L4: Skin and soft tissue infection Flashcards
Cellulits
Infection of dermis and subcutaneous tissue
Often seen around injury site or deep abscesses
Superficial skin infections
Impetigo: infection of dermis with group A strep, S. Aureus, vesicles, crusted over, very contagious (school sores)
Erysipelas: usually group A strep (S. pyogenes), infection of upper dermis and superficial lymphatics, clear line between inflammed and normal (bright red, firm, swollen, raised border)
Infection and inflammation
- Infection leads to tissue damage and activation of mast cells
- Release of heparin and histamine from mast cells (increase delivery of blood, plasma and cells to site of injury)
- Innate immune mechanisms (PAMPs, complement) lead to activation of resident macrophages
- Release of pro-inflammatory cytokines and chemokines
- Vasodilation and increased permeability of vessels (vascular leakage, swelling)
- Leukocyte extravasate from blood and migrate to site
- Migration guided by chemokine IL-8 (macrophages) and C5a (complement)
Innate immune response
- Non-specific, generic response to pathogens
- Immediate
- Does not confer long-lasting protective immunity
PAMPs
= pathogen associated molecular patterns
- Recognised by pattern recognition receptors on macrophages
- > secretion of pro-inflammatory cytokines
e. g. Lipopolysaccharides found on most gram neg bacteria, recognised by toll-like receptor 4 (TLR4)
Leukocyte extravasation
= diapedesis
- Pro-inflammatory cytokines upregulate molecules on endothelial membranes (e.g. E-selectin)
- Adhesion is weak and leukocytes roll along slowly
- Cytokines open gaps between endothelial cells, neutrophils enter tissue and follow chemotactic gradient
Complement system
Classical pathway: ABs bind to pathogen, complements then bind to ABs
Lectin pathway: protein lectin binds to mannose on bacteria, allowing complement binding
Alternative pathway: complement binds to pathogen surface
- 3 pathways merge at conversion of C3 -> C3a and C3b
- C3b facilitates opsonisation: binds to bacteria and allows macrophage binding (cascade creating pore -> lysis)
- C5b helps form pore complex
- C5a is a cytokine (neutrophil attraction)
Organisms causing SSTIs
- Streptococcus pyogenes
- Staphylococcus aureus
- Other bacteria, fungi, viruses etc
Streptococcus
- Gram positive, spherical or oval cocci
- Catalase negative (in contrast to staph)
- SSTI, severe systemic disease (streptococci toxic shock syndrome), pharyngitis, acute rheumatic fever
- Lancefield classification by serotyping: S. pyogenes only one with group A antigen on surface
Group A Streptococus infectivity
= S. pyogenes
- GAS found only in humans
- Asymptomatic colonisation of oropharynx of 15-20% of population
- Transient colonisation of skin
- Transmission with human contact
- High infection rate in overcrowding, kindergartens etc
Colonisation of skin by S. pyogenes
- MSCRAMMS (microbial surface components recognising adhesive matrix molecules) on bacterial surface
- MSCRAMMS interact with ECM proteins, e.g. elastin, laminin, fibronectin, collagen
Evasion of immune system by S. pyogenes
Hyaluronic acid capsule: prevents opsonisation and phagocytosis
M protein: binds factor H -> prevents C3b opsonisation
Secretion of toxins:
- Streptolysins (lyse immune cells)
- C5a peptidase (prevents chemotaxis)
- DNAses (destroys neutrophil extracellular traps)
SpyCEP: destroys IL-8 -> prevents chemotaxis
Spreading factors of S. pyogenes
Proteases, lipases, hyaluronidase, streptokinase (anticoagulant which activates plasminogen -> plasmin, degrades fibrin)
Necrotising fasciitis
“flesh-eating disease”
- Deep infection of skin, destruction of tissue and fascia
- Often development into severe systemic disease with high mortality (>50%)
- Red, swollen, very painful
- Surgical exploration and debridement, IV antibiotics
Diagosis of SSTIs
- Swab of purulent material (pus) and maybe blood culture (hospital)
- Cultivate and identify causative organism
- Swab of intact skin not useful due to commensal skin bacteria
- Positive culture (bacteraemia) could lead to other complications (sepsis, streptococcal toxic shock syndrome)
