Antipruritic Effect of Topical Acetaminophen Gel in Histaminergic and Non-histaminergic Itch Provocation: A Double-blind, Vehicle-controlled Pilot Study.

There is a need for new topical antipruritics that are effective on many types of itch. This study examined the antipruritic efficacy of a new formulation of topical acetaminophen. In vitro skin permeability studies showed that 2.5% and 5% formulations are able to rapidly deliver an adequate amount of the drug into the skin. In a double-blind, vehicle-controlled, randomized study in 17 healthy volunteers, 1%, 2.5% and 5% acetaminophen gels and a vehicle gel were applied to the skin prior to histaminergic and non-histaminergic itch induction and assessment of thermal pain thresholds. The 2.5% and 5% gel formulations significantly reduced the itch intensity time course and the area under the curve for both histamine and cowhage itch. No effect was noted on heat pain thresholds and no adverse effects were observed. These results suggest that topical acetaminophen would be a safe and effective over-the-counter medication for itch.

Hydrolysed formula, delayed food introduction and fatty acids for atopic dermatitis prevention in infancy.

AIM: The role of nutrition in preventing atopic diseases including atopic dermatitis has recently gained interest in the medical community. Caregivers of infants and children at an increased risk for developing atopic dermatitis often employ exclusion diets or other measures in hopes of preventing the development of this burdensome disease. This paper reviews the current literature in regard to the role of preventative dietary measures in the context of atopic dermatitis, with a special focus on the topics of hydrolysed formula, early vs. delayed introduction of certain foods and fatty acid supplementation. METHODS: Literature pertaining to preventative dietary measures for infants at risk for atopic dermatitis was reviewed. RESULTS: Analysis of the literature suggests that hydrolysed formula should not be routinely offered to infants for prevention of atopic dermatitis. Formulas utilised should contain concentrations of polyunsaturated fatty acids similar to that in breast milk. Finally, infant caregivers should not delay or restrict introduction of food, which can be more harmful than helpful to the patient. CONCLUSION: Recommendations to caretakers providing for infants at risk for atopic dermatitis should include infant consumption of breast milk and avoid delayed introduction of foods.

Use of Butorphanol as Treatment for Cholestatic Itch.

BACKGROUND: Pruritus is a debilitating symptom of cholestatic diseases such as primary biliary cholangitis and primary sclerosing cholangitis and often results in major reduction in quality of life for afflicted patients. Classic treatment options for the treatment of cholestatic pruritus include antihistamines, bile acid resins, serotonin reuptake inhibitors, and mu-opioid antagonists. Unfortunately, these drugs are not always successful in treating pruritus of cholestasis and may be associated with adverse effects. Recent advances in our understanding of itch pathophysiology have led to the use of butorphanol, a kappa-opioid agonist and mu-opioid antagonist, for the treatment of various forms of pruritus. Reports of butorphanol to treat cholestatic itch specifically are rare. AIMS: To better understand the role of butorphanol in the treatment of cholestatic pruritus, including characterization of its side effect profile. METHODS: We present a case series of eight adult patients with cholestatic disease who were treated with butorphanol in hopes of alleviating intractable pruritus. Patients were identified through a clinical data request form serviced by University of Miami Information Technology. RESULTS: Five out of eight patients (62.5%) reported successful reductions in itch severity after treatment with butorphanol, two patients reported no (or transient) change in itch severity, and one patient reported a paradoxical increase in itching. Side effects included somnolence, sedation, nausea, vomiting, and dizziness. CONCLUSIONS: Butorphanol was safe and leads to clinically significant symptomatic improvement. Clinicians should be aware of butorphanol as an off-label treatment option for pruritus of cholestasis. Further studies are needed to better characterize the effect of butorphanol on cholestatic itch.

Dupilumab use in atopic dermatitis and beyond in skin diseases.

Atopic dermatitis (AD) is a chronic inflammatory condition that affects 5-10% of adults and 9-18% of children and its pathology is rooted in the Th-2-mediated immune response. Dupilumab is a fully human IgG4 monoclonal antibody that targets the IL-4 receptor alpha subunit that is endogenously bound by the Th-2 cytokines IL-4 and IL-13. Successful clinical trials of dupilumab showing marked improvements in clinical signs of AD, patient reported symptoms and quality of life measures led to its approval for clinical use for moderate-to-severe AD in 2017. This review details the current body of evidence on the drug's mechanism of action, pharmacology, clinical efficacy and safety as well as post market and real world use.

Emerging drugs for the treatment of chronic pruritic diseases.

INTRODUCTION: Chronic pruritus is non-histaminergic and mediated through a complex interplay of peripheral and central immune and neural pathways. Significant developments in the understanding of chronic pruritus have emerged and paved the way for new, emerging therapies. AREAS COVERED: This review details the emerging drug landscape for chronic pruritus treatment, focusing on monoclonal antibody agents that target key cytokines and their receptors as well as small molecule agents that inhibit mediators of the immune and neural pathways. The article provides background regarding the currently available therapies and the rationale for the development of new agents based on the current market and recent scientific developments. EXPERT OPINION: Identification of new targets along neuroimmune itch pathways has allowed for the development of targeted drugs which can be utilized for effective therapy. As we enter a new era of chronic itch treatments, we face exciting prospects and challenges.

Current and emerging systemic treatments targeting the neural system for chronic pruritus.

INTRODUCTION: Pruritus is a debilitating symptom that significantly affects the quality of life of patients who suffer from it. Many current and emerging systemic treatments targeting the neural system have been successful in treating itch of various underlying etiologies. AREAS COVERED: A complete search of the PUBMED and Google Scholar databases was completed and literature pertinent to current and emerging systemic anti-pruritic drugs which target the neural system was compiled. The purpose of this review is to give the reader with an overview of the current and emerging systemic therapeutic options which target the neural system for chronic pruritus. The authors then provide the reader with their expert perspectives on the future of these therapies. EXPERT OPINION: Exciting new anti-pruritic therapies targeting the neural system which show promise include NK-1 inhibitors, opioid receptor modulators, and drugs targeting specific itch receptors such as Mrgpr, Nav1.7, and PAR2, as well as selective GABA modulators. Future studies should be conducted in order to fully understand these exciting therapeutic options.

Itch in Organs Beyond the Skin.

PURPOSE OF REVIEW: The purpose of this review was to explore mechanisms, causes, and therapies of itchy conditions involving organs beyond the skin including the eyes, ears, nose, and genital region. RECENT FINDINGS: Conditions which cause itch in these locations vary from skin diseases that extend to these areas (i.e., atopic dermatitis, seborrheic dermatitis, and psoriasis) to allergic conditions (i.e., allergic rhinitis and conjunctivitis) and to neuropathic conditions that relate to afferent nerve fiber damage (i.e., lumbosacral radiculopathies in genital disease) as well as some psychological components. Similar to the skin, itch in these locations involves a complex interaction between epithelial cells, unmyelinated C nerve fibers, and cytokines. There is also a significant component of neural sensitization phenomena. Mechanisms of itch beyond the skin are currently an understudied topic that affects millions of patients. Future research should be done in order to further understand the pathophysiology of itch in these body sites.

Psychiatric Comorbidities in Non-psychogenic Chronic Itch, a US-based Study.

Research suggests that itch and psychiatric diseases are intimately related. In efforts to examine the prevalence of psychiatric diagnoses in patients with chronic itch not due to psychogenic causes, we conducted a retrospective chart review of 502 adult patients diagnosed with chronic itch in an outpatient dermatology clinic specializing in itch and assessed these patients for a co-existing psychiatric disease. Psychiatric disease was identified and recorded based on ICD-10 codes made at any point in time which were recorded in the patient's electronic medical chart, which includes all medical department visits at the University of Miami. Fifty-five out of 502 (10.9%) of patients were found to have a comorbid psychiatric diagnosis based on ICD-10 codes. The most common psychiatric diagnoses were anxiety disorders (45.5%), followed by major depressive disorder (36.4%). There was no significant association of any specific type of itch to a particular psychiatric disorder. No unique itch characteristics were noted in patients with underlying psychiatric diagnoses.

Effects of Stress on Itch.

PURPOSE: Psychological stress and ensuing modulation of the immune and nervous systems can have a significant impact on itch. Stress can exacerbate itch and vice versa, resulting in a vicious cycle that can greatly impair a patient's quality of life. This review summarizes the association between stress and itch, elucidates the mechanism by which these two phenomena influence one another, and explores treatment modalities that aim to reduce stress-induced itch. METHODS: A complete search of the PubMed and Google Scholar databases was completed and literature pertinent to this review was compiled. FINDINGS: Both acute and chronic stress can significantly affect itch in healthy individuals and in those diagnosed with itchy skin diseases as well as systemic diseases, thus resulting in a vicious cycle in which stress exacerbates itch and vice versa. The mechanisms by which stress induces or aggravates itch include both central and peripheral activation of the hypothalamic-pituitary-adrenal axis and sympathetic nervous system. Activation of these systems, in turn, affects the mast cells, keratinocytes, and nerves that secrete neuropeptides, such as substance P, nerve growth factor, acetylcholine, histamine, and itchy cytokines. A dysfunctional parasympathetic response is thought to be involved in the chronic stress/itch response. Brain structures associated with emotion, such as the limbic system and periaqueductal gray, which work on the descending facilitation of itch, play a significant role in stress-induced itch. IMPLICATIONS: As specific brain structures are associated with stress, drug treatments targeting these areas (ie, γ-aminobutyric acid-ergic drugs, serotonin and norepinephrine reuptake inhibitors) may help to modulate itch. Stress can also be combatted using nonpharmacologic treatments such as cognitive-behavioral therapies and stress-relieving holistic approaches (eg, yoga, acupuncture).

Factors associated with long-term cardiac dysfunction in neonatal lupus.

OBJECTIVES: Cardiac manifestations of neonatal lupus (NL) have been associated with significant morbidity and mortality; however, there is minimal information on long-term outcomes of affected individuals. This study was initiated to evaluate the presence of and the risk factors associated with cardiac dysfunction in NL after birth in multiple age groups to improve counselling, to further understand pathogenesis and to provide potential preventative strategies. METHODS: Echocardiogram reports were evaluated in 239 individuals with cardiac NL: 143 from age 0-1 year, 176 from age >1-17 years and 64 from age >17 years. Logistic regression analyses evaluated associations of cardiac dysfunction at each age group with demographic, fetal and postnatal factors, using imputation to address missing data. RESULTS: Cardiac dysfunction was identified in 22.4% at age 0-1 year, 14.8% at age >1-17 years and 28.1% at age >17 years. Dysfunction in various age groups was significantly associated with male sex, black race, lower fetal heart rates, fetal extranodal cardiac disease and length of time paced. In 106 children with echocardiograms at ages 0-1 year and >1-17 years, 43.8% with dysfunction at age 0-1 year were also affected at age >1-17 years, while the others reverted to normal. Of children without dysfunction at age 0-1 year, 8.9% developed new dysfunction between ages >1 and 17 years. Among 34 with echocardiograms at ages >1-17 years and >17 years, 6.5% with normal function at age >1-17 years developed dysfunction in adulthood. CONCLUSIONS: Risk factors in fetal life can influence cardiac morbidity into adulthood.Although limited by a small number of cases, cardiac dysfunction in the first year often normalises by later childhood. New-onset dysfunction, although rare, can occur de novo after the first year.