This month's news from across the specialty

June 1, 2021

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

The debate over the curative benefit of radiotherapy for aggressive cutaneous invasive squamous cell carcinoma continues. The inflection point between curative and palliative radiotherapy is poorly understood and hides in the patient data between multiple cutaneous primaries and subclinical metastatic spread. Within the cohort studies that direct our clinical guidance, the inclusion and exclusion criteria of cohort studies can read both sides of the same flipped coin. Following a report from Ruiz et al (JAMA Derm. 2019, 155(10): 1193-95), Leus et al recently reported their experience with postoperative radiotherapy after incomplete excision (JAMA Derm. 2021, 157(3): 349-51). While the divergent curative claims of 82% and 20% respectively appear to conflict, both studies reinforce the challenges of prognostic guidance to our individual patients as they collect signs of an eventual spread of treatment-resistant disease.

As evidenced by the inclusion of BWH T1 tumor stage in a third of the cohort from Groningen and none in the Boston cohort, the clinical practice patterns for addressing incomplete excisions from the two centers create different inclusion criteria and independent hypotheses. These two studies appear to highlight the spectrum of possible clinical scenarios with "microscopic disease" from a fully involved margin to narrowly approaching a margin. I interpret the results of both studies to support the aggressive pursuit of surgical margins for patients with tumors that are being considered for radiotherapy. Further, in counseling my patients on our plans to include radiotherapy in their care, I will continue to frame expectations within a "possible" benefit against a poor prognosis of progression of an aggressive disease.

Recently, our country bore witness to the horrific murder of multiple members of the Black community including George Floyd, Breonna Taylor, and Tony McDade, among others. These events shined a crucial light on the need for collaborative efforts to battle racism and improve social justice in all sectors across the United States. The American Academy of Dermatology recently launched a three-year strategy to increase dermatologic care through diversity, equity, and inclusion. Drs. Jenna Lester and Susan Taylor’s recent JAMA Dermatology Viewpoint “Resisting racism in dermatology: A call to action” should be considered required reading for each member of the Academy to play a crucial role in this effort (JAMA Derm. 2021; 157(3): 267-268). In this piece, the authors outline four key steps that every dermatologist can participate in to help dismantle structural racism in dermatology. Strategies highlighted include: (1) Increasing diversity in the dermatology workforce via recruitment of underrepresented-in-medicine (UIM) resident physicians and faculty at academic dermatology departments; (2) Recommending academic institutions increase funding for UIM medical student research fellowships; (3) Imploring all dermatologists to mentor UIM students from the high school level onward; and (4) Ensuring dermatology education, at all levels of training, covers crucial topics surrounding antiracism, health equity, and skin of color. Dismantling systemic racism in medicine will not happen passively or exclusively secondary to the action of equity leaders in our field — each of us must engage in this work. This article provides powerful and tangible steps to take part in this effort.

I read with great interest about the association of potent and very potent topical corticosteroids (TCS) with the risk of osteoporosis and major osteoporotic fractures (MOF) in JAMA Dermatology (doi: 10.1001/jamadermatol.2020.4968). This is a knowledge and practice gap in dermatology, and a common concern voiced by our patients! Counseling in this context is a balancing act when considering known outcomes of steroid phobia yielding suboptimal outcomes.

This was a nationwide retrospective cohort study that included 723,251 Danish adults treated with at least potent TCS from 2003-2017. Exposure data was based on filled prescriptions converted in equipotent doses to mometasone furoate (1mg/g). The reference group included patients who filled prescriptions of 200-499 grams, whereas the exposed group filled ≥500 grams.

Dose-response associations were found between increased use of potent or very potent TCS and the risk of osteoporosis and MOF. A 3% relative risk increase of osteoporosis and MOF was observed per doubling of the cumulative TCS dose. The overall population-attributable risk (e.g., risk attributed to TCS exposure) was 4.3% (95% CI, 2.7%-5.8%) for osteoporosis, and 2.7% (95% CI, 1.7%-3.8%) for MOF. The risk due to TCS, especially at conventional doses, is low. For perspective, the exposure needed for one additional patient to be harmed (ENH), was 4,544 person-years for osteoporosis when exposed to 500-999 grams. At a dose of ≥10,000 grams, the ENH decreased to 1,136 person-years. Of note, patients exposed to ≥10,000 grams comprised only 1.8% of the study population. Similarly, ENH for major osteoporotic fractures, for those exposed to 500-999 grams and ≥10,000 grams were 12,250 person-years and 454 person-years, respectively.

Even though TCS risk is markedly lower than that attributed to systemic steroids, our judicious use of potent TCS and openness to switching to steroid-sparing agents when possible, are fundamental to our charge as physicians.

The American Contact Dermatitis Society has announced the allergen of the year for 2021: acetophenone azine, a recently discovered allergen found in shin pads and footwear containing foam (Dermatitis. 2021. 32(1):5-9). Several cases have been described in patients presenting with significant allergy to shin pads. One of these first patients identified, tested positive only to the ethyl vinyl acetate foam used in the shin guard. Through collaboration between dermatology and chemists, high-performance liquid chromatography was performed, and the allergen was identified as acetophenone azine. Other cases of patients wearing shin pads, as well as footwear, have been reported in the literature. The dermatitis can present either under the shin pads as an exuberant dermatitis or on the feet if secondary to footwear. It is believed that sweat and occlusion enhance the reaction under the shin pad. Occasionally, widespread dissemination has been seen. Most of the patients reported are children or teenagers and, to date, are primarily in Europe.

Acetophenone azine is also known as 1-phenylethan-1-one (1-pheynlethylidene), hydrazone, or methylphenyl ketazine. This chemical is typically used as an intermediate in organic synthesis and it is thought that the chemical is a manufacturing byproduct. This chemical is not commercially available at this time. If testing is done, the chemical must be obtained from a distributor of chemical products. The best concentration identified at this time is acetophenone azine 0.1% in acetone or petrolatum. The authors of the article believe that many current cases of dermatitis are being attributed to irritant contact dermatitis because this allergen is not yet available for testing and as this allergen becomes more readily available, many other sources of the allergen will be identified.

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