix, an epithelial keratinizing structure that, like hair follicles, expresses IL-15. This may activate NKG2D-expressing CD8 T cells, resulting in the release of INF-γ and the establishment of a positive feedback loop. By breaking this loop, JAK-STAT inhibitors could potentially treat nail dystrophy.3 Upadacitinib, a second-generation selective JAK1 inhibitor, has received approval from numerous global regulatory agencies for the treatment of various chronic inflammatory conditions and has demonstrated favorable benefit-risk profiles.4 Theoretically, Upadacitinib’s selective action minimizes the off-target effects commonly associated with broader JAK inhibitors, potentially reducing side effects. In summary, Upadacitinib offers broad application prospects for the treatment of TND, particularly in patients who find it challenging to tolerate the pain associated with local injections. To our knowledge, this case marks the first documented success of oral Upadacitinib in the treatment of idiopathic TND. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil Conflicts of interest There are no conflicts of interest.
He et al. (Thu,) studied this question.