Acta Dermato-Venereologica 98-9CompleteContent | Page 20

904 SHORT COMMUNICATION Efficacy of Oral Ruxolitinib in a Patient with Refractory Chronic Spontaneous Urticaria Atsushi FUKUNAGA 1 , Mitsuhiro ITO 2 and Chikako NIHIGORI 1 Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, Hyogo, 650-0017, and Laboratory of Hematology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Hyogo, Japan. E-mail: [email protected] 1 2 Accepted Jul 5, 2018; Epub ahead of print Jul 6, 2018 Chronic spontaneous urticaria (CSU) is a skin disorder that is characterized by the spontaneous development of wheals that last for 6 weeks or more (1). CSU is highly prevalent, affecting up to 1% of the population, and has a significant negative impact on a patient’s quality of life and health (2). Histamine and other mediators, such as platelet- activating factor and cytokines from activated mast cells, are mainly involved in the pathophysiological aspects of CSU. Inflammatory cytokines, such as Th1-, Th2-, Th17-, and Th22-related cytokines, which are released into the peripheral circulatory micro-environment, have been proposed to determine the disease activity in CSU (3). Significant interactions between the interferon (IFN)-γ, interleukin (IL)-2, and IL-21 networks, which are asso- ciated with Janus kinase-signal transducer and activator of transcription (JAK-STAT) signalling, have recently been proposed in CSU (3). The JAK-STAT pathway is used by cytokines, including ILs and IFNs, to transmit signals from the cell membrane to the nucleus. Ruxolitinib, a potent small-molecule inhibitor of JAK1/2, is Food and Drug Administration-approved to treat myeloproliferative disorders and is associated with marked clinical benefits in patients with myelofibrosis (4). It reduces symptoms that are related to proinflammatory cytokine release in haematological disorders. JAK inhibitors are also ef- ficacious in dermatological disorders, including atopic dermatitis, alopecia areata, psoriasis, and vitiligo vulgaris (5). The efficacy of ruxolitinib was reported in a case of systemic mastocytosis, a mast cell-mediated disorder (6), but not in patients with urticaria. We present here a case of a woman with refractory CSU in whom complete control of urticarial symptoms was achieved after treatment with oral ruxolitinib. CASE REPORT A 61-year-old woman presented with a 1-year history of recurrent spontaneous urticaria that was resistant to various treatments (H1 antihistamines, oral corticosteroids, and repeated i.v. systemic corticosteroid) and often accompanied by shortness of breath. H1 antihistamines (fexofenadine hydrochloride 120 mg/day, cetirizine hydrochloride 10 mg/day) and oral prednisolone (15 mg/day) had been prescribed by a family doctor before the first visit, but her symptoms remained. The patient’s negative history, provocation testing results, negative prick test results for food, and negative food challenge results excluded chronic inducible urticarias and food allergy. She had not experienced angioedema, unexplained fever, or joint pain in her history, and the mean duration of her wheals was several hours. She did not use anti-inflammatory drugs at the first visit. Therefore, she was diagnosed with CSU (Fig. 1a). A skin biopsy of a urticarial lesion demonstrated oedema in the upper and mid-dermis, interstitial infiltration of eosinophils and neutrophils in the upper and deep dermis, extended infiltration of eosinophils and neutrophils into the subcutaneous tissue, and no signs of leukocytoclastic vasculitis (Fig. 1c,d). Blood tests showed high blood counts (no blast cells), normal complement levels, and negative C-reactive protein. An autologous serum skin test was positive, indicating the presence of serum histamine-releasing autoantibodies. During the subsequent 6 years, her urticarial symp- toms became resistant to several treatments, including updosing of second-generation H1 antihistamines, H2 antagonists, antileu- kotrienes, systemic corticosteroids, and cyclosporine. Because cerebral infarction occurred during her follow-up, warfarin was started. The warfarin partially improved the urticarial symptoms. However, her urticarial symptoms remained poorly controlled while we waited for the Japanese authorities to approve omalizu- mab for CSU. Although routine blood tests were performed many times during this follow-up period and showed no abnormality, ensuing blood tests denoted that a peripheral blood smear detec- ted megathrombocytes and blastoid cells. Histological analysis of a subsequent bone marrow biopsy showed hypercellular bone marrow with myelofibrosis and abnormal hematopoietic cells, suggesting chronic myeloproliferative disease. The JAK2 V617F mutation was identified in peripheral blood cells. An abdomi- nal computed tomography (CT) scan revealed splenomegaly. Therefore, she was diagnosed with primary myelofibrosis. She began treatment with oral ruxolitinib (20 mg/day, twice dail y) for abdominal discomfort, which was accompanied by rapid aggravation of splenomegaly. At the time oral ruxolitinib was initiated incidentally by a haematologist in addition to drugs for CSU, including fexofenadine hydrochloride, ebastine, lafutidine, and warfarin. At the start of ruxolitinib, her disease activity and control of CSU remained poor (weekly urticarial activity score (UAS7) = 40, Dermatology Life Quality Index (DLQI) score = 12, urticaria control test (UCT) = 0) (1, 7, 8). Her urticarial symptoms, Fig. 1. Clinical appearance: (a) before administration of ruxolitinib; and (b) 5 weeks after initiation with ruxolitinib. Histopathological features: (c) in the dermis; and (d) in the subcutaneous tissue (haematoxylin-eosin staining; original magnification (b: 100×, c: 200×) (before the start of ruxolitinib). doi: 10.2340/00015555-3006 Acta Derm Venereol 2018; 98: 904–905 This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2018 Acta Dermato-Venereologica.