Proteomic Profiling of Central Centrifugal Cicatricial Alopecia Reveals Role of Humoral Immune Response Pathway and Metabolic Dysregulation.

Proteomic profiling on other primary cicatricial alopecias, such as frontal fibrosing alopecia and lichen planopilaris, have suggested a T helper 1-mediated inflammatory pathway, but in central centrifugal cicatricial alopecia (CCCA), the protein expression patterns are unknown. In this study, we sought to characterize protein expression patterns in CCCA to identify biomarkers of disease activity that will identify potential therapeutic avenues for treatment. Scalp protein quantification was performed to understand protein expression patterns in affected versus unaffected scalps in CCCA. A total of 5444 proteins were identified, of which 148 proteins were found to be differentially expressed in CCCA-affected scalp, with upregulation of adaptive immune pathways (IGHG3, P = .034; IGHG4, P = .01; IGG1, P = .026) and markers of fibrosis (ITGA1, P = .016; SFRP2, P = .045; TPM2, P = .029; SLMAP, P = .016) and downregulation of metabolic proteins (ALOX15B, P = .003; FADS2, P = .006; ELOVL5, P = .007; FA2H, P = .017; FAR2, P = .011; SC5D, P < .001). Our analysis revealed, to our knowledge, previously unknown humoral immune canonical pathways, notably IgG, implicated in CCCA and additionally confirmed aberrant lipid metabolism pathways implicated in diabetes mellitus, suggesting unique mechanisms of disease in patients with CCCA.

Comparing the Efficacy and Tolerability of Moderate to Severe Hyperpigmentation and Skin Unevenness.

Dyschromia is the result of irregular facial pigmentation. These cutaneous manifestations can have a significant impact on the quality of life of those affected, especially among females and skin of color. In this randomized, double-blinded, two-cell, single-center, 16-week clinical study, all subjects had moderate to severe (scores 4-9 on the modified Griffiths Scale) hyperpigmentation and skin unevenness of the face such that approximately 20% of subjects had post-inflammatory hyperpigmentation (PIH), 40% had overall mottled hyperpigmentation, and 40% had superficial melasma (Superficial Melasma was determined by Wood's Lamp Assessment). Study participants received either Product A (proprietary new formulation - Cysteamine HSA) or Product B (current marketed product - Cyspera®) and used the test product either in the morning or at night, beginning with every other day application, and then advanced to every day, or as tolerated. The results revealed that both Product A (Cysteamine HSA) and Product B (Cyspera®) had statistically significant improvement in facial hyperpigmentation and skin unevenness, however, Product A (Cysteamine HSA) had better tolerability results for scaling, peeling, burning, stinging, erythema, and dryness, indicating that Product A (Cysteamine HSA) outperformed Product B (Cyspera®). J Drugs Dermatol. 2024;23(1):1260-1265.     doi:10.36849/JDD.7584.

Skin tone representation in dermatologic direct-to-consumer advertisements: a cross-sectional analysis and call to action.

Background: Direct-to-consumer advertisements (DTCAs) in medical marketing serve as a prominent modality to deliver information to an increasingly diverse audience of consumers and increase prescription sales. In dermatology, advertisements have the potential to shape the public's opinions, aid in the understanding of skin conditions, and raise awareness of available treatments. Objective: To investigate and characterize the representation of skin tones in DTCAs. Methods: Nielsen ratings were utilized to identify the networks most watched by Black viewers in 2022. Programming on NBCUniversal, ABC, CBS, and FOX that aired in the District of Columbia, suburban Maryland, and Northern Virginia from June 2022 to July 2022 was reviewed for DTCAs. DTCAs were then analyzed to determine the skin tones of models and skin conditions depicted on models with darkly pigmented skin. Results: Of the 106 DTCAs related to dermatologic conditions, there were 13 unique advertisements featuring 32 unique models. Four advertisements depicted the skin condition on darkly pigmented skin tones. Using the Monk Skin Tone (MST) scale to assess the 32 unique individuals, only 25% (n = 8) were rated at an MST 7 or above, and 6.25% (n = 2) were rated at an MST 10. Limitations: This study has the limitation of only sampling DTCAs from Washington, District of Columbia which does not fully represent all dermatology-related DTCAs in the United States. Conclusion: Results of this content analysis demonstrate that the number of persons of color within dermatologic DTCAs is 23%, whereas there are 13.6% Black individuals in the 2021 US census. This suggests that DTCAs are becoming more diverse since 2018. However, findings also show that the vast majority of DTCAs do not include models with darkly pigmented skin, and there remains a lack of advertisements depicting skin disease among people of color. Given the role of DTCAs in informing and aiding patients' requests for prescription drugs, representation of all skin tones is essential for this communication to be effective, especially in the field of dermatology.

Reduction of Erythema in Moderate-Severe Rosacea by a Low Molecular Weight Heparan Sulfate Analog (HSA).

Rosacea changes are a result of an immune mediated response and the angiogenic properties of the LL-37 peptide. This peptide induces an inflammatory signal that activates the NLRP3-mediated inflammasome, triggering rosacea pathogenesis. Research findings show that LL-37 peptide is inhibited by binding to a cell surface glycosaminoglycan, heparan sulfate. Heparan Sulfate Analog (HSA) is a proprietary low molecular weight analog of heparan sulfate that has been formulated into a Dermal Repair Cream (DRC), specifically to aid in such immune mediated responses. Herein, in vitro studies using human epidermal keratinocytes showed an increase in HSA decreased LL-37 toxicity and IL-8 cytokine release. A single-center, randomized double-blind trial included 16 subjects (Fitzpatrick skin types I-IV) with a clinical diagnosis of type 1 rosacea and moderate to severe facial erythema, who were undergoing Pulsed Dye Laser (PDL) treatment. The clinical improvements of their facial erythema were assessed at baseline, 2 weeks, 4 weeks, and 8 weeks. Results revealed that low molecular weight HSA significantly improves the clinical signs of rosacea during the 8 weeks of use likely resulting from inhibition of LL-37 induced IL-8 cytokine release. These findings support the use of DRC in rosacea topical treatment regimens as it demonstrates visible skin benefits and improves tolerability of PDL therapy in a shorter duration of time as compared with PDL alone.George R, Gallo RL, Cohen JL, et al. Reduction of erythema in moderate-severe rosacea by a low molecular weight Heparan Sulfate Analog (HSA). J Drugs Dermatol. 2023;22(6):546-553. doi:10.36849/JDD.7494.

The Skin of Color Society's Meeting the Challenge Summit, 2022: Diversity in Dermatology Clinical Trials Proceedings.

Importance: Clinical trials remain the cornerstone for determining the safety and efficacy of an intervention. A diverse participant pool in dermatology clinical trials is critical to ensure that results are generalizable among the patient population who will ultimately depend on the efficacy of the intervention. The Skin of Color Society hosted the inaugural Meeting the Challenge Summit: Diversity in Dermatology Clinical Trials in Washington, DC, from June 10 to 11, 2022. The summit was an interactive and collaborative effort to advance discussions regarding the need for broader inclusion of racial and ethnic minority patients in dermatology clinical trials. Observations: The summit focused on 3 principal areas: (1) understanding the current clinical trials landscape; (2) breaking down patient, clinician, industry, and regulatory barriers; and (3) effecting change through a diversity-focused strategy. The program hosted thought-provoking panel talks and discussions with various stakeholder groups, including a keynote presentation from the family of Henrietta Lacks. Conclusions and Relevance: Panel discussions and insightful presentations from physicians, industry leaders, community trailblazers, and patients fostered new collaborations. The summit provided recommendations and suggested strategies for future initiatives designed to increase the representation of minority individuals in dermatology clinical trials.

Neutralizing Anti‒DNase 1 and ‒DNase 1L3 Antibodies Impair Neutrophil Extracellular Traps Degradation in Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a debilitating inflammatory skin disorder characterized by abscess-like nodules and boils resulting in fistulas and tissue scarring. We previously reported evidence of an autoimmune signature in HS, characterized by enhanced neutrophil extracellular trap (NET) infiltration in HS skin lesions and dysregulation of the adaptive immune system characterized by the presence of autoantibodies. Timely removal of NETs is critical for tissue homeostasis to prevent a dysregulated generation of modified autoantigens and tissue damage. DNases 1 and 1L3 play important roles in proper NET removal. We tested the hypothesis that NETs in patients with HS are not effectively cleared owing to the presence of antibodies against DNase 1 and DNase 1L3. We report that HS serum poorly degraded NETs. Addition of exogenous DNase 1 restored NET degradation capabilities in a subset of HS samples. DNase 1 activity was significantly decreased in HS sera. Anti‒DNase 1 and ‒DNase 1L3 antibodies were detected in serum samples and skin lesions from patients with HS. Purified IgGs from HS decreased DNase 1 activity and NET degradation. Taken together, this identification of neutralizing antibodies against nucleases in HS expands the understanding of the pathogenesis of this disease to support an autoimmune mechanism in its underlying pathogenesis.

What's Race Got to Do With It? CRP Levels in Immune Mediated Skin Diseases: Considerations for Hidradenitis Suppurativa.

Currently, there is a lack of racial/ethnic heterogeneity in research databases, exposing a systematic issue in studies exploring inflammation-mediated diseases, such as hidradenitis suppurativa (HS). HS is a chronic inflammatory skin condition that disrupts normal structure and functioning of terminal hair follicles, resulting in the formation of recurrent abscesses, nodules, and sinus tracts within intertriginous regions. Studies have described higher serum levels of inflammation-mediated C-reactive protein (CRP) in patients with HS, a disease that predominantly affects skin of color (SOC) populations. Herein, we explore the role of CRP levels in the context of HS disease presentation, management, and psychosocial implications in SOC patients to determine existing disparities in research studies.

Diagnostic accuracy of a rapid diagnostic test for the early detection of COVID-19.

OBJECTIVES: This study was undertaken to evaluate the diagnostic performance of the BinaxNOW COVID-19 Ag Card rapid antigen assay (Abbott; Chicago, IL, USA) in the detection of COVID-19 infection compared to the reference standard of PCR testing. METHODS: We evaluated the BinaxNOW COVID-19 Ag Card rapid antigen assay relative to a standard reference PCR test. We tested 3810 nasal swabs from symptomatic and asymptomatic adults undergoing surveillance COVID-19 testing at Howard University using one swab for each nostril. One swab was tested using the rapid antigen assay and the other using the PCR test. RESULTS: The sensitivity of the BinaxNOW COVID-19 Ag Card rapid antigen assay was 91.84% (95% confidence interval (CI): 80.40-97.73%) and the specificity was 99.95% (95% CI: 99.81-99.99%). The range of Ct values for the N gene was 10.74-34.90 (M = 26.88, SD=4.86). Fourteen (28.6%) samples had an N gene Ct value > 30. The average N gene Ct value for rapid test negative (i.e. false negative) samples was 31.92. CONCLUSIONS: The sensitivity of the test in our symptomatic and asymptomatic cohort was lower than the manufacturer's reported sensitivity in a symptomatic cohort (97.1%). Despite their relatively lower sensitivity (especially in asymptomatic individuals), rapid tests have undeniable benefits (i.e., ease of use and rapid results) that make them a helpful tool in the control of the SARS-CoV-2 pandemic. Given the diagnostic accuracy of these tests as evidenced by this study, rapid tests can be thoughtfully employed in situations where swift results are critical.

Autoantibodies Present in Hidradenitis Suppurativa Correlate with Disease Severity and Promote the Release of Proinflammatory Cytokines in Macrophages.

Hidradenitis suppurativa (HS), also known as acne inversa, is a debilitating inflammatory skin disorder that is characterized by nodules that lead to the development of connected tunnels and scars as it progresses from Hurley stages I to III. HS has been associated with several autoimmune diseases, including inflammatory bowel disease and spondyloarthritis. We previously reported dysregulation of humoral immune responses in HS, characterized by elevated serum total IgG, B-cell activation, and antibodies recognizing citrullinated proteins. In this study, we characterized IgG autoreactivity in HS sera and lesional skin compared with those in normal healthy controls using an array-based high-throughput autoantibody screening. The Cy3-labeled anti-human assay showed the presence of autoantibodies against nuclear antigens, cytokines, cytoplasmic proteins, extracellular matrix proteins, neutrophil proteins, and citrullinated antigens. Most of these autoantibodies were significantly elevated in stages II‒III in HS sera and stage III in HS skin lesions compared with those of healthy controls. Furthermore, immune complexes containing both native and citrullinated versions of antigens can activate M1 and M2 macrophages to release proinflammatory cytokines such as TNF-α, IL-8, IL-6, and IL-12. Taken together, the identification of specific IgG autoantibodies that recognize circulating and tissue antigens in HS suggests an autoimmune mechanism and uncovers putative therapeutic targets.

Hidradenitis suppurativa in skin of colour.

Hidradenitis suppurativa/acne inversa (HS) more prevalent and disproportionally affects African American females. Although there are limited studies in HS skin of colour populations in the USA, there is more scarcity of HS skin of colour studies in other countries, which limits the overall understanding of the disease among these patients. Herein, our overview of the 10th European Hidradenitis Suppurativa Foundation (EHSF) e.V. Conference provided a crude example of the limited number of skin of colour physicians, physician scientists and inclusion of skin of colour patients highlighting the need to increase awareness of this important issue. We summarized the epidemiology, pathogenesis, clinical picture and focused on treatment options from southeast Asia and Africa. Our outlined general recommendations for diagnosis will render better clinical care and outcomes for diverse patient populations.

Pathogenic and therapeutic role for NRF2 signaling in ultraviolet light-induced skin pigmentation.

Mottled skin pigmentation and solar lentigines from chronic photodamage with aging involve complex interactions between keratinocytes and melanocytes. However, the precise signaling mechanisms that could serve as therapeutic targets are unclear. Herein, we report that expression of nuclear factor erythroid 2-related factor 2 (NRF2), which regulates reduction-oxidation reactions, is altered in solar lentigines and photodamaged skin. Moreover, mottled skin pigmentation in humans could be treated with topical application of the NRF2 inducer sulforaphane (SF). Similarly, UV light-induced pigmentation of WT mouse ear skin could be treated or prevented with SF treatment. Conversely, SF treatment was unable to reduce UV-induced ear skin pigmentation in mice deficient in NRF2 or in mice with keratinocyte-specific conditional deletion of IL-6Rα. Taken together, NRF2 and IL-6Rα signaling are involved in the pathogenesis of UV-induced skin pigmentation, and specific enhancement of NRF2 signaling could represent a potential therapeutic target.

What causes hidradenitis suppurativa ?-15 years after.

The 14 authors of the first review article on hidradenitis suppurativa (HS) pathogenesis published 2008 in EXPERIMENTAL DERMATOLOGY cumulating from the 1st International Hidradenitis Suppurativa Research Symposium held March 30-April 2, 2006 in Dessau, Germany with 33 participants were prophetic when they wrote "Hopefully, this heralds a welcome new tradition: to get to the molecular heart of HS pathogenesis, which can only be achieved by a renaissance of solid basic HS research, as the key to developing more effective HS therapy." (Kurzen et al. What causes hidradenitis suppurativa? Exp Dermatol 2008;17:455). Fifteen years later, there is no doubt that the desired renaissance of solid basic HS research is progressing with rapid steps and that HS has developed deep roots among inflammatory diseases in Dermatology and beyond, recognized as "the only inflammatory skin disease than can be healed". This anniversary article of 43 research-performing authors from all around the globe in the official journal of the European Hidradenitis Suppurativa Foundation e.V. (EHSF e.V.) and the Hidradenitis Suppurativa Foundation, Inc (HSF USA) summarizes the evidence of the intense HS clinical and experimental research during the last 15 years in all aspects of the disease and provides information of the developments to come in the near future.

Bonds and bridges: the role of social capital in building a more diverse dermatology workforce.

Several calls to action have been made in response to the lack of racial diversity in dermatology, but we have yet to explore how differences in social capital perpetuate homogeneity in dermatology training programs and the workforce. Herein, the concept of social capital is applied to this problem in dermatology and is used as a scaffold to suggest interventions that may ameliorate the systemic barriers faced by underrepresented-in-medicine (UIM) students.