Long-Term Clinical Landscapes of Spinal Hypertrophic Pachymeningitis With Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis.

Abstract

Spinal hypertrophic pachymeningitis (HP) is an extremely rare disorder characterized by the thickening of the spinal dura mater, which harbors distinct repertoires of immune cells due to the unique partitioning of the arachnoid blood-CSF barrier. The objectives were to identify the pathogenesis and therapeutic strategies for spinal HP. This retrospective cohort study analyzed the clinical and pathologic profiles of patients with idiopathic/immune-mediated HP including spinal HP. Among 61 patients with idiopathic/immune-mediated HP, all 6 Japanese patients with spinal HP, with a median observation period of 88.8 months, were myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA)-seropositive. The MPO-ANCA⁺ spinal HP cohort had the following characteristics: (1) a predominance of older women; (2) all patients were classified as having microscopic polyangiitis based on the 2022 American College of Rheumatology/European League Against Rheumatism criteria; (3) 83% of patients developed subacute/chronic myelopathy due to extramedullary spinal cord compression; (4) 50% of patients had lesion extension to the epidural compartment and vertebral column; (5) 50% of patients presented with chronic sinusitis, otitis media, or mastoiditis; (6) 33% of patients had involvement of the lower airways or kidneys; (7) a higher disease activity of the nervous system was noted based on the Birmingham Vasculitis Activity Score (BVAS), in contrast to MPO-ANCA⁺ cranial HP; (8) granulomatous inflammation with myofibroblasts, immune cells including granulocytes, and B-cell follicle-like structures were observed in the thickened dura mater; (9) immunotherapies (with or without surgical decompression) were effective in reducing the modified Rankin Scale score and reduced BVAS during the first active insults; (10) combined immunotherapies with glucocorticoids and cyclophosphamide/rituximab helped in reducing relapses in the long term; and (11) surgical decompression, including laminectomy and duraplasty, was necessary for compressive myelopathy. These data suggest that MPO-ANCA⁺ spinal HP shares common features with MPO-ANCA⁺ cranial HP (1, 2, 6, 8, 9, and 10), but also has unique clinical features (3, 4, 5, 7, and 11). Our findings highlight the significant pathogenic role of ANCA in spinal HP. MPO-ANCA⁺ spinal HP, as an organ-threatening disease, should be positioned as having unique characteristics, whether limited to the CNS or as part of a generalized form in ANCA-associated vasculitis.