佐藤 健夫

The patient was an 81-year-old man who was found to have bacteremia due to Raoultella planticola, which might have entered the circulation through the bile duct during the passing of a gallbladder stone. In the present case, we screened for malignancies because most cases of R. planticola bacteremia occur after trauma, invasive procedures, or in patients with malignancy (70.6%). Early gastric cancer was detected. Although the association between R. planticola bacteremia and malignancy remains speculative in the present case, it may be useful to scrutinize similar cases involving low-virulence bacteremia for possible malignancies or immune conditions.

Aim: The tuberculin skin test (TST) is used to diagnose tuberculosis; however, the influence of tumor necrosis factor (TNF) inhibitors on the test is unclear. This study investigated whether therapy with TNF inhibitors suppresses the TST reaction due to immunosuppression or whether the TST reaction increases due to reactivation of latent Mycobacterium tuberculosis infection. Method: Ninety-one patients with rheumatoid arthritis receiving TNF inhibitors (40 using infliximab and 51 using etanercept) were studied. The TST was performed before starting TNF inhibitors (T1) and more than 1 year after starting them (T2). Results: At T1, the reaction was negative in 45 patients, weakly positive in 21 patients, moderately positive in 18 patients and strongly positive in seven patients, while the numbers at T2 were 44, 20, 16 and 11, respectively. There were no significant differences of the TST reaction between T1 and T2 in all patients (P = 0.657), patients using infliximab (P = 0.462) or patients using etanercept (P = 1.00). No patients with a strongly positive TST reaction at T1 became negative at T2. However, two patients who were negative at T1 became strongly positive at T2. Although they had no signs of M. tuberculosis infection, isoniazid prophylaxis was given. Conclusion: The TST reaction was not suppressed after more than 1 year of therapy with TNF inhibitors. Patients in whom the TST reaction changes from negative to strongly positive may need appropriate prophylaxis.

Objective: To correlate the serotype specificity to myeloperoxidase (MPO) and proteinase-3 (PR3) with clinical characteristics in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods: Clinical characteristics and outcomes of patients with AAV in our division from 2005 to 2014 were retrospectively compared on the basis of ANCA subtype. Results: We collected the data from 88 patients with MPO-ANCA vasculitis, and 17 with PR3-ANCA vasculitis. Patients with PR3-ANCA vasculitis were younger, and had higher involvement-rates in the eye, nose, and ear. In both MPO- and PR3-ANCA vasculitis, the most frequently involved organ was the respiratory system. Interstitial pneumonia was more frequent in MPO-ANCA vasculitis (52.3% versus 5.9%, p<0.01), whereas nodular shadow was more frequent in PR3-ANCA vasculitis (9.1% versus 58.8%, p<0.01). Multivariable Cox proportional hazard regression analysis showed that the hazard ratio of PR3-ANCA for relapse was 2.48 (95% confidence interval 1.14-5.42, p=0.02). There was no difference in the survival and the progression to end-stage kidney disease and respiratory failure between the two vasculitides. Conclusion: MPO-ANCA vasculitis was a predominant form of AAV in Japan. Classification based on ANCA subtype would be clinically relevant in the prediction of organ involvement and relapse.

Objectives: The objective of this study is to evaluate the pharmacokinetics and pharmacodynamics of methotrexate-polyglutamates (MTX-PGs) in erythrocytes in patients with rheumatoid arthritis and correlate them with the efficacy.Methods: MTX-PG concentrations in erythrocytes were measured in 42 MTX-naive patients repeatedly for 24 weeks by high-performance liquid chromatography. In 56 patients receiving stable MTX doses for at least 12 weeks, the correlation between MTX doses and MTX-PG concentrations was examined. The efficacy was measured by the change of DAS28CRP (DAS28CRP).Results: There were moderate correlations between MTX dose and MTX-PG 3, 4, and 5. At 24 weeks, MTX-PG2, 3, 4, and 1-5 were higher in patients with DAS28CRP >1.2 than in those with 1.2. The cutoff value of MTX-PG1-5 to discriminate DAS28CRP >1.2 from 1.2 at 24 weeks was 68.7nM. Among 20 patients with MTX-PG1-5>50.6nM at 8 weeks, seven already improved at 8 weeks and additional 11 improved at 24 weeks (p<0.001). On the contrary, among the nine patients with MTX-PG1-550.6nM at 8 weeks, none improved at 8 weeks and only one improved at 24 weeks (p=0.500).Conclusions: Erythrocyte MTX-PGs might be a potential indicator and predictor of MTX efficacy.

症例は60歳，女性．半年以上診断が確定しなかった発熱の経過中に失行，構音障害，幻覚などの多彩な中枢神経症状が加わり，増悪した．血管内リンパ腫を疑い，骨髄生検と肝生検をはじめとする検査を施行したが診断は確定しなかった．皮疹は認められなかったが，ランダム皮膚生検によって血管内リンパ腫が確定し，化学療法が奏功した．<br>

Objective. To elucidate the factors associated with poor prognosis of LEF-induced lung injury in patients with RA. Methods. The background and clinical and laboratory features of LEF-induced lung injury were examined and compared between patients who died of and who recovered from it. Results. Among 22 patients who developed LEF-induced lung injury, 9 died of and 13 recovered from it. The patients who died tended to have pre-existing interstitial pneumonia (8/9 vs 6/13, P=0.07). The loading and maintenance doses, serum concentration of the LEF metabolite A771726 and administration period did not differ between the groups. Patients who died had more frequently hypoxaemia of &lt; 60 Torr and mechanical ventilation, and had a high serum CRP level (19.3 +/- 9.4 vs 10.1 +/- 8.1 mg/dl, P=0.03) and a low albumin level (2.7 +/- 0.6 vs 3.3 +/- 0.5 g/dl, P=0.03) at the lung injury onset. The peripheral blood lymphocyte count decreased in both groups at the lung injury onset, and it remained low until fatal outcome, in contrast to a re-increase upon recovery (406 +/- 394 vs 1203 +/- 399/mu l, P=0.006). The main histopathological finding in two autopsied patients was diffuse alveolar damage, in contrast to the alveolitis observed in a biopsied patient who recovered. Conclusions. Pre-existing interstitial pneumonia, extremely high serum CRP and low albumin levels, severe hypoxaemia and mechanical ventilation indicated poor prognosis. Peripheral blood lymphocytopenia developed in association with lung injury, and a sustained low lymphocyte count indicated a fatal outcome.

Objectives. The possible link between LEF and interstitial lung disease (ILD) has evoked increasing concern. The aim of the present study was to elucidate the prevalence and risk factors for newly developed and/or exacerbated ILD, based on post-marketing surveillance data, in which all RA patients receiving LEF were pre-registered and monitored for 24 weeks in Japan. Methods. We analysed data from a cohort of 5054 RA patients who were prescribed LEF since its launch in September 2003 in Japan. Multivariable logistic analysis was performed to identify the risk factors for newly developed and/or exacerbation of ILD. Results. Sixty-one (1.2%) of 5054 RA patients who received LEF were reported to have development and/or exacerbation of ILD as an adverse drug reaction to LEF, judged by the attending physicians. Multivariable logistic regression analysis identified pre-existing ILD [odds ratio (OR) 8.17; 95% CI 4.63, 14.4], cigarette smoking (3.12; 95% CI 1.73, 5.60), a low body weight (&lt;40 kg vs &gt;50 kg) (2.91; 95% CI 1.15, 7.37) and the use of a loading dose (3.97; 95% CI 1.22, 12.9) as independent risk factors for LEF-induced ILD. Conclusions. Pre-existing ILD was the most important risk factor for LEF-induced ILD. We suggest that LEF should not be prescribed for RA patients complicated with ILD.

We described clinicopathological features of eight patients (six females and two males) with isolated polyarteritis nodosa (PN). The age range of the patients was from 22 to 85 years. Six patients presented with fever, skin involvement and/or peripheral neuropathy related to the vasculitis. One patient presented with appendicitis, and the other patient presented with ovarian cyst. Biopsy specimens were obtained from 5 patients with skin and/or peripheral nerve involvement, and surgically resected specimens were obtained from one patient with appendicitis and from one patient with ovarian cyst. Fibrinoid necrosis of small to medium sized arteries was observed in all specimens. After resection, a patient with necrotizing vasculitis of the vermis and a patient with necrotizing vasculitis of the genital tract have not developed systemic vasculitis during the follow-up years. Four patients with peripheral nerve involvement responded well to high dose prednisolone therapy, however, two patients with PN confined to the skin (cutaneous PN) had frequent relapses, indicating that cutaneous PN has not necessarily a benign course.

Among the 5,043 consecutive patients registered in the postmarketing surveillance for leflunomide, 61 were reported to have lung injury and 24 died from it. The adjusted multivariate logistic regression analysis of the risk factors showed that preexisting interstitial lung disease posed the greatest risk, as well as loading dose, smoking history, and low body weight of 40 kg or less with odds ratios of 8.17, 3.97, 3.12, and 2.91, respectively. In 12 patients, lung injury developed even 2 months after leflunomide withdrawal. When patients with (n = 9) and without (n = 13) fatal outcome were compared, eight out of the former, and six out of the latter had preexisting interstitial lung disease; the former showed severe hypoxemia, high serum C-reactive protein level, hypoalbuminemia, and continuous lymphocytopenia, and required mechanical ventilation. On the basis of these results and literature review, the committee proposes that leflunomide should only be recommended as a second-line drug, should not be administered to patients with preexisting interstitial lung disease, should also not be administered to patients with smoking history or those with low body weight, and should be administered without loading dose. Careful monitoring is necessary, and when lung injury develops, leflunomide elimination using colestyramine is mandatory.

A 70-year-old woman with a 6-year history of seropositive rheumatoid arthritis (RA) and asymptomatic interstitial lung disease (ILD) began taking etanercept for ongoing arthritis despite treatment with methotrexate (MTX) and bucillamine. MTX was discontinued before introduction of etanercept. She developed lung injury 8 weeks after starting etanercept. Etanercept was discontinued and oral prednisolone 40 mg/day was begun, and her clinical findings gradually improved. Lung injury, although rare, is a recently noticed, potentially fatal adverse effect of all 3 licensed biological anti-tumor necrosis factor (TNF) agents. We recommend caution in the use of anti-TNF agents in elderly RA patients with preexisting ILD.

A 38-year-old woman with pancytopenia and liver dysfunction was diagnosed with active systemic lupus erythematosus (SLE). On days 9 and 10 of admission, peripheral blood smears showed macrophages phagocytosing platelets, and reactive hemophagocytic syndrome (HPS) was diagnosed. Hemophagocytic syndrome was successfully treated with high-dose prednisolone therapy and one course of methylprednisolone pulse therapy. Detection of hemophagocytosing macrophages in peripheral blood smears would be a useful and noninvasive method of diagnosing SLE-associated HPS. © Japan College of Rheumatology 2006.

A 27-year-old man who had a history of bronchial asthma, eosinophilic enteritis, and eosinophilic pneumonia presented with fever, skin eruptions, cervical lymphadenopathy, hepatosplenomegaly, atypical lymphocytosis, and eosinophilia two weeks after receiving trimethoprim (TMP)-sulfamethoxazole (SMX) treatment. After the withdrawal of TMP-SMX and the administration of high-dose steroid, these systemic symptoms gradually resolved. During the disease course, the patient showed a transient increase in anti-human herpesvirus (HHV)-6 antibody titers and HHV-6 DNA in the peripheral blood, indicating the reactivation of a latent HHV-6 infection. This is the first case of TMP-SMX-induced hypersensitivity syndrome associated with the reactivation of a latent viral infection.

A 45-year-old woman had bleary eyes and recurrent episodes of fever and arthritis in the knees and ankles. The patient had anterior uveitis, negative findings of the tuberculin test, and an increased serum lysozyme level, but bilateral hilar lymphadenopathy (BHL) was absent. During the course of her disease, the serum calcium and angiotensin- converting enzyme levels gradually increased to above the normal level, and the patient was clinically diagnosed as having sarcoidosis. The clinical features of arthritis were typical of those of Lofgren's syndrome although BHL and erythema nodosum were absent. The patient was successfully treated with 15 mg/day of prednisolone.

A 75-year-old woman was admitted to our hospital because of abnormal lung shadow and necrosis of the left feet She had a history of Raynaud's phenomenon from her twenties. On admission, she was diagnosed as having diffuse systemic sclerosis (SSc) and Sjögren's syndrome (SjS) because of scleroderma, interstitial pneumonia (IP), positive result of anti-Scl-70 and SS-A antibody, sicca, decreased tear excretion, and dysfunction of salivary glands. Seventy days after amputation of her left leg, she presented with edema, hypoxemia, chest discomfort, and fever. Blood test revealed inflammation and cardiac echography revealed pericardial effusion with a collapse sign of right atrium, thereby leading to the diagnosis of cardiac tamponade. After starting the daily dose of 20 mg of prednisolone, the pericardial effusion and cardiac tamponade sign disappeared. Pericarditis is seen in half of patients with SSc and rarely with SjS, and is usually asymptomatic. Pericarditis due to SSc has been reported unresponsive to steroid therapy, but several cases of steroid responsive pericarditis due to SSc or SjS have been reported. Clinically, they shared inflammatory responses and the presence of IP in the cases of SSc, which will be important when considering the pathogenesis and treatment of pericarditis due to SSc or SjS.

症例は気管支喘息とアレルギー性鼻炎の既往がある92歳男性.経過中にメチシリン耐性ブドウ球菌・多剤耐性腸球菌による敗血症を繰り返したため抗生剤を投与した.抗生剤投与中に皮疹・肝障害・末梢血液中好酸球数増加が出現し, その経過に一致して心不全による呼吸困難感および胸水貯留, 心電図異常, び漫性心筋収縮能低下が出現した.抗生剤中止とステロイド剤投与により, 皮疹・肝障害・末梢血液中好酸球増多は改善, それに伴い心不全も軽快した.治療経過より好酸球増多は塩酸バンコマイシンもしくはテイコプラニンによる薬剤性を疑った.薬剤性好酸球増多症による心筋障害は稀であるが, 生命予後を左右する重大な合併症の一つである.本例は抗生剤投与中止とステロイド剤投与により治療し得た.

The characteristics of Pneumocystis carinii pneumonia (PCP) in patients with connective tissue diseases (CTDs) were examined retrospectively. Nine patients were enrolled in this study. Their mean age was 57.1 years. All the patients received a high-dose steroid or immunosuppressant. The onset (mean 6.6 days) of fever, cough, breathlessness, and geographical ground-glass opacities revealed by chest computed tomography was acute. The serum β-D-glucan level increased with a simultaneous increase in the Krebs von den Lungen (KL)-6 or surfactant protein D level. The serum immunoglobulin G (IgG) and albumin levels and the peripheral blood lymphocyte count at the onset of PCP were low, but only the serum IgG level decreased significantly. The patients were treated with trimethoprim-sulfamethoxazole or pentamidine isetionate. Six patients died eventually: two patients of progressive respiratory failure, two probably due to a recurrence of the PCP, and two with microbial respiratory infections other than PCP. Five of the six patients required mechanical ventilation. Three patients received secondary prophylaxis and survived. In conclusion, the acute onset was characteristic of PCP in patients with CTDs. High-dose steroids, immunosuppressants, and hypogammaglobulinemia are risk factors and respiratory failure requiring mechanical ventilation, severe secondary infections, and a lack of secondary prophylaxis are poor prognostic factors. Secondary prophylaxis is recommended for all of these patients. © Japan College of Rheumatology and Springer-Verlag Tokyo 2005.

Recently, a cardiac disorder characterized by ballooning and hypokinesis at the apex has been described as takotsubo (ampulla-shaped) cardiomyopathy. We encountered a patient with a rare case of takotsubo cardiomyopathy associated with microscopic polyangiitis. A 70-year-old woman suddenly presented with ventricular dysfunction during the active phase of microscopic polyangiitis. The findings on echocardiograms and electrocardiograms were consistent with those of takotsubo cardiomyopathy. The ventricular dysfunction completely resolved after treatment with 40 mg/day of prednisolone and methylprednisolone pulse therapy. This unique type of cardiomyopathy can be a complication of microscopic polyangiitis.

A 70-year-old woman presented with fever and pain in the right lower extremity. Fat-suppressed gadolinium-enhanced T1-weighted magnetic resonance imaging (MRI) showed contrast-enhanced fascia, fluid accumulation, and hypointense signals in the muscles. Surgical interventions including incisions and insertion of drainage tubes were performed on the basis of the MRI findings. The histopathological examinations of surgically obtained biopsy specimens demonstrated suppurative fasciitis, widespread myonecrosis, and thromboses of the vessels, all of which were compatible with a diagnosis of necrotizing fasciitis. The bacterial cultures were positive for a coagulase-negative staphylococcus. Following the surgical interventions, the patient was successfully treated by aggressive antimicrobial therapy. MRI can thus be useful for differentiating necrotizing fasciitis from nonnecrotizing soft tissue infection and for planning the treatment of necrotizing fasciitis. © Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases 2005.

We report the case of a patient who presented with acquired hemophilia associated with rheumatoid arthritis. The patient's factor VIII activity was less than 1% and factor VIII inhibitor was detected. Based on the blood analysis, the patient was diagnosed as having the factor VIII inhibitor. She was successfully treated with prednisolone, cyclophosphamide, and gammaglobulin to suppress the factor VIII inhibitor, and the administration of recombinant activated factor VII was effective in controlling severe bleeding episodes. © Japan College of Rheumatology and Springer-Verlag Tokyo 2004.

皮膚筋炎に特徴的な皮疹を呈するが筋症状を欠くamyopathic dermatomyositis(ADM)の56歳女性例を報告した.経過中,肺実質病変と縦隔気腫を伴った.肺病変と皮膚病変はステロイド・シクロスポリン併用に反応性が乏しく,サイクロホスファミドパルスを加えることで改善が得られた.これ迄に経験したADMの3例は,いずれも肺実質病変,縦隔気腫,皮膚血管病変を合併していた.又,3例とも皮膚粘膜に潰瘍病変や網状皮斑等の所見があることから,縦隔気腫の成因として,気道粘膜の血管病変により組織の壊死が生じ,そこから空気が漏れ出るという機序が想定された