Atopic Dermatitis Treatment & Management

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 (moisturizer) 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. ^[49]

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. ^[50]

Targeted biologic therapeutics in atopic dermatitis

Anti-IL-4Ra therapy (dupilumab)

Dupilumab is a monoclonal antibody that inhibits interleukin (IL)–4 and IL-13 signaling by blocking the shared IL-4Ra and originally demonstrated efficacy in phase 2 clinical trials. ^{[51, 52]} It was approved by the US Food and Drug Administration (FDA) in 2017 for adults with moderate-to-severe atopic dermatitis not adequately controlled with topical prescription therapies or when those therapies are not advisable. In 2019, this indication was expanded to include adolescents aged 12 years or older, and in 2020 to include children as young as 6 years. It is a subcutaneous injection 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 (EASI) was reported in significantly more patients who received each regimen of dupilumab than in patients who received placebo (P< .001). ^[53] Approval in adolescents was based on a phase 3 trial showing statistically significant improvement of EASI-75 in the dupilumab-treated group compared with placebo. ^[54]

Results from the phase 3 trial (LIBERTY AD PEDS; n = 367) in children aged 6-11 years showed 75% of those taking dupilumab plus topical corticosteroids achieved EASI-75 at 16 weeks compared with 26-28% of children using topical corticosteroids alone (P< .001). ^[55]

Given its unprecedented efficacy, dupilumab is emerging as a first-line therapeutic for moderate-to-severe atopic dermatitis.

IL-13 antagonist (tralokinumab)

Tralokinumab (Adbry) is a monoclonal antibody that inhibits the IL-13 cytokines, which ultimately prevents the release of cytokines, chemokines, and IgE. This IL-13 antagonist was FDA-approved for the treatment of moderate-to-severe AD for adults whose disease is inadequately controlled with topical therapies or when those therapies are not advisable. ^[56]

Approval was based on the phase 3 trials, ECZTRA 1, 2, and 3, which assessed the efficacy of tralokinumab in 1934 adults with moderate-to-severe AD who were inadequately controlled with topical medications. ECZTRA 1 and 2 trials studied tralokinumab as monotherapy for 52 weeks, and ECZTRA 3 studied tralokinumab in combination with topical corticosteroids for 32 weeks. ^[56]

At week 16 in the ECZTRA 1 and 2 trials, 16% and 21% of patients treated with tralokinumab 300 mg SC every other week achieved clear or almost clear skin (Investigator’s Global Assessment [IGA] 0 or 1) compared to placebo (7% and 9%). In the same treated group, 25% and 33% of patients had an improvement of at least 75% in Eczema Area and Severity Index (EASI-75) compared to placebo (13% and 10%). At week 52 in the ECZTRA 1 and 2 trials, 51% and 60% of treated patients who responded at week 16 maintained an IGA 0 or 1. Also, 60% and 57% of those patients maintained an EASI-75. ^[56]

In ECZTRA 3 trials, patients treated with tralokinumab in combination with topical corticosteroids also had results superior to those of placebo at achieving an IGA 0 or 1 and EASI-75. ^[56]

Anti-IL-33 therapy (ANB020)

IL-33 is an epithelial cell–derived cytokine that promotes downstream type 2 cytokine (eg, IL-4) responses by acting on multiple cell types, including Th2 cells, basophils, and ILC2s. A 2017 small phase 2a study using a therapeutic anti-IL-33 antibody (ANB020) demonstrated promising results in terms of EASI as early as at day 15. ^[57] However, larger randomized trials are required to fully determine the efficacy of this drug.

Janus kinase (JAK) inhibitors

Multiple proinflammatory cytokines, including type 2 cytokines, are dependent on the JAK-STAT signaling pathway to mediate their effects. ^[58] Thus, in addition to cytokine receptor blockade, clinical trials have been performed for both oral and topical JAK inhibitors. ^[59] In support of the direct antipruritus effect of JAK inhibitors, a 2017 study identified that neuronal JAK1 signaling critically regulates AD-associated itch in mice, independently of any effect on the immune system. ^[19] Thus, these studies may explain why JAK inhibitors are demonstrating such unique anti-itch properties in clinical trials. 

Ruxolitinib topical

The first topical JAK inhibitor, ruxolitinib topical cream 1.5% (Opzelura), gained FDA approval for short-term and noncontinuous long-term treatment of mild-to-moderate atopic dermatitis in non-immunocompromised adults and adolescents whose disease is not adequately controlled with other topical prescription therapies or when those therapies are not advisable. Significantly more patients achieved success at Week 8 as measured by the Investigator's Global Assessment using ruxolitinib cream (0.75% or 1.5%) compared with vehicle cream (P < 0.0001). ^[60]  

Upadacitinib

The oral JAK1-selective inhibitor upadacitinib (Rinvoq) was FDA-approved for treatment of refractory, moderate to severe AD in patients aged ≥12 years whose disease is not adequately controlled with other systemic drug products, including biologics, or who are unable to use such therapies.

Approval was based on 3 double-blind, phase 3 trials (Measure Up 1; Measure Up 2; AD Up), where 2584 patients aged ≥12 years with moderate to severe AD who were candidates for systemic therapy were randomized to receive upadacitinib 15mg and 30mg PO qDay. In Measure Up 1 and 2, upadacitinib was evaluated as monotherapy; in AD Up, upadacitinib was evaluated in combination with topical corticosteroids.

The coprimary endpoints for all the trials were the proportion of patients achieving at least a 75% improvement in the Eczema Area Severity Index (EASI 75) and a validated Investigator’s Global Assessment for Atopic Dermatitis (vIGA-AD) of clear or almost clear (0/1) at week 16. 

Results from the Measure Up 1 and Measure Up 2 trials showed a higher number of patients treated with upadacitinib 15 mg and 30 mg achieved EASI 75 and vIGA-AD 0/1 at week 16 compared to placebo. Patients treated with upadacitinib met secondary endpoints including EASI 90, EASI 100, and at least a 4-point improvement in the Worst Pruritus Numerical Rating Scale (NRS) at week 16. Upadacitinib-treated group reported a reduction in itch as early as Day 2. ^[61]

In the AD Up trial, 65% and 77% of patients treated with upadacitinib 15mg and 30mg plus topical corticosteroids achieved EASI 75 at week 16 compared to placebo with topical corticosteroids (26%). A greater proportion of the upadacitinib/corticosteroids arm achieved vIGA-AD 0/1 at week 16 (40% and 59% [15mg and 30mg plus topical corticosteroids]) compared to 11% of patients who received placebo plus topical corticosteroids. ^[62]

Abrocitinib

Another once-daily oral JAK1 inhibitor, abrocitinib (Cibinqo), is also indicated for treatment for patients aged 12 years and older with moderate to severe atopic dermatitis.

Approval for adults was based on 5 clinical trials in a program of more than 1600 patients. The 5 clinical trials composed of 3 randomized, placebo-controlled, phase 3 trials for safety and efficacy of abrocitinib, a dose-ranging trial, and an ongoing, long-term, open-label extension trial. The FDA approved abrocitinib for adolescents in February 2023 based on clinical trials resulting in similar efficacy to that of adults. ^{[63, 80]}   

In the trials, abrocitinib demonstrated improvements in skin clearance, extent of disease, and severity, as well as rapid improvement in itch after 2 weeks.

In the JADE MONO-1 trial, the Investigator Global Assessment (IGA) response rate at week 12 was 24% (100-mg dose) and 44% (200-mg dose), and 8% in the placebo group. Also, EASI-75 response rate was 40%, 62%, and 12%, respectively. ^[63]

The JADE MONO-2 trial found similarly encouraging results, with an IGA response rate at week 12 of 28% (100-mg dose), 38% (200-mg dose), and 9% in the placebo group, respectively. EASI-75 response rate of 44% (100-mg dose), 61% (200-mg dose), and 10%, respectively. ^[64]  

In the JADE compare trial, abrocitinib at a dose of either 200 mg or 100 mg once daily resulted in significantly greater reductions in signs and symptoms of moderate-to-severe atopic dermatitis than placebo at weeks 12 and 16. The 200-mg dose, but not the 100-mg dose, of abrocitinib was superior to dupilumab with respect to itch response at week 2. ^[65]   

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). ^[66]

In March 2020, the FDA expanded the indication to include infants and children aged 3 months or older. Use in pediatric patients aged 3 months to less than 2 years was supported by data from a 28-day open-label, safety, and pharmacokinetics trial (n=137). ^[67]

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. ^[68] 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. ^{[69, 70]} 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. ^{[71, 72]}

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), ^{[73, 74]} 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. ^[75] 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.

Consulting an allergist may be necessary, particularly if the patient develops asthma and/or hay fever or an acute reaction to a food.

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.

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.

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.

Sleep disturbance is common in AD patients, owing to the incessant pruritus. Sleep disturbances can significantly impact quality of life.

Moisturization is important on an ongoing basis and may prevent flares.