Overweight and obesity may play a role in the pathogenesis of chronic spontaneous urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) is one of the commonest diseases in allergological and dermatological practice. It constitutes an interdisciplinary problem, and its pathogenesis is not always easily determined. It has been suggested that metabolic syndrome and hyperlipidaemia are more frequent in patients with CSU, but the influence of overweight and obesity on the development of CSU has not been thoroughly investigated. AIM: To assess the association between body parameters and the development of CSU. METHODS: The study enrolled 85 patients with CSU, who were divided into three subgroups: patients whose only symptoms were weals, patients whose only symptom was angio-oedema, and patients with urticaria and accompanying angio-oedema. Mean weight, height, body mass index (BMI), body surface area, disease duration and age of disease onset were recorded RESULTS: There was a statistically significant association between CSU and heavier weight, higher BMI, greater affected body surface area and older age at disease onset. Subjects with higher BMI values had a tendency towards longer disease duration. There were no statistically significant differences between the three subgroups. CONCLUSIONS: Our results suggest that CSU, especially if of long duration, may be associated with overweight and obesity, while increased body mass can result in later onset of urticaria symptoms. Further analyses to confirm the presented results and possible association between obesity and CSU occurrence are needed.

Possible contribution of chemokine receptor CCR2 and CCR5 polymorphisms in the pathogenesis of chronic spontaneous autoreactive urticaria.

BACKGROUND: Autoimmune mechanisms play a role in the pathophysiology of chronic urticaria. As the genetic background of autoimmunity is well proven, the role of genetics in chronic urticaria is hypothesised. METHODS: 153 unrelated chronic spontaneous urticaria patients with a positive result of autologous serum skin test were included into the study, as were 115 healthy volunteers as control group. In all subjects we analysed CCR2 G190A and CCR5 d32 polymorphisms. RESULTS: We noticed higher prevalence of CCR2 A allele as well as lower frequency of CCR5 d32 in chronic urticaria group in comparison to control group, with borderline statistical significance. Additionally, we assumed haplotype Gd statistically significant negative chronic urticaria association with tendency to higher frequency of Aw haplotype in this group. CONCLUSIONS: The results of our study imply the role of autoimmune components in chronic urticaria pathogenesis and present chronic urticaria as possibly genetically related disorder.

CTLA-4 polymorphism in the pathogenesis of chronic spontaneous autoreactive urticaria.

BACKGROUND: Autoimmune mechanisms are considered to play a significant role in chronic urticaria pathophysiology. Additionally, clinical experience emphasises the coexistence of chronic urticaria manifestation with thyroid autoimmunity. As the role of CTLA-4 polymorphism in autoimmune thyroid diseases is well proven we speculated on the possible role of this polymorphism in the background of chronic urticaria. MATERIALS AND METHODS: We included 128 chronic spontaneous autoreactive urticaria patients (87 females and 41 males) and 101 healthy volunteers (71 females and 30 males). In all examined subjects CTLA-4 A49G polymorphism was analysed. Disease severity with Urticaria Activity Score as well as age of disease onset was also studied. RESULTS: No statistically significant differences in the allele or genotype distribution between urticaria patients and controls were observed. Furthermore, we found no association between CTLA4 polymorphism and urticaria severity as well as the age of disease onset. CONCLUSIONS: Our data suggest that there is no contribution of CTLA-4 A49G polymorphism to chronic spontaneous autoreactive urticaria susceptibility. We recommend further research on other polymorphisms in chronic urticaria patients to explore in detail the potent role of the genetic background in the pathogenesis of this disorder.

Acute phase inflammatory markers in patients with non-steroidal anti-inflammatory drugs (NSAIDs)-induced acute urticaria/angioedema and after aspirin challenge.

BACKGROUND: Active chronic urticaria, identified as a mast cell- and basophil-dependent inflammatory disorder of the skin is able to elicit acute phase response (APR). However, systemic inflammatory response in different types of urticaria is poorly characterized. AIM: To determine APR pattern in a clearly defined group of patients with acute urticaria and/or angioedema - induced by NSAIDs. METHODS: Plasma IL-6 and serum C-reactive protein (CRP) concentrations were studied in 17 patients with NSAIDs-induced acute urticaria/angioedema (NSAIDsAU) and in 20 healthy controls. Eleven patients who used NSAIDs were presented at the emergency room with acute urticaria/angioedema while the remaining six manifested the symptoms during the aspirin challenge test. Patients were examined in a dynamic manner: during the acute phase, and next, after subsidence of the symptoms. RESULTS: CRP and IL-6 concentrations increased significantly in patients with NSAIDsAU as compared with their asymptomatic period and the healthy subjects. In addition, NSAIDsAU patients showed elevated concentration of the biomarkers following aspirin provocation with the baseline values recovered in the asymptomatic period. CONCLUSION: These results indicate that an acute systemic inflammatory response is activated in patients with NSAIDs-induced urticaria and/or angioedema. The study supports the evidence proving that up-regulation of CRP and IL-6 in urticaria/angioedema does not necessarily reflect any concomitant infection or other inflammatory processes, but may be due to the disease itself.

Practical guide to skin prick tests in allergy to aeroallergens.

This pocket guide is the result of a consensus reached between members of the Global Allergy and Asthma European Network (GA(2) LEN) and Allergic Rhinitis and its Impact on Asthma (ARIA). The aim of the current pocket guide is to offer a comprehensive set of recommendations on the use of skin prick tests in allergic rhinitis-conjunctivitis and asthma in daily practice. This pocket guide is meant to give simple answers to the most frequent questions raised by practitioners in Europe, including 'practicing allergists', general practitioners and any other physicians with special interest in the management of allergic diseases. It is not a long or detailed scientific review of the topic. However, the recommendations in this pocket guide were compiled following an in-depth review of existing guidelines and publications, including the 1993 European Academy of Allergy and Clinical Immunology position paper, the 2001 ARIA document and the ARIA update 2008 (prepared in collaboration with GA(2) LEN). The recommendations cover skin test methodology and interpretation, allergen extracts to be used, as well as indications in a variety of settings including paediatrics and developing countries.

PTPN22 polymorphism presumably plays a role in the genetic background of chronic spontaneous autoreactive urticaria.

BACKGROUND: The association of chronic urticaria (CU) with autoimmune disorders is relatively well proved. Protein tyrosine phosphatase-22 (PTPN22) is considered to be one of the strongest genetic factors for human autoimmunity. We decided to evaluate whether additional, non 1858C>T, PTPN22 variants are independent contributors to the risk of CU occurrence in the Polish population. METHODS: A total of 91 CU patients with a positive result of autologous serum skin test and 100 healthy volunteers were enrolled in the study. The Urticaria Activity Score was used in disease intensity assessment. In all subjects rs3811021, rs1310182 and rs2488457 polymorphisms were genotyped. RESULTS: We found a higher prevalence of -1123 C allele among CU patients. No differences in the allele and genotype distribution were found in the other analyzed polymorphisms. Haplotype construction of the three SNPs revealed statistically significant CU association of rs2488457C, rs1310182T and rs3811021T. CONCLUSIONS: Contrary to previous findings, the contribution of PTPN22 to disease susceptibility is suggested. We can speculate that CU is a genetically complex disease and that its occurrence needs multiple genetic and environmental risk factors.

The German version of the Chronic Urticaria Quality-of-Life Questionnaire: factor analysis, validation, and initial clinical findings.

BACKGROUND: Chronic urticaria (CU) is a common skin disorder that causes a substantial burden on patients' quality-of-life (QoL). The aim of this work was to generate and validate a German version of the Chronic Urticaria Quality of Life Questionnaire (CU-Q(2)oL) and to provide reference assessments of QoL. METHODS: The Italian CU-Q(2)oL was translated into German and administered to 157 CU patients. They also completed two well-established general dermatology QoL questionnaires, the Dermatology Life Quality Index (DLQI) and Skindex-29. Factor analysis was used to identify scales of the German CU-Q(2)oL. Correlation to the DLQI and Skindex-29 was used for validation. Multiple linear regression was used to determine which patient characteristics were associated with which dimensions of QoL. RESULTS: The factor analysis identified six scales of the German CU-Q(2)oL: functioning, sleep, itching/embarrassment, mental status, swelling/eating, and limits looks, which accounted for 70% of the data variance. Five of these six scales showed good internal consistency, and another five demonstrated convergent validity. On a percentile scale, they had these median CU-Q(2)oL scores: 29 functioning, 44 sleep, 50 itching/embarrassment, 50 mental status, 31 swelling/eating, 31 limits looks. Disease severity significantly predicted scores on all scales. Age predicted functioning, sleep, itching/embarrassment, and swelling/eating. Sex predicted itching/embarrassment and limits looks. CONCLUSION: This study yielded a robust validation of the German version of the CU-Q(2)oL. It confirmed previous studies that CU has a clinically meaningful burden on QoL, especially for sleep and mental health, and that women are more severely affected by pruritus. The German CU-Q(2)oL should be widely adopted in clinical research on the treatment of CU.

EAACI/GA(2)LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria.

This guideline, together with its sister guideline on the management of urticaria [Zuberbier T, Asero R, Bindslev-Jensen C, Canonica GW, Church MK, Giménez-Arnau AM et al. EAACI/GA(2)LEN/EDF/WAO Guideline: Management of urticaria. Allergy, 2009; 64:1427-1443] is the result of a consensus reached during a panel discussion at the 3rd International Consensus Meeting on Urticaria, Urticaria 2008, a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2)LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO). Urticaria is a frequent disease. The life-time prevalence for any subtype of urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria do not only cause a decrease in quality of life, but also affect performance at work and school and, as such, are members of the group of severe allergic diseases. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors, and pathomechanisms. In addition, it outlines evidence-based diagnostic approaches for different subtypes of urticaria. The correct management of urticaria, which is of paramount importance for patients, is very complex and is consequently covered in a separate guideline developed during the same consensus meeting. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS).

EAACI/GA(2)LEN/EDF/WAO guideline: management of urticaria.

This guideline, together with its sister guideline on the classification of urticaria (Zuberbier T, Asero R, Bindslev-Jensen C, Canonica GW, Church MK, Giménez-Arnau AM et al. EAACI/GA(2)LEN/EDF/WAO Guideline: definition, classification and diagnosis of urticaria. Allergy 2009;64: 1417-1426), is the result of a consensus reached during a panel discussion at the Third International Consensus Meeting on Urticaria, Urticaria 2008, a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2)LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO). As members of the panel, the authors had prepared their suggestions regarding management of urticaria before the meeting. The draft of the guideline took into account all available evidence in the literature (including Medline and Embase searches and hand searches of abstracts at international allergy congresses in 2004-2008) and was based on the existing consensus reports of the first and the second symposia in 2000 and 2004. These suggestions were then discussed in detail among the panel members and with the over 200 international specialists of the meeting to achieve a consensus using a simple voting system where appropriate. Urticaria has a profound impact on the quality of life and effective treatment is, therefore, required. The recommended first line treatment is new generation, nonsedating H(1)-antihistamines. If standard dosing is not effective, increasing the dosage up to four-fold is recommended. For patients who do not respond to a four-fold increase in dosage of nonsedating H(1)-antihistamines, it is recommended that second-line therapies should be added to the antihistamine treatment. In the choice of second-line treatment, both their costs and risk/benefit profiles are most important to consider. Corticosteroids are not recommended for long-term treatment due to their unavoidable severe adverse effects. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS).

Serum Irisin, Adropin, and Preptin in Obese Patients 6 Months After Bariatric Surgery.

BACKGROUND/OBJECTIVES: The reduction of body mass after bariatric surgery affects energy metabolism and may involve changes in irisin, preptin, and adropin production. SUBJECTS AND METHODS: Fifty-five morbidly obese patients with a mean body mass index (BMI) of 45.7 ± 5.8 kg/m2 were treated with either laparoscopic sleeve gastrectomy(n = 30) or laparoscopic adjustable gastric banding (n = 25). Forty-six (83.6%) were followed-up 6 months after surgery. The control group included 15 healthy non-obese participants. Anthropometric measurements, lipid profiles, HbA1c, and serum irisin, preptin, and adropin were assessed at baseline and on follow-up. RESULTS: The serum concentrations of all three peptides were higher at 6 months than at baseline but only irisin (p = 0.02) and adropin (p = 0.000001) were significantly higher. The increase in preptin was borderline significant (p = 0.051). Changes of serum concentrations of all three peptides were bidirectional. CONCLUSION: Body mass reduction resulting from bariatric procedures may change the production of energy regulating peptides, but not always in a favorable manner.

Sex hormones and urticaria.

Chronic urticaria is characterized by mast cells/basophils activation which initiate the inflammatory response. Pathogenetically, the disease may in many cases represent an autoimmune phenomenon. Altered function of the neuro-endocrine-immune system due to stress and other factors has also been implicated its pathogenesis. Sex hormones modulate immune and inflammatory cell functions, including mast cell secretion, and are regarded as responsible for gender and menstrual cycle phase-associated differential susceptibility and severity of some autoimmune and inflammatory diseases. Chronic urticaria is approximately twice more frequent in women than in men. In addition, urticaria may be associated with some diseases and conditions characterized by hormonal changes, including endocrinopathy, menstrual cycle, pregnancy, menopause and hormonal contraceptives or hormone replacement therapy. Hypersensitivity reactions to endogenous or exogenous female sex hormones have been implicated in the pathogenesis of urticarial lesions associated with estrogen and autoimmune progesterone dermatitis. We observed lower serum dehydroepiandrosterone sulfate (DHEA-S) concentration in patients with chronic urticaria with positive and negative response to autologous serum skin test. Thus, the influence of fluctuations in the hormonal milieu and altered sex hormone expression on the triggering-off, maintenance or aggravation of urticaria should be taken into account. In addition, the possible impact of estrogen mimetics, in the environment and in food, on the development of disease associated with mast cell activation must be considered. This review endeavours to outline what is known about the possible influence of sex hormones in the expression of urticaria.

Platelet activating factor as a mediator and therapeutic approach in bronchial asthma.

Platelet activating factor (PAF) is a potent phospholipid mediator involved in anaphylaxis and chronic inflammatory disorders, including bronchial asthma. PAF is able to act both, directly as a chemotactic factor and indirectly through the release of other inflammatory agents. Apart from its known potent ability to activate platelets, PAF influences other immune and inflammatory cells function involved in asthma, which may be of importance in the pathogenesis of the disease. In addition, PAF administration can mimic some of abnormalities observed in asthma, including bronchoconstriction, bronchial hyper responsiveness, and gas exchange impairment, which may be mediated by leukotrienes acting as secondary mediators of some PAF effects. Therefore, there has been an extensive interest in the role of PAF in human asthma and major efforts have been continued to discover drugs acting thorough inhibition of PAF effects in the disease. Surprisingly, PAF receptor antagonists have not clearly proven their clinical benefits. It may appear that the combined blockage of PAF effects and other mediators involved in asthma is a way to improve clinical efficacy and also an interesting approach to control inflammation in the disease. This review will focus on two main issues: the role of PAF and PAF antagonists in asthma.

Antioxidant enzyme activity and malondialdehyde concentration in the plasma and erythrocytes of patients with urticaria induced by nonsteroidal anti-inflammatory drugs.

BACKGROUND: It has been suggested that oxidative stress is a crucial event in some forms of urticaria. AIM: To evaluate the blood oxidant/antioxidant profile of patients suffering from urticaria induced by nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: We measured the activity of the antioxidant enzymes copper-zinc superoxide dismutase (Cu/ZnSOD), glutathione peroxidase (GSH-Px), and catalase (CAT), and the levels of malondialdehyde (a marker of lipid peroxidation) in the plasma and erythrocytes of 12 females with NSAID-induced urticaria and in 19 healthy controls. RESULTS: The enzyme activity in plasma (CuZn/SOD) and in erythrocytes (CuZn/SOD, GSH-Px, and CAT) did not differ significantly between urticaria patients and controls. Moreover, the levels of malondialdehyde in plasma and erythrocytes did not differ significantly between the 2 groups. CONCLUSIONS: It seems that processes associated with urticaria induced by NSAIDs may not modify antioxidant enzyme activity and may not enhance lipid peroxidation in peripheral blood.

Serum concentration of dehydroepiandrosterone sulfate and testosterone in women with severe atopic eczema/dermatitis syndrome.

BACKGROUND: Although a growing body of evidence indicates that androgens modulate immune response and certain alterations in sex hormone metabolism and balance are thought to predispose an individual to immune-mediated diseases, few studies have investigated the role of androgens in atopic eczema/dermatitis syndrome (AEDS). OBJECTIVE: We evaluated serum concentration of dehydroepiandrosterone sulfate (DHEA-S) and total testosterone in women with severe AEDS to characterize the hormonal milieu of such patients. METHODS: Serum concentrations of DHEA-S and total testosterone in 13 female patients with severe AEDS were compared with concentrations in weight- and age-matched healthy controls. Measurement was by electrical chemiluminescence immunoassay. RESULTS: There were no significant differences in serum concentrations of DHEA-S or testosterone between the 2 groups. We found no correlation between serum concentrations of DHEA-S and total immunoglobulin E. CONCLUSION: This small study suggests there may be no abnormalities in peripheral blood concentrations of DHEAS-S and total testosterone in women with severe AEDS.

Side-effects of injective allergen immunotherapy administered to intermittent or persistent allergic rhinitis patients.

AIM: Evaluation of the side-effects of conventional subcutaneous allergen immunotherapy in inhalant allergy. MATERIAL AND METHODS: Retrospective analysis of early and late, local and systemic, short-term and long-term side-effects of 4723 injections given to 224 patients suffering from intermittent or persistent allergic rhinitis. RESULTS: There were 65 systemic reactions in 48 patients (21%) after 61 injections (1.29%). Most of them were late, and included dyspnoea, rhinorrhoea, fever, fatigue and urticaria. Incidence of systemic reactions did not correlate to age or sex, but was higher in grass pollen than in house dust mite allergy and during the up-dosing phase of treatment. Late intense local reactions were observed after 1.6% of injections. CONCLUSIONS: Allergen immunotherapy in inhalant allergy is a safe method of treatment.

Platelet function in anaphylaxis.

Human platelets, following immunological or nonimmunological activation, are capable of releasing a variety of biologically active mediators and are able to actively participate in hypersensitivity reactions, including anaphylaxis. These cells constitutively express functional receptors for the Fc fragment of IgE, both the low affinity receptor (Fc epsilonRII) and the high affinity receptor (Fc epsilonRI), and could be activated via IgE. Alterations in platelet function have been demonstrated in patients with allergy and nonallergic hypersensitivity, including hypersensitivity to acetylsalicylic acid. Moreover, activated platelets may be responsible for anaphylactic transfusion reactions. Various haemostatic disturbances, particularly a drop in platelet number, were observed during anaphylactic shock. The current review summarises the data from human and experimental studies on platelet function in anaphylactic reactions.

Identification of Risk Factors Associated With Clostridium difficile Infection in Liver Transplantation Recipients: A Single-Center Analysis.

Clostridium difficile remains the leading cause of health care-associated infectious diarrhea, and its incidence and severity are increasing in liver transplant recipients. Several known risk factors for C difficile infection (CDI) are inherently associated with liver transplantation, such as severe underlying illness, immunosuppression, abdominal surgery, and broad-spectrum antibiotic use. We conducted a single-center retrospective case control study to characterize risk factors for CDI among patients who received a liver transplant from January 2008 to December 2012. We also examined the associations of post-transplantation CDI with transplant outcomes. Cases were defined as having diarrhea with a positive test for C difficile by either toxin A/B enzyme immunoassay (EIA) or glutamate dehydrogenase EIA and polymerase chain reaction within 1 year after transplantation. Sixty-five consecutive patients were evaluated, of which 15 (23%) developed CDI. The median time from transplantation to CDI diagnosis was 65 days (interquartile range [IQR] 13-208) and more than one-half (53%) had severe infection. Risk factors that were associated with CDI among liver transplant recipients included: (1) previous history of CDI (20% vs 0%; P = .001); (2) exposure to proton-pump inhibitor therapy (93% vs 60%; P = .015); (3) antimicrobial therapy before transplantation (47% vs 18%; P = .039); (4) a prolonged length of stay before transplantation (1 day [IQR, 1-19] vs 1 day [IQR, 0-1]; P = .028); and (5) chronic kidney disease (53% vs 20%; P = .011). There was no significant differences in patient survivals at 6 months (93% vs 96%; P = .67) and 12 months (87% vs 94%; P = .35) among CDI case and control subjects, respectively.