title: Hypertrophic pachymeningitis: significance of myeloperoxidase anti-neutrophil cytoplasmic antibody.
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.
authors.affiliation: 1 Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Yokoseki
authors.forename: Etsuji
authors.initials: E
authors.lastname: Saji
authors.forename: Musashi
authors.initials: M
authors.lastname: Arakawa
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kosaka
authors.forename: Mariko
authors.initials: M
authors.lastname: Hokari
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Toyoshima
authors.forename: Kouichirou
authors.initials: K
authors.lastname: Okamoto
authors.forename: Shigeki
authors.initials: S
authors.lastname: Takeda
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sanpei
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Kikuchi
authors.forename: Shunsei
authors.initials: S
authors.lastname: Hirohata
authors.forename: Kouhei
authors.initials: K
authors.lastname: Akazawa
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kakita
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Masatoyo
authors.initials: M
authors.lastname: Nishizawa
authors.forename: Izumi
authors.initials: I
authors.lastname: Kawachi
mesh_terms: D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood* / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D006984:Hypertrophy / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000201:enzymology; D008297:Male; D008581:Meningitis / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000201:enzymology; D008875:Middle Aged; D009195:Peroxidase / Q000097:blood* / Q000134:cerebrospinal fluid*; D012189:Retrospective Studies; D014657:Vasculitis / Q000097:blood / Q000134:cerebrospinal fluid / Q000201:enzymology*
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D015415:Biomarkers; D009195:Peroxidase
keywords: MPO-ANCA; PR3-ANCA; granulomatosis with polyangiitis; hypertrophic pachymeningitis; limited form