Moderators: Dr. K. Krishnan Unni and Dr. Franco Bertoni
Case 4 -
Tuberculosis of Knee
Dr. Nirmala Jambhekar
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28 year old male history of pain in the right knee region for the past four months
Case 4 - Slide 1
Tuberculosis of Knee
Tuberculosis of Bone & Joints
In many other parts of the world especially in the Asian countries Tuberculosis has always remained an
important cause of mortality and morbidity. Tuberculous osteomyelitis was found to be the single most
frequent disease affecting the musculoskeletal system as observed in an Indian Bone Registry. Out of
2557 biopsy evaluated specimens of various musculoskeletal sites, 57.2% cases were diagnosed as due to
tuberculous infection. But to quote Dr Bullough " in developed countries tuberculosis has become
unusual enough that there is a real risk that it may remain clinically undetected " . However
Tuberculosis is a re-emerging disease in the western world due to global migration and its association
with AIDS. The fact that 25% of non-tumourous lesions of the bone particularly infections mimic bone
tumours is an additional reason to study tuberculosis of bone.
Pulmonary disease is by far the most common manifestation of tuberculous infection and it is
responsible for more than to two–thirds of the total disease burden . The remaining cases manifest
clinical symptoms due to extrapulmonary involvement often affecting the Lymph nodes, the
musculoskeletal system, the central nervous system, the Genitourinary system , the intestines especially
the ileocaecal junction.However vitually every organ in the body can be affected by tuberculosis thus
leading to protean clinical manifestations.
Osteoarticular tuberculosis is the result of haematogenous spread from a primary pulmonary focus
though the pulmonary lesion may be latent , healed or quiescent and not clinically manifest at the time
of presentation of the muculoskeletal disease. Musculoskeletal tuberculosis can affect patients of any
age and either sex with equal frequency. Almost half of the osseus tuberculous lesions occur in the
spine followed by the hip joint and the knee joint which constitute the second and third most frequent
sites.However the wrist joint , small bones of the hands and feet, clavicle, sternum and practically
almost any bone in the body could get affected. In the spine half of the lesions affect the
thoracolumbar vertebrae. Vertebral involvement begins either in the bone adjacent to the disc , or in
the anterior portion, or centrally to involve the body of the vertebra .Destruction of the vertebra at
these specific vertebral sites respectively leads to either loss of disc space, wedging of the anterior
portion, or total collapse leading to gibbus. In a given patient several vertebrae ,sometimes away from
the site of the original vertebra, may show involvement due to extensive subligamentous spread of
disease. In long bones the disease starts either in the subchondral epiphyseal bone, or the metaphysic,
whereas in the joint the disease often starts at the site of synovial reflexion close to the periphery
of the articular cartilage. Eventually both bone and joint are involved if the disease is not
controlled early by treatment.
The clinical symptomatology varies with the site of involvement but pain , restriction of movement ,
swelling are often present and f requently the local symptoms are associated with constitutional
symptoms such as fever, especially evening rise of temperature, fatigue and tiredness. Neurological
symptoms such as radiculopathy,or paraplegia due to compression of the nerve roots or spinal cord are
well-known .The swelling is the result of synovitis , effusion , or due to the mass formed by the
degenerated and necrotic material ( caseous debris ). The latter may track along fascial planes and
produce a soft fluctuant swelling known as a "cold abscess" at a site distal from the site of primary
osseus disease. This feature is not uncommon with vertebral involvement wherein the paraspinal necrotic
material trickles down to the lateral thoracic cage or the groin.. Tuberculous lesions are generally
not associated with the redness, pain and heat of pyogenic diseases and hence the term "cold abscess".
These abcesses may burst through the dependent area in the skin and produce non healing discharging
Radiologically several appearances are known depending on the site of disease , the extent of
disease, and the complications if present. To state briefly reduction of joint space, soft tissue
swelling , erosion of cartilage , marginal erosion of bone, and osteopenia are frequently seen . Late
stages reveal destruction of subchondral bone leading to osteolytic cavities and feathery sequestrae
and eventually deformity due to collapse of bone and and fibrosis of joints.
Gross examination of the the synovium shows oedema, congestion and fine granularity representing the
tubercles.This granulation tissue is also seen in the soft tissue . The involved bone reveals destruction
with separation and engulfment of the articular cartilage in the tuberculous granulation tissue Advanced
disease reveals large areas of cheesy – caseous- necrotic debris – in which degenerating cartilage and
dead bone are seen. The subchondral bone may get exposed..
The nature of the material received for diagnosis could be a needle core biopsy , a curettage or a
needle aspirate The micoscopic diagnosis of tuberculous infection is achieved by identifying the
tuberculous granulation tissue comprising the typical tubercles which show a central area of caseous
necrosis surrounded by ovoid to plump epitheliod histiocytes having " slipper-like nuclei " . The
characteristic Langhans giant cells wherein the nuclei are arranged peripherally in a horseshoe-like
pattern are variably seen .The lesions abound in lymphocytes. In addition neutrophils, plasma cells.
dead bone fragments may be variably present.
Numerous variations in this theme occur and this leads to difficulty in the correct recognition of
tuberculous infection in general - but particularly in the bone which often does not show all the
features mentioned above. The granulomas are sometimes not well formed and scattered epithelioid cells
are the only feature seen . Or else, there may be extensive caseous necrosis without any identifiable
giant cells or epithelioid cells. This problem is particularly acute in case of small needle biopsies
from difficult sites such as the spine .In such a situation differentiating Tuberculous and pyogenic
infection and also recognizing reactive or necrotic tissue adjoining a metastatic deposit or a
degenerative condition becomes very difficult.
Cytological examination of the Fine needle aspirate of the soft necrotic material is often a useful
method to establish the diagnosis. When adequate representative material is received it often reveals
the typical epithelioid granulomas in addition to caseous necrosis and giant cells.
The mycobacterial strains causing tuberculosis comprises organisms listed in the " tuberculosis
Complex " namely M.tuberculosis, M. Africanum, and M. Bovis. Traditional methods of tissue examination,
which includes culture, microscopy, and Zeihl-Neelson stain are considered as "gold standards" but these
are not always successful for confirmation of tuberculous infection especially of extra-pulmonary origin.
Culture as well as acid fast staining often show low positivity or negative results In contrast, rapid
techniques based on nucleic acid amplification such as PCR are more sensitive and specific as they
attempt to detect specific DNA sequences of the organism present in extremely miniscule quantities. The
scope of doing PCR on formalin fixed paraffin embedded decalcified tissues for detecting tuberculous
infection has remained largely unexplored The identification of the exact species by modern methods will
help distinguish the organisms of the " Tuberculosis complex ' from the organisms responsible for disease
caused by Mycobacteria other than tuberculosis , namely "MOTT".
A detailed account of the scope and limitations of the various microbiological methods and
molecular techniques are beyond the scope of this case presentation.
The treatment for osteoarticular tuberculosis is essentially with antitubercular drugs employing a
three-drug regimen . The treatment needs to be taken for about 10months. Complete recovery can be
expected in early cases. More advanced disease needs surgical intervention either to tackle residual
disease or correct deformity.
The differential diagnosis of Tuberculosis includes diseases caused by MOTT, Fungi, sarcoid ,
brucellosis , tuberculoid Leprosy and granulomas secondary to amyloid deposits.
MOTT infection ( or infection by Atypical mycobacteria ) is due to the Environmental strains of
mycobacteria , often introduced accidentally by trauma due to puncture wounds, surgical incisions,
injury due to thorns, or by working in water contaminated with infected marine animals/fish, or from
the soil. Various species of mycobacteriae such as avium, fortuitium, marinum, kansasii, cholonae,
gordonii, xenopi, malmoense etc have been demonstrated in specific situations. These diseases may or
may not show typical granulomas and often show large number of histiocytes, and chronic inflammatory
cells. MOTT infection is essentially managed by surgical debridemant of the affected tissue.
Fungal granulomas are often associated with an eosinophil rich exudate and the giant cells are often
of the foreign body type, with no evidence of caseous necrosis. Cryptococci , candidia, blastomycosis
and other fungi have been incriminated in fungal granulomas of the bone. Identification of the fungal
bodies on morphology, and additionally culture, or immunostains if available helps to clinch the
Sarcoidoisis usually causes hard non- caseating granulomas devoid of Langhans giant cells.
Clinical and biochemical methods help separation from tuberculosis.Brucellosis and leprosy are less
- Chitale AR, Jambhekar NA. Report of bone registry, 1970-1982. Indian J. Pathol Microbiol 1987; 30: 201-218.
- Bullough PG . Mycobacterial Infections (Tuberculosis ) ch 5 Bone & Joint infection; Orthopaedic Pathology, ed four 2004 Mosby pp 138-142
- Tuli SM . Tuberculosis of the Knee joint ch 9 In Tuberculosis of the skeletal System ( Bones, Joints, Spine and Bursal sheaths ); Section II ; Extra spinal Regional Tuberculosis, ed three 2004 Jaypee Brothers Medical Publishers ( P ) Ltd pp 108-126
- Griffiths JF, Kumta SM, Leung PC, Cheng JCY , et al . Imaging of Musculoskeletal tuberculosis : A new Look at an old disease.Clin Orthop, 398, 32-39, 2002
- Hoffman, EB, Allin J , Campbell, JAB, Leisegang FM. Tuberculosis of the knee Clin . Orthop. 398 , 100-106,2002
- Enneking WF, The issue of the biopsy (editorial) J Bone Joint Surg 64A: 1119-1120,1982
- Mondal A. Cytological diagnosis of vertebral tuberculosis with fine needle aspiration biopsy. J Bone Joint Surg 76A , 181-184,1994
- Vohra R, Kang HS, Dogra S, Saggar RR, Sharma R. Tuberculous osteomyelitis. J Bone Joint Surg [Br] 1997; 79-B: 562-566.
- Berk RH, Yazici M, Atabey N, OzdamAr OS, Pabuccuoglu U, Alici E. Detection of mycobacterium tuberculosis in formaldehyde solution-fixed, paraffin-embedded tissue by polymerase chain reaction in Potts disease. Spine1996; 21: 1991-1995.
- In press )