Acute bacterial arthritis is usually designated gonococcal or nongonococcal. In the case of cmc arthritis right icd 10how to cmc arthritis right icd 10 for gonococcal arthritis, N. gonorrhoeae possesses a variety of virulence factors on the cell surface. N. gonorrhoeae is able to attach to cell surfaces via filamentous outer-membrane appendages, or pili. Another outer membrane protein, protein I, has forms IA and IB. Protein IA binds the host factor H and inactivates complement component C3b, circumventing the host's complement system.21 Protein IA also prevents phagolysomal fusion in neutrophils, enabling survival of the organism within the phagocytes. Lipo-oligosaccharide is a gonococcal molecule similar to lipopolysaccharide of other Gram-negative bacteria and possesses endotoxin activity, which contributes to the joint damage seen in gonococcal arthritis.22
S. aureus is the most common organism that causes nongonococcal arthritis. The virulence of S. aureus is associated with its ability to attach to host tissue within the joint, evade host defenses, and cause damage to the joint. cmc arthritis right icd 10how to cmc arthritis right icd 10 for Table 109-2 lists some of these virulence factors and their mechanisms of action. The attachment of S. aureus to the joint tissues is facilitated by microbial surface components recognizing adhesive matrix molecules (MSCRAMMs). MSCRAMMs are embedded in the cell wall peptidoglycan of S. aureus (Figure 109-1).23 They bind to host matrix proteins, including collagen, fibrinogen, elastin, vitronectin, laminin, and fibronectin. Gene knockout experiments in animal models showed that the gene coding for the protein that binds collagen is an important virulence factor for S. aureus joint infections. the 1 last update 2020/07/02 2424 Most S. aureus isolates also express the fibronectin-binding proteins, FnbpA and FnbpB. Disruption of the respective genes, fnbpA and fnbpB, by knockout gene experiments completely obliterates adherence of S. aureus to fibronectin-coated surfaces (e.g., prosthetic joints).25
The genes of several S. aureus cell surface proteins (e.g., protein A, fibronectin-binding proteins, coagulase) and exotoxins (e.g., toxic shock syndrome toxin [TSST]-1, enterotoxin B, proteases, and hemolysins) are regulated by the accessory gene regulator agr.26 At low cell numbers, such as at the time of infection, production of cell surface proteins for attachment to host tissues is facilitated by the agr gene. When the cells have attached to tissue or an orthopedic device and have passed from the exponential to stationary phase of growth, agr represses the expression of genes coding for cell surface proteins and activates genes coding for exotoxins and tissue-destroying exoenzymes. Because of this complex effect on the different stages of infection, inhibitors of agr may reduce tissue destruction but enhance tissue colonization. This effect could have implications for chronic infections such as occur with prosthetic joints.
Adherence receptors may allow intra-cellular movement of S. aureus into host cells (e.g., osteoblasts, endothelial cells, neutrophils).27 The ability of S. aureus to switch from a normal colony phenotype to a slow-growing, antibiotic-resistant, small-colony variant phenotype may partially explain why this organism causes persistent and recurrent infections.28 When internalized, the organism is protected from the host's immune system and from anti-microbial agents. After adherence to the joint tissue, the bacteria activate the host immune response. Opsonization and phagocytosis are key defenses to eradicate the organism. S. aureus possesses two virulence factors, protein A and capsular polysaccharide, which interfere with these defenses. Protein A interferes with binding of complement by binding to the fragment crystallizable (Fc) portion of immunoglobulin (Ig)G. Protein A has been termed a superantigen for B cells because 30% of human B cells show Fab-mediated binding of the protein A molecule.29 Binding of protein A by B cells leads to activation and, subsequently, to depletion of B cells through apoptosis. for 1 last update 2020/07/02 3030 This process may have implications regarding the ability of the immune system to control infection with S. aureus. The gene coding for protein A had been experimentally disrupted, and joint infection caused by the altered strain in a mouse model resulted in less joint destruction than infection caused by the wild-type strain.31
Capsular polysaccharide interferes with opsonization and phagocytosis. Of the 11 reported capsule serotypes of S. aureus, types 5 and 8 account for 85% of clinical infections.cmc arthritis right icd 10how to cmc arthritis right icd 10 for 32 The capsule of these two serotypes is thinner, which facilitates the attachment to host fibronectin and fibrin.33 When attached to these host proteins, capsule production is upregulated to form a thicker capsule, which makes the bacteria more resistant to opsonization and phagocytosis. The thicker capsule can also conceal the highly immunogenic adherence proteins (MSCRAMMs).34 A mutant of the type 5 capsule in a murine model had a lower rate of infection and resulted in less severe arthritis compared with mice infected with the wild-type strain.35 A vaccine consisting of types 5 and 8 polysaccharide reduced S. aureus bacteremia by more than half in hemodialysis patients.36 The duration of protection was approximately 40 weeks after a single vaccination.
S. aureus exotoxins (e.g., TSST-1 and enterotoxins) act as superantigens that bind to host class II major histocompatibility complex (MHC) molecules and T cell receptors, resulting in clonal expansion and activation of some T cells. This activation triggers the release of numerous cytokines, including IL-2, interferon (IFN)-γ, and TNF.37 Induction of these cytokines results in systemic toxicity and joint damage. The stimulated T cells initially proliferate but later disappear, likely because of apoptosis, and result in immunosuppression.38 Internalized organisms that had been protected from this inflammatory response may cause fulminant or persistent infection. Mice injected with strains of S. aureus lacking TSST-1 and enterotoxins rarely develop arthritis; when arthritis is induced, it is much milder compared with arthritis in animals injected with the wild-type strain.37 Vaccination of mice with for 1 last update 2020/07/02 a mutated, recombinant form of enterotoxin A devoid of superantigen function was associated with a significant reduction in mortality.39S. aureus exotoxins (e.g., TSST-1 and enterotoxins) act as superantigens that bind to host class II major histocompatibility complex (MHC) molecules and T cell receptors, resulting in clonal expansion and activation of some T cells. This activation triggers the release of numerous cytokines, including IL-2, interferon (IFN)-γ, and TNF.37 Induction of these cytokines results in systemic toxicity and joint damage. The stimulated T cells initially proliferate but later disappear, likely because of apoptosis, and result in immunosuppression.38 Internalized organisms that had been protected from this inflammatory response may cause fulminant or persistent infection. Mice injected with strains of S. aureus lacking TSST-1 and enterotoxins rarely develop arthritis; when arthritis is induced, it is much milder compared with arthritis in animals injected with the wild-type strain.37 Vaccination of mice with a mutated, recombinant form of enterotoxin A devoid of superantigen function was associated with a significant reduction in mortality.39
In response to bacterial infection of the joint space, the host releases a variety of cytokines and inflammatory mediators. Initially, IL-1β and IL-6 are released into the joint space, leading to an influx of inflammatory cells. These neutrophils and macrophages engulf invading bacteria and release additional cytokines, including TNF, IL-1, IL-6, and IL-8. Blocking TNF with a monoclonal antibody and IL-1 with an IL-1 receptor antagonist inhibited leukocyte infiltration into the joint by 80% in a rabbit model of S. aureus–induced arthritis when the cytokine inhibitors were given simultaneously with S. aureus.40 When the same inhibitors were given 24 hours after infection, however, there was no effect on leukocyte infiltration, suggesting the crucial roles of TNF and IL-1 in the early stages of S. aureus–induced arthritis. Release of IFN-γ is associated with the influx of T cells, which occurs a few days after infection. In a mouse model of S. aureus septic arthritis, IFN-γ has been associated with a worsening of the severity of arthritis while protecting the animals from septicemia.41 The host's early cytokine response may aid the clearance of organisms and limit infection in the host. A late cytokine response may amplify the destructiveness of an established infection.