The editors and current author would like to thank and acknowledge the significant contribution of the previous author of this chapter from the 2002 first edition Dr. Floyd S. Ota. This current third edition chapter is a revision and update of the original author’s work.
A 2 year old male presents with fever and refusal to walk for two days. He complains of pain and points to his right lower extremity. The pain has become increasingly worse, and he is unable to sleep at night. His appetite is decreased. There is a recent history of an upper respiratory infection about two weeks ago but no recent trauma. The pain is not known to migrate. He has no past medical history, but his immunizations are delayed (last immunizations at two months of age). There is no history of cough, headache, abdominal pain, vomiting, diarrhea, hematuria, or known tick exposure. Family history is negative for sickle cell disease and arthritis.
Exam: VS T 39.5, P 120, R 18, BP 100/50, oxygen saturation 100% on room air, weight 10th percentile, height 50th percentile. He is thin appearing and refuses to walk. He is not fussy and nontoxic. HEENT exam is normal. His neck has a normal range of motion without pain. Heart, lungs, abdomen, and genital exams are normal. He is lying in a hospital bed with his right lower extremity externally rotated, abducted, and motionless. He has severe discomfort with minimal internal and external rotation of the right hip despite attempts to distract him. His other joints and neurological exam are normal. There are no notable skin lesions.
Laboratory studies show WBC 20,000, 80% segmental neutrophils, 10% bands, 8% lymphocytes, 2% monocytes, hemoglobin/hematocrit 14/43, platelet count 265,000. ESR 55, CRP 120, serum glucose 95 mg/dL. UA SG 1.020, negative for blood. EKG normal sinus rhythm. Hip radiographs show widening of the acetabular space on the right. A bedside ultrasound confirms a large hip effusion.
An orthopedic surgeon is consulted. An arthrocentesis of the right hip is performed, which shows WBC 110,000 per mm3, glucose 35 mg/dL, gram stain shows many WBCs and few gram positive cocci. Surgical debridement of the right hip is performed. Empiric treatment with vancomycin and ceftriaxone is initiated after cultures are obtained. ASO, ANA and rheumatoid factors are negative. PPD is negative. Synovial fluid culture grows out Staphylococcus aureus sensitive to methicillin. Blood culture is also positive for methicillin sensitive S. aureus. Vancomycin and ceftriaxone are discontinued and the patient is treated with oxacillin. Within three days of treatment onset, his fever declines and he slowly begins to ambulate. His appetite returns and he is eventually transitioned to high dose oral antibiotics to complete four weeks of treatment. He is discharged with home care physical therapy services.
Septic arthritis generally refers to bacterial infection of the joint space; however fungal and mycobacterium can also cause disease (1). Septic arthritis is a medical emergency and failure to provide prompt diagnosis and treatment may lead to severe morbidity and disability. The incidence in the United States for children has been down-trending for the last two decades and currently is estimated to be 3 to 4 per 100,000 individuals (2). Children under the age of 5 are most affected, the most involved joints are the knee and hip, and there is a male-to-female predilection of 1.7 (2). Infants rarely develop septic arthritis unless there is a neonatal complication such as maternal infection at the time of delivery, invasive procedure, osteomyelitis, or prematurity (3). Risk factors for older children include bacteremia, concomitant osteomyelitis, immunocompromised state, and/or hemoglobinopathy (4).
Diarthrodial joints (cartilaginous coverings to the articulating surfaces within a synovial joint capsule) have a synovial lining that coats the inside surface of the joint capsule, producing synovial fluid that lubricates the joint and separates the adjacent articular cartilages. This histologic lining is extremely vascular and lacks a basement membrane (5). This tissue produces synovial fluid, a viscous media that has an electrolyte and glucose concentration similar to that of plasma and acts as a lubricant to the adjacent cartilage. This fluid is normally sterile, but if invaded by bacteria, it provides a good environment for bacterial growth. The three main routes of joint infection are: 1) hematogenous (most common in children), 2) contiguous spread, and 3) direct inoculation from a procedure or trauma (1,5). The amount of blood flow to the synovium is high, equivalent to that of the brain. Thus, transient bacteremia can cause a large number of organisms to be delivered to this region. Bacteria normally cleared by synovial macrophages can be overwhelmed when presented with a large quantity of organisms. Proteolytic enzymes produced by bacteria and inflammatory cytokines incite damage to the articular cartilage. This process begins early in the infection, and its effects may render the articular surface susceptible to future degenerative joint disease. Ex vivo studies have shown that cartilage damage occurs within 8 hours of bacterial inoculation; hence, rapid diagnosis and appropriate management are critical to preserving long-term joint health (6). Furthermore, in cases of hip septic arthritis, swelling of the joint capsule may predispose the femoral head to avascular necrosis due to ischemia of the capital femoral epiphysis. Dislocation or subluxation can also result from the increased intracapsular pressure (5). Notably, the inflammatory process and tissue damage may progress even after appropriate treatment has eradicated the causative organisms (5).
Septic arthritis presents acutely with fever, joint pain, swelling, and limited and painful range of motion. The most commonly affected joints are the knees and hips followed by the ankle, elbow, wrist, and shoulders (1,7). While presentation can vary by age, children with septic arthritis all present with one common feature: pain to the affected limb. This limb pain is due to stretching of the joint capsule secondary to edema or effusion. In infants, pain may present as a pseudo paralysis, or a lack of movement in the impacted limb (7). Additionally, infants may be febrile, irritable, lose their appetite, cry when being carried, fuss during diaper changes, or have swelling of their affected limb. Along with constitutional symptoms of fever, tachycardia, and irritability, older children may present with refusal to walk or bear weight or to utilize the affected limb (7). A history of trauma or upper respiratory infection in the weeks prior is sometimes elicited (8). Septic arthritis may be a complication for patients with a history of recent surgery, femoral venipuncture, urinary tract infection, and infection due to varicella zoster virus (due to secondary cutaneous infection of the lesions with S. aureus or group A streptococci) (1).
On physical exam, swelling, tenderness, erythema, and warmth may be apparent to joints with little overlying tissue; however, in a deep, well enclosed joint, such as the hip, these findings may be minimal or absent. Subtle findings, such as a loss of natural body contours or normal skin creases (such as asymmetric buttock creases), may be all that is present. Thus, examination of the opposite side for symmetry is an important aspect of the physical exam. Children with septic arthritis often have significantly decreased and painful range of motion, as any movement that stretches the joint capsule produces severe discomfort. In infants with septic arthritis of the hip, the classic physical finding is a child lying motionless with his/her leg externally rotated and abducted. In septic arthritis of the axial skeleton and pelvis, direct compression of the joints may be the only way to produce clinical signs. It is important to examine all the joints of the lower extremities in a child with a limp due to the possibility of referred pain. For example, the child may present with complaints of knee pain, when in fact the hip is affected but is causing referred pain to the knee. Examination for signs of meningitis and performing a lumbar puncture when indicated is important in children who are susceptible to Haemophilus influenza, type B (HiB). HiB infections are currently very rare because of widespread effective HiB immunization. In the neonatal period, septic arthritis often is present concurrently with acute osteomyelitis of the adjacent bone (6). Hepatomegaly may be found in cases of septic arthritis due to brucella, and one should be suspicious particularly in cases of children with a history of recent travel or consumption of unpasteurized milk products (9).
The differential diagnosis of a child with fever and joint pain includes: septic arthritis, transient synovitis, reactive arthritis, trauma, acute rheumatic fever, Henoch-Schoenlein purpura, Kawasaki disease, serum sickness, Lyme disease arthritis, inflammatory bowel disease, hematologic cancer, and connective tissue disease (e.g., juvenile rheumatoid arthritis, systemic lupus erythematosus). Frequently a diagnostic dilemma for the clinician, transient synovitis (also known as toxic synovitis) of a joint is a viral or post infectious process causing acute arthritis which may clinically mimic septic arthritis. Transient synovitis of the hip or knee is often preceded by an upper respiratory infection or pharyngitis in previously healthy children, with a peak incidence of 3 to 6 years of age (7). The etiology of transient synovitis is unclear; however, children with this condition may have a predisposition for hypersensitivity reactions. Laboratory work-up, such as CBC, ESR and CRP, are often normal or only minimally elevated, and radiological studies often fail to show impressive changes. Rarely is joint aspiration performed, despite the presence of a hip effusion, if the clinical findings and laboratory studies are suggestive of this diagnosis. Transient synovitis is a diagnosis of exclusion, and treatment consists of non-steroidal anti-inflammatory medications and rest. Overall prognosis is usually good (about 70% of patients have resolution of their symptoms within two weeks), but avascular necrosis may occur in some patients.
Laboratory evaluations for septic arthritis are important to rule out non-infectious causes of joint pain and to direct appropriate management. The most important lab studies for septic arthritis are blood cultures, CBC, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) (1). These values can be elevated in the presence of acute septic arthritis and are non-specific indicators of acute inflammation (please refer to the chapter on osteomyelitis for a discussion of CRP and ESR). ESR and CRP are not adequate to rule septic arthritis in or out; yet highly elevated values are known to represent greater risk than minimally elevated value. White blood count (WBC) can be elevated in 30% to -60% of patients with septic arthritis; but the sensitivity increases to 70% with associated increase in neutrophil-precursor band cells or a "left shift" (10). A CBC can be helpful to reduce the likelihood of other diagnoses (such as leukemia), and thus it is an integral part of the workup. Lyme titers should be obtained for patients in endemic areas or with recent travel (11). The Kocher criteria has been used to consolidate these laboratory tests and provide a score to evaluate clinical and laboratory findings to differentiate between septic hip arthritis and transient synovitis of the hip using the following criteria: ability to weight-bear on impacted limb, temperature >38.5°C/101.3°F, ESR > 40 mm/hr, WBC > 12,000/mm3 (12). According to the Kocher criteria, a child with 3 or more of the above criteria has a 93% likelihood of having septic arthritis with a sensitivity of 84% (13). The Kocher criteria has been evaluated in joints other than the hip and is not as reliable. For example, when applied to the knee, the sensitivity of Kocher criteria is only 52%, limiting the utility of this score only to the pediatric hip.
Joint aspiration, or arthrocentesis, is the most helpful test to make the diagnosis of septic arthritis. Arthrocentesis should be obtained immediately and should not be delayed for results of blood cultures or inflammatory laboratory studies (7). Delayed diagnosis and treatment have a poorer prognosis, increasing the risk of joint damage, especially if joint aspiration and correct antibiotic administration is initiated four or more days after symptom onset (9). Aspiration accuracy can be improved with the use of ultrasound-guided techniques to ensure entry into the joint space. The synovial fluid sample should be analyzed for WBC count and differential, gram stain, culture and sensitivity testing, and PCR for Kingella kingae and Lyme disease (4,11,14). Septic arthritis is the most common diagnosis when the synovial WBC count ranges from 25,000 to 75,000 with >90% polymorphonuclear leukocytes (PMNs) (4,9,12). Glucose concentrations are decreased to about 30% of the serum glucose. This helps to differentiate septic arthritis from other etiologies of acute joint pain. Typically, WBC count and glucose values are not as dramatically affected in cases of transient synovitis, reactive arthritis, and juvenile rheumatoid arthritis (JRA). Bacterial culture and gram stain, when positive, are very helpful in the diagnosis and management of acute septic arthritis. Identification of the offending organism and antibiotic sensitivities are an extremely important aspect to guide therapy. A negative culture or gram stain does not rule out septic arthritis, since 50% to 70% of patients have a false negative, particularly with gram-negative organisms (1). The most common organism isolated is Staphylococcus aureus, identified in 50% of cases, half of which were isolated as MRSA (15). S. aureus is followed by group A Streptococcus, Streptococcus pneumonia, Kingella kingae, and HiB (1,4,5,15). Neisseria gonorrhoeae (GC) should be considered in neonates and sexually active adolescents. GC septic arthritis may present with a polyarticular presentation and skin lesions, which is unusual for other causes of septic arthritis. In newborns with suspected GC, cultures of the cerebrospinal fluid, blood, and eye discharge should also be obtained (9). Other pathogens to consider in the newborn period are group B Streptococci and Escherichia coli. Recently, Kingella kingae has become a more recognized pathogen (1,4).
Imaging should start with plain film radiographs, typically including the contralateral limb for comparison to assess for subtle radiographic changes in the affected joint. When the clinical concern is septic arthritis of the hip, AP and frog leg views of the pelvis should be obtained to allow for comparison of the affected and unaffected side. Septic arthritis is suggested when there is displacement of normal fat pads, subluxation of the joint, and/or widening of the joint space due to capsular swelling from an effusion (10). These signs are subtle and may not be present early in the disease process. Bony changes, such as epiphyseal, metaphyseal or subchondral bony erosion, typically become visible on radiographs 2 to 4 weeks after symptom onset (9) .Ultrasound is a quick, and more sensitive means of detecting the presence of a hip effusion that does not require sedation (4,5,16). CT scanning has significant radiation exposure issues. Nuclear medicine bone scans have radiation exposure, poor availability after hours, and the procedure itself is very slow. MRI scanning can help to differentiate between septic arthritis in the presence or absence of a concurrent osteomyelitis. MRI is preferable when possible because it offers more anatomic information without the use of radiation.
Treatment of acute septic arthritis consists of drainage, surgical debridement, lavage, and antibiotic treatment. The risk for poor prognosis is increased if any of the following factors are present: a delay in initiation of treatment, age less than six months, history of prematurity, the presence of S. aureus as the infectious etiology, involvement of the hip, and the presence of a concurrent osteomyelitis (5-7,10,17). Early intervention is required to minimize morbidity and preserve the integrity of the synovium, articular cartilage, and surrounding bone. The three treatment options for drainage include arthrotomy, arthroscopy, and needle aspiration (9). Drainage and lavage allow for opening and reducing pressure of the joint space as well as removal of loculations and infected, inflamed, or damaged tissue. Surgical arthrotomy for the hip and shoulder is preferred for improved visualization and joint space access, as inadequate drainage increases the likelihood of poor outcomes (18). It is unclear if arthrotomy or arthroscopic debridement is superior, as arthrotomy is more invasive, while arthroscopy may have limited joint space visualization and access. Surgical drainage and debridement are not always indicated for involvement of smaller joints; needle aspiration may be sufficient to decompress the joint space and remove some debris.
The purpose of drainage and lavage is to produce an environment with minimal inflammatory products, so that antimicrobial therapy is maximized in order to sterilize the joint space. After surgical or needle aspiration intervention, empiric parenteral antibiotic coverage for Staphylococcus aureus should be initiated. The drug of choice is vancomycin due to the high risk (currently about 30%) that the organism may be resistant to cephalosporins and methicillin (MRSA). Clindamycin is another antibiotic choice that will cover most strains of MRSA, but it is not 100% effective, so vancomycin is preferred. A third-generation cephalosporin should be added if the child is at risk for HiB or gonococcal disease. If CNS infection is suspected, meningitic doses should be implemented. The antibiotic regimen can then be narrowed once the cultures and sensitivities are received. Traditionally, treatment duration has been for 3 to 4 weeks; however, several trials have shown no differences in outcomes with shorter antibiotic courses (7). Peripherally inserted central IV catheters can be placed and home IV antibiotics can be arranged with home care. Alternatively, oral antibiotics (usually high dose) have become an accepted option to complete home therapy instead of parenteral antibiotics. This can be done because antibiotic concentrations in the synovium are often higher than that of the serum due to slow reabsorption of the drugs (from the synovium). All of the following criteria must be met in order to switch to oral antibiotics: child is 1 month of age or older, the patient is immunocompetent, infectious organism is identified and sensitivity to oral antibiotics is documented, the patient is able to take and keep down oral antibiotics, a clear response to parenteral treatment is demonstrated, and routine compliance is assured (9). Following labs, including CBC and CRP at routine intervals may be helpful to monitor clinical progress and monitor for side effects.
Questions
1. True/False: Septic arthritis is a disease most commonly found in adolescent males.
2. True/False: In septic arthritis, the hips and knees are the most commonly affected joints.
3. True/False: In a child with septic arthritis of the hip, redness, swelling, and warmth are often detectable on physical exam.
4. True/False: Children with transient synovitis never present with fever.
5. True/False: The ESR and CRP can usually distinguish between transient synovitis and septic arthritis.
6. True/False: The most common bacterial etiology of septic arthritis is Staphylococcus aureus.
7. True/False: Haemophilus influenzae type B used to be a common cause of septic arthritis in young children, but this is very uncommon today.
8. True/False: Surgical arthrotomy is always warranted for cases of septic arthritis.
Related x-rays
Ankle septic arthritis: Young LL. Aspirating the Ankle Joint. In: Yamamoto LG, Inaba AS, DiMauro R. Radiology Cases in Pediatric Emergency Medicine, 1995, volume 3, case 6. Available online at: http://www.hawaii.edu/medicine/pediatrics/pemxray/v3c06.html
Septic arthritis of the hip: Rosen MH. Fever and Refusal to Walk in a 4-Year Old. In: Yamamoto LG, Inaba AS, DiMauro R. Radiology Cases in Pediatric Emergency Medicine, 1996, volume 4, case 17. Available online at: www.hawaii.edu/medicine/pediatrics/pemxray/v4c17.html
Hip effusion in a case of osteoid osteoma: Yamamoto LG. Osteoid Osteoma. In: Yamamoto LG, Inaba AS, DiMauro R. Radiology Cases in Pediatric Emergency Medicine, 1996, volume 4, case 15. Available online at: www.hawaii.edu/medicine/pediatrics/pemxray/v4c15.html
References
1. Krogstad P. Chapter 56. Septic Arthritis. In: Cherry JD, Harrison GJ (eds). Feign and Cherry’s Textbook of Pediatric Infectious Diseases, 8th edition, 2019. Elsevier: Philadelphia. pp: 529-534.
2. Okubo Y, Nochioka K, Marcia T. Nationwide survey of pediatric septic arthritis in the United States. J Orthop. 2017;14(3):342-346. doi:10.1016/j.jor.2017.06.004
3. Sreenivas T, Nataraj AR, Kumar A, Menon J. Neonatal septic arthritis in a tertiary care hospital: a descriptive study. Eur J Orthop Surg Traumatol Orthop Traumatol. 2016;26(5):477-481. doi:10.1007/s00590-016-1776-9
4. Erkilinc M, Gilmore A, Weber M, Mistovich RJ. Current Concepts in Pediatric Septic Arthritis. J Am Acad Orthop Surg. 2021;29(5):196-206. doi:10.5435/JAAOS-D-20-00835
5. Swami S. Chapter 105. Bone and Joint Infections. In: Zaoutis LB, Chiang VW (eds). Comprehensive Pediatric Hospital Medicine, 2nd edition, 2018. McGraw Hill Education, New York. pp: 566-582.
6. Klosterman MM, Villani MC, Hamilton EC, Jo C, Copley LA. Primary Septic Arthritis in Children Demonstrates Presumed and Confirmed Varieties Which Require Age-specific Evaluation and Treatment Strategies. J Pediatr Orthop. 2022;42(1):e27-e33. doi:10.1097/BPO.0000000000001976
7. Donders CM, Spaans AJ, van Wering H, van Bergen CJ. Developments in diagnosis and treatment of paediatric septic arthritis. World J Orthop. 2022;13(2):122-130. doi:10.5312/wjo.v13.i2.122
8. Pääkkönen M, Kallio MJT, Lankinen P, Peltola H, Kallio PE. Preceding trauma in childhood hematogenous bone and joint infections. J Pediatr Orthop Part B. 2014;23(2):196-199. doi:10.1097/BPB.0000000000000006
9. Krogstad P. Bacterial arthritis: Clinical features and diagnosis in infants and children. UpToDate. Published online 2022.
10. Long B, Koyfman A, Gottlieb M. Evaluation and Management of Septic Arthritis and its Mimics in the Emergency Department. West J Emerg Med. 2019;20(2):331-341. doi:10.5811/westjem.2018.10.40974
11. Baldwin KD, Brusalis CM, Nduaguba AM, Sankar WN. Predictive Factors for Differentiating Between Septic Arthritis and Lyme Disease of the Knee in Children. J Bone Joint Surg Am. 2016;98(9):721-728. doi:10.2106/JBJS.14.01331
12. Heyworth BentonE, Shore BenjaminJ, Donohue KynaS, Miller PatriciaE, Kocher MininderS, Glotzbecker MichaelP. Management of Pediatric Patients with Synovial Fluid White Blood-Cell Counts of 25,000 to 75,000 Cells/mm3 After Aspiration of the Hip. J Bone Jt Surg. 2015;97(5):389-395. doi:10.2106/JBJS.N.00443
13. Obey MR, Minaie A, Schipper JA, Hosseinzadeh P. Pediatric Septic Arthritis of the Knee: Predictors of Septic Hip Do Not Apply. J Pediatr Orthop. 2019;39(10):e769-e772. doi:10.1097/BPO.0000000000001377
14. Carter K, Doern C, Jo CH, Copley LAB. The Clinical Usefulness of Polymerase Chain Reaction as a Supplemental Diagnostic Tool in the Evaluation and the Treatment of Children With Septic Arthritis. J Pediatr Orthop. 2016;36(2):167-172. doi:10.1097/BPO.0000000000000411
15. Yi J, Wood JB, Creech CB, et al. Clinical Epidemiology and Outcomes of Pediatric Musculoskeletal Infections. J Pediatr. 2021;234:236-244.e2. doi:10.1016/j.jpeds.2021.03.028
16. Jaramillo D, Dormans JP, Delgado J, Laor T, St Geme JW. Hematogenous Osteomyelitis in Infants and Children: Imaging of a Changing Disease. Radiology. 2017;283(3):629-643. doi:10.1148/radiol.2017151929
17. Ernat J, Riccio AI, Fitzpatrick K, Jo C, Wimberly RL. Osteomyelitis is Commonly Associated With Septic Arthritis of the Shoulder in Children. J Pediatr Orthop. 2017;37(8):547-552. doi:10.1097/BPO.0000000000000709
18. 23. Thompson RM, Gourineni P. Arthroscopic Treatment of Septic Arthritis in Very Young Children. J Pediatr Orthop. 2017;37(1):e53-e57. doi:10.1097/BPO.0000000000000659
Answers to questions
1. False. It is a condition that usually affects younger children early in the first decade of life.
2. True
3. False. The hip joint is deep and has a significant amount of surrounding tissue, thus inflammation may not be easily detected on physical exam. Exam findings may be subtle, such as asymmetry or loss of function. Decreased and painful range of motion is the best way to detect an effusion by physical exam.
4. False. They also can present with fever. This is why differentiating between transient synovitis and septic arthritis can be a difficult clinical problem.
5. This is true in most instances. Low ESR and CRP values make septic arthritis unlikely. Very high ESR and CRP values make septic arthritis more likely. Intermediate ESR and CRP values are not very helpful in distinguishing transient synovitis from early septic arthritis. In clinical medicine, the ESR and CRP values are coupled with the clinical factors that permit the clinician to establish a pre-test risk probability of septic arthritis versus transient synovitis. If the pre-test probability of septic arthritis is low and the ESR/CRP are low, then it is very likely that the patient has transient synovitis. If the pre-test probability of septic arthritis is high and the ESR/CRP are high, then it is very likely that the patient has septic arthritis. Any other combination of clinical risk and ESR/CRP results in substantial uncertainty in the diagnosis.
6. True
7. True
8. False. In larger joints surgical intervention is almost always performed; however in cases of septic arthritis of smaller joints, medical management can be carried out with good results. Orthopedic surgical consult should always be obtained expeditiously whenever the diagnosis is considered.