Comprehensive genetic and phenotype analysis of 95 individuals with mosaic tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a neurogenetic disorder due to loss-of-function TSC1 or TSC2 variants, characterized by tumors affecting multiple organs, including skin, brain, heart, lung, and kidney. Mosaicism for TSC1 or TSC2 variants occurs in 10%-15% of individuals diagnosed with TSC. Here, we report comprehensive characterization of TSC mosaicism by using massively parallel sequencing (MPS) of 330 TSC samples from a variety of tissues and fluids from a cohort of 95 individuals with mosaic TSC. TSC1 variants in individuals with mosaic TSC are much less common (9%) than in germline TSC overall (26%) (p < 0.0001). The mosaic variant allele frequency (VAF) is significantly higher in TSC1 than in TSC2, in both blood and saliva (median VAF: TSC1, 4.91%; TSC2, 1.93%; p = 0.036) and facial angiofibromas (median VAF: TSC1, 7.7%; TSC2 3.7%; p = 0.004), while the number of TSC clinical features in individuals with TSC1 and TSC2 mosaicism was similar. The distribution of mosaic variants across TSC1 and TSC2 is similar to that for pathogenic germline variants in general TSC. The systemic mosaic variant was not present in blood in 14 of 76 (18%) individuals with TSC, highlighting the value of analysis of multiple samples from each individual. A detailed comparison revealed that nearly all TSC clinical features are less common in individuals with mosaic versus germline TSC. A large number of previously unreported TSC1 and TSC2 variants, including intronic and large rearrangements (n = 11), were also identified.

Improvement of dermatological symptoms in patients with Bachmann-Bupp syndrome using difluoromethylornithine treatment.

Bachmann-Bupp syndrome (OMIM #619075) is a novel autosomal dominant disorder caused by variants in the c-terminus of the ornithine decarboxylase 1 gene, resulting in increased levels of ornithine decarboxylase. This case report includes two patients diagnosed with Bachmann-Bupp syndrome who were treated with difluoromethylornithine through compassionate use approval from the United States Food and Drug Administration. In both patients, treatment with difluoromethylornithine has resulted in improved dermatologic signs, including regrowth of eyebrow and scalp hair and cessation of recurrent follicular cyst development.

Therapeutic implications of personality disorders in dermatology.

There is a significant psychiatric comorbidity that exists in multiple dermatological conditions, stemming from the patient''s own psychological make up. This article reviews personality disorders and their types, which influence the course and prognosis of several psychodermatological disorders. Self-inflicted skin lesions, for example, are usually associated with obsessive-compulsive behavior, but they also share connections to Narcissistic and Borderline personality disorders. Body dysmorphic disorder is another psychodermatological condition seen in dermatology, aesthetic, and cosmetic surgery clinics, which is influenced by patient's personality type. In general, there is a significantly high proportion of personality disorders seen in aesthetic and cosmetic surgery. The management of patients with personality disorders is challenging, but joint liaison between psychiatry and dermatology has proven helpful and can provide patients with the best care for their psychological needs and dermatologic care.

Representation of Racially Minoritized Patients on Dermatology Private Practice Websites.

Images on the homepages of private practice dermatology websites often do not reflect the racial diversity of the metropolitan area in which each practice is located. A Google Maps scraper (Apify) was used to identify websites for private practices in 27 United States metropolitan areas selected from the 2020 U.S. Census list of 100 largest areas where non-white individuals makeup more than 50% of the population. Homepages from the top ten websites listed by the search engine were analyzed for images, use of non-English language, and mention of "Skin of Color" or "Ethnic Skin." One hundred seventeen websites were included. Two mentioned "Skin of Color" or "Ethnic Skin"; seven mentioned a non-English language. A significantly lower percentage of non-white-presenting patients (p < 0.001) and providers (p < 0.001) were pictured on the selected dermatology websites than reported in the Census. These findings suggest that the images on the homepages of private practice dermatology websites were not reflective of the racial diversity of the metropolitan area in which each practice is located. Private practice dermatologists should be mindful of how their services are represented online, as it may dissuade potential minoritized patients from seeking dermatologic care.

Doxycycline-Associated Hyperpigmentation: A Case Report and Literature Review.

Drug-induced hyperpigmentation is an adverse cutaneous effect; it has been associated with several systemic medications. A healthy 40-year-old man developed facial and dorsal hand hyperpigmentation within two weeks of beginning doxycycline monohydrate 100 milligrams twice daily for acne. Skin pigmentation significantly diminished at a follow-up evaluation two months after discontinuing the medication. Doxycycline-associated skin hyperpigmentation, albeit uncommon, has been described in 18 patients in the literature, including our patient. The demographics included 13 males and five females ranging in age from 11 to 87 years; eight of the patients were less than 50 years old and ten of the patients were over 60 years old. Doxycycline-associated hyperpigmentation frequently occurs on the face and can occur at the site of a previous scar. In most cases, doxycycline was discontinued with the resolution of hyperpigmentation.

Real-Time Reflectance Confocal Microscopy of Cutaneous Graft-versus-Host Disease Correlates with Histopathology.

Reflectance confocal microscopy (RCM) allows noninvasive, real-time evaluation of the skin at a resolution akin to histopathology (HP), but its application in cutaneous graft-versus-host disease (GVHD) has not been extensively assessed. We describe RCM features of cutaneous GVHD including acute (aGVHD), late acute, chronic (cGVHD; sclerotic and nonsclerotic subtypes), and inactive GVHD and correlate RCM with same-site HP for a subset of patients. Thirty-two adult and pediatric allogeneic hematopoietic cell transplantation (allo-HCT) recipients with cutaneous GVHD received RCM imaging of ≥1 lesions (n = 44), 13 of which necessitated skin biopsy. RCM images were deidentified and assessed by 2 RCM experts blinded to clinical and HP findings to reach a consensus on the features and patterns of the inflammatory dermatoses. Major RCM features (present in ≥65% of lesional sites) and patterns were reported. To determine the correlation between RCM and HP, detection of cellular features and patterns of inflammatory dermatoses were compared using percent agreement and prevalence-adjusted, bias-adjusted kappa estimates. Seven patients with early or late aGVHD (7 lesions) had irregular honeycombing, spongiosis, dermoepidermal junction (DEJ) and dermal inflammation, and melanophages; those with early aGVHD also had hyperkeratosis, dilated vessels, and coarse connective tissue. Both groups had an interface dermatitis pattern. Eighteen patients with nonsclerotic cGVHD (24 lesions) had irregular honeycombing, spongiosis, DEJ and dermal inflammation, dilated vessels, coarse connective tissue, and interface and spongiotic dermatitis patterns. Three sclerotic patients with cGVHD (7 lesions) had irregular honeycombing, DEJ and dermal inflammation with an interface dermatitis pattern. Four patients with inactive GVHD (6 lesions) showed minimal inflammation. RCM and HP had similar detection rates for 6 of 13 features and overall patterns important for diagnosis in 2 patients with late aGVHD (2 lesions; 15%) and 10 with nonsclerotic cGVHD (11 lesions; 85%) necessitating skin biopsy. RCM can detect features commonly reported in cutaneous GVHD and is comparable to HP. Additional characterization of cutaneous GVHD by RCM may enable future use in diagnosing, monitoring, or predicting disease in real time.

Social Media in Dermatology and an Overview of Popular Social Media Platforms.

PURPOSE OF REVIEW: Social media provides an accessible and increasingly popular avenue for sharing healthcare information, networking, and outreach in dermatology. We provide an overview of prominent social media platforms, also known as applications or apps, as well as a discussion of their influence and implications for the field. RECENT FINDINGS: The various collaborative features of Facebook, Twitter, Instagram, TikTok, YouTube, Snapchat, and other emerging platforms have proven appealing to organizations and users seeking dermatology-related content and medical advice. However, the potential for propagation of inaccurate or even dangerous information is high. SUMMARY: Despite the risks associated with social media usage, dermatology can benefit from opportunities to connect and engage with audiences through these platforms. Dermatologists should be encouraged to increase their presence on multiple social media apps to dispel and counteract misleading posts with evidence-based knowledge.

NAA10 variant in 38-week-gestation male patient: a case study.

We present a male patient born at 38-wk gestation with rhizomelic shortening of extremities, hepatomegaly, ventriculomegaly, heart failure, severely depressed left ventricular function, biventricular hypertrophy, and biatrial enlargement. Additional physical findings included anteriorly displaced anus, vertebral anomalies, and brachydactyly. The patient's cardiac malformations led to persistent hypotension, sinus tachycardia, and multiorgan failure in the absence of arrhythmias. Rapid whole-exome sequencing was ordered on day of life (DOL) 8. The patient's family elected to withdraw supportive care, and he passed away that evening. Whole-exome sequencing returned posthumously and identified a variant in NAA10, E100K. The genotype-phenotype was closest to Ogden syndrome or amino-terminal acetyltransferase deficiency. Typical features of this rare X-linked syndrome include progeroid appearance, failure to thrive, developmental delays, hypotonia, and cardiac arrhythmias. Other family members were tested and the patient's mother, who has a history of mild intellectual disability, as well as a daughter born later, were identified as carriers. All carriers showed no cardiac findings. The carrier sister has manifested developmental delay and cortical atrophy. Protein modeling, evolution, dynamics, population variant assessments, and immunoprecipitation depict the deleterious nature of the variant on the interactions of NAA10 with NAA15 These findings had subsequent implications for posthumous diagnosis of the index patient, for female carriers, and regarding family planning. We highlight how these rapid genetic tests and variant characterization can potentially lead to informed decision-making between health-care providers and family members of patients with critical or lethal conditions when treatment options are limited.