Treatment for central centrifugal cicatricial alopecia-Delphi consensus recommendations.

BACKGROUND: There is no established standard of care for treating central centrifugal cicatricial alopecia (CCCA), and treatment approaches vary widely. OBJECTIVE: To develop consensus statements regarding the use of various pharmacological therapies in treating adults with CCCA. METHODS: We invited 27 dermatologists with expertise in hair and scalp disorders to participate in a 3-round modified Delphi study between January and March 2023. Statements met strong consensus if 75% of respondents agreed or disagreed. Statements met moderate consensus if 55% or more but less than 75% agreed or disagreed. RESULTS: In round 1, 5 of 33 (15.2%) statements met strong consensus, followed by 9 of 28 (32.1%) in round 2. After the final round 3 meeting, strong consensus was reached for 20 of 70 (28.6%) overall statements. Two statements achieved moderate consensus. LIMITATIONS: This study included only English-speaking, US-based dermatologists and did not consider nonpharmacological therapies. CONCLUSION: Despite varying opinions among dermatologists, consensus was reached for several statements to help clinicians manage CCCA. We also highlight areas that lack expert consensus with the goal of advancing research and therapeutic options for CCCA.

Single variant, yet "double trouble": TSC and KBG syndrome because of a large de novo inversion.

Despite the advances in high-throughput sequencing, many rare disease patients remain undiagnosed. In particular, the patients with well-defined clinical phenotypes and established clinical diagnosis, yet missing or partial genetic diagnosis, may hold a clue to more complex genetic mechanisms of a disease that could be missed by available clinical tests. Here, we report a patient with a clinical diagnosis of Tuberous sclerosis, combined with unusual secondary features, but negative clinical tests including TSC1 and TSC2 Short-read whole-genome sequencing combined with advanced bioinformatics analyses were successful in uncovering a de novo pericentric 87-Mb inversion with breakpoints in TSC2 and ANKRD11, which explains the TSC clinical diagnosis, and confirms a second underlying monogenic disorder, KBG syndrome. Our findings illustrate how complex variants, such as large inversions, may be missed by clinical tests and further highlight the importance of well-defined clinical diagnoses in uncovering complex molecular mechanisms of a disease, such as complex variants and "double trouble" effects.

Model Organism Modifier (MOM): a user-friendly Galaxy workflow to detect modifiers from genome sequencing data using Caenorhabditis elegans.

Genetic modifiers are variants modulating phenotypic outcomes of a primary detrimental variant. They contribute to rare diseases phenotypic variability, but their identification is challenging. Genetic screening with model organisms is a widely used method for demystifying genetic modifiers. Forward genetics screening followed by whole genome sequencing allows the detection of variants throughout the genome but typically produces thousands of candidate variants making the interpretation and prioritization process very time-consuming and tedious. Despite whole genome sequencing is more time and cost-efficient, usage of computational pipelines specific to modifier identification remains a challenge for biological-experiment-focused laboratories doing research with model organisms. To facilitate a broader implementation of whole genome sequencing in genetic screens, we have developed Model Organism Modifier or MOM, a pipeline as a user-friendly Galaxy workflow. Model Organism Modifier analyses raw short-read whole genome sequencing data and implements tailored filtering to provide a Candidate Variant List short enough to be further manually curated. We provide a detailed tutorial to run the Galaxy workflow Model Organism Modifier and guidelines to manually curate the Candidate Variant Lists. We have tested Model Organism Modifier on published and validated Caenorhabditis elegans modifiers screening datasets. As whole genome sequencing facilitates high-throughput identification of genetic modifiers in model organisms, Model Organism Modifier provides a user-friendly solution to implement the bioinformatics analysis of the short-read datasets in laboratories without expertise or support in Bioinformatics.

Scalp Infection, Inflammation, and Infestation.

Tinea capitis, folliculitis, seborrheic dermatitis, and pediculosis capitis are four common scalp conditions. Although tinea capitis and seborrheic dermatitis are found more commonly in patients with skin of color and highly textured hair, all of these conditions have special diagnostic or management considerations in these populations. This article reviews the diagnosis and management of these common scalp conditions.

Diversity in the Dermatology Workforce and in Academic Medicine.

Health disparities exist in marginalized patient populations throughout medical specialties, including in dermatology. It is important that the physician workforce reflect the diversity of the US population to address these disparities. At present, the dermatology workforce does not reflect the racial or ethnic diversity of the US population. The subspecialties of pediatric dermatology, dermatopathology, and dermatologic surgery are even less diverse than the dermatology workforce as a whole. Although women make up over half of the population of dermatologists, disparities still exists in areas such as compensation and presence in leadership positions.

Genome sequencing of C. elegans balancer strains reveals previously unappreciated complex genomic rearrangements.

Genetic balancers in Caenorhabditis elegans are complex variants that allow lethal or sterile mutations to be stably maintained in a heterozygous state by suppressing crossover events. Balancers constitute an invaluable tool in the C. elegans scientific community and have been widely used for decades. The first/traditional balancers were created by applying X-rays, UV, or gamma radiation on C. elegans strains, generating random genomic rearrangements. Their structures have been mostly explored with low-resolution genetic techniques (e.g., fluorescence in situ hybridization or PCR), before genomic mapping and molecular characterization through sequencing became feasible. As a result, the precise nature of most chromosomal rearrangements remains unknown, whereas, more recently, balancers have been engineered using the CRISPR-Cas9 technique for which the structure of the chromosomal rearrangement has been predesigned. Using short-read whole-genome sequencing (srWGS) and tailored bioinformatic analyses, we previously interpreted the structure of four chromosomal balancers randomly created by mutagenesis processes. Here, we have extended our analyses to five CRISPR-Cas9 balancers and 17 additional traditional balancing rearrangements. We detected and experimentally validated their breakpoints and have interpreted the balancer structures. Many of the balancers were found to be more intricate than previously described, being composed of complex genomic rearrangements (CGRs) such as chromoanagenesis-like events. Furthermore, srWGS revealed additional structural variants and CGRs not known to be part of the balancer genomes. Altogether, our study provides a comprehensive resource of complex genomic variations in C. elegans and highlights the power of srWGS to study the complexity of genomes by applying tailored analyses.

Drug Reaction with Eosinophilia and Systemic Syndrome in Revision Arthroplasty for a Prosthetic Knee Infection: A Case Report.

CASE: A 51-year-old woman underwent stage I of a 2-stage revision for a prosthetic knee infection with a vancomycin-impregnated articulating cement spacer followed by IV vancomycin and ceftriaxone. Four weeks later, she developed fevers, a diffuse cutaneous eruption, lymphadenopathy, transaminitis, and acute renal tubular necrosis before being diagnosed with drug reaction with eosinophilia and systemic syndrome (DRESS). CONCLUSION: DRESS is a rare, potentially life-threatening adverse drug reaction with cutaneous manifestations and multiorgan involvement. Although rare, its incidence in orthopaedic patients is likely to increase with the aging population. It must be recognized early to minimize end-stage organ dysfunction and mortality.

Hair and scalp disorders in adult and pediatric patients with skin of color.

As increasing numbers of patients of African descent seek treatment for hair and scalp-related diseases, it is imperative that all dermatologists be adequately trained to address the concerns of this patient population. We present must-know information to effectively approach the concerns of patients with seborrheic dermatitis, acquired trichorrhexis nodosa, acne keloidalis nuchae, pseudofolliculitis barbae, alopecia, and common pediatric hair and scalp disorders.

Approach to treatment of medical and cosmetic facial concerns in skin of color patients.

Facial concerns in skin of color (SOC) patients vary and can be a source of emotional and psychological distress. This article discusses 4 common facial concerns in SOC patients: acne, rosacea, facial hyperpigmentation, and cosmetic enhancement. Treatment recommendations are provided as well as management pearls.

Guidelines of care for the management of primary cutaneous melanoma. American Academy of Dermatology.

The incidence of primary cutaneous melanoma has been increasing dramatically for several decades. Melanoma accounts for the majority of skin cancer-related deaths, but treatment is nearly always curative with early detection of disease. In this update of the guidelines of care, we will discuss the treatment of patients with primary cutaneous melanoma. We will discuss biopsy techniques of a lesion clinically suspicious for melanoma and offer recommendations for the histopathologic interpretation of cutaneous melanoma. We will offer recommendations for the use of laboratory and imaging tests in the initial workup of patients with newly diagnosed melanoma and for follow-up of asymptomatic patients. With regard to treatment of primary cutaneous melanoma, we will provide recommendations for surgical margins and briefly discuss nonsurgical treatments. Finally, we will discuss the value and limitations of sentinel lymph node biopsy and offer recommendations for its use in patients with primary cutaneous melanoma.

Skin from various ethnic origins and aging: an in vivo cross-sectional multimodality imaging study.

BACKGROUND: Ethnic differences in skin structural features have not been thoroughly investigated, and the few reported studies are contradictory. Thus, we have carried out a set of in vivo measurements on the skin of about 400 volunteers from various ethnic origins living in the same environment. METHODS: Female subjects were distributed into four ethnic groups: African Americans, Mexicans, Caucasians, and Chinese. Inter- and intra-ethnic skin structural differences, according to age and anatomic site, were investigated using three non-invasive skin-imaging methods: ultrasound (US) at 25 and 150 MHz, and optical coherence tomography (OCT). RESULTS: The thickness of the skin is higher on the cheek compared with the dorsal and ventral forearm, with no ethnic or age-related specificity. We confirm that the sub-epidermal non-echogenic band is a sensitive marker of skin aging, and reveal for the first time that it is less pronounced in African Americans. From OCT images, we bring out evidence that the thickness of the dermal-epidermal junction (DEJ) decreased with age, and was higher in African Americans than in Caucasians. Finally, by comparing US images at 150 MHz with OCT images, we show that papillary dermis thickness can be measured and appears to be quite constant irrespective of age or ethnic group. CONCLUSION: Our study confirms that skin imaging is very attractive to further our knowledge of the morphology of skin from various ethnic origins. Regarding age effects, quantitative parameters have shown that they would be delayed in African Americans compared with all other ethnic populations.

Comparative study of the hydration of the stratum corneum between four ethnic groups: influence of age.

BACKGROUND: Several recent overviews have reported that significant work remains to be performed to understand and quantify the ethnic differences in skin properties. In this way, we have carried out a set of in vivo biophysical experiments on the skin of American women from different ethnic populations living in the same environment. Inter- and intraethnic skin micro relief results were already published, skin hydration differences are now reported here. METHODS: The skin water content was evaluated taking advantage of the new skin capacitance imaging technique which allows to study stratum corneum hydration without suffering of the influence of the skin micro-relief and hair on the measurement. Three hundred and eleven American women from four ethnic groups were enrolled in this study. The investigation was performed during the summer season of 2004 on the major relatively distinct ethnic groups of Chicago, which is to say: African American, Chinese, Caucasian and Mexican. The hydration of the skin was investigated on the dorsal and ventral forearm sites as a function of ethnicity and age. RESULTS: Skin dryness is higher on sun exposed sites for lighter skin tones, such as in Chinese and Caucasian women, than on sites that are primarily out of the sun; while, no skin dryness differences are seen on either site for African American and Mexican women whose skin is darker. The skin dryness does not change as a function of ethnicity for the younger group for either the ventral and dorsal site of the forearm. With age, however, the dryness of the skin is higher for African American and Caucasian women than for the two other ethnic groups, with a higher percentage increase in Caucasian women. CONCLUSIONS: This study has revealed that the hydration of the skin is different according to ethnicity and that the age effects are influenced by ethnicity, suggesting anatomical or physiological property differences in ethnic skin. This study has also pointed out that the SkinChip seems to be a convenient and fast way to investigate both the micro relief as previously published and the dryness of the skin on a large number of subjects, and in this way will be very useful to improve our knowledge about skin of people from different ethnic groups and helping to develop specific products that are customized to all these populations.