Detection and Analysis of Commonly Used Infection Indicators in Patients with Acute Urticaria.

INTRODUCTION: In this study, we investigated the correlation and clinical significance of peripheral blood leukocytes, neutrophils, C-reactive protein (CRP), and procalcitonin (PCT) in patients with acute urticaria. METHODS: Complete blood count with differential, CRP, and PCT tests were conducted on patients with acute urticaria. A total of 614 patients with acute urticaria were divided into three groups: the first group consisted of patients with elevated leukocyte and neutrophil count, the second group consisted of patients with normal leukocyte and neutrophil count, and the third group consisted of patients with abnormal leukocyte and neutrophil count. A correlation analysis was conducted to investigate the levels of leukocytes, neutrophils, CRP, and PCT in the three groups. RESULTS: The results of Kruskal-Wallis' nonparametric test revealed statistically significant variations in leukocytes, neutrophils, CRP, and PCT among the three groups (p < 0.001). However, CRP and PCT showed no statistically significant differences between the second and third groups (p < 0.001, p = 0.0041, p = 0.0032). Additional multiple comparisons in Spearman correlation analysis indicated statistically significant differences (p = 0.55). Across all groups, there was a statistically significant difference in the correlation between CRP-PCT and leukocytes-neutrophils (p = 0.53). CONCLUSION: Leukocytes and neutrophils are sensitive to the impact of medications and stress on the body. Combining CRP and PCT, as well as routine blood test, may be a comprehensive assessment of infection presence and severity in patients, providing guidance for antibiotic treatment.

The Alarmin Triad-IL-25, IL-33, and TSLP-Serum Levels and Their Clinical Implications in Chronic Spontaneous Urticaria.

This study delves into the critical role of alarmins in chronic spontaneous urticaria (CSU), focusing on their impact on disease severity and the quality of life (QoL) of patients. We investigated the alterations in alarmin levels in CSU patients and their correlations with the Urticaria Activity Score (UAS7) and the Dermatology Life Quality Index (DLQI). We analyzed serum levels of interleukin-25 (IL-25), interleukin-33 (IL-33), and thymic stromal lymphopoietin (TSLP) in 50 CSU patients, comparing these to 38 healthy controls. The study examined the relationship between alarmin levels and clinical outcomes, including disease severity and QoL. Elevated levels of IL-33 and TSLP in CSU patients (p < 0.0001) highlight their potential role in CSU pathogenesis. Although IL-25 showed higher levels in CSU patients, this did not reach statistical significance (p = 0.0823). Crucially, IL-33's correlation with both UAS7 and DLQI scores underscores its potential as a biomarker for CSU diagnosis and severity assessment. Of the alarmins analyzed, IL-33 emerges as particularly significant for further exploration as a diagnostic and prognostic biomarker in CSU. Its substantial correlation with disease severity and impact on QoL makes it a compelling candidate for future research, potentially serving as a target for therapeutic interventions. Given these findings, IL-33 deserves additional investigation to confirm its role and effectiveness as a biomarker and therapeutic target in CSU.

miR-126-3p and miR-16-5p as novel serum biomarkers for disease activity and treatment response in symptomatic dermographism.

Symptomatic dermographism (SD) is the most common form of physical urticaria. So far no promising serum biomarkers for SD have been reported. Recently, microRNAs (miRNAs) have been reported to be serum biomarkers for chronic spontaneous urticaria. However, association of miRNAs with SD remains unclear. We enrolled 55 SD patients and 52 healthy controls in this study. We found that serum expressions of miR-126-3p and miR-16-5p were significantly downregulated in active SD patients and upregulated in remission. The area under the curve values of miR-126-3p (0.769) and miR-16-5p (0.789) showed significant ability to diagnostic SD. Serum level of vascular endothelial growth factor (VEGF)-A, a known target of the two miRNAs, was significantly increased in active SD patients and decreased in remission. Moreover, serum VEGF-A level was inversely correlated with expressions of miR-126-3p and miR-16-5p. Our findings indicate that miR-126-3p and miR-16-5p can serve as potential serum biomarkers for SD.

Hereditary alpha-tryptasemia in 101 patients with mast cell activation-related symptomatology including anaphylaxis.

BACKGROUND: Hereditary alpha-tryptasemia (HαT) is an autosomal dominant genetic trait characterized by multiple copies of the alpha-tryptase gene at the TPSAB1 locus. Previously described symptomatology involves multiple organ systems and anaphylaxis. The spectrum of mast cell activation symptoms is unknown, as is its association with specific genotypes. OBJECTIVE: To describe clinical, laboratory, and genetic characteristics of patients referred for the evaluation of mast cell activation-related symptoms and genotype-confirmed HαT. METHODS: We retrospectively describe clinical characteristics, baseline tryptase, and tryptase genotype in 101 patients. Patients were referred for mast cell activation-related symptoms and underwent genotyping to confirm diagnosis of HαT. RESULTS: Of 101 patients, 80% were female with average tryptase of 17.2 ng/mL. Tryptase was less than 11.4 ng/mL in 8.9% and greater than 20 ng/mL in 22.3% (range 6.2-51.3 ng/mL). KIT D816V mutation was negative in all subjects tested. 2α:3ß was the most common genotype but did not correlate with tryptase levels. Unprovoked anaphylaxis was noted in 57% of the subjects with heterogeneous genotypes. Most common symptoms include gastrointestinal, cutaneous, psychiatric, pulmonary, cardiovascular, and neurologic. A total of 85% of patients were taking H1- or H2-antihistamines with partial symptom relief. Omalizumab was effective at suppressing anaphylaxis or urticaria in 94% of the patients. CONCLUSION: HαT encompasses a broad range of baseline tryptase and should be considered in patients with symptoms of mast cell activation and tryptase levels greater than 6.2 ng/mL. Patients may present with complex symptomatology including cutaneous, gastrointestinal, neurologic, and psychiatric symptoms and anaphylaxis, some of which respond to omalizumab.

D-dimer concentrations in acute urticaria in children.

INTRODUCTION: Urticaria is a clinical entity presenting as wheals, angioedema, or both simultaneously. Elevated D-dimer levels were reported in the course of chronic spontaneous urticaria. Data regarding D-dimer levels in acute urticaria in children are limited. OBJECTIVES: To assess potential associations between duration of glucocorticosteroid (GCS) therapy and D-dimer concentrations in children with acute urticaria. PATIENTS, MATERIALS, AND METHODS: Hospital records of 106 children (59 females), aged 5.57 ± 4.91 years, hospitalized in 2014-2018 were analyzed retrospectively. The study group consisted of pediatric patients admitted to the hospital due to severe acute urticaria resistant to antihistaminic treatment that was ordered in the ambulatory care (out-patient clinic). Patients were divided into subgroups: no GCS treatment, short-duration treatment (up to 5 days) and long-duration treatment (6 and more days) GCS treatment. Simultaneously, patients received antihistaminic drugs. D-dimer level and other inflammatory factors such as white blood cell (WBC) count, platelet (PLT) count, and C-reactive protein (CRP) in each group were analyzed. RESULTS: The D-dimer level was elevated in 51% of cases. In the subgroup with longer GCS treatment, D-dimer concentration was significantly higher in comparison to patients with a shorter GCS course. There were no differences in the distribution of CRP, PLT, and WBC concentrations between these subgroups. CONCLUSIONS: In the studied group of children, there was a tendency for higher D-dimer levels in patients, who required a longer GCS treatment. This finding is hypothesis-generating and requires further investigation to confirm if D-dimers can be used as a prognostic factor in acute urticaria in children.

Correlations between disease activity, autoimmunity and biological parameters in patients with chronic spontaneous urticaria.

Summary: Background. Biomarkers of disease activity/severity and criteria of autoimmune chronic spontaneous urticaria (CSU) are still a matter of debate. Objective. To investigate possible correlations between clinical and biological markers and their associations with: 1) disease activity, 2) resistance to H1-antihistamines, 3) autoimmunity and 4) autologous serum skin test (ASST) in patients with CSU. To also analyze biological parameter modifications in patients with CSU treated with omalizumab. Materials and methods. Disease activity, H1-antihistamines response and presence of concomitant autoimmune disease were prospectively recorded in 95 patients with CSU. For 60 of them, ASST was performed. Broad biological analysis were performed. Results. C-reactive protein (CRP) serum levels were higher in H1-antihistamines unresponders (p less-than 0.0001) and in more active diseases (p = 0.033). D-dimer plasma levels were higher in H1-antihistamines unresponders (p = 0.008) and in patients with autoimmune status (concomitant autoimmune disease and/or with autoantibodies) (p = 0.016). Total immunoglobuline E (IgE) serum level was lower in patients with positive ASST. Blood basophil counts were lower in patients with CSU and especially in H1-antihistamines unresponders (p = 0.023), in patients with more active disease (p = 0.023), with positive ASST (p = 0.001), and with autoimmune status (p = 0.057). Conversely, under omalizumab, a decrease of CRP (p = 0.0038) and D-dimer serum/plasma levels (p = 0.0002) and an increase of blood basophil counts (p = 0.0023) and total IgE serum levels (p = 0.0007) were observed. Conclusions. This study brings additional evidences of interest to investigate IgE, D-dimer serum/plasma levels and basophil blood counts in patients with CSU as they could be correlated to disease activity, response to treatment and/or autoimmunity.

Characteristics of patients with bullous pemphigoid: comparison of classic bullous pemphigoid to non-bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is the most common subepidermal autoimmune blistering disease. Patients occasionally present with a clinical picture of pruritus/urticaria alone for months and do not even develop blisters over time. Only few studies have investigated this subgroup of non-bullous pemphigoid (NBP). OBJECTIVE: To evaluate the demographic and clinical characteristics of BP patients with or without blisters at the time of diagnosis. METHODS: A retrospective study based on the medical records of 115 BP patients. Collected data included demographic characteristics, clinical presentation, treatment and response to treatment. RESULTS: Thirty-six patients presented with pruritus/urticaria (31.3%), and 79 presented with blisters (68.7%), with mean ages of 77.5 and 76.0, respectively, at diagnosis and an equal female:male ratio. The level of immunoglobulin E (IgE) was 4.1 times higher, and the mean blood eosinophil count was significantly increased in the pruritus/urticaria group. Remission rate at 3 months and relapse rate were similar between the groups. Median follow-up period was 9 months (range 3-18). Only 23% of the patients with pruritus/urticaria developed blisters. CONCLUSIONS: A significant number of BP patients present without blisters. We found no significant epidemiological or clinical differences from the classic BP patients aside from significantly elevated IgE and blood eosinophil levels. Similar results in larger cohort studies might be the foundation for a change in clinical protocols regarding the diagnosis and recommended treatment for the elderly presenting with pruritus/urticaria only.

Is vitamin D concentration an indicator of the severity of atopic dermatitis and chronic spontaneous urticaria in adults?

Atopic dermatitis (AD) and chronic spontaneous urticaria (CSU) are common chronic and recurrent dermatoses. The role of vitamin D in the immunological processes, including the development of inflammation, has been the subject of numerous studies. The feasible measurement of vitamin D serum concentration and possibly supplementation necessitates the assessment of its impact on the clinical severity of mentioned diseases. AIM: The aim of the study was to determine the relationship between blood serum vitamin D concentration and the severity of clinical symptoms in the group of adults suffering from AD or CSU. MATERIALS AND METHODS: The study was conducted in 2018 on groups of patients suffering from AD or CSU. Serum vitamin D concentration was determined by electrochemiluminescence assay. Student's t-test was adopted to compare vitamin D levels between groups. Spearman's rank correlation coefficient was used to assess the correlation between vitamin D concentration and the severity of AD (according to the SCORAD scale) and CSU (according to the UAS 7 scale). RESULTS: There was not found any statistically significant relationship between the severity of skin lesions scores in the course of AD and CSU and serum vitamin D concentration.

Vibratory Urticaria Associated with a Missense Variant in ADGRE2.

Patients with autosomal dominant vibratory urticaria have localized hives and systemic manifestations in response to dermal vibration, with coincident degranulation of mast cells and increased histamine levels in serum. We identified a previously unknown missense substitution in ADGRE2 (also known as EMR2), which was predicted to result in the replacement of cysteine with tyrosine at amino acid position 492 (p.C492Y), as the only nonsynonymous variant cosegregating with vibratory urticaria in two large kindreds. The ADGRE2 receptor undergoes autocatalytic cleavage, producing an extracellular subunit that noncovalently binds a transmembrane subunit. We showed that the variant probably destabilizes an autoinhibitory subunit interaction, sensitizing mast cells to IgE-independent vibration-induced degranulation. (Funded by the National Institutes of Health.).

Serum miR-125a-5p and CCL17 Upregulated in Chronic Spontaneous Urticaria and Correlated with Treatment Response.

Chronic spontaneous urticaria (CSU) is a common skin disorder associated with autoimmunity. MicroRNAs (miRNAs) are endogenous noncoding RNA molecules reported to be potential biomarkers for some autoimmune diseases. In this study, we investigated the association of miRNAs with CSU. A quantitative PCR (qPCR)-based array was generated from sera as obtained from 20 active CSU patients and 20 healthy controls. Upregulated or downregulated miRNAs were validated by reverse transcription qPCR in sera from 59 active CSU patients and 58 healthy controls. The expression of miR-125a-5p was significantly upregulated in CSU sera and serum levels of CCL17 were also significantly increased in CSU patients. Serum miR-125a-5p expressions were found to be further upregulated in refractory CSU cases (n = 10). In 12 CSU patients in remission, serum miR-125a-5p expression and CCL17 levels were significantly decreased as compared with that obtained in active phase patients. These results indicated that miR-125a-5p and CCL17 can serve as potential serum biomarkers for CSU.

Predictors of response to omalizumab and relapse in chronic spontaneous urticaria: a study of 470 patients.

BACKGROUND: Chronic spontaneous urticaria (CSU) is defined as spontaneous occurrence of wheals and/or angioedema for ≥6 weeks. Omalizumab is a monoclonal anti-IgE antibody effective in refractory CSU, but its mechanism of action and markers predictive of response remain not completely defined. OBJECTIVES: To correlate baseline levels of two proposed biomarkers, total IgE (bIgE) and d-dimer (bd-dimer), and clinical parameters to omalizumab response and to relapses after drug withdrawal. METHODS: In this retrospective Italian multicentre study, clinical data were collected in 470 CSU patients, and bIgE and bd-dimer were measured in 340 and 342 patients, respectively. Disease activity was determined by Urticaria Activity Score 7 (UAS7) at week 1 and 12 after omalizumab starting. Relapses were evaluated during a 2- and 3-month interval after a first and a second course of treatment, respectively. RESULTS: bIgE correlated to a good response to omalizumab since levels were significantly higher in responders than non-responders (P = 0.0002). Conversely, bd-dimer did not correlate to response. There was no correlation between both bIgE and d-dimer and either first or second relapse. Disease duration was significantly longer in patients who experienced either first or second relapse (P < 0.0001 and P = 0.0105, respectively), while baseline UAS7 correlated only to first relapse (P = 0.0023). CONCLUSIONS: Our study confirms bIgE as a reliable biomarker predicting response to omalizumab in CSU, while it does not support the usefulness of bd-dimer unlike previous findings. CSU duration before omalizumab and baseline UAS7 may be clinical markers of relapse risk.

IL-24 is a common and specific autoantigen of IgE in patients with chronic spontaneous urticaria.

BACKGROUND: The efficacy of omalizumab (anti-IgE) and increased IgE levels in patients with chronic spontaneous urticaria (CSU) suggest autoallergic mechanisms. OBJECTIVE: We sought to identify autoallergic targets of IgE in patients with CSU. METHODS: Serum samples of patients with CSU together with those of patients with idiopathic anaphylaxis and healthy control subjects (7 of each) were screened for IgE autoantibodies by using an array of more than 9000 proteins. Sera of 1062 patients with CSU and 482 healthy control subjects were used in an IgE-anti-IL-24-specific ELISA to investigate the association of IgE-anti-IL-24 and CSU. RESULTS: By using array analyses, more than 200 IgE autoantigens were found in patients with CSU that were not found in control subjects. Of the 31 IgE autoantigens detected in more than 70% of patients, 8 were soluble or membrane bound and expressed in the skin. Of these, only IgE autoantibodies to IL-24 were found in all patients with CSU. In vitro studies showed IL-24 to release histamine from human mast cells sensitized with purified IgE of patients with CSU but not control subjects. By using ELISA, mean ± SD levels of IgE-anti-IL-24 were 0.52 ± 0.24 IU/mL in patients with CSU and 0.27 ± 0.08 IU/mL in control subjects, with 80% of patients with CSU but only 20% of control subjects having levels greater than 0.33 IU/mL (P < .0001). IgE-anti-IL-24 showed acceptable predictive properties for CSU, with a likelihood ratio of 3.9. Clinically, IgE-anti-IL-24 levels showed an association with disease activity, as assessed by the urticaria activity score and with reduced basophil counts. CONCLUSION: Our findings show that patients with CSU frequently exhibit IgE autoantibodies against many autoantigens and that IL-24 is a common, specific, and functional autoantigen of IgE antibodies in patients with CSU.

The effect of omalizumab on hematological and inflammatory parameters in patients with chronic spontaneous urticaria.

PURPOSE: The mechanism of action of omalizumab in chronic spontaneous urticaria (CSU) is not exactly known. In previous studies, d-dimer which is a fibrin-degradation product and interleukin-31 which has a role in inflammation were found to be decreased in patients with chronic urticaria treated with omalizumab. However, to our knowledge, there is no study on the effects of omalizumab on the ratio of neutrophil to lymphocyte (NLR) and the ratio of platelet to lymphocyte (PLR) which are inflammatory parameters in patients with CSU in the PubMed database. In this study, we aimed to evaluate the effects of omalizumab on hematological and inflammatory parameters in patients with CSU. MATERIALS AND METHODS: One hundred six CSU patients treated with omalizumab were evaluated retrospectively. Complete blood count (CBC) and C-reactive protein (CRP) levels before treatment and at the third month of treatment were recorded. NLR and PLR were calculated from the CBC results. CBC parameters, CRP levels, NLR and PLR of the patients before treatment and at the end of third month of treatment were compared. RESULTS: There was a significant decrease in white blood cell count, platelet count, neutrophil count, CRP level, NLR and PLR and a significant increase in mean platelet volume and eosinophil count with omalizumab treatment in CSU patients (p < 0.05). Basophil count increased; but there was no statistically significant difference (p = 0.293). CONCLUSION: This study shows that omalizumab has not only anti Ig E effect, but also it may have inhibitory effects on inflammation and coagulation in patients with CSU. Further prospective studies are warranted in order to evaluate the effect of omalizumab on hematological and inflammatory parameters and correlation between omalizumab response rate and these inflammatory parameters in patients with CSU.

Epidemiology of hypocomplementaemic urticarial vasculitis (anti-C1q vasculitis).

Objectives: The aim was to describe the clinical characteristics and epidemiology of hypocomplementaemic urticarial vasculitis (HUV; anti-C1q vasculitis) in two geographically defined areas of Sweden. Methods: In the health-care districts surrounding Skåne University Hospital (mean population 950 560) and Linköping University Hospital (mean population 428 503), all incident cases of HUV residing within the study areas at the onset of disease were identified during the years 2000-15. The diagnosis of HUV was confirmed by review of medical records. Only patients meeting the proposed diagnostic HUV criteria and/or the 2012 Chapel Hill consensus definitions in combination with an ever-positive anti-C1q antibody test were included. Results: Sixteen patients (14 females) were identified during the study period. The median (interquartile range) age at diagnosis was 51 (40.7-56.7) years. Median (interquartile range) time of follow-up from diagnosis to 31 December 2015, or death, was 94 (46.5-136.2) months. The most frequent manifestations at diagnosis were urticaria (100%), arthritis (88%), followed by biopsy-proven glomerulonephritis (19%), episcleritis/scleritis (19%) and recurrent abdominal pain (13%). The annual incidence rate per million inhabitants was estimated as 0.7 (95% CI: 0.4, 1.1). Sixty-three per cent suffered from pulmonary disease at the last follow-up. Two patients died during the follow-up period. One patient underwent lung transplantation, and two patients proceeded to end-stage renal disease. The point prevalence on 31 December 2015 was 9.5/million (95% CI: 4.5, 14.5). Conclusion: Hypocomplementaemic urticarial vasculitis constitutes a rare, but not always benign condition. Renal and lung manifestations were severe in some cases, highlighting the need for careful screening and monitoring of this potentially serious condition.

The clinical response to omalizumab in chronic spontaneous urticaria patients is linked to and predicted by IgE levels and their change.

BACKGROUND: Omalizumab is an effective and well-tolerated treatment for chronic spontaneous urticaria (CSU). Markers and predictors of response are largely unknown, but needed to optimize omalizumab treatment. Omalizumab targets IgE, and IgE levels may be linked to the effects of treatment. We evaluated whether response rates to treatment with omalizumab in patients with CSU are linked to their baseline IgE levels, their IgE levels after omalizumab treatment, and the ratio of on treatment IgE and baseline IgE levels. METHODS: Chronic spontaneous urticaria (CSU) patients (n = 113) were treated with omalizumab 300 mg/4 weeks for 12 weeks, when their treatment responses, that is, no, partial, or complete response, were assessed by use of the urticaria activity score, physician and patient visual analog scale, and treatment effectiveness score. Total IgE levels were measured before treatment (bIgE) with omalizumab and 4 weeks thereafter (w4IgE). RESULTS: Nonresponders to omalizumab had significantly lower bIgE levels (17.9, 17.0-55.0 IU/mL) than partial responders (82.0, 46.2-126.5 IU/mL, P = .008) and complete responders (73.7, 19.45-153.8 IU/mL, P = .032). Nonresponders also had lower w4IgE levels and lower ratios of w4IgE/bIgE levels than partial and complete responders (P < .001). Nonresponse to omalizumab was best predicted by patients' w4IgE/bIgE ratios, significantly better than by bIgE levels (P = .016). CONCLUSIONS: In CSU, total IgE levels and their change predict the response to treatment with omalizumab. The assessment of pre- and post-treatment IgE levels and their ratio may help to improve the management of CSU in patients who require omalizumab treatment.

C-reactive protein is linked to disease activity, impact, and response to treatment in patients with chronic spontaneous urticaria.

BACKGROUND: Elevated levels of C-reactive protein (CRP), a sensitive marker of inflammation, have been consistently reported in chronic spontaneous urticaria (CSU). Here, we retrospectively analyzed data from 1253 CSU patients from 2 centers to answer the following questions: (i) What is the prevalence of elevated levels of CRP in CSU? (ii) Why do CSU patients show elevated levels of CRP? (iii) Are elevated CRP levels relevant? METHODS: Serum levels of CRP were measured by the nephelometric method. We collected information regarding various laboratory tests including ESR, CBC with differential, D-dimer, fibrinogen, C3, C4, IL-6, etc. For most patients, we also collected data on age, gender, duration of CSU, presence of angioedema, activity (UAS at the time of blood sampling and for 7 days), quality of life (CU-Q2oL and/or DLQI), comorbidities and possible causes of CSU, and autologous serum skin test (ASST) response. The efficacy of second-generation antihistamines was evaluated on the day of blood collecting. RESULTS: One-third of CSU patients had elevated levels of CRP. Higher levels of CRP were associated with ASST positivity (P = .009) and arterial hypertension (P = .005), but not with other possible causes or comorbidities of CSU. C-reactive protein correlated with urticaria activity (P < .001), quality of life impairment (P = .026), and inflammatory and coagulation markers (P < .001). C-reactive protein levels were significantly higher in nonresponders to antihistamines as compared to responders (P < .001). CONCLUSION: Elevated levels of CRP are common and relevant in CSU patients. The assessment of CRP levels may help to optimize the management of patients with CSU.

In chronic spontaneous urticaria, IgE against staphylococcal enterotoxins is common and functional.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a frequent disorder with recurrent itchy wheals and/or angioedema. Despite the known effectiveness of omalizumab therapy, the relevant IgE antigens are largely unknown. Recently, increased rates of elevated levels of IgE towards Staphylococcus aureus enterotoxins (SEs) were described in CSU. AIM: To assess the prevalence and functional relevance of IgE to SEs in CSU. METHOD: We investigated serum levels of IgE against SEs in 49 CSU patients and in 15 CSU patients additional specific IgE to SE components and basophil histamine release (BHR). Sera of 15 healthy controls (HCs) served as control group. RESULTS: Twenty-five (51%) of the CSU patients had detectable levels of SE-IgE as compared to 5 (33%) of HCs. Specific IgE to one of the SEs, Staphylococcus enterotoxin B (SEB), was present in 5 (33%) of 15 randomly selected CSU patients vs 3 (20%) of HC. Total IgE serum levels in CSU patients were significantly correlated with SE-IgE (r = .52, P < .001) and SEB-IgE (r = .54, P = .04) serum concentrations. Interestingly, SEB-IgE levels were strongly correlated with disease activity (UASday) in CSU patients (r = .657, P = .01). Furthermore, BHR in response to SEB was significantly higher in basophils loaded with the serum of CSU patients compared to HC (P < .05) and was clinically correlated with duration of disease (r > .51, P < .05). DISCUSSION: IgE against SEs may contribute to the pathogenesis of CSU in a subpopulation of patients. Its role and relevance in the pathophysiology of CSU need to be further analysed.

Eosinophils are a Major Source of Interleukin-31 in Bullous Pemphigoid.

Bullous pemphigoid (BP) is characterized by substantial skin and blood eosinophilia as well as intensive pruritus. Since the pruritogenic cytokine interleukin (IL)-31 is increased in inflammatory skin diseases the aim of this study was to determine whether IL-31 plays a role in BP. Using immunofluorescence, IL-31 expression was analysed in eosinophils derived from blister fluids and skin from patients with BP and IL-31 levels in blister fluids, serum and culture supernatants were determined by enzyme-linked immunoassay (ELISA). High levels of IL-31 expression were observed in BP blister fluids, but they were only marginally elevated in BP serum compared with healthy controls. Eosinophils from either BP blister fluids or skin biopsies showed strong expression of IL-31. Furthermore, peripheral blood eosinophils from patients with BP, but not healthy controls, released high levels of IL-31, reflecting those in blister fluids. In conclusion, eosinophils are a major source of IL-31 in BP and this cytokine may contribute to itch in patients with BP.

Hyperlipidemia in association with pro-inflammatory cytokines among chronic spontaneous urticaria: case-control study.

Summary: Chronic spontaneous urticaria (CSU) is a disorder characterized by recurrent transient itchy wheels of 6 weeks duration or longer. The cause cannot be pinpointed in about 40% of patients. To elucidate the possible association between CSU and hyperlipidemia, 40 CSU patients and 40 group matched healthy individuals were assessed for hyperlipidemia. Data on history, urticaria activity score (UAS-7), physical examination and routine laboratory investigations including (serum IL6 and TNF α) were recorded. Statistically significant increase of serum cholesterol, triglycerides (TG), low density lipoprotein (LDL), IL6, TNFα and decrease of high density lipoprotein (HDL) was found in CSU in comparison to control group. Regarding the different disease variables, both TG and cholesterol were positively correlated with duration of illness, urticaria score and TNF α. Serum LDL detected significant had a positive correlation with duration of illness, urticaria score, CRP and TNF α, while serum HDL detected had a significant negative correlation with TNF α. IL6 and TNFα associated systemic inflammation could be a common pathogenic mechanism of CSU and hyperlipidemia. Patients with CSU should be evaluated for hyperlipidemia.

Chronic spontaneous urticaria and the extrinsic coagulation system.

Chronic spontaneous urticaria (CSU) is a common skin disorder characterized by daily or almost daily recurring skin edema and flare with itch. Recently, the activation of the blood coagulation cascade has been suggested to be involved in CSU, but the trigger of the coagulation cascade remains unclear. In this article, we review recent understanding of the relationship between the pathogenesis of CSU and extrinsic coagulation reactions. In CSU, vascular endothelial cells and eosinophils may play a role as TF-expressing cells for activating the extrinsic coagulation pathway. Moreover, the expression of TF on endothelial cells is synergistically enhanced by the activation of Toll-like receptors and histamine H1 receptors. The activated coagulation factors may induce plasma extravasation followed by degranulation of skin mast cells and edema formation recognized as wheal in CSU. Molecules involved in this cascade could be a target for new and more effective treatments of urticaria.