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In atopic dermatitis, Nonlesional skin
can be deceiving

Current evidence suggests that nonlesional skin is not normal skin,
owing to persistent subclinical inflammation throughout the body1-4


Suárez-Fariñas M, et al. Nonlesional atopic dermatitis skin is characterized by broad terminal differentiation defects and variable immune abnormalities. J Allergy Clin Immunol. 2011;127(4):954-964.
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Immunohistochemistry (IHC) staining of terminal differentiation proteins in clinically uninfected/nonlesional atopic dermatitis (ANL), lesional atopic dermatitis (AL), and normal skin. Based on genomic and histologic profiling of both ANL and AL skin lesions (n=12, each), compared with normal human skin (n=10). Scale bar=100 µm.

Current findings show that nonlesional skin exhibits subclinical defects similar to lesional skin, including1,3,4:

  • Skin barrier defects
  • Increased epidermal thickness
  • Ongoing inflammation

In some patients, skin barrier dysfunction, resulting from either genetic defects and/or Th2 immunologic defects, ultimately5,6:

  • Weakens the skin barrier
  • Increases sensitivity to allergens
  • Increases the chance of pathogenic infection

Nonlesional skin in patients with atopic dermatitis is not histologically normal and is indicative of the subclinical inflammation inherent to atopic dermatitis.3,4

In nonlesional skin, there are elevated levels of cutaneous inflammatory T-cell
and epidermal cell proliferation4

Epidermal abnormalities:

  • Increased epidermal thickness in nonlesional skin in atopic dermatitis vs normal, healthy skin; thickening is further increased in lesional skin
  • Significant increase (218%) in the Ki-67 staining, a measure of keratinocyte proliferation, in nonlesional skin vs normal skin (P<0.05)

Immune abnormalities:

  • Nonlesional skin has a significant increase in infiltrating dermal CD3 T cells compared with normal skin; 86% (P<0.001)

Underlying inflammation is a source of lesions and itch, the primary signs and symptoms of atopic dermatitis.2-4 Atopic dermatitis is a chronic inflammatory skin disease that is characterized by intense pruritus and eczematous lesions.7 The Th2 cytokines IL-4 and IL-13 are key drivers involved with the underlying inflammatory process.2

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This has changed my perspective that nonlesional skin is not normal skin

References: 1. De Benedetto A, Rafaels NM, McGirt LY, et al. Tight junction defects in patients with atopic dermatitis. J Allergy Clin Immunol. 2011;127(3):773-786. 2. Gittler JK, Shemer A, Suárez-Fariñas M, et al. Progressive activation of Th2/Th22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis. J Allergy Clin Immunol. 2012;130(6):1344-1354. 3. Leung DYM, Boguniewicz M, Howell MD, Nomura I, Hamid QA. New insights into atopic dermatitis. J Clin Invest. 2004;113(5):651-657. 4. Suárez-Fariñas M, Tintle SJ, Shemer A, et al. Nonlesional atopic dermatitis skin is characterized by broad terminal differentiation defects and variable immune abnormalities. J Allergy Clin Immunol. 2011;127(4):954-964. 5. Guttman-Yassky E, Suárez-Fariñas M, Chiricozzi A, et al. Broad defects in epidermal cornification in atopic dermatitis identified through genomic analysis. J Allergy Immunol. 2009;124(6):1235-1244. 6. Elias PM, Schmuth M. Abnormal skin barrier in the etiopathogenesis of atopic dermatitis. Curr Opin Allergy Clin Immunol. 2009;9(5):437-446. 7. Torrelo A, Ortiz J, Alomar A, Ros S, Pedrosa E, Cuervo J. Health-related quality of life, patient satisfaction, and adherence to treatment in patients with moderate or severe atopic dermatitis on maintenance therapy: the CONDA-SAT study. Actas Dermosifiliogr. 2013;104(5):409-417.