This month’s news from across the specialty
What’s hot
August 1, 2023
In this monthly column, members of the DermWorld Editorial Advisory Workgroup identify exciting news from across the specialty.
SARMs is a growing and dangerous social media trend.
The U.S. Food and Drug Administration (FDA) issued a warning that they are receiving adverse event reports related to “selective androgen receptor modulators,” popularly known as SARMs. SARMs are chemicals that mimic the effects of testosterone and anabolic steroids and are not FDA approved. Social media targeting teenagers and young adults promote SARMs as fast-track methods to improve physical appearance, gain muscle mass, and increase athletic performance. Although they are being labeled as dietary supplements, the FDA emphasizes that they are not dietary supplements — they are unapproved drugs that have not been reviewed by the FDA for safety or effectiveness. It has also issued warning letters to companies selling SARMs and has pursued criminal actions against distributors.
As dermatologists, we are likely to see SARMs causing severe scarring acne, elevated ALT (for example during isotretinoin laboratory monitoring), or androgenic alopecia. SARMs have also been reported to cause rhabdomyolysis, tendon rupture, heart attacks, strokes, psychosis, hallucinations, sleep disturbance, sexual dysfunction, acute liver failure, infertility, miscarriage, and testicular shrinkage (J Xenobiot. 2023 Jun;13(2): 218-36).
Dermatologists should consider screening young patients with severe acne, elevated ALT, or hair loss for the use of products that increase muscle mass or enhance athletic performance. In young patients who are using performance-enhancing substances, a better choice is to concentrate on training, conditioning, eating well, staying hydrated, and getting plenty of rest. Adverse events to SARMs should be reported to the FDA’s MedWatch Adverse Event Reporting Program.
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It has been amazing to witness the considerable progress achieved in the treatment of metastatic melanoma. When I started my dermatology residency, dacarbazine and interleukin-2 were the only FDA-approved therapies, and neither was particularly effective. Today, oncologists can consider using drugs that inhibit CTLA-4 (ipilimumab), PD-1 (pembrolizumab, nivolumab), LAG-3 (relatimab), BRAF kinase (vemurafenib, dabrafenib), or MEK (trametinib, cobimetinib), as well as an oncolytic virus (talimogene laherparepvec).
The most recent advance, however, has not been another drug, but rather the knowledge of when to optimally use a drug (like most things in life, timing really is everything!). In a phase 2 randomized trial, among patients undergoing surgical resection for stage III or IV melanoma, two-year, event-free survival was significantly longer with neoadjuvant plus adjuvant pembrolizumab (72%) compared to adjuvant pembrolizumab alone (49%) (NEJM. 2023; 388: 813-823). In other words, giving three out of 15 total doses of pembrolizumb prior to surgery was a better strategy than proceeding directly to surgery and having all 15 doses of pembrolizumab given afterwards. These data add to a growing body of evidence supporting the use of neoadjuvant immunotherapy in oncology, as shown with non-small-cell lung cancer and triple-negative breast cancer. The reason for improved responses with neoadjuvant immunotherapy is likely due to the availability of antitumor T cells, allowing functional inhibition of the immune checkpoint. If these antitumor T cells are removed during surgical resection of metastatic disease before giving immune checkpoint inhibitors, the immune response generated is simply not as broad and robust.
The two most common causes of acquired facial hyperpigmentation (AFH), post-inflammatory hyperpigmentation (PIH) and melasma, are relatively common, psychologically distressing issues among skin of color patients. Varied treatment algorithms are mostly guided by expert opinions as outlined in JAMA Dermatology (doi:10.1001/jamadermatol.2023.1414).
Mild AFH can be addressed with hydroquinone (HQ) 4% using a 12-week pulse, tapering regimen, then HQ holiday/maintenance with non-HQ topicals. Moderate to severe AFH requires compounding hydroquinone with topical retinoid and steroid. An annual schedule is nightly use for 12 weeks in the summer, reducing to weekend-only use in the fall/spring, and taking HQ winter breaks.
In severe or refractory disease, consider oral tranexamic acid (TXA) 325 mg BID for three months, tapered to QD for three months versus summer pulsing only, then using HQ and non-HQ topicals in fall/spring. TXA requires careful patient counseling on the risks of thrombotic events, teratogenicity, etc.
Non-HQ based topicals used for prevention of recurrence, maintenance, and when appropriate in pregnancy/lactation include topical retinoid, azelaic acid, topical TXA, niacinamide, kojic acid, etc. Procedures such as chemical peels and microneedling (+/- PRP, topical TXA) can be incorporated with caution. Routine use of lasers to manage AFH in patients with skin of color is less frequently recommended due to associated risks.
AFH is chronic, persistent, and relapsing, requiring multimodal and continuous treatment that must incorporate a defined maintenance plan. Management begins with careful patient selection with history taking/questionnaires and lab tests when indicated. Document the discussion and make sure patients understand the risks/adverse effects/costs. Get consent and pretreatment photos. The patient must commit to diligent skincare and photoprotection with high SPF, broad-spectrum, iron oxide-containing sunscreen.
Concern for exogenous ochronosis is warranted, especially with the rising popularity of brief, low-cost, online “consultations” that lead to super-potent HQ prescriptions. Given the relapsing nature of AFH, the U.S. rate of exogenous ochronosis may start to resemble the mind-boggling numbers in countries where HQ is available OTC. Emphasizing this risk to the patient, as well as early incorporation of concomitant, non-hydroquinone-based topicals are crucial for prevention.
More What’s Hot!
Check out more What’s Hot columns from the DermWorld Editorial Advisory Workgroup.
