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June 2014

IgG4-Related Hypertrophic Pachymeningitis: Clinical Features, Diagnostic Criteria, and Treatment

Author Affiliations
  • 1Vanderbilt University School of Medicine, Nashville, Tennessee
  • 2Unit of Medicine and Clinical Immunology, Università Vita-Salute San Raffaele, San Raffaele Scientific Institute, Milan, Italy
  • 3Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston
  • 4Department of Neurology, Vanderbilt University School of Medicine, Nashville, Tennessee
JAMA Neurol. 2014;71(6):785-793. doi:10.1001/jamaneurol.2014.243

Importance  IgG4-related hypertrophic pachymeningitis (IgG4-RHP) is an increasingly recognized manifestation of IgG4-related disease, a fibroinflammatory condition that can affect virtually any organ. It is estimated that IgG4-RHP may account for a high proportion of cases of hypertrophic pachymeningitis once considered idiopathic.

Objective  To summarize the current knowledge on IgG4-RHP including its pathological, clinical, and radiological presentations. Particular emphasis is placed on diagnostic and therapeutic implications.

Evidence Review  This review is based on 21 reports published in the English medical literature since 2009. PubMed was searched with the following terms: IgG4, pachymeningitis, IgG4-related pachymeningitis, IgG4-related disease, IgG4-related, and IgG4 meningitis. Only cases with biopsy-proven IgG4-RHP were considered and included in this review.

Findings  Little is known with certainty regarding the pathogenesis of IgG4-RHP. The presence of oligoclonally restricted IgG4-positive plasma cells within inflammatory meningeal niches strongly suggests a specific response against a still unknown antigen. Clinical presentation of IgG4-RHP is not distinguishable from other forms of hypertrophic pachymeningitis and reflects mechanical compression of vascular or nerve structures, leading to functional deficits. Signs of systemic IgG4-related disease may concomitantly be present. Diagnostic process should rely primarily on magnetic resonance imaging, cerebrospinal fluid analysis, and meningeal biopsy. In particular, hallmark histopathological features of IgG4-RHP are a lymphoplasmacytic infiltration of IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. High-dose glucocorticoids are still the treatment of choice for IgG4-RHP because immunosuppressive agents have shown variable efficacy in reducing the meningeal hypertrophy. Rituximab is a promising therapeutic approach but experience with B-cell depletion strategies remains limited.

Conclusions and Relevance  IgG4-related disease accounts for an increasing proportion of cases of idiopathic hypertrophic pachymeningitis. Clinicians should become familiar with this alternative differential diagnosis because a prompt, specific therapeutic approach may avoid long-term neurological complications.

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