Current Topical and Systemic Therapies for Itch

Itch is a common distressing symptom which may be caused by multifactorial aetiologies including inflammatory skin diseases, systemic diseases, neuropathic conditions and psychogenic disorders. Itch is a term used synonymously with pruritus and is defined as acute if it lasts less than 6 weeks or chronic if it persists for more than 6 weeks. It can have the same impact on the quality of life as chronic pain and shares many of the same pathophysiological pathways. Depending on the aetiology of the itch, different pathogenic mechanisms have been postulated with a number of mediators identified. These include histamine, leukotrienes, proteases, neuropeptides, cytokines and opioids, which may activate peripheral itch-mediating C-fibres via receptors on the nerve terminals and central neuronal pathways. Therefore, there is no single universally effective anti-itch treatment available. First-line treatments for itch include topical therapies, such as emollients, mild cleansers (low pH), topical anaesthetics, steroids, calcineurin inhibitors and coolants (menthol). Treatment with systemic therapies can vary according to the aetiology of the chronic itch. Non-sedating antihistamines are helpful in conditions such as urticaria where the itch is primarily histamine mediated. Although the itch of eczema is not mediated by histamine, sedating antihistamines at night are helpful to break the itch-scratch cycle. Chronic itch may also be treated with other systemic therapies, such as anticonvulsants, antidepressants as well as mu-opioid antagonists, kappa-opioid agonists and phototherapy, depending on the cause of the itch. This article summarises the topical and systemic therapies available with our current understanding of the pathophysiology of itch

Meta-analysis of individual-patient data from EVAR-1, DREAM, OVER and ACE trials comparing outcomes of endovascular or open repair for abdominal aortic aneurysm over 5 years.

BACKGROUND: The erosion of the early mortality advantage of elective endovascular aneurysm repair (EVAR) compared with open repair of abdominal aortic aneurysm remains without a satisfactory explanation. METHODS: An individual-patient data meta-analysis of four multicentre randomized trials of EVAR versus open repair was conducted to a prespecified analysis plan, reporting on mortality, aneurysm-related mortality and reintervention. RESULTS: The analysis included 2783 patients, with 14 245 person-years of follow-up (median 5·5 years). Early (0-6 months after randomization) mortality was lower in the EVAR groups (46 of 1393 versus 73 of 1390 deaths; pooled hazard ratio 0·61, 95 per cent c.i. 0·42 to 0·89; P = 0·010), primarily because 30-day operative mortality was lower in the EVAR groups (16 deaths versus 40 for open repair; pooled odds ratio 0·40, 95 per cent c.i. 0·22 to 0·74). Later (within 3 years) the survival curves converged, remaining converged to 8 years. Beyond 3 years, aneurysm-related mortality was significantly higher in the EVAR groups (19 deaths versus 3 for open repair; pooled hazard ratio 5·16, 1·49 to 17·89; P = 0·010). Patients with moderate renal dysfunction or previous coronary artery disease had no early survival advantage under EVAR. Those with peripheral artery disease had lower mortality under open repair (39 deaths versus 62 for EVAR; P = 0·022) in the period from 6 months to 4 years after randomization. CONCLUSION: The early survival advantage in the EVAR group, and its subsequent erosion, were confirmed. Over 5 years, patients of marginal fitness had no early survival advantage from EVAR compared with open repair. Aneurysm-related mortality and patients with low ankle : brachial pressure index contributed to the erosion of the early survival advantage for the EVAR group. Trial registration numbers: EVAR-1, ISRCTN55703451; DREAM (Dutch Randomized Endovascular Aneurysm Management), NCT00421330; ACE (Anévrysme de l'aorte abdominale, Chirurgie versus Endoprothèse), NCT00224718; OVER (Open Versus Endovascular Repair Trial for Abdominal Aortic Aneurysms), NCT00094575