The Burden of Melasma: Race, Ethnicity, and Comorbidities.

INTRODUCTION: In an effort to define the characteristics of populations affected by melasma, we utilized a large global health research network database from 108 health care organizations (TriNetx) to quantify the associations between race, ethnicity, and comorbidities. METHODS: We identified the cohort of all patients with melasma from the TriNetx database, and subsequently generated a control cohort. ICD-10 codes were used to identify the prevalence of various comorbidities associated with melasma. RESULTS: A total of 41,283 patients with melasma (93% female, mean [SD] age 48.8 [12.6] year) were identified. The most frequently associated risk factors included hypertension (25% of the melasma cohort) and hormonal contraception (24%). Rosacea (OR=5.1), atopic dermatitis (OR=3.3), lupus (OR=2.5), history of skin cancer (OR=2.5), history of internal malignancy (OR=2.1), and hormonal contraception use (OR=2.1) possessed the highest odds ratios for development of melasma (all P< 0.01). A statistically significant association was identified for melasma in Asian or Other/Unknown races (OR=2.0 and OR=1.7, P< 0.01), as well as Hispanic ethnicity (OR=1.3, P< 0.01). White, Black/African American, and Not Hispanic groups all revealed slightly lower odds (all 0.8, P< 0.01). CONCLUSION: This latest global update on the etiopathology of melasma further supports findings from prior epidemiologic study reporting preference in melanized phenotypes (Fitzpatrick skin type III-V), but less so in extreme skin types (I, II, VI). Increased associations with rosacea, atopic dermatitis, and history of cancer may emphasize the importance of treating concurrent inflammatory environments and the consideration of more frequent malignancy surveillance. J Drugs Dermatol. 2024;23(8):691-693.  doi:10.36849/JDD.8233.

Safety and Tolerance Evaluation of a Suncare Product in Ethnically Diverse Children With Atopic Dermatitis-Prone Skin

Atopic Dermatitis (AD) is a common chronic inflammatory skin condition, with high prevalence in children. Sun protection is important for children with eczema and AD-prone skin, yet many sunscreens can cause skin irritation due to their formulations. In this study, we evaluated the safety and tolerance of an SPF 50 sunscreen in ethnically diverse children with a history of AD over 4 weeks of product use. A total of 45 children from diverse racial/ethnic backgrounds, aged 3 to 12 years old with skin phototypes I-VI, plus a history of eczema and perceived sensitive skin completed the study. All participants applied sunscreen daily on the face and body, at least 15 minutes prior to sun exposure and as needed. After 4 weeks, evaluations were performed by a dermatologist and by participants for tolerability. Product performance questionnaires were also completed by parents/guardians of pediatric participants. After 4 weeks of sunscreen application, tolerability assessments of skin dryness, peeling, erythema, and edema were all absent in children participants. Parent/guardian evaluations of sunscreen tolerability for their child also revealed no perceived skin issues. These results were consistent with no adverse event being observed throughout the study. Parents/guardians reported that sunscreen application on children was smooth and even, with the absence of a white cast appearance on children with skin of color. We conclude from this study that this SPF 50 sunscreen is safe to use in ethnically diverse children with a history of AD and sensitive skin. J Drugs Dermatol. 2024;23(8):669-673.  doi:10.36849/JDD.8282.

Image Analysis of Xerosis and Atopic Dermatitis Following Prebiotic Skincare Regimen in Ethnically Diverse Patients.

Variations in the epidemiology, clinical presentation, and disease course in atopic dermatitis (AD) patients with Skin of Color (SOC) compared with white counterparts have been reported. In this study, we evaluated the capability of a new imaging device (SkinCam) in quantifying skin texture changes in diverse patients, presenting with AD or xerosis, after using a prebiotic skincare routine over 10 weeks.  A total of 39 subjects from diverse racial/ethnic backgrounds, aged 3 to 76 years old, with Fitzpatrick skin phototypes I to VI, presenting with mild AD and moderate to severe xerosis, were enrolled in the study. All subjects used a prebiotic cleanser on its own for 2 weeks, followed by a prebiotic moisturizer in conjunction for an additional 8 weeks. Standardized images of the subjects' legs were taken with SkinCam at several time points (baseline, week 2, and week 10), and analyzed for skin texture parameters. Our results demonstrate that both skin texture irregularity and skin color patterns significantly improve over time with a prebiotic skincare regimen in AD (n=12) and xerosis (n=24) subjects. Interestingly, image analyses showed more improvement over time in xerosis and AD SOC patients (n=18, Fitzpatrick IV-VI). Lastly, skin texture analyses from SkinCam imaging correlated with clinical assessments, showing significant improvement by prebiotic skincare regimen in all subjects by week 10. In summary, our results demonstrate that the SkinCam imaging device has the capability to effectively monitor skin texture parameters over time in both AD and xerosis patients with lightly and darkly pigmented skin. J Drugs Dermatol. 2024;23(7):557-563.  doi:10.36849/JDD.8371.

Special Considerations of Atopic Dermatitis in Skin of Color.

Atopic dermatitis (AD) is a chronic inflammatory skin condition with heterogeneous presentations and prevalence across different skin tones. In this chapter, AD is explored through the lens of racial and ethnic diversity, emphasizing the special considerations among patients with skin of color (SOC). Specific ethnic groups may exhibit unique AD phenotypes, and these differences pose unique diagnostic and management challenges, especially given the disproportionate impact of AD in African American and Asian populations due to environmental exposures and social factors (i.e., decreased access to healthcare resources). Addressing these social disparities, increasing representation in medical education and the clinical space, as well as ongoing research can help better serve this patient population.

A 1% colloidal oatmeal OTC cream is clinically effective for the management of mild to moderate atopic dermatitis in Black or African American children.

BACKGROUND: The efficacy and safety of an over-the-counter (OTC) 1% colloidal oatmeal cream versus a ceramide-based prescription barrier cream in children with mild-to-moderate atopic dermatitis (AD) were previously described. OBJECTIVES: Here, findings are reported for the Black/African American subgroup. METHODS: Patients were randomized to 1% oatmeal cream or prescription barrier cream twice daily or as needed for three weeks. Assessments included Eczema Area and Severity Index (EASI) scores, Investigator's Global Atopic Dermatitis Assessment (IGADA) scores, and patients'/caregivers' assessment of eczema signs and symptoms. RESULTS: Overall, 49 Black/African American children aged 2-15 years with mild/moderate AD were included. At week 3, mean (SD) changes from baseline in EASI scores were -2.4 (1.7) with 1% oatmeal cream and -2.1 (2.3) with barrier cream; improvements were observed from week 1. At week 3, mean (SD) changes from baseline in IGADA scores were -0.6 (0.7) and -0.7 (0.6), respectively. Improvements in subjective ratings of signs/symptoms of eczema were observed. Both study treatments were well tolerated. CONCLUSION: OTC 1% oatmeal cream was at least as effective and safe as prescription barrier cream in this population, providing a novel, fast-acting, and cost-effective option for the symptomatic treatment of mild-to-moderate AD in Black/African American children.

Efficacy and safety of crisaborole ointment in Chinese and Japanese patients aged ≥2 years with mild-to-moderate atopic dermatitis.

Atopic dermatitis is a chronic inflammatory skin disease with a significant impact on the overall wellbeing of patients and their families. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor approved for the treatment of mild-to-moderate atopic dermatitis in multiple countries. However, in the key pivotal trials, a low proportion of the overall patient population was Asian, therefore the safety and efficacy of crisaborole in the Asian population with atopic dermatitis remains unclear. CrisADe CLEAR was a multicenter, randomized, double-blind, vehicle-controlled, phase 3 study (NCT04360187) to assess the efficacy and safety of crisaborole ointment in Chinese and Japanese patients aged ≥2 years with mild-to-moderate atopic dermatitis involving ≥5% treatable body surface area. Patients were randomly assigned 2:1 to receive crisaborole or vehicle twice daily for 28 days. The primary endpoint was percentage change from baseline in the Eczema Area and Severity Index total score at day 29. Additional endpoints were improvement and success per Investigator's Static Global Assessment score at day 29 and change from baseline on the Peak Pruritus Numerical Rating Scale at week 4. Safety was assessed using rates of treatment emergent adverse events, serious adverse events, and clinically significant changes in vital signs and clinical laboratory parameters. Crisaborole-treated patients showed a significantly greater reduction versus vehicle in percentage change from baseline in Eczema Area and Severity Index total score at day 29 (P = 0.0002). Response rates for achievement of Investigator's Static Global Assessment improvement and success at day 29 were significantly higher for patients treated with crisaborole versus vehicle (P = 0.0124 and P = 0.0078, respectively). Crisaborole-treated patients showed a significantly greater reduction versus vehicle in change from baseline on the Peak Pruritus Numerical Rating Scale at week 4 (P = 0.0009). No new safety signals were identified. Treatment with crisaborole was effective and well tolerated in Chinese and Japanese patients with mild-to-moderate atopic dermatitis.

TLR4 polymorphisms as potential predictors of atopic dermatitis in Chinese Han children.

BACKGROUND: Toll-like receptor 4 (TLR4) is considered to be involved in the pathogenesis and progression of atopic dermatitis (AD). In the present study, we evaluated the relationship between TLR4 gene polymorphisms and the susceptibility or severity of AD among Chinese Han children. METHODS: A total of 132 AD patients and 100 healthy controls were enrolled in this study. Four single-nucleotide polymorphisms (rs19277914, rs11536891, rs7869402, and rs11536889) of the TLR4 gene were genotyped by multiplex PCR combined with next-generation sequencing. RESULTS: Our results showed that a significantly reduced risk for AD was associated with C allele [p = 0.008; odds ratio (OR) = 0.41, C vs. T], TC genotype (p = 0.022; OR = 0.41, TC vs. TT), and TC + CC genotype (p = 0.010; OR = 0.39, TC + CC vs. TT) of TLR4 rs11536891. The frequency of the haplotype GCCG (rs1927914-rs11536891-rs7869402-rs11536889) in AD patients was lower than that in the controls (p = 0.010; OR = 0.38). Moreover, the results indicated that a higher risk of severe AD was related to the T allele (p = 0.019; OR = 2.97, T vs. C) and the TC genotype (p = 0.021; OR = 3.34, TC vs. CC) of TLR4 rs7869402. A risk haplotype of TLR4 (GTTG) was found in severe AD patients (p = 0.010; OR = 5.26). CONCLUSIONS: Our data suggested that TLR4 rs11536891 polymorphism was associated with the susceptibility to AD in Chinese Han children. And TLR4 rs7869402 might confer the severity of pediatric AD patients.

Vitamin D, skin filaggrin, allergic sensitization, and race.

BACKGROUND: In addition to its involvement in both the innate and adaptive immune systems, vitamin D has been found to affect keratinocyte function and proliferation, suggesting a possible role for vitamin D in cutaneous allergic sensitization. OBJECTIVE: To explore the role of circulating vitamin D levels in allergic sensitization. METHODS: Serum 25-hydroxyvitamin D (25(OH)D) levels were measured in a subset of children (N = 323) enrolled in the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children cohort, a prospective early life cohort of children with atopic dermatitis. Allergic sensitization was determined using skin prick testing, and FLG expression in the keratinocytes was measured by quantitative polymerase chain reaction. Multiple Poisson regression was used to evaluate interaction effects between serum 25(OH)D levels and FLG expression with sensitization load as the outcome. RESULTS: Black participants had significantly lower mean levels of serum 25(OH)D compared with non-Black participants (29.3 vs 32.9 ng/mL; P < .001). FLG expression and sensitization load were negatively correlated in non-Black participants with 25(OH)D levels less than 27.2 ng/mL (Rho = -0.45; P = .02). No association between FLG expression and sensitization load was found in Black participants or participants with 25(OH)D levels greater than or equal to 27.2 ng/mL. Multiple Poisson regression models confirmed that 25(OH)D levels interact with FLG expression to affect sensitization load in non-Black participants. CONCLUSION: Despite lower vitamin D levels in Black participants, sensitization load was associated with nonlesional skin FLG expression in non-Black, but not Black, children with low vitamin D levels. Thus, a complex interplay of factors determines the impact of vitamin D on allergic sensitization.

Reframing racial and ethnic disparities in atopic dermatitis in Black and Latinx populations.

Black people in the United States experience greater atopic dermatitis (AD) prevalence, severity, and persistence when compared with White people. Although very little published literature describes AD in the Latinx population, additional differences in severity, persistence, and age of onset exist in contrast to White people. Thus far, genetic polymorphisms associated with increased risk and/or severity of AD are less common among Black people, so should confer reduced, rather than the observed increased, AD risk among Black people. Little is known regarding genetic risk factors in Latinx people. In contrast, there is consistent evidence that socioeconomic, environmental, and health care factors influence AD prevalence, severity, and/or persistence, and these same risk factors are more common among racial and ethnic minority populations as a result of racism. Researchers too often pursue genetic explanations for racial and ethnic AD disparities when the evidence points to the importance of contextual, rather than genetic, causes of these disparities. Reframing the prevailing view that innate differences among racial and ethnic groups are responsible for these disparities by emphasizing the role of racism and its downstream effects on contextual factors will be a critical first step toward shrinking these disparities.

Association of KIR Genes and MHC Class I Ligands with Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic illness that is associated with immune dysregulation. NK cell function has previously been associated with AD. NK cells directly interact with polymorphic HLA class I ligand variants using killer cell Ig-like receptors (KIRs). The purpose of this study was to identify potential associations between NK cell function and AD by evaluating variation in the presence of KIR genes as well as KIR gene interactions with the appropriate HLA class I KIR-specific ligands. Human DNA from the genetics of AD case-control study was used to genotype HLA class I KIR-specific ligands and the presence of KIR genes. In the full cohort, an increased risk of AD was noted for KIR2DL5 (1.51 [1.13, 2.01]), KIR2DS5 (1.72 [1.26, 2.34]), and KIR2DS1 (1.41 [1.04, 1.91]). Individuals with KIR2DS5 or KIR2DS1 and the HLA-C*C2 epitope were at an increased risk of AD (1.74 [1.21, 2.51] and 1.48 [1.04, 2.12], respectively). The HLA-B*-21T (TT) leader sequence increased the risk of AD across ethnicity. African Americans with KIR2DL2, KIR2DS1, KIR2DL5, and KIR2DS5 are more likely to have AD, and the risk increased for KIR2DS1 and KIR2DS5 in the presence of appropriate HLA-C C2 epitope. The risk of AD also increased for individuals with the HLA-B*-21T leader sequence. Future studies should focus on KIR gene allelic variation as well as consider cell-based measurements of KIR and the associated HLA class I epitopes.

Atopic dermatitis.

THE COMPARISON: A) Pink scaling plaques and erythematous erosions in the antecubital fossae of a 6-year-old White boy. B) Violaceous, hyperpigmented, nummular plaques on the back and extensor surface of the right arm of a 16-month-old Black girl. C) Atopic dermatitis and follicular prominence/accentuation on the neck of a young Black girl.

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

BACKGROUND: Atopic dermatitis (AD) is a common disease, with particularly high prevalence found in Africa. It is increasingly recognized that patients with AD of different ethnic backgrounds have unique molecular signatures in the skin, potentially accounting for treatment response variations. Nevertheless, the skin profile of patients with AD from Africa is unknown, hindering development of new treatments targeted to this patient population. OBJECTIVE: To characterize the skin profile of patients with AD from Africa. METHODS: Gene expression studies, including RNA sequencing (using threshold of fold change of >2 and false discovery rate of <0.05) and real-time polymerase chain reaction, were performed on skin biopsies of Tanzanian patients with moderate-to-severe AD and controls. RESULTS: Tanzanian AD skin presented robust up-regulations of multiple key mediators of both T helper 2 (TH2) (interleukin 13 [IL-13], IL-10, IL-4R, CCL13,CCL17,CCL18,CCL26) and TH22 (IL22, S100As) pathways. Markers related to TH17 and IL-23 (IL-17A, IL-23A, IL-12, PI3, DEFB4B) and TH1 (interferon gamma, CXCL9,CXCL10,CXCL11) were also significantly overexpressed in AD tissues (FDR<.05), albeit to a lesser extent. IL-36 isoforms revealed substantial up-regulations in African skin. The barrier fingerprint of Tanzanian AD revealed no suppression of hallmark epidermal barrier differentiation genes, such as filaggrin, loricrin, and periplakin, with robust attenuation of lipid metabolism genes (ie, AWAT1). CONCLUSION: The skin phenotype of Tanzanian patients with AD is consistent with that of African Americans, exhibiting dominant TH2 and 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 and the need to develop unique treatments targeting patients with AD from these underrepresented populations.

Transcriptomic analysis of atopic dermatitis in African Americans is characterized by Th2/Th17-centered cutaneous immune activation.

Atopic dermatitis (AD) often presents more severely in African Americans (AAs) and with greater involvement of extensor areas. To investigate immune signatures of AD in AAs with moderate to severe pruritus, lesional and non-lesional punch biopsies were taken from AA patients along with age-, race-, and sex-matched controls. Histology of lesional skin showed psoriasiform dermatitis and spongiotic dermatitis, suggesting both Th2 and Th17 activity. Gene Set Variation Analysis showed upregulation of Th2 and Th17 pathways in both lesional versus non-lesional and lesional versus control (p < 0.01), while Th1 and Th22 upregulation were observed in lesional versus control (p < 0.05). Evidence for a broad immune signature also was supported by upregulated Th1 and Th22 pathways, and clinically may represent greater severity of AD in AA. Furthermore, population-level analysis of data from TriNetX, a global federated health research network, revealed that AA AD patients had higher values for CRP, ferritin, and blood eosinophils compared to age-, sex-, and race-matched controls as well as white AD patients, suggesting broad systemic inflammation. Therefore, AA AD patients may feature broader immune activation than previously thought and may derive benefit from systemic immunomodulating therapies that modulate key drivers of multiple immune pathways.

RNA-Seq Identifies Marked Th17 Cell Activation and Altered CFTR Expression in Different Atopic Dermatitis Subtypes in Chinese Han Populations.

Background: Patients with atopic dermatitis (AD) exhibit phenotypic variability in ethnicity and IgE status. In addition, some patients develop other allergic conditions, such as allergic rhinitis (AR), in subsequent life. Understanding the heterogeneity of AD would be beneficial to phenotype-specific therapies. Methods: Twenty-eight Chinese AD patients and 8 healthy volunteers were enrolled in the study. High-throughput transcriptome sequencing was conducted on lesional and nonlesional skin samples from 10 AD patients and matched normal skin samples from 5 healthy volunteers. Identification of differentially expressed genes (DEGs), KEGG pathway analyses, and sample cluster analyses were conducted in the R software environment using the DEseq2, ClusterProfiler, and pheatmap R packages, respectively. qRT-PCR, Western blotting, and ELISA were used to detect gene expression levels among subtypes. Correlation analysis was performed to further investigate their correlation with disease severity. Results: A total of 25,798 genes were detected per sample. Subgroup differential expression analysis and functional enrichment analysis revealed significant changes in the IL17 signaling pathway in Chinese EAD patients but not in IAD patients. DEGs enriched in cytokine-cytokine receptor interactions and gland secretion were considered to be associated with atopic march. Further investigations confirmed a marked IL17A upregulation in Chinese EAD with a positive relationship with total IgE level and AD severity. In addition, increased IL17A in AD patients with AR demonstrated a closer association with AR severity than IL4R. Moreover, AQP5 and CFTR were decreased in the lesions of AD patients with AR. The CFTR mRNA expression level was negatively associated with the skin IL17A level and AR severity. Conclusion: Our research characterized marked Th17 activation in Chinese EAD patients, and altered expression of IL17A, IL4R, AQP5, and CFTR in AD patients with AR was associated with AR severity. It partially explained the phenotypic differences of AD subtypes and provided potential references for endotype-targeted therapy.

Quality of life of Turkish children and families of Caucasian origin with atopic dermatitis.

INTRODUCTION AND OBJECTIVES: To determine the quality of life (QoL) in Caucasian children with atopic dermatitis (AD) and their families and possible factors that might impact their QoL. MATERIALS AND METHODS: In this cross-sectional study, 83 children aged 2-7 with AD and their families were enrolled as the study group, and 83 age-matched healthy children were included as controls. All patients in the AD and control groups were sorted into two age-based groups: (1) 2-4 and (2) 5-7 years of age. The parents of all children completed the Turkish version of the Pediatric Quality of Life Inventory (PedsQL).The Family Impact Scale for Dermatological Diseases (FIS-DD) was administered to the study group. Disease severity was evaluated with the Patient-Oriented Scoring Atopic Dermatitis (PO-SCORAD) scale. RESULTS: In both age groups, a negative correlation between the PedsQL and the FIS-DD scores (p < 0.001) was found. A positive correlation was found between the PO-SCORAD and FIS- DD scores among the second age group (p = 0.011). In the first age group, AD patients with comorbid allergic diseases had higher FIS-DD scores than those without any other allergic problems (p = 0.007). CONCLUSIONS: We suggest that considering family QoL may positively contribute to the treatment of pre-school age AD children.