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Atopic dermatitis (Atopic eczema)

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A chronic relapsing pruritic skin condition manifested by erythematosus changes scaly changes with lichenification, excoriation, and pigment changes.

A common chronic inflammatory skin disease associated with itch, pain, sleep disturbances, anxiety, depression, and increased health utilization.

The most prevalent chronic inflammatory skin disease with a worldwide prevalence of approximately 20% among children, and 2-7% among adults.
Newer data suggests that adult-onset  atopic dermatitis occurs in up to 26% of patients.
The condition abates with age in most patients, however, the lifetime prevalence of atopic dermatitis is 10 to 30%.
AD manifestations include chronic pruritus and inflamed skin, along with coexisting conditions, that impair quality of life and substantial burden of disease.
Sleep disturbances, primarily due to itching, is common and has a major effect on quality of life.
AD negatively affects quality of life, social interactions, and work productivity.
It has an annual US healthcare cost exceeding $5.3 billion.

AD is characterized by epidermal barrier disruption, T-cell activation, and imbalance of the skin microbiome.

Pathophysiology related to complex relations with genetic , environmental psychological, skin barrier and immunological factors.

Pathogenesis of AD is primarily driven by type 2 helper T (TH2) lymphocytes, with considerable contributions from TH17 and TH22 cells, which releases cytokines,  resulting in elevated IgE production and skin inflammation.
The dysregulation of type 2 helper T cells, which preferentially produce cytokines, such as interleukins, 4, 13, and 31 play essential role in the pathogenesis of AD.
Interleukin 13 is implicated as the primary cytokine in AD, and serum levels of interleukin 13 correlate with disease severity.

Known as atopic eczema or atopic dermatitis.

A chronic skin disease manifested by inflammation and small vesicles with severe itching.

Commonly associated with generalized skin dryness, early onset, and atopy.

Approximately 85% of cases begin before age 5 years.

Associated with changes in microbiome.

Patients have more gram positive organisms on skin.

Up to 90% of patients with eczema have gram-positive Staphylococcus aureus on their skin, which can worsen flare ups and cause serious staph infections.

Associated features include hyperlinearity of the palms and soles, Dennie-Morgan lines, and Herrthoge’s sign..

Is a result of multiple factors including hyperstimulated cutaneous immune system,

genetically determined compromised skin barrier, and exposure to triggering agents in the environment.

Usually appears between the ages of 2-3 months and 2 years in the form of red patches and small vesicles and usually regresses at 5 years to disappear in most cases to 12 years.

Can have a profound effect on the quality-of-life patients and their families.

Can impair sleep, behavior, mood , and cause absences from work and school.

Outbreaks are often triggered by infections in children and stress in adults.

Prevalence estimates is adults is around 10%.

Affects 13% of children.

Environmental allergens and familial predisposition are two major causes of eczema.

More common in children, but eczema occurs in approximately 2% of adults.

One of the most common chronic diseases and affects up to 1/5 of population in developed countries.

Lifetime prevalence has shown worldwide increase overall past three decades.

Prevalence plateaus and about 10-20%, whereas it is lower in many developing countries.

An allergic phenomenon.

Children affected have a genetic predisposition.

Approximately 60% of the cases the disease manifests during the first year of life, but

can start at any age.

Earliest clinical signs or skin dryness and roughness.

Patients are pre-disposed to ocular complications, such as blepharitis, keratoconjunctivitis, keratoconus, rhegmatogenous retinal detachment, and cataract.

Associated with anterior subscapular cataracts as well as posterior subscapular cataracts.

Eczematous lesions usually do not occur before the second month of life.

Its clinical course can be continuous for long periods of time, or of a relapsing-remitting nature with repeated flareups.

The disease is mild in about 80% of affected children.

Other allergic manifestations often accompany eczema such as allergic rhinitis, conjunctivitis, asthma or urticaria.

The rash can be associated with four symptoms: itch, blisters, crusting and scarring.

Itching may be systematic.

After several years, the skin may undergo lichenification in areas like the face, neck, flexures and bust.

Skin of patients with atopic dermatitis prone to secondary infections, particularly S. aureus.

Symptoms are characteristically sawtooth relapsing, and remitting.

Contact eczema is caused by contact with an allergenic highly localized area.

Birth cohort studies suggest in up to 70% the disease greatly improves or resolves until late childhood, and early and severe onset, family history, and early allergen sensitizations are risk factors for a long course.

Skin tests can identify the trigger.

A systemic Th2-cell dominated immune shift with frequent elevations of total and allergen specific IgE levels.

Skin changes include erythematous changes with edema, vesicles and weeping in the acute stages and with skin thickening in the chronic stages.

10% of children and 4.7% of young adults have pruritic eczematous skin lesions due to activation of T cells in skin and an imbalance of cytokine production.

Affects approximally 10% of US adults and children.

In patients with atopic dermatitis S. aureus is colonized in 60 to 90% of patients.

Prevalence varies from 2-20% worldwide in children 6-7 years of age.

Approximately 84% of cases are mild, 14% are moderate and 2% are severe.

In infants it often involves the face, scalp and extensor surfaces of the body.

In children involvement of the flexure surfaces of the extremities.

50% of patients exhibit the process before 1 year of age and 80% before 5 years of age.

Affects 7-17% of schoolchildren.

Up to 60% of children with clinical phenotype do not have IgE mediated sensitivity to allergens.

Elevated total or allergen-specific serum IgE concentrations are noted in many patients.

10% of cases in hospital settings start in adults.

In the first two years of life up to two thirds of infants with moderate to severe disease show sensitivity to food allergens.

Food allergy seems to affect about 30% of early and severe cases of atopic dermatitis and is much lower in mildly affected and older children in very rare in adults.

Allergies to milk, eggs and wheat typically resolved during childhood, but allergies to nuts and fish often persist.

As children grow older sensitization pattern shift towards inhalant allergens.

Asthma develops in 30% of children.

Allergic rhinitis develops in 35% of children.

70% of patients have a family history of atopic dermatitis, asthma or allergic rhinitis.

Resolves in 50% of affected children by adolescence.

Although many children will clear their symptoms by adolescence up to 50% may have adulthood recurrences.

Early onset of disease, associated asthma, hay fever, and positive family history predict for a more persistent course of disease.

Prognosis related to severity of disease and serum levels of IgE antibodies to food and inhalant allergens.

Distribution of the skin lesions include the face and extensor surfaces in infants, flexural areas and lichenification in older children and adults.

Findings: ichthyoids, hyper linear palms, xerosis, keratoses pilaris, infections, nipple eczema, cheilitis, conjunctivitis, periorbital darkening, pityriasis alba, itching, and

Flares manifest as increasing priorities of red, rough, and flaky tissue which may be fissured and become chronically thickened, rough and discolored.

Diagnosis relies exclusively on clinical features as there is no specific laboratory or histological findings.

Essential diagnostic features are pruritus and eczematous lesions that can be acute, subacute or chronic.

Scratching associated with pruritus may induce mechanical damage to the skin, which may enhance inflammatory reactions and worsen providers.

Lesions can affect any art of the body but typically show age-related morphology and distribution.

TREATMENT:

Goals of treatment include decreasing inflammation of the skin, skin hydration, decreasing itch, managing associated skin infections and providing psychological support.

Topical therapy first- line treatment.

Medical treatment include corticosteroids applied locally.

Topical corticosteroids are the first line recommended therapy when non-pharmacological measures have failed

Topical corticosteroids reduces acute and chronic signs of disease and reduce itch associated with AD.

No clear-cut benefit of any specific topical corticosteroid over another and there’s limited evidence how to dose such drugs without standards for application or body surface area to weight ratio adjustments.

The challenge of topical agents is that they require regular use and an acceptance by the patient due to the sensations of the agent on the skin.

Patients with AD are at increased risk of irritant and allergic contact dermatitis precipitated by topical agents and care must be taken in choosing products with flow sensitization.

Topical corticosteroids should not be stopped abruptly but gradually.

Topical corticosteroids used in a proactive manner on sites of frequent flares may be effective at preventing relapses.

Mid-potency corticosteroids are the first-line treatment of atopic dermatitis.

Atopic dermatitis may fail to respond to topical corticosteroids initially or lose response over time, a phenomenon known as tachyphylaxis.

When the response to topical therapy is inadequate  in patients with moderate to severe disease, the addition of systemic therapy or photo therapy, or both, is recommended.

Monoclonal antibodies, such as dupilumab, and tralokimumab, as well as Janus kinase inhibitors have been approved to treat moderate to severe atopic dermatitis.

Nonadherence to medication is the most likely cause of treatment resistance in patients with atopic dermatitis.

For itching, antihistamines improve symptoms.

The fight against dry skin is a priority.

Skin abnormality includes skin barrier defect that leads to increased transepidermal water loss and progressive skin dryness.

Topical calcineurin inhibitors or anti-inflammatory agents effective in management.

Tacrolimus ointment safe and effective treatment.

Tacrilomus is effective as mid potency topical corticosteroids whereas pimecrolimus is less efficacious than mid and high potency topical steroids.

The anti-pruritic affect of antihistamines is limited in patients with atopic dermatitis.

Topical calcineurin inhibitors recommended a steroid sparing agents in the treatment of AD.

Topical calcineurin inhibitors do not cause cutaneous atrophy and are useful in sites of thin or sensitive skin.

Topical calcineurin inhibitors can be used proactively and as maintenance to prevent flares at sites of recurrent disease.

Systemic glucocorticosteroids, are the most frequently used treatment, but with little evidence of efficacy.

Cyclosporine is recommended for first-line, treatment

Azathioprine is recommended for second-line treatment; and methotrexate and IFN-γ for third-line treatments.

Strong recommendations are only possible for the short-term use of cyclosporin A.

Moisturizers shown in multiple clinical trials to have significant benefits.

Wet wrap therapy incorporating topical medications,and moisturizers , or both, is recommended management for significant flares or recalcitrant disease.

Dipulumab is approved for adolescents aged 12 to 17 years and adults with moderate-to-severe atopic dermatitis poorly controlled with topical prescription therapies or when those therapies are not advisable.

The oral Janus kinase inhibitor abrocitinib at a dose of the 200 or 100 mg once daily resulted in greater reductions in signs and symptoms of moderate to severe a topic dermatitis then placebo at 12 and 16 weeks.

The oral Janus kinase inhibitor abrocitinib at a dose of the 200 mg  was superior to dupilumab with respect to itch response at week 2, otherwise no significant differences at week 16.

Subcutaneous nemolizumab in addition to topical agents for a topic dermatitis results in a greater reduction in pruritus than placebo plus topical agents.

Lebrikizumab,a high affinity IgG4, monoclonal antibodies targeting interleukin 13 prevents the formation of interleukin 13 receptor signaling complex, and is effective in adolescents and adults with moderate to severe atopic dermatitis (Silverberg, JI).

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