Acne Vulgaris

Definition & Overview

• Dermatology 2-Volume Set 5e, p. 2252
• Andrews' Diseases of the Skin, p. 280

Epidemiology

• Affects ~85% of young people between ages 12-24 years
• Peak incidence at ages 15-18 in both genders
• Males tend to have more severe nodulocystic disease
• Persists into adulthood in 35% of women and 20% of men in their 30s
• About 12% of women and 3% of men continue to have clinical acne until age 44
• Preadolescent acne (ages 7-11) is becoming more common with earlier puberty onset
• Risk groups: XYY karyotype, polycystic ovarian syndrome (PCOS), hyperandrogenism, hypercortisolism, precocious puberty
• Dermatology 2-Volume Set 5e, p. 2262-2263

Pathogenesis

1. Follicular hyperkeratinization - Keratinization of the lower follicular infundibulum forms a keratin plug that blocks sebum outflow
2. Sebaceous gland hypertrophy - Driven by androgens at puberty; castrated males historically did not develop acne
3. Cutibacterium acnes (formerly Propionibacterium acnes) - Lipase-synthesizing bacteria colonize the hair follicle, converting sebum lipids into proinflammatory free fatty acids; also activates toll-like receptors and triggers cytokine release
4. Inflammation - Rupture of the comedone wall releases oily/keratinous debris, triggering a foreign-body inflammatory reaction

• Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 134
• Harrison's Principles of Internal Medicine 22E, p. 434

Clinical Features

Lesion Types

Distribution

• Face: cheeks (most common), nose, forehead, chin; ears (comedones in concha, cysts in lobes)
• Neck: especially nuchal area - large cystic lesions
• Upper trunk and upper arms (chest and back common)

Temporal Pattern

• Comedonal acne starts first (forehead and cheeks at ages 8-12)
• More severe inflammatory disease develops in mid-teens
• Women: papulopustular flares ~1 week premenstrually
• Adult female acne (20-35 years): papules, pustules, and deep painful nodules on jawline, chin, and upper neck

Sequelae

• Post-inflammatory erythema (reddish-purple macules) - short-lived in light skin
• Post-inflammatory hyperpigmentation (PIH) - in dark skin, may persist months
• Scar types: ice pick scars (temples/cheeks), canyon-type atrophic scars (face), hypertrophic/keloidal scars (neck/trunk), anetoderma-type scars (trunk)
• Andrews' Diseases of the Skin, p. 280-281
• Harrison's Principles of Internal Medicine 22E, p. 433-434

Exacerbating Factors

• Friction/trauma (headbands, chin straps, athletic helmets)
• Comedogenic cosmetics or hair preparations
• Industrial chemical exposure (cutting oils, chlorinated hydrocarbons, coal tars)
• Drugs: glucocorticoids (topical or systemic), progestin-only contraception, lithium, isoniazid, androgens, EGFR inhibitors, anabolic steroids
• High-glycemic diet (evidence is moderate but relevant)
• Large quantities of skim milk (the skim milk - insulin-IGF-1 hypothesis)
• Obesity / insulin resistance / metabolic syndrome
• Harrison's Principles of Internal Medicine 22E, p. 434
• Andrews' Diseases of the Skin, p. 282

Classification (Severity)

• Severe | Nodules, cysts, confluent lesions; significant scarring risk |

Treatment

Topical Agents

Oral Systemic Agents

• Doxycycline: 100 mg BID or extended-release preparations; first-line; also has anti-inflammatory properties independent of antibacterial effect
• Minocycline: 50-100 mg once or twice daily; less affected by food; watch for vestibular side effects (vertigo), pigmentation (skin/mucosa/scars), and rare lupus-like syndromes
• Sub-antimicrobial doxycycline (20 mg BID or 40 mg SR daily): anti-inflammatory dose only; no resistance risk
• Amoxicillin: for those intolerant to tetracyclines, or during pregnancy (category B)
• Adequate response expected at 3 months; limit duration to prevent resistance

• Oral contraceptive pills (OCPs): several are FDA-approved for acne; target androgen-driven sebum production
• Spironolactone: safe, effective, and durable antiandrogen; particularly useful for adult female acne with jawline/chin distribution

• Reserved for severe nodulocystic acne unresponsive to other therapies
• Mechanism: strong antisebaceous action; also reduces C. acnes colonization and inflammation
• Dosing: weight-based, cumulative dose-driven duration
• Side effects: dry skin, cheilitis (very common); rare severe extracutaneous effects
• Highly teratogenic: regulated under iPLEDGE program in the US; requires two negative pregnancy tests before initiation and negative test before each refill
• Results are excellent in appropriately selected patients
• Harrison's Principles of Internal Medicine 22E, p. 434-435
• Andrews' Diseases of the Skin, p. 282-284

Treatment by Severity (Andrews' Box 13.1 Summary)

Special Situations

Neonatal Acne (Neonatal Cephalic Pustulosis)

• Develops days after birth; male preponderance; transient facial papules/pustules
• Most clear spontaneously within days to weeks
• Persistent cases may need topical benzoyl peroxide

Adult Female Acne

• Distribution: jawline, chin, upper neck
• Deep, painful, persistent nodules
• Responds well to hormonal therapy (spironolactone, OCPs)

Acne with PCOS

• More severe, less responsive to standard therapy
• Dietary counseling (low-glycemic diet, reduce skim milk) important, especially with insulin resistance

Differential Diagnosis

• Rosacea (no comedones; central facial erythema and telangiectasia)
• Perioral/periorificial dermatitis
• Folliculitis (staphylococcal, gram-negative, Malassezia, eosinophilic)
• Drug-induced acneiform eruptions (steroids, EGFR inhibitors, lithium)
• Keratosis pilaris (follicular plugging without inflammation)
• Angiofibromas (as in tuberous sclerosis)
• Syndromes: PAPA, PAPASH, SAPHO, Apert syndrome
• Dermatology 2-Volume Set 5e, p. 2693-2720

Patient Education Points

• Overly vigorous scrubbing aggravates acne by mechanically rupturing comedones
• Avoid comedogenic cosmetics (use noncomedogenic, pressed powder preferred over oil-based)
• High-glycemic foods and large amounts of skim milk may worsen acne
• Treatment takes 8-12 weeks to show effect - adherence is the most common cause of treatment failure
• Apply topical treatments to the entire affected area, not just individual lesions
• Distinguish active inflammatory lesions from resolved PIH macules (the latter do not need active treatment)

Recent Evidence (2024-2026)

• A 2025 systematic review on acne and the cutaneous microbiome (PMID 39269130) highlights the role of the skin microbiome in pathogenesis and its implications for treatment selection - supporting the move toward microbiome-preserving strategies rather than broad antibiotic use.
• A 2025 meta-analysis (PMID 39509291) found that isotretinoin combined with laser/light-based treatments outperforms isotretinoin alone for acne vulgaris, supporting combination approaches in appropriate candidates.
• A 2024 network meta-analysis (PMID 39110247) compared microneedling combinations for acne scarring, confirming microneedling with PRP or radiofrequency as effective options for post-acne scarring management.

• Harrison's Principles of Internal Medicine 22E (2025), pp. 433-435
• Andrews' Diseases of the Skin - Clinical Dermatology, pp. 279-284
• Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 134
• Dermatology 2-Volume Set 5e, pp. 2252-2265, 2691-2742

1. Most common cause of acne - Cutibacterium acnes (formerly Propionibacterium acnes)
2. Primary lesion - Comedone
3. Open comedone (blackhead) - Color due to oxidized melanin, NOT dirt
4. Closed comedone (whitehead) - Precursor to inflammatory lesions
5. Pathogenesis - Androgen → ↑ sebum → follicular plugging → C. acnes → free fatty acids → inflammation
6. Drug of choice for severe nodulocystic acne - Isotretinoin (13-cis-retinoic acid)
7. Isotretinoin MOA - Strong antisebaceous action (reduces sebum production)
8. Most teratogenic anti-acne drug - Isotretinoin
9. Topical antibiotic always combined with - Benzoyl peroxide (to prevent resistance)
10. Topical androgen receptor antagonist - Clascoterone (FDA approved)
11. Antiandrogen for adult female acne - Spironolactone
12. Sub-antimicrobial doxycycline - 40 mg SR once daily; anti-inflammatory only, no resistance
13. First-line topical maintenance - Retinoids (tretinoin, adapalene)
14. Acne NOT seen in - Castrated males (androgens are permissive)
15. Scarring type on face - Ice pick scars (temples/cheeks); keloidal scars on trunk/neck
16. Adult female acne distribution - Jawline, chin, upper neck
17. Drug causing acneiform eruption - Steroids, lithium, isoniazid, EGFR inhibitors

Recent Treatment Protocols for Severe Acne Scarring (2023-2025)

Scar Classification - Treatment Foundation

• Jennings et al., J Am Acad Dermatol 2024 [PMID: 35792196]

Core Principle: Combination Therapy is Superior to Monotherapy

1. Lasers and Energy-Based Devices

Ablative Fractional Lasers (AFL)

• CO2 (10,600 nm) and Er:YAG (2940 nm) - the most effective overall for atrophic scars
• AFL offers the greatest improvement but with more downtime (7-14 days), risk of post-inflammatory hyperpigmentation (PIH), and longer healing
• CO2 fractional laser is preferred for moderate-to-severe atrophic scarring on the face
• Er:YAG has a better safety profile in darker skin types (Fitzpatrick III-VI)

Non-Ablative Fractional Lasers (NAFL)

• 1550 nm (Fraxel Restore), 1540 nm - heat dermis without ablating epidermis
• Less downtime (2-3 days), lower risk of PIH
• Requires more sessions (4-6), less dramatic single-treatment improvement
• Better tolerated in darker skin types

Combination: Ablative + Non-Ablative

• A 2023 RCT (Kim et al., PMID: 37992744) found that combining fractional microneedling radiofrequency (FMRF) + ablative fractional CO2 laser significantly outperformed ablative laser alone for both acne and acne scars

Pulsed Dye Laser (PDL, 595 nm)

• First-line for hypertrophic scars, keloidal scars, and erythematous PIH
• Also used alongside isotretinoin (see below)

IPL (Intense Pulsed Light)

• Effective for erythema and mild pigmentary changes post-acne
• Useful adjunct, not primary treatment for textural scarring
• Ziebart et al., J Drugs Dermatol 2024 [PMID: 39630683]

2. Microneedling and Combinations

1. Microneedling + Chemical Peel - best overall in degree of improvement, patient satisfaction, and efficacy
2. Microneedling + PRP - strong results, widely used
3. Microneedling + Botulinum toxin-A - promising, especially for rolling scars
4. Microneedling + Hyaluronic acid - good for skin texture
5. Microneedling alone - effective but inferior to combinations
6. PRP alone and Chemical Peel alone - less effective than microneedling combinations

• Li et al., Arch Dermatol Res 2024 [PMID: 39110247]

Fractional Microneedling Radiofrequency (FMRF)

• Delivers RF energy directly into dermis via insulated needles
• Stimulates deep collagen remodeling
• Particularly effective for rolling and boxcar scars
• Safer in darker skin types compared to ablative lasers (less epidermal damage)
• Evidence supports combination with ablative CO2 laser for enhanced results

3. Isotretinoin + Energy-Based Devices (Updated Evidence)

• PDL, NAFL, and FMRF are safe and effective during or immediately after isotretinoin treatment
• The evidence does not justify delaying energy-based interventions for patients on isotretinoin
• This is a significant protocol shift - early treatment of scars while controlling active acne is now recommended
• Xu et al., J Cosmet Dermatol 2024 [PMID: 38845186]

⚠️ Note: Ablative CO2 laser remains cautious territory on isotretinoin - the evidence for safety is stronger for non-ablative and PDL modalities.

4. Chemical Peels

5. Subcision

• Technique: hypodermic needle or Nokor needle breaks fibrous bands tethering rolling scars to deep dermis
• Most effective for rolling scars
• Often combined with fillers (HA) or PRP injected immediately after to maintain separation
• Repeated sessions (3-5) typically needed
• Evidence is lower quality (uncontrolled studies) but clinical utility is well-established

6. Dermal Fillers

• Hyaluronic acid (HA) fillers: temporary (6-12 months), good for atrophic rolling/boxcar scars
• Poly-L-lactic acid (PLLA): biostimulatory, longer lasting
• Autologous fat grafting / lipoaspirate: emerging evidence for volume restoration in severe scarring

7. Platelet-Rich Plasma (PRP)

• Used as an adjunct, not monotherapy
• Injected alone or combined with microneedling, laser, or subcision
• Promotes collagen synthesis via growth factor release (TGF-β, PDGF, EGF)
• A 2025 systematic review (Periodontol 2000, PMID: 39086171) confirmed PRP's role in aesthetic regeneration, including acne scars

8. Punch Techniques (Surgical)

Practical Protocol by Severity

Mild Atrophic Scarring

• Topical retinoids + AHA/BHA
• Superficial chemical peels (glycolic/salicylic)
• 1-2 sessions microneedling

Moderate Atrophic Scarring (Mixed Types)

• Fractional non-ablative laser (4-6 sessions) OR FMRF
• Microneedling + PRP or chemical peel
• Subcision if rolling scars present
• TCA CROSS for any ice pick scars

Severe Atrophic Scarring

• Ablative fractional CO2 laser (1-3 sessions, spaced 3-4 months)
• Combined FMRF + AFL for maximal collagen remodeling
• Subcision + HA filler for rolling scars
• Punch excision/elevation for isolated deep scars
• Start energy treatments early - do not wait 6 months post-isotretinoin if using PDL or NAFL

Hypertrophic/Keloidal Scarring

• Intralesional triamcinolone (10-40 mg/mL) every 4-6 weeks
• PDL (595 nm) - reduces vascularity and flattens
• Silicone gel sheets (continuous use)
• Combined steroid + PDL superior to either alone

Key 2024-2025 Protocol Updates

Summary of Evidence Strength

• Kim et al. (2023) - FMRF + CO2 laser RCT - Yonsei Med J
• Kim EY et al. (2023) - Evidence-based management of atrophic acne scarring - Arch Dermatol Res
• Li et al. (2024) - Microneedling network meta-analysis, 24 RCTs - Arch Dermatol Res
• Xu et al. (2024) - Isotretinoin + energy devices systematic review - J Cosmet Dermatol
• Ziebart et al. (2024) - Lasers for acne scarring review - J Drugs Dermatol
• Jennings et al. (2024) - JAAD acne scarring: pathophysiology and diagnosis - J Am Acad Dermatol

Acne Scarring Treatment - NEET PG Quick Revision

Scar Types (Memory First)

Treatment by Scar Type - High Yield

Treatment Ladder (Severity-Based)

MILD → Topical retinoids + Chemical peels
   ↓
MODERATE → Microneedling + NAFL (non-ablative laser)
   ↓
SEVERE → Ablative CO2 laser + Subcision + Punch techniques

One-Liners for MCQs

1. Best overall for atrophic scars - Ablative fractional CO2 laser
2. Best for ice pick scars - TCA CROSS
3. Best for rolling scars - Subcision
4. Best for keloidal scars - Intralesional triamcinolone + PDL
5. Best combination (network meta-analysis 2024) - Microneedling + Chemical peel
6. PRP - Used as adjunct (NOT monotherapy); combined with microneedling/laser
7. FMRF - Safer than CO2 in dark skin (Fitzpatrick III-VI); less PIH risk
8. TCA CROSS - High concentration TCA (65-100%) applied focally into ice pick base
9. Subcision tool - Nokor needle or hypodermic needle; breaks dermal tethering bands
10. Punch excision - For single deep ice pick scars unresponsive to other treatment

Isotretinoin + Lasers - Exam Trap ⚠️

Old rule (WRONG now): Wait 6 months after isotretinoin before lasers

Current evidence (2024): PDL, non-ablative laser, FMRF are SAFE during/after isotretinoin - no delay needed

Skin Type Matters (Fitzpatrick)

Quick Mnemonics

• "SLIM" for atrophic scar treatments - Subcision, Laser, Injectable fillers, Microneedling
• PDL = Pulsed Dye Laser = Red/vascular lesions (erythema, keloids, telangiectasia)
• TCA CROSS = only for ice pick (focal, not full face)

Acne Vulgaris Treatment — UG Level (MBBS)

The 4 Goals of Treatment

1. Reduce sebum production
2. Normalize follicular keratinization (unclog pores)
3. Kill Cutibacterium acnes
4. Reduce inflammation

Step 1 — Classify Severity First

Step 2 — Treatment by Severity

🟡 MILD Acne

• Topical retinoid (tretinoin 0.025-0.05%) — mainstay; comedolytic
• Benzoyl peroxide (BPO) 2.5-10% — bactericidal, no resistance
• Salicylic acid — keratolytic, OTC option
• Apply to entire face, not just spots
• Takes 8-12 weeks to show effect

🟠 MODERATE Acne

⚠️ Always combine topical antibiotic with BPO to prevent C. acnes resistance ⚠️ Never use topical antibiotic alone long-term

🔴 SEVERE / Nodulocystic Acne

📌 iPLEDGE Program (USA) — mandatory registration to prevent fetal exposure

Step 3 — Special Situations

Female Patients with Hormonal Acne

Pregnancy

• Topical azelaic acid — safe
• Topical BPO — relatively safe
• Amoxicillin oral — if systemic needed (Category B)
• ❌ Avoid: tetracyclines, isotretinoin

All Topical Agents — Summary Table

Oral Antibiotics — Summary

📌 Limit antibiotics to 3 months — then switch to topical maintenance

Antibiotic Resistance — Prevention Rules

1. Always combine oral/topical antibiotic with BPO
2. Don't use oral + topical different antibiotics simultaneously
3. Limit duration — move to isotretinoin if can't wean off antibiotics
4. Same antibiotic on re-treatment unless lost efficacy

One Flow Chart

Acne
 ├── Mild ──────→ Topical retinoid ± BPO
 ├── Moderate ──→ Topical retinoid + BPO + Oral doxycycline
 ├── Severe ────→ Oral Isotretinoin
 └── Female ────→ Add OCP or Spironolactone

Must-Know Exam Facts (UG)

Eccrine Gland (Eccrine Sweat Gland)

Structure

1. Secretory Coil (Acinus)

• Located deep in the dermis (or superficial panniculus in thick-skinned areas like the back)
• Blind-ended, coiled structure
• Lined by two cell types:
  • Clear (pale) cells - large, glycogen-rich; initiate primary sweat formation
  • Dark cells - smaller, darker; function like duct cells; reabsorb Na⁺
• Surrounded by a layer of myoepithelial cells (contract to express sweat pulsatilely; hydrostatic pressure can exceed 500 mmHg)
• Rich microvascular network surrounds the entire gland

2. Duct

• Long, wavy tube passing outward through dermis → epidermis → sweat pore
• Double layer of cuboidal epithelial cells, lined by an eosinophilic cuticle on the luminal side
• Reabsorbs Na⁺ and Cl⁻, making final sweat hypotonic
• Rich in mitochondria (high energy demand for sustained ion transport)
• Andrews' Diseases of the Skin; Medical Physiology (Boron)

Location

• Found at virtually all skin sites in humans (unlike other mammals, where apocrine is dominant)
• Highest density: palms, soles, axillae, forehead
• Total number: ~2-4 million eccrine glands in humans

Eccrine vs Apocrine - Key Comparison

Physiology of Secretion

Step 1 - Primary Secretion (Coil)

1. Stimulus → Heat / emotional stress → postganglionic sympathetic (cholinergic) fibers release acetylcholine
2. ACh activates muscarinic receptors on acinar cells → activates phospholipase C → ↑ PKC + ↑ [Ca²⁺]ᵢ
3. This triggers Cl⁻ secretion: Na⁺/K⁺/2Cl⁻ cotransporter brings Cl⁻ into cell across basolateral membrane → Cl⁻ exits apically through Cl⁻ channel
4. Lumen-negative charge drives Na⁺ out paracellularly
5. NaCl + urea + lactate in lumen → osmotic gradient → water follows → primary secretion is isotonic to plasma

Step 2 - Modification (Duct)

1. Duct cells reabsorb Na⁺ via apical ENaC (epithelial Na⁺ channel)
2. Cl⁻ reabsorbed via CFTR (cystic fibrosis transmembrane conductance regulator)
3. Duct has low water permeability → water cannot follow → final sweat is hypotonic

Final sweat composition

• Hypotonic to plasma
• Contains: Na⁺, Cl⁻, K⁺, urea, lactate
• Same electrolytes as plasma but more dilute
• Medical Physiology (Boron & Boulpaep), p. 1778-1779

Flow Rate and NaCl Content

Acclimatization to heat → aldosterone → ↑ ENaC expression in duct → more Na⁺ reabsorption → more hypotonic sweat → salt conservation

Cystic Fibrosis - Classic Eccrine Connection

• CFTR is the Cl⁻ channel in duct cells
• In CF: CFTR mutated → Cl⁻ cannot be reabsorbed → Na⁺ stays in lumen too → sweat rich in NaCl
• Basis of the sweat chloride test: sweat Cl⁻ >60 mEq/L = diagnostic of CF
• Medical Physiology (Boron), p. 1779

Development

• Palmoplantar eccrine glands: first to develop; begin during 1st trimester
• Fully developed by 2nd trimester
• Canalization of dermal duct: complete by 16 weeks EGA
• Canalization of epidermal duct: complete by 22 weeks EGA
• Interfollicular (general body) eccrine glands: form during 5th month of gestation
• Eccrine glands mature and become functional postnatally (unlike apocrine, which is transiently active in utero then quiescent)
• Dermatology 2-Volume Set 5e, p. 2632-2636

Disorders of Eccrine Glands

Miliaria Subtypes (High Yield)

High-Yield Facts for Exams

• Andrews' Diseases of the Skin; Medical Physiology (Boron); Dermatology 2-Volume Set 5e; Fitzpatrick's Dermatology

Rosacea

Papulopustular rosacea (Andrews' Diseases of the Skin, Fig. 13.23)

Definition

Epidemiology

• Affects up to 3% of the US population
• Most common in light-skinned women aged 30-50 (Celtic/northern European descent)
• Severe phymatous type (rhinophyma) occurs almost exclusively in men
• Ocular rosacea occurs equally in men and women
• Associated comorbidities: migraine, cardiovascular disease, IBD

Subtypes (2017 NRS Classification)

Morbihan disease = solid facial edema complicating papulopustular/glandular rosacea; forehead, eyelids, cheeks affected

Clinical Images

Rhinophyma - phymatous rosacea (Andrews' Diseases of the Skin, Fig. 13.25)

Stages (Robbins)

1. Pre-rosacea - flushing episodes only
2. Persistent erythema + telangiectasia
3. Papules and pustules
4. Rhinophyma - permanent nasal thickening from sebaceous gland hypertrophy + follicular plugging

Triggers (Aggravating Factors)

• Sun exposure (most important)
• Heat, hot beverages, hot baths
• Alcohol (esp. red wine)
• Spicy foods
• Emotional stress
• Exercise
• Cold weather
• Topical corticosteroids (long-term use on face can induce/worsen rosacea)

Key exam fact: Flushing lasts >10 minutes, without sweating, lightheadedness, or palpitations (distinguishes from carcinoid/phaeochromocytoma)

Pathogenesis

1. Innate immune dysregulation
   • ↑ cutaneous cathelicidin antimicrobial peptides (qualitatively abnormal due to alternative processing by kallikrein 5 / stratum corneum tryptic enzyme)
   • TLR2 activation → upregulates kallikrein 5 in keratinocytes → aberrant cathelicidin → inflammation + vascular dilation
   • When cathelicidin peptides from rosacea patients are injected into mice - they induce rosacea-like changes
2. Neurovascular dysregulation
   • Abnormal vasomotor response to thermal and other stimuli
   • Chronic vasodilation → edema → compromise of lymphatic drainage → telangiectasia + fibrosis
3. Chronic solar damage
   • Important especially in ETR subtype; dermal matrix and ground substance damage
4. NOT implicated (despite popular belief):
   • Demodex and Helicobacter pylori - extensively investigated; not central to etiology
   • Pilosebaceous/androgen abnormalities - not typically part of pathogenesis (except possibly glandular type)

• Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 158-159
• Andrews' Diseases of the Skin, p. 292-293

Histopathology (Robbins)

• Nonspecific perifollicular infiltrate - lymphocytes + dermal edema + telangiectasia
• Pustular phase: neutrophils colonize follicles; follicle rupture → granulomatous dermal response
• Rhinophyma: hypertrophy of sebaceous glands + follicular plugging by keratotic debris

Ocular Rosacea

• Blepharitis, recurrent chalazion, conjunctivitis
• Keratitis, iritis, episcleritis (sight-threatening)
• Abnormal Schirmer test in 40% of rosacea patients
• Symptoms: gritty, stinging, itchy, burning eyes; photophobia; foreign body sensation
• May precede skin disease - always ask about eye symptoms in rosacea
• Managed by ophthalmologist in conjunction with dermatologist

Treatment

General Measures (All Types)

• Sun protection - broad-spectrum SPF ≥30 daily (most important)
• Identify and avoid individual triggers (food diary, avoid alcohol, spicy foods)
• Gentle non-irritating skincare; avoid harsh cleansers, astringents
• Green-tinted cosmetics to neutralize redness

Topical Therapy (Mild-Moderate)

Ivermectin vs metronidazole: Ivermectin 1% once daily is superior to metronidazole 0.75% twice daily for papulopustular rosacea (multiple RCTs)

Systemic Therapy (Moderate-Severe)

2025 meta-analysis (King et al., PMID: 39239956): Low-dose isotretinoin is effective and safe for rosacea management - particularly for the glandular and papulopustular subtypes unresponsive to antibiotics.

Physical/Laser Treatments

2024 meta-analysis (Zhai et al., PMID: 39240125): Both IPL and PDL are effective for rosacea; IPL may have a slight advantage for erythema reduction, PDL for individual telangiectasia.

Steroid-Induced Rosacea - Special Protocol

1. Stop topical corticosteroid
2. Start topical tacrolimus (calcineurin inhibitor)
3. Cover with short-term oral doxycycline or minocycline (tacrolimus alone can paradoxically worsen flushing)
4. Resolution expected within 2 months

Ocular Rosacea Treatment

• Lid hygiene (warm compresses, lid scrubs)
• Lubricating eye drops
• Topical cyclosporine eye drops
• Oral doxycycline - first-line systemic; improves both skin and eye disease
• Ophthalmology referral for keratitis, iritis, or vision-threatening disease

Key Differentiating Features

Rosacea vs Acne Vulgaris

Rosacea vs SLE Malar Rash

Exam High-Yield Summary

• Andrews' Diseases of the Skin, pp. 291-295
• Goldman-Cecil Medicine 2-Volume Set, p. 4452-4457
• Robbins, Cotran & Kumar Pathologic Basis of Disease, pp. 158-164
• King et al., J Eur Acad Dermatol Venereol 2025 [PMID: 39239956] - low-dose isotretinoin for rosacea
• Zhai et al., J Cosmet Dermatol 2024 [PMID: 39240125] - IPL vs PDL meta-analysis

Nikolsky Sign, Pseudo-Nikolsky Sign & Related Signs

Nikolsky Sign (True / Direct)

Definition

Mechanism

How to Elicit

• Apply gentle lateral tangential pressure with a finger on:
  • Normal-looking skin adjacent to a lesion (perilesional)
  • Can also be elicited by rubbing normal uninvolved skin in active disease
• Positive = epidermis peels off/shears sideways → denuded dermis
• Negative = skin stays intact

Level of Split

• Intraepidermal (above the basement membrane)
• Blister roof = very thin (just the superficial epidermis)
• Blisters are therefore flaccid (thin-walled, easily ruptured)

Diseases Where Nikolsky Sign is POSITIVE

Important: In TEN/SJS - Nikolsky sign is positive but the split is subepidermal (at dermal-epidermal junction due to full-thickness necrosis), unlike pemphigus where it is intraepidermal. Still a positive sign clinically.

• Dermatology 2-Volume Set 5e, p. 2333-2334; 2012-2014

Diseases Where Nikolsky Sign is NEGATIVE

Key rule: Flaccid blisters = Nikolsky positive (intraepidermal, thin roof) | Tense blisters = Nikolsky negative (subepidermal, thick roof = full epidermis)

Asboe-Hansen Sign (= Indirect Nikolsky / Nikolsky II Sign)

Definition

Mechanism

Also called

• Indirect Nikolsky sign
• Nikolsky II sign
• Bulla-spread phenomenon

Positive in

• Pemphigus vulgaris (classic)
• TEN (the flaccid blisters extend sideways with thumb pressure - "wet cigarette paper" sign)
• Dermatology 2-Volume Set 5e, p. 2334

Pseudo-Nikolsky Sign (False Nikolsky Sign)

Definition

Key Feature

• The split is not intraepidermal acantholysis
• It is caused by pre-formed toxin-mediated cleavage or necrotic epidermis already detached

Classic Example: SSSS vs TEN

Why SSSS is "pseudo": The epidermis splits because a circulating toxin has already enzymatically cleaved desmoglein 1 throughout the skin. Lateral pressure reveals this pre-existing cleavage plane. There is no active acantholysis happening at that moment - the split was already created by the toxin. Hence it simulates, but is not identical to, true Nikolsky sign.

Complete Summary Table

High-Yield One-Liners for Exams

1. Nikolsky sign = lateral pressure on normal skin → epidermis peels - seen in pemphigus, SJS, TEN, SSSS
2. Negative Nikolsky = bullous pemphigoid (tense blisters, subepidermal, BP180/BP230 antibodies)
3. Asboe-Hansen sign = pressure on intact bulla → fluid spreads laterally = also called Nikolsky II
4. SSSS Nikolsky = pseudo - toxin (exfoliatin) cleaves desmoglein 1 subcorneally; no true acantholysis
5. SSSS vs TEN differentiator: SSSS = no mucosal involvement, subcorneal split, children; TEN = mucosal involvement, full-thickness necrosis, adults
6. Flaccid blister → Nikolsky + | Tense blister → Nikolsky -
7. Tzanck smear (acantholytic cells) = confirms true Nikolsky diseases (pemphigus); absent in SSSS and TEN

• Dermatology 2-Volume Set 5e (Pemphigus Vulgaris section, p. 2333-2334; TEN section, p. 2012-2028)
• Henry's Clinical Diagnosis and Management by Laboratory Methods (BP section)
• Fitzpatrick's Dermatology (SSSS section)
• K.J. Lee's Essential Otolaryngology

Session Summary - Dermatology Topics Covered

1. Acne Vulgaris (Full Coverage)

Mild → Topical retinoid ± BPO
Moderate → Topical combo + Oral doxycycline
Severe → Isotretinoin
Female → Add OCP / Spironolactone

2. Acne Scarring Treatment (Recent Evidence 2023-2025)

3. Eccrine Gland

• Crystallina = stratum corneum (most superficial, clear vesicles)
• Rubra = stratum spinosum (prickly heat, red, itchy)
• Profunda = DEJ (flesh-colored, tropics)

4. Rosacea

• Central facial erythema + telangiectasia + flushing
• NO comedones (key difference from acne)
• Rhinophyma = almost exclusively men
• Pathogenesis: abnormal cathelicidin → TLR2 → kallikrein 5

5. Nikolsky Sign

• SSSS = children, no mucosa, subcorneal split, antibiotics
• TEN = adults, mucosa involved, full-thickness necrosis, stop drug

Master Exam Table - "DOC" Facts

False (Pseudo) Nikolsky Sign — Deep Dive

The Core Concept

Usage 1: SSSS (Most Classic "Pseudo-Nikolsky")

What happens in SSSS

• Staphylococcus aureus phage group II (types 55, 71) produces exfoliative toxin A and B (ET-A, ET-B)
• These toxins are serine proteases that specifically cleave desmoglein 1 (DSG-1) in the granular layer
• The toxin reaches the skin hematogenously from a distant focus (e.g., nasopharynx, conjunctiva, umbilicus in neonates)
• The split is already created chemically throughout the skin before you ever touch the patient

Why it is "pseudo/false"

• You are NOT causing acantholysis - the toxin already did it
• You are merely revealing a pre-existing cleavage plane
• There is no inflammatory infiltrate in the blister (sterile blister fluid)
• No acantholytic cells on Tzanck smear (unlike true pemphigus)
• Biopsy: subcorneal split within/just below stratum granulosum, paucity of inflammatory cells

So "positive Nikolsky" in SSSS = FALSE/PSEUDO Nikolsky

• Fitzpatrick's Dermatology (SSSS section); histology: intraepidermal cleavage within stratum granulosum, no leukocytes in blister

Usage 2: Bullous Pemphigoid (BP) — Pseudo-Nikolsky Phenomenon

• When pressure is applied to a tense bulla in BP, the blister does NOT spread laterally (unlike pemphigus)
• However, occasionally the blister roof can be sheared off giving an appearance superficially similar to Nikolsky
• This is NOT true Nikolsky because:
  • There is no intraepidermal acantholysis
  • The split is subepidermal (below the basement membrane zone)
  • The intact epidermis above the split is full thickness and thick - it cannot be spread laterally
  • True Nikolsky = negative in BP

Direct Comparison: True vs Pseudo Nikolsky

The 3 Nikolsky-Type Signs — Complete Exam Table

Key Histology Comparison (Exam Favourite)

Critical differentiator: SSSS and Pemphigus foliaceus both split at the same level (subcorneal/granular layer), but:

• SSSS = no acantholysis, no inflammatory cells, toxin-mediated
• Pemphigus foliaceus = true acantholysis, inflammatory cells, autoantibody-mediated

One-Liners for MCQs

1. Pseudo/False Nikolsky = SSSS - toxin pre-cleaves DSG-1; no true acantholysis
2. SSSS blister culture = sterile (toxin acts remotely from distant infection focus)
3. SSSS Tzanck smear = negative (no acantholytic cells)
4. Bullous pemphigoid = Nikolsky NEGATIVE (tense blisters, subepidermal, full epidermis intact)
5. SSSS vs PF: same split level (subcorneal) but SSSS = no acantholysis, no inflammation in blister
6. Asboe-Hansen = pressure on intact bulla → fluid spreads = Nikolsky II = indirect Nikolsky
7. Toxin in SSSS = Exfoliative toxin A/B, serine protease, cleaves desmoglein 1 specifically