Infectious Diseases of the Skin

1. Infectious Diseases of the Skin Dermatology Lecture 6 Dr Tim Scott-Taylor Health and Human Sciences

2. 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

3. 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

4. Primary and Seconday Infection • A variety bacteria normally inhabit the skin staphylcocci, corynebacteria, Propionibacterium acneshelps 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

5. 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)

6. 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

7. 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

8. 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

9. 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

10. Plasma Enzymes Plasma contains four interconnected mediator sytems; kinin clotting fibrinolytic complement Endothelial damage Hageman factor Factor X11 activation clotting of fibrinolytic cascade system Prekallikrein FibrinPlasmin 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

11. Plasma Enzymes Plasma contains four interconnected mediator sytems; kinin clotting fibrinolytic complement Endothelial damage Hageman factor Factor X11 activation clotting of fibrinolytic cascade system Prekallikrein FibrinPlasmin 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

12. 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

13. 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

14. 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

15. 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.

16. 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

17. Pyogenic Infection Pus cell (neutrophil) Streptococci

18. Pyogenic Infection Staphylococci Pus cell

19. Pyogenic Infection Meningococci (Neisseria meningitidis) Pus cells

20. Pyogenic Bacteria • Cause superficial pyodermas impetigo erysipelas furuncles carbuncles folliculitis cellulitis

21. 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

22. 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

23. 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.

24. 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

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

26. 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

27. 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

28. 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

29. 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

30. Cellulitis diffuse oedematous pale Spread beyond bacterial localisation

31. Cellulitis Diffuse, spreading, acute inflammation within skin tissues Characterized by; hyperaemia WBC infiltration oedema Most common cause: Streptococcus pyogenes group AB,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

32. Streptococcus pyogenes Infection Initial point of infection Infection is spreading to neighbouring tissues

33. Bacterial Enzymes Eg ALPHA-LECITHINASE Source:Clostridium perfringens Action: splits lecithin – found on the surface of many cells Result: major tissue damage

34. Clostridium perfringens Gram positive rod (bacillus) Box car shape

35. Clostridium perfringenes Infection Results in deep seated infection Gas in muscle Gas gangrene Rapidly diseminating toxin Amputation or death

36. 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

37. 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

38. 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

39. 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

40. Lipopolysaccharide LPS directly affects; mast cells liver platelets endothelium leukocytes Causing; inflammation oedema clotting fever

41. 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

42. DIC Purpuric lesions

43. DIC

44. DIC

45. DIC Acute respiratory distress syndrome (ARDS)

46. 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

47. 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

48. Conventional antigen MHC class II molecule T cell receptor Antigen presenting cell T cell alpha beta superantigen 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 TNF-alpha inteferon-γ

49. Multiorgan pathology

50. 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)