December 2017

12/14/2017 | BY Megan Mignemi, MD; Monroe Carell Jr. Children’s Hospital at Vanderbilt Medical Center

Pediatric Musculoskeletal Infection

Pediatric Musculoskeletal Infection

Topics covered in this section:

  • The Acute Phase Response
  • Osteomyelitis
  • Septic Arthritis
  • Pyomyositis


The Acute Phase Response

  • Acute phase response initated by the release of IL-6 as a result of tissue injury from infection
    • Coagulant phase - procoagulants produce a fibrin/platelet web to seal off damaged tissue
    • Inflammatory phase –fibrin/platelet web recruits leukocytes to kill pathogens
    • Regenerative phase – growth factors stimulate regenerative cells to repair damaged tissue; fibrinolysis removes the fibrin/platelet web
  • Aspects of the acute phase reponse can by dysregulated and manipulated by pathogens
  • Staphylococcus Aureus
    • Uses procoagulant factors to hide within the fibrin/platelet web and proliferate within the web without being detected by the host immune response (abscess formation)
      • Coagulase – activates prothrombin to thrombin, causing cleavage of fibrinogen to fibrin - forms clot and abscess
        • Resistant to anti-thrombin III/thrombin inhibitors
      • Von Willebrand factor binding protein (vWBP) – promotes antithrombin resistance by binding to prothrombin; promotes bacterial adhesion to blood vessel walls allowing hematogenous spread of bacteria
      • Clumping Factors A and B (ClfA/B) – promote clot/abscess formation
      • Fibronectin binding proteins A and B (FnBPA/B) – promote clot/abscess formation
      • Staphylococcal protein A, nuclease, adenosine synthase – interfere with immune system to prevent phagocytosis of abscess
    • Activates the fibrinolytic system to rapidly break apart the abscess and disseminate
      • Staphylokinase – causes fibrinolysis through activation of plasminogen to plasmin leading to abscess rupture and dissemination
  • Streptococcus pyogenes
    • Bypasses procoagulant step, immediately expresses fibrinolytic proteins
      • Streptokinase – activates plasminogen to plasmin to cause fibrinolysis
      • Plasminogen binding group A streptococcal M protein (PAM), GAPDH, alpha-enolase - enhance fibrinolysis and changes the plasmin on the surface of the bacteria to promote dissemination and tissue destruction
        • Necrotizing fasciitis
      • Streptolysin O – activates platelets to form complexes with lymphocytes that cause microvascular occlusions
        • Shock, organ failure
      • DNAse – cleaves DNA to prevent antimicrobial clearance
  • Musculoskeletal infection is a continuous tissue injury that intensely activates the acute phase response
    • Inflammatory and coagulation markers are senstivite indicators of musculoskeletal infection
      • CRP, ESR, fibrinogen, platelet count
    • Dysregulation of the coagulation system leads to thromboembolism, sepsis, DIC (MSK review JBJS)

Additional Readings:
  • An TJ, Benvenuti MA, Mignemi ME, Thomsen IP, Schoenecker JG. Pediatric Musculoskeletal Infection: Hijacking the Acute Phase Response. JBJS Reviews 2016;4(9):e4.
  • Montgomery NI, Rosenfeld S. Pediatric Osteoarticular Infection Update. JPO 2015 Jan;35(1):74-81.
 

Osteomyelitis

  • Incidence, Etiology, Risk factors
    • Most common pathogens: MSSA, MRSA, group A strep
      • Neonates - enterobacter, group B strep
      • Sickle cell – salmonella
    • Risk factors
      • Immunocompromise
      • Diabetes mellitus
      • Hemoglobinopathy
      • Systemic inflammatory conditions – JIA, etc.
    • Mechanism
      • Hematogenous seeding from transient bacteremia
      • Slow blood flow in metaphyseal capillaries adjacent to growth plate
      • Infection breaks through cortex – subperiosteal abscess
      • Intraarticular metaphyses – septic arthritis (hip, shoulder, elbow, ankle) 
  • Diagnosis, Classification
    • Clinical exam: fever, refusal to bear weight, point tenderness
    • Laboratory: Elevated CRP, ESR, WBC
    • Imaging
      • Xray normal during acute phase
      • Non-contrasted MRI: increased signal intensity within bone on T2; decreased signal intensity within bone on T1, MRI can also identify contiguous sources of infection
    • Classification: acute vs. chronic
      • Duration of symptoms
      • Formation of sequestrum (necrotic bone) and involucrum (new bone)
      • Brodie’s abscess
  • Treatment
    • Multidisciplinary treatment team consisting of orthopaedics, infectious disease, general pediatrics
    • Medical (antibiotics)
      • 1st line treatment if no abscess present and child is not septic.
      • Always obtain blood culture before starting, otherwise timing depends on clinical scenario
        • If child stable with no signs of disseminated disease or developing sepsis, ok to wait until after cultures obtained
      • Choice of antibiotic depends on clinical scenario and local microbiology/resistance patterns of the community
        • Clindamycin or Vancomycin empiric antibiotic of choice for most cases
      • Monitor for improvement in fever, inflammatory markers (CRP), and clinical symptoms
    • Surgical
      • Indications:
        • Patient fails medical treatment
          • Persistent fever, elevated inflammatory markers, clinical symptoms despite antibiotic therapy
        • Evolving sepsis
        • Absces formation (intra-osseous, sub-periosteal, extra-periosteal)
      • Debridement of infected or necrotic bone/decompression of abscesses
        • Cortical window in the region of affected bone
      • Consider limiting activity/weight bearing postop depending on location and severity of infection, extent of debridement
      • Postoperative imaging difficult to interpret and not indicated unless concern for ongoing source of infection
  • Complications, Prognosis
    • 50% decline in CRP within 4 days after treatment
    • CRP normalizes within 1-2 weeks, ESR within 3-6 weeks
    • Clinical exam should normalize over 6-12 weeks
    • If child does not improve as expected, consider repeat imaging to look for other sources of infection, or for involucrum/sequestrum
    • Complications
      • Pathologic fracture
      • Growth disturbance
      • AVN

Additional Readings:
  • Gafur OA, Copley LA, Hollmig ST, Browne RH, Thornton LA, Crawford SE. The impact of current epidemiology of pediatric musculoskeletal infection on evaluation and treatment guidelines. JPO 2008 Oct-Nov; 28(7): 777-85.
  • Peltola H, Paakkonen M, Kallio P, Kallio MJT. Short– versus long-term antimicrobial treatment for acute hematogenous osteomyelitis of childhood. Pediatr Infect Dis J. 2010;29(12):1123-8

 

Septic Arthritis

  • Incidence, Etiology, Risk factors
    • Most common pathogens: MSSA, MRSA, group A strep
      • Neonates – group B strep
      • Children < 4 yo – kingella kingae, requires culture in blood culture bottle or by PCR
      • Adolescents – Neisseria gonorrhoeae
    • Hematogenous seeding from transient bacteremia
    • Spread from contiguous site of infection
  • Diagnosis, Classification
    • Clinical exam: joint irritability with limited ROM, refusal to bear weight, fever
      • Hip – leg held in flexion and external rotation
    • Laboratory: Elevated CRP, ESR, WBC
    • Imaging
      • Xray normal/subtle joint space widening
      • US - effusion
      • Non-contrasted MRI: fluid within joint capsule, can identify contiguous sources of infection (ie. proximal femoral osteo, periarticular pyomyositis)
    • Kocher Criteria – used to identify septic hip arthritis vs. transient synovitis
      • Refusal to bear weight
      • ESR >40 mm/h
      • Fever >38.5°C
      • WBC >12,000 cells/uL
      • CRP >20 mg/L or >2mg/dL (not part of original criteria, but shown to be most reliable indicator)
      • Does not distinguish between septic arthritis and other contiguous sites of infection around the hip joint (proximal femoral osteo, pyomyositis)
    • Hip Aspiration
      • >50,000 cells/mm3, >75% segmented neutrophils
      • Positive gram stain
      • Positive culture
    • Differential Diagnosis
      • Transient synovitis – CRP lower, usually <20mg/L, improvement after administration of NSAIDs
      • Lyme arthritis– Borrelia burgdorferi, endemic locations (Northeastern united states), diagnosis based on positive joint culture results or supplemental blood tests
  • Treatment
    • Surgical debridement
      • Open arthrotomy vs. arthroscopic washout
      • Monitor for improvement in clinical symptoms, fever, CRP
      • Short course of IV antibiotics followed by oral antibiotics once improvement in clinical symptoms and laboratory markers
  • Complications, Prognosis
    • Excellent prognosis if diagnosis made acutely
    • Delay in diagnosis can lead to joint destruction
    • Complications:
      • Contracture
      • Growth disturbance
      • AVN

Additional Readings:
  • Kocher MS, Zurakowski D, Kasser JR. Differentiating between septic arthritis and transient synovitis of the hip in children: an evidence-based clinical prediction algorithm. JBJS 199; 81(12):1662-70.
  • Heyworth BE, Shore BJ, Donohue KS, Miller PE, Kocher MS, Glotzbecker MP. Management of pediatric patients with synovial fluid white blood-cell counts of 25,000 to 75,000 cells/mm3 after aspiration of the hip. JBJS. 2015;97(5):389-95.


Pyomyositis

  • Incidence, Etiology, Risk factors
    • More prevalent than previously thought
      • Twice as common as septic hip arthritis in some populations
    • Commonly affects the muscles around the hip joint
    • Most common pathogens: MSSA, MRSA, group A strep
    • Mechanism
      • Hematogenous seeding from transient bacteremia
      • Usually preceeded by minor injury
  • Diagnosis, Classification
    • Clinical exam: joint irritability, fever, refusal to bear weight, point tenderness
    • Laboratory: Elevated CRP, ESR, WBC
    • Imaging
      • Xray normal
      • Non-contrasted MRI: ranges from inflammation/edema within muscle to frank abscess formation
  • Treatment
    • Medical (antibiotics)
      • 1st line treatment if no abscess present on MRI
      • Monitor for improvement in fever, inflammatory markers (CRP), and clinical symptoms
    • Surgical
      • Indications:
        • Patient fails medical treatment
          • Persistent fever, elevated inflammatory markers, clinical symptoms despite antibiotic therapy
        • Evolving sepsis
        • Abscess present on advanced imaging
      • Debridement of of abscess
        • Pericapsular pyomyositis around the hip commonly involves the obturator musculature, can use medial approach for drainage
    • Complications, Prognosis
      • Complications
        • Spread to continguous sites if not recognized

Recommended readings:
  • Mignemi ME, Menge TJ, Cole HA, Mencio GA, Martus JE, Lovejoy SJ, Stutz CM, Schoenecker JG. Epidemiology, diagnosis, and treatment of pericapsular pyomyositis of the hip in children. JPO 2014 Apr-May;34(3):316-25
  • Rosenfeld S, Bernstein D, Daram S, Dawson J, Zhang W. Predicting the presence of adjacenet infections in septic arthritis in children. JPO 2015;1.