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.

Keloids and Hypertrophic Scars.

Keloids are an exuberant response to skin wound healing in which abundant scar tissue grows beyond the boundaries of the inciting insult. Age, race, location, family history and personal history of keloids are relevant factors concerning the risk of developing keloids. Because keloids are prone to recurrence after surgical excision, post-operative management plays an important role in the treatment of keloids. There are many modalities that can be used to treat keloids or prevent their recurrence; a multimodal approach is often necessary in difficult cases.

A retrospective study on the association of keloids with underlying health conditions in African-American Women.

Keloids are disfiguring benign scars that develop due to an exaggerated response to cutaneous wound healing, growing beyond the boundaries of the cutaneous insult into normal, previously uninvolved skin. The association of keloids with other underlying health conditions has been postulated, but not well characterized. Objective: This study aims to identify whether there is any association of keloids with underlying health conditions in African-American women. Methods: This study was done via the use of the National Inpatient Sample, a subset of the Healthcare Cost and Utilization Project. African-American women with keloids who had undergone cesarean sections were compared with a control group of African-American women with no history of keloids who had undergone cesarean sections. Results: A total of 301 African-American inpatient encounters with patients with keloids were compared with 37,144 encounters in the control group. The keloid patients had an increased association with peritoneal adhesions compared with the control group. Limitations: results are limited to one race and restricted age range; also, unable to differentiate keloids from hypetrophic scarring with ICD-10 codes. Conclusion: These findings suggest that keloids and peritoneal adhesions may have similar inflammatory processes.

Punctate Palmoplantar Keratoderma: A Case Report.

Palmoplantar keratoderma (PPK) is an umbrella term for a group of heterogeneous disorders, acquired or inherited, that are characterized by hyperkeratosis of palmar and/or plantar surfaces. Punctate PPK (PPPK) has been shown to have an autosomal dominant pattern of inheritance. It is linked with two loci on chromosomes 8q24.13-8q24.21 and 15q22-15q24. In type 1 PPPK, also known as Buschke-Fischer-Brauer disease, loss-of-function mutations in either the AAGAB or the COL14A1 genes have been associated with the disorder. We report here the clinical and genetic features of a patient with findings most consistent with type 1 PPPK.

The Keloid Area and Severity Index (KASI): an objective tool for the evaluation of keloids.

To aid in the standardization of evaluating patients with multiple keloids, a Keloid Area and Severity Index (KASI) was developed using patient feedback, previous literature, and clinical expertise. The system was validated using intrarater and interrater reliability assessments. Here, we present a verified, reliable method of assessing keloid area and severity in clinical and research settings.

A severe presentation of acute generalized exanthematous pustulosis with non-infectious circulatory shock in an adolescent.

We present a severe case of acute generalized exanthematous pustulosis (AGEP) secondary to trimethoprim-sulfamethoxazole complicated by non-infectious circulatory shock in a 16-year-old boy. Hemodynamic instability has been reported as a complication of AGEP in adults, but is rarely observed in pediatric patients. The patient we present demonstrated characteristic cutaneous findings of AGEP including isolated non-follicular, sterile pustules on a background of erythema with involvement at intertriginous areas and subsequently developed non-infectious circulatory shock. This case expands the spectrum of possible clinical presentations for AGEP in pediatric patients.

Biallelic variants in RNU12 cause CDAGS syndrome.

CDAGS Syndrome is a rare congenital disorder characterized by Craniosynostosis, Delayed closure of the fontanelles, cranial defects, clavicular hypoplasia, Anal and Genitourinary malformations, and Skin manifestations. We performed whole exome and Sanger sequencing to identify the underlying molecular cause in five patients with CDAGS syndrome from four distinct families. Whole exome sequencing revealed biallelic rare variants that disrupt highly conserved nucleotides within the RNU12 gene. RNU12 encodes a small nuclear RNA that is a component of the minor spliceosome and is essential for minor intron splicing. Targeted sequencing confirmed allele segregation within the four families. All five patients shared the same rare mutation NC_000022.10:g.43011402C>T, which alters a highly conserved nucleotide within the precursor U12 snRNA 3' extension. Each of them also carried a rare variant on the other allele that either disrupts the secondary structure or the Sm binding site of the RNU12 snRNA. Whole transcriptome sequencing analysis of lymphoblastoid cells identified 120 differentially expressed genes, and differential alternative splicing analysis indicated there was an enrichment of alternative splicing events in the patient. These findings provide evidence of the involvement of RNU12 in craniosynostosis, anal and genitourinary patterning, and cutaneous disease.

Human cutaneous neurofibroma matrisome revealed by single-cell RNA sequencing.

Neurofibromatosis Type I (NF1) is a neurocutaneous genetic syndrome characterized by a wide spectrum of clinical presentations, including benign peripheral nerve sheath tumor called neurofibroma. These tumors originate from the Schwann cell lineage but other cell types as well as extracellular matrix (ECM) in the neurofibroma microenvironment constitute the majority of the tumor mass. In fact, collagen accounts for up to 50% of the neurofibroma's dry weight. Although the presence of collagens in neurofibroma is indisputable, the exact repertoire of ECM genes and ECM-associated genes (i.e. the matrisome) and their functions are unknown. Here, transcriptome profiling by single-cell RNA sequencing reveals the matrisome of human cutaneous neurofibroma (cNF). We discovered that classic pro-fibrogenic collagen I myofibroblasts are rare in neurofibroma. In contrast, collagen VI, a pro-tumorigenic ECM, is abundant and mainly secreted by neurofibroma fibroblasts. This study also identified potential cell type-specific markers to further elucidate the biology of the cNF microenvironment.

A Review of Current Keloid Management: Mainstay Monotherapies and Emerging Approaches.

Commonly affecting those with skin of color, keloids are an aberrant wound response that leads to wound tissue expanding above and beyond the original cutaneous injury. Keloids are notoriously and particularly difficult to treat because of their tendency to recur after excision. The current standard of care is intralesional steroid (triamcinolone acetonide). However, because no therapy has yet proven to be fully curative, keloid treatments have expanded to include a number of options, from injections to multimodal approaches. This review details current treatment of keloids with injections (bleomycin, verapamil, hyaluronic acid and hyaluronidase, botulinum toxin, and collagenase), cryotherapy, laser, radiofrequency ablation, radiation, extracorporeal shockwave therapy, pentoxifylline, and dupilumab.

Patient-reported outcomes for keloids: a systematic review.

INTRODUCTION: Keloids are exuberant responses to cutaneous wound healing. Many research studies utilize keloid recurrence, scar thickness, and objective physician-reported data as outcome measures. Patients may have different perceptions and evaluations of treatment success from physicians, however. This review discusses available patient-reported outcome measures for keloids, as well as patient-reported outcomes across current treatment modalities. EVIDENCE ACQUISITION: A literature search of PubMed, Ovid/Medline, and EMBASE was conducted from inception to April 2018. Studies involving the evaluation of keloids with at least one patient-reported outcome measure were included. EVIDENCE SYNTHESIS: 30 relevant studies were identified. Topics included patient-reported outcome measures, health-related quality of life, and treatment options such as: topical treatments, intralesional treatments, cryotherapy, postsurgical intralesional treatments, postsurgical pressure therapy, postsurgical radiotherapy, and postsurgical brachytherapy. The Patient and Observer Scar Assessment Scale (POSAS) was used by 21 (70%) of the included studies. Patient component scores did not correlate well with observer component scores in 7 studies using the POSAS, with 4 studies having significantly worse patient scores. Quality of life in keloid patients was significantly worse compared to controls in 3 studies. Multimodal treatment options generally received more positive patient-reported outcomes. CONCLUSIONS: Patient-reported outcomes provide valuable insights into the perceptions, treatment goals, and quality of life of keloid patients. Development of more patient-reported outcome measures specific to keloids, especially those that incorporate both scar and quality of life assessments, may help refine our current understanding of keloid management.