Atopic Dermatitis

Atopic dermatitis is a chronic, relapsing, pruritic inflammatory skin disease. Prevalence is 15 to 20% in children and 2 to 10% in adults in high-income countries, with onset before age 5 in about 85% and before 1 year in 60%. About 60% of children outgrow it by adolescence, but a significant proportion persist or begin in adulthood.

Pathophysiology

• Skin barrier dysfunction: loss-of-function filaggrin (FLG) mutations (in 20 to 30% of European patients), reduced ceramides, raised transepidermal water loss and elevated skin pH.
• Type 2 immune dysregulation: IL-4, IL-13 and IL-31 drive IgE class switching, eosinophilia, barrier impairment and itch. Chronic disease adds Th1, Th17 and Th22 components. TSLP and IL-33 from keratinocytes initiate the response.
• Microbiome: Staphylococcus aureus colonisation in 70 to 90% of lesional skin with reduced diversity, aggravating inflammation through superantigens and delta toxin.
• Neuroimmune itch circuit and scratching that perpetuates the itch-scratch cycle.
• Triggers: irritants (soap, detergents, wool), allergens (dust mite, pollen, pet dander), infection, sweat, heat, stress, dry climate, and rarely food allergy in young children with severe disease.
• Atopic march: the association with food allergy, allergic rhinitis and asthma. Severe early-onset eczema is a risk marker for peanut allergy. Skin barrier emollient interventions in infancy have not reliably prevented disease.

Complications

Bacterial infection (S. aureus impetiginisation), eczema herpeticum (HSV superinfection, an emergency), eczema coxsackium, molluscum contagiosum (more extensive), sleep loss, ADHD and anxiety or depression association, cataracts and keratoconus, growth effects with severe disease or excessive steroid, and quality of life impact comparable to other major chronic diseases.

Age-dependent patterns

• Infants (under 2 years): erythematous, oozing, crusted patches on cheeks, scalp and extensor limbs, sparing the nappy area.
• Childhood: flexural dermatitis (antecubital and popliteal fossae), neck, wrists and ankles, with lichenification.
• Adolescents and adults: flexural, hands, eyelids, face, neck, with lichenified plaques and prurigo nodules. Hand eczema is common. Head and neck dermatitis (Malassezia sensitisation) can be prominent.

Hallmarks

• Intense pruritus (worse at night), xerosis, excoriations, lichenification, and a chronic relapsing course.
• Minor features: Dennie-Morgan infraorbital folds, hyperlinear palms, keratosis pilaris, pityriasis alba, periorbital darkening, nipple eczema, cheilitis, white dermographism, and food intolerance. Skin of colour may show papular, follicular or lichenoid forms with prominent hyperpigmentation or hypopigmentation rather than erythema.
• Diagnostic criteria (Hanifin and Rajka, UK Working Party): itchy skin plus three or more of: flexural involvement, personal history of atopy, history of dry skin, visible flexural eczema, onset under age 2.
• Severity: SCORAD, EASI (0 to 72, mild 1.1 to 7, moderate 7.1 to 21, severe 21.1 to 50, very severe above 50), IGA, and patient-reported measures (POEM, DLQI, itch NRS).
• Differential diagnosis: seborrhoeic dermatitis, contact dermatitis (allergic and irritant), scabies, psoriasis, tinea, cutaneous T-cell lymphoma (in adults with refractory disease), Netherton syndrome, hyper-IgE syndrome, Wiskott-Aldrich syndrome, nutritional deficiency (zinc), histiocytosis, and immunodeficiency.
• Red flags: sudden painful vesiculopustular eruption with fever (eczema herpeticum), failure to thrive, recurrent severe infections, onset in adulthood after 50 years, erythroderma, and treatment resistance (biopsy for lymphoma).

• Diagnosis is clinical. Investigations answer specific questions.
• Skin swab for bacterial culture when weeping, crusted or pustular. HSV PCR from vesicle fluid when eczema herpeticum is suspected.
• Patch testing for adult-onset, hand, eyelid, facial or treatment-resistant disease to find allergic contact dermatitis (nickel, fragrances, preservatives, rubber, topical steroid allergy).
• Specific IgE or skin prick testing guided by history of immediate reactions (food or aeroallergen), not for routine use. Food challenges for suspected food-triggered flares in young children with moderate-severe disease. Total IgE is nonspecific.
• Skin biopsy for atypical or refractory adult presentations (spongiosis, acanthosis, lymphocytic infiltrate).
• Baseline CBC (eosinophilia), liver tests, creatinine, hepatitis B and C, HIV and tuberculosis screening before systemic immunosuppressants or JAK inhibitors. Pregnancy test before certain agents.
• Assess for comorbid asthma, rhinitis, sleep disturbance, mood disorders, and eye disease (conjunctivitis on dupilumab).

Stepwise approach with emollient and trigger avoidance as the base.

Basic care (all patients)

• Liberal emollients at least twice daily (about 250 g per week in children and 500 g per week in adults), with ceramide-containing preparations. Apply within minutes after bathing.
• Bathing in lukewarm water for 5 to 10 minutes, soap-free cleansers, and wash substitutes. Avoid irritants, wool, fragrances, and overheating. Short fingernails and cotton clothing. Wet wrap therapy for severe flares: damp tubular bandages over topical steroid for 24 to 72 hours.
• Education and written action plans. Reduce dust mite exposure only when sensitisation is clinically relevant.

Topical anti-inflammatory therapy

• Topical corticosteroids (fingertip unit: one FTU, 0.5 g, covers two adult palm areas):
  • Mild potency (hydrocortisone 1%) for face, flexures, genitals and infants.
  • Moderate (betamethasone valerate 0.025%, clobetasone butyrate 0.05%) for children and trunk.
  • Potent (mometasone furoate 0.1%, betamethasone valerate 0.1%) for adults, limbs and lichenified skin.
  • Very potent (clobetasol propionate 0.05%) for short courses (7 to 14 days) on thick adult plaques. Avoid on face and flexures.
  • Apply once or twice daily for flares for up to 2 to 4 weeks, then taper. Proactive therapy: twice weekly application to previously affected sites reduces relapse.
• Topical calcineurin inhibitors: tacrolimus 0.03% (children 2 to 15 years) or 0.1% (adults) ointment twice daily, pimecrolimus 1% cream twice daily for mild-moderate disease, especially face, eyelids and flexures, and for steroid-sparing maintenance (twice weekly). Burning on first applications. Safe long term.
• Topical PDE4 inhibitors: crisaborole 2% ointment twice daily (age 3 months and above), difamilast 1% in some regions.
• Topical JAK inhibitor: ruxolitinib 1.5% cream twice daily for mild-moderate disease in ages 12 and over, up to 20% body surface area.
• Antiseptic baths (dilute bleach: 1/4 to 1/2 cup of 6% bleach in a full bath, twice weekly, or chlorhexidine) reduce infection in moderate-severe disease.

Infection management

• Localised impetiginisation: topical fusidic acid 2% or mupirocin 2% three times daily for 5 to 7 days. Extensive: flucloxacillin 250 to 500 mg four times daily (children 25 to 50 mg/kg/day divided) or cefalexin for 7 days. MRSA: clindamycin or doxycycline (over 12 years).
• Eczema herpeticum: medical emergency. Aciclovir 10 mg/kg IV every 8 hours (children 250 to 500 mg/m2 or 10 mg/kg) until improvement, then oral valaciclovir 1 g three times daily or aciclovir 400 mg five times daily to complete 10 to 14 days. Ophthalmology review for periocular disease. Stop topical immunomodulators until resolved.

Itch and sleep

• Emollients and effective anti-inflammatory treatment control itch. Sedating antihistamines (hydroxyzine 10 to 25 mg or chlorphenamine at night) may help sleep for short periods. Non-sedating antihistamines have little effect on itch. Habit-reversal and wet wraps help.

Phototherapy

• Narrowband UVB two to three times weekly for moderate-severe disease unresponsive to topicals (adolescents and adults). UVA1 for acute flares. PUVA for resistant adult disease. Counselling about skin cancer risk with cumulative exposure.

Systemic therapy for moderate-severe disease (inadequate response to optimised topical care)

• Dupilumab (IL-4 receptor alpha blocker): adults 600 mg SC loading then 300 mg every 2 weeks. Paediatric dosing by weight (6 months to 17 years: 100 to 300 mg every 2 to 4 weeks). About 40 to 60% achieve EASI-75 at 16 weeks. Adverse effects: conjunctivitis and keratitis (10 to 20%), facial or neck erythema, injection site reactions, and eosinophilia. It reduces comorbid asthma.
• Tralokinumab (IL-13): 600 mg loading then 300 mg every 2 weeks (every 4 weeks after clearing). Lebrikizumab: 500 mg at weeks 0 and 2, then 250 mg every 2 weeks, then every 4 weeks for maintenance. Nemolizumab (IL-31 receptor) for itch and prurigo.
• JAK inhibitors (ages 12 and over, or adults): upadacitinib 15 or 30 mg daily, abrocitinib 100 or 200 mg daily, baricitinib 2 to 4 mg daily. Rapid itch relief, higher efficacy than dupilumab in head-to-head trials. Counsel and monitor for infections (herpes zoster), acne, cytopenias, lipids, creatine kinase, venous thromboembolism, major adverse cardiovascular events and malignancy. Avoid or use with caution in age over 65, smokers, and those with cardiovascular or thrombotic risk.
• Conventional immunosuppressants: ciclosporin 3 to 5 mg/kg/day in two divided doses for short-term control (up to 1 to 2 years), monitoring blood pressure, creatinine and magnesium. Methotrexate 10 to 25 mg weekly with folic acid 5 mg weekly. Azathioprine 1 to 3 mg/kg/day (check TPMT). Mycophenolate mofetil 1 to 2 g daily.
• Oral corticosteroids: avoid long-term use. Short course of prednisolone 0.5 mg/kg for 1 to 2 weeks as a bridge only in severe flares, with taper to prevent rebound.
• Live vaccines are contraindicated with JAK inhibitors. Biologics do not preclude vaccination.

Special situations

• Food allergy: confirm with testing and supervised challenge before elimination. Unnecessary food avoidance causes nutritional deficiency and may increase allergy risk.
• Infants: early introduction of peanut and egg in high-risk infants (severe eczema) after assessment, following allergy guidance.
• Pregnancy and lactation: emollients, topical corticosteroids, UVB, and ciclosporin or azathioprine if essential. Avoid JAK inhibitors, methotrexate and mycophenolate. Dupilumab data are reassuring but limited.
• Hand eczema: strict irritant avoidance, potent steroid, alitretinoin 10 to 30 mg daily for chronic hand eczema (teratogenic), PUVA.

Follow-up

• Review within 2 to 4 weeks of changing therapy, then every 3 to 6 months. Screen for mood disorders, sleep problems, and school or work impact. Assess for ocular symptoms on biologics. Annual eye examination in severe disease.