Therapeutic options for treating atopic dermatitis (AD) in children, including the differences between topical corticosteroids and topical calcineurin inhibitors, are reviewed in an article in the October issue of Pediatrics. The review also highlights new treatment strategies being used by specialists in AD, including comprehensive “education-as-intervention” models, wet wraps, bleach baths, and systemic immunomodulatory therapies.
“Parents of patients with…AD turn to their primary caregivers for guidance regarding this physically demanding and psychologically stressful condition,” write Andrew C. Krakowski, MD, from the University of California, San Diego, and colleagues. “It is a chronic illness that requires a multifaceted treatment strategy in the setting of limited therapeutic options. Balancing safety concerns with efficacious treatment is of particular importance in the pediatric population.”
One of the most prevalent skin disorders in young children is AD, affecting 10% to 20% of children younger than 10 years and often adversely affecting the child’s overall health and development. Onset is usually by age 1 year in approximately 60% of affected infants and by age 5 years in approximately 85% of affected children.
The cornerstone for treatment of AD is still topical corticosteroids because of their broad-spectrum anti-inflammatory activity as well as their antiproliferative, immunosuppressive, and vasoconstrictive actions. One of the chief mechanisms of action is thought to be suppression of the release of inflammatory cytokines. Concerns about potential long-term risks for corticosteroid use, particularly in young children, have been to some extent alleviated by recent evidence.
Regimens of corticosteroid therapy may include starting treatment with a more potent preparation to induce remission, followed by a relatively quick tapering down of preparation potency as the AD improves, with a subsequent stepwise model allowing as-needed management on the basis of disease activity. Another strategy is to use short bursts of a potent preparation followed by a steroid-free “holiday period” of emollient use only until relapse occurs. Yet another strategy is use of more prolonged, continuous treatment with less potent preparations.
“Regarding dosage frequency, 1 large systematic review revealed that using twice-daily applications of topical corticosteroids was no more effective than once-daily application,” the study authors write. “Ultimately, providers should consider drug-specific FDA [US Food and Drug Administration] indications when educating and instructing patients on topical corticosteroid usage.”
For children with severe and/or refractory AD, wet wraps with once-daily application of topical corticosteroids appear to be effective and safe in the short-term, although temporary systemic bioactivity of the corticosteroids has been reported as a serious adverse effect. If overused or used incorrectly, wet wraps may also cause maceration of the skin and secondary infections, and they may promote skin dryness if sufficient emollients are not included in the regimen.
For selected patients, notably those who are prone to frequent flares and who need AD treatment in sensitive skin areas, such as around the eye, face, neck, and genital area, topical calcineurin inhibitors appear to be an effective therapeutic option that can offer targeted anti-inflammatory activity and can also reduce steroid use.
Some patients may require systemic anti-inflammatory activity offered by oral immunomodulating agents, such as azathioprine, cyclosporine, and mycophenolate. Phototherapy is also proposed to have anti-inflammatory activity.
Available treatments target various features of AD. Emollients, moisturizers, and barrier devices relieve xerosis by moisturizing dry skin and helping to repair the defective skin barrier. Topical or orally administered anti-infective agents are used to treat cutaneous bacterial, fungal, or viral infections. Another approach to reducing infections is use of bleach baths, which are proposed to decrease the microbial load on colonized and/or superinfected skin.
In selected patients, antihistamines may be useful as adjunctive therapy. Their sedating effect may help children sleep through the night, thereby indirectly decreasing night-time scratching resulting in skin excoriation.
Overall management depends not only on pharmacotherapy but also on a multiprong approach. Clinicians should educate caregivers about the chronic, unpredictable course of AD, typically marked by flares that can occur despite optimal management. Because of the compromised epidermal barrier in AD, it is essential to pay careful attention to proper skin care.
Realizing that AD is a multifactorial disease, with one of the proposed mechanisms being immune dysfunction, clinicians should counsel their patients to avoid potential triggers, which helps prevent known allergic reactions and inflammatory responses.
Potential triggers may be those associated with direct contact, such as toiletries containing alcohol, astringents, or fragrances; harsh detergents or soaps; or abrasive clothing made of wool or synthetics. Physiologic and emotional stressors precipitating AD flares may include psychological stress; infections with Staphylococcus aureus, viruses, or fungi; and overheating or sweating.
Dietary triggers include food allergens found in cow’s milk, eggs, peanuts, tree nuts such as walnuts or cashews, soy, wheat, fish, shellfish, or foods processed with any of the above.
To achieve long-term success for patients with AD, a team-oriented approach is needed, including primary care clinicians, specialists, nurses, psychologists, behavioral therapists, and other healthcare professionals.
“Successful management involves educating patients and their families about AD, reducing signs and symptoms of the condition, preventing and decreasing the degree and frequency of flares, modifying the overall disease course, and, possibly, slowing the atopic march,” the study authors conclude. “A comprehensive long-term strategy that encompasses education, trigger avoidance, excellent skin care, and treatment (pharmacologic and nonpharmacologic measures) is vital. Physicians should use their understanding of the variety of available treatment options to develop a personalized therapeutic strategy that is tailored to the individual child’s age and needs, extent and localization of AD at presentation, and overall disease course (including persistence, frequent flares, etc).”
Two of the study authors have disclosed serving as investigators and consultants for multiple pharmaceutical-sponsored studies on atopic dermatitis.
AD affects 10% to 20% of children, according to Larsen and Hanifin in the February 2002 issue of Immunology and Allergy Clinics of North America. The primary factors in AD are epidermal barrier function defects and skin inflammation. The diagnosis of AD is based on combined essential, important, and associated nonspecific features. Essential features include pruritus, eczematous dermatitis, typical morphologic features with age-specific patterns, and chronic or relapsing nature.
This review of AD describes the management of AD, including topical corticosteroids, topical calcineurin inhibitors, and new treatments.
- Education is a crucial part of management:
- A 6-week education program for parents resulted in improved quality of life and eczema severity for their children older than 12 months.
- Comprehensive centers can provide care in dermatology, allergy, infectious disease, and behavioral psychology.
- Trigger avoidance measures include mattress covers, low-pile carpet, pets that do not produce dander, and avoidance of known food allergens.
- The American Academy of Pediatrics 2008 breast-feeding guidelines recommend exclusive breast-feeding for at least 4 months to decrease AD incidence in the first 2 years of life in children at high risk for AD.
- There is no evidence that delaying solid food, including cow’s milk, fish, eggs, and peanut-containing foods, after ages 4 to 6 months protects against AD.
- Studies on probiotic effects on risk for AD had conflicting results.
- Skin care recommendations include dye-free, fragrance-free emollients and moisturizers applied at least twice a day, ointments, and ceramide-rich products.
- “510(k) medical devices” are approved by the US Food and Drug Administration as new barrier products.
- Bathing in lukewarm water with moisturizing cleanser for several minutes once or twice a day should be followed by use of a towel to pat dry and emollients.
- Avoid fragrance soaps or bubble baths.
- First-line treatment of AD flares is topical corticosteroids:
- Class I are most potent and class VII, least potent.
- Adverse effects are skin atrophy, striae, telangiectasias, hypopigmentation, rosacea, perioral dermatitis, acne, cataracts, glaucoma, hypothalamic-pituitary-adrenal axis suppression, growth retardation, and bone density reduction.
- Twice-a-day use has the same effect as once-a-day use.
- The topical calcineurin inhibitors tacrolimus and pimecrolimus are second-line treatment for short-term and noncontinuous long-term use in immunocompetent patients at least 2 years old with moderate to severe AD:
- Long-term safety is not known, according to 2006 US Food and Drug Administration boxed warning.
- Indications include AD persistence or frequent flares requiring almost continuous topical corticosteroids and involvement of sensitive skin areas.
- Sedating antihistamines hydroxyzine and diphenhydramine might improve sleep but do not directly affect AD-related pruritus.
- Possible complications include overgrowth of S aureus, Molluscum contagiosum, eczema herpeticum, eczema vaccinatum, and fungal infections.
- If bacterial superinfection occurs, culture for methicillin-resistant S aureus should be considered.
- Diluted bleach baths can decrease local skin infections and need for systemic antibiotics.
- Wet wraps and once-daily topical corticosteroids are effective for severe or refractory AD, but close supervision is needed because of risk for skin maceration or secondary infection.
- Systemic immunomodulatory therapies can be used for refractory AD:
- Multiple phototherapy sessions
- Short-term cyclosporine; long-term use can be linked with hypertension and renal toxicity
- Azathioprine monotherapy; monitor blood cell counts and liver function tests
- Mycophenolate mofetil appears safe; prospective controlled studies are needed.
- Dermatology referral indications include moderate or severe AD, poor response to moderate-potency topical corticosteroids, persistent AD, frequent flares, AD-related hospitalization, and systemic therapy.
- Other specialty referrals include allergy referral for suspected specific triggers and gastroenterology or immunology referral for possible eosinophilic gastroenteritis or esophagitis with failure to thrive or frequent systemic infections.
Pearls for Practice
- In children with atopic dermatitis, the first-line treatment is topical corticosteroids, with potency ranging from the least potent class VII to the most potent class I. Second-line treatment of frequent flares or sensitive skin areas is a topical calcineurin inhibitor, for use in children 2 years or older.
- New treatment modalities for children with atopic dermatitis include education models; bleach bath; wet wraps; and systemic immunomodulatory therapies, including phototherapy, cyclosporine, azathioprine, and mycophenolate mofetil
|A 12-month-old child who was recently diagnosed with atopic dermatitis presents to your office for a flare-up of the condition. The physical examination is significant for erythematous, mildly excoriated areas in the antecubital fossa. There is no crusting or folliculitis. The parents are currently using a fragrance-free moisturizer twice a day. Which of the following is the most appropriate next step in management?|
|a) Topical calcineurin inhibitor|
|b) Topical steroid class I|
|c) Topical steroid class VII|
|d) Antibiotic treatment of methicillin-resistant S aureus|
|e) All of the above|
|Which of the following statements about the treatment of atopic dermatitis in children is most accurate?|
|a) Multiple phototherapy treatments are effective|
|b) Incorrect use of wet wraps is linked with skin maceration|
|c) Bleach baths can reduce the need for systemic antibiotics|
|d) Liver function tests should be monitored if azathioprine is used|
|e) All of the above|
Below are all the test questions with an explanation of the correct answer.
According to the study by Krakowski and colleagues, the first-line treatment of atopic dermatitis is topical corticosteroids. Potency decreases from class I to class VII. Topical calcineurin inhibitors are indicated for persistent or frequent flares of disease and for children at least 2 years or older. Antibiotic treatment of methicillin-resistant S aureus should be considered in cases of secondary bacterial infection.
According to the study by Krakowski and colleagues, phototherapy can be effective treatment of refractory atopic dermatitis. Overuse or incorrect use of wet wraps can cause skin maceration or secondary infection. Bleach baths can decrease local skin infection and thus decrease the need for antibiotics. Azathioprine is effective monotherapy but requires monitoring of blood cell counts and liver function tests.