Module 2 Integumentary System Disorders - Comprehensive Study Notes

Background and Functions of the Integumentary System

Integumentary system includes skin, hair, nails, glands; skin is the primary organ involved in protection, sensation, temperature regulation, vitamin D production, and immune defense.
Primary functions: protect against microorganisms, UV radiation, fluid loss, and mechanical stress; may function as part of innate immunity as the first line of defense.
Skin harbors commensal bacteria that help protect against pathogenic bacteria.
Additional roles: regulate body temperature via sweating and shivering (vasodilation/vasoconstriction); production of vitamin D; detection of sensory information through touch and pressure receptors.
Surface area: skin is the largest organ, accounting for about $20\%$ of body weight.
Skin structure: three layers – epidermis (outer), dermis (deeper), and subcutaneous layer.
Accessory structures: hair, nails, glands.

Skin Structure and Key Cell Types

Epidermis: thin outer layer composed of squamous epithelial cells; does not contain blood vessels but houses immune and sensory cells.
Cells in the epidermis:
- Keratinocytes: produce keratin, the insoluble protein forming skin, hair, and nails; provide barrier against mechanical damage, pathogens, UV, heat, and water loss; originate in the basal layer and move upward to the stratum corneum.
- Melanocytes: located in the basal layer; produce melanin, the pigment determining skin color; derived from oxidation of the amino acid tyrosine; melanin production is stimulated by melanin-stimulating hormone (MSH) during UV exposure; melanin helps absorb UV light to protect underlying cells.
- Langerhans cells: specialized dendritic cells from bone marrow that migrate to the epidermis; process and present antigens to T cells to initiate adaptive immune responses.
- Merkel cells: mechanoreceptors that serve as sensory cells involved in touch.
Dermis: connective tissue rich in collagen, elastin, and reticulin; provides mobility and elasticity for skin; contains hair follicles, sebaceous glands, sweat glands, blood vessels, lymphatics, nerves, and other cells like:
- Fibroblasts: synthesize connective tissue.
- Mast cells: release histamine; involved in hypersensitivity reactions.
- Macrophages: participate in immune responses and phagocytosis.
Subcutaneous layer (hypodermis): contains fat cells organized into lobules separated by collagen; houses large blood vessels.

Clinical Lesions: Primary and Secondary Skin Lesions

Primary lesions: include plaques (elevated, firm, rough with flat top), and papules (elevated, firm lesions).
A table in the reference (Tables 46.3 and 46.4) classifies primary vs secondary lesions; common examples include erythema, scales, vesicles, and crusts.

Inflammatory Skin Disorders

Dermatitis (eczema) is the most common inflammatory skin disorder; characterized by pruritus, lesions with indistinct borders, and epidermal changes.
Lesions may present as erythema (redness) or hyperpigmentation, depending on skin tone; can appear as papules or scales.
Four major hypersensitivity mechanisms (from Module 1):
- Type I (IgE-mediated, immediate): allergic responses such as urticaria;
- Type II (not detailed in transcript);
- Type III (not detailed in transcript);
- Type IV (cell-mediated, delayed, T-cell mediated).
Focus on two eczema types:
- Atopic dermatitis (allergic dermatitis): chronic inflammatory condition with relapsing/remitting course; associated with type I hypersensitivity; activation of mast cells, eosinophils, and other immune cells due to allergen exposure; evidence of impaired skin barrier; common with family history; frequently co-occurs with asthma, allergic rhinitis, and food allergies; features include erythema, pruritus, scaling, and thickened skin (lithification); more common in infancy/childhood; papules can appear violet in darker skin.
- Allergic contact dermatitis: type IV hypersensitivity (delayed) triggered by contact with allergens (hapten molecules, chemicals, metals, latex, etc.); latex can induce either type I or type IV reactions; sensitization involves hapten binding to skin proteins, processing by Langerhans cells, presentation to T cells, and cytokine/chemokine release leading to leukocyte infiltration and inflammation.
Clinical manifestations of allergic contact dermatitis: erythema, swelling, pruritus, vesicular lesions at contact sites. Poison ivy is a classic example where hapten molecules bind skin proteins to form sensitizing antigens; memory T cells cause rapid inflammatory response upon re-exposure.
Urticaria (hives): type I hypersensitivity with histamine release causing endothelial contraction and increased vascular permeability; wheals or welts; can be triggered by drugs (e.g., penicillin, aspirin), foods (strawberries, shellfish, dyes), and environmental agents (pollen, dander, insect bites); treated with antihistamines; steroids for severe attacks; lesions vary in color, size, shape and location; pruritus and swelling common.

Papillosquamous Disorders: Psoriasis and Acne Vulgaris

Papillosquamous disorders involve inflammatory processes with papules, plaques, scales, and erythema; psoriasis is a chronic autoimmune, relapsing inflammatory disease with scaly, thick, silvery plaques commonly on scalp, elbows, knees; high keratinocyte turnover causing thickening and plaque formation.
Pathophysiology of psoriasis:
- Unknown antigenic trigger activates Langerhans/dendritic cells; they secrete IL-12 and IL-23 to activate Th1 and Th17 cells.
- Th1/Th17 cells migrate to skin and secrete cytokines such as IL-17, IFN-γ, TNF-α, and chemokines, recruiting more immune cells and promoting keratinocyte hyperproliferation and altered differentiation.
- Result: dermal/epidermal thickening and plaque formation; cytokines TNF-α, IL-17, and IL-23 are central; biologic therapies target these cytokines or T cell subsets to reduce inflammation.
Acne vulgaris:
- Very common, especially ages 12–25; affects ~85% of population.
- Lesions occur in sebaceous follicles (hair follicle + sebaceous gland) on face, upper trunk.
- Classified as non-inflammatory (comedones) and inflammatory.
- Comedones: open (blackheads) or closed (whiteheads); inflammation occurs when closed comedones rupture and release sebum into dermis.
- Pathophysiology includes (a) hyperkeratinization leading to follicular plugging, (b) increased sebum production (androgens such as during puberty), (c) colonization by bacteria that shift from symbiotic to pathogenic, (d) inflammatory response to debris and bacteria; can lead to cystic nodules and scarring.
Visual progression: mild non-inflammatory acne shows open/closed comedones; moderate inflammatory acne shows redness, hyperpigmentation in darker skin, with pustules and papules; severe inflammatory acne shows nodules, scarring, crusting.

Viral Skin Infections: Varicella Zoster Virus

Varicella zoster virus (VZV) causes varicella (chickenpox) and herpes zoster (shingles).
Highly contagious; spreads via airborne droplets or close contact.
Incubation ≈ 14 days; itchy, blistering trunk-dominant rash lasting ~5–10 days, with scabbing; lesions can affect keratinocytes in the epidermis.
After recovery, VZV remains latent in sensory neurons (trigeminal or dorsal root ganglia) and can reactivate under immunosuppression or stress to cause shingles (herpes zoster).
Shingles affects ≈ 10% of individuals who had chickenpox; characterized by itching, tingling, or pain in a dermatome followed by vesicular rash and crusting; thoracic/lumbar dermatomes most commonly involved; typically a single episode.
Dermatome concept: each spinal nerve supplies sensation to a specific skin area; shingles lesions follow the infected nerve without crossing the midline due to each side’s dermatomal innervation.

Bacterial Skin Infections

Primary infections arise from breaks in the skin; secondary infections can follow underlying dermatoses.
Common pathogens: Staphylococcus aureus, Streptococcus pyogenes; clinically important infections include:
- Folliculitis: infection of hair follicles, commonly due to S. aureus; presents with papules/pustules around hair-bearing areas.
- Cellulitis: infection of dermis and subcutaneous tissue; risk factors include diabetes, edema, peripheral vascular disease; red, warm, swollen, painful area with poorly defined borders.
- Impetigo: superficial infection, especially in children 2–5 years; commonly on face and hands; can be non-bullous or bullous; caused by S. aureus or S. pyogenes; thin honey-colored crusts form after rupture of vesicles.

Fungal (Mycotic) Skin Infections

Mycoses = fungal disorders; dermatophytes cause most fungal skin infections; fungi thrive on keratin.
Candida albicans (candidiasis) affects mucous membranes and skin folds; can become pathogenic in immunosuppressed individuals.
Dermatophyte infections (tinea) are named by location (scalp, foot, groin, nails, palms); ringworm is a common descriptor for tinea corporis; characteristic ring-shaped lesions on the skin.
Important terms:
- Mycosis: fungal disorder overall.
- Dermatophyte: fungus causing most superficial skin infections.
- Tinea infections: ringworm infections by location (e.g., tinea capitis, tinea pedis, tinea cruris).
- Candidiasis (candidal infections) affect mucosal surfaces and skin folds; can be superficial but problematic in immunocompromised hosts.

Vitamin D, Sunlight, and Skin Cancer

Ultraviolet (UV) radiation is classified by wavelength:
- UV-A: $ext{Wavelength } 315\text{ to }400\ \text{nm}$ ; penetrates deeply; not strongly absorbed by the ozone layer; constitutes the majority of UV reaching Earth’s surface (~ $95\%$ of UV at ground level).
- UV-B: $ext{Wavelength } 290\text{ to }315\ \text{nm}$ ; more directly mutagenic; absorbed by ozone but more present when ozone is thinner; accountable for sunburn and much of carcinogenic risk (~ $5\%$ at ground level).
- UV-C: $ext{Wavelength } 200\to 290\ \text{nm}$ ; absorbed by ozone; not a major contributor to skin cancer at the surface.
Sunlight exposure leads to synthesis of vitamin D in the skin: photoconversion at ≈ $300\ \text{nm}$ converts 7-dehydrocholesterol into pre-vitamin D3.
Vitamin D metabolism:
- Pre-vitamin D3 (produced in skin) and dietary vitamin D are transported in the blood by carrier proteins.
- In the liver, vitamin D is hydroxylated to 25-hydroxyvitamin D (25(OH)D), the main circulating and storage form: $ext{Vitamin D}3 \rightarrow 25{-}OH\text{Vitamin D}3$ .
- In the kidney, 25(OH)D is further hydroxylated to the biologically active 1,25-dihydroxyvitamin D (1,25(OH)₂D): $25{-}OH\text{Vitamin D}3 \rightarrow 1{,}25{-}OH2\text{Vitamin D}$ .
- The active form is a fat-soluble steroid hormone that regulates calcium and phosphorus homeostasis and bone health; serum 25(OH)D levels reflect body stores but are a precursor to the active form.
Vitamin D beyond bone health:
- Modulates immune responses; can promote anti-inflammatory effects; may inhibit clonal proliferation in various cancers; influences hematopoiesis; can affect pancreatic insulin secretion; may reduce inflammation in vascular cells.
Vitamin D synthesis and sun exposure balance: excessive UV exposure does not infinitely raise vitamin D due to negative feedback and production of inactive metabolites; sunscreen use can decrease circulating vitamin D, though dietary sources and supplements can compensate.
Dietary sources of vitamin D and supplements are important to meet daily requirements if sun exposure is limited.
Skin cancer risk factors and public health context:
- Sun exposure (environmental) and host factors (skin type, genetics) influence risk; the International Agency for Research on Cancer classifies solar radiation as carcinogenic to humans due to DNA damage and impaired repair, and immunosuppression.
- Skin type matters: fairer skin (e.g., Fitzpatrick type I) has higher risk of burns and skin cancer compared to darker skin tones (type VI+).
- Indoor tanning before age 35 substantially increases melanoma risk (about an increase of $59\%$ , i.e., relative risk $\approx 1.59$ ).
- Skin cancer is the most common cancer in Canada; sunscreen and protective measures reduce risk; protective strategies include wide-brim hats, protective clothing, shade, UV-protective sunglasses.

Non-Melanoma Skin Cancers (BCC and SCC)

Non-melanoma skin cancers account for ~ $2{\sim}3\times 10^6$ new cases per year; incidence rising in North America (roughly $3{-}8\%$ per year in some regions).
Basal cell carcinoma (BCC): most common non-melanoma cancer, ≈ $80\%$ of non-melanoma cases; more common in men; incidence higher on head and neck (~ $85\%$ of BCCs); arises from mutations in tumor suppressor genes (notably p53) leading to impaired DNA repair and apoptosis; usually local and rarely metastasize; clinically presents as nodules with potential depressed centers and rolled borders; may ulcerate as it grows.
Squamous cell carcinoma (SCC): second most common non-melanoma cancer; more likely to metastasize than BCC; commonly occurs on the head, neck, and hands; associated with UV-induced mutations in tumor suppressor genes (p53); can be in situ (confined to epidermis/dermis) or invasive (arises from malignant precursors), with invasion through basement membrane allowing lymphatic spread.
Melanoma (malignant tumor of melanocytes) is discussed separately due to distinct biology and prognosis.

Melanoma: Malignant Melanocytes and Moles (Nevi)

Melanoma arises from melanocytes; often relates to development of nevi (moles) which are clusters of melanocytes; nevi can be benign but require assessment for malignant transformation.
Melanoma pathogenesis involves multiple mutations including activation of oncogenes, inactivation of tumor suppressor genes, and impairment of DNA repair genes.
Melanoma staging (summary):
- Stage I/II: tumor size differences; local disease.
- Stage III: any tumor size with cancer cells in regional lymph nodes.
- Stage IV: any size with distant metastases.
ABCDE rule for melanoma assessment:
- A: Asymmetry – one half unlike the other.
- B: Border irregularity – uneven, scalloped, or poorly defined borders.
- C: Color variation – multiple colors or uneven distribution.
- D: Diameter – larger than $6\ \text{mm}$ is concerning.
- E: Evolution – changes in size, shape, color, or symptoms over time.

Mechanisms of UV-Induced DNA Damage and Repair

UVB directly damages DNA by causing base-pair substitutions; particularly mutates tumor suppressor genes (e.g., $p53$ ).
UVA contributes to DNA damage indirectly by generating reactive oxygen species (ROS) and oxidative stress.
DNA repair: nucleotide excision repair (NER) removes damaged DNA segments and allows DNA polymerase to resynthesize correct sequences. If damage exceeds repair capacity, p53 is activated to induce DNA repair, cell cycle arrest, senescence, or apoptosis.
p53 role: transcription factor that governs cell cycle and apoptosis; activation following DNA damage prevents propagation of mutated cells; high frequency of p53 mutations is observed in SCC and other cancers.
Oncogenes vs tumor suppressors:
- Proto-oncogenes promote cell growth; when mutated become oncogenes driving proliferation.
- Tumor suppressor genes inhibit proliferation; loss of function promotes cancer.
- Balance between oncogenes and tumor suppressors maintains homeostasis; mutations that activate oncogenes or inactivate tumor suppressors disrupt this balance and promote cancer progression.

Practical and Public Health Implications

Prevention and protection: safe sun exposure, protective clothing, sunscreen, shade, UV-protective eyewear.
Early detection: awareness of ABCDE criteria; prompt evaluation of suspicious lesions.
Public health data highlight high incidence of non-melanoma skin cancers and melanoma in certain populations; indoor tanning poses a substantial risk especially in youth.
Vitamin D: sun exposure contributes to vitamin D synthesis but must be balanced against skin cancer risk; dietary sources and supplements can help achieve adequate levels; no universal time-for-sun recommendations due to variability in skin type, geography, and lifestyle.

Summary Connections to Foundational Principles

Integumentary system integrates immune defense (Langerhans cells, barrier function) with sensory and metabolic roles (vitamin D synthesis).
Skin disorders illustrate the interplay between innate and adaptive immunity (eczema, psoriasis), hypersensitivity mechanisms (Type I vs Type IV), and how environmental triggers (allergens, UV exposure) interact with genetic predispositions.
Cancer biology in skin cancer models core concepts: DNA damage from UV radiation, DNA repair capacity (NER), p53-mediated responses, and the balance between pro-proliferative oncogenes and anti-proliferative tumor suppressors.
Vitamin D biology connects dermatology with endocrinology and immunology, illustrating how a skin-produced hormone influences bone health, immune function, and disease risk beyond the skin.

Notable Numerical References and Formulas

Skin accounts for about $20\%$ of body weight.
Varicella (chickenpox) incubation ≈ $14\text{ days}$ ; contagious period starts ~ $24\text{ hours}$ before lesions; lesions crust over in ~ $5{-}6\ days$ .
Shingles (herpes zoster) reactivation risk in those with prior chickenpox ≈ $0.10$ (10%).
Dermatome concept: ≈ 31\$\sp{spinal nerves} (excluding C1) map to dermatomes; rash follows a dermatome and typically does not cross midline.
Ultraviolet wavelengths:
- $\text{UVA}: 315{-}400\,\text{nm}.$
- $\text{UVB}: 290{-}315\,\text{nm}.$
- $\text{UVC}: 200{-}290\,\text{nm}.$
Ground-level UV mix: approximately $95\%$ UVA and $5\%$ UVB.
Vitamin D synthesis: conversion at around $\lambda \approx 300\ \text{nm}$ producing pre-vitamin D3 from 7-dehydrocholesterol.
Vitamin D metabolism:
- $\text{Vitamin D}3 \xrightarrow{\text{liver}} 25{-}\text{OH Vitamin D}3$
- $25{-}\text{OH Vitamin D}3 \xrightarrow{\text{kidney}} 1{,}25{-}\text{(OH)}2\text{Vitamin D}$
Non-melanoma cancer approximate distribution: basal cell carcinoma ≈ $80\%$ of non-melanoma cases; exposure-related.
Indoor tanning and melanoma risk: increase by ≈ $59\%$ (RR ≈ $1.59$ ).
Non-melanoma annual incidence: ≈ $2{\sim}3\times10^6$ new cases/year.
Ringworm (tinea) locations include scalp, foot (tinea pedis), groin (tinea cruris), nails (onychomycosis).

References to Key Pathways and Processes (Recap)

Epidermal turnover: typical $26{-}30\,\text{days}$ ; psoriasis shortens to $3{-}4\,\text{days}$ , driving rapid plaque formation.
Psoriasis cytokine axis: keratinocyte hyperproliferation driven by cytokines (TNF-α, IL-17, IL-23) originating from activated dendritic cells and T cells; Th1/Th17 pathways critical; biologics target these mediators.
UV-induced carcinogenesis: direct DNA damage (UVB) vs oxidative DNA damage (UVA); repair via NER; p53-mediated outcomes; mutation burden contributes to risk of basal/SCC/melanoma.

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