Neuroimmune Mediators of Pruritus in Hispanic Scalp Psoriatic Itch.

Scalp psoriatic itch is a common, bothersome, yet understudied, condition with numerous associated treatment challenges. The aim of this study was to enhance our understanding of the pathophysiology of scalp psoriatic itch. Immunohistochemical analysis of known neuroimmune mediators of pruritus was conducted using scalp biopsies from 27 Hispanic psoriatic patients. Patients were categorized into mild/moderate or severe itch groups according to their itch intensity rating of scalp itch. Protease activated receptor (PAR2), substance P, transient receptor potential (TRP)V3, TRPM8 and interleukin-23 expression all correlated  significantly with itch intensity. The pathophysiology of scalp psoriasis is largely non-histaminergic, mediated by PAR2, interleukin-23, transient receptor potential channels, and substance P.

Autoimmune Progesterone Dermatitis: A Systematic Review.

ABSTRACT: Autoimmune progesterone dermatitis (AIPD) is a cyclical, cutaneous reaction to endogenous progesterone that occurs throughout the menstrual cycle. The cutaneous manifestations of AIPD vary greatly from patient to patient, ranging anywhere from urticaria to erythema multiforme to anaphylaxis. As such, recognition, diagnosis, and management of this condition are difficult for clinicians. In the present article, we conducted a systematic review of 112 articles and 132 individual cases to summarize the clinical features and presentation of AIPD while also summarizing the successes and failures of different treatment plans. Despite the great variety in clinical presentations, it is clear from the data that ovulation-suppressing medical therapies and surgery have the greatest success in treating AIPD, whereas more commonly used therapies such as antihistamines and systemic corticosteroids frequently fail in providing any relief. Further research is necessary to determine the exact pathogenesis of AIPD and allow for more targeted treatment.

When topical therapy of atopic dermatitis fails: a guide for the clinician.

INTRODUCTION: While topical medications are the first line of treatment for mild-to-moderate atopic dermatitis, they are ineffective in individuals with diffuse disease and moderate-to-severe atopic itch. For these individuals, as well as those who do not respond to topical treatments, systemic medicines are typically essential and helpful. AREAS COVERED: We conducted a review of the literature to identify established systemic therapies, novel biologic agents, and recent advances in the pathophysiology of atopic dermatitis. The review discusses these data, which show that the majority of atopic itch medications now in development target the type 2 immune axis and brain sensitization, two main etiologies of atopic itch. We emphasize the evidence, efficacy, and side effect profiles of currently available systemic medications for atopic itch, as well as future potential for tailored therapy. EXPERT OPINION: We give our professional opinion on the current state of knowledge about atopic eczema pathogenesis and the innovative targets and therapies for atopic itch that include MRGPRX2, periostin, gabaergic medicines, and JAK/STAT inhibitors. Additionally, we discuss patient populations that stand to benefit the most from targeting these molecules or utilizing these drugs, as well as those who may face a disproportionate weight of adverse effects.

Current Clinical Options for the Management of Itch in Atopic Dermatitis.

Pruritus is the most burdensome and prevalent symptom in patients suffering from atopic dermatitis. Treating atopic itch has historically been a challenge due to multiple underlying mechanisms within its pathogenesis and an incomplete understanding of them. In recent years, our understanding of these mechanisms have increased tremendously and subsequently, new treatments have reached the market that target the pathophysiology of atopic itch from different angles. In addition, there are several promising new treatments currently in development and trials. In the current article, we discuss these currently available treatment options, their available evidence and efficacy, and highlight some of the more recent advancements in the field.

Approach to the Patient with Chronic Pruritus.

Chronic pruritus (itch lasting ≥6 weeks) is a bothersome chief complaint that may present in a broad variety of diseases. Most itch-causing diagnoses fit into 1 of 5 categories (inflammatory, secondary to systemic disease, neuropathic, chronic pruritus of undetermined origin, and psychogenic itch) and this broad differential can be narrowed using key findings in the history and physical. In this article, we discuss which key findings are most pertinent for narrowing this differential and guiding further workup and treatment, as well as how to treat many itchy conditions.

The pruritogenic role of the type 2 immune response in diseases associated with chronic itch.

While there is a vast array of aetiologies that may lead to chronic pruritus, recent data suggests that many of these conditions share similar interactions between keratinocytes, nerves, and the immune system. Specifically, the type 2 immune response, including Th2 T Cells and their related cytokines, has been noted to play a major role in the development of pruritus in a variety of itchy conditions. To date, atopic dermatitis is the most striking example of this pathogenesis. However, the body of literature supporting its role in many other itchy conditions, including other inflammatory, bullous, as well as systemic diseases, continues to grow. In addition, new treatments targeting this type 2 immune system continue to be developed and investigated. In the current review, we present the current body of literature supporting the role of the type 2 immune response in itchy conditions beyond atopic dermatitis as well as potential therapeutic options that target this pathway for chronic itch.

Clinical management of chronic kidney disease-associated pruritus: current treatment options and future approaches.

Chronic kidney disease (CKD)-associated pruritus (CKD-aP) is an underdiagnosed yet severely distressing condition that impacts 60% of patients on dialysis and many nondialysis patients with Stages 3-5 CKD. However, despite its high prevalence, there are currently limited treatment options available for these patients and a lack of treatment guidelines for clinicians. In this manuscript, we reviewed the available literature in order to evaluate the current management and treatment options for CKD-aP, including dialysis management, topical treatments, gabapentinoids, opioids and alternative medicine. We also review the available data on CKD-aP treatments in development and propose new guidelines for managing patients with CKD-aP.

Substance use disorders and chronic itch.

Chronic pruritus is one dermatologic manifestation of an underlying substance use disorder. Recent literature has uncovered similarities between the general neurologic mechanisms of addiction and chronic itch, largely involving activation of the dopaminergic reward circuits within the brain and imbalances between mu and kappa opioid receptor activation. It is likely that the use of specific drugs, like central nervous system stimulants and opioids, results in further activation and imbalances within these pathways, perpetuating both addiction and pruritus simultaneously. Opioid users often present to dermatology clinics with a generalized pruritus, whereas individuals using central nervous system stimulants like cocaine and methylenedioxymethamphetamine (MDMA), as well as legally prescribed drugs like treatments for attention deficit hyperactivity disorder, frequently complain of crawling, delusional infestation-like sensations underneath the skin. Because of these overlapping mechanisms and similar clinical presentations to many other chronically itchy conditions, it is necessary for dermatologists to consider and investigate an underlying substance use disorder to effectively treat these patients.

An evaluation of difelikefalin as a treatment option for moderate-to-severe pruritus in end stage renal disease.

Introduction: Chronic kidney disease-associated pruritus (CKD-aP), or uremic pruritus, is a severely distressing condition that occurs in greater than 60% of patients undergoing dialysis. However, there are currently no FDA approved treatments for CKD-aP in the United States or Europe. Difelikefalin (DFK) is a kappa opioid receptor agonist with limited central nervous system (CNS) penetration that aims to fill this void by effectively and safely reducing itch in these patients.Areas covered: Through a review of the current literature (using PubMed and Google Scholar keyword searches of difelikefalin, CR845, pruritus, itch, opioids, hemodialysis, chronic kidney disease, uremic pruritus), the authors review DFK's mechanism of action and use published clinical trial data to evaluate its effectiveness in treating CKD-aP both individually and comparatively to other treatment alternatives.Expert opinion: DFK's IV formulation seems to provide safe, rapid-acting and effective itch reduction in hemodialysis patients without many of the negative mu opioid receptor (MOR)- or CNS- related side effects or drug-drug interactions of other currently available opioids. Its administration through IV bolus immediately after dialysis sessions at dialysis centers also increases availability to and ease of drug scheduling for this target population.