· granulomatous disease due to infection with Mycobacterium
· great fall in incidence in Western World
· 1900 - 80% infected before age 20
· 1940 - 80% infected after age 50
· 1980 - 2% infected before age 20
· 1990 - 5% infected (due to immigration)
· reduction due to
· improved standards of living
· reduced risk of late progression
· more prompt recognition and treatment of infected cases
· incidence increased in
· Asian immigrants
· aboriginals
· renal transplant patients (300 x normal)
· drug addicts
· AIDS
· 10%-15% of TB is extrapulmonary
· 10% of extrapulmonary is skeletal
· spine 50%
· hip
· knee
· 90% mono articular
· 2 species affect humans
· Mycobacterium tuberculosis (most common)
· Mycobacterium bovis
· thin straight rods
· neither Gram positive nor Gram negative
· acid-fast
· Ziehl-Neelsen technique
· due to waxiness
· significant lipid content in wall
· obligate aerobes
· slow growth
· cultured on egg-yolk with inhibitors of other bacteria (Lowenstein-Jensen medium)
· resistant to chemicals and drying
· produces no toxins or enzymes
· sensitisation occurs 2-4 weeks after innoculation
· indicates infection
· results from delayed (cell-mediated, type IV) hypersensitivity
· indicated by positive tuberculin test
· sensitisation remains present for life
· on first exposure, bacilli act as inert particulate matter
· evoke nonspecific neutrophilic inflammatory response
· phagocytosed by macrophages
· may multiply and drain
· in lymphatics to regional nodes
· in bloodstream to distant sites
· when sensitisation appears, reaction becomes granulomatous
· T cells become sensitised
· induce aggregation and activation of macrophages
· result is formation of granuloma
· consists of
1. aggregation of macrophages
· pallisading histiocytes
· rounded and plump
· called epithelioid cells (vaguely resemble epithelial cells)
2. may also be Langhan’s cells
· multinucleated giant cells
· formed from fusion of macrophages or nuclear division without cytoplasmic division
3. rim of round cells
· lymphocytes
· fibroblasts
4. central caseous necrosis
· combination of liquefactive and coagulation necrosis
· bacteria enters body via
· lung (droplet infection)
· gut (infected milk products)
· conjunctivae or skin (rare)
· inhalation most important
· particles originate from liquid caseum of infected person
· excreted in aerosolised droplets when patient coughs, sneezes and speaks
· most particles trapped by mucociliary escalator of upper respiratory tract
· if particle small enough, reaches respiratory bronchiole
· infection of unsensitised individual
· usually in lung
· occurs in lower part
· subjacent to pleura of fissure between upper and lower lobes
· inhaled particle phagocytosed
· organisms multiply in macrophages
· spread to regional lymph nodes
· characteristic tissue response in affected regions
· in form of tuberculous granuloma
· called primary or Ghon focus
· lesion plus nodes makes up primary or Ghon complex
· usually no clinical illness
· primary site usually heals with
· fibrosis
· calcification
· if does not heal, may progress to
· progressive primary tuberculosis of lung
· distant haematogenous seeding (miliary tuberculosis)
· sequelae of infection
· reservoir of bacilli in nodes
· body sensitised to toxin (positive tuberculin test)
· phase of tuberculous infection arising in previously sensitised individual
· tubercle bacilli may be
· endogenous (reactivation) - more common
· exogenous (reinfection)
· most commonly begins in apical segment of lung
· probably seeded during early phase of bacteraemia
· called Simon’s focus
· favoured by high pO2 of area
· produces minimal granulomatous lesion
· varied course
1. healing, scarring and calfication
· arrested TB
2. spread to other areas of lung
· progressive pulmonary TB
3. spread to pleura
· TB empyema
4. coughed up to involve upper respiratory tree
· tracheobronchial TB
5. swallowed
· intestinal TB
6. disseminated in bloodstream
· miliary TB
7. progression in seeded organ
· tertiary TB
· disease occurs if dormant lesions multiply
· most commonly affects
· lymph nodes (scrofula)
· meninges (TB meningitis)
· kidney (renal TB)
· adrenals (Addison’s disease)
· genital tract (genital TB)
· bones (TB osteomyelitis)
· multiple lesions in 30%
· initial tuberculous infection usually produces no clinical illness
· may be
· slight malaise and fever
· cervical lymphadenopathy
· pleurisy
· variable symptoms with secondary TB
· fevers with night-sweats
· malaise (weakness, loss of appetite)
· weight loss
· cough and haemoptysis
Chest x-ray
· suggestive features
· apical lesion
· multinodular infiltration with cavitation
· only absolute proof is culture of M tuberculosis
· usually from sputum
· early morning specimen
· bronchial washings
· may need multiple specimens
· examine with Ziehl-Neilsen stain
· positive in 30%
· culture for 6 wks
· positive in 80%
Tuberculin skin test
· tuberculin is protein fraction of tubercle bacilli
· if injected into skin, produces cell-mediated immune response in infected patients
· in form of skin thickening
· due to oedema and accumulation of lymphocytes
· 0.1 ml tuberculin solution injected into skin on volar forearm
· test read 48 hrs later
· results are
· positive if skin thickening > 10 mm
· doubtful if 5-10 mm
· negative if < 5 mm
· with BCG (bacillus Calmette-Guerin)
· live attenuated strain of bovine tubercle bacilli
· efficacy questioned
· may not reduce chance for infection
· prevents development of serious disease when infection occurs
· use questionable in areas with low incidence
· invalidates result of tuberculin test
· prevents early detection
Isoniazid
Action
· interferes with DNA synthesis
Side-effects
1. competes with pyridoxine
· results in peripheral neuropathy and anaemia
· combated with pyridoxine administration
2. hepatocellular toxicity
· most serious side-effect
Rifampicin
Actions
· inhibits RMA synthesis
Side-effects
· jaundice
· GIT symptoms
· fever
· combination of isoniazid and rifampicin
· duration of 9 months
· other drugs for resistant organisms
· due to haematogenous seeding
· osseous abscess develops
· due to
· haematogenous seeding of synovium
· spread from bony abscess
· unusual in that infection can cross physis
· synovium thickened and oedematous
· marked effusion
· rice bodies produced
· pannus of granulation tissue spreads across joint
· gradual destruction of articular cartilage
· no proteolytic enzymes
· destruction by pannus
· may be incomplete
· increased vascularity causes local osteoporosis
· healing usually by fibrous ankylosis
Soft tissues
· infection may spread into surrounding tissue
· produces cold abscess
· abscess may
· point at overlying skin
· track along planes and point at distant site
· indolent disease with insidious onset
· long history of mild/ moderate joint pain
· swelling and frequent effusions
· weight loss and night sweats
· thickened synovium
· effusion
· little warmth but not hot, red, active and tender
· severe muscle atrophy
· early
· slight decrease range of motion
· late
· flexion contracture
· joint deformity
· fibrous or bony ankylosis
Bone
· severe osteopenia early
· soft tissue swelling
· may be calcified
· marginal bone erosions
· metaphyseal osteolytic lesion with sclerotic margin
· may cross physis and involve epiphysis
· cartilage space preserved in early stage
· joint becomes disorganized
· resembles Charcot joint
· early cases with no articular cartilage damage
· results of chemotherapy equal to surgery and chemotherapy
· late cases with advanced joint destruction require
· debridement
· fusion
· drug therapy same as for pulmonary TB
· syn. Pott's disease of the spine (1779)
· spine is most common site of osseous involvement in TB (50%)
· no sex or age prediliction
· involves L1 most often
· then with decreasing frequency proceeding in either direction from here
· rare in cervical and sacral spine
· usually involves more than one vertebral body
· affected vertebrae are in contiguity in one segment of spine
· haematogenous dissemination from primary infected visceral focus
· spread is most likely arterial
· rather than via Batson's venous plexus
· bacillus typically settles in paradiscal area of anterior vertebral body
· abscess formation and caseation occurs
· infection may spread to adjacent vertebral discs by means of
· extension of infection beneath anterior and posterior longitudinal ligaments to peripheral discal tissue
· extension of infection through subchondral bone plate and overlying cartilagenous end plate to enter disc
· weakening of bone leading to discal herniation into vertebral body and subsequent spread into disc
· infection can then extend to involve multiple vertebral bodies
· posterior elements rarely involved
· anterior and posterior longitudinal ligaments and periosteum stripped from vertebral bodies
· leads to loss of periosteal blood supply
· this and endarteritis leads to ischaemic infarction and necrosis of involved bone
· vertebral body weakened by destruction and necrosis
· compression fracture occurs
· result is usually sharp kyphotic deformity (gibbus)
· extension usually anterolaterally
· abscess may burrow for long distances
· lumbar abscess may extend beneath psoas fascia to form psoas abscess
· this may extend into groin and thigh
· abscess may penetrate various organs, esp. lung
· may occur from
· pressure from abscess
· pressure from caseous material
· pressure from sequestrum
· ischaemia from spinal artery thrombosis
· progressive kyphosis
· long history of ill health
· backache
· angular kyphos
· cold abscess in loin or groin
· parasthesiae or weakness of legs (Pott's paraplegia)
Plain x-rays
· typical to see more than one vertebra involved (av. 3.4)
· early findings
· narrowing of disc space
· osteopaenia of two adjacent vertebrae
· more advanced disease
· paravertebral shadow from extension of tuberculous granulation tissue and formation of paraverebral abscess
· more obvious bone destruction
· late changes
· collapse of adjacent vertebral bodies into each other
· resulting angular deformity of spine
· healed disease
· increased bone density
· bony fusion of adjacent vertebral bodies
· persisting deformity
· calcification of paravertebral abscesses
CT and MRI
· for investigation of cord compression
· Mantoux test positive
· ESR raised in acute stage
· eradicate or arrest disease
· prevent or correct deformity
· prevent or treat paraplegia
· Medical Research Working Party on Tuberculosis of the Spine set up to investigate several different methods of management
· series of controlled trials carried out in Korea, Rhodesia, Hong Kong and South Africa over past 20 years
Findings
· clinically favourable outcome defined as
· no sinus or clinically evident abscess
· no myelopathy with functional impairment
· full physical activity
· no modification of allocated therapy
· radiographically favourable outcome defined as disease quiescent on x-ray
· bony fusion
· sclerosis
Chemotherapy
· ambulant outpatient chemotherapy very effective
· protocol of 18 months of isoniazid plus PAS
· 88% favourable outcome (96% if those who had modification of allocated therapy but otherwise favourable were included)
· addition of streptomycin did not improve results
· effective alternative is 6 months of isoniazid plus rifampicin
· 92% clinically favourable outcome
· myelopathy showed good response to treatment
· during 10 yr followup, kyphosis increased an average 17 degrees
· usually in 1st 18 months
Rest
· no extra benefit from either rest in bed for six months or application of plaster jacket for nine months
Surgery
· no advantage in simple debridement
· no clear improvement in favourable outcome with radical operation with anterior resection of tuberculous focus and bone grafting
· only advantage was less further bony loss and deformity and more rapid bony fusion
· such surgery carries risks and is not possible in most centres
· supporters argue that radical surgery give
· early complete eradication of infection
· prevention of spinal deformity
Conclusion
· role of surgeon largely diagnostic
· short course ambulatory chemotherapy is mainstay of treatment
· main problem is organisation and supervision of chemotherapy