Immunoglobulin G4-related hypertrophic pachymeningitis: A case-oriented review

Abstract

Objective: Meningeal 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).

Methods: Two 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.

Results: Forty-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/conclusion: IgG4-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.

Figure 1. MRI of both patients with IgG4-HP and spinal cord arteriography of the first patient

(A) Multiple T2 hyperintense signals (white arrows) (A.a) all enhanced after gadolinium injection (A.b) of the posterior half of the cervico-thoracic spinal cord. T2 hypointense signal of the posterior subarachnoid space from C5 to D3 suggesting a dural fistula (red arrow) (A.c), confirmed by medullary arteriography (A.d) with opacification of a venous peloton opposite the meninge of the left lateral part of the dural sheath corresponding to the medullary veins visible on MRI. (B) Intra-ductal, intra-dural, postero-median, polylobulated tumor lesion, well-defined, in T1 isointense signal (B.a), intensely and homogeneously enhanced after injection of gadolinium (B.b), T2 hypointense signal (B.c), next to D2-D3 realizing a mass effect on the spinal cord. There is an extensive intramedullary edema supra and under-lesion (B.d). (C) Bi-frontal meningeal thickening enhanced by gadolinium invading the sheaths of optic nerves and cavernous sinuses (white arrows) (C.a and c). T2/FLAIR hyperintense signal of the left optic nerve testifying to radiologic optic neuritis, white arrows (C.b d). FLAIR = fluid attenuated inversion recovery.

Figure 2. Classification of IgG4-HP

^a–cOther locations of IgG4-RD involvement by patients: ^a1. Orbital pseudotumor, kidney and lung. 2. Pancreas. 3. Lymph nodes, submandibular glands and lung. 4. Retroperitoneal fibrosis. 5. Mastoid. 6. Retroperitoneal fibrosis. 7. Aortitis. 8. Episcleritis. 9. Hypophysitis. 10. Lacrymal and submandibular glands. 11. Orbital pseudotumor. 12. Maxillary pseudotumor. 13. Episcleritis. ^b1. Orbitory pseudotumor. 2. Pulmonary pseudo-tumor and hypophysitis. 3. Orbitary pseudotumor. 4. Retroperitoneal fibrosis. ^c1. Submandibular gland. IgG4-HP = IgG 4-related hypertrophic pachymeningitis; IgG4-RD = IgG 4-related disease; NS = non-specified.

Figure 3. Treatment algorithm for IgG4-HP

* Oral steroid therapy should be reduced over a period of 1-year minimum. AZA = azathioprine; CYC = cyclophosphamide; IgG4-HP = IgG 4-related hypertrophic pachymeningitis; MMF = mycofenolate mofetil; MTX = methotrexate.