Mosaic RASopathies concept: different skin lesions, same systemic manifestations?

BACKGROUND: Cutaneous epidermal nevi are genotypically diverse mosaic disorders. Pathogenic hotspot variants in HRAS, KRAS, and less frequently, NRAS and BRAF may cause isolated keratinocytic epidermal nevi and sebaceous nevi or several different syndromes when associated with extracutaneous anomalies. Therefore, some authors suggest the concept of mosaic RASopathies to group these different disorders. METHODS: In this paper, we describe three new cases of syndromic epidermal nevi caused by mosaic HRAS variants: one associating an extensive keratinocytic epidermal nevus with hypomastia, another with extensive mucosal involvement and a third combining a small sebaceous nevus with seizures and intellectual deficiency. Moreover, we performed extensive literature of all cases of syndromic epidermal nevi and related disorders with confirmed pathogenic postzygotic variants in HRAS, KRAS, NRAS or BRAF. RESULTS: Most patients presented with bone, ophthalmological or neurological anomalies. Rhabdomyosarcoma, urothelial cell carcinoma and pubertas praecox are also repeatedly reported. KRAS pathogenic variants are involved in 50% of the cases, especially in sebaceous nevi, oculoectodermal syndrome and encephalocraniocutaneous lipomatosis. They are frequently associated with eye and brain anomalies. Pathogenic variants in HRAS are rather present in syndromic keratinocytic epidermal nevi and phacomatosis pigmentokeratotica. CONCLUSION: This review delineates genotype/phenotype correlations of syndromic epidermal nevi with somatic RAS and BRAF pathogenic variants and may help improve their follow-up.

Immune checkpoint inhibitors unleash pathogenic immune responses against the microbiota.

Immune checkpoint inhibitors (ICIs) are essential components of the cancer therapeutic armamentarium. While ICIs have demonstrated remarkable clinical responses, they can be accompanied by immune-related adverse events (irAEs). These inflammatory side effects are of unclear etiology and impact virtually all organ systems, with the most common being sites colonized by the microbiota such as the skin and gastrointestinal tract. Here, we establish a mouse model of commensal bacteria-driven skin irAEs and demonstrate that immune checkpoint inhibition unleashes commensal-specific inflammatory T cell responses. These aberrant responses were dependent on production of IL-17 by commensal-specific T cells and induced pathology that recapitulated the cutaneous inflammation seen in patients treated with ICIs. Importantly, aberrant T cell responses unleashed by ICIs were sufficient to perpetuate inflammatory memory responses to the microbiota months following the cessation of treatment. Altogether, we have established a mouse model of skin irAEs and reveal that ICIs unleash aberrant immune responses against skin commensals, with long-lasting inflammatory consequences.

Reemergence of Clade IIb-Associated Mpox, Germany, July-December 2023.

In July 2023, clade IIb-associated mpox reemerged in Germany at low levels, mainly affecting men who have sex with men. We report a representative case and phylogeny of available genome sequences. Our findings underscore the need for standardized surveillance and indication-based vaccination to limit transmission and help prevent endemicity.

Precision Dermatology: A Review of Molecular Biomarkers and Personalized Therapies.

The evolution of personalized medicine in dermatology signifies a transformative shift towards individualized treatments, driven by the integration of biomarkers. These molecular indicators serve beyond diagnostics, offering insights into disease staging, prognosis, and therapeutic monitoring. Specific criteria guide biomarker selection, ensuring attributes like specificity, sensitivity, cost feasibility, stability, rapid detection, and reproducibility. This literature review, based on data from PubMed, SCOPUS, and Web of Science, explores biomarkers in Hidradenitis Suppurativa (HS), Psoriasis, Atopic Dermatitis (AD), Alopecia Areata (AA), Vitiligo, and Chronic Spontaneous Urticaria (CSU). In HS, TNF-α, IL-1ß, and MMPs serve as biomarkers, influencing targeted therapies like adalimumab and anakinra. Psoriasis involves biomarkers such as TNF-α, IL-23, and HLA genes, shaping treatments like IL23 and IL17 inhibitors. AD biomarkers include ECP, IL-4, IL-13, guiding therapies like dupilumab and tralokinumab. For AA, lipocalin-2, cytokines, and genetic polymorphisms inform JAK inhibitors' use. Vitiligo biomarkers range from cytokines to genetic markers like TYR, TYRP1, guiding treatments like JAK inhibitors. CSU biomarkers encompass IgE, cytokines, and autologous serum tests, influencing therapies like omalizumab and cyclosporine. Comparing conditions, common proinflammatory markers reveal limited specificity. While some biomarkers aid diagnosis and standard treatments, others hold more scientific than clinical value. Precision medicine, driven by biomarkers, has shown success in skin malignancies. Future directions involve AI-powered algorithms, nanotechnology, and multi-omics integration for personalized dermatological care.

CKBA suppresses mast cell activation via ERK signaling pathway in murine atopic dermatitis.

Atopic dermatitis (AD) is a common inflammatory skin disorder. Mast cells play an important role in AD because they regulate allergic reactions and inflammatory responses. However, whether and how the modulation of mast cell activity affects AD has not been determined. In this study, we aimed to determine the effects and mechanisms of 3-O-cyclohexanecarbonyl-11-keto-ß-boswellic acid (CKBA). This natural compound derivative alleviates skin inflammation by inhibiting mast cell activation and maintaining skin barrier homeostasis in AD. CKBA markedly reduced serum IgE levels and alleviated skin inflammation in calcipotriol (MC903)-induced AD mouse model. CKBA also restrained mast cell degranulation both in vitro and in vivo. RNA-seq analysis revealed that CKBA downregulated the extracellular signal-regulated kinase (ERK) signaling in BM-derived mast cells activated by anti-2,4-dinitrophenol/2,4-dinitrophenol-human serum albumin. We proved that CKBA suppressed mast cell activation via ERK signaling using the ERK activator (t-butyl hydroquinone) and inhibitor (selumetinib; AZD6244) in AD. Thus, CKBA suppressed mast cell activation in AD via the ERK signaling pathway and could be a therapeutic candidate drug for AD.

Association of Cutaneous Keloids, Hypertrophic Scarring, and Fibrosis with Risk of Postoperative Proliferative Vitreoretinopathy.

PURPOSE: To assess an association between cutaneous keloids, hypertrophic scarring, and fibrosis (KHF) and risk of postoperative proliferative vitreoretinopathy (PVR) after rhegmatogenous retinal detachment (RRD) repair. DESIGN: Retrospective, population-based cohort study. PARTICIPANTS: Patients aged ≥ 18 years who underwent initial retinal detachment (RD) repair with pars plana vitrectomy with or without scleral buckle (SB) (Current Procedural Terminology [CPT] 67108), pneumatic retinopexy (67110), and primary SB (67107) from January 1, 2003, to March 1, 2023. METHODS: A de-identified electronic health record database through TriNetX, a global health research network, was used to analyze patients. Patients were queried for International Classification of Diseases, 10th Revision (ICD-10) codes L91.0 (hypertrophic scar) and L90.5 (scar conditions and fibrosis of skin). Frequency of subsequent diagnosis of PVR (H35.2) and CPT codes for secondary surgery including complex RD repair (67113) were determined. Patients with proliferative diabetic retinopathy (PDR) (ICD-10 H10.35/H11.35) were excluded. Descriptive statistics (Z-test) and propensity score matching (PSM) were used to match for age, sex, and race. MAIN OUTCOME MEASURES: Prevalence of H35.2 and CPT 67113 within 180 days after RRD repair in the KHF cohort versus the non-KHF cohort. RESULTS: Among patients with CPT 67108, 1061 in each cohort (KHF and non-KHF) were analyzed after PSM. The mean (standard deviation) age was 60.7 (15.2) years. Within 180 days, 10.1% of patients in the KHF cohort and 3.4% in the non-KHF cohort had a diagnosis of PVR (H35.2) (P < 0.001, odds ratio [OR], 3.2; 95% confidence interval [CI], 2.13-4.71). A total of 8.3% of patients in the KHF cohort and 5.4% of patients in the non-KHF cohort underwent complex RD repair (CPT 67113) (P = 0.008; OR, 3.2; 95% CI, 1.13-2.25). When including all RD repair types (CPT 67108, 67110, 67107), the rate of PVR diagnosis was still significantly greater in the KHF cohort than in the non-KHF cohort (9.0% vs 4.2%, P < 0.01; OR, 2.28; 95% CI, 1.64-3.16). CONCLUSIONS: A dermatologic history of KHF may be a risk factor for PVR after RD repair. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Pigmented acuminated condylomas seborrhoeic keratosis-like: a new entity?

BACKGROUND: Condyloma acuminatum is caused by human papillomavirus (HPV), which typically presents as excrescent, pedunculated, papillomatous lesions which may be of a pale colour. On rare occasions, we have observed pigmented genital lesions that are similar to seborrhoeic keratoses, but with histological findings of condyloma acuminatum and positive genotyping for HPV. We have termed these 'seborrhoeic keratosis-like' type condylomas. METHODS: This is an observational retrospective study. The following clinical data were collected: age, sex, time of evolution, location, isolated or multiple lesions, monomorphous or polymorphous/mixed lesions. HPV genotyping was performed in all cases, and excision for histological study in eight cases. RESULTS: A total of 31 patients were diagnosed with this type of pigmented condylomata acuminata. Of these, 16 had isolated lesions (less than five lesions) and 15 had multiple lesions. 67% of the lesions exhibited slow growth, with an evolution period of greater than 1 year. The most frequent location was the base of the penis and pubis. HPV genotyping of the lesions was positive in all cases, with the HPV-6 genotype predominating (28 cases, 90.3%). The lesions exhibited dermoscopic differences from other pigmented lesions and histological findings attributable to HPV infection (pseudoparakeratosis, koilocytosis, etc) and others similar to those observed in seborrhoeic keratoses. CONCLUSIONS: A total of 31 patients were diagnosed with pigmented verrucous lesions, excrescents, isolated or multiple, in the genital region. These lesions exhibited clinical characteristics similar to seborrhoeic keratoses, with positive genotyping for HPV. In the majority of cases, the genotype was HPV-6. These lesions have been named 'pigmented condylomata acuminata seborrhoeic keratosis-like'. Only 10 cases of these lesions have been described in the literature.

A deep learning algorithm to detect cutaneous squamous cell carcinoma on frozen sections in Mohs micrographic surgery: A retrospective assessment.

Intraoperative margin analysis is crucial for the successful removal of cutaneous squamous cell carcinomas (cSCC). Artificial intelligence technologies (AI) have previously demonstrated potential for facilitating rapid and complete tumour removal using intraoperative margin assessment for basal cell carcinoma. However, the varied morphologies of cSCC present challenges for AI margin assessment. The aim of this study was to develop and evaluate the accuracy of an AI algorithm for real-time histologic margin analysis of cSCC. To do this, a retrospective cohort study was conducted using frozen cSCC section slides. These slides were scanned and annotated, delineating benign tissue structures, inflammation and tumour to develop an AI algorithm for real-time margin analysis. A convolutional neural network workflow was used to extract histomorphological features predictive of cSCC. This algorithm demonstrated proof of concept for identifying cSCC with high accuracy, highlighting the potential for integration of AI into the surgical workflow. Incorporation of AI algorithms may improve efficiency and completeness of real-time margin assessment for cSCC removal, particularly in cases of moderately and poorly differentiated tumours/neoplasms. Further algorithmic improvement incorporating surrounding tissue context is necessary to remain sensitive to the unique epidermal landscape of well-differentiated tumours, and to map tumours to their original anatomical position/orientation.

Effect of abrocitinib on skin biomarkers in patients with moderate-to-severe atopic dermatitis.

BACKGROUND: This is the first report on the effects of abrocitinib, a Janus kinase 1-selective inhibitor, on the expression of skin biomarkers in patients with moderate-to-severe atopic dermatitis (AD). METHODS: JADE MOA (NCT03915496) was a double-blind Phase 2a trial. Adults were randomly assigned 1:1:1 to receive monotherapy with once-daily abrocitinib 200 mg, abrocitinib 100 mg, or placebo for 12 weeks. The primary endpoint was change from baseline in markers of inflammation (matrix metalloproteinase [MMP]-12), epidermal hyperplasia (keratin-16 [KRT16]), T-helper 2 (Th2) immune response (C-C motif chemokine ligand [CCL]17, CCL18, and CCL26), and Th22 immune response (S100 calcium binding protein A8, A9, and A12 [S100A8, S100A9, and S100A12]) in skin through 12 weeks. RESULTS: A total of 46 patients received abrocitinib 200 mg (n = 14), abrocitinib 100 mg (n = 16), or placebo (n = 16). Abrocitinib improved AD clinical signs and reduced itch. Gene expression of MMP-12, KRT16, S100A8, S100A9, and S100A12 was significantly decreased from baseline with abrocitinib 200 mg (at Weeks 2, 4, and 12) and abrocitinib 100 mg (at Weeks 4 and 12) in a dose-dependent manner. Abrocitinib 200 mg resulted in significant decreases from baseline in CCL17 expression at Week 12 and CCL18 expression at Weeks 2, 4, and 12; no significant decreases were observed for CCL26. CONCLUSIONS: Alongside improvements in clinical signs and symptoms of AD, 12 weeks of abrocitinib treatment resulted in downregulation of genes associated with inflammation, epidermal hyperplasia, and Th2 and Th22 immune responses in the skin of patients with moderate-to-severe AD.

Clinical and molecular effects of oral CCR4 antagonist RPT193 in atopic dermatitis: A Phase 1 study.

BACKGROUND: RPT193 is an orally administered small molecule antagonist of the human C-C motif chemokine receptor 4 (CCR4) that inhibits the migration and downstream activation of T-helper Type 2 (Th2) cells. We investigated single- and multiple-ascending doses of RPT193 in healthy subjects, and multiple doses of RPT193 in subjects with moderate-to-severe atopic dermatitis (AD). METHODS: This was a first-in-human randomized, placebo-controlled Phase 1a/1b monotherapy study (NCT04271514) to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and CCR4 surface receptor occupancy in eligible healthy subjects and subjects with moderate-to-severe AD. Clinical efficacy and skin biomarker effects of RPT193 monotherapy were assessed as exploratory endpoints in AD subjects. RESULTS: In healthy (n = 72) and AD subjects (n = 31), once-daily RPT193 treatment was generally well tolerated, with no serious adverse events reported and all treatment-emergent adverse events reported as mild/moderate. In AD subjects, numerically greater improvements in clinical efficacy endpoints were observed with RPT193 monotherapy versus placebo up to the end of the treatment period (Day 29), with statistically significant improvement, compared to Day 29 and placebo, observed 2 weeks after the end of treatment (Day 43) on several endpoints (p < .05). Moreover, significant changes in the transcriptional profile were seen in skin biopsies of RPT193-treated versus placebo-treated subjects at Day 29, which were also significantly correlated with improvements in clinical efficacy measures. CONCLUSIONS: To our knowledge, this is the first clinical study with an oral CCR4 antagonist that showed clinical improvement coupled with modulation of the cutaneous transcriptomic profile in an inflammatory skin disease.

Implementation of Direct-to-Patient Mobile Teledermatology in VA.

BACKGROUND: Innovative technology can enhance patient access to healthcare but must be successfully implemented to be effective. OBJECTIVE: We evaluated Department of Veterans Affairs' (VA's) implementation of My VA Images, a direct-to-patient asynchronous teledermatology mobile application enabling established dermatology patients to receive follow-up care remotely instead of in-person. DESIGN /PARTICIPANTS/APPROACH: Following pilot testing at 3 facilities, the app was introduced to 28 facilities (4 groups of 7) every 3 months using a stepped-wedge cluster-randomized design. Using the Organizational Theory of Implementation Effectiveness, we examined the app's implementation using qualitative and quantitative data consisting of encounter data from VA's corporate data warehouse; app usage from VA's Mobile Health database; bi-monthly reports from facility representatives; phone interviews with clinicians; and documented communications between the operational partner and facility staff. KEY RESULTS: Implementation policies and practices included VA's vision to expand home telehealth and marketing/communication strategies. The COVID-19 pandemic dominated the implementation climate by stressing staffing, introducing competing demands, and influencing stakeholder attitudes to the app, including its fit to their values. These factors were associated with mixed implementation effectiveness, defined as high quality consistent use. Nineteen of 31 exposed facilities prepared to use the app; 10 facilities used it for actual patient care, 7 as originally intended. Residents, nurse practitioners, and physician assistants were more likely than attendings to use the app. Facilities exposed to the app pre-pandemic were more likely to use and sustain the new process. CONCLUSIONS: Considerable heterogeneity existed in implementing mobile teledermatology, despite VA's common mission, integrated healthcare system, and stakeholders' broad interest. Identifying opportunities to target favorable facilities and user groups (such as teaching facilities and physician extenders, respectively) while addressing internal implementation barriers including incomplete integration with the electronic health record as well as inadequate staffing may help optimize the initial impact of direct-to-patient telehealth. The COVID pandemic was a notable extrinsic barrier. CLINICAL TRIALS REGISTRATION: NCT03241589.

The Effect of Co-Morbid Psoriasis Diagnosis on Chronic Rhinosinusitis Immunopathology.

INTRODUCTION: Psoriasis is a papulosquamous condition characterized by type 1 (T1) inflammation, while chronic rhinosinusitis (CRS) concurrent with asthma is commonly a type 2 (T2) process. Since psoriasis is predictive for higher rates of CRS, our objective was to determine whether CRS with concurrent psoriasis would share its T1 pathogenic signature. In comparison to T1 CRS, a T2 process can be predicted by presence of more extensive sinus disease via Lund-MacKay score, reduced sense of smell, and greater concurrence of purulent drainage and pain/pressure. METHODS: Subjective measurements of CRS included the Sino-Nasal Outcome Test (SNOT-22) and objective measurements included Lund-MacKay sinus CT score and endoscopic scoring. Outcomes were compared with control subjects with CRS co-presenting with allergies, asthma, or aspirin-exacerbated respiratory disease (AERD). RESULTS: A total of 62 patients (12 CRS alone, 14 CRS/psoriasis, 12 CRS/AERD, 12 CRS/allergic asthmatic, 12 CRS/non-allergic asthmatic) were included. Comparative analysis utilizing χ2 revealed no significant differences in any factor between CRS/psoriatic patients and all other groups associated with T2 presentations. Specifically, psoriatic patients had comparable reductions in smell, similar complaints of pain/pressure, negligible purulent drainage/crusting, and comparable extent of disease on their CT scan, as well as similar blood eosinophilia. The only significant difference was in lack of productivity (p < 0.05) with trends toward reduced concentration, waking up tired, and lack of sleep parameters presumably related to systemic psoriatic manifestations. CONCLUSIONS: Despite the increased prevalence of CRS in psoriasis patients, our data suggest that when present, psoriasis does not predict the presence of a T1 process in the sinuses.

Screening of dermatology drugs for aberrant use-patterns: An application of epidemiologic estimates and measures of inequality in drug use.

AIMS: Dermatology treatments require adherence for safe and effective use. Real-world healthcare databases can reveal drug utilization patterns and uncover inappropriate or unexpected use. This study aimed to analyse dermatology drug utilization patterns using epidemiological and inequality measures, leveraging Danish nationwide registries. It also assessed the feasibility of this method for detecting aberrant drug use. METHODS: We formed a 2019 cohort of all patients treated for skin conditions through Danish healthcare registries. We calculated prevalence, incidence rates and treatment duration for dermatological drugs. Inequality in drug utilization was assessed using Lorenz curves, Gini coefficients and other measures. RESULTS: The study encompassed 1 021 255 patients using 94 dermatology drugs. Most usage aligned with 'expected clinical use', but we detected inequality, with some drugs having high Gini coefficients and disproportionate consumption by the top percentile of users. Notable findings included potential inappropriate antibiotic use, excessive topical corticosteroid use and unexpected drug use duration. CONCLUSIONS: In Denmark, dermatology drugs are used primarily as anticipated, with minimal unexpected patterns. Specific follow-up is required to draw conclusions about inappropriate use. This approach demonstrates broad applicability for screening aberrant drug utilization.

Scaling and periorificial crusts in a pediatric patient.

This case reports a 14-month-old child with Staphylococcal Scalded Skin Syndrome (SSSS). The child presented generalized scaling erythema accompanied by skin pain, and perioral crusts and fissures and she required hospital admission for antibiotic treatment with intravenous cloxacillin and hidroelectrolyte replacement.SSSS is a blistering skin disorder, mainly affecting children, caused by specific Staphylococcus aureus strains producing exfoliative toxins. It shows erythema in skin folds progressing to blisters within 48 h, often with perioral crusts and fissures. Its diagnosis relies on clinical assessment and it often requires intravenous antibiotics for its treatment.

How to explain the beneficial effects of platelet-rich plasma.

Platelet-rich plasma (PRP) is the platelet and leukocyte-containing plasmatic fraction of anticoagulated autologous blood. While evidence supporting the clinical use of PRP in dentistry is low, PRP is widely used in sports medicine, orthopedics, and dermatology. Its beneficial activity is commonly attributed to the growth factors released from platelets accumulating in PRP; however, evidence is indirect and not comprehensive. There is thus a demand to revisit PRP with respect to basic and translational science. This review is to (i) recapitulate protocols and tools to prepare PRP; (ii) to discuss the cellular and molecular composition of PRP with a focus on platelets, leukocytes, and the fibrin-rich extracellular matrix of coagulated plasma; and finally (iii) to discuss potential beneficial effects of PRP on a cellular and molecular level with an outlook on its current use in dentistry and other medical fields.

Pregnancy, parturition and postpartum considerations among patients with vulvar lichen sclerosus: A retrospective cross-sectional online survey.

OBJECTIVE: Characterise VLS and obstetric considerations among women during pregnancy, parturition and postpartum. DESIGN: Retrospective cross-sectional online survey, 2022. SETTING: International, English-speakers. POPULATION: Self-identified individuals aged 18-50 diagnosed with VLS with symptom onset prior to pregnancy. METHODS: Participants recruited from social media support groups and accounts, completed a 47-question survey including yes/no, multiple answer, and free-text responses. Data were analysed with frequency, means and the Chi-square test. MAIN OUTCOME MEASURES: VLS symptom severity, mode of delivery, perineal laceration, source and sufficiency of information provided about VLS and obstetrics, anxiety about delivery, and postpartum depression. RESULTS: Of 204 responses, 134 met inclusion criteria, encompassing 206 pregnancies. Mean respondent age was 35 years (SD 6) and mean age of VLS symptom onset, diagnosis and birth, was 22 (SD 8), 29 (SD 7) and 31 (SD 4) years, respectively. Symptoms decreased in 44% (n = 91) of pregnancies and increased during the postpartum period in 60% (n = 123). In all, 67% (n = 137) of pregnancies resulted in vaginal birth and 33% (n = 69) in caesarean birth. Anxiety for delivery due to VLS symptoms was reported by 50% (n = 103); 31% (n = 63) experienced postpartum depression. Of respondents previously diagnosed with VLS, 60% (n = 69) used topical steroids prior to pregnancy, 40% (n = 45) were treated during pregnancy and 65% (n = 75) postpartum. In all, 94% (n = 116) reported receiving an insufficient amount of information on the topic. CONCLUSION: In this online survey, we found reported symptom severity remained unchanged or decreased during pregnancy, but increased postpartum. Use of topical corticosteroids decreased during pregnancy compared with before and after pregnancy. Half of the respondents reported anxiety regarding VLS and delivery.

Risk factors and outcomes of melanoma in children and adolescents: A retrospective multicenter study.

BACKGROUND: Pediatric melanoma presents with distinct clinical features compared to adult disease. OBJECTIVE: Characterize risk factors and negative outcomes in pediatric melanoma. METHODS: Multicenter retrospective study of patients under 20 years diagnosed with melanoma between January 1, 1995 and June 30, 2015 from 11 academic medical centers. RESULTS: Melanoma was diagnosed in 317 patients, 73% of whom were diagnosed in adolescence (age ≥11). Spitzoid (31%) and superficial spreading (26%) subtypes were most common and 11% of cases arose from congenital nevi. Sentinel lymph node biopsy was performed in 68% of cases and positive in 46%. Fatality was observed in 7% of cases. Adolescent patients with melanoma were more likely to have family history of melanoma (P = .046) compared to controls. LIMITATIONS: Retrospective nature, cohort size, control selection, and potential referral bias. CONCLUSION: Pediatric melanoma has diverse clinical presentations. Better understanding of these cases and outcomes may facilitate improved risk stratification of pediatric melanoma.

The 2023 Annual Report of DataDerm™: The Database of The American Academy of Dermatology (AAD).

The American Academy of Dermatology (AAD) launched DataDerm™ in 2016 as the clinical data registry platform of AAD. DataDerm has evolved to be the largest database in the world containing information about dermatology patients, capturing information about their course of disease, associated therapeutic interventions, and health outcomes. As of December 31, 2022, DataDerm contained data from 14.2 million unique patients and 53.5 million unique patient visits, with 415 practices representing 1,663 clinicians actively participating in DataDerm in 2022. This article is the fourth in a series of Annual Reports about the status of DataDerm. This year's 2023 annual report presents the progress DataDerm has made in conjunction with OM1, the data analytics partner of DataDerm, with a special highlight on the longitudinal care of common dermatologic conditions in the registry and a detailed focus on skin cancer. Furthermore, we review the current status of DataDerm as a robust representation of real world specialty data, reflecting the day-to-day dermatologic care of patients over time.

The 2022 Annual Report of DataDerm: The database of the American Academy of Dermatology.

The American Academy of Dermatology (AAD) launched DataDerm in 2016 as the clinical data registry platform of AAD. DataDerm has evolved to be the largest database containing information about dermatology patients in the world. As of December 31, 2021, DataDerm contained data from 13.2 million unique patients and 47.0 million unique patient visits, with 403 practices representing 1670 clinicians actively participating in DataDerm in 2021. Of the 1670 clinicians participating in DataDerm in 2021, the majority were dermatologists (978) followed by physician assistants (375) and nurse practitioners (163) who are employed by AAD members and meet the AAD definition of the AAD DermCare team. Furthermore, in 2021, 834 clinicians submitted data via DataDerm to the Merit-based Incentive Payment System of the Centers for Medicare & Medicaid Services. This article is the third annual report about the status of DataDerm. This year's 2022 annual report presents the progress DataDerm has made over the past year in conjunction with OM1, the data analytics partner of DataDerm, as well as the current status and future plans of DataDerm.

Noninvasive treatment of cutaneous neurofibromas (cNFs): Results of a randomized prospective, direct comparison of four methods.

BACKGROUND: People with Neurofibromatosis Type 1 (NF1) suffer disfigurement and pain when hundreds to thousands of cutaneous neurofibromas (cNFs) appear and grow throughout life. Surgical removal of cNFs under anesthesia is the only standard therapy, leaving surgical scars. OBJECTIVE: Effective, minimally-invasive, safe, rapid, tolerable treatment(s) of small cNFs that may prevent tumor progression. METHODS: Safety, tolerability, and efficacy of 4 different treatments were compared in 309, 2-4 mm cNFs across 19 adults with Fitzpatrick skin types (FST) I-IV: radiofrequency (RF) needle coagulation, 755 nm alexandrite laser with suction, 980 nm diode laser, and intratumoral injection of 10 mg/mL deoxycholate. Regional pain, clinical responses, tumor height and volume (by 3D photography) were assessed before, 3 and 6 months post-treatment. Biopsies were obtained electively at 3 months. RESULTS: There was no scarring or adverse events > grade 2. Each modality significantly (P < .05) reduced or cleared cNFs, with large variation between tumors and participants. Alexandrite laser and deoxycholate were fast and least painful; 980 nm laser was most painful. Growth of cNFs was not stimulated by treatment(s) based on height and volume values at 3 and 6 months compared to baseline. LIMITATIONS: Intervention was a single treatment session; dosimetry has not been optimized. CONCLUSIONS: Small cNFs can be rapidly and safely treated without surgery.