What you Need to Know About Atopic Dermatitis

In 2015, the annual estimated cost of atopic dermatitis in the United States was 5 billion dollars.^1,2 The onset of atopic dermatitis usually occurs in childhood. The majority of patients present with this disease prior to 12 months of age and 85% of patients develop this disease before age 5 years.¹ Typically, atopic dermatitis has a chronic, relapsing course that may persist from childhood well into adulthood. In this article, we address frequently asked questions from patients.

1. If eczema is adequately controlled, is the risk of developing other disorders in the atopic march reduced?

The atopic march refers to the progression of diseases in certain patients. These patients usually start with atopic dermatitis and subsequently develop asthma, allergic rhinitis, food allergies, or other atopic diseases throughout their life.³ For example, approximately 30% to 50% of patients with atopic dermatitis also have allergic rhinitis and the prevalence of asthma among patients with atopic dermatitis is about 26%.^4,5 A dysfunctional skin barrier can cause sensitization to antigens leading to other atopic diseases and a number of studies show that early treatment of eczema can reduce the risk of developing other atopic disorders.⁶

2. What factors cause exacerbation of atopic dermatitis?

Some of the most common triggers include anxiety, dry skin, high temperatures, ichthyosis, irritants, itching, stress, and sweat.

Maintaining skin hydration is crucial in atopic dermatitis and emollients are one of the mainstay treatments for this condition. Regular emollient use can decrease the need for topical corticosteroids. Most providers recommend a water-based, fragrance-free moisturizer. Patients should apply emollients at least daily, particularly after swimming and bathing, and avoid taking long, hot showers. They should also avoid or limit their use of nonsoap cleansers. Irritants include detergents, perspiration, solvents, wool, and other rough materials.

Scratching can exacerbate and maintain the inflammation and drive the itch-scratch cycle, so any measures that decrease inflammation and scratching may decrease symptoms and skin findings. Patients should also avoid high humidity, temperature extremes, and attempt to decrease their stress as much as possible.

3. How does atopic dermatitis affect quality of life (QOL)?

It significantly decreases [a patient’s] QOL. In one study, among all chronic conditions in children, atopic dermatitis had the second highest impact on QOL.⁷ In adults, QOL is also severely impacted by the symptoms and emotional impact of this disease.² In some cases, patients with atopic dermatitis may even change their occupation because of the skin condition.² Atopic dermatitis can cause constant itching or scratching, difficulty sleeping, and embarrassment.

This skin condition is also associated with cardiovascular, inflammatory, and psychiatric conditions.^8,9 Many of the symptoms of atopic dermatitis, such as sleep disturbance and decreased self-esteem, are risk factors for the development of psychiatric disorders. Atopic dermatitis is also associated with increased risk of anxiety and depression.¹⁰

4. How does atopic dermatitis evolve over time?

In infants, atopic dermatitis primarily affects the face, scalp, and extensor surfaces of the extremities. In children, atopic dermatitis primarily affects the flexural folds of the extremities and neck. In adults, atopic dermatitis primarily affects the hands and inner creases of the elbows and knees. Older kids and adults with severe itching and behavioral issues may be at risk for prurigo nodularis, which presents as dramatically thickened plaques and nodules in these areas or at times disseminated.

5. What is the standard of care?

Standard of care can vary depending on the severity of the disease. In general, topical emollients and corticosteroids are the mainstay therapies.¹¹

Topical corticosteroids decrease inflammation, colonization of Staphylococcus aureus, and pruritus. The potency should be based on the severity and location of the atopic dermatitis. For patients with atopic dermatitis in regions where corticosteroid use is not recommended, such as the face or skin folds, topical calcineurin inhibitors can be used. These include the tacrolimus ointment and pimecrolimus cream, which were approved nearly a decade ago, and these medications should be considered as an alternative treatment for atopic dermatitis.¹² Although a black box warning was implemented in 2005 for the topical calcineurin inhibitors because of limited safety data and concern of risk of malignancies (despite protests by the American Academy of Dermatology and American Academy of Allergy, Asthma, and Immunology), long-term studies showed no evidence for these claims.

Emollients are also crucial in atopic dermatitis because they improve the barrier function and prevent dryness.¹¹ Along with medications, skin protective measures should be emphasized to avoid exacerbations of the disease. In addition, many patients have trouble sleeping and melatonin can be helpful.

For many of the topical medications and emollients, providers often underestimate the quantity needed. The quantity should depend on the severity and surface area of the skin that is involved. For reference, approximately 2 g are required for a single application to the face, 3 g are required for a single application to 1 arm, and 4 g are required for a single application to 1 leg. Approximately 30 to 60 g are needed to cover the entire body for a single application. For 3 daily applications to the entire body for 2 weeks, approximately 42 to 84 oz are needed.

6. Is topical steroid use safe and effective for treating atopic dermatitis?

Studies have consistently demonstrated that topical steroids are effective in treating atopic dermatitis and topical steroids are currently one of the mainstay therapies for the treatment of this disease.¹¹ They are safe in adults and children when used appropriately with careful discussion of frequency and length of application with guidelines for specific body sites. All patients should be counseled on the possible adverse effects of corticosteroids, including atrophy and striae.

7. How can bleach baths help patients with atopic dermatitis? How does the formation of biofilms complicate treatment?

Patients with atopic dermatitis have more flares and greater eczema severity with higher levels of S aureus on their skin.^13,14 Liquid chlorine beach, which is sodium hypochlorite 6% solution, is active against S aureus and therefore diluted bleach baths with mildly warm water may improve symptoms in many patients.¹⁵ Staphylococcus species can form biofilms in these patients, which makes the bacteria resistant to many antibiotics and the immune response.¹⁶

8. What are some of the new and evolving therapies for atopic dermatitis?

Crisaborole is a topical phosphodiesterase inhibitor that was approved by the US Food and Drug Administration (FDA) in 2016 for adults and children aged as young as 2 years and in 2020, it was approved for infants as young as 3 months.¹⁷ Studies have shown that crisaborole is safe for long-term use.¹⁷

Dupilumab, an interleukin (IL)-4 and IL-13 receptor-alpha antagonist, was also recently approved by the FDA for children aged 6 years or older with severe atopic dermatitis.¹⁸

9. Are low vitamin D levels an issue and does supplementation help?

Vitamin D plays a role in the barrier function of the skin and immune regulation. Serum vitamin D levels are lower in patients that have atopic dermatitis and vitamin D supplementation may be beneficial for some patients.¹⁹

10. If topical medications do not adequately treat the atopic dermatitis, what are the next steps?

Patients with moderate to severe disease despite adequate topical treatments may be treated with phototherapy. Patients with severe unresponsive disease may also respond to off-label systemic agents including methotrexate, cyclosporine, mycophenolate, and azathioprine. The newer systemic agents include dupilumab, as mentioned above, and other biologics. Dupilumab requires no routine laboratory monitoring and is much safer for long-term use compared with off-label systemic agents.^20,21

11. What to expect in the next few years?

There are many medications that may be used for atopic dermatitis in the future. As discussed above, crisaborole and dupilumab were recently approved by the FDA.

Future medications that show promise include the JAK-STAT inhibitors, baricitinib, upadacitinib, PF-04965842, ASN002, tofacitinib, ruxolit inib, and delgocit inib.22 Other medications that show promise include tapinarof (aryl hydrocarbon receptor modulating agent), lebrikizumab and tralokinumab (IL-4/IL-13 antagonists), and nemolizumab (IL-31Rα antagonist).²²

Conclusion

Because of the high prevalence among children, it is crucial for pediatricians to be familiar with atopic dermatitis. As summer approaches, it is important to recognize that heat can lead to dryness of the skin and histamine release in the skin. Furthermore, the warm weather leads to sweat production, which irritates the skin. Thus, summertime is associated with increased atopic dermatitis flare-ups.

Atopic dermatitis has a significant effect on a patient’s QOL. The mainstay therapy for atopic dermatitis includes topical corticosteroids and emollients. Early treatment of atopic dermatitis can prevent the development of subsequent atopic disorders. Alternative treatments include diluted liquid chlorine bleach baths and phototherapy. Several off-label systemic agents, such as methotrexate and cyclosporine, can also be used. However, dupilumab, a new biologic drug that was recently approved for atopic dermatitis, is much safer than systemic agents.

References

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3. Oliveira C, Torres T. More than skin deep: the systemic nature of atopic dermatitis. Eur J Dermatol. 2019;29(3):250-258. doi:10.1684/ejd.2019.3557
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5. Ravnborg N, Ambikaibalan D, Agnihotri G, et al. Prevalence of asthma in patients with atopic dermatitis: a systematic review and meta-analysis. J Am Acad Dermatol. 2021;84(2):471-478. doi:10.1016/j.jaad.2020.02.055
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7. Beattie PE, Lewis-Jones MS. A comparative study of impairment of quality of life in children with skin disease and children with other chronic childhood diseases. Br J Dermatol. 2006;155(1):145-151. doi:10.1111/j.1365-2133.2006.07185.x
8. Paller A, Jaworski JC, Simpson EL, et al. Major comorbidities of atopic dermatitis: beyond allergic disorders. Am J Clin Dermatol. 2018;19(6):821-838. doi:10.1007/s40257-018-0383-4
9. Silverberg JI. Comorbidities and the impact of atopic dermatitis. Ann Allergy Asthma Immunol. 2019;123(2):144-151. doi:10.1016/j.anai.2019.04.020
10. Thyssen JP, Hamann CR, Linneberg A, et al. Atopic dermatitis is associated with anxiety, depression, and suicidal ideation, but not with psychiatric hospitalization or suicide. Allergy. 2018;73(1):214-220. doi:10.1111/all.13231
11. Eichenfield LF, Tom WL, Berger TG, et al. Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014;71(1):116-132. doi:10.1016/j.jaad.2014.03.023
12. Ashcroft DM, Dimmock P, Garside R, Stein K, Williams HC. Efficacy and tolerability of topical pimecrolimus and tacrolimus in the treatment of atopic dermatitis: meta-analysis of randomised controlled trials. BMJ. 2005;330(7490):516. doi:10.1136/bmj.38376.439653.D3
13. Alsterholm M, Strömbeck L, Ljung A, et al. Variation in Staphylococcus aureus colonization in relation to disease severity in adults with atopic dermatitis during a five-month follow-up. Acta Derm Venereol. 2017;97(7):802-807. doi:10.2340/00015555-2667
14. Tauber M, Balica S, Hsu C-Y, et al. Staphylococcus aureus density on lesional and nonlesional skin is strongly associated with disease severity in atopic dermatitis. J Allergy Clin Immunol. 2016;137(4):1272-1274.e3. doi:10.1016/j.jaci.2015.07.052
15. Mohan GC, Lio PA. Comparison of dermatology and allergy guidelines for atopic dermatitis management. JAMA Dermatol. 2015;151(9):1009-1013. doi:10.1001/jamadermatol.2015.0250
16. Gonzalez T, Biagini Myers JM, Herr AB, Khurana Hershey GK. Staphylococcal biofilms in atopic dermatitis. Curr Allergy Asthma Rep. 2017;17(12):81. doi:10.1007/s11882-017-0750-x
17. Paller AS, Tom WL, Lebwohl MG, et al. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. J Am Acad Dermatol. 2016;75(3):494-503.e6. Published correction appears in J Am Acad Dermatol. 2017;76(4):777.
18. Simpson EL, Akinlade B, Ardeleanu M. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2017;376(11):1090-1091. doi:10.1056/NEJMc1700366
19. Kim MJ, Kim S-N, Lee YW, Choe YB, Ahn KJ. Vitamin D status and efficacy of vitamin D supplementation in atopic dermatitis: a systematic review and meta-analysis. Nutrients. 2016;8(12):789. doi:10.3390/nu8120789
20. Deleuran M, Thaçi D, Beck LA, et al. Dupilumab shows long-term safety and efficacy in patients with moderate to severe atopic dermatitis enrolled in a phase 3 open-label extension study. J Am Acad Dermatol. 2020;82(2):377-388. doi:10.1016/j.jaad.2019.07.074
21. Blauvelt A, de Bruin-Weller M, Gooderham M, et al. Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial. Lancet. 2017;389(10086):2287-2303. doi:10.1016/S0140-6736(17)31191-1
22. Nguyen HL, Anderson KR, Tollefson MM. New and emerging therapies for pediatric atopic dermatitis. Paediatr Drugs. 2019;21(4):239-260. doi:10.1007/s40272-019-00342-w