Publications by authors named "Emma Guttman-Yassky"

225 Publications

Immune and barrier characterization of atopic dermatitis skin phenotype in Tanzanian patients.

Ann Allergy Asthma Immunol 2021 May 8. Epub 2021 May 8.

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

Background: Atopic dermatitis/AD is a common disease, with particularly high prevalence seen in Africa. It is increasingly recognized that AD patients of different ethnic backgrounds have unique molecular signatures in skin, potentially accounting for treatment response variations. However, the skin profile of AD patients from Africa is unknown, hindering development of new treatments targeted to this patient population.

Objective: To characterize the skin profile of AD patients from Africa.

Methods: Gene-expression studies including RNA-sequencing (using threshold of foldchange/FCH>2 and false discovery rate/FDR<0.05) and real-time PCR were performed on skin biopsies of Tanzanian moderate-to-severe AD patients and controls.

Results: Tanzanian AD skin presented robust up-regulations of multiple key mediators of both Th2 (IL-13, IL10, IL-4R, CCL13/CCL17/CCL18/CCL26) and Th22 (IL22, S100As) pathways. Markers related to Th17/IL-23 (IL-17A, IL-23p19/IL-23A, IL-23p40/IL-12, PI3, DEFB4B) and Th1 (IFNγ, CXCL9/CXCL10/CXCL11) were also significantly overexpressed in AD tissues, albeit to a lesser extent. IL-36 isoforms showed significant upregulations in African skin. The barrier fingerprint of Tanzanian AD showed no suppression of hallmark epidermal barrier differentiation genes, such as filaggrin/FLG, loricrin/LOR, and periplakin/PPL, with robust attenuation of lipid metabolism genes (i.e AWAT1).

Conclusion: The skin phenotype of Tanzanian AD patients is consistent with that of African-Americans, exhibiting dominant Th2/Th22-skewing, minimal dysregulation of terminal differentiation, and even broader attenuation of lipid metabolism-related products. These data highlight the unique characteristic of AD in black individuals, as well as the need to develop unique treatments targeting AD patients of these under-represented populations.
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http://dx.doi.org/10.1016/j.anai.2021.04.023DOI Listing
May 2021

Selective sweep for an enhancer involucrin allele identifies skin barrier adaptation out of Africa.

Nat Commun 2021 May 7;12(1):2557. Epub 2021 May 7.

Division of Dermatology, Department of Medicine, Washington University in St. Louis School of Medicine, St. Louis, MO, 63110, USA.

The genetic modules that contribute to human evolution are poorly understood. Here we investigate positive selection in the Epidermal Differentiation Complex locus for skin barrier adaptation in diverse HapMap human populations (CEU, JPT/CHB, and YRI). Using Composite of Multiple Signals and iSAFE, we identify selective sweeps for LCE1A-SMCP and involucrin (IVL) haplotypes associated with human migration out-of-Africa, reaching near fixation in European populations. CEU-IVL is associated with increased IVL expression and a known epidermis-specific enhancer. CRISPR/Cas9 deletion of the orthologous mouse enhancer in vivo reveals a functional requirement for the enhancer to regulate Ivl expression in cis. Reporter assays confirm increased regulatory and additive enhancer effects of CEU-specific polymorphisms identified at predicted IRF1 and NFIC binding sites in the IVL enhancer (rs4845327) and its promoter (rs1854779). Together, our results identify a selective sweep for a cis regulatory module for CEU-IVL, highlighting human skin barrier evolution for increased IVL expression out-of-Africa.
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http://dx.doi.org/10.1038/s41467-021-22821-wDOI Listing
May 2021

Single-cell transcriptomics applied to emigrating cells from psoriasis elucidate pathogenic vs. regulatory immune cell subsets.

J Allergy Clin Immunol 2021 Apr 28. Epub 2021 Apr 28.

Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA. Electronic address:

Background: Inflammatory cells in previous human skin single-cell data constituted only a small fraction of the overall cell population, such that functional subsets were difficult to ascertain.

Objective: Our aims were to overcome the limitation by applying single-cell transcriptomics to emigrating cells from skin and elucidate ex vivo gene expression profiles of pathogenic vs. regulatory immune cell subsets in psoriasis skin.

Methods: We harvested emigrating cells from human psoriasis skin after incubation in culture medium without enzyme digestion or cell sorting and analyzed cells with single-cell RNA sequencing and flow cytometry simultaneously.

Results: Unsupervised clustering of harvested cells from psoriasis and control skin identified NK cells, T-cell subsets, dendritic cell subsets, melanocytes, and keratinocytes in different layers. Comparison between psoriasis vs. control cells within each cluster identified: 1) Cutaneous Type 17 T-cells display highly differing transcriptome profiles depending on IL-17A vs. IL-17F expression and IFNγ vs. IL-10 expression, 2) Semimature dendritic cells are regulatory dendritic cells with high IL-10 expression but a subset of semimature dendritic cells expresses IL-23A and IL-36G in psoriasis, and 3) CCL27-CCR10 interaction is potentially impaired in psoriasis due to decreased CCL27 expression in basal keratinocytes.

Conclusion: We propose that single-cell transcriptomics applied to emigrating cells from human skin provide an innovative study platform to compare gene expression profiles of heterogenous immune cells in various inflammatory skin diseases.
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http://dx.doi.org/10.1016/j.jaci.2021.04.021DOI Listing
April 2021

Mapping atopic dermatitis and anti-IL-22 response signatures to Type 2-low severe neutrophilic asthma.

J Allergy Clin Immunol 2021 Apr 20. Epub 2021 Apr 20.

Clinical and Experimental Sciences and Human Development in Health, University of Southampton Faculty of Medicine, Southampton; NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton; and David Hide Asthma and Allergy Research Centre, St Mary's Hospital, Newport, Isle of Wight. UK.

Background: Transcriptomic changes in patients who respond clinically to biological therapies may identify responses in other tissues or diseases.

Objective: To determine whether a disease signature identified in atopic dermatitis (AD) is seen in adults with severe asthma (SA) and whether a transcriptomic signature for AD patients who respond clinically to anti-IL-22 (Fezakinumab, FZ) is enriched in SA.

Methods: An AD disease signature was obtained from analysis of differentially expressed genes (DEGs) between AD lesional and non-lesional skin biopsies. DEGs from lesional skin from therapeutic super-responders before and after 12 weeks FZ treatment defined the FZ-response signature. Gene Set Variation Analysis (GSVA) was used to produce enrichment scores (ES) of AD and FZ-response signatures in the U-BIOPRED asthma cohort.

Results: The AD disease signature (112 up-regulated genes) encompassing inflammatory, T-cell, Th2 and Th17/Th22 pathways was enriched in the blood and sputum of asthmatics with increasing severity. Asthmatics with sputum neutrophilia and mixed granulocyte phenotypes were the most enriched (p<0.05). The FZ-response signature (296 down-regulated genes) was enriched in asthmatic blood (p<0.05) and particularly in neutrophilic and mixed granulocytic sputum (p<0.05). These data were confirmed in sputum of the ADEPT (Airway Disease Endotyping for Personalized Therapeutics) cohort. IL-22 mRNA across tissues did not correlate with FZ-response ES, but this response signature correlated with Th22/IL-22 pathways.

Conclusions: The FZ-response signature in AD identifies severe neutrophilic asthmatics as potential responders to FZ therapy. This approach will help identify patients for future asthma clinical trials of drugs used successfully in other chronic diseases.
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http://dx.doi.org/10.1016/j.jaci.2021.04.010DOI Listing
April 2021

A plea for standardization of confocal microscopy and optical coherence tomography parameters to evaluate physiological and para-physiological skin conditions in cosmetic science.

Exp Dermatol 2021 Apr 21. Epub 2021 Apr 21.

Dermatology Unit, University of Modena and Reggio Emilia, Modena, Italy.

Background: Non-invasive Reflectance Confocal Microscopy (RCM) and Optical Coherence Tomography (OCT) have been extended to the dermo-cosmetic field, for skin pathophysiology understanding and therapeutics monitoring. However, standardized methodology and parameters to interpret structures and changes in these settings are still lacking.

Objective: to propose a validated standard methodology and a list of defined parameters for objective non-pathological skin assessments in the cosmetically sensitive cheekbone area of the face.

Methods: OCT and RCM quantitative, semi-quantitative, and qualitative features were considered for assessments. Validation process included 50 sets of images divided into 2 age groups. Inter-rater reliability was explored to assess the influence of the proposed methodology.

Results: Quantitative OCT parameters of "epidermal thickness", "density and attenuation coefficients" and "vascular density" were considered and calculated. Severity scales were developed for semi-quantitative OCT features of "disruption of collagen" and "vascular asset", while extent-scales were produced for semi-quantitative RCM "irregular honeycomb", "mottled pigmentation" and "polycyclic papillary contours". Qualitative assessment was obtained for RCM type of collagen and comparison between age-groups was performed for all features considered. Severity visual scales assistance proved excellent inter-rater agreement across all semi-quantitative and qualitative domains.

Conclusions: The assistance of shareable software systems allows for objective OCT quantitative parameters measurement. The use of standard reference scales, within a defined assessment methodology, offers high inter-rater reliability, and thus reproducibility for semi-quantitative and qualitative OCT and RCM parameters. Taken together, our results may represent a starting point for a standardized application of RCM and OCT in dermo-cosmetic research and practice.
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http://dx.doi.org/10.1111/exd.14359DOI Listing
April 2021

Vascular inflammation in moderate-to-severe atopic dermatitis is associated with enhanced Th2 response.

Allergy 2021 Apr 18. Epub 2021 Apr 18.

Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: In atopic dermatitis (AD), some studies have shown an association with increased cardiovascular disease in certain populations. However, other investigations found modest or no association. Despite conflicting results, molecular profiling studies in both AD skin and blood have demonstrated upregulation of atherosclerosis and cardiovascular risk-related markers. However, the underlying mechanisms connecting AD to vascular inflammation/atherosclerosis are unknown. In this study, we aim to determine factors associated with vascular inflammation/atherosclerosis in AD patients.

Methods: We used 18-FDG PET-CT to characterize vascular inflammation in AD patients and healthy subjects. In parallel, we assessed their skin and blood immune profiles to determine AD-related immune biomarkers associated with vascular inflammation. We also assessed levels of circulating microparticles, which are known to be associated with increased cardiovascular risk.

Results: We found significant correlations between vascular inflammation and Th2-related products in skin and blood of AD patients as well as atherosclerosis-related markers that were modulated by dupilumab. Circulating levels of endothelial microparticles were significantly higher in severe AD patients and tended to correlate with vascular inflammation assessed by PET-CT.

Conclusion: Vascular inflammation in AD is associated with enhanced Th2 response and clinical severity, which may explain cardiovascular comorbidities observed in select AD populations. Larger prospective studies are needed to further evaluate vascular inflammation and cardiovascular events and mortality in AD patients. Finally, as dupilumab treatment demonstrated significant modulation of atherosclerosis-related genes in AD patients compared to placebo, these data suggest that modulation of vascular inflammation with systemic treatment should be explored in patients with AD.
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http://dx.doi.org/10.1111/all.14859DOI Listing
April 2021

Emerging Systemic Therapeutic Biologics and Small Molecules for Atopic Dermatitis: How to Decide Which Treatment Is Right for Your Patients.

J Allergy Clin Immunol Pract 2021 Apr;9(4):1449-1460

Department of Dermatology, Oregon Health & Science University, Portland, OR. Electronic address:

The evolving discoveries in atopic dermatitis (AD) broaden our understanding of the pathogenesis of the disease and, above all, enable better management for patients. Dupilumab was the first biologic for AD, and since its approval, many new treatments have emerged in both late- and early-stage clinical trials. These trials have led to a further understanding of the pathogenesis of AD and to the identification of additional potential therapeutic targets. This review will highlight the emerging therapies and provide approaches on how to choose the right treatment for your patients.
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http://dx.doi.org/10.1016/j.jaip.2021.02.003DOI Listing
April 2021

High-dimensional analysis defines multicytokine T-cell subsets and supports a role for IL-21 in atopic dermatitis.

Allergy 2021 Apr 5. Epub 2021 Apr 5.

Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: Flow cytometry is a well-accepted approach for immune profiling; however, its value is restricted by the limited number of markers that can be analyzed simultaneously. Mass cytometry/CyTOF offers broad-scale immune characterization integrating large number of parameters. While partial blood phenotyping was reported in atopic dermatitis (AD), patients' comprehensive profiling, critical for leveraging new targeted treatments, is not available. IL-21 may be involved in inflammatory skin diseases but its role in AD is not well established.

Methods: We studied T-cell polarization in the blood of 20 moderate-to-severe AD and 15 controls. Using CyTOF and an unsupervised analysis, we measured the frequencies and mean metal intensities of activated polar CD4 /CD8 T-cell subsets. Immunohistochemistry, immunofluorescence, and qRT-PCR were used to analyze skin samples.

Results: Examining 24 surface, intracellular markers, and transcription factors, we identified six CD4 and five CD8 T-cell metaclusters. A CD4 skin-homing IL-13 monocytokine and a novel IL-13 IL-21 multicytokine metaclusters were increased in AD vs. controls (p < .01). While IL-13 signature characterized both clusters, levels were significantly higher in the IL-21 group. Both clusters correlated with AD severity (r = 0.49, p = .029). Manual gating corroborated these results and identified additional multicytokine subsets in AD. Immunohistochemistry and immunofluorescence, validated by mRNA expression, displayed significantly increasedIL-21 counts and colocalization with IL-13/IL-4R in AD skin.

Conclusion: A multicytokine signature characterizes moderate-to-severe AD, possibly explaining partial therapeutic responses to one cytokine targeting, particularly in severe patients. Prominent IL-21 signature in blood and skin hints for a potential pathogenic role of IL-21 in AD.
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http://dx.doi.org/10.1111/all.14845DOI Listing
April 2021

A phase 2a randomized, placebo-controlled study to evaluate the efficacy and safety of the oral Janus kinase inhibitors ritlecitinib and brepocitinib in alopecia areata: 24-week results.

J Am Acad Dermatol 2021 Mar 20. Epub 2021 Mar 20.

Pfizer, Cambridge, Massachusetts.

Background: Alopecia areata (AA) is an autoimmune form of hair loss with limited treatments.

Objective: To evaluate the efficacy and safety of the Janus kinase inhibitors ritlecitinib and brepocitinib in patients who have AA with ≥ 50% scalp hair loss.

Methods: Patients were randomized to once-daily ritlecitinib, brepocitinib, or placebo. The primary efficacy endpoint was a 24-week change from baseline in the Severity of Alopecia Tool (SALT) score. The key secondary efficacy endpoint was the proportion of patients achieving 30% improvement in SALT score (SALT).

Results: The ritlecitinib, brepocitinib, and placebo groups included 48, 47, and 47 patients, respectively. At week 24, least-squares mean difference from placebo in SALT score change from baseline was 31.1 (95% confidence interval [CI], 18.8-43.5) for ritlecitinib and 49.2 (95% CI, 36.6-61.7) for brepocitinib (P < .0001 for both comparisons with placebo). SALT was achieved by 50% (90% CI, 38%-62%) of patients receiving ritlecitinib, 64% (90% CI, 51%-75%) receiving brepocitinib, and 2% (90% CI, 0%-9%) receiving placebo. Two patients experienced a serious adverse event (rhabdomyolysis) in the brepocitinib group only.

Limitations: Only a single-dosage regimen of each study drug was included.

Conclusion: Treatment with ritlecitinib or brepocitinib for 24 weeks was efficacious and generally well tolerated.
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http://dx.doi.org/10.1016/j.jaad.2021.03.050DOI Listing
March 2021

An integrated scalp and blood biomarker approach suggeststhe systemic nature of alopecia areata.

Allergy 2021 Mar 15. Epub 2021 Mar 15.

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

Background: Alopecia areata (AA) is characterized by immunedysregulation in both scalp and blood, but a largescale approach establishing biomarkersof AA incorporating both scalp tissue and serum compartments is lacking. We aimed to characterize thetranscriptomicsignature of AA lesional and nonlesional scalp compared to healthy scalp and determine its relationship with the blood proteome in the same individuals, with comparative correlations to clinical AA disease severity.

Methods: We evaluated lesional and nonlesional scalp tissues and serum from patients with moderate-to-severe AA (n=18) and healthy individuals (n=8). We assessed 33,118 genes in AA scalp tissue using RNAseq transcriptomic evaluation and 340 inflammatory proteins in serum using OLINK high-throughput proteomics. Univariate and multivariate approaches were used to correlate disease biomarkers with Severity of Alopecia Tool (SALT).

Results: 608 inflammatory genes were differentially expressed in lesional AA scalp (fold change/FCH>1.5, false-discovery-rate/FDR<0.05) including Th1 (IFNG/IL12B/CXCL11), Th2 (IL13/CCL18), and T-cell activation-related (ICOS) products. Th1/Th2-related markers were significantly correlated with AA clinical severity in lesional/nonlesional tissue, while keratins (KRT35/KRT83/KRT81) were significantly downregulated in lesional compared to healthy scalp(P<0.05). Expression of cardiovascular/atherosclerosis-related markers (MMP9/CCL2/IL1RL1/IL33R/ST2/AGER) in lesional scalp correlated with their corresponding serum expression (P<0.05). AA scalp demonstrated significantly greater biomarker dysregulationcompared to blood. An integrated multivariateapproach combining scalp and serum biomarkers improved correlations with disease severity/SALT.

Conclusion: This study contributes a unique understanding of the phenotype of moderate-to-severe AA with an integrated scalp and serum biomarker model suggesting the systemic nature of the disease, advocating for the need for immune-based systemic treatment.
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http://dx.doi.org/10.1111/all.14814DOI Listing
March 2021

Biologics for Treatment of Atopic Dermatitis: Current Status and Future Prospect.

J Allergy Clin Immunol Pract 2021 Mar;9(3):1053-1065

Department of Allergy and Immunology, Boston Children's Hospital, Boston, Mass; Department of Pediatrics, Harvard Medical School, Boston, Mass. Electronic address:

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by intense pruritus and recurrent eczematous lesions that significantly impair quality of life. It is a heterogeneous disease affecting both children and adults. The treatment of moderate-to-severe forms of AD is challenging, as topical corticosteroids are often insufficient to achieve disease control or inappropriate and off-label use of immunosuppressants may have significant undesirable side effects. The development of targeted biologic therapies specifically for AD is thus highly desirable. Dupilumab is the only biologic therapy that is Food and Drug Administration approved for the treatment of moderate-to-severe AD in patients 6 years and older, with consistent long-term efficacy and safety trial data. In this article, we review the mechanisms, safety, and efficacy of dupilumab from recent clinical trials, and we review the current data, mechanism of action, clinical efficacy, and limitations of new biologics currently in phase 2 and 3 clinical trials (lebrikizumab, tralokinumab, nemolizumab, tezepelumab, and ISB 830).
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http://dx.doi.org/10.1016/j.jaip.2020.11.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7951162PMC
March 2021

IL-36 and IL-17A Cooperatively Induce a Psoriasis-Like Gene Expression Response in Human Keratinocytes.

J Invest Dermatol 2021 Mar 3. Epub 2021 Mar 3.

Laboratory of Investigative Dermatology, The Rockefeller University, New York, New York, USA. Electronic address:

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http://dx.doi.org/10.1016/j.jid.2021.01.019DOI Listing
March 2021

Baricitinib in patients with moderate-to-severe atopic dermatitis: Results from a randomized monotherapy phase 3 trial in the United States and Canada (BREEZE-AD5).

J Am Acad Dermatol 2021 Feb 16. Epub 2021 Feb 16.

K Papp Clinical Research and Probity Medical Research, Waterloo, Ontario, Canada.

Background: Baricitinib, an oral selective Janus kinase 1/Janus kinase 2 inhibitor, is being studied for moderate-to-severe atopic dermatitis (AD) in adults.

Objective: To evaluate the efficacy and safety of baricitinib monotherapy in a North American phase 3 trial (BREEZE-AD5/NCT03435081) of adults with moderate-to-severe AD who responded inadequately or were intolerant to topical therapy.

Methods: Patients (N = 440) were randomized 1:1:1 to once-daily placebo or baricitinib (1 mg or 2 mg). The primary endpoint was the proportion of patients achieving ≥75% reduction in the Eczema Area and Severity Index at week 16. A key secondary endpoint was the proportion of patients achieving a validated Investigator Global Assessment for AD score of 0 (clear)/1(almost clear) with ≥2-point improvement.

Results: At week 16, the proportion of patients achieving Eczema Area and Severity Index was 8%, 13%, and 30% (P < .001, 2 mg vs placebo) and those with a validated Investigator Global Assessment for AD score of 0/1 were 5%, 13%, and 24% (P < .001, 2 mg vs placebo) for placebo, baricitinib 1 mg, and baricitinib 2 mg, respectively. Safety findings were similar to those of other baricitinib AD studies.

Limitations: Short-term clinical trial results may not be generalizable to real-world settings.

Conclusion: Baricitinib was efficacious for patients with moderate-to-severe AD with no new safety findings over 16 weeks.
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http://dx.doi.org/10.1016/j.jaad.2021.02.028DOI Listing
February 2021

Whole genome sequencing identifies novel genetic mutations in patients with eczema herpeticum.

Allergy 2021 Feb 6. Epub 2021 Feb 6.

Division of Allergy and Clinical Immunology, Johns Hopkins University, Baltimore, MD, USA.

Background: Eczema herpeticum (EH) is a rare complication of atopic dermatitis (AD) caused by disseminated herpes simplex virus (HSV) infection. The role of rare and/or deleterious genetic variants in disease etiology is largely unknown. This study aimed to identify genes that harbor damaging genetic variants associated with HSV infection in AD with a history of recurrent eczema herpeticum (ADEH+).

Methods: Whole genome sequencing (WGS) was performed on 49 recurrent ADEH+ (≥3 EH episodes), 491 AD without a history of eczema herpeticum (ADEH-) and 237 non-atopic control (NA) subjects. Variants were annotated, and a gene-based approach (SKAT-O) was used to identify genes harboring damaging genetic variants associated with ADEH+. Genes identified through WGS were studied for effects on HSV responses and keratinocyte differentiation.

Results: Eight genes were identified in the comparison of recurrent ADEH+to ADEH-and NA subjects: SIDT2, CLEC7A, GSTZ1, TPSG1, SP110, RBBP8NL, TRIM15, and FRMD3. Silencing SIDT2 and RBBP8NL in normal human primary keratinocytes (NHPKs) led to significantly increased HSV-1 replication. SIDT2-silenced NHPKs had decreased gene expression of IFNk and IL1b in response to HSV-1 infection. RBBP8NL-silenced NHPKs had decreased gene expression of IFNk, but increased IL1b. Additionally, silencing SIDT2 and RBBP8NL also inhibited gene expression of keratinocyte differentiation markers keratin 10 (KRT10) and loricrin (LOR).

Conclusion: SIDT2 and RBBP8NL participate in keratinocyte's response to HSV-1 infection. SIDT2 and RBBP8NL also regulate expression of keratinocyte differentiation genes of KRT10 and LOR.
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http://dx.doi.org/10.1111/all.14762DOI Listing
February 2021

EAACI Biologicals Guidelines-dupilumab for children and adults with moderate-to-severe atopic dermatitis.

Allergy 2021 04 27;76(4):988-1009. Epub 2020 Dec 27.

Department of Clinical Immunology, University of Wroclaw, Wroclaw, Poland.

Atopic dermatitis imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity, co-morbidities, complexity in care pathways and differences between national or regional healthcare systems. Better understanding of the mechanisms has enabled a stratified approach to the management of atopic dermatitis, supporting the use of targeted treatments with biologicals. However, there are still many issues that require further clarification. These include the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home-based), its cost-effectiveness and long-term safety. The EAACI Guidelines on the use of dupilumab in atopic dermatitis follow the GRADE approach in formulating recommendations for each outcome and age group. In addition, future approaches and research priorities are discussed.
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http://dx.doi.org/10.1111/all.14690DOI Listing
April 2021

Biomarkers in atopic dermatitis-a review on behalf of the International Eczema Council.

J Allergy Clin Immunol 2021 Apr 28;147(4):1174-1190.e1. Epub 2021 Jan 28.

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

Atopic dermatitis (AD) is a common yet complex skin disease, posing a therapeutic challenge with increasingly recognized different phenotypes among variable patient populations. Because therapeutic response may vary on the basis of heterogeneous clinical and molecular phenotypes, a shift toward precision medicine approaches may improve AD management. Herein, we will consider biomarkers as potential instruments in the toolbox of precision medicine in AD and will review the process of biomarker development and validation, the opinion of AD experts on the use of biomarkers, types of biomarkers, encompassing biomarkers that may improve AD diagnosis, biomarkers reflecting disease severity, and those potentially predicting AD development, concomitant atopic diseases, or therapeutic response, and current practice of biomarkers in AD. We found that chemokine C-C motif ligand 17/thymus and activation-regulated chemokine, a chemoattractant of T2 cells, has currently the greatest evidence for robust correlation with AD clinical severity, at both baseline and during therapy, by using the recommendations, assessment, development, and evaluation approach. Although the potential of biomarkers in AD is yet to be fully elucidated, due to the complexity of the disease, a comprehensive approach taking into account both clinical and reliable, AD-specific biomarker evaluations would further facilitate AD research and improve patient management.
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http://dx.doi.org/10.1016/j.jaci.2021.01.013DOI Listing
April 2021

Conjunctivitis in Dupilumab Clinical Trials for Adolescents with Atopic Dermatitis or Asthma.

Am J Clin Dermatol 2021 Jan;22(1):101-115

Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.

Background: Conjunctivitis is a known comorbidity of atopic dermatitis. Dupilumab clinical trials for moderate-to-severe atopic dermatitis in adults showed a higher conjunctivitis incidence for dupilumab-treated patients than placebo-treated patients, whereas trials for uncontrolled asthma reported lower rates for both dupilumab and placebo.

Objective: The objective of this study was to evaluate the incidence and severity of conjunctivitis in dupilumab clinical trials in adolescents with moderate-to-severe atopic dermatitis or uncontrolled asthma.

Methods: We evaluated the incidence of conjunctivitis in adolescents (aged 12 to < 18 years) in three phase III trials. Ocular events were diagnosed and treated based on patient-reported symptoms and an external eye examination by study investigators, in most cases without an ophthalmologic referral. In LIBERTY AD ADOL (16-week, randomized, placebo-controlled, double-blinded trial), adolescents with moderate-to-severe atopic dermatitis were randomized to subcutaneous placebo, dupilumab 300 mg every 4 weeks, or dupilumab every 2 weeks (200 mg, patients < 60 kg at baseline; 300 mg, ≥ 60 kg at baseline). In LIBERTY AD PED-OLE (open-label extension), pediatric patients from previous dupilumab atopic dermatitis trials received dupilumab 2 mg/kg or 4 mg/kg weekly (up to 300 mg) or 300 mg every 4 weeks. In LIBERTY ASTHMA QUEST (randomized, double-blinded, placebo-controlled trial), patients with uncontrolled moderate-to-severe asthma were randomized to 52 weeks of add-on therapy with dupilumab 200 or 300 mg every 2 weeks or matched-volume placebo.

Results: In ADOL, more dupilumab-treated (17/165; 10.3%) than placebo-treated patients (4/85; 4.7%) reported one or more conjunctivitis event. All events were mild to moderate in severity; 12 (7.3%) dupilumab-treated and 4 (4.7%) placebo-treated patients received treatment. Most patients with conjunctivitis (dupilumab, 12/17; placebo, 4/4) recovered/resolved during the treatment period. The risk of conjunctivitis showed no relationship with dupilumab serum concentration. In PED-OLE, 12/275 adolescents (4.4%) reported one or more conjunctivitis event. Most conjunctivitis events were mild to moderate. Ten patients received treatment for conjunctivitis. Ten patients recovered/resolved during the study. In QUEST, similar low proportions of dupilumab-treated (2/68, 2.9%) and placebo-treated (1/39, 2.6%) adolescents reported one or more conjunctivitis event. All events were mild to moderate. One dupilumab-treated patient received treatment for conjunctivitis. All cases recovered/resolved during the study. No patients in these trials discontinued study treatment temporarily or permanently because of conjunctivitis. In ADOL, one case of unspecified viral keratitis (specific viral etiology not known) in the dupilumab 300-mg every 4 weeks group and one case of allergic blepharitis in the placebo group were reported; both events resolved during the treatment period, and neither led to treatment discontinuation.

Conclusions: Dupilumab-treated adolescents in atopic dermatitis trials had a higher incidence of conjunctivitis than placebo-treated patients, whereas overall rates of conjunctivitis among adolescents in the asthma trial were lower than in atopic dermatitis trials and were similar for dupilumab- and placebo-treated patients. Most events were mild to moderate, most recovered/resolved, and none prompted study withdrawal. These results are similar to those reported in adult trials and support a drug-disease interaction. CLINICALTRIALS.

Gov Identifiers: NCT03054428, NCT02612454, NCT02414854. Conjunctivitis in Dupilumab Clinical Trials for Adolescents with Atopic Dermatitis or Asthma (MP4 18453 kb).
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http://dx.doi.org/10.1007/s40257-020-00577-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847457PMC
January 2021

Dupilumab Improves Asthma and Sinonasal Outcomes in Adults with Moderate to Severe Atopic Dermatitis.

J Allergy Clin Immunol Pract 2021 Mar 13;9(3):1212-1223.e6. Epub 2021 Jan 13.

Regeneron Pharmaceuticals, Inc, Tarrytown, NY.

Background: Dupilumab has demonstrated efficacy with acceptable safety in clinical trials in patients with moderate to severe atopic dermatitis (AD).

Objective: To assess dupilumab's impact on asthma and sinonasal conditions in adult patients with moderate to severe AD in four randomized, double-blinded, placebo-controlled trials.

Methods: In LIBERTY AD SOLO 1 (NCT02277743), SOLO 2 (NCT02755649), CHRONOS (NCT02260986), and CAFÉ (NCT02755649), patients received placebo, dupilumab 300 mg every 2 weeks (q2w), or dupilumab 300 mg weekly (qw). In CHRONOS and CAFÉ, patients received concomitant topical corticosteroids. This post hoc analysis assessed Asthma Control Questionnaire-5 (ACQ-5) scores in patients with asthma, Sino-Nasal Outcome Test-22 (SNOT-22) scores in patients with sinonasal conditions, and AD signs and symptoms in all patients.

Results: Of the 2444 patients, 463 had asthma with baseline ACQ-5 ≥ 0.5 (19%); 1171 had sinonasal conditions (48%); and 311 had both (13%). At week 16, ACQ-5 scores (least squares mean change from baseline [standard error]) improved by 0.27 (0.07), 0.59 (0.08), and 0.56 (0.07) in placebo-, q2w-, and qw-treated patients with asthma, respectively, whereas SNOT-22 scores improved by 5.1 (0.8), 9.9 (0.9), and 10.8 (0.8) in patients with sinonasal conditions (P < .01 for all dupilumab vs placebo). Improvements in ACQ-5 and SNOT-22 were also seen in patients with both conditions. Dupilumab also significantly improved AD signs and symptoms among all subgroups.

Conclusions: In this first analysis of patients with comorbid moderate to severe AD, asthma, and/or chronic sinonasal conditions, dupilumab improved all three diseases in a clinically meaningful and statistically significant manner (vs placebo), based on validated outcome measures.
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http://dx.doi.org/10.1016/j.jaip.2020.12.059DOI Listing
March 2021

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

Drugs for the Treatment of Chronic Hand Eczema: Successes and Key Challenges.

Ther Clin Risk Manag 2020 31;16:1319-1332. Epub 2020 Dec 31.

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

Chronic hand eczema (CHE) is a common and burdensome inflammatory skin condition seen in up to 10% of the population, more often in high-risk occupational workers. Topical therapeutics comprise the standard of care, but up to 65% of cases do not resolve after treatment, and moderate-to-severe cases are often resistant to topical therapeutics and require systemic options instead. To date, there are no systemic therapeutics approved to treat CHE in the United States, but several drugs are under investigation as potential treatments for CHE. The primary focus of this review is on the novel therapeutics, topical and systemic, that are under investigation in recently completed or currently ongoing trials. This review also briefly outlines the existing treatments utilized for CHE, often with limited success or extensive adverse effects. CHE represents a major challenge for physicians and patients alike, and efforts to improve the minimally invasive diagnostic tools and treatment paradigms are ongoing. In the near future, CHE patients may benefit from new topical and systemic therapeutics that specifically target abnormally expressed immune markers.
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http://dx.doi.org/10.2147/TCRM.S292504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780849PMC
December 2020

Health-related quality of life with tralokinumab in moderate-to-severe atopic dermatitis: A phase 2b randomized study.

Ann Allergy Asthma Immunol 2021 05 15;126(5):576-583.e4. Epub 2020 Dec 15.

Department of Dermatology and Allergy, Ludwig Maximilian University, Munich, Germany.

Background: Atopic dermatitis (AD) is associated with a substantial burden on quality of life (QoL).

Objective: To evaluate the effects of tralokinumab on health-related QoL in patients with moderate-to-severe AD using patient-reported outcomes.

Methods: This was a phase 2b, randomized, double-blind, placebo-controlled, dose-ranging study in adults with moderate-to-severe AD. The patients received subcutaneous tralokinumab or placebo (1:1:1:1) every 2 weeks for 12 weeks and class 3 topical corticosteroid cream or ointment at least once daily from the run-in to end of follow-up. Patient-reported outcome end points were change from baseline to week 12 in the Dermatology Life Quality Index (dermatology life quality index (DLQI); prespecified secondary objective), the Short Form 36 Health Survey (SF-36) version 2, and sleep interference numeric rating scale score (prespecified exploratory objectives).

Results: A total of 204 patients were randomized to placebo (n = 51) or tralokinumab (45 mg, n = 50; 150 mg, n = 51; 300 mg, n = 52). Tralokinumab 300 mg every 2 weeks improved total Dermatology Life Quality Index vs placebo at week 12 (placebo-adjusted mean change, -3.51 [95% confidence interval, -6.00 to -1.02]). At week 12, both the mental component summary (4.23 [0.98-7.47]) and the physical component summary (4.26 [1.83-6.69]) and all 8 domains of the Short Form 36 Health Survey were improved in patients treated with tralokinumab 300 mg vs placebo. Sleep interference was improved at week 12 with all tralokinumab doses vs placebo.

Conclusion: Tralokinumab improved health-related QoL in patients with moderate-to-severe atopic dermatitis, providing further evidence of the value of targeting interleukin-13 in such patients.

Trial Registration: ClinicalTrials.gov identifier: NCT02347176; https://clinicaltrials.gov/ct2/show/NCT02347176.
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http://dx.doi.org/10.1016/j.anai.2020.12.004DOI Listing
May 2021

RNA Sequencing Keloid Transcriptome Associates Keloids With Th2, Th1, Th17/Th22, and JAK3-Skewing.

Front Immunol 2020 23;11:597741. Epub 2020 Nov 23.

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

Keloids are disfiguring, fibroproliferative growths and their pathogenesis remains unclear, inhibiting therapeutic development. Available treatment options have limited efficacy and harbor safety concerns. Thus, there is a great need to clarify keloid pathomechanisms that may lead to novel treatments. In this study, we aimed to elucidate the profile of lesional and non-lesional keloid skin compared to normal skin. We performed gene (RNAseq, qRT-PCR) and protein (immunohistochemistry) expression analyses on biopsy specimens obtained from lesional and non-lesional skin of African American (AA) keloid patients compared to healthy skin from AA controls. Fold-change≥2 and false-discovery rate (FDR)<0.05 was used to define significance. We found that lesional versus normal skin showed significant up-regulation of markers of T-cell activation/migration (ICOS, CCR7), Th2- (IL-4R, CCL11, TNFSF4/OX40L), Th1- (CXCL9/CXCL10/CXCL11), Th17/Th22- (CCL20, S100As) pathways, and JAK/STAT-signaling (JAK3) (false-discovery rate [FDR]<0.05). Non-lesional skin also exhibited similar trends. We observed increased cellular infiltrates in keloid tissues, including T-cells, dendritic cells, mast cells, as well as greater IL-4rα, CCR9, and periostin immunostaining. In sum, comprehensive molecular profiling demonstrated that both lesional and non-lesional skin show significant immune alternations, and particularly Th2 and JAK3 expression. This advocates for the investigation of novel treatments targeting the Th2 axis and/or JAK/STAT-signaling in keloid patients.
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http://dx.doi.org/10.3389/fimmu.2020.597741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719808PMC
November 2020

The role of circulating eosinophils on COVID-19 mortality varies by race/ethnicity.

Allergy 2021 03 26;76(3):925-927. Epub 2020 Dec 26.

Division of Clinical Immunology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

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http://dx.doi.org/10.1111/all.14708DOI Listing
March 2021

International observational atopic dermatitis cohort to follow natural history and treatment course: TARGET-DERM AD study design and rationale.

BMJ Open 2020 11 27;10(11):e039928. Epub 2020 Nov 27.

Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Introduction: As new topical and systemic treatments become available for atopic dermatitis (AD), there is a need to understand how treatments are being used in routine clinical practice, their comparative effectiveness and their long-term safety in diverse clinical settings.

Methods And Analysis: The TARGET-DERM AD cohort is a longitudinal, observational study of patients with AD of all ages, designed to provide practical information on long-term effectiveness and safety unobtainable in traditional registration trials. Patients with physician-diagnosed AD receiving prescription treatment (topical or systemic) will be enrolled at academic and community clinical centres. Up to 3 years of retrospective medical records, 5 years of prospective medical records, and optional biological samples and patient-reported outcomes will be collected. The primary aims include characterisation of AD treatment regimens, evaluation of response to therapy, and description of adverse events.

Ethics And Dissemination: TARGET-DERM has been approved by a central IRB (Copernicus Group IRB, 5000 Centregreen Way Suite 200, Cary, North Carolina 27513) as well as local and institutional IRBs. No additional Ethics Committee reviews. Results will be reviewed by a publications committee and submitted to peer-reviewed journals.

Trial Registration Number: NCT03661866, pre-results.
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http://dx.doi.org/10.1136/bmjopen-2020-039928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703415PMC
November 2020

Dupilumab Significantly Modulates Pain and Discomfort in Patients With Atopic Dermatitis: A Post Hoc Analysis of 5 Randomized Clinical Trials.

Dermatitis 2020 Nov 5. Epub 2020 Nov 5.

Regeneron Pharmaceuticals, Tarrytown, NY.

Background: Pain is a frequent symptom of atopic dermatitis (AD).

Objectives: The aims of the study were to evaluate the effects of dupilumab on pain/discomfort in AD and to determine whether pain correlates with other outcomes.

Methods: This was a post hoc analysis of 5 randomized, placebo-controlled clinical trials in which adults with chronic AD received placebo or dupilumab 300 mg every 2 weeks or once weekly with and without topical corticosteroids. Proportions of patients with no pain/discomfort on this dimension of the 5-dimension EuroQoL (EQ-5D) at week 16 (all trials) and week 52 (CHRONOS) were compared between placebo and dupilumab. Correlations were evaluated between pain/discomfort and signs and symptoms of AD.

Results: Among 2632 evaluated patients, 72.9% to 83.1% reported at least moderate pain/discomfort at baseline. Higher proportions treated with dupilumab reported no pain/discomfort at week 16 relative to placebo; risk differences ranged from 22.3% (95% confidence interval = 11.5%-33.1%) to 42.2% (95% confidence interval = 26.6%-57.8%, all P ≤ 0.0001), with similar effects observed at week 52. Correlations at baseline of pain/discomfort with signs and symptoms of AD were low to moderate.

Conclusions: Pain/discomfort, present in a substantial proportion of patients with moderate-to-severe AD, was significantly reduced by dupilumab treatment. Given the low-to-moderate correlations with other AD symptoms at baseline, pain likely represents a distinct AD symptom.

Trial Registration: ClinicalTrials.gov identifiers NCT01859988, NCT02277743, NCT02277769, NCT02260986, and NCT02755649.
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http://dx.doi.org/10.1097/DER.0000000000000698DOI Listing
November 2020

The erythema Q-score, an imaging biomarker for redness in skin inflammation.

Exp Dermatol 2021 Mar 30;30(3):377-383. Epub 2020 Nov 30.

Laboratory of Investigative Dermatology, The Rockefeller University, New York, NY, USA.

Physician rating of cutaneous erythema is central to clinical dermatological assessment as well as quantification of outcome measures in clinical trials in a number of dermatologic conditions. However, issues with inter-rater reliability and variability in the setting of higher Fitzpatrick skin types make visual erythema assessment unreliable. We developed and validated a computer-assisted image-processing algorithm (EQscore) to reliably quantify erythema (across a range of skin types) in the dermatology clinical setting. Our image processing algorithm evaluated erythema based upon green light suppression differentials between affected and unaffected skin. A group of four dermatologists used a 4-point Likert scale as a human evaluation of similar erythematous patch tests. The algorithm and dermatologist scores were compared across 164 positive patch test reactions. The intra-class correlation coefficient of groups and the correlation coefficient between groups were calculated. The EQscore was validated on and independent image set of psoriasis, minimal erythema dose testing and steroid-induced blanching images. The reliability of the erythema quantification method produced an intra-class correlation coefficient of 0.84 for the algorithm and 0.67 for dermatologists. The correlation coefficient between groups was 0.85. The EQscore demonstrated high agreement with clinical scoring and superior reliability compared with clinical scoring, avoiding the pitfalls of erythema underrating in the setting of pigmentation. The EQscore is easily accessible (http://lab.rockefeller.edu/krueger/EQscore), user-friendly, and may allow dermatologists to more readily and accurately rate the severity of dermatological conditions and the response to therapeutic treatments.
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http://dx.doi.org/10.1111/exd.14224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049083PMC
March 2021

Alopecia Areata: A Complex Cytokine Driven Disease.

J Investig Dermatol Symp Proc 2020 11;20(1):S55-S57

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

Alopecia areata (AA) has been recently shown to also include T-helper cell type 2/IL-23 activation, in addition to T-helper cell type 1/IFN-skewing. The success of Jak inhibition together with IL-4Rα antagonism and limited response to IL-17A and PDE4 (protein) inhibition in AA are increasing our understanding of the complex immune interplay in AA. Trials testing targeted therapeutics are needed to further elucidate the pathogenic contribution of various cytokines.
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http://dx.doi.org/10.1016/j.jisp.2020.04.007DOI Listing
November 2020

Clinical Relevance of Skin Pain in Atopic Dermatitis.

J Drugs Dermatol 2020 10;19(10):921-926

Skin pain is increasingly recognized as an impactful symptom in atopic dermatitis (AD) because of its association with patient discomfort, disease burden, and reduced quality of life. Although the nature of skin pain in AD has not been systematically studied and is therefore not well understood, patients report soreness, discomfort, and tenderness that may reflect peripheral and central pain sensitization. The high prevalence of skin pain suggests that it is not adequately addressed by current therapies for AD and may be undertreated compared with other symptoms. This review discusses the clinical relevance of skin pain with respect to its experience, pathophysiology, relationship with itch, and treatment implications. Recent studies suggest that skin pain presents as a neuropathic symptom independent from itch and the “itch-scratch cycle”, and poses a unique burden to patients. Recognition of the significant consequences of skin pain and discomfort should reinforce the need to assess and treat this symptom in patients with moderate-to-severe AD. J Drugs Dermatol. 2020;19(10)921-926. doi:10.36849/JDD.2020.5498.
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http://dx.doi.org/10.36849/JDD.2020.5498DOI Listing
October 2020

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

J Allergy Clin Immunol 2021 Apr 1;147(4):1369-1380. 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
April 2021