infectious diseases of the skin dermatology lecture 6 dr tim scott-taylor health and human sciences
Post on 18-Dec-2015
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TRANSCRIPT
To review the types and consequences of host damage as a result of surface bacterial infection
Direct tissue damage: acute inflammationextracellular
enzymes toxinssepsis
Immunopathology: immune complex disease molecular mimicry autoimmunityhypersensitivity
Aims
- Explain the types of tissue damage caused by bacterial infection.
- Know some of the mechanisms of action of bacterial toxins
- Understand how infection may cause kidney and heart damage.
- List the types of hypersensitivity of microbial origin.
- Know the causes of common bacterial skin infections
Learning Objectives
Primary and Seconday Infection
A variety bacteria normally inhabit the skin staphylcocci, corynebacteria, Propionibacterium acnes helps to interpret culture results.
Bacterial infection may be the primary cause of a skin lesion by infection or colonization may be secondary to another skin disease
Primary infections (eg, impetigo, erysipelas) usually respond promptly to systemic antibiotics, whereas secondary infections tend to clear more slowly, requiring more complicated treatment regimens
Bacterial Infection can cause1. Acute Inflammatory Changes2. Damage by Bacterial Enzymes3. Exotoxins4. Endotoxin and other causes of sepsis5. Superantigen mediated e.g. toxic shock
syndrome
6. Immunopathology; immune complex disease (type III hypersensitivity) molecular mimicrycellular immune response
(type IV hypersensitivity)
Types of Host Damage
Acute Inflammatory Changes
Symptoms of Infection
Local symptoms (inflammation)Redness, swelling, warmth, pain, loss of functionPus – pyogenic infection
Systemic symptomsFever, rigors, chills, tachycardia, tachypnoea
Local symptoms mainly secondary to response of the local small blood vessels with
• increased blood flow (redness, warmth)
increased permeability to fluid and plasma proteins (swelling, pain)
increased stickiness of vascular endothelium
emigration of phagocytes to site of infection
Acute Inflammatory Changes
Inflammatory response is triggered by release of products from the bacteria
e.g. toxins, enzymes, LPS
And amplified by release of products from host cells
e.g. histamine, prostaglandins, leukotrienes, kinins
Acute Inflammatory Changes
Acute Phase Proteins Histamine; from endothelium, mast cells, basophils
Serotonin; from platelets
causes vasodilation and increased permeability
Kinins; plasma enzymes produced by tissues and liver kallikreins serine proteases release kinins from kininogen
induce vasodilation and contraction of smooth muscle. C reactive protein; produced by liver, stored in plasma
vasodilation and increased permeability Fibrin; fibrinogen made in liver, forms bridges between platelets
dimer composed of 6 paired polypeptide chains, α, β, γ conversion to fibrin monomer by thrombin cross linked by factor XIII to form a clot
Plasma Enzymes
vasodilationvascular permeabiliitypainmuscle contraction
vascular permeabiliityneutrophil chemotaxis
vascular permeabiliityextravasationneutrophil chemotaxismast cell degranulation
Plasma contains four interconnected mediator sytems;
kininclotting
fibrinolyticcomplement
Endothelial damage
Hageman factorFactor X11
activation clotting of
fibrinolytic cascade system
Prekallikrein Fibrin Plasmin
Kallikrein Clot complement activation
activation degradation
Bradykinin Kininogen
Plasma Enzymes
vasodilationvascular permeabiliitypainmuscle contraction
vascular permeabiliityneutrophil chemotaxis
vascular permeabiliityextravasationneutrophil chemotaxismast cell degranulation
Plasma contains four interconnected mediator sytems;
kininclotting
fibrinolyticcomplement
Endothelial damage
Hageman factorFactor X11
activation clotting of fibrinolytic cascade system
Prekallikrein Fibrin Plasmin
Kallikrein Clot activation activation
degradation complement
Bradykinin Kininogen
Process of Inflammation
Vasodilation: Increase capillary diameter Tissue redness and temperature rise
Increased vascular permeability: Plasma exudate Swelling and pain
Influx of leukocytes: Margination, diapedisis, chemotaxis Cytotoxic and phagocytic activity; neutralisation Pus and scavenging; removal of dead cells
Tissue repair: Regeneration of tissue; healing Deposition of fibrous tissue; scarring
Results is accumulation of phagocytes, mainly neutrophils (pus cells) and some monocytes, complement and other factors, and exudate at the site of infection
Pyogenic infection; pyogenic organisms include
Staphylococci streptococci meningococci viruses
Acute Inflammatory Changes
Herpes Simplex
• DNA virus of two antigenic types, 1 and 2. Type 1 is common on skin and cold sores
• initiates with a ‘tingling’ sensation, forming a blister appears which soon breaks down giving a crusted lesion,
•
reccurs due to persistent virus in nerve cell bodies
• Sensitive to acyclovir a thymidine analogue
Varicella zoster
• Chickenpox; a highly contagous DNA virus
• incubation is 14-21 days. Infection starts with 1-2 days of fever and malaise before crops of small blisters appear that crust after 1-2 days
• Shingles; reactivation of the same virus, which lies dormant in the posterior root ganglia.
Warts
• Warts = veruccae; common, contagious, epithelial tumors caused by ~60 types of papillomavirus
• most frequent in older children, rare in elderly. Often develop by autoinoculation
• sharply demarcated, rough-surfaced, round or irregular, firm, nodules 2 to 10 mm in diameter.
•
most often on sites subject to trauma; fingers, elbows, knees, face and sole of the foot = plantar warts
Pyogenic Bacteria
Cause superficial pyodermas
impetigoerysipelasfurunclescarbunclesfolliculitiscellulitis
Impetigo
• red raw on the skin soon become covered with a yellow crust
• blisters are a prominent feature called bullous impetigo
• particularly common in childhood and can be highly contagious
• caused by Strep. pyogenes or more rarely Staph. aureus
• topical antibiotic cream such as fucidin or oral flucloxacillin
Erysipelas
• well demarcated, shiny, red, edematous, indurated, tender lesion
• superficial cellulitis with marked lymphatic vessel involvement
• group A (C or G) -hemolytic streptococci
• penicillin V or erythromycin 500 mg >= 2 wk
Erythrasma
A superficial skin infection in intertriginous areas, caused by Corynebacterium minutissimum.
It occurs most commonly in adults, especially in patients with diabetes. The incidence is higher in the tropics.
Symptoms, Signs, and Diagnosis Erythrasma resembles a chronic fungal infection or intertrigo. Scaling,
fissuring, and slight maceration may occur in the toe webs, most commonly confined to the 3rd and 4th interspaces. In the genitocrural region, principally where the thighs contact the scrotum, sharply marginated patches are initially irregular and pink, later becoming brown with a fine scale (see Plate 112-3-1). Erythrasma may widely involve the axillae, submammary or abdominal folds, and perineum, particularly in obese middle-aged women or in patients with diabetes mellitus.
Differentiation from ringworm is essential. Diagnosis is established with a Wood's light, under which erythrasma fluoresces a characteristic coral-red color.
Treatment Prompt clearing follows administration of oral erythromycin or tetracycline
250 mg qid for 14 days, but recurrence 6 to 12 mo later is usual. Antibacterial soaps may control the infection. Topical erythromycin preparations, readily available commercially and used to treat acne, are also usually effective.
Folliculitis
• Superficial or deep bacterial infection and inflammation of the hair follicles
• caused by S. aureus but occasionally caused by Pseudomonas aeruginosa especially in hot-tubs
• Topical antibiotics and antiseptics eg chlorhexidine may be useful adjuncts to systemic therapy
Paronychial Infections
• abscess in the paronychial fold adjacent to the nail plate
• occupational in prolonged water contact eg, waiters, bartenders, dishwashers or is secondary to finger sucking
• usually S. aureus, also Pseudomonas, Proteus sp, Candida albicans or herpes simplex virus
• systemic dicloxacillin 250 mg cephalexin 250 mg
Furuncles
• boils; acute, tender, perifollicular inflammatory nodules resulting from infection by staphylococci
•teenagers living in crowded quarters with relatively poor hygiene
•most frequently on the neck, breasts, face, and buttocks
• treatment is incision and drainage or cleaning with soap containing either chlorhexidine gluconate with isopropyl alcohol
e.g. HYALURONIDASE
Origin: Streptococci e.g. Streptococcus pyogenes
Action: breaks down hyaluronic acid
Result: Disruption of tissue mosaic allowing bacteria and inflammatory exudate to travel deeper and further
Bacterial Enzymes
Symptoms and Signs Infection is most common in the lower extremities Usually follows abnormality; skin trauma
ulceration tinea pedis dermatitis
Recognition; local erythema, indistict border hot red tender skin
lymphangitis and lymphadenopathy skin of an orange (peau d'orange)
fever, chills, headache may be present but many patients do not appear ill.
Cellulitis
areas of oedema esp. susceptible
Cellulitis
Diffuse, spreading, acute inflammation within skin tissues
Characterized by; hyperaemiaWBC infiltration oedema
Most common cause: Streptococcus pyogenes group A B,C,D,G -hemolytic Strep
Staphylococcus aureus
Pathology; diffuse infection: streptokinaseDNAsehyaluronidase enzymes destroy cell components that would contain and localize the inflammation
superficial cellulitis open wound
Initial point of infection
Infection is spreading to neighbouring tissues
Streptococcus pyogenes Infection
Eg ALPHA-LECITHINASE
Source: Clostridium perfringens
Action: splits lecithin – found on the surface of many cells
Result: major tissue damage
Bacterial Enzymes
Gas in muscle
Clostridium perfringenes Infection
Results in deep seated infection
Gas gangreneRapidly diseminating toxinAmputation or death
Most exotoxins are proteins secreted by the bacterium. May act in a variety of ways;
• Enzymatic lysis e.g.alpha-lecithinase
• Pore formation
• Inhibition of protein synthesis
• Hyperactivation
• Effects on nerve-muscle transmission
Bacterial Exotoxins
Exotoxins are made by many bacteria
both Gram-positive and Gram-negative species
May also be classified by;
Molecular structure – e.g. subunits
Site of action e.g. enterotoxins
Bacterial Exotoxins
• An integral part of the bacterial cell
• Found only in Gram-negative bacteria
• Usually only released when the bacterial cell is damaged
• Evoke a variety of effects at many different sites
Endotoxin
Staphylococcal Scalded Skin Syndrome
• Acute, widespread erythema and epidermal peeling caused by exotoxin.
• children <6 yr old, immunosuppressed adults or adults with renal failure
• toxin is an exfoliatin or epidermolysin. Epidermolytic; splits off the upper part of the epidermis just beneath the granular cell layer• The toxin enters the circulation and affects the skin systemically, as in scarlet fever
Lipopolysaccharide
LPS directly affects; mast cells
liver platelets endothelium leukocytesCausing;
inflammation oedema clotting fever
Activation of macrophage/monocyte cells• release of IL-1
IL-6tumor necrosis factor (TNF-alpha)
• Cytokines act at various sites; endotheliumliver
clotting cascadecomplement
cascade
Actions of Endotoxin
Results in; hypotension shock
fever increased vascular
permeability
leading to; disseminated intravascular coagulation multiple organ failure
Bacteraemia bacteria in blood
Septicaemia bacteria in blood with Sepsis symptoms
Systemic inflammatory response syndrome (SIRS)
Gram positive organisms e.g. Stapylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae may also cause septicaemia/SIRS
Disseminated Infection
Toxins produced by certain strains of;
Staphylococcus aureus; Toxic shock syndrome toxin (TSST)
Streptococcus pyogenes; Streptococcal pyrogenic exotoxin (SPE)
These toxins may act as SUPERANTIGENS
Toxic Shock Syndrome
Antigen presenting cell
T cell
MHC class II molecule T cell receptor
betaalpha
superantigen
Conventional antigen
Able to react simultaneously with: MHC class II antigens on Antigen Presenting Cells AND specific Vβ regions of T-lymphocyte receptor
Superantigens
Potently activates macrophage/monocytes elicits IL-1
IL-6 TNF-alpha
inteferon-γ
Humoral immunity
- production of antibodies by B-lymphocytes
- can lead to immune complex disease (type I hypersensitivty)
Cellular immunity
- T-lymphocytes for specific immune response
- can lead to cellular pathology (type IV hypersensitivty)
Immunopathology
• Host produces antibodies against streptococcal antigens
• Antibodies bind to antigens to form immune complexes
• Complexes are deposited in samll vessels
• Immune reaction sets in and destroys local tissue
Immune Complex Disease
Type III hypersensitivity reaction e.g. Streptococcus pyogenes glomerulonephritis
destruction of kidneys
•Antibodies against streptococcal cell wall antigens
•Antibodies cross-react with antigens of the host due to similar molecular structure
eg. Throat infection with Streptococcus pyogenes
Sites of cross reactivity include;myocardium synoviumbrain
Molecular Mimicry
Rheumatic heart disease/ Rheumatic fever
Cross reactions demonstrated between;
Group A carbohydrate M protein
Streptococcus
Streptococcus
and and
heart valve cardiac structural glycoprotein muscle
Molecular Mimicry
Activation of complement influx of inflammatory cells release of damaging enzymes
Cross reacting antibodies also lead to;
synovium neurons
inflammation of joints involuntary movement arthritis Sydenham’s chorea St Vitus’s dance
Molecular Mimicry
Activation of complement influx of inflammatory cells release of damaging enzymes
• T helper cells react to specific antigens
• T cells release cytokines; TNFα activation of macrophages IL-1• Toxic products may cause tissue damage• Formation of granuloma; epithelioid and giant cells• Necrosis common, described as caseous (cheesy)
• In chronic infection tissue damage may be extensive
e.g. Mycobacterium tuberculosis (TB)Mycobacterium leprae (leprosy)
Treponema palidum (syphilis) schistosomiasis eggs
Type IV Hypersensitivity
Type IV Hypersensitivity
damaged parasites and cells release endotoxins and antigens activating macrophages and neutrophils and leading to granuloma formation and tissue necrosis
M = epithelioid macrophages
L = Langhans’ giant cell
CN = caseous (cheesy) necrosis
necrosis is typical of Mycobacteria leprae
Type IV Hypersensitivity
Summary
Most skin infections arise from a prior disturbance
Skin bacteria are commonly involved in pyodermas of varying superficiality
Bacterial infection can have consequences to tissue far removed by; exotoxins, enzymes immunopathology
Hypersensitivity type II, type IV hypersensitivity and diseminated coagulation can have life threatening consequences