[in Japanese]

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Chronic　granulomatous　disease（CGD）is　a　primary　immunodeficiency　characterized　by　an　inability　of phagocytes　to　produce　reactive　oxygen　species， resulting　in　recurrent　life-threatening　infections．　Although　CGD patients　frequently　develop　inflammatory　granuloma　due　to　prolonged　production　of　inflammatory　cytokines，　the treatment　with　corticosteroid　and　immunosuppressive　drugs　are　limited　because　the　anti-inflammation　therapy for granuloma　formation　would　increase　susceptibility　to　infection　in　CGD．　Herein　we　described　two　CGD patients　who　suffered　from　granulomatous　interstitial　pneumonia (GIP) and　received　thalidomide　therapy　for three　months．　Their　serum　level　of　KL-6　was　high　and　CT　lung　images　showed　increased　reticulonodular opacities．　Pathological　findings　for　GIP　patient　reveal　inflammation　and　micro-granuloma　formation　of　interstitial lung　tissue，　which　are　similar　to　those　of　hypersensitivity　pneumonia．　Reticulo-nodular　opacities　on　CT　image were　disappeared　and　the　KL-6 1evels　were　reduced　after　three　months　of　thalidomide　therapy　in　CGD　patients with　GIP．Although　further　works　are　required，our　findings suggest　that　thalidomide　therapy　would　be therapeutic　effect　on　pulmonary　inflammatory　granuloma　in　the　CGD　patients．

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Angiopoictins（Ang）l　and　2　are　important　regulators　of　endothelial　cell　function．　To　assess　the　role　of Ang-l　and　2　dysregulation　in　the　pathogenesis　of　systemic　juvenile　idiopathic　arthritis（s-JIA）associated macrophage　activation　syndrome（MAS），　and　to　investigate　clinical　significance　of serum　Ang　2/l　ratio　in　s-JIA/ MAS，　we　measured　serum　Ang　l/2 1evels　by　enzyme-linked　immunosorbent　assay．　Twenty five　patients　with s-JIA　including　10　patients　with　MAS，　11　patients　with　polyarticular　JIA　and　15　healthy　children　were　analyzed． Results　were　compared　with　clinical　features　of　s-JIA．　Serum　Ang－l　levels　during　MAS　phase　were　significantly decreased　compared　to　those　during　acute　phase　in　s-JIA　patients．　Serum　Ang　2/1　ratio　during　MAS　phase　were significantly　elevated　compared　to　those　during　acute　phase　in　s-JIA　patients．　The　Ang　2／l　ratio　was　rapidly　and extremely　elevated　during　MAS　phase，　Ang　2/l　ratio　was　also　rapidly　decreased　after　treatment．　The　Ang　2/l ratio　correlated　positively　with　LDH　and　FDP-D　dimer．　Serum　Ang　2/l　ratio　levels　to　reflect　endothelial　damage might　be　a　promising　indicator　of disease　activity　for　s-JIA/MAS．

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Low　dose　weekly　methotrexate（MTX）is　one　of　the　most　effective　drugs　in　the　treatment　for　juvenile idiopathic　arthritis（JIA）．The　purpose　of　the　present　study　was　to　investigate　the　current　state　of　MTX　therapy for　JIA　ill　Japan．　A　questionnaire　was　sent　to　15　pediatricians　including　l2 pediatric　rheumatologists　in　Japan．　It was　the　most　common　method　that　starting 　weekly　dose　was　6mg/m2　and dosage was increased to 10mg/m2　by 2mg/m2　every　l - 2 weeks．　Folate　supplement　was　variably　performed．　Abdominal　discomfort　and　nausea　were frequently　observed．　The　assessment　of　efficacy　was　performed　after　three　months　of treatment．　The　criteria　for withdrawal　or　discontinuation　of　MTX　therapy　were　variable．　These　results　revealed　that　there　was　still　a significant　variation　of　MTX　treatment　among　institutes　in　Japan．　Toward　the　establishment　of　all　appropriate MTX　therapy，a　national　wide　population based　study　is　desired．

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This　study　aimed　to　establish　the　characteristics　of bone　markers　among　pediatric　patients　with　rheumatic diseases．　We　examined　correlations　between　bone　markers　and　bone　mineral　density（BMD，　and　evaluated　the effect　of　glucocorticoid（GC）on　their　bone　metabolism．58 %of　the　patients　presented　elevated　bone　resorption marker（TRACP-5b，　and　only　8 % of　them　presented　low　bone　formation　marker (BAP)，which　indicates　their bone　resorption　is　increased　and　formation　is　not　suppressed．　Although　patients　with　GC　therapy　have　Lower BMD，　their　bone　markers　are　not　significantly　different　from　those　without　GC　therapy．　In　addition　to　GC treatment，　inflammatory　cytokines　and　reduced　physical　activity　also　appear　to　contribute　to　the　bone　fragility． Considering　pathophysiology　of　these　patients．　bisphosphonates　are　good　candidates　to　prevent　GC-induced osteoporosis．　In　conclusion，　we　have　shown　two　unique　aspects　of　bone　metabolism　of　our　patients．　One　is　that the　bone　resorption　is　increased　in　more　than　half of　the　cases．　The　other　is　that　the　patients　with　GC　therapy have　lower　BMD，　but　their　bone　markers　are　not　significantly　different　from　those　without　GC　therapy．　We　need to　collect　more　follow-up　data　to　establish　a　basis　to　start　bisphosphonates　and　to　evaluate　the　effect　of them．

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Uveitis　is　one　of the　lost　important　symptoms　other　than　arthritis　in　juvenile　idiopathic　arthritis（JIA）． In　some　cases,　uveitis　is　refractory　to　anti－inflammatory　treatments　and　can　cause　loss　of　vision．　Recently， adalimumab (ADA),　a　monoclonal　antibody　against　tumor　necrosis　factor α，　has　been　gaining　recognition　as an important　therapeutic　modality　for　refractory　uveitis．　We　report　two　patients　with　refractory　JlA　associated uveitis, successfully　treated　with　ADA．　Patient　1；A 2-year-old　Japanese　girl　was　referred　to　us　with　arthritis　of right　ankle．　The　diagnosis of oligo-articular　JlA was　made．　She　had　uveitis．　Her　uveitis　was　refractory　and　oral corticosteroid　was　started　since　she　was　six　years　old．　However,　her　uveitis　subsequently　became　steroid dependent．　ADA　was　initiated，　following　which　her　uveitis　markedly　improved．　Oral　corticosteroid　therapy was　successfully　tapered．　She　is　currently　undergoing　treatment　with　ADA，　and　no　adverse　effects have occurred．　Patient　2；A 5-year-old　Japanese　boy　was　referred　to　us　with　arthritis　of　left　knee．　The　diagnosis　of oligo-articular　JIA　was　lnade．　He　also　had　u、icitis．　Methotrexate（MTX）and　topical　steroid　was　started　and　his arthritis　and　uveitis　were　improved．　At　the　six-year　of　age，　he　suffered　infectious　mononucleosis　and　MTX treatment　was　stopped．His　uveitis　was　relapsed　three　months　later．　The　treatment　with　MTX，　oral　and　topical corticosteroid　was　stated，　but　his　uveitis　subsequently　became　steroid　dependent．　ADA　was　initiated，following which　his　uveitis　markedly　improved.　Oral　corticosteroid　therapy　was　successfully　tapered．　He　is　currently undergoing　treatment　with　ADA．　and　no　adverse　effects　have　occurred，　ADA　is　considered　effective　for　the treatment　of　childhood　refractory　uveitis，including　JIA　associated　uveitis．　Additional　indication　of　ADA for refractory　uveitis　is　desired．

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A20-year-old　woman　with　undifferentiated　arthritis　juvenile　idiopathic　arthritis（JIA）developed　a　red excoriated　plantar　skin　lesion　at　the　age　of　19 years．　She　was　diagnosed　with　JIA　at　the　age　of　l5　years．　Her disease　was　controlled　with　the　treatment　of　methotrexate　and　etanercept（ETA）．　Skin　biopsy　of　plantar　skin lesion　revealed　a　psoriasiform　hyperplasia　in　the　epidermis．　The　diagnosis　of　psoriasiform　skin　lesion　induced by　ETA　was　made．　There　was　no　improvement　with　topical　antibiotics　and　steroids．　Because　of　severe　skin lesions，ETA　was　discontinued　and　tocilizumab　therapy　was　started．　The　skin　lesions　had　resolved　six　months later．　Psoriasifbrm　skin　lesions　induced　by　TNF-α antagonists　are　rare，but　pediatricians　should　remain　aware of the　possibility　of psoriasis　arising　in　JIA　patients　treated　with　TNF-α antagonists．

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We　herein　report　two cases　comprising　three　pregnancies　associated　with　juvenile　idiopathic　arthritis（JIA）、　 The　first　patient　was　a　31-year-old　female　with　rheumatoid　factor（RF）-positive　poly-JIA　and　systemic lupus　erythematosus．　She　wished　to　conceive　at　27　years　of　age　after　undergoing　successfull　treatment　with methotrexate　and　infliximab．　She　became　pregnant　after　the　discontinuation　of　these　drugs；however，the arthritis　flared　up．　At　gestational　week（GA）34、　she　delivered　a　baby　weighing　982g　via　Caesarean　section　due to　severe　intrauterine　growth　restriction.　She　subsequently　conceived　a　second　child　under　conditions　of　a moderate　disease　activity　despite　the　administration　of　etanercept．　At　GA　25，　she　delivered　a　baby　weighing 592g via　emergent　Caesarean　section　due　to　preeclampsia，　The　second　patient　was　an　l6-year-old　female　with RF　positive　poly-JIA．　ADA　was　discontinued　without　any　flare-ups　when　unexpected　pregnancy　was　identified． At　GA　37，she　gave　birth　to　a　child　weighing　2,932g． 　　　Based　on　our　experience，　we　believe　that　patients　with　JIA　who　are　considering　pregnancy　or　who　become pregnant　should　achieve　good　control　of　their　disease　activity　with　an　appropriate　form　of　effective　treatment， Intensive　obstetric　care　is　also　required　throughout　pregnancy．　Furthermore，　Pediatric　rheumatologists　should be　careful　to　check　for　not　only　psychological, but　also　sexual　issues，in　adolescent　JIA　patients．

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　This　case　is　l4 years　old　girl　who　diagnosed　with　polyarticular juvenile　idiopathic　arthritis　at　the　age　of 10 years　old.　Rheumatoid　factor　and　anti-cyclic　citrullinated　peptide　antibody　is　positive．　She　has　a　congenital heart　disease　which　is　a　common　atrium，　atrioventricular　septal　defect，　absence　of　the　inferior　vena　cava，　and polysplenia　syndrome．　She　was　operated　for　two　ventricular　repair　and　mitral　valve　plasty　at　the　age　of　l　year old．　At　first、　we　started　to　use　the　medicine　of　PSL　and　MTX，　however　the　effect　is　limited　for　her．　So　we planned　use　of　biologics (Tocilizumab)．　It　is　unknown　the　side　effect　against　heart　damage　of　using Tocilizumab．　We　assessed　that　her　cardiac　function　was　normal．　Therefore　we　treated　her　with　Tocilizumab． Her　cardiac　function　remains　stable．　It　is　suggested　that　the　use　of　Tocilizuinab　is　safe　for　JIA　with　congenital heart　disease．

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The　patient　ill　this　case　was　a　17-year-old　girl　with　systemic　lupus　erythematosus （SLE)．　Ten　years　after onset, the　SLE　recurred　accompanied　by　nephrotic　syndrome．　Lupus　nephritis　of　International　Society　of Nephrology　class　lV　G（A/C）was　diagnosed　according　to　kidney　biopsy　results．　The　patient　underwent　4 courses　of　steroid　pulse　therapy．　but　her　urinary　protein　levels　gradually　increased．　Her　systemic　symptoms included　marked　edema　and　accumulation　of　pleuroperitoneal　and　pericardial　fluids．　She　was　admitted　to　the hospital　at　age　17 years　6　months．　Plasmapheresis　was　performed　to　eliminate　autoantibodies，which　improved the　nephrotic　symptoms　and　relieved　the　edema　and　accumulated　pleuroperitoneal　and　pericardial　fluids． Thereafter，the　urinary　protein　levels　gradually　decreased．　Cyclophosphamide　pulse　therapy　was　selected　as maintenance　immunosuppression　therapy．　After　8　months，　remission　of the　nephrotic　syndrome　was　achieved、 　　　Lupus　nephritis　is　a　serious　complication　of　SLE，　which　can　be　a　determining　factor　of　patient　quality of　life　and　prognosis．　In　addition　to　steroids，　combined　use　of　mycophenolate　mofetil　and　cyclophosphamide pulse　therapy　is　necessary　for　the　treatment　of　lupus　nephritis　class　IV．　In　severe　cases　of　nephrotic　syndrome， plasmapheresis　is　considered　as　all　effective，　life-saving　treatment　in　the　acute　phase．

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Arthritis　is　one　of　the　major　complications　in mixed　connective　tissue　disease (MCTD)．　It　is　mostly presented　with　non-erosive,　mild-to-moderate　synovitis．　We　describe　a　MCTD　case　of　14-years-old　girl、who had　a　shoulder　pain　during　MTX　therapy　for　refractory　constitutional　symptoms　at　three　years　after　onset． Arthroscopy　revealed　pannus　formation　with　massive　bone　erosive　area，　which　was　a　close　resemble　to synovitis　in　rheumatoid　arthritis．　She　was　diagnosed　as　MTX-resistant　arthritis　with　MCTD　and　was successfully　treated　with　synovectomy　followed　by　tocilizumab，　an　effective　biologics　for　rheumatoid　arthritis． This　case　reminds　us　the　importance　of　practical　interventions　based　on　pathophysiologic　features,　especially when　facing　multisystem　disorders　such　as　collagen　diseases．　Also　suggests　tocilizumab　has　a　therapeutic potential　for　treating　arthritis　with　collagen　diseases．

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　It　is　extremely　rare　that　Behcet's　disease　arises　as　a　complication　of nephrotic　syndrome（NS）．　The　case described　herein　is　that　of　a　l3-year-old　boy．　NS　onset　occurred　at　six　years　old,　progressing　to　frequently relapsing　NS．　However，　mizoribin（MZR）high-dose　therapy　can　achieve　long-term　remission．　He　came　to repeat　erythema　and　stomatitis　from　MZR　high-dose　therapy．　Orthodontic　therapy　had　been　started．　He　was diagnosed　as　having　Behcet's　disease　taking　the　ocular　attack　as　an　opportunity　7　years　after　NS　development． Human　lymphocyte　antigen（HLA）typing　was　positive　for　HLA-B51． 　　　The　causes　of　Behcet’s　disease　and　NS　remain　unclear．　ln　this　case，　therapeutic　agents　including steroids　and　MZR，　as　well　as　HLA　and　oral　mucosal　irritation，　might　have　affected　Behcet's　disease　development． 　This　extremely　interesting　case　is　useful　to　elucidate　the　pathogenic　mechanism　of Behcet's　disease．

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　Parry-Romberg　syndrome　is　a　rare　neurocutaneous　syndrome　characterized　by　slow　progressive hemifacial　atrophic　changes．　This　report　presents　a　rare　case　of　Parry-Romberg　syndrome　associated　with localized　sclerodernia．　A　7-year-old　female　presented　with　white　linear　atrophy　of　the　right　lower　lip　and　a white　spot　on　the　right　submaxilla．　As　the　atrophy　spread　diffusely　to　the　right　cheek　and　submaxilla，　the　right half of　the　patient's　face　became　deformed　for　5　mollths．　In　parallel，　the　white　spot　lesion　multiplied　on　the right　supermaxilla，　the　right　buccal　mucosa．　and　the　right　side　of　the　tongue．　Examination　of　tissue　from　the white　spot　revealed　infiltration　of　inflammatory　cells　and　deposition　of　collagenous　fibers　in　the　dermis， indicating　localized　scleroderma．　Though　PRS　is　a　rare　syndrome，　we　should　think　about　association　with localized　scleroderlna．

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　A 10-year-old　girl　had　a　right　hip　pain　from　2　years　earlier，　and　was　referred　to　us　with　a　3-month history　of　pain　and　functional　impairment　in　the　right　hip．　Physical　examinations　were　unremarkable，　except of　muscle　wasting　of　her　right　thigh.　She　had　severely　restricted　range　of　motion　of　right　hips，　with　a　flexion contracture　of　the　right　hip．　Standard　radiograph　of　the　pelvis　showed　loss　of joint　space　in　the　right　hip．　MRI of　the　hip　revealed　narrowing　of　the　right　hip　joint　space　and　bone　marrow　edema　within　right　femoral　head with　cartilage　loss　and　small　volume　of joint　effusion　with　no　signs　of　synovial　thickening　or　enhancement which　is　characteristic　of juvenile　idiopathic　arthritis（JIA）．　The　diagnosis　of　idiopathic　chondrolysis　of　hip （ICH）was　made．　The　treatment　of　intra-articular　corticosteroid　injection　followed　by　oral　ibuprofen　and physiotherapy　was　started．　Her　symptoms　and　standard　radiograph　findings　improved　6　months　later． 　　　ICH　is　an　unknown　cause　pediatric　musculoskeletal　disorder．　It　presents　with　progressive　articular cartilage　destruction　and　joint　space　narrowing，　resulting　in　secondary　osteoarthritis．　The　cardinal　symptoms of lCH　are　strong　pain　of hip joint　and　disturbance　of excursion．　ICH　occurs　predominantly　in　adolescent　girls， therefere，　it　is　necessary　to　be　differentiated　from　JIA．

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