Acne Vulgaris — Pathogenesis, Grading, Topical and Oral Treatment, Isotretinoin and Hormonal Therapy

Acne vulgaris is a common inflammatory disorder of the pilosebaceous unit with a chronic course. It produces comedones, papules, pustules or nodules, mainly on the face, but also the upper arms, trunk and back — wherever large, hormonally responsive sebaceous glands are abundant. The primary lesion is the comedo, and the precursor of every acne lesion is the microcomedo: a small hyperkeratotic plug of corneocytes in the lower follicular infundibulum.

• Age: usually adolescents (prevalence 35% to over 90%), but it can start at ages 7 to 12 (preadolescent acne) or first appear in adulthood. Adolescent acne is commoner in males; post-adolescent acne predominantly affects females.
• Acne in ages 1 to 6 is rare and may point to an underlying disorder, so it needs evaluation.
• About 20% of patients develop severe acne that may scar.
• Genetics matter: heritability estimates range from 50% to 90%.

Androgens. Most acne patients have normal androgen levels; the sebaceous gland is hypersensitive to them. Sebaceous glands convert DHEAS to testosterone, and type I 5-alpha reductase converts testosterone to dihydrotestosterone (DHT), which has a greater affinity for the androgen receptor than testosterone. Excess androgen states — PCOS, congenital adrenal hyperplasia, adrenal or ovarian tumours — cause acne, whereas males with androgen insensitivity do not develop it. Acne typically does not begin before adrenarche.

Open versus closed comedones. A closed comedo (whitehead) is a dome-shaped papule where keratin and sebum block the orifice beneath the surface. As the orifice distends it becomes an open comedo (blackhead); its black colour comes from oxidised lipids and melanin, not dirt. C. acnes strains linked to acne activate Th17 cells and the NLRP3 inflammasome, producing IL-1 and attracting neutrophils that cause follicular rupture.

Severity is not graded by lesion type alone. StatPearls adds the psychological impact, treatment response and scarring or sinus tracts: nodular inflammatory acne is severe, and inflammatory pustular acne with scarring is also severe even without nodules. Even mild comedonal acne that causes major distress may warrant moderate-to-severe-type treatment.

• Drugs: lithium, corticosteroids and anticonvulsants can induce or worsen acne.
• Endocrine: PCOS, pregnancy and the luteal phase; premenstrual flares occur in up to 70% of menstruating patients. Hyperandrogenism clues: hirsutism, acanthosis nigricans, irregular menses.
• Diet: milk and high-glycaemic-load diets are associated with acne (via IGF-1); no substantial evidence that chocolate worsens it.
• Mechanical: occlusive clothing or equipment, oil-based cosmetics, scrubbing with soaps and picking.
• Prolonged antibiotics can produce Gram-negative folliculitis, a mimic of treatment-resistant acne that responds to isotretinoin.

Differentials include rosacea (telangiectasia, papules and pustules but no comedones), perioral dermatitis (grouped papules sparing the lip margin) and Demodex folliculitis. For skin structure background see layers of the epidermis.

• Oral antibiotics: tetracyclines (doxycycline, minocycline, sarecycline) are preferred because they are also anti-inflammatory. Limit to the shortest period, ideally 3 to 4 months, and combine with benzoyl peroxide or a topical retinoid. Contraindicated in pregnancy, breastfeeding and children aged 9 or younger (tooth enamel hypoplasia or discolouration).
• Combined oral contraceptives reduce androgen action; FDA-approved acne COCs include norgestimate/EE and drospirenone/EE. Improvement takes 3 to 6 months. Progestin-only pills with androgenic progestins are not effective and may worsen acne. Avoid in thrombophilia or previous thromboembolism.
• Spironolactone blocks androgen receptors and inhibits androgen synthesis, reducing sebum secretion by about 50%; usual dose 25 to 50 mg daily, up to 100 mg. Adverse effects: breast tenderness, menstrual irregularity, hyperkalaemia, orthostatic hypotension.
• Hormonal therapy suits post-menarchal females with severe acne, premenstrual flares, hyperandrogenism or those wanting contraception.

Oral isotretinoin is the only drug that counters all four pathogenic factors: it reduces sebaceous gland size and sebum production, normalises keratinisation and has anti-inflammatory effects. It is the treatment for severe recalcitrant nodular acne with scarring, and is increasingly used for moderate acne with psychological distress, recurrence or scarring risk. Its non-antibiotic mechanism avoids resistance.

Procedures such as waxing, dermabrasion and laser are traditionally avoided during therapy and for about 6 months afterwards; newer evidence suggests comedone extraction, peels and lasers can be done safely with proper technique. Related drug topics: corticosteroids and vitamin deficiencies (retinoid background).

Complications need their own management: post-inflammatory hyperpigmentation (photoprotection, retinoids, azelaic acid, hydroquinone, superficial peels), ice-pick scars (TCA CROSS, punch excision), rolling scars (subcision) and keloids (intralesional triamcinolone).