Intestinal tuberculosis

Japanese: 腸結核

Definition/Concept: Mycobacterium tuberculosis invades the intestines, causing inflammation and forming ulcers. It often occurs in the terminal ileum, cecum, and ascending colon. Small and large intestinal tuberculosis are collectively called intestinal tuberculosis.
Classification: Tuberculosis is classified into primary intestinal tuberculosis, which occurs when the initial focus of infection is in the intestinal tract, and secondary intestinal tuberculosis, which occurs when tuberculosis bacteria from a pulmonary tuberculosis focus reach the intestine through swallowing sputum and directly invade the intestinal mucosa, causing the disease.
Epidemiology: The incidence rate of tuberculosis in Japan in 2010 (number of newly registered tuberculosis patients per 100,000 population) was 18.2, a decrease of 0.8 from the previous year, but there are still more than 23,000 tuberculosis patients in the country (Ministry of Health, Labour and Welfare, 2010 Tuberculosis Registration Information Survey Annual Report Summary (Overview)). It has been reported that 46-70% of cases of pulmonary tuberculosis are accompanied by intestinal tuberculosis, and while the number of cases of intestinal tuberculosis is decreasing as the number of pulmonary tuberculosis decreases, the number of cases of intestinal tuberculosis associated with immunodeficiency such as in the elderly, diabetes, renal failure, post-organ transplantation, and AIDS is increasing.
PathologyUlcers accompanied by caseating granulomas are characteristic, and extensive fibrosis is often observed afterwards. Inflammatory cells gather in the ulcerated area, forming deep ulcers, and in some cases, leakage and anal lesions can also be seen. In the early stages of the disease, a large number of acid-fast bacilli (Ziehl-Neelsen staining), which are tuberculosis bacteria, can be seen in the ulcerated area accompanied by caseating granulomas, but in the chronic stage, significant fibrosis and stenosis occur, and a mass called a tuberculous nodule is formed. Furthermore, acid-fast bacteria are rarely seen in the fibrotic areas.
Clinical symptoms : Although some cases are asymptomatic, common symptoms include abdominal pain, fever, loss of appetite, diarrhea, weight loss, constipation, flatulence, and bloody stools. Small intestinal tuberculosis in particular can cause a sudden deterioration in nutritional status and weight loss, and in the chronic stage, the intestinal tract can narrow, resulting in symptoms of intestinal obstruction such as nausea and vomiting. Abdominal masses (tuberculous nodules) can also be palpable, most of which are found in the right lower quadrant.
inspection
Colonoscopy is the first choice for the examination of results . Typically, an ulcer in the ileocecal area, called an annular ulcer (Figure 8-5-23), which runs along the transverse axis of the intestine, is seen, and caseous granulomas are seen in a biopsy histopathological examination. If acid-fast bacilli are found in Ziehl-Neelsen staining, the diagnosis is definitive. However, typical caseous granulomas are found in less than 50% of biopsy tissues, and diagnosis is often difficult. Recently, PCR, a method for amplifying the DNA of tuberculosis bacteria, has become widespread, and this PCR method can detect tuberculosis bacteria from biopsy tissue with a sensitivity of 64-86%. Of course, there is also a method to detect tuberculosis bacteria by stool culture, but this takes at least 1-2 weeks and the positive rate is low at 10%, so PCR of biopsy tissue is more useful. There is also a PCR method for stool, but the detection rate is even lower than that of the culture method, so it is not recommended. Although a barium enema examination can also reveal characteristic findings such as ulcers, stenosis, and leakage, colonoscopy, which also allows for biopsy, is preferred due to the issue of radiation exposure. CT and abdominal ultrasound can reveal thickened intestinal walls.
In addition, blood tests may reveal elevated inflammatory responses such as CRP and erythrocyte sedimentation rate, as well as mild anemia and malnutrition.Recently, the usefulness of an auxiliary diagnostic method called the whole blood interferon-gamma response assay (QuantiFERON), which can diagnose the presence or absence of tuberculosis infection from collected blood, has been recognized.
Differential diagnosis/DiagnosisThe first thing that comes to mind in the differential diagnosis is Crohn's disease, which has recently become increasingly prevalent in Japan. Crohn's disease is characterized by longitudinal ulcers that run longitudinally along the long axis of the intestine, which distinguishes it from the annular ulcers of intestinal tuberculosis. Furthermore, while the majority of cases of intestinal tuberculosis in pathological tissue are caseous granulomas, approximately half of the cases of Crohn's disease are non-caseating granulomas. Other differential diagnoses include Yersinia enteritis, enteritis caused by nontuberculous mycobacteria, histoplasmosis, cytomegalovirus enteritis, and lymphoma.
Treatment : Antituberculosis chemotherapy is based on a four-drug combination of isoniazid (INH), rifampicin (RFP), pyrazinamide (PZA), ethambutol (EB) or streptomycin (SM) for four months, and INH and RFP for two months, for a total of six months. This combination of drugs kills tuberculosis bacteria without causing resistance. Side effects of long-term administration include visual, hearing, peripheral nerve, and liver damage, so caution is required. In addition, tuberculosis culture takes a long time, and treatment after the results are available may be too late and may be fatal. Therefore, when intestinal tuberculosis is strongly suspected, antituberculosis drugs may be administered before a definitive diagnosis as a diagnostic treatment. Furthermore, surgery may be required if there are complications such as stenosis, intestinal obstruction, perforation, fistula formation, abdominal mass formation, or severe bleeding.
Course and prognosis: If the tuberculosis bacteria is not multidrug-resistant, abdominal pain and fever will disappear within 2-3 weeks with the administration of anti-tuberculosis drugs, and ulcers will scar within 4-8 weeks, and the prognosis will be good, even in patients with immunodeficiency such as AIDS. However, if diagnosis is delayed and treatment is not administered, it can be fatal. Furthermore, because treatment is long, lasting approximately six months, interrupting it midway can cause the tuberculosis bacteria to become drug-resistant, making the condition difficult to treat, so it is important to continue the treatment without interruption. If tuberculosis is diagnosed, it is a Class II infectious disease, so notification must be made "immediately" under the Infectious Diseases Act, and medical expenses related to tuberculosis treatment will be covered by public funds. If the patient only has intestinal tuberculosis and no bacteria are being excreted, they will be treated as an outpatient without isolation. [Okusa Satoshi]
■ References
Fantry GT, Fantry LE, et al: Chronic infections of the small intestine, Tuberclosis. In: Textbook of Gastroenterology 5th ed (Yamada T ed), pp1234-1236, Wiley-Blackwell, Chichester, 2009.
Kobayashi, Kiyonori, Sada, Miwa, et al.: Intestinal tuberculosis, Clinical Research, 82: 1437-1442, 2004.

Source : Internal Medicine, 10th Edition About Internal Medicine, 10th Edition Information

Japanese:

定義・概念
　結核菌（Mycobacterium tuberculosis）が腸に侵入し，炎症を起こして潰瘍を形成する病気で，回腸の末端部と盲腸，上行結腸に発生することが多い．また，小腸結核と大腸結核を総称して腸結核という．
分類
　腸管に初感染巣をつくる原発性（一次性）腸結核と，肺結核病巣の結核菌が痰の嚥下によって腸に達し，直接腸粘膜に侵入して発病する続発性（二次性）腸結核とに分類される．
疫学
　日本の結核の平成22年度の罹患率（人口10万人対の新登録結核患者数）は18.2と対前年比0.8減であるが，国内ではいまだ23000人以上の結核患者が発生している（厚労省平成22年結核登録者情報調査年報集計結果（概況））．肺結核の46～70％に腸結核が併発されると報告されており，肺結核の減少に伴い腸結核も減少しているが，高齢者，糖尿病，腎不全，臓器移植後，AIDSなどの免疫不全に伴う腸結核が増加している．
病理
　乾酪性肉芽腫を伴う潰瘍が特徴であり，その後に広範な線維化がみられることが多い．潰瘍部には炎症性細胞が集簇しており，深い潰瘍をつくって漏孔や肛門部病変も認められることもある．病初期には乾酪性肉芽腫を伴った潰瘍部に多数の結核菌である抗酸菌（Ziehl-Neelsen染色）がみられるが，慢性期になると著明な線維化や狭窄となり，結核結節として腫瘤を形成する．なお，線維化部分には抗酸菌はほとんどみられなくなる．
臨床症状
　無症状のこともあるが，症状としては腹痛が多く，発熱，食欲不振，下痢，体重減少，便秘，鼓腸，血便などがみられる．特に小腸の結核では栄養状態が急に悪化し体重減少したり，慢性期になると腸管が狭窄し，悪心や嘔吐といった腸閉塞症状が出ることもある．腹部腫瘤（結核結節）が触知されることもあり，その多くは右下腹部で認められる．
検査
成績
　検査法としては大腸内視鏡検査が第一選択であり，典型的には回盲部に輪状潰瘍といわれる腸管の横軸方向の潰瘍（図8-5-23）がみられ，生検病理組織検査で乾酪性肉芽腫が認められる．そして，Ziehl-Neelsen染色で抗酸性の桿菌がみられれば確定診断となる．しかし，生検組織で典型的乾酪性肉芽腫が認められるのは50％以下であり，診断に苦慮することが多い．最近になり結核菌のDNA増幅法であるPCR法が普及し，このPCR法により生検組織から64〜86％の感度で検出されるようになってきた．　もちろん，便培養により結核菌を検出する方法もあるが，最低でも1～2週間かかり，かつ陽性率は10％と低いので，生検組織のPCR法の方が有用である．また，糞便のPCR法もあるが，培養法よりさらに検出率は低いので勧められない．バリウム注腸検査でも潰瘍，狭窄，漏孔などの特徴的な所見が得られるが，被曝の問題もあるので，生検もできる大腸内視鏡検査が優先される．CTや腹部超音波検査では，肥厚した腸管壁が描出される．
　そのほか，血液検査ではCRPや赤沈といった炎症反応の上昇や軽度の貧血，低栄養状態がみられる．最近では，採取した血液から結核感染の有無を診断する，全血インターフェロン-γ応答測定法（クオンティフェロン）といわれる補助診断法の有用性が認められてきている．
鑑別診断・診断
　鑑別診断でまず第一にあげられるのは，最近日本で増加の著しいCrohn病である．Crohn病は腸管の長軸方向に縦走する縦走潰瘍が特徴的であり，腸結核の輪状潰瘍との鑑別点となる．また，病理組織で腸結核では乾酪性肉芽腫がほとんどであるのに対して，Crohn病では約半数が非乾酪性肉芽腫である．このほかに鑑別として，エルシニア腸炎，非結核性抗酸菌による腸炎，ヒストプラズマ症，サイトメガロウイルス腸炎，リンパ腫などがあげられる．
治療
　抗結核薬による化学療法として，イソニアジド（INH）とリファンピシン（RFP），ピラジナミド（PZA），エタンブトール（EB）かストレプトマイシン（SM）を4カ月，INHとRFPを2カ月，計6カ月投与するといった，４者併用療法が基本になる．この多剤併用により耐性菌を生じさせることなく結核菌を死滅させる．　長期投与の副作用として視覚，聴覚，末梢神経，肝障害などがあるので注意が必要である．また，結核菌培養には長時間を要し，結果が出てからの治療は手遅れとなり致命的ともなる場合もあるので，腸結核が強く疑われる場合は，診断的治療として確定診断前に抗結核薬の投与を行うことがある．さらに，狭窄，腸閉塞，穿孔，瘻孔形成，腹部腫瘤形成，大出血などの合併症のある場合は手術が必要になることがある．
経過・予後
　多剤耐性の結核菌でなければAIDSなどの免疫不全状態の患者でも，抗結核薬の投与により，腹痛・発熱は２～３週間で消失し，潰瘍は４～８週間で瘢痕化し予後は良好である．ただし，診断が遅れ治療が行われなかった場合は致命的となる．また，治療は約半年と長期のため，中途で中断すると結核菌の薬剤耐性のもととなり難治性となるので，中断せず続けさせることも重要である．　結核と診断された場合，二類感染症なので感染症法により，「直ちに」届出が必要であり，結核の治療に関する医療費は公費負担となる．腸結核だけで排菌のない場合は隔離せずに外来治療となる．［大草敏史］
■文献
Fantry GT, Fantry LE, et al: Chronic infections of the small intestine, Tuberclosis. In: Textbook of Gastroenterology 5th ed (Yamada T ed), pp1234-1236, Wiley-Blackwell, Chichester, 2009.
小林清典，佐田美和，他：腸結核，臨床と研究，82: 1437-1442, 2004．

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