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結核 第 89 巻 第 11 号 2014 年 11 月 802

Abstract [Background] Drugs for tuberculosis and non-tuberculosis mycobacterial diseases are limited. In particular, no new drugs for non-tuberculosis mycobacterial disease have been developed in recent years. Antimycobacterial drugs have many adverse reactions, for which drug desensitization therapy has been used.

 [Purpose] Rapid drug desensitization (RDD) therapy, including antituberculosis drugs and clarithromycin, has been implemented in many regions in Europe and the United States. We investigated the validity of RDD therapy in Japan.  [Patients and Method] We report our experience with RDD therapy in 13 patients who developed severe drug allergy to antimycobacterial treatment. The desensitization protocol reported by Holland and Cernandas was adapted.

 [Result] The underlying diseases were 7 cases of pulmonary

Mycobacterium avium complex disease and 6 cases of pul-monary tuberculosis. Isoniazid was readministered in 2 (100 %) of 2 patients; rifampicin, in 8 (67.7%) of 12 patients; ethambutol, in 4 (67.7%) of 6 patients; and clarithromycin, in 2 (100%) of 2 patients.

 [Conclusion] In Japan, the desensitization therapy recom-mended by the Treatment Committee of the Japanese Society for Tuberculosis have been implemented generally. We think RDD therapy is effective and safe as the other desensitization therapy. We will continue to investigate the efficiency of RDD therapy in patients who had discontinued antimycobacterial treatment because of the drug allergic reaction.

Key words: Mycobacterial disease, Antimycobacterial drug, Tuberculosis, Non-tuberculosis mycobacterial disease, Desen-sitization, Rapid drug desensitization therapy

1Respiratory Medicine Division, Respiratory Disease Center,

Fukujuji Hospital, Japan Anti-Tuberculosis Association (JATA)

2Department of Pharmacy, Fukujuji Hospital, JATA

Correspondence to: Yuka Sasaki, Respiratory Medicine Divi-sion, Respiratory Disease Center, Fukujuji Hospital, JATA, 3_ 1_ 24, Matsuyama, Kiyose-shi, Tokyo 204_ 8522 Japan. (E-mail: sasakiy@fukujuji.org)

−−−−−−−−Original Article−−−−−−−−

EXPERIENCE OF RAPID DRUG DESENSITIZATION THERAPY

IN THE TREATMENT OF MYCOBACTERIAL DISEASE

1Yuka SASAKI, 1Atsuyuki KURASHIMA, 1Kozo MORIMOTO, 1Masao OKUMURA, 1Masato WATANABE, 1Takashi YOSHIYAMA, 1Hideo OGATA, 1Hajime GOTOH,

1Shoji KUDOH, and 2Hiroaki SUZUKI

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結核 第 89 巻 第 11 号 2014 年 11 月 806

Abstract [Purpose] Several reports show smoking as a risk factor of tuberculosis (TB) infection, especially in prisoners, emigrants, the homeless, or people in areas where TB is en-demic. These reports mostly used the tuberculin test to detect TB. However, there is no report evaluating smoking as a risk factor of TB infection among people coming into contact with TB with the use of the Interferon-Gamma Release Assays (IGRA) test.

 [Material & Method] We compared TB infection in smokers and non-smokers who came into contact with TB infection by using the IGRA test. We retrospectively collected information about people coming into contact with TB who visited the Daiichi Dispensary from July 1, 2011 to June 30, 2012. They were divided into 2 groups (IGRA positive or negative) and smoking (present/ past or never).

 [Result] Out of 390 subjects who came into contact with TB examined, 229 were male and 161 were female. The mean age was 39.0 years, 98 were present smokers, 69 were past smokers, and 223 were never-smokers. There were 19 IGRA-positive and 371 IGRA-negative subjects. The IGRA positive rate was 4.9%. Out of 19 IGRA-positive subjects, 13 were smokers or ever-smoker (68.4%). Out of 371 IGRA-negative subjects, 154 cases were smoker or ever-smoker (41.5%). Smoking experience (present and past) was statistically significant in the

IGRA-positive group. There were no significant differences in sex, age, drinking habits, and level of contact. Multivariate analysis showed smoking was only one independent risk factor for being IGRA-positive (odds ratio 3.06, 95% confidence interval: 1.14_8.21, p=0.027).

 [Discussion] Our results suggest that smoking experience in subjects coming into contact with TB is a risk factor for TB infection. TB cases in smokers are reported to be more severe and have delayed detection of disease. They are also more likely to infect those who come in contact with them. If TB source cases and their contacts are both smokers and co-exist in a narrow and limited area, the contacts might be at higher risk of exposure to TB-contaminated air than non-smokers.

Key words: Tuberculosis, Infection, Smoking, Risk Daiichi Dispensary, Japan Anti-Tuberculosis Association Correspondence to: Hitoshi Tagawa, Daiichi Dispensary, Japan Anti-Tuberculosis Association, 1_ 3_ 12, Misaki-cho, Chiyoda-ku, Tokyo 101_ 0061 Japan.

(E-mail: h-tagawa@jatahq.org) −−−−−−−−Short Report−−−−−−−−

ASSOCIATION BETWEEN SMOKING AND TUBERCULOSIS INFECTION

Hitoshi TAGAWA, Hironobu SUGITA, Tomoaki NAKAZONO, Kiyoko TAKAYANAGI,

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結核 第 89 巻 第 11 号 2014 年 11 月 812

Abstract A 48-year-old woman, who had been suffering from systemic lupus erythematosus for one year and receiving steroid therapy, was admitted to our hospital because of pulmonary tuberculosis. The tuberculosis was treated with INH, RFP, EB, and PZA after having doubled the dose of steroid, but terminated three weeks later due to the appearance of erythema exsudativum multiforme. Treatment was resumed with PZA, SM, and LVFX after resolution of the eruption. However, the addition of INH to the regimen provoked a recurrence of the eruption, which progressed rapidly to toxic epidermal necrolysis (TEN). Steroid pulse therapy stopped progression of the TEN, and treatment for tuberculosis was resumed. Although the choice of drug was rendered difficult by other adverse reactions, the patient was able to complete her tuberculosis treatment with RFP, EB, and TH. INH was

most likely to be the offending agent in this case. Eruptions induced by antitubercular drugs are often seen, but there are few reports of severe toxic epidermal necrolysis.

Key words: Drug rash, Toxic epidermal necrolysis, Systemic lupus erythematosus, Isonicotinic acid hydrazide, Tuberculosis

1Department of Respiratory Medicine, 2Department of

Derma-tology, Tokyo Metropolitan Tama Medical Center, 3Department

of Respirology, Graduate School of Medicine, Chiba University Correspondence to : Yu Sato, Department of Respiratory Medicine, Tokyo Metropolitan Tama Medical Center, 2_ 8_ 29, Musashidai, Fuchu-shi, Tokyo 183_ 8524 Japan. (E-mail: garnet01@oboe.ocn.ne.jp)

−−−−−−−−Case Report−−−−−−−−

A CASE OF ANTITUBERCULAR DRUG-INDUCED TOXIC EPIDERMAL NECROSIS

IN A SYSTEMIC LUPUS ERYTHEMATOSUS PATIENT DURING TREATMENT

FOR PULMONARY TUBERCULOSIS

1Yu SATO, 1Kengo MURATA, 1, 3Akane SASAKI, 1Akihiko WADA, 2Yukihiko KATO, and 1Mikio TAKAMORI

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Uses of New Anti-TB Drug / T. Mori et al. 815 査の所見などについて第三者機関と連絡を取り,当該新 薬の使用について重大な知見は直ちに現場に還元される よう計らうことが必要である。  第三者機関は,上記とは別に指定施設と連絡を取り合 って,当該新薬を用いた患者の治療成績や安全性に関し て随時分析 ・ 検討を行い,その結果を指定施設に還元す る。  日本でまだ抗結核薬として承認されていないいくつか の薬剤の早期承認を引き続き薬事当局に要請していく。  著者の COI(confl icts of interest)開示:本論文発表内 容に関して特になし。

文   献

1 ) Frieden T, ed.: Toman s Tuberculosis. Case detection, Treat-ment, and Monitoring. Questions and Answers. 2nd ed., WHO, Geneva, 2000, 122.

2 ) Iseman MD: A Clinician s Guide to Tuberculosis. Lippincott Williams & Wilkins, Philadelphia, 2000, 271.

3 ) Cochrane AL: Effectiveness and Efficiency. Random reflec-tions on health services. Nuffield Provincial Hospitals Trust, London, 1971.

4 ) Tuberculosis Coalition for Technical Assistance: Inter-national Standards for Tuberculosis Care (ISTC). Tubercu-losis Coalition for Technical Assistance, The Hague, 2006. 5 ) WHO: Global tuberculosis report 2012, WHO/HTM/TB/

2012. 6. 6 ) 森 亨, 御手洗聡, 吉山 崇:文献・資料からみた近 年の日本における多剤耐性結核. 結核. 2012 ; 87 : 565 575. 7 ) 日本結核病学会治療委員会:「結核医療の基準」の見 直し―2008年. 結核. 2008 ; 83 : 529 535. 8 ) 日本結核病学会抗酸菌検査法検討委員会:抗酸菌検査 施設を対象とした薬剤感受性検査. 外部精度評価第 8 回(2010年度)結果. 結核. 2012 ; 87 : 87 91.

9 ) Horsburgh CR, Haxaire-Theeuwes M, Lienhardt C, et al.: Compassionate use of and expanded access to new drugs for drug-resistant tuberculosis. Int J Tuberc Lung Dis. 2013 ; 17 : 146 152.

Abstract We, group of tuberculosis experts, made discus-sions over how to improve the quality of treatment of multi-drug resistant tuberculosis using a newly developed anti-tuberculosis drug, and at the same time, how to prevent the disadvantages of the treated patients and also that of persons who would be infected with newly produced drug-resistant bacilli, by preventing the emergence of resistance to the new drug. A series of proposals are made.

Key words: Multi-drug resistant tuberculosis, Anti-tubercu-losis drug, Chemotherapy, Drug development

1Research Institute of Tuberculosis, Japan Anti-Tuberculosis

Association (JATA), 2National Hospital Organization (NHO)

Higashi Nagoya National Hospital, 3NHO Higashihiroshima

Medical Center, 4Japan Anti-Tuberculosis Association, 5NHO

Kinki-chuo Chest Medical Center, 6NHO Tokyo National

Hospital, 7Osaka Anti-Tuberculosis Association Osaka

Hos-pital, 8Fukujuji Hospital, JATA

Correspondence to : Toru Mori, Research Institute of Tuber-culosis, JATA, 3_1_24, Matsuyama, Kiyose-shi, Tokyo 204_8533 Japan. (E-mail: tmori-rit@jata.or.jp)

−−−−−−−−Issue−−−−−−−−

CONSIDERATIONS ON USES OF NEWLY DEVELOPED ANTI-TUBERCULOSIS DRUGS

FOR MULTI-DRUG RESISTANT TUBERCULOSIS

1Toru MORI, 2Kenji OGAWA, 3Eriko SHIGETO, 4Tadao SHIMAO,

5Katsuhiro SUZUKI, 5Kazunari TSUYUGUCHI, 6Hideaki NAGAI, 7Tomoshige MATSUMOTO, 1Satoshi MITARAI, and 8Takashi YOSHIYAMA

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