矢部 寛樹

症例は56歳女性で、GPAに合併した鞍鼻変形の治療目的で当科紹介となった。初診時、鼻根部の著明な陥凹を認め、CTで鼻骨の平坦化と鼻中隔の萎縮がみられたため、腸骨移植による隆鼻術を施行した。術後3ヵ月で鞍鼻変形は改善し、患者の満足度も高かったが、術後2年の時点で皮膚・軟部組織の萎縮が進行し、やや不自然な形態を呈しており、長期的に変化を観察する必要があると考えられた。

Adult-onset Still's disease may cause intestinal pseudo-obstruction via a cytokine storm. Early diagnosis and treatment are the key for patient survival before the development of serious complications such as macrophage activation syndrome.

症例は72歳男性。当院リウマチ外来受診1ヵ月前に前医で肺炎球菌ワクチン(23価肺炎球菌多糖体ワクチン:PPSV23)の接種を左上腕外側に受け、翌日に接種部位の腫脹と両股関節痛を生じた。翌々日、近医整形外科を受診し、C反応性蛋白(CRP)値9.0mg/dLの炎症所見を指摘されたが、リウマチ因子(RF)陰性であった。接種5日後に両肩関節と両膝痛を自覚し、次第に寝返りやベッドからの起き上がりが困難となった。接種2週後に左手関節の痛みと腫れを生じ、当院内科を紹介受診した。ワクチンの副反応が疑われロキソプロフェンを処方されたが関節痛は改善せず、当院リウマチ外来を受診した。左手及び両足に浮腫と多数の圧痛関節を認め、RFは弱陽性ながら陽転化しており、ワクチン接種を契機とし新たに関節リウマチ(RA)を発症したと考えた。プレドニゾロン(PSL)内服治療(15mg/日)を開始し、CRP値および病勢は次第に低減した。PSLはメトトレキサート併用のもと漸減中止され、RAの臨床的寛解は維持された。(著者抄録)

70歳女性。7ヵ月前にANCA関連血管炎性中耳炎(OMAAV)を発症し、ステロイド(PSL)による治療を開始した。治療開始後は難聴の著明な改善を認めたが、PSLの漸減により右眼の視野障害、眼痛が出現した。右球後視神経炎の診断でステロイドパルス、PSL治療を受け症状は改善し、POCYを追加されるも視神経炎が再燃したたため当科入院となった。入院後はPSL、IVCYを行い、症状は一時改善したが、入院4ヵ月後に視神経炎とOMAAVが再燃したため、リツキシマブ投与を4コース行ったところ、症状は改善した。現在、メソトレキセートを追加し、再燃なく経過している。

症例は41歳女性。当院初診3年2ヵ月前に乳癌に対しドセタキセル治療を、2年7ヵ月前に乳房温存術および放射線照射を受けた。2年前より右上肢リンパ浮腫を生じ、浮腫は左上肢、頸部に拡大。1年10ヵ月前から両上肢、両手部の皮膚硬化が進行、関節拘縮へ発展し、6ヵ月前からRaynaud現象、開口障害が出現し、当科を受診した。びまん皮膚硬化型全身性強皮症と診断し、入院の上、プレドニゾロン内服(20mg/日)を開始、進行する皮膚症状の改善目的にステロイドパルスを追加し、関節拘縮改善を認めた。本例はドセタキセル治療後の発症であり、上腕、前腕に浮腫、皮膚硬化が強く、一般の強皮症の末梢から体幹に拡がる皮膚硬化パターンと異なるため、ドセタキセル誘発皮膚硬化と考えた。一方、抗RNAポリメラーゼIII抗体陽性であり、皮膚硬化進行後にRaynaud現象を認めた経過から一般的な全身性強皮症の特徴を併せもつようになったと推測した。(著者抄録)

＜文献概要＞44歳,女性。気管支喘息の既往あり。18日前より自覚した右頬部のしびれと,その後出現した同部の腫脹,鼻閉を主訴に受診した。初診時は血管性浮腫,蜂窩織炎を疑った。初診5日後,右頬部はさらに腫脹し紫斑を伴い,末梢血好酸球が増加した。MPO-ANCA,PR3-ANCAは陰性であった。病理組織所見で真皮から皮下の血管周囲の著明な好酸球浸潤と血管壁の破壊があり,好酸球性血管炎の像を呈した。多発性単神経炎,腹痛も認め,好酸球性多発血管炎性肉芽腫症と診断した。ステロイドパルス療法中にヘパリン起因性血小板減少症が誘因と推測される脳出血を併発した。本疾患の皮膚病変は下腿に好発するが,顔面に限局した極めてまれな症例と考えた。

Background: Some patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) also have positivity of rheumatoid factor (RF). However, the clinical significance of this occurrence remains unknown in AAV patients. The aim of this study was to clarify an association between the presence of RF and clinical features in patients with AAV. Results: Forty-seven patients diagnosed with AAV who were not complicated with RA were enrolled in this study. We compared clinical manifestations of AAV between an RF-positive subset (n = 29) and an RF-negative subset (n= 18). The Birmingham Vasculitis Activity Score (BVAS) was higher (P = 0.026) in the RF-positive subset than in the RF-negative subset. The levels of CRP and ESR were higher in the RF-positive patients (P = 0.020 and P = 0.007, respectively) compared to the RF-negative subset. IgM-RF titers were significantly correlated with the BVAS (r = 0.50, P = 0.0004). In addition, the IgM-RF titers had significant correlations with the levels of CRP (r= 0.41, P = 0.004), ESR (r = 0.39, P = 0.016), IgM (r = 0.36, P = 0.016) and IgG (r = 0.37, P = 0.015). The frequency of commencement of dialysis therapy, usage of mechanical ventilation and mortality were higher in the RF-positive subset than in the RF-negative subset. Conclusions: In patients with AAV, RF titers were significantly correlated with disease activity and the levels of inflammatory markers. The presence of RF could be a poor prognostic factor in patients with AAV.

We herein report a rare case of a 66-year-old woman who had synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome with marked sternal osteitis and bilateral pleural effusions. SAPHO syndrome was diagnosed based on the characteristic features of a hyperostotic sternum and thoracic spine. The inflammatory changes of sternal osteitis and involvement of the adjacent soft tissue were assumed to be the cause of the pleural effusions. The effusions decreased during the natural course of the disease and resolved after methotrexate therapy. The pain dramatically decreased with oral tramadol. Physicians should consider the possibility of SAPHO syndrome in patients with anterior chest pain and pleural effusions.

31歳女性。大動脈炎症候群の治療中に、血便を認め当センターに入院した。下部消化管内視鏡検査にて、終末回腸に縦走潰瘍を認め、小腸型クローン病と診断した。寛解導入療法として、栄養療法とメサラジン製剤の内服に加え、生物学的製剤アダリムマブを投与した。寛解を得た後、プレドニゾロン・メトトレキセートの減量を行ったが、両疾患とも再燃・悪化なく経過している。両疾患の合併は稀であり、本邦からの報告例が19例、国外からの報告例を加えると55例に過ぎない。発症の順序に規則性は認めない。今回貴重な症例を経験したので、文献的考察を加え、報告する。(著者抄録)

65歳女。13年前に関節リウマチ(RA)を発症し、メトトレキサート(MTX)、プレドニゾロン(PSL)、タクロリムス(TAC)投与により寛解を維持していた。PSLは入院3ヵ月前には中止していた。入院3週間前にTAC血中濃度が著明に上昇したため、0.5mg/日に減量した。その後、全身倦怠感、発熱、労作時息切れが出現し、歩行困難となり受診した。CTでびまん性にモザイク状のスリガラス影を認めたことから、ニューモシスチス肺炎(PCP)が疑われ緊急入院となった。服薬歴を聴取したところ、他院より感冒様症状に対してクラリスロマイシンが投与されていたことが判明した。病歴と典型的なCT所見より、PCPの診断的治療を開始した。症状は速やかに改善したが、治療開始14日目に皮疹が出現し、ST合剤からペンタミジンに変更した。

症例は32歳女性で、レイノー現象、手指の皮膚硬化を認め、手指のこわばり、皮膚硬化が進行したため受診し、瀰漫性皮膚硬化型強皮症(deSSc)と診断された。抗Scl-70抗体陽性、食道拡張、間質性肺炎を認めた。プレドニゾロン(PSL)、IVCYを投与されタクロリムス(TAC)を併用し、TAC増量、PSL減量とした。さらにTACをシクロホスファミド(CY)内服に変更した。胸部CTで診断時に比べ明らかに間質性肺炎の進行を認めた。TAC、CYにも治療抵抗性で自己末梢血幹細胞移植を選択した。予防的抗菌薬としてフルコナゾール、アシクロビル、レボフロキサシンを投与していたが、幹細胞輸注前に発熱したため、レボフロキサシンをセフェピムに変更した。合併症なく11日後に血球は回復した。

Cancer polyarthritis is a very rare condition. Here, we present a case of cancer polyarthritis, who also had mononeuritis simplex as a manifestation of paraneoplastic neuralgic syndrome. A 71-year-old man, who initially presented symmetrical polyarthritis and unilateral posterior interosseous nerve palsy, was subsequently diagnosed to have gastric cancer. Total gastrectomy was performed, and his polyarthritis and the palsy simultaneously disappeared within 2 weeks after the resection. His gastric cancer was found to be metastasized to his liver 16 months after the total gastrectomy; however, the polyarthritis and the palsy did not recurrent throughout his course. The polyarthritis in this case was diagnosed as a cancer polyarthritis from its features. On the other hand, the isolated posterior interosseous nerve palsy in this case met the diagnostic criteria for paraneoplastic neurological syndrome. This case was also unique in that the manifestations of paraneoplastic syndromes did not recur even after the metastasis of the primary cancer, suggesting that some specific clones in the cancer were responsive to the manifestations of paraneoplastic syndromes. Our case suggested that relapse of the manifestations of paraneoplastic syndromes may not always herald the recurrence of primary or metastatic tumour, and other tumour markers and signs should be periodically followed to search for the recurrence of the tumours.

Spontaneous spinal epidural hematoma (SSEH) is an uncommon but clinically important disease, and delayed diagnosis of this condition can have severe consequences. General physicians should consider the possibility of SSEH when they encounter a patient with a sudden onset of unexplained cervical or back pain or subsequent radicular symptoms during anticoagulant therapy. Immediate magnetic resonance imaging is essential for early diagnosis. In this article, we present a rare case of an 80-year-old man who developed cervical SSEH during warfarin therapy.

Background: Ewing's sarcoma family of tumors (ESFT) is one of the most malignant groups of tumors in young people. Human leukocyte antigen (HLA) class I displays endogenously processed peptides to CD8+ T lymphocytes and has a key role for host immune surveillance. In ESFT, the investigation concerning both HLA class I expression and T-cell infiltration has yet to be reported. Methods: Biopsy specimens from 28 ESFT patients were evaluated by immunohistochemistry with the anti-HLA class I monoclonal antibody (mAb) EMR8-5 and anti-CD8 mAb, respectively. Results: Expression of HLA class I was negative in 10 tumors and down-regulated in 22 tumors. The status of CD8+ T cell infiltration was closely associated with the expression levels of HLA class I. ESFT patients with down-regulated or negative expression of HLA class I showed significantly poorer survival than the rest of the patients. Conclusions: Our results suggested that CD8+T cell-mediated immune response restricted by HLA class I might play an important role in immune surveillance of ESFT, and we revealed for the first time that the status of HLA class I expression affects the survival of the patients with ESFT. J. Surg. Oncol. 2011; 103: 380-385. (C) 2010 Wiley-Liss, Inc.

3カ月前から始まった手指・顔面の多発結節性皮疹と手指関節炎を主訴に来院した76歳女性．皮膚生検にて多核巨細胞の集簇を認めmulticentric reticulohistiocytosisと診断.従来有効な治療がなく急速に関節破壊に至った疾患であるが，浸潤細胞はマクロファージの形質を示し抗TNF療法が有効との報告がある．本例にインフリキシマブ投与が著効し，本症治療の第一選択肢と考えられた．<br>

In two patients with primary bone lymphoma (PBL) treated in our clinic, serum levels of soluble interleukin-2 receptor (sIL-2R) reflected the clinical course. In both cases, sIL-2R levels were high before treatment and normalized with the therapeutic effects of chemotherapy, coinciding with the changes in lactate dehydrogenase levels and radiographic findings. Adding to the recently reported results of the diagnostic ability of sIL-2R in PBL, our case study highlights the clinical significance of serum sIL-2R levels as a tumor marker in PBL cases. © 2011 S. Karger AG, Basel.

A 74-year-old woman diagnosed with Churg-Strauss syndrome (CSS) complained of difficulty in flexing her left thumb and index finger. Electromyography demonstrated isolated anterior interosseous nerve (AIN) palsy, with no other peripheral neuropathy. We diagnosed this case as spontaneous AIN palsy complicated with CSS, the first case of this kind. Surgical treatment should be considered if no sign of recovery is seen within six months of onset.

Since the term synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome was proposed by Chamot et al. (Rev Rhum Mal Osteoartic 54:187-196, 1987), clinical reviews concerning this syndrome have been mainly reported from Europe. We carried out a retrospective analysis of 11 Japanese patients with SAPHO syndrome, and reviewed the clinical features of our series in comparison with those in a European large case study. In this study the major features of SAPHO syndrome were chronic osteitis of the anterior chest wall and pustulotic arthro-ostitis with middle age onset, and mucosal lesions seemed to be a minor complication of SAPHO syndrome. The non-erosive peripheral large joints arthritis and the particular HLA types (HLA-B51, B52, or A26), which had been reported to be increased in Behcet&apos;s disease, were frequently seen in SAPHO syndrome with mucosal lesions. This study also suggests that SAPHO syndrome with mucosal lesions may be part of a broader disease spectrum including Behcet&apos;s disease.

Purpose: We aimed to identify novel prognostic biomarkers for Ewing&apos;s sarcoma by investigating the global protein expression profile of Ewing&apos;s sarcoma patients. Experimental Design: We examined the proteomic profile of eight biopsy samples from Ewing&apos;s sarcoma patients using two-dimensional difference gel electrophoresis. Three patients were alive and continuously disease-free over 3 years after the initial diagnosis (good prognosis group) and five had died of the disease within 2 years of the initial diagnosis (poor prognosis group). Results: The protein expression profiles produced using two-dimensional difference gel electrophoresis consisted of 2,364 protein spots, among which we identified 66 protein spots whose intensity showed &gt;2-fold difference between the two patient groups. Mass spectrometric protein identification showed that the 66 spots corresponded to 53 distinct gene products. Pathway analysis revealed that 31 of 53 proteins, including nucleophosmin, were significantly related to bone tissue neoplasms (P &lt; 0.000001). The prognostic performance of nucleophosmin was evaluated immunohistochemically on an additional 34 Ewing&apos;s sarcoma cases. Univariate and multivariate analyses revealed that nucleophosmin expression significantly correlated with overall survival (P &lt; 0.01). Conclusions: These results establish nucleophosmin as a candidate of independent prognostic marker for Ewing&apos;s sarcoma patients. Measuring nucleophosmin in biopsy samples before treatment may contribute to the effective management of Ewing&apos;s sarcoma.

We describe two patients with SAPHO (synovitis-acne-pustulosis-hyperostosis-ostitis) syndrome who presented some of the classic features of Behcet's disease. The first case is a man diagnosed as SAPHO at 74 years old. His major complaint is pain and swelling of the bilateral sterno-clavicular region for more than 14 years. Another conspicuous complication was bilateral glaucoma and episodes of iritis were recognized during the follow-up period. The second case is a 65-year-old woman, who first consulted us with right knee pain. As she had a past history of palmoplantar pustulosis and anterior chest pain, her sterile knee arthritis was diagnosed as SAPHO. She also had been suffering from recurrent oral aphthous ulceration since 6 months before visiting our hospital. Considering the clinical courses of our two cases and a review of five previously reported cases, these conditions may imply that classic features of Behcet's disease are minor complications of SAPHO syndrome. Human leukocyte antigen typing and frequent association of sacroiliitis in our cases and in the review of the literature for SAPHO syndrome with some of the classic features of Behcet's disease may indicate this condition to be a closely related disease with seronegative spondylo-arthritis.

Ewing's sarcoma family of tumors (ESFT) is comprised of highly malignant bone and soft tissue tumors in children and young adults. Despite intensive treatments for patients with ESFT, disease which presents with metastatic spread or relapses after primary treatment remains incurable in the majority of cases, indicating the importance of efforts to develop new treatment modalities, including immunotherapy. The present study was designed to examine the expression profile of papillomavirus binding factor (PBF), which we previously defined as an osteosarcoma-associated antigen, and its prognostic significance for patients with ESFT. Biopsy specimens from 20 ESFT were stained with an anti-PBF antibody. Survival was estimated using Kaplan-Meier plots and the prognostic significance of several variables, including the expression status of PBF, on disease-free and overall survival was determined by univariate analysis using the log-rank test. Of 20 specimens, 18 (90%) reacted positively to the anti-PBF antibody. Fifteen specimens (75%) were graded as PBF overexpression. Of the I I variables analyzed, stage III disease, inadequate surgical margins and PBF overexpression were significantly associated with decreased disease-free and overall survival. None of the other variables, including age, gender, origin of tumor, tumor site or levels of LDH, ALP, CRP and ESR, showed any significant association. These findings indicate that the overexpression of PBF is a factor indicative of poor prognosis in ESFT. PBF may also serve as a putative target antigen in immunotherapy for patients with ESFT that have a poor prognosis and PBF overexpression.