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Peripheral joints arthritis of TB and BRUCELLOSIS

Azami Ahad. MD.

Rheumatologist

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TB Peripheral Joint Arthritis

EPIDEMIOLOGY: As many as 2 billion people are infected

with M. TB and 2 million people die each year

Extra pulmonary TB accounted for 20% of TB infections in 2001

Skeletal involvement with TB constitutes 1% to 3% of all cases of tuberculosis

Males and females are affected equally

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• TB incidence in Iran declined from 100 cases per 100,000 people in 1979 to 13 cases per 100,000 people in 2008

• TB prevalence in Iran of 1.3% in 2008, down from more than 10% in 1979

Global health reporting.org [March 13, 2009]

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Risk factors:

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Microbiology:

M. TB & M. bovis :are associated with significant human disease.

M. TB is the most common cause of TB.

Aerobic, non-spore forming, non-motile & slow -growing bacillus with a rod-shaped morphology

Humans are its only known reservoir.

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1. Transmission: Inhalation of respiratory droplets → bacillus deposited in alveolus. Engulfed by macrophages.

2. Infection, Proliferation, and Dissemination Bacilli may survive and proliferate, kill macrophages → replicates

at primary focus and in lymphohematogenous metastatic foci

3. Host Response (Cell-Mediated Immunity)Macrophages present antigens to T-cells (CD4 lymphocytes) →

lymphs proliferate, activate macrophages , secrete TNF-a , interferon-γ → microbicidal (cellular immunity) – get involution of primary lesion / granuloma formation (epitheliod cells/Langerhans giant cells are highly stimulated macrophages) (3-9 wks?)

4. Liquefaction and Proliferation: Reactivation with cavity formation lymphohematogenous metastatic synovium or Bone 8

Clinical patterns of musculoskeletal TB:

• Spondylitis (50-60%)

• Septic arthritis

• Osteomyelitis

• Tenosynovitis& bursitis

• Soft tissue abscess

• Reactive arthritis (Pancet's disease)

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Typical presentation:

• Chronic & insidious monoarticular arthritis & polyarticular (Rarely)

• Large & medium joints:hip and knee (most commonly)

• SI, shoulder, elbow, ankle, carpal, tarsal joints(less commonly)

• Cold joint

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Symptoms & Signs

Stage I is synovitis: Joint pain Joint swelling Flexion, abduction and external rotation of the hipConstitutional symptoms (30%)

Stage I1 is early arthritis with osseous lesions: Joint painJoint swelling Most commonly flexion, adduction, and internal rotation of the hipApparent shortening of the affected limbLimping gait 11

Symptoms & Signs:

Stage 111 is the arthritic stage:Articular surfaces destruction with loss of joint space True shortening of the limb occurs Movement of the joint is exquisitely painfulStage IV is advanced arthritis: Albus tumorJoint painComplete destruction of the joint spaceAnkylosisDraining cold abscessMuscle atrophy

Duration for any stage: weeks to12 month 12

Other joints arthritis:knee:15%Pain& swelling, limping gait, flex-contracture, muscle atrophy, deformity

Foot & ankle:8-10%

Sacroiliac:7-10%Unilateral (usually), pain, constitutional signs(frequent) & severe SI tenderness

Elbow13

Poncet's disease:Polyarthritis associated with E-pulmonary TB with no evidence of bacteria in joint

More often in young people

Clinical findings: fever, malaise & polyarthritis of large joints such as knees, ankles& at times wristsArthritis can be destructive and persists until anti-TB therapy is initiated

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Radiography:

Stage I : osteopenia & soft tissue swelling epiphyseal hypertrophy

Stage I1:

Disease has progressed to produce epiphyseal or metaphyseal erosions, but a normal joints space

Stage I11: is frank arthritis & joint space narrowing

Stage IV: Is advanced arthritic changes and disorganization of the joint Characteristic radiographic findings : (Phemister's triad)

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Sonography CT-scans MRI

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CBC

ESR Are non-specific findings

CRP

HIV-test?

PPD-test

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SYNOVIAL FLUID

• Color

• WBC & diff: 10,000-30,000 cell/ml & PMN dominancy

(like to other chronic synovitis)

• Glucose, protein

AFB-smier (10-20% +)

Synovial fluid culture (79% +)20

Synovial biopsies :Rice bodies, pannus, necrosis, caseating or noncaseating granulomas ( 94% ) D.D: fungal, atypical mycobacterial infections, brucellosis& sarcoidosis

Synovial culture :confirms osteoarticular TB in ( 94% )

PCR 21

New Diagnostics:

Interferon Gamma Release Assays (IGRA’S)

Rapid Molecular Amplification

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Diagnosis:

• The diagnosis of TB requires a high index of suspicion

• Diagnosis rests upon a combination of clinical presentation, pathologic findings, and culture results

• In endemic area?

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Differential diagnosis?

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Peripheral Arthritis Of

Brucellosis

Brucellosis is a zoonotic disease of domestic animals and humans.

The Many Names of Brucellosis: Malta Fever Undulant Fever Mediterranean Fever Gastric Fever

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History:

• 1861: Marston published description of “Mediterranean gastric remittent fever”

• 1886: Sir David Bruce, microbe isolated from a soldier with Malta Fever; named it Micrococcus mellitensus

• 1897: Bernard Bang, first isolated B. abortus from cattle

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Brucella species:

Four species can be pathogenic in humans: B. melitensis, B. abortus, B. canis and B. suis.

They are highly infectious, especially B. melitensis and B. suis.

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BRUCELLANon-motile

Non-spore forming

Intracellular

Lack capsules

Gram-negative coccobacilliEnvironmental persistence

Temp, pH, humidityFrozen and aborted materials

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Pathogenecity:

Infection of non-phagocytic cellsMechanism of invasion not clearly understood

Localize in rough endoplasmic reticulum

Infection of phagocytic cells Invasion of PMN or MN cells by suppression of

bactericidal responses

S-LPS (smooth) plays major role in intracellular survival; survive more effectively than rough

low toxicity for macrophages

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Pathogenecity:

Virulence Elimination of virulent organisms depends on activated macrophages

and development of Th1 cell-mediated response to antigens

DeterminantsS-LPS is main antigen responsible for protection

Inhibition of phagolysosome fusion

Activation of myelo-peroxidase-halide system

Production of TNF

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Epidemiology:

Worldwide, particularly Mediterranean, Africa, Middle East, Latin America

True incidence unknownEndemic areas: >200/100,000

U.S.: <1/100,000

In Iran, Brucellosis represents a major health problem

Iran J Radiol 2009, 6(1) 32

TRANSMISSION:

• Oral entry - most common route

Ingestion of contaminated animal products (often raw milk or its derivatives)

contact with contaminated fingers

• Aerosols

Inhalation of bacteria

Contamination of the conjunctivae

• Percutaneous :infection through skin

abrasions or by accidental inoculation

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Human Disease• Incubation period:2-4 week

• Can affect any organ or organ system

• All patients have a cyclical fever

• clinical signs & symptoms:HeadacheWeaknessArthralgiaDepressionWeight lossFatigue Liver dysfunction 34

Human Disease:Duration of disease?days to months& year if untreated

Osteoarticular complications (In 20-60% of cases)

1. Reactive arthritis

2. Septic arthritis(38.8%)

3. Spondylitis (6.8%)

4. Sacroiliitis(46.6%)

5. Tendonitis&bursitis35

Sacroiliitis:

• Usually unilateral& nondestructive• Often Presents acutely& dramaticly• Severe low back& buttock pain• Difficulty in walking& standing• Fever(80%)• Direct tenderness on involve SIj• Bone scan is the most sensitive technique

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Peripheral arthritis:

• Often presents acutely (or subacutely)• The most common cause is b.melitensis• Particulary affected the large joints of lower

extremities• Often monoarticular• The most common are knee>hip>ankle • Pain is predominant,• Effusion frequently, no synovial thickening• Tenderness& limitation of motion

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Reactive arthritis

Sterile polyarthritis Non-destructive Intermittent & self-limited

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Paraclinics:

• WBC: NL or & lymph • CRP, ESR:NL or

• Synovial fluid:• WBC:10,000-15,000/ml & lymph-dominancy• The yield of organism culture is low(50%)

• Plain x-ray is not diagnostic

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Diagnosis in Humans:

• Isolation of organism– Blood, bone marrow, other tissues

• Serum agglutination test (wright test)

Titers?– Fourfold or greater rise in titer

– Samples 2 weeks apart

• ELISA

• PCR• Tissue biopsy: noncaseating granulomas

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