Atopic Eczema

1. Clinical Overview

Summary

Atopic eczema (atopic dermatitis, AD) is a chronic, relapsing inflammatory skin condition characterised by intense pruritus and eczematous lesions with typical age-dependent distribution patterns. It is the most common chronic skin disease worldwide, affecting up to 20% of children and 3% of adults in developed countries. [1] Atopic eczema is part of the "atopic march" alongside asthma and allergic rhinitis, with 60% of patients developing these conditions. [2]

The underlying pathophysiology involves a complex interplay of epidermal barrier dysfunction (commonly associated with filaggrin mutations), type 2 immune dysregulation (Th2-predominant response with IL-4, IL-13, IL-31 overexpression), skin microbiome dysbiosis (Staphylococcus aureus colonisation), and neurogenic inflammation. [3] This triad of barrier defect, immune dysregulation, and microbial imbalance creates the characteristic itch-scratch cycle that perpetuates disease.

Management centres on restoring and maintaining skin barrier integrity with liberal emollient use (250-500g/week), reducing inflammation with topical corticosteroids or calcineurin inhibitors, and avoiding triggers. Moderate-to-severe cases require step-up therapy including phototherapy, systemic immunomodulators (ciclosporin, methotrexate, azathioprine), or targeted biologics. Dupilumab, an anti-IL-4/IL-13 receptor antibody, represents a paradigm shift in severe disease management with significant efficacy and favourable safety profile. [4] JAK inhibitors (baricitinib, upadacitinib, abrocitinib) offer additional therapeutic options for refractory disease. [5]

Key Facts

• Prevalence: 15-20% of children; 2-3% of adults; increasing in industrialised nations [1]
• Age of onset: 60% before 1 year; 85% before 5 years; bimodal peak (infancy and adulthood) [6]
• Atopic triad: Eczema precedes asthma (60%) and allergic rhinitis (50%) [2]
• Key genetic factor: Filaggrin (FLG) loss-of-function mutations in 20-50% of moderate-severe cases [7]
• Treatment cornerstone: Emollients (≥250g/week) + topical corticosteroids (step-wise approach)
• Life-threatening complications: Eczema herpeticum (3-5% of AD patients); bacterial sepsis; erythroderma [8]
• Quality of life impact: Equivalent to other chronic diseases (diabetes, epilepsy); significant sleep disturbance (2-3 hours/night lost) [9]

Clinical Pearls

"The Itch That Rashes": Eczema pruritus precedes the rash. Scratching causes lichenification and perpetuates inflammation. Breaking the itch-scratch cycle through effective anti-pruritic therapy (topical anti-inflammatories, emollients, antihistamines at night) is fundamental to management. IL-31 is the "itch cytokine" responsible for neurogenic pruritus. [10]

Emollients Are Not Optional: Emollients restore the lipid barrier and are the foundation of all treatment. Patients should use 250-500g per week (adults); 500g weekly usage correlates with reduced flare frequency. Ointments (greasier) are superior to creams for severely dry skin due to greater occlusion and fewer preservatives. [11]

The Fingertip Unit (FTU) Rule: One FTU = 0.5g of cream/ointment from the distal interphalangeal joint to fingertip. 1 FTU covers two adult hand palms (approximately 2% BSA). Use this to guide topical steroid dosing and ensure adequate emollient application.

Filaggrin Deficiency = Barrier Breakdown: Filaggrin mutations (null alleles) reduce natural moisturising factors (NMF), increase transepidermal water loss (TEWL), elevate skin pH, and facilitate allergen penetration. FLG mutation carriers have 3-fold increased AD risk and more severe, persistent disease. [7]

Staph aureus Thrives in AD Skin: 90% of AD lesions are colonised with S. aureus (vs 5% healthy skin). Bacterial toxins act as superantigens, driving Th2 inflammation and IgE production. This creates a vicious cycle: barrier defect → colonisation → inflammation → further barrier damage. [12]

Red Flag: Eczema Herpeticum: Punched-out monomorphic erosions with haemorrhagic crusting, fever, and malaise in AD patient = eczema herpeticum (disseminated HSV). This is a dermatological emergency requiring IV aciclovir and admission. Mortality 10% if untreated. [8]

Why This Matters Clinically

Atopic eczema causes profound morbidity beyond visible skin lesions. Sleep deprivation from nocturnal pruritus affects neurocognitive development in children and work productivity in adults. Chronic inflammation drives systemic effects including elevated cardiovascular risk, mental health disorders (anxiety, depression in 30%), and increased infection susceptibility. [13] Patient education, treatment adherence, and early recognition of complications are essential to prevent long-term sequelae and improve quality of life. The emergence of targeted biologics and JAK inhibitors has transformed outcomes for severe disease previously requiring systemic immunosuppression.

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2. Epidemiology

Incidence & Prevalence

• Children: 15-20% in developed countries (UK, USA, Australia); 10-15% in developing regions [1]
• Adults: 2-3% (most are childhood-onset with persistence; 10-30% of childhood cases persist) [6]
• Lifetime prevalence: Up to 20% globally
• Trend: 2-3 fold increase in prevalence over past 30 years in industrialised nations (hygiene hypothesis) [14]
• Incidence: 230 per 100,000 person-years (children); 40 per 100,000 (adults)

Demographics

Risk Factors

Natural History

• Resolution: 60-70% of childhood AD resolves by adolescence [6]
• Persistence: 10-30% persist into adulthood; severe early disease and FLG mutations predict persistence
• Remission: Relapsing-remitting pattern; 40% experience flares as adults even after apparent resolution
• Atopic march: AD → food allergy (30-40%) → asthma (60%) → allergic rhinitis (50%) [2]

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3. Aetiology & Pathophysiology

Atopic eczema results from a complex interplay of genetic susceptibility, epidermal barrier dysfunction, immune dysregulation, and environmental triggers. The pathophysiology can be conceptualised as three interconnected pillars: barrier defect, type 2 inflammation, and microbiome dysbiosis. [3]

Genetic Factors

Filaggrin (FLG) Gene Mutations

• Function: Filaggrin aggregates keratin filaments, generating natural moisturising factors (NMF: amino acids, urocanic acid, pyrrolidone carboxylic acid)
• Mutations: Loss-of-function alleles (R501X, 2282del4 most common in Europeans) present in 20-50% of moderate-severe AD [7]
• Consequences:
  • Reduced NMF → decreased stratum corneum hydration
  • Increased transepidermal water loss (TEWL)
  • Elevated skin pH (promotes protease activity → further barrier damage)
  • Enhanced allergen penetration → immune sensitisation
  • Increased risk of eczema herpeticum, asthma, and food allergy
• Clinical correlation: FLG null genotype associates with early onset, severe, persistent AD and atopic comorbidities [7]

Other Genetic Loci

• Immune genes: IL-4, IL-13, IL-31, TSLP (thymic stromal lymphopoietin) promoter variants
• Barrier genes: SPINK5 (serine protease inhibitor), claudin-1, loricrin
• Heritability: 75-80% based on twin studies; polygenic inheritance pattern

Epidermal Barrier Dysfunction

Step 1: Structural Defects

• Filaggrin deficiency → impaired keratinocyte differentiation and cornified envelope formation
• Lipid abnormalities: Reduced ceramides (especially ceramide 1 and 3), free fatty acids, and cholesterol in stratum corneum [16]
• Tight junction disruption: Decreased claudin-1 and occludin expression
• Protease/antiprotease imbalance: Elevated kallikreins (KLK5, KLK7) degrade barrier proteins

Step 2: Functional Consequences

• Increased TEWL: 2-3 fold higher than normal skin; xerosis (dry skin)
• Elevated skin pH: 5.5-6.0 (normal 4.5-5.0); promotes bacterial colonisation and protease activity
• Allergen penetration: Epicutaneous sensitisation to foods, aeroallergens, microbes
• Loss of antimicrobial peptides: Reduced β-defensins, cathelicidin (LL-37) → infection susceptibility [17]

Immune Dysregulation

Type 2 Inflammation (Acute Phase)

• Th2 cell activation: IL-4, IL-13, IL-5 drive eosinophilia and IgE production
• IL-31: "Itch cytokine" activates sensory neurons → pruritus [10]
• IL-25, IL-33, TSLP: Alarmins released by keratinocytes amplify Th2 response
• Consequences:
  • IgE-mediated allergen sensitisation (elevated serum IgE in 80%)
  • Eosinophil infiltration (acute lesions)
  • Mast cell degranulation (histamine release)
  • Inhibition of antimicrobial peptides and filaggrin expression [17]

Chronic Inflammation

• Th1 and Th22 activation: Chronic lesions show mixed Th2/Th1/Th22 profile
• IL-22: Induces keratinocyte hyperplasia → lichenification
• IFN-γ: Contributes to chronicity and epidermal thickening
• Dendritic cell dysfunction: Impaired viral defence in eczema herpeticum-prone patients [8]

Microbiome Dysbiosis

Staphylococcus aureus Colonisation

• Prevalence: 90% of AD lesions; 70% of non-lesional skin (vs 5% in controls) [12]
• Mechanisms:
  • Reduced skin pH and antimicrobial peptides create niche for S. aureus
  • Bacterial adhesion to fibronectin and fibrinogen (damaged barrier)
  • Biofilm formation protects from immune clearance
• Pathogenic effects:
  • "Superantigens (enterotoxins A, B, TSST-1): Non-specific T cell activation → massive cytokine release"
  • "α-toxin: Keratinocyte damage, barrier disruption, promotes HSV infection [8]"
  • "Proteases: Degrade barrier proteins"
  • "Th2 skewing: Toxins drive IL-4/IL-13 production and IgE elevation"

Reduced Microbiome Diversity

• AD skin shows decreased bacterial diversity (Shannon index 2.5 vs 4.0 in healthy skin)
• Loss of commensal Staphylococcus epidermidis, Cutibacterium, Corynebacterium species
• S. epidermidis produces antimicrobial peptides that normally inhibit S. aureus [12]

The Itch-Scratch Cycle

Initiation of Pruritus

• IL-31: Binds IL-31 receptor on sensory neurons → itch sensation [10]
• TSLP, IL-4, IL-13: Activate pruritogenic pathways
• Histamine: Mast cell mediator (lesser role in AD vs urticaria)
• Neuropeptides: Substance P, nerve growth factor (NGF) amplify itch

Perpetuation by Scratching

• Physical trauma → keratinocyte damage → release of alarmins (IL-33, IL-25)
• Barrier disruption → increased TEWL, allergen entry
• Nerve fiber proliferation in epidermis (intraepidermal nerve fiber density increased 2-fold)
• Lichenification: Chronic scratching → epidermal hyperplasia and thickening

Clinical Consequence

• Sleep disturbance (average 2-3 hours lost per night) [9]
• Psychological distress amplifies itch perception (central sensitisation)
• Secondary infection from excoriation and bacterial inoculation

Distribution Patterns by Age

The age-dependent distribution reflects changes in skin anatomy, mechanical stress, and immune maturation:

Classification of AD Phenotypes

By IgE Status

• Extrinsic (IgE-associated): 70-80% of cases; elevated serum IgE, allergen sensitisation, early onset
• Intrinsic (non-IgE): 20-30%; normal IgE, later onset, less atopic comorbidity

By Age of Onset

• Early-onset (< 2 years): Better prognosis; 60% resolution by adolescence
• Late-onset (adult): More persistent; associated with occupational factors (hand eczema)

By Severity (EASI/SCORAD)

• Mild: < 20% BSA, EASI < 7, intermittent symptoms
• Moderate: 20-50% BSA, EASI 7-21, frequent flares
• Severe: 50% BSA, EASI 21, continuous symptoms despite treatment

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4. Clinical Presentation

Cardinal Features (UK Working Party Diagnostic Criteria)

Essential Feature

• Pruritus: Hallmark symptom; intensity often correlates poorly with visible inflammation; worse at night (circadian rhythm of cytokine release and transepidermal water loss) [10]

Plus 3 or More of:

1. History of flexural involvement (antecubital/popliteal fossae, wrists, ankles, neck)
2. History of dry skin (xerosis) in past year
3. Onset before age 2 years
4. Visible flexural dermatitis (or cheek/forehead/extensor involvement if < 4 years)
5. Personal history of asthma or allergic rhinitis (or first-degree relative if < 4 years)

Sensitivity/Specificity: 85%/96% for AD diagnosis [18]

Symptoms

Signs: Acute Eczema

• Erythema: Ill-defined pink-red patches
• Oedema: Epidermal spongiosis (intercellular oedema)
• Papules and vesicles: Small fluid-filled blisters (spongiotic vesicles)
• Exudate and crusting: Serous weeping; honey-coloured crust if secondarily infected (S. aureus)
• Excoriations: Linear scratch marks; sign of active pruritus
• Scaling: Fine desquamation

Signs: Chronic Eczema

• Lichenification: Thickened, leathery skin with accentuated skin markings (chronic scratching)
• Fissuring: Painful linear cracks (especially hands, feet, eyelids)
• Dyspigmentation: Post-inflammatory hyperpigmentation (darker skin types) or hypopigmentation (pityriasis alba)
• Scaling: Coarse, dry scale
• Papules: Persistent, flesh-coloured papules (prurigo nodularis pattern in severe cases)

Stigmata of Atopy (Associated Features)

• follicular keratotic papules on upper arms, thighs | 40-50% | | Anterior neck folds | Horizontal creases on anterior neck | 30-40% | | Allergic shiners | Dark circles under eyes (venous congestion from chronic allergic inflammation) | 60% | | White dermographism | White line after stroking skin (paradoxical vasoconstriction vs normal red flare) | 70% | | Ichthyosis vulgaris | Fine scaling (especially legs); associated with FLG mutations | 20-30% | | Hyperlinear palms | Accentuated palmar creases | 30-40% | | Cheilitis | Dry, fissured, inflamed lips | 20-30% |

Complications Requiring Urgent Assessment

[!CAUTION] Red Flags — Urgent Dermatology/ED Assessment Required:

Eczema Herpeticum (Kaposi Varicelliform Eruption) [8]

• Punched-out monomorphic erosions (2-3mm) with haemorrhagic crusting
• Rapid onset (< 48 hours); painful rather than pruritic
• Distribution: face, neck, trunk most common
• Systemic features: fever (38-40°C), malaise, lymphadenopathy
• Complications: keratoconjunctivitis, meningitis, disseminated HSV
• Management: IV aciclovir 10mg/kg TDS (400mg/m² TDS in children); admit for monitoring; eye exam if periorbital involvement
• Mortality: 10% if untreated; < 1% with early IV aciclovir

Bacterial Superinfection/Sepsis

• Widespread weeping, crusting (honey-coloured), pustules
• Fever, tachycardia, lethargy, poor feeding (infants)
• Pathogens: S. aureus (90%), β-haemolytic Streptococcus
• Management: Flucloxacillin 500mg QDS PO (or IV if septic); skin swab for culture

Erythroderma

• 90% BSA involvement; generalised erythema, scaling, oedema
• Thermoregulatory instability, high-output cardiac failure, protein loss
• Management: Hospital admission; emollients, topical steroids, treat infection; monitor fluid balance, temperature, cardiac status

Failure to Thrive (Infants)

• Weight loss or static weight; inadequate caloric intake (pain/itch), protein loss (exudative lesions), hypermetabolism (inflammation)
• Assess growth trajectory, nutritional intake, psychosocial factors

Severe, Treatment-Resistant Disease

• No response to potent topical corticosteroids after 2-4 weeks
• Consider: non-adherence, contact allergy (to emollients/steroids), misdiagnosis (psoriasis, CTCL, immunodeficiency), need for systemic therapy

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5. Clinical Examination

Structured Approach

General Inspection

• Distribution pattern: Note age-appropriate distribution (extensor vs flexural)
• Body surface area (BSA): Estimate using patient's palm = 1% BSA (rule of nines for extensive disease)
• Severity assessment: Erythema intensity, excoriation, lichenification, exudate
• Signs of infection: Crusting, pustules, erythema spreading beyond eczema borders
• Symmetry: AD typically bilateral and symmetrical (vs contact dermatitis often asymmetrical)

Skin Examination

• Acute lesions: Erythema, oedema, vesicles, exudate, excoriations
• Chronic lesions: Lichenification, fissures, dyspigmentation, scaling
• Non-lesional skin: Xerosis, ichthyosis, keratosis pilaris (reflects underlying barrier defect)

Stigmata of Atopy

• Face: Dennie-Morgan folds, allergic shiners, periorbital darkening, Hertoghe sign, cheilitis
• Eyes: Conjunctival erythema (allergic conjunctivitis), eyelid eczema, keratoconus (chronic rubbing)
• Nails: Shiny nails (chronic rubbing), nail pitting (psoriasis differential)
• General: White dermographism, hyperlinear palms

Examination for Complications

• Infection: Pustules, honey-coloured crust, folliculitis, lymphadenopathy
• Eczema herpeticum: Monomorphic punched-out erosions, grouped vesicles, haemorrhagic crust
• Contact allergy: Sudden worsening, localised pattern (e.g., preservative allergy to emollient)
• Psychological impact: Assess mood, sleep quality, school/work impact

Severity Scoring Tools

Severity Categories

• Mild: EASI < 7, SCORAD < 25, POEM < 7, IGA 1-2 → Topical therapy
• Moderate: EASI 7-21, SCORAD 25-50, POEM 8-16, IGA 3 → Step-up to potent topicals ± second-line
• Severe: EASI 21, SCORAD 50, POEM 16, IGA 4 → Consider systemic therapy

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6. Differential Diagnosis

Key Differentials

Red Flags for Alternative Diagnosis

• Onset at birth or in neonatal period (consider ichthyosis, immunodeficiency)
• Severe disease with recurrent infections (immunodeficiency syndromes)
• Poor response to standard therapy (consider CTCL, contact allergy, non-adherence)
• Systemic features (fever, lymphadenopathy, hepatosplenomegaly)
• Unusual distribution (exclusively sun-exposed areas, genital-only)

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7. Investigations

Clinical Diagnosis

Atopic eczema is a clinical diagnosis based on history and examination. Investigations are not routinely required but are indicated for:

• Diagnostic uncertainty
• Severe, refractory disease
• Suspected complications (infection, contact allergy)
• Pre-treatment screening (systemic therapy)

UK Working Party Diagnostic Criteria (Clinical)

Must have: Pruritus Plus ≥3 of:

1. Onset before age 2
2. History of flexural involvement
3. History of dry skin (xerosis) in past year
4. Personal history of atopy (or FH if < 4 years)
5. Visible flexural eczema (or cheek/extensor if < 4 years)

Sensitivity 85%, Specificity 96% [18]

Investigations When Indicated

When NOT to Investigate

• Typical childhood AD with good response to treatment → no investigations needed
• Routine IgE/allergy testing without clear trigger history → low yield, risk of false positives leading to unnecessary dietary restrictions

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8. Management

The management of atopic eczema follows a stepwise approach based on severity, with emollients forming the foundation at all stages. The goal is to restore skin barrier function, reduce inflammation, prevent flares, and minimise complications. [20]

Management Algorithm

                        ATOPIC ECZEMA MANAGEMENT
                                  ↓
┌────────────────────────────────────────────────────────────────┐
│  FOUNDATION: EMOLLIENTS (ALL PATIENTS, ALL STAGES)             │
│  - Use liberally: 250-500g/week (adults), 500g+ (children)     │
│  - Ointments > creams for very dry skin                        │
│  - Apply 2-4× daily minimum (ideally after bathing)            │
│  - Continue even when skin clear (maintenance)                 │
└────────────────────────────────────────────────────────────────┘
                                  ↓
┌────────────────────────────────────────────────────────────────┐
│  STEP 1: MILD DISEASE (EASI less than 7, less than 20% BSA, IGA 1-2)            │
├────────────────────────────────────────────────────────────────┤
│  - Emollients (foundation)                                     │
│  - MILD topical corticosteroids (face/flexures)                │
│    • Hydrocortisone 1% BD for 5-7 days                        │
│  - MODERATE topical corticosteroids (body)                     │
│    • Clobetasone 0.05% BD for 7-14 days                       │
│  - Trigger avoidance (soap → substitutes)                      │
│  - Patient education (itch-scratch cycle, application)         │
└────────────────────────────────────────────────────────────────┘
                                  ↓
┌────────────────────────────────────────────────────────────────┐
│  STEP 2: MODERATE DISEASE (EASI 7-21, 20-50% BSA, IGA 3)      │
├────────────────────────────────────────────────────────────────┤
│  - Emollients + POTENT topical corticosteroids                 │
│    • Betamethasone valerate 0.1% BD for 7-14 days (body)      │
│    • Moderate TCS for face (clobetasone 0.05%)                 │
│  - Consider TOPICAL CALCINEURIN INHIBITORS (steroid-sparing)   │
│    • Tacrolimus 0.03% (children), 0.1% (adults) BD             │
│    • Pimecrolimus 1% BD (milder disease)                       │
│    • Use for face, eyelids, flexures (steroid atrophy risk)    │
│  - Treat infection if present (flucloxacillin)                 │
│  - Sedating antihistamines PRN (night-time itch)               │
│  - Bandages/wet wraps (if severe excoriation)                  │
└────────────────────────────────────────────────────────────────┘
                                  ↓
┌────────────────────────────────────────────────────────────────┐
│  STEP 3: SEVERE DISEASE (EASI > 21, > 50% BSA, IGA 4)           │
│          OR INADEQUATE RESPONSE TO STEP 2                      │
├────────────────────────────────────────────────────────────────┤
│  - Emollients + potent/very potent TCS                         │
│  - PHOTOTHERAPY (if 12 years, no photosensitivity)           │
│    • Narrowband UVB 3× weekly × 12 weeks                       │
│  - SYSTEMIC IMMUNOSUPPRESSION (short-term)                     │
│    • Ciclosporin 2.5-5 mg/kg/day (rapid control, max 2 years) │
│    • Methotrexate 7.5-25 mg weekly (slower onset)              │
│    • Azathioprine 1-3 mg/kg/day (steroid-sparing)              │
│  - BIOLOGIC THERAPY (first-line for severe chronic disease)    │
│    • Dupilumab 600mg loading, then 300mg SC Q2W                │
│      (IL-4/IL-13 inhibitor; gold standard for severe AD)       │
│  - JAK INHIBITORS (severe refractory disease)                  │
│    • Baricitinib 2-4mg PO daily                                │
│    • Upadacitinib 15-30mg PO daily                             │
│    • Abrocitinib 100-200mg PO daily                            │
└────────────────────────────────────────────────────────────────┘
                                  ↓
┌────────────────────────────────────────────────────────────────┐
│  MAINTENANCE STRATEGY (PROACTIVE THERAPY)                      │
├────────────────────────────────────────────────────────────────┤
│  - Daily emollients (continue indefinitely)                    │
│  - Weekend maintenance TCS (applied 2×/week to previously      │
│    affected areas to prevent relapse)                          │
│  - OR Tacrolimus 2×/week (face, flexures)                      │
│  - Trigger avoidance, education, psychosocial support          │
└────────────────────────────────────────────────────────────────┘

1. Emollients (Foundation of All Treatment)

Emollients restore the lipid barrier, increase stratum corneum hydration, reduce TEWL, and decrease need for topical corticosteroids. [11]

Examples:

• Ointments: Emulsifying ointment, 50:50 white soft paraffin/liquid paraffin, Epaderm
• Creams: Diprobase, Doublebase, Cetraben, Aveeno
• Lotions: E45 lotion, QV lotion

Application

• Frequency: Minimum 2-4× daily; apply within 3 minutes after bathing (trap moisture)
• Quantity: 250-500g/week for adults; 500g+/week for children with moderate-severe disease [11]
• Technique: Apply in direction of hair growth (reduce folliculitis risk); gentle downward strokes (not rubbing)
• Timing: Apply emollient first, wait 15-30 minutes, then apply TCS (debate exists; some apply TCS first)

Patient Education

• "You cannot use too much emollient" — liberal use is essential
• Soap substitutes (aqueous cream, emulsifying ointment) for washing (soap strips lipids)
• Avoid sharing pots (infection risk); use pump dispensers or spoon/spatula
• Flare-ups often due to under-use of emollients or switching to less greasy formulation

2. Topical Corticosteroids (TCS)

TCS reduce inflammation via multiple mechanisms: suppress cytokine production, inhibit immune cell migration, induce vasoconstriction. [20]

Potency Classification

Application Principles

• Fingertip Unit (FTU): 1 FTU = 0.5g (from distal interphalangeal joint to fingertip)
  • 1 FTU covers 2 adult hand palms (~2% BSA)
  • "Face/neck: 2.5 FTU"
  • "One arm: 3 FTU"
  • "One leg: 6 FTU"
  • "Trunk (front or back): 7 FTU"
• Frequency: BD (once daily may suffice for potent/very potent TCS)
• Duration: Short bursts (5-14 days for acute flare); step down to lower potency as improves; avoid abrupt cessation (rebound)
• Sites: Use lowest potency that controls disease; face/flexures = mild-moderate only; body = moderate-potent; palms/soles = potent-very potent

Step-Down Strategy

1. Start with appropriate potency for severity and site
2. Apply BD until improvement (7-14 days)
3. Step down to lower potency OR reduce frequency (e.g., BD → OD → alternate days)
4. Transition to weekend maintenance (2×/week) to prevent relapse [20]

Side Effects

• Local: Skin atrophy (striae, telangiectasia, purpura), perioral dermatitis, acne, rosacea, hypopigmentation
• Systemic (rare, with very potent TCS or occlusion): HPA axis suppression, Cushing syndrome, growth suppression (children), glaucoma (periorbital use)
• Prevention: Use lowest effective potency; avoid very potent TCS on face/flexures; limit very potent TCS to < 50g/week or 2 weeks continuous use

Steroid Phobia

• 70% of patients/parents fear TCS side effects → under-treatment → poor control
• Education: Appropriate use is safe; risk of under-treatment > risk of appropriate TCS use
• Written action plans with clear duration/potency instructions improve adherence

3. Topical Calcineurin Inhibitors (TCIs)

Non-steroidal anti-inflammatory agents; inhibit calcineurin → block T-cell activation and cytokine release. [21]

Advantages over TCS

• No skin atrophy → safe for face, eyelids, flexures, long-term use
• Proactive maintenance (2×/week) reduces flare frequency by 50%
• Safe in children 2 years

Application

• Apply BD to affected areas until clear, then 2×/week maintenance
• Can use with TCS (apply to different sites or alternate days)
• Initial stinging/burning (warn patients); resolves within 1 week in 80%

Black Box Warning (FDA/MHRA)

• Theoretical cancer risk (lymphoma, skin cancer) based on animal studies and immunosuppressed transplant patients
• Real-world data: No increased malignancy risk in AD patients after 10+ years follow-up [21]
• Advice: Avoid on malignant/pre-malignant skin lesions; use sun protection

Cost: More expensive than TCS; may require prior authorisation/specialist initiation

4. Phototherapy

Narrowband UVB (NB-UVB): First-line phototherapy for AD

Indications

• Moderate-severe AD inadequately controlled with topical therapy
• Age 12 years (impractical in young children due to compliance)
• Widespread disease (20% BSA)

Regimen

• 3× weekly (e.g., Mon-Wed-Fri) for 12-24 weeks
• Start with 70% minimal erythema dose (MED), increase by 20% each session if no erythema
• Expect improvement by week 4-6

Efficacy

• 60-70% achieve 50% improvement (EASI-50)
• Mechanism: Immunomodulation (Th2 suppression), induction of apoptosis in infiltrating T cells, vitamin D synthesis

Side Effects

• Short-term: Erythema (sunburn), pruritus, xerosis
• Long-term: Photoaging, increased melanoma/non-melanoma skin cancer risk (cumulative dose-dependent)
• Contraindications: Photosensitive disorders (lupus, porphyria), history of melanoma, immunosuppression

Alternatives

• UVA1: Deeper penetration; used in severe acute flares (less available)
• PUVA (psoralen + UVA): Higher efficacy but greater side effects; third-line

5. Systemic Immunosuppressants

Reserved for severe, refractory AD uncontrolled by topical therapy and phototherapy.

A. Ciclosporin (Cyclosporine)

Mechanism: Calcineurin inhibitor → blocks IL-2 production → T-cell suppression

Indications: Severe AD requiring rapid control; bridge to biologics

Dosing

• 2.5-5 mg/kg/day PO in 2 divided doses
• Start low (2.5 mg/kg), increase by 0.5 mg/kg every 2 weeks to max 5 mg/kg
• Onset: Rapid (improvement within 2-4 weeks)
• Duration: Short-term (3-6 months); max 2 years (nephrotoxicity risk)

Monitoring

• Baseline: BP, U&E, creatinine, LFTs, lipids, FBC, urinalysis
• Monthly: BP, U&E, creatinine (stop if creatinine ↑30% from baseline)
• 3-monthly: FBC, LFTs, lipids

Side Effects

• Nephrotoxicity: Dose-dependent; usually reversible if detected early
• Hypertension: 10-20% (monitor BP monthly)
• Infections: Bacterial, viral (HSV, VZV reactivation)
• Malignancy: Lymphoma, skin cancer (long-term use)
• Other: Gingival hyperplasia, hirsutism, tremor, paraesthesia, GI upset

Contraindications: CKD, uncontrolled hypertension, active infection, malignancy, pregnancy

B. Methotrexate

Mechanism: Folate antagonist → inhibits DNA synthesis → immunosuppression and anti-inflammatory effects

Indications: Moderate-severe AD; steroid-sparing; slower onset than ciclosporin (use when rapid control not needed)

Dosing

• Adults: 7.5-25 mg PO/SC once weekly (usually start 10-15 mg)
• Children: 0.2-0.4 mg/kg once weekly (max 25 mg)
• Folic acid: 5 mg once weekly (different day from methotrexate, e.g., take MTX Monday, folic acid Thursday)
• Onset: 6-12 weeks
• Duration: Can use long-term (years) with monitoring

Monitoring

• Baseline: FBC, U&E, LFTs (especially ALT), hepatitis B/C serology, chest X-ray (if risk factors for TB), pregnancy test
• Monthly × 3 months, then 2-3 monthly: FBC (macrocytosis, cytopenias), LFTs (transaminitis)

Side Effects

• Hepatotoxicity: Transaminitis (10-30%); cirrhosis (rare, cumulative dose 1.5g)
• Myelosuppression: Leukopenia, thrombocytopenia, anaemia (check FBC regularly)
• GI: Nausea (30%), stomatitis (take folic acid to reduce)
• Pulmonary: Pneumonitis (rare, 1-5%; presents with dry cough, dyspnoea)
• Teratogenicity: Contraindicated in pregnancy; stop 3-6 months before conception

Contraindications: Pregnancy, breastfeeding, significant liver disease, alcoholism, renal impairment

C. Azathioprine

Mechanism: Purine analogue → inhibits DNA synthesis → suppresses T and B cell proliferation

Indications: Moderate-severe AD; steroid-sparing; alternative to methotrexate

Dosing

• 1-3 mg/kg/day PO (usually start 1 mg/kg, titrate up)
• Check TPMT (thiopurine methyltransferase) before starting:
  • Normal/high activity → standard dose
  • Intermediate activity → reduce dose by 50%
  • Low/absent activity → avoid (severe myelosuppression risk)
• Onset: 6-12 weeks
• Duration: Long-term (years)

Monitoring

• Baseline: FBC, U&E, LFTs, TPMT genotype/phenotype
• Weekly × 4 weeks, then monthly × 3 months, then 3-monthly: FBC, LFTs

Side Effects

• Myelosuppression: Dose-dependent; especially in low TPMT activity
• Hepatotoxicity: Transaminitis, cholestasis
• GI: Nausea, vomiting, diarrhoea (take with food)
• Infections: Bacterial, viral, fungal
• Malignancy: Lymphoma, skin cancer (long-term use)

Contraindications: Pregnancy (teratogenic), low/absent TPMT activity

6. Biologic Therapy

Dupilumab (Dupixent)

Mechanism: Fully human monoclonal antibody against IL-4 receptor alpha (IL-4Rα) → blocks IL-4 and IL-13 signalling → inhibits Th2 inflammation [4]

Indications

• Moderate-to-severe AD inadequately controlled by topical therapy
• Adults and children ≥6 months (FDA approved; check local licensing)
• First-line systemic therapy in many guidelines due to efficacy and safety profile

Dosing

• Adults: 600 mg SC loading dose (two 300 mg injections), then 300 mg SC every 2 weeks (Q2W)
• Children (6 months-5 years): Weight-based (200 mg Q4W if < 15 kg; 300 mg Q4W if ≥15 kg)
• Children/adolescents (6-17 years): Weight-based Q2W or Q4W regimen
• Self-injection: Pre-filled syringe or pen; can be administered at home

Efficacy

• SOLO 1 & 2 trials [4]: 16 weeks monotherapy
  • "IGA 0-1 (clear/almost clear): 38% dupilumab vs 10% placebo (p< 0.001)"
  • "EASI-75: 51% dupilumab vs 15% placebo (p< 0.001)"
  • "Pruritus NRS ≥4-point improvement: 41% vs 12% (p< 0.001)"
  • "Onset: Pruritus improvement within 1-3 days; skin lesions improve by week 2-4"
• Long-term data: Sustained efficacy and safety up to 3 years

Side Effects

• Conjunctivitis: 10-20% (most common AE); usually mild; manage with lubricant eye drops; refer ophthalmology if severe/persistent
• Injection site reactions: 10%; usually mild and transient
• Eosinophilia: Transient; rarely clinically significant
• Herpes simplex: Reduced frequency vs placebo (blocks Th2-mediated HSV reactivation)
• Overall: Excellent safety profile; no routine lab monitoring required (unlike traditional immunosuppressants)

Advantages

• Targeted mechanism (Th2 blockade) → less systemic immunosuppression than ciclosporin/methotrexate
• No routine blood monitoring (unlike ciclosporin, methotrexate, azathioprine)
• Can use long-term (years)
• Rapid onset (itch improvement within days)
• Also treats asthma and nasal polyps (bonus if comorbid)

Cost: Expensive (£10,000-15,000/year); requires prior authorisation; NICE approved for severe AD failing topical therapy

7. JAK Inhibitors (Janus Kinase Inhibitors)

Newer class targeting intracellular signalling pathways (JAK-STAT) involved in multiple cytokines (IL-4, IL-13, IL-31, IFN-γ). [5]

Approved Agents

Efficacy

• BREEZE-AD7 (baricitinib 4mg) [5]: EASI-75 at week 16: 48% vs 15% placebo
• Measure Up 1&2 (upadacitinib 30mg): IGA 0-1: 48-52% vs 8-16% placebo
• Rapid onset: Improvement in pruritus within 1-2 days (faster than dupilumab)

Side Effects & Black Box Warning (FDA)

• Serious infections: TB reactivation, herpes zoster (8-10%), opportunistic infections
• Thromboembolism: VTE risk (especially tofacitinib in RA patients 50 years + CV risk factors)
• Cardiovascular events: MI, stroke (tofacitinib RA data; unclear if applies to dermatology)
• Malignancy: Lymphoma, lung cancer (long-term data limited in AD)
• Cytopenias: Anaemia, neutropenia, lymphopenia (monitor FBC)
• Lipid abnormalities: Elevated LDL/HDL (monitor lipids)
• Common: Upper respiratory infections, nasopharyngitis, nausea, headache, acne

Monitoring

• Baseline: TB screening (IGRA/TST, chest X-ray), hepatitis B/C serology, FBC, LFTs, lipids, pregnancy test
• 4 weeks: FBC (cytopenias)
• 12 weeks, then 3-monthly: FBC, lipids, LFTs
• Annual: Skin cancer screening (NMSC risk)

Contraindications

• Active serious infection, TB
• Severe hepatic impairment
• Pregnancy, breastfeeding
• Absolute neutropenia (< 1.0 × 10⁹/L), lymphopenia (< 0.5 × 10⁹/L), Hb < 8 g/dL

Place in Therapy

• Second-line after dupilumab failure OR patients needing rapid symptom control (faster onset than dupilumab)
• Oral administration may be preferred by some patients (vs SC injection)
• Concerns about long-term safety (black box warning) limit first-line use

8. Adjunctive Therapies

Antibiotics (Secondary Infection)

Indications: Clinical signs of bacterial superinfection (honey-coloured crusting, weeping, pustules, fever, sudden worsening)

Topical Antibiotics

• Fusidic acid 2%: BD for 7 days (limited role; resistance concerns)
• Usually avoided due to resistance; systemic antibiotics preferred if infection significant

Systemic Antibiotics

• Flucloxacillin: 500 mg QDS PO × 7-14 days (adults); 12.5-25 mg/kg QDS (children)
• If penicillin allergy: Clarithromycin 500 mg BD or doxycycline 100 mg BD
• If MRSA: Doxycycline or co-trimoxazole (check sensitivities)
• Skin swab before starting antibiotics (to guide therapy, check for MRSA)

Controversial: Antibiotics Without Clinical Infection

• Routine use in AD exacerbation without overt infection is not recommended (no benefit, promotes resistance) [20]
• Antiseptic baths (dilute bleach baths, see below) may reduce S. aureus burden without antibiotics

Antiseptic Baths (Bleach Baths)

Rationale: Reduce S. aureus colonisation without antibiotics

Regimen

• Add sodium hypochlorite (bleach) to bath water: 0.005% solution (equivalent to swimming pool chlorination)
  • "Standard full bath (100 litres): Add 40 mL household bleach (5% sodium hypochlorite)"
  • "Half-bath: 20 mL bleach"
• Soak for 5-10 minutes, 2× weekly
• Rinse with clean water, pat dry, apply emollient immediately

Evidence: Mixed; some studies show reduced infection/flares, others no benefit. NICE does not routinely recommend. [20]

Safety: Avoid if skin very broken/weeping (stinging); rare allergic contact dermatitis to chlorine

Antihistamines

Sedating antihistamines (for nocturnal pruritus/sleep disturbance)

• Promethazine (Phenergan): 10-25 mg PO at bedtime (adults); 5-10 mg (children 2-5 yrs)
• Hydroxyzine: 25 mg at bedtime (adults)
• Chlorphenamine: 4 mg at bedtime (adults)
• Evidence: Limited efficacy for itch (histamine not primary mediator in AD); sedative effect may improve sleep
• Duration: Short-term only (tolerance develops; daytime drowsiness)

Non-sedating antihistamines (cetirizine, loratadine)

• No proven benefit for AD itch (itch is IL-31/neuropeptide-mediated, not histamine)
• May help if comorbid urticaria or allergic rhinitis

Wet Wrap Therapy

Technique: Apply emollient ± diluted TCS, cover with wet bandages, then dry bandages overnight

Indications: Severe, widespread, excoriated eczema; acute flares; children

Method

1. Apply generous emollient (or diluted TCS: e.g., 1:10 dilution of potent TCS with emollient)
2. Apply wet tubular bandages (e.g., Tubifast soaked in warm water and wrung out)
3. Apply dry layer of tubular bandages over wet layer
4. Leave overnight (8-12 hours); remove in morning
5. Duration: 3-14 days (not long-term)

Benefits: Cooling, rehydration, occlusion (enhances TCS absorption), physical barrier to scratching

Risks: Maceration, secondary infection, increased TCS absorption (use diluted TCS or emollient only)

Dietary Modification

When to Consider

• Young children (< 5 years) with moderate-severe AD AND clear history of immediate reaction to specific food (urticaria, angioedema, anaphylaxis after ingestion)
• Confirmed food allergy on testing (specific IgE or oral food challenge)

Common Culprits: Milk, egg, peanut, wheat, soy, fish

Evidence: Only beneficial if true IgE-mediated food allergy (10-30% of young children with moderate-severe AD). Elimination diets without confirmed allergy do NOT improve AD and risk malnutrition. [20]

Recommendation: Do NOT routinely restrict diet; refer to allergy specialist if suspected food trigger

9. Managing Complications

Eczema Herpeticum

Recognition: Punched-out erosions (2-3mm), grouped vesicles, haemorrhagic crust, rapid onset, painful, fever [8]

Management

1. Admit to hospital (dermatology/paediatrics)
2. IV aciclovir 10 mg/kg TDS (adults 5 mg/kg TDS; higher dose in children due to better renal clearance)
3. Viral swab/PCR (confirm HSV; result should not delay treatment)
4. Ophthalmology review if periorbital involvement (keratitis risk)
5. Systemic antibiotics if secondary bacterial infection
6. Continue emollients; avoid topical corticosteroids until healing (may worsen viral replication; debated)
7. Duration: IV aciclovir until no new lesions (typically 5-7 days), then switch to PO aciclovir/valaciclovir to complete 10-14 days

Prevention: Avoid contact with active HSV lesions (cold sores); consider suppressive aciclovir if recurrent eczema herpeticum

Prognosis: Mortality < 1% with early treatment; 10% if untreated; risk of dissemination (visceral organs), keratitis, meningitis

Bacterial Superinfection

Management

• Flucloxacillin 500 mg QDS × 7-14 days PO (or IV if septic)
• Skin swab for culture and sensitivities
• Continue emollients and topical anti-inflammatories
• If recurrent infections: consider antiseptic baths, nasal decolonisation (mupirocin ointment to nares BD × 5 days)

Erythroderma

Management

• Hospital admission
• Emollients liberally; gentle topical corticosteroids (avoid very potent; risk of systemic absorption)
• Monitor temperature, fluid balance, cardiac status (high-output failure risk)
• Treat infection
• Avoid triggers (stop any new medications)

10. Trigger Avoidance & Lifestyle Modifications

Note: Allergen avoidance only if proven relevance (positive test + clear clinical correlation). Unnecessary avoidance (e.g., eliminating foods without evidence) is harmful.

Proactive vs Reactive Therapy

Reactive (Traditional)

• Emollients daily; apply TCS only when flare occurs; stop when clear
• Problem: Subclinical inflammation persists → frequent relapses

Proactive (Recommended) [20]

• Emollients daily; use TCS/TCI 2× weekly on previously affected areas even when skin appears clear
• Evidence: Reduces flare frequency by 50%, prolongs remission, reduces TCS burden overall
• Regimen: After acute flare controlled, continue TCS 2×/week (e.g., weekend therapy: Saturday and Wednesday) to high-risk sites (flexures, hands, previously severe areas)
• Safety: Long-term weekend TCS (moderate potency) or tacrolimus 2×/week is safe and effective [20,21]

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9. Complications

Immediate/Acute Complications

Chronic Complications

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10. Prognosis & Outcomes

Natural History

Prognostic Factors

Quality of Life Impact

• Sleep deprivation: 60% report sleep disturbance; average 2-3 hours lost/night in severe cases [9]
• QoL scores: DLQI comparable to psoriasis, diabetes, epilepsy
• Work/school: Absenteeism (10-20 days/year in moderate-severe AD); impaired concentration
• Mental health: 30% comorbid anxiety/depression [13]; increased suicidal ideation in severe AD
• Economic burden: £297-500 million annually (UK NHS); indirect costs (lost work) exceed direct medical costs

Long-Term Outcomes with Modern Therapies

• Dupilumab: Sustained efficacy up to 3 years; 40-50% maintain EASI-75; excellent safety profile; transforms severe AD prognosis [4]
• JAK inhibitors: Rapid symptom relief (days); long-term safety data still emerging (concerns re: malignancy, VTE) [5]
• Proactive maintenance TCS/TCI: Reduces flare frequency by 50%; prolongs remission [20,21]

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11. Prevention & Screening

Primary Prevention (Prevention of AD Onset)

Evidence for Strategies

Secondary Prevention (Prevention of Flares in Established AD)

Proactive Maintenance Therapy [20]

• Daily emollients (250-500g/week)
• Weekend TCS (2×/week) to previously affected areas → reduces flares by 50%
• Tacrolimus 2×/week maintenance (face, flexures) → reduces flares, steroid-sparing [21]

Trigger Avoidance

• Soap substitutes, avoid irritants, manage stress, treat infection promptly
• Only avoid allergens if proven relevance (unnecessary avoidance harmful)

Screening (No Routine Screening for AD)

Screening for Complications in Established AD

• Eczema herpeticum risk: No specific screening; educate patients on recognition (punched-out lesions, rapid onset, pain); avoid contact with active HSV
• Eye complications: Ophthalmology review if visual symptoms, periorbital eczema, chronic rubbing (keratoconus risk)
• Growth monitoring: All children with moderate-severe AD (plot weight/height)
• Mental health: Assess anxiety/depression at each visit (30% prevalence) [13]
• Allergy screening: Only if clear history suggestive of food/aeroallergen trigger; do NOT routinely test (high false positive rate)

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12. Evidence & Guidelines

Key Guidelines

1. NICE NG57: Atopic Eczema in Under 12s (2007, updated 2021) [20]

   • UK standard for diagnosis and management
   • Stepwise approach: emollients → TCS → TCI → referral
   • Recommends against routine dietary restriction, routine allergy testing, probiotics
   • nice.org.uk/guidance/ng57

2. BAD Guidelines: Atopic Eczema (2024 update) [British Association of Dermatologists]

   • Comprehensive UK guidance for all ages
   • Evidence grading for all interventions
   • Proactive maintenance therapy recommended

3. AAD Guidelines: Atopic Dermatitis (2014, update in progress) [American Academy of Dermatology]

   • Evidence-based recommendations for US practice
   • Includes phototherapy, systemic therapy

4. EADV Guidelines: Atopic Eczema (European) [European Academy of Dermatology and Venereology]

   • European consensus; similar to NICE but broader systemic therapy guidance

5. JAK Inhibitor Safety Guidance (FDA/EMA 2021-2022)

   • Black box warning for VTE, malignancy, CV events based on tofacitinib RA data
   • Applies to all JAK inhibitors; relevance to dermatology unclear

Landmark Trials & Systematic Reviews

1. Dupilumab SOLO 1 & 2 Trials (2016) [4]

• Simpson EL, et al. N Engl J Med. 2016;375:2335-2348. PMID: 27690741
• Design: Two identical phase 3 RCTs; 1379 adults with moderate-severe AD; dupilumab 300mg weekly/Q2W vs placebo × 16 weeks
• Primary outcome: IGA 0-1 + ≥2-point improvement: 38% dupilumab Q2W vs 10% placebo (p< 0.001)
• Secondary outcomes: EASI-75: 51% vs 15%; pruritus NRS ≥4-point improvement: 41% vs 12%
• Safety: Conjunctivitis (10%), injection site reactions (10%) more common; AD exacerbation and infections less common than placebo
• Impact: First biologic approved for AD; transformed severe AD management

2. Filaggrin Mutations and AD Meta-analysis (2011) [7]

• Rodríguez E, et al. J Allergy Clin Immunol. 2009;124:507-13. PMID: 19733298
• Meta-analysis: FLG null mutations (R501X, 2282del4) increase AD risk 3-fold (OR 3.12, 95% CI 2.6-3.8)
• FLG mutations associate with early onset, severe, persistent AD and atopic comorbidities (asthma, allergic rhinitis)
• Established genetic basis for barrier dysfunction in AD

3. Emollients Cochrane Review (2017) [11]

• van Zuuren EJ, et al. Cochrane Database Syst Rev. 2017. PMID: 28166390
• Systematic review of emollients for eczema
• Finding: Emollients reduce TEWL, improve barrier function, reduce TCS use; limited data on optimal type/frequency
• Recommendation: Regular emollient use is cornerstone of therapy; patient preference important (adherence)

4. Tacrolimus Cochrane Review (2015) [21]

• Cury Martins J, et al. Cochrane Database Syst Rev. 2015. PMID: 26086818
• Systematic review: Tacrolimus effective for moderate-severe AD; comparable to moderate-potent TCS; safe for face/flexures
• Long-term safety: No increased malignancy risk in real-world data (10+ years follow-up)

5. Atopic Dermatitis Pathogenesis (Nature Reviews, 2018) [3]

• Weidinger S, et al. Nat Rev Dis Primers. 2018;4:1. PMID: 29930242
• Comprehensive review: AD pathophysiology involves barrier defect (filaggrin), Th2 inflammation (IL-4/IL-13/IL-31), microbiome dysbiosis (S. aureus), neuroinflammation (itch)
• Framework for understanding disease and targeted therapies

6. Eczema Herpeticum in AD (Allergy, 2021) [8]

• Traidl S, et al. Allergy. 2021;76:3017-3027. PMID: 33844308
• Review: EH affects 3-5% AD patients; HSV-1 (95%); mortality 10% untreated
• Risk factors: FLG mutations, severe AD, Type 2 skewing, impaired IFN response
• Dupilumab reduces EH risk (blocks Th2-mediated viral susceptibility)

7. JAK Inhibitors Safety in Dermatology (2023) [5]

• Samuel C, et al. Dermatol Ther (Heidelb). 2023;13:729-749. PMID: 36790724
• Review: JAK inhibitor safety in dermatology patients
• VTE rates 0-0.5% (similar to placebo); serious infections 0.4-4.8%; NMSC 0-0.9%
• Most AEs in patients with baseline risk factors; dermatology safety profile better than RA

8. Global S. aureus Antimicrobial Susceptibility in AD (2024) [12]

• Elizalde-Jimenez IG, et al. JAMA Dermatol. 2024;160:1171-1181. PMID: 39320869
• Systematic review & meta-analysis: 4091 S. aureus isolates from AD patients
• Antimicrobial susceptibility: methicillin 85%, erythromycin 73%, clindamycin 79%, fusidic acid 80%
• Implication: Empirical antibiotic choice should consider local resistance patterns; MRSA in 15%

9. Rhinitis Prevalence and Association with AD (2021) [2]

• Meta-analysis: Rhinitis prevalence 40.5% in AD patients vs 18% controls (OR 2.9)
• Supports "atopic march" concept; AD precedes allergic rhinitis in 50%

10. Skin Microbiome in AD (2020)

• Edslev SM, et al. Acta Derm Venereol. 2020;100:adv00164. PMID: 32419029
• Review: AD skin shows 90% S. aureus colonisation (vs 5% healthy); reduced diversity
• S. aureus virulence factors (superantigens, α-toxin) drive Th2 inflammation
• Filaggrin deficiency promotes S. aureus colonisation

Evidence Strength Summary

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13. Patient/Layperson Explanation

What is Atopic Eczema?

Atopic eczema (also called atopic dermatitis or just "eczema") is a very common skin condition that causes dry, itchy, inflamed skin. It often runs in families and is linked with asthma and hay fever (collectively called "atopy"). Eczema affects about 1 in 5 children and 1 in 30 adults.

Why does it happen?

Eczema occurs because:

1. The skin barrier is weaker than normal — your skin loses moisture easily and lets irritants and germs in. Some people have genetic changes (like filaggrin mutations) that make the barrier even weaker.
2. The immune system overreacts — your body's defence system becomes too active, causing redness, swelling, and itching.
3. Bacteria on the skin — a bacterium called Staphylococcus aureus thrives on eczema skin and makes inflammation worse.

Together, these create a vicious cycle: itching leads to scratching, which damages the skin further, causing more inflammation and itching (the "itch-scratch cycle").

What are the symptoms?

• Itching — often severe, worse at night
• Dry, rough skin
• Red, inflamed patches — on the face and body in babies; in the creases (elbows, knees, wrists) in older children and adults
• Weeping or crusting if infected
• Thickened skin from long-term scratching

How is it treated?

There is no cure for eczema, but it can be controlled with the right treatment:

1. Moisturisers (emollients) — THE MOST IMPORTANT TREATMENT

   • Use lots every day (a big tub every 1-2 weeks)
   • Apply at least 2-4 times daily, especially after bathing
   • Ointments (greasier) work better than creams for very dry skin
   • Keep using even when skin looks clear (prevents flare-ups)

2. Steroid creams — Reduce redness and itching during flare-ups

   • Use as directed by your doctor (strength depends on age and location)
   • Apply to inflamed areas only, for short periods (usually 5-14 days)
   • Don't be afraid of steroids — when used correctly, they are safe and essential for controlling flares
   • Not using enough steroid cream is a bigger problem than using too much

3. Other creams — For sensitive areas (face, eyelids) or steroid-sparing:

   • Tacrolimus or pimecrolimus (non-steroid anti-inflammatory creams)
   • Safe for long-term use on the face

4. Avoid triggers:

   • Use soap substitutes (not regular soap or bubble bath)
   • Wear cotton clothing (avoid wool, synthetics)
   • Keep cool (heat and sweating worsen itch)
   • Avoid scratching (keep nails short, consider cotton gloves at night)

5. Stronger treatments (for severe eczema):

   • Light therapy (phototherapy)
   • Tablets or injections that calm the immune system (dupilumab is a very effective injection for severe cases)

What to expect

• Most children with eczema improve as they get older (6 out of 10 are much better by their teens)
• Eczema can come and go throughout life (flare-ups and remissions)
• Good skincare habits (daily moisturising) help control symptoms and reduce flare-ups

When to seek urgent help

Go to A&E or call 111 urgently if:

• There are painful, "punched-out" blisters with fever (may be eczema herpeticum — a serious viral infection needing urgent treatment)
• Widespread weeping, crusting, and fever (may be a bacterial infection)
• Eczema suddenly covers most of the body and your child is unwell
• Eczema is not improving despite treatment, or your child is not gaining weight

Where to get help and support

• National Eczema Society: eczema.org — patient support, helpline, information
• British Association of Dermatologists: bad.org.uk — patient information leaflets
• Your GP, pharmacist, or dermatologist for medical advice

Remember: Eczema is manageable. With the right treatment and skincare routine, most people can keep their eczema under good control and live normal, active lives.

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14. References

Primary Guidelines

1. Deckers IAG, et al. Investigating international time trends in the incidence and prevalence of atopic eczema 1990-2010: a systematic review of epidemiological studies. PLoS One. 2012;7(7):e39803. doi:10.1371/journal.pone.0039803. PMID: 22808063

2. Tsakok T, et al. Does atopic dermatitis cause food allergy? A systematic review. J Allergy Clin Immunol. 2016;137(4):1071-1078. doi:10.1016/j.jaci.2015.10.049. PMID: 26897122

3. Weidinger S, Beck LA, Bieber T, Kabashima K, Irvine AD. Atopic dermatitis. Nat Rev Dis Primers. 2018;4(1):1. doi:10.1038/s41572-018-0001-z. PMID: 29930242

4. Simpson EL, et al. Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis (SOLO 1 and SOLO 2). N Engl J Med. 2016;375(24):2335-2348. doi:10.1056/NEJMoa1610020. PMID: 27690741

5. Samuel C, Cornman H, Kambala A, Kwatra SG. A Review on the Safety of Using JAK Inhibitors in Dermatology: Clinical and Laboratory Monitoring. Dermatol Ther (Heidelb). 2023;13(3):729-749. doi:10.1007/s13555-023-00892-5. PMID: 36790724

6. Margolis JS, et al. Persistence of mild to moderate atopic dermatitis. JAMA Dermatol. 2014;150(6):593-600. doi:10.1001/jamadermatol.2013.10271. PMID: 24696036

7. Rodríguez E, et al. Meta-analysis of filaggrin polymorphisms in eczema and asthma: robust risk factors in atopic disease. J Allergy Clin Immunol. 2009;124(3):507-13. doi:10.1016/j.jaci.2009.06.021. PMID: 19733298

8. Traidl S, Roesner L, Zeitvogel J, Werfel T. Eczema herpeticum in atopic dermatitis. Allergy. 2021;76(10):3017-3027. doi:10.1111/all.14853. PMID: 33844308

9. Ramirez FD, et al. Sleep disturbance in atopic dermatitis: A systematic review. J Am Acad Dermatol. 2019;80(6):1693-1699. doi:10.1016/j.jaad.2018.11.057. PMID: 30529107

10. Ruzicka T, et al. Anti-Interleukin-31 Receptor A Antibody for Atopic Dermatitis. N Engl J Med. 2017;376(9):826-835. doi:10.1056/NEJMoa1606490. PMID: 28249150

11. van Zuuren EJ, et al. Emollients and moisturisers for eczema. Cochrane Database Syst Rev. 2017;2(2):CD012119. doi:10.1002/14651858.CD012119.pub2. PMID: 28166390

12. Elizalde-Jimenez IG, et al. Global Antimicrobial Susceptibility Patterns of Staphylococcus aureus in Atopic Dermatitis: A Systematic Review and Meta-Analysis. JAMA Dermatol. 2024;160(11):1171-1181. doi:10.1001/jamadermatol.2024.3360. PMID: 39320869

13. Rønnstad ATM, et al. Association of atopic dermatitis with depression, anxiety, and suicidal ideation in children and adults: A systematic review and meta-analysis. J Am Acad Dermatol. 2018;79(3):448-456.e30. doi:10.1016/j.jaad.2018.03.017. PMID: 29549960

14. Asher MI, et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys. Lancet. 2006;368(9537):733-743. doi:10.1016/S0140-6736(06)69283-0. PMID: 16935684

15. Silverberg JI, et al. Association Between Adult Atopic Dermatitis, Cardiovascular Disease, and Increased Heart Attacks in Three Population-Based Studies. Allergy. 2015;70(10):1300-1308. doi:10.1111/all.12685. PMID: 26119467

16. Janssens M, et al. Lipid to protein ratio plays an important role in the skin barrier function in patients with atopic eczema. Br J Dermatol. 2014;170(6):1248-1255. doi:10.1111/bjd.12908. PMID: 24655043

17. Ong PY, et al. Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med. 2002;347(15):1151-1160. doi:10.1056/NEJMoa021481. PMID: 12374875

18. Williams HC, et al. The U.K. Working Party's Diagnostic Criteria for Atopic Dermatitis. III. Independent hospital validation. Br J Dermatol. 1994;131(3):406-416. doi:10.1111/j.1365-2133.1994.tb08532.x. PMID: 7918017

19. Leshem YA, et al. What the Eczema Area and Severity Index score tells us about the severity of atopic dermatitis: an interpretability study. Br J Dermatol. 2015;172(5):1353-1357. doi:10.1111/bjd.13662. PMID: 25580670

20. National Institute for Health and Care Excellence (NICE). Atopic eczema in under 12 s: diagnosis and management (NG57). 2021. nice.org.uk/guidance/ng57

21. Cury Martins J, et al. Topical tacrolimus for atopic dermatitis. Cochrane Database Syst Rev. 2015;(7):CD009864. doi:10.1002/14651858.CD009864.pub2. PMID: 26086818

22. Thaçi D, Simpson EL, Deleuran M, et al. Efficacy and safety of dupilumab monotherapy in adults with moderate-to-severe atopic dermatitis: a pooled analysis of two phase 3 randomized trials (LIBERTY AD SOLO 1 and LIBERTY AD SOLO 2). J Dermatol Sci. 2019;94(2):266-275. doi:10.1016/j.jdermsci.2019.02.002. PMID: 31109652

Further Resources

• National Eczema Society: eczema.org
• British Association of Dermatologists: bad.org.uk
• DermNet NZ: dermnetnz.org

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Last Reviewed: 2026-01-09 | MedVellum Editorial Team

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