Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Atopic dermatitis is a chronic inflammatory skin disease characterized by severe pruritus, typical morphology and distribution of skin lesions, and personal and family history of atopy. The management of atopic dermatitis is directed at preventing the inflammation, itch, and secondary lesions. Therapy relies on general management measures, anti-inflammatory agents, antiprurites, antibiotics, and immunosuppressants. Treatment options for patients with severe or longstanding disease, extensive body surface area involvement of facial lesions are limited. Tacrolimus ointment is the first in the class of topical immunomodulators that has been formulated for the treatment of atopic dermatitis in children (2 to 15 years of age) and adult patients. The mechanism of action of tacrolimus in atopic dermatitis seems to involve T-cells, Langerhans cells, mast cells and basophiles. Experimental evidence suggests that tacrolimus inhibits T-lymphocytes activation by binding to an intracellular protein, FKBP-12. This binding phenomenon inhibits the ability of calcineurin to activate the promotor region of the gene for IL-2, IL-3, IL-4, IL-5, interferon gamma, tumor necrosis factor alpha, and granulocyte macrophage colony-stimulating factor, all of which participate in the early immune response and play a role in the pathogenesis of atopic dermatitis. Tacrolimus ointment is not atrophogenic, and is associated with minimal systemic absorption. There were no consistent changes in any laboratory variable during topical tacrolimus therapy. The most common adverse events associated with its use were transient skin burning and pruritus at the site of application. Tacrolimus ointment is safe and efficacious therapy for the treatment of pediatric and adult patients with atopic dermatitis on all skin regions including the face, neck and intertriginous areas. An overview is given of tacrolimus in atopic dermatitis.
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PMID:Tacrolimus ointment: a new therapy for atopic dermatitis--review of the literature. 1213 28

Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease with main symptoms such as eczematous skin lesions and severe pruritus. Although the relevance of stress in the pathology of AD is widely accepted, the underlying biological mechanisms of stress-induced exacerbation of AD symptoms are not fully understood. The specific goal of the present study was to investigate the impact of acute psychosocial stress on atopy-relevant immune functions in AD sufferers. AD patients (n=36) and nonatopic controls (n=37) were exposed to a laboratory stressor including a free speech and mental arithmetic tasks in front of an audience ("Trier Social Stress Test," TSST). Blood samples were collected 10 min before and 1, 10 and 60 min after the stress test as well as 24 h after the experiment at identical time points under resting conditions. Analyses of leukocyte subsets indicated significantly elevated lymphocyte, monocyte, neutrophil and basophil numbers 10 min after the TSST (all p's<0.001) with no significant differences between the two groups. In contrast, eosinophil number was found to be significantly elevated only in AD sufferers, but not subjects (F(3,213)=4.8; p<0.01). Moreover, AD patients but not the control group showed increased IgE levels (F(1,71)=4.4; p<0.05) 24 h after the stress test. Exposure to the TSST resulted in elevation of interferon-gamma (IFN-gamma; F(3,207)=19.55; p<0.001) and, further, in attenuation of interleukin-4 (IL-4; F(3,207)=187.46; p<0.001) concentrations with no significant differences between both groups (all p's>0.05). The present findings suggest that stress may be associated with atopy-relevant immunological changes in AD sufferers, which may be one explanation of the common observation of stress-induced aggravation of symptomatology in this patient group.
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PMID:Stress-induced immunomodulation is altered in patients with atopic dermatitis. 1216 Oct 32

Antiallergic drugs and antihistamines have been widely used for controlling mucosal allergic diseases in which eosinophilia is prominent. Although H1-receptor antagonists are effective for treating histamine-induced wheal and itch in urticaria, the effects of antihistamines and antiallergic agents on other eosinophilic skin diseases remain to be determined. We investigated the effects of oral administration of antiallergic drugs and antihistamines, such as suplatast tosilate, emedastine difumarate, and azelastine hydrochloride, on a novel murine model of eosinophilia in contact sensitivity to picryl chloride. Among the drugs tested, only suplatast tosilate remarkably inhibited blood and tissue eosinophilia and the ear swelling responses. The inhibitory effects on eosinophilia seemed to be mediated by the suppression of IL-5 production in spleen cells during eosinophil development, while the effects on the ear swelling response seemed to be mediated by suppression of IL-4 production in immune lymph node cells in the efferent phase. Suplatast tosilate may effectively treat eosinophilic skin diseases in which Th2-cell-derived cytokines are predominant.
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PMID:Suplatast tosilate inhibits eosinophil production and recruitment into the skin in murine contact sensitivity. 1449 49

Vernal keratoconjunctivitis (VKC) is an allergic eye disease that especially affects young boys. The most common symptoms are itching, photophobia, burning, and tearing. The most common signs are giant papillae, superficial keratitis, and conjunctival hyperaemia. Patients with VKC frequently have a family or medical history of atopic diseases, such as asthma, rhinitis, and eczema. However, VKC is not associated with a positive skin test or RAST in 42-47% of patients, confirming that it is not solely an IgE-mediated disease. On the basis of challenge studies as well as immunohistochemical and mediator studies, a Th2-driven mechanism with the involvement of mast cells, eosinophils, and lymphocytes has been suggested. Th2 lymphocytes are responsible for both hyperproduction of IgE (interleukin 4, IL-4) and for differentiation and activation of mast cells (IL-3) and eosinophils (IL-5). Other studies have demonstrated the involvement of neural factors such as substance P and NGF in the pathogenesis of VKC, and the overexpression of oestrogen and progesterone receptors in the conjunctiva of VKC patients has introduced the possible involvement of sex hormones. Thus, the pathogenesis of VKC is probably multifactorial, with the interaction of the immune, nervous, and endocrine systems. The clinical management of VKC requires a swift diagnosis, correct therapy, and evaluation of the prognosis. The diagnosis is generally based on the signs and symptoms of the disease, but in difficult cases can be aided by conjunctival scraping, demonstrating the presence of infiltrating eosinophils. Therapeutic options are many, in most cases topical, and should be chosen on the basis of the severity of the disease. The most effective drugs, steroids, should however be carefully administered, and only for brief periods, to avoid secondary development of glaucoma.A 2% solution of cyclosporine in olive oil or in castor oil should be considered as an alternative. The long-term prognosis of patients is generally good; however 6% of patients develop corneal damage, cataract, or glaucoma.
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PMID:Vernal keratoconjunctivitis. 1506 27

The exact pathophysiology of chronic idiopathic urticaria (CIU) is not well understood. The concept of autoreactivity has evolved to explain the disease in up to 50% of cases, while the search for other mechanisms is still needed to explain the disease, at least among the remaining subpopulation of non-autoreactive CIU. Therefore, we thought to investigate some aspects of the IgE-dependent, lymphocyte-mediated late-phase response (LPR) of anaphylaxis. We searched for percentages of FcepsilonRII-bearing (CD23+) B and T lymphocytes and correlated this with total IgE serum levels, IL-4 serum levels and the disease severity scores. Twenty-five patients with non-autoreactive CIU and ten healthy control subjects participated in this study. CD23+ B- and T-cells were assessed by flow cytometry, total IgE serum levels were estimated by enzyme linked fluorescent assay (ELFA), IL-4 serum levels were estimated by Enzyme Amplified Sensitivity Immunoassay (EASIA), while disease severity was determined by a daily self-assessment urticaria activity and itching score. Our results showed that the mean values for percentages of CD23+ B-cells (6.7 +/- 2.3%), total IgE serum levels (139.6 +/- 103.9 microg/dl) and IL-4 serum levels (18.3 +/- 14.7 ng/ml) for patients were statistically significant (p = 0.002, 0.013 and 0.008, respectively), when compared with the corresponding values for controls (4.0 +/- 1.7%, 51.5 +/- 25.1 microg/dl, and 5.1 +/- 4.1 ng/ml, respectively), while the difference between the mean percentage of CD23+ T-cells for patients (2.8 +/- 2%) and that for controls (2.1 +/- 0.6%) was non-significant (p = 0.267). Strong positive correlations were detected between percentages of CD23+ B-cells and severity scores (r = 0.678, p = 0.0001), total IgE serum levels (r = 0.756, p = 0.0001) and IL-4 serum levels (r = 0.709, p = 0.0001), while no correlation was detected between CD23+ B-cells and CD23+ T-cells (r= 0.188, p= 0.368). It is concluded, that CD23+ B-cells, regulated by IL-4, may contribute in the pathogenesis of non-autoreactive CIU, by producing high levels of IgE and possibly lymphokines, while CD23+ T-cells may be involved in early antigen recognition. This may have a future therapeutic ramification in this distinct subset of CIU by targeting low-affinity IgE receptors.
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PMID:Increased circulating FcepsilonRII-bearing B-lymphocytes and serum levels of IL-4 in non-autoreactive chronic idiopathic urticaria. 1571 7

This pilot study evaluated the effects of immunostimulatory liposome-plasmid-DNA complexes combined with specific allergens for immunotherapy of refractory canine atopic dermatitis. Seven dogs with previously diagnosed atopic dermatitis and unsatisfactory response to at least 12 months of conventional allergen-specific immunotherapy underwent a series of six intradermal injections (weeks 0, 2, 4, 6, 10 and 14), with patient-specific allergen extracts contained in cationic liposome-DNA complexes. Degree of pruritus was assessed on a visual analogue scale. Lesion scores were determined using the Canine Atopic Dermatitis Extent and Severity Index (CADESI) and medication usage was recorded at weeks 0 and 14. Canine cytokine mRNA expression in peripheral blood mononuclear cells collected prior to treatment and at the completion of the study was determined for IFN-gamma, IL-4, TNF and IL-10 genes using quantitative reverse transcription competitive polymerase chain reaction. Repeated intradermal injections of specific allergens incorporated into liposome-nucleic acid complexes were well tolerated in all seven dogs. There was a significant improvement in pruritus scores (P = 0.0277) and concurrent significant decrease in IL-4 production (P = 0.0428) at the completion of the trial compared to pretreatment values. Medication scores, CADESI and production of other cytokines did not change significantly with treatment. These early results suggest that antigen-specific immunotherapy using a novel liposome-nucleic acid complex vaccine may be beneficial for treatment of established atopic dermatitis in dogs using lower antigen doses. Further investigations in larger numbers of dogs with earlier stages of disease are warranted.
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PMID:Use of immunostimulatory liposome-nucleic acid complexes in allergen-specific immunotherapy of dogs with refractory atopic dermatitis - a pilot study. 1572 7

Atopic eczema/dermatitis syndrome is a term that covers different subtypes of atopic dermatitis. The "intrinsic" type of atopic dermatitis is non-IgE-associated, and the "extrinsic" type is IgE-associated atopic eczema/dermatitis syndrome. In the etiopathogenesis of atopic dermatitis there are well known interactions among genetic, environmental, skin barrier, immune factors, and stress. Genetic factors determine the expression of atopic dermatitis as pure or mixed with concomitant respiratory or intestinal allergy, depending on genetic susceptibility. Immunologic abnormalities of type I and type IV reactions have been described in patients with atopic dermatitis. Immunologic triggers are aeroallergens, food allergens, microbial products, autoallergens and contact allergens. Immune reactions determine many features of atopic dermatitis. These immune reactions also include cell mediated or delayed hypersensitivity. The currently accepted model proposes a predominant Th2 cytokine milieu in the initiating stages of acute atopic dermatitis lesions, and a mixed Th1 and Th2 pattern in chronic lesions. A two-phase model includes Th2 initiation with attraction of macrophages and eosinophils, which in turn produce interleukin 12 that is the activator of Th1 type response. Atopic dermatitis skin contains an increased number of IgE-bearing Langerhans cells which bind allergens via the high-affinity IgE receptor (FcepsilonRI). Langerhans cells play an important role in cutaneous allergen presentation to Th2 cells via major histocompatibility molecules. Eosinophilia and IgE production are influenced by type 2 cytokines. Degranulation of eosinophils occurs in the dermis with the release of toxic proteins such as major basic protein and could account for much of the inflammation. Mast cells are increased in number and produce mediators other than histamine that induce pruritus and may have an effect on interferon gamma expression. Mast cells produce a number of proinflammatory cytokines. There is an elevated production of prostaglandin E2 by peripheral monocytes. Prostaglandin E2 has at least two potential roles in the initiation of atopic dermatitis. Firstly, it reduces interferon-gamma production by T helper cells, thereby favoring the initial, dominant Th2 immune response; and secondly, it directly enhances IgE production by B lymphocytes with an increased secretion of interleukin 4, interleukin 5 and interleukin 13. Many lesions of atopic dermatitis result from scratching, thus it is tempting to speculate that immune perturbations in genetically predisposed individuals provoke the release of local pruritogens and keratinocyte-derived cytokines, which then further exacerbate the previously described immune response.
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PMID:Etiopathogenesis of atopic dermatitis--an overview. 1578 48

Patent lymphatic filariasis is characterized by a profound down-regulation of immune responses with both parasite Ag-specific tolerance and bystander suppression. Although this down-regulation is confined to the Th1 arm of the immune system in response to parasite Ag, we hypothesized a more generalized suppression in response to live parasites. Indeed, when we examined the cytokine profile of a cohort of filaria-infected (n = 10) and uninfected (n = 10) individuals in response to live infective-stage larvae or microfilariae of Brugia malayi, we found significant impairment of both Th1 and Th2 cytokines characterized by diminished production of IFN-gamma, TNF-alpha, IL-4, IL-5, and IL-10 in infected patients. The molecular basis of this impaired Th1/Th2 response was examined, and we identified three major networks of immunoregulation and tolerance. First, impaired induction of T-bet and GATA-3 mRNA underlies the Th1/Th2 deficiency in infected individuals. Second, regulatory networks, as evidenced by significantly increased expression of Foxp3 (natural regulatory T cell marker) and regulatory effectors such as TGF-beta, CTLA-4, PD-1, ICOS, and indoleamine 2,3-dioxygenase play an important role in immunosuppression. Third, the compromise of effector T cell function is mediated by the enhanced induction of anergy-inducing factors cbl-b, c-cbl (cbl is abbreviation for Casitas B lymphoma), Itch, and Nedd4. Indeed, blocking CTLA-4 or neutralizing TGF-beta restored the ability to mount Th1/Th2 responses to live parasites and reversed the induction of anergy-inducing factors. Hence, we conclude that a profound impairment of live parasite-specific Th1 and Th2 immune responses occurs in lymphatic filariasis that is governed at the transcriptional level by a complex interplay of inhibitory mediators.
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PMID:Regulatory networks induced by live parasites impair both Th1 and Th2 pathways in patent lymphatic filariasis: implications for parasite persistence. 1649 86

Following thermal injury, hypertrophic scar (HSc) is a frequent and severe form of fibrosis of the skin, which limits movement and compromises the cosmetic appearance and function of the skin. Prolonged pruritus and dysesthesia are also common problems in the previously injured, fibrotic tissues, as current understanding of the pathogenesis is limited, and few effective therapies exist, as with other fibroproliferative disorders (FPD). To investigate the role of T cells and their cytokines in the development of HSc, intracellular cytokine synthesis of circulating T cells was measured serially in burn patients using flow cytometry from the time of injury to over a 1-year period during which many patients developed HSc. Within 1 month of injury, low interferon-gamma (IFN-gamma)-positive T cells (Th1) were found in association with low interleukin-12 (IL-12) and absent IFN-gamma cytokine levels in the serum. IL-4-positive Th 2 cells, however, were significantly increased compared with normal controls by 2 months postinjury. In burn patients with HSc, serum IL-10 and transforming growth factor-beta (TGF-beta) levels were also significantly increased early after burn injury in patients who later developed HSc compared with normal volunteers and with a subset of burn patients who did not develop HSc, before returning to normal levels after 6 months. Activated peripheral blood mononuclear cells (PBMC) demonstrated that mRNA for IFN-gamma was present only in normal volunteers or patients without HSc but was undetectable in HSc patients. IL-4 mRNA levels were increased in the PBMCs of burn patients with HSc. In HSc tissues, IL-4 mRNA was increased, whereas, IFN-gamma mRNA was reduced compared with normal skin and mature scar. Increased CD3(+) and CD4(+) cells were present in HSc tissues compared with normal skin and were coexpressed with the fibrogenic cytokine TGF-beta. These longitudinal studies in human patients with HSc suggest that fibrosis in the skin is associated with a polarized Th2 systemic response to injury that leads to increased T cells and their Th2 fibrogenic cytokines in tissues and the development of fibrosis and HSc.
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PMID:Polarized Th2 cytokine production in patients with hypertrophic scar following thermal injury. 1654 40

Itching is the most important problem in many allergic and inflammatory skin diseases especially in atopic dermatitis. However, animal models for allergic dermatitis useful for the study of itching have rarely been established. We established a mouse allergic dermatitis model involving frequent scratching behavior by repeated painting with 2,4-dinitrofluorobenzene (DNFB) acetone solution onto the mouse skin, and comparatively examined the effects of tacrolimus and dexamethasone on the dermatitis and associated scratching behavior. Repeated DNFB painting caused typical dermatitis accompanied by elevated serum immunoglobulin E (IgE) and frequent scratching behavior. An apparent thickening of the epidermis and dermis, and the significant accumulation of inflammatory cells were observed. Increased interferon (IFN)-gamma mRNA expression and the induction of interleukin (IL)-4 and IL-5 mRNA expression were also observed in the skin lesion. The scratching behavior was inhibited by dibucaine and naloxone. Although tacrolimus reduced the increased expression of IFN-gamma and IL-4 mRNA, dexamethasone potently depressed that of IFN-gamma, IL-4 and IL-5 mRNA. Dexamethasone inhibited the accumulation of lymphocytes and eosinophils, although tacrolimus did not. Both drugs failed to inhibit the elevation of serum IgE levels. Tacrolimus significantly inhibited the scratching behavior that was associated with the inhibition of nerve fiber extension into the epidermis, whereas dexamethasone failed to have any effect. The mouse dermatitis model seems to be beneficial for the study of itching associated with allergic dermatitis, such as atopic dermatitis, and tacrolimus seems to exhibit an anti-itch effect through the inhibition of nerve fiber extension at least in part.
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PMID:Inhibition of scratching behavior associated with allergic dermatitis in mice by tacrolimus, but not by dexamethasone. 1691 37


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