Kyle O. Lee, BM BS, CCFP1; Patrick Fleming, MD, MSc, FRCPC2,3; Charles Lynde, MD, FRCPC2,3

1Lecturer, Department of Family and Community Medicine, St. Michael’s Hospital, Toronto, ON, Canada
2Assistant Professor, Division of Dermatology, University of Toronto, Toronto, ON, Canada
3Associate Professor, Division of Dermatology, University of Toronto, Toronto, ON, Canada

Introduction

Atopic dermatitis (AD) is a chronic and pruritic inflammatory disease that affects a wide age range of patients causing significant impact on their quality of life. There has been a recently updated consensus paper on the treatment of mild-to-moderate AD published by an expert panel of dermatologists and pediatricians.1 The primary objective of this article is to review the prevalence, pathophysiology, clinical features, diagnosis and treatment options for atopic dermatitis. The secondary objective is to disseminate the updated treatment algorithm suggested by the authors of the consensus paper for the primary care providers.

Prevalence

  • Atopic dermatitis affects both pediatric and adult populations.
  • Up to 20% of children have been reported to suffer from AD.2
  • AD is more common in patients with a history of atopy such as allergic rhinitis or asthma.
  • The majority of patients with AD have a positive family history of atopy.3

Pathogenesis

  • AD is associated with impaired skin barrier, increased inflammation and altered microbiome.4
  • A mutation in the filaggrin (FLG) gene that affects the natural skin barrier function is the most important genetic association.5
  • There has been further evidence to suggest that there is a complex mechanism involving the JAK-STAT pathway and other immune responses via TH2 and TH22.
  • Finally, AD is also associated with overproduction of phosphodiesterase 4 (PDE4) and subsequent pro-inflammatory cytokines.6

Clinical Features

  • Atopic dermatitis has an intermittent nature and variable distribution that may change with age.
  • Common clinical features include dry skin, pruritus and hyperreactivity to environmental exposures.
  • The characteristic lesions of atopic dermatitis are ill-defined, erythematous, scaly, vesicular, excoriated and/or oozing papules and plaques that may become lichenified and fissured.
  • In infants, AD often affects head, neck and extensor surfaces.
  • In older children and adults, the antecubital/popliteal fossae, wrists and ankles are most commonly affected.

Diagnosis

  • Atopic dermatitis is a clinical diagnosis. In unusual cases, a punch biopsy may help rule out potential mimics. Patch testing may help diagnose allergic contact dermatitis.
  • The differential diagnosis for AD includes:
    • Irritant contact dermatitis
    • Allergic contact dermatitis
    • Seborrheic dermatitis
    • Plaque psoriasis
    • Scabies
  • The most widely accepted diagnostic criteria by Williams et al.7 include:
    • Evidence of itchy skin AND three or more of:
      • Involvement of creases
      • History of asthma or hay fever (or history of atopic disease in children under four years of age)
      • Visible dermatitis involving flexural surfaces (including cheeks or forehead and outer aspects of limbs in children under four years of age)
      • Personal or family history of asthma or hay fever
      • Generally dry skin in the past year
      •  Onset in a child under two years of age
    • Severity scales for atopic dermatitis are available but not widely used by clinicians

Co-Morbidities

  • Psychiatric disorders
    • Depression8
    • Suicide9
    • Attention deficit hyperactive disorder10
  • Obesity

Treatment

The new DERMA Atopic Dermatitis Algorithm was developed for management of AD (Figure 1).

Diagnosis/Distribution
Education/ Emollients
Red/Itchy
Medication/Maintenance
Assessment /Adherence

Diagnosis and Management of Atopic Dermatitis for Family Physicians: A Clinical Review - image
Figure 1: DERMA Atopic Dermatitis Algorithm. BID indicates twice daily; DERMA, Diagnosis/Distribution; E: Education/Emollients; R: Red/Itchy; M: Medication/Maintenance; A: Assessment/Adherence; PDE4, phosphodiesterase-4; TCIs, topical calcineurin inhibitors; TCS, topical corticosteroids.
*Approved in Canada for ages ≥ 2 years.
†At present, only tacrolimus has Canadian approval for maintenance therapy.
Reprinted with permission from “Clinical Insights About Topical Treatment of Mild-to-Moderate Pediatric and Adult Atopic Dermatitis,” by C. W. Lynde, J. Bergman, L. Fiorillo, et al. 2019, Journal of Cutaneous Medicine and Surgery, 23, p. 7. Copyright 2019 by publisher SAGE Publications.

Education

  • The mainstay of treatment is patient education.
  • Counselling should include:
    • Consistent use of emollients
    • Luke-warm bathing (with non-soap cleansers)
    • Avoidance of irritants such as fragrance

Emollients

  • Emollients control xerosis and improve the epidermal barrier, with some suggesting products with humectants, lipids and/or ceramides.11
  • Application of moisturizers should be done immediately after bathing.

Topical Anti-Inflammatories

  • The majority of AD patients have mild-to-moderate disease and only require topical therapies.
  • Topical therapies include anti-inflammatory agents such as topical corticosteroids (TCSs), topical calcineurin inhibitors (TCIs) or phosphodiesterase-4 (PDE4) inhibitors in various vehicles.
  • Ointments are generally better tolerated for nonintact “raw” skin as they do not contain preservatives, tend not to sting and can be more potent.
  • Creams are often more cosmetically appealing but can sting on nonintact skin.
  • Gels, sprays, lotions and foams may be useful for hair-bearing sites.
  • Providers should re-assess patients for adherence, severity, and diagnosis after four weeks of continuous topical anti-inflammatory use.

TCSs

  • Corticosteroids remain effective first-line treatments.
  • Long-term adverse effects in sensitive areas include:
    • Local cutaneous atrophy
    • Striae formation
    • Telangiectasia
    • Impaired wound healing
    • Acneiform eruptions
    • Allergic contact dermatitis

TCIs

  • Pimecrolimus 1% and tacrolimus 0.03% or 0.1% are safe and approved for children over age two.
  • Common side effects are burning or stinging sensation on applications that subside over time.
  • There exists a black box warning for possible lymphoma risk. However, patients should be counselled that causal relationship for this is unclear.12

PDE4 Inhibitors

  • Crisaborole 2% ointment (Eucrisa©) is a novel topical applied twice daily to reduce symptoms of mild-to-moderate atopic dermatitis approved for patients two years and older.13
  • Crisaborole showed efficacy by day 8 in clinical trials compared to vehicle and itch improves in less than two days.14
  • Since there is no risk of steroid-atrophy, PDE4 inhibitors may be applied on the face and other sensitive areas of the body. Similar to TCIs, crisaborole is an alternative for steroid-phobic patients and/or caregivers.
  • The most common side effect is application site burning, which is temporary.

Further Options

For severe AD, treatment options beyond topical therapies may involve phototherapy and/or systemic therapies such as cyclosporine, methotrexate, azathioprine, mycophenolate mofetil, or dupilumab.

Practical Tips

What about oral antihistamines?
A recent systemic review showed a lack of consistent evidence for use of oral antihistamines (e.g. cetirizine, loratadine, fexofenadine) when compared to placebo in decreasing symptoms of atopic dermatitis.15

What about food allergens?
Although patients with AD often have food allergies to cow’s milk, egg, wheat and peanut, there is no evidence that dietary interventions provide any benefit in the treatment of AD.16

What about bath additives?
Although some guidelines in Europe support the use of bath additives, there is no consistent data to demonstrate its efficacy in controlling pruritus.17

What about allergy testing?
Patch testing is not required to diagnose atopic dermatitis. It is only necessary for excluding the alternative diagnosis of irritant contact dermatitis.18

Conclusion

There are several topical therapy options available for the management of AD such as TCIs and PDE4 inhibitor. Family physicians are well equipped to manage mild-to-moderate AD in the majority of cases, but referral to dermatologists may be required in severe cases or alternative diagnoses.

References



  1. Lynde CW, et al. J Cutan Med Surg. 2019 May/Jun;23(3_suppl):3S-13S.

  2. The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee. Worldwide variation in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC. Lancet. 1998;351:1225-32.

  3. Wen HJ, et al. Br J Dermatol. 2009 Nov;161(5):1166-72.

  4. Irvine AD, McLean WH, Leung DY. N Engl J Med. 2011 Oct 6;365(14):1315-27.

  5. Weinstein M et al. Atopic Dermatitis: A Practical Guide to Management. Eczema Society of Canada. 2016.

  6. Baumer W, et al. Inflamm Allergy Drug Targets. 2007 Mar;6(1):17-26.

  7. Williams HC, et al. Br J Dermatol. 1994 Sep;131(3):406-16.

  8. Kimata H. Suicide Life Threat Behav. 2006 Feb;36(1):120-4.

  9. Sandhu JK, et al. JAMA Dermatol. 2019 Feb 1;155(2):178-87.

  10. Simpson EL. Curr Dermatol Rep. 2012 Mar 1;1(1):29-38.

  11. van Zuuren EJ, et al. Cochrane Database Syst Rev. 2017 Feb 6;2:CD012119.

  12. Siegfried EC, Jaworski JC, Hebert AA. Am J Clin Dermatol. 2013 Jun;14(3):163-78.

  13. Eichenfield LF, et al. J Am Acad Dermatol. 2017 Oct;77(4):641-649.e5.

  14. Paller A et al. J Am Acad Dermatol. 2016 Sep;75(3):494-503.e6.

  15. Matterne U1, et al. Cochrane Database Syst Rev. 2019 Jan 22;1:CD012167.

  16. Bath-Hextall F, Delamere FM, Williams HC. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD005203.

  17. Santer M, et al. BMJ. 2018 May 3;361:k1332.

  18. Vender RB. Skin Therapy Lett. 2002 Jun;7(6):4-6.