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.

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.

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.

Chronic urticaria in myasthenia gravis patients - More than occasional coexistence?

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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

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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

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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.

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.

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.

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.

Safety considerations in the management of allergic diseases: focus on antihistamines.

OBJECTIVE: To conduct a systematic review of evidence supporting the safety profiles of frequently used oral H(1)-antihistamines (AHs) for the treatment of patients with histamine-release related allergic diseases, e.g. allergic rhinitis and urticaria, and to compare them to the safety profiles of other medications, mostly topical corticosteroids and leukotriene antagonists (LTRA). RESEARCH DESIGN AND METHODS: Systematic search of the published literature (PubMed) and of the regulatory authorities databases (EMA and FDA) for oral AHs. RESULTS: Similarly to histamine, antihistamines (AHs) have organ-specific efficacy and adverse effects. The peripheral H(1)-receptor (PrH1R) stimulation leads to allergic symptoms while the brain H(1)-receptor (BrH1R) blockade leads to somnolence, fatigue, increased appetite, decreased cognitive functions (impaired memory and learning), seizures, aggressive behaviour, etc. First-generation oral AHs (FGAHs) inhibit the effects of histamine not only peripherally but also in the brain, and additionally have potent antimuscarinic, anti-α-adrenergic and antiserotonin effects leading to symptoms such as visual disturbances (mydriasis, photophobia, and diplopia), dry mouth, tachycardia, constipation, urinary retention, agitation, and confusion. The somnolence caused by FGAHs interferes with the natural circadian sleep-wake cycle and therefore FGAHs are not suitable to be used as sleeping pills. Second-generation oral AHs (SGAHs) have proven better safety and tolerability profiles, much lower proportional impairment ratios, with at least similar if not better efficacy, than their predecessors. Only SGAHs, and especially those with a proven long-term (e.g., ≥12 months) clinical safety, should be prescribed for young children. Evidence exist that intranasally applied medications, like intranasal antihistamines, have the potential to reach the brain and cause somnolence. CONCLUSIONS: Second-generation oral antihistamines are the preferred first-line treatment option for allergic rhinitis and urticaria. Patients taking SGAHs report relatively little and mild adverse events even after long-term continuous treatments. An antihistamine should ideally possess high selectivity for the H(1)-receptor, high PrH1R occupancy and low to no BrH1R occupancy.

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.

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).

Blood rheological properties in patients with atopic dermatitis (AD).

Inflammatory processes and psychological states may mutually enhance each other as well as contribute to haemorheological alterations. The objective of the recent study was to determine blood rheological profile in patients with AD at different clinical stages. Blood rheology, as estimated by blood viscosity as well as deformability (elongation index-EI) and aggregation of erythrocytes (aggregation half time (AT1/2)--expressing the kinetic aspects and syllectogram amplitude (AMP)--representing total aggregation extent) were measured in 25 female AD patients, who showed clinical features of mild to severe AD and in 14 healthy subjects. There were no significant differences in blood rheological properties between patients with mild AD and the controls. A significant decrease in erythrocytes AT1/2 and AMP as well as EI were observed in severe AD patients as compared to other groups. Whole blood and plasma viscosity were similar in all groups. Both erythrocytes deformability and aggregation may be affected by pathophysiological processes associated with AD. Only AD patients with severe skin changes showed increased aggregability and decreased deformability of erythrocytes, suggesting that the phenomenon might be related to the disease activity.

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.

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.