Crisaborole 2% Ointment for Mild-to-Moderate Atopic Dermatitis

Aryan Riahi, BSc; Joseph M. Lam, MD, FRCPC

Disclosures

Skin Therapy Letter. 2021;26(1) 

In This Article

Overview: Diagnosis and Pathogenesis

The diagnosis of AD is clinical. Skin biopsy and laboratory testing such as serum immunoglobulin E (IgE) levels are not routinely performed in the evaluation of suspected AD, but may be useful in ruling out other skin conditions.[7] Adverse impacts from AD are wide ranging and include impairments to general health, quality of life, and mental health, with the financial cost of disease management posing a significant concern for patients and their families. Scratching may expose patients to secondary infections, which can exacerbate the severity of AD.[8] The differential diagnosis for AD includes irritant or allergic contact dermatitis, serborrheic dermatitis, psoriasis, and scabies. Intractable, chronic itch is a hallmark of AD. Scratching may expose patients to secondary infections, which can exacerbate the disease severity.[6]

The pathogenesis of AD is determined by numerous factors including abnormalities in the skin barrier, a skewed T helper type 2 (Th2) immune response, impaired innate immunity, and changes in the resident microbial flora of the skin.[9] The epidermis of patients with AD is prone to increased transepidermal water loss.[10] The filaggrin (FLG) protein, which is produced by keratinocytes and encoded by the FLG gene, serves a critical role in skin barrier formation.[11] Patients with AD have lower levels of expression of skin barrier-related proteins including FLG-2, corneodesmosin, and enzymes necessary for skin hydration and water retention at the stratum corneum.[12] In addition to a barrier defect, the underlying immune system is also dysregulated in patients with AD. The innate immune response depends on toll-like receptors, which are stimulated by tissue damage and microorganisms, and enhance the strength of tight junctions to prevent allergen and microorganism penetration.[13] Grouping patients with AD into one endotype may be overly simplistic. AD has a variety of endotypes depending on age groups, ethnicities, FLG mutations, and IgE levels.[14] These include Asian versus European American, adults versus children, and presence or absence of family history of FLG mutations.[14] Since increased Th2 cell levels are common across the spectrum of AD, targeting this factor should theoretically be therapeutic for all phenotypes of AD. However, phase 3 trials of dupilumab, an interleukin (IL)-4 and IL-13 blocker targeting the Th2-mediated pathway, was only able to reduce the Investigator's Global Assessment score of patients down to 1 or 0 in 36–38% of cases.[15] This suggests that other immune mediators outside of Th2 cells may be involved in the pathogenesis and treatment of AD.

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