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Saturday, January 17, 2009

ARTHRITIS, INFECTIOUS, BACTERIAL

ARTHRITIS, INFECTIOUS, BACTERIAL - Bruce M. Rothschild, MD
BASICS
DESCRIPTION
• Invasion of joints by live micro-organisms or their fragments. One of the few curable causes of arthritis. May allow early recognition of systemic infection/disease.
• System(s) Affected: Musculoskeletal
• Synonym(s): Suppurative arthritis; Septic arthritis
GENERAL PREVENTION
Condoms and discretion for STD protection
EPIDEMIOLOGY
• Predominant age (1, 2, 3)[A]
- Neisserial: Especially 15-40 years of age; can occur at any age
- Non-Neisserial
 Years 2: 27% Staphylococcus, 20% Streptococcus, 33% Haemophilus, and 13% other Gram-negative rods, 7% miscellaneous
 Years 2-14: 34% Staphylococcus, 29% Streptococcus, 13% Haemophilus, and 13% other Gram-negative rods, 11% miscellaneous
 Adult: 34% Staphylococcus, 38% Streptococcus, 2% Haemophilus, and 26% other Gram-negative rods
• Predominant sex
- Neisserial: Female > Male (4:1)
- Non-Neisserial: Male > Female (2:1)
- Subacute bacterial endocarditis-related: Male = Female
Prevalence
• Neisserial
- Responsible for 50% of infectious arthritis
- 0.6% of the 3% of women with gonorrhea
- 0.1% of the 0.7% of men with gonorrhea
- Arthritis occurs in 7% of individuals with Neisseria meningitidis
• Non-Neisserial: Half as frequent as Neisserial
RISK FACTORS
• Young patient with venereal exposure
• Concurrent extra-articular infection
• Prior arthritis in infected joint
• Trauma
• Joint puncture or surgery
• Prosthetic joint (4)[A]
• Prior antibiotic, corticosteroid, or immunosuppressive therapy
• Serious chronic illness (e.g., diabetes, liver disease, malignancy, primary immunodeficiency)
• Defective phagocytic mechanisms (e.g., chronic granulomatous disease)
• IV drug abuse
• Unusual travel/habitat history
• Sickle cell anemia
• C8 deficiency
• Systemic infection; infection elsewhere
• Immunodeficiency; immunosuppression
• Rheumatoid arthritis
ETIOLOGY
• Hematogenous invasion (80-90%)
• Contiguous spread (10-15%)
• Direct penetration of microorganisms secondary to trauma or joint injection


DIAGNOSIS
SIGNS AND SYMPTOMS
• Predominantly monoarticular (90%). (Haemophilus may be pauciarticular and Mycoplasma often a migratory polyarthritis.)
• Limited or loss of joint use/motion
• Joint effusion, tenderness
• Joint warmth: Present in 50%
• Joint redness: Present in 50%
• Tenosynovitis
• Sudden flare of 1 or 2 joints in patient with underlying joint disease
• Fever: In 90% during course of infection
• Chills
• Malaise
• Cutaneous lesions
• Peripheral neuropathy
• Back pain: Subacute bacterial endocarditis (5)[A]
• Hypertrophic osteoarthropathy: Rare, secondary to endocarditis
• Dermato-arthritis
- Usually pustular skin lesions in gonorrhea
- Usually petechial rash in meningococcemia
• Bacteremic phase: Migratory polyarthritis, Tenosynovitis, high fever, chills, pustules
• Localized phase:
- Usually monoarticular
- Low-grade fever (80%)
TESTS
Lab
Synovial fluid (6)[A]
• Synovial fluid is usually cloudy with >50,000 WBC/HPF. (Caveat: Cell count must be performed within 1 hour of obtaining specimen to be valid.)
• Synovial-fluid white count can be recognized as elevated (in presence of trauma) if RBC/WBC ratio is significantly less than 700.
• Polymorphonuclear leukocytes usually predominate in synovial fluid.
• Synovial-fluid glucose is often more than 40 mg/dL (2.22 mmol/L) less than simultaneously obtained serum glucose value (in fasting patient).
• Decreased levels of complement
• Crystals (e.g., urate or calcium pyrophosphate) do not exclude infectious arthritis.
• Joint fluid: For Gram stain (positive in 50%); culture (positive in 50-70%)
• Serum cidal level assessment of antibiotic is suggested (10-fold margin suggested)
Serum Testing
• Westergren erythrocyte sedimentation rate: Often elevated, but normal in 20%
• Rheumatoid factor: Positive in 50%, if endocarditis present and in viral arthritis
• Elevated peripheral white blood cell count in 50-90% of the patients
• Cryoglobulins
• Immune complexes
• Febrile agglutinins (to include Brucella and rickettsial-related titers)
• Antistreptolysin O titer usually normal, exclusive of streptococcal infections
• Depressed serum levels of complement
• Microscopic hematuria in subacute bacterial endocarditis (5)[A]
• Blood, orifice, urine cultures
• "Bedside culture" is recommended to enhance isolation of fastidious organisms.
• All cultures should be preserved and observed for 3 days to 2 weeks (3, 6-8)[A].
• Neisserial infection generally requires use of special agars (e.g., chocolate or Thayer Martin)
• Drugs that may alter lab results: Antibiotics
• Countercurrent immunoelectrophoresis or complement fixation for specific bacterial antigens
• Polymerase chain reaction for specific bacterial DNA (8,9)[A]
Imaging
• X-ray (8)[A]
- Soft-tissue swelling
- Juxta-articular osteoporosis
- Radiolucent area (gas) in a joint space from gas-forming organisms (Caveat: May be normal as a "vacuum phenomenon.")
- Effacement of obturator fat pad (with hip involvement)
- X-ray changes usually a late phenomenon
- Rarefaction of subchondral bone may occur
- Joint-space loss (secondary to cartilage destruction) may occur in 4-10 days.
- Erosions
- Joint destruction with ankylosis may occur.
• Other imaging techniques
- Technetium joint scans: Reveal distribution of inflammation; sensitive, not specific
- Gallium or Ceretec WBC scan, Indium scans: Reveal inflammation as well as infection
- CT: To identify sequestration
- MRI: Effusion, perhaps early cartilage damage, osteomyelitis
Diagnostic Procedures/Surgery
• Arthrocentesis with Gram stain and culture: Positive in 50-70% (7)[A]
- Must always be done when possibility of infectious arthritis considered
- Arthrocentesis should probably be performed within 12 hours of suspicion.
• Arthrocentesis approach must avoid contaminated tissue (e.g., overlying cellulitis).
Pathological Findings
Synovial biopsy will reveal polymorphonuclear leukocytes and possibly the causative organism, if synovial fluid and blood cultures are negative.
DIFFERENTIAL DIAGNOSIS
• Gout
• Pseudogout (calcium pyrophosphate deposition disease)
• Spondyloarthropathy (Reiter syndrome, psoriatic arthritis, ankylosing spondylitis, arthritis of inflammatory bowel disease)
• Juvenile rheumatoid arthritis
• Type IIa hyperlipoproteinemia
• Foreign-body synovitis
• Rheumatoid arthritis
• Rheumatic fever
• AIDS
• Cellulitis
• Palindromic rheumatism
• Neuropathic arthropathy
• Lyme arthritis
• Sarcoidosis
• Granulomatous arthritis
TREATMENT
GENERAL MEASURES
• Hospitalization for parenteral therapy
• Outpatient treatment rarely possible for extremely compliant patient with known organism
• Repeat arthrocentesis to drain joint as fluid re-accumulates.
• Avoid anti-inflammatory therapy to allow assessment of therapeutic response to antibiotic.
• If joint prosthesis is present in an infection, removal of the prosthesis must be considered.
• Continue treatment for 1-2 weeks after total resolution of all signs of inflammation, 3-4 weeks for Gram-negative organisms, and 6-8 weeks, if joint was previously diseased.
• Intra-articular antibiotics not required and may actually aggravate the arthritis
Diet
No special diet
Activity
Limit activity or splint joint initially. Alternative approach: Continuous passive motion
MEDICATION (DRUGS)
First Line
• Neisserial (3,8)[A]
- Ceftriaxone 1 g IM or IV every day for 14 days (but at least 7 days after symptoms resolve)
- Spectinomycin 2 g IM q12h  10 days
• Non-Neisserial (3,8)[A]
- Gram-positive cocci in chains or clumps: Nafcillin 150 mg/kg per day q4-6h IV/IM
- Gram-positive diplococci: Penicillin G 1.4 million units q6h
- Gram-negative bacilli: Neonates, penicillin and gentamicin; ages 6 months-4 years, cefuroxime; adult, penicillin or cephalosporin plus gentamicin, all at full dose. Add clindamycin, at full dose, in presence of retroperitoneal or pelvic abscess.
- Gram-negative pleomorphic organisms: Clindamycin at full dose (clindamycin has Gram-negative activity only against anaerobes)
- No bacteria seen on smear: Penicillin or cephalosporin plus gentamicin
• Contraindications: Tetracycline not for use in pregnancy or children 8 years
• Precautions
- Observe for allergic reactions/serum sickness
- Tetracycline may cause photosensitivity; sunscreen recommended
• Significant possible interactions
- Tetracycline: Avoid concurrent administration with antacids, dairy products, or iron
- Broad-spectrum antibiotics: May reduce effectiveness of oral contraceptives; barrier method recommended
Second Line
• Non-Neisserial
- In children age 6 months-4 years: Ampicillin; chloramphenicol may be required to cover resistant Haemophilus
- Infectious disease consult strongly advised to supplement rheumatologist input for Haemophilus infections
• Neisserial and Non-Neisserial:
- Quinonlones (e.g., ciprofloxacin)
SURGERY
Arthrotomy indicated only if fluid accumulated is loculated and/or not amenable to needle drainage
FOLLOW-UP
PROGNOSIS
• Early treatment should allow cure.
• Delayed recognition/treatment complicated by morbidity and mortality
COMPLICATIONS
• Death (9-33% in elderly)
• Limited joint range of motion
• Flail or fused or dislocated joint
• Carpal tunnel syndrome
• Septic necrosis
• Sinus formation
• Ankylosis
• Osteomyelitis
• Postinfectious synovitis
• Shortening of limb (in children)
PATIENT MONITORING
• Recurrent arthrocentesis as fluid re-accumulates to verify sterilization of joint and reversion of inflammatory signs to normal
• If no improvement within 48 hours, reevaluate.
• Complete blood count, liver and kidney function, and urinalysis twice a week while on antibiotics (with creatinine when gentamicin used)
• Gentamicin levels
• Essential to follow up 1 week and 1 month after stopping antibiotics to detect any relapse
REFERENCES
1. Dubost JJ, Soubrier M, De Champs C, et al. No changes in distribution of organisms responsible for septic arthritis over a 20 year period. Ann Rheum Dis. 2002;61:257-260.
2. Garcia-De La Torre I. Advances in the management of septic arthritis. Rheum Dis Clin N Am. 2003;29:61-75.
3. Gonzalez-Juanatey C. Rheumatic manifestations of infective endocarditis in non-addicts: A 12-year study. Medicine. 2001;80:9-19.
4. Gershwin ME, Robbins DL. Musculoskeletal Diseases of Children. New York, NY: Grune  Stratton; 1983.
5. Gupta MN, Sturrock RD, Field M. Prospective comparative study of patients with culture proven and high suspicion of adult onset septic arthritis. Ann Rheum Dis. 2003;62:327-331.
6. Khachatourians AG, Patzakis MJ, Roidis N, Holtom PD. Laboratory monitoring in pediatric acute osteomyelitis and septic arthritis. Clin Orthop. 2003;(409):186-194.
7. Ross JJ, Hu LT. Bacterial and Lyme arthritis. Curr Infect Dis Rep. 2004;5:380-387.
8. Tarkin IS, Dunman PM, Garvin KL. Improving the treatment of musculoskeletal infections with molecular diagnostics. Clin Orthop Rel Res. 2005;437:83-88.
9. Wilkinson NZ, Kingsley GH, Jones HW, et al. The detection of DNA from a range of bacterial species in the joints of patients with a variety of arthritides using a nested, broad-range polymerase chain reaction. Rheumatol. 1999;38:260-266.
10. Zimmerli W, Trampuz A, Ochsner PE. Prosthetic joint infections. N Engl J Med. 2004;351:1645-1654.
MISCELLANEOUS
See also: Reiter Syndrome

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