Infectious Arthritis¶

Chapter 135 | Part 5: Infectious Diseases · Part 5 – Infectious Diseases: Bacterial · Chapter 135

Key Clinical Points¶

Staphylococcus aureus is the most common cause of nongonococcal bacterial arthritis in adults of all ages.
Neisseria gonorrhoeae is the most common cause in young adults and adolescents (<40 years).
Synovial fluid cell count >100,000/μL with >90% neutrophils is characteristic of acute bacterial infection.
Timely drainage of pus and necrotic debris is required for a favorable outcome to prevent cartilage destruction.
Gonococcal arthritis typically presents as a syndrome of arthritis-dermatitis with negative synovial fluid cultures.
Lyme arthritis responds to oral doxycycline (100 mg twice daily for 28 days) or amoxicillin.
Tuberculous arthritis primarily involves large weight-bearing joints (hips, knees, ankles) and requires 6–9 months of therapy.
Prosthetic joint infections often require removal of the prosthesis and delayed reimplantation.
Preoperative screening for S. aureus with decolonization is recommended for joint replacement candidates.

1. DEFINITION & OVERVIEW¶

Infectious arthritis is an inflammation of the joint caused by a pathogen. Acute bacterial infection can destroy articular cartilage rapidly, requiring immediate evaluation to exclude noninfectious processes and determine appropriate antimicrobial therapy and drainage procedures.

Classification Criteria: • By Acuity: Acute vs. subacute/chronic. • By Distribution: Monoarticular vs. polyarticular.

Clinical Patterns: • Acute bacterial infection: Typically involves a single joint or few joints (mono- or oligoarthritis), except in rheumatoid arthritis. • Subacute/chronic monoarthritis: Suggests mycobacterial or fungal infection. • Episodic inflammation: Occurs in syphilis, Lyme disease, and reactive arthritis. • Viral infections: Often cause polyarticular inflammation.

1.1 Pathogenesis¶

• Routes of Entry: ◦ Hematogenous spread (most common for all age groups). ◦ Contiguous infection. ◦ Direct inoculation (e.g., trauma, injection). • Mechanism of Damage: ◦ Bacteria escape synovial capillaries → neutrophilic infiltration within hours. ◦ Cartilage degradation begins within 48 h due to: ◦ Increased intraarticular pressure. ◦ Protease/cytokine release. ◦ Bacterial invasion. • Histologic Findings: ◦ Abscesses in synovium/cartilage and pannus formation. ◦ S. aureus factors: Adhesins and endotoxins promote chondrocyte breakdown.

2. EPIDEMIOLOGY¶

• Primary Pathogens: ◦ Staphylococcus aureus: Most common cause of nongonococcal bacterial arthritis in adults of all ages. ◦ Neisseria gonorrhoeae: Most common cause in young adults and adolescents (<40 years). • Risk Factors for Infection: ◦ Rheumatoid arthritis (due to chronically inflamed joints and glucocorticoid therapy). ◦ Comorbidities: Diabetes, hemodialysis, IV drug use. ◦ Immunosuppression: TNF inhibitors; HIV (increases risk for pneumococcal, salmonella, and H. influenzae). ◦ Specific Deficiencies: Primary immunoglobulin deficiency (predisposes to mycoplasmal arthritis). • Specific Contexts: ◦ IV Drug Users: Staphylococcal/streptococcal infections from own flora. ◦ Fungal Outbreaks: Linked to contaminated injections (e.g., Exserohilum rostratum).

2.1 Pathogen Distribution by Age Group¶

• Infants: Group B streptococci, gram-negative bacilli, S. aureus. ◦ Children <5 years: S. aureus, S. pyogenes, Kingella kingae. ◦ Young adults/adolescents: N. gonorrhoeae. ◦ Adults: S. aureus (including MRSA) for nongonococcal cases. ◦ Older adults: Gram-negative bacilli, pneumococci, β-hemolytic streptococci in 1/3 of cases. ◦ Immunocompromised: Pseudomonas, coagulase-negative staphylococci (prosthetic joints), anaerobes (human bites), polymicrobial infections (trauma).

3. ETIOLOGY & PATHOPHYSIOLOGY¶

• Hematogenous spread: Most common route for all age groups. • Specific Organism Pathogenesis: ◦ Gonococcal arthritis: Follows DGI (unrecognized in 1/3 of cases); synovial fluid cultures often negative. ◦ Tuberculous arthritis: Part of disseminated TB or reactivation; involves hips, knees, and ankles; coexisting pulmonary TB is rare. ◦ Fungal arthritis: Hematogenous seeding or direct extension from bony lesions (Coccidioides, Blastomyces, Histoplasma). ◦ Lyme arthritis: Responds to doxycycline/amoxicillin; failure linked to HLA-DR4 and OspA reactivity. ◦ Candida: From surgical procedures, injections, or hematogenous spread in immunocompromised patients.

4. CLINICAL FEATURES¶

• Acute Septic Arthritis: ◦ Symptoms: Joint pain, swelling, erythema, and limited motion. ◦ Distribution: 90% monoarticular; most commonly the knee. ◦ IV Drug Users: Often present with spine/sacroiliac infections. • Polyarticular Infection: Resembles rheumatoid arthritis flares. • DGI Syndrome: ◦ Presentation: Arthritis-dermatitis with fever, rash (hemorrhagic pustules on trunk/extremities), and tenosynovitis. ◦ Synovial Fluid: 50,000 leukocytes/μL; gonococcus rarely seen on Gram stain. • Tuberculous Arthritis: ◦ Presentation: Large joints with slow progression. ◦ Lab Findings: 20,000/μL cell count (~50% neutrophils); acid-fast staining positive in <1/3 cases. • Fungal Infections: ◦ Prevalence: Rare; sporotrichosis shows male predominance. ◦ Lab Findings: Synovial fluid has 10,000–40,000 cells/μL (~70% neutrophils). • HIV-associated Arthritis: ◦ Includes reactive arthritis (HLA-B27), psoriatic arthritis, and HTLV-1 oligoarthritis.

4.1 Clinical Manifestations and Laboratory Findings¶

• DGI syndrome: Arthritis-dermatitis with fever, rash (hemorrhagic pustules on trunk/extremities), tenosynovitis. ◦ Synovial fluid: 50,000 leukocytes/μL; gonococcus rarely seen on Gram stain. • Lyme arthritis: Borrelia DNA in 85% of synovial fluid NAATs. • TB arthritis: Acid-fast staining positive in <1/3 cases; cultures positive in 80%. • Fungal arthritis: Synovial fluid has 10,000–40,000 cells/μL with ~70% neutrophils.

5. DIFFERENTIAL DIAGNOSIS¶

• Acute Monarticular: S. aureus, S. pneumoniae, β-hemolytic streptococci, Gram-negative bacilli, N. gonorrhoeae, Candida, crystal-induced arthritis, fracture, hemarthrosis, foreign body. • Chronic Monarticular: TB, nontuberculous mycobacteria, Lyme disease, syphilis (Treponema pallidum), fungal infections (Candida, Sporothrix, Coccidioides, Blastomyces, Aspergillus, Cryptococcus), Nocardia, Brucella, Legg-Calvé-Perthes disease, osteoarthritis. • Polyarticular: DGI syndrome, bacterial endocarditis, HIV, parvovirus B19, reactive arthritis, rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis.

5.1 Distinguishing Features¶

• Acute bacterial infection: Single/few joints with >90% neutrophils in synovial fluid. ◦ Subacute/chronic monoarthritis: Mycobacterial/fungal infections (30–70% neutrophils). ◦ Episodic inflammation: Syphilis, Lyme disease, reactive arthritis. ◦ Acute polyarticular: Endocarditis, rheumatic fever, viral hepatitis.

6. INVESTIGATIONS & DIAGNOSIS¶

Arthrocentesis and Synovial Fluid Analysis:
Acute bacterial: >100,000/μL leukocytes (>90% neutrophils), turbid/purulent appearance.
DGI syndrome: 10,000–20,000/μL leukocytes (negative cultures).
TB arthritis: 20,000/μL cell count (~50% neutrophils); acid-fast staining <1/3 positive; cultures positive in 80%; synovial tissue biopsy in ~90%.
Fungal arthritis: 10,000–40,000/μL cells (~70% neutrophils).
Imaging (Ultrasound, CT, MRI):
Used to detect effusions and sacroiliac/spine infections.
Microbiology & Molecular Testing:
Blood cultures: Positive in 50–70% S. aureus infections.
NAAT: Detects gonococcal DNA in 85% of Lyme cases.

6.1 Diagnostic Criteria and Thresholds¶

• Acute bacterial: Synovial cell count >100,000/μL (>90% neutrophils). ◦ Mycobacterial/fungal: 10,000–30,000/μL (50–70% neutrophils). ◦ Gonococcal septic arthritis: >50,000 leukocytes/μL. ◦ DGI syndrome: 10,000–20,000 leukocytes/μL. ◦ TB arthritis: Cultures positive in 80%, synovial tissue biopsy in ~90%.

7. MANAGEMENT & TREATMENT¶

Immediate Intervention:
Prompt antibiotics and joint drainage to prevent cartilage destruction.
Empiric Antibiotic Therapy (Gram-positive):
Vancomycin: 15–20 mg/kg every 8–12 h.
Cefazolin: 2 g every 8 h (if MRSA is unlikely).
Gonococcal Arthritis Treatment:
Ceftriaxone: 2 g IV.
Doxycycline: 100 mg PO BID for 4 weeks.
Lyme Arthritis Treatment:
Doxycycline: 100 mg BID ×28 days.
Amoxicillin: 500 mg TID ×28 days.
Tuberculous Arthritis Treatment:
Duration: 6–9 months.
Regimen: Rifampin, isoniazid, pyrazinamide, ethambutol.
Prosthetic Joint Infections:
Surgical debridement.
Prosthesis removal.
Delayed reimplantation.
Preoperative Preparation:
S. aureus decolonization for joint replacement candidates (mupirocin nasal ointment + chlorhexidine baths).

7.1 Gonococcal Arthritis Treatment¶

Ceftriaxone (2 g IV) + doxycycline (100 mg PO BID) for 4 weeks. Note: Synovial fluid cultures often negative; NAATs may detect gonococcal DNA.

7.2 Prosthetic Joint Infections Treatment¶

Surgical debridement, prosthesis removal, and delayed reimplantation. Preoperative S. aureus decolonization (mupirocin nasal ointment + chlorhexidine baths) recommended for joint replacement candidates.

8. PROGNOSIS & COMPLICATIONS¶

• Untreated Acute Bacterial Arthritis: → Leads to cartilage destruction, postinfectious degenerative arthritis, and deformity. • Tuberculous Arthritis: → Requires 6–9 months of therapy; risk of relapse with inadequate treatment. • Prosthetic Joint Infections: → High morbidity requiring surgical intervention. • Delayed Diagnosis (DGI): → May lead to chronic fatigue syndromes.

9. SPECIAL CONSIDERATIONS¶

• Preoperative Screening: - S. aureus screening and decolonization (mupirocin + chlorhexidine) for joint replacement candidates. • HIV-infected Patients: - Monitor for reactive arthritis (HLA-B27) and psoriatic arthritis. • Immunocompromised Hosts: - Require prompt antifungal therapy for Candida/Aspergillus infections.

9.1 Prevention¶

Preoperative S. aureus screening with decolonization (mupirocin + chlorhexidine) for joint replacement candidates. HIV-infected patients should be monitored for reactive arthritis and psoriatic arthritis.

10. KEY PEARLS & CLINICAL TRAPS¶

• Pearls: ◦ DGI syndrome may mimic gonococcal septic arthritis but has negative synovial fluid cultures. ◦ Lyme arthritis responds to doxycycline/amoxicillin; failure linked to HLA-DR4. ◦ TB arthritis often involves hips/knees/ankles with slow progression. • Traps: ◦ Overlooking DGI syndrome in young adults with rash/arthritis. ◦ Misdiagnosing fungal arthritis as crystal-induced disease due to similar synovial fluid appearance.

Reference Tables¶

TABLE 135-1 Differential Diagnosis of Arthritis Syndromes¶

Harrison's 22e, p.1055

ACUTE MONARTICULAR ARTHRITIS	CHRONIC MONARTICULAR ARTHRITIS	POLYARTICULAR ARTHRITIS
Staphylococcus aureus Streptococcus pneumoniae β-Hemolytic streptococci Gram-negative bacilli Neisseria gonorrhoeae Candida spp. Crystal-induced arthritis Fracture Hemarthrosis Foreign body Osteoarthritis Ischemic necrosis Monoarticular rheumatoid arthritis	Mycobacterium tuberculosis Nontuberculous mycobacteria Borrelia burgdorferi Treponema pallidum Candida spp. Sporothrix schenckii Coccidioides immitis Blastomyces dermatitidis Aspergillus spp. Cryptococcus neoformans Nocardia spp. Brucella spp. Legg-Calvé-Perthes disease Osteoarthritis	Neisseria meningitidis N. gonorrhoeae Nongonococcal bacterial arthritis Bacterial endocarditis Candida spp. Poncet’s disease (tuberculous rheumatism) Hepatitis B virus Parvovirus B19 HIV Human T-lymphotropic virus type 1 Rubella virus Arthropod-borne viruses Sickle cell disease flare Reactive arthritis Serum sickness Acute rheumatic fever Inflammatory bowel disease Systemic lupus erythematosus Rheumatoid arthritis/ Still’s disease Other vasculitides Sarcoidosis
135	Infectious Arthritis Nongnooch Poowanawittayakom, Lawrence C. Madoff