Diagnosing Atopic Dermatitis in Skin of Color.

Atopic dermatitis (AD) is a pruritic inflammatory skin disease that disproportionately affects skin of color patients. African American, Asian, and Hispanic patients carry disproportionate disease burdens, with increased prevalence, disease severity, and health care utilization. AD has a unique clinical presentation in skin of color patients, often with greater extensor involvement, dyspigmentation, and papular and lichenified presentations. Erythema is also more difficult to appreciate and can result in an underappreciation of disease severity in skin of color patients. In this review, we highlight the important manifestations of AD across all skin types, including nuances in treatment.

A Polygenic Risk Score for Predicting Racial and Genetic Susceptibility to Prurigo Nodularis.

Prurigo nodularis (PN) is an understudied inflammatory skin disease characterized by pruritic, hyperkeratotic nodules. Identifying the genetic factors underlying PN could help to better understand its etiology and guide the development of therapies. In this study, we developed a polygenic risk score that predicts a diagnosis of PN (OR = 1.41, P = 1.6 × 10-5) in two independent and continentally distinct populations. We also performed GWASs, which uncovered genetic variants associated with PN, including one near PLCB4 (rs6039266: OR = 3.15, P = 4.8 × 10-8) and others near TXNRD1 (rs34217906: OR = 1.71, P = 6.4 × 10-7; rs7134193: OR = 1.57, P = 1.1 × 10-6). Finally, we discovered that Black patients have over a two-times greater genetic risk of developing PN (OR = 2.63, P = 7.8 × 10-4). Combining the polygenic risk score and self-reported race together was significantly predictive of PN (OR = 1.32, P = 4.7 × 10-3). Strikingly, this association was more significant with race than after adjusting for genetic ancestry. Because race is a sociocultural construct and not a genetically bound category, our findings suggest that genetics, environmental influence, and social determinants of health likely affect the development of PN and may contribute to clinically observed racial disparities.

Associations between hidradenitis suppurativa and dermatological conditions in adults: a national cross-sectional study.

Hidradenitis suppurativa (HS) is a chronic, inflammatory condition associated with numerous comorbidities, but there has been no broad-spectrum investigation into the dermatological comorbidities that are associated with HS using nationally representative data. We therefore analysed the 2016-2018 National Inpatient Sample for adult patients with and without HS and used multivariable logistic regression to determine correlations between HS and 25 dermatological conditions, adjusting for age, ethnicity and race, sex and insurance type. As seen previously, HS is more likely to affect women and Black people. The prevalence of having any of the 25 dermatological conditions was higher in patients with HS than without (24.60% vs. 5.30%, P < 0.001) and HS was specifically associated with 18 of the 25 dermatological conditions. This research confirms anecdotal disease relationships and identifies novel correlations between HS and dermatological conditions using a national patient population.

Reduced serum pyridoxine and 25-hydroxyvitamin D levels in adults with chronic pruritic dermatoses.

Little is known about the role nutritional factors play in the pathogenesis of chronic pruritic dermatoses (CPD). In this study, we analyzed nutritional deficiencies in CPD patients compared to matched controls. We conducted a population-based study from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2006. The main outcomes of the study were laboratory data on serum vitamin levels in participants who answered affirmatively to the questionnaires on CPD as well as matched healthy controls. We identified 877 cases of CPD among 9817 adults in the US aged 20 to 59 years. These findings revealed a slightly higher percentage of females with CPD. Low vitamin B6 (OR 0.697; 95% CI: 0.696-0.699, p = 0.025) and vitamin D (OR 0.794; 95% CI: 0.789-0.799, p = 0.037) levels were associated with a higher rate of CPD compared to healthy controls. Our study suggests that low levels of Vitamin B6 and Vitamin D inversely correlates with the presence of CPD. These vitamin deficiencies suggest further studies on the effect of vitamin supplementation may help in patients with CPD.

Risk of Hematologic Cancer in Patients With Undifferentiated Pruritus.

Importance: Although pruritus is common in patients with hematologic cancers, it is unknown whether patients with undifferentiated pruritus have higher risk of developing hematologic cancer. Furthermore, it is unclear whether serum lactate dehydrogenase (LDH) level, commonly ordered for cancer workup, has diagnostic utility in patients with pruritus. Objective: To assess the risk of hematologic cancer and the diagnostic utility of LDH level in patients with undifferentiated pruritus. Design, Setting, and Participants: This retrospective population-level cohort analysis was conducted using the TriNetX Research Network, a global health records database encompassing more than 69 million patients, from 2002 to 2020. The study included 327 502 eligible patients diagnosed with unspecified pruritus, excluding those with existing chronic pruritic dermatoses or systemic diseases known to cause pruritus, along with 327 502 matched controls. Exposures: Development of hematologic cancer within 1 year, 5 years, and 10 years following unspecified pruritus diagnosis. Main Outcomes and Measures: Primary study outcomes were 1-year, 5-year, and 10-year relative risks (RRs) for development of 9 hematologic cancers in patients with pruritus compared with control patients. Secondary outcomes were 1-year, 5-year, and 10-year RRs for any hematologic cancer at different LDH cutoffs (250 U/L and 500 U/L). Results: After matching, the pruritus and control cohorts each had 327 502 patients (68.1% female patients; 0.4% American Indian or Alaska Native patients; 3.5% Asian patients; 22.2% Black patients; 0.1% Native Hawaiian or Pacific Islander patients; 59.3% White patients; mean [SD] age, 42.2 [22] years). Patients with pruritus had increased 1-year risk of Hodgkin lymphoma (RR, 4.42; 95% CI, 2.83-6.88), myeloid leukemia (RR, 2.56; 95% CI, 1.79-3.67), multiple myeloma (RR, 2.38; 95% CI, 1.66-3.41), non-Hodgkin lymphoma (RR, 2.35; 95% CI, 1.96-2.82), monoclonal gammopathy (RR, 1.90; 95% CI, 1.55-2.32), myelodysplastic syndrome (RR, 1.74; 95% CI, 1.14-2.64), and lymphocytic leukemia (RR, 1.47; 95% CI, 1.07-2.02). After 12 months, the cancer risk was comparable with that of controls. Patients with pruritus had increased LDH levels, which were not associated with increased hematologic cancer risk. Conclusions and Relevance: In this cohort study, the RR of hematologic cancer in patients with undifferentiated pruritus was highest in the first 12 months, and LDH level had limited diagnostic utility in these patients. Clinicians should consider a thorough review of symptoms and assessment of cancer risk factors when deciding on workup for patients presenting with undifferentiated pruritus.

Racial differences in dysregulation of the renin-angiotensin-aldosterone system in patients with prurigo nodularis.

BACKGROUND: There are limited data characterizing the association between renal disease and prurigo nodularis (PN). OBJECTIVE: To characterize the association and describe mechanistic disease linkages between PN and renal comorbidities. METHODS: We conducted a cross-sectional analysis of renal comorbidities in PN using TriNetX, a global health research network providing access to medical records. Epidemiological findings provided the basis for translational studies on plasma and skin biopsy samples from PN patients stratified by race. RESULTS: PN was associated with stages 1-5 of chronic kidney disease (CKD), end-stage renal disease, nephritic syndrome, nephrotic syndrome, glomerular disease, and tubulointerstitial disease, but the associations were significantly stronger in black patients. Compared to controls, CKD progression was faster (HR 2.88, 95% CI: 1.01-8.26) only in black PN (10-year survival: 63.5% black vs. 85.5% white). Circulating plasma angiotensinogen levels were dysregulated (P < 0.001) only in black PN patients. Cutaneous transcriptomic analysis of genes related to the renin-angiotensin-aldosterone system (RAAS) revealed considerable dysregulation in PN lesions with greater dysregulation in black patients. CONCLUSIONS: Significant dysregulation of the cutaneous and systemic RAAS in black PN patients may explain the increased incidence and severity of renal disease.

Itch: Pathogenesis and treatment.

Itch pathogenesis is broadly characterized into histaminergic and nonhistaminergic pathways and transmitted via 2 main receptor families: G protein-coupled receptors and transient receptor potential channels. In the skin, itch is primarily transmitted by unmyelinated type C and thinly myelinated type Aδ nerve fibers. Crosstalk between the immune and neural systems modulates itch transmission at the skin, spinal cord, and brain. Among the many known pruritogens, Th2 cytokines, such as interleukin-4, interleukin-13, interleukin-31, and thymic stromal lymphopoietin, are particularly important mediators that signal through shared Janus kinase pathways, representing novel targets for novel itch therapeutics. Emerging evidence has also revealed that the opioidergic system is a potent modulator of itch transmission, with increased µ-opioid activity and decreased κ-opioid activity contributing to itch pathogenesis. Optimal management of itch requires that treatment approaches be tailored to specific etiologic itch subtypes. When the etiology is unknown and patients are given a diagnosis of chronic pruritus of unknown origin, treatment should be guided by the presence of Th2 polarization, often reflected by increased blood eosinophils. In the second article of this 2-part series, we outline our current understanding of itch pathogenesis and discuss available and emerging treatments for itch.