Atopic dermatitis Revised: February 17, 2012

Copyright Elsevier BV. All rights reserved.

Key points

Atopic dermatitis is a chronic skin disease characterized by barrier defects and allergic inflammation

Barrier defects predispose skin with atopic dermatitis to environmental triggers, infections, and,

subsequently, inflammation

Atopic dermatitis usually presents with dry skin, poorly defined erythema with infiltration, papules,

weeping in the acute stage, and lichenification in the chronic stage. It also may be accompanied by

viral, bacterial, or fungal superinfections

The diagnosis is primarily based on clinical presentation; additional laboratory tests are usually

unnecessary

Management of atopic dermatitis includes proper skin care, identification and eradication of

triggers, and anti-inflammatory treatment. Current treatment options include topical corticosteroids,

topical calcineurin inhibitors, antihistamines, barrier creams, and systemic corticosteroids

Certain adjunctive measures (eg, wet wraps, phototherapy) may also be beneficial

Treatment

Summary approach

The goals of treatment are relief of symptoms; prevention of flares and secondary infection; and

improvement of quality of life, including sleep, work, school, and social development

The first-line treatment for symptom relief is topical corticosteroids . Other options include topical

calcineurin inhibitors , barrier creams , antihistamines , and systemic corticosteroids

Certain adjunctive measures (eg, wet-wraps , phototherapy , psychotherapy ) also may be beneficial

There is no convincing evidence that various other therapies are effective in the treatment of atopic

dermatitis. Indeed, some of them have been proven to be ineffective by double-blind placebo-

controlled trials: specific allergen immunotherapy, omalizumab, montelukast, intravenous

immunoglobulin, probiotics, andMycobacterium vaccaevaccination

Complementary and alternative therapies (eg, silver- or antimicrobial-coated fabrics, vitamin D,

bleach baths, and various herbal and homeopathic preparations) also have been used in the

treatment of atopic dermatitis; however, large and/or randomized studies are needed to confirm

their efficacy

Medications

Topical corticosteroids

Indication

Hydrocortisone and desonide (low-potency corticosteroids) are considered first-line therapy for

atopic dermatitis

Triamcinolone and betamethasone (medium-potency corticosteroids) are necessary in more severe

disease

Fluocinonide (high-potency corticosteroid) should be used for brief periods to produce a rapid

reduction of inflammation, then the patient should be switched to a low- to moderate-potency

corticosteroid

Dose information

Adult

Betamethasone (0.05%-0.1%):

Apply a small amount to the affected area(s) twice a day

Treatment course: 1 to 2 weeks

Desonide (0.05%):

Apply a small amount to the affected area(s) every 6 to 12 hours

Treatment course: 1 to 2 weeks

Fluocinonide (0.05%-0.1%):

Apply a small amount to the affected area(s) every 6 to 12 hours

Treatment course: 1 to 2 weeks

Hydrocortisone (0.5%-2.5%):

Apply a small amount to the affected area(s) every 6 to 12 hours

Treatment course: 1 to 2 weeks

Triamcinolone (0.025%-0.5%):

Apply a small amount to the affected area(s) every 6 to 12 hours

Treatment course: 1 to 2 weeks

Pediatric

Low-potency corticosteroids (eg, hydrocortisone) may be used in children; however, moderate- to

high-potency corticosteroids should not be used in patients younger than 12 years. Children have a

greater susceptibility to topical corticosteroid-induced hypothalamic-pituitary-adrenal axis

suppression and Cushing syndrome than do mature patients because of a larger skin surface area to

body weight ratio

Major contraindications

Acute bronchospasm (triamcinolone)

Benzyl alcohol hypersensitivity (triamcinolone)

Corticosteroid hypersensitivity (betamethasone, fluocinonide, triamcinolone)

Fungal infection (hydrocortisone, triamcinolone)

Idiopathic thrombocytopenia (betamethasone,

Neonatal prematurity (triamcinolone)

Status asthmaticus (triamcinolone)

Comments

Common concerns among patients and parents regarding topical corticosteroids are skin thinning

and adverse effects on bones and growth. Frequently, topical corticosteroids are also misunderstood

to be the same as androgenic steroids. Therefore, it is important to clarify these issues

While explaining the benefits and adverse effects of topical corticosteroids to patients or parents, it is

important to make the distinction between systemic (oral or injection) corticosteroids and topical

corticosteroids. Topical corticosteroids are categorized in different strengths. An understanding of

the strengths and adverse effects of topical corticosteroids may improve compliance among patients

or parents or patients

Evidence

A systematic review of 11 randomized, controlled trials (RCTs) found that topical corticosteroids are

significantly more effective than placebo for the treatment of atopic dermatitis in children and

adults. [1] Level of evidence: 1

An RCT compared hydrocortisone buteprate cream (0.1%) versus placebo in patients with atopic

dermatitis. Patients treated with hydrocortisone buteprate had a significantly better outcome than

the controls. [2] Level of evidence: 1

Six double-blind, multicenter trials involving 485 patients (209 with atopic dermatitis; 276 with

plaque psoriasis) found that hydrocortisone valerate cream (0.2%) produced significant

improvement compared with the controls. [3] Level of evidence: 1

A small RCT compared betamethasone dipropionate with placebo in patients with atopic dermatitis;

94% had a good or excellent clinical response, compared with 13% of the controls. [4] Level of

evidence: 1

Another small RCT compared betamethasone dipropionate with placebo in patients with atopic

dermatitis. Betamethasone dipropionate produced a significant reduction in itch intensity compared

with placebo. [5] Level of evidence: 1

A systematic review assessed 31 trials including 8,019 subjects to compare the effectiveness of topical

pimecrolimus to two topical corticosteroids (triamcinolone and betamethasone), and to topical

tacrolimus. At 3 weeks, pimecrolimus patients suffered a greater incidence of burning skin and

patient withdrawals from the regimen than did patients treated with topical corticosteroids. Another

finding was that pimecrolimus was less effective than tacrolimus at 6 weeks' duration of therapy;

again with more withdrawals from the regimen, this time due to lack of efficacy. The review suggests

that topical pimecrolimus is not as effective as topical corticosteroids or tacrolimus in treatment of

atopic dermatitis. [6] Level of evidence: 1

References

Topical calcineurin inhibitors

Indication

Short-term treatment of moderate to severe atopic dermatitis

These medications also can be used to treat cases of atopic dermatitis resistant to steroids

Dose information

Tacrolimus

Adult:

Topical (0.03%-0.1%): Apply a small amount to the affected area(s) twice a day

Treatment course: 7 to 14 days; continue for 7 days after clearing of signs and symptoms

Pediatric:

Topical (0.03%): Apply a small amount to the affected area(s) twice a day

Treatment course: 7 to 14 days; continue for 7 days after clearing of signs and symptoms

Pimecrolimus

Topical (1%): Apply a small amount to the affected area(s) twice a day

Treatment course: 7 to 14 days

Safety and efficacy in children younger than 2 years have not been established; avoid use due to

potential increased risk of cancer

Major contraindications

Polyoxyethylated castor oil hypersensitivity (tacrolimus)

Comments

These medications have a black box warning from the U.S. Food and Drug Administration (FDA) on

a possible risk of cancer with continuous, long-term use. The warning is based on animal studies and

rare reports of skin cancer and lymphoma in patients who have used these medications. Long-term

studies are ongoing to confirm the safety of these medications. In the meantime, the FDA

recommends short-term use of these medications only on the affected areas

Topical calcineurin inhibitors do not decrease the synthesis of collagen in the skin, making them

useful for treating lesions on the face, eyelids, and other parts of the body with thin skin

If the rash does not improve within 6 weeks, patient should be re-examined to confirm the diagnosis

Evidence

A systematic review assessed 31 trials including 8,019 subjects to compare the effectiveness of topical

pimecrolimus to two topical corticosteroids (triamcinolone and betamethasone), and to topical

tacrolimus. At 3 weeks, pimecrolimus patients suffered a greater incidence of burning skin and

patient withdrawals from the regimen than did patients treated with topical corticosteroids. Another

finding was that pimecrolimus was less effective than tacrolimus at 6 weeks' duration of therapy;

again with more withdrawals from the regimen, this time due to lack of efficacy. The review suggests

that topical pimecrolimus is not as effective as topical corticosteroids or tacrolimus in treatment of

atopic dermatitis. [6] Level of evidence: 1

References

Antihistamines (sedating)

Indication

Treatment of symptoms associated with atopic dermatitis such as pruritus

Dose information

Diphenhydramine

Adult:

25 to 50 mg orally every 4 to 6 hours, when required

Maximum: 300 mg/d

Pediatric (>6 years):

12.5 to 25 mg every 4 to 6 hours, when required

Maximum: 300 mg/d

Comments

Antihistamines are used in the treatment of patients with atopic dermatitis mainly for their sedative

effect

Antihistamines also may be used to treat comorbid conditions of atopic dermatitis, such as allergic

rhinoconjunctivitis, dermatographism, urticaria, and sleep disruption. However, they are not

effective in treating pruritus associated with atopic dermatitis, as the itching in atopic dermatitis is

not solely secondary to histamine release

Long-acting and topical antihistamines are not useful in the treatment of atopic dermatitis because

of their minimal or lack of sedative effect

Barrier creams

Indication

Barrier creams, such as zinc oxide , are used for skin barrier repair

Dose information

Apply to the affected area(s) twice a day

Comments

Rather than providing the skin with an inert barrier like emollients do, these creams aim to repair

the skin barrier

They may be effective in mild atopic dermatitis, but there is inadequate evidence that they are

effective in moderate to severe disease

These nonsteroidal creams can be used by any age group

Evidence

An RCT compared a barrier cream to a mid-potency topical corticosteroid in the treatment of

moderate to severe atopic dermatitis. The barrier cream was shown to be as effective as the topical

corticosteroid in controlling atopic dermatitis after 28 days. These results have yet to be reproduced.

[7] Level of evidence: 3

References

Systemic corticosteroids

Indication

Systemic corticosteroids are used to treat severe and intractable atopic dermatitis

Dose information

Prednisone

Adult:

60 mg/d orally for 2 days, then 30 mg/d for 2 days, then 15 mg/d for 2 days, then 7.5 mg/d for 2

days, then stop

Treatment course: 8 days

Pediatric:

1 to 2 mg/kg/d orally in divided doses

Use of systemic corticosteroids in children is still controversial. In special cases, however, pediatric

patients may be given prednisone. Growth and development of pediatric patients should be carefully

observed during prolonged therapy

Major contraindications

Fungal infection

Comments

Systemic corticosteroids have been shown to be capable of reducing atopic dermatitis flares,

however, long-term or frequent intermittent use of these medications is associated with potential

adverse effects, including stunted growth, osteoporosis, cataract, adrenal suppression, and rebound

flare

Several corticosteroid regimens are available, such as alternate-day administration, intramuscular

injection, or pulsed high-dose treatment. The dosage and route of administration of systemic

steroids for atopic dermatitis, however, are still controversial. The dose should be tapered for 1 week

because there is a chance of a severe rebound effect after discontinuation of the treatment

Summary of evidence

Evidence

Topical corticosteroids and topical calcineurin inhibitors:

A systematic review of 11 randomized, controlled trials (RCTs) found that topical corticosteroids are

significantly more effective than placebo for the treatment of atopic dermatitis in children and

adults. [1] Level of evidence: 1

An RCT compared hydrocortisone buteprate cream (0.1%) versus placebo in patients with atopic

dermatitis. Patients treated with hydrocortisone buteprate had a significantly better outcome than

the controls. [2] Level of evidence: 1

Six double-blind, multicenter trials involving 485 patients (209 with atopic dermatitis; 276 with

plaque psoriasis) found that hydrocortisone valerate cream (0.2%) produced significant

improvement compared with the controls. [3] Level of evidence: 1

A small RCT compared betamethasone dipropionate with placebo in patients with atopic dermatitis;

94% had a good or excellent clinical response, compared with 13% of the controls. [4] Level of

evidence: 1

Another small RCT compared betamethasone dipropionate with placebo in patients with atopic

dermatitis. Betamethasone dipropionate produced a significant reduction in itch intensity compared

with placebo. [5] Level of evidence: 1

A systematic review assessed 31 trials including 8,019 subjects to compare the effectiveness of topical

pimecrolimus to two topical corticosteroids (triamcinolone and betamethasone), and to topical

tacrolimus. At 3 weeks, pimecrolimus patients suffered a greater incidence of burning skin and

patient withdrawals from the regimen than did patients treated with topical corticosteroids. Another

finding was that pimecrolimus was less effective than tacrolimus at 6 weeks' duration of therapy;

again with more withdrawals from the regimen, this time due to lack of efficacy. The review suggests

that topical pimecrolimus is not as effective as topical corticosteroids or tacrolimus in treatment of

atopic dermatitis. [6] Level of evidence: 1

Barrier creams:

An RCT compared a barrier cream to a mid-potency topical corticosteroid in the treatment of

moderate to severe atopic dermatitis. The barrier cream was shown to be as effective as the topical

corticosteroid in controlling atopic dermatitis after 28 days. These results have yet to be reproduced.

[7] Level of evidence: 3

Psychological and behavorial therapy:

A systemic review showed psychological intervention may have some beneficial effects on atopic

dermatitis, but this cannot be confirmed due to variability of the studies reviewed. Future studies

using psychological intervention should include more acceptable methods for subject randomization,

description, and measuring atopic dermatitis disease severity. [8] Level of evidence: 2

Treatment of secondary infections:

An RCT comparedS aureuscolonization in patients with atopic dermatitis treated with topical

corticosteroids versus similar patients treated with tacrolimus. The study, which included 60

patients, also randomized patients within the two treatment arms to cohorts with and without

adjunctive topical antibiotic therapy. The RCT found similar results with use of both types of primary

therapy, with or without topical antibiotics: reduction inS aureusnumbers, reduction in patient

symptom scores, and a small number of patients (2) developed resistant organisms. The results

suggest that topical anti-inflammatory therapy may serve as an alternative to topical antibiotic

therapy to improve skin inflammation from skin colonization byS aureus; a corollary suggestion is

that topical antibiotics might best be reserved for use in patients on a short-term basis when acute

infection arises. [9] Level of evidence: 2

References

References

Evidence references

1. 1. Hoare C, Li Wan PA, Williams HC. A systematic review of treatments for atopic eczema. Health

Technol Assess. 2000;4:1-191

View In Article

2. 2. Sears HW, Bailer JW, Yeadon A. Efficacy and safety of hydrocortisone buteprate 0.1% cream in

patients with atopic dermatitis. Clin Ther. 1997;19:710-9

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3. 3. Sefton J, Loder JS, Kyriakopoulos AA. Clinical evaluation of hydrocortisone valerate 0.2%

ointment. Clin Ther. 1984;6:282-93

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4. 4. Vanderploeg DE. Betamethasone dipropionate ointment in the treatment of psoriasis and atopic

dermatitis: a double-blind study. South Med J. 1976;69:862-3

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5. 5. Wahlgren CF, Hägemark O, Bergström R, Hedin B. Evaluation of a new method of assessing

pruritus and antipruritic drugs. Skin Pharmacol. 1988;1:3-13

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6. 6. Ashcroft DM, Chen LC, Garside R, Stein K, Williams HC. Topical pimecrolimus for eczema.

Cochrane Database Syst Rev. 2007:CD005500

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7. 7. Sugarman JL, Parish LC. Efficacy of a lipid-based barrier repair formulation in moderate-to-severe

pediatric atopic dermatitis. J Drugs Dermatol. 2009;8:1106-11

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8. 8. Ersser SJ, Latter S, Sibley A, Satherley PA, Welbourne S. Psychological and educational

interventions for atopic eczema in children. Cochrane Database Syst Rev. 2007:CD004054

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9. 9. Hung SH, Lin YT, Chu CY, et al. Staphylococcus colonization in atopic dermatitis treated with

fluticasone or tacrolimus with or without antibiotics. Ann Allergy Asthma Immunol. 2007;98:51-6

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Guidelines

The National Collaborating Centre for Women's and Children's Health has produced the following:

Atopic eczema in children. Management of atopic eczema in children from birth up to the age of 12 years . London

(UK): National Institute for Health and Clinical Excellence (NICE); 2007. 39 p. (Clinical guideline;

no. 57)

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