Relapsing Polychondritis with Central Nervous System Involvement Presented as Encephalitis : 7 Cases and Literature Review

C l i n M e d International Library Citation: Zhou A, Li X, Zhao L, Liu Y, Zhang X (2017) Relapsing Polychondritis with Central Nervous System Involvement Presented as Encephalitis: 7 Cases And Literature Review. J Rheum Dis Treat 3:045. doi.org/10.23937/2469-5726/1510045 Received: October 03, 2016: Accepted: February 10, 2017: Published: February 13, 2017 Copyright: © 2017 Zhou A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. DOI: 10.23937/2469-5726/1510045


Introduction
Relapsing polychondritis (RP) is a rare autoimmune systemic inflammatory disease characterized by recurrent episodes of inflammatory and progressive destruction of the cartilaginous structures of the nose, ears, joints and tracheobronchial tree, it also affected eyes, inner ear, kidneys bloods vessels [1].It was first described by Jaksch-Wartenhorst in 1923 and was named by Pearson in 1960.The annual incidence of the disease is about 3.5 cases per million, with greater than 600 cases worldwide, and the average age when diagnosis is 44-51 years old [2].
Clinically, the disease can involve the CNS and lead to neurological dysfunction.CNS involvement manifests in diversity including encephalitis.In 2004, Ohta reported the first case of RP with non paraneoplastic limbic encephalitis, which presented fever, headache, mental disorder, epilepsy, weakness, dizziness and so on, easily misleading to encephalitis.The reports about CNS involvement of RP are relatively rare.Here, we reported 7 cases with RP who basal ganglia, corona radiate and centrum semiovale and corpus callosum could also be involved (Figure 1F, Figure 1H, Figure 1I, Figure 1J and Figure 1L).One case had meningeal enhancement in anterior longitudinal fissure (Figure 1N).

Treatment and follow-up
All of Our patients were given intravenous methylprednisolone (500 mg/d, 5 days) or dexamethasone (20 mg/d, 7 days), then oral prednisone (60 mg/d) followed and tapered gradually.After steroid therapy, both CNS and no CNS symptoms improved remarkably.

Discussion
RP is a rare disease with the incidence of approximately 3.5 per million/year [5].CNS involvement in RP is estimated to occur with an incidence of 3% RP patients [6].Encephalitis is one of manifestations of CNS involvement, which was first reported by Ohta, et al. in 2004 occurred at the same time in two cases, and CNS symptoms appeared before cartilaginous features in four cases.There was also a case that cartilaginous manifests appeared ahead.

Serum and CSF analysis
Blood WBC counts elevated in 6 cases, ESR increased in 5 cases, and CRP increased in 6 cases (Table 2).In 3 cases, intracranial pressure was high.CSF WBC count increased in six cases and protein elevated in three cases.All the findings in blood and CSF implied the possibility of inflammation in CNS.

Brain MRI
All cases got brain MRI scanning.MRI finding was in diversity without specific signs.2 cases had normal MRI. 4 cases had abnormal signals in brain parenchyma (cerebellum: 2 cases (Figure 1E and Figure 1K), pons: one case (Figure 1M), and cerebral cortex: one case (Figure 1G).Moreover, thalamus, tissue [7].In our patients, two cases had three clinical features, and the others had two.All of them lacked of tissue biopsy.It should be stressed that all of our patients had auricular chondritis and ocular inflammation which may be a symbol of RP.
Patients with CNS involvement in RP sometimes have CSF profiles mimicking meningoencephalitis.Wang, et al. described 4 patients with RP who were suspected as meningoencephalitis upon elevated WBC and protein in CSF [8].All of our patients were considered as viral encephalitis or meningitis at the local hospital based on the elevation of WBC count (4 cases) and increase of protein content (2 cases) in CSF.These findings remind us that encephalitis should be differentiated carefully.One should pay much attention to extra-CNS manifestations which maybe is a clue of final diagnosis, for example, swelling nose, cauliflower ears and redness eyes are helpful to the diagnosis of RP. [7].Besides encephalitis, other manifestions of CNS involvement included headache, seizures, hemiplegia, aseptic meningitis, and cerebral aneurysms [5].In our series, symptoms of CNS involvement included fever, headache, mental disorder, dizziness, weakness or speech difficulty.
Due to the lack of specific biomarkers, the diagnosis of RP is still a challenge.McAdam criteria [3] is now widely accepted, in which RP is mainly diagnosed based on clinical features including auricular and nasal chondritis, ocular inflammation, nonerosive inflammatory polyarthritis, respiratory tract chondritis and audiovestibular damage.A definite RP is made when three of six clinical features are present along with the histological findings of affected cartilage which are loss of basophilic staining of the cartilage matrix, perichondrial inflammation, and eventual destruction of cartilage replaced by fibrotic The pathogenesis of RP arises from an immunologic reaction to type II collagen, with specific circulating antibodies present in approximately two-thirds of patients with RP [9].The mechanism of CNS involvement in RP may be related to vasculitis [10].However, Kashihara, et al. found positive anti-CluR antibodies in sera and CSF of a RP patient with limbic encephalitis [11], thus mechanism of CNS involvement in RP may be complicated.
Brain MRI findings in CNS involvement of RP are no specific.In a report, some RP patients presented with encephalitis had lesions in the temporal lobes on brain MRI [12].Another paper described a RP patient with bilateral, small disseminated high-intensity signals with vague margins in the medial temporal lobe, hippocampus, and insular cortex [13], which was similar to brain MRI findings in our patient 2. Our patient 4 showed multiple lesions in the thalamus, basal ganglia, corona radiate and centrum semiovale, which were similar to 3 reports [14][15][16].Ohta Y, et al. [7] reported a 57-year-old man with non paraneoplastic limbic encephalitis whose brain MRI showed hyperintense lesions in bilateral hippocampi, amygdaloidal bodies, left para-ventricular deep white matter, bilateral caudate nuclei and left putamen.Lesions in bilateral hippocampi, amygdaloidal bodies and left putamen were enhanced with Gd-DTPA.Our cases had similar findings (Figure 1F, Figure 1H, Figure 1I and Figure 1G).Ota M, et al. [17] described a RP patient whose brain MRI showed leptomeningeal enhancement in the frontal, parietal, and posterior regions, which was similar to our patient (Figure 1N).Ducci, et al. [18] reported a RP patient with neurological symptoms who had diffuse thickening of the dura in the frontal lobes similar to our patient 3. We also found the lesions in cerebellum hemisphere, cerebellum vermis and corpus callosum which had never been reported in the previously literatures.
Glucocorticoids are effective to RP. Intravenous pulse methylprednisolone (1 g/d for 3 consecutive days) is a common option, then followed by oral prednisone [16].Our cases improved remarkably after steroid.However, the optimal dose and the duration of steroid are still uncertain.Further study is needed.

Conclusion
In summary, CNS involvement in RP has no specific findings both in symptoms and in brain MRI findings.The diagnosis is still difficult.However, when one patient presenting with encephalitis has extra-CNS manifestations such as eye and ear abnormalities, CNS involvement of RP should be suspected.Immunotherapy including steroids and immunosuppressants may be a choice.Long-term follow-up is necessary.

Table 1 :
Summary of the clinical information, CSF and blood results in 7 RP cases with CNS involvement.

Table 2 :
The lab results in CSF and blood.