Skin and Respiratory Diseases

Skin Anatomy, Physiology, and Ecology

  • Skin has two layers:
    • Epidermis: Surface layer of flat cells.
      • Outermost cells are dead, filled with keratin (water-resistant).
      • These cells flake off and are replaced from deeper layers, shedding microbes.
    • Dermis: Connective tissue containing nerves, glands, and blood and lymphatic vessels.
  • Subcutaneous tissue: Supportive layer with fat and blood vessels.

Normal Skin Microbiota

  • Different skin regions have different microbial inhabitants.
    • Drier areas (e.g., back) have fewer bacteria (around 1,000/cm21,000/cm^2) than moist areas (e.g., groin, armpit) which have more than 10<br/>million/cm210 <br /> million/cm^2.
  • Three main microbial groups:
    • Diphtheroids: In oily regions like the forehead, upper chest, and back. Cutibacterium is the most common, an obligate anaerobe in hair follicles.
    • Staphylococci: Salt-tolerant, use nutrients, and produce antimicrobial substances against other Gram-positive bacteria.
    • Fungi: Malassezia species: lipid-dependent yeasts.

Diphtheroids

  • Characteristics: Variably shaped, non-motile, Gram-positive rods from Cutibacterium (Propionibacterium) and Corynebacterium genera.

Staphylococci

  • Characteristics: Gram-positive cocci in packets or clusters; facultatively anaerobic.

Fungi

  • Characteristics: Small yeasts of the genus Malassezia, require oily substances for growth.

Bacterial Skin Diseases

  • Few bacteria can directly invade intact skin; hair follicles provide a route.

Acne Vulgaris

  • Commonly starts at puberty.
    • Signs and symptoms:
      • Enlarged sebaceous glands, increased sebum secretion.
      • Hair follicle epithelium thickens, clumps, and blocks the follicle, leading to blackheads and whiteheads.
    • Causative agent: Cutibacterium acnes
      • Gram-positive rods, anaerobic.
      • Utilize sebum as a nutrient source, multiplying in trapped sebum.
Pathogenesis
  • Metabolic products from C. acnes cause an inflammatory response.
  • Neutrophils are recruited, releasing enzymes that damage the follicle wall, potentially forming an abscess.
  • Pus consists of living and dead neutrophils, bacteria, and tissue debris.
Epidemiology
  • Most people have C. acnes on their skin.
  • Higher incidence during puberty is linked to excess sebum production due to increased hormones and stress.
Treatment and Prevention
  • Usually mild; medications available.
  • Squeezing lesions can introduce bacteria into the bloodstream.

Hair Follicle Infections

  • Generally mild.
    • Signs and symptoms:
      • Folliculitis: Inflammation causing red bumps (pimples).
      • Furuncle (boil): Infection in adjacent tissues, causing localized redness, swelling, tenderness, and pain; may drain pus.
      • Carbuncle: Large area of redness, swelling, pain, and draining pus, often on thick skin (e.g., back of neck); fever may be present.

Diseases Caused by Staphylococcus aureus

  • Staphylococcus aureus commonly causes hair follicle infections and produces coagulase and clumping factor (virulence factors).
    • Food poisoning: Caused by consuming exotoxin in food.
    • Hair follicle infections: Folliculitis, carbuncles, furuncles.
    • Impetigo: Superficial skin disease with pus production.
    • Infective endocarditis: Infection of heart valves or inner lining of the heart.
    • Staphylococcal scalded skin syndrome: Toxin-mediated skin disease.
    • Toxic shock syndrome: Superantigens causing low blood pressure and organ failure.
    • Wound infections: Colonization of wounds; possible systemic complications.
Virulence Factors of Staphylococcus aureus
  • Capsule: Inhibits phagocytosis.
  • Clumping factor: Attaches bacterium to fibrin, fibrinogen, and plastic devices.
  • Coagulase: May slow leukocyte progress into infected areas by producing clots in surrounding capillaries.
  • Enterotoxins: Superantigens causing food poisoning if ingested; toxic shock if systemic.
  • Exfoliatin: Destroys material binding outer epidermis layers, causing scalded skin syndrome.
  • Fibronectin-binding protein: Attaches bacterium to acellular tissue substances, endothelium, epithelium, clots, indwelling plastic devices.
  • Hyaluronidase: Breaks down hyaluronic acid, allowing infection spread.
  • Leukocidin: Kills neutrophils or causes them to release enzymes.
  • Lipase: Breaks down fats.
  • Proteases: Degrade collagen and other tissue proteins.
  • Protein A: Binds to Fc portion of antibody, interfering with opsonization.
  • Toxic shock syndrome toxin: Causes rash, diarrhea, and shock.
  • α-Toxin: Makes holes in host cell membranes.

Impetigo

  • Most common type of pyoderma (skin infection with pus production).
    • Infection of insect bite, burn, scrape, or other wound.
      • Signs and symptoms: Patches of inflammation.
      • Thin-walled blisters develop in 2-5 days; break and are replaced by oozing crusts of drying plasma.
      • Usually little fever or pain; nearby lymph nodes may enlarge.
    • Causative agent: Often Streptococcus pyogenes
      • Gram-positive, chain-forming, group A streptococcus.
      • May also be caused by Staphylococcus aureus.
Streptococcus pyogenes vs. Staphylococcus aureus
  • Streptococcus pyogenes:
    • Morphology: Chains of Gram-positive cocci.
    • Growth: Beta-hemolytic colonies; catalase-negative, coagulase-negative, obligate fermenter.
    • Virulence Factors: Cell wall contains group A polysaccharide, Fc receptor (protein G), and M protein; produces hemolysins (streptolysins O and S), streptokinase, DNase, hyaluronidase, and others.
    • Diseases: Impetigo, strep throat, wound infections, scarlet fever, puerperal fever, toxic shock, and necrotizing fasciitis; complications include glomerulonephritis and rheumatic fever.
  • Staphylococcus aureus:
    • Morphology: Clusters of Gram-positive cocci.
    • Growth: Golden, beta-hemolytic colonies, catalase-positive, coagulase-positive, facultative anaerobe.
    • Virulence Factors: Cell wall contains Fc receptor (protein A); produces hemolysins, leukocidin, hyaluronidase, nuclease, protease, and others.
    • Diseases: Boils, staphylococcal scalded skin syndrome, wound infections, abscesses, bone infections, impetigo, food poisoning, and staphylococcal toxic shock syndrome.

Viral Skin Diseases

Varicella (Chickenpox)

  • Signs and symptoms: Fever, headache, malaise, rash; incubation 10-21 days.
    • Most childhood cases are mild.
    • Reactivation of latent virus causes shingles later in life.
    • All lesion types present during rash.
    • Occurs anywhere but often begins on head, chest, back; may occur on mucous membranes.
    • Lesions are pruritic (itchy); scratching can lead to serious secondary infection by S. pyogenes or S. aureus.
    • Causative agent: Varicella-zoster virus (VZV) of Herpesviridae: enveloped, double-stranded DNA virus
    • Vaccine: Attenuated virus vaccine available.

Fungal Diseases of the Skin

Superficial Cutaneous Mycoses

  • Mycoses are diseases caused by fungi.
  • Dermatophytes invade hair, nails, and keratin in the skin.
  • Results in jock itch, athlete’s foot, ringworm; Latinized names describe location: tinea capitis (scalp), tinea barbae (beard), tinea axillaris (armpit), tinea corporis (body), tinea cruris (groin), and tinea pedis (feet).
    • Causative agents: Dermatophytes (Epidermophyton, Microsporum, and Trichophyton)
      • Grown on media for molds; identified by colonial and microscopic appearance.
      • Nutritional requirements and biochemical tests also used.
    • Treatment and prevention: Prescription and over-the-counter medications.

Other Fungal Diseases

  • Malassezia furfur: Generally harmless, commonly found.
    • Can cause scaly face rash, dandruff, or tinea versicolor.
    • Tinea versicolor: Patchy scaliness and increased or decreased pigmentation.
  • Yeast Candida albicans: Found in normal microbiota.
    • Can invade deep layers of skin and subcutaneous tissues.
    • Often no precise cause for invasion.

Respiratory System Infections

  • Enormous variety; range from trivial to fatal.
    • Divided into infections of the upper respiratory tract (head and neck) and the lower respiratory tract (chest).
    • Upper respiratory infections (e.g., colds) are common and uncomfortable, but not life-threatening.
    • Lower respiratory infections (e.g., pneumonia, tuberculosis) are often serious, may be fatal.

Normal Microbiota of the Upper Respiratory System

  • Corynebacterium: Pleomorphic, often club-shaped Gram-positive rods; non-motile; aerobic or facultatively anaerobic; diphtheroids.
  • Fusobacterium, Porphyromonas, Prevotella: Gram-negative rods; obligate anaerobes; found in space between teeth and gums.
  • Haemophilus: Small, Gram-negative rods; facultative anaerobes; commonly include potential pathogen H. influenzae.
  • Moraxella: Gram-negative diplococci and diplobacilli; aerobic; some microscopically resemble pathogenic Neisseria species such as N. meningitidis.
  • Staphylococcus: Gram-positive cocci in clusters; facultative anaerobes; potential pathogen Staphylococcus aureus commonly inhabits nostrils.
  • Streptococcus: Gram-positive cocci in chains; aerotolerant (obligate fermenters); viridans streptococci are α-hemolytic, and non-hemolytic streptococci are common; β-hemolytic streptococci and the potential pathogen S. pneumoniae may also be present.

Anatomy, Physiology, and Ecology of the Upper Respiratory Tract

  • Eyes and lining of eyelids covered by conjunctiva.
    • Bathed in tears rich in lysozyme and secretory IgA, cleaned by blinking reflex; few bacteria present; infection termed conjunctivitis.
    • Tear ducts connect to the nasal cavity.
  • Ears have three parts: external, middle, and inner.
    • External ear protected by cerumen (ear wax).
    • Middle ear sterile, connected by Eustachian tubes to pharynx to allow drainage, equalize pressure; infection is otitis media.
    • Inner ear is typically microbe-free.

Anatomy, Physiology, and Ecology of the Lower Respiratory Tract

  • Usually sterile; includes larynx (voice box), trachea (windpipe), bronchi, lungs.
    • Inflammation of larynx is laryngitis, causing hoarseness.
    • Trachea branches into two bronchi; infection is bronchitis, often from viral infection; coughing due to smoking.
    • Bronchioles end in alveoli, the sites of gas exchange; inflammation of lungs is pneumonitis; called pneumonia when alveoli fill with pus and fluid.
    • Lung tissue contains many macrophages to prevent infection.

Bacterial Infections of the Upper Respiratory System

Pink Eye, Earache, and Sinus Infections

  • Causative agents: Haemophilus influenzae (Gram-negative rod) and Streptococcus pneumoniae (Gram-positive encapsulated diplococcus) are common causes; others also involved.
    • Strains that infect conjunctiva have adhesins.
    • Approximately one third of otitis media and sinusitis cases are caused by respiratory viruses.
  • Pathogenesis of conjunctivitis:
    • Organisms likely from airborne respiratory droplets or contaminated hands.
    • Resist destruction by lysozyme.
    • Attachment sometimes aided by degradation of mucin (protective component of epithelial surface mucous).
    • Release tissue-damaging enzymes and sometimes toxins.

Streptococcal Pharyngitis (“Strep Throat”)

  • Signs and symptoms:
    • Sore throat, difficulty swallowing, fever.
    • Throat is red with patches of pus, tiny hemorrhages.
    • Most patients recover after about a week; some have mild or no symptoms.
  • Causative agent is Streptococcus pyogenes
    • Gram-positive; grows in chains.
    • β-hemolysis of blood agar.
    • Group A streptococcus (GAS) from Lancefield grouping.
Pathogenesis of Streptococcus pyogenes
  • Structural components of outer cell wall allow evasion of host defenses.
    • M protein acts as adhesin (80 different types); antibodies that bind to it prevent infection, but antibodies to one strain do not stop others.
    • Protein F adheres to fibrin of epithelial cells in throat.
    • DNase, hyaluronidase, proteases degrade intracellular connections; streptokinase breaks blood clots.
Post-Streptococcal Sequelae
  • Complications that develop after streptococcal infections; thought to result from immune response.
    • Acute rheumatic fever: Begins approximately 3 weeks after recovery; fever, joint pains, chest pains, rash, nodules under skin; uncontrollable body movements (chorea) can occur; carditis develops in 30-50% of patients, can lead to chronic rheumatic heart disease; heart valve damage; infective endocarditis (cross reactive antigen); thought to involve autoimmune response; occurs in up to 3% of severe untreated cases, results in about 10 to 20 million cases per year globally.
Acute Post-Streptococcal Glomerulonephritis
  • Fever, fluid retention, high blood pressure; blood and protein in urine.
  • S. pyogenes generally eliminated before symptoms appear.
  • Damage to kidneys from inflammatory reaction to streptococcal antigens in kidney glomeruli; antibodies bind, activate complement system.
  • Only a few strains of S. pyogenes cause this.

Viral Infections of the Upper Respiratory System

The Common Cold

  • Causative agents: “Cold viruses.”
    • 100 or more types of human rhinoviruses cause approximately 30-50%; members of Picornavirus family (small RNA viruses); non-enveloped, single-stranded RNA genome; grown in cell culture at 3333 degrees Celsius and slightly acid pH; inactivated in acid of stomach.
    • Many other viruses, some bacteria produce cold signs and symptoms.
Treatment and Prevention of Common Cold
  • No proven treatments.
    • Viruses not affected by antibiotics or antibacterial medications.
    • Analgesics and antipyretics can reduce symptoms, but may prolong symptoms and duration.
    • Prevention of spread effective: Handwashing, avoiding touching face, avoiding crowded places and infected individuals in first few days of symptoms.
    • No vaccine due to large number of causative viruses.
  • Signs and symptoms: Malaise, runny nose, sneezing, cough, sore throat, hoarseness.
  • Incubation period: 1 to 2 days.
  • Pathogenesis: Viruses attach to respiratory epithelium; ciliary action stops, and cells slough; secretion of mucus increases, and inflammatory reaction occurs.
  • Epidemiology: Inhalation of infectious droplets; transfer of infectious mucus to nose or eye by contaminated fingers.

Pneumonias Compared

  • Pneumococcal Pneumonia:
    • Signs and symptoms: Cough, sudden chills and fever, shortness of breath, chest pain, cyanosis, rust-colored sputum from blood.
    • Incubation period: 1 to 3 days.
    • Causative agent: Streptococcus pneumoniae (pneumococcus); encapsulated strains.
    • Pathogenesis: Inhalation of encapsulated pneumococci; colonization of alveoli triggers an inflammatory response; fluid and inflammatory cells fill the alveoli.
    • Epidemiology: High carrier rates for S. pneumoniae; risk of pneumonia increases with conditions such as alcoholism, narcotic use, and viral infections that impair the mucociliary escalator; other risk factors are chronic heart or lung disease, diabetes, and cancer.
    • Treatment and prevention: Antibiotics; PCV13: conjugate vaccine against 13 serotypes; PPSV23: polysaccharide vaccine against 23 serotypes.
  • Klebsiella Pneumonia:
    • Signs and symptoms: Cough, repeated chills, fever, shortness of breath, chest pain, cyanosis, bloody jelly-like sputum.
    • Incubation period: 1 to 3 days.
    • Causative agent: Klebsiella pneumoniae, encapsulated enterobacterium.
    • Pathogenesis: Inhalation of colonized mucus droplets from the throat; destruction of lung tissue and abscess formation common; infection spreads via blood to other body tissues.
    • Epidemiology: Klebsiella species and other Gram-negative rods are common causes of fatal healthcare-associated pneumonias; often resistant to antibiotics.
    • Treatment and prevention: Combination of antibiotics; resistance is a problem; no vaccine available.
  • Mycoplasmal Pneumonia:
    • Signs and symptoms: Gradual onset of dry cough, fever, fatigue, headache, and muscle aches.
    • Incubation period: 2 to 3 weeks.
    • Causative agent: Mycoplasma pneumoniae; lacks cell wall.
    • Pathogenesis: Inhalation of infected droplets; bacterial cells attach to receptors on respiratory epithelium; inhibition of ciliary motion and destruction of cells.
    • Epidemiology: Mild infections are common; infected people spread the disease.
    • Treatment and prevention: Antibiotics, excluding cell wall synthesis inhibitors; no vaccine available; avoid crowding in schools and military facilities.

Bacterial Infections of Lower Respiratory System

Tuberculosis (TB)

  • Once very common; incidence declined in industrialized nations as living standards improved.
    • In 1985, incidence began to rise due to expanding AIDS epidemic, increasing prevalence of drug-resistant strains.
    • CDC developed plan to increase efforts to identify and treat cases in high-risk groups; incidence began to decrease by 1993.
    • Causative agent: Mycobacterium tuberculosis
      • Slender, acid-fast, rod-shaped bacterium.
      • Strict aerobe with generation time over 16 hours.
      • Unusual cell wall contains mycolic acids: cells resist drying, disinfectants, strong acids and alkali; responsible for acid-fast staining; easily killed by pasteurization.
Pathogenesis of Tuberculosis
  • Airborne cells inhaled into lungs.
    • Alveolar macrophages quickly engulf; unable to destroy.
    • Mycolic acids prevent fusion of phagosome with lysosomes.
    • Bacteria exit, multiply within macrophage cytoplasm.
    • Pro-inflammatory response recruits more macrophages.
    • Some fuse to form giant multinucleated cells; others induced by bacteria to accumulate oil droplets, become foamy macrophages.
    • Lymphocytes wall off infected area, granuloma forms called tubercles.
    • Tubercle ruptures, releases bacteria, dead material, spreads bacteria in lungs.
    • Lung cavity persists, enlarges for months or years, spreads bacteria; can be transmitted by coughing.
Treatment and Prevention of Tuberculosis
  • In U.S., skin or blood tests, lung X-rays used to identify cases; both TB disease and LTBI (Latent Tuberculosis Infection) are treated.
    • Antibiotics are used for treatment.
    • Prevention and control are global challenge.
    • BCG vaccine used in many countries (live attenuated from M. bovis); prevents childhood TB, but ineffective against LTBI reactivation; discouraged in U.S. as it causes positive tuberculin test and interferes with disease prevention; not safe in severely immunocompromised patients.

Inhalation Anthrax

  • Causative agent: Bacillus anthracis
    • Endospore-forming, Gram-positive, non-hemolytic, non-motile, rod-shaped bacterium.
    • Vegetative cells have capsule composed of amino acid polymer.
Pathogenesis of Inhalation Anthrax
  • Endospores inhaled, taken up by macrophages, carried to lymph nodes in chest where they germinate.
    • Anthrax toxin composed of three proteins; results in pulmonary edema and cell death.
      • Protective antigen (PA).
      • Edema factor (EF) or Lethal factor (LF).
    • Toxin-producing, encapsulated cells enter bloodstream, overwhelm defenses, damage tissues.
    • Untreated, case-fatality rate is near 95%; early treatment reduces fatalities to about 45%.
Epidemiology of Inhalation Anthrax
  • Zoonosis transmitted to humans working with animals or animal products; not transmitted from person to person.
Treatment and Prevention of Inhalation Anthrax
  • Antimicrobials doxycycline or ciprofloxacin, along with monoclonal antibody that binds to protective antigen (PA), preventing it from attaching to host cells.
    • Prophylactic antimicrobial treatment for those suspected of having been exposed; up to 60 days.
    • Control by reducing infection in livestock.
    • Acellular vaccine available for those at increased risk.

Viral Infections of the Lower Respiratory System

Influenza (“Flu”)

  • Antigenic changes responsible for serious annual epidemics; infects approximately 20% of humans annually.
    • Three major virus types based on protein coat; type A causes most serious disease.
    • Influenza viruses do not cause “stomach flu.”
    • Signs and symptoms: Headache, muscle aches, fever, sore throat, fatigue; peaks in 6 to 12 hours; dry cough develops and worsens over a few days (incubation period approximately 2 days); acute symptoms last approximately 1 week; lingering cough, fatigue, weakness lasts additional days or weeks.
Influenza Virus
  • Causative agent: Influenza A in Orthomyxoviridae.
    • Enveloped virus with 8 segments of single-stranded RNA.
    • Glycoprotein spikes embedded in envelope: hemagglutinin antigen (HA) and neuraminidase antigen (NA).
      • HA attaches to receptors on host epithelial cells.
      • NA critical in release: destroys surface receptors that bind budding virions.
    • Subtypes based on HA and NA.
      • 1997 “avian flu” was H5N1; 2009 “swine flu” was H1N1.
Epidemiology of Influenza
  • Only small percentage of cases are fatal, but there are many cases, so overall number of deaths is high.
    • Most deaths due to secondary bacterial infections (e.g., pneumonia).
    • Epidemics occur annually; pandemics periodically.
    • Antigenic drift: Minor mutations in HA and NA genes; responsible for seasonal influenza; immunity developed from previous year less effective.
    • Antigenic shift: Uncommon; concurrent infection allows mixture of 8 RNA segments; causes pandemic influenza; human strain can gain novel HA and/or NA antigens to which humans have no immunity.