Anti-Cyclic Citrullinated Peptide Antibody-Positive Meningoencephalitis in the Preclinical Period of Rheumatoid Arthritis

Abstract

Rheumatoid meningoencephalitis (RM) is a rare complication of rheumatoid arthritis (RA). This report describes a 63-year-old man with complaints of high-grade fever, headache, and vomiting for several days before admission. Both his serum and cerebrospinal fluid were positive for anti-cyclic citrullinated peptide (CCP) antibody and rheumatoid factor, and contrast-enhanced fluid-attenuated inversion recovery magnetic resonance imaging (MRI) showed abnormal gadolinium enhancement of the meninges and high-intensity lesions in the subarachnoid spaces. The patient was diagnosed with RM despite lack of signs suggesting RA. His symptoms drastically improved with intravenous infusion of high-dose methylprednisolone. Two months later, he developed RA. The findings in this patient suggest that RM could develop prior to the onset of RA. Anti-CCP antibody and MRI findings may be useful for the diagnosis of RM, regardless of RA history.

Use of Cerebrospinal Fluid Biomarkers in Diagnosis and Monitoring of Rheumatoid Meningitis

“…Patients diagnosed at autopsy almost all display meningeal rheumatoid noduli, while patients diagnosed with meningeal biopsy most often show non-specific inflammation (2, 7). In some previous cases correlation between strongly elevated CSF RF and Il-6 and RM has been proposed (12, 13, 23, 24), however this still needs validation as a diagnostic tool.…”

“…Brain MRI with patchy leptomeningeal contrast enhancement and cerebrospinal fluid (CSF) rheumatoid factor (RF) are useful to guide, but diagnosis still relies on pathological examination of a meningeal biopsy often showing unspecific inflammation, rheumatic noduli, and in some cases vasculitis (2, 7–11). Four recent cases have shown presence of CSF anti-cyclic citrullinated peptide (anti- CCP) in patients with RM (12–15). Here, we describe a patient with RM with strongly positive anti-CCP, IgM RF, and chemokine (C-X-C motif) ligand 13 (CXCL13) levels in CSF that normalized after treatment suggesting a potential use of these markers in both diagnosis and treatment management of RM.…”

Autoimmune Encephalitis as an Extra-articular Manifestation of Rheumatoid Arthritis

“…The CSF levels of RF have been used as a diagnostic marker of rheumatoid meningitis (7). The CSF levels of IL-6 (7) or CCP-antibodies (5,9) are also reported to be correlated with the clinical symptoms of rheumatoid meningitis. In this case, RF was not elevated in the CSF, but both IL-6 and CCP-antibodies were elevated in the CSF, although the exact upper limit of the normal CSF levels is not available.…”

“…Although the central nervous system (CNS) is rarely involved in RA, a variety of neurological manifestations occur associated with vasculitis, pachymeningitis, meningitis, opportunistic infection, drug adverse effects, or other comorbid rheumatologic disorders (2-4). A case of meningoencephalitis with leptomeningeal enhancement was previously reported (5), but autoimmune encephalitis (AE) with extensive changes in the parenchymal brain magnetic resonance imaging (MRI) findings associated with RA has not been reported yet.…”

Rheumatoid meningitis sine arthritis

“…Since 1954, around fiftyfour histopathologically proven cases of rheumatoid meningitis have been published, most of them in patients with a longstanding history of seropositive R.A. In only five reported cases, the diagnosis of rheumatoid meningitis preceded the diagnosis of R.A within the first 3 months of initial presentation or were diagnosed simultaneously [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] . Here, we present the first case of biopsy proven rheumatoid meningitis in a patient without any prior history or new development of clinical arthritis after one year of follow up, and we highlight the value of testing for rheumatoid factor (R.F) and anti-cyclic citrullinated peptide (CCP) antibodies in aseptic meningitis of unclear etiology, even in the absence of arthritis.…”