Atopic dermatitis, frequently referred to as eczema, is a common chronic inflammatory skin disease that currently affects about 20% of people worldwide and is increasing in prevalence.[1] It is associated with other markers of atopy, such as asthma, allergic rhinitis, seborrheic dermatitis, and food allergy. Several factors have been implicated in its pathogenesis, including immune defects, structural abnormalities of the skin, and changes in skin microbial flora.[2] The condition usually starts early in life and resolves in childhood; however, a significant portion of the population has atopic dermatitis that may persist indefinitely. About 80% of cases start in infancy or childhood. Whereas the point prevalence in children varies from 2.7-20.1% across countries, it ranges from 2.1-4.9% in adults.[3],[4]

Presentation depends on patient age and disease severity. In general, dry skin and pruritus are the most common symptoms. Young children usually have itching and subsequent erythematous plaques or patches with scaling and papular features on extensor surfaces and the face.[5] Teens and adults tend to have more localized areas (mostly skin flexures), thickened skin with lichenification and excoriated and fibrotic papules, reflecting the chronicity of the disease.[6] Severe cases may present in any distribution. Patients with atopic dermatitis are at increased risk for viral, bacterial, and/or fungal skin infections.

Risk Factors

Personal or family history of atopy. Maternal disease seems to be a stronger risk factor than paternal disease.[7] About 70% of those with atopic dermatitis have a relative with atopic disease.[8] A history of food allergy, allergic rhinitis, or asthma is associated with atopic dermatitis.

Filaggrin (FLG) gene mutations. This gene, which is involved in skin barrier structure, has been strongly associated with increased risk of atopic dermatitis and other skin conditions and allergies.[9]

Antigens. Variations in antigen exposure may affect risk of disease. Developed countries appear to have higher rates of disease.[10]

Some evidence suggests that exclusive breastfeeding for at least the first 3 months of life, along with early exposure to daycare and companion animals, may be associated with reduced risk among infants with a family history of atopy.[11]

Diagnosis

Major diagnostic criteria for atopic dermatitis include pruritus, relapsing disease, age-appropriate distribution of lesions (face and extensor surfaces in children and flexor surfaces in adults), and a family history of atopy. Nonspecific minor criteria that may aid diagnosis include periorbital darkening, dry skin, and keratosis pilaris on the skin over the triceps region.[12] Other diseases, such as hyperimmunoglobulin E syndrome and scabies, can resemble atopic dermatitis in appearance. In atopic dermatitis, intertriginous regions are not usually affected (unlike psoriasis, in which these areas may be involved.)

No laboratory tests definitively diagnose atopic dermatitis; however, up to 80% of patients will have an elevated serum immunoglobulin E (IgE) and positive skin tests for immediate hypersensitivity reactions to common allergens.[13] These tests are not routinely performed and are not required for diagnosis.

Recurrent skin infections may occur in atopic dermatitis-damaged skin, and they may also exacerbate disease. Skin infections occur much more commonly in atopic dermatitis patients than in psoriasis patients, suggesting that factors aside from skin breakdown are involved in predisposition to skin infection.[14]

Treatment

Initial treatment of atopic dermatitis should seek to eliminate exacerbating agents, such as soaps and detergents, food allergens, and cosmetics. Excessive bathing or use of lotions should be discouraged, as evaporation of water from the skin exacerbates the condition.[15] Some patients may be surprised to learn that water-based lotions actually increase evaporation of water from the skin. Humidifiers may be tried in dry climates. Basic management and flare prevention consists of short (5-10 minutes) daily showers or baths with lukewarm water followed immediately by the application of emollients and moisturizers, and avoidance of triggers such as irritants, aero- or food allergens, and extremes of heat, cold, or humidity.[16] Treatment will also depend on disease severity.

Education about the disease is an integral part of treatment.[17] Psychological approaches to mitigate stress may reduce the risk of exacerbations.[18]

Emollient creams or ointments should be applied liberally, especially after bathing, to lock in moisture. Occlusive bandages, gloves, or socks can be worn nightly to aid skin hydration.

Antihistamines (e.g., diphenhydramine, fexofenadine, cetirizine) are commonly used to relieve pruritus.

Topical corticosteroids (e.g., desonide, hydrocortisone) should be used in the lowest possible therapeutic strength to treat active atopic dermatitis. Depending on severity and location, they can be used once or twice per day, for no longer than 4 weeks at a time due to possible atrophy/thinning of skin.

Topical tacrolimus and other topical calcineurin inhibitors (immunomodulators) are similar in strength to medium potency topical steroids and are usually considered second-line agents. While effective as adjunctive treatments, they are used less commonly because of concerns about their carcinogenic potential. They are approved for use in patients 2 years and older who have not responded to other agents. Unlike corticosteroids, topical calcineurin inhibitors do not cause skin atrophy, so they can be used on sensitive areas, such as the face, eyelids, and underarms.[19] Patients treated with tacrolimus ointment should be aware that a facial flush reaction can occur within 5-15 minutes of alcohol ingestion.[20]

Crisaborole, a phosphodiesterase 4 (PDE-4) inhibitor is approved for treatment of mild-to-moderate AD in patients aged 2 years and older.[21]

Systemic corticosteroids, such as prednisone, may be used in adolescents and adults for a short duration when acute exacerbations occur.

Antibiotics may be effective when patients develop a bacterial infection (e.g., Staphylococcus aureus) in the affected area or have pustular disease.

Severe Disease

Phototherapy using ultraviolet light (UVA, UVB, and narrow-band UVB) is helpful, but prolonged treatment may increase the risk of melanoma and other types of skin cancer.[22]

Oral tacrolimus and cyclosporine may be used for moderate to severe cases, with close monitoring for systemic side effects. It should be noted that a possible risk of skin and lymph cancers is associated with calcineurin inhibitors.

Methotrexate, azathioprine, and mycophenolate mofetil are other immunosuppressants that may be occasionally prescribed by a dermatologist for severe cases. These therapies should be generally avoided in children.

Monoclonal antibodies (dupilumab) are now the immunosuppressant agent of choice when disease cannot be controlled with topical or phototherapy. Compared with conventional immunosuppressants, dupilumab has a better safety profile, but cost is typically a limiting factor. Dupilumab is approved for adolescents and adults for the treatment of moderate-to-severe AD that has not adequately responded to topical prescription therapies or when such therapies are not advisable. Dupilumab has dramatically improved outcomes for adults with severe disease.[23]

Desensitization through allergen-specific immunotherapy (SIT) is sometimes used for severe dust mite-induced disease.

Melatonin, probiotics, leukotriene receptor antagonists, and herbal preparations, including Flos lonicerae, Herba menthae, Cortex moutan, Rhizoma atractylodis, and Cortex phellodendri, are under study as possible treatment options.[24]

Nutritional Considerations

There are indications that diet-related factors, including body weight, fatty acid nutrition, and inflammatory responses, among others, may influence the incidence of atopic disease.[25],[26] The following factors are under investigation for their potential benefit:

Maintenance of a healthy bodyweight. A 2015 meta-analysis found that overweight or obese children had a 24-44% greater risk for having atopic eczema, respectively, compared with normal weight children. Among adults, overweight or obese individuals had a 29-56% greater risk for this disease, respectively, compared with normal weight adults.[27]

Avoidance of a Western dietary pattern. In the Korean National Health and Nutrition examination of more than 17,000 individuals, those whose diets contained the greatest amounts of meats and processed foods had a 57% greater risk for atopic dermatitis when compared with individuals whose diets contained the smallest amount.[28] Conversely, the International Study on Asthma and Allergy in Children (ISAAC) study of Colombian children found that children whose diets contained the highest amounts of traditionally eaten foods (e.g., fresh fruit and legumes) had an almost 40% lower risk for having atopic dermatitis compared to those eating the lowest amounts of these foods.[29]

Eliminating allergy-causing foods. A systematic review reported that atopic dermatitis is often associated with food allergies.[30] Food allergy occurs in roughly 30% of children with atopic dermatitis compared with 4-10% in the general pediatric population. Although nearly 80% of children with this condition have elevated food- or pollen-specific IgE levels and 40-90% of infants have positive skin-prick tests for various foods, only 35-40% of patients have clinical signs and symptoms of food allergy, according to multiple double-blind, placebo-controlled food challenge studies.[31] In these children, cow’s milk, eggs, peanuts, wheat, soy, nuts, and fish are responsible for > 90% of food allergies. In contrast, older children and adults may be more likely to react to birch pollen-associated foods (e.g., apple, carrot, celery, and hazelnut).[32]

A review found that evidence for the effectiveness of elimination of cow’s milk or eggs for children with atopic dermatitis was lacking. An exclusion diet was found more likely to be useful in patients with a clinical history of IgE-mediated allergic reactions and in young patients with severe disease.[33]

Oral food challenges (OFCs) are considered the gold standard by which true food allergy as a cause of atopic dermatitis is determined. In a retrospective study of 325 patients who underwent an OFC, nearly 9 of 10 patients had a negative response. Elimination diets may not be reliable if symptomatic improvements might be due to a placebo effect.[32]

Vegetarian diets. Preliminary evidence indicates that a vegetarian diet results in significant improvement in symptoms of atopic eczema, as judged by SCORAD (SCORing Atopic Dermatitis), a clinical tool for objectively assessing the severity of atopic dermatitis. This improvement appears to be related to reductions in circulating blood levels of eosinophils and neutrophils and decreased monocyte production of PGE2, an inducer of IgE and T helper 2 (Th2) cell production.[34] A low-energy diet (55% of estimated energy needs) conferred similar benefit for individuals with atopic dermatitis, although the practicality of energy-restricted regimens for long-term use is not established.[35]

Prebiotics and probiotics. Probiotics (mainly Lactobacillus rhamnosus) are orally administered microorganisms that have been used for atopic diseases because they may have anti-inflammatory and antiallergic properties by stimulating Th1 cytokines and by down-regulating CD34+ cells involved in the symptoms of dermatitis, while increasing those with anti-inflammatory effects (e.g., interferon-γ).[36],[37] A meta-analysis of randomized controlled trials found the use of synbiotics (combinations of prebiotics and probiotics) for at least 8 weeks with mixed-strain bacterial species had a significant effect on improving the SCORAD index in children more than 1 year old.[38] Other meta-analyses found that probiotics reduced the risk for atopic dermatitis in children whether given during pregnancy or during the perinatal period.[39],[40]

Fatty acids may be of some help. Studies on fatty acid supplementation in atopic eczema have been controversial. Defects in certain genes (FADS, ELOVL) that are responsible for the desaturation and elongation of essential fatty acids to their long-chain derivatives are often present in individuals with atopic disease. These in turn affect both the barrier and immunologic functions of the skin.[41] It has been suggested that a Western diet may aggravate this condition through the provision of saturated and trans-fatty acids in place of essential fatty acids. Controlled clinical trials of gamma-linolenic acid (GLA) from evening primrose, black currant seed, or borage oil have revealed varying degrees of benefit, including a steroid-sparing effect.[42] In a study of maternal GLA supplementation that continued through the second year of life in children, a significantly lower prevalence of atopic eczema was found during the first year of life in infants. However, this difference disappeared during the second year, as the amounts of saturated fat relative to polyunsaturated fat (which is close to recommended intakes during the first year of life) increased in children’s diets to that of adult diets.[43] A systematic review and meta-analysis of studies on fish intake or fish oil supplementation found an almost 50% reduction in the incidence of atopic eczema when compared with low fish intake or placebo.[44]

Vitamin D supplementation. Although data are mixed regarding the benefit of vitamin D supplementation, benefits are clearer in those with baseline low vitamin D levels or with frequent skin infections.[43]

Orders

See Basic Diet Orders chapter.

Elimination diet if specific triggers for dermatitis have not been found.

What to Tell the Family

Atopic dermatitis is a persistent ailment with a significant hereditary component. Some evidence indicates that the risk for developing this disease can be moderated through breastfeeding and allergen avoidance. In persons with established disease, effective management of symptoms is possible through combinations of topical ointments, diet modification, dietary supplements, and if necessary, systemic medications.

References