G.W.M. Millington iD , A. Collins, C.R. Lovell, T.A. Leslie, A.S.W. Yong, J.D. Morgan, T. Ajithkumar, M.J. Andrews, S.M. Rushbook, R.R. Coelho, S.J. Catten, K.Y.C. Lee, A.M. Skellett, A.G. Affleck, L.S. Exton, M.F. Mohd Mustapa and N.J. Levell Dermatology Department, Haematology Department, Nephrology Department and Hepatology Unit, Norfolk and Norwich University Hospital, Colney Lane, Norwich NR4 7UY, U.K. Dermatology Department, Royal United Hospital, Combe Park, Bath BA1 3NG, U.K. Dermatology Department, Royal Free Hospital, Pond Street, London NW3 2QG, U.K. General Practitioner, Chet Valley Medical Practice, 40–48 George Lane, London NR14 6QH, U.K. Oncology Department, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2QQ, U.K. Dermatology Department, St George’s Hospital, Blackshaw Road, London SW17 0QT, U.K. Dermatology Department, Ninewells Hospital, Dundee DD1 9SY, U.K. British Association of Dermatologists, Willan House, 4 Fitzroy Square, London W1T 5HQ, U.K.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/bjd.16117

British Association of Dermatologists’ guidelines for the investigation and management of generalized pruritus in adults without an underlying dermatosis, 2018

Background Itch in patients with chronic kidney disease (CKD) is common, often very distressing and associated with depression, reduced quality of life, and increased death. The most common first-line treatment has been the use of antihistamines despite the lack of substantial evidence for its use for uraemic itch. Few recommendations and guidelines exist for treatment. Objectives We aimed to determine: 1) the benefits and harms (both absolute and relative) of all topical and systemic interventions for the treatment of uraemic itch, either alone or in combination, when compared with placebo or standard care; and, 2) the dose strength or frequency, stage of kidney disease or method of dialysis used (where applicable) in cases where the effects of these interventions vary depending on co-interventions. Search methods We searched the Cochrane Kidney and Transplant Register of Studies up to 17 December 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Selection criteria Randomised controlled trials (RCTs) in adults with CKD stages 4 or 5 comparing treatments (pharmacological, topical, exposure, dialysis modality) for CKD associated itch to either placebo or other established treatments. Data collection and analysis Two authors independently abstracted study data and assessed study quality. Data were analysed using a random effects meta-analysis design estimating the relative effects of treatment versus placebo. Estimates of the relative effects between treatments are included where possible. For continuous measures of severity of itch up to three months, mean difference (MD) or standardised mean difference (SMD) were used. When reported, adverse effects were tabulated. The certainty of the evidence was estimated using GRADE. Main results Ninety-two RCTs, randomising 4466 participants were included. Fifty-eight studies (3285 participants) provided sufficient data to be meta-analysed. Of these, 30 compared an intervention to a placebo or control. The 10 cm Visual Analogue Scale (VAS) was the dominant instrument utilized for itch reporting and the Duo score was used in a minority of studies. GABA analogues including, gabapentin and pregabalin, reduce itch in patients with CKD (5 studies, 297 participants: 4.95 cm reduction, 95% CI 5.46 to 4.44 lower in VAS compared to placebo; high certainty evidence). Kappa opioid agonists, including nalfurafine also reduced itch in this population (6 studies, 661 participants: 1.05 cm reduction, 95% CI 1.40 to 0.71 lower in VAS compared to placebo; high certainty evidence). Ondansetron had little or no effect on itch scores (3 studies, 183 participants: 0.38 cm reduction, 95% CI 1.04 lower to 0.29 higher in VAS compared to placebo; high certainty evidence). Reduction in the severity of itch was reported with oral montelukast, turmeric, zinc sulfate and topical capsaicin. For all other interventions, the certainty of the evidence was low to moderate, and the interventions had uncertain effects on uraemic pruritus. Six studies have disclosed significant financial support from their respective manufacturers, six were affected by lack of blinding, and 11 studies have 15 participants or less. Older, smaller RCTs often failed to follow intention-to-treat protocols with unexplained dropouts after randomisation. Adverse effects were generally poorly and inconsistently reported across all RCTs. No severe adverse events were reported for any intervention. Authors' conclusions The RCTs of this meta-analysis contain a large array of interventions with a diverse set of comparators. For many interventions, trials are sparse. This served to make informative meta-analysis challenging. Of all treatments for uraemic pruritus, gabapentinoids (gabapentin and pregabalin) were the most studied and show the greatest reduction in itch scores. Further RCTs, even of the scale of the largest trials included in this review, are unlikely to significantly change this finding. Kappa-opioid agonists (mainly nalfurafine) also may reduce itch, but indirect comparison suggests a much more modest effect in comparison to GABA analogues. Evidence for oral montelukast, turmeric, zinc sulfate, and topical capsaicin also showed an itch score reduction. However, these reductions were reported in small studies, and warrant further investigation. Ondansetron did not reduce itch. It is somewhat unlikely that a further study of ondansetron will change this result.

Interventions for itch in people with advanced chronic kidney disease

Background
People living with chronic kidney disease (CKD) experience a range of symptoms and often have complex comorbidities. Many pharmacological interventions for people with CKD have known risks of adverse events. Acupuncture is widely used for symptom management in patients with chronic diseases and in other palliative care settings. However, the safety and efficacy of acupuncture for people with CKD remains largely unknown.

Objectives
We aimed to evaluate the benefits and harms of acupuncture, electro-acupuncture, acupressure, moxibustion and other acupuncture-related interventions (alone or combined with other acupuncture-related interventions) for symptoms of CKD. In particular, we planned to compare acupuncture and related interventions with conventional medicine, active non-pharmacological interventions, and routine care for symptoms of CKD.

Search methods
We searched the Cochrane Kidney and Transplant Specialised Register up to 28 January 2016 through contact with the Information Specialist using search terms relevant to this review. We also searched Korean medical databases (including Korean Studies Information, DBPIA, Korea Institute of Science and Technology Information, Research Information Centre for Health Database, KoreaMed, the National Assembly Library) and Chinese databases (including the China Academic Journal).

Selection criteria
We included randomised controlled trials (RCTs) and quasi-RCTs that investigated the effects of acupuncture and related point-stimulation interventions with or without needle penetration that involved six sessions or more in adults with CKD stage 3 to 5, regardless of the language and type of publication. We excluded studies that used herbal medicine or co-interventions administered unequally among the study groups.

Data collection and analysis
Two authors independently extracted data and assessed risk of bias. We calculated the mean difference (MD) or standardised mean difference (SMD) with 95% confidence intervals (CI) for continuous outcomes and risk ratio (RR) for dichotomous outcomes. Primary outcomes were changes in pain and depression, and occurrence of serious of adverse events.

Main results
We included 24 studies that involved a total of 1787 participants. Studies reported on various types of acupuncture and related interventions including manual acupuncture and acupressure, ear acupressure, transcutaneous electrical acupuncture point stimulation, far-infrared radiation on acupuncture points and indirect moxibustion. CKD stages included pre-dialysis stage 3 or 4 and end-stage kidney disease on either haemodialysis or peritoneal dialysis.

None of the included studies assessed pain outcomes, nor formally addressed occurrence of serious adverse events, although three studies reported three participant deaths and three hospitalisations as reasons for attrition. Three studies reported minor acupuncture-related harms; the remainder did not report if those events occurred.

All studies were assessed at high or unclear risk of bias in terms of allocation concealment. Seventeen studies reported outcomes measured for only two months.

There was very low quality of evidence that compared with routine care, manual acupressure reduced scores of the Beck Depression Inventory score (scale from 0 to 63) (3 studies, 128 participants: MD -4.29, 95% CI -7.48 to -1.11, I2 = 0%), the revised Piper Fatigue Scale (scale from 0 to 10) (3 studies, 128 participants: MD -1.19, 95% CI -1.77 to -0.60, I2 = 0%), and the Pittsburgh Sleep Quality Index (scale from 0 to 21) (4 studies, 180 participants: MD -2.46, 95% CI -4.23 to -0.69, I2 = 50%).

We were unable to perform further meta-analyses because of the paucity of data and problems with clinical heterogeneity, such as different interventions, comparisons and timing of outcome measurements.

Authors' conclusions
There was very low quality of evidence of the short-term effects of manual acupressure as an adjuvant intervention for fatigue, depression, sleep disturbance and uraemic pruritus in patients undergoing regular haemodialysis. The paucity of evidence indicates that there is little evidence of the effects of other types of acupuncture for other outcomes, including pain, in patients with other stages of CKD. Overall high or unclear risk of bias distorts the validity of the reported benefit of acupuncture and makes the estimated effects uncertain. The incomplete reporting of acupuncture-related harm does not permit us to assess the safety of acupuncture and related interventions. Future studies should investigate the effects and safety of acupuncture for pain and other common symptoms in patients with CKD and those undergoing dialysis.

Acupuncture and related interventions for symptoms of chronic kidney disease

Objectives: Acupuncture is an important Traditional Chinese Medicine modality based on the fundamental theory that disease is caused by disruptions in the body's qi. Understanding the use of acupuncture in dermatology is important due to the rising prevalence of complementary and alternative medicine use. A systematic review published in 2015 found that acupuncture improves outcomes in several dermatological diseases. We performed a systematic review of studies that have been done since then to present updated evidence. Methods: A systematic search of MEDLINE, EMBASE, and the Cochrane Central Register was performed. Studies were limited to clinical trials, controlled studies, case reports, comparative studies, and systematic reviews published in the English language. Studies involving moxibustion, electroacupuncture, or blood-letting were excluded. Results: Results showed that acupuncture improves clinical outcomes in uremic pruritus, atopic dermatitis, urticaria, and itch. Acupuncture does not significantly reduce postoperative itch in patients undergoing cesarean section under spinal anesthesia. Conclusions: While there are some promising studies that support the use of acupuncture for skin diseases, additional large-scale, randomized, sham-controlled trials need to be performed to present consistent high-level evidence of acupuncture's role in dermatology.

Acupuncture in Dermatology: An Update to a Systematic Review.

Uremic pruritus is an unpleasant sensation and one of the most common disabling symptoms occurs for patients undergoing hemodialysis. Aromatherapy as a part of complementary and alternative medicine (CAM) has been reported to have multiple beneficial properties for management of uremic pruritus. The aim of the study was to evaluate the effect of aromatherapy on uremic pruritus among patients undergoing hemodialysis. A quasi experimental design (pretest-posttest one control group design) was utilized to achieve the aim of the study. Adult male and female conscious patients diagnosed with chronic kidney disease undergoing hemodialysis were recruited in this study. The study carried out at renal insufficiency and dialysis unit at one of the university hospitals in Cairo governorate. Structured interview questionnaire and 5domain pruritus scale were used for data collection. Results: The study results revealed that (53%) of the study participants were 31-40 years old whereas (47%) of them were from 41-50 years old. Regarding duration of kidney problems, (3.3%) of the studied participants had kidney problems in for less than 3 years, as well as (13.3%) had kidney problems from 3 to 6 years, while (13.3%) and (70%) of them had kidney problems from 6 to less than 9 years and 9 years to 12 year respectively. There was highly statistical significant difference before and after aromatherapy using (t = 5.81, p = 0.000***). Conclusion: Aromatherapy can be effective in the treatment of pruritus. It is natural, available, cheap, and with fewer side effects than other medication used for uremic pruritus treatment.

/pdf/effect-of-aromatherapy-on-uremic-pruritus-among-patients-bvgg3i8zl6.pdf

Effect of Aromatherapy on Uremic Pruritus among Patients Undergoing Hemodialysis

Background. Uremic pruritus (UP) is a common symptom in patients undergoing maintenance hemodialysis for end-stage renal disease (ESRD). Objective. To determine the clinical efficacy of auricular acupressure therapy on pruritus in hemodialysis patients and to explore possible underlying mechanisms. Methods. Patients receiving maintenance hemodialysis at a referral medical center were recruited and assigned to intervention (n = 32) and control (n = 30) groups. The intervention group underwent auricular acupressure treatment three times a week for six weeks. Auricular acupressure was not applied to patients in the control group. However, tape without Vaccaria seeds was applied to the same six auricular acupoints as the intervention group. Pruritus scores were assessed using VAS scores, and enzyme-linked immunosorbent assays (ELISA) were used to measure levels of other possible contributory biochemical factors. Results. There was a significant difference in mean VAS scores between the postintervention and control groups during follow-up (3.844 ± 1.687 versus 5.567 ± 2.285, F = 22.32, P < 0.0001). Compared to the control group, serum histamine levels in the postintervention group at the six-week follow-up had decreased significantly (F = 5.01, P = 0.0290). Conclusion. Our findings suggest that auricular acupressure may be a useful treatment in the multidisciplinary management of UP in ESRD patients.

/pdf/effect-of-auricular-acupressure-on-uremic-pruritus-in-2b44yv9a3b.pdf

Effect of Auricular Acupressure on Uremic Pruritus in Patients Receiving Hemodialysis Treatment: A Randomized Controlled Trial

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Effect of Auricular Acupressure on Uremic Pruritus in Patients Receiving Hemodialysis Treatment: A Randomized Controlled Trial