Basic Sciences Relevant to Skin
Domain 1 tests how structure and molecular machinery explain clinical signs: why the epidermis splits at a given level, why a keratin mutation produces a specific pattern, and how cutaneous immunity shapes infection and drug reactions.
Structure and molecules
- Keratins pair by layer: K5/K14 in basal cells, K1/K10 suprabasal, K6/K16 in hyperproliferative epidermis, K9 palmoplantar. Mutations cause epidermolysis bullosa simplex (K5/K14) and epidermolytic ichthyosis (K1/K10).
- Basement membrane zone, top to bottom: hemidesmosome (BPAG1/BP230, BPAG2/BP180/collagen XVII, integrin alpha6beta4), lamina lucida, lamina densa (collagen IV, laminin-332), anchoring fibrils (collagen VII).
- Dermis: type I and III collagen, elastic fibres, glycosaminoglycans. Type IV belongs to basement membrane, not dermal interstitium.
- Immunity: Langerhans cells present antigen, resident memory T cells patrol epidermis, dermal dendritic cells and mast cells shape inflammation; keratinocytes release IL-1 and IL-36.
Genetics and mosaicism
Blaschko lines reflect ectodermal cell migration. X-linked dominant conditions such as incontinentia pigmenti and mosaic mutations follow these lines, which is why distribution itself is diagnostic evidence.
Worked example
A neonate has trauma-induced blisters, dystrophic nails and no family history. Immunofluorescence mapping shows absent type VII collagen, and electron microscopy shows missing anchoring fibrils. This is recessive dystrophic epidermolysis bullosa (COL7A1). Reasoning: cleavage below the lamina densa damages anchoring fibrils, predicting scarring and milia.
Traps
Do not place BP180 in the lamina densa; it is a hemidesmosomal transmembrane protein. Do not pair K6/K16 with normal resting skin. Do not label every subepidermal blister pemphigoid, because level and immunofluorescence decide.