今日の臨床サポート

ハンセン病

著者: 山口さやか 琉球大学病院

監修: 細川直登 亀田総合病院

著者校正/監修レビュー済:2022/03/16
参考ガイドライン:
患者向け説明資料

概要・推奨   

  1. ハンセン病の治療では単剤ではなく多剤併⽤療法が強く推奨される(推奨度1)
  1. ハンセン病の患者では眼科へのコンサルトおよび連携が勧められる(推奨度1)
  1. BI陰転化まで治療を継続し、特に治療開始時のBIが高いMB患者では、治療終了後も再発に留意してフォローする必要がある(推奨度1)
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
山口さやか : 特に申告事項無し[2022年]
監修:細川直登 : 未申告[2022年]

改訂のポイント:
  1. 定期レビューを行い、加筆修正を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. ハンセン病は、抗酸菌の一種であるらい菌(Mycobacterium leprae)による慢性感染症である。
  1. 主に皮膚と末梢神経を主病変とし、末梢神経障害に伴う感覚・運動障害により変形や機能不全を呈することが特徴である。
  1. 感染様式は、主に飛沫による経気道感染と考えられており、一般に感染の成立には、免疫能が完全でない乳幼児期に多量・頻回にらい菌にさらされることが重要と考えられている。潜伏期間はきわめて長く、数年から数十年と考えられている。人の体内に侵入しても、発病することはきわめてまれである。
  1. WHOによると、2019年に全世界で約20万人が新規感染者として登録された[1]。日本では、年間10例以下の新規発症者がみられ、ほとんどが在日外国人である。日本人の新規発症者は数年に1人程度で、全例が60歳以上の高齢者である[2]
  1. 患者数が減少したため、日本の医師のほとんどは診療経験がなく、初診から診断までに時間を要することが多い。見落とさないためには、流行国からの渡航者や在留外国人、流行国にて長期滞在歴のある患者や日本人高齢者に、皮膚病変部の病理検査で肉芽腫の所見が見られる場合、ハンセン病を鑑別しなくてはならない。
病型・分類  
WHO分類:
  1. WHOでは、人材や設備の問題により病理検査が困難な国での診断および治療を想定し、皮疹の数および皮膚スメア検査の結果のみをもとに少菌型(paucibacillary:PB、皮膚スメア検査陰性もしくは皮疹が1~5個)か、多菌型(multibacillary:MB、皮膚スメア検査陽性もしくは皮疹が6個以上)の2つに分類・診断し、同時に治療薬と治療期間が決定される[3]
 
Ridley-Jopling分類:
  1. 皮膚スメア検査によるらい菌の数、皮疹の性状や数、神経障害の程度(知覚障害、神経肥厚、運動麻痺など)、病理組織所見などからRidley-Jopling分類(発症初期のindeterminate[I群]、免疫応答の高いtuberculoid[TT]型、まったく反応しないlepromatous(LL)型、これらの中間型のB群(borderline tuberculoid[BT]型、mid-borderline[BB]型、borderline lepromatous[BL]型)に分類する[4]
  1. これは免疫学的な概念をもとに作られた分類で、治療開始後に予想される臨床経過や、反応性病変、末梢神経障害、後遺症や合併症などを予測するのに有用である。TT型やBT型はWHO分類の少菌型に該当し、BB型、BL型、LL型は多菌型に相当する。

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文献 

World Health Organization
WHO Expert Committee on Leprosy.
World Health Organ Tech Rep Ser. 2012;(968):1-61, 1 p following 61.
Abstract/Text Since the introduction of multidrug therapy for leprosy in 1981, an estimated 15 million patients have been cured of the disease and disabilities have been prevented in some 2-3 million individuals. These remarkable results have been brought about by the synergistic efforts of WHO, governmental and nongovernmental bodies, academia, industry and affected communities throughout the world. Nevertheless, much remains to be done--both to sustain this progress and to effect a further reduction in the impact of leprosy on patients and their families. This report presents the conclusions and recommendations of the WHO Expert Committee on Leprosy, whose eighth meeting reflected the recent shift in emphasis of leprosy elimination to reducing of the impairments and disabilities caused by the disease and ensuring the quality and sustainability of leprosy services. The Committee analysed the global leprosy situation, discussed elements of epidemiology, and reviewed developments in treatment of the disease and management of complications. Sociocultural issues were addressed, as was the need for community care, accessibility of health services, and effective referral systems. Indicators for monitoring and evaluation were outlined and research priorities were set out.

PMID 22970604
D S Ridley, W H Jopling
Classification of leprosy according to immunity. A five-group system.
Int J Lepr Other Mycobact Dis. 1966 Jul-Sep;34(3):255-73.
Abstract/Text
PMID 5950347
Risk of relapse in leprosy. The Leprosy Unit, WHO.
Indian J Lepr. 1995 Jan-Mar;67(1):13-26.
Abstract/Text Until the introduction by WHO of the standard regimens using multidrug therapy (MDT) for the treatment of leprosy, there was a general unwillingness to release patients from treatment. This was mainly due to the high risk of relapse after dapsone monotherapy. After almost a decade of MDT implementation and after releasing more than 4 million patients, it was necessary for WHO to review the risk of relapse following WHO-recommended MDT. The results of this study, carried out on more than 20,000 MB and 50,000 PB patients, revealed that the risk of relapse is very low, 0.77% for MB and 1.07% for PB, nine years after stopping MDT. In comparison to dapsone monotherapy, the risk is 10-times lower. Thus, over the last decade, MDT implementation has probably prevented close to half-a-million relapses.

PMID 7622926
Diana Nj Lockwood
Leprosy.
BMJ Clin Evid. 2007 Apr 1;2007. Epub 2007 Apr 1.
Abstract/Text INTRODUCTION: The World Health Organization field leprosy classification is based on the number of skin lesions: single-lesion leprosy (1 lesion), paucibacillary leprosy (2-5 skin lesions), and multibacillary leprosy (more than 5 skin lesions). Worldwide, about 720,000 new cases of leprosy are reported each year, and about 2 million people have leprosy-related disabilities.
METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent leprosy? What are the effects of treatments for leprosy? We searched: Medline, Embase, The Cochrane Library and other important databases up to March 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS: We found 20 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: Bacillus Calmette Guerin (BCG) plus killed Mycobacterium leprae vaccine; BCG vaccine; ICRC vaccine; multidrug treatment; multiple-dose treatment; mycobacterium w vaccine; single-dose treatment.

PMID 19454067
I N Shaw, M M Natrajan, G S Rao, K Jesudasan, M Christian, M Kavitha
Long-term follow up of multibacillary leprosy patients with high BI treated with WHO/MDT regimen for a fixed duration of two years.
Int J Lepr Other Mycobact Dis. 2000 Dec;68(4):405-9.
Abstract/Text Forty-six, newly detected, previously untreated multibacillary (MB) patients with a bacterial index (BI) of > or = 3+ who had received WHO/MDT for 2 years were followed up for a total duration of 424 person-years and a mean duration of 9.26 +/- 2.98 years per patient. The BIs of the patients continued to fall, and all of the patients, except one, reached skin-smear negativity. WHO/MDT was well accepted and well tolerated. Relapse, which was defined as an increase in the BI of 1+ or more with or without clinical evidence of activity, was observed in only one patient, giving a relapse rate of 2.2% or 0.23 per 100 person-years in patients with a BI of > or = 3+ after long-term follow up. This patient was started on a second course of WHO/MDT to which he responded favorably. WHO/MDT for a fixed duration of 2 years for MB patients as recommended by the WHO is vindicated.

PMID 11332283
D M Scollard, T Smith, L Bhoopat, C Theetranont, S Rangdaeng, D M Morens
Epidemiologic characteristics of leprosy reactions.
Int J Lepr Other Mycobact Dis. 1994 Dec;62(4):559-67.
Abstract/Text An 8-year prospective study of a cohort of 176 newly diagnosed leprosy patients was conducted to examine the possible influence of age, sex, multidrug therapy (MDT), and duration of illness on the risk of either type 1 or type 2 reactions. Patients were enrolled over a 5-year period (1984-1989) and followed for a minimum of 3 years. All reactions studied were severe enough to warrant hospital admission. Overall, 45% of this cohort developed a reaction; 32% of patients considered at risk developed type 1 reactions, and 37% of patients considered at risk developed type 2 reactions. Despite the predominance of men among the leprosy patients, type 1 reactions occurred with significantly greater frequency in women, and did not appear to be influenced by age of onset of leprosy. Individuals experiencing one type 1 reaction were not likely to experience a recurrence, suggesting that the immunologic mechanisms of this reaction may be limited or regulated by genetic or immunologic factors. Type 2 reactions, on the other hand, occurred with equal frequency in both males and females, but were highly associated with onset of leprosy in the second decade of life. Individuals who experienced type 2 reactions often had one or more recurrence of the reaction. No increased risk was seen for either reaction with longer duration of leprosy or longer duration of treatment. The mechanisms by which these differences relate to the pathogenesis of leprosy reactions remains unclear, but future studies of clinical and immunological parameters of leprosy reactions may benefit from stratification of data by gender and age of onset of leprosy in addition to the routine grouping of results by leprosy classification.

PMID 7868954
Bhushan Kumar, Sunil Dogra, Inderjeet Kaur
Epidemiological characteristics of leprosy reactions: 15 years experience from north India.
Int J Lepr Other Mycobact Dis. 2004 Jun;72(2):125-33. doi: 10.1489/1544-581X(2004)072<0125:ECOLRY>2.0.CO;2.
Abstract/Text A retrospective analysis of patient's leprosy clinic records at PGIMER, Chandigarh, India for the period 1983 to 1998 was undertaken to study the frequency, time of onset, and risk factors for leprosy reactions. Of the 2600 cases analyzed, 1494 were multibacillary and 1106 had paucibacillary disease. Presentation with reaction was common with 30.9% of our patients having reactions at the time of first visit. The incidence of reversal reaction (RR) was highest during 6 to 12 months after starting multi-drug therapy (MDT), thereafter declining gradually. Late RR occurred in 9.5% of all cases and was noted up to 7 years after treatment. Female gender, widespread disease, and multibacillary disease were identified as risk factors for RR. Erythema nodosum leprosum (ENL) reactions were noted to occur mostly during second or third year after starting MDT. Of the total number of patients who experienced ENL, 64.3% had recurrent episodes which continued for up to 8 years after the start of treatment. Lepromatous leprosy, female gender, and high Bacterial Index (>/=3) were recognized as risk factors for developing ENL. Occurrence of recurrent and late reactions, even though of mild severity, highlights the importance of recognizing and treating them promptly to prevent or reduce morbidity, complications, and further deterioration in the disability status. Although it is hoped that leprosy will have been eliminated at all levels by 2005, the recognition and management of these reactions will continue to be the most essential/significant task in the post elimination era.

PMID 15301592
D M Scollard, L B Adams, T P Gillis, J L Krahenbuhl, R W Truman, D L Williams
The continuing challenges of leprosy.
Clin Microbiol Rev. 2006 Apr;19(2):338-81. doi: 10.1128/CMR.19.2.338-381.2006.
Abstract/Text Leprosy is best understood as two conjoined diseases. The first is a chronic mycobacterial infection that elicits an extraordinary range of cellular immune responses in humans. The second is a peripheral neuropathy that is initiated by the infection and the accompanying immunological events. The infection is curable but not preventable, and leprosy remains a major global health problem, especially in the developing world, publicity to the contrary notwithstanding. Mycobacterium leprae remains noncultivable, and for over a century leprosy has presented major challenges in the fields of microbiology, pathology, immunology, and genetics; it continues to do so today. This review focuses on recent advances in our understanding of M. leprae and the host response to it, especially concerning molecular identification of M. leprae, knowledge of its genome, transcriptome, and proteome, its mechanisms of microbial resistance, and recognition of strains by variable-number tandem repeat analysis. Advances in experimental models include studies in gene knockout mice and the development of molecular techniques to explore the armadillo model. In clinical studies, notable progress has been made concerning the immunology and immunopathology of leprosy, the genetics of human resistance, mechanisms of nerve injury, and chemotherapy. In nearly all of these areas, however, leprosy remains poorly understood compared to other major bacterial diseases.

PMID 16614253
Stephen L Walker, Diana N J Lockwood
Leprosy type 1 (reversal) reactions and their management.
Lepr Rev. 2008 Dec;79(4):372-86.
Abstract/Text The type of leprosy that affects an individual depends on the immune response mounted against the organism. This leads to a spectrum of disease which may be complicated by immunological phenomena called reactions. Antimicrobial chemotherapy is effective in treating the Mycobacterium leprae infection but up to 30% of individuals with borderline disease experience Type 1 reactions (T1Rs). T1Rs are immunologically mediated episodes, localised in skin and nerves, which are a major cause of nerve function impairment. Nerve function impairment may result in disability and deformity. We review the frequency and features of Type 1 reactions. The data from the limited number of randomised controlled trials of treatment are discussed. These four randomised controlled trials were all conducted in south Asia. The accepted treatment of T1Rs is with oral corticosteroids but there is no consensus about the dose or duration of treatment due to the lack of data. One randomised controlled trial showed that patients treated with a 5 month course of prednisolone (total dose 2.31 g) were less likely to need additional prednisolone than those treated with a 3 month course of prednisolone (total dose 2.94 g). This study did not use nerve function as an outcome measure. The improvement in nerve function impairment with steroid treatment is highly variable, with 33-73% of nerves recovering fully. Optimal steroid regimes and alternative treatments need to be identified if the disability associated with leprosy is to be minimised. Search strategy Papers for this review were identified by repeated searches of the Cochrane Clinical Trials Register, PubMed and LILACS with various combinations of the following search terms 'leprosy', 'lepra', 'reaction', 'steroids', 'corticosteroids', 'reversal', 'Type 1', 'Hansen*'. Searches were complete to the end of November 2008.

PMID 19274984
Abstract/Text This paper presents a retrospective study on the detection of the treatment of leprosy reactions in a field situation, and the effect of prednisone on the various affected nerves. Two patient cohorts were analysed. The leprosy control programme in the testing area is not backed up by a specialized referral leprosy hospital, but patients are treated on an ambulatory basis at peripheral health centres by trained multipurpose health workers supervised by the health centre doctors. For operational purposes the guidelines and procedures for reaction management in the field were adjusted and partially simplified. In both studies it appeared that the time of the occurrence of severe reactions was the same: 80% or more of the severe reactions occurred in the first year of treatment, the majority in the first few months after the start of the multidrug (MDT) treatment. One third of all reaction patients suffered from a silent neuritis. Well-instructed fieldworkers proved to be competent in detecting and treating leprosy reactions. Treatment of severe reactions with prednisone in the field situation can preserve or considerably improve the functions of the affected nerves. It is interesting that often the motor function of a nerve was found to be impaired without any loss in sensibility, which was tested using the ballpoint pen method.

PMID 9364823
W J Britton
The management of leprosy reversal reactions.
Lepr Rev. 1998 Sep;69(3):225-34.
Abstract/Text
PMID 9805878
Natasja H J van Veen, Peter G Nicholls, W Cairns S Smith, Jan Hendrik Richardus
Corticosteroids for treating nerve damage in leprosy. A Cochrane review.
Lepr Rev. 2008 Dec;79(4):361-71.
Abstract/Text OBJECTIVE: Corticosteroids are commonly used for treating nerve damage in leprosy. We assessed the effectiveness of corticosteroids for treating nerve damage due to leprosy.
METHODS: A systematic search was undertaken to identify randomised controlled trials (RCTs) comparing corticosteroids with placebo or with no treatment. Two authors independently assessed quality and extracted data. Where it was not possible to perform a meta-analysis, the data for each trial was summarised.
RESULTS: Three RCTs involving 513 people were found. Two trials compared prednisolone with placebo. One trial treated mild sensory impairment of less than 6 months duration and the other trial treated nerve function impairment of 6 to 24 months duration. Both trials examined nerve function improvement 12 months from the start of treatment, but found no significant difference between the two groups. The third trial compared three corticosteroid regimens for severe type 1 reactions. After 12 months, a significantly higher proportion of individuals on a 3 month course required extra corticosteroids compared to the groups with a high-dose and low-dose regimen of 5 months duration. Diabetes and peptic or infected ulcers were not significantly more often reported in the corticosteroid compared to the placebo group.
CONCLUSIONS: Evidence from RCTs does not show a significant long-term effect for either long-standing nerve function impairment or mild sensory impairment. A 5 month corticosteroid regimen was significantly more beneficial than a 3 month corticosteroid regimen. Further RCTs are needed to establish the effectiveness and optimal regimens of corticosteroids and to examine new therapies.

PMID 19274983
J SHESKIN
THALIDOMIDE IN THE TREATMENT OF LEPRA REACTIONS.
Clin Pharmacol Ther. 1965 May-Jun;6:303-6.
Abstract/Text
PMID 14296027
M Hogeweg
Ocular leprosy.
Int J Lepr Other Mycobact Dis. 2001 Jun;69(2 Suppl):S30-5.
Abstract/Text
PMID 11757176
T J Ffytche
The prevalence of disabling ocular complications of leprosy: a global study.
Indian J Lepr. 1998 Jan-Mar;70(1):49-59.
Abstract/Text A world-wide study on the ocular complications of leprosy has been carried out over the past ten years. The data from 4772 patients, designed to give baseline information for a five-year incidence study, have been analysed. Blindness due to leprosy was seen in 3.2% of the sample and 7.1% had Grade 2 visual disability. The causes of visual impairment in the disease are discussed and it is emphasized that a high proportion of these are preventable, particularly through the early use of multidrug therapy. The active participation of ophthalmologists in the management of the disease is still required since many of the blinding complications respond well to surgery.

PMID 9598405
M Matsuoka, Y Kashiwabara, M Namisato
A Mycobacterium leprae isolate resistant to dapsone, rifampin, ofloxacin and sparfloxacin.
Int J Lepr Other Mycobact Dis. 2000 Dec;68(4):452-5.
Abstract/Text Mycobacterium leprae were isolated from a Japanese patient, and susceptibility to antileprosy drugs was examined by the mouse foot pad method. The isolate was susceptible to clofazimine and clarithromycin, and resistant to dapsone, rifampin, ofloxacin and sparfloxacin. Mutations were identified in the genes associated with resistance to these drugs. The risk of the emergence of leprosy with multidrug resistance is emphasized.

PMID 11332288
S Maeda, M Matsuoka, N Nakata, M Kai, Y Maeda, K Hashimoto, H Kimura, K Kobayashi, Y Kashiwabara
Multidrug resistant Mycobacterium leprae from patients with leprosy.
Antimicrob Agents Chemother. 2001 Dec;45(12):3635-9. doi: 10.1128/AAC.45.12.3635-3639.2001.
Abstract/Text Sequences of the folP1, rpoB, and gyrA genes were analyzed for 88 isolates of Mycobacterium leprae from leprosy patients in Japan, Haiti, Indonesia, Pakistan, and the Philippines. Thirteen isolates (14.8%) showed representative mutations in more than two genes, suggesting the emergence of multidrug-resistant M. leprae.

PMID 11709358
Stephen L Walker, Dina N J Lockwood
Leprosy.
Clin Dermatol. 2007 Mar-Apr;25(2):165-72. doi: 10.1016/j.clindermatol.2006.05.012.
Abstract/Text Leprosy is a granulomatous disease affecting the skin and nerves caused by Mycobacterium leprae. It continues to be a significant public health problem. Despite multidrug therapy, immunologic reactions continue to occur, leading to disability and deformity due to neuropathy. It is important that dermatologists are aware of the neurologic as well as the skin manifestations of the condition so that nerve involvement can be identified and treated rapidly.

PMID 17350495
B H Ji
Drug resistance in leprosy--a review.
Lepr Rev. 1985 Dec;56(4):265-78.
Abstract/Text
PMID 3908861
WHO Expert Committee on Leprosy.
World Health Organ Tech Rep Ser. 1988;768:1-51.
Abstract/Text
PMID 3140498
Abstract/Text Thirty-five multibacillary (MB) leprosy patients were treated with 2 years of multidrug therapy (MDT) and followed up regularly for relapse. Relapse was defined as: a) an increase of the bacterial index (BI) by 2+ over the previous value from any single site of old lesions and b) the occurrence of definite new skin lesion(s) which demonstrated a higher BI than any pre-existing lesion. After a mean duration of 72.7 +/- 17.3 months of follow up per patient, seven relapses were diagnosed; the mean incubation period of relapse was 62.7 +/- 18.7 months. The overall relapse rate was 20.0% (or 3.3 per 100 patient-years), very significantly higher than the figures obtained from the same group of patients analyzed 2 1/2 years earlier, indicating that relapses occurred late (at least 5 +/- 2 years) after stopping MDT. Further analysis indicated that the relapse rate was closely correlated with the bacterial load of the patient, occurring far more frequently among patients with a BI of > or = 4.0 before MDT or with a BI of > or = 3.0 at the end of MDT. To avoid the alarmingly high relapse rate, it is proposed that the duration of MDT be doubled to 4 years in patients with an average BI of > or = 4.0 before MDT.

PMID 7602214
Abstract/Text
PMID 7731336
Robert H Gelber, Victoria F Balagon, Roland V Cellona
The relapse rate in MB leprosy patients treated with 2-years of WHO-MDT is not low.
Int J Lepr Other Mycobact Dis. 2004 Dec;72(4):493-500. doi: 10.1489/1544-581X(2004)72<493:TRRIML>2.0.CO;2.
Abstract/Text A group of multibacillary patients is clearly at high risk for relapse following 2-yr WHO-MDT. Relapse is largely confined to BL or LL patients with a high BI initially, and occurs long after the discontinuation of therapy. This important group of patients at risk for treatment failure presents several important issues: the need to identify those at risk and the operational requirements needed for their long term follow-up. Also, this group of patients might well benefit from an alternative antimicrobial regimen from the outset, as well as upon relapse.

PMID 15755209

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以下の優待コードを入力いただくと、

契約期間が通常12ヵ月のところ、14ヵ月ご利用いただけます。

優待コード: (利用期限:まで)

ご契約はこちらから