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Eczema (Atopic Dermatitis) — Comprehensive Review

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1. Definition & Overview

Harrison's Principles of Internal Medicine, 21st Ed., p. 1520

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2. Classification of Eczema

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3. Epidemiology

• Affects ~15–30% of children and 2–10% of adults globally
• Prevalence increasing in developed nations (hygiene hypothesis)
• Onset: >50% present before age 1, >85% before age 5
• ~70% have spontaneous remission by adolescence; 30% persist into adulthood
• Equal sex prevalence in childhood; slight female predominance in adults

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4. Etiology & Risk Factors

Genetic Factors

• Filaggrin (FLG) gene mutations — most significant genetic risk factor; impairs skin barrier integrity (loss-of-function variants in ~30% of European AD patients)
• Family history of AD, asthma, or allergic rhinitis
• HLA associations

Immunologic Factors

• Th2-skewed immune response in acute phase → elevated IL-4, IL-5, IL-13, IL-31, IgE
• Th1 response in chronic phase
• Defective regulatory T-cell function
• Elevated serum IgE in ~80% of patients

Environmental Factors

• Aeroallergens: house dust mites, pollen, pet dander
• Food allergens (especially in children): eggs, milk, peanuts, wheat, soy
• Harsh soaps, detergents, wool fabrics, sweat
• Climate: low humidity, extreme temperatures
• Stress, infections (Staph. aureus colonization)

The "Outside-In" vs "Inside-Out" Debate

• Outside-In: Barrier defect (FLG mutation) allows allergen penetration → sensitization → inflammation
• Inside-Out: Immune dysregulation is primary → leads to barrier dysfunction
• Current consensus: both operate simultaneously

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5. Pathophysiology

Genetic susceptibility (FLG mutation, etc.)
        ↓
Defective skin barrier
        ↓
Increased transepidermal water loss (TEWL)
        ↓
Allergen/irritant/microbe penetration
        ↓
Keratinocyte release of TSLP, IL-25, IL-33
        ↓
Activation of innate lymphoid cells (ILC2) + dendritic cells
        ↓
Th2 polarization → IL-4, IL-13 → IgE class switching
                → IL-31 → PRURITUS (key mediator)
                → IL-5 → eosinophilia
        ↓
Chronic: Th2 + Th22 + Th1 mixed → lichenification

• Superantigen release (SAgs)
• Staphylococcal proteases disrupting FLG
• Toxin-induced Th2 skewing

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6. Clinical Features & Diagnosis

Atopic Dermatitis: Update on Skin-Directed Management, p. 2

Diagnostic Criteria (Hanifin & Rajka / UK Working Party)

1. Pruritus (itch is mandatory)
2. Typical morphology and distribution (flexural involvement in adults; face/extensor in infants)
3. Chronic or chronically relapsing course
4. Personal or family history of atopy

Age-Based Distribution

Important: In darkly pigmented skin, erythema may be subtle; dyspigmentation and follicular eczema are more prominent features. (AD: Update on Skin-Directed Management, p. 2)

Clinical Image

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7. Severity Assessment

SCORAD (SCORing Atopic Dermatitis)

• Combines extent (rule of nines), intensity (6 items: erythema, edema, oozing, excoriation, lichenification, dryness), and subjective symptoms (itch, sleep loss)
• Score: <25 = mild, 25–50 = moderate, >50 = severe

EASI (Eczema Area and Severity Index)

• Assesses 4 body regions × 4 signs (erythema, edema/papulation, excoriation, lichenification)
• Range 0–72; widely used in clinical trials

IGA (Investigator's Global Assessment)

• 5-point scale (0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, 4 = severe)
• Used as primary endpoint in drug trials

POEM (Patient-Oriented Eczema Measure)

• 7-question patient-reported outcome; most useful for real-world monitoring

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8. Investigations

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9. Differential Diagnosis

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10. Management

Step 1 — Education & Trigger Avoidance (ALL patients)

• Patient/parent education on chronic disease course
• Identify and avoid personal triggers (allergens, irritants, stress)
• Avoid wool, harsh soaps, extreme temperatures
• Nail cutting to reduce scratch damage

Step 2 — Baseline Skincare (Emollients)

• Emollients are the cornerstone of all AD management
• Apply liberally (at least 250–500 g/week in adults) and frequently (2–3×/day)
• Best applied within 3 minutes of bathing ("soak and seal")
• Types: ointments (most occlusive, best for dry skin), creams, lotions
• Reduces TEWL, restores barrier, decreases flare frequency
• Preferred: fragrance-free, preservative-free formulations

Step 3 — Topical Anti-inflammatory Therapy

Topical Corticosteroids (TCS) — First-line for flares

Topical Calcineurin Inhibitors (TCIs) — Steroid-sparing

• Tacrolimus 0.03% / 0.1% ointment — moderate-to-severe AD; approved ≥2 years
• Pimecrolimus 1% cream — mild-to-moderate AD; approved ≥2 years
• Preferred for: face, eyelids, skin folds, genitalia (sensitive sites)
• No skin atrophy risk
• Side effect: transient burning/stinging on first application
• Black box warning: theoretical malignancy risk (not proven in long-term studies)

Topical PDE4 Inhibitors

• Crisaborole 2% ointment — mild-to-moderate AD; approved ≥3 months
• Non-steroidal; inhibits PDE4 → ↓ cAMP degradation → ↓ inflammatory cytokines

Topical JAK Inhibitors (newer)

• Ruxolitinib 1.5% cream — mild-to-moderate AD; approved ≥12 years
• Fast onset of itch relief; safe short-term profile

Step 4 — Adjunct Therapies

Step 5 — Systemic Therapy (Moderate-to-Severe)

Biologics (Targeted)

• Significant reduction in EASI, IGA, pruritus scores
• Side effects: injection site reactions, conjunctivitis (10–20%), facial redness
• Safe in pregnancy (Category B equivalent)

Oral JAK Inhibitors

Conventional Immunosuppressants (when biologics unavailable)

Step 6 — Allergen Immunotherapy

• Subcutaneous or sublingual immunotherapy for house dust mite-sensitized AD
• Emerging evidence; not yet standard of care

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11. Management of Special Situations

Infected Eczema (Eczema Herpeticum)

• Caused by HSV-1/2 spreading over eczematous skin
• Clinical: sudden widespread punched-out vesicles/erosions, fever, malaise
• Treatment: IV/oral acyclovir — urgent; can be life-threatening

Eczema in Pregnancy

• Dupilumab: preferred biologic (limited data but favorable safety profile)
• TCS: use lowest effective potency; avoid very potent on large areas
• Avoid systemic retinoids, methotrexate

Eczema in Infants

• Focus on emollients, mild TCS, avoid TCIs in <2 years
• Dupilumab approved from 6 months of age

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12. Case Study

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Case Presentation

• Asthma (on salbutamol PRN, low-dose inhaled corticosteroid)
• Allergic rhinitis (on cetirizine)
• Food allergy: egg (outgrown by age 4)

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Physical Examination

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Investigations

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Diagnosis

1. Severe Atopic Dermatitis (SCORAD 58, POEM 22)
2. Secondary bacterial infection — MSSA on right forearm
3. Atopic triad — AD + Asthma + Allergic Rhinitis

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Management Plan

Immediate (Acute Phase)

• Oral cefalexin 25 mg/kg/day divided q8h for 7 days (MSSA infection)
• Topical mupirocin 2% ointment TDS to right forearm for 5 days
• Bleach baths (0.005% NaOCl) 3×/week to reduce S. aureus burden

• Fragrance-free emollient ointment (e.g., Epaderm, white soft paraffin) — apply liberally 3–4 times daily
• Soak-and-seal technique after bathing

• Mometasone furoate 0.1% cream (moderate-potent) to lichenified body plaques OD for 2 weeks, then proactive 2×/week
• Tacrolimus 0.03% ointment to face, neck, and skin folds BD (steroid-sparing, no atrophy risk)

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Escalation (Week 2–4, Inadequate Response to Topicals)

• Loading dose: 600 mg SC (two 300 mg injections), then 300 mg SC every 4 weeks (pediatric dosing, 15–30 kg)
• Counseling: injection technique, watch for conjunctivitis

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Long-Term Plan

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Outcome

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13. Complications

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14. Prognosis

• ~60–70% of childhood AD resolves by adolescence
• Persistence predictors: severe early-onset disease, FLG mutations, sensitization to multiple allergens, concurrent asthma
• Adults with persistent AD have significant quality-of-life burden (comparable to psoriasis and diabetes)
• With biologics (dupilumab), >50% achieve EASI-75 at week 16, transforming the prognosis for moderate-to-severe disease

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Summary Flowchart

ALL patients: Emollients + Trigger Avoidance + Education
        ↓
Mild AD → Low-potency TCS / Pimecrolimus / Crisaborole
        ↓
Moderate AD → Mid-potency TCS + Tacrolimus + Bleach baths
        ↓
Severe AD or inadequate topical response
        ↓
Dupilumab (preferred) OR Oral JAK inhibitor (abrocitinib/upadacitinib)
        ↓
Refractory: Cyclosporine / Methotrexate / NB-UVB

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• Harrison's Principles of Internal Medicine, 21st Ed., p. 1520
• Atopic Dermatitis: Update on Skin-Directed Management, p. 2
• NICE Guideline NG190: Atopic Eczema in Under 12s (2023)
• AAD Guidelines on Management of AD (2023)
• EDF/EADV Consensus on Systemic Treatment of AD (2022)