Clinical Presentation, Investigation Findings, and Outcomes of IgG4-Related Pachymeningitis:A Systematic Review

Sara Terrim, MD1; João Vitor Mahler, MD1; Flávio Vieira Marques Filho, MD1; et al

2024년 11월 18일

JAMA Neurol. 2025;82(2):193-199.

doi:10.1001/jamaneurol.2024.3947

Abstract

Importance 

Immunoglobulin G4 (IgG4)–related disease is an increasingly recognized fibroinflammatory condition that can involve multiple organs, including the pachymeninges. The understanding of IgG4-related pachymeningitis (IgG4-RP) remains limited because of its rarity and the predominance of knowledge derived from case reports and case series.

Objective 

To systematically review and synthesize the clinical presentation, investigation findings, and prognosis of IgG4-RP to better understand its diagnosis and management

Evidence Review 

A comprehensive systematic review was conducted following guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-analyses. PubMed/MEDLINE, Embase, and Scopus were searched from their inception until May 30, 2023, using terms related to IgG4-related disease and pachymeningitis without language or publication restrictions. Case reports and series that met the 2020 Revised Comprehensive Diagnostic Criteria or the 2019 American College of Rheumatology/European League Against Rheumatism classification criteria were included. Data on clinical presentations, investigation findings, and treatment outcomes were extracted and summarized.

Findings

A total of 148 case reports contributed data from 208 patients. Their median (IQR) age was 52 (39-62) years; 132 patients were male (63.5%) and 76 female (36.5%). Headache and cranial nerve dysfunctions were the most common neurological manifestations. Systemic involvement was identified in nearly half of the patients. Diagnostic imaging often showed preferential involvement of cavernous sinus and middle fossa. Laboratory results highlighted elevated serum IgG4 levels in 97 of 147 patients (65%) of patients and cerebrospinal fluid pleocytosis in 43 of 82 patients (52%). Storiform fibrosis or obliterating phlebitis were uncommon pathological findings. Mortality was below 1% (1/134; 0.7%), but only a third of patients presented complete clinical improvement, and the recurrence rate was 60 patients (40%) in a median (IQR) follow-up time of 9 (1-20) months. Glucocorticoids were the most commonly prescribed treatment, in 143 of 169 patients (85%); rituximab was prescribed as maintenance therapy in 53 of 169 patients (31%).

Conclusions and Relevance 

IgG4-RP commonly presents with headaches and cranial nerve dysfunction, posing diagnostic challenges due to the significant absence of systemic manifestations, low IgG4 serum levels, and atypical pathological findings. Current treatment outcomes are limited by incomplete recovery and frequent relapses underscoring the necessity for new treatment strategies.

Key Points

Question  What are the clinical presentations, investigation findings, and treatment outcomes of immunoglobulin G4–related pachymeningitis (IgG4-RP)?

Findings  In this systematic review, the clinical presentation of IgG4-RP was mostly headache and cranial nerve dysfunction; investigation showed predominant involvement of the cavernous sinus and middle fossa and limited sensitivity of serum IgG4 levels, cerebrospinal fluid analysis, and classical pathology features. With treatment with glucocorticoids and immunosuppressants, 37% of patients achieved complete recovery, with relapse occurring in 40% of cases.

Meaning  IgG4-related pachymeningitis often presents without typical pathological features or elevated IgG4 levels, challenging its diagnosis; more accurate biomarkers and tailored treatment approaches are required.

요약

• 소개 : IgG4-관련 경막염(IgG4-RP)은 희귀한 섬유염증성 질환으로, 주로 두통 및 뇌신경 기능 장애를 동반한다. 현재까지는 주로 증례 보고에 의존하여 알려져 있어 진단 및 치료에 대한 이해가 제한적이다. 본 리뷰 논문는 IgG4-RP의 임상 양상, 검사 결과, 치료 경과를 체계적으로 검토한 논문이다.

• 결과 : 총 148개의 증례 보고에서 208명의 환자 데이터를 수집하여 확인한 결과들이다.

  - 환자의 중간 연령은 52세이며, 남성이 63.5%를 차지하였다.

  - 주요 증상: 두통과 뇌신경 기능 장애.

  - 영상 검사: 해면 정맥동 및 중두개와의 병변이 흔히 관찰된다.

  - 혈액 검사: 환자의 65%에서 혈청 IgG4 수치 상승, 52%는 CSF pleocytosis 소견을 보였다.

  - 병리학적 특징: Storiform fibrosis 및 obliterating phlebitis는 드물다.

  - 예후: 사망률 0.7%(1명), 완전 회복 37%, 재발률 40% (중간 추적 기간 9개월).

  - 치료: 85%에서 스테로이드를 사용했으며, 리툭시맙(rituximab)은 31%에서 유지 요법으로 사용된다.

  
  

• 결론 및 의의 : IgG4-RP는 비특이적 증상과 전형적인 병리 소견의 결여로 진단이 어렵다. 또한 혈청 IgG4 수치와 전형적인 병리 소견이 정상 범위에 속하는 경우도 많아 주의가 필요하다. IgG4-RP는 재발률이 높고(40%) 완전 회복률이 낮으며(37%), 새로운 바이오마커와 치료 전략이 필요하다.