鵜沢 顕之

Patients with generalized myasthenia gravis (gMG) suffer from significant physical and social burdens. Although immunotherapies have been widely used for the treatment of gMG, some patients do not achieve or maintain remission. Recently, several molecular-targeting therapies of gMG, including the intravenous infusion of efgartigimod alfa (efgartigimod IV), a neonatal Fc receptor inhibitor, have been developed and are clinically used in Japan. In 2024, combination subcutaneous injection of efgartigimod alfa and vorhyaluronidase alfa (efgartigimod SC) was approved for the treatment of patients with gMG (only when treatment with steroids or non-steroidal immunotherapies does not lead to sufficient response). Efgartigimod SC contains vorhyaluronidase alfa, which temporarily and locally facilitates diffusion of efgartigimod alfa, resulting in its absorption enhancement. An international phase III, ADAPT-SC study in patients with gMG, including Japanese demonstrates the non-inferiority of efgartigimod SC to efgartigimod IV in reduction of total IgG by 4 weeks treatment. An extension ADAPT-SC+ study demonstrates the long-term safety and tolerability as well as repeatable clinical benefit across multiple efgartigimod SC treatment cycles. As a self-injectable drug, efgartigimod SC may not only contribute to satisfy unmet medical needs in gMG therapy, but also improve convenience for patients and healthcare providers. (Received July 11, 2024; Accepted September 13, 2024; Published January 1, 2025).

OBJECTIVES: This study aimed to investigate cerebrospinal fluid (CSF) adenosine deaminase (ADA) levels in various neurological disorders and examine the relationships between CSF ADA levels and immunological parameters. METHODS: Overall, 276 patients whose CSF ADA levels were measured for suspected tuberculous meningitis (TBM) were evaluated. Data on baseline characteristics, final diagnoses, CSF ADA levels, and other laboratory parameters were collected. Thereafter, CSF ADA levels were compared based on final diagnoses, and correlations between CSF ADA levels and other CSF and blood laboratory parameters were evaluated. RESULTS: Five diseases exhibited a significant increase in CSF ADA levels relative to the noninflammatory disease control group (n = 40): (1) TBM (n = 15, p < 0.0001), (2) fungal meningitis (n = 7, p = 0.0400), (3) autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A, n = 7, p < 0.0001), (4) neurosarcoidosis (n = 7, p = 0.0028), and (5) lymphoproliferative disorders (n = 18, p = 0.0001). Strong positive correlations were observed between CSF ADA and CSF parameters, including soluble IL2 receptor (rs = 0.7566, p < 0.0001), albumin (rs = 0.6693, p < 0.0001), lactate dehydrogenase (rs = 0.6452, p < 0.0001), white blood cell count (rs = 0.6035, p < 0.0001), protein (rs = 0.6334, p < 0.0001), and lymphocytes (rs = 0.5954, p < 0.0001). DISCUSSION: CSF ADA levels were elevated in various inflammatory neurological diseases, especially in TBM, fungal meningitis, GFAP-A, neurosarcoidosis, and lymphoproliferative disorders. CSF ADA levels may reflect T-cell hyperactivation in the central nervous system.

BACKGROUND: This case report presents the case of a patient with P369S and R408Q variants in the MEFV gene who exhibited clinical features of Kikuchi disease and Mollaret meningitis. Furthermore, it discusses colchicine as a new potential treatment option for Kikuchi disease-associated meningitis. CASE PRESENTATION: A 41-year-old Japanese woman presented with fever and headache. She had nuchal rigidity and bilateral cervical lymphadenopathies. Her past medical history included multiple episodes of aseptic meningitis and cervical lymphadenopathy for more than twenty years. Lumbar puncture showed increased lymphocytes and IL-6 level and pathognomonic Mollaret cells. Excisional lymph node biopsy revealed histiocytic necrotizing lymphadenitis, confirming the diagnosis of Kikuchi disease. Subsequently, her recurrent Kikuchi disease and meningitis were successfully treated with colchicine. Furthermore, genetic analysis of the MEFV gene revealed heterozygous P369S/R408Q variants in exon 3. CONCLUSION: Mollaret meningitis can be associated with Kikuchi disease, and recurrence of both conditions may be suppressed by colchicine when these two coexist.