Human Pathophysiology II - The Skin Notes

Overview of Skin-Related Disorders

Papulosquamous Disorders
  • A broad category of skin conditions characterized by papules and scales.
Desquamation
  • The shedding of the outer layer of skin cells.
Acneiform Lesions
  • Includes a variety of skin lesions resembling acne.
Benign & Malignant Lesions

Benign & Malignant Lesions

Acquired Melanocytic Nevi (Mole)
  • Definition: Benign proliferations of a type of melanocyte known as "nevus cells."
  • Histological Types:
    1. Common (Banal): Typically small, symmetric, evenly pigmented.
    2. Atypical/Dysplastic: May exhibit features suggestive of malignancy.
  • Histological Depth:
    • Junctional Nevi: Nests located at the dermal-epidermal junction.
    • Compound Nevi: Nests at the dermal-epidermal junction and in the dermis.
    • Intradermal Nevi: Nests located exclusively in the dermis.
  • Pathophysiology: Melanocytes migrate from the dermal-epidermal junction into the dermis, causing elevation and reduced pigmentation.
Predisposing Factors for Melanocytic Nevus
  • Genetic Influence: Family history may impact nevus formation.
  • Sun Exposure: Ultraviolet (UV) radiation increases risk.
  • Environmental and Medical Factors: Various external factors can influence the development of nevi.
  • Cutaneous Phenotype: Skin type can affect nevus characteristics.
  • Immunosuppression: Reduced immune response can lead to altered nevus behavior.
Clinical Features of Common Acquired Melanocytic Nevi
  • Appearance: Begin as small brown macules in childhood and increase in number through adolescence.
  • Characteristics: Small (≤6 mm), symmetric, round or oval, with even pigmentation and defined borders.
  • Distribution: Commonly found on sun-exposed areas.
  • Genetic Factors: Involvement of genes such as BRAF V600E mutations.

Congenital Melanocytic Nevi (CMN)

  • Definition: Benign melanocyte proliferations that occur during embryogenesis.
  • Clinical Features:
    • Present at birth or develops within the first months of life.
    • Color varying from tan to black or blue-black; often geographic, irregular borders.
    • Large CMNs often have smaller satellite nevi.
  • Anatomical Distribution:
    • Defined regions termed the "six Bs": Bolero, Back, Bathing trunk, Breast/belly, Body extremity, and Body.
  • Pathogenesis:
    • Often linked to mutations in BRAFV600E or NRAS for larger nevi.

Atypical (Dysplastic) Nevi

  • Definition: Benign nevi with clinical features akin to melanoma (large diameter, irregular borders, multiple colors).
  • Risks: Increased melanoma risk correlates with the number of atypical nevi, especially with a personal or family history of melanoma.
  • Clinical Characteristics:
    • Location: Common on trunk and extremities.
    • Size: Diameter >5 mm; irregular, asymmetrical borders, multicolored.
Pathogenesis
  • Development largely genetic, UV light as a modifier.
  • BRAF V600E mutations are common.
  • Related syndromes, like FAMM, show inherited susceptibility to melanomas.

Melanoma: Development and Pathways

  • Initial Step: BRAFV600E mutation leads to melanocyte proliferation.
  • Malignant transformation involves genetic alterations, evasion of senescence, and activation of oncogenic pathways.
  • MAPK Pathway: Commonly activated, leading to aggressive melanoma behavior and metastasis. BRAF inhibitors provide new treatment options.
ADCDEs of Melanoma (Warning Signs)
  1. Asymmetry: If a line through the middle does not yield matching halves, it may indicate malignancy.
  2. Border: Uneven, scalloped borders are a red flag.
  3. Color: Variegated color patterns suggest melanoma risk.
  4. Diameter: Melanomas tend to be larger than 6 mm.
  5. Evolving: Any change in shape, size, or color warrants a medical evaluation.

Skin Cancers Overview

Basal Cell Carcinoma (BCC)
  • Definition: Most common skin cancer arising from the epidermal basal layer; often seen in sun-exposed areas.
  • Risk Factors: Include UV exposure, genetic predisposition, and various environmental factors.
  • Clinical Presentations:
    • Nodular, superficial, and morpheaform/infiltrative types, each with distinct physical appearances.
  • Molecular Pathogenesis:
    • Often linked to PTCH1 and SMO mutations associated with the Hedgehog pathway.
Cutaneous Squamous Cell Carcinoma (cSCC)
  • Definition: Malignant growth of epidermal keratinocytes.
  • Risk Factors: Include UV exposure, history of sunburns, and immunosuppression.
  • Clinical Manifestations: Bowen's disease (in situ) appears as scaly patches, while invasive forms present as firm, indurated papules.

Bacterial Infections in Dermatology

Impetigo
  • Definition: Contagious superficial bacterial infection, common in children aged 2-5.
  • Microbiology: Often caused by Group A Streptococcus or Staphylococcus aureus.
  • Clinical Features: Begin as papules that evolve into vesicles surrounded by erythema.

Other Pigmentary Disorders

Acanthosis Nigricans
  • Definition: Characterized by velvety, gray-brown plaques on the neck and axillae, associated with insulin resistance.
Vitiligo
  • Definition: Acquired depigmentation disorder, frequently correlates with autoimmune diseases.
  • Clinical Presentation: Characterized by asymptomatic white patches that lack inflammation.
  • Pathogenesis:
    • Involves genetic, autoimmune, and oxidative stress factors contributing to the loss of melanocytes.
Vitiligo Classification
  • Nonsegmental: Generalized, symmetric distribution, onset usually before age 30.
  • Segmental: Unilateral distribution that matches a dermatome. Characterized by early onset and may include rare forms like vitiligo minor.
  • Pathogenesis: Indicates involvement via autoimmunity and oxidative stress theories.