cryopyrin - associated periodic syndromes ( caps ) have been proposed to describe cryopyrin - related diseases with heterogenous phenotype severity . the mildest condition is the familial cold auto - inflammatory syndrome , patients with muckle  wells syndrome have an intermediate phenotype , the chronic infantile neurological cutaneous and articular syndrome ( cinca ) also known as neonatal onset multisystem inflammatory disease ( nomid ) is the most severe disease in this spectrum [ 1 , 2 ] . the patients are presenting urticaria and life - like skin rash from early in life , variable articular involvement ( arthralgia / arthritis is associated in 30% of cases with hypertrophic arthropathies ) , chronic aseptic meningitis , and neurosensorial involvement associated with biologic markers of neutrophil - driven inflammation . an international collaborative study based on a questionnaire including 31 patients described the optic disc changes as the most common feature ( 83% ) , including optic disc edema , pseudopapilledema , and optic atrophy . anterior segment manifestations varying from mild to severe ( 42% ) ; chronic anterior uveitis ( 55% ) . caps are all caused by dominantly inherited or de novo mutations in cias1 , a gene that encode for nlrp3 ( also known as cryopyrin / nalp3/pypaf1 ) [ 4 , 5 ] . nlrp3 is a component of interleukin-1 ( il-1 ) inflammasome that regulates il-1 production , a strong pro - inflammatory cytokine . mutations of cias1 associated with caps result in a gain - of - function effect . thanks to substantial advances in understanding genetic basis and mechanisms of these disorders , new therapeutics targeting the il-1 pathway could be proposed as recombinant nonglycosylated homolog of human interleukin-1 receptor antagonist ( il-1ra ) , anakinra that competitively inhibits binding of il-1 and il-1 to il-1 receptor . previous studies showed remarkable efficacy of anakinra in patients suffering from cias1-associated diseases . in the presenting case of cinca / nomid successfully treated by anakinra , we report and document normalization of ophthalmologic involvement undertreatment . the patient , an 8-year - old caucasian girl , was referred to the pediatric immuno - hematology and rheumatology department for diagnosis and treatment of cinca / nomid syndrome . she was born preterm at 30.5  weeks of gestational age with normal weight and height for age ( 2,010  g and 41.5  cm ) . she was issued from a twin pregnancy . because the twin child was diagnosed with trisomy 13 , in utero reduction was performed . she presented with daily urticaria - like rash associated with fever since 1  week of age . arthralgia and transient haunch swelling revealed with nonsteroidal anti - inflammatory drugs were reported at the age of 3  years . since the age of two diagnosis of caps was genetically confirmed ( after the parents provided written informed consent according to the recommendations of the declaration of helsinki ) and revealed a previously reported mutation , d303n , in the cias1 gene . biologic inflammatory markers were increased [ c - reactive protein 40  mg / dl ( normal < 5 ) ] , white blood cell count 11,800  cells / mm , and neutrophil count 7,860  cells / mm ) . bone x - ray confirmed the absence of arthropathy . lumbar puncture was performed and cerebrospinal fluid ( csf ) examination revealed pleocytosis ( 25  cells/l with 90% neutrophils ) , increased proteinorachia ( protein level 0.71  mg / l ) , and high open pressure ( 21  h20  cm ) . brain mri ( with flair imaging and contrast injection ) was normal ( absence of abnormalities of small vessels of the basal ganglia and periventricular white matter lesions ) . slit lamp biomicroscopy revealed bilateral anterior , nummular , stromal keratitis , and absence of anterior uveitis ( fig .  1 ) . on fundus examination and photographs of both eyes , we observed a bilateral papilledema without vitritis . anterior segment photograph illustrates anterior stromal infiltrations of the cornea , these were well defined and corneal epithelium is respected ( fluorescein test was negative ) . the anterior chamber was calm ( absence of tyndall and synechiae ) baseline biomicroscopic examination . anterior segment photograph illustrates anterior stromal infiltrations of the cornea , these were well defined and corneal epithelium is respected ( fluorescein test was negative ) . the anterior chamber was calm ( absence of tyndall and synechiae ) the patient did not receive any steroids or immunosuppressive treatment before initiation of anakinra treatment . follow - up period is 30  months ; initial dose of 2  mg / kg / day in subcutaneous injection has been maintained . all symptoms related to the diseases ( rash , headaches , arthralgia , and chronic fatigue ) ceased durably in few days . biologic inflammatory markers [ c - reactive protein ( crp ) , erythrocyte sedimentation rate ( esr ) ] , white blood cells , and neutrophil numerations rapidly decrease 1  month after initiation of the anti - il-1 treatment . inflammation markers rates were normalized and stabilized during the follow - up ( fig .  2 ) . the velocity of growth was restarted and the height and weight increased progressively during the treatment . 2change in level of c - reactive protein ( crp ) with anakinra treatment after 30  months of follow - up . crp was normalized and stabilized during the follow - up change in level of c - reactive protein ( crp ) with anakinra treatment after 30  months of follow - up . crp was normalized and stabilized during the follow - up six  months after the introduction of anakinra , the corneal infiltrates disappeared . on fundus examination and photographs of both eyes , we observed a pale optic disc corresponding to the resolution of the papilledema ( fig . the campimetry was not modified by the treatment and the blind spot enlargement was stable between the different exams . a baseline ophthalmologic examination : color fundus photograph shows bilateral papilledema without vitritis or vasculitis in the right eye ( a1 ) and in the left eye ( a2 ) . funduscopy show bilateral pale optic disc without edema , ( b1 ) right eye and ( b2 ) left eye funduscopy follow - up after anakinra introduction . a baseline ophthalmologic examination : color fundus photograph shows bilateral papilledema without vitritis or vasculitis in the right eye ( a1 ) and in the left eye ( a2 ) . funduscopy show bilateral pale optic disc without edema , ( b1 ) right eye and ( b2 ) left eye the patient , an 8-year - old caucasian girl , was referred to the pediatric immuno - hematology and rheumatology department for diagnosis and treatment of cinca / nomid syndrome . she was born preterm at 30.5  weeks of gestational age with normal weight and height for age ( 2,010  g and 41.5  cm ) . she was issued from a twin pregnancy . because the twin child was diagnosed with trisomy 13 , in utero reduction was performed . she presented with daily urticaria - like rash associated with fever since 1  week of age . arthralgia and transient haunch swelling revealed with nonsteroidal anti - inflammatory drugs were reported at the age of 3  years . since the age of two diagnosis of caps was genetically confirmed ( after the parents provided written informed consent according to the recommendations of the declaration of helsinki ) and revealed a previously reported mutation , d303n , in the cias1 gene . biologic inflammatory markers were increased [ c - reactive protein 40  mg / dl ( normal < 5 ) ] , white blood cell count 11,800  cells / mm , and neutrophil count 7,860  cells / mm ) . bone x - ray confirmed the absence of arthropathy . lumbar puncture was performed and cerebrospinal fluid ( csf ) examination revealed pleocytosis ( 25  cells/l with 90% neutrophils ) , increased proteinorachia ( protein level 0.71  mg / l ) , and high open pressure ( 21  h20  cm ) . brain mri ( with flair imaging and contrast injection ) was normal ( absence of abnormalities of small vessels of the basal ganglia and periventricular white matter lesions ) . slit lamp biomicroscopy revealed bilateral anterior , nummular , stromal keratitis , and absence of anterior uveitis ( fig .  1 ) . on fundus examination and photographs of both eyes anterior segment photograph illustrates anterior stromal infiltrations of the cornea , these were well defined and corneal epithelium is respected ( fluorescein test was negative ) . the anterior chamber was calm ( absence of tyndall and synechiae ) baseline biomicroscopic examination . anterior segment photograph illustrates anterior stromal infiltrations of the cornea , these were well defined and corneal epithelium is respected ( fluorescein test was negative ) . the anterior chamber was calm ( absence of tyndall and synechiae ) the patient did not receive any steroids or immunosuppressive treatment before initiation of anakinra treatment . follow - up period is 30  months ; initial dose of 2  mg / kg / day in subcutaneous injection has been maintained . all symptoms related to the diseases ( rash , headaches , arthralgia , and chronic fatigue ) ceased durably in few days . biologic inflammatory markers [ c - reactive protein ( crp ) , erythrocyte sedimentation rate ( esr ) ] , white blood cells , and neutrophil numerations rapidly decrease 1  month after initiation of the anti - il-1 treatment . inflammation markers rates were normalized and stabilized during the follow - up ( fig .  2 ) . the velocity of growth was restarted and the height and weight increased progressively during the treatment . 2change in level of c - reactive protein ( crp ) with anakinra treatment after 30  months of follow - up . crp was normalized and stabilized during the follow - up change in level of c - reactive protein ( crp ) with anakinra treatment after 30  months of follow - up . crp was normalized and stabilized during the follow - up six  months after the introduction of anakinra , the corneal infiltrates disappeared . on fundus examination and photographs of both eyes , we observed a pale optic disc corresponding to the resolution of the papilledema ( fig . the campimetry was not modified by the treatment and the blind spot enlargement was stable between the different exams . a baseline ophthalmologic examination : color fundus photograph shows bilateral papilledema without vitritis or vasculitis in the right eye ( a1 ) and in the left eye ( a2 ) . funduscopy show bilateral pale optic disc without edema , ( b1 ) right eye and ( b2 ) left eye funduscopy follow - up after anakinra introduction . a baseline ophthalmologic examination : color fundus photograph shows bilateral papilledema without vitritis or vasculitis in the right eye ( a1 ) and in the left eye ( a2 ) . funduscopy show bilateral pale optic disc without edema , ( b1 ) right eye and ( b2 ) left eye here we report a case of cinca / nomid with chronic inflammation and neurosensorial involvement but without hypertrophic arthropathy successfully treated with il-1ra , anakinra . the recombinant form of the naturally occurring il-1ra is called anakinra ( rmethuil-1ra ) , and differs from the native human protein that is not glycosylated and has an additional n - terminal methionine . anakinra competitively inhibits binding of large number of il-1 receptors , as these receptors are expressed on all cells except red blood cells . il-1 is a major inflammatory mediator and induces fever , anorexia , hypotension , leucopenia , and thrombocytopenia . il-1 also stimulates the hypothalamic  pituitary  adrenal axis   and promotes th17 differentiation . ophthalmologic involvement in caps are pleiotropic as episclera , anterior chamber , vitreous , and optic disc can be affected [ 10 , 11 ] . to the best of our knowledge , corneal infiltrates were not previously reported . the explanation proposed regarding reversal nummular infiltrates included   cellular inflammatory infiltration in the stroma or   reversal amyloid deposits . the first hypothesis seems to be more rational because in this case , systemic amyloidosis was not present . anakinra was dramatically efficient to treat systemic inflammation , articular pain and recurrent headaches were also relieved . unfortunately , visual field does not improve because of papilledema duration before anti - il-1ra treatment and alteration of the optic nerve fibers . the auto fluorescence fundus photographs did not show hyper signal resulting in auto fluorescent material accumulation ( not shown ) . unfortunately , visual field does not improve because of papilledema duration and alteration of the optic nerve fibers . we confirmed improvement in fundus examination and regulation of csf white cell counts with il-1 receptor antagonism in the treatment of auto - inflammatory conditions . also , we suggest , early in the course of the disease , the use of il-1 receptor antagonist as a therapeutic option to chronic papilledema in order to prevent irreversible consequence of chronic excessive intracranial pressure and final optic atrophy .
an 8-year - old patient with genetically confirmed chronic infantile neurological cutaneous and articular syndrome was treated with interleukin-1 receptor antagonist , anakinra . 
 she initially presented with recurrent episodes of fever , rash , chronic fatigue , frequent headaches , ocular involvement ( corneal infiltrate and papillary edema ) , and permanent increased biologic inflammatory markers . following treatment with anakinra , 
 all symptoms and inflammation resolved . 
 ophthalmologic signs normalized . 
 this ophthalmologic description ( optic nerve and cornea ) has never been illustrated , even if ocular affections are classic in the cryopyrin - associated periodic syndromes .