Atopic Dermatitis (Eczema)

Genetic Factors

1. Filaggrin Gene Mutations:
   • Loss-of-function mutations in the filaggrin (FLG) gene, located on chromosome 1q21.3, predispose individuals to impaired skin barrier function. This increases antigen exposure and susceptibility to eczema.
   • Filaggrin facilitates the formation of the stratum corneum, maintaining hydration and preventing environmental allergen penetration. Mutations disrupt this process, leading to increased transepidermal water loss and inflammation.
2. Other Genetic Associations:
   • Genome-wide association studies (GWAS) have identified loci associated with cytokine regulation and immune system function, including OVOL1, ACTL9, and KIF3A. These loci contribute to immune dysregulation and epidermal proliferation.
3. Familial Patterns:
   • Family history significantly increases risk. Concordance rates are 77% in monozygotic twins and 15% in dizygotic twins. Sibling prevalence ranges from 22% to 24%.
     
     

Environmental Factors

1. Skin Irritants:
   • Common irritants include soaps, detergents, and bubble baths. These exacerbate skin dryness and inflammation.
2. Infections:
   • Skin colonisation with Staphylococcus aureus frequently worsens eczema flares. Viral superinfections, such as eczema herpeticum caused by herpes simplex virus, are also observed.
3. Climate:
   • Extremes in temperature and humidity can exacerbate symptoms. Dry, cold air increases xerosis, while sweating in hot climates worsens pruritus.
4. Hygiene Hypothesis:
   • Reduced exposure to microbial antigens in early life, as seen in smaller families or urban settings, correlates with increased eczema prevalence. Early exposure to farm animals and endotoxins may provide protective effects.
5. Water Hardness:
   • High calcium carbonate levels in domestic water have been epidemiologically linked to an increased risk of eczema. However, randomised controlled trials have shown limited clinical efficacy of reducing water hardness.
6. Dietary Factors:
   • The role of food allergens (e.g., cow's milk, eggs, nuts) in exacerbating eczema remains controversial. While acute allergic reactions like urticaria are common, most cases do not benefit from elimination diets.
7. Seasonal and Geographic Variations:
   • Birth during autumn or winter in the northern hemisphere correlates with higher risk, possibly due to reduced skin barrier function in low humidity conditions.
8. Other Triggers:
   • Exposure to tobacco smoke has been linked to the onset and exacerbation of eczema in both children and adults.
     
     

Immune Dysregulation

1. Th2-Mediated Inflammation:
   • In the acute phase, eczema is driven by Th2 cells producing cytokines such as IL-4, IL-5, and IL-13. These cytokines promote IgE synthesis and inflammation.
   • Chronic eczema involves a Th1 response, leading to lichenification and persistent inflammation.
2. Microbiome Dysbiosis:
   • Patients with eczema exhibit reduced bacterial diversity and increased Staphylococcus aureus colonisation. Superantigens produced by S. aureus exacerbate inflammation by activating T cells and mast cells.
     
     

Two Key Hypotheses

1. Immune Dysfunction Hypothesis:
   • Involves primary immune dysregulation, particularly an imbalance in T helper (Th) cell subsets:
     • Acute AD: Dominance of Th2 cells leads to increased production of type 2 cytokines (IL-4, IL-5, IL-13), promoting IgE synthesis and allergic inflammation.
     • Chronic AD: Shift to Th1 predominance with increased IL-12 production. Th17 and Th22 cells are also implicated, particularly in more severe cases.
   • Group 2 innate lymphoid cells (ILC2s), basophils, and mast cells amplify this immune response by releasing type 2 cytokines (IL-4, IL-5, IL-13). Cytokines such as IL-31 contribute to pruritus, while IL-33, IL-25, and thymic stromal lymphopoietin (TSLP), derived from damaged keratinocytes, further perpetuate inflammation.
2. Epithelial Barrier Hypothesis:
   • A primary defect in the skin barrier allows environmental allergens and pathogens to penetrate, initiating immune responses:
     • Filaggrin (FLG) mutations are the strongest genetic risk factor for AD. Filaggrin is critical for forming the stratum corneum and maintaining hydration. Loss-of-function mutations result in increased transepidermal water loss, xerosis, and increased antigen penetration.
     • Reduced antimicrobial peptides (e.g., β-defensins) contribute to microbial colonisation and infection, especially with Staphylococcus aureus.
       
       

Genetic Contributions

• FLG Mutations:
  • FLG mutations predispose to ichthyosis vulgaris and AD, with early-onset and persistent disease being more common. Only 30% of European patients with AD carry FLG mutations, indicating other genetic factors play a role.
• Other Genetic Variants:
  • Variants in cytokine-regulating genes (e.g., IL-4, IL-13, IL-31) and loci associated with immune function (e.g., chromosome 5q31-33) influence susceptibility.
  • TSLP genetic variants interact with FLG mutations to exacerbate disease persistence.
    
    

Key Immunologic and Inflammatory Mechanisms

1. Type 2 Inflammation:
   • Dominant in acute phases, with IL-4 and IL-13 suppressing keratinocyte differentiation genes and reducing antimicrobial peptides. This weakens the barrier and amplifies inflammation.
2. Chronic Inflammation:
   • Persistent scratching and inflammation lead to lichenification and the predominance of Th1, Th17, and IL-12-driven pathways.
3. Neuroimmune Interactions:
   • IL-31, produced by Th2 cells, triggers pruritus through direct action on sensory neurons, contributing to the itch-scratch cycle.

Microbial Influence

• Staphylococcus aureus:
  • Found in up to 90% of AD patients, S. aureus produces superantigens, which exacerbate inflammation by stimulating T cells and mast cells. Lesions with reduced microbial diversity tend to flare more severely.
    
    

Clinical Implications of Barrier Dysfunction

• Increased Allergen Sensitivity:
  • The leaky skin barrier allows the entry of allergens and irritants from various sources (e.g., dust mites, food, and air pollutants), amplifying the immune response.
• Association with Atopic March:
  • FLG mutations and barrier defects are linked to comorbidities such as asthma and allergic rhinitis.
    
    

Therapeutic Insights

1. Targeting Type 2 Cytokines:
   • Blocking IL-4 and IL-13 pathways with biologics such as dupilumab has shown significant efficacy in reducing inflammation and itch.
2. Barrier Restoration:
   • Emollients and moisturisers remain central to managing AD by improving hydration and reducing antigen penetration.
     
     

Global Prevalence and Trends

• Children: AD affects 15–30% of children in developed countries, with variation in prevalence ranging from 0.9% (Jodhpur, India) to 22.5% (Quito, Ecuador) among children aged 6–7 years. Adolescents aged 13–14 years show prevalence rates from 0.2% (Tibet, China) to 24.6% (Barranquilla, Columbia).
• Adults: Prevalence in adults ranges from 2–10% in developed countries and is estimated at 7% in the United States. Scandinavian studies report prevalence rates of 10–14% in adults.
• Geographic Variation: Higher prevalence is noted in Africa, Oceania, and Asia-Pacific regions compared to the Indian subcontinent and Northern/Eastern Europe. Immigration to developed countries also increases AD prevalence in populations from underdeveloped regions.
• Temporal Trends: Rising prevalence has plateaued in high-prevalence countries (e.g., the UK and New Zealand) but continues to increase in low-income countries such as those in Latin America and Southeast Asia.
  
  

Prevalence in the United States

• Children: Approximately 10–20% of children are affected. Prevalence is highest among African-American children (22%), compared to European-American children (16.1%).
• Adults: Prevalence estimates range from 0.9% to 7%. Increases in office visits for AD between 1997 and 2004 were higher among Black and Asian populations than White populations.
  
  

Demographic and Socioeconomic Factors

• Age: AD typically manifests in early childhood, with 85% of cases presenting in the first year of life and 95% before age five. Remission occurs in 60–75% of cases by age 15, although relapses may occur in adulthood. Late-onset AD is reported in approximately 25% of adults with the condition.
• Sex: There is a slight female predominance in childhood, with a male-to-female ratio of 1:1.4.
• Race and Ethnicity: In the US, eczema prevalence is higher in non-Hispanic Black populations (19.3%) compared to Hispanic and non-Hispanic White populations. Globally, socioeconomic factors such as poverty are associated with increased prevalence.
• Urban vs. Rural: Urban environments show higher prevalence rates, likely due to increased exposure to allergens, pollution, and decreased microbial diversity.

Hallmark Symptoms

• Pruritus (Itchiness):
  • The central and most debilitating symptom, often present within the first few weeks of life.
  • Pruritus becomes evident around three months of age when the itch-scratch cycle intensifies.
  • Severe itching can lead to secondary skin damage, including excoriations and lichenification.
    
    

Course of the Disease

• Intermittent Flares and Remissions:
  • The disease course typically alternates between exacerbations and remissions. Triggers for flares may be environmental, infectious, or stress-related, though sometimes no specific cause can be identified.
• Natural Subtypes:
  • A study identified five patterns of disease progression. The most frequent subtype involves early onset (before age two) and persistence into adulthood.
    
    

Risk Factors and Associations

1. Family History:
   • A strong association exists with atopy, including allergic rhinitis, asthma, and other type I hypersensitivity disorders.
   • Monozygotic twins show a concordance rate of 77%, compared to 15% in dizygotic twins.
2. Age of Onset:
   • 85% of cases present before the age of five, with 45% diagnosed by six months.
   • Early onset correlates with a higher likelihood of persistent disease and severe atopic manifestations (e.g., asthma, allergic rhinitis).
3. Genetic Mutations:
   • Loss-of-function mutations in the filaggrin gene are associated with impaired skin barrier function and increased AD susceptibility.
     
     

Diagnostic Features from History

1. Essential Features:
   • Chronic or relapsing history of eczema.
   • Severe itching, often reported as disproportionately distressing relative to visible skin changes.
2. Supporting Features:
   • Early onset.
   • Personal or familial history of atopy (eczema, asthma, allergic rhinitis).
     
     

Clinical Presentations Across Age Groups

1. Infants (0–2 Years):
   • Red, scaly, crusted lesions primarily on the cheeks, scalp, and extensor surfaces. The diaper area is often spared.
   • Lesions may be vesicular with serous exudates during flares.
2. Children and Adolescents (2–16 Years):
   • Lichenified plaques commonly involve the flexural areas (e.g., antecubital and popliteal fossae, wrists, ankles, and neck).
   • Reticulate pigmentation (e.g., “dirty neck”) is a common feature.
3. Adults:
   • Flexural involvement persists, but lesions frequently affect the face, neck, and hands.
   • Chronic lichenified dermatitis is prevalent, often associated with severe itching.
     
     

Associated Historical Findings

• Allergic Diseases:
  • Up to 50% of patients with AD have concurrent asthma or allergic rhinitis.
• Environmental Triggers:
  • Smoke exposure, irritants (e.g., soaps, detergents), and climate changes can exacerbate symptoms.
• Psychosocial Impact:
  • Chronic pruritus disrupts sleep and daily activities, impacting quality of life.
    
    

Key Findings

1. Primary Features:
   • Xerosis (Dry Skin):
     • A universal finding in AD, often generalised and severe.
   • Eczematous Lesions:
     • Acute Phase: Erythematous patches or plaques, often vesicular, with exudation and crusting.
     • Subacute Phase: Scaly, red, excoriated papules.
     • Chronic Phase: Thickened, hyperkeratotic, lichenified skin.
   • Excoriations:
     • Result from scratching and are often seen in easily accessible areas.
   • Crusting:
     • Common during acute exacerbations, sometimes with serous oozing.
2. Essential Diagnostic Features:
   • Pruritus (manifested indirectly by excoriations and lichenification).
   • Typical eczematous morphology:
     • Infants: Cheeks, scalp, extensor surfaces.
     • Children and Adults: Flexural areas (antecubital and popliteal fossae).
   • Chronic or relapsing course.
3. Associated Findings:
   • Keratosis Pilaris: Follicular, hyperkeratotic papules on extensor surfaces (e.g., arms, thighs).
   • Periorbital Changes:
     • Dennie-Morgan folds (extra skin folds under the eyes).
     • Darkened areas (allergic shiners).
   • Other Skin Changes:
     • Perioral or periauricular lesions.
     • Hyperlinear palms, particularly in older children and adults.
     • Pityriasis alba (hypopigmented patches on the face).
4. Age-Specific Distribution:
   • Infants:
     • Lesions often involve the face (cheeks and forehead) and extensor surfaces but spare the diaper area.
     • Lesions are ill-defined, erythematous, scaly, and crusted.
   • Children:
     • Commonly involves flexural areas, such as the antecubital and popliteal fossae.
     • Lichenification becomes more prominent due to chronic scratching.
   • Adults:
     • Diffuse lesions with erythema and scaling. Commonly affects the face, neck, hands, and flexures.
     • May develop the "dirty neck sign" (brown pigmentation around the neck).
5. Patterns in Skin of Color:
   • Erythema may appear violaceous or hyperpigmented rather than red.
   • Post-inflammatory hyperpigmentation or hypopigmentation is frequently observed.
6. Other Morphological Findings:
   • Lichenification: Thickened plaques from chronic scratching, often in flexural areas.
   • Hypopigmentation/Hyperpigmentation:
     • Common following inflammation, particularly in darker skin tones.
       
       

Examination Tools for Disease Severity

1. Eczema Area and Severity Index (EASI):
   • Evaluates redness, thickening, excoriations, and lichenification.
2. SCORing Atopic Dermatitis (SCORAD):
   • Combines objective findings with patient-reported symptoms.
3. Numerical Rating Scale:
   • Subjective scoring of itch intensity.
     
     

Key Investigations

• Bacterial Swabs:
  • Used to identify secondary bacterial infections, commonly caused by Staphylococcus aureus or Streptococcus species.
  • Antibiotic sensitivity testing can guide therapy.
• Viral PCR:
  • Helpful in identifying herpes simplex virus (HSV) infection and diagnosing eczema herpeticum.

• Eosinophilia:
  • Elevated eosinophil counts may support an allergic or atopic diagnosis.
• Thrombocytopenia:
  • Helps exclude immunodeficiency syndromes such as Wiskott-Aldrich syndrome.

• Elevated IgE:
  • A nonspecific marker that may support the diagnosis in certain cases.
  • High levels may indicate increased atopic predisposition, especially in severe cases.

• Not routinely recommended:
  • High sensitivity but low specificity can lead to false positives.
  • Should be reserved for patients with a clear history of food-triggered eczema exacerbations or severe cases unresponsive to optimal management.
• Oral Food Challenges:
  • Conducted for suspected food allergies in infants and young children with moderate-to-severe eczema unresponsive to standard treatment.

• Indications:
  • Useful in suspected allergic contact dermatitis that complicates AD.
  • Common allergens include nickel, neomycin, fragrances, formaldehyde, and rubber chemicals.
• Procedure:
  • Suspected allergens are applied to unaffected skin on the back for 48 hours and evaluated for delayed reactions.

• Purpose:
  • Used to exclude fungal infections such as tinea corporis.
    
    

• Histological Findings:
  • Acute Phase: Spongiosis (intercellular oedema), lymphocytic infiltration, and vesicle formation.
  • Chronic Phase: Epidermal hyperplasia, hyperkeratosis, and persistent dermal inflammation with eosinophils and mast cells.
• Indications:
  • Rarely performed but may help differentiate AD from conditions like cutaneous T-cell lymphoma or psoriasis.
    
    

Investigations for Differential Diagnoses

• Wiskott-Aldrich Syndrome:
  • CBC showing thrombocytopenia.
• Fungal Infections:
  • Potassium hydroxide (KOH) preparation or fungal culture.
• Contact Dermatitis:
  • Patch testing to identify specific allergens.
    
    

Points of Caution

• Laboratory tests, such as skin prick testing or IgE levels, should only be performed after optimising skin care and topical treatments.
• Routine testing is unnecessary in most cases and should be reserved for atypical presentations or suspected complications.
  
  

Common Differential Diagnoses

• Features:
  • Greasy, yellowish scales primarily affecting the scalp (cradle cap), intertriginous areas, and face.
  • Little to no pruritus compared to AD.
  • Xerosis and generalised dryness are absent.
• Distinguishing Features:
  • AD presents with dry, crusted lesions and pruritus, which are not typical of SD.
  • SD more commonly affects the diaper area and eyebrows, while AD typically spares these regions.

• Subtypes:
  • Allergic Contact Dermatitis:
    • Well-circumscribed, pruritic, erythematous lesions with vesicles and crusting.
    • Often localised to specific areas in contact with allergens (e.g., nickel from clothing snaps).
  • Irritant Contact Dermatitis:
    • Commonly affects the face, hands, and diaper area, resulting from exposure to irritating substances.
    • Typically less pruritic and less chronic than AD.
• Distinguishing Features:
  • AD often begins earlier in life and is associated with xerosis and flexural involvement.
  • Patch testing can identify allergens in suspected cases of contact dermatitis.

• Features:
  • Severe, nocturnal pruritus.
  • Polymorphic eruption with burrows, papules, nodules, and vesicles.
  • Commonly affects warm, moist areas such as the interdigital spaces, axillae, and groin.
  • Family members often report similar symptoms.
• Distinguishing Features:
  • Scabies rarely affects the face, unlike AD in infants.
  • Diagnosis can be confirmed by identifying mites, eggs, or scybala through skin scraping or dermoscopy.

• Features:
  • Well-demarcated erythematous plaques with silvery scales, commonly on extensor surfaces (e.g., elbows, knees).
  • Nail changes, such as pitting, are often present.
• Distinguishing Features:
  • Unlike AD, psoriasis typically spares the flexural areas in infants and does not involve xerosis.
  • Psoriasis has minimal pruritus compared to AD.

• Features:
  • Annular, scaly plaques with central clearing and active borders.
  • Commonly affects the trunk, arms, and legs.
• Distinguishing Features:
  • AD often has poorly demarcated lesions and involves flexural areas.
  • Diagnosis of tinea can be confirmed by potassium hydroxide (KOH) preparation or fungal culture.
    
    

• Features:
  • Hypopigmented or erythematous plaques with scaling, often in a random distribution.
  • Tends to occur in older patients (≥50 years of age).
• Distinguishing Features:
  • AD generally presents at a younger age and involves typical eczematous patterns.
  • Skin biopsy and flow cytometry are necessary to confirm the diagnosis of mycosis fungoides.
    
    

Less Common Differential Diagnoses

1. Primary Immunodeficiencies:
   • Wiskott-Aldrich Syndrome: Associated with thrombocytopenia, recurrent infections, and bleeding.
   • Hyperimmunoglobulin E Syndrome: Recurrent skin infections and abscesses.
2. Nutritional Deficiencies:
   • Zinc Deficiency (Acrodermatitis Enteropathica): Periorificial and acral dermatitis with diarrhea.
3. Netherton Syndrome:
   • Congenital ichthyosis, hair shaft abnormalities, and recurrent infections.
     
     

Diagnostic Approach

1. Clinical Examination:
   • Consider lesion morphology, distribution, and associated systemic symptoms.
2. Patch Testing:
   • Useful for identifying allergens in suspected allergic contact dermatitis.
3. Microscopy and Culture:
   • Skin scraping for fungal infections.
   • Microscopy for scabies mites or viral polymerase chain reaction (PCR) for suspected viral superinfections.
4. Biopsy:
   • May be required for conditions like mycosis fungoides or other unclear diagnoses.
     
     

General Principles of Management

1. Patient and Family Education:
   • Educate patients and caregivers about the chronic, relapsing nature of AD.
   • Provide guidance on skin care routines, recognising flares, and proper use of treatments.
   • Address psychological aspects of living with AD, including its impact on mood, sleep, and quality of life.
2. Avoidance of Triggers:
   • Identify and minimise exposure to allergens, irritants, and environmental factors that exacerbate symptoms.
     
     

First-Line Management

• Role:
  • Rehydrate the skin and improve barrier function.
  • Reduce itch and pain by minimising dryness and exposure to allergens.
• Guidance:
  • Use emollients liberally and frequently, even when the skin appears clear.
  • Select emollients without fragrances or additives to minimise irritation.
• Additional Considerations:
  • Newer formulations may include ceramides, filaggrin breakdown products, or lipids to mimic natural skin composition.

• Role:
  • Reduce inflammation and pruritus.
• Usage:
  • Mild potency for mild eczema.
  • Moderate or potent preparations for flares, with consideration of body site (e.g., mild potency for face and intertriginous areas).
  • Use twice daily during flares; maintenance therapy with twice-weekly application may reduce relapses.
• Adverse Effects:
  • Prolonged use of high-potency corticosteroids can lead to skin atrophy, striae, and systemic effects such as adrenal suppression.
    
    

Second-Line Management

• Examples:
  • Tacrolimus, pimecrolimus.
• Indications:
  • Moderate to severe eczema unresponsive to corticosteroids or for areas where skin thinning is a concern (e.g., face, eyelids).
• Adverse Effects:
  • Local irritation (burning, redness).
  • Theoretical risk of malignancy, though long-term data suggest no significant increase in risk.

• Example:
  • Crisaborole.
• Indications:
  • Approved for mild to moderate eczema in patients aged 3 months and older.
• Adverse Effects:
  • Application site reactions (burning, stinging).
    
    

Adjunctive Therapies

• Indications:
  • Moderate to severe flares.
• Benefits:
  • Enhances absorption of topical treatments, reduces water loss, and provides a physical barrier to scratching.
• Guidance:
  • Use short-term (7–14 days) under specialist supervision.
    
    

• Role:
  • Use oral antibiotics only for confirmed bacterial infections (e.g., cellulitis, impetigo).
  • Bleach baths or sodium hypochlorite may help reduce colonisation in severe cases.

• Indications:
  • Moderate to severe disease unresponsive to topical therapies.
• Types:
  • Narrowband UVB is most commonly used.
• Limitations:
  • Requires frequent visits, is time-intensive, and not suitable for young children or patients with skin cancer risk.
    
    

Systemic Therapy

• Examples:
  • Dupilumab (IL-4 and IL-13 inhibitor), tralokinumab (IL-13 inhibitor).
• Indications:
  • Moderate to severe eczema unresponsive to topical or phototherapy.
• Benefits:
  • Significant reduction in pruritus and inflammation with few systemic side effects.
    
    

• Examples:
  • Upadacitinib, abrocitinib, baricitinib.
• Indications:
  • For patients with severe eczema refractory to other systemic treatments.
• Cautions:
  • Regular monitoring for infections, cardiovascular events, and other systemic side effects is required.
    
    

• Examples:
  • Ciclosporin, methotrexate, azathioprine, mycophenolate.
• Indications:
  • Moderate to severe disease unresponsive to other treatments.
• Cautions:
  • Require regular monitoring for organ toxicity and other adverse effects.
    
    

Psychological and Lifestyle Considerations

• Support:
  • Provide counseling and support for patients and families to address the psychosocial burden of AD.
• Written Action Plans:
  • Offer written instructions on skin care routines, bathing, and trigger management to reinforce education.
    
    

General Prognosis

• Resolution in Childhood: Approximately 60% to 75% of children experience symptom resolution as they enter puberty; however, relapses occur in about 50%.
• Persistence into Adulthood: Longitudinal studies show that mild-to-moderate AD symptoms often persist into adolescence and adulthood, with more than 80% of patients reporting continued symptoms or requiring treatment from age 2 to 26 years.
• Medication-Free Periods: By age 20, about half of the patients have at least one six-month period free of symptoms and medication.
  
  

Factors Influencing Prognosis

1. Disease Severity:
   • Patients with milder disease may be managed with emollients and occasional topical therapy during flares.
   • Severe cases often require systemic therapies or phototherapy for control.
2. Atopic Sensitization:
   • Associated with a more aggressive disease course and greater likelihood of comorbid conditions such as asthma and allergic rhinitis.
3. Environmental and Familial Factors:
   • Living in regions with high pollen exposure, wool contact, or exposure to pets, cigarette smoke, and detergents is linked to symptom persistence.
   • Family history of atopy is a strong predictive factor.
     
     

Comorbidities and Complications

1. Atopic Triad:
   • Up to 30% of patients develop asthma, and 35% have allergic rhinitis, highlighting the interconnected nature of atopic diseases.
2. Infections:
   • Bacterial: Frequent colonisation with Staphylococcus aureus; infections may involve S. aureus, Streptococcus pyogenes, or methicillin-resistant S. aureus (MRSA).
   • Viral: Increased risk of eczema herpeticum (Kaposi varicelliform eruption) caused by herpes simplex virus, which requires timely antiviral therapy to prevent severe outcomes.
   • Fungal: Rare but possible secondary infections, particularly in eczematous areas.
3. Food Allergies:
   • Patients with AD are at higher risk for urticaria and anaphylaxis triggered by peanuts, eggs, milk, soy, and seafood.
4. Allergic Reactions:
   • Increased prevalence of contact allergies to latex and nickel.
5. Psychosocial Impact:
   • Sleep disturbances from incessant pruritus significantly impact quality of life.
   • In children, AD contributes to psychological burden, school absences, and family stress.
     
     

Mortality

• Death from AD is rare. Severe infections like eczema herpeticum or complications from immunosuppressive therapy can lead to morbidity but are usually manageable with timely intervention.
• Historical concerns such as eczema vaccinatum from smallpox vaccination no longer apply, although physicians should remain vigilant about this in potential future bioterrorism contexts.

Long-Term Impact

1. Financial Burden:
   • Comparable to chronic diseases such as asthma, arthritis, and diabetes due to costs of medication, medical visits, and missed work or school.
2. Sleep and Quality of Life:
   • Persistent itch disrupts sleep and negatively affects daily functioning, contributing to a diminished quality of life.
3. Late-Onset AD:
   • While less common, late-onset AD (after age 20) is increasingly recognised, often presenting as a more persistent and severe form of the disease.
     
     

Dermatological Complications

1. Skin Infections:
   • Bacterial: Staphylococcus aureus and Streptococcus pyogenes are common pathogens, often causing secondary infections during flares.
     • Symptoms: Erythema, pustules, or crusting.
     • Treatment: Topical antibiotics for localised infections or systemic antibiotics for more severe cases. Bleach baths may help reduce colonisation.
   • Viral:
     • Eczema Herpeticum:
       • Caused by herpes simplex virus, leading to grouped vesicles or pustules that progress to ulcerations.
       • May require hospitalisation and systemic antiviral therapy.
     • Molluscum Contagiosum and Verrucae Vulgaris:
       • These viral infections may be more widespread and resistant to treatment in AD patients.
   • Fungal: Though less common, fungal infections may complicate severe AD cases.
2. Topical Corticosteroid Adverse Effects:
   • Cutaneous: Skin atrophy, hypopigmentation, striae, purpura, and telangiectasia, particularly with prolonged use or higher-potency formulations.
   • Topical Steroid Withdrawal (TSW):
     • May present as burning, exudative, or itchy skin after discontinuing corticosteroids, with prolonged recovery.
     • Associated with inappropriate long-term use of potent steroids.
3. Treatment-Induced Changes:
   • Calcineurin Inhibitors:
     • Theoretical risk of malignancy, though clinical evidence is conflicting. Long-term use should be limited to affected areas.
   • Systemic Therapies:
     • Methotrexate: Risk of hepatic toxicity, nausea, pancytopenia, and pulmonary complications.
     • Azathioprine: Hepatotoxicity, myelotoxicity, and possible malignancy with prolonged use. Testing for thiopurine methyltransferase (TPMT) activity is recommended before initiation.

Systemic Complications

1. Atopic March:
   • Progression to related conditions such as asthma, allergic rhinitis, and food allergies. Approximately 30% of AD patients develop asthma, and 35% experience nasal allergies.
2. Anaphylaxis and Food Allergies:
   • Increased risk of reactions to peanuts, eggs, milk, soy, fish, and seafood. Nickel and latex allergies are also more prevalent in AD patients.
3. Systemic Corticosteroid Effects:
   • Rare but include adrenal suppression, reduced growth rate, Cushing syndrome, and decreased bone density. Use of systemic corticosteroids should be limited to short-term therapy during severe flares.
     
     

Psychological and Quality of Life Impacts

1. Psychological Stress:
   • Chronic itch and visible skin lesions can lead to significant psychological distress, social withdrawal, and reduced self-esteem.
   • Sleep disturbances due to persistent pruritus negatively affect mood, academic or work performance, and family dynamics.
2. Economic Burden:
   • Comparable to other chronic conditions such as asthma and diabetes, with costs associated with treatment, missed workdays, and caregiver burden.
     
     

Rare Complications

1. Kaposi Varicelliform Eruption:
   • A severe skin infection caused by herpes simplex virus or vaccinia virus (no longer common due to cessation of smallpox vaccination).
   • Symptoms: Rapidly spreading vesicular lesions in areas of eczema.
   • Treatment: Systemic antivirals and hospitalisation if necessary.
2. Sleep Disturbances:
   • Incessant pruritus disrupts sleep, further exacerbating the physical and psychological burden.
     
     

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