Septic Arthritis

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Introduction

Septic arthritis is defined as the infection and inflammation of one or more joints by a pathogenic infectious agent. 

The most common cause of infection is Staphylococcus aureus, which enters the joint through direct inoculation or haematogenous spread from a different site, commonly a soft tissue infection.1

Septic arthritis is an important differential for a red, hot, painful, and swollen joint with restricted movement. Septic arthritis is an orthopaedic emergency with substantial morbidity and mortality.2

Septic arthritis can occur in adults and children and occur in native and prosthetic joints. However, to give information more appropriate for medical students, this article has been written to provide the information needed to recognise, diagnose, and treat cases of native joint septic arthritis in adults

Epidemiology

Overall, septic arthritis is relatively rare, with around 6 cases per 100,000 per year in developed countries and has a peak incidence in those over the age of 70.3

Septic arthritis resulting from prosthetic joint infection (PJI) is an important complication of joint replacement and has an incidence around 10 times higher than in native joints, with an incidence of around 70 cases per 100,000 per year.4

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Aetiology

Septic arthritis can rarely be caused by viral, fungal or parasitic species. However, most cases are caused by bacterial infection. Around 91% of cases are caused by staphylococci or streptococci, with Staphylococcus aureus cited as the most common causative agent, followed by Streptococcus pneumoniae.1

Despite this, it is important to consider alternative causative agents in the following groups:1

  • Sexually active (young) patients: Neisseria gonorrhoea
  • Immunosuppressed patients: gram-negative organisms, Mycobacterium tuberculosis
  • Patients from areas of high TB prevalence: Mycobacterium tuberculosis
  • Nursing home residents, patients recently discharged from hospital, patients with leg ulceration or indwelling catheters: methicillin-resistant Staphylococcus aureus (MRSA)

Less common bacterial causes include Streptococcus pyogenes, Haemophilus influenza and Escherichia coli.

Transmission

Any joint (fibrous, cartilaginous, or synovial) may be affected, with the knee and hip being the most common, and there are several routes for the infectious agent to invade the joint.

Haematogenous spread is the most common, from distant abscesses, wounds, respiratory tract infections or sexually transmitted infections. This method of transmission is further facilitated by neovascularisation resulting from previous joint disease and inflammation.

Direct inoculation can be caused by joint injections, arthrocentesis, arthroscopic surgery, trauma, foreign objects, and infected wounds.

Bacteria may also undergo contiguous spread from local infections, such as osteomyelitis, septic bursitis, and abscesses.

Pathophysiology

Research suggests a strong pathogenic role for both the host immune response and the invading bacteria in septic arthritis: 5

  1. Bacterial colonisation: bacteria enter and colonise the joint space, a process facilitated by the increased levels of adhesion proteins resulting from previous joint inflammation.
  2. Immune response: synovial cells and macrophages detect pathogen-associated molecular patterns (PAMPs) and induce an immune response, recruiting macrophages, T cells and B cells. Underlying joint disease impairs the phagocytic and bactericidal properties of healthy synovial cells and fluid.
  3. Acute inflammatory response: host factors are released, including pro-inflammatory cytokines which recruit more immune cells, and histamine release from mast cells, which stimulates vasodilation and increases vascular permeability.
  4. Bacterial factor release: toxins, enzymes, adhesins and cell wall proteins are released into the joints space. These can exacerbate the immune response, causing more severe inflammation as well as directly contributing to articular destruction.
  5. Bone and cartilage necrosis: articular destruction resulting from the immune response, bacterial factors and the resulting increase in intra-articular pressure which compresses the blood supply to the joint.

Risk factors

Risk factors for septic arthritis can be categorised as those predisposing an individual to infection, those providing opportunity for the pathological agent to gain access to the joint, and a past medical history of joint disease or inflammation which facilitates bacterial invasion through neovascularisation, increased expression of adhesion factors and an impaired synovial immune response.6,7

Predisposition to infection

Risk factors include:

  • Immunosuppression (medication, HIV/AIDS)
  • Diabetes mellitus
  • Alcohol use disorder
  • Sickle cell disease (joint inflammation but strongly associated with salmonella septic arthritis)

Past medical history

Risk factors include:

  • Rheumatoid arthritis
  • Osteoarthritis
  • Crystal arthritides
  • Joint prosthesis (through contamination during surgery, wound infection or otherwise disruption to the normal joint defences)

Pathogen access

Risk factors include:

  • Cutaneous ulcers
  • Chronic skin infections
  • Intravenous drug use
  • Intra-articular corticosteroid injections

Clinical features

History

Septic arthritis classically presents as an acutely hot, swollen, and tender joint with restriction of both active and passive movement.

In 80% of cases, this presents in a single joint, most commonly the knee (53%), followed by the hip, shoulder ankle and wrists.

Typical symptoms of septic arthritis include:7

  • Joint pain (70-80%)
  • Joint swelling (71-85%)
  • Fever (52-62%)
  • Sweats (20-34%)
  • Rigors (15-24%)

Other important areas to cover in the history include:

  • Past medical history: identification of risk factors discussed above
  • Drug history
  • Social history
  • Sexual history: gonococcal arthritis is an important differential in sexually active young adults

Clinical examination

A clinical examination of the affected joint should be performed, following the classic ‘look, feel, move’ approach. 

Typical clinical findings in septic arthritis include:

  • Look: swelling and erythema
  • Feel: warmth, joint pain & tenderness (particularly on knee flexion when the intra-articular space is reduced), joint effusion
  • Move: reduced active and passive range of motion, reduced function (inability to walk)

Differential diagnoses

Table 1 lists alternative diagnoses for a hot, swollen, tender joint. Many of these conditions present differently compared to septic arthritis and can be excluded with synovial fluid analysis. Fluid analysis in other conditions will show no micro-organisms and reveal the presence of crystals, in the case of gout and pseudogout. 

Table 1. Differential diagnoses for septic arthritis.10

Diagnosis Differences

Gout

  • Previous history of gout
  • Symptoms presenting in foot joints

Pseudogout

  • Previous history of pseudogout

Osteoarthritis

  • Previous history of osteoarthritis
  • Symptoms fitting a chronic picture
  • Bilateral symptoms
  • No systemic symptoms
  • Presence of bony deformities
  • Involvement of small joints

Rheumatoid arthritis

  • Previous history of rheumatoid arthritis
  • Symptoms fitting a chronic picture
  • Deformity (swan neck, Boutonniere’s, ulnar deviation)
  • Rheumatoid nodules

Reactive arthritis

  • Asymmetrical and polyarticular
  • HLA-B27 genetic association

Psoriatic arthritis

  • Polyarticular
  • Cutaneous manifestations (psoriasis)
  • Dactylitis (DIP joints)

Trauma/haemarthrosis

  • Previous history of bleeding diathesis
  • Traumatic event
  • Joint aspiration reveals blood

Investigations

The British Society of Rheumatology recommends a low threshold for suspecting septic arthritis, stating that a presentation of a hot, swollen, tender joint with restricted movement should be considered as septic arthritis until proven otherwise. This necessitates prompt joint arthrocentesis for synovial fluid aspiration.8

Joint arthrocentesis

Arthrocentesis should be performed in a sterile environment by a clinician with adequate expertise using a close-needle approach. Hip involvement will require referral to orthopaedics for ultrasound-guided aspiration, and prosthetic involvement will require an orthopaedic surgeon to perform the procedure in a sterile operating theatre.

Aspirate samples should be sent for crystal microscopy, gram staining, culture, and sensitivity testing. Immediate management should involve empirical antibiotics according to local protocols.

Synovial fluid analysis findings

A positive synovial fluid analysis (suggestive of septic arthritis) may have the following features:

  • Appearance: yellow/green on aspiration (as opposed to clear and colourless when uninfected)
  • White cell count: raised (particularly neutrophil count), though this is not 100% sensitive or specific and can be raised in other arthropathies
  • Culture: identification of the causative bacterium and its sensitivities

A negative culture does not exclude the diagnosis and may necessitate the use of alternative testing, depending upon the risk factors present and the clinical impression of the causative organism.

Bedside investigations

Relevant bedside investigations include:

  • Urinalysis: raised nitrites in urinary tract infections
  • Swabs (oropharynx, vagina, cervix, urethra, anus/rectum): presence of N. gonorrhoea

Laboratory investigations

Relevant laboratory investigations include:

  • Full blood count: white cell count is raised in 50% of cases, but is not 100% sensitive or specific
  • CRP/ESR: may be elevated or normal, this can also be used to monitor treatment response
  • Blood culture: these should always be taken, but a negative result does not exclude a diagnosis
  • U&Es: may be deranged due to sepsis and can be used as a baseline prior to antibiotic therapy
  • LFTs: can be used as a baseline prior to antibiotic therapy

Imaging

Relevant imaging investigations include:

  • X-ray: not diagnostic but recommended as a baseline and to reveal degenerative changes, chondrocalcinosis and underlying joint disease
  • Ultrasound: not diagnostic but can be used to guide hip aspiration
  • MRI: low specificity in diagnosis, can identify associated osteomyelitis (bone marrow oedema, abscess margins)

Diagnosis

The Kocher criteria is a useful tool to determine the probability of septic arthritis.

Table 2. The Kocher criteria for diagnosing septic arthritis.9

Finding Score

Non-weight-bearing on the affected side

+1

Erythrocyte sedimentation rate > 40mm/hr

+1

Fever > 38.5 °C

+1

White blood cell count > 12,000 cells/mm3

+1

Interpretation of the Kocher criteria is as follows:

  • Score of 1: 3% probability of septic arthritis
  • Score of 2: 40% probability of septic arthritis
  • Score of 3: 93% probability of septic arthritis
  • Score of 4: 99% probability of septic arthritis

Management

Patients with suspected septic arthritis are at risk of developing sepsis, irreversible joint damage and death.

These patients should be admitted to hospital in the first instance and guidelines from BMJ Best Practice and the British Society for Rheumatology suggest urgent joint aspiration to dryness (for investigation and symptoms relief) follow by immediate empirical antibiotic therapy.8,10

Consider initiation of the sepsis six protocol if initial assessment suggests systemic bacteraemia.

Synovial fluid aspiration

Affected joints should be aspirated to dryness as frequently as required to remove infection and reduce pressure and pain. If the joint is accessible, this may be performed using anatomical landmarks.

Inaccessible joints, including the hip, will require orthopaedic referral and consideration of ultrasound-guided aspiration, or arthrocentesis in a sterile operating theatre. Prosthetic joints require urgent orthopaedic referral for surgical arthrocentesis and washout.10

Antibiotic therapy

Patients should be given empirical antibiotic treatment, often intravenous flucloxacillin, following local guidelines immediately following synovial fluid aspiration and blood culture.

Culture and sensitivity results will inform further antibiotic therapy. The specific regimes are beyond the knowledge required for medical students, however, brief recommendations from the BNF are listed below.

Table 3. Antibiotic therapy in septic arthritis.11

Pathogen Antibiotic

Staphylococcus aureus (methicillin-sensitive)

Flucloxacillin

Clindamycin if penicillin-allergic

Streptococcus spp

Neisseria gonorrhoeae

Cefotaxime or ceftriaxone

Salmonella (non-typhi)

Amoxicillin

Salmonella (typhi/paratyphi)

Ceftriaxone

Staphylococcus aureus (methicillin-resistant)

Vancomycin or teicoplanin


Complications

Septic arthritis carries significant morbidity and mortality, with a single-joint case fatality rate of 11%.12

Poor outcomes have been shown to be associated with older age, underlying joint disease, and joint prosthesis. 

Treatment must be adequate and prompt to avoid irreversible joint destruction and disability.13

Complications associated with septic arthritis and its management include: 10

  • Joint destruction: inflammatory destruction of joint cartilage occurs in up to 50% of patients. Orthopaedic referral may be required for surgical solutions.
  • Osteomyelitis: the infection may spread contiguously to the surrounding bone. This may be seen on MRI and will require advice from infectious disease and orthopaedic consultants.
  • Sepsis: the colonising bacteria may enter the bloodstream, causing bacteraemia, sepsis, and septic shock. Initiation of the sepsis six protocol should be seriously considered in septic arthritis patients.
  • Antibiotic allergy: antibiotic therapy should avoid patient allergies.

Key points

  • Septic arthritis is the infection of one or more native or prosthetic joints and is considered an orthopaedic emergency.
  • The most common cause of infection is Staphylococcus aureus, but consider Neisseria gonorrhoea in young, sexually active patients, and MRSA in nursing home residents or those recently discharged from hospital.
  • Bacteria can enter the joint through haematogenous spread from distal infections, contiguous spread from local infections or through direct inoculation.
  • Important risk factors include underlying joint disease, joint prosthesis, skin and soft tissue infections, immunosuppression, intra-articular corticosteroid injections and intravenous drug use.
  • Septic arthritis typically presents as an acutely hot, swollen, and tender joint with movement restriction, most commonly in the knee; consider this presentation septic arthritis until proven otherwise.
  • Immediate investigations include prompt joint arthrocentesis and synovial fluid analysis (crystal microscopy, gram staining, culture, and sensitivity testing), which will require orthopaedic referral.
  • Empirical antibiotics should be started immediately, most often intravenous flucloxacillin, with tailored antibiotic therapy following culture and sensitivity.
  • Good prognosis requires prompt treatment, and complications include joint destruction and disability, osteomyelitis and sepsis.

Reviewer

Dr Steve Laird

Consultant Physician in Infectious Disease


Editor

Dr Chris Jefferies


References

  1. Dubost, J. J., et al. No changes in the distribution of organisms responsible for septic arthritis over a 20 year period. 2002. Available from: [LINK]
  2. NICE CKS. Knee pain – assessment. July 2017. Available from: [LINK]
  3. Tarkowski, A. Infection and musculoskeletal conditions: Infectious arthritis. 2006. Available from: [LINK]
  4. Kaandorp, Carola JE, et al. Incidence and sources of native and prosthetic joint infection: a community based prospective survey. 1997. Available from: [LINK]
  5. Mathews, Catherine J., et al. Bacterial septic arthritis in adults. 2010. Available from: [LINK]
  6. Kaandorp, Carola JE, et al. Risk factors for septic arthritis in patients with joint disease. 1995. Available from: [LINK]
  7. Margaretten, Mary E., et al. Does this adult patient have septic arthritis? Available from: [LINK]
  8. Coakley, G., et al. BSR & BHPR, BOA, RCGP and BSAC guidelines for management of the hot swollen joint in adults. 2006. Available from: [LINK]
  9. Kocher, Mininder S., David Zurakowski, and James R. Kasser. Differentiating between septic arthritis and transient synovitis of the hip in children: an evidence-based clinical prediction algorithm. Available from: [LINK]
  10. BMJ Best Practice. Septic arthritis. 2021. Available from: [LINK]
  11. BNF British National Formulary. Musculoskeletal system infections, antibacterial therapy. 2021. Available from: [LINK]
  12. Kaandorp, Carola JE, et al. Incidence and sources of native and prosthetic joint infection: a community based prospective survey.  1997. Available from: [LINK]
  13. Kaandorp, Carola JE, et al. The outcome of bacterial arthritis. A prospective community‐based study. Available from: [LINK]

 

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