• Affects 5–20% of children worldwide, on a rising trend ^[1][6]
• One of the most prevalent childhood diseases globally — in Hong Kong, the prevalence in schoolchildren is approximately 15–20%, consistent with the high prevalence seen in urbanised, developed regions
• The rising prevalence in developed countries supports the hygiene hypothesis: reduced early microbial exposure in modern urban environments may skew the immune system towards a Th2-dominant state, promoting atopic disease

• Onset < 5 years old in the vast majority ^[2]
• 60% have onset before age 1 year, 85% before age 5 years ^[1][6]
• Very early onset (first few months of life) is common — often presents around 2–6 months of age when the infant's immune system first encounters environmental antigens

• Slight female predominance: M:F ≈ 1:1.3 ^[1][2][6]

• Majority are clear of eczema by late childhood (50% by 12 years, 75% by 16 years) ^[1][6]
• Mild disease may clear without treatment, but rarely spontaneously resolves in severe disease ^[1][6]
• Risk factors for persistence into adulthood: onset at age 6–11 years, severe disease, prolonged disease course, female sex ^[1][6]

• Family history of atopic disease (70%) — the strongest single risk factor ^[1][6]
• 30% risk in offspring if one parent affected; 80% risk if both parents affected ^[2]
• Heavy genetic component: concordance rate MZ twins 80% vs DZ twins 20% ^[1][6] — this dramatic difference demonstrates the large genetic contribution
• Family history of any atopic condition (eczema, asthma, allergic rhinitis, food allergy) counts

• Personal history of asthma, allergic rhinitis, allergic conjunctivitis, urticaria, food allergy ^[2]
• The presence of one atopic condition significantly increases the risk of developing others

Exacerbating factors ^[2]:

• Heat or low humidity environment — dries out the already compromised skin barrier
• Exposure to solvents and detergents — strips natural lipids from the stratum corneum
• Excessive bathing without subsequent moisturisation — removes natural moisturising factors (NMFs) and lipids
• Aeroallergens, food and contact allergens — trigger immune responses in sensitised individuals
• Superimposed skin infections — S. aureus colonises >90% of AD skin; superantigens amplify inflammation
• Stress and anxiety — via neuro-immune pathways (cortisol dysregulation, neuropeptide release)

Additional triggers from lecture content:

• Cutaneous hyperreactivity to various environmental stimuli, e.g. food/inhalant allergens, irritants, changes in physical environment, microbial infection, stress ^[1][6]
• Rough clothing (especially wool), pets, hot water ^[3]
• Following infection and vaccination, these conditions can deteriorate → superantigen abnormality ^[7]

The epidermis consists of 4–5 layers (from deep to superficial):

1. Stratum basale (basal layer) — mitotically active keratinocytes
2. Stratum spinosum (spinous layer) — keratinocytes connected by desmosomes
3. Stratum granulosum (granular layer) — contains keratohyalin granules (containing profilaggrin) and lamellar bodies (containing lipids)
4. Stratum lucidum (only in thick skin, e.g. palms/soles)
5. Stratum corneum (horny layer) — the actual barrier: anucleate corneocytes embedded in a lipid matrix ("bricks and mortar" model)

• Corneocytes ("bricks"): flattened, dead keratinocytes filled with keratin filaments bundled by filaggrin breakdown products. Filaggrin breakdown also produces natural moisturising factors (NMFs) — amino acids, urocanic acid, pyrrolidone carboxylic acid — which retain water in the stratum corneum
• Lipid matrix ("mortar"): ceramides, cholesterol, free fatty acids secreted from lamellar bodies — forms the hydrophobic barrier preventing transepidermal water loss (TEWL)
• Tight junctions: in the stratum granulosum, form a secondary barrier
• Corneodesmosomes: hold corneocytes together (composed of corneodesmosin, desmoglein, etc.)

When any component of this "bricks and mortar" barrier is defective:

• Water escapes outward → dry skin (xerosis)
• Allergens, irritants, and microbes penetrate inward → immune activation
• This is the essence of the "outside-in" hypothesis ^[1][6]

Skin inflammation initiated by either skin barrier dysfunction (outside-in hypothesis) vs immune dysregulation (inside-out hypothesis) → still controversial ^[1][6]. In reality, both mechanisms likely operate simultaneously and reinforce each other in a vicious cycle.

Genetically impaired barrier function → ↑ transepidermal water loss → ↑ allergen entry ^[1][6]

The sequence:

1. Defective filaggrin/lipids/tight junctions → compromised stratum corneum
2. ↑ TEWL → xerosis (dry skin) — the hallmark of AD. Skin barrier function is abnormal → dryness is a hallmark of the disease ^[7]
3. ↑ Penetration of allergens (house dust mite, food proteins, pollen), irritants (soap, detergent), and microbes (S. aureus, Malassezia)
4. These antigens are captured by Langerhans cells and dermal dendritic cells → presented to T cells → immune activation
5. Initial exposure → Th2-skewed response (IL-4, IL-13, IL-31, IL-5) → this is the acute/subacute phase
6. Chronic stimulation → additional Th1 response (IFN-γ) and Th22 response (IL-22) → chronic phase with lichenification

• S. aureus colonises > 90% of AD skin (vs < 5% in healthy skin)

  • Why? Deficient antimicrobial peptides + disrupted barrier + alkaline skin pH (normal acidic "acid mantle" is lost due to reduced filaggrin breakdown products)
  • S. aureus superantigens (SEA, SEB, TSST-1) non-specifically activate large numbers of T cells → massive cytokine release → disease flares
  • This is the superantigen abnormality referenced in lectures ^[7]
  • Also forms biofilms on the skin surface → chronic colonisation

• Malassezia spp. — a lipophilic yeast commensal; may contribute to AD especially in head/neck distribution (produces allergens that cross-react with self-proteins)

Unlike psoriasis which has well-defined genetics, eczema is much more complicated ^[7]:

Three hallmark features + epidermal changes by phase ^[3]:

This is crucial for paediatric exams — presentation varies with age ^[1][6]:

Severity scoring tools (for grading and monitoring treatment response):

In clinical practice, severity is broadly classified as:

• Mild: dry skin, infrequent itching, little impact on daily activities/sleep
• Moderate: frequent itching, moderate impact on daily activities/sleep, erythema/excoriation
• Severe: widespread, continuous itching, extensive skin loss/bleeding/oozing, severely impaired sleep and psychosocial functioning

Other atopic conditions: allergic rhinitis, asthma, food allergy ^[1][6]

Food allergy: often occurs together in paediatrics ( < 2% in adults) ^[1][6]

• ↑ Severity of AD → ↑ risk of food allergy (1/3 in moderate/severe, 2/3 in severe/refractory < 2 years) ^[1][6]
• Should be considered when: ^[1][6]
  1. History of immediate symptoms (urticaria, angioedema, vomiting within minutes of food exposure)
  2. Moderate/severe AD not controlled by optimal management
  3. GI dysmotility, failure to thrive

• Ichthyosis vulgaris (10–30%) ^[1][6]
• Psychiatric disorders: depression, anxiety, ADHD ^[1][6]
• Sleep disturbance → impacts growth, cognition, family functioning

Seborrhoeic dermatitis: most common differential diagnosis in infants ^[2][10]

• What it is: Inflammatory dermatitis caused by host reaction to Malassezia spp. (lipophilic yeast) at sites rich in sebaceous glands ^[1][6]
• Why it mimics AD: Both present in infants with scalp and facial involvement, erythematous scaly patches
• How to tell them apart:

• Pathophysiology: Sebaceous glands are transiently active in neonates (driven by maternal androgens) → lipid-rich environment → Malassezia proliferates → inflammatory reaction. The glands become quiescent after maternal hormones clear, which is why infantile seborrhoeic dermatitis resolves spontaneously.

Psoriasis presents with well-demarcated erythematous patches with little scaling ^[2] (in children, scaling may be less prominent than adults)

• Psoriasis: chronic inflammatory skin condition characterised by a state of hyperproliferation ^[3]
• Why it mimics AD: Both are chronic, relapsing, can affect children, can involve scalp and limbs
• How to tell them apart:

• Pathophysiology difference: Psoriasis is Th1/Th17-driven (IL-17, IL-23, TNF-α) with keratinocyte hyperproliferation → thickened epidermis with parakeratosis → silvery scale. AD is Th2-dominant (acute) with spongiosis (intercellular oedema) → vesicles/weeping.

Scabies: presents as diffuse eruption mimicking atopic dermatitis ^[2]

• What it is: Infestation by the mite Sarcoptes scabiei var. hominis; the mite burrows into the stratum corneum
• Why it mimics AD: Intensely pruritic (especially at night), widespread eczematous eruption in infants
• How to tell it apart:

• Pathophysiology: The itch in scabies is due to a Type IV hypersensitivity reaction to mite proteins/faeces. This is why there is a 2–6 week delay between infestation and symptom onset (sensitisation period), and why the itch persists for weeks after successful treatment (residual antigen).

This is a crucial paediatric-specific category. Several primary immunodeficiency (PID) syndromes present with eczema-like rashes, and missing them can be life-threatening.

Genetic or metabolic disorders featuring atopic eczema with or without raised IgE level, e.g. Ataxia telangiectasia, Wiskott-Aldrich syndrome ^[10]

Genetic/Metabolic/Immunodeficiency syndromes featuring eczema and ↑ IgE level: Wiskott-Aldrich syndrome, Hyper-IgE syndrome, DiGeorge syndrome, Ataxic telangiectasia, SCID ^[2]

Why immunodeficiency causes eczema-like rashes: In many PIDs, there is a Th2 skew (because the Th1 arm is deficient) → excess IL-4/IL-13 → IgE overproduction + eczematous inflammation. Additionally, disrupted immune surveillance allows S. aureus colonisation → further skin inflammation.

• What it is: Fungal infection of the skin by dermatophytes (Trichophyton, Microsporum, Epidermophyton)
• Why it mimics AD: Erythematous, scaly, pruritic patches in children
• How to tell it apart:
  • Annular morphology: tinea characteristically has central clearing with an advancing, raised, scaly edge ("ringworm")
  • Asymmetric: usually a single or few discrete patches (AD is typically bilateral and symmetric)
  • KOH preparation: scraping from the active edge shows fungal hyphae
  • Well-defined border (unlike AD's ill-defined borders)
• Tinea can be misdiagnosed as eczema and treated with topical steroids → tinea incognito (the steroid masks the scale and central clearing, making it harder to diagnose while the fungus continues to spread)

Hanifin and Rajka criteria: ≥ 3 major + ≥ 3 minor criteria ^[1][6]

These are more comprehensive but more complex, originally designed for research.

Major Criteria (need ≥ 3):

1. Pruritus
2. Typical morphology and distribution (flexural in older children/adults; facial/extensor in infants)
3. Chronic or chronically relapsing dermatitis
4. Personal or family history of atopy

Minor Criteria (need ≥ 3): — a long list of associated features and stigmata of atopy:

In practice, the Hanifin & Rajka criteria are too cumbersome for daily clinical use (there are 23 minor criteria). The UK Working Party criteria are simpler and equally validated.

Once AD is diagnosed, severity scoring guides treatment decisions:

Monitor response to biologics using SCORAD / EASI ^[14]

Skin swabs for bacterial and viral culture: during exacerbation or infection ^[2]

• When: suspected secondary infection (impetiginisation or eczema herpeticum)
• Bacterial swab (for culture and sensitivity):
  • Identifies S. aureus (or less commonly S. pyogenes) in impetiginised eczema
  • Guides antibiotic selection (especially important with rising MRSA prevalence)
  • Clinical signs prompting swab: yellow/golden crusting, pustules, increased oozing, sudden worsening, failure to respond to topical therapy
• Viral swab (HSV PCR):
  • Urgently indicated if eczema herpeticum is suspected (clusters of monomorphic punched-out erosions, vesicles with umbilication, pain, fever)
  • HSV PCR from a de-roofed vesicle is the fastest and most sensitive test
  • Do not wait for results before starting empirical IV aciclovir in suspected eczema herpeticum

Skin Scraping

Skin scraping: fungus / scabies mites ^[11]

• KOH preparation: for suspected tinea (annular lesion with central clearing, asymmetric) — scrape the active edge
• Scabies: scrape a burrow → microscopy for mites, eggs, or faecal pellets (scybala); or use dermoscopy to visualise the "delta sign" (mite head)

Skin biopsy: usually clinical diagnosis sufficient, but skin biopsy can help ^[9]

• When: diagnostic uncertainty, atypical features (e.g. persistent unilateral lesion, erythroderma, resistance to treatment, suspicion of Langerhans cell histiocytosis or cutaneous T-cell lymphoma)
• Method: Punch biopsy: should include epidermis, dermis and subcutaneous fat ^[3]; full-thickness tissue obtained via punch or excisional biopsy, including the edge and the thickest or most abnormal area ^[11]
• Histological findings in AD:

• Histology is non-specific — spongiotic dermatitis can be seen in many types of eczema. It supports the morphological diagnosis but does not distinguish AD from other eczema subtypes.

Dermatological examination: dermoscopy, diascopy, Wood's light ^[11]

In paediatrics, education targets both the caregivers and the child (age-appropriate). Key messages:

• Nature of the disease: "This is a chronic condition — it comes and goes. We cannot cure it, but we can control it very well."
• Skin barrier concept: "Your child's skin is like a wall with cracks — moisture escapes out, and irritants get in. Emollients seal those cracks."
• Address steroid phobia (extremely common in Hong Kong families): explain that appropriately used topical steroids are safe; undertreating is more harmful than the steroid itself
• Written eczema action plan: like an asthma action plan — clear instructions for daily care, flare management, and when to seek help

Emollients: essentially vehicles without active drug → important in moisturising skin in eczema ^[6][17]

Why emollients are fundamental: Recall that the core defect in AD is a dysfunctional skin barrier (filaggrin deficiency → ↓NMFs → ↓water retention + abnormal lipid matrix → ↑TEWL). Emollients:

1. Form an occlusive layer that traps water and reduces TEWL
2. Supplement the deficient lipid matrix
3. Restore the "bricks and mortar" architecture
4. Reduce itch (by hydrating dry, fissured skin that activates itch fibres)

Choosing the right formulation ^[2]:

Cream or ointments with low water and high oil content better protect against xerosis ^[2]

Moisturisers containing ceramide and natural moisturising factor may be beneficial — atopic skin is deficient in stratum corneum lipids especially ceramide and natural moisturising factor ^[2]

Practical application in paediatrics:

• Apply liberally and frequently — at least 2–3 times daily, more in dry/cold weather
• Apply emollient after bathing (within 3 minutes, while skin is still damp — "soak and seal")
• Use approximately 250–500g per week for a child (parents often under-apply)
• Avoid fragranced products (irritant potential)
• Use a pump dispenser or spoon to scoop (not fingers directly into tub → bacterial contamination)

Avoid bathing or showering too long and use warm water but NOT hot water ^[2]

• Short, lukewarm baths (5–10 minutes) — warm water is OK, hot water strips lipids and worsens barrier
• Use soap substitutes (e.g. aqueous cream as a wash, emollient bath oils) — avoid soap, fragranced cleansers ^[2]
• Pat skin dry with cotton towel after bath and don't rub ^[2]
• Apply emollient immediately after patting dry

Topical calcineurin inhibitor (tacrolimus): non-steroidal immunomodulating agents that do not cause skin atrophy or other corticosteroid adverse effects ^[2]

Alternative to treat mild to moderate atopic dermatitis involving the face including eyelids, neck and skin folds ^[2]

Agents available:

• Tacrolimus (Protopic) ointment: 0.03% (children ≥ 2 years) and 0.1% (adults/adolescents ≥ 16 years)
• Pimecrolimus (Elidel) cream: 1% (children ≥ 2 years)

Mechanism of action: Calcineurin (from Latin calci- = calcium + neur- = nerve/signal + -in = protein) is a calcium/calmodulin-dependent phosphatase that activates NFAT (nuclear factor of activated T cells). NFAT translocates to the nucleus and drives transcription of IL-2 and other T-cell activating cytokines. Tacrolimus/pimecrolimus bind to FK-binding protein (FKBP) → the drug-FKBP complex inhibits calcineurin → blocks NFAT → suppresses T-cell activation → ↓IL-2, IL-4, IL-5, IL-13, TNF-α → anti-inflammatory effect.

Why they are valuable in paediatric AD:

1. Do not cause skin atrophy — critical advantage over TCS for the face, eyelids, neck, and skin folds where atrophy risk is highest
2. Can be used for proactive maintenance (2×/week on previously affected sites)
3. Effective as steroid-sparing agent in chronic disease

Indications ^[2][16]:

• Face including eyelids, neck and skin folds — areas where TCS side effects are most concerning
• Steroid-sparing: replacing TCS in children who need prolonged therapy
• Proactive maintenance therapy
• Steroid phobia (when parents refuse TCS — pragmatic use)
• Adjunctive therapy for refractory cases ^[16]

Side effects:

• Application-site burning/stinging: most common — occurs in ~50% initially, typically resolves after 1 week of use. Caused by transient activation of TRPV1 (vanilloid) receptors on sensory nerves. Warn parents.
• Theoretical malignancy risk: FDA black box warning (2006) based on theoretical concern from systemic calcineurin inhibitor-associated lymphoma in transplant patients. Long-term post-marketing surveillance has NOT shown increased skin cancer or lymphoma risk with topical use. Nevertheless, avoid use under occlusion and in children < 2 years.

Contraindications/Cautions:

• Age < 2 years (off-label use may occur under specialist supervision)
• Active skin infection (must treat infection first — TCI suppresses local immunity)
• Do not use under occlusion
• Avoid in immunocompromised patients

• Mechanism: inhibits phosphodiesterase 4 (PDE4) → ↑intracellular cAMP → suppresses NF-κB-mediated inflammatory cytokine production
• Approved for mild-to-moderate AD in children ≥ 2 years (some jurisdictions ≥ 3 months)
• Alternative non-steroidal option, less potent than tacrolimus
• Side effect: application-site pain/burning

• Topical ruxolitinib cream 1.5% (a JAK1/JAK2 inhibitor) — approved for mild-to-moderate AD in patients ≥ 12 years
• Mechanism: blocks JAK-STAT signalling downstream of multiple pro-inflammatory cytokines (IL-4, IL-13, IL-31, IFN-γ)
• Rapid onset of itch relief (within 12–36 hours)
• Available in some centres; not yet widely used in paediatric Hong Kong practice

JAK inhibitors (but since so many, no consensus of which one is best in children) ^[16]

Mechanism: Janus kinases (JAK1, JAK2, JAK3, TYK2) are intracellular tyrosine kinases that mediate signalling downstream of cytokine receptors. When a cytokine binds its receptor → JAKs phosphorylate STAT proteins → STATs dimerise and translocate to the nucleus → gene transcription. JAK inhibitors block this step, shutting down signalling from multiple pro-inflammatory cytokines simultaneously.

Side effects (class effects):

• Infection risk (herpes zoster reactivation, serious infections) — JAKs are critical for interferon signalling (antiviral defence)
• AD patient started on JAK inhibitor → developed complication → superimposed herpes simplex infection → eczema herpeticum ^[9] — this is a real clinical risk
• Thromboembolic events (DVT/PE) — primarily a concern in older adults with cardiovascular risk factors, less relevant in paediatrics
• Hyperlipidaemia, elevated CK
• Myelosuppression (especially with JAK1/2 inhibitors — JAK2 mediates erythropoietin and thrombopoietin signalling)
• Theoretical malignancy concern (long-term data still accumulating)

Pre-treatment screening: CBC, LFTs, lipid profile, viral hepatitis serology, VZV status (vaccinate if not immune before starting), TB screening

• Clinical signs: yellow/honey crusting, pustules, sudden worsening
• Localised: topical antiseptic (chlorhexidine wash) ± topical antibiotic (mupirocin or fusidic acid) — short courses only (avoid resistance)
• Widespread/severe: oral antibiotics targeting S. aureus — flucloxacillin (first-line in non-MRSA), or co-amoxiclav; clindamycin or doxycycline (≥ 12y) for MRSA

• Emergency: widespread severe eruption ^[1][6] — can be life-threatening
• Start IV aciclovir empirically without waiting for results (10mg/kg IV 8-hourly in children; adjust for neonates)
• Stop TCS/TCI at the affected site (immunosuppression worsens viral spread)
• Swab for HSV PCR, bacterial culture (often co-infected)
• Ophthalmology review if periorbital involvement (risk of HSV keratitis)

• Erythroderma (> 90% BSA) from AD is rare but serious — "skin failure"
• Supportive: close monitoring, replace fluid and electrolytes, prevent hypothermia, treat infections ^[3]
• Topical corticosteroids over affected area; oral antihistamines for sedating effect ^[6]
• May need systemic immunosuppression

Impetiginisation: secondary infection by S. aureus → associated with disease exacerbation ^[1][6]

Staphylococcus aureus infection is common; presents with pustules, crusting, discharge or oozing ^[2]

Secondary impetiginisation due to primary atopic dermatitis → purulent crusting, weepy discharge ^[16]

Pathophysiology:

• S. aureus colonises > 90% of AD skin (vs < 5% of healthy skin)
• Why? ↓Antimicrobial peptides + ↑pH + disrupted barrier + S. aureus adheres preferentially to fibronectin exposed in damaged skin + biofilm formation
• S. aureus produces superantigens (staphylococcal enterotoxins A/B, TSST-1) → these bypass normal antigen presentation and activate 5–30% of all T cells non-specifically → massive cytokine storm → disease exacerbation ^[1][6]
• Following infection and vaccination, these conditions can deteriorate → superantigen abnormality ^[7]

Clinical features:

• Sudden worsening of existing eczema
• Yellow/honey-coloured crusting (classic sign of staphylococcal impetigo on eczematous skin)
• Pustules, increased oozing, purulent discharge
• Regional lymphadenopathy, fever (if extensive)
• If untreated → may progress to cellulitis, abscess, or (rarely) septicaemia

Management:

• Localised: topical antiseptic (chlorhexidine wash) ± topical antibiotic (mupirocin 2% ointment or fusidic acid cream) — short course (5–7 days maximum to avoid resistance)
• Widespread/severe: oral antibiotics targeting S. aureus — flucloxacillin first-line (covers MSSA); co-amoxiclav if mixed flora; clindamycin or TMP-SMX for suspected MRSA
• Continue emollients; can continue topical steroids (they reduce the inflammatory substrate that bacteria exploit)
• Skin swab for culture and sensitivity if not responding

Eczema herpeticum: secondary infection by HSV → widespread severe eruption ^[1][6]

Eczema herpeticum (Kaposi's varicelliform eruption): rapid dissemination of HSV infection on affected skin of patients with atopic dermatitis ^[2]

This is a dermatological emergency in paediatrics.

Pathophysiology:

• HSV (usually HSV-1, occasionally HSV-2) infects the disrupted eczematous skin
• Because the barrier is broken and local antiviral defences are impaired (↓TLR9, ↓cathelicidin LL-37, ↓NK cell function in Th2-skewed environment), HSV spreads rapidly across the skin surface
• The virus replicates in keratinocytes → cell lysis → superficial erosions/vesicles
• Can disseminate to cause viremia → encephalitis, keratitis, hepatitis (rare but life-threatening)

Clinical features (key for recognition in exams):

• Clustered, monomorphic vesicles/erosions — "monomorphic" means they all look the same (unlike the polymorphic lesions of AD itself)
• Discrete, monomorphic erosions with crust, in a patient with a background of atopic dermatitis ^[9]
• Vesicles are often dome-shaped with central umbilication ("punched-out" appearance)
• Pain (not just itch) — this is a distinguishing feature; regular AD eczema itches but doesn't usually hurt
• Fever, malaise, irritability
• Swollen, tender regional lymph nodes
• Most commonly affects the face and neck initially, then can spread to trunk and limbs
• Vesicles may be filled with clear fluid, purulent material, or blood-stained (red, purple or black)
• Older blisters crust over and form sores (erosions); lesions heal over 2–6 weeks

Risk factors for eczema herpeticum:

• Severe/widespread AD
• Early-onset AD
• History of high total serum IgE
• Use of immunosuppressive agents — AD patient started on JAK inhibitor → developed complication → superimposed herpes simplex infection → eczema herpeticum ^[9]
• Contact with someone with active HSV (cold sore)

Management — Treat as an emergency:

1. Systemic aciclovir — start empirically, do NOT wait for confirmatory results
   • IV aciclovir 10–20 mg/kg/dose 8-hourly in children (neonates: 20 mg/kg/dose 8-hourly)
   • Switch to oral valaciclovir/aciclovir when improving
2. Stop topical immunosuppressants (TCI, topical steroids) at the infected area — they worsen viral dissemination
3. Swab for HSV PCR from de-roofed vesicle — most sensitive and rapid test
4. Bacterial swab — co-infection with S. aureus is common → may need concurrent antibiotics
5. Ophthalmology review if periorbital involvement → risk of HSV keratitis → corneal scarring → blindness
6. Monitor for systemic dissemination (encephalitis, hepatitis) — especially in neonates/infants

Molluscum contagiosum; Warts ^[2]

• Molluscum contagiosum (poxvirus): pearly, dome-shaped, umbilicated papules; spreads easily on eczematous skin via autoinoculation (scratching transfers virus to new sites). In AD children, lesions tend to be more numerous and widespread because of the impaired barrier and local immune deficiency. Usually self-limiting but may trigger eczema flares around the lesions ("molluscum dermatitis").

• Warts (HPV): verrucous papules; more common and persistent in AD children (same reasons — disrupted barrier allows HPV inoculation, impaired local immunity delays clearance). Treatment: cryotherapy, salicylic acid, or immunotherapy (imiquimod).

• Malassezia spp. (lipophilic yeast): commensal organism that can exacerbate AD, particularly in the "head and neck" distribution pattern. Malassezia-specific IgE is found in some AD patients → contributes to inflammation. May benefit from topical or oral antifungals (ketoconazole).
• Dermatophyte infections (tinea): more common in disrupted skin; may be misdiagnosed as AD flare; risk of tinea incognito if treated with topical steroids.

Eczema causes skin breakage → allows entrance of allergens into body, sensitisation of T-cells to become reactive to allergens ^[16]

Studies where peanut allergens floating in the air will activate and sensitise T-cells in babies with atopic dermatitis → develops peanut allergy, part of the atopic march. Whereas for babies that don't have atopic dermatitis (and thus no skin breakage), it is likely they will be exposed to peanut via GI tract first, where there are a lot of Treg cells → before skin exposure, NO PEANUT ALLERGY ^[16]

This is the epicutaneous sensitisation hypothesis, one of the most important concepts in paediatric allergy:

1. Infant has AD → disrupted skin barrier
2. Environmental allergens (food proteins like peanut, egg; aeroallergens like dust mite, pollen) penetrate through broken skin
3. Allergens are captured by skin dendritic cells → presented to T cells → Th2-skewed sensitisation → IgE production against these allergens
4. The child is now "sensitised" through the skin (epicutaneous route)
5. When these allergens are subsequently encountered at mucosal surfaces (airway → asthma; nasal mucosa → rhinitis), the pre-existing IgE triggers immediate hypersensitivity reactions

Contrast with the oral tolerance pathway: if the child encounters food allergens through the GI tract first (before epicutaneous sensitisation), the gut-associated lymphoid tissue (GALT) — rich in regulatory T cells (Tregs) — promotes immune tolerance rather than sensitisation. This is the rationale for early introduction of allergenic foods (e.g. peanut from 4–6 months in high-risk infants — the LEAP trial principle).

Food allergy: often occurs together in paediatrics ( < 2% in adults) ^[1][6] ↑Severity of AD → ↑risk of food allergy (1/3 in moderate/severe, 2/3 in severe/refractory < 2 years) ^[1][6]

Sensitisation to environmental or food allergens is clearly associated with atopic dermatitis phenotype but is NOT a causative factor ^[2]

This is a nuanced point: while food allergy and AD co-exist frequently, and epicutaneous sensitisation explains the link, food allergens are generally not the primary cause of AD. Most AD flares are driven by intrinsic barrier dysfunction and immune dysregulation, not by food exposure. Therefore:

• Most patients with atopic dermatitis are sensitised to certain food but the timing of solid food introduction or food avoidance strategy in pregnancy does not appear to influence risk of atopic dermatitis ^[2]
• Environmental exposure to food allergens through an impaired skin barrier is a plausible route for food sensitisation and allergy ^[2]

When to consider food allergy investigation ^[1][6]:

1. History of immediate symptoms after food exposure (urticaria, angioedema, vomiting, anaphylaxis)
2. Moderate/severe AD not controlled by optimal management
3. GI dysmotility, failure to thrive

• Approximately 50% of children with AD develop asthma; ~75% develop allergic rhinitis
• Risk factors for progression: early-onset AD, severe AD, positive family history, FLG mutation, high total IgE, specific IgE sensitisation to aeroallergens
• Why does asthma come before rhinoconjunctivitis? Still unsure, more research needed ^[16]

Atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC): ocular comorbidities in patients with atopic dermatitis. Presents with ocular itching, burning, tearing and mucus discharge ^[2]

• AKC: chronic bilateral conjunctival inflammation; can cause corneal scarring, keratoconus, cataracts
• VKC: seasonal, affects boys more; giant papillae on tarsal conjunctiva ("cobblestone" appearance); shield ulcers

Keratoconus: chronic eye rubbing (from periorbital itch in AD) → progressive corneal thinning → cone-shaped cornea → visual impairment. Important to counsel children and parents to avoid eye rubbing.

Ichthyosis vulgaris (10–30%) ^[1][6] Presents with hyperlinear palms and keratosis pilaris ^[2]

• Autosomal semi-dominant condition caused by FLG loss-of-function mutations (the same gene implicated in AD barrier dysfunction)
• Fish-scale-like scaling, predominantly on the shins
• Often co-exists with AD because they share the same genetic substrate