What's hot?
What's hot
January 29, 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
Many of us struggle with patients with refractory pruritus who have tried many combinations of antihistamine, tricyclic, and immunomodulatory agents and continue to scratch. Finally, progress is now being made in better understanding the pathways involved in the itch-scratch cycle.
Brian Kim, MD, co-director of the Center for the Study of Itch at Washington University, is focused on the innate immune mechanisms that underlie skin inflammation and the sensation of itch. His group has identified certain key cytokines in atopic dermatitis (IL-4 and IL-13) that also function directly as key master regulators of the sensation of chronic itch. Kim’s group showed that the TH2 cytokines IL-4 and -13 directly activate sensory neurons through a shared IL-4 receptor subunit, which is also shared by Janus kinase (JAK) 1 (Cell. 2017; 171: 217-28.e13). IL-31 is another TH2 mediated cytokine which has been implicated in atopic dermatitis and other pruritic conditions such as prurigo nodularis and CTCL (J Allergy Clin Immunol. 2018; 142: 1375-90).
Dissecting the mediators of itch (also known as pruritogens) could have immediate impact on our patients. They are already benefiting our pets. Oclacitinib, a JAK 1/3 inhibitor, was approved in 2013 to treat dog scratching/atopic dermatitis. Cytopoint® is a caninized monoclonal antibody which neutralizes IL-31 and was approved in 2016 for canine atopic dermatitis. It remains to be seen if dupilumab — which blocks IL-4 and -13 and is approved for adults with moderate/severe atopic dermatitis — or related drugs in the pipeline, will lead to similar benefit in humans with chronic pruritus without atopic disease.
Deepti Gupta, MD
The landscape for genetic discovery and therapeutic targets in vascular anomalies has significantly changed over the years. Arteriovenous malformations (AVM) have benefitted from gene discovery. All AVMs progress throughout life causing significant morbidity and even mortality due to pain, bleeding, deformity, and at times, cardiac dysfunction. They are difficult to treat, with limited therapeutic options and high rates of reoccurrence. Work published earlier this year discovered multiple mosaic-activating mutations in the RAS/MAPK pathway, which is a pathway commonly found activated in certain cancers. Specifically, mutations were found in KRAS, BRAF, and most commonly in MAP2K1 (J Clin Invest. 2018; 128(4): 14961508). MAP2K1 encodes mitogen-activating protein kinase 1 (MEK1), and endothelial cells carrying this mutation form abnormal vascular channels and networks between arteries and veins. A recent case report uses trametinib, a MEK inhibitor, for the treatment of an AVM (JAMA Dermatology. doi:10.1001/jamadermatol.2018.4653). After one year of treatment there was improvement in symptoms and significant decrease in volume of the AVM. BRAF inhibitors, such as vemurafenib, have also been implicated in treatment of AVMs. There are still many questions left unanswered regarding use of MEK and BRAF inhibitors in AVM, such as duration of therapy and long-term sequelae. Use of these inhibitors may offer a promising targeted therapy, albeit not a cure, for a disease with limited therapeutic options and high morbidity.
Corey Hartman, MD
Rosacea is thought to be associated with factors involved in metabolic syndrome (MetS). Relative muscle mass is negatively associated with increased rosacea severity, suggesting that skeletal muscle could be protective against rosacea exacerbation.
Researchers in a cross-sectional study investigated the link between rosacea severity and relative muscle mass. Study participants were patients at a hospital screening center in Korea and had regular skin checkups for two years. Dermatologists took polarized light photographs of participants’ faces and evaluated them. Similarly, participants’ skeletal muscle index (SMI) was estimated with a bioelectrical impedance analyzer (% = total skeletal muscle mass in kg/body weight in kg x 100). The associations between SMI and rosacea severity were evaluated using a logistic regression model.
84.5% of 110 participants had erythematotelangiectatic rosacea and 15.5% with papulopustular rosacea. Mild rosacea was seen in 75.5% of participants, moderate rosacea in 24.5% and severe rosacea in 0 participants. A significant decreasing trend was seen in rosacea severity with increasing SMI.
This association was not observed for mild rosacea. After the findings were analyzed according to sex, this association was observed in women, but was inconspicuous in men. The conclusion of the study is that it is likely that skeletal muscle is a protective factor for severe rosacea (J Dermatol. doi: 10.1111/1346-8138.14689).
Michel McDonald, MD
Close observation with routine skin surveillance is a reasonable approach to moderately dysplastic nevi according to a recent study in JAMA Dermatol. (2018:154(12):1401-1408). In a study of 467 moderately dysplastic nevi with positive histologic margins, no lesion developed into cutaneous melanoma. The mean follow-up time was 6.9 years. There are some limitations including that patients were only reviewed if they had more than three years of follow-up, so if anyone developed a melanoma within three years that would not have been detected. Incidentally, the authors noted that patients with two or more biopsied moderately dysplastic nevi had an increased risk for melanoma at a separate site. While a larger study is preferable and no recommendation for follow-up intervals can be gleaned from this study, it does add to the literature that it may be appropriate to monitor patients with moderately dysplastic nevi with positive margins on biopsy.
Christopher Messana, DO, JD
Will your patient’s undifferentiated pleomorphic sarcoma behave indolently or aggressively? A recently published multicenter, retrospective chart and histopathologic review of 319 patients with skin and soft tissue spindle cell neoplasms that are currently classified as undifferentiated pleomorphic sarcoma (UPS), was conducted to identify clinical and histopathologic features that predict aggressive behavior. The authors of this large review found that invasion of the tumor deep into the subcutaneous fat and tumor size larger than 2 cm in diameter significantly predicted a more aggressive tumor. Older age at diagnosis, tumor invasion into lymphovascular space, and a history of immunosuppression were also associated with significantly increased risk of mortality.
Because of the prognostic impact of tumor depth, the authors propose that UPS be subcategorized into superficial UPS and deep UPS. This study reminds us of the importance of adequate deep sampling and histopathologic evaluation of the tumor, and may help guide clinicians in recommending adjuvant treatment and frequency of surveillance (J Am Acad Dermatol. 2018;853-9).
Christen Mowad, MD
A recent article in Dermatitis — reporting on the North American Contact Dermatitis Group’s (NACDG) most recent patch test results — highlights the importance of patch testing as the standard criterion diagnostic tool for evaluating patients with suspected allergic contact dermatitis, as well as the benefit of expanded testing trays. Every few years this group reports on their patch test findings, a collective data set from 13 centers in North America. They highlight new allergens, most common allergens and allergens with the highest relevance, as well as how likely smaller screening series would be able to fully detect and manage patients. In this reporting cycle, nickel remains the most commonly detected allergen. The European Union has implemented regulations that limit the level of nickel available to consumers through skin contact. Limitations in nickel exposure in the United States would help to decrease allergy and allergic reactions to this allergen and the American Contact Dermatitis Society is making efforts to encourage similar limitations. Methylisothiazolinone, recently added to the screening series in 2013, was the second most positive reaction. Methylisothiazolinone was previously tested as a mix with methylchloroisothiazolinone and it is now also tested alone. The rate of positivity has increased from the last study and it also has the highest significance-prevalence index number (SPIN) — highlighting the importance of this allergen which would not be detected with standard 36 testing series. Fragrance mix was the third most common allergen reported and had the second highest SPIN. In addition to highlighting many other allergen trends, the authors estimated that standard allergen trays of 36 would hypothetically miss 25-40% of reactions detected by their larger NACDG series. Additionally, 23% of patients (many occupationally related cases) required more extensive testing than even the expanded NACDG series in order to detect causative allergens. This study reinforces the benefits gained in the management of allergic contact dermatitis when adequate history, physical examination, and extended patch testing is conducted (Dermatitis. 29(6):297-309).
