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Background The prophylaxis for hepatitis B virus (HBV) reactivation assumes that hepatic injury after reactivation is often rapidly progressive and can evoke fulminant hepatitis. The incidence and prognosis of reactivation in patients with rheumatoid arthritis (RA) may be different from those receiving organ transplantation and cancer chemotherapy. This study aimed to investigate the incidence, risk factors, and clinical course of HBV reactivation and develop a scoring system for risk stratification in RA patients with resolved infection. Methods HBV DNA was measured using real-time polymerase chain reaction, and patient data were collected for 4 years in RA patients with resolved HBV infection who were treated with steroids or synthetic or biologic immunosuppressive drugs. Results Among 1127 patients, HBV DNA was detected in 57 patients (1.65/100 person-years); none of the reactivated patients exhibited worsening of hepatic function. Multivariate logistical analysis revealed that age > 70 years and HB core antibody (HBcAb) positivity alone were independent risk factors for HBV reactivation. HBV DNA ≥ 2.1 log copies/mL was observed in 15 patients (0.43/100 person-years); seven patients were treated with nucleic acid analogs (NAAs), whereas the remaining eight were observed without treatment. Among reactivated cases, 15 cases changed to HBV DNA-negative status spontaneously, whereas 24 cases remained HBV DNA positive 70 years) + 2 × (HBcAb positivity alone) + 1 × (treatment other than methotrexate monotherapy). This revealed that patients with the highest score had an odds ratio of 13.01 for HBV reactivation, compared to those with the lowest score. Conclusions Rapid progression and poor outcomes after HBV reactivation were not frequent in RA patients with resolved infection. Our new risk scoring system might be useful for screening and optimization of prophylactic treatment by distinguishing patients with significantly lower reactivation risk.

BackgroundAlthough the reactivation of hepatitis B virus (HBV) is recognised as a serious complication in patients with rheumatic disease (RD) receiving immunosuppressive drugs (ISDs), the incidence and risk factors for reactivation remain controversial.ObjectivesTo investigate the incidence and risk factors for HBV reactivation in patients with RD.MethodsWe performed a multicentre, observational, prospective study over 2 years in patients with resolved HBV infection. Patients with RD treated with a dose of ≥5 mg/day prednisolone and/or synthetic or biological ISDs with negative HB virus surface antigen and positive anti-HB virus surface antibody (HBsAb) and/or anti-HB virus core antibody (HBcAb) were enrolled. Quantitative HBV DNA results and related data were regularly recorded.ResultsAmong 1042 patients, including 959 with rheumatoid arthritis, HBV DNA was detected in 35 (1.93/100 person-years), with >2.1 log copies/mL observed in 10 patients (0.55/100 person-years). None of the reactivated patients, including seven treated with a nucleic acid analogue, showed overt hepatitis. Low HBsAb titres and advanced age seemed to be risk factors for HBV reactivation; however, reactivation was observed in three patients with positive HBsAb and negative HBcAb test results. The risk of reactivation was lower with methotrexate but higher with prednisolone among the different types of ISDs. The intervals from the start of ISD to reactivation were relatively long (3–182 months; median, 66 months).ConclusionsThe incidence of HBV reactivation with ISD use was 1.93/100 person-years in patients with RD with resolved HBV infection. No overt hepatitis was observed in the reactivated patients.

Background Patients may receive negative results from a specific IgE (sIgE) test such as the ImmunoCAP (CAP) despite a documented history of systemic reaction to a Hymenoptera sting. Thus, further testing may be required using another serological method or venom skin prick tests to confirm allergy diagnosis and correct species. Objective To evaluate the sensitivity and the specificity of CAP and IMMULITE 3gAllergy (IMMULITE) for detecting sIgE to Paper wasp (WA) and Yellow Jacket (YJ) venoms using patient clinical history as the comparator. Methods Sera from 70 participants with a history of systemic reactions (SR) to WA and/or YJ stings were tested using CAP and IMMULITE. Fifty participants from this group had negative results on CAP. To assess specificity, sera from 71 participants who had never experienced either a WA or YJ sting were tested using CAP and IMMULITE. Fifty participants from this group tested positive using CAP. Results In participants with a history of systemic reaction to a Hymenoptera sting, yet who tested negative for WA and/or YJ sIgE according to CAP, the positivity rate according to IMMULITE was 20-42% using 0.10 IUA/mL as the limit of detection (LoD), per the manufacturer's specification. When the LoD for CAP (0.35 IUA/mL) was applied to the IMMULITE results, positivity according to IMMULITE was 14-26%. Overall, sensitivity, specificity, and agreement with SR were greater for IMMULITE than for CAP. For YJ: sensitivity (IMMULITE:CAP), 42.8%:28.5%; specificity, 53.5%:39.4%; agreement, 48.2%:34%. For WA, sensitivity (IMMULITE:CAP), 58.6%:28.5%; specificity, 49.3%:47.8%; agreement, 43.9%:38.3%. Conclusion The IMMULITE performed well for detecting sIgE to Hymenoptera venom

症例は16 歳女性,咳嗽,発熱,左前胸部痛を主訴に来院.胸部CT にて内部不均一な径7 cm の前縦隔腫瘍及び左舌区・下葉の完全無気肺を確認,また,MRI にて前縦隔腫瘍内に脂肪組織と同一の吸収域を認め,成熟型奇形腫穿破による膿胸と診断.膿胸に対し胸腔内繊維素溶解療法,ドレナージ及び抗生剤にて加療,膿胸改善を確認した上で,前縦隔腫瘍摘出術施行,病理にて嚢胞性成熟型奇形腫と診断した.病理組織にて膵類似の腺組織を確認,穿破の原因として,腫瘍内膵酵素の存在が考えられた.成熟型縦隔奇形腫は穿破により重篤な合併症発生の危険性があり,また経過中悪性転化する可能性もあることから,早期の外科治療が重要と考えられた., A 16-year-old female visited our hospital, complaining ofcough, fever, and left precordial pain. Chest computed tomographyshowed a heterogeneous anterior mediastinal tumormeasuring 7 cm in diameter and complete atelectasis inthe lingula and lower lobe of the left lung. Magnetic resonanceimaging also showed an area of intensity identical tothat of adipose tissue in the anterior mediastinal tumor.Thus, empyema due to rupture of a mature teratoma wasdiagnosed. The empyema was treated with intra-pleural fibrinolytictherapy, drainage, and antibiotics. After confirmingresolution of the empyema, we resected the anteriormediastinal tumor and pathologically diagnosed it as cysticmature teratoma. Histopathological examination showedglandular tissue resembling the pancreas, suggesting thatthe rupture had been caused by pancreatic enzymes in thetumor. Mediastinal mature teratoma carries a risk of seriouscomplications developing due to rupture and the possibilityof malignant transformation during the diseasecourse. Thus, early surgical treatment is important.

79 歳男性.発熱,咳嗽で発症し,鼻閉の既往,空洞を伴う両下肺の浸潤影,顕微鏡的血尿,急速進行する腎機能障害およびPR3-ANCA 高値を示し,Wegener 肉芽腫症( WG) と診断された.一時シクロフォスファミド併用を含む,高用量副腎ステロイド療法が開始され,臨床および検査所見は改善した.ステロイド薬は漸減され,3 ヶ月後にはC-ANCA は陰性化した.WG は寛解していたが,8 ヶ月後に胸部下行大動脈瘤形成を認め,その1 ヶ月後に突然大喀血し,死亡した.動脈瘤形成は疾患活動性とは関連なく,経過中注意深い観察の継続を要する., A 79-year-old man was admitted because of fever andcough. He had been diagnosed with Wegener's granulomatosis(WG) on the basis of 10-year history of stuffy nose,pulmonary infiltrates with cavity formation, rapidly progressedrenal dysfunction with microscopic hematuria, andhigh level of PR3-ANCA. He was treated with high dose ofglucocorticoid( GC) temporarily in combination with cyclophosphamide,accordingly, the clinical manifestation and thelaboratory results had been recovering. The dose of GC wastapered down, and 3 months after the initiation of therapy,C-ANCA testing was negative. Despite remission was obtained,8 months after, chest computed tomography (CT)scan showed aneurysm formation on the descending aorta.One month after that, the patient had an abrupt onset ofcoughing up a massive amount of blood, and died. Aneurysmformation may develop independently of disease activityin WG and may be unpredictable, so that a carefulobservation whether aneurysm is formed should be continuouslyconsidered in the follow-up during the entire course.

35歳男性.入院約6週前より喀痰,咳嗽出現.数日前に左上肺空洞影指摘,喀痰中抗酸菌(3+)検出され入院.INH,RFP,PZA 及びEB による標準化学療法が開始された.咳嗽,呼吸困難,両肺野狭窄音聴取及び多量排菌持続し,気管支鏡所見上気管〜両側主気管支に隆起性潰瘍病変を認め,気管支結核を確定.高度の呼吸器症状遷延のため中等量のステロイド点滴投与を開始し,症状ならびに気道粘膜病変は改善した.高率に気管・気管支瘢痕収縮へ移行しうる気道粘膜像であったが,中等量の全身ステロイド療法により回避された.気道瘢痕狭窄回避のため,気管支結核活動性病変には中等量以上の全身ステロイド療法を考慮すべきと考えられた., A 35-year-old man admitted to the hospital because of acavitary lesion in the lung and acid-fast bacilli (AFB) (3+) in a sputum specimen, a polymerase-chain-reaction ofwhich revealed positive for M. tuberculosis. He had beenwell until approximately 6 weeks before admission, whenproductive cough developed. He also had temperature of upto 38 ℃, hoarseness, and shortness of breath couple of daysbefore. Intractable cough, dyspnea, wheeze in both lungfields, and numerous AFB in a sputum sustained, despiteprompt introduction of conventional chemotherapy containingINH, rifampicin, pyrazinamide, and ethambutol. Diagnosisof EBTB was confirmed by fibroptic bronchoscopy,which revealed granulomatous ulceration in the mucosa oftrachea and both main bronchi. Accordingly, intravenousmedium-dose methylprednisolone was administered, resultingrelief from serious respiratory manifestation and avoidanceof cicatricial stenosis of trachea and bronchi. This outcomesuggested that the current early intervention withglucocorticoid should be considered in serious active lesionof tracheal and bronchial mucosa in patients with EBTB.

Although anti-IgE antibody (Ab) therapy was recently shown to be effective in patients with bronchial asthma, no study has reported the effect of IgE therapy in the prevention of wasp venom anaphylaxis. In this study, we used a mouse model of wasp venom allergy to investigate the effect of anti-IgE Ab on wasp venom anaphylaxis.We developed a mouse model of wasp venom allergy by intraperitoneally (i.p.) injecting wasp venom into BALB/c mice twice on experimental day (day) 0 and 7. On day 20, a group of mice received an i.p. injection of mouse anti-IgE Ab as a pretreatment, and another group received rat anti-IgG1 Ab. On day 21, the animals were challenged by i.p. injection of wasp venom, and 30 min later, body temperature was measured and serum levels of leukotriene (LT) B4 and LTC4 were determined using enzyme immunoassay.The body temperature of mice treated with anti-IgE Ab and controls before and after wasp venom challenge was 37.8±0.2 vs 37.7± 0.3°C before challenge and 37.8±0.2 vs 37.1± 0.3°C after challenge, respectively, showing that anti-IgE Ab treatment significantly prevented body temperature from falling (p0.05). Furthermore, anti-IgE Ab treatment reduced total serum IgE levels in the treated mice (42.2±15.9 pg/ml), compared with controls (105.9±23.1 pg/ml, p0.05), and inhibited the secretion of LTC4 in the treated mice (32.0±18.8 pg/ml), but not in the controls (162.4±12.4 pg/ml, p0.05), following challenge with wasp venom.The results of the present study indicate that anti-IgE Ab treatment is an effective preventive measure against wasp venom-induced anaphylaxis.

Background Although the reactivation of hepatitis B virus (HBV) is recognized as a serious complication in patients with connective tissue disease (CTD) receiving immunosuppressive drugs (ISDs), the incidence and risk factors of reactivation remain controversial. Objectives We performed a multicentre, observational, prospective study across 16 Japanese Red Cross hospitals to clarify the prevalence and pathophysiology of HBV reactivation in patients with CTD. We report the results of 2-year observations in patients with resolved HBV infection. Methods Patients with CTD, treated with a dose of ≥5 mg/day prednisolone, and/or synthetic or biological ISDs, with negative HBs antigen and positive anti HBs and/or HBc antibody (Ab), were enrolled. HBV-DNA (RT-PCR) and related data were registered regularly. Results Among 1040 patients, including 950 rheumatoid arthritis, HBV-DNA was detected in 32 patients (1.75/100 person-years), and >2.1 log copy/ml was observed in 9 cases (0.49/100 person-years) over 1–2 years of observation. None of the reactivated patients, including six treated with a nucleic acid analogue, showed overt hepatitis. Low HBs Ab titres and advanced age seemed to be risk factors for HBV reactivation; however, reactivation was observed in 3 patients with positive HBs Ab and negative HBc Ab. The risk of reactivation among the different types of ISDs was not statistically different. The intervals from the start of ISD to reactivation were longer than previous reports (4–157 months, average 58.9 months). Conclusions HBV reactivation with ISD was 1.75/100 person-years in CTD patients with resolved HBV infection. Overt hepatitis was observed in none of the reactivated patients, and low HBs antibody titres and advanced age were risk factors for reactivation. Patients with positive HBs Ab and negative HBc Ab are not free from the risk of reactivation of HBV. References B. J Hepatol 2012: 57. 167–185 Disclosure of Interest None declared