Arthritis, infectious

Description of Medical Condition

Invasion of joints by live microorganisms or their fragments. One of the few curable causes of arthritis. May allow early recognition of systemic infection/disease.

System(s) affected: Musculoskeletal

Genetics: N/A

Incidence/Prevalence in USA:

Neisserial:

• Responsible for 50% of infectious arthritis
• Arthritis occurs in 0.6% of the 3% of women with gonorrhea
• Arthritis occurs in 0.1% of the 0.7% of men with gonorrhea
• Arthritis occurs in 7% of individuals with N. meningitidis

Non-Neisserial:

– Half as frequent as Neisserial

Predominant age:

Neisserial:

• Especially 15-40, can occur at any age

Non-Neisserial:

• Prior to age 2:27% Staphylococcus, 20% Streptococcus, 33% Haemophilus, and 13% other gram negative rods, 7% miscellaneous
• Age 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

Medical Symptoms and Signs of Disease

• Predominantly monoarticular (90%). (Haemophilus may be pauciarticular and Mycoplasma often presents as a migratory polyarthritis).
• Limited joint use/motion (especially in children)
• Joint effusion, tenderness
• Joint warmth — present in less than 50%
• Joint redness- present in less than 50%
• Loss of joint motion
• Tenosynovitis
• Sudden flare of one or two joints in a patient with underlying joint disease
• Fever — in 90% at some time during the course of the infection
• Chills, malaise
• Cutaneous lesions
• Peripheral neuropathy
• Back pain — especially in subacute bacterial endocarditis (SBE)
• Hypertrophic osteoarthropathy — rare, secondary to endocarditis
• Fretfulness — especially in children
• 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%)

What Causes Disease?

• Hematogenous invasion by microorganisms (80-90%)
• Contiguous spread (10-15%) from adjacent osteomyelitis in children
• Direct penetration of micro-organisms secondary to trauma or joint injection

Risk Factors

• Young patient with venereal exposure
• Concurrent extra-articular infection
• Prior arthritis in infected joint
• Trauma
• Joint puncture or surgery
• Prosthetic joint
• 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)
• Intravenous drug abuse
• Travel/habitat history
• Sickle cell anemia
• C8 deficiency

Diagnosis of Disease

Differential Diagnosis

• Gout
• Pseudogout (calcium pyrophosphate deposition disease)
• Spondyloarthropathy (Reiter syndrome, psoriatic arthritis, ankylosing spondylitis, the arthritis of inflammatory bowel disease)
• Juvenile rheumatoid arthritis
• Type Ha hyperlipoproteinemia
• Foreign body synovitis
• Rheumatoid arthritis
• Rheumatic fever
• AIDS
• Cellulitis
• Palindromic rheumatism
• Neuropathic arthropathy
• Lyme arthritis
• Sarcoidosis
• Granulomatous arthritis

Laboratory

• Synovial fluid usually cloudy with > 50,000 WBC/HPF (high power field), but may have fewer white blood cells present or over 100,000. (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 significantly less than 700
• Polymorphonuclear leukocytes usually predominate in synovial fluid
• Synovial fluid glucose often more than 40 mg/dL (2.22 mmol/L) less than in a simultaneously obtained serum glucose value (in fasting patient). However, arthrocen-tesis should not be delayed simply to obtain fasting synovial fluid glucose level.
• Westergren erythrocyte sedimentation rate — often elevated, but normal in 20%
• Rheumatoid factor positive in 50% — if endocarditis present and in viral arthritis
• Anti-teichoic acid antibodies — with Staphylococcus infection
• Elevated peripheral white blood cell count (in 50-90%)
• Cryoglobulins
• Immune complexes
• Febrile agglutinins (to include Brucella and rickettsial-related titers)
• Antistreptolysin O (ASO) titer is usually normal, exclusive of streptococcal infections
• Depressed synovial fluid and occasionally depressed serum levels of complement
• Microscopic hematuria in subacute bacterial endocarditis (SBE)
• Presence of crystals (e.g., urate or calcium pyrophosphate) does not exclude infectious arthritis

Drugs that may alter lab results: Antibiotics

Disorders that may alter lab results: N/A

Pathological Findings

Synovial biopsy will reveal polymorphonuclear leukocytes and possibly the causative organism — if cultures are negative of fluid

Special Tests

• Joint fluid — for gram stain (positive in 50%); culture (positive in 50-70%)
• Serum cidal level assessment of antibiotic adequacy is suggested with virulent organisms or therapeutic unresponsiveness (tenfold margin suggested)
• Blood, orifice, urine cultures. “Bedside culture” is recommended to enhance isolation of fastidious organisms.
• All cultures should be preserved and observed for at least 3 days and preferably 2 weeks. Observing synovial fluid cultures for at least 3 days allows isolation of fastidious organisms such as those of rat bite fever (Streptobacillus moniliformis and Spirillum minus).
• Neisserial infection generally requires use of special agars (e.g., chocolate or Thayer Martin) and relative anaerobic culturing conditions
• Countercurrent immunoelectrophoresis or complement fixation for specific bacterial antigens
• Polymerase chain reaction for specific bacterial DNA

Imaging

• X-ray
  • Soft tissue swelling
  • Juxta-articular osteoporosis
  • Radiolucent area (gas) in a joint space from gas forming organisms. (Caveat — may also occur normally as a “vacuum phenomenon”).
  • Effacement of the obturator fat pad (with hip involvement)
  • X-ray changes are usually a late phenomenon
  • Rarefaction of subchondral bone may occur as early as 2-7 days
  • Joint space loss (secondary to cartilage destruction) may be seen as early as 4-10 days
  • Erosions
  • Joint destruction with ankylosis may occur as early as 2 weeks
• 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

• Arthrocentesis with gram stain and culture — only positive in 50-70% dependent on organism. Must be done in all patients when possibility of infectious arthritis is considered. Arthrocentesis should probably be performed within 12 hours of suspicion.
• Arthrocentesis approach must avoid contaminated tissue (e.g., overlying cellulitis)

Treatment (Medical Therapy)

Appropriate Health Care

• Hospitalization for parenteral therapy
• Rarely an extremely compliant patient with a very sensitive organism might be treated as an outpatient

General Measures

• Repeat arthrocentesis to drain the joint, as fluid re-accumulates
• Avoid adding anti-inflammatory therapy so as not to compromise assessment of therapeutic response to antibiotic
• If a joint prosthesis is present in an infection, the infection is very difficult to eradicate, without removal of the prosthesis
• Treatment is continued for 1-2 weeks after total resolution of all signs of inflammation, 3-4 weeks for gram negative organisms, and 6-8 weeks if the joint was previously diseased (e.g., involved by arthritis)
• infra-articular antibiotics are not required and may actually aggravate the arthritis

Surgical Measures

Arthrotomy indicated only if fluid accumulated is loculated and/or not amenable to needle drainage, or if antibiotics fail

Activity

Limit activity or splint the joint initially. Continuous passive motion may be used as an alternative approach.

Diet

No special diet

Medications (Drugs, Medicines)

Drug(s) of Choice

Neisserial

• Ceftriaxone 1 gm IM or IV every day for 14 days (but at least 7 days after symptoms resolve)
• Spectinomycin 2 gm IM every 12 hours for 10 days

Non-Neisserial:

• Gram positive cocci in chains or clumps- nafcillin 150 mg/kg/dayq4-6hlV/IM
• Gram positive diplococci — penicillin G 1.4 million units q6h
• Gram negative bacilli: In neonates — penicillin and gentamicin; in children age 6 months to 4 years — cefuroxime; in adult — penicillin or cephalosporin plus gentamicin, all at full dose. Add clindamycin, at full dose, in the 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, all at full dose

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 the effectiveness of oral contraceptives; barrier method recommended.

Alternative Drugs

• Non-Neisserial
  • In children age 6 months to 4 years — ampicillin; chloramphenicol may be required to cover resistant Haemophilus
  • Infectious disease consult strongly advised to supplement rheumatologist input for Haemophilus infections
• Quinolones (e.g., ciprofloxacin)

Patient Monitoring

• Recurrent arthrocentesis, as fluid re-accumulates — to verify sterilization of the joint and to verify reversion of inflammatory signs to normal
• If no definitive improvement within 48 hours, re-evaluate completely
• Complete blood count, liver and kidney function and urinalysis twice a week, while on antibiotics (perhaps with creatinine every other day when gentamicin used)
• Gentamicin levels
• It is essential to followup one week and a month after stopping antibiotics to detect any relapse

Prevention / Avoidance

• Prophylaxis in presence of predisposing joint condition
• Condoms and discretion forSTD protection for Neis-seria

Possible 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 the limb (in children)

Expected Course / Prognosis

• Early treatment should allow cure
• Delayed recognition/treatment complicated by morbidity and mortality

Miscellaneous

Associated Conditions

• Systemic infection; infection elsewhere
• Immunodeficiency; immunosuppression
• Rheumatoid arthritis

Age-Related Factors

Pediatric: N/A

Geriatric: N/A

Pregnancy:N/A

Synonyms

• Suppurative arthritis
• Septic arthritis

International Classification of Diseases

711.00 Pyogenic arthritis, site unspecified

See Also

Reiter syndrome