2013.11.26
Hypertrophic pachymeningitis: significance of myeloperoxidase anti-neutrophil cytoplasmic antibody
（Brain. 2014 Feb;137(Pt 2):520-36. doi: 10.1093/brain/awt314. Epub 2013 Nov 22.）
Yokoseki A1, Saji E1, Arakawa M1, Kosaka T2, Hokari M1, Toyoshima Y2, Okamoto K3, Takeda S4, Sanpei K5, Kikuchi H6, Hirohata S7, Akazawa K8, Kakita A2, Takahashi H2, Nishizawa M1, Kawachi I1.
1 Department of Neurology, Brain Research Institute, Niigata University
2 Department of Pathology, Brain Research Institute, Niigata University
3 Department of Neurosurgery, Brain Research Institute, Niigata University
4 Department of Pathology, Niigata Neurosurgical Hospital and Brain Research Centre, Niigata
5 Department of Neurology, Sado General Hospital, Niigata
6 Department of Internal Medicine, Teikyo University School of Medicine, Tokyo
7 Department of Rheumatology and Infectious diseases, Kitasato University School of Medicine, Kanagawa
8 Department of Medical Informatics, Niigata University
Abstract
The aim of this study was to elucidate the characteristics, pathogenesis and treatment strategy of hypertrophic pachymeningitis that is associated with myeloperoxidase anti-neutrophil cytoplasmic antibody (ANCA). We retrospectively investigated clinical, radiological, immunological and pathological profiles of 36 patients with immune-mediated or idiopathic hypertrophic pachymeningitis, including 17 patients with myeloperoxidase-ANCA, four patients with proteinase 3-ANCA, six patients with other immune-mediated disorders, and nine patients with 'idiopathic' variety. Myeloperoxidase-ANCA-positive hypertrophic pachymeningitis was characterized by: (i) an elderly female predominance; (ii) 82% of patients diagnosed with granulomatosis with polyangiitis (previously known as Wegener's granulomatosis) according to Watts' algorithm; (iii) a high frequency of patients with lesions limited to the dura mater and upper airways, developing headaches, chronic sinusitis, otitis media or mastoiditis; (iv) a low frequency of patients with the 'classical or generalized form' of granulomatosis with polyangiitis involving the entire upper and lower airways and kidney, or progressing to generalized disease, in contrast to proteinase 3-ANCA-positive hypertrophic pachymeningitis; (v) less severe neurological damage according to the modified Rankin Scale and low disease activity according to the Birmingham Vasculitis Activity Score compared with proteinase 3-ANCA-positive hypertrophic pachymeningitis; (vi) increased levels of CXCL10, CXCL8 and interleukin 6 in cerebrospinal fluids, and increased numbers of T cells, neutrophils, eosinophils, plasma cells and monocytes/macrophages in autopsied or biopsied dura mater with pachymeningitis, suggesting TH1-predominant granulomatous lesions in hypertrophic pachymeningitis, as previously reported in pulmonary or renal lesions of granulomatosis with polyangiitis; and (vii) greater efficacy of combination therapy with prednisolone and cyclophosphamide compared with monotherapy with prednisolone. Proteinase 3-ANCA may be considered a marker for more severe neurological damage, higher disease activity and a higher frequency of the generalized form compared with myeloperoxidase-ANCA-positive hypertrophic pachymeningitis. However, categorization into 'granulomatosis with polyangiitis' according to Watts' algorithm and immunological or pathological features were common in both proteinase 3- and myeloperoxidase-ANCA-positive hypertrophic pachymeningitis. These data indicate that most patients with myeloperoxidase-ANCA-positive hypertrophic pachymeningitis should be categorized as having the central nervous system-limited form of ANCA-associated vasculitis, consistent with the concept of ophthalmic-, pulmonary- or renal-limited vasculitis.
