LAUSR

Pruritus, commonly known as itch, has a substantial impact on quality of life in skin disease. Irritation of one of the largest organs of the body does not just directly impact upon the organ itself but underlies a plethora of indirect consequences for the patient that goes way beyond the desire to scratch. The psychological issues associated with chronic pruritus combine with disfigurement from scratching and sleep disturbance to produce mental health problems in many cases. While itch may be a consequence of cutaneous inflammation, symptom improvement by modulation of pruritus represents an important pharmacological target. There has been a lot of activity in the field recently, at both preclinical and clinical ends of the spectrum, providing a compelling case for a joint virtual issue between the BJP and BJD with a focus on novel therapeutics for pruritus. As the editors of the two journals we have each picked seven recent articles to share with our combined audiences. Readers of BJP may not be aware that the BJD has a focus on particular core methodologies that determine the main sections of the journal: translational, trials, outcomes and qualitative research, epidemiology, and evidence-based dermatology. Similarly, BJD readers may not be aware that BJP is often the journal of choice for those researchers interrogating the mechanisms of pruritis and the testing of novel entities in appropriate in vitro and in vivo experimental models. Considering translational research first, our virtual issue contains a review of substance P and neurokinin 1 receptor as targets for the treatment of chronic pruritus. Both entities are overexpressed in multiple chronic pruritic conditions, providing a rationale for translational therapeutic applications. The review covers several recent phase II clinical trials of neurokinin 1 receptor antagonists demonstrating potential clinical benefit. In addition, we include two original articles providing greater depth into our understanding of the mechanisms involved in activation of the sensory neurones containing these neuropeptides. We share evidence implicating both TMEM16A and reactive nitrogen species in activating TRPV1 and TRPA1 channels localized to nerve endings, thus identifying potential new avenues for limiting the itch sensation. BJP has long been a journal home to developments in histamine and histamine receptor pharmacology. Accordingly, in this issue we share the most recent updates on the role and targeting of histamine in itch and associated pain, and recent progress in application of molecules targeting the H4 receptor particularly. The journal is also home to some of the best pharmacology in purified natural products, an area with an explosion of interest over the last decade. This explosion is exemplified by a recent article demonstrating the potential of salvinorin A analogues in preventing mast cell degranulation, which in this way can potentially break the continuous cycle created by physical disruption of mast cells of itch–relief–itch. BJP also has a long history in publishing research emanating from the prostaglandin field, being a title that has published some of the most highly cited papers in the field. These include a paper by the Nobel prize-winning pharmacologist Sir John Vane, the 20-year anniversary of which was recently celebrated in a separate themed issue in the journal. In this virtual issue we also include some exciting evidence identifying further utility for the somewhat maligned cyclooxygenase2 inhibitors in modifying TRPV3 activity. Oral Janus kinase (JAK)/spleen tyrosine kinase (SYK) inhibitors are among the new small molecules that are under development for dermatological applications, including the pruritus associated with atopic dermatitis (AD). In a phase IB randomized controlled trial investigating ASN002, an oral JAK/SYK inhibitor for moderate-to-severe AD, a 50% reduction in Eczema Area and Severity Index was reached by a significantly higher proportion of patients who received higher doses of ASN002 compared with placebo. The BJD has established a strong pedigree in publishing outcomes research, which usually requires a qualitative aspect in the form of patient interviews to demonstrate content validity. Yosipovitch and colleagues combined patient interviews with trial data to establish that the Peak Pruritus Numerical Rating Scale is a reliable, sensitive and valid scale for assessing worst itch intensity in adults with moderate-to-severe AD. As mentioned in the introductory paragraph, one important potential consequence of chronic pruritus is a detrimental effect on mental health. Silverberg and colleagues performed a cross-sectional, population-based study of 2893 U.S. adults with AD and found significantly increased risks of anxiety and depression, using Hospital Anxiety and Depression Scale (HADS) scores, compared with those without AD. Some of the individuals with elevated HADS scores had not received a formal diagnosis, emphasizing the need for vigilance in this patient group. The BJD champions evidence-based dermatology. A review article included in this virtual issue considers the problem of severe, treatment-resistant pruritus associated with primary biliary cholangitis, in which destruction of liver bile ducts leads to intrahepatic cholestasis. Our understanding of its