The skin is the largest organ of the body, serving as the primary mechanical and immunological barrier against external pathogens, chemicals, and ultraviolet radiation. Structurally, it consists of three main layers:
Barrier dysfunction is a central feature in many dermatological disorders. When intercellular lipids like ceramides are depleted, transepidermal water loss increases, leading to dry, fissured skin that readily permits allergen and microbial entry.
Skin inflammation is triggered when resident cells—such as keratinocytes, mast cells, and cutaneous dendritic cells (Langerhans cells)—detect tissue injury, microbial invasion, or allergens. Upon activation, these cells release preformed inflammatory mediators like histamine, along with newly synthesized cytokines (tumor necrosis factor-alpha, interleukins) and chemokines.
These chemical signals cause local vasodilation and increased vascular permeability, allowing plasma proteins and leukocytes to migrate into the tissue. Neutrophils arrive first during the acute phase, followed by lymphocytes and macrophages. Chronic skin inflammation involves sustained immune cell infiltration and persistent signaling, which alters normal epidermal cell proliferation and leads to characteristic tissue thickening, scaling, or blistering.
Primary skin lesions are the initial, unaltered manifestations of pathological changes in the skin. Understanding their underlying cellular mechanisms helps differentiate various disease processes:
Pruritus (itching) and pain are distinct sensory experiences transmitted through overlapping yet separate neural pathways in the skin. Unmyelinated C-fibres located at the dermal-epidermal junction serve as the primary receptors for both sensations.
Pruritus is mediated by specific pruritogens, most notably histamine, tryptase, and substance P, which bind to specialized receptors on nerve endings. This signal travels via the spinal cord to the thalamus and sensory cortex, provoking the scratch reflex. Chronic scratching causes epidermal hyperplasia and lichenification, creating an itch-scratch cycle that worsens barrier damage.
Cutaneous pain shares similar peripheral nerve pathways but is typically triggered by mechanical, thermal, or chemical nociceptor activation via inflammatory prostaglandins and bradykinin.
Infectious dermatoses occur when bacteria, viruses, fungi, or parasites breach the skin barrier and overwhelm local immune defenses.
Immune-mediated dermatoses involve aberrant or overactive immune responses targeting normal skin structures. In psoriasis, an autoimmune-driven cycle causes T-cells to accumulate in the skin and release cytokines that accelerate keratinocyte proliferation. Instead of taking the usual four weeks, skin cells migrate to the surface in days, forming thick silvery plaques.
In autoimmune blistering diseases like pemphigus vulgaris, circulating autoantibodies attack desmogleins, the proteins that bind epidermal cells together. This loss of cell adhesion (acantholysis) causes fluid to accumulate between cells, resulting in fragile, flaccid blisters that rupture easily.
Skin wound healing progresses through four overlapping phases: hemostasis, inflammation, proliferation, and remodeling. During hemostasis, platelets form a fibrin clot to stop bleeding and release growth factors. The proliferative phase involves fibroblast migration, angiogenesis, and the deposition of new extracellular matrix, primarily type III collagen.
During the remodeling phase, type III collagen is gradually replaced by stronger type I collagen, and excess capillaries regress. When this regulatory process fails, pathological scarring occurs: