Atopic Dermatitis: Study Notes

• Atopic dermatitis, or eczema, is a chronic, autoimmune, pruritic (itchy), inflammatory skin condition.
• It affects approximately 5-20% of children worldwide, often starting in childhood and has a predilection for affecting skin creases and flexure surfaces.

Atopic Triad

• Atopic dermatitis is associated with other conditions forming the "atopic triad" linked to increased immunoglobulin E levels.
• The atopic triad includes atopic dermatitis, allergic rhinitis, and asthma.
• Approximately 80% of those with atopic dermatitis will develop allergic rhinitis, asthma, or both.
• Food allergies, such as urticaria, are commonly associated with atopic dermatitis with 10-20% experiencing food-related allergic reactions.
• Early-onset atopic dermatitis (within the first 3 months of life) is linked to specific food allergies like egg, milk, and peanuts.

Pathogenesis of Atopic Dermatitis

• Pathogenesis is multifactorial, driven by an interplay of epidermal barrier dysfunction and immune dysregulation, host genetics, and environmental factors.
• Involves a defective epidermal barrier and immune dysregulation.

Defective Epidermal Barrier:

• The outermost epidermal protein and lipid barrier is impaired.
• Primarily reflects decreased expression of epidermal differentiation proteins like filaggrin.
• Decreased tight junctions (primary barrier against transepidermal water loss) such as claudins.
• Decreased concentration of very long-chain fatty acids and ceramides.
• Results in increased susceptibility to external insults like microbes, pro-inflammatory allergens, toxins, and irritants.
• Involves protease-antiprotease activity imbalance.
• Related to problems with proteins kallikrein and LEKTI.
• Tight junction abnormalities in the skin.

Immune dysregulation:

• Involves the innate and adaptive immune systems.
• The innate immune system shows reduced TLR-2 and TLR-9 function.
• The adaptive immune system has increased expression of TH2, TH17, and TH22 cytokines.
• Reduced antimicrobial peptide (AMP) production in response to triggers impairs the normal defense response to environmental pathogens in adults.
• Reduction in T helper type 1 (Th1) cytokines may blunt the antimicrobial response in affected children.
• Antigen-presenting cells take up immunogenic antigens for presentation to primarily CD4+ T cells.
• Keratinocytes release chemokines including CCL17 (TARC) and cytokines such as thymic stromal lymphoprotein (TSLP), interleukin-1β, IL-25, and IL-33.
• Results in an immune response predominantly skewed towards Th2 cells.
• Increased quantities of signature Th2 cytokines such as IL-4, IL-5, IL-13, and IL-31.
• Th2 cytokines, especially IL-4 and IL-13, contribute to additional Th2 cell polarization.
• Th2 Cytokines promote IgE class-switching and eosinophil recruitment.
• Th2 Cytokines further impair epidermal barrier function by inhibiting epidermal differentiation, lipid production, and AMP expression.
• While Th2 skewing is universal among AD patients, activation of other T helper cell driven pathways (i.e., Th1 in adults, Th17 in children and Asians) is more heterogenous and may be related to other patient factors, including age and race.
• Exogenous (e.g., allergens, irritants, pathogens) and endogenous (e.g., cytokines, neuropeptides, lipids) signals act as pruritogens. These directly signal and/or modulate the sensation of itch by activating receptors on sensory neurons of the dorsal root ganglion.
• Activation of cytokine receptors (e.g., IL-4, IL-13, IL-31, IL-33, TSLP), G-protein coupled receptors, and transient receptor potential channels results in action potentials, which both propagate sensory information to central nervous system and stimulate local production of inflammatory mediators, such as calcitonin gene related peptide and substance P.

Risk Factors, Triggers, and Protective Factors

Influencing Factors (Risk Factors/Triggers):

• A family history of atopic dermatitis is present in approximately 70% of individuals with the condition.
• A loss-of-function mutation of the filaggrin gene is a strong risk factor.
• Allergies increase the likelihood of atopic dermatitis due to associations in the atopic triad.
• Hardness and mineral content in water can worsen or trigger atopic dermatitis.

Protective Factors:

• Early daycare exposure can be protective.
• Exposure to pets can reduce the risk.
• Exposure to farm animals can reduce the risk.
• These protective factors relate to the hygiene hypothesis.

Atopic Stigmata (Skin Findings)

• Keratosis pilaris/Hyper keratosis pilaris, colloquially called "chicken skin" presents as small, raised red bumps.
• Dennie-Morgan fold presents as wrinkling or changes in skin color underneath the eyes.
• Hertoghe's sign presents as thinning or absence of the lateral eyebrows.
• Pityriasis alba presents as whitening or lightening of skin tone in certain areas due to scarring from previous eczema.
• Palmer hyper linearity presents as an increased number of palmar lines on the hands.
• Retro auricular fissure presents as chafing or scarring behind the ear.

Diagnosis of Atopic Dermatitis

• Diagnosis is generally clinical, based on observation.
• A United Kingdom working group established objective, criteria-based diagnostics.
• Requires one mandatory criterion, plus three or more additional criteria.
• Mandatory: Pruritic (itchy) skin lesions.
• Additional criteria: Skin creases involved (antecubital fossa, popliteal fossa, neck, around eyes), a history of asthma or hay fever, generally dry skin within the past year, symptoms beginning before the age of two or visible dermatitis involving flexural surfaces.

Treatment and Management

• Avoid allergens and triggers that can cause flares.
• Heat or low humidity environments should be avoided.
• Stress and anxiety should be avoided.
• Dietary considerations: some believe certain foods worsen atopic dermatitis (e.g., dairy) but this is controversial.
• Eliminating certain foods to observe symptom improvement may be helpful.
• Treatments include:
• Topical corticosteroids like 2.5% hydrocortisone cream.
• Topical calcineurin inhibitors for the face, eyelids, neck, and skin folds.
• Phototherapy for severe cases.
• Cyclosporine for acute flares only, and for a limited duration.
• Antihistamines for pruritus.
• Melatonin may be a mild aid in helping with symptoms, but more research is needed.