• Changes in Quality of life (anxiety, depressive symptoms, fatigue, mobility, pain interference, peer relationships) as assessed by PROMIS Pediatric Profile 25 and Correlation of changes with clinical responsiveness and biomarker PDE4A expression levels [ Time Frame: Baseline (Day 1) and Day 28 ]
  Changes in quality of life will be measured by comparing standardized PROMIS T-scores for each domain at Day 28 with baseline. The PROMIS Pediatric Profile 25 is a 25-item questionnaire and assesses anxiety, depressive symptoms, fatigue, mobility, pain interference, and peer relationships. Each item has five response options. The HealthMeasures Scoring Service will be used to calculate T-scores for each domain. A T-score of 50 is the average for the United States general population with a standard deviation of 10. A higher T-score represents more of the concept being measured. Responsiveness will be determined by comparing clinician-assessed disease severity by ISGA and EASI scores at baseline and Day 28.
• Changes in Quality of life (symptoms and feelings, leisure, school or holidays, personal relationships, sleep, treatment) as assessed by CDLQI and Correlation of Quality of life changes with clinical responsiveness and biomarker PDE4A expression levels [ Time Frame: Baseline (Day 1) and Day 28 ]
  Changes in quality of life will be measured by comparing CDLQI scores at Day 28 with baseline. The CDLQI is a 10-item questionnaire assessing symptoms and feelings, leisure, school or holidays, personal relationships, sleep, and treatment. Scores range from 0 to 30 and are calculated by summing the scores of each question. The higher the score, the more impaired quality of life. Responsiveness will be determined by comparing ISGA and EASI scores at baseline and Day 28.
• Correlation of TEWL with clinical responsiveness and biomarker PDE4A expression levels [ Time Frame: Baseline (Day 1) and Day 28 ]
  Diffusion of water through the skin is measured using the AquaFlux instrument. Responsiveness will be determined by comparing ISGA and EASI scores at baseline and Day 28.

The overall study design is an intervention open-label non-randomized clinical trial of Eucrisa treatment (Eucrisa is an FDA approved drug for this indication and in this age group) twice daily for 28 days in 5-17 year old children. This study intends to enroll 30 total participants. The main purpose of this study is to develop biomarkers to predict responsiveness to Eucrisa. The hypothesis that PDE4A is a strong driver of inflammation in atopic dermatitis (AD) patients with high PDE4A skin expression, and that they will be highly responsive to Eucrisa.

Based on a previously published study to use minimally invasive tape strip biomarkers to differentiate patient groups, a 30-fold difference was noted when comparing PDE4A expression levels between TH2 high and TH2 low patients (total n=30). The investigators anticipate that ~50% of patients will be responders per the primary outcome of improvement in clinician assessed disease severity (Investigator Global Assessment of Investigator's Static Global Assessment (ISGA)) defined as clear (0) or almost clear (1) with a 2-grade or more improvement from baseline. With a total sample size of 30, the investigators estimate ~15 will be responders and ~15 non-responders, with alpha=0.05, power=0.8, assuming standard deviation of log(2) to log(5) in mRNA expression difference. This would give power to see a difference in fold expression in the range of 1.9-4.1, and adequate power to see expected differences in the chosen biomarkers. Assuming 80% power, the investigators are also powered for secondary analyses to see correlations with biomarkers and secondary outcomes, with a correlation coefficient ≥ 0.5.

The investigators will recruit directly from the various clinics of Ann & Robert H. Lurie Children's Hospital (LC). Patients will be contacted for screening over the phone 2 weeks prior to their clinic visit and recruited in clinic for study participation.

If participants give permission over the phone, study staff will meet them when they come in for their Allergy or Dermatology clinic visit. On Days 1 (baseline visit) and 28 (final visit), the following procedures will be done. Their skin will be examined by a clinician, and transepidermal water loss (TEWL) will be measured using the non-invasive AquaFlux instrument. Skin samples will be taken from the participant's antecubital fossa and photographs will be taken only of the collection site via the tape stripping protocol. The samples will be stored without identifiers, only with the participant's study identification (ID) number. Photos will be stored on a password-protected computer, accessible only by study staff, without any identifiers and will be coded with study ID. Participants and their caregivers will also be asked to fill out questionnaires, including Patient-Reported Outcomes Measurement Information System (PROMIS) itch forms, PROMIS sleep items, and PROMIS Profile 25. The child will additionally complete a Patient-Oriented Eczema Measure (POEM) and a Children's Dermatology Life Quality Index (CDLQI). Parent and child will also complete daily diary entries regarding the child's Eucrisa application and will include a 10-point pruritus scale. All of these forms will be administered electronically, and the collected data will be maintained in a secure REDCap database. The electronic forms are set up such that participants must answer every item to complete the study. If they do not feel comfortable answering certain items, they may choose to discontinue involvement in the study without consequence. If, at the baseline visit only, the participant is already having blood drawn for another clinical indication, blood will additionally be drawn with their consent for study purposes (15 mL) for later RNA sequencing. Plasma and peripheral blood mononuclear cells (PBMCs) drawn at the initial visit in this subset of patients, will be frozen and stored (de-identified, in a locked freezer) at -80°C for later processing and correlation with tape strip biomarkers. The correct method of therapy application will be reviewed with the patient and/or caregiver. They will be advised to discontinue Eucrisa and seek medical attention immediately if signs or symptoms of hypersensitivity occur and to contact the study doctor. The research team will submit incident reports regarding adverse events to the Lurie Children's Institutional Review Board (IRB) via their Cayuse system. Subject ID numbers will be maintained separately from the data set. Source documents and case report forms are kept in a secured area (in a locked cabinet in a locked room) in the Department of Allergy & Immunology at Lurie Children's, and all electronic data is password-protected and will not be transmitted outside the Lurie server.

After isolating expression of putative biomarkers, specifically PDE4A. Primary analysis will compare baseline mean expression levels of PDE4A in "responder" versus "non-responder" groups. This will be defined by the primary clinical outcome of disease severity improvement by clinician assessment. The investigators anticipate data with a normal distribution, so a t-test will compare significance of average expression levels. If data is not normally distributed, comparisons will be made using the Mann-Whitney U test. Secondary analyses will look at mean differences between other biomarkers (TH2 (IL13, IL4R, CCL26), TH17/22 (IL36G), itch (ENKUR), and epidermal genes (FLG, LOR and S100A9) in the "responder" versus "non-responder" groups. In exploratory analyses, the investigators will evaluate whether these biomarkers changed while on Eucrisa at the 4 week follow up. Specifically, a paired samples t-test will be used (or Wilcoxon signed-rank test if data not normally distributed). Magnitude of change in biomarkers will also be descriptively compared to magnitude of clinical improvement in disease, similar to previously published methods.

To correlate quality of life measures at baseline with PDE4A expression levels, initially data will be graphed to visually inspect the distribution and association, with PDE4A expression on the X-axis and quality of life measures on the Y-axis. Pearson correlation coefficient will be used to evaluate the strength of the association, if non-normally distributed data, a Spearman correlation coefficient will be used to test associations. In exploratory analyses, the investigators will look at the relationship of these genes after treatment with PDE4A. Further analyses will be conducted to determine if patients will be categorized as responders or non-responders on all measures tested using clinically important differences in the tested measures. The investigators will compare responses to quality of life measures using descriptive statistics. Additionally, the investigators will also consider average PDE4A levels in responders versus non-responders using these assessment measures.

The investigators will also attempt to develop a logistic regression model to predict Eucrisa responders. Specifically, the investigators will look at the association between each biomarker and the outcome of interest. If significant, the investigators will include in the final model to determine the key biomarkers predicting Eucrisa responders.

The Lurie Children's IRB and will ensure that the research complies with all applicable policies and regulations through their Post-Approval Monitoring program. Their staff will review study documents, schedule and perform site visits with the investigators, and follow up with the research team on any findings to take the appropriate actions, if any.

• Atopic Dermatitis
• Eczema

• Dyjack N, Goleva E, Rios C, Kim BE, Bin L, Taylor P, Bronchick C, Hall CF, Richers BN, Seibold MA, Leung DYM. Minimally invasive skin tape strip RNA sequencing identifies novel characteristics of the type 2-high atopic dermatitis disease endotype. J Allergy Clin Immunol. 2018 Apr;141(4):1298-1309. doi: 10.1016/j.jaci.2017.10.046. Epub 2018 Jan 6.
• Paller AS, Tom WL, Lebwohl MG, Blumenthal RL, Boguniewicz M, Call RS, Eichenfield LF, Forsha DW, Rees WC, Simpson EL, Spellman MC, Stein Gold LF, Zaenglein AL, Hughes MH, Zane LT, Hebert AA. 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 Sep;75(3):494-503.e6. doi: 10.1016/j.jaad.2016.05.046. Epub 2016 Jul 11. Erratum in: J Am Acad Dermatol. 2017 Apr;76(4):777.
• Paton DM. Crisaborole: Phosphodiesterase inhibitor for treatment of atopic dermatitis. Drugs Today (Barc). 2017 Apr;53(4):239-245. doi: 10.1358/dot.2017.53.4.2604174. Review.
• Hamilton JD, Suárez-Fariñas M, Dhingra N, Cardinale I, Li X, Kostic A, Ming JE, Radin AR, Krueger JG, Graham N, Yancopoulos GD, Pirozzi G, Guttman-Yassky E. Dupilumab improves the molecular signature in skin of patients with moderate-to-severe atopic dermatitis. J Allergy Clin Immunol. 2014 Dec;134(6):1293-1300. doi: 10.1016/j.jaci.2014.10.013.
• Simpson EL, Paller AS, Boguniewicz M, Eichenfield LF, Feldman SR, Silverberg JI, Chamlin SL, Zane LT. Crisaborole Ointment Improves Quality of Life of Patients with Mild to Moderate Atopic Dermatitis and Their Families. Dermatol Ther (Heidelb). 2018 Dec;8(4):605-619. doi: 10.1007/s13555-018-0263-0. Epub 2018 Oct 22.
• Chamlin SL, Mattson CL, Frieden IJ, Williams ML, Mancini AJ, Cella D, Chren MM. The price of pruritus: sleep disturbance and cosleeping in atopic dermatitis. Arch Pediatr Adolesc Med. 2005 Aug;159(8):745-50.

Inclusion Criteria:

• AD diagnosis by dermatologist or allergist based on Hanifin and Rajka criteria
• 5% or more treatable body surface area involvement
• baseline Investigator's Static Assessment (ISGA) score of mild (2) or moderate (3)
• patient on stable regimens (consistent use 14 days before day 1 of enrollment) of inhaled corticosteroids and antihistamines
• must have lesional skin in the antecubital fossa

Exclusion Criteria:

• use of topical corticosteroid, calcineurin inhibitor, or PDE4 inhibitor within 14 days of enrollment
• significant active infection
• any previous use of biologic therapy
• no pruritus at baseline visit, or other pruritic condition
• washing/moisturizer use 24 hours prior to tape strip biomarker collection at site
• uncontrolled asthma, uncontrolled allergic rhinitis, or other sleep disturbing condition