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Chapter 19: Infections of the Skin & Eye November 7, 2023 Guest Lecturer: Mackenzie Melvin (Msc.) Chapter 18: Case Study Review Patient information: • 3-month-old baby • Healthy, but experiences frequent diaper rashes Symptoms: • Day 1: Red skin and small, painful, bubbly blisters forming around t...
Chapter 19: Infections of the Skin & Eye November 7, 2023 Guest Lecturer: Mackenzie Melvin (Msc.) Chapter 18: Case Study Review Patient information: • 3-month-old baby • Healthy, but experiences frequent diaper rashes Symptoms: • Day 1: Red skin and small, painful, bubbly blisters forming around the diaper area • Day 2: Redness running down legs, blisters have crusted. Skin sloughs off when wiped. Accompanied by fever Blood and fecal cultures ordered once seen at hospital Chapter 18: Case Study Review Culture results: • Blood + skin cultures were negative for growth • Swab of nasal abscess positive for growth • Subculture of nasal swab on blood agar and mannitol salt agar plate were both positive • Blood agar plate showed alpha toxin presence Gram-stain results: • Colonies from the mannitol salt plate were gramstained • Gram-positive staphylococci Tube coagulase results: • Colony of bacteria placed in tube of rabbit plasma and mixed • Positive results Diagnosis: Presumptive identity of a Gram-positive Q u e st o n 1 Clicker Question Coagulase is an _____. A. exotoxin B. endotoxin C. exoenzyme D. antigen E. None of the above Q u e st o n 1 Clicker Question - Answer Coagulase is an _____. A. exotoxin B. endotoxin C. exoenzyme D. antigen E. None of the above Chapter 18: Case Study Review Diagnosis: • Based on the clinical appear and the identity of bacteria, was diagnosed with staphylococcal scalded skin syndrome (SSSS) Kirby-Baurer assay: • Used to determine antibiotic susceptibility • Determine if the bacteria is a strain MSSA or MRSA Treatment: • Assay showed that the bacteria was a strain of MSSA treated with IV nafcillin Additional information: • The red skin clinical appearance is due to the exfolitatin exotoxin produced by S. aureus, it acts as a protease and as a Q u e st o n 2 Clicker Question A superantigen _____. A. causes an allergic response B. causes a delayed reaction of the immune system C. causes an overreaction of the immune system D. causes a shut down of the immune system E. None of the above Q u e st o n 2 Clicker Question - Answer A superantigen _____. A. causes an allergic response B. causes a delayed reaction of the immune system C. causes an overreaction of the immune system D. causes a shut down of the immune system E. None of the above Chapter 19: Case Study #1 Background: • On vacation in Naples, Italy Patient information: • 69-year-old man • Type 2 diabetic Symptoms: • Tingling sensation from spine to middle of ribcage • Severe pain the next morning • Small blisters that formed a line along the skin • Red skin Chapter 19: Case Study #1 Diagnosis: • St. Anthony’s fire • Caused by the same virus that causes chickenpox Treatment: • Antiviral and pain relief medications • Close monitoring of blood sugar levels Follow-up: • His family physician clarified that the disease is known as shingles in Canada Structure of the Skin The skin is the largest human organ: • 16-22 square feet of surface • Barrier that blocks microbial access to deeper tissues • Hosts 1 trillion microbes Superficial layer is known as the epidermis: • Five sublayers of epithelial cells • Secretes waterproofing substances to prevent water loss • Stratum corneum is made of dead keratinocytes (make keratin) Deeper layer is called the dermis: • Contains connective tissue, blood Skin Rashes Change in colour and texture of the skin: • Exanthem: widespread with systemic symptoms (fever, headache, etc.) • Enanthem: mucous membranes Caused by a reaction to a toxin produced by an infectious agent: • Reaction to the organism itself • Physical damage to the skin by the organism • Host immune response Rashes can also be non-infectious that result from allergies Consist of lesions that may be localized or cover the entire surface: Skin Rashes There are different types of rashes: • Macular: flat/red, less than 1cm in diameter (A) • Papular: small, solid, and elevated (C) • Pustular: papule filled with pus (D) • Maculopapular: papule that is reddened • Vesicular: small blisters (B) Mucous Membranes Called mucosae (plural) or mucosa (singular): • Epithelial linings • Serve as a protective barrier • Line the inside of the body, such as the GI and urogenital tract • Continuous with the skin in several places • Not all produce mucus Q u e st o n 3 Clicker Question Which of the following statements about rashes is NOT true? a. A change in color and texture of the skin is usually b. c. d. e. referred to as a rash. An exanthem is a widespread skin rash accompanied by systemic symptoms. An enanthem is a rash on mucous membranes. Exanthems are usually caused by infectious agents, and enanthems are usually caused by allergic reactions. A variety of situations can affect the skin and cause a rash. Q u e st o n 3 Clicker Question - Answer Which of the following statements about rashes is NOT true? a. A change in color and texture of the skin is usually b. c. d. e. referred to as a rash. An exanthem is a widespread skin rash accompanied by systemic symptoms. An enanthem is a rash on mucous membranes. Exanthems are usually caused by infectious agents, and enanthems are usually caused by allergic reactions. A variety of situations can affect the skin and cause a rash. Chickenpox • • Herpesviridae family Varicella-Zoster virus (VZV) capsid contains a linear double-stranded DNA genome that is surrounded by a host-derived lipid envelope Initial exposure causes chickenpox: • Virus remains latent in dorsal root ganglia • Re-emerges later in life in about 20% of patients, which causes shingles Shingles occurs more frequently in older individuals • Due to cell-mediated immunity decreasing Chickenpox and shingles are usually diagnosed clinically, but antibody and DNA tests can also detect virus Chickenpox Contracted by inhaling infected particles from skin lesions: • Virus replicates in nasopharynx and infects the regional lymph nodes viremia • Secondary viral replication in liver & spleen secondary viremia (14-16 days post-infection) VSV invades capillary endothelial cells and the deepest layer of epidermis: • Causes fluid accumulation & vesicle formation Children do not usually have prodromal symptoms: • First sign is itchy rash that includes maculopapules, vesicles, pustules, and scabs • Usually, a mild disease Chickenpox Life threatening in immunocompromised patients Latency is established when viral DNA integrates into host DNA: • Can last for decades • Infects & travels along nerve endings of skin to ganglia where they are dormant • Virus reactivation occurs when virus particles travel along sensory nerves of skin to produce a rash known as shingles • Symptoms are much worse than chickenpox Acyclovir (antiviral) is used to treat shingles or severe chickenpox cases Varicella vaccination: • Routine childhood vaccination • Live, attenuated form of VSV Smallpox (variola) Member of the Poxviridae family: • Two variants: variola major and variola minor • Variants are very similar to the vaccina virus (cowpox) which is used to make a vaccine against smallpox Only known reservoir is humans: • Eradicated from population in 1979 Transmitted by direct or indirect contact: • Inhalation of small aerosolized particles • Handling fomites containing the virus Smallpox (variola) Smallpox replicates in the lymph nodes and lymphoid organs: • Occurs in two sequential viremias • Infects internal organs and bone marrow • Begins as small spots on oral mucosa (enanthem, vesicular) • Progresses to pox pustule on skin (exanthem) Smallpox treatment: • Diagnosis made based on viral cultures & serology • No FDA approved treatment • Children no longer routinely vaccinated against smallpox Thought question: Do you think smallpox vaccination is required for anyone? Why or why not? Staphylococcal skin infections Gram-positive bacteria that grow in clusters Species that are associated with infection include S. epidermidis and S. aureus: • S. aureus is found inside the nose and can gain access to the dermis via cuts near hair follicles S. aureus possesses enzymes that contribute to disease: • Coagulase coats the bacteria with fibrin and blocks the infection from the immune system and antibiotics promotes abscess formation • S. epidermidis does not have coagulase • Infections regularly require surgical Staphylococcal skin infections Exotoxins damage host tissue and weaken host defences: • Toxic shock syndrome toxin (TSST): superantigen that causes toxic shock syndrome • Exfoliative toxin: superantigen that causes a blistering conditions called scaled-skin syndrome S. aureus infection of hair follicles can be superficial or deep, resulting in: • Folliculitis (superficial) (A) • Boli or furuncle (deep) (B) • Carbuncles (boils joined together, deep) (C) Staphylococcal skin infections Methicillin-resistant S. aureus (MRSA) has emerged over the past decade: • Resistant to the antibiotic methicillin which interferes with cell wall synthesis • 60% of S. aureus strains have evolved to resist methicillin • Treated with vancomycin Originally appeared strictly in the hospital (nosocomial infection): • Now, it is not confined to the hospital and occurs as a community acquired infection • Epidemic rates in the United States Case Study #2 Background: • Patient was camping and suffered a minor cut to her finger which she properly bandaged • Also injured the left side of her body while playing sports with her kids Day 2 Symptoms: • Vomiting, diarrhea, fever • Severe pain where she injured her side accompanied by bruising even though the skin did not appear broken Day 3 Symptoms: • Barely able to get out of bed • Difficult breathing, not able to see • Case Study #2 Hospital diagnosis: • Patient admitted in septic shock • Diagnosed as necrotizing fasciitis Treatment: • Given vasopressors (constrict blood vessels) to raise her blood pressure back to normal • 7% of her body surface was removed in surgery and could not be skin grafted until infection cleared Follow-up: • Continued use of vasopressors resulted in gangrene in her fingers and lower extremities • Streptococcus pyogenes Gram-positive cocci that grows in chains S. pyogenes has natural reservoirs in the nasopharynx and skin Causes necrotizing fasciitis (flesh-eating disease): • Two types: polymicrobial and one microorganism • Can also be caused by Staphylococcal aureus, Clostridium perfringens, and Vibrio vulnificus • Treatment involves antibiotics like metronidazole Incidence of necrotizing fasciitis is rising due to increase in the use of NSAIDs which increase your susceptibility to infection by S. pyogenes S. pyogenes virulence factors • • • • • Capsule: helps organism avoid phagocytosis Pilus-like M protein: binds complement regulatory protein (factor H) Lipoteichoic acid: cell wall component that facilitates adherence to host cells Streptolysins: lyse blood cells Peptidoglycan: activates the alternative complement pathways and a MAMP that binds NOD-like receptors, causing inflammation Degrading enzymes: • DNAses DNA • Streptokinase fibrin • Hyaluronidase connective tissue S. pyogenes virulence factors Streptococcal pyogenic exotoxins (SPEs): • Superantigens that cause massive amounts of cytokines to be released • Produces high levels of inflammation which lead to shock Many streptococci produce hemolysin: • Enzyme that lyses red blood cells (RBCs) • When plated onto agar containing RBCs, hemolysin-secreting strains lyse RBCs around the colony to produce a clear zone called beta hemolysis • These streptococci are subclassified into groups A-O according to cell wall antigens • S. pyogenes is the main pathogen in group A Fungal infections of the skin Fungi includes molds and yeasts: • Eukaryotic microbes • Can be filamentous or single-celled Fungal pathogens that colonize human skin are called dermatophytes: • Infect cool, moist, keratinized tissues (hair follicles, skin, nails) • Epidermophyton, Trichophyton, and Microsporum cause the majority of infections Diseases caused by these fungi are named after the location of infection instead of the fungi itself: • Tinea capitis (scalp) • Tinea corporis (body) • Tinea cruris (jock itch) • Tinea pedis (foot) Candida albicans infection C. albicans is a dimorphic yeast that can infect the skin, mucous membranes, and the body organs: • Has natural reservoirs in the body such as the GI tract, oral cavity, and skin Most common infection is called candida intertrigo as it occurs where skin rubs together Fungal infections are diagnosed via: • Clinical appearance • Microscopic examination of potassium hydroxide (KOH) preparations of skin flakes or hair destroys skin cells but leaves behind mycelia/spores • Culturing on fungal-specific Sabouraud agar Q u e st o n 4 Clicker Question A patient presents with cellulitis caused by Grampositive cocci that grow in chains. The bacterium is encapsulated and contains the M protein on its surface. What is the most likely identity of the bacterium? a. b. c. d. Staphylococcus aureus Streptococcus pyogenes Candida albicans Propionibacterium acnes Q u e st o n 4 Clicker Question - Answer A patient presents with cellulitis caused by Grampositive cocci that grow in chains. The bacterium is encapsulated and contains the M protein on its surface. What is the most likely identity of the bacterium? a. b. c. d. Staphylococcus aureus Streptococcus pyogenes Candida albicans Propionibacterium acnes Structure of the Eye External: • Eyelids, cornea, lens, iris, pupil, sclera The external parts of the eye, except the cornea, are covered with conjunctiva: • Moist, transparent mucous membrane that is continuous with conjunctiva • Covers the inside of eyelids Internal: • Retina, macula, vitreous humor Inside of the eye is lined by neuronal tissue: • Originates from the optic nerve retina • Macula is the centre of retina Herpes zoster opthalmicus Caused by an outbreak of shingles along the ophthalmic division of the trigeminal nerve: • Trigeminal nerve originates from the brain • The ophthalmic division extends into the eye and tip of nose to gather sensory information Results in eruption of vesicular lesions on the forehead, eyelids, nose, and eye Causes symptoms of corneal inflammation and eye pain/sensitivity Treated with oral antiviral medications such as acyclovir and valacyclovir Chlamydia trachomatis Obligate intracellular bacterial pathogen Can cause inclusion conjunctivitis in newborns during birthing process: • Self-limiting infection • Prevented by treating all newborns with antibiotics eyedrops (erythromycin) Can also cause trachoma which is the most frequent cause of infectious blindness: • Spread by direct contact with eye, nose, and throat secretions • Conjunctiva (mucous membrane lining) of inner eyelid becomes pebbled, and eyelashes turn inwards trichiasis • Eyelashes then rake across cornea, which becomes scarred • Treated with oral antibiotics (azithromycin) and topical tetracycline Fungal keratitis Fungi have a hard time infecting the eye as they cannot penetrate the intact corneal epithelium: • Injury can provide opportunity to cause ocular infections • Wearing contact lenses or getting a small foreign body in the eye may cause an abrasion sufficient to cause infection Fungal keratitis is caused by species of Fusarium, Aspergillus, and Candida: • Diagnosis is made by fungal culture from corneal scraping, PCR amplification, or confocal microscopy • Invasive lesions require systemic therapy (oral or intravenous medications) or surgery • Superficial lesions are treated with antifungal medications like natamycin (filamentous fungi) or Amphotericin B (yeast) Q u e ti o n 5 Clicker Question Herpes zoster ophthalmicus caused by reactivation of the herpes zoster virus can occur during a(n) ____________ outbreak. a. b. c. d. acne chickenpox gas gangrene shingles Q u e ti o n 5 Clicker Question - Answer Herpes zoster ophthalmicus caused by reactivation of the herpes zoster virus can occur during a(n) ____________ outbreak. a. b. c. d. acne chickenpox gas gangrene shingles