Cause Of Itch Research Articles

Oxytocin increases itch sensitivity of mice in late pregnancy and its peripheral receptor mechanism of itch-promoting effect

Oxytocin (OXT) is secreted in a large amount during the middle and late pregnancy. Except for the regulation of functions related to childbirth, OXT is involved in the regulation of cognition, social behavior, addiction, pain and so on. Our aim is to confirm the increase of OXT content in mice in late pregnancy is the main cause of itch during pregnancy and observe whether exogenously administered OXT can induce or increase itch sensitivity. The research shows that itch sensitivity of mice increased significantly in late pregnancy and basically returned to normal one day after delivery. The number of OXT-positive neurons in paraventricular nucleus (PVN) and the content of OXT in serum of the late pregnant mice increased significantly, and decreased sharply after delivery. Intradermal injection of low concentration of OXT (0.2 nmol/L) could not induce scratching behavior in mice, but high concentration of OXT (5 nmol/L, 10 nmol/L) could do this in a dose-dependent manner. Low concentration of OXT significantly increased the itch sensitivity to histamine. Intradermal injection of oxytocin receptor (OXTR) or arginine vasopressin-1a receptor (AVPR1A) antagonist did not affect histamine-induced scratching behavior, but both reversed the increase of itch sensitivity in late pregnant mice or the facilitated itch sensitivity by OXT. Study suggests that both endogenous and exogenous increases in OXT can increase the body's sensitivity to itch, and even induce itch directly. Pruritus during pregnancy is closely related to the increase of OXT content in vivo. In the periphery, the itch-promoting effect of OXT is mediated by OXTR and AVPR1A.

Multifactorial causes of chronic itch in diabetes: More than just neuropathy.

Chronic pruritus is common in patients with diabetes though its pathophysiology is unknown and difficult to pinpoint given the multi-system manifestations of diabetes. Herein, we aim to evaluate the severity of chronic itch in patients with diabetes and its association with glycaemic control, microvascular complications and quality of life. We conducted a retrospective study of 105 adults with diabetes evaluated by a dermatologist at a tertiary care centre in Mexico City. Degree of chronic pruritus and its impact on quality of life as well as laboratory, clinical and demographic data were collected. Patients without chronic pruritus (n = 62) were compared to those with chronic pruritus (n = 43). The latter cohort was further stratified by itch severity, and characteristics of their itch were quantified. Neuropathy and loss of protective sensation were more common in patients with chronic pruritus, compared to those without chronic pruritus (p = 0.007 and p = 0.001, respectively). Anxiety and depression were more common in individuals with chronic pruritus (p = 0.009), and these group reported higher effect of pruritus on their quality of life (p < 0.0001). The most common sites of itch were the head, back and arms. Among patients with chronic itch, increasing itch severity was associated with decreasing eGFR (p = 0.080). The underlying cause of chronic itch in patients with diabetes is likely multifactorial and owing to microvascular complications such as neuropathy and nephropathy. Better understanding of the causes of itch in these patients can allow for more targeted treatment, leading to improved quality of life.

A phase IV, randomised, double-blind, controlled, parallel group trial to evaluate the effectiveness and safety of Balneum Plus versus emollient in the treatment of chronic kidney disease-associated pruritus in haemodialysis patients.

Chronic kidney disease-associated pruritus (CKD-aP) is a common, distressing complaint in patients with advanced renal disease that is frequently overlooked. Treatment is often unsatisfactory. Balneum Plus (Almirall, Barcelona, Spain) is a cream containing 3% lauromacrogols and 5% urea, commonly used to treat atopic dermatitis. It has not been studied in CKD-aP to date. Adult haemodialysis patients were randomised 1:1 to apply Balneum Plus or E45 (Reckitt Beckiser, Slough, UK) to compare the active ingredients of lauromacrogol and urea with a control cream. Itch was defined as three episodes of itching during the last 2weeks, appearing a few times a day, lasting a few minutes and troubling the patient [1]. Patients with other causes of itch, e.g. eczema and liver disease, were excluded. The primary outcome was a reduction in itch as measured by the visual analogue scale (VAS) score at 4weeks and analysed using an analysis of covariance approach. A total of 314 patients were screened and 58 patients were randomised, 29 in each group. Three patients dropped out in each group. The median baseline VAS scores were 6.5 [interquartile range (IQR) 4.4-8.0] in the Balneum Plus group and 6.3 (IQR 5.1-7.3) in the E45 group. After 4weeks, VAS scores decreased to 2.6 (IQR 0.9-4.5) and 2.0 (IQR 0.5-4.8) in the Balneum Plus and E45 groups respectively (P=0.64 for the difference). Using a validated questionnaire to assess secondary outcomes, we found that the Balneum Plus group had longer itching episodes, more difficulty staying asleep and itching was more annoying than in the E45 group. There was no significant difference in adverse events between the two groups. One patient reported inflamed spots on the abdominal skin in the Balneum Plus group. This is the first randomised controlled study of two different emollients for the treatment of CKD-aP and is a negative study. We found no significant difference in itch scores between Balneum Plus and E45.

Itch in Adult Population with Type 2 Diabetes Mellitus: Clinical Profile, Pathogenesis and Disease-Related Burden in a Cross-Sectional Study.

Simple SummaryAlthough it is well accepted that itch might be one of the symptoms related to diabetes mellitus, very little is known about this topic from previous studies. In the current study, we aimed to investigate itch sensation in type 2 diabetes mellitus with special emphasis on the potential underlying causes. According to our study, itch was a relatively frequent symptom, present in about 36% of subjects, causing significant impairment to quality of life. Based on our findings and previous literature data, it seems that the primary cause of itch in this group of subjects is poor diabetes control with subsequent skin dryness and diabetic polyneuropathy.Background: Despite growing interest in itch, data regarding itch in type 2 diabetes mellitus (DM2) are still limited, and mostly based on outdated studies. This study aimed to evaluate the clinical characteristics of itch in the adult population with DM2 and explore potential underlying causes. Methods: The study group consisted of 109 adult patients with DM2. Standardized questionnaires were completed in order to assess the itch intensity [Numerical Rating Scale (three days, 24hours) (NRS)] and the Four-item Itch Questionnaire (4IIQ) and to assess the psychological impact of itch [ItchyQoL, Six-Item Stigmatization Scale (6-ISS), Hospital Anxiety and Depression Scale (HADS)]. Skin dryness was evaluated clinically and by non-invasive assessment of epidermis moisturizing. Neuropathy was assessed using the clinical Katzenwadel neuropathy scale. Results: Itch occurred in 35.8% of adult patients with DM2, with NRSmax three days 6.31 ± 2.16 and 8.1 ± 3.5 points in 4IIQ. Itchy patients have had significantly higher FPG levels compared with the non-itchy population (p = 0.01). Patients with itch had a significantly higher possibility of neuropathy compared with non-itchy subjects (p < 0.01). Skin xerosis was significantly more advanced in patients with itch compared to those without (p < 0.01). The mean ItchyQol score was assessed as 41.2 ± 13.4 points, indicating mild life quality impairment and correlated positively with itch intensity. Itchy subjects had significantly higher scores in both anxiety and depression dimensions of HADS (in each p < 0.01). Conclusions: We suggest that the primary cause of itch is prolonged poor diabetes control with altered glucose and insulin levels, subsequently causing skin dryness and neuropathy in long-lasting DM2.

Do you feel itchy? A guide towards diagnosis and measurement of chronic kidney disease-associated pruritus in dialysis patients.

ABSTRACTChronic kidney disease-associated pruritus (CKD-aP) is a potentially distressing condition that affects a significant proportion of patients with end-stage kidney disease undergoing dialysis. CKD-aP may lead to worsening of patients’ physical and mental health-related quality of life (HRQoL) and has also been linked with worse clinical outcomes, including increased mortality. Despite these detrimental effects, evidence from real-world studies shows that CKD-aP still remains overlooked by nephrologists and underreported by patients in clinical practice. Itch is subjective and therefore its diagnosis is often dependent on patients reporting this symptom. There is an opportunity to reduce the burden of CKD-aP on dialysis patients by increasing awareness about this condition and the availability of effective treatments. It is particularly important that nephrologists and other healthcare providers routinely ask their patients if they are experiencing itch. The differential diagnosis of CKD-aP requires a step-by-step identification and exclusion of possible alternative or concomitant causes of itch. Several simple validated self-reported assessment scales are available to evaluate the presence and severity of itch in a time-efficient manner, making them suitable for use in everyday clinical practice. The impact of CKD-aP on haemodialysis patients’ HRQoL should also be assessed on a regular basis. This review provides a comprehensive overview of the differential diagnosis of CKD-aP and the diagnostic tools that are available to identify itch and quantify its severity and impact on patient HRQoL. A suggested algorithm to guide the screening, diagnosis and assessment of CKD-aP among dialysis patients in real-world practice is provided.

Modern concept of pruritus diagnosis and therapy

Modern concept of pruritus diagnosis and therapy Abstract. Pruritus can be best treated when the cause of itching is known, allowing a targeted treatment. To find the cause of itching it is recommended to consult the itch classification system of the «International Forum for the Study of Itch» (IFSI). In here three groups of conditions are distinguished: Pruritus on diseased (inflamed) skin (group I) is caused by a pruritic skin disorder that has to be diagnosed properly; correct treatment of the skin disorder will be the treatment of pruritus. Pruritus on non-diseased (non-inflamed) skin (group II) can be due to an internal disease or a consequence of drugs; elimination of the cause - as far as possible - will also eliminate itch. In pruritus presenting with severe chronic secondary scratch lesions (group III) the aim will be to prevent patients from further scratching. If causative treatment is not possible or the cause of itch remains unknown a symptomatic treatment will be seeked following a step-by-step procedure. In a step 1 a basic therapy with moisturizers and anthistamines is recommended. Step 2 comprises a symptomatic causative adapted therapy. In step 3 phototherapy and systemic treatments are considered including the use of anticonvulsants, antidepressants or anti-inflammatory agents.

Causes, pathophysiology, and treatment of pruritus in the mature patient

Chronic itch is a common and debilitating health condition in the elderly. There are several common causes of itch in the mature population, such as skin xerosis, immunosenescence, and neuropathic changes. In addition, skin diseases, such as seborrheic dermatitis and stasis dermatitis, systemic conditions (end-stage renal disease and diabetes), or psychogenic derailments, such as depression, anxiety, and dementia, can all serve as triggers of pruritus. Polypharmacy, a common occurrence among the elderly population, may also serve as a cause of itch that may or may not be accompanied by dermatitis. Such medications as μ opioids and calcium channel blockers have been found to have a connection with pruritus in the advanced aging population.Determining the exact trigger for pruritus in the elderly may be especially challenging, because itch can be idiopathic in many cases. The role of treatments should not only take into account elimination of various underlying cutaneous, systemic, or psychogenic conditions associated with itch but also focus on the skin changes that are characteristic of the aging process. Development of such treatment options can be guided by elucidation of the mechanisms underlying the pathophysiology of itch in the geriatric population.

Psychotropics in different causes of itch: systematic review with controlled studies.

Among the wide range of symptoms neglected or resistant to conventional treatments in clinical practice, itch is emerging gradually as a theme to be studied. Itch complaints and the negative effects in the quality of life are observed in several medical fields. Although the partially obscure pathophysiology, some researchers decided to check and test the use of psychotropic drugs in resistant itch to conventional topical treatments and antihistamines. The objective of this study was to evaluate scientific evidence in psychotropic use in the treatment of itch of various causes. This is a systematic review of scientific literature. The following databases were used: PubMed, Web of Science, Scopus and Scielo. Randomized controlled trials that should focus on treatment with psychotropic drugs of pruritus of various causes were the inclusion criteria. All articles were analyzed by the authors, and the consensus was reached in cases of disagreement. Fifteen articles were included after analysis and selection in databases, with the majority of clinical trials focusing on psychopharmacological treatment of itch on account of chronic kidney disease. Clinical trials with psychotropic drugs mostly indicated significant improvement in the itching. In most trials of chronic kidney disease as basal disease for itch, greater effectiveness was observed with the use of psychotropic drugs compared with placebo or other antipruritic. However, the small amount of controlled trials conducted precludes the generalization that psychiatric drugs are effective for itch of various causes.

Itch Management in the Elderly.

Itch is a common symptom in the elderly population over 65 years old, and is often a chronic condition lasting more than 6 weeks. As in all age groups, but especially in the elderly, there can be a significant effect on the general health status and quality of life, with impaired daily activities and lack of sleep, which can also lead in some cases to depression or anxiety. The cause of chronic itch in the elderly is often multifactorial due to physiological changes in the aging skin, including impaired skin barrier function, and also due to decline in immunological (immunosenescence), neurological, and psychological changes associated with age. Common causes of chronic pruritus in the aging skin include xerosis (dry skin), dermatological disorders (eczema, psoriasis, lichen planus), and systemic (renal, hepatic, endocrine), neurodegenerative, and psychological diseases. Comorbidities in the elderly population lead to polypharmacy, increasing the potential risk of drug side effects, which can result in causing or exacerbating itch in the elderly patient. It is essential to obtain a detailed history, including drugs, as well as a thorough clinical examination with appropriate subsequent investigations. Management of the elderly patient with chronic pruritus should include treatment with topical therapies such as emollients as well as other agents for symptomatic relief. Systemic therapies should be directed at any underlying cutaneous or systemic diseases. Often the cause of itch in the elderly cannot be found and some systemic treatments can be used for symptomatic control of the itch, including antihistamines, gabapentin, and selective antidepressants. A holistic approach needs to be taken on an individual basis to relieve chronic pruritus, as the management of itch in the elderly can be a challenge.

Diagnostic Procedures of Itch.

A complex and multifactorial pathogenesis of itch makes the proper diagnosis of underlying disease a difficult and challenging clinical problem. The examination of every patient with itch should be started by gathering an accurate history. During the anamnesis it is important to obtain data about the beginning of the appearance of symptoms, its location, diurnal variation, and the factors influencing itch perception. After careful anamnesis the patient should undergo a detailed physical examination, with particular attention to the skin in order to look for any signs of skin lesions. Special attention should be paid to distinguish the primary lesion from the changes resulting from scratching. In patients in whom the etiology of the itch cannot be identified on the basis of the medical examination, a panel of primary screen laboratory examination may be required, and if necessary, depending on the results of basic laboratory results and data from medical history, additional diagnostic tests should be considered. In patients in whom an organic cause of itching has not been established, itch is most likely of undetermined origin; however, psychogenic causes should also be suspected and ruled out. In conclusion, it could be stated that itch is a common symptom of many skin diseases, systemic of neurological diseases. Despite the complex etiology of the disease, an exact cause of itch should be searched for in each patient, as successful therapy is largely dependent on the determination of the cause of the itching.

Itch in Special Skin Locations Management.

Itch management can be particularly complicated in some small areas like the scalp or the anogenital region for many reasons: the frequently poor diagnosis of the causes of itch in these areas, the dense innervation of these areas, and the symbolic value of these areas for the human psyche. The diagnosis of itchy scalp is easier than that of anogenital pruritus. Clinical examination and a careful inventory of all diseases of the patient and of the local environment are necessary. Localized treatments are frequently used at both sites, whereas specific pharmaceutical formulations are necessary for the pilose or the mucous environment. Nonetheless, systemic treatments or psychological interventions can be very useful.

A review of itch

Itch can be one of the most difficult complaints for physicians to treat. The cause of itch, especially if chronic, is often elusive. A body of research has emerged that has shed light on many of the mechanisms governing this common complaint. These mechanisms include the detection of pruritogens (p

Mediators of Chronic Pruritus in Atopic Dermatitis: Getting the Itch Out?

For centuries, itch was categorized as a submodality of pain. Recent research over the last decade has led to the realization that itch is in fact a separate and distinct, albeit closely related, sensation. Chronic itch is a common complaint and has numerous etiologies. Various receptors (TRPA1, TRPV1, PAR2, gastrin-releasing peptide receptor (GRPR), Mas-related G proteins), secreted molecules (histamine, nerve growth factor (NGF), substance P (SP), proteases), and cytokines/chemokines (thymic stromal lymphopoietin (TSLP), IL-2, IL-4, IL-13, and IL-31) are implicated as mediators of chronic pruritus. While much remains unknown regarding the mechanisms of chronic itch, this much is certain: there is no singular cause of itch. Rather, itch is caused by a complex interface between skin, keratinocytes, cutaneous nerve fibers, pruritogenic molecules, and the peripheral and central nervous systems. Atopic dermatitis is one of the most itchy skin dermatoses and affects millions worldwide. The sensation of atopic itch is mediated by the interplay between epidermal barrier dysfunction, upregulated immune cascades, and the activation of structures in the central nervous system. Clinicians are in possession of an arsenal of different treatment options ranging from moisturizers, topical immunomodulators, topical anesthetic ion channel inhibitors, systemic immunomodulators, as well as oral drugs capable of reducing neural hypersensitization. Emerging targeted therapies on the horizon, such as dupilumab, promise to usher in a new era of highly specific and efficacious treatments. Alternative medicine, stress reduction techniques, and patient education are also important treatment modalities. This review will focus on the mediators of chronic pruritus mainly associated with atopic dermatitis (atopic itch), as well as numerous different therapeutic options.

3-iodothyroacetic acid, a metabolite of thyroid hormone, induces itch and reduces threshold to noxious and to painful heat stimuli in mice.

Itch is associated with increased sensitization to nociceptive stimuli. We investigated whether 3-iodothyroacetic acid (TA1), by releasing histamine, induces itch and increases sensitization to noxious and painful heat stimuli. Itch was evaluated after s.c. administration of TA1 (0.4, 1.32 and 4 μg·kg(-1) ). Mice threshold to noxious (NHT) and to painful heat stimuli were evaluated by the increasing-temperature hot plate (from 45.5 to 49.5°C) or by the hot plate (51.5°C) test, respectively, 15 min after i.p. injection of TA1 (0.4, 1.32 and 4 μg·kg(-1) ). Itch, NHT and pain threshold evaluation were repeated in mice pretreated with pyrilamine. Itch and NHT were also measured in HDC(+/+) and HDC(-/-) following injection of saline or TA1 (1.32, 4 and 11 μg·kg(-1) ; s.c. and i.p.). pERK1/2 levels were determined by Western blot in dorsal root ganglia (DRG) isolated from CD1 mice 15 min after they received (i.p.): saline, saline and noxious heat stimulus (46.5°C), TA1 (0.1, 0.4, 1.32, 4 μg·kg(-1) ) or TA1 1.32 μg·kg(-1) and noxious heat stimulus. TA1 0.4 and 1.32 μg·kg(-1) induced itch and reduced NHT; pyrilamine pretreatment prevented both of these effects. TA1 4 μg·kg(-1) (i.p.) reduced pain threshold without inducing itch or modifying NHT. In HDC(-/-) mice, TA1 failed to induce itch and to reduce NHT. In DRG, pERK1/2 levels were significantly increased by noxious heat stimuli and by TA1 0.1, 0.4 and 1.32 μg·kg(-1) ; i.p. Increased TA1 levels induce itch and an enhanced sensitivity to noxious heat stimuli suggesting that TA1 might represent a potential cause of itch in thyroid diseases.

Interneurons scratch an itch.

Itch is immensely frustrating. Most studies focus on the cause of itch. In this issue of Neuron, Kardon et al. (2014) find that itch can be modulated by inhibitory neurons that produce dynorphin, an endogenous agonist of κ-opioid receptors.

Quoi de neuf sur le prurit ?

Pruritus (itch) is defined as an unpleasant sensation that causes the desire or reflex to scratch. Research in this field has increased dramatically in the past ten years, allowing a much better understanding of pruritus and resulting in new therapeutic options. Consequently, several generally accepted ideas are now being challenged. Pruritus is usually not due to an allergy, especially in the case of pruritus sine material. Drugs should be regarded systematically as putative causes of itch. It is a very frequent symptom: one third of the European population reported having felt pruritus in the preceding week. Histamine does not play an important role, especially in atopic dermatitis.

Assessment of Pruritus Characteristics and Impact on Burn Survivors

The goal of this cross-sectional study was to characterize and describe persistent postburn pruritus. Cause and treatment of postburn itch is elusive. It has been suggested that burn survivors with persistent pruritus should be divided into acute itch (≤6 months postinjury) and chronic itch (>6 months postinjury) because the cause of itch may be different. Cross-sectional data of itch characteristics reported here are from the baseline data of a prospective, randomized, double-blind, controlled pilot study of 23 subjects with frequent and bothersome postburn pruritus. Subjects self-completed validated scales for variables of itch sensation, affect of itch, and severity. Variables of quality of life, frequency, pain and itch intensity, skin condition, scar, and medication were also recorded. Itch frequency revealed that 87% of subjects experienced itching daily, 96% experienced three or more episodes a day, and 52% had episode durations lasting 5 to 30 minutes per incidence. Itch was reported as unbearable by 94% of subjects with chronic itch and by 86% of subjects with acute itch, whereas bothersome was 88 and 100%, respectively. Itch sensation dimension of stinging was 74% in both acute and chronic itch subjects. Crawling and burning sensations were often severe. Potential itch triggers and relief activities were identified. Differences in sensory and affective itch components were detected between acute and chronic itch subjects. Combinations of itch mechanisms probably contribute to the development of and changes in pruritus. Characterizing the sensation and affective itch dimensions in conjunction with inflammation, burn injury, recovery, scar maturation, medication, and psychological status should better elucidate postburn itch.

Willan's itch and other causes of pruritus in the elderly

Itch in the elderly presents a diagnostic and therapeutic challenge. A thorough history, review of systems, and physical examination are critical to determining its cause. Examination of the skin may be misleading. There are frequently only secondary lesions, eczematous changes, lichenification, and excoriation, which may be misdiagnosed as a primary dermatitis. Xerosis may be the cause, but it is sometimes merely coincidental. If primary lesions are present, a skin biopsy can enable a diagnosis to be made. Systemic causes of itch, such as cholestasis, uremia, hyperthyroidism, medications, or lymphoma, must be considered. If the cause remains elusive, idiopathic itching of the elderly or so-called "senile pruritus" may be considered. However, we propose to discard the term "senile pruritus", which can be offensive and frightening. We propose to replace it with "Willan's itch". Robert Willan (1757-1812) is honored as one of the founders of modern dermatology thanks to his book, On Cutaneous Diseases, and its morphological approach to skin disease. He was probably the first to give a good clinical description of itching in the elderly. The diagnosis of Willan's itch should be reserved for generalized pruritus in the absence of xerosis or other recognizable cause. The pathophysiology of this form of pruritus is poorly understood, but it is likely that age-related changes of the skin, cutaneous nerves, and other parts of the nervous system play a role. Anecdotal and limited data suggest that gabapentin, cutaneous field stimulation, serotonin antagonists, and ultraviolet B phototherapy may attenuate itch in some of these patients.

Management of common vulval conditions.

Community-based surveys indicate that about a fifth of women have significant vulval symptoms lasting over three months at some time in their lives. Common causes of itch or pain are dermatitis, recurrent candidiasis and the recently recognised pain syndromes--vulvar vestibular syndrome and dysaesthetic vulvodynia. Diagnosis is usually apparent after a thorough history and examination, although conditions commonly coexist and are complicated by prior treatment. Skin lesions not responding to treatment require biopsy. Treatment aims to control symptoms rather than to cure; avoiding soaps and other irritants is central to management. An early, accurate diagnosis should enhance management of vulval conditions, particularly pain syndromes.

The incidence of hydroxyethyl starch-associated pruritus.

Pruritus due to hydroxyethyl starch (HES) is reported with a very variable frequency but appears to be relatively uncommon in the U.K. compared with other European countries. To determine the frequency of HES-related pruritus in patients discharged from intensive care units (ICUs) in two U.K. hospitals. A questionnaire survey was given to 253 patients after discharge from ICU. Questions were designed to exclude pre-existing skin disease and other causes of pruritus. One hundred and fifty-nine completed questionnaires were suitable for analysis. Seventeen of 135 (12.6%) subjects who had received HES reported itch, as did one of 24 who had not received HES. There was no apparent relationship between the occurrence of HES-related pruritus and either the surgical indication or the brand or volume of HES infused. HES-related pruritus is a problem that dermatologists need to recognize; however, its frequency in the U.K., when other causes of itch are excluded, appears to be lower than suggested in some previous reported studies.