This month’s news from across the specialty
What’s hot
October 1, 2023
In this monthly column, members of the DermWorld Editorial Advisory Workgroup identify exciting news from across the specialty.
Chronic pruritus is burdensome for patients with chronic kidney disease (CKD) and can be incredibly difficult for dermatologists to manage. Difelikefalin (Korsuva) is the first and only FDA-approved treatment specifically designed for hemodialysis-associated pruritus. A kappa opioid receptor agonist, difelikefalin is currently approved for administration intravenously after dialysis. Pruritus is also common in patients with non-dialysis dependent CKD. However, currently, all treatment for non-dialysis-dependent CKD is off-label and often times ineffective.
A recent phase 2 study of oral difelikefalin in subjects with both non-dialysis and dialysis-dependent CKD and moderate-to-severe pruritus showed a significant reduction in itch intensity (J Am Acad Dermatol. 2023 Aug; 89(2):261-268). Two hundred sixty-nine subjects were randomized to receive oral difelikefalin or placebo once daily for 12 weeks. At week 12, 38.6% of patients receiving difelikefalin 1mg daily achieved complete response as compared to 14.4% receiving placebo. Notably, the effect was rapid starting at week two, and was sustained throughout the treatment period. Treatment was generally well tolerated. Adverse events were mild and included dizziness, fall, constipation, diarrhea, gastroesophageal reflux disease, fatigue, hyperkalemia, hypertension, and urinary tract infection. These positive findings warrant continued exploration of the oral use of this medication which may one day serve as a potential tool in the dermatologist’s toolbox for CKD-associated pruritus.
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Artificial intelligence (AI) is quickly entering the field of medicine. In dermatopathology, we will see increasing methods of utilization with the rapid implementation of whole slide imaging. In a recent study published in Diagnostics from the Netherlands, researchers developed a computer-assisted algorithm to detect mitotic figures in whole slide images. They studied 99 various melanocytic lesions. The algorithm detected mitoses in lesional cells. In other words: It detected mitotic figures in the melanocytic cells, and not the keratinocytes, lymphocytes, or blood vessels. The study found that the overall diagnostic concordance, with or without the algorithm was comparable in most cases (there was no improvement in accurate diagnosis using the algorithm). However, by using this artificial intelligence, there was a small increase in concordance for nevoid melanomas. This type of melanoma is the most difficult for pathologists to detect because it resembles a nevus. While more investigation is needed in this arena, AI could prove to be a valuable benefit to pathologists, dermatopathologists, and their patients.
VEXAS is everywhere! VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a severe adult-onset inflammatory disorder due to an acquired missense somatic mutation in the ubiquitin-like modifier activating enzyme 1 (UBA1) gene of the X chromosome (N Engl J Med. 2020 Dec. 31;383(27):2628-38). Somatic mutations in UBA1 involve hematopoietic stem and myeloid blood cells. The syndrome is much more prevalent than initially suspected. In people over 50 years old, disease-causing UBA1 mutations were found 1 in 4,000 men. Among women in that age bracket, about 1 in 26,000 had the mutations. VEXAS syndrome is underdiagnosed because most physicians have never heard of it. More than 15,000 people in the United States may be suffering from this syndrome, but only 88 patients have been found to date. Patients with VEXAS syndrome have been misdiagnosed with other conditions, including Sweet syndrome, relapsing polychondritis, IgG4-related disease, polyarteritis nodosa. Almost all patients have a macrocytic anemia and go on to develop bone marrow failure. Patients are steroid-dependent and the median survival time from the onset of symptoms is 10 years. Physicians should avoid the use of anakinra in VEXAS, since it has been associated with severe skin reaction at the injection site, for which the mechanism is unknown.
More What’s Hot!
Check out more What’s Hot columns from the DermWorld Editorial Advisory Workgroup.
Ariela Marshall may be a hematologist, but her recent “Piece of My Mind” article in JAMA, titled “Escaping the Siren Song — Transitioning to Part-Time Work” will likely resonate with many dermatologists. It certainly did with me. (Full disclosure: I’m reducing my own clinical workload in the coming months.)
When she completed her fellowship training in 2015 and began a career in academic medicine, her thoughts about part-time work were clear: “That will never be me.”
Fast-forward eight years. Dr. Marshall realized she was logging too many hours at work, when she really wanted more family time; spending too much time seeing outpatients, when she really preferred inpatient consultations; and focusing too much professionally on clinical medicine, when she really enjoyed advocacy work.
By 2023, her thoughts about part-time work had changed: “That is me.”
She has sacrificed financially in transitioning to part-time work. More difficult than the economics, however, was what she describes as “the emotional battle I fought to justify the decision to myself.” She had to reject, she writes, “a false hierarchy of an outdated and biased system of medical training and practice that focuses on titles and publications rather than personal well-being, happiness, and adequate work-life integration.”
“Everyone must decide what success means to them and recognize that this definition can and will change over time,” Dr. Marshall writes. She concludes, “Accommodating those changes by altering one’s priorities and career at different points throughout one’s life is not only necessary but essential to happiness, health, and well-being.” Amen.
