Reduced serum pyridoxine and 25-hydroxyvitamin D levels in adults with chronic pruritic dermatoses.

Little is known about the role nutritional factors play in the pathogenesis of chronic pruritic dermatoses (CPD). In this study, we analyzed nutritional deficiencies in CPD patients compared to matched controls. We conducted a population-based study from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2006. The main outcomes of the study were laboratory data on serum vitamin levels in participants who answered affirmatively to the questionnaires on CPD as well as matched healthy controls. We identified 877 cases of CPD among 9817 adults in the US aged 20 to 59 years. These findings revealed a slightly higher percentage of females with CPD. Low vitamin B6 (OR 0.697; 95% CI: 0.696-0.699, p = 0.025) and vitamin D (OR 0.794; 95% CI: 0.789-0.799, p = 0.037) levels were associated with a higher rate of CPD compared to healthy controls. Our study suggests that low levels of Vitamin B6 and Vitamin D inversely correlates with the presence of CPD. These vitamin deficiencies suggest further studies on the effect of vitamin supplementation may help in patients with CPD.

A systematic review of evidence based treatments for lichen simplex chronicus.

Lichen simplex chronicus (LSC) is a disorder characterized by thickened areas of skin from repeated rubbing or scratching. The multifactorial nature of LSC makes management difficult and there are currently no evidence-based guidelines for treatment. We conducted a systematic review of the literature to evaluate treatments for LSC and provide an evidence-based summary of the current treatments as well as highlight novel therapies. A total of 21 studies were included which comprised 682 patients with LSC involving various areas. The most robust evidence was seen with the use of topical corticosteroids (n = 7 RCTs) and limited data suggest benefit with other treatments such as topical immunomodulators, topical antipruritic agents, oral antihistamines, antiepileptics and antidepressants. We also discuss novel treatment approaches using transcutaneous electrical nerve stimulation, focused ultrasound, and phototherapy. Despite emerging evidence there remains a paucity of high-quality studies supporting treatments for LSC and larger controlled trials are needed.

A Dermatologist's Guide to Implementation of Gene Expression Profiling in the Management of Melanoma.

BACKGROUND. With the advent of effective therapeutics, melanoma mortality rates have decreased, yet incidence rates are continuing to rise, making accurate prognostication for risk of recurrence increasingly important. Gene expression profiling (GEP) is a clinically available, objective metric that can be used in conjunction with traditional clinicopathological staging to help physicians stratify risk in melanoma patients. There is a gap in guidance from the American Joint Committee on Cancer (AJCC) and the National Comprehensive Cancer Network (NCCN) regarding how to utilize GEP in melanoma care. OBJECTIVE. An expert panel of 31-GEP test users sought to provide clarification of use options and a rational clinical workflow to guide appropriate application of the 31- GEP test in everyday practice. METHODS. The authors participated in an in-depth review of the literature and panel discussion regarding current limitations of melanoma risk assessment and opportunities for improvement with GEP. The panel reviewed 1) validation and clinical impact data supporting the use of sentinel lymph node biopsy (SLNB), 2) existing primary data and meta-analyses for 31-GEP testing in melanoma risk assessment, 3) AJCC, NCCN, and Melanoma Prevention Working Group (MPWG) data and guidelines for GEP use in melanoma risk assessment, and 4) experiences, rationales, and scenarios in which 31-GEP testing may be helpful for risk assessment. RESULTS. The 31-GEP test is useful and actionable for patient care when applied in accordance with current NCCN guidelines. Stratification of patients into low (Class 1a), intermediate (Class 1b or 2a), or high (Class 2b) risk categories can inform multidisciplinary conference discussion and can assist with determining the intensity of imaging, surveillance, and follow-up care. Patient-specific features of the disease and individual circumstances should be considered in the decision to use 31-GEP testing. CONCLUSION. The authors suggest a clinical workflow that integrates 31-GEP testing under the umbrella of current national guidelines. Application of the test in appropriate patient populations can improve risk assessment and inform clinical decision-making.

Prurigo nodularis: Pathogenesis and management.

Prurigo nodularis is a chronic skin condition characterized by severely pruritic nodules that cause a profound negative impact on quality of life. The second article in this 2-part continuing medical education series focuses on reviewing the pathogenesis of prurigo nodularis and exploring management algorithms for this condition. In addition, we discuss some emerging and novel therapies for treating prurigo nodularis. The first article in this 2-part series describes the broader epidemiology, patient demographics, physical examination findings, and symptoms to aid in the timely recognition and diagnosis of prurigo nodularis.

Cannabinoids for the treatment of chronic pruritus: A review.

Medical marijuana is becoming widely available to patients in the United States, and with recreational marijuana now legalized in many states, patient interest is on the rise. The endocannabinoid system plays an important role in skin homeostasis in addition to broader effects on neurogenic responses such as pruritus and nociception, inflammation, and immune reactions. Numerous studies of in vitro and animal models have provided insight into the possible mechanisms of cannabinoid modulation on pruritus, with the most evidence behind neuronal modulation of peripheral itch fibers and centrally acting cannabinoid receptors. In addition, human studies, although limited due to differences in the cannabinoids used, disease models, and delivery method, have consistently shown significant reductions in both scratching and symptoms in chronic pruritus. Clinical studies have shown a reduction in pruritus in several dermatologic (atopic dermatitis, psoriasis, asteatotic eczema, prurigo nodularis, and allergic contact dermatitis) and systemic (uremic pruritus and cholestatic pruritus) diseases. These preliminary human studies warrant controlled trials to confirm the benefit of cannabinoids for treatment of pruritus and to standardize treatment regimens and indications. In patients who have refractory chronic pruritus after standard therapies, cannabinoid formulations may be considered as an adjuvant therapy where it is legal.

Thalidomide for the treatment of chronic refractory prurigo nodularis.

Prurigo nodularis (PN) is a highly pruritic skin condition that is caused by chronic scratching. It occurs in patients with chronic itch and is characterized by multiple hyperkeratotic papules and nodules. The pathogenesis of PN is unclear, but involves a complex interplay of numerous pathways including neurogenic and inflammatory factors. As such, PN is very difficult to treat and patients are often refractory to multiple medications before finding a treatment that is effective. We present a woman with a 20-year history of exuberant prurigo nodularis who failed multiple therapies, including dapsone, azathioprine, mycophenolic acid, prednisone, topical steroids, and phototherapy. She only obtained significant relief of chronic pruritus and lesion flattening with thalidomide 100mg daily. Thalidomide is an antipruritic and anti-inflammatory agent that has shown to be very effective in treating a variety of dermatologic conditions. However, its use today is limited by concerns for its teratogenic and neuropathic side effects. With strict adherence to medication protocols, these adverse effects can be minimized. As such, thalidomide should be considered for patients with refractory dermatologic conditions.

Food and drug administration approval process for dermatology drugs in the United States.

AIM: The purpose of this review is to elucidate the steps involved in the FDA's approval of new dermatology drugs. METHODS: To help illustrate the process of drug approval, we use examples from the recent approval of dupilumab (REGN668; Regeneron Pharmaceuticals). RESULTS: In general, new dermatology drugs must undergo pre-clinical studies on non-human subjects and three phases of clinical trials in humans before undergoing review by the Food and Drug Administration (FDA). This review process involves an interdisciplinary team of scientists that determines if the drug should be brought to market based on its efficacy, risk-to-benefit ratio, and ability to be labeled. The team that specifically reviews dermatology drugs within the Center for Drug Evaluation and Research (CDER) at the FDA is the Division of Dermatologic and Dental Drug Products. CONCLUSIONS: The drug development process is enhanced by clinician input during all stages of development.

Aprepitant for the Treatment of Chronic Refractory Pruritus.

Chronic pruritus is a difficult condition to treat and is associated with several comorbidities, including insomnia, depression, and decreased quality of life. Treatment for chronic itch includes corticosteroids, antihistamines, and systemic therapies such as naltrexone, gabapentin, UV light therapy, and immunomodulatory treatments, including azathioprine, methotrexate, and cellcept. However, some patients still remain refractory to conventional therapy. Aprepitant is a neurokinin-1 receptor antagonist approved for the prevention of chemotherapy-induced and postoperative nausea and vomiting (CINV, PONV). Recently, aprepitant has demonstrated effectiveness in several case series and open label trials in relieving pruritus for patients refractory to other treatments. Patients with pruritus associated with Sézary syndrome, mycosis fungoides, lung adenocarcinoma, breast carcinoma, sarcomas, metastatic solid tumors, chronic kidney disease, hyperuricemia, iron deficiency, brachioradial pruritus, and Hodgkin's lymphoma have experienced considerable symptom relief with short-term use of aprepitant (up to two weeks). Due to differences in reporting and evaluation of drug effects, the mechanism of aprepitant's role is difficult to understand based on the current literature. Herein, we evaluate aprepitant's antipruritic effects and discuss its mechanism of action and adverse effects. We propose that aprepitant is an alternative for patients suffering from pruritus who do not obtain enough symptom relief from conventional therapy.

Gabapentin and pregabalin for the treatment of chronic pruritus.

Chronic pruritus is a distressing symptom that is often refractory to treatment. Patients frequently fail topical therapies and oral over-the-counter antihistamines, prompting the clinician to consider alternative therapies such as neuroactive agents. Herein, the use of gabapentin and pregabalin, 2 medications well known for treating neuropathic pain and epilepsy that are occasionally used for relieving chronic pruritus is explored. The findings from original sources published to date to evaluate the use of gabapentin and pregabalin as antipruritic agents are explored. They are found to be promising alternative treatments for the relief of several forms of chronic pruritus, particularly uremic pruritus and neuropathic or neurogenic itch, in patients who fail conservative therapies.