Case 4 -

Tuberculosis of Knee Dr. Nirmala Jambhekar

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Case History: 28 year old male history of pain in the right knee region for the past four months Case 4 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Diagnosis : Tuberculosis of Knee Summary : 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 sinuses. 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. Use mouse to enlarge 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. Use mouse to enlarge 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 subtype 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 common aetiologies. Recommended Reading 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 )