relapsing polychondritis ( rp ) is an uncommon disorder of unknown etiology that is characterized by recurrent and progressive inflammation of cartilaginous structures . a minority of patients with rp develop central nervous system ( cns ) manifestations , and limbic encephalitis has also been reported . glucocorticoid has been used as the first - line therapeutic agent , but a standardized second - line therapeutic protocol for rp with cns manifestations has not been established . the effects of anti- tumor necrosis factor ( tnf ) - agents have been reported recently . we report a patient with limbic encephalitis associated with rp who was refractory to initial high - dose glucocorticoid therapy , but subsequently responded to infliximab and discontinued therapy without recurrence . we also reviewed cases of rp with cns manifestations using pubmed with regard to clinical manifestations and treatment . a 58-year - old japanese male architect was brought to our institution by his wife , presenting with amnesia , disorientation , emotional liability and urinary incontinence . one year prior to admission , he had bilateral ear pain with swelling and erythema which improved without any treatment over a 4-week period . nine months prior to admission , he experienced iritis and scleritis in addition to recurrent pain in bilateral auricles . subsequent biopsy of the left auricle revealed infiltration of inflammatory cells in the perichondrium ( fig . 1 ) . diagnosis of rp was made based on mcadam s criteria , modified by damiani and levine . inflammation of bilateral auricles disappeared without any treatment , while iritis and scleritis were controlled by topical glucocorticoid therapy . one month prior to admission , he developed difficulty with drawing architectural drafts and finding his way home , together with emotional liability and urinary incontinence . past medical history revealed well - controlled diabetes mellitus by diet and dipeptidyl peptidase-4 inhibitor ( hba1c was 6.4 to 6.7% ) . on admission , his body temperature was 36.7c , blood pressure was 112/66 mmhg and heart rate was 68 beats per minute . head , eye , ear , nose , chest and abdominal examinations were unremarkable . neurological examination revealed poor tandem gait and poor finger - nose - finger test , but other examinations such as the cranial nerve , sensory and motor systems were unremarkable . his mini - mental states examination ( mmse ) result was 16 out of 30 . antinuclear antibodies , anti - neutrophil cytoplasmic antibodies , rheumatoid factor , anti - thyroid peroxydase antibody , anti - thyroglobulin antibody , urinalysis and serological tests for human immunodeficiency virus ( hiv ) and treponema pallidum were all normal or negative . cerebrospinal fluid ( csf ) analysis showed 33 cells/l with 32 polymorphonuclear leukocytes , glucose 81 mg / dl and protein 92 mg / dl . csf cultures for bacteria and mycobacterium tuberculosis and polymerase chain reaction of herpes simplex virus and cytology were also negative . both anti - n - methyl - d - aspartate type glutamate receptor ( glur ) n2b antibody and anti - glur 2 antibody were positive in csf , but neither were positive in serum . whole body fluorine-18 fludeoxyglucose positron emission tomography ( [ 18f]fdg - pet ) with ct to detect tumor revealed no abnormal uptake . comparing current brain magnetic resonance imaging ( mri ) result with the previous ones indicated limbic system atrophy resulting in ventricular enlargement ( fig . 2-a , b ) . diffusion weighted image , fluid - attenuated inversion recovery image ( flair ) and gadolinium enhancement showed no abnormality . electroencephalogram showed diffuse dominant theta waves with no spike . considering his clinical symptoms like emotional lability and amnesia , limbic system atrophy in mri and increased number of csf cells limbic encephalitis was diagnosed . because other causes such as hiv encephalitis , herpes simplex encephalitis , tumor - associated limbic encephalitis or hashimoto encephalopathy were ruled out , limbic encephalitis associated with rp was diagnosed , clinically . a course of intravenous 1 g methylprednisolone for 3 days was administered , followed by oral prednisolone 1 mg / kg per day . his head mri had no change but mmse score was improved gradually , ataxia disappeared through 4 doses of infliximab over a 3-month period , and problematic behavior disappeared . because of his stable condition as well as the high cost of infliximab , he and his wife refused further infliximab therapy . the patient was followed up for an additional 9 months after stopping prednisolone without recurrence ( fig . , he could continue active daily living independently , but could not resume his work . rp , a rare episodic and progressive inflammatory disease presumed to have autoimmune etiology , was first described in 1923 . rp affects cartilage in multiple organs , such as the ear , nose , larynx , trachea , bronchi , and joints . in addition , it can affect proteoglycan - rich tissues such as the eyes , aorta , heart and skin . mcadam criteria modified by damiani and levine , which is commonly used as a criterion to confirm the diagnosis of rp , consists of : a ) at least 3 of 6 clinical criteria ( bilateral auricular chondritis , nonerosive seronegative inflammatory polyarthritis , nasal chondritis , ocular inflammation , respiratory chondritis and audiovestibular damage ) ; b ) 1 or more of the previously - mentioned clinical criteria and biopsy confirmation of cartilage inflammation ; or c ) chondritis at 2 or more separate anatomic locations with response to steroids and/or dapsone . we searched medline in march 2014 using ( " polychondritis , relapsing " [ mesh ] or " relapsing polychondritis " ) and ( " encephalitis " [ mesh ] or " limbic encephalitis " [ mesh ] or encephalitis or encephalopathy or " limbic encephalitis " or " meningoencephalitis " [ mesh ] or meningoencephalitis or " nervous system " ) as keywords . we retrieved a total of 54 articles , 26 of them including 31 cases that met inclusion criteria ( case report or case series written in english or japanese ) ( table 1 ) . as shown in table 1 , 28 out of 31 patients have been treated with a high dose of glucocorticoid . twenty - two out of those 28 patients had symptoms which were well - controlled by initial therapy , but only one could discontinue glucocorticoid therapy . additional therapy ( cyclophosphamide , intravenous immune globulin , tacrolimus , plasmapheresis , methotrexate and cyclosporin ) showed no remarkable effect and 3 patients died . only one who was treated with inflixmab had a good outcome , so we chose infliximab as a second - line agent . this is the first case report of rp with cns manifestations treated with an anti - tnf- agent who did not show deterioration of signs and symptoms after stopping therapy . infliximab may be a good choice for rp with cns manifestation refractory to initial glucocorticoid therapy . infliximab has a large molecular weight , so it is impossible for it to permeate the blood - brain barrier . one potential explanation is that breakdown of the blood - brain barrier by inflammation may permit infliximab to access cerebral parenchyma , resulting in the suppression of tnf- mediated inflammatory processes . although theoretically it may be reasonable to stop infliximab when neurologic symptoms are stable , if breakdown of the blood - brain barrier by inflammation is important for the effect of infliximab , it would be wise to closely observe the clinical course when discontinuing infliximab . anti - tnf- agents may be a treatment of choice for rp with cns manifestations refractory to initial glucocorticoid therapy . in addition , anti - tnf- agents may be discontinued , but it would be prudent to closely observe the clinical course when stopping infliximab . histopathological examination of ear biopsy ( hematoxylin - eosin stain ) showed infiltration of inflammatory cells ( histiocytes , lymphocytes , neutrophils and eosinophils ) in perichondrium and chondrium . ( a ) t2wi one year before admission ; ( b ) t2wi of day 1 showed ventricular enlargement compared to one year before admission ; ( c ) there was no change after 6 months . other patients received no treatment or the results were unknown . * the clinical course after the second pulse is not shown .