Relapsing Polychondritis with Central Nervous System Involvement: Experience of Three Different Cases in a Single Center

Relapsing polychondritis (RP) is a rare autoimmune disorder characterized by inflammation in cartilaginous structures (1). It mainly involves the cartilage of the ears, nose, larynx, and tracheobronchial tree but it frequently present as a systemic disease showing arthritis, ocular inflammation, audiovestibular involvement, skin lesions, heart valve incompetence, and vasculitis (2). Involvement of central nervous system (CNS) in RP is a fatal condition but it is difficult to diagnose due to rare frequency and variable presentation of disease. There have been papers on CNS involvement of RP but they are few in number and are only sporadic. We have experienced 3 cases of RP with distinct CNS manifestations.

Neurological involvement of RP is rare and affects about 3% of patients but it is an important cause of death (3). The pathogenesis of CNS involvement in RP is still unknown but seems to be related with autoimmunity. Autoantibodies to glutamate receptor GluRɛ2 (4) and neutral glycosphingolipids are detectable in the CSF and sera obtained from patients with encephalitis (5). Vasculitis is the major pathological change. In some studies, biopsy showed perivascular lymphocytic cuffing and infiltration in small vessels, with loss of nerve cells and gliosis (6, 7). As for clinical manifestations, cranial nerve palsy (V and VII) are the most common form of neurologic manifestations and aseptic meningitis, meningoencephalitis, stroke, and cerebral aneurysm may develop (2).

Meningitis and enephalitis in RP can show various symptoms like cognitive impairment, psychomotor abnormality, confusion, and disorientation (8). Characteristic MRI pattern has not been established but multifocal hyper-intensity lesions, especially in basal ganglia and periventricular and subcortical white matter are the most common findings (7, 9, 10). Cerebrospinal fluid analysis shows marked pleocytosis with a predominance of PMN but some cases show predominance of lymphocytosis. Sugar level is usually normal and protein is slightly elevated (7, 11). In the first case of this report, the patient had meningoencephalitis and imaging and CSF findings were similar to previous reports. One unique aspect of the case was occlusion of cerebral arteries. There have been few reports on combination of meningitis and stroke in RP (12). Stenosis or aneurysmal change due to vasculitis or vascular thrombus formation has been suggested as the cause of stroke in RP (12, 13). The prognosis of patients with RP complicated by meningoencephalitis is poor and the reported mortality of meningitis is 12% and that of encephalitis is 36.4% (9).

Limbic encephalitis results from bilateral damage to the medial temporal lobes. It is caused by the herpes simplex virus or by non-herpetic disorders (non-herpetic viruses, Hashimoto’s encephalopathy, CNS lupus, gliomatosis cerebri, intravascular malignant lymphomatosis, and paraneoplastic conditions) (6). RP also is a cause of limbic encephalitis. It can present as cognitive dysfunction, memory impairment, seizures, depression, anxiety and hallucinations (6). In the second case, the patient showed hallucination and agitation, which are symptoms of limbic encephalitis. The findings of EEG, generalized slowing and/or epileptiform activity, also support the diagnosis (14). Though there was no detectable changes in brain MRI, there have been some reports suggesting that it takes time to see a noticeable change on a brain MRI and repeated testing is often required (15, 16).

There have been few reports on dementia from RP. The time to develop dementia after diagnosis of RP was a few months to 1 year (16, 17, 18). In addition to memory loss, changes in behavior, emotional lability, and language and movement abnormalities have been described (16, 17, 18). Atrophy of cerebral cortex, especially in temporal lobe could be observed in either autopsy or brain MRI. Diffuse vasculitis and gliosis in cerebral cortex, especially in hippocampus was a common pathological feature (16, 17). In the third case of our report, the patient had been diagnosed with RP 17 months before the onset of dementia. Similar to previous reports, the CSF finding was compatible with aseptic meningitis.

In regard to diagnosis of RP, McAdam’s criteria require the presence of three or more of the following features: bilateral auricular chondritis, nonerosive seronegative inflammatory polyarthritis, nasal chondritis, ocular inflammation, respiratory tract chondritis, and audiovestibular damage (1). But there have been some modifications on these criteria and some suggest that one McAdam’s criterion and a positive histologic confirmation, or two McAdam’s criteria and a positive response to the administration of corticosteroids or dapsone can suffice the diagnosis (19). In our report, we could not perform cartilage biopsy in all patients and diagnosed RP based on clinical manifestations.

Diagnosis of CNS complication of RP is mainly clinical and is challenging because it can present with varying clinical features. In addition, CNS vasculitis may develop in the absence of detectable systemic vasculitis (18) and complication is not always parallel with the auricular presentation (7).

With regard to treatment of CNS involvement of RP, for it is a very rare complication, treatment is largely empirical. Steroids in high dose or pulse range are the mainstay of treatment. For patients who are refractory to steroid or are requiring long-term steroid therapy, immunosuppressive or cytotoxic treatments are indicated (3, 7, 12). There have been a few reports in which treatment with TNF blocking agent, infliximab has been effective to CNS involvement resistant to steroid and cytotoxic agents (9, 20).

CNS involvement is a very rare complication of RP and diagnosis of this condition is very challenging due to its various presentation and lack of efficient tools. Early suspicion and prompt management may prevent disability and mortality.