BIO-123: Skin Infections

epidermis contents

epidermis contents

• Stratum corneum – outermost layer – hosts microbiome and made up of flattened dead keratinized cells covered in oil and salt – cells replaced ~ every month.

• Stratum granulosum – keratinizes skin and waterproofs it

• Stratum spinosum -contains dendritic (Langerhans) cells (phagocytes/APCs) and karatinocytes

• Stratum basale – contains basal cells and melanocytes and adheres to Dermis

dermis contents

• Contains blood vessels, nerve endings, sebaceous glands (which also harbor microbiota), hair follicles

hypodermis contents

Contains fat cells – subcutaneous and not technically part of the skin, but anchors the skin to underlying tissue

Hyaluronic acid (HA)

glycosaminoglycan found in skin, joints, and tissues as part of the ECM. Capable of retaining moisture and acts as a lubricant to maintain elasticity.

collagen

a protein found in skin that also makes up the main component of connective tissue and the ECM. It’s wound into strong, pliable fibers.

members of skin microbiome

• Viruses – (HPVs)

• Yeast

  • Malassezia (eat sebum and can cause hyperpigmentation in immunocompromised people)

  • Candida albicans - can cause candidiasis (yeast infections) if populations grow out of control

• Gram positive bacteria – these tolerate higher salt concentrations

  • Staphylococcus (most common is Staph epidermidis)

  • Micrococcus (like M. luteus)

  • Diphtheroids

    • Corynebacteria

folliculitis etiology

S. aureus, S. epidermidis — normally doesn’t cause disease unless it “follows” S. aureus 

folliculitis mode of transmission

Direct contact, indirect contact via fomites, endogenous infection

folliculitis virulence factors

enzymes and exotoxins like hyaluronidase, coagulase, cytolytic toxins

folliculitis signs/symptoms

Inflamed hair follicles - red, painful and/or itchy bumps or whiteheads near hair follicles; may be clustered or deep. May feel warm to the touch; deep infections may also trigger fever

folliculitis diagnosis

• Usually diagnosed clinically by signs/symptoms alone

  • Bacteria isolated from pus can be cultured

  • S. aureus differentiated from S. epidermidis by coagulase test – it is coagulase positive (can clot blood)

  • Staph can be differentiated from Strep using the catalase test – Staph is catalase positive (can break down H2O2)

folliculitis treatment

• Pus is drained and skin cleaned, then treated with topical mupirocin (inhibits isoleucyl tRNA-synthetase) or clindamycin/erythromycin (macrolides). Warm compress and OTC analgesics. Oral antibiotics for deeper infection: Clindamycin (macrolide), sulfa, or doxycycline (tetracycline)

MRSA etiology

S. aureus

MRSA mode of transmission

can begin as folliculitis; Direct contact, indirect contact via fomites, endogenous infection

MRSA virulence factors

Staphylococcus aureus strains resistant to penicillin, methicillin, macrolides, aminoglycosides, cephalosporin

MRSA signs/symptoms

You cannot tell by looking at the skin if infection is caused by this

MRSA diagnosis

•  can be detected from clinical samples via: 

  • Culturing bacteria and performing disk-diffusion assays with various antibiotics

  • PCR to detect the mecA gene encoding Penicillin Binding Protein (PBP2a)

  • Agglutination assay to detect PBP2a on the surface of S. aureus cells

MRSA treatment

clindamycin, tetracyclines, sulfa drugs, linezolid, or rifampin (but rifampin is only used in combination with other agents because of resistance)

MRSA prevention

• Staph is impossible to eliminate – normal resident of many people

• Aseptic treatment of non-intact skin, wounds, and surgical openings, handling of catheters and needles, and hand washing

• People with staph lesions should avoid working with food, sharing personal items like towels, clothing, and razors, and should keep them clean and covered until they heal. They should also frequently wash their hands.

Staphylococcal Scalded Skin Syndrome (SSSS) etiology

Staphylococcus aureus

Staphylococcal Scalded Skin Syndrome (SSSS) mode of transmission

• Direct person-to-person contact; usually affects infants, but also elderly and immunocompromised patients

Staphylococcal Scalded Skin Syndrome (SSSS) virulence factors

•  Exfoliative toxin (AKA epidermolysin or exfolatin) in addition to others (like coagulase)

Staphylococcal Scalded Skin Syndrome (SSSS) signs/symptoms

•  Epidermis separates from underlying tissue – looks like skin that has been boiled/scalded. Skin blisters and peels off in sheets.

Staphylococcal Scalded Skin Syndrome (SSSS) diagnosis

•  Usually diagnosed clinically. Can also perform a tissue biopsy/histological examination from cultures of the blood, urine, nose, throat, and skin.

Staphylococcal Scalded Skin Syndrome (SSSS) treatment

• Hospitalization, IV semisynthetic beta-lactams like flucloxacillin since S. aureus can produce beta-lactamases. May be caused by MRSA – vancomycin (aminoglycoside), linezolid, could be used instead. Skin should be treated as it is for burns. 

impetigo etiology

Streptococcus pyogenes, Staphylococcus aureus

impetigo mode of transmission

• direct contact from another person or oneself (ex. by wiping runny nose on sleeve); indirect contact less common.

impetigo virulence factors

• Strep – M protein; Staph – exotoxins

impetigo signs/symptoms

• Flat, red superficial patches/blisters – mostly on face and limbs. Patches ooze pus break and form an itchy honey-colored crust (pyogenic). Rarely causes fever.

impetigo diagnosis

• Clinical evaluation; cannot differentiate strep or staph though; can do this in the lab using a catalase test.

impetigo treatment

• Applying wet compress, removing scabs, and applying topical mupirocin (targets ribosomes), then covering the sores to prevent spread. Oral amoxicillin (beta- lactam), doxycycline, macrolides are options.

impetigo prevention

• Regular hand-washing, clipping children’s fingernails, covering open wounds until they heal

Erysipelas etiology

Streptococcus pyogenes

Erysipelas mode of transmission

Direct or indirect contact

Erysipelas virulence factors

M protein, exotoxins

Erysipelas signs/symptoms

Distinct, raised (edema), bright redness (erythema) on the face and limbs with obvious margin, swollen lymph nodes, fever, chills, and elevated leukocytes

Erysipelas diagnosis

Clinical evaluation; distinct appearance. Cultures only performed if multiple pathogens are suspected.

Erysipelas treatment

Oral penicillin (beta-lactam) first choice, then macrolides (erythromycin)

Erysipelas prevention

practice good hand hygiene and wounds should be cleaned and treated

Necrotizing fasciitis etiology

Streptococcus pyogenes (Group A Strep or GAS)

Necrotizing fasciitis mode of transmission

Direct or indirect contact through breaks in skin or from transient bacteremia (bacteria in the bloodstream). Portal of entry not always defined.

Necrotizing fasciitis virulence factors

Streptolysin S, protease, and DNase, M protein

Necrotizing fasciitis signs/symptoms

Can begin with sunburn-like rash or a small area of red swelling with heat and pain. Pain can either be unusually intense or absent due to neuropathy. Tissue progressively darkens from red→purple→blue→black. Bullae (blisters) form and fill with straw-colored fluid which then becomes bloody. Black necrotic eschar forms as tissue dies. High fever, tachycardia (increased HR) common with more involved infection.

Necrotizing fasciitis diagnosis

Clinical examination, gram stain and culture from samples. CT or MRI can detect subcutaneous or facial edema but should not delay treatment.

Necrotizing fasciitis treatment

Surgeons clean/remove/debride tissue; IV broad-spectrum antibiotics (usually) clindamycin (macrolide) + penicillin (beta-lactam). Maggot Debridement Therapy (MDT) has also been implemented

Necrotizing fasciitis prevention

diabetes, cancer, and chickenpox are risk factors. Prevention means not taking small compromises in skin for granted - issues as harmless as needlesticks and insect bites have been linked to this

acne vulgaris etiology

Cutibacterium acnes (formerly called Propionibacterium acnes)

acne vulgaris mode of transmission

endogenous infection caused by one's own bacteria overgrowing

acne vulgaris virulence factors

lipases, adhesins for biofilm formation, and hyaluronidases

acne vulgaris signs/symptoms

Papules, pustules, nodules, and cysts

acne vulgaris diagnosis

Clinical examination; contributing factors and severity assessed

acne vulgaris treatment

• Antibiotics: oral doxycycline (tetracycline) or topical clindamycin (macrolide)

• Topicals like benzoyl peroxide: increases cell turnover reduces lipids on skin surface; kills bacteria.

• Isotretinoin (Accutane) – vitamin A derivative that inhibits sebum formation but has potentially severe side effects including fetal birth defects, liver effects, increased blood fats, and severe skin drying

• Hormonal birth control/estrogens – can affect hormonal acne / sebum production

• Spironolactone – not FDA approved for acne but used off-label for blocking androgen hormones since it is an aldosterone antagonist (is used as a diuretic to high blood pressure and edema)

• UVB/UVA light can kill bacteria, but can also cause skin damage

• Dietary interventions – decreasing consumption of dairy and high glycemic index foods have been linked to improvement

P. aeruginosa (burn infections) etiology

Pseudomonas aeruginosa

P. aeruginosa (burn infections) mode of transmission

direct or indirect contact; often from fomites; ubiquitous and therefore easy to acquire and difficult to avoid

P. aeruginosa (burn infections) virulence factors

Fimbriae and adhesins, Capsule, Neuraminidase, Elastase, Endotoxin (lipid A), Exotoxin A and Exoenzyme S, Pyocyanin

P. aeruginosa (burn infections) signs/symptoms

Fruity, sweet smell emanating from wounds; green pigmentation of dressings and drainage.

P. aeruginosa (burn infections) diagnosis

Samples from infection cultured to confirm; antibiotic susceptibility testing conducted as well.

P. aeruginosa (burn infections) treatment

• Treatment can be difficult – bacteria are resistant to numerous drugs and antibacterial agents like soaps (quats)

  • Usually treated with combination of ceftazidime (beta-lactam) and an aminoglycoside.

P. aeruginosa (burn infections) prevention

Almost impossible to prevent exposure, but isn’t able to invade intact tissue. Proper hand hygiene and frequent hospital cleaning is imperative.

Gas Gangrene etiology

Clostridium perfringens

Gas Gangrene mode of transmission

Transmitted by endospores entering “dirty” trauma wounds. Grows in anaerobic environments like deep tissue.

Gas Gangrene virulence factors

• Colonizes wounds and can replicate RAPIDLY ~10 minute generation time

• Secretes 17 toxins (alpha toxin and perfringolysin O are the most important). Similar to streptolysin, they lyse erythrocytes and leukocytes, vasodilate blood vessels, and kill cells – necrosis. Also make collagenase, hyaluronidase, hemolysins, to spread more deeply

Gas Gangrene signs/symptoms

Rapid heart rate, fever, low BP and hypoxia, foul-smelling “sickly sweet” discharge from lesions, pain, black, purple, or dark red necrotic tissue with black “bubble” lesions - gas under skin (crepitus).

Gas Gangrene diagnosis

Clinical examination; X-ray, CT, or MRI imaging to look for gas in tissues; culturing and Gram stain to confirm bacteria

Gas Gangrene treatment

IV penicillin (beta-lactam) plus clindamycin (macrolide), surgical debridement/removal of affected tissue, hyperbaric oxygen therapy

Gas Gangrene prevention

Proper debridement of deep wounds

Dermatophytoses etiology

Tinea species

Dermatophytoses mode of transmission

direct contact or indirect contact from fomites

Dermatophytoses virulence factors

lipases and keratinases to digest lipids and keratin

Dermatophytoses signs/symptoms

Red, swollen, itchy and peeling skin; sin can crack and scale as well. often produces a circular spot or produce a bald spot on the scalp.

Dermatophytoses diagnosis

Clinical inspection of the skin; KOH scrapings can be examined microscopically to look for fungal hyphae

Dermatophytoses treatment

Azoles – antifungal drugs. Topical terbinafine or oral griseofulvin for weeks-months in stubborn cases. Avoid steroid creams

Dermatophytoses prevention

Keep active infection covered; keep skin dry and clean; be wary of places like public showers.

Candidiasis etiology

Candida albicans

Candidiasis mode of transmission

Endogenous infection caused by fungal overgrowth; often induced by antibiotic treatment or becoming immunocompromised

Candidiasis virulence factors

Adhesins, dimorphism (grow as pseudohyphae or budding yeast depending on the environment)

Candidiasis signs/symptoms

Patchy rash with redness and intense itching; skin may become cracked, sore.

Candidiasis diagnosis

Clinical examination; KOH skin scrapings can be examined under the microscope or cultured; the KOH destroys normal skin cells leaving the fungi behind. Look for abundant budding yeast and/or pseudohyphae.

Candidiasis treatment

Antifungal azoles or polyenes. Topical miconazole powder or nystatin (polyene) cream. Oral fluconazole. Treatment may take 2-4 weeks

Candidiasis prevention

These fungi thrive in moist skin folds; keeping skin dry and wearing “breathable” garments can help. Beware of signs and symptoms if taking antibiotics

Chickenpox and Shingles etiology

Varicella-Zoster Virus (VZV)

Chickenpox and Shingles mode of transmission

Highly contagious and transmitted in airborne particles or by direct contact with fluid from skin lesions. Most communicable in prodromal period before skin lesions appear.

Chickenpox and Shingles virulence factors

adhesins

Chickenpox and Shingles signs/symptoms

• 2-3 weeks after infection, patient develops fever and lesions on the trunk, face, and limbs

• Macules -> papules -> fluid-filled vesicles -> dry up and crust

Chickenpox and Shingles diagnosis

Clinical examination and antibody-based serologic tests or PCR to confirm. IgM and IgG titers can be done via ELISA

Chickenpox and Shingles treatment

usually self-limiting; can help manage symptoms with antihistamines and acetaminophen; other drugs to reduce severity and duration such as Acyclovir (nucleoside analog)

Chickenpox and Shingles prevention

live attenuated VZV vaccine will protect against this

measles (Rubeola) etiology

Measles virus (MV) or Measles morbillivirus (MeV)

measles (Rubeola) mode of transmission

one of the most contagious viruses – transmitted via airborne respiratory particles and contact with droplets

measles (Rubeola) virulence factors

adhesins that allow attachment to host cells; ability to make syncytia - envelope makes a fusion protein that allows virus to fuse cells together so it can “tunnel” and avoid immune system

measles (Rubeola) signs/symptoms

fever, sore throat, headache, dry cough, conjunctivitis – after 2 days of symptoms Koplik’s spots appear on mucous membranes of mouth (definitive diagnosis). Maculopapular rash appears on face and spreads to the trunk, limbs, and even to palms and soles of feet.

measles (Rubeola) diagnosis

Clinically with presence of Koplik’s spots, but confirmed with serological testing for IgM or testing for virus using RT- PCR in nasopharyngeal samples or serum samples.

measles (Rubeola) treatment

no specific treatments. Hospitalization can support the body if complications arise. Severe cases are treated with vitamin A – this acts as an immunomodulator and support’s the immune system’s functions to improve disease outcomes

measles (Rubeola) prevention

MMR vaccine – live attenuated or MMRV vaccine

Rubella (German measles) etiology

Rubella Virus (RuV) (Rubivirus)

Rubella (German measles) mode of tranmission

vehicle transmission by droplets from respiratory secretions or transplacental transmission. Can be transmitted 2 weeks before and after signs and symptoms appear

Rubella (German measles) virulence factors

adhesins that allow attachment

Rubella (German measles) signs/symptoms

Most cases are mild; swollen lymph nodes, low-grade fever. 50% of those infected experience a widespread pink fine rash after 7-14 days post-infection.

Rubella (German measles) diagnosis

clinical observation and serological testing for anti-RuV IgMs

Rubella (German measles) treatment

no specific treatment; supportive care only