Immunoglobulin G4-related hypertrophic pachymeningitis

Abstract

ObjectiveMeningeal involvement in Immunoglobulin G (IgG)-4-related disease is rare and only described in case reports and series. Because a review into the disease is lacking, we present 2 cases followed by a literature review of IgG4-related hypertrophic pachymeningitis (IgG4-HP).MethodsTwo IgG4-HP cases were reported, one involving the spinal cord and responding to surgical management and a second involving the brain and responding to Rituximab therapy. We then review clinical cases and case-series of histologically proven IgG4-HP that were published in the PubMed-NCBI database.ResultsForty-two case reports and 5 case-series were studied (60 patients, 20 women). The median age was 53. Eighteen patients had systemic involvement and 24 had single-organ IgG4-HP. Fifty-five percent of patients had an elevated serum IgG4. Treatment was surgical in 20/53 cases. Steroid therapy and immunosuppressors were effective in 85% and more than 90% of the cases, respectively. The rate of disease relapse was 42.1% after steroid therapy was discontinued.Discussion/conclusionIgG4-HP is characterized by the lack of extra-neurologic organ-involvement and systemic signs. Histopathologic studies should be performed as it is crucial for diagnosis because serum markers are rarely informative. 18F-FDG positon tomography can be useful to characterize systemic forms. There is no specific CSF marker for IgG4-HP and the diagnostic value of CSF IgG4 levels needs to be studied with larger samples. We provide a treatment algorithm for IgG4-HP. Such treatment strategies rely on early surgery, steroids, and early immunosuppressive therapy to prevent neurologic complications.

Inflammatory Manifestations of Systemic Diseases in the Central Nervous System

“…IgG4-related disease (IgG4-RD) manifests as plasma cell infiltration into almost any organ with histopathologic findings of lymphoplasmacytic infiltration and storiform fibrosis in the setting of a high ratio of IgG-4-positive plasma cells [ 48 – 50 ]. Systemically, patients present with diffuse masses or swelling in organs concerning for malignancy, but IgG4-RD hypertrophic pachymeningitis is characterized by the lack of other organ involvement [ 50 , 51 ]. Patients may also demonstrate isolated or concomitant spinal cord disease, either masses, spinal dural enhancement, or transverse myelitis [ 51 , 52 ].…”

“…Systemically, patients present with diffuse masses or swelling in organs concerning for malignancy, but IgG4-RD hypertrophic pachymeningitis is characterized by the lack of other organ involvement [ 50 , 51 ]. Patients may also demonstrate isolated or concomitant spinal cord disease, either masses, spinal dural enhancement, or transverse myelitis [ 51 , 52 ]. CSF may show IgG4 10× normal level even though 56% of cases show normal serum IgG4 [ 50 – 52 ].…”

“…A treatment algorithm for isolated hypertrophic pachymeningeal disease has been proposed which begins with decompression of the inflammatory mass if there is adjacent structure compression [ 51 ]. Intravenous solumedrol, 1000 mg daily for 3–5 days is recommended first line therapy followed by an oral taper of 1 mg/kg/day prednisone.…”

“…For severe neurological disease or neurological and systemic disease involvement, steroids with rituximab is recommended for induction and maintenance [ 2 •, 53 ]. If a patient relapses, intravenous or oral cyclophosphamide should be considered for induction [ 51 ].…”

N2 year in review

“…20 Neurologic manifestations can be seen as part of the multiorgan fibroinflammatory involvement, mostly represented by meningeal and spinal cord disease and often presented as hypertrophic pachymeningitis and hypophysitis. In this context, Levraut et al 29 in the July issue report on 2 cases of hypertrophic pachymeningitis and suggest that PET imaging increased intrathecal IgG4 levels, and histopathologic studies are essential in arriving at proper diagnosis and early therapy initiation.…”