Expulmonary tuberculosis Extrapulmonary Tuberculosis (TB) is TB which occurs in any other part of the body outside the lungs.

Many people do not realise it but TB can infect almost any place in the body: the inner organs, the bone, the brain, the spine etc. n fact, the only place that TB cannot infect is our hair or nails. !ne in fi"e TB patients are infected with extrapulmonary TB and these strains are often much more difficult to diagnose. Extrapulmonary TB is especially pre"alent in countries with a low pre"alence of TB and, as a conse#uence, it is often o"erloo$ed as doctors will not immediately thin$ that TB is the problem when diagnosing illnesses outside of the lungs. Risk factors for extrapulmonary tuberculosis. To control for potential confounders, we used a series of logistic regression models. %ll models included sex, age, and race&ethnicity' other "ariables were added indi"idually. %fter ad(ustment, sex, race&ethnicity, and ) * status remained strongly associated with extrapulmonary tuberculosis (table +). ,atients with extrapulmonary tuberculosis were more li$ely to be female, non-)ispanic blac$, and ) *-positi"e, whereas excessi"e alcohol use appeared to be negati"ely associated with extrapulmonary tuberculosis. %lthough other "ariables, such as homelessness, residence in a long-term care facility, and nonin(ection drug use, appeared to ha"e a significant association with extrapulmonary disease using uni"ariate analysis, these factors did not show a statistically significant association with extrapulmonary disease after controlling for potential confounders using multi"ariate logistic regression analysis. Because of the small si.e of the subpopulation of patients identified as %merican ndians and %sian&,acific slanders, these + groups were combined into a single group, designated as other, for analysis' this group showed an increased ris$ for extrapulmonary tuberculosis, compared with non-)ispanic whites. / 01/ %12 /3M,T!M/ Extrapulmonary tuberculosis (TB) n some cases, TB can occur outside the lungs, which is $nown as extrapulmonary TB. Extrapulmonary TB is more common in people with a wea$ened immune system, particularly people with an ) * infection. 3ou are also more li$ely to de"elop extrapulmonary TB if you ha"e pre"iously been infected with TB but ha"en4t had any symptoms (a latent TB infection). % TB infection can affect the: -lymph nodes (lymph node TB) -bones and (oints (s$eletal TB) -the digesti"e system (gastrointestinal TB) -the bladder and reproducti"e system (genitourinary TB) -the ner"ous system (central ner"ous system TB) These types of extrapulmonary TB can cause additional symptoms, which are described below. 5ymph node TB 5ymph nodes are small glands that are part of the immune system. They remo"e unwanted

bacteria and particles from the body. /ymptoms of lymph node TB include: persistent, painless swelling of the lymph nodes, which usually affects nodes in the nec$, but swelling can occur in nodes throughout your body o"er time, the swollen nodes can release fluid through the s$in /$eletal TB /ymptoms of s$eletal TB include: -bone pain -cur"ing of the affected bone or (oint -loss of mo"ement or feeling in the affected bone or (oint -wea$ened bone that may fracture easily 0astrointestinal TB /ymptoms of gastrointestinal TB include: -abdominal pain -diarrhoea -rectal bleeding 0enitourinary TB /ymptoms of genitourinary TB include: -a burning sensation when you urinate -blood in your urine -a fre#uent urge to pass urine during the night -groin pain 6entral ner"ous system TB 3our central ner"ous system consists of your brain and spinal cord. /ymptoms of central ner"ous system TB include: -headaches -being sic$ -stiff nec$ -changes in your mental state, such as confusion -blurred "ision -fits (sei.ures) 2 %01!/T 6 %,,7!%6)

Step-by-step diagnostic approach Many forms of extrapulmonary TB (E,TB) are paucibacillary, and the diagnosis of E,TB is therefore challenging. %cid-fast bacilli (%8B) smear of biological specimens is often negati"e. Tuberculin s$in testing (T/T) and interferon-gamma release assays ( 07%) are ad(uncti"e diagnostic tools, at best. 6onstitutional symptoms associated with E,TB, (such as fe"er, wea$ness, and weight loss) may be infre#uent and non-

specific. n addition, E,TB is less common than pulmonary tuberculosis (,TB) and may be less familiar to clinicians. % high le"el of suspicion is important in e"aluating a patient with presence of ris$ factors (for full details please refer to ris$ factor section). The firm diagnosis of TB re#uires culturing of Mycobacterium tuberculosis and is important for drugsusceptibility testing. %ppropriate specimens are obtained and tested microbiologically and histologically. %lthough culture remains the diagnostic standard, it can ta$e up to 9 to :; wee$s using a solid media, and in :;< to :=< of patients the diagnosis of TB is based on clinical grounds. 2elays in diagnosis and initiation of therapy are associated with increased mortality. Tests for all suspected EPTB %s the lungs may be in"ol"ed in patients with E,TB, sputum for %8B smear and culture is indicated for all suspected patients. 6ulture-positi"e sputum becomes useful when the specimens from extrapulmonary sites are culture-negati"e, and it may also add further information on the infectiousness of the patient. 6hest x-ray should be part of the basic initial wor$-up and may show e"idence of acti"e or old TB. Tuberculin s$in test (T/T) is also done in all patients with suspected E,TB, although the sensiti"ity may range from >;< to ?;< depending on the site of disease. % positi"e T/T is helpful for diagnosis, but a negati"e T/T does not rule out acti"e disease. %n 8B6 should be sent and may show abnormalities. f the suspicion of TB is high or the patient is "ery ill, consideration can be gi"en to starting antituberculous medicines as soon as diagnostic specimens are obtained. nterferon-gamma release assay ( 07%) is an in "itro test, which the 6enters for 2isease 6ontrol and ,re"ention (626) recommends can be used in all circumstances in which the T/T is currently used, including contact in"estigations, e"aluation of recent immigrants, and se#uential-testing sur"eillance programmes for infection control (e.g., those for healthcare wor$ers). The sensiti"ity of 07% to diagnose E,TB is suboptimal. /e"eral molecular diagnostic methods (nucleic acid amplification tests) are a"ailable. They are based on amplification of mycobacterial nucleic acid. These methods enable the laboratory to pro"ide the results to clinicians within a day, with higher specificity and sensiti"ity than %8B smear. t is recommended that all patients with TB ha"e an ) * test within + months of diagnosis. n +;;9, @< of patients with TB were $nown to be ) *-positi"e. ) * infection and its treatment may alter the treatment of TB' treatment of ) * may be crucial to the morbidity of ) *-infected TB patients.

TB lymphadenitis ,atients most commonly present with enlarged lymph nodes in the cer"ical or supracla"icular areas that may be unilateral or bilateral. f a patient with superficial lymphadenitis is suspected of ha"ing TB, the first diagnostic test is 81%, especially if the lymph node is fluctuant. f the diagnosis remains in #uestion, then a surgical consultation is obtained for lymph node excision (not incisional biopsy, due to the ris$ of sinus tract formation). f the patient has inaccessible lymphadenitis (e.g., mediastinal), excisional biopsy is obtained with mediastinoscopy or thoracoscopy. Pleural TB ,leural TB usually presents with symptoms such as pleurisy, pleuritic chest pain, cough, and fe"er, and a chest x-ray showing a unilateral effusion. The effusion is commonly small to moderate in si.e' bilateral TB effusions are rare and associated with disseminated disease. n addition to a chest x-ray, sputum cultures, and T/Ts, a thoracentesis is done. 6hest x-ray may show no ob"ious parenchymal disease in =;< of patients with pleural TB' sputum cultures are positi"e in +;< to >;< of those without definite parenchymal in"ol"ement. 8alse-negati"e T/Ts are also common. ,leural fluid analysis is performed on the sample obtained from thoracentesis. ,leural fluid is sent for %8B smear and culture, cell count with differential, protein, 52), glucose, and p). %8B smear is rarely positi"e. ,leural fluid analysis usually shows an exudati"e effusion that is lymphocyte-predominant and often has low glucose le"el. The adenosine deaminase (%2%) le"el may be measured because it is often ele"ated in pleural TB (sensiti"ity and specificity approximately ?;<). %lthough results of pleural fluid analysis may be helpful, they will seldom confirm a diagnosis of pleural TB. Because a malignancy may also cause a lymphocytepredominant exudati"e effusion, the diagnosis of pleural TB is based on microbiology, pathology (granulomas), and negati"e cytology. t is important to obtain a TB isolate for susceptibility testing. Therefore pleural biopsy is indicated when the patient has a lymphocyte-dominant exudati"e effusion, or e"en at the same time as thoracentesis if clinical suspicion for TB is "ery high. The combination of %8B culture and histology from pleural biopsy is the most sensiti"e to diagnose pleural TB. f results of biopsy are non-diagnostic, thoracoscopy or thoracotomy may be indicated. Skeletal TB

%bout A;< percent to ?;< of patients may ha"e a positi"e T/T. !ne half of cases will ha"e abnormalities on chest x-ray consistent with TB. ,ain of the in"ol"ed area is the most common complaint in s$eletal TB' constitutional symptoms are usually absent. 2iagnosis is based on tissue biopsy. !nset of pain is gradual (o"er wee$s to months) and diagnosis is fre#uently delayed. 5ocal swelling and limitation of mo"ement may be present. 6old abscesses (non-tender) with sinus tracts may form. f s$eletal TB is suspected, M7 (especially in spinal in"ol"ement) or 6T is obtained. Microbiological confirmation of TB is also essential. %8B smears are unli$ely to be positi"e due to low bacillary loads. 6old abscesses, if present, may be aspirated for %8B smear and culture. 6T-guided biopsy in "ertebral TB will ha"e positi"e microbiological or histological yields in @=< to ?;< of patients. /yno"ial biopsy should be done to diagnose TB arthritis. Biopsy may yield culture positi"e in ?;< to ?=< and can be performed if the diagnosis of TB arthritis remains in #uestion. n (oint in"ol"ement, e"aluation of syno"ial fluid is usually not diagnostic' BB6 counts in TB arthritis are usually :;,;;; to +;,;;;&m5, but can be much higher. %8B smear is positi"e in C+;< but culture may be positi"e in up to 9;<. C S TB 61/ TB may present with meningitis or intracranial tuberculomas. 2iagnosis of TB meningitis is dependent upon 6/8 examination, and its rapid diagnosis is essential for impro"ed outcomes. /igns and symptoms of meningeal TB include headache, nec$ stiffness, altered mental status, and cranial ner"e abnormalities. !nly >9< of children with TB meningitis ha"e fe"er and ?< report photophobia. /ei.ures are common in children and the elderly. n the presence of meningeal signs, the patient undergoes lumbar puncture and the 6/8 is submitted for cell count with differential, glucose, protein, %8B smear and culture, 0ram stain, and bacterial culture. The usual results of analysis include a lymphocyte predominance, ele"ated protein, and reduced glucose. %lthough smears of spinal fluid are fre#uently negati"e, the diagnostic yield is dependent on the "olume of 6/8 submitted and the #uality of examination. n order to maximise the sensiti"ity of TB diagnosis by spinal fluid analysis, some experts suggest increased 6/8 "olume (at least @ m5 of spinal fluid for %8B) and repeated sampling (up to > lumber punctures on different days).

%8B culture is the definiti"e standard for diagnosis but treatment must not wait until culture results are a"ailable. Treatment is initiated presumpti"ely based on clinical suspicion, ris$ factors, and 6/8 results. )ead 6T or M7 may show oedema, hydrocephalus, basilar meningeal thic$ening, or tuberculomas. Tuberculomas present as a slowly growing focal lesion, or, rarely, with signs and symptoms consistent with increased intracranial pressure. 6/8 analysis is usually normal and diagnosis is based on 6T or M7 findings. Dp to =;< of patients ha"e chest x-ray abnormalities consistent with pulmonary TB. !bdominal TB T/T may be positi"e in A;< and chest x-ray may show e"idence of old TB. %bdominal TB includes TB peritonitis and TB of the 0 tract. 2efiniti"e diagnosis is based on culture growth of M tuberculosis from ascitic fluid or a biopsy of the lesion. ,atients may ha"e disease for months before the diagnosis is made. ,eritoneal disease is the more common presentation. The presenting symptoms include abdominal swelling, abdominal pain, fe"er, and change in bowel habits. n TB enteritis (TB of the 0 tract), the ileocaecum is the most commonly in"ol"ed area, followed by the ileum, caecum, and ascending colon. 6hronic abdominal pain is the most common symptom in addition to changes in bowel habits and haem-positi"e stool. ,atients may de"elop small bowel obstruction or a 75E mass. 6T scan of the abdomen, ascitic fluid analysis, and peritoneal biopsy are done initially. 6T scan may show ascites, bowel-wall thic$ening, or abdominal lymphadenopathy. %scitic fluid analysis is non-specific and rarely %8B smear-positi"e. %lthough the sensiti"ity of culture from peritoneal fluid is high (?+<), results re#uire up to 9 wee$s and delay in initiating treatment is associated with higher mortality. ,eritoneal biopsy (laparoscopy or laparotomy) is the most effecti"e means for diagnosis. 2irect inspection may re"eal miliary nodules o"er the peritoneum and allow a presumpti"e diagnosis in 9;< to ?=<. Biopsy demonstrates caseating granulomas (up to :;;<) and the presence of %8Bs on examination in @A< of samples. 6olonoscopy and biopsy are carried out to diagnose TB enteritis. 6olonoscopy will re"eal ulcers, pseudopolyps, or nodules. 2efiniti"e diagnosis is based on biopsy, which usually shows granulomas and culture positi"e for TB. "enitourinary TB

6hest x-ray is abnormal in F;< to A=< of patients. T/T is positi"e in up to ?;< of patients. 2iagnosis relies on culturing TB from morning urine samples (> are recommended) or biopsy of the lesion. The common symptoms are dysuria, haematuria, and urinary fre#uency. /ymptoms may be absent in +;< to >;< of patients. 0enital TB in men may present as a scrotal mass and in women may be asymptomatic or cause pel"ic pain. 6onstitutional symptoms are rare. Extensi"e renal destruction may ha"e occurred by the time 0D TB is diagnosed. Drinalysis is done initially. 7esults commonly show pyuria, haematuria, or proteinuria, although they may be normal. Drine culture for TB may be positi"e in 9;< of patients' > samples for culture impro"e sensiti"ity. The classic finding of sterile pyuria is neither sensiti"e nor specific. 2efiniti"e diagnosis of genital TB is based on tissue biopsy. Pericardial TB 6hest x-ray shows cardiomegaly (in A;< to ?=< of cases) and pleural effusion (in about =;<). E60 is low "oltage (in about +=<) and shows T-wa"e in"ersion (in about ?;<). Echocadiography, 6T, or M7 shows pericardial effusion and thic$ness across the pericardial space. 2iagnosis of pericardial TB re#uires aspiration of pericardial fluid or, usually, pericardial biopsy. ,ericardial fluid is exudati"e with increased leu$ocytes, predominantly lymphocytes. )aemorrhagic effusion is often seen. %8B smear of the fluid is commonly negati"e and cultures are positi"e in =;< to @;< of cases. ,ericardial biopsy offers a higher diagnostic yield. #isseminated TB The diagnosis of disseminated TB concentrates on the organs most li$ely to be in"ol"ed. The most commonly in"ol"ed organs (in order) are lungs, li"er, spleen, $idneys, and bone marrow. ,atients with disseminated TB will typically ha"e constitutional symptoms including fe"er (?;<), anorexia (A9<), and sweats (A@<). f disseminated TB is suspected, chest x-ray (if non-diagnostic, consider a chest 6T), sputum for %8B smear and culture, blood culture for mycobacteria, and first-morning"oid urine for %8B are obtained' lumber puncture and biopsy of superficial lymph nodes are also done if applicable. /putum smear will be positi"e in one-third of patients with culture positi"e in about @;<. T/T is positi"e in only F=< of patients with disseminated disease. %s delays in treatment are associated with increased mortality, a rapid diagnostic test (i.e., faster than culture results) is fre#uently needed. f sputum smears are negati"e and chest x-ray is abnormal, bronchoscopy with transbronchial biopsies are indicated.

f results are non-diagnostic, bone marrow or li"er biopsy is also done. Both ha"e similar sensiti"ities, but bone marrow biopsy may be preferred because of its lower procedure ris$. f thrombocytopenia or leu$openia are present, the sensiti"ity of bone marrow biopsy is increased.
T7E%TME1T %,,7!%6) The basic principles of treatment for extrapulmonary tuberculosis (E,TB) are the same as pulmonary tuberculosis (,TB) with a few exceptions. The goals of treatment of TB are to cure the patient clinically and minimise the chance of relapse, and to pre"ent further transmission of TB to others. Therapy for E,TB re#uires a minimum of @ months of treatment. The treating physician acts in a public health role and is responsible for ensuring that the patient successfully completes treatment. Therefore, many physicians share that responsibility with a local public health department. ,atients can recei"e treatment through direct obser"ation of therapy (2!T) whereby the patient is pro"ided with the tablets and is obser"ed swallowing them. This is often done in con(unction with a local public health department. Treatment consists of an initial intensi"e phase and subse#uent continuation phase. The decision on the use of directly obser"ed therapy as opposed to self-administered daily therapy depends on the resources a"ailable to local public health, collaboration with community partners, and prioritisation of cases. The high priority should generally be gi"en to situations such as treatment failure, drug resistance, relapse, ) * co-infection, current or prior substance abuse, psychiatric illnesses, memory impairment, and cases in children&adolescents. Treatment of drug-resistant TB, especially multidrug-resistant (M27) TB, should be attempted only with expert ad"ice. %lthough there are many TB patients co-infected with ) * globally, expert ad"ice should be sought if the clinician is not familiar with management of TB patients coinfected with ) *. $nitial phase Microbiological confirmation of E,TB can ta$e se"eral wee$s and this delay in treatment initiation may increase mortality in some forms (61/, disseminated, peritoneal). Therefore, antituberculous therapy is initiated based on clinical suspicion after optimal diagnostic samplings. nitial intensi"e-phase treatment in"ol"es the first-line drugs of isonia.id, rifampicin, pyra.inamide, and ethambutol, with drug-susceptibility testing for those agents. $nitial phase for multidrug resistance M27 may be suspected on the basis of historical or epidemiological information. M27 isolates are resistant to at least both isonia.id and rifampicin. n this case, consultation with an expert in treatment of M27 TB is necessary to determine the most appropriate antituberculous therapy.

Continuation phase f the Mycobacterium tuberculosis isolate is sensiti"e to isonia.id, rifampicin, and pyra.inamide, then isonia.id and rifampicin are gi"en for F months in the continuation phase (i.e., @ months of total treatment). Total therapy for ? months is considered for patients with extensi"e s$eletal TB, especially when large (oints are in"ol"ed with slow clinical response. ,atients with 61/ TB recei"e A to :; months of continuation phase (? to :+ months total). ,atients with M27 should ha"e their final regimen based on the results of drug-susceptibility testing, in consultation with an expert. %dministration of therapy on an intermittent basis, as opposed to daily dosing, facilitates 2!T, thereby impro"ing the outcome in patients suitable for this regime. 61/ or pericardial TB ,atients who ha"e 61/ or pericardial TB recei"e ad(uncti"e corticosteroid treatment. ,yra.inamide-unsuitable patients ,yra.inamide is not recommended for patients experiencing acute gout or for pregnant women because of little safety information. Those patients who do not recei"e pyra.inamide during the intensi"e phase should recei"e A months of continuation phase (? months total). 5i"er in(ury /e"eral TB medicines (e.g., isonia.id, rifampicin, and pyra.inamide) are metabolised by the li"er and may potentially cause or exacerbate hepatic in(ury. Mild hepatitis may re#uire only closer monitoring without changes in the standard regimen. )owe"er, se"ere hepatitis while on TB treatment may ma$e it necessary to hold medicines and use an alternate li"er-sparing regimen. f drug-induced li"er in(ury (2 5 ) occurs, potentially hepatotoxic drugs are stopped and alcohol is a"oided. %n asymptomatic, mild increase in %/T occurs in +;< of patients' if this is C=x upper limit of normal (D51) with no symptoms, or C>x D51 with symptoms, TB medicines can be continued but li"er function tests (58Ts) and symptoms are monitored closely. Bhile 58Ts are normalising and symptoms are impro"ing, at least > drugs without hepatotoxic effects (e.g., ethambutol, fluoro#uinolone, and an in(ectable) may be gi"en, especially if the burden of TB disease is more than minimal. Bhen %/T becomes C+x D51, first-line drugs are serially reintroduced one by one, waiting F to A days before adding next drug. Before introducing each new drug 58Ts are chec$ed. f an increase in %/T occurs, the most recently introduced drug is li$ely responsible for hepatitis. Expert opinion should be sought. 7enal insufficiency This complicates treatment as some medicines and their metabolites (e.g., ethambutol,

streptomycin, pyra.inamide) are cleared by the $idneys. 2osing changes are needed. ) *-positi"e ntermittent twice-wee$ly administration not recommended for ) *-positi"e patients with 62FG count C:;; cells&m5. nstead, either a daily or thrice-wee$ly regimen is recommended. /eriously ill TB meningitis 2isseminated TB TB pericarditis TB peritonitis H gastrointestinal TB Bilateral or extensi"e pleurisy /pinal TB with 1eurological complications 0DT TB Type of patient 1ew sputum smearpositi"e ,TB /eriously illII new sputum smear- negati"e ,TB /eriously illII new E,TB /putum smearrelapse /putum smear8ailure /putum smearTreatment after others III positi"e positi"e positi"e default, +)>7>J>GF)>7> 1ot seriously ill 5ymph node TB ,leural effusion Bone excluding spine ,eripheral (oints

6ategory of treatment 6ategory :

7egimen +)>7>J>GF)>7>

6ategory +

+/>)>7>J>E>G:)>7>J>E>G=)>7>E>

6ategory >

1ew sputum smearnegati"e ,TB 1ew E,TB, not seriously ill

1o. before the letters refers to the mos. !f treatment' the subscript after the letters refer to the no. of doses per wee$ ,%T E1T M%1%0EME1T 7espiratory hygiene&cough eti#uette comprises of: -co"ering the nose&mouth with a tissue when coughing or snee.ing' -using tissues to contain respiratory secretions' -spitting into a tissue if spitting is necessary'

-disposing of tissues into the nearest rubbish bin after use' and -performing hand hygiene after contact with respiratory secretions and contaminated ob(ects&materials e.g. tissue ,atient %ccommodation -/ingle room with ensuite facilities -2oor to remain closed -%irborne precautions sign to be placed prominently on entrance to room -1egati"e pressure air-conditioning to be used (if a"ailable) -2o not use a positi"e pressure air conditioning system. f this type of system is installed it must be turned off during the patient4s isolation - f no negati"e pressure is a"ailable and there is no possibility of air currents resulting in TB transmission, the window may be opened (consult with TB or nfection 6ontrol 6oordinator)' and -2o not cohort TB patients in multi-bedded rooms, due to the possibility of multi-drug resistant TB (M27-TB) )and hygiene -)and hygiene to be performed as per the = Moments for )and hygiene -)and hygiene to be performed on lea"ing the room and after remo"al of ,,E using an antiseptic hand wash solution or alcohol based hand rub or gel Mas$s -% particulate filter personal respiratory protection de"ice or ,+&1?= mas$, is a close fitting mas$ worn for %irborne ,recautions, which is capable of filtering ;.>Km particles -% ,+&1?= mas$ must comply with %/&1J/ :A:@ -% mas$ must be discarded once it has been worn, or becomes "isibly soiled or moist, and must not be used again. Bhen the mas$ becomes moist from the wearer, or from contamination, the barrier has been breached and the mas$ is no longer effecti"e -% mas$ must be remo"ed by touching the strings&ties or loops only -The ,+&1?= mas$ (for airborne precautions) should be remo"ed outside the room, after the door has been closed ,atients -,atients must wear a fluid resistant surgical mas$ when lea"ing the room for any reason -,atients on oxygen therapy must be changed to nasal prongs and wear a fluid resistant surgical mas$ o"er the top of the nasal prongs if condition allows -Must be pro"ided with instructions for donning and remo"al of mas$' and ,atients are not re#uired to wear a mas$ when the staff or "isitors are entering their room )ealth 6are Bor$ers -,articulate mas$ (,+ or 1?=) to be worn by all )6Bs entering the room of patients diagnosed or with a pro"isional diagnosis of TB and remo"ed after lea"ing the room -,erform hand hygiene after remo"ing and discarding mas$

*isitors&8amily -*isitors must wear a particulate mas$ (,+ or 1?=) on entering the room and remo"ed after lea"ing the room ,erform hand hygiene after remo"ing and discarding mas$