Musculoskeletal Tuberculosis: The Great Mimic

Dr. Jonathan Stein, PGY3
Rheumatology Rounds
August 23, 2005

Outline
TB Background & Epidemiology Pathophysiology of Infection MSK Tuberculosis Use of TNF Inhibitors Summary

In 1882, German microbiologist Robert Koch isolated a rod-shaped bacterium now called Mycobacterium tuberculosis, or simply, the tubercle bacillus.
www.lung.ca/tb/tbtoday/

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Mycobacteria Tuberculosis Aerobic slow growing bacteria acquired by inhalation of aerosolized droplets Approximately 80% of non-HIV±related TB cases present with pneumonitis TB may spread to regional lymph nodes and then throughout the body Among patients who have HIV. . two thirds present with extra-pulmonary involvement.

lung.http://www.ca/tb/tbhistory/ .

Epidemiology Incidence: 8 million new cases per year Prevalence: 1/3 of the world's population Untreated. 1/3 of patients who have active TB die within 1 year and half die within 5 years TB remains a leading infectious killer and causes 2 million deaths annually .

S. 6 cases/100.Epidemiology Canada 3 cases/100.000 population .000 population Spain 25 cases/100.A.000 population Sub-Saharan Africa 300 cases/100.000 population U.

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TB in Canada 1952 .INH developed http://www.lung.ca/tb/tbtoday .

lung. http://www.ca/tb/tbtoday/ .TB in Canada Major causes of death in Canada in 1926. and less than 1% in 1990-included under "infectious diseases. Tuberculosis accounts for 7% of deaths in 1926. and in 1990.

ca/tb/tbtoday/ .TB in Canada Distribution of reported TB cases among population groups in Canada.lung. www. in 1996.

lung. http://www. it was caught before it spread.ca/tb/tbhistory/ .Public education and awareness campaigns played a large part in convincing the general public to show up at TB clinics. By surveying the entire population for tuberculosis.

Immune Defense Against Tuberculosis Ingestion of organisms by pulmonary macrophages Cell-mediated immunity (CD4+T cells) Cytokine-mediated activation of macrophages (TNF.. IFN . IL-12 Granulomas: contain organisms preventing their spread .

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Latent Tuberculosis 95% of adults control the initial infection TB is not eradicated 10% of patients with latent TB infection reactivate and become symptomatic .

Tuberculous Seeding Pulmonary (75%)  Extra-pulmonary (25%)  MSK Lymph nodes Reproductive / urinary CNS Peritoneum Liver/spleen .

Clinical Symptoms Fatigue Weakness Weight loss Anorexia Low grade fever Night sweats Productive cough Hemoptysis .

http://www.lung.ca/tb/tbtoday .

Musculoskeletal TB .

weight bearing surfaces initially preserved .Musculoskeletal TB 1% to 5% of all patients with TB Men > women Hematogenous seeding most likely through arteries Disease starts in bone or synovial membrane Articular cartilage destruction begins peripherally.

Tuberculous Spondylitis Pott s Disease 

Most common site of MSK involvement (50%) Thoracic spine > Lumbar > Cervical Hematogenous spread Vertebral bodies have both anterior and posterior arterial supply 

 

Musculoskeletal TB

Pathophysiology Of Tuberculous Spondylitis Vuyst. Imaging features of musculoskeletal tuberculosis. . 2003. D. et al.

Tuberculous spondylitis Clinical Symptoms:     Low grade evening fever Loss of appetite with weight loss Progressive local pain Difficulty in daily functioning due to painful and restricted spinal mobility Affection of the nervous system's function  .

Clinical orthopedics and related research.Tuberculous Spondylitis Radiological Findings Griffith. J. Imaging of Musculoskeletal Tuberculosis: A new look at an old disease. . 2002.

J. 2002. Imaging of Musculoskeletal Tuberculosis: A new look at an old disease. Clinical orthopedics and related research.Imaging Features that Favor Spinal TB Rather than Neoplastic Disease Griffith. .

warm or painful as other abscesses Hidden deep inside the body May burst out leaving behind a track. pus   . or sinus. which discharges sinus.Tuberculous spondylitis Cold Abscesses  Not as hot.

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Tuberculous spondylitis .

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lung.http://www.ca/tb/tbhistory/ .

extend to proximal thigh Present with groin mass In thoracic region mediastinal mass posterior    .Paraspinal Infection  Abscess occurs in 70% of patients with spinal TB (epidural extension) Lumbar region psoas abscess are large.

et al. . Pyogenic Vuyst. 2003.TB vs. Imaging features of musculoskeletal tuberculosis. D.

glenohumeral. Transphyseal spread not found in pyogenic arthritis . SIJ. sternoclavicular Primary TB metaphyseal focus crosses the epiphyseal plate. wrist.Tuberculous Arthritis Monoarticular Most common: hip and knee Less common: elbow.

  juxta-articular osteoporosis peripherally located erosions. iii. gradual joint space narrowing .Tuberculous Arthritis  Reactive hyperemia results in osteoporosis Leads to erosions. bone destruction Phemister s triad: i. ii.

Tuberculosis of the Hip     15% of all cases of osteoarticular Tb Age of presentation ~ 20 s and 30 s Presents with limping. night pain Painful. inflammatory trochanteric bursitis that may proceed to erosion of the bone .

2002. S. Osteoarticular Tuberculosis: Extraspinal Tuberculosis. .Tuberculosis of the Hip Babhulkar. Clinical orthopedics and related research.

.Babhulkar. S. Osteoarticular Tuberculosis: Extraspinal Tuberculosis. 2002. Clinical orthopedics and related research.

S.Babhulkar. Osteoarticular Tuberculosis: extra-spinal Tuberculosis Clinical orthopedics and related research. . 2002.

and osteonecrosis.Tuberculosis of the Hip  DDx: transient synovitis. traction. If not treated. progressive pattern of destruction Treatment: drug therapy. osteoarthritis. rheumatoid arthritis. and supervised mobilization produces good results in patients with early stages of the disease   .

Tb Tenosynovitis   Synovial membrane of tendon sheaths Flexor or extensor tendons of hands most common Tendon. synovium or both may be thickened and hyperemic Spread to soft tissues. bones and joints Biopsy or synovectomy may be required    .

et al. .Tuberculous Dactylitis Vuyst. 2003. Imaging features of musculoskeletal tuberculosis. D.

Cervical Tuberculosis Griffith. . Clinical orthopedics and related research. J. 2002. Imaging of Musculoskeletal Tuberculosis: A new look at an old disease.

http://www.lung.ca/tb/tbhistory/ .

ca/tb/tbhistory/ .http://www.lung.

Latent TB & TNF Inhibitors Cytokine-mediated activation of macrophages and TNF.production leads to granuloma Granulomas contain organisms and prevent their spread TNF inhibitors ± increased incidence of TB reactivation .

respiratory tract 21%. urinary 11%. Gomez-reino. Treatment of Rheumatoid Arthritis with Tumor Necrosis Factor. skin 13%. 2003. 48(8): 2122-2127 . Arthritis & Rheumatism. Inhibitors May Predisopose to Significant Increase in Tuberculosis Risk. J.Multicentre Active-Surveillance     Observational study 1540 patients 71 participating centres in Spain 85% infliximab. 14% etanercept Infections in 118 patients.

15 of these were RA patients.Multicentre Active-Surveillance  17 cases of TB in patients with infliximab.000 (year 2000)   . Liver-spleen. 65% had extrapulmonary sites (LN. disseminated) Estimated incidence of TB with infliximab in RA patients: 1893 per 100.

Recommendations:  Treat for 9 months with 5mg/kg body weight of INH if: 1) History of untreated TB. or exposure to active case of TB 2) CXR indicative of prior TB infection 3) Reaction >5mm on PPD skin test .

Study Limitations   Authors did not report capture rate What is the completeness of the database? What proportion of patients receiving TNF inhibitors registered?  .

Lithograph http://www. 1934.Elizabeth Olds (1896-1991)Tuberculosis Tests for Children.ca/tb/tbhistory/ .lung.

Infliximab Monoclonal antibody with high affinity and specificity for its target cytokine Binds to soluble TNF monomers and trimers. forming a stable complex Prevents TNF-alpha from binding to its receptor and triggering a biological response . as well as membrane-bound TNF-alpha.

Infliximab vs.  . Etanercept  Mice with only transmembrane TNF are relatively resistent against mycobacteria Transmembrane signalling is preserved with use of etanercept and may provide sufficient residual protective immunity against TB to prevent reactivation.

Adalimumab (Humira)  Adalimumab is a recombinant IgG antibody Binds to TNF-alpha. not to lymphotoxin (TNF-beta) Blocks its interaction with the p55 and p75 cell surface TNF receptors Modulates responses that are regulated by TNF.. levels of adhesion molecules responsible for leukocyte migration    .e. i.

Semin Arthritis Rheum. . 2005.Hochberg. M. The Benefit/Risk Profile of TNF-Blocking Agents: Findings of a Consensus Panel.

TNF inhibitors Increase Risk of TB Reactivation  TB skin test +  Must rule out active disease CXR. sputum  If latent TB. 4 medications  Start TNF inhibitor after completion  High index of suspicion for reactivation . INH for 9 months  Start TNF-I after 1 month of INH  If active disease.

M. . 2005.Hochberg. Semin Arthritis Rheum. The Benefit/Risk Profile of TNF-Blocking Agents: Findings of a Consensus Panel.

Summary Tuberculosis causes significant morbidity and mortality worldwide MSK TB affects spine and hip mimics other pyogenic infections TNF inhibitors take abrogate the main defense mechanism keeping latent TB at bay High index of suspicion needed .

lung.ca/tb/tbhistory/ .http://www.

Thank You ! .

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