The autologous serum skin test in the follow-up of patients with chronic urticaria

BACKGROUND: The presence of anti-FcepsilonRI and anti-IgE autoantibodies in a subset of patients with chronic urticaria suggests their aetiopathogenetic role. In clinical practice, the presence of these antibodies is usually considered when the autologous serum skin test (ASST) is positive. AIMS: To evaluate if the positive ASST follows up the activity of chronic urticaria. METHODS: Autologous serum skin test and thyroid autoantibody detection were performed in 82 patients with chronic urticaria and repeated 1 year later, when the vast majority of patients were symptom-free. Twenty patients with Hashimoto thyroiditis (HT), who had never suffered from urticaria, represented the control group. RESULTS: At the start of the study, the prevalence of positive ASST was 46.6%. The association of HT-urticaria was 29.3%. ASST was positive in 62 and 39% of patients with and without HT, respectively (P > 0.05 ns). One year later, 28 of 34 patients with a positive ASST were symptom-free, but 50% of them were positive for ASST. The ASST was positive in 86.7 and 8% of patients with and without HT, respectively (P < 0.001). In the control group, ASST was always negative. CONCLUSIONS: The co-existence of autoimmune thyroiditis with chronic urticaria seems to induce a significant difference in the persistence of a positive ASST. Consistent with previous reports, a positive ASST correlates with disease exacerbation in chronic urticaria patients without thyroiditis. In patients with thyroiditis and urticaria, positive ASST persists even after the urticaria has disappeared, thus questioning whether a positive ASST to be a surrogate marker of the functional role of anti-FcepsilonRI and anti-IgE autoantibodies.     

High prevalence of autoimmune urticaria in children with chronic urticaria

BACKGROUND: The etiology of chronic urticaria (CU) in childhood often remains unrecognized. Recently, in adults it has been shown that approximately 40% of patients with CU have autoimmune urticaria (AU); however, no data are available in children. OBJECTIVE: To determine the prevalence and possible risk factors for AU in children with CU. METHODS: Ninety-three consecutive children (52 male; median age, 7.8 years) with CU were evaluated for AU by means of autologous serum skin test (ASST) in all and serum-induced basophil histamine release (HR-urticaria test) in 52. All other known causes of CU were excluded as appropriate. RESULTS: A cause for CU was identified in 44 children (47%), whereas 49 (53%) remained idiopathic. ASST and HR-urticaria test had positive results in 22 of 49 (45%) and in 16 of 31 (52%) children with idiopathic CU compared with 1 of 44 (2%) and 5 of 21 (24%) with CU of a known cause, respectively ( P <.00001; P=.09). Sensitivity, specificity, and positive and negative predictive values of the ASST for diagnosing AU are 78%, 85%, 74%, and 88%. The prevalence of AU in childhood is 31% (15/52; 95% CI, 24%-51%). None of the variables studied were predictive for development of AU. CONCLUSION: Our results demonstrate for the first time that children have the same ability as adults to produce functionally active autoantibodies directed against IgE or IgE receptor and that AU occurs in children in as many as 30% of cases. The addition of screening for AU dramatically decreases the rate of the idiopathic form from 52% to 20%.     

Clinical and laboratory parameters in predicting chronic urticaria duration: a prospective study of 139 patients

BACKGROUND: Despite the disabling nature of chronic urticaria (CU), little is known about the disease's duration or the efficacy of adopting aggressive therapeutic regimens such as cyclosporine A. OBJECTIVES: The aim of this study was to evaluate whether parameters such as angioedema, autologous serum test, anti-thyroid antibodies, and total IgE could predict both CU duration and severity. PATIENTS AND METHODS: One hundred and thirty-nine patients suffering from CU were prospectively followed over a 5-year period for disease duration, severity and the presence of angioedema. Also investigated was the association between these clinical parameters and the subsequent detection of autologous serum test, anti-thyroid antibodies, and total IgE. RESULTS: CU lasted over 1 year in more than 70% of cases and in 14% it still existed after 5 years. Angioedema co-existed or appeared during the course of CU in 40% of patients and was associated with disease duration. Autologous serum test and anti-thyroid antibodies were found positive in 28 and 12% of patients, respectively, compared to none of normal individuals, P = 0.001. CU duration was associated with the presence of both autologous serum test and anti-thyroid antibodies; however, autologous serum test and not anti-thyroid antibodies was found in association with CU severity. CONCLUSION: We demonstrate for the first time that CU duration is associated with clinical parameters such as severity and angioedema, and with laboratory parameters such as autologous serum test and anti-thyroid antibodies. The ability to predict CU duration may facilitate decisions regarding the possible early initiation of cyclosporine A as a means by which to reduce disease severity and duration.     

Plasma of patients with chronic urticaria shows signs of thrombin generation, and its intradermal injection causes wheal-and-flare reactions much more frequently than autologous serum

BACKGROUND: Several aspects of the pathogenesis of chronic urticaria (CU) remain contradictory. Autologous serum skin tests (ASSTs) and in vitro histamine release assays seem to look into distinct aspects of the disease, and the specificity of ASST has been questioned. OBJECTIVE: We compared the autologous plasma skin test (APST) with ASST to detect autoreactivity in patients with CU. The clotting process was investigated as well by measuring in vivo thrombin generation. METHODS: A total of 96 adults with CU underwent ASST; 71 of them underwent APST with Na citrate-anticoagulated plasma. Prothrombin fragment 1+2 plasma levels were measured by a sandwich ELISA in Na citrate-anticoagulated plasmas from 28 patients and 27 controls. RESULTS: Fifty-one of 96 (53%) patients scored positive on ASST, whereas 61 of 71 (86%) patients scored positive on APST (21/30 [70%] ASST-negative and 40/41 [98%] ASST-positive). Plasma prothrombin fragment 1+2 was higher in patients than controls (3.06 [SD 3.36] vs 0.80 [0.34]; P < .001) and in ASST-positive/APST-positive than in ASST-negative/APST-positive patients (3.89 [SD 3.68] vs 1.33 [1.64]; P = 0.058) and was directly related to urticaria severity (r = 0.37; P < .05). CONCLUSION: Most patients with CU are positive on APST-Na citrate. CU is associated with the generation of thrombin, a serine protease able to activate mast cells and to cause relevant increase in permeability of endothelium. APST and ASST only partially depend on the presence of circulating antibodies to FcepsilonRI or to IgE. CLINICAL IMPLICATIONS: These findings provide new insights into the pathogenesis of CU and suggest new therapeutic opportunities for treating this disease.     

Correlation between T-cell and mast cell activity in patients with chronic urticaria

BACKGROUND: The presence of autoantibodies reacting with the high affinity IgE receptor (FcepsilonRIalpha) usually indicates a more severe form of chronic urticaria (CU). Previously, we showed an increased lymphocyte reactivity in CU patients; however, the relation between enhanced cellular immunity and the presence of anti-FcepsilonRIalpha-specific autoantibodies has not been investigated. METHODS: Cellular and humoral immune reactivity of 50 CU patients and 28 healthy controls was studied.Serum sIL-2R, neopterin, and tryptase levels were measured to assess T-cell, monocyte/macrophage and mast cell activity, respectively. Helicobacter pylori (HP)-specific IgG antibody, and IgE levels were also tested. Anti-FcepsilonRIalpha-specific autoantibody was determined by Western blotting. In vivo histamine-releasing activity of patients' sera was assessed by the autologous serum skin test (AST). RESULTS: 17/50 CU patients, who both had IgG-type anti-FcepsilonRIalpha-antibodies by Western blotting and a positive AST response, were classified as autoimmune CU. All patients with CU had significantly higher serum sIL-2R and tryptase levels than healthy controls (p = 0.000257, p = 0.000166, respectively), indicating T-cell and mast cell activation. Patients with higher sIL-2R levels also had higher tryptase levels; the strongest correlation was shown in the autoimmune subgroup of patients (rho = 0.688, p = 0.002). There was a tendency towards higher tryptase levels in the autoimmune subgroup, as compared to the nonautoimmune CU patients. While the serum IgE was significantly lower in autoimmune than in nonautoimmune CU (p = 0.000836), there was no significant difference in their sIL-2R, neopterin and HP-specific IgG antibody levels. CU patients with a positive AST response (38/50) had significantly higher tryptase levels (p = 0.0107) when compared to the negative skin test group. CONCLUSIONS: The significant correlation between sIL-2R and tryptase levels in patients with CU indicates that T cell activation is proportional to mast cell degranulation in these patients. The increased level of tryptase in autoimmune CU may suggest more severe disease.     

Chronic urticaria sera increase basophil CD203c expression

BACKGROUND: Approximately 40% of patients with chronic idiopathic urticaria have antibodies to the alpha subunit of the high-affinity IgE receptor. CD203c is a basophil activation marker known to be upregulated by cross-linking of the FcepsilonRIalpha receptor and may serve as a useful marker to identify these patients. OBJECTIVE: The primary objective was to assess the affect of sera from patients with chronic idiopathic urticaria on basophil CD203c expression. Secondary objectives were to correlate CD203c expression with basophil histamine release and size of the autologous serum skin test and to determine whether the mechanism is mediated by an IgG antibody. METHODS: Sera were obtained from patients with chronic idiopathic urticaria and positive autologous serum skin test or negative autologous serum skin test and normal controls. Sera were incubated with donor whole blood. Activated basophils from whole blood were identified by flow cytometry on the basis of the presence of CD203c on high-expressing IgE positive cells. RESULTS: Incubation of donor basophils with sera from patients with chronic idiopathic urticaria and positive autologous serum skin test demonstrated significant upregulation of CD203c. IgG depletion of representative sera from patients with chronic idiopathic urticaria resulted in significant decrease in CD203c expression on donor basophils. CD203c expression correlated with basophil histamine release and the size of the autologous serum skin test. CONCLUSION: Sera from patients with chronic idiopathic urticaria and positive autologous serum skin test significantly upregulate basophil CD203c and correlate with basophil histamine release. CLINICAL IMPLICATIONS: This article describes an activation marker on basophils whose expression is increased by sera from patients with chronic idiopathic urticaria.     

Chronic urticaria and Helicobacter pylori

Background: Helicobacter pylori (HP) have recently emerged as a novel eliciting factor for chronic urticaria (CU). The possible association between HP and CU has enormous potential, as eradicating HP could cure CU. Aims and Objectives: We conducted a study to assess the prevalence of HP infection and effect of bacterium eradication on skin lesions in patients of chronic idiopathic urticaria (CIU). Settings and Design: Four hundred sixty patients of CU attending the allergy clinic, SMS hospital, Jaipur during the period February 6, 2004, to February 6, 2006, were screened for possible eliciting factors. Patients with CIU were enrolled and others were excluded. Materials and Methods: Sixty-eight patients of CIU and similar number of age and sex matched controls, attending the allergy clinic, SMS Hospital, Jaipur were enrolled in the study. All patients underwent endoscopy with antral biopsy for urease and histopathology to identify HP-associated gastritis. Infected patients were given HP eradication therapy. Eradication of bacterium was confirmed by fecal antigen assay. Subjective response to treatment was judged using chronic urticaria quality-of-life questionnaire (CU-Q 2 oL) while objective response to treatment was judged by need for 'rescue medication' (antihistaminics). Statistical Analysis: Data were analyzed using Chi square and paired't' test for their level of significance. Results: HP associated gastritis was present in 48 (70.58%) patients, out of which 39 (81.25%) patients responded to eradication therapy. Ten (50.00%) patients without HP associated gastritis showed response to symptomatic therapy. Overall 49 (72.05%) patients responded and 19 (27.94%) showed no response. The value of chi2 was 28.571 (P = 0.003), which showed significant association between presence of HP and response to eradication regimen. Conclusion: The response of HP eradication therapy in infected patients of CIU is significant. HP should be included in diagnostic workup of patients with CIU.     

Brain‐derived neurotrophic factor is increased in serum and skin levels of patients with chronic spontaneous urticaria

Background Chronic spontaneous urticaria is triggered by many direct and indirect aggravating factors including autoreactive/autoimmune mechanisms, infections, non‐allergic and pseudoallergic intolerance reactions. However, the role of neuroimmune mechanisms in chronic spontaneous urticaria so far is unclear. Objective Thus, we wanted to address the regulation of the neurotrophin brain‐derived neurotrophic factor (BDNF) in serum and inflammatory skin of patients with chronic spontaneous urticaria in comparison to subjects with healthy skin. Methods Fifty adult patients with chronic spontaneous urticaria and 23 skin‐healthy subjects were studied. Chronic spontaneous urticaria was defined as recurrent weals for more than 6 weeks. Autologous serum skin test was performed in all patients with chronic spontaneous urticaria and BDNF serum levels were analysed by enzyme immunoassay in all subjects. Furthermore, skin biopsies were taken from weals of eight patients with chronic spontaneous urticaria as well as from healthy skin of eight controls to evaluate the expression of BDNF and its receptors including tyrosine kinase (trk) B and pan‐neurotrophin receptor p75^NTR by immunohistochemistry. Results BDNF serum levels were detectable in all subjects studied. However, BDNF levels were significantly higher in patients with chronic spontaneous urticaria compared to non‐atopic skin‐healthy controls (P<0.001). Furthermore, epidermal and dermal expression of BDNF and epidermal expression of p75^NTR was significantly higher in patients with chronic spontaneous urticaria compared with controls (P<0.05–0.001). There was no difference with regard to the expression of trkB between chronic spontaneous urticaria and controls and no difference in BDNF serum levels between autologous serum skin test‐positive (n=23) and ‐negative (n=27) patients with chronic spontaneous urticaria. Conclusions and Clinical Relevance This study shows that BDNF is increased in serum and diseased skin of patients with chronic spontaneous urticaria, suggesting a role for neurotrophins in the pathophysiology of this chronic inflammatory skin disease. Further studies are needed to address the functional role of BDNF on key target effector cells in chronic spontaneous urticaria to establish new therapeutic implications. Cite this as: K. Rössing, N. Novak, S. Mommert, F. Pfab, M. Gehring, B. Wedi, A. Kapp and U. Raap, Clinical & Experimental Allergy, 2011 (41) 1392–1399.     

Validation of basophil histamine release against the autologous serum skin test and outcome of serum-induced basophil histamine release studies in a large population of chronic urticaria patients

BACKGROUND: Endogenous histamine-releasing factors (HRFs) are involved in 30-60% of patients with chronic urticaria (CU). Evidence for their existence comes from in vivo studies of autoreactivity with the autologous serum skin test (ASST), in vitro immunoassays demonstrating autoantibodies against the immunoglobulin E (IgE) or the high affinity IgE receptor (FcepsilonRI) and serum-induced histamine release (HR) from basophils and mast cells. We have examined the correlation between the ASST and a new basophil histamine-releasing assay (the HR-Urtikaria test) in a group of well-characterized CU patients and subsequently determined the frequency of HR-Urticaria-positive sera from a larger population of CU patients. SUBJECTS: Group 1 consisted of 28 patients with CU (16 were ASST-positive) 20 patients with atopic dermatitis, 24 patients with allergy to birch and nine healthy controls. Group 2 consisted of 873 unselected CU patients. METHODS: White blood cells containing 1-2% basophils from a healthy nonatopic donor were incubated with patients sera in the presence of interleukin (IL)-3. Histamine was measured by the glass fibre method. RESULTS: Using the ASST as the true outcome, the HR-Urticaria test showed a sensitivity and specificity of 75% in group 1 using a cut-off value for HR of >16.5%. None of the controls was positive in the HR-Urticaria test. In group 2, we found no difference in the frequency of positives between male (34.6%, n = 254) and female adults (35.1%, n = 576) but twice as many females as males were tested. CONCLUSIONS: Our studies have shown that the HR-Urticaria test has a good sensitivity and specificity for endogenous HRFs demonstrated by the ASST in patients with CU and that about one-third of unselected patients with CU have a positive result.     

Serum-induced basophil CD63 expression by means of a tricolour flow cytometric method for the in vitro diagnosis of chronic urticaria

BACKGROUND: Functional autoantibodies against the alpha-chain of the high-affinity IgE receptor (FcepsilonRIalpha) identify a subset of patients with chronic urticaria (CU) due to autoreactivity, as assessed by an in vivo positive response to autologous serum skin test (ASST). We performed a study to standardize the serum-induced basophil activation assay by flow cytometry (FCM) using a new tricolour method, assessing the diagnostic performance of this test in discriminating between ASST+ and ASST- CU patients. METHODS: Sera of 64 CU patients (22 ASST+ CU and 42 ASST- CU) and 10 healthy subjects were tested for their ability to induce basophil CD63 expression when incubated with whole blood of both atopic (DA) and non-atopic donors (DNA). Using a triple-labelled strategy with anti-CD123, anti-HLA-DR and anti-CD63 antibodies, CD63+ basophils were identified on a selected population of CD123+ HLA-DR- cells. In 3 ASST+ CU patients who underwent cyclosporine therapy, the assay was performed before and after treatment. RESULTS: The ASST+ CU sera resulted in a significant higher induction of basophil CD63 expression compared with ASST- CU and healthy donors sera; when whole blood from DA was used, sensitivity and specificity of the assay were 95.5% and 90.5% respectively. ASST+ CU serum activity was significantly decreased during cyclosporine A treatment, in parallel with clinical remission. CONCLUSIONS: Chronic urticaria serum-induced CD63 expression assay performed on DA whole blood by means of our tricolour FCM method could be the most useful tool for identification of a subset of patients with autoimmune CU and may become a promising tool also for monitoring treatment efficacy.     

Plasma levels and skin-eosinophil-expression of vascular endothelial growth factor in patients with chronic urticaria

Background:  Although chronic urticaria (CU) is often regarded as autoimmune in nature, only less than 50% of sera from CU patients contain histamine-releasing autoantibodies. This suggests that other factors may contribute to its pathogenesis. We evaluated the possible involvement of vascular endothelial growth factor (VEGF), one of the major mediators of vascular permeability, in CU.
Methods:  Eighty consecutive adult patients with CU and 53 healthy subjects were studied. VEGF and prothrombin fragment F₁₊₂ were measured by enzyme immunoassays. Autologous plasma skin test (APST) was performed in CU patients and, in six of them, skin biopsy specimens were taken from wheals to evaluate the immunohistochemical expression of VEGF and eosinophil cationic protein (ECP).
Results:  Plasma VEGF concentrations were higher in CU patients (8.00 ± 0.90 pmol/l) than in controls (0.54 ± 0.08 pmol/l) ( P  =   0.0001) and tended to parallel both the severity of CU and to correlate with F₁₊₂ levels. APST was positive in 85.1% of patients. VEGF concentration was significantly higher in APST-positive than in APST-negative patients ( P  =   0.0003). Immunohistochemically, all specimens from patients with CU showed a strong expression of VEGF ( P  =   0.002) that colocalized with ECP, a classic eosinophil marker.
Conclusions:  VEGF plasma levels are elevated in CU and parallel the disease severity. This supports a possible role of this molecule in CU pathophysiology. Eosinophils are the main cellular source of VEGF in CU lesional skin.     

Chronic urticaria serum induces histamine release, leukotriene production, and basophil CD63 surface expression--inhibitory effects ofanti-inflammatory drugs

BACKGROUND: A role of potential histamine-releasing autoantibodies against the high-affinity IgE receptor on the surface of basophils and mast cells is discussed in the pathogenesis of chronic urticaria. This so-called autoimmune urticaria may be diagnosed by a positive intracutaneous autologous serum skin test, which is found in about 30% of patients with chronic urticaria. OBJECTIVE: Our purpose was, first, to compare the effect of complement-inactivated sera of 20 patients with chronic urticaria and positive autologous serum skin tests, 20 patients with chronic urticaria and negative skin tests, and 20 control subjects without chronic urticaria (10 atopic and 10 nonatopic subjects) and, second, to analyze the effect of anti-inflammatory drugs on the serum activity. METHODS: The following assay systems were used: release of histamine in whole blood samples, surface expression of the activation marker CD63 on basophils, and sulfidoleukotriene de novo production in leukocyte suspensions. Whole blood, basophils, and leukocyte suspensions were obtained from a nonatopic and an atopic donor. RESULTS: Sera of patients with autologous serum skin test positive chronic urticaria resulted not only in significantly increased histamine release compared with skin test-negative chronic urticaria sera but also in a significant higher induction of basophil CD63 surface expression and sulfidoleukotriene de novo production. However, serum activity was neither characteristic for chronic urticaria nor for chronic urticaria with a positive autologous serum skin test. Preincubation with dapsone, chloroquine, and lidocaine dose dependently resulted in a significant reduction of all histamine release, CD63 expression, and sulfidoleukotriene production. In addition, mizolastine was able to inhibit serum-induced sulfidoleukotriene production. CONCLUSION: Further studies investigating the in vivo effect of these drugs will have to clarify their role in the management of the subset of patients with chronic urticaria demonstrating serum-induced inflammatory effects.     

Elevated serum B-cell activating factor in patients with chronic urticaria

The B and T cells abnormalities that have been described among CU patients, lend support to its regard as an autoimmune disease. In this study we compared serum B-cell activation factor (BAFF) levels in 46 CU patients to 24 healthy controls and evaluated a possible association between elevated serum BAFF in CU patients and the presence of autologous serum skin test, anti-thyroid antibodies, antinuclear antibodies, high total IGE levels, and urticaria disease severity. We found that serum BAFF levels is elevated statistically significant in CU patients compared to healthy control (1228±342 pg/ml vs. 758±313 pg/ml, P<0.0001). CU patients with severe disease activity had significantly higher serum BAFF levels compared to patients with mild CU (1394.6±299.6 vs. 1097.6±221.3, P=0.0008). No association was found between the presence of positive autologous serum skin test, anti-thyroid antibodies or antinuclear antibodies or high levels of total IgE and serum BAFF levels in CU Patients. We conclude that CU patients have higher levels of serum BAFF which associate with disease severity.     

Circulating level of the platelet-derived CXC chemokine platelet factor 4 in chronic urticaria patients with or without coexistent euthyroid Hashimoto's thyroiditis

The concept of autoimmune aetiology of some cases of chronic urticaria (CU) has been supported by several observation including wheal-and-flare reaction induced by intradermal injection of autologous serum as well as association with other autoimmune diseases, in particular Hashimoto's thyroiditis (HT). It is known that activated platelets may actively participate in immune-inflammatory processes. Therefore, we assessed whether autoimmune phenomenon associated with CU influence the systemic platelet activity measured by circulating level of platelet factor 4 (PF-4). Plasma level of PF-4 was analysed using enzyme-linked immunosorbent assay in twelve women with strong positive response to autologous serum skin test (ASST) suffering from CU, twelve female patients with strong positive ASST suffering from both CU and untreated, HT as well as sixteen healthy women. All the subjects were clinically and biochemically euthyroid. There were no statistically significant differences between the CU patients with or without euthyroid HT and plasma PF-4 level in healthy controls. In patients with both CU and thyroiditis, plasma level of PF-4 did not correlate significantly with the level of antibodies against thyroperoxidase. It seems that circulating level of the platelet-derived chemokine is not increased in CU patients with positive response to ASST, regardless the occurrence of euthyroid HT.     

Food-additive-induced urticaria: a survey of 838 patients with recurrent chronic idiopathic urticaria

BACKGROUND: Recurrent chronic idiopathic urticaria (RCIU) is a common skin condition that affects 0.1-3% of the population in the USA and Europe and accounts for nearly 75% of all 'ordinary' chronic urticaria (CU) cases. METHODS: We studied 838 consecutive patients with RCIU referred to hospital between 1998 and 2003. Patients with known causes of CU were excluded. Clinical history, physical examination, and symptom diaries were evaluated during two periods, a diet-free period (1 week) and a food-additive-free diet (FAFD) period (4 weeks), respectively, and two double-blind placebo-controlled (DBPC) challenges of six food additives were administered. The first DBPC challenge included a mixture of the six food additives (DBPCmixed) given to all patients. The second DBPC challenge comprised the single food additives, administered at increasing doses (DBPCsingle) to patients with a positive DBPCmixed test and 105 patients with a negative DBPCmixed test, as a control. RESULTS: The DBPCmixed challenge was positive in 116 patients. None of the 105 control patients had a positive DBPCsingle test. Only 31 DBPCsingle tests were positive in patients with positive DBPCmixed challenge. Twenty-four of the 116 patients showing a positive DBPCmixed challenge also had a positive DBPCsingle result. CONCLUSIONS: Our results confirmed that food additive hypersensitivity reactions occurred in few RCIU patients using DBPCsingle challenge. The combination of the results of FAFD and DBPCmixed challenge seems to be of considerable practical interest for allergists, internists and dermatologists, rather than the data of clinical history and the results of DBPCsingle challenge, in patients with RCIU.     

慢性荨麻疹患者幽门螺杆菌检测的意义

目的：研究慢性荨麻疹与幽门螺杆菌（Helicobacter pylori ,HP）感染的相关性,探讨HP检测在慢性荨麻疹患者诊疗中的意义。方法：选取2014年4月至2015年7月门诊治疗的慢性荨麻疹患者420例,并随机选取同期体检中心健康体检者450例为健康对照组,采用胶体金法检测患者及健康体检者血清HP尿素酶抗体,分析慢性荨麻疹组和健康对照组两组HP的阳性情况;同时将162例慢性荨麻疹HP阳性患者分为实验组88例和对照组74例,对照组患者应用常规荨麻疹治疗,实验组患者在对照组治疗基础上增加抗HP三联疗法,分析HP检测阳性的慢性荨麻疹患者采用不同治疗方法的临床疗效。结果：慢性荨麻疹组HP阳性率为38.6%,健康对照组HP阳性率为14.4%,差异有统计学意义（P<0.05）;HP检测阳性患者实验组临床疗效有效率显著高于对照组的有效率,差异有统计学意义（P<0.05）。结论：慢性荨麻疹与HP感染之间存在密切的相关性, HP检测对慢性荨麻疹患者的诊疗具有重要的临床意义。     

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.     

Chronic urticaria: novel clinical and serological aspects

BACKGROUND: Recently, distinct studies have shown that: (a) chronic idiopathic urticaria (CIU) is autoimmune in 30-50% of cases; (b) in patients with CIU the autologous serum skin test is inhibited by heparin; and (c) basophil histamine release induced in vitro by CIU sera maybe complement-dependent. OBJECTIVE: To carry out a comprehensive clinical and serological study on CIU based upon these observations. METHODS: Three hundred and six adults with CIU underwent intradermal (ID) test with autologous serum; 57 of them with autologous heparinized plasma as well. Sera from 121 patients (plasmas from 17) were employed to induce in vitro histamine release from basophils of normal donors. The effects of heating (56 degrees C, 60 min), filtration through membrane, and preincubation with heparin were evaluated as well. RESULTS: Autologous serum and plasma induced a weal and flare reaction in 205 out of 306 (205/306; 67%) and in 8/57 (14%) patients, respectively. Positive plasma skin tests were observed only in patients showing strongly positive serum skin tests. Plasma did not elicit any skin reaction in 3/3 patients with dermatographism who showed a positive intradermal test with saline. Sera from 20/121 (16.5%) patients induced significant histamine release from basophils of normal donors. 19/20 sera were from patients with a positive intradermal test; thus, basophil histamine release assay was positive in 19/87 (21.8%) patients with a positive serum skin test. Heating at 56 degrees C x 1 h markedly reduced the histamine-releasing activity of both serum and plasma from in vitro reactors. Ultrafiltered fractions > 100 kDa of both sera tested retained the histamine-releasing activity, whereas fractions < 100 kDa were not able to induce any histamine release. Heparin dose-dependently inhibited histamine release induced by sera and plasma, and by basophil agonists such as anti-IgE, formyl-methionyl-leucyl-phenilalanine, and interleukin (IL)-3. CONCLUSIONS: 67% of our patients with CIU showed a positive autologous serum skin test. Sera from about 20% of those positive on autologous serum skin test induced histamine release from normal basophils in vitro probably as a consequence of the presence of functional autoantibodies. The marked difference between in vivo and in vitro findings could reflect the existence of a mast cell-specific histamine-releasing factor which does not release histamine from basophils of healthy blood donors. However, it might be also the result of in vivo priming of patients' cutaneous mast cells or of heterogeneity of basophil donors. At least in some cases complement seems essential for histamine-releasing activity of serum from patients with CIU. Heparin inhibits histamine release from both basophils (in vitro) and mast cells (in vivo), probably acting directly at a cellular level.     

EAACI taskforce position paper: evidence for autoimmune urticaria and proposal for defining diagnostic criteria

An autoimmune subset of chronic spontaneous urticaria is increasingly being recognized internationally, based on laboratory and clinical evidence that has accrued over the last 20 years. This evidence has been reviewed by a taskforce of the Dermatology section of the European Academy of Allergy and Clinical Immunology. Functional autoantibodies in chronic urticaria (CU) patient sera have been demonstrated against IgE and FcεRIα by basophil and mast cell histamine release assays and by basophil activation assays. Antibody specificity has been confirmed by immunoassay, but there is a poor correlation between functionality and immunoreactivity. Approximately 25% of CU patients have a positive basophil histamine release assay and show autoreactivity (a positive autologous serum skin test), whereas 50% are negative regarding both. Functionality of CU sera appears to be complement dependent on mast cells but not exclusively on basophils. Basophil activation by CU sera is predominantly restricted to IgG1 and IgG3 subclasses. Circumstantial evidence for CU being an autoimmune disease comes from an observed association with other autoimmune diseases, a strong association between serum functionality and HLA‐DR4 haplotype and the good response of CU patients to immunotherapies. It was proposed that a study should be undertaken to prospectively validate potentially relevant clinical criteria (from the history, examination and routinely available clinical investigations) against a new ‘gold standard’ for the diagnosis of ACU (positive autoreactivity, functional bioassay and immunoassay) to define preliminary criteria sets for the diagnosis of ACU based on clinical and laboratory features with highest individual sensitivity and specificity.     

EAACI/GA2LEN task force consensus report: the autologous serum skin test in urticaria

Injection of autologous serum collected during disease activity from some patients with chronic spontaneous urticaria (CU) into clinically normal skin elicits an immediate weal and flare response. This observation provides a convincing demonstration of a circulating factor or factors that may be relevant to the understanding of the pathogenesis and management of the disease. This test has become known as the autologous serum skin test (ASST) and is now widely practised despite incomplete agreement about its value and meaning, the methodology and the definition of a positive response. It should be regarded as a test for autoreactivity rather than a specific test for autoimmune urticaria. It has only moderate specificity as a marker for functional autoantibodies against IgE or the high affinity IgE receptor (FcεRI), detected by the basophil histamine release assay, but high negative predictive value for CU patients without them. It is usually negative in other patterns of CU, including those that are physically induced. Positive ASSTs have been reported in some subjects without CU, including those with multiple drug intolerance, patients with respiratory allergy and healthy controls, although the clinical implications of this are uncertain. It is essential that failsafe precautions are taken to ensure that the patient's own serum is used for skin testing and aseptic procedures are followed for sample preparation and handling. CU patients with a positive ASST (ASST⁺) are more likely to be associated with HLADR4, to have autoimmune thyroid disease, a more prolonged disease course and may be less responsive to H1-antihistamine treatment than those with a negative ASST (ASST⁻) although more evidence is needed to confirm these observations conclusively.