We report a case of a five-year-old girl suffering from systemic-onset juvenile idiopathic arthritis (S-JIA). Her joint symptoms and hypercytokinemia persisted despite treatment with tocilizumab plus cyclosporine A or tacrolimus. In order to decrease the steroid dose, we introduced thalidomide in her treatment. Some foreign reports have indicated the effectiveness of 23 mg/kg of thalidomide, but in our case, even 5 mg /kg of thalidomide was not sufficiently effective to decrease the steroid dose, though serum IL-18 did decrease slightly. Subtle constipation was noticed during thalidomide treatment, but no other side effects, including peripheral neuropathy, were evident. When the efficacy of tocilizumab for S-JIA is not enough, we must grope for another means of treatment, and it appears that thalidomide, with meticulous attention to side effects, can be an option, although it is not clear why the drug was not significantly effective in our case.

View full abstract

Influenza　infection　is　an　important　exacerbating　factor　in　systemic　juvenile　idiopathic　arthritis（s-JIA）． Influenza　vaccination　is　encouraged　in　s-JIA　patients　to　prevent　primary　influenza　infection．　Previous　report showed　there　is　no　increase　in　disease　activity　after　vaccination　and　patients　with　s-JIA　can undergo　infiuenza vaccination．　We　experienced　the　case　of　a　patient　with（s-JIA）receiving　tocilizumab（TCZ）who　experienced relapses　of　s-JIA　after　receiving　influenza　vaccination．　A 3-year-old　girl　with　steroid　dependent　s-JIA　was treated　with　TCZ　and　long-term remission was achieved．　She　subsequently　received　a　subcutaneous　injection　of commercially　available　inactivated　influenza　vaccine　in　Japan．　Seven　days　later，　she　had　a　relapse　of　arthritis　of her　left　shoulder．　She　responded　to　additional　therapy　with　methylprednisolone　pulse　therapy　and　methotrexate． Four　weeks　after　the　first　vaccination，　she　received　another　subcutaneous　injection　of　inactivated　influenza vaccine．　Seven　days　later，　she　had　a　relapse　of　arthritis　of　her　left　ankle．　The　serum　CRP　level　remained　normal during　both　relapses，　but　the　serum　levels　of　IL-6　and　IL-18were　extremely　elevated．　Systemic　symptoms　of s-JIA　could　be　masked　during　TCZ　therapy．　Carefu1　observation　with　the　monitoring　of　serum　interleukin (IL)-18 and　IL-6　levels　may　be　useful．

View full abstract

　　　Macrophage　activation　syndrome（MAS）has　been　observed　in　patients　with　systemic　lupus　erythematosus（ SLE）．Recognition　of　MAS　in　patients　with　SLE　may　be　particularly　challenging　because　it　may　mimic the　clinical　features　of　the　underlying　disease　or　be　confused　with　an　infectious　complication．　We　present　a　case of　SLE　associated　MAS（SLE-MAS）．　The　patient　showed　the　distinct　cytokine　profile　of　SLE-MAS　compared to　systemic　juvenile　idiopathic　arthritis　associated　MAS．　The　observed　TNF-α dominant　increase　appears to　be　characteristic　of　SLE-MAS．IgM　type　antilymphocyte　antibody（ALAB）was　detected　on　the　surface of　lymphocytes　during　the　acute　phase　and　disappeared　when　the　patient　was　in　remission．　The　patient　had　a heterozygous　P369S-R408Q　mutation　in　the　MEFV　gene．　Our　results　suggest　that　ALAB　and　a　MEFV　mutation might　play　important　roles　in　the　pathogenesis　of　SLE-MAS．　Furthermore，the　cytokine　profile　of　SLE-MAS differs　from　that　of　S-JIA-MAS：the　TNF-α dominant　increase　appears　to　be　characteristic．

View full abstract

The　symptom　and　change　along　with　time　and　new　other　symptoms　occasionally　develop　in　a　clinical course　of mixed　connective　tissue　disease（MCTD）． 　　　We　describe　a　17-year-old　girl　with　8-year　history　of　MCTD　whose　clinical　course　was　unique．　She suffered　from　common　symptoms　such　as　Raynaud’s　phenomenon　and　high　titers　of　anti-Ul-RNP　antibodies， SLE-like　findings（with　low　titers　of　anti-Sm　antibodies），　polymyositis-like　findings　and　JIA-like　findings at　the　first　visit．　A　diagnosis　of　MCTD　was　established．　HLA　typing　was　DR2　positive．　Other　manifestation included　asymptomatic　Sjogren　syndrome，　but　anti－Ro/La　antibodies　were　negative．　Inflammatory　myositis was　markedly　diminished　and　anti-Sm　antibodies　disappeared　following　corticosteroid/methotrexate　treatment． Four　years　later，　hypocomplementemia　persisted　and　anti-Sm　antibodies　reappeared．　Renal　biopsy　showed diffuse　proliferative　glomerulonephritis．　During　corticosteroid/azathioprine　treatment，hypocomplementemia reappeared　and　anti-dsDNA　antibodies　developed．　The　combination　of　anti-Sm　antibodies，　HLA-DR2　and　anti dsDNA 　antibodies　would　be　associated　with　refractory　diffuse　proliferative　glomenllonephritis．　ln　addition，　anti- Ro　antibodies　developed　and　increase　in　level　of　anti-Ro　antibodies　was　associated　with　clinical　exacerbations　of photosensitivity　rash． 　　　Since　change　of　symptom　and　sign　is　the　nature　of　the　disease，thorough　and　frequent　evaluation　of children　with　MCTD　and　HLA　typing　is　important　to　detect　organ　involvement．

View full abstract

Juvenile　dermatomyositis（JDM）is　a　chronic　multisystem　pediatric　inflammatory　myopathy primarily　affecting　the　muscles　and　skin．　Corticosteroids　are　the　first-line　therapy，　however，　long-term　use of　corticosteroids　is　associated　with　many　side　effects．　Recently，　the　B　cell-depleting　anti-CD20　monoclonal antibody　rituximab（RTX）has　been　successfully　used　in　patients　with　refractory　JDM　to　improve　muscle strength　and/or　skin　manifestations．　We　describe　a　case　of　refractory　JDM　successfully　treated　with　RTX，　which led　to　long-term　remission．　RTX　can　be　effective　in　treating　refractory　JDM．　Prospective　randomized　trials　are required　to　evaluate　the　optimal　therapeutic　dose　schedule　of　RTX　and　to　determine　as　a　proper　maintenance immunosuppressive　therapy．

View full abstract

We　experienced　3　cases　of　refractory　juvenile　dermatomyositis　that　intravenous　immune　globulin （IVIG）has　responded．　Case　l　is　5-y-o　boy．　He　was　treated　with　intravenous　methylprednisolone（IVMP）， oral　corticosteroid　and　methotrexate　at　the　onset，and　he　had　maintained　remission．　After　10　months，　he　had　a relapse．　We　underwent　intravenous　cyclophosphamide（IVCYC）in　addition　to　the　change　from　methotrexate to　azathioprine，　but　he　did　not　respond．　Therefore，we　performed　IVIG，　added　methotrexate　and　changed　from azathioprine　to　cyclosporin　A，and　he　was　in　remission．After　that　he　relapsed，we　underwent　IVIG　again　and changed　from　cyclosporin　A　to　tacrolimus．　Case　2　is　11-y-o girl．　Her　symptoms　were　improved　IVMP　and　oral corticosteroid，but　worsened　according　as　decreasing　corticosteroid　after 5　months　from　the　start　of　treatment． Despite　increasing　corticosteroid　and　administrating　methotrexate　she　was　not　improved．Accordingly，we performed　IVIG　and　added　cyclosporin　A，and　she　was　in　remission．　After　4　months，on　account　of　relapse　she was　administered　IVIG　again．　Since　then，she　has　maintained　in　remission（she　has　on　no　medication　after 4 years　and　5　months　after　last　IVIG）．　Case　3　is　15-y-o boy．　He　was　complicated　by　interstitial　pneumonia．　We treated　him　with　IVMP，oral　corticosteroid　and　azathioprine．We　changed　from　azathioprine　to　cyclosporin A，performed　IVCYC（8　times）and　replaced　cyclosporine　A　with　tacrolimus　after　IVCYC，　for　interstitial pneumonia．　His　myositis　relapse　as　decreasing　corticosteroid，and　we　performed　IVIG,　increased　corticosteroid and　added　methotrexate．　Then　he　has　been　in　remission． 　　　　Their　symptoms　of　myositis　were　in　effect　of　IVIG　immediately　and　also　observed　in　the　effects　of cutaneous　symptoms　as　well.

View full abstract

Chronic　nonbacterial　osteitis/osteomyelitis（CNO）is　a　rare　and　possibly　autoinflammatory　disease characterized　by　chronic　and　recurrent　bone　pain　often　associated　with　low　grade　fever　or　general　malaise． We　report　an　eight-year-old　girl　with　CNO　presenting　with　recurrent　spiking　fever　and　bone　pain．　Her　febrile episodes　were　associated　with　elevated　erythrocyte　sedimentation　rate，　serum　C-reactive　protein　and　IL- 181evels　but　not　with　serum　levels　of　IFN-γ，　IL-6，or　TNF-α．　Positron　emission　tomography　demonstrated fluorodeoxyglucose　accumulation　in　epiphyses　of　bilateral　distal　femurs　and　tarsal　bones．　Bone　edema-1ike lesions　with　high　intensity　in　short-tau　inversion　recovery　image　and　low　in　Tl　weighted　image　were　documented in　magnetic　resonance　imaging　of　lower　extremities．　Bacterial　osteomyelitis　and　bone　neoplasm　were　excluded by　bone　biopsy　of　distal　femur．　All　of　these　findings　were　consistent　with　the　diagnosis　of　CNO．　Her　fever　and bone　pain　responded　to　a　short　course　of　corticosteroid　therapy　but　not　to　non-steroidal　anti-inflammatory　drugs． We　suggest　that　CNO　should　be　considered　as　a　diagnosis　of　high　grade　fever　particularly　associated　with　bone pain，and　that　innate　immune　mechanisms　are　involved　in　the　pathogenesis．

View full abstract

We　present　a　patient　diagnosed　with　inflammatory　bowel　disease　type　unclassified（IBDU）who　had multiple　whitish　papules　consistent　with　those　of　malignant　atrophic　papulosis（Degos　disease），which　appeared during　a　flare　of　her　disease．　Twelve-year-old　girl　developed　recurrent　abdominal　pain，　hematochezia，and diagnosed　as　ulcerative　colitis　as　a　result　of　colonoscopy．Mesalazine　treatment　relieved　her　symptoms，whereas upper　gastrointestinal　involvement　developed　after　2　weeks　of　treatment．　After　treatment　with　prednisolone，　she developed　multiple　papules　on　both　upper　and　lower　extremities．　The　lesions　of　malignant　atrophic　papulosis are　said　to　be　pathognomonic；nevertheless，　various　diseases　with　similar　clinical　lesions　have　been　described． In　present　case，　elevated　PR3-ANCA　and　arthritis　assumed　complication　of　vasculitis，　which　is　involved　in　both IBDU　and　Degos　disease．

View full abstract

The　subject　was　a　5-year　old　girl　in　whom　prednisolone　and　methotrexate　administered　fbr　oligo-articular 　juvenile　idiopathic　arthritis　in　the　right　knee-joint．　The　girl　was　referred　to　our　department　at　the　age　of 2 years　and　10 months．　Although　pain　disappeared　after　administering　etanercept，the　joint　mobility　continued　to decrease．　Etanercept　was　replaced　with　tocilizumab，after　which　the　pain　in　the　right　knee-joint　disappeared，　and images　showed　that　the　inflammation　had　disappeared．　Contracture　of　the　right　knee-joint　was　nearly　stabilized by　continuous　physiotherapy．　Further，　because　of　the　improvement　in　the　range　of mobility，invasive　mobilization surgery　and　synovectomy　were　performed．　During　surgery，　fibrous　adhesion　and　fibrillization　of　the　synovial membrane　were　discovered．After　surgery，the　range　of　mobility　in　the　right　knee-joint　improved；subsequent continuous　physiotherapy　enabled　marked　improvement　in　the　restriction　of　mobility，thereby　allowing　the subject　to　walk　normally．In　recent　years，the　popularization　of　immunosuppressants　and　biopharmaceuticals has　reduced　the　number　of　surgical　opportunities　in　cases　of juvenile　idiopathic　arthritis．　For　children　in　their growth　period，however，maintaining　the　mobility，particularly　in　the　joints，is　vital．　Therefbre，　synovectomies and　invasive　mobilization　surgery　should　be　actively　encouraged　in　patients　who　are　unresponsive　to　medical treatment　and　who　have　fibrous　adhesion　or　fibrillization　of　the　synovial　membranes，after　the　inflammation　has been　resolved．

View full abstract