Chronic urticaria and Helicobacter pylori.

BACKGROUND: Although the clinical manifestations of chronic urticaria (CU) are similar in most patients, a variety of factors should be taken into consideration. In general, the cause of CU cannot be determined in most patients, and it is considered idiopathic. In the past several years, relationships between some patients with CU and hepatitis C or autoimmune thyroid diseases have been established. Similarly, other factors may also be considered as possible causes to explain certain patients with CU. Previously, some patients with CU have had their disease attributed to Helicobacter pylori (HP), but the relationship was only clinical. OBJECTIVE: None of the patients previously described included an immunological study. Thus, we studied a patient with CU, who showed marked clinical improvement after eradication of HP, to demonstrate an IgE relationship with this skin disease. METHODS: First, blood analytical parameters, roentgenograms, fecal examination for parasites, and skin tests were performed to try to establish an etiology. In addition, endoscopy with gastric biopsy confirmed HP colonization, and eradication treatment was prescribed. To investigate an immunological relationship, other tests performed included the following: HP-specific IgG, histamine release induced by HP, HP-specific IgE, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis with immunoblotting. RESULTS: The blood analytical parameters, roentgenograms, fecal examination for parasites, and skin tests were all negative. In contrast, the tests for HP-specific IgG, histamine release induced by HP, and HP-specific IgE were all positive. In addition, the sulfate-polyacrylamide gel electrophoresis with immunoblotting showed specific IgE binding to an extract of HP. CONCLUSIONS: Our results may indicate an immunological IgE relationship between HP colonization and CU in this particular patient.     

Increased responsiveness of basophils of patients with chronic urticaria to sera but hypo-responsiveness to other stimuli

BACKGROUND: Although it has been shown that basophils from patients with chronic ordinary urticaria (CU) are less responsive than normal basophils when stimulated with anti-IgE, very few studies have examined the response of those cells to alternative stimuli. OBJECTIVE: To compare releasability between basophils from healthy donors and patients with CU. METHODS: We examined the response of IL-3-treated basophils from healthy donors, atopic controls and CU patients to anti-IgE, monocyte chemoattractant protein-1 (MCP-1), bradykinin, C5a and to sera obtained from other urticaria patients and normal controls. We also compared the response of basophils from CU patients whose sera activate normal basophils (autoimmune CU) from those who do not (idiopathic CU). RESULTS: Basophils of CU patients release significantly less histamine than basophils of normal controls when stimulated with anti-IgE, and to a lesser degree with C5a. No differences were observed when basophils from patients were incubated with Bradykinin or MCP-1. However, when basophils of CU patients were incubated with sera from other CU patients or even normal sera, we found significantly higher histamine release compared with the response of basophils from normal donors. We could not distinguish responsiveness of basophils of patients with chronic autoimmune urticaria from patients with chronic idiopathic urticaria. CONCLUSION: Basophils of patients with chronic idiopathic urticaria and chronic autoimmune urticaria are hypo-responsive to anti-IgE and C5a, normally responsive to MCP-1 or bradykinin, and hyper-responsive to serum. The serum factor to which a response has not yet been identified; however, basophils of patients with chronic urticaria, in general, appear to have abnormal regulation of signaling pathways.     

Chronic idiopathic urticaria: natural course and association with Helicobacter pylori infection.

BACKGROUND: Chronic urticaria is a common disease, though only few data on its natural course are available. In most cases the cause cannot be determined. Recently a relationship of chronic urticaria to infection with Helicobacter pylori (HP) has been postulated, but no controlled study has been performed to prove this association. METHODS: In this prospective study the clinical course and rate of HP infection in 46 patients with chronic 'idiopathic' urticaria were investigated. Infected patients were treated in a double-blind placebo-controlled crossover study with amoxycillin and lansoprazol. Eradication and clinical course were followed up 2 months after each treatment, respectively, 3 and 6 months after the first consultation. RESULTS: In 19/46 (41%) the chronic 'idiopathic' urticaria resolved within 6 months. 12 patients (24%) were infected with HP, which corresponds to the infection rate of the population at comparable ages without urticaria in Switzerland. Eradication of HP was achieved in 3, but only in 1 was the eradication associated with the resolution of urticaria. CONCLUSIONS: Our data show that in young patients with a rather short history of chronic urticaria frequently a rather favourable natural course of chronic idiopathic urticaria can be seen. No association between HP infection and chronic urticaria could be demonstrated.     

Improvement of chronic idiopathic urticaria with l-thyroxine: a new TSH role in immune response?

BACKGROUND: The association between chronic idiopathic urticaria (CIU) and autoimmune thyroiditis (AT) is known, as well as major prevalence of antithyroid antibodies in the allergical subjects and other autoimmune diseases. We have evaluated the effects of l-thyroxine on clinical symptoms of CIU in AT patients suggesting the hypothesis of a new thyroid-stimulating hormone (TSH) role in immune system. METHODS: In 20 female patients with CIU + AT, both hypothyroid and euthyroid, we have investigated the therapeutic effects of l-thyroxine dosed to suppress the TSH. Free-T3, Free-T4, TSH, antithyroperoxidase and antithyroglobulin antibodies, total immunoglobulin (Ig)E, Rheuma test and eritro-sedimentation rate were monitored during treatment. Results: In 16 patients a strong decrease of urticaria symptoms has happened after 12 weeks. The TPO Ab and HTG Ab clearly decreased in 14 patients. Furthermore, in two patients with rheumatoid arthritis and in two patients with pollen allergy a strong decrease of rheuma test titer and total IgE has happened. Conclusion: The reason of AT is associated to CIU and others allergical and autoimmune diseases is poorly known. The exclusive hormonal therapy reduces the symptoms of CIU and inflammatory response in many chronic diseases associated to AT. We suggest a stimulatory effect of TSH able to produce considerable changes of the immune response and immune tolerance in patients with AT causing target organs damage. The causal mechanism involves immune, nervous and endocrine system, sharing a common set of hormones, cytokines and receptors, in a unique totally integrated loop (the neuro-immuno-endocrine axis).     

The role of autoimmune testing in chronic idiopathic urticaria

BackgroundThe clinical implications of autoimmune testing in chronic idiopathic urticaria (CIU) are not well established.ObjectiveTo identify the association of autoimmune biomarkers in CIU with disease severity.MethodsWe retrospectively evaluated 195 patients with a diagnosis of CIU for the presence of antinuclear antibody (ANA), anti-thyroglobulin antibody (ATG), anti-thyroperoxidase antibody (ATPO), and Chronic Urticaria (CU) Index. The patients were categorized into controlled and refractory subgroups based on their response to antihistamines with or without a leukotriene receptor antagonist.ResultsThe percentage of patients with a positive test for ANA (titer>1:160), ATG, ATPO, and CU Index were 29%, 6%, 26%, and 38%, respectively. Among those tested, the percentage of patients categorized as refractory was significantly higher in those with a positive CU index (80% vs 46%; P = .01) or a positive ANA titer (50% vs 30%; P = .04) than those with negative test results; however, a similar relationship was not observed for ATPO or ATG antibodies. Odds ratios of individual or combinations of autoimmune biomarkers in CIU were examined for associations with refractoriness to antihistamines with or without a leukotriene receptor antagonist. The CU Index alone has an odds ratio of 4.5 (P = .005), whereas the combination of ANA, ATG, and ATPO has an odds ratio of 3.1 (P = .01) and ANA alone has an odds ratio of 2.3 (P = .04) for correlating with a refractory outcome.ConclusionOur data indicate the CU Index independently has the strongest correlation with disease severity followed by the combination of ANA, ATG, and ATPO and the ANA alone.     

Basophil histamine release activity and disease severity in chronic idiopathic urticaria.

BACKGROUND: Altered basophil degranulation phenotypes are found in patients with chronic idiopathic urticaria (CIU). OBJECTIVE: To evaluate CIU disease severity in relation to basophil histamine release (HR) characteristics. METHODS: Patients with CIU were recruited from allergy and dermatology clinics. Patients with recent use of systemic corticosteroids or immunosuppressants were excluded. Patients completed disease severity surveys and had blood basophils isolated and stimulated for HR using polyclonal goat anti-human IgE and N-formyl-met-leu-phe. The HR was measured using automated fluorometry. Multivariate linear regression analyses were used to investigate relationships between HR data and CIU disease measures. RESULTS: Fifty patients completed surveys, of which 34 were further categorized into 2 subgroups based on basophil HR response to anti-IgE stimulation: responders (> or = 10% HR) and nonresponders (< 10% HR). Responders and nonresponders reported similar use of oral corticosteroids, work absences, and quality-of-life impairment but differed in their patterns of medications used for CIU. Basophil responders had a trend of higher use of the emergency department for CIU management. Multivariate regression revealed that patients with the basophil responder phenotype experienced significantly higher current itch scores (P = .02) compared with nonresponders. CONCLUSIONS: Quality-of-life impairment is similar in CIU basophil subsets. Patients with CIU with a basophil responder phenotype report longer disease duration, a higher frequency of emergency department use, and significantly higher itch severity.     

幽门螺杆菌抗体检测对慢性特发性荨麻疹的临床意义

目的探讨幽门螺杆菌（ Helicobacter pylori , HP）检测对慢性特发性荨麻疹（chronic idiopathic urticaria,CIU）的诊疗意义。方法采用ELISA法检测慢性特发性荨麻疹患者与正常对照组血清抗幽门螺杆菌血清抗体,血清阳性的荨麻疹患者随机分为2组,一组给予左旋西替利嗪片（5mg／d）治疗：另一组给予左旋西替利嗪片（5mg／d）、奥美拉唑（20mg,2次／d）、阿莫西林（1g,2次／d）、克拉霉素（500mg,2次／d）联合治疗。两组均连续用药4周,停药4周后观察,观察内容包括瘙痒、风团数量、风团大小、风团持续时间．比较各组治疗效果,分析CIU与HP之间关系。结果127例慢性特发性荨麻疹患者中,57（44．9％）例HPIgG阳性,而100名健康者仅6（6％）例阳性,CIU患者HP阳性率明显高于健康组（χ^2=42．18,P〈0．01）。停药4周后,联合治疗组有效率为92．9％,单一治疗组有效率为55．2％,联合疗法与单纯抗过敏治疗相比,前者的总有效率明显优于后者（χ^2=10．43,P〈0．01）;停药8周后,联合治疗组有效率为92．9％,单一治疗组有效率为44.8％．联合疗法与单纯抗过敏治疗相比,前者的总有效率明显优于后者（χ^2=15．21,P〈0．01）。结论慢性荨麻疹患者的血清HPIgG抗体阳性率显著高于正常人群,针对清除HP的联合疗法治疗HP阳性CIU患者近期（停药4周）以及远期（停药8周）有效率都优于单独抗过敏治疗的方案。结果提示,幽门螺杆菌与部分荨麻疹的发病有一定关系,另外,联合抗幽门螺杆菌的治疗对减少荨麻疹的复发有一定帮助。     

Helicobacter pylori infection affects eosinophilic cationic protein in the gastric juice of patients with idiopathic chronic urticaria

BACKGROUND: Helicobacter pylori, the main cause of gastritis and peptic ulcer, has been associated with idiopathic chronic urticaria (ICU), an immunological skin disorder of unknown origin. Eosinophilic cationic protein (ECP) is a cytotoxic molecule secreted by the activated eosinophils involved in the pathogenesis of ICU. We assessed serum/gastric juice ECP levels and gastric mucosal eosinophil infiltration in ICU patients infected or not with H. pylori and evaluated the modification after bacterium eradication. METHODS: 33 patients with ICU and 25 dyspeptic controls underwent upper gastrointestinal endoscopy for histological evaluation and assessment of H. pylori infection. One-week triple therapy was given to H. pylori-positive patients. Serum and gastric juice ECP levels, eosinophil infiltration from gastric mucosal sections and urticaria symptoms were evaluated in all patients at enrollment and 8 weeks after eradication. RESULTS: 19 of 33 (57%) ICU patients and 16 of 25 (64%) controls were found to be infected with H. pylori. Serum ECP was significantly higher in ICU patients compared to controls, regardless of infectious status. Gastric juice ECP and gastric eosinophil infiltration were significantly higher in infected ICU patients when compared both to uninfected ICU patients and controls. H. pylori eradication determined a significant decrease in gastric juice ECP and gastric eosinophil infiltration only in ICU patients. Moreover, a total or partial remission of urticaria symptoms was observed only in ICU patients in whom the bacterium was eradicated. CONCLUSIONS: Although H. pylori infection affects gastric juice ECP and eosinophil infiltration of ICU patients, the role of the bacterium in the pathogenesis of this skin disorder still remains uncertain.     

Allergy-like asthma and rhinitis. A cross-sectional survey of a respiratory cohort and a diagnostic approach using the autologous serum skin test

BACKGROUND: Chronic idiopathic urticaria is considered an allergy-like skin disorder, and in some cases an auto-reactivity caused by mast cell degranulating factors has been demonstrated. A positive reaction to the autologous serum skin test (ASST), reflecting the presence of factors capable to degranulate the mast cells, is regarded as a reliable in vivo diagnostic test in chronic urticaria patients. About one out of three patients complaining for rhinitis or asthma does not show sensitization to any allergenic source. No data are available on the application of ASST to respiratory patients. METHODS: A cohort of respiratory patients, aged 1 to 80 years, complaining about suspected respiratory symptoms was screened using a panel of inhalant allergens by means of SPT and IgE. Current and past information on skin and respiratory symptoms were recorded for each patient. Patients were divided in 'allergy' and 'allergy-like' whether or not they react to at least one allergenic source. Age and gender distribution were analyzed. A control group fulfilling criteria for chronic idiopathic urticaria (CIU) was selected as well. The ASST was applied to the control CIU group, to the allergy-like and allergy subsets, and to a group of 58 healthy adult subjects. RESULTS: Allergy and allergy-like patients were differently distributed in relation to age and gender. Allergy-like children were prevalent before age six, whereas the prevalence of allergics steadily increased with age representing the large majority of patients in late childhood. The ratio of allergy/allergy-like subjects continues to increase in adult males, whereas adult females represent the large majority of the adult patients mainly within the allergy-like subset. Fifty-eight percent of CIU control patients reacted to the ASST. Among allergy-like patients ASST was positive in 47% of the adults (male 26%, female 54%), and in 84% of the children (no gender differences). The percentage of reactive subjects increased in the adult allergy-like subset if a CIU was associated (65%). Eighty-six percent of the pediatric patients and 61% of the adults having an allergy respiratory disease associated with an allergy-like condition had a positive ASST reactivity. Pure allergy patients reacted in 73% and 40% of the cases in the children and adults subgroups, respectively. Forty-five percent of healthy controls reacted to the ASST as well, and statistically significant gender differences were still recorded. CONCLUSIONS: An ASST reactivity is reported for the first time in allergy-like respiratory patients. A higher prevalence of reactive subjects has been recorded in all the pediatric subsets without gender differences, whereas female reactivity is prevalent among adults. The ASST reactivity seems to parallel the patient distribution within the entire respiratory cohort. Further studies are needed to demonstrate that the serum factors causing the ASST reactivity in respiratory patients are the same as for CIU affected subjects. In the light of recent in vitro findings, the ASST reactivity of healthy subjects could lead to a new interpretation of the autologous serum reactivity.     

Serological evidence that activation of ubiquitous human herpesvirus‐6 (HHV‐6) plays a role in chronic idiopathic/spontaneous urticaria (CIU)

Acute infection with viral pathogens in the herpesviridae family can trigger acute urticaria, and reactivation of herpesviridae is associated with cutaneous urticarial‐like syndromes such as drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DRESS). Reactivation of latent herpesviridae has not been studied systematically in chronic idiopathic/spontaneous urticaria (CIU). This review proposes that CIU is an inflammatory disorder with autoimmune features (termed ‘CVU’ for chronic viral urticaria), based on serology consistent with the hypothesis that reactivation of a latent herpesvirus or ‐viruses may play a role in CIU. Serology obtained from a cohort of omalizumab (Xolair)‐dependent patients with severe CIU was consistent with previous HHV‐6 infection, persistent viral gene expression and replication. CIU patients also exhibited serological evidence of increased immune response to HHV‐4 (Epstein–Barr virus, or EBV) but not all CIU patients were infected with EBV. These observations, combined with case reports of CIU response to anti‐viral therapy, suggest that HHV‐6, possibly interacting with HHV‐4 in cutaneous tissues, is a candidate for further prospective study as a co‐factor in CIU.     

Detection of basophil-activating IgG autoantibodies in chronic idiopathic urticaria by induction of CD 63

BACKGROUND: Approximately 40% to 50% of patients with chronic idiopathic urticaria (CIU) have functional IgG autoantibodies against FcepsilonRIalpha or IgE, which induce histamine release from basophils and cutaneous mast cells. A positive autologous serum skin test response is believed to reflect the presence of these autoantibodies. OBJECTIVE: We sought to further define the functional properties of and develop a sensitive functional assay for detection of autoantibodies in patients with CIU. METHODS: Sera from patients with CIU (n=61) and sera from healthy control subjects (n=23) were incubated with donor basophils. Activation of basophils was determined on the basis of CD 63 surface expression, as analyzed on a FACScan flow cytometer. RESULTS: A positive basophil activation test result was found in 51% of patients with CIU, and basophil-activating properties were present in the IgG fractions of sera. When both the in vitro test and the autologous serum skin test were considered, basophil/mast cell-activating autoantibodies were present in 62% of the patients. Patients with a positive basophil activation test result had a significantly higher prevalence of other autoantibodies, had more severe urticaria, and were more likely to have angioedema. CONCLUSION: The results demonstrate the presence of basophil-activating autoantibodies in about 50% of patients with CIU. The data support the autoimmune cause of the disease and provide a simple test for detection of these autoantibodies.     

Intolerance to nonsteroidal anti-inflammatory drugs might precede by years the onset of chronic urticaria

BACKGROUND: Recent studies have found that most otherwise normal subjects with a history of acute urticaria induced by several nonsteroidal anti-inflammatory drugs (NSAIDs) show a wheal-and-flare reaction on intradermal injection of autologous serum. This phenomenon has been previously observed in patients with chronic urticaria (CU) and suggests a possible common background in CU and NSAID-induced urticaria. A relationship between these 2 conditions is further suggested by the fact that up to 30% of patients with CU have a worsening of their skin disorders after the ingestion of chemically unrelated NSAIDs. OBJECTIVE: I sought to assess whether otherwise normal subjects with multiple or single NSAID intolerance show a propensity to have CU. METHODS: Two hundred eighty otherwise normal patients with an unequivocal history of acute urticaria induced by NSAIDs seen during the last 10 years were studied. On the basis of both clinical history and oral challenge tests with at least 2 alternative NSAIDs, the patients were classified as having single or multiple NSAID intolerance. All the patients were re-evaluated within the end of 2002, 1 to 10 years after the first visit, to assess the onset of CU. One hundred allergic adults without a history of CU and of drug allergy followed up for 1 to 10 years were used as control subjects. RESULTS: One hundred fifty-nine and 121 patients were finally considered as having single or multiple NSAID intolerance, respectively. At the follow-up visit, 93 (33%) of 280 patients had CU. The prevalence of CU was very similar in subjects with single or multiple NSAID intolerance (48/159 [30%] vs 45/121 [37%], respectively; P = not significant). Only 1 (1%) of 100 atopic control subjects had CU during the follow-up period (P <.001). Among single NSAID reactors, patients who had CU had a significantly higher prevalence of intolerance to aspirin than those who did not have CU (36/48 [75%] vs 41/111 [37%], P <.001), whereas the latter had a markedly higher prevalence of intolerance to pyrazolone drugs (52/111 [47%] vs 10/48 [21%], P <.01). Altogether, only 12 (15%) of 82 patients intolerant to drugs other than aspirin versus 36 (47%) of 77 aspirin reactors had CU (P <.001). CONCLUSION: NSAID intolerance might precede the onset of CU by years. Both multiple and single NSAID reactors with a history of aspirin-induced urticaria seem at higher risk for CU than patients with a history of single intolerance to NSAIDs other than aspirin.     

Classification of anti-FcepsilonRI and anti-IgE autoantibodies in chronic idiopathic urticaria and correlation with disease severity

BACKGROUND: Circulating autoantibodies against FcepsilonRI, IgE, or both occur in approximately one third of patients with chronic idiopathic urticaria (CIU), but not all autoantibodies initiate histamine release. OBJECTIVE: We sought to classify patients with CIU into subsets on the basis of serum bioactivity and immunoreactivity and to examine the relationship between newly defined subtype and disease severity. METHODS: Sera from patients with CIU (n = 78), dermog-raphism (n = 15), and cholinergic urticaria (n = 10) and sera from healthy subjects (n = 39) were analyzed by means of Western blot analysis for anti-FcepsilonRI autoantibodies and for histamine release from basophils and dermal mast cells. In vivo reactivity of autologous serum was tested by means of intradermal injection, and CIU severity was determined on the basis of clinical interview. RESULTS: We classified sera from patients with CIU into 5 subsets: immunoreactive histamine-releasing anti-FcepsilonRI autoantibodies (n = 20 [26%]); immunoreactive anti-FcepsilonRI autoantibodies without histamine-releasing activity (n = 12 [15%]); anti-IgE-like autoantibodies (n = 7 [9%]); serum containing a mast cell-specific histamine-releasing factor (n = 7 [9%]); and sera with no identifiable factor (n = 32 [41%]). Patients with serum histamine-releasing activity had more severe urticaria than patients without such activity. Positive skin test responses to autologous sera were associated with histamine-releasing anti-FcepsilonRI autoantibodies but not with non-histamine-releasing anti-FcepsilonRI autoantibodies. Neither healthy subjects nor patients with dermographism or cholinergic urticaria had his-tamine-releasing anti-FcepsilonRI autoantibodies. CONCLUSION: These data support the specificity of functional anti-FcepsilonRI autoantibodies to CIU. The identification of distinctive subsets of patients suggests that other pathogenic mechanisms occur in CIU in addition to direct ligation of FcepsilonRI by autoantibodies causing dermal mast cell degranulation. Elucidating these mechanisms might lead to new treatments for CIU.     

Helicobacter pylori infection: prevalence in chronic urticaria patients and incidence of autoimmune urticaria (study in Dr. Cipto Mangunkusumo Hospital, Jakarta)

AIM: To determine the prevalence of Hp infection in patients with chronic urticaria (CU) and to evaluate the result of autologous serum skin test (ASST) in CU patients with Hp infections. METHODS: In this cross-sectional study, 16 patients with chronic urticaria and 16 non-urticaria volunteers were investigated (matched for age and sex). All subjects were examined for Hp infection with the 13C-urea breath test. Autologous serum skin test was performed in patients with proven Hp infection. RESULTS: Helicobacter pylori was detected in 12.5% of patients and 0% of the control group. There was no significant difference between the two groups (p = 0.484 using Fisher exact test). Autologous serum skin test was positive in 1 of 2 CU patients with Hp infection. CONCLUSION: In this study, there was no significant difference in the seroprevalence of Hp infection between CU patients and controls. Autologous serum skin test was positive in 1 of 2 CU patients with Hp infection.     

The effect of heat-inactivated Helicobacter pylori on the blastogenic response of peripheral blood mononuclear cells of patients with chronic urticaria.

BACKGROUND: Helicobacter pylori, the most important etiologic factor of gastritis and peptic ulcer, has recently been associated with several extradigestive diseases. Previous studies reported conflicting results on H. pylori eradication in chronic urticaria, in that some studies showed a benefit, while others found no effect. METHODS: Peripheral blood mononuclear cells of 24 chronic urticaria patients (13 seropositive/11 seronegative for H. pylori) and 18 healthy controls (9 seropositive/9 seronegative) were stimulated with whole heat-inactivated H. pylori (8 x 10(5), 8 x 10(6 )and 8 x 10(7) bacteria/well), phytohemagglutinin (2 microg/ml) and pokeweed mitogen (5 microg/ml). The proliferative response was determined by (3)H-thymidine incorporation. Helicobacter-specific IgG antibody response was determined by ELISA. RESULTS: There were significantly higher proliferative responses to various concentrations of whole heat-inactivated H. pylori antigen in 6- to 7-day cultures of peripheral blood mononuclear cells of chronic urticaria patients compared to healthy controls. We found a tendency to exhibit a higher proliferative response to either Helicobacter antigens or mitogens in seropositive compared to seronegative patients. CONCLUSION: Our results support the hypothesis that there is an increased lymphocyte reactivity in chronic urticaria, perhaps further enhanced by the presence of H. pylori which, therefore, may be involved as a trigger in the pathogenesis of chronic urticaria.     

Quality of life and patients' satisfaction in chronic urticaria and respiratory allergy

BACKGROUND: Few articles are available about chronic urticaria (CU) impact on patients' quality of life (QoL). The aim of our study was to evaluate QoL in CU patients both focusing on health status and subjective satisfaction. We adopted two generic tools: SF-36 (an health status questionnaire) and SAT-P (a satisfaction profile). METHODS: Twenty-one untreated patients (five males, 16 females; aged 46.3 +/- 12.4) affected by CU, were enrolled. SF-36 and SAT-P scores of CU patients were compared with scores of a group of 27 patients with respiratory allergy. Published reference values of 608 and 241 Italian healthy subjects were used as controls, respectively, for SF-36 and SAT-P. RESULTS: Patients with CU compared with allergic patients referred significantly lower scores in physical functioning (P = 0.046), role physical (P = 0.01), bodily pain (P = 0.0001), general health (P = 0.0043) and role emotional (P = 0.04), and compared with reference sample reported lower scores in all SF-36 domains (P < 0.0001). SAT-P scores of CU patients compared with patients with respiratory allergy and with reference sample were significantly lower in many aspects of daily life. CONCLUSIONS: These results show a significant impact on health status and on subjective satisfaction in patients with CU: the symptoms affect everyday life, limiting and impairing physical and emotional functioning, and acts as an indirect burden on life satisfaction.     

Basophil FcepsilonRI histamine release parallels expression of Src-homology 2-containing inositol phosphatases in chronic idiopathic urticaria

BACKGROUND: Basophils are implicated in the pathogenesis of chronic idiopathic urticaria (CIU). Autoantibodies to the IgE receptor (FcepsilonRI) and serum histamine releasing activity have been detected in some subjects with CIU, although their role in vivo is unclear. Basophils of patients with CIU have altered FcepsilonRI-mediated histamine release (HR); however, the mechanism is unknown. In the basophil FcepsilonRI signaling pathway, protein levels of Src-homology 2-containing-5'-inositol phosphatase (SHIP)-1 are inversely correlated with the release of mediators or releasability. A related phosphatase, SHIP-2, is a negative regulator of monocyte IgG receptor (FcgammaR) signaling . We hypothesized that SHIP levels are altered in CIU basophils. METHODS: Blood basophils were isolated from cold urticaria, CIU, or normal donors, and FcepsilonRI-dependent and independent HR were quantified. Protein levels of SHIP-1, SHIP-2, spleen tyrosine kinase, and phosphorylated Akt were determined by Western blotting. Subjects' serum was tested for serum histamine releasing activity and anti-FcepsilonRIalpha antibodies. RESULTS: CIU basophils displayed a bimodal response to anti-IgE activation. One half of CIU subjects' basophils had reductions in anti-IgE-induced HR and were designated nonresponders (CIU NR). CIU NR basophil HR remained diminished at 10-fold to 30-fold higher doses of anti-IgE. CIU anti-IgE responder basophils had HR similar to normal subjects. SHIP-1 and SHIP-2 proteins were increased in CIU NR basophils and were linked to reduced phosphoAkt after anti-IgE stimulation. CIU basophil anti-IgE response was not related to the presence of serologic factors. CONCLUSION: In CIU basophils, the observed changes in FcepsilonRI signaling pathway molecule expression may underlie changes in releasability. CLINICAL IMPLICATIONS: Patients with CIU can be segregated on the basis of basophil functional phenotype.     

The relationship between persistent secretion of RANTES and residual infiltration of eosinophils and memory T lymphocytes after Helicobacter pylori eradication

Helicobacter pylori (HP)-infected gastric mucosa displays a conspicuous infiltration of mononuclear cells as well as neutrophils. RANTES is a potent chemoattractant peptide for memory T lymphocytes and eosinophils. RANTES protein concentration and the numbers of RANTES-, CD45RO-, and major basic protein (MBP)-positive cells were therefore evaluated in the gastric mucosa from 51 patients with HP-positive chronic gastritis before and after HP eradication and from 22 HP-negative healthy volunteers. RANTES protein concentration was significantly elevated in HP-positive cases and remained high after HP eradication. The numbers of RANTES-, CD45RO-, and MBP-positive cells were significantly increased in HP-positive cases and were well correlated with RANTES protein levels. All tended to decrease after HP eradication, but did not reach the level of HP-negative cases, even at 24 months after HP eradication. It was concluded that persistent expression and secretion of RANTES were closely related to residual infiltration of memory T lymphocytes and eosinophils, for a prolonged period after HP eradication. This seems to be an important mechanism of prolonged gastric mucosal immune response against HP infection, even after HP eradication, and of persistent mucosal damage and atrophy.     

Rupatadine in the treatment of chronic idiopathic urticaria: a double-blind, randomized, placebo-controlled multicentre study

BACKGROUND: Chronic urticaria is one of the most common and disturbing cutaneous condition. The treatment of chronic idiopathic urticaria (CIU) is still a challenge. Antihistamines are recommended as first-line treatment. Rupatadine is a new potent nonsedative anti-H1. OBJECTIVE: To study rupatadine efficacy and safety for moderate to severe CIU treatment. METHODS: This randomized, double-blind, placebo-controlled, parallel-group, multicentre, study was designed to assess primarily mean pruritus score (MPS) reduction with rupatadine, 10 and 20 mg, administered once daily for 4 weeks. Three hundred and thirty-three patients with active episodes of moderate-to-severe CIU were included. RESULTS: A 57.5% (P < 0.005) and 63.3% (P = 0.0001) significative MPS reduction from baseline, was observed at week 4 with 10 and 20 mg rupatadine, respectively, compared with placebo (44.9%). Both doses of rupatadine were not significantly different at any time point, with respect to their effects on pruritus severity, number of wheals and total symptoms scores. Rupatadine 10 mg had an overall better adverse event profile. CONCLUSION: Rupatadine 10 mg is a fast, long-acting, efficacious and safe treatment option for the management of patients with moderate-to-severe CIU.