Sandbox:septic arthritis pathogenesis
Pathophysiology
Presence of extreme vasularity and absence of limiting of basement membrane, promotes the easy access of infections into the synovial space.[1]
Hematogenous spread: Septic arthritis most commonly develop as a result of hematogenous spreading bacteria into the vascular synovial membrane.[2] Hematogenous spread is commonly associate with injection drug use, presence of indwelling catheters, and an underlying immunocompromised state such as HIV infection.
Direct inoculation: Direct inoculation of microorganisms may occur during deep penetrating injuries, intra-articular steroid injection, arthroscopy or prosthetic joint surgery, particularly in association with knee and hip arthroplasties and contiguous osteomyelitis rupturing into the joint.[3][4]
Bone infection such as osteomyelitis can spread by breaking through its outer cortex and then into the intracapsular region that lead to joint infection. This kind of spread is more common in children as the small capillaries can cross the epiphyseal growth plate and permit extension of infection into the epiphysis and joint space.[5][6]
Pathogenesis of septic arthritis depends on multiple factors and it mainly depends on the balance between virulence of the microbial pathogen and the host immune response against the pathogen.
Non-gonococcal arthritis
Staph. aureus is the most common pathogen non gonococcal pathogen that causes septic arthritis. The pathogenesis of septic arthritis by staphylococcus can be a better representation for pathogenesis of most non gonococcal arthritis.
Bacterial colonization and adherence into the synovium
Mechanism of infection transmission
Hematogenous spread: Septic arthritis most commonly develop as a result of hematogenous spreading bacteria into the vascular synovial membrane.[2] Hematogenous spread is commonly associate with injection drug use, presence of indwelling catheters, and an underlying immunocompromised state such as HIV infection.
Determinants of hematognous seeding:[2]
- Well vascularized synovium
- Absence of limiting basement membrne
- Recent joint surgery, induces the production of host-derived extracellular matrix proteins( e.g. collagen) that aids in post surgical healing process, can assist bacterial attachment and progression to infection
- Virulence of microorganism
- Susceptibility of synovial membrane for microorganism
Direct inoculation: Direct inoculation of microorganisms may occur during deep penetrating injuries, intra-articular steroid injection, arthroscopy or prosthetic joint surgery, particularly in association with knee and hip arthroplasties.[3][4]
Contiguous spread: Bone infection such as osteomyelitis can spread by breaking through its outer cortex and then into the intracapsular region that lead to joint infection.
Role of bacterial products in pathogenesis
Non-gonococcal arthritis
| Bacterial colonization and adherence into the synovium ⬇ | ||
|---|---|---|
| Mechanism of transmission | Hematogenous spread: Septic arthritis most commonly develop as a result of hematogenous spreading bacteria into the vascular synovial membrane.[2] Hematogenous spread is commonly associate with injection drug use, presence of indwelling catheters, and an underlying immunocompromised state such as HIV infection.
Determinants of hematognous seeding:[2]
Direct inoculation: Direct inoculation of microorganisms may occur during deep penetrating injuries, intra-articular steroid injection, arthroscopy or prosthetic joint surgery, particularly in association with knee and hip arthroplasties.[3][4] Contiguous spread: Bone infection such as osteomyelitis can spread by breaking through its outer cortex and then into the intracapsular region that lead to joint infection. | |
| Role of bacterial products in pathogenesis | Bacterial attachment protein receptors termed as microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) that attach host joint extracellular matrix proteins such as collagen, laminin, elastin etc. and promote colonization and initiate the infectious process.[7][8] The role of bacterial products is activation of host immune response and deteriorate the tissue destruction.[9] | |
| Escape mechanism developed by pathogen | Adherence of pathogen to fibronectin on host tissue with its fibronectin receptors[10] ⬇ Internalization of pathogen by host mechanisms such as pseudopod formation or through receptor-mediated endocytosis via clathrin-coated pits[11] After internalization pathogen into the host cells such as osteoblasts, it survives intracellularly and induces apoptosis in the other cells through the activation of host immune response[12] | |
| Host immune response | Due to rapid proliferation of bacteria predesposes to activation of host acute inflammatory response
⬇ Synovial cells releases host inflammatory cytokines such as IL-1 and IL-6 into the synovium[13] ⬇ Activation of acute phase reactants by Interleukins[14] ⬇ Acute phase reactants bind to pathogen and promote opsonization and phagocytosis and activates complement system[15] ⬇ Phagocytosis of pathogen by macrophages, synovial cells and neutrophils with the release of inflammatory cytokines such as tumor necrosis factor, IL-6 and nitric oxide.[16] |
|
| Humoral immunity and adaptive immunity also activates by superantigens of pathogens and promote clearance of pathogen by releasing Interferon-gamma, IL-4, IL-10 that reduces the host mortality and joint destruction.[17][18] |
References
- ↑ Goldenberg DL, Reed JI (1985) Bacterial arthritis. N Engl J Med 312 (12):764-71. DOI:10.1056/NEJM198503213121206 PMID: 3883171
- ↑ 2.0 2.1 2.2 2.3 2.4 Klein RS (1988) Joint infection, with consideration of underlying disease and sources of bacteremia in hematogenous infection. Clin Geriatr Med 4 (2):375-94. PMID: 3288326
- ↑ 3.0 3.1 3.2 Atcheson SG, Ward JR (1978) Acute hematogenous osteomyelitis progressing to septic synovitis and eventual pyarthrosis. The vascular pathway. Arthritis Rheum 21 (8):968-71. PMID: 737020
- ↑ 4.0 4.1 4.2 Gray RG, Tenenbaum J, Gottlieb NL (1981) Local corticosteroid injection treatment in rheumatic disorders. Semin Arthritis Rheum 10 (4):231-54. PMID: 6787706
- ↑ Barton LL, Dunkle LM, Habib FH (1987) Septic arthritis in childhood. A 13-year review. Am J Dis Child 141 (8):898-900. PMID: 3498362
- ↑ Buckholz JM (1987) The surgical management of osteomyelitis: with special reference to a surgical classification. J Foot Surg 26 (1 Suppl):S17-24. PMID: 3559051
- ↑ Herrmann M, Vaudaux PE, Pittet D, Auckenthaler R, Lew PD, Schumacher-Perdreau F et al. (1988) Fibronectin, fibrinogen, and laminin act as mediators of adherence of clinical staphylococcal isolates to foreign material. J Infect Dis 158 (4):693-701. PMID: 3171224
- ↑ Rydén C, Tung HS, Nikolaev V, Engström A, Oldberg A (1997) Staphylococcus aureus causing osteomyelitis binds to a nonapeptide sequence in bone sialoprotein. Biochem J 327 ( Pt 3) ():825-9. PMID: 9581562
- ↑ Yacoub A, Lindahl P, Rubin K, Wendel M, Heinegård D, Rydén C (1994) Purification of a bone sialoprotein-binding protein from Staphylococcus aureus. Eur J Biochem 222 (3):919-25. PMID: 8026501
- ↑ Lammers A, Nuijten PJ, Smith HE (1999) The fibronectin binding proteins of Staphylococcus aureus are required for adhesion to and invasion of bovine mammary gland cells. FEMS Microbiol Lett 180 (1):103-9. PMID: 10547450
- ↑ Essawi T, Na'was T, Hawwari A, Wadi S, Doudin A, Fattom AI (1998) Molecular, antibiogram and serological typing of Staphylococcus aureus isolates recovered from Al-Makased Hospital in East Jerusalem. Trop Med Int Health 3 (7):576-83. PMID: 9705193
- ↑ Ram S, Mackinnon FG, Gulati S, McQuillen DP, Vogel U, Frosch M et al. (1999) The contrasting mechanisms of serum resistance of Neisseria gonorrhoeae and group B Neisseria meningitidis. Mol Immunol 36 (13-14):915-28. PMID: 10698346
- ↑ Koch B, Lemmermeier P, Gause A, v Wilmowsky H, Heisel J, Pfreundschuh M (1996) Demonstration of interleukin-1beta and interleukin-6 in cells of synovial fluids by flow cytometry. Eur J Med Res 1 (5):244-8. PMID: 9374445
- ↑ Osiri M, Ruxrungtham K, Nookhai S, Ohmoto Y, Deesomchok U (1998) IL-1beta, IL-6 and TNF-alpha in synovial fluid of patients with non-gonococcal septic arthritis. Asian Pac J Allergy Immunol 16 (4):155-60. PMID: 10219896
- ↑ Verdrengh M, Tarkowski A (1998) Granulocyte-macrophage colony-stimulating factor in Staphylococcus aureus-induced arthritis. Infect Immun 66 (2):853-5. PMID: 9453655
- ↑ Sakiniene E, Bremell T, Tarkowski A (1997) Inhibition of nitric oxide synthase (NOS) aggravates Staphylococcus aureus septicaemia and septic arthritis. Clin Exp Immunol 110 (3):370-7. PMID: 9409638
- ↑ Hultgren O, Kopf M, Tarkowski A (1999) Outcome of Staphylococcus aureus-triggered sepsis and arthritis in IL-4-deficient mice depends on the genetic background of the host. Eur J Immunol 29 (8):2400-5. PMID: 10458752
- ↑ Puliti M, von Hunolstein C, Bistoni F, Mosci P, Orefici G, Tissi L (2000) Influence of interferon-gamma administration on the severity of experimental group B streptococcal arthritis. Arthritis Rheum 43 (12):2678-86. <2678::AID-ANR7>3.0.CO;2-A DOI:10.1002/1529-0131(200012)43:12<2678::AID-ANR7>3.0.CO;2-A PMID: 11145025