What's hot?
What's hot
March 28, 2019
In this monthly column, members of the Dermatology World Editorial Advisory Workgroup identify exciting news from across the specialty.
Edward W. Cowen, MD, MHSc
The title says it all: Lack of a U.S. Food and Drug Administration indication should not limit access to appropriate treatment. In this brief statement piece (J Am Acad Dermatol. 2019; 80:577-8), the American Academy of Dermatology Association Task Force on Drug Pricing and Transparency provide a document for the expressed purpose of inclusion in a prior approval’ packet to obtain insurance coverage. The authors also include a statement that medication access should not be limited to the FDA-approved age guidelines.
Although properly controlled clinical trials are critical to evidence-based practice, the reality is that pivotal trials required for FDA approval are unlikely to be performed for the vast majority of the skin diseases we treat. In some cases, an agent is already the standard of care’ or the relative rarity of the skin disease does not lend itself to a cost-effective proposition for a drug company to pursue an FDA indication. In other situations, the drug may already be available in generic form, so there is no financial incentive for a company to pursue an FDA indication. Restriction of access to useful medications that help our patients is not the answer to the burgeoning cost of health care. A better alternative may be to investigate the cost of the drugs themselves (both branded and generic). According to a recent study of market competition and generic drug prices of topical agents (JAMA Dermatol. 2018; 154:1441-6), the price of some generic drugs (e.g., clobetasol ointment, econazole nitrate cream) increased by >900% between 2013 and 2016.
Deepti Gupta, MD
Infantile hemangiomas (IH) have a unique growth pattern with their proliferative growth phase usually completed by nine months of age. However, a recent multicenter retrospective study demonstrated that late growth can be seen in children older than three years of age and even as late as 8.5 years of age (J Am Acad Dermatol. 2019; 80:493-9). Features associated with late growth of IH were: larger size of the hemangioma — with 76% of these hemangiomas being >10cm2 and 44% being >100cm2 — segmental morphology with the S3 segment of the face most represented, deep cutaneous or subcutaneous involvement, presence of PHACE syndrome, and head and neck location. Specific anatomic locations on the face including the nasal tip, lip, and eyelid. These areas were at higher risk for late growth, even with presentation of fairly small hemangiomas. This phenomenon may be secondary to residual hemangioma stem cells persisting in these locations even after involution of the IH. Physicians should be aware that IH can uncommonly undergo this late growth phase beyond three years of age, and not all classically complete their proliferative phases by nine to 12 months. This will help with patient counseling, as well as treatment and diagnostic considerations.
Corey Hartman, MD
L-Cysteamine is a biological antioxidant produced during the coenzyme A metabolism cycle and is naturally present in all mammalian cells. Kligman’s formula (hydroquinone, fluocinonide, and tretinoin) has been through many modifications through the years, yet they all contain hydroquinone. Historically, there’s been some back and forth on the safety of hydroquinone. In 1982, the U.S. Food and Drug Administration recognized the ingredient as safe and effective. Despite its safety, there are still potential side effects to long-term use of hydroquinone and patients for whom the formulation is ineffective.
A 44-year-old female patient with type V skin used a Kligman formulation (5% hydroquinone, 1% dexamethasone, and 0.05% retinoic acid) for one year with only mild improvement in melasma. The patient experienced skin redness and burning when she attempted to discontinue the cream, as well as an intensity in the hyperpigmentation. Woods lamp examination confirmed the hyperpigmentation to be of epidermal nature, and also confirmed the presence of perilesional hypopigmentation. Dermatoscopic examinations confirmed the presence of telangiectasia in the erythematous parts of the skin.
The diagnosis was recalcitrant melasma and corticoidinduced skin atrophy. The patient was asked to stop the application of Kligman formulation and to start the application of cysteamine cream, once daily at bedtime to the whole face. Cysteamine cream was washed out after 15 minutes of application. After four months of treatment, the therapeutic response was significant. Hyperpigmented lesions were significantly attenuated, and the perilesional hypopigmentation and erythema disappeared. Skin telangiectasia was significantly improved on dermatoscopic examination. Dermacatch skin colorimetry showed a significant reduction in melanin content in melasma lesions (J Cosmet Dermatol. 2019 Feb;18(1): 293-295. doi: 10.1111/jocd.12837).
Michel McDonald, MD
While mitotic rate is no longer a part of the staging system for melanoma in the American Joint Committee on Cancer system, there appears to be value in evaluating dermal mitotic rate when considering a decision about sentinel lymph node biopsy. A new analysis of patients in the National Cancer Database aimed to further identify predictors of sentinel lymph node positivity in thin melanomas (J Am Acad Dermatol. 2019; 80:441-7). Patients with Breslow thickness less than 1 mm were included, and the authors focused on this subset as approximately 70% of all newly diagnosed melanomas are in this category. Dermal mitoses increased the odds of sentinel lymph node positivity by 95%, and ulceration increased the odds by 63%. Patients who had no ulceration, but did have dermal mitoses, had 92% increased sentinel lymph node positivity. Dermal mitoses were an important predictor even when accounting for ulceration and Breslow depth. Other important predictors associated with an increased risk of a positive sentinel lymph node were Clark level IV and V, patient age less than 60 years, and Breslow thickness greater than 0.8 mm. While there is a possible role for dermal mitoses as a predictor, further evaluation of predictors of positivity is necessary to establish clear guidelines in thin melanomas.
Christopher Messana, DO, JD
The number of skin cancers diagnosed in the United States continues to increase, and dermatologists and non-dermatologist clinicians must recommend the most appropriate treatment for their patients’ skin cancer. A retrospective study by Bostanci, et al of 24 basal cell carcinomas (BCC), of different histologic subtypes, in various anatomic locations, treated with imiquimod cream concluded that imiquimod cream “is a strong alternative” to surgical excision or Mohs surgery “for different BCC subtypes” (Dermatol Surg. 2018; 44:3641).
A commentary on the Bostanci article published in Dermatologic Surgery highlights that 15 of the 24 BCCs in the Bostanci study may be classified as high-risk BCC (2019; 45:144-5). All five treatment failures in the Bostanci study were high-risk. The clinical clearance of high-risk BCC was only 66.7%. The authors remind us that recurrent BCCs not only have a higher risk of incomplete excision and recurrence after treatment, but also the risk of multiple surgical procedures with an inferior cosmetic outcome and the risk of development into advanced BCC. Clinicians should carefully weigh all relevant patient and tumor factors and use caution before recommending a non-invasive therapy for treatment of high-risk BCC. These days, many patients do their own research — often online — and sometimes have a strong interest in a particular treatment prior to consultation with an expert. If we as experts are to order treatment for high-risk BCC other than surgery or radiotherapy, there should exist meaningful contraindications and patients should understand the potential short- and long-term disadvantages of their decision.
Christen Mowad, MD
Parabens have been named by the American Contact Dermatitis Society (ACDS) as the non-allergen of the year for 2019. For 20 years the ACDS has chosen an allergen to highlight as one of importance for a variety of reasons. Sometimes it is a new allergen. Sometimes it is an emerging or changing allergen, and in this case, it is to highlight a non-allergen. Parabens have been an issue of controversy for many years, regarding allergenicity and systemic health concerns. In a Dermatitis article reviewing parabens, the authors comment that parabens are an effective biocide and are safe preservatives with decades of experience and low reports of allergic reactions when large databases are studied. They point out several other concerns regarding nonallergic effects such as endocrine activity, carcinogenesis, infertility, adipogenesis, and psychologic and environmental effects. Some of these concerns have been based on animal data. They discuss many of the findings regarding these potential claims but conclude that parabens are effective biocides with a long history and clinical experience, with a relative lack of evidence-based studies to verify many of the health claims. As such, removing them from consumer products by calling them potentially unsafe may be unwise, given the current available scientific data and the possibility of other chemicals being used with less clinical experience (Dermatitis. 2019; Jan/Feb;30(1):32-45).
