Skin therapy letter最新文献

Interleukin (IL)-17 is important in the pathophysiology of psoriasis and has proven to be an effective therapeutic target. Brodalumab, the third commercially available IL-17 antagonist, was approved by the US FDA in February 2017 for the treatment of moderate-tosevere plaque psoriasis. As brodalumab enters the marketplace, it is imperative to investigate its safety profile. We conducted a safety assessment of brodalumab using publically available adverse event data from phase II and III clinical trials. The most common adverse events were nasopharyngitis, upper respiratory tract infection, and candidiasis. The FDA issued a black box warning after six patients treated with brodalumab across four clinical trials committed suicide, but no causal relationship was identified. Current evidence suggests a similar safety profile for brodalumab compared to other IL-17 antagonists used to treat moderate-to-severe plaque psoriasis.

Fabry disease (FD) is an X-linked lysosomal storage disease. A lack of alpha-galactosidase activity results in the accumulation of globotriaosylceramide in cells of various systems, leading to multi-systemic effects. The cutaneous hallmark of FD is a specific distribution of angiokeratoma. Other common symptoms include cornea verticillata, acroparesthesia, and sweating abnormalities. FD-specific symptoms, history, as well as examination of angiokeratoma can assist in the differential diagnosis. Enzyme replacement therapy is the current mainstay of treatment.

Hereditary angioedema is characterized by severe, episodic edema of the subcutaneous and mucosal tissue. The disease carries significant morbidity and mortality due to involvement of the gastrointestinal tract and upper airway. Recent advances in the treatment of hereditary angioedema include new techniques used to isolate and purify human-derived C1 inhibitor, the production of a recombinant form of C1 inhibitor, and the development of drugs that target the kallikrein-kinin pathway. This paper reviews the mechanisms, efficacy, and adverse reactions associated with these medications.

An increasing body of research indicates that dietary change may serve as a component of therapy for certain skin conditions. This includes conditions such as acne, atopic dermatitis, aging skin, psoriasis, and rosacea. Certain nutrients, foods, or dietary patterns may act as disease "triggers", while others may prove beneficial. Avoidance or elimination diets may be helpful in some conditions, although testing may be recommended first. In terms of beneficial effects, an eating pattern that emphasizes the consumption of whole foods over highly processed foods may help in the treatment of certain skin conditions, and will certainly help in the prevention of associated co-morbidities.

Approximately 16 million Americans have rosacea, an inflammatory cutaneous disorder with central facial erythema, papules, pustules, telangiectasia, flushing, and swelling being among the more commonly recognized features. Overexpression of cathelicidin peptide LL-37 has been implicated in the pathophysiology of rosacea. Azelaic acid has been found to inhibit the pathologic expression of cathelicidin, as well as the hyperactive protease activity that cleaves cathelicidin into LL-37. Given these findings, a small prospective, open-label, interventional trial was undertaken to assess the effects of azelaic acid 15% gel on inflammatory lesions of papulopustular rosacea in a real-world setting. Use of azelaic acid was associated with a significant reduction in inflammatory lesions, which persisted beyond the active treatment phase. Overall, azelaic acid 15% gel is an appropriate initial topical therapy for the treatment of moderate facial rosacea.

Atopic dermatitis (AD) is the most common chronic inflammatory disease affecting 2-10% of adults and up to 15-30% of children. Despite a rising prevalence, effective and safe therapeutics for patients with moderate-to-severe AD are limited due to toxicity and side effects. Dupilumab, an interleukin (IL)-4 and IL-13 antagonist that limits type 2 T helper (Th2) driven inflammatory activity, is a promising therapeutic option. In clinical trials, it has demonstrated efficacy by reducing clinical activity and symptoms, and showed improvement in the AD genomic phenotype, including a significant reduction in Th2 chemokines and reversal of key epidermal markers of AD. It also has a favorable safety profile. This review discusses the role of dupilumab in treating Th2 related inflammation, and its efficacy and safety, as demonstrated in clinical trials. Dupilumab (Dupixent®) recently gained US FDA approval for patients with moderate-to-severe AD, and is poised to revolutionize the management of this chronic, relapsing condition.

Epidermal growth factor receptor (EGFR) inhibitors are part of an emerging class of anticancer medicines known as "targeted therapy," which target pathways more specific to neoplastic proliferation than traditional chemotherapeutic agents. Adverse effects of such treatments are thought to be less severe, but can still be significant. Because EGFR is preferentially expressed in epithelial tissues, including the skin and hair follicle, cutaneous side effects of these agents are quite common. Not only can these toxicities severely affect patients' quality of life, but in some specific instances, they can be associated with increased response to therapy. It is of paramount importance that clinicians familiarize themselves with and understand the basic management of the range of cutaneous adverse effects caused by these drugs.

Nicotinamide, an amide form of vitamin B3, has shown the potential to treat a variety of dermatological conditions, including acne, rosacea, and atopic dermatitis. Recent studies have demonstrated the role of nicotinamide, in both topical and oral forms, as a chemopreventive agent against skin cancer. Its anti-carcinogenic role may be due to its ability to enhance DNA repair and prevent ultraviolet (UV)-induced immunosuppression, which is known to contribute to the progression of pre-malignant lesions. Furthermore, nicotinamide is a precursor of essential coenzymes for many important reactions in the body, including the production of nicotinamide adenine dinucleotide (NAD). NAD is a key coenzyme in the synthesis of adenosine triphosphate (ATP), which transports chemical energy within cells. Therefore, nicotinamide plays a significant role in supporting energy-dependent cellular processes, including DNA repair.

While there are several commercially available treatment options for psoriasis and psoriatic arthritis, there remains a large number of individuals who are refractory to current modalities. In the recent past, there has been increasing evidence that interleukin (IL)-17 plays a vital role in the pathophysiology of psoriasis. Preclinical, phase II, and phase III studies of secukinumab (Cosentyx®) targeting IL-17 and its receptor have thus far proved to be promising. We reviewed the results of phase II and phase III clinical trials for secukinumab in the treatment of psoriasis and psoriatic arthritis. Only published studies were considered in the present review. We also performed an English language literature search from January 2003 to September 2015 using PubMed with any of the following key words: (secukinumab OR AIN457) AND (psoriasis OR psoriatic arthritis). In our review of the literature, seven phase III and five phase II clinical trials, as well as open-label extension studies with unpublished findings were found. Results from phase III clinical trials indicated secukinumab to be efficacious and safe for the treatment of psoriasis and psoriatic arthritis according to Psoriasis Area and Severity Index (PASI) and American College of Rheumatology (ACR) scores. The safety profile of this agent was similar across all studies, with the most frequently reported adverse events of nasopharyngitis, upper respiratory infections, headache, and injection site reaction. Secukinumab demonstrates rapid and robust clinical improvement accompanied by a favorable short- term safety profile. The results of the phase III trials continue to reinforce the theory that the IL-17 pathway is an essential target in psoriasis and psoriatic arthritis treatment. Additional extension studies of lower level evidence are needed to further understand the safety profile of the drug.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are common, worldwide viral illnesses that potentially impact the clinician's ability to manage patients with immunosuppressive medications such as biological therapy. In light of recent literature reviews, patients with HBV and HCV should be referred to a hepatologist or infectious disease expert prior to initiation of biological therapy.