Septic arthritis

Acute septic arthritis, infectious arthritis, suppurative arthritis, pyogenic arthritis,<ref>Template:Cite web</ref> osteomyelitis, or joint infection is the invasion of a joint by an infectious agent resulting in joint inflammation. Generally speaking, symptoms typically include redness, heat and pain in a single joint associated with a decreased ability to move the joint. Onset is usually rapid. Other symptoms may include fever, weakness and headache. Occasionally, more than one joint may be involved, especially in neonates, younger children and immunocompromised individuals.<ref name=AFP2011>Template:Cite journal</ref><ref name=NORD2009>Template:Cite web</ref><ref name=el-sobky2021>Template:Cite journal</ref> In neonates, infants during the first year of life, and toddlers, the signs and symptoms of septic arthritis can be deceptive and mimic other infectious and non-infectious disorders.<ref name=el-sobky2021/>

In children, septic arthritis is usually caused by non-specific bacterial infection and commonly hematogenous, i.e., spread through the bloodstream.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Septic arthritis and/or acute hematogenous osteomyelitis usually occurs in children with no co-occurring health problems. Other routes of infection include direct trauma and spread from a nearby abscess. Other less common cause include specific bacteria as mycobacterium tuberculosis, viruses, fungi and parasites.<ref name="NORD2009" /> In children, however, there are certain groups that are specifically vulnerable to such infections, namely preterm infants, neonates in general, children and adolescents with hematologic disorders, renal osteodystrophy, and immune-compromised status. In adults, vulnerable groups include those with an artificial joint, prior arthritis, diabetes and poor immune function.<ref name="AFP2011" /> Diagnosis is generally based on accurate correlation between history-taking and clinical examination findings, and basic laboratory and imaging findings like joint ultrasound.<ref name=el-sobky2021/>

In children, septic arthritis can have serious consequences if not treated appropriately and timely. Initial treatment typically includes antibiotics such as vancomycin, ceftriaxone or ceftazidime.<ref name=AFP2011/> Surgery in the form of joint drainage is the gold standard management in large joints like the hip and shoulder.<ref name=AFP2011/><ref name=el-sobky2021/><ref>Template:Cite journal</ref> Without early treatment, long-term joint problems may occur, such as irreversible joint destruction and dislocation.<ref name=AFP2011/> Template:TOC limit

Signs and symptoms

Children

In children septic arthritis usually affects the larger joints like the hips, knees and shoulders. The early signs and symptoms of septic arthritis in children and adolescents can be confused with limb injury.<ref name=el-sobky2021/> Among the signs and symptoms of septic arthritis are: acutely swollen, red, painful joint with fever.<ref name="pmid29388627">Template:Cite journal</ref> Kocher criteria have been suggested to predict the diagnosis of septic arthritis in children.<ref>Template:Cite journal</ref>

Importantly, observation of active limb motion or kicking in the lower limb can provide valuable clues to septic arthritis of hip or knee. In neonates/new born and infants the hip joint is characteristically held in abduction flexion and external rotation. This position helps the infant accommodate maximum amount of septic joint fluid with the least tension possible. The tendency to have multiple joint involvements in septic arthritis of neonates and young children should be closely considered.<ref name=el-sobky2021/>

Adults

In adults, septic arthritis most commonly causes pain, swelling and warmth at the affected joint.<ref name="AFP2011" /><ref name=":0">Template:Cite book</ref> Therefore, those affected by septic arthritis will often refuse to use the extremity and prefer to hold the joint rigidly. Fever is also a symptom; however, it is less likely in older people.<ref name=":2">Template:Cite journal</ref> In adults the most common joint affected is the knee.<ref name=":2" /> Hip, shoulder, wrist and elbow joints are less commonly affected.<ref name=":1">Template:Cite web</ref> Spine, sternoclavicular and sacroiliac joints can also be involved. The most common cause of arthritis in these joints is intravenous drug use.<ref name=":0" /> Usually, only one joint is affected. More than one joint can be involved if bacteria are spread through the bloodstream.<ref name=":0" />

Prosthetic joint

Template:Main For those with artificial joint implants, there is a chance of 0.86 to 1.1% of getting infected in a knee joint and 0.3 to 1.7% of getting infected in a hip joint.

There are three phases of artificial joint infection: early, delayed and late.<ref name="AFP2011" />

• Early – infection occurs in less than 3 months. Usual signs and symptoms are fever and joint pain, with redness and warmth over the joint operation site. The mode of infection is during the joint implant surgery. The usual bacteria involved are Staphylococcus aureus and gram negative bacilli.<ref name="AFP2011" />
• Delayed – infection occurs between 3 and 24 months. There would be persistent joint pain, due to loosening of the implant. The mode of infection is during the implant surgery. Common bacteria are coagulase-negative Staphylococcus and Cutibacterium acnes.<ref name="AFP2011" />
• Late – more than 24 months. It is usually presented with a sudden onset of joint pain and fever. The mode of infection is through the bloodstream. The bacteria involved are the same as those in septic arthritis of a normal joint.<ref name="AFP2011" />

Cause

Septic arthritis is most commonly caused by a bacterial infection.<ref name=":4">Template:Cite journal</ref> Bacteria can enter the joint by:

• The bloodstream from an infection elsewhere (most common)
• Direct penetration into the joint (arthrocentesis, arthroscopy, trauma)<ref name="AFP2011" />
• A surrounding infection in the bone or tissue (uncommon, from osteomyelitis, septic bursitis, abscess)<ref name="AFP2011" /><ref name=":1" /><ref name=":4" />

Microorganisms in the blood may come from infections elsewhere in the body such as wound infections, urinary tract infections, meningitis or endocarditis.<ref name=":1" /> Sometimes, the infection comes from an unknown location. Joints with preexisting arthritis, such as rheumatoid arthritis, are especially prone to bacterial arthritis spread through the blood.<ref name=":1" /> In addition, some treatments for rheumatoid arthritis can also increase a person's risk by causing an immunocompromised state.<ref name="AFP2011" /> Intravenous drug use can cause endocarditis that spreads bacteria in the bloodstream and subsequently causes septic arthritis.<ref name="AFP2011" /> Bacteria can enter the joint directly from prior surgery, intraarticular injection, trauma or joint prosthesis.<ref name=":0" /><ref name=":4"/><ref name=":3">Template:Cite book</ref>

Risk factors

In children, although septic arthritis occurs in healthy children and adolescents with no co-occurring health issues, there are certain risk factors that may increase the likelihood of acquiring septic arthritis. For example, children with renal osteodystrophy or renal bone disease, certain hematological disorders and diseases causing immune suppression are risk factors for childhood septic arthritis.<ref name=el-sobky2021/>

The rate of septic arthritis varies from 4 to 29 cases per 100,000 person-years, depending on the underlying medical condition and the joint characteristics. For those with a septic joint, 85% of the cases have an underlying medical condition while 59% of them had a previous joint disorder.<ref name="AFP2011" /> Having more than one risk factor greatly increases risk of septic arthritis.<ref name=":1" />

• Age over 80 years<ref name="AFP2011" /><ref name=":1" />
• Diabetes mellitus<ref name="AFP2011" /><ref name=":1" />
• Osteoarthritis<ref name="AFP2011" />
• Rheumatoid arthritis.<ref name=":1" /> Risk of septic arthritis increases with anti-tumor necrosis factor alpha treatment.<ref name="AFP2011" />
• Immunosuppressive medication<ref name="AFP2011" />
• Intravenous drug abuse<ref name="AFP2011" />
• Recent joint surgery<ref name=":1" />
• Hip or knee prosthesis and skin infection<ref name="AFP2011" /><ref name=":1" />
• HIV infection<ref name="AFP2011" /><ref name=":1" />
• Other causes of sepsis<ref name="AFP2011" />

Organisms

Most cases of septic arthritis involve only one organism; however, polymicrobial infections can occur, especially after large open injuries to the joint.<ref name=":3" /> Septic arthritis is usually caused by bacteria, but may be caused by viral,<ref name="pmid27037381">Template:Cite journal</ref> mycobacterial, and fungal pathogens as well. It can be broadly classified into three groups: non-gonococcal arthritis, gonococcal arthritis, and others.<ref name="AFP2011" />

• Non-gonococcal arthritis – These bacteria account for over 80% of septic arthritis cases and are usually staphylococci or streptococci.<ref name="AFP2011" /> Such infections most commonly come from drug abuse, cellulitis, abscesses, endocarditis, and chronic osteomyelitis.<ref name="AFP2011" /> Methicillin-resistant Staphylococcus aureus (MRSA) may affect 5 to 25% of the cases while gram negative bacilli affects 14 to 19% of the septic arthritis cases. Gram negative infections are usually acquired through urinary tract infections, drug abuse, and skin infections. Older people who are immunocompromised are also prone to get gram negative infections. Common gram negative organisms are: Pseudomonas aeruginosa and Escherichia coli.<ref name="AFP2011" /> Both gram positive and gram negative infections are commonly spread through the blood from an infective source; but can be introduced directly into the joint or from surrounding tissue.<ref name=":0" /> It often affects older people, and often happens suddenly, involving only one joint. Joint aspiration cultures are positive in 90% of cases, while only 50% of blood cultures yield any organisms.<ref name="AFP2011" />
• Gonococcal arthritis – Neisseria gonorrhoeae is a common cause of septic arthritis in people who are sexually active and under 40 years old.<ref name="AFP2011" /><ref name=":0" /> The bacteria is spread through the blood to the joint following sexual transmission. Other symptoms of disseminated gonococcal infection can include migration of joint pain, tenosynovitis and dermatitis.<ref name="AFP2011" /><ref name=":3" /> Synovial fluid cultures are positive in 25 to 70% of the cases while blood cultures are seldom positive.<ref name="AFP2011" /> Apart from blood and joint cultures, swabs from urethra, rectum, pharynx, and cervix should also be taken. Polymerase chain reaction (PCR) is another useful way of identifying gonococcal infections if diagnosis is difficult and clinical presentation is similar to reactive arthritis.<ref name="AFP2011" />
• Others – Fungal and mycobacterial infections are rare causes of septic arthritis and usually have a slow onset of joint symptoms. Mycobacterial joint infection most commonly affects hip and knee joints, caused by reactivation of past mycobacterial infections, with or without signs and symptoms of tuberculosis in lungs. Synovial fluid cultures will be positive in 80% of the cases. However, acid fast smears are not useful. Histology is not specific to myocobacterial infection as there are other granulomatous diseases that can show similar histology.<ref name="AFP2011" /> Borrelia burgdorferi, a bacterium that causes lyme disease, can affect multiple large joints such as the knee. Confirmation of Lyme disease is done through enzyme-linked immunosorbent assay (ELISA) followed by confirmation using Western Blot test. It cannot be cultured from synovial fluid. However, PCR testing yields 85% positive result from synovial fluid.<ref name="AFP2011" /> Viruses such as rubella, parvovirus B19, chikungunya, and HIV infection can also cause septic arthritis.<ref name=":0" />
• Prosthetic joint infection – Artificial joint infection are usually caused by coagulase negative Staphylococci, Staphylococcus aureus, and gram negative bacilli. Concurrent infections by multiple organisms is also reported in 20% of the cases. The risk factors of prosthetic joint infections are: previous fracture, seropositive rheumatoid arthritis, obesity, revision arthroplasty, and surgical site infections.<ref name="AFP2011" />

List of organisms

• Staphylococci (40%)<ref name="AFP2011" />
  • Staphylococcus aureus – the most common cause in most age groups. Can be caused by skin infection, previously damaged joint, prosthetic joint or intravenous drug use.<ref name=":1" /><ref name=":3" />
  • coagulase-negative staphylococci – usually due to prosthetic joint<ref name=":0" />
• Streptococci – the second-most common cause<ref name="AFP2011" /><ref name=":3" /> (28%)<ref name="AFP2011" />
  • Streptococcus pyogenes – a common cause in children under 5<ref name=":0" />
  • Streptococcus pneumoniae
  • Group B streptococci – a common cause in infants<ref name=":1" />
• Haemophilus influenzae<ref>Template:Cite journal

Template:Cite journal</ref>

• Neisseria gonorrhoeae – the most common cause of septic arthritis in young, sexually active adults.<ref name="Malik2010">Template:Cite journal</ref> Multiple macules or vesicles seen over the trunk are a pathognomonic feature.<ref name="Kaandorp">Template:Cite journal
  Template:*Template:Cite journal</ref>
• Neisseria meningitidis<ref name=":1" /><ref name=":3" />
• Escherichia coli – in the elderly, IV drug users and the seriously ill<ref name=":1" />
• Pseudomonas aeruginosa – IV drug users or penetrating trauma through the shoe<ref name=":0" /><ref name=":3" />
• M. tuberculosis, Salmonella spp. and Brucella spp. – cause septic spinal arthritis<ref name="Axford">Template:Cite book</ref>
• Eikenella corrodens – human bites<ref name=":0" />
• Pasteurella multocida, bartonella henselae, capnocytophaga – animal bites or scratches<ref name=":0" />
• Fungal species – immunocompromised state<ref name=":1" />
• Borrelia burgdorferi – ticks, causes lyme disease<ref name=":1" />
• Spirillum minus, Streptobacillus moniliformis – rat bites

Diagnosis

Template:Synovial fluid analysis Septic arthritis should be considered whenever a person has rapid onset pain in a swollen joint, regardless of fever. One or multiple joints can be affected at the same time.<ref name="AFP2011" /><ref name=":0" /><ref name=":2" />

Laboratory studies such as blood cultures, white blood cell count with differential, ESR, and CRP should also be included. However, white cell count, ESR, and CRP are nonspecific and could be elevated due to infection elsewhere in the body. Serologic studies should be done if lyme disease is suspected.<ref name=":0" /><ref name=":3" /> Blood cultures can be positive in 25 to 50% of those with septic arthritis due to spread of infection from the blood.<ref name="AFP2011" /> CRP more than 20 mg/L and ESR greater than 20 mm/hour together with typical signs and symptoms of septic arthritis should prompt arthrocentesis from the affected joint for synovial fluid examination.<ref name="pmid29388627"/>

The synovial fluid should be collected before the administration of antibiotics and should be sent for gram stain, culture, leukocyte count with differential, and crystal studies.<ref name=":0" /><ref name=":1" /> This can include NAAT testing for N. gonorrhoeae if suspected in a sexually active person.<ref name=":3" />

In children, the Kocher criteria is used for diagnosis of septic arthritis.<ref>Template:Cite journal</ref>

Differential diagnosis

The differential diagnosis of septic arthritis is broad and challenging. First, it has to be differentiated from acute hematogenous osteomyelitis. This is because the treatment lines of both conditions are not identical. Noteworthy, septic arthritis and acute hematogenous osteomyelitis can co-occur. Especially in the hip and shoulder joints their co-occurrence is likely and represents a diagnostic challenge. Therefore, physicians should have a high suspicion index in that regard. This is because in both the hip and shoulder joints the metaphysis is intra-articular which in turn facilitates the spread of hematogenous osteomyelitis into the joint cavity. Conversely, joint sepsis may spread to the metaphysis and induce osteomyelitis.<ref name=el-sobky2021/> Acute exacerbation of juvenile idiopathic arthritis and transient synovitis of the hip both of which are non-septic conditions may mimic septic arthritis. More serious and life-threatening disorders as bone malignancies e.g. Ewing sarcoma and osteosarcoma may mimic septic arthritis associated with concurrent acute hematogenous osteomyelitis. In this regard, Magnetic resonance imaging may play an important role in the differential diagnosis.<ref name=el-sobky2021/><ref>Template:Cite journal</ref>

Joint aspiration

In children, joint synovial fluid aspiration techniques aim at isolating the infectious organism by culture and sensitivity analysis. Cytological analysis of the joint aspirate can point to septic arthritis. However, a negative culture and sensitivity test does not rule out the presence of septic arthritis. Various clinical scenarios and technique-related factors may impact the validity of results of the culture and sensitivity. Additionally, results of cytological analysis, though important, should not be interpreted in isolation of the clinical settings.<ref name=el-sobky2021/><ref>Template:Cite journal</ref>

File:SepticJointFluid.jpg

Synovial fluid from a knee with septic arthritis

In the joint fluid, the typical white blood cell count in septic arthritis is over 50,000–100,000 cells per 10⁻⁶/l (50,000–100,000 cell/mm³);<ref name=":5">Template:Cite journal</ref> where more than 90% are neutrophils is suggestive of septic arthritis.<ref name="AFP2011" /> For those with prosthetic joints, white cell count more than 1,100 per mm³ with neutrophil count greater than 64% is suggestive of septic arthritis.<ref name="AFP2011" /> However, septic synovial fluid can have white blood cell counts as low as a few thousand in the early stages. Therefore, differentiation of septic arthritis from other causes is not always possible based on cell counts alone.<ref name=":1" /><ref name=":5" /> Synovial fluid PCR analysis is useful in finding less common organisms such as Borrelia species. However, measuring protein and glucose levels in joint fluid is not useful for diagnosis.<ref name="AFP2011" />

The Gram stain can rule in the diagnosis of septic arthritis, however, cannot exclude it.<ref name=":1" />

Synovial fluid cultures are positive in over 90% of nongonoccocal arthritis; however, it is possible for the culture to be negative if the person received antibiotics prior to the joint aspiration.<ref name=":0" /><ref name=":1" /> Cultures are usually negative in gonoccocal arthritis or if fastidious organisms are involved.<ref name=":0" /><ref name=":1" />

If the culture is negative or if a gonococcal cause is suspected, NAAT testing of the synovial fluid should be done.<ref name=":0" />

Positive crystal studies do not rule out septic arthritis. Crystal-induced arthritis such as gout can occur at the same time as septic arthritis.<ref name="AFP2011" />

A lactate level in the synovial fluid of greater than 10 mmol/L makes the diagnosis very likely.<ref name=Car2011>Template:Cite journal</ref>

Blood tests

Laboratory testing includes white blood cell count, ESR and CRP. These values are usually elevated in those with septic arthritis; however, these can be elevated by other infections or inflammatory conditions and are, therefore, nonspecific.<ref name="AFP2011" /><ref name=":0" /> Procalcitonin may be more useful than CRP.<ref>Template:Cite journal</ref>

Blood cultures can be positive in up to half of people with septic arthritis.<ref name="AFP2011" /><ref name=":1" />

Imaging

Imaging such as x-ray, CT, MRI or ultrasound are nonspecific. They can help determine areas of inflammation but cannot confirm septic arthritis.<ref name=":4" />

When septic arthritis is suspected, x-rays should generally be taken.<ref name=":1" /> This is used to assess any problems in the surrounding structures<ref name=":1" /> such as bone fractures, chondrocalcinosis, and inflammatory arthritis which may predispose to septic arthritis.<ref name="AFP2011" /> While x-rays may not be helpful early in the diagnosis/treatment, they may show subtle increase in joint space and tissue swelling.<ref name=":0" /> Later findings include joint space narrowing due to destruction of the joint.<ref name=":4" />

Ultrasound is effective at detecting joint effusions.<ref name=":4" />

CT and MRI are not required for diagnosis; but if the diagnosis is unclear or the joints are hard to examine (ie.sacroiliac or hip joints); they can help to assess for inflammation/infection in or around the joint (i.e. Osteomyelitis),<ref name=":1" /><ref name=":4" /> bone erosions, and bone marrow oedema.<ref name="AFP2011" /> Both CT and MRI scans are helpful in guiding arthrocentesis of the joints.<ref name="AFP2011" />

Differential diagnosis

• Crystal induced arthritis such as gout or pseudogout<ref name=":1" /><ref name=":3" />
• Inflammatory arthritis<ref name=":1" /><ref name=":3" />
  • Rheumatoid arthritis
  • Seronegative spondyloarthropathy such as ankylosing spondylitis or reactive arthritis
• Traumatic arthritis due to hemarthrosis, fracture or foreign body<ref name=":1" />
• Osteoarthritis<ref name=":1" /><ref name=":3" />

Treatment

Treatment is usually with intravenous antibiotics, analgesia and washout and/or aspiration of the joint.<ref name=":0" /><ref name=":1" /> Draining the pus from the joint is important and can be done either by needle (arthrocentesis) or opening the joint surgically (arthrotomy).<ref name="AFP2011" />

Empiric antibiotics for suspected bacteria should be started. This should be based on Gram stain of the synovial fluid as well as other clinical findings.<ref name="AFP2011" /><ref name=":0" /> General guidelines are as follows:

• Gram positive cocci – vancomycin<ref name="AFP2011" /><ref name=":1" />
• Gram negative cocci – Ceftriaxone<ref name="AFP2011" />
• Gram negative bacilli – Ceftriaxone, cefotaxime, or ceftazidime<ref name=":1" />
• Gram stain negative and immunocompetent – vancomycin<ref name=":1" />
• Gram stain negative and immunocompromised – vancomycin + third generation cephalosphorin<ref name=":1" />
• IV drug use (possible pseudomonas aeruginosa) – ceftazidime +/- an aminoglycoside<ref name=":0" /><ref name=":1" />

Once cultures are available, antibiotics can be changed to target the specific organism.<ref name=":0" /><ref name=":1" /> After a good response to intravenous antibiotics, people can be switched to oral antibiotics. The duration of oral antibiotics varies, but is generally for 1–4 weeks depending on the offending organism.<ref name="AFP2011" /><ref name=":0" /><ref name=":1" /> Repeated daily joint aspiration is useful in the treatment of septic arthritis. Every aspirate should be sent for culture, gram stain, white cell count to monitor the progress of the disease. Both open surgery and arthroscopy are helpful in the drainage of the infected joint. During surgery, lysis of the adhesions, drainage of pus, and debridement of the necrotic tissues are done.<ref name="AFP2011" /> Close follow up with physical exam & labs must be done to make sure the person is no longer feverish, pain has resolved, has improved range of motion, and lab values are normalized.<ref name="AFP2011" /><ref name=":1" />

In infection of a prosthetic joint, a biofilm is often created on the surface of the prosthesis which is resistant to antibiotics.<ref>Template:Cite web</ref> Surgical debridement is usually indicated in these cases.<ref name="AFP2011" /><ref name=":6">Template:Cite web</ref> A replacement prosthesis is usually not inserted at the time of removal to allow antibiotics to clear infection of the region.<ref name=":4" /><ref name=":6" /> People that cannot have surgery may try long-term antibiotic therapy in order to suppress the infection.<ref name=":4" /> The use of prophylactic antibiotics before dental, genitourinary, gastrointestinal procedures to prevent infection of the implant is controversial.<ref name="AFP2011" />

Low-quality evidence suggests that the use of corticosteroids may reduce pain and the number of days of antibiotic treatment in children.<ref>Template:Cite journal</ref>

Outcomes

Risk of permanent impairment of the joint varies greatly.<ref name=":1" /> This usually depends on how quickly treatment is started after symptoms occur as longer lasting infections cause more destruction to the joint. The involved organism, age, preexisting arthritis, and other comorbidities can also increase this risk.<ref name=":4" /> Gonococcal arthritis generally does not cause long term impairment.<ref name=":0" /><ref name=":1" /><ref name=":4" /> For those with Staphylococcus aureus septic arthritis, 46 to 50% of the joint function returns after completing antibiotic treatment. In pneumococcal septic arthritis, 95% of the joint function will return if the person survives. One-third of people are at risk of functional impairment (due to amputation, arthrodesis, prosthetic surgery, and deteriorating joint function) if they have an underlying joint disease or a synthetic joint implant.<ref name="AFP2011" /> Mortality rates generally range from 10 to 20%.<ref name=":4" /> These rates increase depending on the offending organism, advanced age, and comorbidities such as rheumatoid arthritis.<ref name=":1" /><ref name=":4" /><ref name=":3" />

Epidemiology

In children and adolescence septic arthritis and acute hematogenous osteomyelitis occurs in about 1.34 to 82 per 100,000 per annual hospitalization rates.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> In adults septic arthritis occurs in about 5 people per 100,000 each year.<ref name=NORD2009/> It occurs more commonly in older people.<ref name=NORD2009/> With treatment, about 15% of people die, while without treatment 66% die.<ref name=AFP2011/>