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)

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

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

Proteinase-activated receptor-2 (PAR2) is a seven transmembrane spanning, G-protein-coupled receptor, present on the membrane of many cell types including keratinocytes. In skin, PAR2 is suggested to play a regulatory role during inflammation, epidermal barrier function, and pruritus. PAR2 is activated by trypsin-like proteases by a unique mechanism where cleavage of the receptor leads to the release of a small peptide, which activates the receptor as a tethered ligand. The endogenous activators of PAR2 on keratinocytes have not been identified as of yet. Potential candidates are kallikrein-related peptidases (KLKs) expressed by epidermal cells. Therefore, the ability of four human skin-derived KLKs was examined with regard to their capacity to activate PAR2 in vitro. PAR2 cleavage was followed by immunofluorescence analysis and functional activation by measurements of changes in intracellular calcium levels. We found that KLK5 and KLK14, but neither KLK7 nor KLK8, induced PAR2 signalling. We conclude that certain, but not all, epidermal KLKs are capable of activating PAR2. We could also show the coexpression of KLK14 and PAR2 receptor in inflammatory skin disorders. These in vitro results suggest that KLKs may take part in PAR2 activation in the epidermis and thereby in PAR2-mediated inflammatory responses, including epidermal barrier repair and pruritus. The role of KLKs in PAR2 activation in vivo remains to be elucidated.
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PMID:Activation of proteinase-activated receptor-2 by human kallikrein-related peptidases. 1762 93

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

There are numerous studies of the pruritus-producing effects of histamine, serotonin, tryptase, substance P and interleukin-2 in humans and mice, but very little reported in dogs even though a common reason dogs are presented to veterinarians is pruritus. The aim of this study was to determine whether substances known to cause pruritus in humans also cause pruritus in dogs. Twenty-five clinically healthy research beagle dogs were included in the study. All dogs first received an intradermal injection of 0.05 mL saline as a control substance and were video-recorded for 20 min before and after the injection. Twenty-four hours later the dogs were randomly divided into five groups of five dogs each and randomly assigned to receive histamine, serotonin, tryptase, substance P or interleukin-2 injected intradermally each at the volume of 0.05 mL. On subsequent days, increasing concentrations of each substance were used. Before (baseline) and after the injection of each concentration of the substances, the dogs were video-recorded for 20 min. The frequency and character of pruritus episodes (scratching, licking, chewing, rubbing or rolling) were noted and these data were used for statistical analysis. The number of pruritus episodes was compared among baseline, saline and the different concentrations of each substance. The results showed that dogs did not have a significant increase in pruritic behaviour above baseline or saline after injection of any of the investigated substances (generalized linear model; P = 0.23).
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PMID:Investigation of the pruritogenic effects of histamine, serotonin, tryptase, substance P and interleukin-2 in healthy dogs. 1915 12

Systemic mastocytosis is an extremely rare disease characterised by abnormal mast cell production and accumulation of mast cells in the bone marrow or organs, and to some extent also in the skin (urticaria pigmentosa). To date there have been no descriptions of death caused by systemic mastocytosis. The present first description of such a fatality is based upon a case of anaphylactic histamine shock, probably caused by the consumption of peanuts. The affected person suffered from urticaria pigmentosa and developed a fairly typical pruritus prior to death. In the serum sample taken post-mortem the tryptase concentration was markedly elevated. The diagnosis of systemic mastocytosis was established on the basis of two primary and three secondary criteria according to the WHO classification, which underlines the importance of histological investigations in cases where the cause of death is unclear.
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PMID:[Sudden death in the presence of systemic mastocytosis and urticaria pigmentosa]. 1921 69

This study investigated the involvement of tryptase and proteinase-activated receptor (PAR) subtypes in spontaneous scratching, an itch-associated behavior, in NC mice. This strain of mice showed chronic atopy-like dermatitis and severe spontaneous scratching, when kept a long time in a conventional environment. The trypsin-like serine proteinase inhibitor nafamostat mesilate (1 - 10 mg/kg) dose-dependently inhibited spontaneous scratching in mice with dermatitis. The activity of tryptase was increased in the lesional skin, which was inhibited by nafamostat at a dose inhibiting spontaneous scratching. Enzyme histochemistry revealed the marked increase of toluidine blue-stained cells, probably mast cells, with tryptase activity in the dermis of the lesional skin. Intravenous injection of anti-PAR(2) antibody suppressed spontaneous scratching of mice with dermatitis. Intradermal injection of the PAR(2)-activating peptide SLIGRL-NH(2), but not PAR(1), (3), (4)-activating peptides, elicited scratching at doses of 10 - 100 nmol/site in healthy mice. PAR(2)-immunoreactivity was observed in the epidermal keratinocytes in healthy and dermatitis mice. These results suggest that PAR(2) and serine proteinase(s), mainly tryptase, are involved in the itch of chronic dermatitis.
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PMID:Involvement of Tryptase and Proteinase-Activated Receptor-2 in Spontaneous Itch-Associated Response in Mice With Atopy-like Dermatitis. 1927 Apr 28


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