Pruritus In Children Research Articles

Cholestatic Pruritus in Children: Conventional Therapies and Beyond.

Pruritus in the setting of cholestatic liver disease is difficult to treat and occurs in patients ranging in age from infancy to adulthood. Likely multifactorial in etiology, this symptom often involves multimodal therapy targeting several pathways and mechanisms proposed in the underlying etiology of cholestatic pruritus. Many patients in both the pediatric and adult populations continue to experience unrelenting pruritus despite maximal conventional therapy. Options are further limited in treating pediatric patients due to sparse data regarding medication safety and efficacy in younger patients. Conventional therapies for the treatment of cholestatic pruritus in children include ursodeoxycholic acid, cholestyramine, hydroxyzine, and rifampin. Certain therapies are more routinely used in the adult populations but with limited data available for use in child and adolescent patients, including opioid antagonists and selective serotonin reuptake inhibitors. Recently, ileal bile acid transport inhibitors have been shown to alleviate pruritus in many children with Alagille syndrome and progressive familial intrahepatic cholestasis and is an additional therapy available for consideration for these patients. Ultimately, surgical options such as biliary diversion or liver transplantation are considered in specific circumstances when medical therapies have been exhausted and pruritus remains debilitating. While further investigation regarding underlying etiologies and effective therapies are needed to better understand itch pathogenesis and treatment in pediatric cholestasis, current considerations beyond conventional management include the use of opioid antagonists, selective serotonin reuptake inhibitors, ileal bile acid transport inhibitors, and surgical intervention.

Development of the Patient- and Observer-Reported PRUCISION Instruments to Assess Pruritus and Sleep Disturbance in Pediatric Patients with Cholestatic Liver Diseases.

IntroductionUnderstanding how patients experience their disease is a vital step in optimal disease management, and patient- and observer-reported outcome (PRO and ObsRO, respectively) measures can add important details to clinical information that is obtained as novel treatments are developed. Instruments that measure meaningful symptoms and impacts from the perspective of pediatric patients with cholestatic liver disease or their caregivers are needed. This study aimed to identify salient concepts in pediatric cholestatic liver disease, develop novel PRO and ObsRO instruments, and establish the instruments’ content validity.MethodsRelevant signs, symptoms, and impacts of cholestatic liver disease were identified through a literature review, interviews with expert clinicians, and concept elicitation interviews with children and caregivers of children who had progressive familial intrahepatic cholestasis (PFIC), Alagille syndrome, biliary atresia, or primary sclerosing cholangitis. Additional cognitive debriefing interviews with patients and caregivers were performed to ensure that participants could understand the instructions, questions, and response scales of the PRO and ObsRO instruments, with modifications made as necessary to improve comprehension and/or usability.ResultsA total of 36 interviews with patients and caregivers were conducted. Pruritus and sleep disturbance (e.g., difficulty falling or staying asleep due to itch) were identified as the most problematic symptom and significant impact, respectively, of the pediatric cholestatic liver diseases assessed. The ObsRO and PRO instruments, called PRUCISION, focus on these key disease features in the morning and evening. Several modifications were made to the draft instruments following cognitive interviews. The final PRUCISION PRO and ObsRO measures are designed as an electronic diary to be completed twice daily. The response scales include pictorial, verbal, and numeric scales.ConclusionNovel PRO and ObsRO PRUCISION instruments were created that evaluate the patient experience of cholestatic pruritus in children with PFIC and other cholestatic liver diseases. The content validity of the PRUCISION instruments is established.

P94: Dupilumab provides long‐term improvement in pruritus in children with severe atopic dermatitis and adolescents and adults with moderate‐to‐severe atopic dermatitis

P94: Dupilumab provides long‐term improvement in pruritus in children with severe atopic dermatitis and adolescents and adults with moderate‐to‐severe atopic dermatitis

Pruritus in the Pediatric Burn Population.

Postburn pruritus is a significant issue that can have a devastating impact on patient quality of life. Despite its known negative impact, few studies have focused on the pediatric population. Thus, the aim of this study was to determine the incidence of pruritus among pediatric burn patients as well as identify its predictive factors and commonly used treatments, including the novel use of laser therapy. A retrospective analysis of all burn patients treated at our pediatric burn center from 2009 to 2017 was conducted. The primary outcome measure was the presence or absence of pruritus at any point following the burn. One thousand seven hundred and eighty-three patients met the inclusion criteria for this study. The mean age at injury was 3.67 years (SD = 4.02) and the mean burn TBSA was 3.48% (SD = 4.81) with most burns resulting from scalds (66%). In total, 665 patients (37.3%) experienced pruritus. Following multivariable logistic regression, TBSA, age >5 years, burns secondary to fire/flame, and burn depth, were identified as significant predictors of pruritus (P < .05). Pruritus was treated with diphenhydramine (85.0%), hydroxyzine (37.3%), and gabapentin (4.2%) as well as massage (45.7%), pressure garments (20.0%), and laser therapy (8.6%). This study addresses the knowledge gap in the literature related to postburn pruritus among pediatric patients and includes one of the largest patient cohorts published to date. Moreover, the results further contribute to our understanding of postburn pruritus in children and may help us to predict which patients are most likely to be affected, so that treatment can be initiated as soon as possible.

Evaluation of the role of bile acids and serotonin as markers of pruritus in children with chronic cholestatic liver disease

Background and study aimsPruritus is an annoying symptom with an unclear pathogenesis accompanied by chronic cholestasis. This cross-sectional study was conducted to define the relationship between serum levels of presumed pruritogens (bile acids (BAs) and serotonin) and severity of pruritus in pediatric patients with chronic cholestatic liver disease. Patients and methodsA total of 28 children suffering from pruritus due to chronic cholestatic liver disease and 29 age- and sex-matched healthy control subjects were examined. Scores obtained used the 5-D itch scale were evaluated among patients. Serum levels of BAs and serotonin were determined using enzymatic assays and high-performance liquid chromatography, respectively. ResultsPatients had higher serum BA levels and lower serotonin levels than control subjects. Serum BA levels were significantly elevated in 61% of patients. The 5-D itch scale scores were significantly higher in cholestatic individuals with normal γ-glutamyl transpeptidase levels. Neither BA nor serotonin levels correlated with the severity of the 5-Ditch scale score. ConclusionNeither BA nor serotonin levels correlated with the severity of pruritus, indicating that they may not be good laboratory markers for the intensity of itch in children with cholestasis. Our findings suggest that it is necessary to identify another potential pruritogenic mediator, most probably of a biliary origin.

Coconut Oil with Vitamins A and E as a New Topical Emollient Mixture for Pruritus in Children with Cholestatic Liver Disease

Coconut Oil with Vitamins A and E as a New Topical Emollient Mixture for Pruritus in Children with Cholestatic Liver Disease

Partial Biliary Diversion May Promote Long-Term Relief of Pruritus and Native Liver Survival in Children with Cholestatic Liver Diseases

Rare cholestatic liver diseases may cause debilitating pruritus in children. Partial biliary diversion (PBD) may relieve pruritus and postpone liver transplantation which is the only other alternative when conservative treatment fails. The aim was to report long-term outcome after PBD in a population of 26 million people during a 25-year period. This is an international, multicenter retrospective study reviewing medical journals. Complications were graded according to the Clavien-Dindo classification system. Thirty-three patients, 14 males, underwent PBD at a median of 1.5 (0.3-13) years at four Nordic pediatric surgical centers. Progressive familial intrahepatic cholestasis was the most common underlying condition. Initially, all patients got external diversion, either cholecystojejunostomy (25 patients) or button placed in the gallbladder or a jejunal conduit. Early complications occurred in 14 (42%) patients, of which 3 were Clavien-Dindo grade 3. Long-term stoma-related complications were common (55%). Twenty secondary surgeries were performed due to stoma problems such as prolapse, stricture, and bleeding, or conversion to another form of PBD. Thirteen children have undergone liver transplantation, and two are listed for transplantation due to inefficient effect of PBD on pruritus. Serum levels of bile acids in the first week after PBD construction were significantly lower in patients with good relief of pruritus than in those with poor effect (13 [2-192] vs. 148 [5-383] μmol/L; p = 0.02). PBD may ensure long-term satisfactory effect on intolerable pruritus and native liver survival in children with cholestatic liver disease. However, stoma-related problems and reoperations are common.

Predictors and Correlates of Pediatric Postburn Pruritus in Preschool Children of Ages 0 to 4.

Pruritus is a common problem following burn injuries; however, the literature to date has focused on adult survivors and/or pediatric survivors of large burns. The current study examines acute postburn pruritus in children under the age of 4 years (N = 256) with smaller burns (mean TBSA = 3.99%), which represents the most common type of patient typically treated in pediatric burn centers. Parents rated their child for pruritus, irritability, and sleep disturbances; additionally, parents completed a self-report of distress. Nearly half (47.3%) were rated by parents as displayed some level of pruritus, with the greatest proportion rated as mild. Regression analysis indicated that child minority status, greater burn TBSA, and more days elapsed since burn predicted higher levels of pruritus. In turn, pruritus was positively correlated with child irritability, delayed sleep onset, sleep disturbance, and parent distress. Thus, our results indicate that parent-rated pruritus in young pediatric burn patients is important to evaluate, as itch is significantly associated with other important clinical outcomes as early as the first month of the burn for pediatric patients and their parents.

Itching at night: A review on reducing nocturnal pruritus in children.

The most common causes of chronic nocturnal itching in children are atopic dermatitis and psoriasis, with lichen simplex chronicus and prurigo nodularis contributing to lesser degrees. Despite the prevalence of nocturnal itching, its pathophysiology remains poorly understood. The most troubling consequence of itching at night is poor quality of sleep. Poor sleep quality in children with nocturnal itching has been linked to adverse neurocognitive, behavioral, and physiologic outcomes, including poor performance in school, attention deficit hyperactivity disorder, short stature, hypertension, obesity, and impaired immune function. There is no consensus on the best management of nocturnal itching in children. We conducted a review of the literature evaluating the efficacy of various treatment options for children with chronic nocturnal pruritus. Our review found three recently conducted randomized controlled trials and one case report demonstrating the efficacy of topical corticosteroids, oral melatonin, and clonidine in reducing nocturnal itching or improving sleep quality in children with nocturnal pruritus. Future research is needed to elucidate the pathophysiology of nocturnal itching to best develop targeted, effective treatment strategies.

An update on the physiopathology and therapeutic management of cholestatic pruritus in children

Pruritus is a disabling symptom accompanying chronic cholestasis. In extreme cases, the refractory nature of pruritus can result in a need for invasive therapies including liver transplantation. The pathogenesis of pruritus in cholestatic disease is poorly understood. It may involve a specific neural pathway (similar to that associated with pain) regulated by several pruritogenic substances such as bile acids, opioids, serotonin, and the more recently identified lysophosphatidic acid. While the therapeutic management of cholestatic pruritus is well established in adults, there is no consensus in children, in light of the difficulty of conducting controlled clinical studies. The currently recommended strategy to manage cholestatic pruritus in children is based on several lines of specific therapies that should be associated with skin hydration and with non-specific treatment of cholestasis including ursodeoxycholic acid. Pruritus should be assessed as objectively as possible between each line of therapy. Rifampicin, a potent CYP3A4 inducer, is the first-line treatment of cholestatic pruritus. Second-line therapies require evaluation of the child in an expert center and are discussed on a case-by-case basis depending on the underlying disease and the experience of the center. These include inhibitors of serotonin reuptake (sertraline), opioid antagonists (naloxone), or ASBT inhibitors. Invasive therapies such as biliary diversion or liver transplantation can also be proposed in the most severe cases. The aim of the current update is to review the physiopathologic mechanisms implicated in cholestatic pruritus and to propose potential therapeutic strategies in children.

Physiopathologie et prise en charge thérapeutique du prurit cholestatique de l’enfant

Pruritus is a disabling symptom accompanying chronic cholestasis. In some cases, refractory pruritus may require invasive therapies including liver transplantation. The pathogenesis of pruritus in cholestatic disease is poorly understood. It may involve a specific neural pathway and several pruritogenic substances such as bile acids, opioids, serotonin, and the more recently identified lysophosphatidic acid. While the therapeutic management of cholestatic pruritus is well established in adult patients, there is no consensus in children, given the difficulty in conducting controlled clinical studies. The currently recommended strategy to manage cholestatic pruritus in children is based on several lines of therapy that should always be associated with local cutaneous care and with nonspecific treatment of cholestasis including ursodeoxycholic acid therapy. Pruritus should be assessed as objectively as possible between each therapeutic step. Rifampicin, an enzyme inducer, is the specific first-line treatment of cholestatic pruritus. The second-line therapies require evaluation of the child in an expert center and are discussed on a case-by-case basis depending on the underlying disease, the experience of the center and the will of the child and his family. It could be inhibitors of serotonin reuptake (sertraline) or an opioid antagonist (naloxone). Invasive therapies such as biliary diversion or liver transplantation can also be proposed in the most severe cases.

CROSS-CULTURAL ADAPTATION AND VALIDATION OF THE ITCHING SEVERITY SCALE IN CHILDREN AND ADOLESCENTS WITH ATOPIC DERMATITIS.

ABSTRACTObjective: To translate, adapt and validate the Itch Severity Scale to a Brazilian version (ISS-Ped) in order to measure the severity of pruritus in children and adolescents with atopic dermatitis.Methods: This is a methodological study of validation of an instrument following recommended protocols. The translated version was evaluated by a group of experts including one professional with experience in instrument validation, three English teachers, one linguistics teacher and seven allergists. After this, the scale was applied to 42 parents of children aged between 2 and 18 years old with atopic dermatitis, and 42 parents of children without pruritic diseases. Results were evaluated according to the severity of atopic dermatitis and disease control, and they were compared between groups with and without atopic dermatitis.Results: More than 90% of the questions were clear to the parents. The ISS-Ped showed a strong positive correlation with the severity of atopic dermatitis (Pearson: 0.74; p<0.001) and a good correlation with the control of dermatitis (point-biserial correlation coefficient: 0.65; p<0.001). The scale showed excellent internal consistency (Cronbach’s α: 0.96) and adequate test and retest agreement (95% confidence interval of intraclass correlation coefficient: 0.89-0.99; p<0.001).Conclusions: The ISS-Ped is a feasible, valid, reliable and satisfactorily equivalent. The translated scale was appropriate to assess the severity of itching in children and adolescents with eczema, allowing comparisons in the clinical practice and in the research setting.

Management of cholestatic pruritus in children with Alagille syndrome: Case report and literature review

Alagille syndrome causes intractable pruritus and disfiguring xanthomas because of retained bile acids and cholesterol. Drug therapy in addition to surgical intervention may be effective in many patients in reducing serum bile acids, cholesterol levels, pruritus, and skin xanthomas. In this report, we describe a child with Alagille syndrome who presented with severe pruritus and xanthomas as a consequence of severe hypercholesterolemia and discuss the treatment modalities.

Chronic Kidney Disease-associated Pruritus in Children.

This study evaluated the frequency and severity of pruritus and dry skin in children with chronic kidney disease (CKD). A total of 103 children were included: 72 with CKD stage 3–5 (34 on dialysis and 38 treated conservatively without dialysis) and 31 as a reference group. Pruritus was assessed using the 4-item Itch Questionnaire and a visual analogue scale. Skin dryness was evaluated clinically, by non-invasive assessment of epidermal hydration and measurement of transepidermal water loss. Pruritus occurred in 20.8% of children with CKD, 18.4% on conservative treatment (receiving supportive care without dialysis) and 23.5% on dialysis. Xerosis was more common in children with pruritus (66.7%) than in those without pruritus (50.9%). Patients with pruritus had a significantly lower estimated glomerular filtration rate and a higher ratio of calcium × phosphate product (Ca × P). In conclusion, CKD-associated pruritus occurs not only in adults, but also in children, and it may already be present in the early stages of CKD.

Pityriasis rosea: a natural history of pediatric cases in theCentral Anatolia Region of Turkey.

This study aimed to evaluate the demographic, clinical, and epidemiological features of pityriasis rosea (PR) in a cohort of 46 children in Yozgat, a city in the Central Anatolia Region of Turkey. Forty-six children with PR were monitored at regular intervals (1, 2, 4, and 12 weeks) for 3 months from the time of diagnosis. A complete evaluation of the patient was performed at each visit. The average age of patients at time of diagnosis was 12 ± 3.9 years. Cases were most common in the winter (rainy, snowy months; n = 14, 31%). Fifteen patients had a medical history significant for the presence of upper respiratory tract infection, while skin PR manifestations were preceded by drug intake in a second group of 15 patients. The presence of a herald patch was observed in 78.3% of patients, most frequently on the trunk (n = 23). Pruritus occurred in 75% of patients. Median PR duration was 3 weeks (range: 1-20 weeks). The course of PR is similar in Turkish children and adults. The high prevalence of pruritus in children with PR in Turkey was also significant. Further evaluation of this finding comparing adults and children is now required.

A naloxone admixture to prevent opioid-induced pruritus in children: a randomized controlled trial.

Morphine administered by continuous opioid infusion (COI) or by patient-controlled analgesia (PCA) is associated with opioid-induced pruritus (OIP). Intravenous naloxone administered separately to the morphine infusion at a dose of 0.25-1.65μg·kg(-1)·hr(-1) can provide effective prevention from OIP. Nevertheless, this strategy requires a dedicated intravenous line and an additional infusion pump. The purpose of this study was to determine whether an admixture of naloxone with morphine in normal saline administered via COI or PCA would also prevent OIP in children without attenuation of analgesia or increased opioid utilization. In this randomized controlled trial, children meeting the inclusion criteria (aged 8-18yr, American Society of Anesthesiologists physical status I-III, normal developmental profile and prescribed COI/PCA morphine for postoperative analgesia) were randomized to receive an infusion containing a naloxone, opioid, and saline admixture (NOSA) of 12μg naloxone per 1mg morphine per 1mL normal saline or morphine only (control). The severity of opioid-induced pruritus was assessed by self-report using a modified colour analogue scale (mCAS; score 0-10). The groups were also compared for opioid utilization, pain scores, and administration of antipruritic medications, which were recorded for up to 48 hr or until the COI/PCA was discontinued. Ninety-two participants were enrolled in the study. The median [interquartile range] dose of naloxone administered to the NOSA participants was 0.37 [0.30-0.48] μg·kg(-1)·hr(-1). The incidence of OIP, determined by self-report and treatment, was not different between groups: 22% in the NOSA group vs 36% in the control group (mean difference, -15%; 95% confidence interval [CI], -33 to 4; P=0.164). The severity of opioid-induced pruritus was similar in the two groups, with a median difference in the participants' mean mCAS score of -0.29 (95% CI, -0.75 to 0.26; P=0.509). Opioid utilization did not differ between groups, with a median difference of -1.35μg·kg(-1)·hr(-1) (95% CI, -5.85 to 7.55; P=0.518), and pain scores did not differ, with a median difference of 0.0 (95% CI, -1.0 to 1.5; P=0.659). This admixture of naloxone and morphine in normal saline did not decrease the incidence or severity of OIP in this sample. Separate administration of naloxone may be the more effective strategy for prevention of OIP. This trial was registered at ClinicalTrials.gov (NCT01071057).

Uremic pruritus

Uremic pruritus

Relationship between serum interleukin-31/25-hydroxyvitamin D levels and the severity of atopic dermatitis in children

Purpose: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease. Vitamin D and interleukin-31 (IL-31) are known to be related to the pathogenesis of AD with pruritus. The purpose of this study was to investigate the relationship between serum levels of 25-hydroxyvitamin D (25(OH)D) and IL-31 and the disease severity of AD in children with AD. Methods: We recruited 160 children with AD and 42 controls. We used the SCORing Atopic Dermatitis (SCORAD) index to measure the severity of AD. Serum IL-31 and 25(OH)D levels were assayed using enzyme-linked immunosorbent assay and high-performance liquid chromatography, respectively. Serum levels of total IgE, specific IgE to common allergens and peripheral blood total eosinophil count were carried out in children with AD. Results: Serum IL-31 level was significantly higher in AD group compared to control group and 25(OH)D level was significantly lower in AD group than control group. Serum IL-31 level showed the highest level in severe AD group followed by moderate and mild AD group, whilst serum 25(OH)D level was the lowest in severe AD group compared to moderate and mild AD group. There was no difference in serum IL-31 level between AD group and nonatopic dermatitis group. IL-31 level was positively correlated with subjective SCORAD index indicating pruritus in children with AD, and 25(OH)D was inversely correlated with SCORAD index. Conclusion: IL-31 and vitamin D may be related to the pathogenesis of AD, especially with regard to the pruritus. (Allergy Asthma Respir Dis 2015;3:396-401)

Prurit sévère révélant un lymphome de Hodgkin chez l’enfant : deux observations

Pruritus in children is a frequent reason for consultation, most often related to a common dermatosis. Where dermatological investigation fails to reveal a dermatological cause, a general cause may be suspected. We report three cases of pruritus revealing Hodgkin's lymphoma in children. Case 1: a 14-year-old girl presented pruritus with diffuse scratching lesions present for 6months, associated with right cervical lymph nodes occurring after the onset of pruritus. Tomodensitometry revealed involvement of the supra- and sub-diaphragmatic lymph nodes as well as pulmonary involvement. Lymph node biopsy confirmed nodular sclerosing Hodgkin's lymphoma. Case 2: a 14-year-old boy was hospitalized for suspected psychogenic pruritus. He presented intense itching, predominantly in the lower extremities and at night, occurring over the previous 6months as well as night sweats. Examination showed that the patient had lost 5kg in 1month and had a low-grade fever of 38°C; he presented linear striated scratching lesions on both legs. Cervical and inguinal lymphadenopathy was seen. The chest scan also revealed supra-diaphragmatic adenomegalies. The biopsy confirmed Hodgkin's lymphoma. Systemic causes of pruritus in children are poorly described in the literature. In these two cases, pruritus allowed a diagnosis of Hodgkin's lymphoma to be made, emphasizing the important role of dermatologists in the early diagnosis of haematological malignancy.

Prevalence and characterization of pruritus in epidermolysis bullosa.

Qualitative data suggest that pruritus is a burdensome symptom in patients with epidermolysis bullosa (EB), but the prevalence of pruritus in children and adults with EB and factors that contribute to pruritus are unknown. The objective of the current study was to quantitatively identify and to characterize pruritus that EB patients experience using a comprehensive online questionnaire. A questionnaire was developed to evaluate pruritus in all ages and all types of EB. Questions that characterize pruritus were included and factors that aggravate symptoms were investigated. Patients from seven North American EB centers were invited to participate. One hundred forty-six of 216 questionnaires were completed (response rate 68%; 73 male, 73 female; median age 20.0 years). Using a 5-point Likert scale (1 = never, 2 = rarely, 3 = sometimes, 4 = often, 5 = always), itchiness was the most bothersome EB complication (mean 3.3). The average daily frequency of pruritus increased with self-reported EB severity. Pruritus was most frequent at bedtime (mean 3.8) and interfered with sleep. Factors that aggravated pruritus included healing wounds, dry skin, infected wounds, stress, heat, dryness, and humidity. Pruritus is common in individuals with EB and can be bothersome. Future studies will need to investigate the most effective treatments given to individuals with EB for pruritus.