What's hot?
What's hot
February 28, 2018
In this monthly column, members of Dermatology World's Editorial Advisory Workgroup identify exciting news from across the specialty.
Rosalie Elenitsas, MD
Malignant melanoma is one of the most serious diagnoses that dermatologists face on a regular basis. While many cases of malignant melanoma are curable with excision, there are still a significant number of patients with malignant melanoma who develop metastatic disease, often leading to death. Many research studies have evaluated the most important risk factors for assessing the prognosis of individual melanomas using clinical and histopathological data. The American Joint Commission on Cancer (AJCC) provides guidance on staging and classification of tumors such as malignant melanoma. The most recent edition of the AJCC staging system (January 2018) has removed mitotic rate as a criterion for staging primary cutaneous malignant melanoma.
A recent paper from Vanderbilt University analyzed 17,204 thin malignant melanomas (thickness less than 1.0 mm) in the National Cancer Database, for high risk features and lymph node status (doi.org/10.1016/j.jaad.2017.11.041). Mitotic rate showed a strong linear relationship with the odds of having a lymph node involved by melanoma. While this paper does not address survival analysis, it highlights the importance of mitotic activity in a melanoma. It is recommended that pathologists should continue to report mitotic rate for primary cutaneous invasive malignant melanoma. Treating dermatologists and surgeons should expect this information in their patients’ pathology reports to assist in optimal counseling and management.
Sylvia Hsu, MD
Out with IVIg, in with cyclosporine. A pivotal study (Nat Med. 2008;14:13431350) found that Fas ligand does not play a major role in epidermal necrolysis, and identified granulysin as the main cell death mediator involved in toxic epidermal necrolysis. Granulysin is a cytolytic protein produced by cytotoxic T lymphocytes and NK cells. Interest in cyclosporine increased due to its theoretical benefit in TEN with its function of inhibiting T lymphocytes and its potential anti-apoptotic effects. The trend in the literature away from IVIg continued when a retrospective review (J Am Acad Dermatol. 2014;71(5):941-7) on the treatment of TEN with IVIg versus cyclosporine found cyclosporine to have greater mortality benefit. A recent systematic review and meta-analysis found no survival benefit with the use of IVIG (JAMA Dermatol. 2017; 153(6):514-522). However, cyclosporine and systemic corticosteroids were found to be promising options for SJS/TEN. A recommended dose of cyclosporine is 3-6 mg/kg ideal body weight/day divided into two daily doses over 7 days followed by a tapering dose. Monitor blood levels (aim: plasma concentration 150-200 ng/ml, measured before morning dose). Consider adding intravenous corticosteroids (50 - 250 mg/day) for a few days (J Invest Dermatol. 2017;137:2047-2049).
Kenneth A. Katz, MD, MSc, MSCE
Here’s more bad news about syphilis: a 100 percent increase in ocular syphilis in North Carolina from 2014 to 2015 (Clin Infect Dis. 2017;65:1676-82). In 2014, 21/1799 (1.2%) syphilis cases in North Carolina had ocular syphilis; in 2015, it was 42/2433 (1.7%). Uveitis was the most common diagnosis in patients with ocular syphilis, which was more common among males, whites, those over age 40, and those living with HIV. The ocular syphilis uptick in North Carolina mirrors nationwide trends (www.cdc.gov/std/syphilis/clinicaladvisoryos2015.htm). That should concern dermatologists, for two reasons. First, ocular syphilis, and neurosyphilis, can occur during early stages of syphilis, alongside (or even before) cutaneous manifestations. For that reason, CDC recommends a neurologic and ophthalmic review of systems, as well as a targeted neurologic examination, in every patient with syphilis. Patients with ocular symptoms, or with neurologic signs or symptoms, should be referred for additional evaluation and management. Second, increases in ocular syphilis have occurred in the context of an overall syphilis epidemic. Primary and secondary syphilis — the infectious stages of the infection — has increased in the United States every year from 2000 (5979 cases) to 2016 (27814 cases). The epidemic has disproportionately affected men who have sex with men (MSM), who accounted for 58% of primary and secondary syphilis cases in 2016; of MSM diagnosed with syphilis, 47% were co-infected with HIV. Dermatologists should be on the lookout for syphilis in general, and keep their eyes peeled in particular for ocular and neurologic manifestations of the disease.
Risa Jampel, MD
Latisse, the topical prostaglandin bimatoprost 0.03%, was FDA approved in 2008 for treatment of short or inadequate eyelashes. Topical prostaglandins have been used by ophthalmologists for 20 years to control eye pressure in patients with glaucoma and multiple adverse local effects have been reported in the literature, including iris hyperpigmentation.
Zaleski-Larsen et al report a retrospective review of 50 women who consistently used Latisse over an average of about 4 years compared to 50 age-matched controls with at least 46% in each group having blue or green eye color (theoretically dark brown eyes will not show the changes and baby blue eyes do not have the melanocytes necessary for the changes) (Dermatol Surg. 2017;43(12):1431-1433). Standardized photographs had been taken at undefined time intervals and were evaluated by a masked evaluator who noted no hyperpigmentation or change in eye color.
This is good news and confirms what we all observe in practice. However, even though this a negative study, the photographs accompanying the article have black ovals covering the eyeballs and I wonder if the distance and lighting of the photographs are adequate for evaluation of pigment change.
CDR Josephine Nguyen, MD, MHCDS
In recent years, FDA restrictions on compounding have severely restricted dermatologists’ ability to access and mix preparations (i.e. buffering of lidocaine with sodium bicarbonate or dilution of triamcinolone with lidocaine).
What can dermatologists do to regain access to office-use compounded drugs for patients?
Write your local representative in support of H.R. 2871, Preserving Patient Access to Compounded Medications Act, which would ensure access to medications while maintaining the safety of compounded medications, using the Academy’s advocacy website.
Why did this happen?
In response to the 2012 New England Compounding Center fungal meningitis outbreak, Congress passed the Drug Quality & Security Act (DQSA). The DQSA gave the FDA oversight over “outsourcing facilities (503B),” to regulate manufacturers of larger batches of compounded drugs. The FDA misinterpreted Congressional intent by prohibiting section 503A compounding pharmacies from dispensing office-use compounded drugs without a patient-specific prescription. The FDA incorrectly assumes that section 503B outsourcing facilities can meet the needs of physicians and their patients. However, outsourcing facilities are designed to produce large quantities that make their business models sustainable, rather than the small quantities needed by physician offices. As a result, physicians and patients are facing issues accessing needed drugs. (Learn more about these issues on p. 38.)
What else do I have to look out for?
State pharmacy boards have followed the FDA’s interpretation of the federal compounding law. As a result, some state pharmacy boards have also prohibited in-office compounding, further complicating dermatologists’ ability to obtain certain compounded medications. Restrictions vary widely state-by-state and it’s essential that you advocate at the local level (state medical society) to protect your rights. Make sure your state medical society is addressing these issues!
Simon Ritchie, MD
The wide variety of new and highly effective psoriasis medications — and the corresponding advertising push by pharma — can make older mediations, such as methotrexate, appear atavistic at best and at worse a disservice to our patients. However, the rising costs of pharmaceuticals compels us to consider these older therapeutic options in certain situations. But, how do we know who are the best candidates for these medications, and when can we make a judgment about their efficacy? In the December JAAD, Gordon et al derived a formula for predicting which psoriasis patients are most likely to respond to methotrexate (2017;77(6):1030-1037). They found that patients on an escalating dose of methotrexate who achieved PASI25 at week 4 were highly likely to go on to achieve PASI75 at week 16. Given that PASI75 is currently considered the gold standard for treatment response, this tool provides a quick and easy way to determine if a patient should stay on methotrexate, or whether a different medication should be considered. The dose was started at 7.5 mg/week and increased to 10 mg/week at week 2, then to 15 mg/week at week 4. The dose was further increased to 20 mg/week at week 8 and 25 mg/week at week 12 if PASI50 was not achieved. At week 4 the rates of serious hematologic and hepatotoxic effects were very low. This prediction tool provides an excellent opportunity to ensure that we continue to provide highly effective and safe care to our patients while helping to control costs.
