Association between pruritus and serum concentrations of parathormone, calcium and phosphorus in hemodialysis patients.

Chronic renal disorders have a progressive course in most cases, and finally result in end-stage renal disease (ESRD). Hemodialysis (HD) is one of the mainstays in the treatment of these patients. Disturbance in calcium (Ca) and phosphorus (P) metabolism and alteration of serum levels of parathormone (PTH) are observed in these patients. One of the most common cutaneous manifestations in patients on HD is pruritus. The aim of this study is to evaluate the association between pruritus and serum concentrations of Ca, P and PTH in patients with chronic renal disease. This analytic, descriptive, cross-sectional study was performed on 120 patients on HD at the Fifth-Azar Hospital in Gorgan, Iran, in 2010. Information related to the patients, including age, gender, pruritus, time of pruritus and duration on dialysis, was extracted from questionnaires. Serum concentrations of intact PTH, Ca and P were measured. Data were analyzed by the chi-square test and SPSS-16 software. A P-value less than 0.05 was considered statistically significant. Among the 120 study patients, 50% were male and the mean age (±SD) was 49 ± 12.3 years. Sixty percent of the patients had pruritus, of whom 33.3% had PTH levels above the normal range. Among the 40% of the patients who did not have pruritus, 39.6% had PTH levels higher than the normal levels. The mean serum Ca and P levels were 8.44 ± 1.65 mg/dL and 5.48 ± 1.81 mg/dL, respectively. The mean (±SD) Ca-P product was 55.46 ± 47.16 and the mean PTH concentration was 274.34 ± 286.53 pg/mL. No significant association was found between pruritus and age, sex, serum PTH and P levels as well as Ca-P product. However, the association between serum Ca levels and pruritus was significant (P = 0.03). Our study showed that most patients with pruritus had serum Ca levels in the abnormal range (lower or higher), and there was no significant correlation between serum iPTH level and pruritis. Thus, good control of serum Ca levels is important to reduce pruritus in these patients

Comparison of gabapentin and ketotifen in treatment of uremic pruritus in hemodialysis patients

Objectives: Uremic pruritus is a common problem in hemodialysis patients. Several treatments have been used for decreasing itching in these patients. Gabapentin and ketotifen are two drugs used for treating uremic patients.The aim of this study was to compare gabapentin and ketotifen in treatment of uremic pruritus in hemodialysis patients. Methods: In this double-blind randomized clinical trial, 52 hemodialysis patients with uremic pruritus referred to 5azarTeaching Hospital in Gorgan in 2013 were studied. Patients were randomly assigned to two groups of 26 subjects (groups G and K). In group G, patients treated with gabapentin capsules 100 mg daily for 2 weeks, and in Group K, patients treated with ketotifen 1 mg twice daily for 2 weeks. Before and at the end of study, pruritus severity was determined based on Shiratori›s severity scores. Collected data were analyzed by SPSS-21 statistical software. Results: There was no significant different between two groups in the age and sex. After two weeks of treatment, severity of pruritus was significantly reduced in both groups (88.4 in group G vs. 76.9 in group K). Gabapentin compared with ketotifen had a better effect on improving itching in the age group of 30-60 years and in males. 5 patients (19.2) in both groups suffered from drowsiness and dizziness, but no serious side effects were observed. Conclusions: The results showed that gabapentin and ketotifen significantly improved pruritus in hemodialysis patients, and no significant difference was observed between two groups. © 2016, Professional Medical Publications. All rights reserved

A Randomized, Controlled, Phase 2 Study of Maralixibat in the Treatment of Itching Associated With Primary Biliary Cholangitis.

Primary biliary cholangitis (PBC) is typically associated with elevated serum bile acid levels and pruritus, but pruritus is often refractory to treatment with existing therapies. This phase 2 study assessed the efficacy and safety of maralixibat, a selective, ileal, apical, sodium-dependent, bile acid transporter inhibitor, in adults with PBC and pruritus. Adults with PBC and pruritus who had received ursodeoxycholic acid (UDCA) for ≥6 months or were intolerant to UDCA were randomized 2:1 to maralixibat (10 or 20 mg/day) or placebo for 13 weeks in combination with UDCA (when tolerated). The primary outcome was change in Adult Itch Reported Outcome (ItchRO™) average weekly sum score (0, no itching; 70, maximum itching) from baseline to week 13/early termination (ET). The study enrolled 66 patients (maralixibat [both doses combined], n = 42; placebo, n = 24). Mean ItchRO™ weekly sum scores decreased from baseline to week 13/ET with maralixibat (-26.5; 95% confidence interval [CI], -31.8, -21.2) and placebo (-23.4; 95% CI, -30.3, -16.4). The difference between groups was not significant (P = 0.48). In the maralixibat and placebo groups, adverse events (AEs) were reported in 97.6% and 70.8% of patients, respectively. Gastrointestinal disorders were the most frequently reported AEs (maralixibat, 78.6%; placebo, 50.0%). Conclusion: Reductions in pruritus did not differ significantly between maralixibat and placebo. However, a large placebo effect may have confounded assessment of pruritus. Lessons learned from this rigorously designed and executed trial are indispensable for understanding how to approach trials assessing pruritus as the primary endpoint and the therapeutic window of bile acid uptake inhibition as a therapeutic strategy in PBC

Emerging Methods to Objectively Assess Pruritus in Atopic Dermatitis.

INTRODUCTION:Atopic dermatitis (AD) is an inflammatory skin disease with a chronic, relapsing course. Clinical features of AD vary by age, duration, and severity but can include papules, vesicles, erythema, exudate, xerosis, scaling, and lichenification. However, the most defining and universal symptom of AD is pruritus. Pruritus or itch, defined as an unpleasant urge to scratch, is problematic for many reasons, particularly its negative impact on quality of life. Despite the profoundly negative impact of pruritus on patients with AD, clinicians and researchers lack standardized and validated methods to objectively measure pruritus. The purpose of this review is to discuss emerging methods to assess pruritus in AD by describing objective patient-centered tools developed or enhanced over the last decade that can be utilized by clinicians and researchers alike. METHODS:This review is based on a literature search in Medline, Embase, and Web of Science databases. The search was performed in February 2019. The keywords were used "pruritus," "itch," "atopic dermatitis," "eczema," "measurements," "tools," "instruments," "accelerometer," "wrist actigraphy," "smartwatch," "transducer," "vibration," "brain mapping," "magnetic resonance imaging," and "positron emission tomography." Only articles written in English were included, and no restrictions were set on study type. To focus on emerging methods, prioritization was given to results from the last decade (2009-2019). RESULTS:The search yielded 49 results in PubMed, 134 results in Embase, and 85 results in Web of Science. Each result was independently reviewed in a standardized manner by two of the authors (M.S., K.L.), and disagreements between reviewers were resolved by consensus. Relevant findings were categorized into the following sections: video surveillance, acoustic surveillance, wrist actigraphy, smart devices, vibration transducers, and neurological imaging. Examples are provided along with descriptions of how each technology works, instances of use in research or clinical practice, and as applicable, reports of validation studies and correlation with other methods. CONCLUSION:The variety of new and improved methods to evaluate pruritus in AD is welcomed by clinicians, researchers, and patients alike. Future directions include next-generation smart devices as well as exploring new territories, such as identifying biomarkers that correlate to itch and machine-learning programs to identify itch processing in the brain. As these efforts continue, it will be essential to remain patient-centered by developing techniques that minimize discomfort, respect privacy, and provide accurate data that can be used to better manage itch in AD

Dupilumab for bullous pemphigoid with intractable pruritus

Bullous pemphigoid (BP) is an autoimmune blistering disorder that predominantly affects the elderly. Treatment regimens typically include topical and systemic immunosuppressive medications. Although effective, systemic corticosteroids are sometimes poorly tolerated in the elderly patient, contributing to the overall morbidity and mortality of BP. Dupilumab is a monoclonal antibody targeting interleukin 4 receptor alpha (IL4R?), approved for the treatment of atopic dermatitis, as well as moderate to severe asthma and chronic rhinosinusitis with nasal polyposis. In recent reports, dupilumab has been successfully used off-label to treat a variety of pruritic disorders, including chronic spontaneous urticaria [1], anal and genital itch [2], allergic contact dermatitis [3], and prurigo nodularis [4, 5]. We report here a case of an elderly patient with refractory BP whose symptoms of pruritus and blistering became well-controlled with the addition of dupilumab to the treatment regimen

Benign recurrent intrahepatic cholestasis : report of two local cases

Benign Recurrent Intrahepatic Cholestasis (BRIC) is a rare disorder characterized by recurrent episodes of cholestasis without permanent liver damage. Familial and sporadic cases have been reported and both autosomal recessive and autosomal dominant inheritance described. We report two children with BRIC without any previous family history.peer-reviewe

Mucocutaneous manifestations and nail changes in patients with end-stage renal disease on hemodialysis.

Mucocutaneous manifestations are common among patients on hemodialysis (HD). This study was undertaken to determine the prevalence of mucocutaneous manifestations in patients with end-stage renal disease (ESRD) who are on HD. In this cross-sectional, descriptive and analytic study conducted in 2009, 100 patients on HD at the Five Azar Hospital in Gorgan city were randomly selected. All the patients underwent detailed examination by a dermatologist to look for lesions in the skin, hair, nail and mucous membranes; if felt necessary, biopsy was obtained from the lesions. The findings were statistically analyzed using SPSS-13 software. For evaluation of normality of distribution, Kolmogorov-Smirnov was used, for quantitative variables Mann-Whitney and T-test (abnormal distribution) were used and for qualitative variables, Chi-2 and Fisher were used. In this study, P-value less than 0.05 was considered significant. Fifty-one males and 49 females were enrolled. The mean age was 49 ± 12 years. Diabetes was the most common cause of ESRD. In 95% of the patients, at least one mucocutaneous manifestation was present. Xerosis (78.3%) was the most common lesion, followed by pruritus (39.1%), lentigo (34.8%), skin discoloration (32.6%), leukonychia (32%) and thinning of the nail bed (24%). Xerosis, scaling, lentigo, folliculitis, idiopathic guttate hypopigmentation, leukonychia and half and half nail were associated with age. A significant relationship was seen between duration on dialysis and skin discoloration and leukonychia. Clubbing had a significant association with calcium-phosphorus product (Ca � P). There was a significant association between serum ferritin level and pruritus and tinea versicolor lesions. Our study shows that mucocutaneous manifestations are common among patients with ESRD. Identification of these manifestations and their association with causative factors are useful for preventing the lesions

Obeticholic acid for the treatment of primary biliary cholangitis in adult patients: clinical utility and patient selection.

Primary biliary cholangitis (PBC), previously known as primary biliary "cirrhosis", is a rare autoimmune liver disease characterized by the hallmark autoantibodies to mitochondrial antigens and immune-mediated destruction of small bile duct epithelial cells leading to cholestasis and cirrhosis. Surprisingly, while immune modulators have not been effective in the treatment of PBC, supplementation with the hydrophilic bile acid (BA) ursodeoxycholic acid (UDCA) has been demonstrated to slow the disease progression. However, a significant minority of PBC patients do not have a complete response to UDCA and remain at risk of continued disease progression. Although the mechanisms of action are not well understood, UDCA provided proof of concept for BA therapy in PBC. Obeticholic acid (OCA), a novel derivative of the human BA chenodeoxycholic acid, is a potent agonist of the nuclear hormone receptor farnesoid X receptor, which regulates BA synthesis and transport. A series of clinical trials of OCA in PBC, primarily in combination with UDCA, have established that OCA leads to significant reductions in serum alkaline phosphatase that are predicted to lead to improved clinical outcomes, while dose-dependent pruritus has been the most common adverse effect. On the basis of these studies, OCA was given conditional approval by the US Food and Drug Administration with plans to establish the long-term clinical efficacy of OCA in patients with advanced PBC

Pruritus is a common feature in sheep infected with the BSE agent.

BACKGROUND: The variability in the clinical or pathological presentation of transmissible spongiform encephalopathies (TSEs) in sheep, such as scrapie and bovine spongiform encephalopathy (BSE), has been attributed to prion protein genotype, strain, breed, clinical duration, dose, route and type of inoculum and the age at infection. The study aimed to describe the clinical signs in sheep infected with the BSE agent throughout its clinical course to determine whether the clinical signs were as variable as described for classical scrapie in sheep. The clinical signs were compared to BSE-negative sheep to assess if disease-specific clinical markers exist. RESULTS: Forty-seven (34%) of 139 sheep, which comprised 123 challenged sheep and 16 undosed controls, were positive for BSE. Affected sheep belonged to five different breeds and three different genotypes (ARQ/ARQ, VRQ/VRQ and AHQ/AHQ). None of the controls or BSE exposed sheep with ARR alleles were positive. Pruritus was present in 41 (87%) BSE positive sheep; the remaining six were judged to be pre-clinically infected. Testing of the response to scratching along the dorsum of a sheep proved to be a good indicator of clinical disease with a test sensitivity of 85% and specificity of 98% and usually coincided with weight loss. Clinical signs that were displayed significantly earlier in BSE positive cases compared to negative cases were behavioural changes, pruritic behaviour, a positive scratch test, alopecia, skin lesions, teeth grinding, tremor, ataxia, loss of weight and loss of body condition. The frequency and severity of each specific clinical sign usually increased with the progression of disease over a period of 16-20 weeks. CONCLUSION: Our results suggest that BSE in sheep presents with relatively uniform clinical signs, with pruritus of increased severity and abnormalities in behaviour or movement as the disease progressed. Based on the studied sheep, these clinical features appear to be independent of breed, affected genotype, dose, route of inoculation and whether BSE was passed into sheep from cattle or from other sheep, suggesting that the clinical phenotype of BSE is influenced by the TSE strain more than by other factors. The clinical phenotype of BSE in the genotypes and breed studied was indistinguishable from that described for classical scrapie cases