Layers of the Epidermis — Strata, Resident Cells, Junctions and the Blistering Diseases They Explain

The epidermis is a keratinised stratified squamous epithelium derived from surface ectoderm. Its cells — mostly keratinocytes — are born in the deepest layer and are pushed upwards, changing shape and contents as they go, until they die and flake off at the surface. That journey is what the five layers describe.

Thick skin is the hairless skin of the palms and soles. It is thickest because it has an extra layer — the stratum lucidum — in the epidermis. Every region without this layer is classed as thin skin, even where the skin as a whole is bulky: among thin-skin regions, the back has the thickest skin because of a thick epidermis (StatPearls).

The lucidum is 2–3 cell layers of flattened, clear cells packed with eleidin, a lipid-rich product of keratohyalin that gives the band its transparent look and adds a water barrier. Pathology texts also note that a lucidum-like layer becomes more prominent in chronically rubbed or scratched skin.

Normal epidermis has four resident cell populations: keratinocytes, melanocytes, Langerhans cells and Merkel cells. Keratinocytes make up the bulk; the other three are scattered among them and are favourite one-liners because each has a distinctive origin, location and marker.

Melanin is passed on by cytocrine secretion: keratinocytes phagocytose the tips of the long melanocyte processes and receive the melanosomes. Variations in skin pigmentation reflect the melanin content of the skin. Langerhans cells are spread thinly — roughly one per 53 keratinocytes — and carry captured antigen to regional lymph nodes.

1. Basale — stem cells divide; daughter cells leave the basement membrane and start upwards.
2. Spinosum — cells enlarge and become polyhedral, bound by desmosomes; keratinocytes here begin to make keratohyalin granules and lamellar bodies (glycosphingolipids, phospholipids and ceramides assembled in the Golgi).
3. Granulosum — cells flatten into diamonds packed with keratohyalin; lamellar-body lipids are exocytosed into the spaces between cells, sealing the barrier.
4. Granulosum–corneum transition — proteins such as loricrin and involucrin are cross-linked at the cell periphery to build the cornified cell envelope; profilaggrin is processed to filaggrin, which aggregates keratin filaments.
5. Corneum — cells lose nuclei and organelles; keratin forms a homogeneous matrix. At the surface, desmosomes are digested (kallikrein-related serine peptidases, activated by the lower surface pH) and the squames shed.

Psoriasis is the classic exception: immune-driven (IL-17, IL-23) hyperproliferation makes keratinocytes move up far faster, producing acanthosis (epidermal hyperplasia) with elongated rete ridges and thick silvery plaques.

Keratohyalin is also the source of eleidin in the stratum lucidum. The name filaggrin itself means "filament aggregating protein" — exactly what it does to keratin in the granular layer.

Both junctions anchor keratin intermediate filaments, but they join different things. A desmosome links one keratinocyte to the next — the spine-like cytoplasmic processes of the stratum spinosum are where neighbouring cells meet at desmosomes. A hemidesmosome is half a junction: it fastens the basal keratinocyte to the basement membrane below.

BP230 is an intracellular plaque protein that binds integrin α6β4 and BP180 at one end and the keratin 5/14 filaments of basal cells at the other; BP180 is transmembrane and is the main pathogenic antigen in pemphigoid.

Pemphigus vulgaris (PV) is caused by IgG autoantibodies against desmoglein 3 and often desmoglein 1. Dsg 3 dominates in the deeper epidermis and in mucous membranes, so PV starts in the mouth in about 80% of patients and the split is just above the basal layer — suprabasal acantholysis, with basal cells left standing on the basement membrane like a row of tombstones. Pemphigus foliaceus is mostly anti-Dsg 1 and spares the oral mucosa.

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease (about 80% of subepidermal immunobullous cases), mostly in people aged 60–80 years. Autoantibodies hit BP180 and BP230 in the hemidesmosome; the whole epidermis separates, giving tense bullae with intense itch and a subepidermal split rich in eosinophils.

On salt-split skin, pemphigoid antibodies bind the epidermal side (roof) of the split, while epidermolysis bullosa acquisita binds the dermal side (floor) — the standard way to tell these two subepidermal diseases apart. For moderate-to-severe pemphigus, rituximab with corticosteroids is the preferred first-line approach (StatPearls).

• Acantholysis — loss of connection between keratinocytes (breakdown of desmosomes) at some level of the epidermis, producing clefts and blisters. Examples: pemphigus vulgaris, Hailey–Hailey disease, eczema herpeticum.
• Spongiosis — intraepidermal oedema that widens the spaces between keratinocytes so the desmosomes become visible as bridges; the cells stay attached. Examples: atopic dermatitis, allergic contact dermatitis.
• Acanthosis — epidermal hyperplasia with elongated rete ridges, as in psoriasis.
• Nikolsky sign — blistering or shearing of the epidermis with minor pressure or trauma. Positive when cell-to-cell adhesion is lost (pemphigus vulgaris); negative in typical bullous pemphigoid, where the epidermis itself is intact.

The sudoriferous (sweat) glands are the two secretory adnexa that sit in the dermis and open to the skin: eccrine and apocrine. Both have a coiled secretory unit with myoepithelial cells and a duct, but they differ in site, outlet, innervation and activity.

• Layer only in thick skin → stratum lucidum (palms, soles).
• Layer that divides / contains stem cells → stratum basale (germinativum).
• Prickle cell layer, desmosomes → stratum spinosum; Langerhans cells are seen here.
• Keratohyalin granules → stratum granulosum; filaggrin defect → ichthyosis vulgaris.
• Anucleate cells → stratum corneum (20–30 layers).
• Neural crest cell in the epidermis → melanocyte; Birbeck granules → Langerhans cell; light-touch mechanoreceptor → Merkel cell.
• Epidermal turnover time → about 4 weeks (basal cell to shed squame).
• Suprabasal split with tombstoning → pemphigus vulgaris (Dsg 3); subepidermal split, linear IgG/C3 → bullous pemphigoid (BP180/BP230).

Practise these with NEET PG Dermatology PYQs and see where skin histology sits among the most repeated topics. The same five strata also explain burn depth — see thermal injuries and the rule of nines — and germ-layer origins are covered in germ layers.