Publications by authors named "Aisleen Diaz"

12 Publications

  • Page 1 of 1

The molecular features of normal and atopic dermatitis skin in infants, children, adolescents, and adults.

J Allergy Clin Immunol 2021 Jan 13. Epub 2021 Jan 13.

Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Ill. Electronic address:

Background: Although atopic dermatitis (AD) often presents in infancy and persists into adulthood, comparative characterization of AD skin among different pediatric age groups is lacking.

Objective: We sought to define skin biopsy profiles of lesional and nonlesional AD across different age groups (0-5-year-old infants with disease duration <6 months, 6-11-year-old children, 12-17-year-old adolescents, ≥18-year-old adults) versus age-appropriate controls.

Methods: We performed gene expression analyses by RNA-sequencing and real-time PCR (RT-PCR) and protein expression analysis using immunohistochemistry.

Results: T2/T22 skewing, including IL-13, CCL17/thymus and activation-regulated chemokine, IL-22, and S100As, characterized the common AD signature, with a global pathway-level enrichment across all ages. Nevertheless, specific cytokines varied widely. For example, IL-33, IL-1RL1/IL-33R, and IL-9, often associated with early atopic sensitization, showed greatest upregulations in infants. T17 inflammation presented a 2-peak curve, with highest increases in infants (including IL-17A and IL-17F), followed by adults. T1 polarization was uniquely detected in adults, even when compared with adolescents, with significant upregulation in adults of IFN-γ and CXCL9/CXCL10/CXCL11. Although all AD age groups had barrier abnormalities, only adults had significant decreases in filaggrin expression. Despite the short duration of the disease, infant AD presented robust downregulations of multiple barrier-related genes in both lesional and nonlesional skin. Clinical severity scores significantly correlated with T2/T22-related markers in all pediatric age groups.

Conclusions: The shared signature of AD across ages is T2/T22-skewed, yet differential expression of specific T2/T22-related genes, other T pathways, and barrier-related genes portray heterogenetic, age-specific molecular fingerprints.
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http://dx.doi.org/10.1016/j.jaci.2021.01.001DOI Listing
January 2021

Mild atopic dermatitis lacks systemic inflammation and shows reduced nonlesional skin abnormalities.

J Allergy Clin Immunol 2020 Oct 1. Epub 2020 Oct 1.

Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address:

Background: Molecular studies in atopic dermatitis (AD) are largely restricted to patients with moderate-to-severe disease.

Objective: Our aim was to evaluate skin and blood abnormalities in mild, moderate, and severe AD.

Methods: Skin and blood samples were obtained from 61 patients with AD (20 with mild or limited disease, 17 with moderate disease, and 24 with severe disease) and 20 healthy subjects. Immune and barrier markers were measured in lesional, nonlesional, and healthy skin by quantitative real-time PCR and immunohistochemistry, and in blood by using the OLINK proteomic assay.

Results: Cellular markers of epidermal hyperplasia and T-cell/dendritic cell infiltration were increased in AD tissues of all patients in all severity groups versus in those of controls, whereas downstream T2 cell-, T22 cell-, T1 cell-, and T17 cell-related mediators demonstrated incremental elevations with increasing disease severity, in both lesional and nonlesional skin. Whereas the levels of the T2 (IL13, CCL17, and CCL26) and T22 (IL-22) cytokines were significantly elevated in both AD lesional and nonlesional skin of all patients regardless of the severity of their disease, patients with mild or limited AD showed increases in their levels of T1 cell (IFNG, CXCL9, and CXCL10) and T17 cell (IL-17A, CCL20, and CXCL1) markers in lesional but not nonlesional skin. Regulatory T-cell-related mediators (IL-10 and FOXP3) were comparably upregulated in all groups, without displaying the severity-based gradient in other immune axes. Unsupervised clustering aligned samples along a severity spectrum, where nonlesional mild or limited AD skin clustered with the samples from healthy controls. Furthermore, whereas the blood profiles of patients with moderate and severe AD showed gradual increases in the levels of T1 cell-, T2 cell-, and T17 cell-related and atherosclerosis and/or cardiovascular risk (CCL7, FGF21, and IGFBP1) proteins, the blood profiles of patients with mild or limited AD lacked significant differences from those of the controls.

Conclusion: Mild and limited AD show high levels of T2/T22 cell activation that is primarily localized to skin lesions and lacks the systemic inflammation of moderate and severe disease.
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http://dx.doi.org/10.1016/j.jaci.2020.08.041DOI Listing
October 2020

A Novel Atypical Presentation of Frontal Fibrosing Alopecia Involving the Frontoparietal Scalp.

Skin Appendage Disord 2020 Jul 12;6(4):250-253. Epub 2020 Jun 12.

Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami L. Miller School of Medicine, Miami, Florida, USA.

Frontal fibrosing alopecia (FFA) is a progressive scarring alopecia of unknown etiology that classically presents with a band of hair loss along the frontotemporal scalp. We report a case of FFA involving a band of alopecia along the frontotemporal scalp extending into 2 symmetrical triangles along the parietal scalp reminiscent of the Greek letter upsilon (υ). Trichoscopy demonstrated loss of follicular ostia and peripilar casts. Histology demonstrated altered follicular architecture with decreased follicular density and focal perifollicular fibrosis with a lichenoid infiltrate. Both the trichoscopy and histology support a diagnosis of FFA.
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http://dx.doi.org/10.1159/000508388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445581PMC
July 2020

Tape strips detect distinct immune and barrier profiles in atopic dermatitis and psoriasis.

J Allergy Clin Immunol 2021 Jan 21;147(1):199-212. Epub 2020 Jul 21.

Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; Laboratory of Investigative Dermatology, The Rockefeller University, New York, NY. Electronic address:

Background: Our current understanding of atopic dermatitis (AD) and psoriasis pathophysiology is largely derived from skin biopsy studies that cause scarring and may be impractical in large-scale clinical trials. Although tape strips show promise as a minimally invasive technique in these common diseases, a comprehensive molecular profiling characterizing and differentiating the 2 diseases in tape strips is unavailable.

Objective: Our aim was to construct a global transcriptome of tape strips from lesional and nonlesional skin of adults with moderate-to-severe AD and psoriasis.

Methods: A total of 20 tape strips were obtained from lesional and nonlesional skin of patients with AD and psoriasis and skin from controls (n = 20 each); the strips were subjected to RNA sequencing (RNA-seq), with quantitative RT-PCR validation of immune and barrier biomarkers.

Results: We detected RNA-seq profiles in 96 of 100 of samples (96%), with 4123 and 5390 genes differentially expressed in AD and psoriasis lesions versus in controls, respectively (fold change ≥ 2; false discovery rate [FDR] < 0.05). Nonlesional tape-stripped skin from patients with AD was more similar to lesional skin than to nonlesional skin of patients with psoriasis, which showed larger differentiation from lesions. AD and psoriasis tissues shared increases in levels of dendritic cell and T-cell markers (CD3, ITGAX/CD11c, and CD83), but AD tissues showed preferential T2 skewing (IL-13, CCL17/TARC, and CCL18), whereas psoriasis was characterized by higher levels of expression of T17-related (IL-17A/F and IL-36A/IL-36G), T1-related (IFN-γ and CXCL9/CXCL10), and innate immunity-related (nitric oxide synthase 2/inducible nitric oxide synthase and IL-17C) products (FDR < 0.05). Terminal differentiation (FLG2 and LCE5A), tight junction (CLDN8), and lipid biosynthesis and metabolism (FA2H and ALOXE3) products were significantly downregulated in both AD and psoriasis (FDR < 0.05). Nitric oxide synthase 2/inducible nitric oxide synthase expression (determined by quantitative PCR) differentiated AD and psoriasis with 100% accuracy.

Conclusion: RNA-seq tape strip profiling detected distinct immune and barrier signatures in lesional and nonlesional AD and psoriasis skin, suggesting their utility as a minimally invasive alternative to biopsies for detecting disease biomarkers.
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http://dx.doi.org/10.1016/j.jaci.2020.05.048DOI Listing
January 2021

Tape strips from early-onset pediatric atopic dermatitis highlight disease abnormalities in nonlesional skin.

Allergy 2021 01 20;76(1):314-325. Epub 2020 Aug 20.

Laboratory of Inflammatory Skin Diseases, Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: Skin biopsies promote our understanding of atopic dermatitis/AD pathomechanisms in infants/toddlers with early-onset AD, but are not feasible in pediatric populations. Tape strips are an emerging, minimally invasive alternative, but global transcriptomic profiling in early pediatric AD is lacking. We aimed to provide global lesional and nonlesional skin profiles of infants/toddlers with recent-onset, moderate-to-severe AD using tape strips.

Methods: Sixteen tape strips were collected for RNA-seq profiling from 19 infants/toddlers (<5 years old; lesional and nonlesional) with early-onset moderate-to-severe AD (≤6 months) and 17 healthy controls.

Results: We identified 1829 differentially expressed genes/DEGs in lesional AD and 662 DEGs in nonlesional AD, vs healthy skin (fold-change ≥2, FDR <0.05), with 100% sample recovery. Both lesional and nonlesional skin showed significant dysregulations of Th2 (CCL17 and IL4R) and Th22/Th17 (IL36G, CCL20, and S100As)-related genes, largely lacking significant Th1-skewing. Significant down-regulation of terminal differentiation (FLG and FLG2), lipid synthesis/metabolism (ELOVL3 and FA2H), and tight junction (CLDN8) genes were primarily seen in lesional AD. Significant negative correlations were identified between Th2 measures and epidermal barrier gene-subsets and individual genes (FLG with IL-4R and CCL17; r < -0.4, P < .05). Significant correlations were also identified between clinical measures (body surface area/BSA, pruritus ADQ, and transepidermal water loss/TEWL) with immune and barrier mRNAs in lesional and/or nonlesional AD (FLG/FLG2 with TEWL; r < -0.4, P < .05).

Conclusion: RNA-seq profiling using tape strips in early-onset pediatric AD captures immune and barrier alterations in both lesional and nonlesional skin. Tape strips provide insight into disease pathomechanisms and cutaneous disease activity.
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http://dx.doi.org/10.1111/all.14490DOI Listing
January 2021

Combination therapy with prednisone and isotretinoin in early erythema dyschromicum perstans: A retrospective series.

JAAD Case Rep 2020 Mar 19;6(3):207-213. Epub 2020 Feb 19.

Department of Dermatology, Kaiser Permanente, Panorama City, California.

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http://dx.doi.org/10.1016/j.jdcr.2019.12.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033289PMC
March 2020

Pigmented lesions on the scalp in a healthy woman.

Int J Dermatol 2020 Jul 20;59(7):e231-e233. Epub 2019 Nov 20.

Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami L. Miller School of Medicine, Miami, FL, USA.

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http://dx.doi.org/10.1111/ijd.14714DOI Listing
July 2020

The proteomic skin profile of moderate-to-severe atopic dermatitis patients shows an inflammatory signature.

J Am Acad Dermatol 2020 Mar 25;82(3):690-699. Epub 2019 Oct 25.

Department of Dermatology and Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address:

Background: Moderate-to-severe atopic dermatitis (AD) is increasingly recognized as a systemic disease, largely due to proteomic blood studies. There are growing efforts to develop AD biomarkers using minimal tissues.

Objective: To characterize the AD skin proteomic signature and its relationship with the blood proteome and genomic skin profile in the same individuals.

Methods: We evaluated lesional and nonlesional biopsy samples and blood from 20 individuals with moderate-to-severe AD and 28 healthy individuals using Olink Proteomics (Uppsala, Sweden), using 10 μg/10 μL for skin and blood and RNA sequencing of the skin.

Results: The AD skin proteome demonstrated significant upregulation in lesional and even in nonlesional skin compared with controls in inflammatory markers (matrix metalloproteinase 12; T-helper cell [Th]2/interleukin [IL]-1 receptor-like 1[IL1RL1]/IL-33R, IL-13, chemokine [C-C motif] ligand [CCL] 17; Th1/C-X-C motif chemokine 10; Th17/Th22/PI3, CCL20, S100A12), and in cardiovascular-associated proteins (E-selectin, matrix metalloproteinases, platelet growth factor, myeloperoxidase, fatty acid binding protein 4, and vascular endothelial growth factor A; false discovery rate, <0.05). Skin proteins demonstrated much higher and significant upregulations (vs controls) compared with blood, suggesting a skin source for the inflammatory/cardiovascular profile. Gene and protein expressions were correlated (r = 0.410, P < .001), with commonly upregulated inflammatory and cardiovascular risk-associated products, suggesting protein translation in skin.

Limitations: Our analysis was limited to 354 proteins.

Conclusions: The AD skin proteome shows an inflammatory and cardiovascular signature even in nonlesional skin, emphasizing the need for proactive treatment. Skin proteomics presents a sensitive option for biomarker monitoring.
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http://dx.doi.org/10.1016/j.jaad.2019.10.039DOI Listing
March 2020

Use of Tape Strips to Detect Immune and Barrier Abnormalities in the Skin of Children With Early-Onset Atopic Dermatitis.

JAMA Dermatol 2019 Oct 9. Epub 2019 Oct 9.

Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.

Importance: Molecular profiling of skin biopsies is the criterion standard for evaluating the cutaneous atopic dermatitis (AD) phenotype. However, skin biopsies are not always feasible in children. A reproducible minimally invasive approach that can track cutaneous disease in pediatric longitudinal studies or clinical trials is lacking.

Objective: To assess a minimally invasive approach using tape strips to identify skin biomarkers that may serve as a surrogate to biomarkers identified using whole-tissue biopsies.

Design, Setting, And Participants: This cross-sectional study of 51 children younger than 5 years recruited children with moderate to severe AD and children without AD from the dermatology outpatient clinics at a children's hospital. Sixteen tape strips were serially collected from the nonlesional and lesional skin of 21 children who had AD and were less than 6 months from disease initiation and from the normal skin of 30 children who did not have AD between January 22, 2016, and April 20, 2018.

Main Outcomes And Measures: Gene and protein expression were evaluated using quantitative real-time polymerase chain reaction and immunohistochemistry.

Results: A total of 51 children younger than 5 years were included in the study; 21 children had moderate to severe AD with less than 6 months of disease duration, and 30 children did not have AD. Of the 21 children with AD, the mean (SD) age was 1.7 (1.7) years, and most were male (15 [71.4%] and white (15 [71.4%]). Of the 30 children without AD, the mean (SD) age was 1.8 (2.0) years, and most were female (20 [66.7%]) and white (22 [73.3%]). Seventy-seven of 79 evaluated immune and barrier gene products were detected (gene detection rate, 97%) in 70 of 71 tape strips (sample detection rate, 99%), with 53 of 79 markers differentiating between children with lesional and/or nonlesional AD from children without AD. Many cellular markers of T cells (CD3), AD-related dendritic cells (Fc ε RI and OX40 ligand receptors), and key inflammatory (matrix metallopeptidase 12), innate (interleukin 8 [IL-8] and IL-6), helper T cell 2 (TH2; IL-4, IL-13, and chemokines CCL17 and CCL26), and TH17/TH22 (IL-19, IL-36G, and S100A proteins) genes were significantlyincreased in lesional and nonlesional AD compared with tape strips from normal skin. For example, IL-4 mean (SE) for lesional was -15.2 (0.91) and normal was -19.5 (0.48); P < .001. Parallel decreases occurred in epidermal barrier gene products (FLG, CLDN23, and FA2H) and negative immune regulators (IL-34 and IL-37). For example, the decrease for FLG lesional was mean (SE) -2.9 (0.42) and for normal was 2.2 (0.45); P < .001. Associations were found between disease severity or transepidermal water loss and TH2 (IL-33 and IL-4R) and TH17/TH22 (IL-36G and S100As) products in lesional and nonlesional AD skin (evaluated using the SCORing Atopic Dermatitis, Eczema Area and Severity Index, and Pruritus Atopic Dermatitis Quickscore tools).

Conclusions And Relevance: In this study, tape strips provide a minimally invasive alternative for serially evaluating AD-associated cutaneous biomarkers and may prove useful for tracking pediatric AD therapeutic response and predicting future course and comorbidities.
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http://dx.doi.org/10.1001/jamadermatol.2019.2983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802262PMC
October 2019

Crisaborole and atopic dermatitis skin biomarkers: An intrapatient randomized trial.

J Allergy Clin Immunol 2019 11 13;144(5):1274-1289. Epub 2019 Aug 13.

Department of Dermatology and Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address:

Background: Crisaborole ointment 2% is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis (AD). The mechanism of action of crisaborole and its effects on lesional measures of disease severity are not yet well defined.

Objective: This phase 2a, single-center, vehicle-controlled, intrapatient study was designed to further characterize the mechanism of action of crisaborole through evaluation of clinical efficacy and changes in skin biomarkers in adults (n = 40) with mild-to-moderate AD.

Methods: Two target lesions were randomized in an intrapatient (1:1) manner to double-blind crisaborole/vehicle applied twice daily for 14 days. Patients then applied crisaborole (open-label) to all affected areas for 28 days. Punch biopsy specimens were collected for biomarker analysis at baseline, day 8 (optional), and day 15.

Results: Crisaborole treatment resulted in early improvement in lesional signs/symptoms versus vehicle, with improvement in pruritus (pruritus numeric rating scale) observed as early as 24 hours after the first application. Crisaborole-treated lesions showed significant percentage improvement from baseline in lesional transcriptomic profile compared with vehicle at day 8 (91.15% vs 36.02%, P < 10) that was sustained until day 15 (92.90% vs 49.59%, P < 10). Crisaborole significantly modulated key AD biomarkers versus vehicle, including T2 and T17/T22 pathways and epidermal hyperplasia/proliferation. Molecular profiles and epidermal pathology normalized toward nonlesional skin and correlated with clinical changes in lesion severity and barrier function.

Conclusion: Crisaborole reversed biomarker profiles of skin inflammation and barrier function, with associated improvements in clinical efficacy measures, highlighting the therapeutic utility of targeting phosphodiesterase 4 in patients with AD.
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http://dx.doi.org/10.1016/j.jaci.2019.06.047DOI Listing
November 2019

Peripilar "Guttate" Hypopigmentation of the Scalp and Idiopathic Guttate Hypomelanosis in Frontal Fibrosing Alopecia.

Skin Appendage Disord 2019 Feb 14;5(2):100-103. Epub 2018 Jun 14.

Department of Dermatology and Cutaneous Surgery University of Miami L. Miller School of Medicine, University of Miami L. Miller School of Medicine, Miami, Florida, USA.

Frontal fibrosing alopecia (FFA) is characterized by progressive band-like scarring alopecia involving the frontotemporal hairline and limbs and irreversible alopecia of the eyebrows. Two opposite types of pigmentary alterations have been reported in FFA: hyper- and hypopigmentation. Here, we report a 57-year-old Hispanic female with FFA who presented with peripilar hypopigmentation and idiopathic guttate hypomelanosis on the upper extremities. To our knowledge, this is the first report of peripilar white halos in a patient of a White Hispanic origin. Upon review of other previous publications on trichoscopy of FFA, this pattern has not been detected. The common pattern of focal absence of melanocytes and melanin in both is another confirmation that FFA is associated with pigmentation abnormalities.
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http://dx.doi.org/10.1159/000489794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388643PMC
February 2019

Topical agents for the treatment of atopic dermatitis.

Expert Rev Clin Immunol 2019 04 8;15(4):369-382. Epub 2019 Jan 8.

a Department of Dermatology , Icahn School of Medicine , New York , NY , USA.

Introduction: Atopic dermatitis (AD) is perhaps the most common inflammatory skin disorder worldwide, with an increasing incidence in developed countries. The mainstay treatment for patients with AD is topical therapies, which are used not only by the mild patients but also by the moderate-to-severe patients, in conjunction with systemic treatment. While topical steroids and calcineurin antagonists are widely used, these are associated with long-term cutaneous adverse effects (AEs) or a black box warning, preventing their chronic use. Areas covered: The aim of this review is to provide a comprehensive overview of new and upcoming topical therapies currently in development and undergoing clinical trials, as well as their safety and efficacy profiles, and discuss current topicals used in the management of AD. Expert opinion: AD is a heterogeneous disease with complex pathophysiology. Treatments available to date for AD provide disease control; however, patients struggle to find an optimized therapeutic regimen they may use long term and without severe effects. Novel therapies are currently under investigation, with the hope of shifting the paradigm of AD management from symptom control to disease eradication.
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http://dx.doi.org/10.1080/1744666X.2019.1564038DOI Listing
April 2019