Prevalence of Demodex spp. in patients with chronic blepharitis.

Blepharitis is a very common disease in ophthalmology, dermatology and allergy practice. It generally follows a chronic course and is frequently associated with objective and/or subjective symptoms such as epiphora, red eye, dandruff, gritty sensation, itching, burning, photophobia, and blurred vision. The purpose of this study is to analyze the prevalence of Demodex spp. in patients with symptoms of chronic blepharitis. An analytical cross-sectional study was conducted in the period between 2016 and 2020. All patients with symptoms of chronic blepharitis who underwent a parasitological test of eyelashes (Rapitest) in the Dermatology Department of the Hospital Italiano de Buenos Aires were included. Those with previously established blepharitis due to another infectious cause were excluded. We analyzed 972 patients. Sixty percent (n=585) underwent a positive Rapitest for the presence of Demodex spp. Seventy five percent (n=728) were women. There were no significant differences in the prevalence associated with sex (p=0.38). Among the patients positive for Demodex spp., 65% (n=628) were older than 60 years old. The most frequently associated symptom was itching, present in 35% (n=342). A statistically significant decrease in the number of consultations was observed during the cold months of the year (May-June-July-August). Our results show a high prevalence of Demodex spp. in patients with chronic blepharitis. As its presence reveals a direct association with age, we recommend looking for this parasite in this age group.

Consensus on the diagnostic algorithm for chronic nodular prurigo. / Consenso sobre el algoritmo diagnóstico del prurigo crónico nodular.

Chronic nodular prurigo (CNP) is a chronic dermatological disease characterized by the presence of chronic pruritus and pruritic nodular lesions. The aim of this study was to reach consensus among a group of experts based on a non-systematic literature review and an algorithm for the clinical diagnosis of CNP. The resulting algorithm is structured in 3 blocks: 1) early identification of the patient with a possible diagnosis of CNP; 2) diagnosis and assessment of CNP; and 3) categorization of CNP (identification of the underlying causes or associated comorbidities). We believe that this clinical algorithm can facilitate the correct diagnosis of patients with CNP. Additionally, it raises awareness on the need for a multidisciplinary approach and specific treatment of CNP, steps of paramount importance to make better therapeutic decisions.

Real-World Clinical, Psychosocial and Financial Burden of Atopic Dermatitis: Results from the Spanish Cohort of the MEASURE-AD Trial. / Carga clínica, psicosocial y económica de la dermatitis atópica en vida real: resultados de la cohorte española del estudio MEASURE-AD.

BACKGROUND: Atopic dermatitis (AD) is one of the most prevalent skin diseases, but there are numerous knowledge gaps surrounding the impact this disease has on quality of life (QoL), mental health, and out-of-pocket expenses involved in the management of AD. The available scientific evidence on the multidimensional burden of AD is usually based on studies with measures reported by patients themselves. METHODS: In this context, the MEASURE-AD trial was developed as a cross-sectional, multicenter, multinational trial using patient- and physician-reported measures to characterize the multidimensional burden of AD in adults with moderate-to-severe AD. RESULTS: This paper presents the results of the Spanish cohort. We found that Spanish adults with moderate-to-severe AD and high EASI score (21.1-72) had a significantly increased disease burden, high severity of symptoms such as itch and sleep disturbances, impaired mental health and QoL, higher use of health care resources, and more out-of-pocket expenses than patients with low EASI scores (0-7 or 7.1-21). CONCLUSIONS: This study provides information to better understand disease burden, and identify aspects to be improved in the management of AD.

A New Paradigm in the Management of Scalp Pruritus: Findings From the SCALP-PR Trial.

PURPOSE: The "Impact of scalp pruritus in dermatological consultations in Spain: The SCALP-PR trial" was initiated to address the common yet often insufficiently examined issue of scalp pruritus in dermatology. This condition leads to an uncontrollable urge to scratch, affecting the patients' quality of life and potentially causing scalp damage. This study aimed to explore the prevalence, patient profile, underlying conditions, and therapeutic approaches for scalp pruritus in Spain, and to assess the safety and efficacy profile, as well as the tolerability of a non-pharmacologic treatment. METHODS: From 2021 through 2022, 75 dermatologists enrolled a total of 359 patients in a study on scalp pruritus, approved by the Bellvitge University Hospital Research Ethics Committee, Barcelona, Spain. This evidence-based research combined a meta-analysis with observational study techniques focused on real-world evidence to examine the therapeutic impact on quality of life (QoL). Utilizing the Dermatology Life Quality Index (DLQI) for QoL assessments, the study evaluated the effectiveness of the topical product over 15 days. Data collection was conducted via an eCRF and analyzed with statistical methods to provide reliable insights into the management of scalp pruritus. RESULTS: The prevalence of scalp pruritus in Spain was found to be 6.9%, predominantly among women with a mean age of 52.5 years. The leading causes identified were seborrheic dermatitis and pruritus of undetermined etiology or sensitive scalp. Stress was noted as a key factor, with corticosteroids and hygienic measures being common therapies. The topical product demonstrated significant reductions in pruritus and scratching in more than 90% of patients after 15 days. Improvements were also seen in dermatological quality of life, with 87.1% of patients showing enhancements in DLQI scores. The product was well-received thanks to its cosmetic properties, with high ratings in texture, ease of application, and fragrance. CONCLUSION: The topical product studied is a safe, effective, and cosmetically appealing treatment, improving scalp pruritus in various etiologies for most patients. The results highlight the need for patient-center treatments in dermatology, providing important insights for clinical practice and future research.

Pruritus in Dermatology: Part 2 - Diseases and Their Treatment. / Prurito en dermatología. Enfermedades y su tratamiento. Parte 2.

Pruritus is the main symptom of many dermatologic and systemic diseases. Atopic dermatitis, psoriasis, contact dermatitis, urticaria, lichen simplex chronicus, mycosis fungoides, scars, autoimmune diseases, kidney or liver diseases among others are all associated with itch that may require different approaches to management. Although antihistamines seem to be the first line of therapy, in reality their role is limited to urticaria and drug-induced reactions. In fact, the pathophysiologic mechanisms of each of the conditions covered in this review will differ. Recent years have seen the emergence of new drugs whose efficacy and safety profiles are very attractive for the management of pruritus in clinical practice. Clearly we are at a critical moment in dermatology, in which we have the chance to be more ambitious in our goals when treating patients with pruritus.

Pruritus in Dermatology: Part 1 - General Concepts and Pruritogens. / Prurito en dermatología. Generalidades y pruritógenos. Parte 1.

Pruritus is the most common symptom of dermatologic and systemic diseases. The diagnosis of pruritus is clinical, although additional tests may be necessary to identify or confirm the cause. Translational medicine has led to the discovery of new mediators of itch, or pruritogens, as well as new receptors. Knowing how to properly recognize the main pathway that mediates itch in each patient is the key to successful treatment. Although the histaminergic pathway predominates in conditions like urticaria or drug-induced pruritus, it is the nonhistaminergic pathway that predominates in nearly all other skin diseases covered in this review. Part 1 of this 2-part review discusses the classification of pruritus, additional testing, the pathophysiology of itch and the pruritogens implicated (including cytokines and other molecules), and central sensitization to itch.

Symptom control.

In addition to symptoms secondary to splenomegaly, microvascular abnormalities, and thrombohemorrhagic complications, patients with MPN may experience a significant symptom burden attributed to an increase in circulating inflammatory cytokines. These symptoms can be severe and limit quality of life. Therefore, in addition to the prevention of complications, one of the objectives of the treatment of MPN is the control of symptoms.

Además de la sintomatología secundaria a la esplenomegalia, a las alteraciones microvasculares y a las complicaciones trombohemorrágicas, los pacientes con neoplasias mieloproliferativas (NMP) pueden experimentar una importante carga sintomática atribuida a un aumento de citocinas inflamatorias circulantes. Estos síntomas pueden ser severos y limitar la calidad de vida. Por ello, además de la prevención de las complicaciones, uno de los objetivos del tratamiento de las NMP es el control de los síntomas.

Plasma Steroids and Endocannabinoids Used as Biomarkers to Assess the Pruritus Severity of Patients With Prurigo Nodularis.

BACKGROUND: Prurigo nodularis (PN) as an extremely pruritic and hyperplastic chronic dermatosis induces psychologically and physiologically stressful responses. PN-induced responses in the hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary-gonadal (HPG) axes and endocannabinoid system (ECS) are abnormal. Extant studies on the PN's pathogenesis mostly focused on the PN's psychological responses. To date, the PN's physiological responses remain not been fully uncovered yet. OBJECTIVES: To investigate the PN-induced physiological responses via the levels of five steroids and two endocannabinoids combined with their ratios in plasma and examine the association between the psychological and physiological responses. MATERIALS AND METHODS: Thirty-six patients with PN, 36 age- and gender-matched healthy controls were recruited. The PN's psychological symptoms including pruritus severity, pain and life quality were measured with the visual analog scale, the prurigo score index, numerical rating scale, verbal rating scale and dermatology life quality index. Their concentrations of steroids and endocannabinoids were determined with liquid chromatography-tandem mass spectrometry. RESULTS: Compared to controls, the PN patients showed lower plasma levels in cortisol, cortisone, N-arachidonoyl-ethanolamine (AEA), and the ratio of DHEA to 1-arachydonoyl glycerol (1-AG), which negatively moderately and over correlated with PN's symptoms, especially with the pruritus severity. Additionally, the PN patients exhibited higher levels in the ratios of testosterone and 1-AG to cortisol, which positively moderately and over correlated with pruritus severity. Thus, the seven biomarkers would be sensitive and reliable biomarkers for assessing the pruritus severity of PN because they met the screening criteria that the biomarkers show intergroup differences and showed moderate or over correlation with the pruritus severity of PN. CONCLUSIONS: To the best of our knowledge, this is the first study exploring PN-induced physiological responses. The findings suggest that alterations in these three endocrine systems may lead to new insights to psychological mechanisms and responses to prurigo nodularis.

Plasma Steroids and Endocannabinoids Used as Biomarkers to Assess the Pruritus Severity of Patients With Prurigo Nodularis. / [Artículo traducido] Esteroides y endocannabinoides plasmáticos utilizados como biomarcadores para evaluar la gravedad del prurito de los pacientes con prúrigo nodular.

BACKGROUND: Prurigo nodularis (PN) as an extremely pruritic and hyperplastic chronic dermatosis induces psychologically and physiologically stressful responses. PN-induced responses in the hypothalamic-pituitary-adrenal, hypothalamic-pituitary-gonadal axes and endocannabinoid system are abnormal. Extant studies on the PN's pathogenesis mostly focused on the PN's psychological responses. To date, the PN's physiological responses remain not been fully uncovered yet. OBJECTIVES: To investigate the PN-induced physiological responses via the levels of 5steroids and 2endocannabinoids combined with their ratios in plasma and examine the association between the psychological and physiological responses. MATERIALS AND METHODS: Thirty-six patients with PN, 36 age- and gender-matched healthy controls were recruited. The PN's psychological symptoms including pruritus severity, pain and life quality were measured with the visual analogue scale, the prurigo score index, numerical rating scale, verbal rating scale and dermatology life quality index. Their concentrations of steroids and endocannabinoids were determined with liquid chromatography-tandem mass spectrometry. RESULTS: Compared to controls, the PN patients showed lower plasma levels in cortisol, cortisone, N-arachidonoyl-ethanolamine, and the ratio of DHEA to 1-arachydonoyl glycerol (1-AG), which negatively moderately and over correlated with PN's symptoms, especially with the pruritus severity. Additionally, the PN patients exhibited higher levels in the ratios of testosterone and 1-AG to cortisol, which positively moderately and over correlated with pruritus severity. Thus, the 7biomarkers would be sensitive and reliable biomarkers for assessing the pruritus severity of PN because they met the screening criteria that the biomarkers show intergroup differences and showed moderate or over correlation with the pruritus severity of PN. CONCLUSIONS: To the best of our knowledge, this is the first study exploring PN-induced physiological responses. The findigs suggest that alterations in these 3endocrine systems may lead to new insights to psychological mechanisms and responses to PN.

Cutaneous Manifestations not Considered Diagnostic Criteria for Neurofibromatosis Type 1. A Case-Control Study. / Hallazgos cutáneos no considerados criterios diagnósticos de la NF1. Estudio de casos y controles.

BACKGROUND: The diagnosis of Neurofibromatosis type 1 (NF1) is usually delayed in children without a family history. We aimed to define the prevalence and characteristics of prevalent skin manifestations in NF1 compared to the general population, which continue to be excluded from the diagnostic criteria for NF1. PATIENTS AND METHODS: Case-control study, matched by age groups, in which 108 patients with a diagnosis of NF1 and 137 healthy controls were included. RESULTS: The prevalence of nevus anemicus (NA) (P<.001) and juvenile xanthogranulomas (JXG) (P<.001) was significantly higher in the population affected by NF1 than in the control population. A specificity of 99.27% (confidence interval): 95.4-99.96%] and a positive predictive value (PPV) of 98.80% [92.54-99.94%] were estimated for NA and a specificity of 99.27% [95.4-99.96%] and a PPV of 92.86% [64.17-99.63%] for JXG in the diagnosis of NF1 in children who present 6 or more Café-au-lait macules. Statistically significant differences were also evidenced in the distribution by phototypes (P=.025) and in relation to generalized itching with no other cause (P<.001). CONCLUSIONS: NA and JXG are relevant clinical findings for the diagnosis of NF1, especially during the first years of life. We consider that its inclusion among the diagnostic criteria of the disease should be evaluated.

Cutaneous Manifestations not Considered Diagnostic Criteria for Neurofibromatosis Type 1. A Case-Control Study.

BACKGROUND: The diagnosis of Neurofibromatosis type 1 (NF1) is usually delayed in children without a family history. We aimed to define the prevalence and characteristics of prevalent skin manifestations in NF1 compared to the general population, which continue to be excluded from the diagnostic criteria for NF1. PATIENTS AND METHODS: Case-control study, matched by age groups, in which 108 patients with a diagnosis of NF1 and 137 healthy controls were included. RESULTS: The prevalence of nevus anemicus (NA) (p<0.001) and juvenile xanthogranulomas (JXG) (p<0.001) was significantly higher in the population affected by NF1 than in the control population. A specificity of 99.27% [confidence interval (CI): 95.4-99.96%] and a positive predictive value (PPV) of 98.80% [92.54-99.94%] were estimated for NA and a specificity of 99.27% [95.4-99.96%] and a PPV of 92.86% [64.17-99.63%] for JXG in the diagnosis of NF1 in children who present 6 or more Café-au-lait macules. Statistically significant differences were also evidenced in the distribution by phototypes (p 0.025) and in relation to generalized itching with no other cause (p<0.001). CONCLUSIONS: NA and JXG are relevant clinical findings for the diagnosis of NF1, especially during the first years of life. We consider that its inclusion among the diagnostic criteria of the disease should be evaluated.

Chronic Nodular Prurigo: A Retrospective Study of 74 Cases. / Prurigo crónico nodular: Estudio retrospectivo de 74 casos.

BACKGROUND AND OBJECTIVE: Chronic nodular prurigo (CNPG) is a recently defined and currently underdiagnosed disease with a variety of causes. It is associated with multiple comorbidities, and its management and treatment have improved with a better understanding of its pathogenesis. The aim of this study was to describe our experience with a series of patients with CNPG. MATERIAL AND METHODS: Single-center, observational, retrospective study of the sociodemographic and clinical characteristics of patients with CNPG seen at the dermatology department of a tertiary care hospital between 2009 and 2021. RESULTS: We included 74 patients, mostly women (63.5%), with a mean age of 57 years. Overall, 39.2% of patients had a concomitant skin condition, mainly atopic dermatitis (62%). Other comorbidities included endocrine disorders (54.1%), cardiovascular disease (44.4%), and psychiatric disorders (36.5%). Skin biopsy helped confirm the clinical diagnosis in 70% of cases. The mean immunoglobulin E level was higher than normal (516 IU/mL), regardless of atopic predisposition. On average, patients received 3 treatments, the most common choices being methotrexate, antihistamines, and topical and oral corticosteroids. Methotrexate was among the most effective options. CONCLUSIONS: CNPG is a complex disease associated with multiple comorbidities. It requires a multidisciplinary approach, with the dermatologist at the center. Classical treatment approaches are probably insufficient.

Patient-Reported Outcome Measures in Real-World Atopic Dermatitis Studies in Spain: A Systematic Review. / Medidas de los resultados percibidos por el paciente en estudios de vida real en dermatitis atópica en España: revisión sistemática de la literatura.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with symptoms such as pruritus that can be a major burden for patients. Patient-reported outcomes (PRO) complement clinician-reported outcomes in AD. This systematic review aims to identify and describe patient-reported outcome measures (PROM) used in observational studies of AD over the last decade in Spain. Eighteen PROM were identified to measure 13 different PRO that assess multiple aspects of the disease, including symptoms and disease severity, impact on daily activities and on work productivity/functioning, psychosocial impact, patient empowerment, and health-related quality of life (HRQoL). HRQoL, symptoms (particularly pruritus), and anxiety/depression were the most frequently assessed PRO, and the Dermatology Quality of Life Index, the Visual Analogue Pruritus Scale, and the Hospital Anxiety and Depression Scale were the most frequently used PROM, respectively. The growing number of observational studies on AD including PROM in Spain suggests that PRO are becoming increasingly important in the management of AD.

Relationship between pruritus and autotaxin in intrahepatic cholestasis of pregnancy.

OBJECTIVE: Intrahepatic cholestasis of pregnancy is a temporary, pregnancy-specific disease that resolves with delivery, characterized by itching (pruritus), as well as high transaminase and serum bile acid levels in the third trimester of pregnancy. Due to the effects of Autotaxin on the physiology of pregnancy, we aimed to investigate Autotaxin activity in patients with intrahepatic cholestasis of pregnancy. PATIENTS AND METHODS: Sixty-nine patients diagnosed with intrahepatic cholestasis of pregnancy and 20 healthy pregnant women were enrolled in the study. Fasting serum bile acid, pruritus intensity, serum parameters, gestational week of the patients at the time of diagnosis were recorded, and birth week and birth weight were monitored. Autotaxin serum level was measured enzymatically. RESULTS: The mean serum bile acid level (n=69; 38.74±35.92µmol/L) in patients with intrahepatic cholestasis of pregnancy (n=69) was detected to be higher than healthy pregnant women (n=20; 5.05±1.88µmol/L) (p<0.001). Weak correlation was detected between serum bile acid level and itch intensity (p=0.014, r=0.295), while no relation was detected between Autotaxin and itch intensity (p=0.446, r=0.09). Although mean Autotaxin (intrahepatic cholestasis of pregnancy: 678.10±424.42pg/mL, control: 535.16±256.47pg/mL) levels were high in patients with intrahepatic cholestasis of pregnancy, it was not statistically significant (p=0.157). CONCLUSION: In our study, we observed that the serum Autotaxin level did not make a significant difference in patients with intrahepatic cholestasis of pregnancy compared to healthy pregnant women. These findings suggest that larger clinical studies are required to reveal the physio-pathological effects of Autotaxin on pregnancy.

Differences Between Men and Women in Chronic Scratching: A Psychodermatologic Study in Lichen Simplex Chronicus.

INTRODUCTION: Chronic scratching is common to many skin disorders. Being a female and presenting a high level of psychopathology are risk factors for chronic scratching. Yet, it is unclear why. Certain personality characteristics that are more prevalent in women are also known to influence emotional states (i.e. emotional tension). OBJECTIVE: The present study aims to explore whether these personality styles might help understand why gender and emotional distress are associated with scratching. MATERIAL AND METHODS: We compared the personality patterns of 103 patients (69.9% women) diagnosed with Lichen Simplex Chronicus, against a sample of healthy individuals. RESULTS: Significant differences were found in the personality styles of men and women with LSC. Women were more pessimistic, oriented to fulfil the needs of others, traditional, insecure, submissive, and reserved, with moderate (d=.43) to strong (d=.96) size effects ranges. Some of these differences, such as in traditionalism, dutifulness, other-orientation, and pessimism, were also observed when compared with healthy men and women, with small (d=.03) to moderate (d=.47) size effects ranges. CONCLUSIONS: These psychological factors may help explain the mechanisms underlying gender differences in chronic scratching, at least in Lichen Simplex Chronicus. The findings might open new avenues for research and treatment.

Notalgia paresthetica: treatment using intradermal botulinum toxin A.

INTRODUCTION: Notalgia paresthetica is a sensory mononeuropathy that affects dorsal segments T2 to T6. It can have a significant effect on quality of life. Numerous treatments have been used with variable results. MATERIAL AND METHODS: Five patients diagnosed with notalgia paresthetica were treated with intradermal botulinum toxin A. None had achieved relief of the pruritus with previous treatments. RESULTS: Variable results were observed after the administration of intradermal botulinum toxin. Complete resolution of the pruritus was not achieved in any of the patients. CONCLUSIONS: Botulinum toxin A appears to be a safe therapeutic option for patients with notalgia paresthetica. However, data currently available come from small patient series, making it difficult to draw definitive conclusions regarding the true efficacy and long-term effects of this treatment.

Acquired perforating dermatosis: a report of 8 cases.

Acquired perforating dermatosis (APD) is an uncommon disease characterized by lesions exhibiting transepidermal elimination of collagen or elastic fibers. APD affects adults and is associated with systemic diseases, mainly diabetes mellitus and renal failure. We present 8 cases of APD. Seven patients had concomitant diabetes mellitus with or without chronic renal failure, and 1 had alcoholic cirrhosis. In the patients with chronic renal failure, the onset of APD coincided with transient worsening of renal function. The mean increase in creatinine concentrations above baseline was 1.14mg/dL. Acute deterioration of renal function may be involved in APD. Further studies are needed to investigate this association.

Information and consensus document for the diagnostic and therapeutic management of pruritus associated with chronic kidney disease in patients on haemodialysis in Spain.

Chronic kidney disease-associated pruritus (CKD-aP) is one of the most common and disabling comorbidities in patients with advanced CKD. In addition, it is associated with an increased risk of mortality, poorer quality of life, sleep disorders, mental health disorders, and increased use of health care resources. The clinical presentation of CKD-aP is very heterogeneous, making it difficult to diagnose and treat. Currently, there are no national guidelines on the management of CKD-aP. The aim of this document is to provide national consensus recommendations for the diagnostic and therapeutic management of CKD-aP. The document was prepared in three phases: a diagnostic and therapeutic management algorithm was proposed by a small group of nephrology specialists; the proposal was validated by a larger group of nephrologists; and a second validation by a multidisciplinary group that also included dermatology specialists. The diagnostic and therapeutic management algorithm attempts to cover the current need of a lack of specific guidelines for the adequate management of CKD-aP. At the same time, it introduces the use of difelikefalin, the first and only drug specifically approved for CKD-aP, with a good safety and efficacy profile.

Perception of Spanish nephrologists on an old unsolved problem: Pruritus associated with chronic kidney disease (CKD-aP).

INTRODUCTION: Pruritus associated with chronic kidney disease is defined as the sensation of itching, in people with chronic kidney disease, in a one area or all over the body that causes the need to scratch, after having ruled out other dermatological or systemic causes. It is an old and known problem whose prevalence has been able to decrease with the improvement of dialytic techniques but which still persists and is underdiagnosed. OBJECTIVES: The objective of this study was to analyse the current perception of nephrologists about this problem that influences the quality of life of people with chronic kidney disease through a survey. RESULTS: 135 nephrologists, most of them engaged in haemodialysis, participated. 86% considered that pruritus associated with chronic kidney disease is still a problem today that affects the quality of life. Most nephrologists believe that the main pathophysiological cause is uremic toxins (60%) and only 16% believe that it is due to the dysregulation of the opioid system/endorphins-dynorphins. Only 16% comment that the prevalence of pruritus in their centre is greater than 20%. 40% believe that the diagnosis is made because it is manifested by the patient and only 27% because it is asked by the doctor. Moreover, it is not usual to use scales to measure it or the codification in the medical records. The main treatment used is antihistamines (96%), followed by moisturizers/anaesthetics (93%) and modification of the dialysis regimen (70%). CONCLUSIONS: Pruritus associated with chronic kidney disease is still a current problem, it is underdiagnosed, not codified and with a lack of indicated, effective and safe treatments. Nephrologists do not know its real prevalence and the different pathophysiological mechanisms involved in its development. Many therapeutic options are used with very variable results, ignoring their efficacy and applicability at the present time. The new emerging kappa-opioid-receptor agonist agents offer us an opportunity to reevaluate this age-old problem and improve the quality of life for our patients with chronic kidney disease.

Etiopathogenesis of chronic kidney disease-associated pruritus: putting the pieces of the puzzle together.

Defined as the unpleasant sensation that causes the desire to scratch, pruritus is the most common skin symptom associated with uremia and appears in almost half of patients with advanced chronic kidney disease (CKD). Beyond its direct impact on quality of life, CKD-associated pruritus (CKD-aP) is an independent predictor of mortality that also has a synergistic effect with other quality of life-related symptoms, such as insomnia, depression, and anxiety. Although different mechanisms have been proposed to explain the origin of Pa-ERC, its etiopathogenesis is still not fully understood. Since new therapeutic targets have been identified and several clinical trials have recently shown promising results, our current understanding of the interrelationships has expanded significantly and the pathophysiological mechanisms underlying CKD-aP are now considered to be multifactorial. The potential triggers of pruritus in patients with CKD are discussed in this review, including hypotheses about skin xerosis, accumulation of uremic toxins, dysregulation of the immune system and systemic inflammation, uremic neuropathy, and imbalances in the endogenous opioid system. Other non-uremic causes of pruritus are also discussed, with the aim of guiding the physicians to apply an adequate aetiopathogenic approach to CKD-aP in their day-to-day clinical practice.