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.