Acne Vulgaris and Rosacea

Non-modifiable host factors

• Pubertal androgen surge: adrenarche and gonadarche raise DHEA-S and testosterone, which 5α-reductase converts to DHT within the sebaceous gland — the reason acne peaks in mid-adolescence and why prepubertal acne warrants an endocrine look
• Genetic predisposition: strong familial clustering for both nodulocystic acne and rosacea; a first-degree relative with severe scarring acne predicts severe disease and earlier escalation to isotretinoin
• Sex: severe nodulocystic acne and rhinophyma are both male-predominant; adult female acne is jawline/lower-face predominant with premenstrual flares
• Fitzpatrick I–II skin / Northern European ancestry: the classic rosacea substrate — thin dermis and photodamaged perivascular collagen amplify vascular instability

Endocrine and systemic drivers

• Hyperandrogenism: PCOS, nonclassic congenital adrenal hyperplasia, and androgen-secreting tumors; the stem plants oligomenorrhea, hirsutism, or rapid virilization with new acne after age 25 — the American Academy of Dermatology acne guideline supports hormonal evaluation in exactly this setting
• Exogenous androgens: anabolic steroids, testosterone therapy, androgenic progestins — abrupt truncal acne in an athlete is the giveaway

Modifiable and exogenous

• Drug-induced acneiform eruption: systemic corticosteroids (monomorphic pustules at one stage, no comedones), lithium, isoniazid, phenytoin, iodides/bromides, and EGFR inhibitors (papulopustular rash correlating with tumor response)
• Occlusion and friction: acne mechanica from helmets, chin straps, shoulder pads, and masks; pomade acne along the hairline; comedogenic cosmetics
• Diet: the AAD acknowledges only limited evidence linking high-glycemic-index diets and skim milk to acne — chocolate and greasy food remain unproven and are a common distractor
• Rosacea triggers: UV exposure, heat, hot beverages, alcohol (especially red wine), spicy food, exercise, and emotional stress; National Rosacea Society guidance makes trigger identification and daily photoprotection foundational therapy
• Topical corticosteroid use on the face: induces steroid rosacea and perioral dermatitis with rebound on withdrawal

Acne Vulgaris—Four Key Pathogenic Mechanisms

• Increased sebum production: Androgens (particularly DHT) stimulate sebaceous gland enlargement and lipid synthesis, explaining the prevalence during puberty and androgen-dominant states; sebum serves as substrate for bacterial growth
• Follicular hyperkeratinization: Abnormal desquamation of follicular epithelium creates comedones (blackheads = oxidized sebum; whiteheads = closed comedones) that obstruct the pilosebaceous duct and trap bacteria
• Cutibacterium acnes (formerly Propionibacterium acnes) proliferation: This gram-positive anaerobic bacillus colonizes sebaceous follicles and produces lipases, proteases, and hyaluronidase that trigger inflammation; produces porphyrins that are photosensitive
• Inflammation and immune dysregulation: TLR2 activation by bacterial lipoproteins triggers NF-κB pathway activation, IL-8 release, and neutrophil recruitment; P. acnes antigens may trigger delayed-type hypersensitivity

Rosacea—Vascular and Immune Dysregulation

• Vascular instability: Abnormal vasodilation responses to triggers (heat, alcohol, spicy foods, UV exposure) cause flushing; chronic dysregulation leads to telangiectasia and persistent erythema
• Innate immune activation: Abnormal TLR2 and TLR4 signaling; elevated kallikrein-5 (KLK5) causes increased bradykinin and substance P (potent vasodilators and inflammatory mediators)
• Altered skin barrier function: Reduced lipid content and impaired claudin-1 tight junction proteins allow increased transepidermal water loss (TEWL) and irritant penetration
• Demodex mite involvement: While not causal, Demodex folliculorum overgrowth may exacerbate inflammation; patients have heightened immune response to mite antigens; relationship remains unclear but increasingly recognized

Acne Vulgaris

• Distribution: Face (most common), neck, chest, and upper back—areas with highest sebaceous gland density
• Lesion morphology:
• Comedonal acne: Blackheads (open comedones—dark due to oxidation, NOT dirt) and whiteheads (closed comedones) without significant inflammation
• Inflammatory acne: Papules and pustules (erythematous, tender 1-5mm lesions); may be preceded by comedones
• Severe/nodulocystic acne: Large, tender, deep nodules (>5mm) and cysts that can scar; indicates need for aggressive intervention (isotretinoin consideration)
• Associated features: Oily skin (seborrhea), post-inflammatory hyperpigmentation (especially in darker skin types), acne scars (ice-pick, boxcar, rolling types develop from severe inflammation)
• Exacerbating factors: Puberty/hormonal fluctuation (premenstrual flare in females), OCPs with androgenic progestins, anabolic steroids, mechanical friction, occlusive products

Rosacea (Four Subtypes)

• Subtype 1 (Erythematotelangiectatic): Persistent central face erythema and flushing with visible telangiectasia; mimics blushing
• Subtype 2 (Papulopustular): Persistent erythema with dome-shaped papules and pustules; frequently misdiagnosed as acne (critical distinction: NO comedones in rosacea)
• Subtype 3 (Phymatous): Severe fibrosis and sebaceous gland hypertrophy causing nodular thickening, most commonly affecting nose (rhinophyma—pathognomonic appearance); predominantly affects males
• Subtype 4 (Ocular): Blepharitis, conjunctivitis, keratitis, and recurrent chalazia; present in ~50% of rosacea patients; vision-threatening if untreated
• Key clinical pearls:
• Symmetric centrofacial distribution (cheeks, nose, chin, forehead)—spares the perioral region (helps distinguish from seborrheic dermatitis)
• Absence of comedones is pathognomonic for rosacea and key differentiating feature from acne
• Burning, stinging, flushing sensations are common subjective complaints; may precede visible lesions
• Triggers include hot beverages, spicy foods, alcohol (especially red wine), extreme temperatures, emotional stress, exercise, menopause

Acne Vulgaris

• Clinical diagnosis based on characteristic lesion morphology and distribution; no laboratory testing required for typical cases
• Severity grading (helps guide treatment intensity):
• Mild: Mostly comedones ± few papules, limited to face
• Moderate: More numerous papules/pustules, may involve chest/back
• Severe: Extensive inflammatory lesions, nodules, significant scarring potential
• Hormonal workup (only if indicated): Consider in women with late-onset acne (>25 years), irregular menses, hirsutism, or rapid progression—evaluate with free testosterone, DHEA-S, LH/FSH ratio to rule out PCOS or adrenal hyperplasia
• Psychological assessment: Screen for depression and body dysmorphic disorder, particularly in nodulocystic acne

Rosacea

• Diagnosis is clinical—no pathognomonic test; based on diagnostic criteria (National Rosacea Society)
• Major criteria (one required): Persistent facial erythema OR flushing
• Minor criteria (two required if major criterion absent): Papules/pustules, telangiectasia, ocular manifestations, edema, phymatous changes, burning/stinging sensation
• Dermoscopy: Telangiectasia and absence of comedones support diagnosis
• Exclusion of mimics: Rule out acne vulgaris (presence of comedones), seborrheic dermatitis (affects nasolabial folds/eyebrows), lupus (positive ANA, malar rash spares nasolabial folds), atopic dermatitis (pruritus, lichenification)
• Ocular examination: Slit lamp exam recommended if ocular symptoms present to assess severity and prevent keratopathy

Acne Vulgaris

• Benzoyl peroxide: 2.5-10% once or twice daily; bactericidal against C. acnes, reduces antibiotic resistance when combined with antibiotics, minimal resistance development; irritation is limiting factor
• Retinoids (address all pathogenic factors):
• Tretinoin (all-trans retinoic acid): 0.025-0.1% nightly, start low (0.025%) and titrate up weekly; gold standard but most irritating; requires strict sun protection (teratogenic, Category X)
• Adapalene: 0.1-0.3% nightly; newer generation with better tolerability and less irritation than tretinoin
• Tazarotene: 0.05-0.1% nightly; potent but high irritation; teratogenic
• Common initial worsening ("retinization") occurs over 6-8 weeks; counsel patients appropriately
• Topical antibiotics + benzoyl peroxide: Clindamycin 1% or erythromycin (less preferred due to resistance) twice daily

Disease-related

• Permanent scarring: dermal collagen destruction from deep inflammation yields ice-pick, boxcar, and rolling atrophic scars, plus keloids on the trunk and jaw in skin of color — the presence of any scarring is itself an indication to escalate therapy rather than wait
• Post-inflammatory hyperpigmentation: melanocyte stimulation by inflammatory mediators; the dominant patient concern in Fitzpatrick IV–VI and often more distressing than the acne
• Psychiatric morbidity: depression, social withdrawal, suicidal ideation, and body dysmorphic disorder; screening is recommended in nodulocystic disease
• Acne fulminans: abrupt ulcerative-crusted nodules with fever, leukocytosis, arthralgias, and osteolytic bone lesions — a systemic emergency; it can be precipitated by starting isotretinoin at full dose, and management pairs systemic corticosteroids with delayed low-dose retinoid re-introduction
• Gram-negative folliculitis: monomorphic pustules erupting after prolonged oral antibiotics as Klebsiella, Proteus, or Enterobacter overgrow the nares
• Ocular rosacea keratitis: corneal neovascularization and ulceration that can progress to perforation — pain, photophobia, or reduced acuity mandates same-day slit-lamp evaluation and ophthalmology referral
• Rhinophyma: irreversible sebaceous hyperplasia and fibrosis requiring surgical/laser debulking; it is not caused by alcohol

Treatment-related

• Isotretinoin teratogenicity: retinoid embryopathy (craniofacial, cardiac conotruncal, and CNS malformations) — the FDA iPLEDGE REMS requires two negative pregnancy tests before starting, monthly testing, and two concurrent forms of contraception
• Isotretinoin metabolic and mucocutaneous effects: cheilitis and xerosis in nearly all patients, hypertriglyceridemia that can precipitate pancreatitis, transaminitis, night blindness, and myalgias — check lipids and hepatic panel at baseline and during titration
• Idiopathic intracranial hypertension: headache with papilledema and visual obscurations; risk rises when isotretinoin is combined with a tetracycline, so the two are never co-prescribed — an emergency requiring imaging and lumbar puncture
• Tetracycline class effects: doxycycline photosensitivity and pill esophagitis (take upright with water); minocycline drug-induced lupus, blue-gray pigmentation, and DRESS
• Hormonal therapy: spironolactone causes hyperkalemia and menstrual irregularity; combined oral contraceptives carry VTE and stroke risk, restricted by CDC US Medical Eligibility Criteria in smokers over 35 and migraine with aura
• Antibiotic resistance: why guidelines forbid topical or oral antibiotic monotherapy and pair them with benzoyl peroxide

• Comedones settle the diagnosis: comedones present = acne vulgaris; centrofacial papulopustules with flushing and telangiectasia and no comedones = rosacea. This single feature is the most tested discriminator on the exam
• Blackheads are oxidized keratin and melanin, not trapped dirt: scrubbing is useless and worsens irritation — a favorite distractor answer
• Isotretinoin is the answer for severe nodulocystic or scarring acne refractory to combination therapy, but the single best next step before the first prescription is pregnancy testing and iPLEDGE enrollment with two forms of contraception, per the FDA REMS
• Never combine isotretinoin with a tetracycline: the association examiners test is idiopathic intracranial hypertension — headache, papilledema, diplopia from CN VI palsy, and transient visual obscurations
• Facial redness treated with a topical corticosteroid is a trap: steroids transiently blanch rosacea and then produce rebound steroid rosacea or perioral dermatitis; the correct move is to stop the steroid and start topical metronidazole, azelaic acid, or ivermectin as supported by AAD rosacea guidance
• Ocular rosacea occurs in roughly half of patients and may precede skin findings: recurrent chalazia or blepharitis in an adult with facial flushing is the setup; eye pain, photophobia, or blurred vision requires urgent slit-lamp exam because keratitis can perforate
• Monomorphic pustules on the trunk and shoulders, all the same age, with no comedones = steroid-induced acneiform eruption; the answer is drug withdrawal, not benzoyl peroxide
• Adult female acne on the jawline with premenstrual flares, hirsutism, and irregular menses points to PCOS; check free testosterone and DHEA-S, and treat with a combined oral contraceptive or spironolactone rather than another antibiotic course
• Do not attribute rhinophyma to alcoholism — it is phymatous rosacea from sebaceous hyperplasia and fibrosis, and it is male-predominant