Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Allergic rhinitis is an inflammatory disorder of the nasal mucosa typified by the symptoms of nasal itch, sneeze, anterior nasal secretions, and nasal blockage. These symptoms arise from the interaction between mediators and neural, vascular, and glandular structures within the nose. Nasal itch, sneezes, and rhinorrhoea are predominantly neural in origin, while nasal obstruction is predominantly vascular. Nasal biopsy studies show accumulation of eosinophils within the lamina propria and epithelium and an increase in tissue and cell surface basophils in both seasonal and perennial allergic rhinitis. These cells are in an activated state. Within the epithelium, increased numbers of mast cells, T cells and Langerhans' cells, which induce T-cell activation, are found. The accumulation of these cells can be linked to chemokine and cytokine generation by the epithelial cells themselves. Thus, the tissue cell recruitment is orchestrated by activated mast cells, T cells, and epithelial cells, with the recruited tissue eosinophils also contributing to their persistence at this site through autocrine mechanisms. Mast cells generate an array of mediators including histamine, tryptase, leukotrienes, and prostaglandins. Histamine is also generated by basophils. Eosinophils and basophils contribute to the leukotriene synthesis within the tissue. Histamine nasal insufflation induces nasal itch, sneeze, and rhinorrhoea as well as nasal blockage, thereby reproducing all the symptoms of allergic rhinitis. These effects are primarily mediated by H1-receptors, and H1-receptor antagonists are a prominent treatment. Antagonism of histamine at these receptors reduces symptoms by about 40-50%, with the greatest effect on the neurally mediated responses. Thus, histamine is a major mediator of allergic rhinitis, but not the sole contributor. Nasal insufflation with leukotrienes, prostaglandins, or kinins is associated with the development of nasal blockage. These mediators act primarily on the nasal vasculature and, in this respect, leukotrienes are potent mediators. Leukotrienes also induce plasma protein exudation, which contributes to the anterior nasal secretions. Studies with combination products have suggested that modifying the effects of both leukotrienes and histamine has complementary effects in relieving nasal symptoms, indicating that both these mediators are relevant to disease expression.
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PMID:Allergic rhinitis: not purely a histamine-related disease. 1129 80

Desloratadine is a new, selective, H(1)-receptor antagonist that also has anti-inflammatory activity. In vitro studies have shown that desloratadine inhibits the release or generation of multiple inflammatory mediators, including IL-4, IL-6, IL-8, IL-13, PGD(2), leukotriene C(4), tryptase, histamine, and the TNF-alpha-induced chemokine RANTES. Desloratadine also inhibits the induction of cell adhesion molecules, plateletactivating factor-induced eosinophil chemotaxis, TNF-alpha-induced eosinophil adhesion, and spontaneous and phorbol myristate acetate-induced superoxide generation in vitro. In animals desloratadine had no effect on the central nervous, cardiovascular, renal, or gastrointestinal systems. Desloratadine is rapidly absorbed, has dose-proportional pharmacokinetics, and has a half-life of 27 hours. The absorption of desloratadine is not affected by food, and the metabolism and elimination are not significantly affected by the subject's age, race, or sex. There are no clinically relevant interactions between desloratadine and erythromycin, ketoconazole, or grapefruit juice. Desloratadine is not a significant substrate of the P-glycoprotein transport system. Once daily administration of desloratadine rapidly reduces the nasal and nonnasal symptoms of seasonal allergic rhinitis, including congestion. In patients with seasonal allergic rhinitis and concomitant asthma, desloratadine treatment was also associated with significant reductions in total asthma symptom score and use of inhaled beta(2)-agonists. Use of desloratadine in patients with chronic idiopathic urticaria was associated with significant reductions in pruritus, number of hives, size of the largest hive, and interference with sleep and daily activities. Clinical experience in over 2300 patients has shown that the adverse event profile of desloratadine is similar to that of placebo; desloratadine has no clinically relevant effects on electrocardiographic parameters, does not impair wakefulness or psychomotor performance, and does not exacerbate the psychomotor impairment associated with alcohol use.
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PMID:Desloratadine: A new, nonsedating, oral antihistamine. 1129 78

We examined whether neuronal proteinase-activated receptor-2 (PAR-2) may be involved in pruritus of human skin. The endogenous PAR-2 agonist tryptase was increased up to fourfold in atopic dermatitis (AD) patients. PAR-2 was markedly enhanced on primary afferent nerve fibers in skin biopsies of AD patients. Intracutaneous injection of endogenous PAR-2 agonists provoked enhanced and prolonged itch when applied intralesionally. Moreover, itch upon mast cell degranulation was abolished by local antihistamines in controls but prevailed in AD patients. Thus, we identified enhanced PAR-2 signaling as a new link between inflammatory and sensory phenomena in AD patients. PAR-2 therefore represents a promising therapeutic target for the treatment of cutaneous neurogenic inflammation and pruritus.
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PMID:Proteinase-activated receptor-2 mediates itch: a novel pathway for pruritus in human skin. 1286

Mastocytosis comprises several diseases characterized by an abnormal increase in tissue mast cells. Cutaneous mastocytosis (CM) is the most common form of mastocytosis, affects predominantly children, and presents as a mast cell hyperplasia limited to the skin. Systemic mastocytosis (SM) comprises multiple distinct entities in which mast cells in filtrate the skin and/or other organs. The diagnosis of SM is based on the presence of one major criterion and one minor criterion or three minor criteria. Major criteria include the presence of multifocal dense infiltrates of > 15 mast cells in bone marrow and/or other extracutaneous organs. Four minor criteria include the presence of elevated serum alpha-tryptase levels > 20 ng/mL, the expression of CD2 and CD25 surface markers in c-kit-positive mast cells from bone marrow or other organs, the presence of a c-kit mutations on bone marrow and/or other tissues mast cells, and the presence of > 25% abnormal spindle-shaped mast cells in bone marrow and/or tissues. Symptoms of CM include pruritus, flushing urticaria, and dermatographism. Symptoms of SM include cutaneous symptoms in association with syncope, gastric distress, nausea and vomiting, diarrhea, bone pain, and neuropsychiatric symptoms. Activating and nonactivating mutations of c-kit (Asp816Val) are seen in adult SM and in some pediatric CM (Gly839Lys), indicating a clonal dysregulation. There is no cure for mastocytosis but the majority of pediatric CM regress at puberty. Women with mastocytosis are fertile and pregnancy and delivery have been successful by blocking mast cell-mediated symptoms. Symptomatic treatment aimed at reducing the effect of mediators is effective with antihistamines and mast cell-stabilizing agents such as sodium cromolyn. To reduce mast cell burden, interferon alpha, steroids, and purine analogs have been used with varying results. Future directions include tyrosine kinase inhibitors and bone marrow transplant.
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PMID:Mastocytosis: classification, diagnosis, and clinical presentation. 1505 60

Recent research in neurophysiology of itch has indicated the existence of itch-dedicated nociceptor neurones. The perception of itch is regulated by tonically inhibitory descending neuronal pathways and nociceptor spinal neuronal circuits. There is at present no convincing evidence of an 'itch centre' in the brain. A classification of itch has been proposed, based on neurophysiological considerations, which stresses the importance of neurogenic and neuropathic itch, and assists in differential diagnosis and selection of treatment. However, more than one class of itch can occur concurrently in the same patient. The importance of cross- talk between dermal mast cells and nociceptor nerve terminals, involving cleavage of proteinase-activated receptor 2 by mast cell tryptase, is highlighted. The pruritus of cholestasis is mediated at least in part by opioid peptides synthesized by the liver, and elevated levels of these mediators are found in the plasma and skin of patients with itch due to cholestasis. The combined use of both mu-receptor antagonists and kappa-receptor agonists (anti-pruritic) is worth exploring.
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PMID:Itch: more than skin deep. 1537 26

Chronic urticaria (CU) is characterized by recurrent itching skin eruptions caused by mast cell degranulation. Relapses can be provoked by food intake. The aim of this study was to investigate if the mast cell number in the gastroduodenal mucosa is increased in CU patients, and whether mast cell counting by pathologists is clinically useful. We defined two study groups: 50 disease controls (16 Belgians and 34 Italians) and 43 Belgian CU patients. Mast cells were detected using immunohistochemistry for tryptase and CD117. The mast cell number in the disease controls was 20.2/high-power filed (HPF; 133.3/mm2) in the stomach and 32.5/HPF (209.2/mm2) in the duodenum. There was no difference between Belgian and Italian controls, indicating that dietary habits have no influence on the normal gastroduodenal mast cell number. In CU patients, mast cell numbers were significantly higher: 32.4/HPF (186.0/mm2) in the stomach (P<0.0001) and 44.8/HPF (246.0/mm2) in the duodenum (P=0.0002). CU is thus associated with mast cell infiltration in the gastroduodenal mucosa, even if patients do not have gastrointestinal symptoms. Mast cell counting in gastroduodenal biopsies of CU patients can be useful in selecting patients who may respond to a therapy with intestinal mast-cell-stabilizing agents.
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PMID:Chronic urticaria is associated with mast cell infiltration in the gastroduodenal mucosa. 1632 51

The pruritogenic potency of tryptase and its involvement in anti-pruritic effect of intravenous nafamostat mesilate (NFM) were studied in mice. An intradermal injection of tryptase (0.05-1 ng/site) elicited scratching in ICR mice, while chymase was without effects at doses of 0.05-50 ng/site. The dose-response curve of tryptase action was bell-shaped and the effect peaked at 0.1 ng/site (approximately 0.7 fmol/site). NFM (10 mg/kg) inhibited scratching induced by tryptase but not by histamine and serotonin. NFM (1-10 mg/kg) produced the dose-dependent inhibition of scratching induced by intradermal compound 48/80 (10 microg/site). The inhibition by NFM (10 mg/kg) was abolished in mast cell-deficient (WBB6F1 W/W(V)) mice, but not in wild-type (WBB6F1 +/+) mice. NFM (10 mg/kg) suppressed tryptase activity in the mouse skin. Proteinase-activated receptor-2 (PAR-2) neutralizing antibody (0.1 and 1 microg/site) and the PAR-2 antagonist FSLLRY (10 and 100 microg/site) inhibited scratching induced by tryptase (0.1 ng/site) and compound 48/80 (10 microg/site). These results suggest that mast cell tryptase elicits itch through PAR-2 receptor and that NFM inhibits itch-associated responses mainly through the inhibition of mast cell tryptase.
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PMID:Potent pruritogenic action of tryptase mediated by PAR-2 receptor and its involvement in anti-pruritic effect of nafamostat mesilate in mice. 1635 60

The aim of this paper is to present the state of knowledge on cutaneous neurogenic inflammation. Peripheral effector functions served by afferent sensory neurons underlie the so-called neurogenic inflammation. The mechanism of cutaneous neurogenic inflammation is connected with the release of neuropeptides from the sensory endings. They also exert a number of functions within the immune system. The activity of neuropeptides in the inflammation of the skin can be observed in the form of erythema, edema, hyperthermia and pruritus. Beside these peptides and their receptors, inflammatory skin response, is regulated by tryptase and proteinase-activated receptor 2 (PAR-2). Capsaicin decreases effects of inflammation-induced sensory neuropeptides, which was used in the treatment of diseases caused by inflammation. The activity of transient receptor potential vanilloid receptor 1 (TRP-V1) is associated with the neurogenic inflammation. In inflammatory processes, the neuro-immuno-cutaneous system undergoes activation, which is responsible for triggering and maintaining the inflammatory conditions, both in the healthy skin as well as in the pathological conditions, like psoriasis. Skin exposure to UV radiation influences the neuro-immuno-cutaneous system and causes the release of neuropeptides, thereby eliciting inflammatory response in photodermatosis. In conclusion, understanding the mechanisms and the factors controlling neurotransmitters and their receptors will lead to the identification of novel therapeutic targets for the treatment of cutaneous diseases e.g. pruritus, psoriasis, alopecia areata.
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PMID:Clinical and experimental aspects of cutaneous neurogenic inflammation. 1653 25

A 41-year-old woman presented with a 2-month history of pruritus and a generalized dermatitis that developed initially on the head and spread to the trunk, legs, and buttocks. The pruritus caused extreme discomfort and was not relieved by antihistamines or topical steroid treatment. The patient denied flushing, syncope, and vomiting. Her medical history included asthma treated with salmeterol/fluticasone propionate inhaler, and status post silicone breast augmentation. Physical examination revealed a papular dermatitis on the trunk and extremities composed of lesions up to 0.5 cm in diameter, surrounded by excoriation marks (Figure 1). There was no hepatosplenomegaly or lymphadenopathy. Darier's sign was negative. Results of complete blood count, peripheral blood film examination, and liver function tests were all with normal limits. A biopsy specimen taken from a lesion and stained with hematoxylin-eosin showed telangiectasias, with an increased number of mast cells around blood vessels (Figure 2). Positive Giemsa (Figure 3) and c-kit stain (Figure 4) indicated an increased number of mast cells. Bone marrow aspiration and total body CT performed to rule out systemic involvement showed no pathology. Protein electrophoresis was normal. Serum tryptase and histamine were within normal limits, and 24-hour urine collection for histamine was normal. Narrow-band UV-B treatment was begun 3 times weekly, reduced to twice weekly after 2 months, and then stopped. The first few treatments resulted in significant relief of the pruritus and regression of lesions. After 3 months without treatment, the patient remained free of pruritus and lesions.
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PMID:Telangiectasia macularis eruptiva perstans: unusual presentation and treatment. 1708

Itch is a common symptom in dry skin related to inflammatory skin diseases, normal aging, and systemic diseases such as chronic renal failure, and HIV. However, correlations between itch and objective measures of barrier function and skin dryness such as skin hydration and transepidermal water loss have been rarely found. Recent experimental evidence indicates that damage to the stratum corneum with acetone/ether and water elicits a scratching response in mice and rats. These responses correlate to the number of PGP 9.5 immunoreactive fibers in the epidermis and to FOS-like immunoreactivity in the spinal cord. Other neuromediators involved in the pathogenesis of itch in dry skin are nerve growth factor (NGF), muscarinic acetylcholine receptors, and opiates. Serine proteases such as tryptase and their respective proteinase-activating receptor 2 (PAR2), recently found in both skin and nerves of patients with atopic eczema, suggest that these molecules may have a role in itch in dry skin. This has also been exemplified in the itchy and hyperkeratotic phenotype of the stratum corneum chymotryptic enzyme (SCCE) transgenic mouse model, which is over-expressing a serine protease. Developing inhibitors to these neuropeptides and mediators may be an attractive strategy for anti-itch treatment. The significant progress made in development of moisturizers may have an additional benefit in reducing the itch associated with dry skin. Formulating topical combination therapies containing moisturizers and anti-pruritics can significantly reduce the itch associated with dry skin. This paper will review the current clinical knowledge on the association between dry skin and itch and the recent advances in understanding the pathophysiology of this problem.
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PMID:Dry skin and impairment of barrier function associated with itch - new insights. 1849 19


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