Extrapulmonary Tuberculosis - Weebly

SHARMA & MOHAN: EXTRAPULMONARY TBpathogens among children46. In England, there hasbeen a decline in LNTB and a rise in NTMlymphadenitis47, and persons of Indian ethnic originwere more often affected than the local residents40,47.Similar results have been reported among nativeAmericans and in persons originating from south eastAsia and Africa48,49. Asians and Hispanic patientsand African American also seem to have a highpredilection for developing mycobacteriallymphadenitis 48,49.Pathogenesis: LNTB is considered to be the localmanifestation of a systemic disease whereas NTMlymphadenitis is thought to be a truly localiseddisease. M. tuberculosis gains entry into the bodyvia the respiratory tract and undergoeshaematogenous and lymphatic dissemination. Hilarand mediastinal lymph nodes are initially involved.This may occur at the time of primary infection ormay occur later in life due to reinfection orreactivation of previous infection. Sometimes, tonsilis an important portal of entry. The infection thenspreads via the lymphatics to the draining cervicallymph nodes. Initially, the nodes are discrete.Periadenitis results in matting and fixation of thelymph nodes. The lymph nodes coalesce and breakdown due to formation of caseous pus. This mayperforate the deep fascia and present as a collar-studabscess. Overlying skin becomes indurated andbreaks down, resulting in sinus formation which mayremain unhealed for years. Healing may occur fromeach of the stages with calcification and scarring. Incontrast NTM, gain entry into the lymph nodesdirectly via oropharyngeal mucosa, salivary glands,tonsils, gingiva or conjunctiva46,50, and lymph nodeinvolvement represents a localised disease.Clinical presentation: LNTB often affects childrenand young adults40-42. Female predilection has beenreported in some studies 40-42,51,52. Patients usuallypresent with slowly enlarging lymph nodes and mayotherwise be asymptomatic. In HIV-negative patients,isolated cervical lymphadenopathy is most often seenin about two-thirds of the patients 40-42,51,52 . Bemet al53 observed that among HIV-negative as well asHIV-positive patients, cervical lymph nodes weremost commonly affected followed by axillary andinguinal lymph nodes. Multifocal involvement was319observed in 39 and 90 per cent among HIV-negativeand HIV-positive patients respectively. In HIVpositive patients, multifocal involvement,intrathoracic and intraabdominal lymphadenopathyand associated pulmonary disease are morecommon 40-42,53,54 . Some patients with LNTB maymanifest systemic symptoms and these include fever,weight loss, fatigue and occasionally night sweats.Patients with mediastinal lymphadenopathy(Fig.2a and 2b) may present with cough anddysphagia 40-42,51-58 . With wider availability ofcomputerised tomographic (CT) scan, it is expectedthat more cases of intrathoracic and intraabdominallymphadenopathy and other associated lesions(Fig.2c and 2d) may be reported.Peripheral tuberculosis lymphadenopathy hasbeen classified into five stages59. These include: (i)stage 1, enlarged, firm mobile discrete nodes showingnon-specific reactive hyperplasia; (ii) stage 2, largerubbery nodes fixed to surrounding tissue owing toperiadenitis; (iii) stage 3, central softening due toabscess formation; (iv) stage 4, collar-stud abscessformation; and (v) stage 5, sinus tract formation.Physical findings depend upon the stage of thedisease. The enlarged lymph nodes may be of varyingsize, are usually firm and may be discrete or matted.If necrosis and abscess formation have taken placethey may become cystic in consistency. The lymphnodes are usually not tender unless secondarybacterial infection has occurred. Physicalexamination may be unremarkable but for palpablelymphadenopathy. Occasionally, lymph node abscessmay burst leading to a chronic non-healing sinus andulcer formation. Classically, tuberculosis sinuseshave thin, bluish, undermined edges with scantywatery discharge. Uncommon manifestationsobserved in patients with mediastinal lymph nodeinvolvement include dysphagia 60,61 , oesophagomediastinal fistula 62-64 , and tracheo-oesophagealfistula 65. Upper abdominal and mediastinal lymphnodes may cause thoracic duct obstruction andchylothorax, chylous ascites or chyluria66,67. Rarely,biliary obstruction due to enlarged lymph nodes canresult in obstructive jaundice 68. Cardiac tamponadehas also been reported due to mediastinal lymph nodetuberculosis69.

320INDIAN J MED RES, OCTOBER 2004Fig.2. Contrast enhanced computerized tomographic (CECT) scan of the chest of a young woman who presented with low gradefever for 3 months, cough and dysphagia showing subcarinal (a) and right hilar (b) lymph nodes. Arrows points to hypodensitywhich indicates necrosis in the lymph node. CECT scan of the abdomen of the same patient showing bilateral psoas abscesses(c) (arrows). Coronal reconstruction of the CECT scan of the abdomen of the same patient showing bilateral psoas abscesses(d) (arrows). CT guided fine needle aspirate from the psoas abscess revealed numerous acid-fast bacilli.

SHARMA & MOHAN: EXTRAPULMONARY TBNontuberculous mycobacterial lymphadenitis: Verylittle is known regarding lymphadenitis due to NTMfrom India. In the western literature, NTMlymphadenitis has often been described in children.Both sexes are equally affected 48,50,59,70. Constitutionalsymptoms seldom develop and the disease generallyremains localised to the upper cervical area. Ifuntreated, the nodes often progress to softening,rupture, sinus formation, healing with fibrosis andcalcification 48,50,59,70.Pleural effusion and empyema thoracisTuberculosis pleural effusion is categorised asextrapulmonary despite an intimate anatomicrelationship between pleura and the lungs71-75.321and intercostal tenderness. Occasionally, tuberculosisempyema may present as a chest wall mass or drainingsinus tract (tuberculosis empyema necessitatis).Abdominal tuberculosisAbdominal tuberculosis is the term used toencompass TB of the gastrointestinal tract,peritoneum, omentum, mesentery and its nodes andother solid intra-abdominal organs such as liver,spleen and pancreas76. Peritoneal and intestinal TBhave been covered in another review article publishedin this issue of the journal 77. Hence, TB at otherabdominal sites such as hepatobiliary, pancreatic andsplenic tuberculosis will be covered.Hepatobiliary, pancreatic and splenic tuberculosisPathogenesis: It is thought that a small subpleuralfocus ruptures into the pleural space, setting up aninteraction between the tubercle bacilli or theirspecific components inducing a delayedhypersensitivity reaction. Recent evidence suggeststhat patients with TB pleural effusion havesignificantly higher levels of IFN-γ in the pleuralfluid as compared to peripehral blood thus exhibitinglocalisation of predominantly Th1-type immunity inthe pleural fluid75. Rupture of a cavity containingcaseous material into the pleural space results inempyema thoracis. Less often, rupture of caseousparatracheal lymph nodes, paravertebral abscess orosteomyelitis of the ribs can result in empyemathoracis.Clinical features: TB pleural effusion usuallypresents as an acute illness and the symptom durationranges from a few days to few weeks. Most patientscomplain of pleuritic chest pain, non-productivecough and dyspnoea. Majority of the patientsmanifest fever, though a few may not have fever.Occasionally, the onset may be less acute, with onlymild chest pain, low-grade pyrexia, cough, weightloss and loss of appetite.Patients with tuberculosis empyema present withchest pain, breathlessness, cough with expectoration,fever, and toxaemia. Anaemia and hypoproteinaemiaare often present. Physical examiantion may revealdigital clubbing, clinical findings suggestive of effusionHepatobiliary and pancreatic TB are rare and areoften associated with miliary tuberculosis, and occurmore often in immunocompromised patients 78. Theclinical manifestations are non-specific and dependon the site and extent of disease. Anorexia, malaise,low grade fever, weight loss, night sweats, malaena,pancreatic mass or abscess or obstructive jaundicehave all been described 79,80 . Pancreatic TB maypresent as acute or chronic pancreatitis or may mimicmalignancy79,80. Isolated splenic tuberculosis is veryrare in immunocompetent persons. Splenomegaly canoccur in patients with disseminated/miliarytuberculosis. Splenic tuberculosis presents ashypersplenism or splenic abscess or as a solitarysplenic lesion81. Multiple tuberculosis abscesses havebeen described in patients with HIV infection82,83. Preoperative diagnosis of tuberculosis at these obscuresites is difficult and the diagnosis is often confirmedon histopathological examination of excisedspecimen.Neurological tuberculosisNeurological tuberculosis may be classified intothree clinico-pathological categories: tuberculosismeningitis (TBM), tuberculoma, and arachnoiditis84-86.Tuberculosis meningitisTBM accounts for 70 to 80 per cent of cases of

322INDIAN J MED RES, OCTOBER 2004neurological tuberculosis84-86. A majority of cases ofTBM are caused by M. tuberculosis. Isolated casesof meningitis caused by NTM have also beendocumented86. Neurological tuberculosis is invariablysecondary to tuberculosis elsewhere in the body. Inthe bacteraemic phase of primary lung infection,metastatic foci can get established in any organ, whichcan become active after a variable period of clinicallatency. The critical event in the development ofmeningitis is the rupture of a subependymally locatedtubercle (Rich focus) resulting in the release ofinfectious material into the subarachnoid space87.Whether the critical subependymal tubercle developsduring primary haematogenous dissemination or dueto secondary haematogenous spread from an area ofextracranial extrapulmonary tuberculosis is not clear.The following features comprise the salientpathological features of TBM: (i) inflammatorymeningeal exudate; (ii) ependymitis; (iii) vasculitis;(iv) encephalitis; and (v) disturbance of cerebrospinalfluid (CSF) circulation and absorption.Clinical features: In the developing world, TBM isstill a disease of childhood with the highestincidence in the first three years of life86. The diseaseusually evolves gradually over two to six weeks.However, acute onset has also been described. Theprodromal phase lasts for two to three weeks andis characterised by a history of vague ill-health,apathy, irritability, anorexia and behaviouralchanges. With the onset of meningitis, headache andvomiting become evident and fever develops. Focalneurological deficits and features of raisedintracranial tension may precede signs of meningealirritation. Focal or generalised seizures, areencountered in 20 to 30 per cent of patients. Cranialnerve palsies can occur in 20 to 30 per cent ofpatients, the sixth nerve involvement being the mostcommon 86,88. Complete or partial loss of vision is amajor complication of TBM. Various mechanismspostulated for the loss of vision include presence ofexudates around the optic chiasma, arteritis,compression of the anterior visual pathways due tohydrocephalus or tuberculoma, and ethambutoltoxicity among others. In untreated cases,progressive deterioration in the level ofconsciousness, pupillary abnormalities andpyramidal signs may develop due to increasinghydrocephalus and tentorial herniation. The terminalillness is characterised by deep coma anddecerebrate or decorticate posturing. Withouttreatment, death usually occurs in five to eightweeks.According to the severity of the illness, patientswith TBM can be categorised into three clinicalstages. The clinical staging helps to optimise therapyand to predict the prognosis. The prognosis of TBMis determined by the clinical stage at the time ofinitiation of treatment. The Medical ResearchCouncil89 and Kennedy and Fallon systems 90 stagethe patients into three categories: stage 1, patientsare conscious and oriented with or without signs ofmeningeal irritation, but no focal neurological deficit;stage 2, patients with altered sensorium or focaldeficits; and stage 3, patients are comatose and havedense deficits. During the last two decades, theclinical presentation of TBM has changed 91,92 .Atypical presentations include acute meningiticsyndrome simulating pyogenic meningitis,progressive dementia, status epilepticus, psychosis,stroke syndrome, locked-in-state, trigeminalneuralgia, infantile spasm and movementdisorders 86,88,93.Intracranial tuberculomas and single, small,enhancing brain lesionsTuberculoma is a mass of granulation tissue madeup of a conglomeration of microscopic smalltubercles 84. The size of cerebral tuberculomas ishighly variable. In most cases their diameters rangefrom a few millimetres (mm) to three to fourcentimeters (cm) 94 . Intracranial tuberculomas inpatients under the age of 20 yr are usuallyinfratentorial, but supratentorial lesions predominatein adults. Solitary tuberculomas are more frequentthan multiple lesions. Although their frequency hasdecreased in the last two to three decades,tuberculomas still constitute about 5 to 10 per centof intracranial space occupying lesions in thedeveloping world 86,95. Patients with epilepsy whoshowed ring enhancing single CT lesions have beendescribed almost exclusively from India96-100. Theenhancing lesion is 2 cm, but may showconsiderable oedema around it. Tuberculosis has been

SHARMA & MOHAN: EXTRAPULMONARY TB323Fig.3a and 3b. Chest radiograph (postero-anterior view) of a patient with tuberculosis pericardial effusion showing a globularheart shadow (a) before treatment. Chest radiograph taken 9 months after antituberculosis treatment (b) reveals considerableresolution of the pericardial effusion.implicated as one of the causes for this form ofpresentation.Neurological involvement is five times morefrequent in HIV-positive compared to HIV-negativepatients101,102. HIV infected patients account for over50 per cent of the cases of TBM seen in theindustrialised nations101,102. Bishburg et al102 reportedthat intravenous drug abusers with AIDS exhibitedincreased risk of developing neurologicaltuberculosis and brain abscesses. Yechoor et al103found that 20 of the 31 patients (65%) identified asdefinite or probable TBM over a 12 yr period wereinfected with HIV. In general, HIV status does notalter the clinical manifestations, CSF findings andresponse to therapy 103 . However, HIV-positivesubjects with TBM can have normal CSF morefrequently101-103.Pericardial tuberculosisPericardial involvement in tuberculosis may resultin acute pericarditis, chronic pericardial effusion,cardiac tamponade or pericardial constriction104-107.In India, TB accounts for nearly two-thirds of thecases of constrictive pericarditis104-106. TB has beenreported to be the cause of acute pericarditis in fourper cent of patients in the developed world and 60 to80 per cent of the patients in the developingworld 104-110. TB pericarditis has been estimated tooccur in one to eight per cent patients withpulmonary tuberculosis 111,112 . In industrialisedcountries TB pericarditis is not so common exceptin patients with HIV infection and AIDS104.Pericardial involvement most commonly resultsfrom direct extension of infection from adjacentmediastinal lymph nodes, or through lymphohaematogenous route from a focus elsewhere. TBpericarditis has the following stages: (i) dry stage;(ii) effusive stage; (iii) absorptive stage; and (iv)constrictive stage 112 . The disease may progresssequentially from first to fourth stage or may presentas any of the stages. Sometimes, pericardial TB canpersent as fever with no clinical localisation. Presenceof cardiomegaly on the chest radiograph may be theonly diagnostic clue and echocardiography mayreveal pericardial effusion.Clinical features: TB pericarditis occurs mostcommonly in the third to fifth decade of life. Thedisease has an insidious onset and presents with fever,malaise and weakness. The patients may manifestpericardial rub, vague chest pain or cardiomegaly ona chest radiograph (Figs.3a and 3b). Acute onset hasbeen reported in 20 per cent of patients and somepatients can present with cardiac tamponade106,107.Dyspnoea, cough, and weight loss are commonsymptoms. Chest pain, orthopnoea and ankle oedemaoccur in nearly 40 to 70 per cent of patients113-116.Pericardial effusion: Patients with TB pericarditisusuallypresent with chronic pericardialeffusion104,113,115,116. Patients may also present acutelywith cardiac tamponade and may manifest severedistress, retrosternal compression, tachycardia and

324INDIAN J MED RES, OCTOBER 2004Fig.3c, 3d and 3e. Contrast enhanced CT scan of the chest of a patient with constrictive pericarditis showing thickened pericardium(black arrow) and dilated right atrium (white arrow) (c). Right and left ventricular pressure tracings (paper speed 100 mm/sec and100 mm Hg gain) of the same patient showing markedly elevated and equal diastolic pressures with mild elevation of right ventricularsystolic pressure (45 mm Hg) (d). Operative photograph showing thickened pericardium (e).raised jugular venous pressure (JVP) with blunt γdescent113,115,116, distant heart sounds, pericardial ruband pulsus paradoxus may be evident.Effusive constrictive pericarditis: In patients witheffusive constrictive pericarditis, constriction can bedue to thickening of either the visceral or the parietalpericardium. Cardiomegaly, pedal oedema and raisedJVP with a blunt γ descent may be present. Afterremoval of fluid, JVP is still raised with a prominentγ descent. This stage could occur within few weeksof TB pericarditis. With effective antituberculosistreatment, some cases may resolve. Commonly,chronic constriction ensues107,117,118.Chronic constrictive pericarditis: In patients withchronic constrictive pericarditis, the inflow of bloodis impeded due to thickened unyielding pericardium,especially in the late diastole (Figs 3c, 3d and 3e).Consequently, these patients have systemic as wellas pulmonary venous congestion and manifestexertional dyspnoea, orthopnoea, ankle oedema andascites. Cardiac output is mildly reduced at rest.Tachycardia, raised JVP with a prominent y descentoccur. The JVP may rise further on inspiration(Kussmaul’s sign). Pulsus paradoxus is seen in lessthan one-third of cases and signifies presence of somefluid or a relatively elastic pericardium. Cardiac sizeis normal. A systolic retraction of apex can beevident104. A pericardial knock may be present butmurmurs are not common. The ascites isdisproportionate to the oedema (ascites praecox)104.Severe elevation of venous pressure may result incongestive splenomegaly and protein losingenteropathy resulting in hypoalbuminaemia. Aftermany years of hepatic venous congestion cardiaccirrhosis may develop in some patients. The diseaseworsens gradually and in chronic cases, significantmyocardial atrophy occurs due to extension ofinflammation and possibly disuse of the muscle. Suchpatients have suboptimal improvement and highermortality with pericardiectomy104.

SHARMA & MOHAN: EXTRAPULMONARY TB325Fig.4. Magnetic resonance imaging (MRI) scan of the dorsolumbar spine, (sagittal view, T1 weighted image) showing centralhypointense lesion (arrow) with reduced vertical height of the vertebra (a). MRI scan of the dorsolumbar spine (sagittal view, T2weighted image) showing destruction of D10 and D11 vertebrae (arrow), reduction in the intervening disc (inset, arrow) withanterior granulation tissue and cord compression (b).Bone and joint tuberculosisSkeletal tuberculosis is a haematogenous infectionand affects almost all bones. Tuberculosis commonlyaffects the spine and hip joint119,120. Other sites ofinvolvement include knee joint, foot bones, elbowjoint and hand bones. Rarely, it also affects shoulderjoint. Two basic types of disease patterns have beenobserved: granular and exudative (caseous). Thoughboth the patterns have been observed in osseous andsynovial tuberculosis infection, one form maypredominate.Spinal tuberculosis (TB spine) is the mostcommon form of skeletal tuberculosis. Majority ofpatients are under thirty years of age at the time ofdiagnosis. Constitutional symptoms such asweakness, loss of appetite and weight, evening riseof temperature and night sweats generally occurbefore the symptoms related to the spine manifest.Lower thoracic and lumbar vertebrae are the mostcommon sites of spinal tuberculosis followed bymiddle thoracic and cervical vertebrae. Usually, twocontiguous vertebrae are involved but severalverebrae may be affected and skip lesions are alsoseen. The infection begins in the cancellous area ofvertebral body commonly in epiphyseal location andless commonly in the central or anterior area ofvertebral body (Figs 4a and 4b). The infection spreadsand destroys the epiphyseal cortex, the intervertebraldisc and the adjacent vertebrae (Fig.4b). It may spreadbeneath the anterior longitudinal ligament to reachneighbouring vertebrae. The vertebral body becomessoft and gets easily compressed to produce eitherwedging or total collapse. Anterior wedging iscommonly seen in the thoracic spine where the normalkyphotic curve accentuates the pressure on theanterior part of vertebrae. The exudate penetrates theligaments and follows the path of least resistancealong fascial planes, blood vessels and nerves, todistant sites from the original bony lesion as coldabscess. In the cervical region, the exudate collectsbehind prevertebral fascia and may protrude forwardas a retropharyngeal abscess. The abscess may track

326INDIAN J MED RES, OCTOBER 2004down to the mediastinum to enter into the trachea,oesophagus or the pleural cavity. It may spreadlaterally into the sternomastoid muscle and form anabscess in the neck119,120.patients cord dysfunction may occur due to nonmechanical causes 119,120 .Clinical presentation of tuberculosis of the hip andknee joints depends on the clinicopathological stageand each stage has a definite pattern of clinical

genitourinary tuberculosis - laryngeal tuberculosis - lymph node tuberculosis - miliary tuberculosis - neurological tuberculosis - pericardial tuberculosis - tuberculosis in otorhinolaryngology - tuberculosis meningitis - tuberculosis pleu