Kyle Tegtmeyer

Cutaneous T-cell lymphomas (CTCLs) are a clinically heterogeneous collection of lymphomas of the skin-homing T cell. To identify molecular drivers of disease phenotypes, we assembled representative samples of CTCLs from patients with diverse disease subtypes and stages. Via DNA/RNA-sequencing, immunophenotyping, and ex vivo functional assays, we identified the landscape of putative driver genes, elucidated genetic relationships between CTCLs across disease stages, and inferred molecular subtypes in patients with stage-matched leukemic disease. Collectively, our analysis identified 86 putative driver genes, including 19 genes not previously implicated in this disease. Two mutations have never been described in any cancer. Functionally, multiple mutations augment T-cell receptor–dependent proliferation, highlighting the importance of this pathway in lymphomagenesis. To identify putative genetic causes of disease heterogeneity, we examined the distribution of driver genes across clinical cohorts. There are broad similarities across disease stages. Many driver genes are shared by mycosis fungoides (MF) and Sezary syndrome (SS). However, there are significantly more structural variants in leukemic disease, leading to highly recurrent deletions of putative tumor suppressors that are uncommon in early-stage skin-centered MF. For example, TP53 is deleted in 7% and 87% of MF and SS, respectively. In both human and mouse samples, PD1 mutations drive aggressive behavior. PD1 wild-type lymphomas show features of T-cell exhaustion. PD1 deletions are sufficient to reverse the exhaustion phenotype, promote a FOXM1-driven transcriptional signature, and predict significantly worse survival. Collectively, our findings clarify CTCL genetics and provide novel insights into pathways that drive diverse disease phenotypes.

In this study, we sought to analyze the readability of online patient education materials (PEMs) related to juvenile dermatomyositis (JDM). We analyzed the top 100 Google results and using six different readability scores, found 53 PEMs which had an average grade reading level of 17.4 (graduate level). PEMs by health care providers were written at higher grade levels than those by non‐health care providers. Our findings demonstrate a clear need for online JDM PEMs that are written at an appropriate reading level and can be comprehended by patients and families of all levels of health literacy.

Antihistamine use for primary treatment of atopic dermatitis (AD) is not recommended, but current guidelines state that sedating antihistamines are favored over non‐sedating antihistamines for relief of burdensome pruritus. We analyzed the National Ambulatory Medical Care Survey data to compare use of antihistamines between dermatologists and non‐dermatologists. Overall, dermatologists are more likely to prescribe sedating than non‐sedating antihistamines when compared to non‐dermatologists (P < .001, δ_abs = 0.45). Patients under 21 years old (P = .03, δ_abs = 0.10) and Black patients (P < .001, δ_abs = 0.19) were also more likely to receive sedating antihistamines than non‐sedating antihistamines. These findings highlight the differential prescribing practices for atopic dermatitis among physicians.

Purpose: Anakinra (Kineret®) is an interleukin-1 receptor antagonist (IL-1Ra) FDA approved for use in rheumatoid arthritis and in neonatal-onset multisystem inflammatory disease (NOMID). It has been used off-label for a variety of dermatologic conditions. A review of the available studies and cases of these off-label uses would be valuable to the dermatologist considering alternative treatments for these oftentimes poorly studied conditions. Materials and methods: The PubMed/MEDLINE, EMBASE, Scopus, and ClinicalTrials.gov databases were searched with the term ‘anakinra.’ Results were manually screened to identify published data on off-label uses of anakinra in dermatologic conditions and systemic conditions with prominent dermatologic manifestations. Results: Anakinra appears to show efficacy for numerous dermatologic conditions, with the strongest evidence for hidradenitis suppurativa, Bechet’s disease, Muckle-Wells syndrome, and SAPHO syndrome. Case reports and case series data are available for numerous other dermatologic conditions. Conclusion: Anakinra is a potential option for patients with certain difficult-to-treat dermatologic diseases, given its relatively benign adverse effect profile and its effectiveness in a wide array of conditions. Overall, anakinra appears to be a promising option in the treatment of numerous dermatologic inflammatory conditions refractory to first line therapies, but further and higher-quality data is needed to clarify its therapeutic role.

Primary cutaneous γδ T cell lymphomas (PCGDTLs) represent a heterogeneous group of uncommon but aggressive cancers. Herein, we perform genome-wide DNA, RNA, and T cell receptor (TCR) sequencing on 29 cutaneous γδ lymphomas. We find that PCGDTLs are not uniformly derived from Vδ2 cells. Instead, the cell-of-origin depends on the tissue compartment from which the lymphomas are derived. Lymphomas arising from the outer layer of skin are derived from Vδ1 cells, the predominant γδ cell in the epidermis and dermis. In contrast, panniculitic lymphomas arise from Vδ2 cells, the predominant γδ T cell in the fat. We also show that TCR chain usage is non-random, suggesting common antigens for Vδ1 and Vδ2 lymphomas respectively. In addition, Vδ1 and Vδ2 PCGDTLs harbor similar genomic landscapes with potentially targetable oncogenic mutations in the JAK/STAT, MAPK, MYC, and chromatin modification pathways. Collectively, these findings suggest a paradigm for classifying, staging, and treating these diseases.

The cost of prescription drugs has increased at rates far exceeding general inflation in recent history, with topical drugs increasing at a disproportionate rate compared to other routes of administration. We assessed the relationship between net changes in the number of therapeutic options, defined as any approved drug or therapeutic equivalent on the market, and prescription topical drug spending. Drugs were divided based on the category of use through pairing of Medicare Part D Prescriber Public Use and Food and Drug Administration (FDA) approved drug products databases. Across drug classes, we modeled the log of the ratio of total spending per unit in 2015 to total spending per unit in 2011 as a linear function of net number of topical therapeutic options over this time period. Primary outcomes include total Medicaid Part D spending on topical drugs and net change in the number of available therapeutic options within each category of use. Total spending on topical drugs increased by 61%, while the number of units dispensed increased by only 18% from 2011–2015. The greatest total spending increases were in categories with few new therapeutic options, such as topical corticosteroid and antifungal medications. Each net additional therapeutic option during 2011–2015 was associated with an reduction in how much relative spending per unit increased (95% CI 2.5%–14.4%, p = 0.013). Stimulating greater competition through increasing the net number of therapeutic options within each major topical category of use may place downward pressure on topical prescription drug spending under medicare Part D.

Precision medicine, which has already begun to make an impact in the field of dermatology, should not only strive to create highly specific, mechanistic therapies for target diseases, but also consider how a patient’s disease profile can affect the potential adverse effects (AEs) of those therapies. Accurate risk assessment of AE profiles for medications—and thus appropriate patient counseling—is extremely difficult and deserves greater attention. Using examples of therapeutics for dermatologic conditions, we show that in order to achieve appropriate, safe and cost-effective prescribing, the AE profile for drugs and how they vary based on specific patient populations and multimorbidity must be adequately considered. For the development of newer drugs such as biologics, there has been closer attention to drug safety and the identification of AEs. For these drugs, the challenge for providers lies in navigating an abundance of information regarding the available guidelines and safety data. There are currently no easy answers for how providers can consistently and adequately account for differing contraindications and side effect profiles. Herein we aim to highlight the need for increased awareness and the collection of relevant data that will allow providers to make more effective and personalized medication selections for their patients.