Infectious Diseases of the Skin

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Infectious Diseases of the Skin

• Dermatology
• Lecture 6
• Dr Tim Scott-Taylor
• Health and Human Sciences

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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
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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
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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

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Types of Host Damage

• Bacterial Infection can cause
• Acute Inflammatory Changes
• Damage by Bacterial Enzymes
• Exotoxins
• Endotoxin and other causes of sepsis
• Superantigen mediated e.g. toxic shock syndrome
• Immunopathology immune complex disease
  (type III hypersensitivity) molecular
  mimicry cellular immune response
  (type IV hypersensitivity)

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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
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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

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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
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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, a, ß, ?
  conversion to fibrin monomer by thrombin
  cross linked by factor XIII to form a clot

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Plasma Enzymes
Plasma contains four interconnected mediator
sytems kinin clotting fibrinolytic compleme
nt

• Endothelial damage
• Hageman factor
• Factor X11
• activation clotting
  of fibrinolytic cascade system
• Prekallikrein Fibrin Plasmin
• Kallikrein Clot complement
  activation activation
• degradation
• Bradykinin Kininogen

vasodilation vascular permeabiliity pain muscle
contraction
vascular permeabiliity neutrophil chemotaxis
vascular permeabiliity extravasation neutrophil
chemotaxis mast cell degranulation
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Plasma Enzymes
Plasma contains four interconnected mediator
sytems kinin clotting fibrinolytic compleme
nt

• Endothelial damage
• Hageman factor
• Factor X11
• activation clotting
  of fibrinolytic cascade system
• Prekallikrein Fibrin Plasmin
• Kallikrein Clot
  activation activation
• degradation complement
• Bradykinin Kininogen

vasodilation vascular permeabiliity pain muscle
contraction
vascular permeabiliity neutrophil chemotaxis
vascular permeabiliity extravasation neutrophil
chemotaxis mast cell degranulation
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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

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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
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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

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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.

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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
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Pyogenic Infection
Pus cell (neutrophil)
Streptococci
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Pyogenic Infection
Staphylococci
Pus cell
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Pyogenic Infection
Meningococci (Neisseria meningitidis)
Pus cells
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Pyogenic Bacteria

• Cause superficial pyodermas
• impetigo
• erysipelas
• furuncles
• carbuncles
• folliculitis
• cellulitis

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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

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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 gt 2 wk
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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.

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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
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Acute Inflammatory Changes
Abscess
Localised area of pus is an abscess Most often
Staphylococcal
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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

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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

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Bacterial Enzymes
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
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Cellulitis

• 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.

• areas of oedema esp. susceptible

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Cellulitis

• diffuse
• oedematous
• pale
• Spread beyond
• bacterial localisation

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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 Staphylococcus
  aureus
• Pathology diffuse infection streptokinase
  DNAse hyaluronidase

superficial cellulitis open wound
enzymes destroy cell components that would
contain and localize the inflammation
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Streptococcus pyogenes Infection
Initial point of infection Infection is
spreading to neighbouring tissues
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Bacterial Enzymes
Eg ALPHA-LECITHINASE Source Clostridium
perfringens Action splits lecithin found on
the surface of many cells Result major tissue
damage
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Clostridium perfringens

Gram positive rod (bacillus)

Box car shape
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Clostridium perfringenes Infection
Results in deep seated infection
Gas in muscle
Gas gangrene Rapidly diseminating
toxin Amputation or death
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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

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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
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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

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Staphylococcal Scalded Skin Syndrome

• Acute, widespread erythema and epidermal
  peeling caused by exotoxin.
• children lt6 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

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Lipopolysaccharide
LPS directly affects mast cells liver
platelets endothelium leukocytes
Causing inflammation oedema
clotting fever
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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 complement cascade

Results in hypotension shock
fever increased vascular
permeability leading to disseminated
intravascular coagulation multiple organ
failure
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DIC
Purpuric lesions
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DIC
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DIC
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DIC
Acute respiratory distress syndrome (ARDS)
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Disseminated Infection
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
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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
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Superantigens
Able to react simultaneously with MHC class
II antigens on Antigen Presenting Cells
AND specific Vß regions
of T-lymphocyte receptor
Potently activates macrophage/monocytes elicits
IL-1 IL-6 TNF-alpha
inteferon-?
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Multiorgan pathology
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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)

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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 destr
uction of kidneys
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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

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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
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Molecular Mimicry
Cross reacting antibodies also lead to
synovium neurons
inflammation of joints involuntary movement
arthritis Sydenhams
chorea St Vituss dance
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Type IV Hypersensitivity

• T helper cells react to specific antigens
• T cells release cytokines TNFa
  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

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Type IV Hypersensitivity
damaged parasites and cells release endotoxins
and antigens activating macrophages and
neutrophils and leading to granuloma formation
and tissue necrosis
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Type IV Hypersensitivity
necrosis is typical of Mycobacteria leprae
M epithelioid macrophages L Langhans giant
cell CN caseous (cheesy) necrosis
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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