HTHSCI 2HH3 - Skin & Soft Tissue Infections

epidermis

thin outer portion consisting of several layers of epithelial cells, effective physical barrier against microbes when unbroken

dermis

thick inner portion; provides strength and flexibility; supports growth of the epidermis, contains blood vessels, nerve endings, hair follicles, sweat & oil glands, follicles & glands can serve as portals of entry for microbes

Why can the skin be an inhospitable environment for microbial growth?

• covered in salt, sweat and sebum which contain antimicrobials

• outer layers of the epidermis are sloughed off and replaced every month

• normal flora must be resistant to drying and high salt concentrations

• over 200 species of bacteria; mainly Gram positives & some yeasts, concentration of microbes vary with available nutrients, moisture, pH, temperature, salt and sebum levels

• after vigorous hand washing, bacteria from hair follicles & sweat glands will reestablish normal skin flora

benefit and risk of the skin microbiome

microbial antagonism, however there is a risk of normal flora entering into tissues

normal skin flora

• ~ 90% Staphylococcus epidermidis (coagulase negative staphylococcus)

• Pathogenic when skin barrier is broken or invaded (e.g., catheterization)

• Other bacteria present; diphtheroids e.g., Cutibacterium acnes, Proprionibacteria

• In warm, moist areas of the body the normal flora changes

• Staphylococcus aureus, Lactobacillus spp., occasionally Gram negatives

• In perineal region, bacteria typical of GI tract microbiota

• largest amount of normal flora is found under the arms and between the legs

skin rashes

• any change in the colour or texture of the skin is commonly referred to as a “rash”

• they are commonly associated with infection due to a reaction to a toxin produced by the bacteria, damage to skin by a pathogen, or immune response to pathogen

• can also be associated with drug reactions, allergies, or autoimmune diseases

• rashes/lesions are described based on form, type, location, pattern of spread, other symptoms

exanthem

skin rash accompanied by systemic symptoms; fever, malaise, and headache

enanthem

rash on mucus membranes accompanied by systemic symptoms such as fever, malaise, and headache

primary skin lesions less than 1 cm

macule, vesicle, papule, pustule

primary skin lesions greater than 1 cm

patch, plaque, bullae, nodule, wheal

macule

flat lesion that cannot be palpated, like a freckle

vesicle

forms from accumulation of fluid under the epidermis

papule

raised lesion resulting from accumulation of material, infectious or otherwise, in the dermis

pustule

pus-filled raised lesion on the skin, the result of a buildup of the cellular debris of inflammatory cells, with or without microorganisms, under the epidermis

patch

large macule, well circumscribed (clear area of infection) discoloured lesion

plaque

large papule, superficial, firm raised lesion ex. psoriasis

bullae

large vesicle, filled with clear fluid; highly fragile ex. necrotizing fasciitis

nodule

soft or firm lesion in dermis or subcutaneous fat

wheal

transient, raised lesion with erythematous periphery and central pallor

skin ulcers

an open sore of the skin often caused by an initial abrasion, and generally maintained by inflammation, infection, and/or medical conditions which impede healing

sampling skin & soft tissue for culture

• normal flora may interfere with sampling

• swabs only sample surface and collect small amount, so they are not used often

• skin scraping - typically used for fungal infections

• biopsy & needle aspiration (fluid & tissue)

• swabs only useful if sample contains suspected pathogen (ex. from leading edge, or deep inside specimen/wound)

• samples should be stored in sterile container for transport and indicate site of collection

How do skin & soft tissue infections occur?

when there is a breakdown in defences (immunosuppression) and exposure to a pathogen (virulence and dose) able to overwhelm these defences

staphylococcus aureus

• Gram-positive cocci, catalase positive, coagulase positive (consider MRSA)

• Colonizes nasopharynx, axillae, rectum, skin (20% of people)

• Causes a variety of infections; skin and soft tissue, bone, joint, heart valves, kidneys, lungs, brain, bacteremia, food poisoning

group A streptococci

• Beta-hemolytic, Gram-positive cocci, catalase negative

• Colonizer of skin and nasopharynx

• Causes a variety of disease including skin and soft tissue infections, bone and joint infections, strep throat, scarlet fever, rheumatic fever, bacteremia, glomerulonephritis

pathogenic factors of s. aureus

• enzymes - coagulase, staphylokinase, lipase, beta-lactamase

• factors that inhibit phagocytosis - polysaccharide slime layer, protein A on cell surface

• toxins - cytolytic toxins, leukocidin, epidermal cell differentiation inhibitor, exfoliative toxin, toxic shock syndrome toxin

pathogenic factors of s. epidermidis

lipase and polysaccharide slime layer, not very pathogenic compared to s. aureus

folliculitis

Localized infection of the hair follicle (red, swollen & pus filled), associated with pain, tenderness and localized edema at the site of infection, lesions vary in size and may scar despite resolution

folliculitis cause and treatment

• staphylococcus aureus, pseudomonas aeruginosa

• treatment depends on extent of infection and pathogen involved

  • antibacterial soap to affected area, warm compress to clean and help drain follicle

  • multiple lesions - topical mupirocin or clindamycin

  • severe multiple lesions - oral antibiotic therapy

• resolves in 1-2 weeks

furuncles (boils)

• Large, painful, raised nodular lesion; extension of folliculitis into surrounding dermis and hypodermis (frequently occurs in areas of friction; neck, axillae, thighs, buttocks)

• Grows larger and more painful (5-7 days) before it develops a yellow white tip that ruptures and drains

carbuncle

• Cluster of furuncles that coalesce through the hypodermis; hard, round & deep infection

• Often develops on back of neck, but also shoulders or thighs, especially in older men, where skin is thickens, slower to heal vs furuncles

• Can be associated systemic symptoms (fever, chills, rigors); increased risk of bacteremia, TSS and necrotizing fasciitis

treatment for furuncles & carbuncles

• Furuncles often rupture and spontaneously begin draining with application of warm compresses

• Larger furuncles and carbuncles often require incision and drainage (> 80% of furuncles will resolve)

• Oral antibiotics should be used if there are systemic signs of infection, or evidence of cellulitis beyond the furuncle or carbuncle

staphylococcal scalded skin syndrome

associated with those < 5 years old, elderly and immunocompromised, skin falls away within 2 days of symptom onset, and resolves within 7-10 days

treatment - IV naficillin or oxacillin, or vancomycin (MRSA) therapy

staphylococcal scalded skin syndrome pathogenesis of infection

• Some strains of S. aureus produce exfoliative exotoxins

• The toxins cause cells within the outer epidermis to separate from each other and from underlying tissues – systemic effect (toxemia)

• Redness and wrinkling of the skin commonly appears first on the mouth, then spreads across entire body, followed by the formation of clear, fluid filled blisters

• Exotoxin travels from site of infection through the bloodstream causing widespread epidermal response to the exotoxin

impetigo/pyoderma

Small, flattened, red patches/lesions on face and limbs; develop into thin-walled vesicles then pustules that rupture and crust over (golden brown, sticky crust), lesions are highly contagious and itchy until healed, vesicles present in various stages simultaneously on the skin, affects epidermis

common in children 2-5 years, peaks in summer

impetigo/pyoderma cause and treatment

• staphylococcus aureus (80%) and staphylococcus pyogenes (20%)

• small abrasions/tears in the skin from rough paper towel or clothes allow bacteria to get in

• treatment depends on extent of infection

  • limited lesions - topical mupirocin

  • multiple severe lesions - PO cloxacillin

• resolves in 1-2 weeks

erysipelas

• Acute infection of the dermis and dermal lymphatics

• Requires a portal of entry, most common in children & elderly (face, arms, legs)

• Characterized by a well demarcated area of painful erythema and induration (raised margin)

• On the face, erysipelas often presents as a “butterfly wing” lesion

• Erythema caused by pyrogenic toxins, skin warm to the touch

• Often preceded by impetigo/streptococcal pharyngitis and concomitant fever

• 5% of patients develop bacteremia, which carries a high rate of mortality if left untreated

erysipelas cause and treatment

• streptococcus pyogenes

• treatment - PO or IV penicillin or amoxicillin therapy

erysipelas signs & symptoms

red, warm skin, pain, fever, chills, swollen lymph nodes, increased WBCs, risk of bacteremia

cellulitis

Acute spreading infection of the skin involving subcutaneous fatty tissues (hypodermis), risk of bacteremia and increased risk of sepsis, requires portal of entry, more common in middle-aged and older adults, most commonly occurs in lower extremities

risk factors - diabetes, obesity, chronic venous stasis, previous cellulitis

cellulitis cause and treatment

• staphylococcus aureus or streptococcus pyogenes (other pathogens in immunocompromised hosts)

• treatment - oral or IV antibiotic therapy, depends on severity of infection and associated pathogen

• area of erythema can spread over the first 48-72 hours of appropriate treatment; monitor for resolution of systemic symptoms and pain reduction

• erythema will spread if treatment is not appropriate

• resolves in 1-2 weeks, but an reoccur

cellulitis signs & symptoms

pain, erythema, edema and warmth, no area of induration or well-defined margins (poorly demarcated), systemic symptoms include chills, fever, malaise

cellulitis and invasive GAS (iGAS) infection

may invade fascial lining causing necrotizing fasciitis resulting in hemodynamic instability, pain disproportionate to clinical findings, sensory deficits, skin findings (bullae, crepitus, necrosis), woody, hard firmness to hypodermis

risk factors for adults include diabetes, cancer, HIV infection, in children chicken pox used to be greatest risk factor for iGAS (before vaccine)

types of necrotizing skin infections

type 1 (polymicrobial) and type 2 (monomicrobial)

type 1 infection

Mixed infection associated with anaerobic, aerobic, and facultative anaerobic bacteria (other than GAS) which act synergistically to fuel a cycle of bacterial colonization and inflammatory tissue necrosis, associated with the post-surgical setting & previously ill patients e.g., patients with risk factors for invasive disease

type 2 infection

Group A Streptococcus (GAS) or Staphylococcus aureus, can occur in patients without known risk factors

necrotizing fasciitis

life-threatening infection located in the deep fascia & necrosis of subcutaneous tissues, associated with trauma or recent surgery as well as streptococcal pharyngitis or varicella (chicken pox) (type 2)

clues to necrotizing fasciitis

• Rapidly progressive (centimeters in an hour), skin findings (bullae, crepitus, may look like cellulitis)

• Pain disproportionate to apparent tissue damage, then anesthesia of effected area

• Prominent systemic symptoms/signs (hemodynamic instability)

• frequently accompanied by streptococcal TSS due to production of superantigen

• diagnosis made surgically - tissue biopsy

• concomitant signs of infections

  • systemic toxicity - fever, tachycardia, hypotension

  • elevated WBC count, pain

necrotizing fasciitis infection progress

• Early infection; area of erythema that quickly spreads over a course of hours to days

  • Margins of infection move into normal skin without being raised or sharply demarcated

• As infection progresses, a dusky/purplish skin discolouration develops near the site of injury

  • Necrosis more advanced than appearance suggests

  • Simultaneous presence of hemorrhagic bullae

  • Eventual anesthesia of effected area due to destruction of nerves

treatment for necrotizing fasciitis

• Polymicrobial (Type 1) Broad spectrum antibiotic coverage of both aerobes and anaerobes (e.g., IV piperacillin/tazobactam)

• Monomicrobial (Type 2) GAS (IV high dose penicillin or ampicillin)

  • Clindamycin to decrease toxin production

  • IVIg may be considered in cases meeting clinical criteria for streptococcal toxic shock syndrome (i.e.: hypotension, renal impairment, coagulopathy, acute respiratory distress syndrome)

• Amputation of affected limb may be necessary

necrotizing fasciitis pathophysiology

• Streptococcus pyogenes releases exotoxins that are superantigens

• Superantigens produce a non-specific and uncontrolled immune response, resulting in widespread tissue damage

  • Uncontrolled immune response causes over-production of cytokines that over-stimulate macrophages

  • Macrophages release massive amounts of oxygen free radicals, causing rapid tissue damage

• Clindamycin is a protein synthesis inhibitor; reduces toxin production

• IVIg administration may neutralize/reduce the effects of the exotoxin and modulate the inflammatory response

pathogenic factors for strains of GAS that cause necrotizing fasciitis

• enzymes - streptokinase (dissolves blood clots), hyaluronidase (breaks down hyaluronic acid between cells), deoxyribonuclease (breaks down DNA released from damaged host cells)

• M protein - on surface of streptococcal cells helps bacteria attach to nose and throat cells, after entry into body, M proteins allows GAS to survive phagocytosis

• streptolysin S - kills human cells, including neutrophils and erythrocytes

• exotoxin A (superantigen) - triggers overactive immune response that further damages healthy tissues

varicella (chickenpox)

• Acute systemic viral infection; incubation period of 8 – 21 days

• Highly contagious (airborne, droplet & direct contact) including 1 – 2 days prior to rash onset

• Pleomorphic rash preceded (1 – 2 days) by fever, malaise, headache, myalgia, pharyngitis, rhinitis and abdominal pain

  • Trunk, head, scalp, face, arms, legs, may affect mouth, pharynx and vagina (10%)

  • Stages: erythematous macules, papules, vesicles, pustules, then dry and crust within 4 – 7 days of rash onset

  • Patient remains contagious until all lesions are crusted over

varicella (chickenpox) cause, diagnosis, and treatment

• varicella-zoster (human herpes virus 3)

• diagnosis based on clinical presentation of pleomorphic rash and history of contact with acute varicella

• treatment

  • Daily baths/showers followed by careful drying of the skin with a towel are recommended in all cases; antihistamines can reduce pruritus; avoid ASA (aspirin)

  • Antivirals (valacyclovir) not recommended in otherwise healthy children (<18 years), benefits do not outweigh potential harms

• vaccine - varivax

  • routine schedule (ontario) - 1 dose @ 15 months, 2 dose @ 4-6 years

herpes zoster (shingles)

• Local reactivation of latent varicella-zoster virus (e.g., after prior primary infection)

  • Virus remains latent in cells of dorsal root and cranial nerve ganglia; reactivation typically associated with age, immunosuppression and certain conditions

  • Virus moves along peripheral nerves into cutaneous sensory nerves of the skin; pain and eruptions follow a dermatomic pattern

• Prodromal phase; fever, malaise, pruritus and pain (burning, piercing, tingling) in a single dermatome precedes lesions by 3 – 4 days and may persist for 1+ week post resolution

• Pleomorphic lesions limited to 1 or 2 adjacent dermatomes; typically distributed around the trunk (thoracic dermatome)

herpes zoster (shingles) treatment

• Treatment: Oral antiviral agents (acyclovir and valacyclovir) and pain management

• Vaccine: Shingrix (2 dose series, publicly funded for those between 65 - 70 years of age)

• Covering affected area of the skin reduces risk of VZV infection for those with direct contact

• Disseminated shingles requires isolation, airborne and contact precautions

herpes simplex virus (HSV)

• HSV-1 and HSV-2 enters the body through mucosal surfaces, or breaks in the skin

• First-episode (primary) typically associated with most severe course, or may be asymptomatic

• Virus enters neuronal cells and is transported to sensory ganglia, where it remains latent

• Reactivation of the virus and subsequent viral shedding (including asymptomatic) is common

HSV-1 infection

• Typically occur in childhood leading to “cold sores” at orolabial sites

• Localized prodromal signs and symptoms; pain, burning, itching, tingling sensations at the site

• Papules evolve into short-lived painful vesicles (that may become pustules) and eventually leading to erosions/ulcerations

• Primary infection may be accompanied by flu-like symptoms (malaise, fever, myalgias)

• Reoccurrence triggered by emotional upset, stress, hormonal fluctuations, other infections, etc.

• Acute symptoms persist for 5 to 7 days, with the lesions healing after ~2 weeks

• Viral shedding in the saliva is observed for 3 weeks, occasionally longer

HSV-1 infection treatment

• Antiviral drugs available to shorten healing time

• Treatment should be started during the prodromal phase, (for recurrent infections, no later than at the onset of cutaneous eruptions)

• Topical creams applied directly to the lesion (docosanol and acyclovir) for mild cases

• Oral antiviral therapy (acyclovir, valacyclovir)

HSV-1 vs HSV-2

• usual disease - cold sores vs genital herpes

• mode of transmission - close contact vs sexual intercourse

• site of latency - trigeminal & brachial ganglia vs sacral ganglia

dermatomycoses (ringworm)

• Fungal (not helminth) infection transmitted via direct contact (people and animals), fomites

• Erythematous and scaling patches that are round or oval

• Lesions start small, then expand outward; open at the center with a raised and scaly border

• Diagnosed by skin scrapings and processed in the lab using potassium hydroxide (KOH) - KOH dissolves epithelial tissue, allowing a clear view of the fungal hyphae

• Treatment: topical antifungal medication