アダリムマブ（ADA）皮下注射製剤（ヒュミラ®皮下注40mgシリンジ）の投与時疼痛軽減を目指し た新製剤が発売された．我々は，ADA投与時疼痛と不安に関する調査を実施し，新・旧製剤間で の疼痛変化や，心理的要素の疼痛への影響を確認することを目的に解析を行った．若年性特発性 関節炎患児で2016年10月時点でADA40mgを使用していた児を対象に，新・旧製剤投与時のそれぞ れで不安の評価尺度と疼痛の自己評価スケールを評価した．また，保護者に対してADA投与時の 負担感についてアンケート調査も行った．対象となった13名中9名から質問票を回収した．ADA投 与直後の疼痛は新製剤で有意に軽減していたが，投与15分後の疼痛や不安尺度は製剤間で差を認 めなかった．保護者の負担感は新製剤で有意に軽減していた．疼痛と不安との関連を解析すると， 旧製剤において，状態不安とADA投与15分後の疼痛強度との間に正の相関がみられた．本調査で は，ADA新製剤への変更でADA投与時疼痛や保護者の負担感が軽減していることが示された．

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Currently, there are no specific diagnostic investigations for systemic juvenile idiopathic arthritis （s-JIA）. Various investigations are considered when making a differential diagnosis. During the 5th Pediatric Rheumatology Workshop held in 2017, we interviewed 17 Japanese pediatric rheumatology experts about the investigations they conduct in the initial diagnostic process for s-JIA. Bone marrow aspiration was preferred by 82％ of experts. Routine use of joint magnetic resonance imaging and measurement of serum IL-18 for an initial diagnostic approach appeared to be controversial. Fluorodeoxyglucose-positron emission tomography or Gallium scintigraphy were not frequently conducted. Although each investigation was known to play a certain role in the diagnosis of s-JIA, they were often not conducted for reasons such as radiation exposure, invasiveness, availability of the investigation in that hospital, and health insurance coverage. In addition, investigations necessary for diagnosis should be selected on an individual basis because patients with s-JIA show diverse initial manifestations. There was consensus among the experts that exclusion of malignancy is important when diagnosing s-JIA； therefore, selected investigations should be performed carefully.

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＜Objective＞ To clarify factors associating with transition readiness in youth/young adults with childhood-onset rheumatic diseases（ coRD） and their parents/caregivers. ＜Methods＞ We enrolled 28 patients with coRD aged 10 years and older and their parents/caregivers. We evaluated transition readiness both in youth/young adults with coRD and in their parents/caregivers by using Transition readiness checklist. Mental disorders and overprotection of parents/caregivers were subjectively evaluated by their attending doctors. ＜Results＞ We did not find any association between achievement score of transition readiness in youth/young adults with coRD and gender, primary diseases, age at the onset of primary disease, duration of primary disease, or age at the enrollment. We found that both achievement score of transition readiness in youth/young adults with coRD and that in parents/caregivers were significantly lower in subjects with overprotection of parents/caregivers. ＜Conclusion＞ Overprotection of parents/caregivers may be an obstructive factor for transition readiness in youth/young adults with childhood-onset rheumatic diseases and their parents/caregivers.

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Introduction : Methotrexate（ MTX） is the only disease modifying anti-rheumatic drugs（ DMARDs） that is approved for juvenile idiopathic arthritis（ JIA） in Japan. Therefor, the patients who had an adverse event for MTX have been taken into consideration of using biological agents. Purpose : We evaluated retrospectively the association between dose of MTX, frequency of adverse events, and introduction of biological agents in articulated JIA. Results : Forty-six patients with JIA were included in this study. The mean age at evaluation was 17 years and mean duration from illness onset was 10 years. Adverse events were observed in 23 patients（ 50%）, and the most common symptom was nausea. The patients who experienced adverse events（ n = 23） received significant higher dose of MTX compared to the patients who did not experienced adverse events（ n = 22）（ 2.6 vs. 7.4 mg/ m2/week ; p =0.0029）, and moreover the patients having MTX tolerance received more biological agents than having MTX intolerance（ 83 vs. 50% ; p =0.0029）. Conclusion: Although MTX is an effective for the patients with JIA, the patients frequently experienced adverse events. There are no other DMARDs we could use instead of MTX in Japan. We expect that other DMARDs will be approved for treatment of JIA, even in consideration of medical economy and appropriate disease management.

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The present case report describes a 14-year-old girl with systemic lupus erythematosus（ SLE）. She presented with butterfly-shaped erythema, oral ulcers, joint pain, proteinuria, pericarditis, leukopenia, elevated anti-dsDNA-, anti-Sm-, and antiphospholipid antibodies, and low complement, and was antinuclear antibody-positive. As she had a cough and bloody sputum on admission, alveolar hemorrhage syndrome was suspected. Therefore, she underwent two courses of steroid pulse therapy, and her symptoms of SLE promptly improved. International Society of Nephrology class Ⅲ （A/C） lupus nephritis was diagnosed according to kidney biopsy results. Due to the possibility of diffuse alveolar hemorrhage, she underwent ovarian tissue cryopreservation to preserve her fertility and cyclophosphamide pulse therapy was initiated four days after. Young women with cancer undergo ovarian tissue cryopreservation when treated with alkylating agent； however, this is the second report of cryopreservation of ovarian tissue for SLE in Japan. SLE affects young women at a high rate； therefore, female patients with SLE should be presented with the option of ovarian tissue cryopreservation before cyclophosphamide pulse therapy.

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【緒言】全身性エリテマトーデス （SLE）はしばしば無月経を伴い，原因は原病によるものと治療 の副作用として出現するものに大別できる．【方法】2014年4月から2016年3月の間に当科にて診断 された小児期発症SLE 6例のうち，原発性無月経を来した5例について診療録を用いて後方視的に 検討した．【結果】平均14.7歳，中央値14.8歳 （14.6〜15.0歳）で，全例で腎生検実施後にステロイド パルス療法2コース後に，プレドニゾロン内服が開始されていた．腎生検でIV型と診断された1例は， 卵巣凍結保存後にシクロホスファミドパルス療法を施行されていた．初発時に続発性無月経を伴っ ていた5例は全例で正常月経が再開していた（治療開始後平均233.8日）．【考察】今回の検討では，5 例ともに初診時に無月経を伴っており，治療開始後に全例で月経が再開していたことから，SLE発 症に伴い消失していた月経が，SLEに対する免疫抑制療法により再開したと考えた．

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症例は12歳発症のループス腎炎（LN）を合併した全身性エリテマトーデス（SLE）の女児．発症1年 後にLNが再発し，シクロホスファミド間歇静注療法（IVCY）とステロイドパルス療法（MPT）を施 行した．1か月後，発熱，頭痛，嘔吐のため前医に入院した．入院10日目に強い腰痛を訴え，時間 単位で両下肢の筋力低下や感覚障害，膀胱直腸障害を認め，転院となった．脊髄造影MRIで第3頸 椎から脊髄円錐までの髄内中央部を中心にT2強調像で高信号の広範な連続性病変や頸髄部の腫大 を認め，髄液細胞数増加よりループス脊髄炎と診断した．頭部MRI所見は異常なく，視神経炎は 認めなかった．MPT，血漿交換，IVCY，免疫グロブリン大量療法などを行ったが，膀胱直腸障 害や臍位以下の知覚・運動覚の完全消失は残存した．本症例はSLE発症1年後のLN再発に対する治 療開始後に横断性脊髄炎の発症を認めた．強力な免疫抑制療法に抵抗性の3椎体を超える長大病変 を生じたため，高度の脊髄神経症状を残したと考えられた．

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小児発症SLEの臓器合併症の1 つである神経精神ループス（NP-SLE）は予後に影響することが知 られている．私たちはEvans症候群の治療経過中に様々な神経症状を合併し，最終的にNP-SLEと 診断した症例を経験した．症例は10歳の女児で，四肢のしびれ，頭痛，貧血の精査を行いEvans症 候群の診断のもと免疫グロブリン，ステロイド（PSL）を投与されたが，痙攣重積，意識障害が出現 し，当院に救急搬送となった．血球減少，凍瘡様皮疹，低補体血症，抗核抗体，自己抗体陽性よ りNP-SLEと判断し平温療法，血漿交換療法（PE）とステロイドパルスを行った．集中治療による 全身管理が奏功し，精神神経所見の回復後からミコフェノール酸モフェチルとPSLによる維持療法 を行った．髄液中のIL-6，抗NR-2抗体，抗リボソームP抗体は陽性であった．NP-SLEの病態はい まだ不明であり，初期治療に統一した見解はない．小児期の神経学的予後に有効な治療のエビデ ンスを蓄積する必要があると考える．

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Patients with childhood-onset systemic lupus erythematosus （SLE） often follow a more acute and severe clinical course compared with those with adult-onset SLE. Herein, we report a case of refractory SLE. An 11-year-old boy was diagnosed with severe lupus nephritis （LN）, classified as IV-S（A） on histology using the International Society of Nephrology/Renal Pathology Society classification. He was treated with methylprednisolone pulse therapy （MPT）, mycophenolate mofetil （MMF）, and intravenous cyclophosphamide for remission. Seven months after treatment initiation, the patient experienced a recurrence of SLE, associated with deteriorated renal function. He was retreated with MPT, MMF, tacrolimus, and hydroxychloroquine. A second renal biopsy was performed； he had progressed to class Ⅳ-G （A/C） on histology with either crescent formation or segmental sclerosis or both in all glomerulus. Therefore, we introduced immuno-adsorption plasmapheresis, as well as repeated rituximab treatment. It took approximately 10 months to achieve normal urinary findings after the recurrence, despite a persistently high level of serum anti-double-stranded DNA antibody. Male sex, childhood onset, and associated LN are adverse prognostic factors of SLE. Thus, remission induction in the early stage of the disease should include treatment with multi-target therapy, immuno-adsorption plasmapheresis and B-cell depletion in male patients with childhood-onset SLE complicated with severe LN.

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Juvenile dermatomyositis（ JDM） is an autoimmune disease presenting with predominantly proximal muscle weakness and characteristic dermatological symptoms. Patients generally have a good prognosis, and the majority of cases are responsive to steroid therapy. However, a fulminant subtype is particularly dangerous, with rapid deterioration of muscle tissue and release of myoglobin into the bloodstream, causing significant myoglobinemia and myoglobinuria, which can trigger acute renal failure. An 8─year─old boy diagnosed with JDM by his previous physician had no symptomatic improvement following intravenous methylprednisolone （IVMP） and methotrexate （MTX）. He was further diagnosed with steroid─resistant JDM, and referred to our hospital for further treatment. The boy was started on intravenous cyclophosphamide upon admission. Subsequent dramatic decline in muscle strength, severe muscle pain, and dysphagia led to a diagnosis of fulminant JDM. Tacrolimus （TAC） and intravenous immunoglobulin （IVIG） were added to his treatment regimen, but his condition still did not improve. Concerned about his risk of renal failure, we decided to perform therapeutic plasma exchange （TPE） to induce remission. Our efforts were successful. Our experience suggests that TPE in combination with immunosuppressants is an effective treatment for acute presentations of treatment─resistant fulminant JDM.

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Juvenile dermatomyositis （JDM） is a rare autoimmune disorder characterized by dermal and muscular symptoms and defined as dermatomyositis that develops under the age of 16. Its prognosis is not always benign especially if the intervention is delayed. Therefore, we should have high index of suspicion for JDM in children having prolonged dermal and muscular symptoms for early diagnosis of JDM. We encountered a 4-year-old girl with JDM who presented with butterfly rash and skin eruptions lasting for more than 3 months. She responded well to the intervention consisting of steroid and methotrexate. In order to clarify the clinical features for the diagnosis of JDM in early infancy, we reviewed the reported cases of JDM which developed younger than 5 years of age including ours. As a result, persistent dermal symptoms were observed dominantly, while signs and symptoms due to myositis were rare in patients with JDM younger than 5 years of age. Therefore, in infants with prolonged dermal signs and symptoms, we should suspect the existence of JDM behind and perform MRI to detect the myositis in infancy.

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【はじめに】腸管Behçet病（BD）は，腹痛，下痢，血便を呈する特殊型BDで，典型的には回盲部中 心の多発深掘れ潰瘍を有する．小児のBDは稀な疾患であり，特に10歳未満のBDでは眼病変が少な く，腸管病変が多い傾向があると報告されている． 【症例】2 歳，女児．発熱と腹痛・血便，口腔内アフタを主訴に入院した．針反応陽性，肛門部潰瘍， 回盲部から上行結腸の多発潰瘍を認め，腸管Behçet病が疑われた．HLA-B51・A26，trisomy 8， TNFAIP3変異は認めなかった．コルヒチン，メチルプレドニゾロンパルス，プレドニゾロン（PSL） 2 mg/kgでも改善せず，メトトレキサート（MTX），インフリキシマブ（IFX）の併用療法を開始し た． 1 か月後の下部消化管内視鏡では腸管病変の改善を確認できたが，解熱は得られずCRP陽性 が持続した．IFXを増量したがPSL減量が困難となり，二次無効と判断しアダリムマブに変更した． 免疫抑制薬も変更を重ね，最終的にミコフェノール酸モフェチルとした．既報と比較しても難治 な症例であり，全エクソーム解析を行ったが、既報の疾患感受性遺伝子に変異は認められなかった． MSH6 に2 か所の変異を認めたが，既報にはなく，現在検討中である． 【考察】6 歳未満の超早期発症炎症性腸疾患（VEO-IBD）では，免疫不全症や自己炎症性疾患が背景 にある可能性が高いことが知られている．特に乳幼児期のBDは好発年齢から外れており，腸管が 侵されやすいなど，その病態が異なる可能性がある．低年齢発症例や難治例ではIBDと同様に遺伝 学的検索についても検討する必要があると考えられた．

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Pyoderma gangrenosum （PG） is a sterile pyoderma that initially forms small pustules and papules predominantly on the lower extremities, and rapidly evolves to ulcers. It is often associated with inflammatory bowel disease, arthritis or vasculitis. A 2-year-old girl presented with a two-week history of fever, tonsillitis, mild abdominal pain and a skin ulcer on her left lower leg. Initially, a small pustule formed on her leg, for which oral antibiotics were not effective. Subsequently, the skin lesion ulcerated. The ulcer improved with cleaning and the application of an ointment （Sulfadiazine silver）, but she showed pathergy and sterile abscesses developed on her finger and lips. Because of the absence of HLA-A26 and B51, major symptoms of Behçet’s disease（ eg. genital ulcer or uveitis）, and vasculitis, we diagnosed Sweet’s syndrome at the first medical examination. After starting prednisolone, all of her symptoms improved. However during the tapering of prednisolone, her symptoms, especially abdominal pain, recurred. Multiple ulcers on her colon were observed during gastrointestinal endoscopy, and we revised the diagnosis to intestinal Behçet’s disease. As the features of skin pathologies of Behçet’s disease, Sweet’s syndrome and PG are similar to each other, attention should be given to the changes in symptoms and diagnosis and treatment should be reviewed. 9：70-75

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We describe the case of linear scleroderma with arthritis of interphalangeal joints of hand as an initial symptom. An 8-year-old girl was referred to us with a 4-month history of swelling and arthralgia of right third metacarpophalangeal （MP） joint and a 3-month history of arthralgia of left second proximal interphalangeal joint. Laboratory examination showed no significant findings. Contrast magnetic resonance imaging （MRI） revealed peritendinitis around the left third MP joint with longitudinal enhancement of flexor tendon, bone marrow edema of the third metacarpal bone and peritendinitis around the right second PIP joint. Linear lesions of scleroderma became gradually clear several months later. The diagnosis of linear scleroderma was made. Cyclosporine was started and abnormal findings at the site of linear lesion on MRI were improved after 1 year treatment with cyclosporine. This patient presented diagnostic difficulties because she had no typical skin lesion of scleroderma. MRI might be useful to diagnose linear scleroderma. Patients with linear scleroderma with arthritis should be treated aggressively with immunosuppressants including cyclosporine to prevent the development of joint contracture leading to permanent dysability.

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