Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ketotifen fumarate, formulated for the treatment of allergic conjunctivitis, is a histamine H1-receptor antagonist, mast cell stabilizer, and eosinophil inhibitor (decreases chemotaxis and activation of eosinophils). In this study, healthy volunteers 3 years of age or older received ketotifen fumarate .025% ophthalmic solution (n = 330) or placebo (n = 165) four times daily for 6 weeks. Ketotifen was safe and well tolerated in the adult and pediatric populations, with an incidence of ocular adverse events of 18.2%, compared with 15.2% with placebo. No ocular rebound vasodilation or itching was observed within 48 hours after treatment. Ketotifen has a favorable safety and tolerability profile, which may have a positive impact on compliance, an important aspect of effective symptomatic control of allergic conjunctivitis.
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PMID:Ocular tolerability and safety of ketotifen fumarate ophthalmic solution. 1243 Oct 41

Urticaria is defined by weals (hives), with or without angioedema, that appear and peak in minutes to hours, usually disappear within 24 h, and are accompanied by pruritus that worsens during the night. Urticaria is caused by cutaneous mast cell degranulation, attributed to immunological, nonimmunological, and idiopathic causes. Chronic idiopathic urticaria (CIU) is the diagnosis when the pathophysiological mechanism of persistent urticaria remains unclear; up to half of patients with CIU have functional autoantibodies directed against the high-affinity receptor for IgE (FcepsilonRI) or against IgE itself, which appear to induce mast cell degranulation. Systemic histamine H1-receptor antagonists, such as desloratadine, are central to the management of CIU. The efficacy and safety of desloratadine, 5 mg once daily, was studied in a double-blind, randomized, placebo-controlled, multicentre trial that included 190 patients, ages 12 and above, with at least a 6-week history of CIU and experiencing a flare of at least moderate severity. Desloratadine was superior to placebo in controlling pruritus and total symptoms after the first dose, and its superiority was maintained throughout the full 6 weeks of the study. Measures of sleep, daily activity, therapeutic response, and global CIU status were also significantly improved with desloratadine after the first dose and maintained throughout the study.
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PMID:Chronic urticaria: impact of allergic inflammation. 1249 25

We describe the treatment of a 60-year old man with severely symptomatic telangiectasia macularis eruptiva perstans (TMEP) with a poor response to several standard therapeutic strategies. At that time, the patient underwent total skin electron beam (TSEB) radiation, based on the theory that by decreasing cutaneous mast cell infiltration, his pruritus would be relieved. He received a total dose of 4000 cGys given in 40 fractionated treatments. The patient had complete resolution of both his cutaneous lesions and pruritus, which has continued through one year of follow-up.
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PMID:Treatment of telangiectasia macularis eruptiva perstans with total skin electron beam radiation. 1276 2

This randomized, double-masked, active-control, parallel-group trial compared the mast cell stabilizers pemirolast potassium 0.1% and nedocromil sodium 2% in the treatment of seasonal allergic conjunctivitis. Pemirolast is currently indicated for four-times-daily administration, nedocromil, for twice-daily dosing. Both ophthalmic solutions were instilled bilaterally twice a day for 8 weeks. The study involved four office visits and two telephone contacts. Participants evaluated their symptoms daily in take-home diaries (itching was the primary efficacy variable) and completed questionnaires to assess comfort. Of a total enrollment of 80, 78 patients completed the study. No significant differences were found between pemirolast and nedocromil on any signs or symptoms of allergic conjunctivitis (redness, chemosis, itching, eyelid swelling). At each visit, pemirolast was rated significantly more comfortable than nedocromil. A significantly higher percentage of the pemirolast group experienced no signs or symptoms at work or school (58% vs 28%; P = .005). The number of adverse events did not differ significantly between groups. Twice-daily administration of pemirolast potassium was as efficacious and safe as twice-daily nedocromil sodium in the 8-week treatment of ragweed allergic conjunctivitis and was superior to nedocromil in comfort. Increased comfort with pemirolast may increase patient satisfaction and compliance with therapy.
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PMID:Two mast cell stabilizers, pemirolast potassium 0.1% and nedocromil sodium 2%, in the treatment of seasonal allergic conjunctivitis: a comparative study. 1277 16

Chronic idiopathic urticaria (CIU) manifests as frequently occurring, short-lived wheals, surrounded by a bright-red flare, and often accompanied by angioedema. The cause of CIU is undefined and its diagnosis requires exclusion of other conditions with somewhat similar symptoms. Recent evidence has indicated that IgG autoantibodies directed against high-affinity IgE receptors (FcepsilonRI) may be involved in the pathophysiology of CIU. Following the release of mast cell or basophil-derived histamine, this mediator binds to H(1) and H(2) receptors, leading to vasodilatation and increased vascular permeability. Individuals with CIU may be unable to conduct normal daily activities; therefore, prompt initiation of effective treatment is essential. General management of patients should include avoidance of substances likely to trigger or intensify episodes. Treatment with antihistamines is the mainstay of pharmacotherapy for CIU. Selection of antihistamine therapy for patients with CIU should be based on the following key properties: (1) proven clinical efficacy in providing a high rate of symptom improvement, (2) rapid onset of action and a long-lasting response, and (3) an excellent safety profile and a high degree of tolerability. The benefit of some second-generation antihistamines is limited by sedation, drug-drug interactions, or a variable therapeutic response. The H(1)-receptor antagonist desloratadine is a new, once-daily treatment option that is potent and nonsedating, and has a low potential for drug-drug interactions. Desloratadine has a rapid onset of action and has been shown to effectively and safely reduce pruritus and the number and size of hives in patients with CIU, leading to improvements in quality of life.
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PMID:Chronic idiopathic urticaria for the generalist. 1279 12

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

A prospective, cross-sectional and randomized cross-over study was conducted to study the clinical features and treatment outcome among Thai patients with vernal keratoconjunctivitis (VKC). History-taking and eye examinations were performed. Mild cases of VKC were given topical antihistamine four times daily. Moderate and severe cases of VKC were treated with topical lodoxamide four times a day. Severe cases of VKC were given topical corticosteroids. Moderate and severe cases of VKC, which were refractory to treatment with either corticosteroids or a mast cell stabilizer had topical cyclosporine 0.5% instilled four times daily. Five patients were exposed to two different treatment regimens in sequence. As main outcome measures, itching, foreign body sensation, photophobia, conjunctival injection, papillae and chemosis were evaluated weekly. The patients with the palpebral type of VKC had daily symptoms, which were more severe and triggered by house-dust with a significant difference among the groups. Limbal VKC was associated with allergic rhinitis more commonly than palpebral VKC. Positive results of skin prick testing to acacia, careless weed, mold, Johnson grass and cow's milk were significantly more common in patients with palpebral VKC. The most common symptoms and signs were found in the mixed type of VKC. Purulent discharge, pannus and lid erythema were found in the palpebral type. Levocabastine hydrochloride was sufficient for mild cases of limbal VKC; lodoxamide for the limbal and mixed types. Prednisolone acetate was the drug of choice in severe cases of any type but only for a short period of time. The success rate of topical cyclosporine in the palpebral type was lower than in the limbal type due to an intolerable burning sensation. Topical cyclosporine used in 4 patients with limbal and palpebral type had a success rate of 100% which was greater than in the lodoxamide group (66.7%, 0%). Compared with topical corticosteroid-treated eyes in one patient, the success rate in topical cyclosporine-treated eyes was not success. Grading the severity of each type of VKC is crucial to obtain good response of any medication and compliance. Topical cyclosporine 0.5% can be an alternative drug to relieve symptoms and signs of VKC in order to avoid steroid-induced glaucoma.
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PMID:Vernal keratoconjunctivitis in Thailand. 1293 48

Racial (ethnic) differences in skin properties may explain racial disparities seen in dermatologic disorders and provide insight into appropriate differences in the management of these disorders. However, racial differences in skin have been minimally investigated by objective methods and the data are often contradictory. Objective methods studied include transepidermal water loss (TEWL), water content (WC), corneocyte variability, blood vessel reactivity, elastic recovery/extensibility, pH gradient, lipid content, surface microflora, microscopic evaluation of mast cell granules, and confocal microscopy. The majority of the evidence (six out of eight studies) indicates that TEWL is greater in Black skin compared with White skin. TEWL measurements of Asian skin are inconclusive as they have been found to be equal to Black skin and greater than Caucasian skin, equal to Caucasian skin, and less than all other ethnic groups in different studies. Racial differences in WC, as measured by resistance, capacitance, conductance and impedance, are also inconclusive as the data are contradictory. While the evidence regarding corneocyte desquamation is minimal, one clinically provocative observation is that Blacks have a 2.5 times greater spontaneous desquamation rate compared with Caucasians and Asians, possibly accounting for an increased frequency of xerosis seen clinically in Blacks. With regards to blood vessel reactivity, studies can not be compared to each other because each uses different vasoactive substances. However, each study, except for one study comparing Hispanics and Whites, and another comparing Japanese and German women, reveal some degree of racial variation in blood vessel reactivity. It has been demonstrated that the pH of Black skin is less than White skin; however, the studies that have demonstrated this have done so under different skin conditions and on different anatomic sites. Racial differences in lipid content are inconclusive. Additionally, there is insufficient and conflicting evidence to make conclusions regarding racial differences in skin biomechanics and skin microflora. Microscopic evaluation reveals that Black skin contains larger mast cell granules, and differences in stuctural properties and enzymes of mast cells compared with White skin, possibly accounting for differences in pruritus experienced by the individuals of these racial groups. There exists substantial evidence to support that Black skin has a higher TEWL, variable blood vessel reactivity, decreased skin surface pH, and larger mast cell granules compared with White skin. Although some deductions have been made about Asian and Hispanic skin, further evaluation needs to be done. Differences in WC, corneocyte desquamation, elastic recovery/extensibility, lipid content and skin microflora, although statistically significant, are inconclusive.
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PMID:Racial (ethnic) differences in skin properties: the objective data. 1464 Jul 77

Ocular allergy is a common condition that usually affects the conjunctiva of the eye and is therefore often referred to as allergic conjunctivitis. The severity of the disease can range from mild itching and redness, as seen in seasonal allergic conjunctivitis, to the more serious vision threatening forms of ocular allergy which affect the cornea, such as atopic keratoconjunctivitis. The pathogenesis of allergic conjunctivitis involves a complex mechanism which centers around IgE-mediated mast cell degranulation and release of multiple preformed and newly formed inflammatory mediators. The diagnosis of allergic conjunctivitis is usually a clinical one which can be made based on a thorough history and careful examination. Treatment of ocular allergy should begin with conservative measures including allergen avoidance, environmental control, ocular irrigation and cold compresses. Pharmacotherapy of allergic conjunctivitis consists of several classes of drugs. Antihistamines are widely used to treat mild conditions such as seasonal and perennial conjunctivitis and potent new agents such as levocabastine and emedastine are now available. Mast cell stabilizers such as sodium cromoglycate are both safe and effective and are commonly used in ocular allergy. More effective mast cell stabilizers such as nedocromil, lodoxamide and olopatadine are now being used. Nonsteroidal antiinflammatory drugs have demonstrated only limited efficacy and, as such, are not widely used. Topical steroids are very effective in treating signs and symptoms but are reserved for only refractory cases due to their serious side effects. Loteprednol and rimexelone are newer corticosteroids which reportedly have less of an effect on intraocular pressure. Cyclosporine has recently been shown to be highly effective in cases of vernal keratoconjunctivitis and atopic keratoconjunctivitis while producing no adverse effects.
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PMID:Ocular allergic disease. 1474 64

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


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