Infectious Diseases of the Skin

DermatologyLecture 6

Dr Tim Scott-TaylorHealth and Human

Sciences

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

Streptococci

Pus cell

(neutrophil)

Pyogenic Infection

Staphylococci

Pus cell

Pyogenic Infection

Meningococci

(Neisseria meningitidis)

Pus cells

Pyogenic Infection

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

Acute Inflammatory Changes

Localised area of pus is an abscess

Most often Staphylococcal

Abscess

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

diffuseoedematouspale

Spread beyond bacterial localisation

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

Box car shape

Gram positive rod (bacillus)

Clostridium perfringens

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

Purpuric lesions

DIC

DIC

DIC

Acute respiratory distress syndrome (ARDS)

DIC

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

Multiorgan pathology

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