Infectious Diseases and Dermatology Quiz

Microbiology of Skin Infections

• This course covers the microbiology of skin infections, including viral, fungal, and bacterial infections.
• Learning outcomes focus on understanding the pathophysiology, etiology, pathogenesis, and microbiology of various skin infections.
• The skin microbiome is initially colonized by coagulase-negative Staphylococci (e.g., Staph epidermidis).
• Other microbes, including fungi and viruses, contribute to the skin microbiome's development.

Learning Outcomes

• Understanding the pathophysiology and clinical features of skin, hair, and nail disorders caused by viruses like HSV, HPV, HZV, and fungi.
• Knowing the basic etiology and pathogenesis of common fungal skin infections (e.g., tinea).
• Understanding the basic etiology and pathogenesis of common viral skin infections (e.g., HSV, varicella, HPV).
• Understanding the basic etiology and pathogenesis of exanthematous skin diseases (e.g., measles, rubella, erythema infectiosum).
• Understanding the basic etiology and pathogenesis of gram-positive bacterial skin diseases associated with toxin production (e.g., Staph and Strep).
• Differentiating between bacterial skin diseases caused by exfoliative and superantigenic toxins.
• Understanding the basic etiology and pathogenesis of gram-negative bacterial skin diseases (e.g., Pseudomonas).

Introduction

• Normal skin (epidermis) is colonized by commensal bacteria after birth.
• Coagulase-negative Staphylococci (Staph epidermidis) are common initial colonizers.
• Fungi, bacteria, and viruses contribute to the skin microbiome.

Staphylococcal Skin Infections

• Staphylococcal infections are common superficial purulent skin infections (pyodermas).
• Roughly 30% of healthy individuals are colonized with Staphylococcus aureus.
• Factors contributing to skin infection include immunosuppression, diabetes, atopic dermatitis, and pre-existing tissue injury.
• Staph epidermidis is mainly commensal, while Staph aureus can be both commensal and pathogenic.
• Staphylococcus aureus produces toxins that damage tissues and evade immune defenses.
• MRSA (methicillin-resistant Staphylococcus aureus) is a significant concern due to resistance to beta-lactam antibiotics.

Strep Pathogenesis

• Group A Streptococcus (GAS) is a common cause of superficial purulent skin infections, such as impetigo, ecthyma, intertrigo.
• Invasive infections caused by GAS include erysipelas, cellulitis, and necrotizing fasciitis, potentially leading to sepsis and multiorgan failure.
• Other GAS infections include lymphangitis, bacteremia, septic arthritis, osteomyelitis, pneumonia, meningitis, and streptococcal toxic shock syndrome.
• Immunologic-mediated conditions like guttate psoriasis, acute rheumatic fever, rheumatic heart disease, and glomerulonephritis can be triggered or follow GAS infections.

Staph Soft Tissue Infections (SSTI)

• Risk factors for SSTI include compromised neutrophil function, cancer, chemotherapy, and genetics.
• Pore-forming toxins (alpha-toxin, gamma-toxin) damage neutrophils and macrophages.
• Phenol-soluble modulins destroy leukocytes and erythrocytes.
• Exfoliative toxins (produced by certain strains or bacteriophages) target desmosomal cadherin and cause staphylococcal scalded-skin syndrome.

Superantigens

• Superantigens trigger a massive immune response, resulting in high fever, hypotension, scarlet fever-like rash, desquamation of skin, and multiorgan dysfunction.
• Examples include toxic shock syndrome toxin 1 (TSST-1), enterotoxins (A, B, C,...), and SE-like superantigens.

Staph – Neutrophil Evasion

• Staphylococcal proteins (e.g., CHIPS, staphopain A) inhibit chemotaxis and block complement receptors.
• Staph superantigen-like 5 and 11 block neutrophil adherence.
• Catalase and other enzymes inhibit reactive oxygen species (ROS) mediated killing.
• Staphylococcal nuclease destroys neutrophil extracellular traps (NETs).

Immune Response Against Staph

• Antimicrobial peptides (e.g., beta-defensins, cathelicidins) produced by skin cells inhibit bacterial growth.
• Neutrophil recruitment by pattern recognition receptors (PRRs) is crucial in controlling infection.
• TLR-2 recognizes peptidoglycan and lipoproteins, NOD-2 recognizes muramyl dipeptide.
• Staph pore-forming toxins activate caspase-1, causing IL-1Beta production, thus promoting neutrophil recruitment.

Exfoliative Toxins

• Exfoliative toxins (ETs) are serine proteases that target cell-adhesion molecule desmoglein-1.
• Loss of cell-cell adhesion leads to skin blistering, characterized by bullous impetigo and staphylococcal scalded-skin syndrome (SSSS).

Pseudomonas Aeruginosa - Intro

• Ubiquitous Gram-negative rod, commonly found in aqueous environments.
• Characterized by a sweet, grape-like odor and blue-green color.
• Often found in warm environments (preferring temperatures above 42 degrees Celsius).
• Can cause skin infections, including green nail syndrome and ecthyma gangrenosum in hospitalized patients.
• Often found in nosocomial or cystic fibrosis settings.

Pseudomonas Aeruginosa - Pathogenesis

• Bacteria use various enzymes to degrade skin structures.
• Exoenzymes like ExoS, ExoT, ExoU, and ExoY disrupt cell membranes, cellular processes, and protein synthesis.
• Exotoxin A interferes with protein synthesis, contributing to cell death.
• Procyanins influence inflammatory reactions and oxidative effects; LPS activates TLR4, potentially leading to septic shock.
• Quorum sensing coordinates gene transcription and biofilm formation.

Pseudomonas Aeruginosa - Pathogenic Features

• Prolonged colonization promotes alginate overproduction, hindering phagocytosis and complement activation.
• Biofilm formation provides protection against antibiotics and antimicrobial peptides.
• Multidrug efflux pumps and beta-lactamases contribute to antibiotic resistance.

Viral Skin Infections (Measles, Rubella, Erythema Infectiosum)

• Measles (rubeola): highly contagious, enveloped RNA virus.
• Rubella (German measles): enveloped RNA virus, lifelong immunity typical.
• Erythema infectiosum (fifth disease): single-stranded DNA virus from Parvoviridae family, causes a rash.

Human Herpesvirus 6 (HHV-6)

• Part of Herpesviridae family.
• HHV-6 infects a wide range of cells (monocytes, macrophages, NK cells, neuronal cells, CD4+ T-cells).
• The virus integrates its DNA with the host.
• Reactivates during immunosuppression (e.g., after stem cell transplantation).

Herpes Simplex Virus (HSV)

• DNA virus, Herpesviridae family.
• Usually causes intermittent reactivation.
• HSV-1 (oral) or HSV-2 (genital) can infect body parts.
• Most primary infections are asymptomatic.
• Transmission frequently occurs during asymptomatic shedding

Varicella-Zoster Virus (VZV)

• From Herpesviridae family, causes chicken pox and shingles.

• Highly contagious viral infection.

• Chickenpox: rash begins on face, spreads to trunk, and may involves extremities.

• Shingles: reactivation of the virus that cause chickenpox, usually in a one side of the body. Causes severe neuropathic pain.

Human Papillomavirus (HPV)

• DNA virus.
• Over 150 types, some with low and some with high risk for malignancy.
• Infections of keratinocytes are common.
• Causes warts, and plays an important role in malignancies.

Dermatophytes

• Fungal keratin infections (e.g., tinea barbae, tinea corporis, tinea cruris, tinea pedis, tinea mannum).
• Transmission common through fomites, autoinoculation, or contact with infected individuals, animals, or the environment.
• Immune response is essential in clearing fungal infection.
• Inflammatory skin reactions at site of the infection are common.

Onychomycosis

• Fungal infection of the nail.
• 90% of cases are caused by Trichophyton rubrum and Trichophyton interdigitale.

Other information

• Pictures and case studies are often included for clinical applications, which are not included in these notes.