Sandbox:septic arthritis

Overview

Septic arthritis is the one of the most serious medical emergency of a patient present with one or more hot and swollen joints.

Bacterial arthritis is the most rapidly destructive joint disease. Septic arthritis is most common in patients with longstanding rheumatoid arthritis. Septic arthritis is a an important consideration in adults presenting with monoarticular arthritis in 80 to 90% of patients. It can involve any joint, but most commonly involves knee > hip > shoulder > ankle. Other joints such as sacroiliac joint, sternoclacicular or costoclavicular joints may be involved in patient with history of intravenous drug abuse (IVDA), penetrating trauma, animal or human bites and local steroid injections.

Classification

Classification Based on the Etiology

Septic arthritis can be classified into 2 types based on the etiology:

• Gonococcal septic arthritis
• Non-gonococcal septic arthritis

Classification Based on the Presentation

Septic arthritis can be classified into 2 types based on the involvement of number of joints involved during presentation:

• Mono articular septic arthritis (MASA)
  • Most common type of presentation
• Poly articular septic arthritis (PASA)
  • Less common presentation (~15% of total septic arthritis cases)
  • commonly caused by staphylococcus aureus and other non gonococcal infections such as streptococci and gram negative bacteria.

Causes

Septic arthritis is due to intra articular seeding of living microorganisms. The most common etiological agent of all nongonococcal causes of septic arthritis in the United States is Staphylococcus aureus. Gram-negative bacilli account for 10 to 20% of septic arthritis causes. ~10% of patients with nongonococcal septic arthritis are due to polymicrobial cause of infections. Anaerobes are also can cause septic arthritis in few cases.

Most common cause of septic arthritis in children age < 2 years are Haemophilus influenzae (in immunized children), Staph. aureus, group A Streptococcal infections and Kingella kingae.

The source of infection in most of the cases (~50%) often from the skin, lungs or bladder.

Causes of infection include

1. Hematogenous dissemination
2. Post operative wound infection such as after arthroscopic procedures
3. Intra articular steriod injections
4. Diagnostic punctures
5. Open traumatc injury to the joint

Common organisms

• Staphylococcus aureus
• Streptococcal pyogenous
• Streptococcal pneumonia
• Escherichia coli
• Staphylococcus epidermidis
• Borrelia burgdorferi

Pathophysiology

Presence of extreme vasularity and absence of limiting of basement membrane, promotes the easy access of infections into the synovial space.

Hematogenous spread: Septic arthritis most commonly develop as a result of hematogenous spreading bacteria into the vascular synovial membrane. Hematogenous spread is commonly associate with injection drug use, presence of indwelling catheters, and an underlying immunocompromised state such as HIV infection.

Direct inoculation: Direct inoculation of microorganisms may occur during deep penetrating injuries, intra-articular steroid injection, arthroscopy or prosthetic joint surgery, particularly in association with knee and hip arthroplasties and contiguous osteomyelitis rupturing into the joint.

Bone infection such as osteomyelitis can spread by breaking through its outer cortex and then into the intracapsular region that lead to joint infection. This kind of spread is more common in children as the small capillaries can cross the epiphyseal growth plate and permit extension of infection into the epiphysis and joint space.

Pathogenesis of septic arthritis depends on multiple factors and it mainly depends on the balance between virulence of the microbial pathogen and the host immune response against the pathogen.

Non-gonococcal arthritis

Staph. aureus is the most common pathogen non gonococcal pathogen that causes septic arthritis. The pathogenesis of septic arthritis by staphylococcus can be a better representation for pathogenesis of most non gonococcal arthritis.

Bacterial colonization and adherence into the synovium

Mechanism of infection transmission

Hematogenous spread: Septic arthritis most commonly develop as a result of hematogenous spreading bacteria into the vascular synovial membrane. Hematogenous spread is commonly associate with injection drug use, presence of indwelling catheters, and an underlying immunocompromised state such as HIV infection.

Determinants of hematognous seeding:

• Well vascularized synovium
• Absence of limiting basement membrne
• Recent joint surgery, induces the production of host-derived extracellular matrix proteins( e.g. collagen) that aids in post surgical healing process, can assist bacterial attachment and progression to infection
• Virulence of microorganism
• Susceptibility of synovial membrane for microorganism

Direct inoculation: Direct inoculation of microorganisms may occur during deep penetrating injuries, intra-articular steroid injection, arthroscopy or prosthetic joint surgery, particularly in association with knee and hip arthroplasties.

Contiguous spread: Bone infection such as osteomyelitis can spread by breaking through its outer cortex and then into the intracapsular region that lead to joint infection.

Role of bacterial products in pathogenesis

Bacterial colonization and adherence into the synovium 🢃
Mechanism of transmission
Hematogenous spread: Septic arthritis most commonly develop as a result of hematogenous spreading bacteria into the vascular synovial membrane. Hematogenous spread is commonly associate with injection drug use, presence of indwelling catheters, and an underlying immunocompromised state such as HIV infection. Determinants of hematognous seeding: Well vascularized synovium Absence of limiting basement membrne Recent joint surgery, induces the production of host-derived extracellular matrix proteins( e.g. collagen) that aids in post surgical healing process, can assist bacterial attachment and progression to infection Virulence of microorganism Susceptibility of synovial membrane for microorganism Direct inoculation: Direct inoculation of microorganisms may occur during deep penetrating injuries, intra-articular steroid injection, arthroscopy or prosthetic joint surgery, particularly in association with knee and hip arthroplasties. Contiguous spread: Bone infection such as osteomyelitis can spread by breaking through its outer cortex and then into the intracapsular region that lead to joint infection.
Role of bacterial products in pathogenesis
Bacterial attachment proteins promote colonization and initiate the infectious process, a number of bacterial products activate the host immune response and increase tissue damage in cases of septic arthritis.

Risk Factors

Common Risk Factors

Most common risk factors that predisposes septic arthritis are rheumatoid arthritis, prosthetic joint or joint replacement and skin infections.

Other common risk factors that predispose septic arthritis are as follows:

Type of risk factor	Examples
Host phagocytic defects	Complement deficiencies especially C7 and C8 Inherited disorders of chemotaxis
Impaired host defense mechanisms	Age >80 years Cancer Immunosuppressive drugs (e.g. azathioprine, methotrexate, or cyclophosphamide) Glucocorticosteroids
Direct penetration	Intravenous drug use Puncture wonds Intra articular steroid injection
Joint damage	Prosthetic joint surgery Degenerative joint diseases such as rheumatoid arthritis ( Prosthetic joint > Rheumatoid arthritis > Osteoarthritis)
Other risk factors	Recent history of bacteremia Cirrhosis Chronic kidney disease Hypogammaglobulinemia Systemic lupus erythematosis Gout Psuedo gout Charcot's arthropathy

Micrbiological Clue Based on Risk factors

Type of risk factor	Examples
Rheumatoid arthritis	Staphylococcus aureus
Immunocompromised patients	Staphylococcus aureus Streptococci Enteric gram-negative bacilli Listeria monocytogenes
Recent joint surgery	Staphylococcus aureus
Intravenous drug use	Staphylococcus aureus Pseudomonas aeruginosa
Diabetes mellitus	Staphylococcus aureus Streptococcus agalactiae
Sexually active young adults Menstruating females	Neisseria gonorrhea
Animal bite (e.g.Cat or dog)	Pasteurella multocida Capnocytophaga spp Anaerobes
Human bite	Eikenella corrodens Viridans streptococci  Anaerobes
Rat bite	Streptobacillus moniliformis
Neonates and children age < 4 years	Kingella kingae Gram-negative bacilli
Unvaccinated children	Haemophilus influenza
Ingestion of unpasteurized dairy products	Brucella spp

• Age >60 years
• Recent history of bacteremia
• Degenerative joint diseases such as rheumatoid arthritis ( Prosthetic joint > Rheumatoid arthritis > Osteoarthritis)
• Corticosteroid therapy
• Diabetes mellitus
• Leukemia
• Cirrhosis
• Granulomatous diseases
• Hypogammaglobulinemia
• Intravenous substance abuse
• Chronic kidney disease
• Cytotoxic chemotherapy
• Alcoholism

• Recent history of joint aspiration or local corticosteroid joint injection.
• History of Rhematoid arthritis
• History of diabetes mellitus

Differential Diagnosis

Differentiating gonococcal arthritis from non-gonococcal arthritis

Characterestic	Gonococcal arthritis	Non gonococcal arthritis
Patient profile	Mostly sexually active young adult Female > male	Patient with history of rheumatoid arthritis or other systemic arthritis Immunocompromised patient Common in extremes of age such as in newborn or elderly
Initial presentation	Migratory polyarthralgia is common Tenosynovitis in majority of patients Dermatitis in majority of patients	Single hot, swollen and painful joint Polyarthralgia is very rare Tenosynovitis and dermatitis are very rare.
Polyarticular involvement	Common (~40–70% of patients) Usually involves 2-3 joints	Rare (~10–20% of patients). Mostly monoarticular involvement (>85%)
Recovery of bacteria	Positive blood culture <10% Positive synovial fluid culture <50%	Positive blood culture 50% Positive synovial fluid culture >90%
Response to antibiotics	Within a few days outcome excellent	Takes weeks Joint drainage must be adequate Outcome often poor

Mycobacterial and fungal arthritis both present with the slow onset of a chronic monoarthritis and they are more prone to weight bearing joints and spine.

Microorganism	Associated risk factors	Key clinical clues	Most definitive tests
Staphylococcus aureus	Rheumatioid arthritis Diabetes mellitus HIV patients	Healthy adult with skin lesions and previously hisoty of damaged joint (eg, rheumatoid arthritis) or prosthetic joint
Streptococcus pyogenes Streptococcal pneumonia	Autoimmune diseases Chronic skin infections Trauma	Healthy adults with spleenic dysfunction
Groups B Streptococcal infection	Immunocompromised patients Diabetes mellitus Malignancy Severe genitourinary or gastrointestinal infections	Healthy adults with spleenic dysfunction
Neisseria gonorrhoeae	Complement deficiency Systemic lupus erythematosus Male homosexuality low socioeconomic status	Healthy young and sexually active adult with Tenosynovitis Skin lesions such as vesicular pustules Complement deficiency (C5-9 deficiency) Culture negativity on synovial fluid analysis
Gram-negative bacilli Pseudomonas Escherichia coli	History of intravenous drug abuse Extremes of age Immunocompromised patients	Immunocompromised patients Recent history gastrointestinal infections such as infectious diarrhea caused by Shigella, Salmonella, Campylobacter, or Yersinia
Haemophilus influenzae	Unimmunized children
Anaerobes	Diabetes mellitus Patients with prosthetic joints	Immunocompromised hosts Recent history of gastrointestinal infection
Mycobacterium spp.	Recent history of travel to endemic areas	Immunocompromised patients Recent history of travel to endemic areas (e.g. India, South Africa, Mexico etc.) Incidious onset of monoarthritis	Synovial fluid analysis Histology Tissue culture
Fungal infection such as Blastomycosis Cryptococcus Coccidioidomycosis Sporotrichosis	Immunocompromised patients	Immunocompromised patients Incidious onset of monoarthritis
Mycoplasma hominis	Recent history of urinary tract procedure	Immunocompromised patients Recent history of urinary tract procedure
Viral arthritis	Immunocompromised patient	Polyarthritis Fever Rash	Serology

Epidemiology and Demographics

• Incidence of septic arthritis approximately varies between 2 to 10 cases per 100,000 per year in the general population.
• Incidence of septic arthritis in patients with history of rheumatoid arthritis and patients with joint prostheses is ~ 30–70 cases per 100,000 per year.
• Incidence of septic arthritis in patients with joint prostheses is 40-68 cases per 100,000 per year.
• The case-fatality rate of septic arthritis is estimated to be 10-25%.
• Even after survival from septic arthritis, 25-50% of the patients suffer from irreversible loss of joint function.

Females are more at risk in getting gonorrheal arthritis and four fold risk compared to men, due to the asymptomatic nature of gonorrheal infection in women.

In children hip is most commonly involved.

PASA is more common in men when compared to women.

Septic arthrtits can be affected by any age group, but most commonly affected are elderly and children <4 years.

The first experimental model of septic arthritis mediated by staph. aureus is developed by Tarkowski and colleagues.

Natural history, Complications and Prognosis

Complications

As the growth plate is in very close to the joint, direct extension of a joint infection to the growth plate can lead to reduced bone growth in children.

Prognosis

Prognosis of septic arthritis depends on several factors.

Patients with history of chronic disease with concurrent septic arthritis can be misdiagnosed as acute flare of underlying chronic disease which often delays the treatment for septic arthritis. This diagnostic delay is an important prognostic factor contribute for the poor outcome of septic arthritis in rheumatoid arthritis, which carries a 30–50% case-fatality rate. If septic arthritis involving multiple joints, case fatality rate will be >50%.

Poor prognostic factors include age >50 years, history of rheumatoid arthritis as an underlying disease, staph. aureus is the causative agent.

Diagnosis

Patients with history of chronic disease with concurrent septic arthritis can be misdiagnosed as acute flareup of underlying chronic disease which often delays the treatment for septic arthritis. So, patients with acute flare of one or two new inflamed joints with underlying chronic joint diseases or with another connective tissue disease, it should be assumed that the joint is septic until proven otherwise, should always rule out concurrent septic arthritis with appropriate diagnostic studies.

In patients with acute effusion of unknown etiology, might have concurrent crystal-induced arthritis and septic arthritis. So, the synovial fluid should always be cultured and examined for crystals in the evaluation of an acute effusion.

History and Symptoms

Abrupt onset of a single hot, swollen, and painful joint indicate non gonococcal arthritis. It can involve any joint, but most commonly knee is the site of infection in 50% of cases of adults and elderly patients. Hip infection is the most common site in children.

Disseminated gonococcal infection(DGI) often present initially with migratory polyarthralgias, tenosynovitis, dermatitis, and fever and less commonly, <50% of patients with DGI will present with purulent joint effusion, most often of the knee or wrist.. Often present with inflamed and tender tendons of the wrist, ankles, and small joints.

Appearance of the Patient

Patient with septic arthritis usually appears toxic and with joint pain that involved

Vital Signs

• Low grade fever. Chills and spiking fever are very rare.
• Hyperthermia over the joint involved
• Tachycardia
• Tachypnea

Skin

• Warm over the joint

• Erythema over the around the joint that involved
• Disseminated gonococcal infection often present with skin lesions, typically multiple, painless macules and papules, most often found on the arms or legs or on the trunk.

Extremities

Most commonly involves knee > hip > shoulder > ankle. Other joints such as sacroiliac joint (~10%), sternoclacicular or costoclavicular joints may be involved in patient with history of intravenous drug abuse (IVDA), penetrating trauma, animal or human bites and local steroid injections.

• Swelling of the joint that involved
• Decreased range of motion
• Patient hold the hip in flexed and externally rotated position if SA involving hip.

Laboratory Tests

The definitive diagnosis of septic arthritis requires identification of bacteria in the synovial fluid by Gram’s stain or by culture.

Clinical suspicion of joint sepsis should prompt for immediate synovial fluid aspiration. Septic arthritis should not be excluded even though the patient have low fever and normal WBC.

Diagnosis of septic arthritis depends maily on the arthrocentesis and isolation of the pathogen from aspirated joint fluid.

If synovial fluid cannot be obtained with closed needle aspiration, the joint should be aspirated again with imaging guidance such as ultrasound guidance, computed tomography or fluoroscopic guidance.

Diagnostic Evaluation

Hot, swollen joint suspecting septic arthritis

Joint aspiration send synovial fluid for Gram stain, culture and cell count

If dry tap: Do image guided joint apiration with ultrasound or CT

Inflammatory/Purulent joint fluid Presence of PMN 50,000-150,000 cells and mostly neutrphils

Non-inflammatory fluid/Crystals Suspect non bacterial arthritis

Gram positive cocci Start empiric Vancomycin or Nafcicillin

Gram negative bacilli Start empiric 3rd generation cephalosporins + aminoglycosides

Negative Gram stain

Follow-up with synovial fluid culture results

If culture positive ❑ Treat for septic arthritis ❑ Change antibiotics according to the culture results ❑ Joint drainage

If culture negative ❑ Assess for true or false positivity of Gram stain ❑ Assess for clinical response

Immunocompromised start empiric Vancomycin and 3rd generation cephalosporins

Immunocompetent start empiric varncomycin

Wait for culture results

If culture positive, ❑ Treat for septic arthritis ❑ Change antibiotics according to the culture results ❑ Joint drainage

If culture negative Confirmed non bacterial arthritis and look for alternative diagnosis

Prevention

Prevention of septic arthritis is possible by intensive treatment of risk factors such as old age patients having rheumatoid arthritis, diabetes mellitus, joint prostheses or joint surgery and skin infection.

Prognosis

Prognosis of septic arthritis depends on several factors.

Patients with history of chronic disease with concurrent septic arthritis can be misdiagnosed as acute flareup of underlying chronic disease which often delays the treatment for septic arthritis. This diagnostic delay is an important prognostic factor contribute for the poor outcome of septic arthritis in rheumatoid arthritis, which carries a 30–50% case-fatality rate.

Poor prognostic factors include age >50 years, history of rheumatoid arthritis as an underlying disease, staph. aureus is the causative agent.