Structure and Function of the Skin Learning Objective 21-1 Describe the structure of the skin and mucous membranes and the ways pathogens can invade the skin.

The Structure of Human Skin Perspiration and sebum contain nutrients Salt inhibits microbes Lysozyme hydrolyzes peptidoglycan Fatty acids inhibit some pathogens Figure 21.1

Mucous Membranes Line body cavities The epithelial cells are attached to an extracellular matrix Cells secrete mucus Often acidic Some cells have cilia In eyes, washed by tears with lysozyme

Normal Microbiota of the Skin Gram-positive, salt-tolerant bacteria Staphylococci Micrococci Diphtheroids Figure 14.1a

Normal Microbiota of the Skin Grow on oils Aerobes on surface Corynebacterium xerosis Anaerobes in hair follicles Propionibacterium acnes Yeast Malassezia furfur

Skin Lesions Figure 21.2

Bacterial Skin Diseases

Staphylococcal Skin Infections Staphylococcus epidermidis Gram-positive cocci, coagulase-negative Staphylococcus aureus Gram-positive cocci, coagulase-positive Clinical Focus, p. 593

Staphylococcus aureus Antibiotic resistant Leukocidin Resists opsonization Survives in phagolysosome Lysozyme resistant Exfoliative toxin Superantigen Clinical Focus, p. 593

MRSA Methicillin-resistant Staphylococcus Aureus (MRSA) is a type of staph bacteria that is resistant to certain antibiotics called beta-lactams. These antibiotics include methicillin and other more common antibiotics such as oxacillin, penicillin, and amoxicillin. In the community, most MRSA infections are skin infections. More severe or potentially life-threatening MRSA infections occur most frequently among patients in healthcare settings. While 25% to 30% of people are colonized* in the nose with staph, less than 2% are colonized with MRSA

Staphylococcal Skin Infections Folliculitis: Infections of the hair follicles Sty: Folliculitis of an eyelash Furuncle: Abscess; pus surrounded by inflamed tissue Carbuncle: Inflammation of tissue under the skin Impetigo: crusting (nonbullous) sores, spread by autoinoculation

Nonbullous Lesions of Impetigo Figure 21.4

Scalded Skin Syndrome Toxic shock syndrome (TSS) Toxic shock syndrome toxin 1 Scalded skin syndrome (Staph spp.) Bullous impetigo Impetigo of the newborn Epidermolytic endotoxin

Lesions of Skin Syndrome Figure 21.5

Streptococcal Skin Infections Streptococcus pyogenes Group A beta-hemolytic streptococci Hemolysins Hyaluronidase Stretolysins M proteins

Streptococcal Skin Infections Necrotizing fasciitis – “flesh-eating diesease” Common in immune compromised Group A streptococcus Staphloccoccus aureus C. perfrinogens Bacteroides fragilis

Infections by Pseudomonads Pseudomonas aeruginosa Gram-negative, aerobic rod Pseudomonas dermatitis Otitis externa, or “swimmer’s ear” Post-burn infections Opportunistic

Cutaneous Anthrax Most common and least dangerous infection caused by Bacillus anthracis Forms a black eschar when endospores enter the skin and germinate there 11 cases occurred following bioterrorist attacks in the fall of 2001 20% mortality rate if untreated CDC

Buruli Ulcer Caused by Mycobacterium ulcerans Deep, damaging ulcers Exceeds incidence of leprosy

Classifications of Acne Comedonal (mild) acne Inflammatory (moderate) acne Nodular cystic (severe) acne

Comedonal Acne Mild Treatment Sebum channels blocked with shed cells Topical agents Salicyclic acid preparations Retinoids Adapalene

Inflammatory Acne Propionibacterium acnes Gram-positive, anaerobic rod Treatment Preventing sebum formation (isotretinoin) Benzoyl peroxide to loosen clogged follicles Visible (blue) light (kills P. acnes) Antibiotics

Nodular Cystic Acne Severe Treatment Isotretinoin Figure 21.9

Warts Papillomaviruses Treatment Removal Cryotherapy Electrodesiccation Salicylic acid Imiquimod (stimulates interferon production) Bleomycin

Poxviruses Smallpox (variola) Monkeypox Smallpox virus (orthopox virus) Variola major has 20% mortality Variola minor has <1% mortality Eradicated by vaccination Monkeypox Prevention by smallpox vaccination

Smallpox Lesions Figure 21.10

Chickenpox Varicella-zoster virus (human herpesvirus 3) Transmitted by the respiratory route Causes pus-filled vesicles Virus may remain latent in dorsal root ganglia Prevention: Live attenuated vaccine Breakthrough varicella in vaccinated people

Figure 21.11a

Chicken Pox

Shingles Reactivation of latent HHV-3 releases viruses that move along peripheral nerves to skin Postherpetic neuralgia Prevention: Live attenuated vaccine Acyclovir may lessen symptoms

Figure 21.11b

Why is there an emergence of shingles among healthy populations?

Hand, Foot, and Mouth Disease (HFMD) Most common in babies and children under age 5 Fever, sore throat, malaise Painful spots inside the mouth Red or blister-like spots on palms of hands and soles of feet and often genitals, buttocks, knees, and elbows Caused by viruses in Enterovirus group Cocksackie virus © Dr. P. Marazzi/Science Source

Vesicular/Pustular Rash Diseases Chickenpox Smallpox Hand, Foot, and Mouth Disease Causative Organism(s) Human herpesvirus 3 (varicella-zoster virus) Variola virus Enteroviruses, usually Coxsackie Common Modes of Transmission Droplet contact, inhalation of aerosolized lesion fluid Droplet contact, indirect contact Direct and droplet contact Virulence Factors Ability to fuse cells, ability to remain latent in ganglia Ability to dampen, avoid immune response N/A Culture/Diagnosis Based largely on clinical appearance Usually based on clinical presentation and history Prevention Live attenuated vaccine; there is also vaccine to prevent reactivation of latent virus (shingles) Live virus vaccine (vaccinia virus) Hand hygiene Treatment None in uncomplicated cases; acyclovir for high risk Cidofovir, immune globulin None Distinguishing Features No fever prodrome; lesions are superficial; in centripetal distribution (more in center of body) Fever precedes rash, lesions are deep and in centrifugal distribution (more on extremities) Fever prodrome, lesions in mouth first Epidemiological Features Chickenpox: vaccine decreased hospital visits by 88%, ambulatory visits by 59%; shingles: 1 million cases annually Last natural case worldwide was in 1977 Category A Bioterrorism Agent Sporadic in most of world; unusual outbreaks in East and Southeast Asia since 1997 caused by an enterovirus

Herpes Simplex Human herpesvirus 1 (HSV-1) and 2 (HSV-2) Cold sores or fever blisters (vesicles on lips) Herpes gladiatorum (vesicles on skin) Herpetic whitlow (vesicles on fingers) Herpes encephalitis HSV-1 can remain latent in trigeminal nerve ganglia

Cold Sores Caused by Herpes Simplex Virus Figure 21.12

HSV-1 in the Trigeminal Nerve Ganglion Figure 21.13

Herpes Simplex HSV-2 can remain latent in sacral nerve ganglia HSV-2 encephalitis: 70% fatality Encephalitis treatment: Acyclovir

Measles (Rubeola) Measles virus Transmitted by respiratory route Macular rash and Koplik's spots Prevented by vaccination Figure 21.14

Sequelae of Measles Small number of cases develop laryngitis, bronchopneumonia, and bacterial secondary infections In 6% of the cases, the virus can cause pneumonia Most serious complication is subacute sclerosing panencephalitis: progressive neurological degeneration of the cerebral cortex, white matter, and brain stem

Reported U.S. Cases of Measles, 1960–2007 Clinical Focus, p. 505

Rubella (German Measles) Rubella virus Macular rash and fever Congenital rubella syndrome causes severe fetal damage Prevented by vaccination Figure 21.15

© James Stevenson/Science Source Congenital Rubella Infection in the first trimester Induces miscarriage Causes multiple permanent defects in the newborn Congenital defects caused by rubella: Deafness Cardiac abnormalities Ocular lesions Mental and physical retardation © James Stevenson/Science Source

Fifth Disease Name derived from a 1905 list of skin rashes, which included 1. Measles 2. Scarlet fever 3. Rubella 4. Filatov Dukes disease (mild scarlet fever), and 5. Fifth disease, or erythema infectiosum Human parvovirus B19 produces mild flu-like symptoms and facial rash

Roseola Caused by human herpesvirus 6 (HHV-6) and 7 (HHV-7) High fever and rash lasting for 1–2 days

Disease Measles (Rubeola) Rubella Causative organism(s) Measles virus Rubella virus Common Modes of Transmission Droplet contact Virulence Factors Syncytium formation, ability to suppress CMI Inhibition of mitosis, induction of apoptosis, and damage to vascular endothelium Culture/ Diagnosis ELISA for IgM, acute/convalescent IgG; genotyping the virus during outbreaks Acute IgM, acute/convalescent IgG Prevention Live attenuated vaccine (MMR or MMRV) Live attenuated vaccine (MMR or MMRV) Treatment No antivirals; vitamin A, antibiotics for secondary bacterial infections N/A Distinguishing Features Starts on head, spreads to whole body, lasts over a week Milder red rash, lasts approximately 3 days Epidemiological Features Incidence increasing in North America; in developing countries incidence is 30 million cases/yr and 1 million deaths Three cases reported in the United States in 2009; worldwide: 100,000 infants/yr born with congenital rubella syndrome

Disease Fifth Disease Roseola Causative Organism(s) Parvovirus B19 Human herpesvirus 6 Common Modes of Transmission Droplet contact, direct contact Unknown Virulence Factors N/A Ability to remain latent Culture/Diagnosis Usually diagnosed clinically Prevention Treatment Distinguishing Features “Slapped-face” rash first, spreads to limbs and trunk, tends to be confluent rather than distinct bumps High fever precedes rash stage; rash not always present Epidemiological Features 60% of population seropositive by age 20 >90% of population seropositive; 90% of disease cases occur before age of 2

Cutaneous Mycoses Dermatomycoses Also known as tineas or ringworm Metabolize keratin

Dermatomycoses Figure 21.16

Cutaneous Mycoses Tinea unguium – Fungal nail infection Treatment Itraconazole Terbinafine

Signs and Symptoms of Cutaneous Mycoses

Candidiasis Candida albicans (yeast) Candidiasis may result from suppression of competing bacteria by antibiotics Occurs in skin and mucous membranes of genitourinary tract and mouth Thrush: An infection of mucous membranes of mouth Topical treatment with miconazole or nystatin

Candida albicans Figure 21.17a

Case of Oral Candidiasis Figure 21.17b

Normal Biota of the Eye Generally sparse Diversity in the bacteria Corynebacterium is the dominant genus Eye microbiome resembles that of the skin: Diphtheroids Coagulase-negative staphylococci Micrococcus Nonhemolytic streptococci Some yeast Neisseria species

Defenses and Normal Biota of the Eye Eyes Mucus in conjunctiva and in tears; lysozyme and lactoferrin in tears Sparsely populated with Corynebacterium, Staphylococcus epidermidis, Micrococcus and Streptococcus species

Bacterial Diseases of the Eye Conjunctivitis An inflammation of the conjunctiva Also called pinkeye or red eye Commonly caused by Haemophilus influenzae Various other microbes can also be the cause Associated with unsanitary contact lenses

Bacterial Diseases of the Eye Ophthalmia neonatorum Caused by Neisseria gonorrhoeae Transmitted to a newborn's eyes during passage through the birth canal Prevented by treating a newborn's eyes with antibiotics

Neonatal Conjunctivitis ©Medical-on-Line/Alamy

Conjunctivitis Disease Table Neonatal Conjunctivitis Bacterial Conjunctivitis Viral Conjunctivitis Causative Organism(s) Chlamydia trachomatis or Neisseria gonorrhoeae Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae,Moraxella, and also Neisseria gonorrhoeae, Chlamydia trachomatis Adenoviruses and others Common Modes of Transmission Vertical Direct, indirect contact Virulence Factors N/A Culture/Diagnosis Gram stain and culture Clinical diagnosis Prevention Screen mothers, apply antibiotic to newborn eyes Hygiene Treatment Topical and oral antibiotics Gatifloxacin or levofloxacin ophthalmic solution None, although antibiotics often given because type of infection not distinguished Distinguishing Features In babies <28 days old Mucopurulent discharge Serous (clear) discharge Epidemiological Features Less than 0.5% in developed world; higher incidence in developing world More common in children More common in adults

Bacterial Diseases of the Eye Chlamydia trachomatis Causes inclusion conjunctivitis, or chlamydial conjunctivitis Transmitted to a newborn's eyes during passage through the birth canal Spread through swimming pool water Treated with tetracycline

Bacterial Diseases of the Eye Chlamydia trachomatis Causes trachoma Leading cause of blindness worldwide Infection causes permanent scarring; scars abrade the cornea leading to blindness

© Western Ophthalmic Hospital/Science Source Ocular Trachoma Chronic infection of the epithelial cells of the eye caused by Chlamydia trachomatis Major cause of blindness around the world Several million cases in Africa, Asia, the Middle East, Latin America, and Pacific Islands © Western Ophthalmic Hospital/Science Source Ongoing or recurrent infections lead to chronic inflammatory damage and scarring

Trachoma Disease Table Causative Organism(s) C. trachomatis serovars A–C Common Modes of Transmission Indirect contact, mechanical vector Virulence Factors Intracellular growth Culture/Diagnosis Detection of inclusion bodies in stained preparations Prevention Hygiene, vector control, prompt treatment of initial infection Treatment Azithromycin or topical erythromycin Epidemiological Features Highest prevalence among children between ages 3 and 5, prevalence as high as 60% in endemic areas

Other Infectious Diseases of the Eye Keratitis Inflammation of the cornea Bacteria (U.S.) Fusarium and Aspergillus (Africa and Asia)

Other Infectious Diseases of the Eye Herpetic keratitis Caused by herpes simplex virus 1 (HSV-1). Infects cornea and may cause blindness Treated with trifluridine