Acute-phase response in chronic urticaria

The patterns of acute-phase response (APR) biomarkers differ upon various inflammatory conditions. Little information is available on the systemic inflammatory response in urticaria/angio-oedema. It has been shown that concentrations of circulating APR biomarkers, IL-6 and C-reactive protein (CRP), are elevated more in severe chronic urticaria (CU) than in patients showing milder urticarial symptoms. It is not clear whether the increase of IL-6 and CRP is merely an epiphenomenon or may contribute to the pathogenesis of CU. It is tempting to speculate that mediators of APR may enhance urticarial inflammation. In addition, there is some association between APR and activation of coagulation/fibrinolysis in CU. It is well known that even slight elevation in CRP baseline concentration is enough to produce significant increase in cardiovascular risk. In this light, one should ask whether CU patients, in particular those showing stronger systemic inflammatory response and long-lasting course are more vulnerable to the cardiovascular events. Apart from highly troublesome symptoms and low quality of life, CU may then involve some remote, serious systemic consequences. Taken together, CU can be identified as a mast cell- and basophil-dependent inflammatory disorder of the skin, which is accompanied by APR. Characterization of APR in CU may appear essential for an insight into the activity of this disease and for assessment of the inflammation degree. Moreover, measurement of these biomarkers might be particularly relevant while assessing CU patients demanding an anti-inflammatory or immunosuppressive therapy. This review summarizes information regarding APR in the course of urticaria/angio-oedema.     

幽门螺杆菌与慢性荨麻疹

为探讨幽门螺杆菌（HP）感染在慢性荨麻疹中的作用，采用^13尿素呼吸试验对28例慢性荨麻疹患者及25名健康对照进行HP检测。结果显示：28例荨麻疹患者中19例HP阳性（68％）；25名健康对照中15例HP阳性（60％）。分别对慢性荨麻疹组及健康对照组中的HP阳性者应用根除HP感染治疗方案，停药6周后，慢性荨麻疹组有17例HP转阴，3例荨麻疹有好转，其余症状和体征均未改善。提示HP感染与慢性荨麻疹发生无明显关系。     

荨麻疹患者外周血CRTH2阳性细胞的研究

目的:研究荨麻疹患者外周血中表达于Th2细胞上的化学诱导趋向性受体(CRTH2) 细胞的变化和嗜碱性粒细胞的活化率.评价嗜碱性粒细胞在慢性荨麻疹发病中的作用.方法:采用流式细胞仪,以CRTH2/CD4/CD63抗体组合,检测正常人及急、慢性荨麻疹患者治疗前和部分慢性荨麻疹患者口服氯雷他定治疗28 d后外周血中CRTH2 胞以及嗜碱性粒细胞的活化率.结果:荨麻疹患者外周血中的CRTH2t细胞较正常人显著降低,急性患者尤为明显;但其中CRTH2 CD4-的嗜碱性粒细胞却较正常人显著增高,慢性荨麻疹患者更为明显;荨麻疹患者的嗜碱性粒细胞活化率显著增高,而急、慢性患者相似;氯雷他定治疗对以上指标无显著影响.结论:慢性荨麻疹反复发作与患者外周血嗜碱性粒细胞水平的持续增高有关.     

Impact of chronic urticaria on systemic lupus erythematosus: A nationwide population‐based study in Taiwan

Chronic urticaria (CU) may be closely pathogenically related to systemic lupus erythematosus (SLE). This study aims to investigate the association between CU and SLE patients in Taiwan. A nationwide population‐based cohort study from 1997 to 2013 was conducted. Investigated subjects were selected from the Taiwan National Health Insurance Research Database using the International Classification of Disease, Ninth Revision code. Participants consisted of 13 845 subjects newly diagnosed with CU from 2003 to 2013. We estimated the incidence risk of SLE among patients with CU by time‐to‐event analysis. Patients with CU were more likely to be female, and had a significant difference in urbanization and length of hospital stays (P < 0.0001). The incidence rates of SLE for the CU and control groups were 3.55 and 1.68, respectively. The crude hazard ratio of SLE among subjects with CU was 2.113 compared with the non‐urticarial control group. After adjusting the demographic, length of hospital stay and comorbidity, the adjusted hazard ratio (aHR) of SLE was still significantly higher in the CU group (aHR = 2.113) compared with the control group. The use of non‐steroidal anti‐inflammatory drugs or corticosteroids may decrease the risk of SLE in patients with CU (P = 0.0216 and 0.0120, respectively). In conclusion, CU is associated with a higher risk of incidental SLE in this population‐based, nationwide, cohort study. Inflammation and immune dysregulation are considered two potential mechanisms. Clinically, patients with urticaria should be carefully evaluated for risk of future SLE.     

Prevalence and relevance of the positivity of skin prick testing in patients with chronic urticaria

Many patients with chronic urticaria (CU) worry that foods or other allergens are responsible for their urticaria. Skin prick testing (SPT) may be one of the investigations used to provide a clear illustration. The purpose of our study was to assess the prevalence of positivity of SPT to food allergens and aeroallergens and their relevance in patients with CU, in order to demonstrate the diagnostic value of SPT in CU. We retrospectively reviewed case record forms of patients with chronic ordinary urticaria who underwent SPT in the Urticaria Clinic, Siriraj Hospital, during the period 2000-2004. The studied allergens included 16 food allergens and 12 aeroallergens. Eighty-eight patients were enrolled. The prevalence of positive SPT among patients with CU was 47.7%. Patients who had personal histories of atopy had statistically significant positive SPT results compared with patients who had negative SPT. Of 88 patients, 26 patients (30%) gave positive results to food allergens, 36 patients (41%) gave positive results to aeroallergens and 20 patients (22.7%) gave positive results to both food and aeroallergens. One-third of the subjects (34.6%) who had positive SPT results to food allergens had clinical relevance of food allergy in some systems but only one patient had clinical relevance of food-induced urticaria. Half of the patients who had a history of aeroallergen sensitivity gave a positive SPT response for aeroallergens; however, there was no clinical relevance to their CU. Our study showed that the prevalence of positive SPT to food allergens and aeroallergens in patients with CU was common but had little clinical relevance to CU.     

Epidemiology of urticaria: a representative cross-sectional population survey

Aim. To investigate the prevalence of urticaria with a focus on chronic urticaria (CU) in a general German population. Methods. A questionnaire survey was sent to a representative cross-sectional sample of 13 300 inhabitants of Berlin, Germany, of whom 4093 responded. All respondents who stated ever having had weals or angio-oedema (n = 767) were interviewed by telephone. Any interviewees with recent symptoms (within the previous 3 years) were invited for personal investigation including allergy tests; double-blind, placebo-controlled food challenge tests; and quality of life (QOL) assessment. Reported prevalence rates were weighted with regard to age, gender and education so that they were representative of the total population of Berlin. Results. Lifetime prevalence rate of urticaria was 8.8% (95% CI 7.9–9.7%) for all types of urticaria. Lifetime prevalence for CU was 1.8% (95% CI 1.4–2.3%), and prevalence for the 12 months before assessment was 0.8% (95% CI 0.6–1.1%), and 70.3% were female. QOL was markedly reduced for people with CU. Unlike other allergic diseases, there was no increased risk associated with higher education or social status. Prick tests found sensitization of ≥ 1 for type 1 allergens in 39.1% of patients. These were related to comorbidities such as allergic rhinitis or oral allergy syndrome, but were never the underlying cause of CU, as proven by double-blind, placebo-controlled provocation tests. Conclusion. Urticaria is a common disease with marked effects on QOL. The lifetime prevalence of 8.8% for urticaria must be regarded as a lower limit as it is based on conservative prevalence rate calculations, and under-reporting of previous disease can be expected in a questionnaire-based study.     

Chronic urticaria is associated with a differential helminth-arthropod-related atopy phenotype

The relationship between atopic sensitization and chronic urticaria is still controversial. In this study, we aimed to compare the prevalence of aeroallergen sensitization in chronic urticaria patients with (CU/As+) and without (CU/As-) sensitization against Anisakis simplex. Forty-nine CU/As+ and 80 CU/As- patients were studied and skin prick tests (SPT) were performed against aeroallergens. We assessed sensitization in a subgroup of patients with allergic rhinoconjunctivitis and/or bronchial asthma (RCBA) and compared the prevalence with a control group of 522 non-urticaria patients with RCBA. Forty-five percent of CU/As- and 60.4% of CU/As+ patients displayed positive SPT to at least one aeroallergen. CU/As+ patients had a higher prevalence of sensitization against pollen, mould or dander (PMD) (52.2% vs 29.1%, P < 0.01), whereas the prevalence of house dust mite (HDM) sensitization was not statistically different (26.3% in CU/As- and 36.7% in CU/As+). However, in chronic urticaria patients with RCBA, 53.8% of CU/As- and 57.9% of CU/As+ patients differed in the prevalence of HDM sensitization compared to the control group (33.5%, P = 0.03), whereas no difference could be stated for PMD sensitization. Compared to RCBA patients, both CU/As+ and CU/As- patients have a higher clinically relevant sensitization rate against HDM, thus displaying a differential atopy phenotype.     

Chronic idiopathic urticaria: prevalence and clinical course

The purpose of our study was to assess the prevalence and clinical course of patients with chronic idiopathic urticaria (CIU), as well as possible causes or associated findings, laboratory findings and the duration of the disease in patients with chronic urticaria (CU). We retrospectively reviewed the 450 case record forms of patients with CU and/or angioedema who attended the Department of Dermatology, Siriraj Hospital, during the period 2000-2004. Of 450 patients with CU, 337 patients (75%) were diagnosed as CIU. Forty-three patients (9.5%) had physical urticaria, while 17 patients (3.8%) had infectious causes. Other possible causes were food, thyroid diseases, atopy, drugs, dyspepsia and collagen vascular diseases. In eighty-nine percent of patients, no abnormalities were detected at the time of physical examination. The most common abnormal laboratory finding was minimal elevation of the erythrocyte sedimentary rate (42%). In 61 patients, autologous serum skin tests had been done. Fifteen patients (24.5%) had positive results i.e. autoimmune urticaria. Anti-thyroglobulin and anti-microsomal antibodies were positive in 16 % and 12% of CIU patients respectively. After 1 year from the onset of the symptoms, 34.5% of CIU patients were free of symptoms and after 1.2 years from the onset of the symptoms, 56.5% of autoimmune urticaria patients were free of symptoms. The median disease duration of CIU and autoimmune urticaria were 390 days and 450 days respectively. Our study provided an overview of CU and CIU in a large series of Thai patients, based on etiological aspects and clinical courses.     

Autoreaktive Urtikaria und Autoimmunurtikaria

Symptoms in patients with autoreactive urticaria (ArU), a sub-form of chronic urticaria (CU), are caused by circulating histamine-releasing signals. ArU patients are readily identified by the autologous serum skin test, in which they exhibit inflammatory reactions to their serum after intracutaneous injection. CU patients who also exhibit functional autoantibodies against IgE and/or its high affinity receptor Fc(epsilon)RI are thought to suffer from autoimmune urticaria (Aiu). ArU and AiU are pathogenetically and clinically different from other sub-forms of CU.     

Evidence-based evaluation and management of chronic urticaria in children

Urticaria affects nearly 25% of the population at some time in their lives. In a subset of children, urticaria will develop into a chronic condition that can greatly affect quality of life. Although numerous causes and triggers are proposed for chronic urticaria (CU) in children, ranging from infections, allergens, and medications to physical factors and autoimmune disease, the exact etiology is not always identifiable. Accordingly, a large subset of cases are designated "chronic idiopathic urticaria." Because of the clinical complexities of CU, as well as the confusing literature on this topic, we have developed a conceptual framework based on the cumulative evidence to assist with the categorization, clinical evaluation, and treatment of CU in children.     

The impact of chronic urticaria on the quality of life

The impact of chronic urticaria (CU) on the quality of life is undocumented. We assessed quality of life in patients with CU, including patients with associated delayed pressure urticaria (DPU). One hundred and forty–two out–patients completed self–administered questionnaires: a disease–specific, purpose designed questionnaire, and the Nottingham health profile (NHP). Many patients reported problems attributable to their skin condition in facets of everyday life including home management, personal care, recreation and social interaction, mobility, emotional factors, sleep, rest and work. The NHP part I scores showed restriction in the areas of mobility, sleep, energy, and demonstrated pain, social isolation and altered emotional reactions. Part II of the NHP showed that patients experienced difficulties in relation to work, looking after the home, social life, home relationships, sex life, hobbies and holidays. The patients with DPU had significantly more problems with mobility, gardening and choice of clothing than the uncomplicated CU patients. They also suffered more pain, had more problems with work and were more restricted in their hobbies.     

Comparative evaluation of Type 1 latex hypersensitivity in patients with chronic urticaria,rubber factory workers and healthy control subjects

Latex hypersensitivity manifests itself most commonly with contact urticaria. In this study, we investigated the frequency of latex hypersensitivity as a possible aetiological factor in patients with chronic urticaria (CU) and compared latex hypersensitivity of CU patients (n = 50) with that of rubber factory workers (n = 50) and healthy controls (n = 50). Prick test with latex and fruit extracts and determination of latex-specific immunoglobulin E (IgE) were performed. As a risk factor, contact dermatitis due to rubber additives was tested by patch test. Latex hypersensitivity was detected in 14% of CU patients, 12% of rubber factory workers and 12% of healthy controls (P > 0.05). Positive patch test with rubber additives was detected in 6% of CU and 4% of rubber factory workers. 3 of 7 CU patients had sensitivity to fruits in addition to latex hypersensitivity. In 1 patient with CU, the clinical complaints were found to be related to latex hypersensitivity. These findings suggest that the frequency of latex hypersensitivity in CU patients is no higher than that in healthy individuals. However, CU patients should be carefully asked about latex allergy, as we demonstrated that 1 of the CU patients had undiagnosed symptomatic latex allergy.     

Blood urokinase plasminogen activator system in chronic urticaria

The evidence gathered has pointed to the fibrinolytic system, which apart from its major role in hemostasis may also be involved in inflammatory and immune processes. To understand better the role of fibrinolysis in urticaria, we measured plasma levels of the urokinase system associated molecules such as urokinase-type plasminogen activator (uPA), its soluble receptor (suPAR; CD87) and an inhibitor, plasminogen activator inhibitor type 1 (PAI-1) activity in chronic urticaria (CU) patients. Plasma was obtained from symptomatic sixteen CU patients (12 females and 4 males) showing positive response to autologous serum skin test (ASST), 28 CU patients with negative ASST (20 females and 8 males) as well as from healthy subjects matched by sex and age. The plasma level of uPA and suPAR antigens, PAI-1 activity did not differ significantly among the three subjects groups. The data obtained suggest that CU patients showing positive response to ASST have plasma profile of the urokinase system-associated proteins, which is not markedly different as compared with CU patients with negative ASST as well as healthy subjects. Our findings have also confirmed the earlier studies, suggesting that systemic fibrinolysis may not be involved in chronic urticaria.This study was supported by a research grant from the Committee for Scientific Research (NN-1-246/03).     

Intravenous immunoglobulin in autoimmune chronic urticaria

Histamine releasing autoantibodies play a central role in the pathogenesis of chronic urticaria (CU) in approximately 30% of affected patients. We investigated the therapeutic effect of high-dose intravenous immunoglobulin (IVIG) on disease activity in patients with severe CU of autoimmune aetiology. Autoimmune urticaria was diagnosed by the development of a weal-and-flare reaction to the intradermal injection of autologous serum and by serum-induced histamine release from the basophil leucocytes of healthy donors in vitro . Ten patients with severe, autoimmune CU, poorly responsive to conventional treatment, were treated with IVIG 0.4 g/kg per day for 5 days. The outcome on cutaneous wealing and itch was monitored using urticaria activity scores, visual analogue scales and autologous intradermal serum tests. Clinical benefit was noted in nine of 10 patients; three patients continue in prolonged complete remissions (3 years follow-up), two had temporary complete remissions, and symptoms in four patients improved subsequent to treatment. There was significant improvement in the urticaria activity scores and visual analogue scores at 2 ( P  < 0.01) and 6 weeks ( P  < 0.01) post-IVIG compared with the baseline values (Wilcoxon matched pairs). The diminution in urticarial activity in the majority of patients corresponded with a reduced weal-and-flare response to the intradermal injection of autologous post-treatment serum compared with the pretreatment serum. Minor side-effects were common, but there were no serious or long-term adverse effects. IVIG represents a novel therapeutic option in selected patients with recalcitrant CU associated with histamine releasing autoantibodies.     

Delayed pressure urticaria treated with the selective serotonin reuptake inhibitor escitalopram

There is increasing evidence of platelet activation and systemic inflammation in chronic spontaneous urticaria and delayed pressure urticaria (DPU). Inflammation may be central to understanding the high comorbidity of depression and anxiety in patients with chronic urticaria (CU). We report a case of DPU and depression in a patient, which responded favourably to treatment with the selective serotonin reuptake inhibitor (SSRI) escitalopram. Sustained administration of SSRIs is associated with downregulation of serotonin transporters/receptors and depletion of platelet stored serotonin, which may reduce the ability of platelets to aggregate after thrombotic triggers. SSRIs are easier to manage and have significantly less disturbing adverse effects and cardiotoxicity than the tricyclic antidepressants (TCAs). SSRIs may represent an alternative to the traditional use of TCAs in treatment of CU.     

Omalizumab is an effective and rapidly acting therapy in difficult-to-treat chronic urticaria: A retrospective clinical analysis

BackgroundOmalizumab (anti-IgE) therapy is effective and safe in chronic urticaria (CU) in placebo-controlled clinical trials but real life clinical data are scarce.ObjectiveTo better understand the effects of omalizumab in CU patients treated outside of clinical trials.MethodsIn this retrospective clinical analysis, we assessed responder rates, optimal dosage, response to up-/downdosing, time to relief of symptoms, rates of return and time of relapse after omalizumab administration, and safety in 51 CU patients, 20 with chronic spontaneous urticaria (CSU) alone, 21 with different forms of chronic inducible urticaria (CindU) and 10 with both.ResultsOmalizumab treatment led to complete remission in 83% of CSU and 70% of CindU patients. When starting with 150 mg omalizumab 4 weekly, only 2/15 CSU and 7/17 CindU patients required updosing to achieve complete remission. In CSU, 57% of complete responses occurred within week one, all on the first day. Relapses were 2–8 weeks in all but six patients, where they were <4 months. Omalizumab was safe. Efficacy was not correlated to baseline IgE levels.ConclusionClinical experience from more than 1250 injections in 51 patients over four years indicates that omalizumab is a rapidly acting, highly effective and safe drug in CSU and CindU patients. Our observations in a real life clinical setting support the recommendation of current EAACI/GA²LEN/EDF/WAO guideline for the management of urticaria to use omalizumab to treat urticaria patients.     

Clinical and Investigative Assessment of Patients with Positive Versus Negative Autologous Serum Skin Test: A Study of 80 South Indian Patients

Background:

Chronic urticaria (CU) is defined as urticaria persisting daily as or almost daily for more than 6 weeks and affecting 0.1% of the population. Mast cell degranulation and histamine release is of central importance in the pathogenesis of CU. About 40-50% of the patients with chronic idiopathic urticaria demonstrate an immediate wheal and flare response to intra-dermal injected autologous serum. This led to the concept of autoimmune urticaria.

Aims:

To determine the occurrence, clinical features, associated clinical conditions, comorbidities of autoimmune urticaria and to compare this with chronic spontaneous urticaria. This study aimed to find the frequency of autologous serum skin test (ASST) positive patients among patients with CU and to identify the clinical and laboratory parameters associated with positive ASST.

Materials and Methods:

Prospective correlation study was done on 80 chronic urticaria patients, more than 6 weeks duration, attending outpatient department of dermatology during a period of November 2007 to January 2010. Patients were subjected to ASST, complete blood count, urine routine examination, liver function tests, renal function tests, thyroid function tests, H. pylori antibody tests, C3 and C4 complement level estimation, antinuclear antibody, and urine analysis.

Results:

ASST was positive in 58.75% and negative in 41.25% of the patients, respectively. Out of 33 patients with history of angioedema, 9 (27.3%) patients were in ASST negative group and 24 were in positive group, this was statistically significant. Both groups showed no statistically significant difference for epidemiological details.

Conclusion:

ASST is considered a screening test for an autoimmune urticaria, which decreases the rate of diagnosis of “idiopathic” form of chronic urticaria. Patients with an autoimmune urticaria have more severe urticaria, more prolonged duration, more frequent attacks, and angioedema. Identification of autoimmune urticaria may permit the use of an immunotherapy in severe disease unresponsive to anti-histamine therapy.     

Effect of Levothyroxine Treatment on Clinical Symptoms in Hypothyroid Patients with Chronic Urticaria and Thyroid Autoimmunity

BackgroundThyroid autoimmunity has been increasingly reported to be associated with chronic urticaria (CU), and the possible clinical benefit of thyroid hormone or anti-thyroid drugs in some CU patients with autoimmune thyroid disease has been studied. However, the effect of thyroid hormone or anti-thyroid drugs on clinical symptoms of CU remains unclear.ObjectiveWe investigated the clinical response of urticaria to the treatment of thyroid dysfunction.MethodsMedical records of patients with CU evaluated for thyroid autoimmunity and thyroid function were collected and reviewed.ResultsOf 184 patients with CU, 43 patients (23.4%) had thyroid autoantibodies and 26 patients (14.1%) had thyroid dysfunction. While none of the five patients with Graves'' disease showed any improvement of urticaria after treatment with anti-thyroid drugs, two of the 10 patients with Hashimoto''s thyroiditis showed improved urticaria after being treated with levothyroxine.ConclusionAlthough levothyroxine treatment was effective in a minority of patients with CU, there may be a causal relationship between CU and thyroid autoimmunity.     

The impact of COVID‐19 pandemic on the management of patients with chronic urticaria: An observational two‐center study from Turkey

The Coronavirus Disease 2019 (COVID‐19) outbreak significantly affected the clinical practice in hospitals and the management of many diseases. The aim of this study was to evaluate the effect of pandemic‐related factors on the severity and course of chronic urticaria (CU). A total of 194 CU patients who were on regular follow‐up, were enrolled in the study. The disease activity was assessed by means of the weekly urticaria activity score (UAS7) and urticaria control test (UCT). Patients were divided into two subgroups according to their disease aggravation as “aggravated” and “non‐aggravated”. Two groups were compared in terms of demographic, clinical, COVID‐19‐associated parameters, and parameters related with the effect of COVID‐19 pandemic on CU management. The omalizumab use was statistically higher (P = .017), and the systemic corticosteroid use was statistically lower (P = .025) in the “aggravated” group. Adherence to quarantine was significantly lower in the “aggravated” group (P = .027). 173 patients (89.2%) were unable to contact a dermatologist during the pandemic. Among 186 patients who received treatment for CU before the pandemic, 48 (25.8%) did not continue the existing treatment during the pandemic. CU aggravated in one patient with COVID‐19 and remained stable in the other. This study showed that CU patients, especially those on omalizumab therapy, had difficulties in attending medical care and even in the maintenance of their existing therapies during the pandemic. Creating novel follow‐up and treatment models as well as the increased use of teledermatology might be beneficial in the management of this life‐disturbing condition.     

Monoclonal gammopathies and malignancies in patients with chronic urticaria

BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) has been described in association with chronic urticaria (CU) in patients with Schnitzler syndrome. Chronic urticaria may be a manifestation of hematologic malignancies. METHODS: This study was conducted to evaluate the frequency and characteristics of MGUS or malignancy in patients with CU. The Mayo Clinic electronic database was reviewed to identify patients with the diagnosis of CU. RESULTS: Of the 1639 patients presenting with CU between 1994 and 2001, 797 (49%) underwent laboratory evaluation for the presence of a coexisting monoclonal protein. Forty-seven CU patients had MGUS, 142 had a malignancy, and 24 had both. Fifteen percent of CU patients with MGUS had a hematologic malignancy compared with 0.9% of CU patients without MGUS (P < 0.001). Patients presenting with a new diagnosis of CU at an older age (> 56 years) were more likely to have associated underlying MGUS. The occurrence of MGUS in this group was higher than the reported incidence of MGUS in the general population. CONCLUSIONS: Patients with CU younger than 43 years were unlikely to have associated MGUS or malignancy. A higher percentage of patients with CU and MGUS had an associated diagnosis of hematologic malignancy.