IgG4-related hypertrophic pachymeningitis: clinical features, diagnostic criteria, and treatment

JAMA Neurol. 2014 Jun;71(6):785-93. 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.

Publication types

  • Review

MeSH terms

  • Autoimmune Diseases / diagnosis*
  • Autoimmune Diseases / drug therapy*
  • B-Lymphocytes / immunology
  • Humans
  • Hypertrophy / diagnosis
  • Immunoglobulin G / immunology*
  • Meningitis / diagnosis*
  • Meningitis / drug therapy*


  • Immunoglobulin G