Efficacy of tacrolimus in Sjögren’s syndrome-associated CNS disease with aquaporin-4 autoantibodies

Abstract

Sirs, We present two patients with central nervous system (CNS) disease associated with Sjogren’s syndrome (SjS) and positive for antiaquaporin-4 water channel autoantibodies (AQP4-Ab) who were treated successfully with tacrolimus. Tacrolimus is an immunosuppressant that acts as a calcineurin inhibitor and suppresses T helper 2 (Th2) cells [1]. Tacrolimus may also act as a neuroprotectant by reducing axonal and myelin damage, as shown in a mouse model of experimental autoimmune encephalomyelitis [2]. SjS is a chronic autoimmune disease characterized by lymphocytic infiltration of the exocrine glands. SjS-associated inflammation sometimes spreads into the CNS (CNS–SjS), occasionally mimics relapsing-remitting multiple sclerosis (MS), and inflammation often involves the brain, spinal cord, and optic nerve [3]. Neuromyelitis optica (NMO) is also a relapsing inflammatory disease of the CNS, characterized by severe attacks of optic nerve neuritis and longitudinally extensive transverse myelitis [4]. NMO is distinguished from MS by the presence of AQP4-Ab and differences in the distribution of inflammatory lesions and pathological findings. Combination therapy with a corticosteroid and azathioprine is the current standard treatment for preventing NMO relapse [5]; however, some patients are refractory to this therapy. Approximately 3% of patients with NMO have coexisting systemic lupus erythematosus (SLE) or SjS, and CNS–SjS patients with optic nerve neuritis or longitudinal myelitis (conditions called ‘‘NMO spectrum disorder’’) often present with positive findings for AQP4-Ab [4, 6, 7]. To our knowledge, this is the first reported assessment of tacrolimus in patients with CNS–SjS with AQP4-Ab. This treatment was approved by the ethical committee of our university, and the patients provided written informed consent. A 48-year-old female (Patient 1, Fig. 1) was admitted to the hospital with rapidly progressive nausea, hiccups, dysphagia, and drowsiness. Magnetic resonance imaging (MRI) revealed T2 hyperintensities of the hypothalamus bilaterally and the dorsal medulla oblongata. After three courses of intravenous high-dose methylprednisolone (IHMP, 1 g/day for 3 days in one course), the patient recovered completely, except for mild dysphagia. One year after the first attack, she developed limb weakness. Laboratory test results revealed high levels of anti-Ro (SSA) antibodies and positive antinuclear antibody. The Schirmer test and the Saxon test revealed decreased salivary secretion (Table 1). She was diagnosed with CNS–SjS [8]. She experienced nine attacks during the entire disease course, and we started treatment with oral tacrolimus during her ninth admission. No recurrent attacks have been observed for 49 months since the start of this treatment. T. Fukuda (&) H. Shiraishi H. Nakamura A. Tsujino Y. Nishiura M. Motomura K. Eguchi First Department of Internal Medicine, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan e-mail: taku-ngs@umin.ac.jp