Dermatology Basics

Skin structure and vocabulary

Epidermis. A keratinized stratified squamous epithelium with five layers. From deep to superficial: stratum basale (mitotically active stem cells, plus melanocytes), stratum spinosum (keratinocytes joined by desmosomes, which look like spines), stratum granulosum (keratohyalin granules), stratum lucidum (only in the thick skin of palms and soles), and stratum corneum (anucleate keratin). Read from the top down, the mnemonic is Come Lets Get Sun Burned.

Junctions explain the blisters. Desmosomes (built with desmogleins) bind keratinocytes to one another, while hemidesmosomes anchor basal cells to the basement membrane. Antibodies against one or the other produce intraepidermal vs subepidermal blisters.

Histology terms.

• Hyperkeratosis: thickened stratum corneum.
• Parakeratosis: nuclei retained in the stratum corneum, where they should be gone (psoriasis).
• Acanthosis: epidermal hyperplasia with a thickened spinosum (psoriasis, acanthosis nigricans).
• Spongiosis: intercellular epidermal edema (eczematous dermatitis).
• Acantholysis: loss of connections between keratinocytes (pemphigus vulgaris).

Inflammatory dermatoses and a cutaneous marker

Psoriasis. Well-demarcated salmon-colored plaques with silvery scale on extensor surfaces (elbows, knees) and the scalp, driven by T-cell cytokines (IL-17, IL-23) that accelerate keratinocyte turnover. Histology shows acanthosis, parakeratosis, Munro microabscesses (neutrophils in the corneum), and a thinned granular layer. Removing the scale causes pinpoint bleeding (Auspitz sign), and new plaques can appear at sites of trauma (Koebner phenomenon). Nail pitting and psoriatic arthritis occur.

Atopic dermatitis (eczema). A pruritic, erythematous, oozing and crusting rash on flexural surfaces; histology shows spongiosis. It belongs to the atopic triad with asthma and allergic rhinitis, and barrier defects (e.g., filaggrin mutations) and elevated IgE are common.

Acanthosis nigricans. Velvety hyperpigmented plaques in flexural areas (axilla, posterior neck). It usually signals insulin resistance (obesity, type 2 diabetes, PCOS), with high insulin stimulating keratinocyte growth through IGF-1 receptors.

Sudden acanthosis nigricans in a lean adult is paraneoplastic, classically from gastric adenocarcinoma.

Autoimmune blistering diseases

Pemphigus vulgaris. IgG autoantibodies against desmoglein 1 and 3 in desmosomes (type II hypersensitivity). Intraepidermal (suprabasal) acantholysis produces flaccid bullae that rupture into erosions, a positive Nikolsky sign (epidermis separates with lateral pressure), and oral mucosal involvement. Direct immunofluorescence shows a reticular (net-like) intercellular IgG pattern; on routine histology, basal cells left attached to the basement membrane resemble a row of tombstones.

Bullous pemphigoid. IgG against hemidesmosome proteins (BP180/BP230) at the basement membrane, also type II hypersensitivity. It produces subepidermal tense bullae with a negative Nikolsky sign, spares the oral mucosa, and affects the elderly. Direct immunofluorescence shows linear IgG and C3 along the basement membrane, and the blister contains eosinophils.

Pemphigus is Superficial (intraepidermal) and more Severe, with oral involvement; pemphigoid is Deeper (subepidermal), tense, milder, and spares the mouth.

Related blistering disease. Dermatitis herpetiformis produces intensely itchy vesicles on extensor surfaces with IgA deposits in the dermal papillae and is associated with celiac disease.

Reactive eruptions: erythema multiforme and SJS/TEN

Erythema multiforme. Targetoid (iris) lesions on the extremities. The most common trigger is HSV infection; others are Mycoplasma pneumoniae, drugs (sulfonamides, β-lactams, phenytoin), and malignancy.

Stevens-Johnson syndrome and toxic epidermal necrolysis. Severe mucocutaneous drug reactions in which cytotoxic T cells trigger keratinocyte death and full-thickness epidermal necrosis. Culprits are sulfa drugs, anticonvulsants (lamotrigine, carbamazepine, phenytoin), and allopurinol. Patients develop fever, mucosal erosions, a targetoid rash, and epidermal detachment with a positive Nikolsky sign. The extent of detachment defines the diagnosis; management is stopping the drug and burn-unit-style supportive care. HLA-B*15:02 strongly predisposes to carbamazepine-induced SJS/TEN in patients of Asian ancestry.

Staphylococcal scalded skin syndrome mimics TEN but its exfoliative toxin splits the superficial epidermis (desmoglein 1 in the granular layer) and spares mucosa, typically in young children.

Skin cancers

Basal cell carcinoma. The most common skin cancer, on sun-exposed skin (face, upper lip). It is a pearly papule with rolled borders, telangiectasias, and central ulceration; histology shows palisading basaloid nuclei. It is locally invasive but rarely metastasizes. PTCH mutations (Hedgehog pathway) drive both sporadic tumors and Gorlin syndrome.

Squamous cell carcinoma. The 2nd most common skin cancer, on sun-exposed skin (lower lip, ears, hands). Its precursor is actinic keratosis, and risks include immunosuppression (e.g., transplant recipients), arsenic, and chronic wounds or scars (Marjolin ulcer). Histology shows keratin pearls, and it metastasizes more often than basal cell carcinoma.

Melanoma. A malignancy of neural crest-derived melanocytes that causes the most skin cancer deaths. Warning signs are the ABCDEs: Asymmetry, Border irregularity, Color variation, Diameter over 6 mm, and Evolving. Breslow depth (vertical tumor thickness) is the most important prognostic factor because it predicts metastasis. S-100 is the marker, and the BRAF V600E mutation is targetable with vemurafenib.