Medical Care
Patients with atopic dermatitis (AD) do not usually require emergency therapy, but they may visit the emergency department for treatment of acute flares caused by eczema herpeticum and bacterial infections.
Moisturization in atopic dermatitis
Depending on the climate, patients usually benefit from 5-minute, lukewarm baths followed by the application of a moisturizer such as white petrolatum. Frequent baths with the addition of emulsifying oils (1 capful added to lukewarm bath water) for 5-10 minutes hydrate the skin. The oil keeps the water on the skin and prevents evaporation to the outside environment. In infants, 3 times a day is not a great burden; in adults, once or twice a day is usually all that can be achieved. Leave the body wet after bathing.
Advise patients to apply an emollient such as petrolatum or Aquaphor all over the body while wet, to seal in moisture and allow water to be absorbed through the stratum corneum. The ointment spreads well on wet skin. The active ingredient should be applied before the emollient. Newer emollients such as Atopiclair and Mimyx have been advocated as having superior results, but they are expensive and need further evaluation.
Topical steroids in atopic dermatitis
Topical steroids are currently the mainstay of treatment. In association with moisturization, responses have been excellent.
Ointment bases are preferred, particularly in dry environments.
Initial therapy consists of hydrocortisone 1% powder in an ointment base applied 2 times daily to lesions on the face and in the folds.
A midstrength steroid ointment (triamcinolone or betamethasone valerate) is applied 2 times daily to lesions on the trunk until the eczematous lesions clear.
Steroids are discontinued when lesions disappear and are resumed when new patches arise.
Flares may be associated with seasonal changes, stress, activity, staphylococcal infection, or contact allergy.
Contact allergy is rare but accounts for increasing numbers of flares. These are seen mostly with hydrocortisone.
The results of a study from the Netherlands by Haeck et al. suggest that the use of topical corticosteroids for AD on the eyelids and periorbital region is safe with the respect to induction of glaucoma or cataracts. [44]
As a maintenance regimen, 1.25% hydrocortisone powder in Acid Mantle used diffusely as a steroid-based emollient is both effective and safe for longer periods (eg, months) to prevent acute flares in addition to using higher-class steroids to treat acute flares rapidly.
Immunomodulators in atopic dermatitis
Tacrolimus (topical FK506) is an immunomodulator that acts as a calcineurin inhibitor. Studies have shown excellent results compared with placebo and hydrocortisone 1%. Little absorption occurs. A stinging sensation may occur following application, but this can be minimized by applying the medication only when the skin is dry. The burning usually disappears within 2-3 days. Tacrolimus is available in 2 strengths, 0.1% for adults and 0.03% for children, although some authorities routinely use the 0.1% preparation in children. Tacrolimus is an ointment and is indicated for moderate-to-severe AD. It is indicated for children older than 2 years.
Pimecrolimus 1% is also an immunomodulator and calcineurin inhibitor. It is more effective than placebo. Pimecrolimus is produced in a cream base for use twice a day; it is indicated for mild AD in persons older than 2 years and is particularly useful on the face.
A 2006 black box warning has been issued in the United States based on research that has shown an increase in malignancy in association with the calcineurin inhibitors. While these claims are being investigated further, the medication should likely only be used as indicated (ie, for AD in persons older than 2 years and only when first-line therapy has failed).
These agents are much more expensive than corticosteroids and should only be used as second-line therapy.
Omalizumab is a monoclonal antibody that blocks IgE function. Case reports suggest that it may be an effective therapy for AD; however, a recent randomized, placebo-controlled trial did not demonstrate improvement in the clinical course. [45]
Dupilumab is a monoclonal antibody that blocks the IL-4 receptor alpha subunit, which is required for both IL-4 and IL-13 signaling. Randomized, double-blind, placebo-controlled trials have demonstrated marked and rapid improvement in AD disease activity. [46] This drug remains to be approved for AD by the US Food and Drug Administration (FDA); however, it is likely to be the first biologic therapeutic for moderate-to-severe AD.
Interleukin inhibitors in atopic dermatitis
Dupilumab is a monoclonal antibody that inhibits IL-4 and IL-13 signaling. In March 2017, it was approved by the FDA for adults with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. It is a subcutaneous injection that is administered every 2 weeks.
Approval of dupilumab was based on clinical trials investigating dupilumab as monotherapy (SOLO 1 and SOLO 2) and in concomitant administration with topical corticosteroids (CHRONOS). Results from the SOLO 1 (n=671) and SOLO 2 (n=708) trials showed 36-38% of patients who received dupilumab had scores of 0 or 1 (clear or almost clear) on the Investigator's Global Assessment scale compared with placebo (8-10%) (P <.001). Additionally, improvement from baseline to week 16 of at least 75% on the Eczema Area and Severity Index was reported in significantly more patients who received each regimen of dupilumab than in patients who received placebo (P <.001). [47]
Topical phosphodiesterase-4 (PDE-4) inhibitors in atopic dermatitis
Crisaborole topical ointment 2% (Eucrisa) was approved by the FDA in December 2016 for mild-to-moderate atopic dermatitis in adults and children aged 2 years or older. The approval was based on two placebo-controlled trials (n=1522). Patients who received crisaborole achieved greater response with clear or almost clear skin after 28 days compared with vehicle-treated patients (P <.001). [48]
Other treatments, effective and ineffective, in atopic dermatitis
Probiotics have recommended as a therapeutic option for the treatment of AD. The rationale for their use is that bacterial products may induce an immune response of the Th 1 series instead of Th 2 and could therefore inhibit the development of allergic IgE antibody production. Some report limited benefit in preventive and therapeutic roles. [49] A meta-analysis of 25 randomized placebo-controlled controlled trials involving 4031 subjects found that prenatal and postnatal administration of probiotics reduced IgE levels in infants and that it may protect against sensitization to hereditary allergies but may not protect against asthma or wheezing. [50, 51] In January 2015, the World Allergy Organization recommend the use of probiotics by pregnant and lactating women and their breastfed infants to prevent the development of AD. The recommendation was based on a meta-analysis of 29 studies in which probiotic use by pregnant women reduced the incidence of eczema by 9% during a 1- to 5-year follow-up period and use by lactating women was associated with a 16% reduction in eczema during a 6-month follow-up period. Probiotic consumption by breastfeeding infants was associated with a 5% reduction in eczema during the 6-month to 6-year follow-up period. [52, 53]
UV-A, UV-B, a combination of both, psoralen plus UV-A (PUVA), or UV-B1 (narrow-band UV-B) therapy may be used. Long-term adverse effects of skin malignancies in fair-skinned individuals should be weighed against the benefits.
In patients with eczema herpeticum, acyclovir is effective.
In patients with severe disease, and particularly in adults, phototherapy, methotrexate (MTX), [54, 55] azathioprine, cyclosporine, and mycophenolate mofetil [4] have been used with success.
Both hydroxyzine and diphenhydramine hydrochloride provide a certain degree of relief from itching but are not effective without other treatments.
Oil of evening primrose was believed to be effective, but in a randomized controlled study, it showed no benefit in children and little improvement in adults.
Unsuccessful therapy with everolimus, a rapamycin-derived macrolide, has been reported in 2 patients with severe AD. Combination therapy with either prednisone or cyclosporine A was not effective. [5] However, reports of the ineffectiveness of everolimus have been questioned. [6]
Results with many other medications, such as thymopentin, gamma interferon, and Chinese herbs, have been disappointing. Many medications are not practical to use, and they can be expensive. Some Chinese herbal preparations contain prescription medications, including prednisone, and have been associated with cardiac and liver problems.
Antibiotics are used for the treatment of clinical infection caused by S aureus or flares of disease. They have no effect on stable disease in the absence of infection. Laboratory evidence of S aureus colonization is not evidence of clinical infection because staphylococcal organisms commonly colonize the skin of patients with AD.
A randomized, investigator-blinded, placebo-controlled trial including 31 patients showed that intranasal mupirocin ointment and diluted bleach (sodium hypochlorite) baths improved AD symptoms in patients with clinical signs of secondary bacterial infection. [7] Multiple studies have now confirmed that bleach baths are highly effective in treating AD by limiting disease severity. [56] The most likely mechanism is reduction of superinfection with bacteria such as S aureus, thereby mitigating proinflammatory stimuli.
Nonmedical efforts in atopic dermatitis
Clothing should be soft next to the skin. Cotton is comfortable and can be layered in the winter. Wool products should be avoided.
Cool temperatures, particularly at night, are helpful because sweating causes irritation and itch.
A humidifier (cool mist) prevents excess drying and should be used in both winter, when the heating dries the atmosphere, and in the summer, when air conditioning absorbs the moisture from the air.
Clothes should be washed in a mild detergent with no bleach or fabric softener.
Food avoidance is discussed in Diet, below, and in Causes.
Consultations
Consulting an allergist may be necessary, particularly if the patient develops asthma and/or hay fever or an acute reaction to a food.
Diet
Avoid foods that provoke acute allergic reactions (hives, anaphylaxis). Most frequently, allergic reactions occur to peanuts (peanut butter), eggs, seafood, milk, soy, and chocolate. Additionally, advise patients to apply a barrier of petroleum jelly around the mouth prior to eating to prevent irritation from tomatoes, oranges, and other irritating foods.
Activity
Advise patients to avoid activities that cause excessive sweating. Also, swimming in an outdoor pool (or wading pool for babies) in summer provides therapeutic benefit by exposing the person to the sun but avoiding the heat.
Complications
If topical corticosteroids are used inappropriately or if superpotent steroids are used in teenagers during rapid growth, striae may occur. Skin thinning can result if steroids are used inappropriately in older patients.
Whether verrucae vulgaris and mollusca contagiosa are more frequent is difficult to assess, but they are more widespread and difficult to eliminate.
Tachyphylaxis to topical steroids occurs if they are not used on a stop-start basis.
Patients may develop other related allergic disorders such as urticaria, food allergy, asthma and allergic rhinitis.
Superinfection with S aureus may require topical and/or systemic antibiotic treatment with antistaphylococcal agents.
Superinfection with herpes simplex virus, referred to as eczema herpeticum, can require admission to the hospital in children for systemic treatment with acyclovir and evaluation of other complications such as herpes keratitis.
Prevention
Moisturization is important on an ongoing basis and may prevent flares.
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Typical atopic dermatitis on the face of an infant.
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Flexural involvement in childhood atopic dermatitis.
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Dirty neck sign in chronic atopic dermatitis.
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Irritation around mouth of an infant with atopic dermatitis.
