Atopic Dermatitis

Atopic dermatitis is a chronic, pruritic inflammatory skin disease that occurs primarily in children. Both environmental and genetic factors drive disease pathology, which is characterized by breakdown of the skin barrier and concurrent inflammation. AD progresses in a chronic intermittent fashion, and is characterized by periods of acute symptom worsening, known as flares, followed by periods of quiescence. Flares can be triggered by a variety of factors including infections, heat, sweating, food allergies, and anxiety.

Acute AD lesions are characterized by itchy, erythematous papules, often with dry skin (xerosis), excoriations, and serous exudate. Chronic AD is characterized by areas with thick, scaly skin (lichenification) along with acute lesions. Current prevalence data indicates that 10-20% of children and 1-3% of adults have AD in developed countries, while considerably fewer are affected in non-developed countries1. The disease typically manifests early in childhood with 85% of AD cases presenting before the age of 5 and 60% presenting in the first year of life.

Approximately 67% of all AD cases present with mild severity2. Notably, the worldwide prevalence of AD is increasing. In an assessment of the National Health Interview Survey data from 1997 to 2011, the Centers for Disease Control and Prevention identified an increase in the prevalence of AD from 7.4% in 1997-1999 to 12.5% in 2009-20113.

Patients with AD often have significant psychosocial comorbidities as a result of their disease. It has been reported that approximately 50% of children with AD have a severely impaired quality of life due to problems with sleep, fatigue, and depression, and also display an elevated risk of attention-deficit hyperactivity disorder4,5,6,7.

 

The current standard of care therapies for AD patients are limited to topical corticosteroids (TCS) and topical calcineurin inhibitors (TCIs). Topical corticosteroids are effective in many patients but are associated with significant safety risks, including skin atrophy and HPA axis suppression if used as a long-term therapy. Additionally, topical calcineurin inhibitors have a boxed warning for increased risk of lymphomas. Inadequate disease control has been cited as a current problem in the management of AD patients, and this appears to be due in large part to undertreatment driven by both steroid phobia and the black box warning present on TCIs2,8,9.

 

These perceived safety risks associated with the standard of care therapies for AD highlight a substantial unmet medical need for treatments that are both safe and effective for pediatric patients. Dermavant is developing targeted and innovative topical therapies to treat patients with AD of all disease severities.

References

  1. Leung, D. Y., Boguniewicz, M., Howell, M. D., Nomura, I., & Hamid, Q. A. (2004). New insights into atopic dermatitis. The Journal of clinical investigation, 113(5), 651-657.
  2. Eichenfield, L. F., Boguniewicz, M., Simpson, E. L., Russell, J. J., Block, J. K., Feldman, S. R., ... & Paller, A. S. (2015). Translating atopic dermatitis management guidelines into practice for primary care providers. Pediatrics, 136(3), 554-565. Chicago
  3. Silverberg, N. A practical overview of pediatric atopic dermatitis, Part 1: Epidemiology and pathogenesis. Cutis. 2016 April;97(4):267-271
  4. Chamlin, S. L. (2006). The psychosocial burden of childhood atopic dermatitis. Dermatologic therapy, 19(2), 104-107.
  5. Tollefson, M. M., & Bruckner, A. L. (2014). Atopic dermatitis: skin-directed management. Pediatrics, 134(6), e1735-e1744.

  1. Schmitt, J., Apfelbacher, C., Chen, C. M., Romanos, M., Sausenthaler, S., Koletzko, S., ... & von Berg, A. (2010). Infant-onset eczema in relation to mental health problems at age 10 years: results from a prospective birth cohort study (German Infant Nutrition Intervention plus). Journal of Allergy and Clinical Immunology, 125(2), 404-410.
  2. Yaghmaie, P., Koudelka, C. W., & Simpson, E. L. (2013). Mental health comorbidity in patients with atopic dermatitis. Journal of Allergy and Clinical Immunology, 131(2), 428-433.
  3. Fleischer, AB. (2006). Black box warning for topical calcineurin inhibitors and the death of common sense. Dermatology online journal, 12(6).
  4. Weidinger, S., Novak, N. (2015). Atopic dermatitis. The Lancet, 387(10023), 1109 – 1122