At a Glance

Infectious arthritis may be due to many different microorganisms, including bacteria, fungi, mycobacteria, and viruses. Septic arthritis generally refers to a bacterial process, but the entity also includes infection due to fungi and mycobacteria. Septic arthritis is considered a rheumatologic emergency because of the potential for rapid joint destruction and patient decompensation. Most cases of bacterial arthritis arise due to hematogenous spread. Risk factors for infectious arthritis include surgery or other trauma and pre-existing abnormal joint architecture, such as that due to rheumatoid arthritis.

In adults with nongonococcal septic arthritis, Staphylococcus aureus(including methicillin resistant S. aureus) and Streptococcus spp. are the most commonly isolated organisms and the arthritis is usually monomicrobial. Gram-negative bacilli are recovered from 5-20% of patients with septic arthritis. Neonates and the elderly are at higher risk for gram-negative septic arthritis; other risk factors include trauma, intravenous drug use, and an immunocompromised state. In children, S. aureus is the most common cause of septic arthritis, followed by Streptococcus agalactiae (< 3 months of age) and Streptococcus pyogenes in older children. In children three months to three years of age, Kingella kingae, a normal inhabitant of the mouth, has replaced Haemophilus influenzae as the primary cause of gram-negative bacterial arthritis in regions where children are routinely vaccinated against H. influenzae type b.

Disseminated infection due to Neisseria gonorrhoeae manifests as:

a triad of tenosynovitis, dermatitis, and migratory polyarthralgias or polyarthritis
a purulent monoarthritis without skin lesions
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Arthritis due to Neisseria meningitidis and Staphylococcus aureus may closely mimic clinical features of disseminated gonococcal infection. Tenosynovitis is rarely seen in other forms of infectious arthritis.

Symptoms of prosthetic joint infections include joint pain, swelling, erythema, and warmth. Infections may be acquired during implantation or due to hematogenous seeding. Early onset infections (< 3 months post-surgery) are usually due to S. aureus or gram-negative bacilli. Delayed onset infections are usually due to the less virulent coagulase-negative staphylococci, Propionibacterium acnes or enterococci. The type of pathogen varies according to the site of implanted joint; for instance, P. acnes is more common after shoulder arthroplasty.

Arthritis due to Mycoplasma hominis can cause arthritis. Human parvovirus B19 is the most common cause of viral arthritis in developed countries. In children, parvovirus B19 arthritis is typically asymmetric and pauciarticular, whereas, in adults, prominent polyarthralgias and joint inflammation are observed. Acute hepatitis B infection may lead to a polyarticular and symmetric arthritis with an urticarial rash. Other rare viral causes of arthritis include rubella and Chikungunya virus. Subacute or chronic arthritis is usually caused by mycobacteria or fungi. Dimorphic fungi are the most common cause of fungal arthritis in healthy hosts. In immunocompromised patients, Candida spp. are more often isolated.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Synovial fluid analysis should include cell count and differential, Gram stain, and culture. As synovial fluid culture sensitivity declines after initiation of antimicrobial therapy, the joint should be tapped before antibiotics are administered. For assessment of prosthetic joint infections, withholding antibiotic therapy for at least two weeks prior to obtaining cultures improves the sensitivity of culture results, if such a practice is feasible.

In suspected nongonococcal septic arthritis, a synovial fluid leukocyte count greater than 50,000 cell/mm³ supports the diagnosis. A polymorphonuclear (PMN) cell count of at least 90% is associated with septic arthritis. However, lower leukocyte counts are also common. Synovial fluid culture yields bacterial growth in 80-90% of cases. Synovial fluid culture yields bacterial growth in 80-90% of non-gonococcal cases.

Sensitivity of the Gram stain, however, only ranges from 30-50%. Joint fluids which are viscous in nature are difficult to cytospin (concentrate) in the laboratory and, therefore, the Gram stain usually is performed on such fluids without concentration. Hence, viscous fluids may occasionally be negative for organisms on Gram stain, but bacteria may grow in culture.

False-positive Gram stains may occur because of artifacts from precipitated stain and mucin, particularly in viscous or purulent joint fluids. Blood cultures are positive in 50-70% of patients with nongonococcal septic arthritis.

In gonococcal septic arthritis, synovial fluid counts are, generally, 50,000-100,000 cells/mm³. Neisseria gonorrhoeae is cultured from joint specimens in only 50% of purulent gonococcal arthritis cases and in 20-30% of cases of disseminated gonococcal infection with tenosynovitis. Patients with disseminated gonococcal infections should also have skin and mucosal surfaces tested for Neisseria, preferably by molecular testing if validated for those sources, or by culture.

In approximately 50% of cases, cultures may be positive in either the urethral, cervical, or rectal mucosal sites. Blood cultures are positive in less than 30% of patients but are more common in patients with disseminated disease and tenosynovitis. Gram stain and culture of the skin lesions are rarely helpful. Patients with known or suspected disseminated gonococcal infections should also be screened for human immunodeficiency virus (HIV) and syphilis, as these infections coexist with other sexually-transmitted diseases.

For documentation of prosthetic joint infections, multiple specimens of tissue and fluid should be submitted for culture (optimally five to seven) to minimize sampling error and increase the chances of detection of fastidious organisms. Since fastidious organisms and anaerobes may also contribute to such infections, the specimens should be rapidly cultured onto media upon arrival in the laboratory.

Sonication of an explanted prosthesis can be helpful in breaking up the biofilm matrix and releasing the organisms. Although sonication is not routine in many clinical laboratories, the technique is relatively simple. If sonication is not available, vigorous vortexing of the device is an alternative. Due to the frequency with which P. acnes is associated with prosthetic joint infections, the aerobic and anaerobic cultures should be held for 10 to 14 days to detect this pathogen. It is necessary to notify the Microbiology Laboratory when a culture from a prosthetic joint is submitted, or when P. acnes is suspected, since standard anaerobic cultures are not generally held longer than 5-7 days and may be falsely negative.

Blood cultures should be obtained in patients with suspected bacterial arthritis and are positive in approximately 50% of cases.

Investigators have assessed the value of polymerase chain reaction (PCR) in the diagnosis of joint infections. Molecular methods of detection, such as broad-range or target-specific PCR, offer advantages over culture for the diagnosis of arthritis due to organisms including Mycoplasma (which is difficult to culture), K. kingae, anaerobes, or other uncommon organisms.

In particular, 16S rDNA PCR has been helpful in diagnosing cases of K. kingae joint infections in children which were missed by culture. The role of PCR in the diagnosis of more common causes of septic arthritis, such as staphylococci or streptococci, is less clear. Since PCR is being increasingly used for diagnosis, clinicians must be aware of the problems associated with PCR. Such problems include the risk of picking up contaminating microbes, the lack of a gold standard for comparison, and the fact that PCR will pick up the DNA of dead organisms.

If tuberculous arthritis is considered, biopsy of the joint with culture must be performed. Diagnosis of parvovirus B19 is aided by peripheral blood PCR or by positive serology. If fungal arthritis is suspected, synovial fluid should be collected in lysis centrifugation tubes for recovery of moulds or dimorphic fungi.

The peripheral white blood cell count, erythrocyte sedimentation rate, and C-reactive protein are nonspecific and do not appreciably increase the pretest probability of disease. Likewise, synovial fluid glucose, protein, and lactate dehydrogenase are not informative because of low sensitivity and specificity.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Inoculation of synovial fluid into bloodculture bottles in addition to direct plating of the specimen onto agarmedia improves recovery of pathogens as compared to direct platingalone. It is suggested that direct plating on agar media is performedalongside inoculation of blood culture bottles. Blood culture bottleinoculation is suggested if K. kingae is suspected. Culture ofthe joint fluid directly into blood culture bottles is most helpful iflarger amounts of fluid (> 2 mL) are collected. It is important toinoculate as much joint fluid as possible into the blood culture bottlein order to increase sensitivity of detection. If < 2 mL of fluid arecollected, fluid may be transported to the laboratory in a syringe withthe needle removed.

Laboratoriesuse either routine blood culture bottles or occasionally lysiscentrifugation tubes for culture of synovial fluid. If synovial fluid isinoculated only into blood culture bottles, a separate portion of thejoint fluid should be sent for Gram stain in a sterile syringe or tube. It is generally preferable to inoculate blood culture bottles in thelaboratory rather than at the bedside.

Cytocentrifugation of the synovial fluid should be performed to increase sensitivity of the direct Gram stain.

Neisseria gonorrhoeaeis a particularly fastidious organism. Synovial fluid from patientswith suspected disseminated gonococcal infections should be transportedimmediately to the laboratory for speedy inoculation onto Neisseria-specific media. Since Neisseria spp. die at cool temperatures, synovial fluid in suspected gonococcal infections must never be refrigerated before plating.

Manylaboratories culture the joint fluid in a liquid broth tube in additionto the solid plate media. If the blood bottle is used as the liquidmedia, it is generally not necessary to inoculate a separate liquidbroth tube as well. Liquid broth medium is helpful in recoveringanaerobes as well as organisms that cannot grow well on solid media. Rarely, an organism may be recovered only from the broth tube media andnot from the solid media. This pattern of growth from liquid medium onlymay be due to the presence of:

an anaerobe, or
an organism present in such low numbers that it could only be recovered from the enriched tube broth medium, or
a contaminant.

Laboratorieswill often report organisms cultured from the liquid broth medium onlywith a comment such as “recovered from broth only.” It is theclinician’s responsibility to decide whether such organisms aresignificant or not.

What Lab Results Are Absolutely Confirmatory?

Confirmatory results are those for which organism recovery from culture matches the clinical presentation. The patient should improve with appropriate antibiotic therapy. Neisseria gonorrhoeae is not a contaminant; therefore, recovery of this fastidious organism in the setting of suspected infectious arthritis is confirmatory.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

If tuberculous arthritis is considered, biopsy of the joint with culture must be performed. Diagnosis of parvovirus B19 is determined by peripheral blood PCR or by positive serology. If fungal arthritis is suspected, synovial fluid should be collected in lysis centrifugation tubes for recovery of molds or dimorphic pathogens.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Cytocentrifugation of the synovial fluid is of questionable significance, but some laboratories centrifuge the fluid before performing the Gram stain. It is believed that cytocentrifugation improves organism visibility. However, potential contaminants may be introduced into the culture with manipulation of the fluid. A fluid that is viscous or visibly purulent is often too difficult to centrifuge.

Many laboratories also culture the joint fluid in a liquid broth medium, in addition to the solid plated media. The liquid broth medium is used to recover anaerobes, as well as organisms that cannot grow well on solid media. Rarely, an organism only recovered from the broth and not from the solid media may be reported. This pattern of growth may be due to:

an anaerobe
an organism that may be present in such low numbers that it could only be recovered from the rich tube broth medium
a contaminant

Laboratories will often report such organisms, followed by a qualifying phrase, such as “recovered from broth only.” It is the clinician’s responsibility to decide whether such organisms are significant or not.

What’s the Evidence?/References

Sharff, KA, Richards, EP, Townes, JM. “Clinical management of septic arthritis”. Curr Rheumatol Rep. vol. 15. 2013. pp. 332(General review of septic arthritis, including diagnosis.)

Butler-Wu, SM, Burns, EM, Pottinger, PS, Magaret, AS, Rakeman, JL, Matsen, FA 3rd, Cookson, BT. “Optimization of periprosthetic culture for diagnosis of Propionibacterium acnes prosthetic joint infection”. J Clin Microbiol. vol. 49. 2011. pp. 2490-5. (Study of optimal recovery of P. acnes from periprosthetic joint infections.)

Chometon, S, Benito, Y, Chaker, M, Boisset, S, Ploton, C, Bérard, J, Vandenesch, F, Freydiere, AM. “Specific real-time polymerase chain reaction places Kingella kingae as the most common cause of osteoarticular infections in young children”. Pediatr Infect Dis J. vol. 26. 2007. pp. 377-81. (Description of the use of molecular methods for diagnosis of K. kingae osteoarticular infections.)

Achermann, Y, Goldstein, EJ, Coenye, T, Shirtliff, ME. “Propionibacterium acnes: from Commensal to Opportunistic Biofilm-Associated Implant Pathogen”. Clin Microbiol Rev. vol. 27. 2014. pp. 419-440. (Overview of P. acnes and role in prosthetic infections.)

Mathews, CJ, Kingsley, G, Field, M, Jones, A, Weston, VC, Phillips, M, Walker, D, Coakley, G. “Management of septic arthritis: a systematic review”. Ann Rheum Dis. vol. 66. 2007. pp. 440-5. (Systematic review of diagnosis and management of septic arthritis.)

Sharff, KA, Richards, EP, Townes, JM. “Clinical management of septic arthritis”. Curr Rheumatol Rep. vol. 15. 2013. pp. 332(General review of septic arthritis, including diagnosis.)

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Infectious Arthritis

At a Glance

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

What Lab Results Are Absolutely Confirmatory?

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

What’s the Evidence?/References

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