Atopic Dermatitis

Etiology

Atopic dermatitis has a complex etiology including genetic and environmental factors which lead to abnormalities in the epidermis and the immune system. Atopic dermatitis is part of the atopic triad (atopic dermatitis, allergic rhinoconjunctivitis, and asthma) which may start simultaneously or in succession in what is known as the "atopic march." Patients with the atopic triad have a defective barrier of the skin, upper respiratory, and lower respiratory tract which leads to their symptomatology. If one parent is atopic, there is more than a 50% chance that their offspring will develop atopic symptoms. If both parents are affected, up to 80% of offspring will be affected. Genetic alterations include loss of function mutations of filaggrin (Filament Aggregating Protein), an epidermal protein that is broken down into natural moisturization factor. Filaggrin mutations are present in up to 30% of atopic dermatitis patients and may also predispose patients to ichthyosis vulgaris, allergic rhinitis, and keratosis pilaris. Food hypersensitivity may also cause or exacerbate atopic dermatitis in 10% to 30% of patients. Ninety percent of such reactions or flares are caused by eggs, milk, peanuts, soy, and wheat.[4][5]

Recent studies indicate that there may be an association between smoking and adult-onset AD.

Epidemiology

Atopic dermatitis is seen in approximately 10% to 30% of children and 2% to 10% of adults in developed countries. This prevalence has increased two to three-fold in recent decades. Atopic dermatitis has a higher incidence at higher latitudes, which may be related to decreased sun exposure and lower humidity levels. Atopic dermatitis is divided into three subsets based on the age of onset:

1. Early-onset atopic dermatitis (birth to 2 years old):  most common type of atopic dermatitis, with approximately 60% of cases starting by age 1. Sixty percent of cases resolve by 12 years old
2. Late-onset atopic dermatitis:  symptoms begin after the onset of puberty
3. Senile onset atopic dermatitis: an unusual subset with onset in patients older than 60 years old.

Pathophysiology

Atopic dermatitis patients have a defective skin barrier that is susceptible to xerosis and environmental irritants and allergens that lead to inflammation, pruritus, and the classic clinical findings of atopic dermatitis. The barrier defect may be caused in part by decreased levels of ceramides, which are sphingolipids in the stratum corneum which play a role in the skin's barrier function and prevent transepidermal water loss. The defective skin barrier allows irritants and allergens to penetrate the skin and cause inflammation via an overactive Th2 response (with increased IL-4, IL-5 cytokines) in acute lesions and Th1 response (with IFN-gamma and IL-12) in chronic lesions. Scratching of the skin also stimulates keratinocytes to release inflammatory cytokines such as TNF-alpha, IL-1, and IL-6. Decreased anti-microbial peptides (human beta-defensins, cathelicidins) in the epidermis of atopic patients also contribute to Staphylococcus aureus colonization seen in more than 90% of atopic dermatitis patients. S. aureus may worsen the inflammation of atopic dermatitis lesions and lead to secondary infection and impetiginization. [6][7]

In AD, there is significant water loss across the epidermis, but why there is dysregulation of the epithelial barrier is not fully understood. It is believed that filaggrin, which is critical for epithelial integrity, may be dysfunctional.

History and Physical

A practitioner should take a patient's history and focus on the following:

• Onset and distribution of lesions
• The severity of pruritus (e.g., keeping patient awake at night)
• Family and/or personal history of the atopic triad
• Presence of contact allergens
• The presence of triggers including allergens (e.g., dust mites, animal dander), hot showers/sweating, soaps, fragrances, food hypersensitivities, and synthetic fabrics such as polyester.

Classic physical exam findings depend on age group. Infants develop edematous papules and plaques that may have vesicles or crust on the scalp, face, and extensor extremities. Infants rarely have atopic dermatitis lesions affecting the diaper area but may be susceptible to other causes of diaper dermatitis such as candida or seborrheic dermatitis. Atopic dermatitis children classically have less exudative patches and plaques on antecubital and popliteal fossae; adults have chronic lichenified (enhanced skin markings) lesions that have a predilection for hands. Individual lesions may also be further classified into acute (edematous, erythematous papules and plaques and/or vesicles/crusting), subacute (erythema, scale, variable crusting), or chronic (thick plaques with lichenification and scale) stages.

Evaluation

Atopic dermatitis is typically a clinical diagnosis given the classic distribution of lesions in each age group. The presence of associated findings (e.g., keratosis pilaris) may facilitate diagnosis. A biopsy will show an eczematous pattern. In childhood cases that are recalcitrant to treatment, fluorescent enzyme immunoassays or skin prick testing can be performed to detect immunoglobulin E (IgE) antibodies against specific allergens, which may or may not be a clinically relevant exacerbating factor.[8][9]

Treatment / Management

The four major components of treatment include trigger avoidance, daily skin care, anti-inflammatory therapy, and other complementary modalities.

Daily skin care includes the application of emollients twice daily, with the application within three minutes of exiting lukewarm shower or bath to prevent skin drying. Ointments are the most occlusive but may be more greasy. Topical steroids, which should be applied before emollients to "lock-in" their effect, are first-line agents for acute flares. The potency should be strong enough to control a flare quickly, and consideration should be given for tapering every other day and for maintenance therapy twice weekly (e.g., weekends) in the usual areas of involvement. Reversible side effects of steroid use include skin atrophy and telangiectasia.

Sensitive areas (including the intertriginous areas of the axilla and groin, in addition to the face) may require topical nonsteroidal agents including calcineurin inhibitors such as tacrolimus and pimecrolimus. Newer non-steroidal agents include crisaborole, which exerts its effect by blocking PDE-4. When atopic dermatitis is not controlled with topical agents, systemic agents include phototherapy (ultraviolet (UV) A, UVB, and narrow-band UVB), cyclosporine, azathioprine, mycophenolate mofetil, and methotrexate.

 A newly FDA-approved biologic therapy is dupilumab, which is a monoclonal antibody that blocks the IL-4 receptor and thus the effect of IL-4 and IL-13.  Other complementary therapies include bleach baths (0.5 cup bleach in full 40 gallon tub) one to two times weekly to decrease S. aureus colonization, low allergen maternal diets during breastfeeding, and probiotic and prebiotic use in pregnant mothers and at-risk infants which has shown 50% decreased frequency of atopic dermatitis at ages 1 to 4 years old compared to placebo.[10][11][12](A1)

Recently Crisaborole topic ointment was approved for mild to moderate AD. The drug is a phosphodiesterase inhibitor and shown to improve skin symptoms.

Some patients may benefit from probiotics; it is believed that the bacterial products may enhance the immune system and prevent the development of allergic IgE antibody response. Further, probiotics are recommended during pregnancy and in breast feeding women.

Numerous studies show that bleach baths may help relieve the symptoms of AD by lowering the risk of superinfection with bacteria.

Differential Diagnosis

• Allergic contact dermatitis
• Lichen simplex
• Lichen planus
• Psoriasis
• Scabies
• Tinea
• Seborrheic

Treatment Planning

Guidelines on the use of cyclosporine

1. Cyclosporine has been approved for use in AD under the following conditions:
2. The patient is older than age 16
3. Continuous treatment is only done if appropriate monitoring is undertaken
4. Intermittent doses of up to 16 weeks are recommended in most patients
5. The dose should be titrated to lower renal toxicity
6. If hypertension develops, the dose should be reduced or discontinued
7. If an infection develops, reduce the dose of cyclosporine and manage the infection
8. All patients should be educated about symptoms of infections and when to seek help
9. Patients need to be monitored for nonmelanoma skin cancer
10. Cyclosporine should not be used at the same time as phototherapy
11. Monitor serum lipid levels

Prognosis

Overall, many patients with AD do improve with time. However, at the same time patients with AD may also have allergic rhinitis and asthma, which may not improve. In most cases of childhood-onset AD, the disorder persists for decades. The condition has relapses and remissions; relapses often require the use of medications. Individuals who are continuously exposed to smoke, tobaccos, pet dander, fumes, pollen, soap, detergent, and wool will have continual symptoms and the overall quality of life is poor.

Persistent and recurrent itching not only is irritating but is costly to manage. A well-known complication of AD is Kaposi varicelliform eruption,  that is linked to a primary herpes infection. The vesicular lesions appear in the eczematous area and can quickly spread to healthy skin. Treatment with acyclovir can help lower the morbidity.

Patients with AD are also prone to skin infections with Staphylococcus and streptococcus.

Complications

• Kaposi varicelliform eruption
• Bacterial infection
• Uriticaria