Prospective Case Series of Cutaneous Adverse Effects Associated With Dabrafenib and Trametinib.

BACKGROUND: Dabrafenib, a novel selective small-molecule inhibitor of BRAF, has been shown to increase overall survival in patients with unresectable metastatic melanoma harboring the BRAF V600E mutation. The development of resistance has led to combination therapy with selective MEK inhibitor trametinib. Compared with vemurafenib, dabrafenib is a more recent BRAF inhibitor approved by the Food and Drug Administration in May 2013 for metastatic melanoma; fewer data are available in the current literature regarding cutaneous toxicity. OBJECTIVES: We sought to present additional cutaneous side effects of dabrafenib and trametinib and follow their evolution and management. METHODS: We carried out a prospective study of 14 patients treated with dabrafenib alone or with trametinib. Patients were followed every 4 weeks, and we collected detailed cutaneous symptoms, photos, and biopsy specimens. RESULTS: All patients presented with at least 1 adverse skin reaction. The mean duration of treatment was 24 weeks. The most common adverse effect was papillomas (7/14), followed by palmoplantar hyperkeratosis (5/14), alopecia (5/14), and seborrheic dermatitis-like eruption (2/14). Three patients who received trametinib developed an acneiform eruption (3/5). One patient developed a keratoacanthoma-like squamous cell carcinoma. Side effects presented as early as 2 weeks after starting therapy, with a mean time of onset of 9 weeks. CONCLUSION: Selective BRAF inhibitor dabrafenib and MEK inhibitor trametinib are associated with multiple skin adverse effects. Given their recent approval and the potential for malignant lesions to develop on treatment, awareness of potential adverse effects and their management is necessary.

"Parabenoia" Debunked, or "Who's Afraid of Parabens?".

Parabens have been used as preservatives in foods, injectables, and topical preparations for nearly 10 decades. Present in nature, rapidly metabolized by skin and liver enzymes, they have an excellent safety record. However, in the past 15 years, they have been under scrutiny for their alleged estrogenic and antiandrogenic effects, as well as their putative role in promoting cancerogenesis through endocrine disruption. Scientific articles supporting these assertions have led the European Community to ban or restrict the use of some parabens. Despite that methylparaben and ethylparaben have negligible endocrine disruption activity, the food, pharmaceutical, and cosmetic industries are under pressure from scare campaigns in the media and are responding by replacing parabens with other biocides that cause multiple cases, and even worldwide epidemics, of allergic contact sensitization. In the present review, we present a balanced account of the published literature about the metabolism and potential toxicology of parabens.

Diagnosis and management of eosinophilic cellulitis (Wells' syndrome): A case series and literature review.

INTRODUCTION: Eosinophilic cellulitis (Wells' syndrome) is an inflammatory dermatitis that is often misdiagnosed as infectious cellulitis due to its similarity in presentation. Misdiagnosis leads to delay of correct treatment and inappropriate use of antibiotics. METHODS: A case series of eosinophilic cellulitis and a literature review are presented. RESULTS: Patients with Wells' syndrome may present with a variety of nonspecific symptoms, such as fever, arthralgia and malaise, as well as myriad cutaneous lesions with associated erythema, presenting as blisters, bullae, papules and/or nodules. Several treatment modalities have been used to treat eosinophilic cellulitis and have been met with variable success rates; these include systemic corticosteroids, topical corticosteroids and antihistamines, with success rates of 91.7%, 50% and 25%, respectively. CONCLUSIONS: A high degree of clinical suspicion must be exercised to diagnose this rare condition. Cellulitis with an atypical presentation or not responding to appropriate antibiotic treatment should trigger suspicion of Wells' syndrome. To date, the most successful treatment method is a short course of systemic corticosteroids.

INTRODUCTION: La cellulite à éosinophiles (syndrome de Wells) est une dermatite inflammatoire souvent diagnostiquée à tort comme une cellulite infectieuse en raison de sa présentation similaire. Le mauvais diagnostic retarde le traitement pertinent et suscite une utilisation inadéquate des antibiotiques. MÉTHODOLOGIE: Les auteurs présentent une série de cas de cellulite à éosinophiles et une analyse bibliographique. RÉSULTATS: Les patients ayant le syndrome de Wells peuvent présenter divers symptômes non spécifiques, tels que la fièvre, l'arthralgie et les malaises, de même qu'une myriade de lésions cutanées associées à un érythème, sous forme de vésicules, de cloques, de papules ou de nodules. Plusieurs modalités thérapeutiques ont été utilisées pour traiter la cellulite à éosinophiles et ont obtenu des taux de succès variés. Ainsi, les corticoïdes systémiques, les corticoïdes topiques et les antihistaminiques ont obtenu des taux de succès de 91,7 %, de 50 % et de 25 %, respectivement. CONCLUSIONS: Il faut un fort degré de présomption clinique pour diagnostiquer cette maladie rare. La cellulite ayant une présentation atypique ou qui ne répond pas à une antibiothérapie convenable devrait soulever la possibilité de syndrome de Wells. Jusqu'à présent, la méthode thérapeutique la plus réussie consiste à administrer un court traitement aux corticoïdes systémiques.