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Clinical Variants of Acne & Treatment of Severe Acne Vulgaris

PART A: CLINICAL VARIANTS OF ACNE

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1. Age-Based Variants

Neonatal Acne (Neonatal Cephalic Pustulosis)

• Onset: First 4 weeks of life
• Erythematous papules and pustules on the face (cheeks, forehead, chin)
• Pathogenesis: Overgrowth of Malassezia species (not true acne); stimulation by maternal androgens
• True comedones are absent; self-limiting, resolves in weeks

Infantile Acne

• Onset: 2–12 months of age
• Comedones are prominent; papules, pustules, and occasionally deep suppurative nodules
• May leave pitted scarring in up to 50% of patients
• Pathogenesis: Elevated LH → testicular testosterone (boys); elevated DHEA from infantile adrenal glands
• Increased risk of severe adolescent acne later
• Treatment: Topical retinoids, benzoyl peroxide; oral erythromycin for inflammatory component; isotretinoin for nodulocystic presentations

Mid-Childhood Acne (Ages 1–7 years)

• Uncommon; mandates evaluation for underlying hyperandrogenism
• Rule out: premature adrenarche, congenital adrenal hyperplasia, androgen-secreting tumor
• Perform bone age X-ray; complete endocrine evaluation if signs of accelerated growth

Preadolescent Acne (Ages 7–11 years)

• Occurs with onset of adrenarche
• Primarily comedonal; favors forehead and T-zone ("centrofacial")
• PCOS and endocrinopathies considered if unusually severe or with signs of hyperandrogenism

Adolescent Acne (Classic Acne Vulgaris)

• Peak incidence ages 12–24 years; affects ~85% of young people
• Full morphological spectrum: comedones, papules, pustules, nodules, cysts
• White males more prone to nodulocystic disease

Adult/Post-Adolescent Acne

• Predominantly affects women beyond 25 years of age
• Mandibular/lower face distribution in ~80%
• Associated with psychological stress, premenstrual flares, PCOS, hyperandrogenism
• A predominantly comedonal form associated with smoking ("smoker's acne") is described

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2. Severity-Based Variants

Acne Conglobata

• Severe form predominantly in males; presents with grouped comedones (often double or triple), large interconnected nodules, abscesses, draining sinuses, and severe scarring
• Distribution: face, neck, chest, back, buttocks, upper arms
• Associated with: SAPHO syndrome, PAPA syndrome (pyogenic arthritis, pyoderma gangrenosum, acne conglobata), PASH syndrome (PG, acne, hidradenitis suppurativa)
• Some cases associated with XYY karyotype
• Treatment: Oral isotretinoin is drug of choice; intralesional corticosteroids for individual nodules

Acne Fulminans

• Most severe form of acne; uncommon
• Primarily affects boys aged 13–16 years
• Abrupt onset of nodular suppurative lesions with systemic manifestations
• Lesions coalesce into painful, friable, hemorrhagic crusted plaques; ulcerate and scar
• Systemic features: Fever, arthralgia, myalgia, hepatosplenomegaly, malaise; erythema nodosum
• Laboratory: Elevated ESR, leukocytosis, proteinuria, anemia
• Bone lesions: Osteolytic lesions of clavicle, sternum, ankles (SAPHO)
• Associated with: Late-onset congenital adrenal hyperplasia, anabolic steroid use, therapeutic testosterone; paradoxically may be triggered by initiation of isotretinoin
• Treatment: Oral prednisolone 0.5–1 mg/kg/day for 2–4 weeks as monotherapy → add low-dose isotretinoin 0.1 mg/kg/day → gradually taper prednisolone and increase isotretinoin over 1–2 months

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3. Special Subtypes

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PART B: TREATMENT OF SEVERE ACNE VULGARIS (10 Marks)

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Definition of Severe Acne

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1. Pathogenesis Targets (Rationale for Treatment)

1. Correcting altered follicular keratinization → retinoids
2. Decreasing sebaceous gland activity → isotretinoin, antiandrogens
3. Reducing follicular bacterial population (Cutibacterium acnes) → antibiotics, benzoyl peroxide
4. Exerting anti-inflammatory effect → antibiotics, corticosteroids, isotretinoin

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2. Topical Medications (Adjunctive in Severe Acne)

• Tretinoin (0.025–0.1% cream/gel), Adapalene (0.1–0.3% gel), Tazarotene (0.05–0.1%)
• Mechanism: Comedolytic + anti-inflammatory; normalize follicular keratinization
• Used as maintenance therapy even after oral isotretinoin
• Adapalene: most tolerable; photostable; targets RAR-γ

• 2.5–10% (gel, wash, cream)
• Bactericidal; reduces C. acnes; no resistance development
• Prevents antibiotic resistance when used with oral/topical antibiotics
• Essential in combination regimens

• Clindamycin 1%, erythromycin 2%
• Never as monotherapy; always combine with BPO to prevent resistance

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3. Systemic Antibiotics

• First-line oral antibiotics for severe inflammatory acne: Doxycycline (50–100 mg BD), Minocycline (50–100 mg BD), Sarecycline (newly approved)
• Mechanism: Suppress C. acnes growth; intrinsic anti-inflammatory via downregulation of TNF, IL-1, IL-6
• Always combine with topical retinoid ± BPO
• Limit to 3–4 months; never as monotherapy (resistance prevention)
• Alternate: Azithromycin (pulse therapy 500 mg × 3 days/week) where tetracyclines contraindicated (children, pregnancy)
• Trimethoprim-sulfamethoxazole: reserved for resistant cases (gram-negative folliculitis)

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4. Isotretinoin — Drug of Choice for Severe Acne

• Severe nodulocystic/conglobata acne
• Acne causing significant scarring
• Acne failing conventional therapy
• Acne with severe psychosocial impact

• Duration: Usually 16–24 weeks
• Cumulative dose of 120–150 mg/kg associated with the lowest relapse rate
• Twice-daily administration with fatty meal improves bioavailability

• Reduces sebaceous gland size and sebum production by up to 90%
• Normalizes follicular keratinization
• Anti-inflammatory
• Reduces C. acnes colonization indirectly

• Baseline: LFTs, fasting lipids, pregnancy test (females)
• Monthly: Pregnancy test; lipids at 4–8 weeks

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5. Hormonal Therapy (Females)

• Oral contraceptive pills: FDA-approved formulations include ethinyl estradiol/norgestimate (Ortho Tri-Cyclen), ethinyl estradiol/drospirenone (Yaz), and ethinyl estradiol/norethindrone (Estrostep)
• Spironolactone: 50–200 mg/day; androgen receptor blocker; 66% achieve ≥90% improvement; monitor for hyperkalemia, irregular menses; teratogenic (avoid in pregnancy)
• Cyproterone acetate: Antiandrogen (combined with ethinyl estradiol as Diane-35); 75–90% show substantial improvement; not available in the US
• Clinical response takes 3–6 months

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6. Physical and Procedural Modalities

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7. Treatment of Acne Conglobata

• First-line: Oral isotretinoin 0.5–1 mg/kg/day to cumulative dose 120–150 mg/kg
• Intralesional triamcinolone for large nodules
• Adjunctive: High-dose oral antibiotics + topical retinoid + BPO
• Refractory cases: Dapsone 50–100 mg/day; biologic agents (adalimumab) being studied

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8. Treatment of Acne Fulminans

1. Step 1 (weeks 1–4): Oral prednisolone 0.5–1 mg/kg/day as monotherapy — to control systemic inflammation before introducing retinoids
2. Step 2 (week 4 onwards): Add low-dose isotretinoin 0.1 mg/kg/day while continuing prednisolone
3. Step 3 (weeks 8–12): Gradually increase isotretinoin dose; slowly taper prednisolone over 1–2 months
4. Important: Isotretinoin must NOT be started alone — it can paradoxically trigger/worsen acne fulminans in the first weeks of therapy

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9. Maintenance Therapy

• Topical retinoid ± BPO (or combination product: adapalene-BPO)
• Prevents recurrence by maintaining comedolytic effect
• Reduces need for retreatment

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Summary Algorithm for Severe Acne (Dermatology 5e)

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• Dermatology 2-Volume Set, 5th Edition (Elsevier/Bolognia) — Chapter 36: Acne Vulgaris
• Fitzpatrick's Dermatology, 9th Edition — Chapter 78: Management of Acne Vulgaris
• Andrews' Diseases of the Skin, 13th Edition — Acne conglobata/fulminans