This month’s news from across the specialty

September 1, 2024

In this monthly column, members of the DermWorld Editorial Advisory Workgroup identify exciting news from across the specialty.  

A novel genetic study that maps mutations in successive stages of cutaneous squamous cell carcinoma (cSCC) in mice has reinforced several theories of carcinogenesis and is offering hope for a future of targeted therapy for individual tumors that are characterized by stem-cell growth patterns.

The authors combined broad population genetics with narrow single cell genetics to find meaning in the large numbers of somatic mutations in cSCC. They started with bulk tumor expression profiling from hundreds of samples from normal skin, benign papillomas, cSCC, and metastatic cSCC. This created an extensive library of the genes that are and are not expressed in cSCC. Next, they applied machine learning to model the relationships in gene expression. Networks of associated genes were named ‘metagenes’ and the authors noted that several metagenes included genes that have been identified in keratinocytic stem cells.

The metagene networks were mapped in thousands of single cells from normal skin, benign papillomas, cSCC, and metastatic cSCC. The single cell data supported the bulk data in that the metagene networks were found to be enriched or diminished in concordance with tumor stage. Additionally, metagenes were associated with divergent cell growth patterns. While individual gene expression was inconsistent, the metagene expression was highly consistent. This work highlights that the near-infinite possible somatic mutation combinations are aligned with only a small number of pathways toward carcinogenesis. The authors confirmed that the metagenes could predict treatment responses. These findings point to a near future in which human cSCC metagene expression profiling directs novel cocktails of old drugs.

Diagnosing lupus in a healthy patient can be a life-altering event. Many patients classified with SLE only have mucocutaneous or laboratory manifestations that do not require treatment. Identifying patients at risk for severe systemic lupus erythematosus (sSLE) is critical.

A recent cohort study enrolled 149 patients with cutaneous lupus erythematosus (CLE) from 2021 to 2023 to investigate factors leading to sSLE (doi: 10.1016/j.jaad.2024.01.041). At baseline, 87% had isolated CLE, and 13% had laboratory abnormalities (lab CLE). Patients with lab CLE were younger (median age 23 vs. 33 years) and more frequently required immunosuppressive therapy. In contrast, those with only CLE were less likely to have higher phototypes (V to VI) or subacute CLE, received fewer treatments, and more often achieved long-term remission. Over a median follow-up of 11.3 years, 7% of patients progressed to sSLE at a median time period of 11.6 years from CLE diagnosis. Lab CLE patients had a significantly higher risk of developing sSLE compared to those with only CLE (hazard ratio 6.69).

The authors proposed a 3-item score to predict sSLE risk, which demonstrated 85.7% sensitivity, 79.1% specificity, and 98.9% negative predictive value in this cohort. Factors in the score included age <25 years at diagnosis (1 point), phototypes V to VI (1 point), and ANA titer ≥1:320 (5 points). No patient with a score ≤2 progressed to sSLE.

This study sheds light on clues to the early identification and monitoring of high-risk CLE patients. Future studies with more diverse populations are needed to validate these findings.

Safety concerns have recently emerged regarding one of our most trusted active ingredients in the treatment of acne, folliculitis, and other follicular occlusion disorders. Benzoyl peroxide is a mainstay in most of our practices and widely available in over-the-counter preparations in various strengths, likely contributing to the traction this story enjoyed in popular media. On March 6, 2024, independent testing laboratory Valisure LLC petitioned the FDA requesting recalls of benzoyl peroxide-containing products due to the presence of benzene, a known human carcinogen. Benzene develops as a product of the decomposition of benzoyl peroxide over time, and as such, Valisure claims that their testing methods of exposing the product to high temperatures during testing — which raised concerns about the validity of their findings — was done to evaluate the product’s stability over its shelf life including transportation and storage. Dr. Christopher Bunick, an associate professor of dermatology and physician at the Yale School of Medicine, has advised that further testing is needed to validate these findings, and in the interim, to consider a proportional response to the Valisure data rather than a full recall. He suggests maintaining temperature control over these products and replacing them every three to six months regardless of expiration date. At this time, no recall has been issued, and the American Academy of Dermatology’s position is that we await further guidance from the FDA.

The use of immunomodulating and immunosuppressing agents during patch testing and their impact on the results of patch testing has been a hot topic of discussion. The North American Contact Dermatitis Group published expert-opinion guidelines regarding immunomodulatory agents in 2012 indicating that TNF-α inhibitors and methotrexate had little or no effect on patch test results; however, other drugs such as prednisone, azathioprine, cyclosporine, and mycophenolate mofetil were felt to have a dose-dependent impact. Since then, many more drugs have entered the marketplace. A recent study looked at the impact of systemic immunomodulating therapies on patch testing results in children. The authors identify a small sample size as a limitation of the study. However, their preliminary results indicate immunomodulating therapies may not have a large negative impact on the development of positive patch test results in children. They found that children on these medications were still able to elicit positive reactions and that patients patch tested both on immunomodulators and in the control group had similar odds of improvement after allergen avoidance. They also noted no significant difference in the odds of having at least one positive reaction in patients on immunomodulators compared to controls and the rate of positive patch test reactions in patients on immunomodulators compared to controls was similar.

Many patch test experts prefer to test off immunomodulating therapies if possible. Recognizing that this is not always possible, studies like this help to affirm that positive results can still be elicited while on these medications. Further studies to determine if certain allergens are impacted or if some patch test reactions are subdued or suppressed will help us better understand the impact of these drugs on patch testing.

Additional DermWorld Resources