Infectious Diseases of the Skin
Dermatology
Lecture 6
Dr Tim Scott-Taylor
Health and Human
Sciences
Aims
To review the types and consequences of host damage
as a result of surface bacterial infection
Direct tissue damage:
acute inflammation
extracellular enzymes
toxins
sepsis
Immunopathology:
immune complex disease
molecular mimicry
autoimmunity
hypersensitivity
Learning Objectives
- 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
Primary and Seconday Infection
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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
Types of Host Damage
Bacterial Infection can cause
1. Acute Inflammatory Changes
2. Damage by Bacterial Enzymes
3. Exotoxins
4. Endotoxin and other causes of sepsis
5. Superantigen mediated e.g. toxic shock syndrome
6. Immunopathology;
immune complex disease
(type III hypersensitivity)
molecular mimicry
cellular immune response
(type IV hypersensitivity)
Acute Inflammatory Changes
Symptoms of Infection
Local symptoms (inflammation)
Redness, swelling, warmth, pain, loss of function
Pus – pyogenic infection
Systemic symptoms
Fever, rigors, chills, tachycardia, tachypnoea
Acute Inflammatory Changes
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 Phase Proteins
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Histamine; from endothelium, mast cells, basophils
from platelets
causes vasodilation and increased
permeability
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Serotonin;
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
Plasma contains four
interconnected
mediator sytems;
Endothelial damage
Hageman factor
Factor X11
clotting
cascade
activation
of fibrinolytic
system
Prekallikrein
Fibrin
Plasmin
Kallikrein
activation
Clot
complement
activation
degradation
Bradykinin
kinin
clotting
fibrinolytic
complement
Kininogen
vasodilation
vascular
permeabiliity
pain
muscle contraction
vascular
permeabiliity
neutrophil
chemotaxis
vascular permeabiliity
extravasation
neutrophil chemotaxis
mast cell degranulation
Plasma Enzymes
Endothelial damage
Hageman factor
Factor X11
clotting
cascade
Prekallikrein
Kallikrein
activation
activation
of fibrinolytic
system
Fibrin
Clot
degradation
Bradykinin
Plasma contains four
interconnected
mediator sytems;
Plasmin
activation
complement
Kininogen
vasodilation
vascular
permeabiliity
pain
muscle contraction
vascular
permeabiliity
neutrophil
chemotaxis
vascular
permeabiliity
extravasation
neutrophil
chemotaxis
kinin
clotting
fibrinolytic
complement
Process of Inflammation
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Vasodilation:
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Increased vascular permeability:
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Plasma exudate
Swelling and pain
Influx of leukocytes:
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Increase capillary diameter
Tissue redness and temperature rise
Margination, diapedisis, chemotaxis
Cytotoxic and phagocytic activity; neutralisation
Pus and scavenging; removal of dead cells
Tissue repair:
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Regeneration of tissue; healing
Deposition of fibrous tissue; scarring
Acute Inflammatory Changes
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
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, roughsurfaced, 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 Infection
Pus cell
(neutrophil)
Streptococci
Pyogenic Infection
Staphylococci
Pus cell
Pyogenic Infection
Meningococci
(Neisseria meningitidis)
Pus cells
Pyogenic Bacteria
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Cause superficial pyodermas
impetigo
erysipelas
furuncles
carbuncles
folliculitis
cellulitis
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
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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
Acute Inflammatory Changes
Abscess
Localised area
of pus is an
abscess
Most often
Staphylococcal
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
Bacterial Enzymes
e.g. HYALURONIDASE
Origin:
Streptococci e.g. Streptococcus
Action:
breaks down hyaluronic acid
Result:
Disruption of tissue mosaic allowing
bacteria and inflammatory exudate
to travel deeper and further
pyogenes
Cellulitis
Symptoms and Signs
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Infection is most common in the lower extremities
Usually follows abnormality;
skin trauma
ulceration
tinea pedis
areas of oedema
dermatitis
esp. susceptible
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
diffuse
oedematous
pale
Spread beyond
bacterial localisation
Cellulitis
Diffuse, spreading, acute inflammation within skin tissues
Characterized by;
hyperaemia
WBC infiltration
oedema
Most common cause: Streptococcus pyogenes group A
B,C,D,G -hemolytic Strep
superficial cellulitis Staphylococcus
aureus
open wound
Pathology; diffuse infection:
enzymes destroy cell components
that would contain and localize the
inflammation
streptokinase
DNAse
hyaluronidase
Streptococcus pyogenes Infection
Initial point of infection
Infection is spreading
to neighbouring tissues
Bacterial Enzymes
Eg ALPHA-LECITHINASE
Source:
Clostridium perfringens
Action:
splits lecithin – found on the surface
of many cells
Result:
major tissue damage
Clostridium perfringens
Gram positive rod (bacillus)
Box car shape
Clostridium perfringenes Infection
Results in deep
seated infection
Gas in muscle
Gas gangrene
Rapidly diseminating toxin
Amputation or death
Bacterial Exotoxins
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
Endotoxin
• 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
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
leukocytes
Causing;
inflammation
oedema
clotting
fever
Actions of Endotoxin
Activation of macrophage/monocyte cells
• release of IL-1
IL-6
tumor necrosis factor (TNF-alpha)
• Cytokines act at various sites; endothelium
liver
clotting cascade
Results in; hypotension
complement cascade
shock
fever
increased vascular permeability
leading to;
disseminated intravascular coagulation
multiple organ failure
DIC
Purpuric lesions
DIC
DIC
DIC
Acute respiratory distress syndrome (ARDS)
Disseminated Infection
Bacteraemia
bacteria in blood
Septicaemia
Sepsis
bacteria in blood with
symptoms
Systemic inflammatory response
syndrome (SIRS)
Gram positive organisms e.g. Stapylococcus
aureus, Streptococcus pyogenes, Streptococcus
pneumoniae may also cause septicaemia/SIRS
Toxic Shock Syndrome
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
Superantigens
Able to react simultaneously with:
MHC class II antigens
on Antigen Presenting Cells
AND
specific Vβ regions
of T-lymphocyte receptor
Potently activates
macrophage/monocytes
elicits IL-1
IL-6
Conventional antigen
TNF-alpha
MHC class II molecule
T cell receptor
inteferon-γ
Antigen
presenting
cell
alpha
beta
superantigen
T cell
Multiorgan
pathology
Immunopathology
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)
Immune Complex Disease
• 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
Type III hypersensitivity reaction
e.g. Streptococcus pyogenes
glomerulonephritis
destruction of kidneys
Molecular Mimicry
•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
synovium
brain
Molecular Mimicry
Rheumatic heart disease/ Rheumatic fever
Cross reactions demonstrated between;
Group A carbohydrate
Streptococcus
and
M protein
Streptococcus
Activation of complement
and
influx of inflammatory cells
release of damaging enzymes
heart valve
structural glycoprotein
cardiac
muscle
Molecular Mimicry
Cross reacting antibodies also lead to;
synovium
neurons
Activation of complement
influx of inflammatory cells
release of damaging enzymes
inflammation of joints
arthritis
involuntary movement
Sydenham’s chorea
St Vitus’s dance
Type IV Hypersensitivity
• 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
damaged parasites
and cells release
endotoxins and
antigens activating
macrophages and
neutrophils and
leading to
granuloma
formation and
tissue necrosis
Type IV Hypersensitivity
necrosis is typical of
Mycobacteria leprae
M = epithelioid macrophages
L = Langhans’ giant cell
CN = caseous (cheesy)
necrosis
Summary
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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