The third patient was a 61-year-old woman admitted for weakness and stiffness in both lower limbs for about 1 year, accompanied by thoracic back pain and constipation for 8 months. The neurological examination on admission revealed paresis in the bilateral lower limbs (3 to 4/5), decreased pain and thermal sensation in the trunk and lower limbs below the T10 level, brisk bilateral knee and Achilles tendon reflexes, and bilateral extensor plantar response. The routine blood tests and inflammatory markers levels were normal. Infections assays were negative. Rheumatologic assays were negative, except for seropositivity for perinuclear ANCA (titer, 1:32), MPO-ANCA (titer, 1:100), and elevated IgG4 (441 mg/dl). Chest and paranasal sinus CT found no abnormalities. A spinal cord MRI revealed a ribbon-like thickening of the dura mater between vertebral levels T7 and T11 (which was moderately enhanced by gadolinium administration) and a compressed and flattened focal spinal cord (Figures 3A-C). Although the patient underwent emergent T7-T11 right pediculectomy and partial corpectomy for decompression and resection of the dural lesion, her neurological deficits did not improve. The CSF analysis during the operation was negative for bacteria, tuberculosis, viruses, and fungi. A broad panel of immunohistochemical markers was assayed, such as S-100, EMA, CK-P, GFAP, Vim, CD20, CD68, CD38, CD138, CD34, and Ki67. A histopathology analysis showed lymphocyte infiltration, high IgG4+ cell infiltration, and a storiform pattern of fibrosis without granulomatous changes (Figures 3D,E).
We systematically searched the PubMed database for studies on humans, written in English, and published between 1976 and April 2022 using the keywords: "pachymeningitis, meningitis, dura, antineutrophil cytoplasmic antibody, myeloperoxidase, and proteinase-3." We excluded cases described in insufficient detail. Ultimately, we analyzed 10 cases, including our three cases. The patients' ages ranged from 48 to 79 years (median 61.5 +- 3.2 years), and the male/female ratio was 1:1. Table 1 summarizes the clinical, radiological, and pathological characteristics of all patients. We re-evaluated the cases according to the Comprehensive Diagnostic Criteria (CDC) for IgG4-RD. Possible IgG4-RD was defined by suggestive organ involvement associated with elevated serum IgG4 levels (>135 mg/dl). We identified probable IgG4-RD by looking for classical histopathological features (i.e., dense lymphoplasmacytic infiltration, storiform fibrosis, obliterative phlebitis, and mild-to-moderate eosinophil infiltration), IgG4/IgG positive plasma cell ratio >40% and >10 IgG4+ cells per high power field. Definitive IgG4-RD was identified by suggestive organ involvement associated with elevated serum IgG4 levels and histological features. For AAV, we used the American College of Rheumatology (ACR) 1990 criteria and the definitions from the 2012 Chapel Hill Consensus Conference and the EMA algorism for GPA, MPA, and EGPA. Due to a lack of histopathological examination, only a possible diagnosis of IgG4-RD was established in our two patients (Nos. 1, 2) according to the currently accepted criteria, although we cannot fully exclude the diagnosis of AAV in the current stage. We diagnosed four cases with definitive IgG4-RD and three with probable and possible Ig4-RD. Eight patients had anti-MPO ANCA, and two had anti-proteinase-3 (PR3) ANCA. Two cases (Nos. 7 and 10) fulfilled the CDC for IgG4-RD and the ACR and Chapel Hill criteria and the EMA algorism for AAV. One had biopsy results compatible with both GPA and IgG4-RD, and the other (No. 7) had a clinical overlap. Eight patients had documented symptom courses, and most of them had a diagnostic delay of several months before admission. In patients with intracranial dura mater involved, headache was the most common symptom, followed by cranial nerve deficits, such as hypoacusis, dysphagia, diplopia, vertigo, hypoglossal nerve palsy, and trigeminal nerve palsy. Headaches were often described as a sense of persistent local crushing with progressive exacerbation and refraction to drugs. Two patients (Nos. 4 and 5) had papilledema, most likely caused by intracranial hypertension. Patients with spinal hypertrophic pachymeningitis often experienced radicular pain and spinal cord compression symptoms (Nos. 3, 6, and 8), but rarely fever. MRI revealed focal pachymeningitis in eight cases, with the posterior fossa and occipital lobe most commonly involved, which might explain the neurological symptoms. Lymphocytosis and oligoclonal bands were commonly found in the CSF, as well as elevated blood non-specific inflammatory indicators, such as CPR and ESR. Eight patients had elevated serum IgG4 levels, while one displayed mild neutrophil-predominant leukocytosis, thrombocytosis, and normocytic anemia. The overall responses to immunosuppressants were good, with six cases attaining great clinical and radiological improvement; two cases suffered from one or two relapses, and only one patient expired from secondary infection.