Early testing and grade of the reaction are affecting factors of skin test positivity in ß-Lactam allergies.

Background: ß-Lactams are the most widely used antibiotic family in the world. Nevertheless, they also stand out as the primary culprits for inducing drug hypersensitivity reactions (HSR). Methods: Between May 2018 and March 2023, patients with suspected HSRs to ß-lactams, who underwent skin tests (ST), were retrospectively screened. The determinants of allergenic penicillin (DAP) tests, which include penicillin minor and major determinants, clavulanic acid, and amoxicillin, along with ampicillin, sulbactam, the identified culprit drugs, and alternative cephalosporins, which include cefuroxime, ceftriaxone prick and/or intradermal tests, were administered. The analysis focused on identifying positive ST results and determining the true HSRs rates in this patient cohort. Results: Of the 147 patients, 78.9% (n = 116) were women and the median (minimum-maximum) age was 41 years (18-71 years). Mild HSRs (grades 1-2) were observed in 72.78% (n = 107), whereas 24.4% (n = 36) had severe reactions (grades 3-4) and 2.7% (n = 4) had an unknown grade. Of the patients, 64% (n = 94) experienced HSRs within the first hour after the last dose of the identified culprit drug. The overall positivity rate for all STs was 26.5% (n = 39). ST positivity rates were notably higher in individuals who had experienced HSRs within the past 6 months (p = 0.02) and those with severe anaphylaxis (p < 0.001). Conclusion: ß-Lactam ST positivity is higher, especially in those with grades 3-4 reactions and consulted a physician within the first 6 months after their HSRs.

The Effectiveness of Biological Agents on Chronic Rhinosinusitis with Nasal Polyposis in Patients with Comorbid Asthma: A Multicenter Real-Life Study from Türkiye.

Background and Objectives: Real-life data on the efficacy of biologic agents (BAs) on asthma-comorbid CRSwNP are needed. Our primary goal is to investigate the effects of BAs on CRSwNP symptoms, as well as endoscopic and tomography scores. Our secondary goal is to show a reduction in the frequency of acute sinusitis exacerbations and the need for surgery. Materials and Methods: We conducted a multicenter, retrospective, real-life study. We screened the patients with asthma-comorbid CRSwNP treated with omalizumab or mepolizumab. A total of 69 patients (40 F/29 M; omalizumab n = 55, mepolizumab n = 14) were enrolled. We compared the visual analog scale (VAS), sinonasal outcome test-22 (SNOT-22), nasal congestion score (NCS), Lund-Mackay computed tomography score (LMS), and total endoscopic polyp scores (TPS) before and after BAs. We evaluated the endoscopic sinus surgery (ESS) and acute exacerbations of chronic rhinosinusitis (AECRS) frequencies separately, according to the BAs. Results: The overall median (min-max) age was 43 (21-69) years. The median (min-max) of biologic therapy duration was 35 (4-113) months for omalizumab and 13.5 (6-32) for mepolizumab. Significant improvements were seen in VAS, SNOT-22, and NCS with omalizumab and mepolizumab. A significant decrease was observed in TPS with omalizumab [95% CI: 0-4] (p < 0.001), but not with mepolizumab [95% CI: -0.5-2] (p = 0.335). The frequency of ESS and AECRS were significantly reduced with omalizumab [95% CI: 2-3] (p < 0.001) and [95% CI: 2-5] (p < 0.001); and mepolizumab [95% CI: 0-2] (p = 0.002) and [95% CI: 2-8.5] (p < 0.001), respectively. There was no significant difference in LMS with either of the BAs. Conclusions: Omalizumab and mepolizumab can provide a significant improvement in the sinonasal symptom scores. BAs are promising agents for CRSwNP patients with frequent exacerbations and multiple surgeries.

CoronaVac/Sinovac COVID-19 Vaccine-Related Hypersensitivity Reactions and Second-Dose Vaccine Administration: Tertiary Allergy Center Experience.

INTRODUCTION: The COVID-19 pandemic has caused a global health crisis. To prevent the disease, the Ministry of Health of Turkey gained approval for the CoronaVac COVID-19 vaccine for emergency use as the first-line. This study aimed to evaluate patients who developed hypersensitivity reactions (HRs) due to the CoronoVac vaccine and to share our experience of administering the second dose of vaccine to these patients. METHODS: The study group included the patients who presented to the Ege University Allergy and Immunology Division between January and May 2021. Demographic data, atopic status, allergic reactions to the first dose of the COVID-19 vaccine and the route of second-dose vaccine administrations were recorded. RESULTS: A total of 7 patients (four healthcare professionals), 6 (86%) of whom were women, with an average age of 53.4 years, were included in the study. The rate of allergic reactions among Ege University health workers was 0.036% (2/5,558). Six of our patients had a history of additional allergic diseases and comorbid diseases. None had any allergic reactions to previous vaccinations and latex allergy. Reactions developed commonly on the skin, as generalized urticaria/angioedema and pruritus. The severity of the reactions was evaluated as mild in 2, moderate in 3, and severe in 2 cases. The second-dose CoronaVac was safely administered by using a gradually increase dose in a total of 6 patients. CONCLUSION: In patients with HRs due to Sinovac in the first dose, the second dose can be safely performed using a gradually increased dose.

Evaluation of association with subtypes and alleles of Blastocystis with chronic spontaneous urticaria.

Blastocystis is a single-celled parasite commonly found in humans and its pathogenic role is still controversial. In recent years, some studies have suggested that Blastocystis may be a possible agent of gastrointestinal and dermatological symptoms such as acute or chronic urticaria, angioedema, rash, itch, palmoplantar, and diffuse pruritus. We aimed to investigate whether there is a relationship between Blastocystis subtypes and alleles in patients with chronic spontaneous urticaria (CSU) as a case-control study. In this study, stool samples were collected from patients with CSU (n=135) and healthy individuals (n=54). The presence of Blastocystis was investigated using the direct saline smear, Lugol's iodine staining, trichrome staining, Jones' medium culture and PCR assays in stool samples and subtypes (STs) were determined by sequencing according to DNA barcoding. The presence of Blastocystis was identified in 30.4% (64/210) the stool samples, including 31.9% (43/135) of the patients with CSU and 14.8% (8/54) of the control group. Moreover, it was found statistically significant the presence of Blastocystis in terms of both groups (p<0.018). ST3 was detected in 45.9% and 62.5 % as the most prevalent subtype the patients with CSU and the control group, respectively. ST1 (18.9%), ST2 (27%) and ST7 (8.1%) was identified in the patients with CSU group. There was no statistically significant correlation between Blastocystis subtypes and both the groups (p<0.240, p<0.323). Allele 4 for ST1; alleles 9, 10, 11 and 12 for ST2; alleles 34, 36 and 38 for ST3; alleles 41 and 101 for ST7 were detected. Allele 34 (ST3) was found significant in the patients with CSU as compared with control group (p<0.020). Moreover, statistically significant association was found between total IgE value and the certain subtypes (ST2 and ST3) (p<0.0001). As a result of this study, the presence of Blastocystis ST3 allele 34 significantly associated with chronic spontaneous urticaria was revealed.

The role of component-resolved diagnosis in Hymenoptera venom allergy in clinical practice.

Background: Hymenoptera venom allergy is an immunoglobulin (Ig) E mediated hypersensitivity reaction to Hymenoptera venoms. Obvious identification of the culprit insect that causes the clinical symptoms and, hence, the accurate selection of venom for curative treatment, is of great importance for the effectiveness and safety of venom immunotherapy. Objective: In this study, the contribution of component-resolved diagnostics (CRD) is evaluated in the diagnosis of Hymenoptera venom allergy. Method: Ninety-three patients from four different centers in Turkey were included in the study. Conventional tests, including prick and intradermal skin tests, with commercial venom extracts and serum specific IgE (sIgE) levels for whole venoms were performed. An sIgE analysis for venom allergen components, including rApi m 1, rApi m 2, rApi m 10, rVes v 1, rVes v 5, were evaluated by immunoblotting. Results: In conventional test results, 17 of 35 patients with bee venom allergy were positive to honey bee venom, whereas 18 patients were positive to bee and wasp venoms. In 28 of 35 patients with bee venom allergy, the diagnosis was confirmed with CRD. CRD revealed a sensitivity of 80% in patients with bee venom allergy. According to conventional tests, 7 of 24 patients with vespid venom allergy demonstrated sensitivity only to Vespula species, whereas 17 patients revealed double positivity. The total diagnostic sensitivity of Ves v 1 and Ves v 5 was calculated as 87.5%. Ten of 23 patients with a history of hypersensitivity to both venoms showed double sensitivity with CRD; one patient had cross-reactivity, one patient was found to be sensitive only to bee venom, and, eight patients were sensitive only to Vespula species. Eleven patients had an uncertain history in terms of the culprit insect type and six of them had double sensitivity in CRD. Conclusion: CRD seemed to be more helpful in diagnosing vespid venom allergy than bee venom allergy. It can also discriminate clinically significant sensitizations from irrelevant ones.

ß-blockers and ACE inhibitors are not a risk factor for severe systemic sting reactions and adverse events during venom immunotherapy.

BACKGROUND: There is controversy whether taking ß-blockers or ACE inhibitors (ACEI) is a risk factor for more severe systemic insect sting reactions (SSR) and whether it increases the number or severity of adverse events (AE) during venom immunotherapy (VIT). METHODS: In this open, prospective, observational, multicenter trial, we recruited patients with a history of a SSR and indication for VIT. The primary objective of this study was to evaluate whether patients taking ß-blockers or ACEI show more systemic AE during VIT compared to patients without such treatment. RESULTS: In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. Of all patients included, 388 (27.2%) took antihypertensive (AHT) drugs (10.4% took ß-blockers, 11.9% ACEI, 5.0% ß-blockers and ACEI). Only 5.6% of patients under AHT treatment experienced systemic AE during VIT as compared with 7.4% of patients without these drugs (OR: 0.74, 95% CI: 0.43-1.22, p = 0.25). The severity of the initial sting reaction was not affected by the intake of ß-blockers or ACEI (OR: 1.14, 95% CI: 0.89-1.46, p = 0.29). In total, 210 (17.7%) patients were re-stung during VIT and 191 (91.0%) tolerated the sting without systemic symptoms. Of the 19 patients with VIT treatment failure, 4 took ß-blockers, none an ACEI. CONCLUSIONS: This trial provides robust evidence that taking ß-blockers or ACEI does neither increase the frequency of systemic AE during VIT nor aggravate SSR. Moreover, results suggest that these drugs do not impair effectiveness of VIT. (Funded by Medical University of Graz, Austria; Clinicaltrials.gov number, NCT04269629).

Deletions in SERPING1 Lead to Lower C1 Inhibitor Function: Lower C1 Inhibitor Function Can Predict Disease Severity.

BACKGROUND: How genotype affects phenotype in hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) has not been totally clarified. In this study, we investigated the relationship between different types of mutations and various phenotypic characteristics. METHODS: Clinical data from 81 patients from 47 families were recorded. Complement proteins were analyzed from 61 untreated patients. The coding exons and the exon-intron boundaries of the SERPING1 gene were sequenced, and deletion/duplication analysis with multiple ligation dependent probe amplification was performed. The relationship of complement protein with the mutation type was analyzed by using generalized estimating equations. RESULTS: Thirty-five different mutations (15 novel and 2/15 homozygous) were identified. There was no causative mutation in 6 patients (7.4%). Patients with deletion and large deletion had the lowest (5.05%, 0-18.7; 5.8%, 0-16.5%, respectively), and the none mutation group had the highest C1 inhibitor function (23.3%, 11-78%, p < 0.001). C1 inhibitor function levels decreased as the age of the disease progressed (r = -0.352, p = 0.005). Lower C1 inhibitor function levels caused severer disease (r = -0.404, p = 0.001) and more frequent annual attacks (r = -0.289, p = 0.024). In the off-attack period, C1q levels were lower than normal in 9.8% of the patients. CONCLUSION: Deletion mutations may represent the most unfavorable effect on C1 inhibitor function. The earlier disease onset age could be a sign for lower C1 inhibitor function levels in adult life. C1q levels could also be low in C1-INH-HAE patients, as in acquired angioedema. Lower C1 inhibitor function can predict disease severity and may have negative impacts on the course of C1-INH-HAE.

In Vitro Fertilization Using Luteinizing Hormone-Releasing Hormone Injections Resulted in Healthy Triplets without Increased Attack Rates in a Hereditary Angioedema Case.

Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) is a rare, autosomal dominant disorder. The management of pregnant patients with C1-INH-HAE is a challenge for the physician. Intravenous plasma-derived nanofiltered C1-INH (pdC1INH) is the only recommended option throughout pregnancy, postpartum, and breastfeeding period. In order to increase pregnancy rates, physicians use fertilization therapies increasing endogen levels of estrogens. Therefore, these techniques can provoke an increase in the number and severity of edema attacks in C1-INH-HAE. Our patient is a 32-year-old female, diagnosed with C1-INH-HAE type 1 since 2004. She had been taking danazol 50-200 mg/day for 9 years. Due to her pregnancy plans in 2013, danazol was discontinued. PdC1INH was prescribed regularly for prophylactic purpose. Triplet pregnancy occurred by in vitro fertilization using luteinizing hormone-releasing hormone (LHRH) injections. In our patient, LHRH injections were done four times without causing any severe attack during in vitro fertilization. Angioedema did not worsen during pregnancy and delivery due to the prophylactic use of intravenous pdC1INH in our patient. According to the attack frequency and severity, there was no difference between the three pregnancy trimesters. To our knowledge, this is the first published case of C1-INH-HAE receiving in vitro fertilization therapies without any angioedema attacks during pregnancy and delivery and eventually having healthy triplets with the prophylactic use of intravenous pdC1INH.

Misleading Allergens in the Diagnosis of Latex Allergy: Profilin and Cross-Reactive Carbohydrate Determinants.

BACKGROUND: It has been suggested that latex-specific IgE analysis may lead to false-positive results, especially in patients with pollen allergy. In the present study, the reasons underlying clinically irrelevant latex-specific IgE positivity were investigated. METHODS: Thirty patients with latex allergy (group 1), 89 patients sensitised to aeroallergens (group 2a), and 98 healthy individuals without allergy (group 2b) were enrolled. Participants from all 3 groups were subjected to skin prick tests with aeroallergens including latex, latex-specific IgE analysis (ImmunoCAP), and nasal provocation test with latex. All cases demonstrating positive latex-specific IgE also underwent specific IgE tests (ImmunoCAP) with latex profilin, birch pollen profilin, peach lipid transfer protein, and pineapple bromelain as cross-reactive carbohydrate determinants. RESULTS: Comparison of the atopic and healthy control groups showed that the rate of positive latex-specific IgE was significantly higher in group 2a. Latex profilin-, birch pollen profilin-, and bromelain-specific IgE were remarkably higher in group 2a. CONCLUSION: False positivity to latex-specific IgE in ImmunoCAP analysis may be observed in approximately 19% of patients with pollen allergy. Profilins and bromelain are the main contributors to clinically irrelevant positive latex-specific IgE.

Evaluation of Inferior Turbinate Stroma with Ultrasound Elastography in Allergic Rhinitis Patients.

BACKGROUND: Diagnosis of allergic rhinitis is primarily based on history, physical examination and allergy testing. A technique that noninvasively evaluates the soft tissue changes in the nasal mucosa of allergic rhinitis patients has not been defined. AIMS: To assess nasal mucosal changes and measure the submucosal fibrosis in allergic rhinitis patients with sonoelastography. STUDY DESIGN: Case control study. METHODS: Eighty-eight turbinates of 44 patients were included in the study. There were 23 prick test positive allergic rhinitis patients. The control group constituted 21 patients. The rhinitis quality of life questionnaire and the visual analogue scale were applied to the allergic rhinitis patients. A higher visual analogue scale score indicated more severe allergic rhinitis symptoms. Sonoelastographic measurements were made from the lateral nasal wall. The propagation speed of sound waves was recorded in m/s. The presence of asthma and the type of allergic rhinitis (seasonal or perennial) was noted. RESULTS: Ten patients had seasonal allergic rhinitis and thirteen patients had perennial allergic rhinitis. Six patients (26.1%) had accompanying asthma along with allergic rhinitis. The median visual analogue scale score was 7 (3-9) in allergic rhinitis patients. The median symptom duration was 7 (1-24) months. The median quality of life questionnaire score was 3.39 (1.68-5.43) points. The median sonoelastography scores of allergic rhinitis patients and healthy subjects were 2.38 m/s (0.9-4.47) and 2.42 m/s (1.62-3.50), respectively. Sonoelastographic measurements of seasonal and perennial allergic rhinitis patients did not differ significantly (p<0.05). The presence of asthma did not have a significant impact on the elastography measurements (<0.05). However, regression analysis revealed a significant inverse correlation (coefficients: B=0.005, standard error=0.097, beta 0=0.008) between the visual analogue scale and sonoelastography scores (p>0.05). CONCLUSION: Sonoelastography was not suitable as a diagnostic tool in allergic rhinitis. Reduced sonoelastography scores were measured in more symptomatic patients. Higher visual analogue scale scores could be an indicator of disease severity.

Quality-of-life in insect venom allergy: validation of the Turkish version of the "Vespid Allergy Quality of Life Questionnaire" (VQLQ-T).

PURPOSE: "Vespid Allergy Quality of Life Questionnaire (VQLQ)" has been used to assess psychological burden of disease. The aim of this study was to evaluate validity, reliability and responsiveness to interventions of the Turkish version. METHODS: The Turkish language Questionnaire (VQLQ-T) was administered to 81 patients with bee allergy and 65 patients with vespid allergy from different groups to achieve cross-sectional validation. To establish longitudinal validity, the questionnaire was administered to 36 patients treated with venom immunotherapy. RESULTS: The cross-sectional validation in patients with vespid venom allergy showed a correlation coefficient of 0.97 (Cronbach α). Spearman's correlation coefficient of the pretreatment VQLQ-T score with Expectation of Outcome (EoO) questionnaire score was 0.55 (p < 0.001). After treatment, correlation between VQLQ-T score and EoO score was 0.64 (p = 0.003) in these patients. The cross-sectional instrument validation for non-beekeepers with bee venom allergy yielded a correlation coefficient of 0.96 (Cronbach α). Spearman's correlation coefficient between pretreatment VQLQ-T score and EoO score was 0.47 (p < 0.001) and after treatment, correlation between VQLQ-T score and EoO score was 0.78 (p = 0.008) in these patients. These findings indicate cross-sectional validity of VQLQ-T. In the longitudinal validation, there was a positive correlation between EoO and VQLQ-T with a correlation coefficient of 0.562 (p < 0.001). While mean (±SD) VQLQ-T score was 5.27 (±1.29) in pretreatment, it was 2.78 (±1.01) after treatment (p < 0.001). The correlation between the mean change in VQLQ-T score and the mean change in EoO score was 0.42 (p = 0.011). CONCLUSIONS: The Turkish version of VQLQ-T enables measurement of Quality of Life (QoL) in patients with either vespid or bee venom allergy. Furthermore, responsiveness of this instrument demonstrates the questionnaire's ability to detect changes over time.

Phagocytic and oxidative burst activity of neutrophils in patients with spinal cord injury.

OBJECTIVE: To evaluate phagocytic activity and neutrophil oxidative burst functions in patients with spinal cord injury (SCI) because alterations in neutrophil metabolic activity can be one of the causes of immune mechanism damage contributing to repeated bacterial infections. DESIGN: A controlled and cross-sectional study. SETTING: Departments of physical medicine and rehabilitation and immunology. PARTICIPANTS: Patients with SCI (N=34) and 28 healthy controls. INTERVENTIONS: Phagocytosis and oxidative burst in whole-blood neutrophils were assessed by flow cytometry. The percentage of phagocytizing cells after in vitro incubation with Escherichia coli, phagocytic activity (mean intensity of fluorescence [MIF]) and the percentage of neutrophiloxidative burst, and the MIF value of the production of reactive oxygen intermediates (ROIs) were analyzed. In addition, clinical assessment including the level of injury, American Spinal Injury Association scores, and functional status were carried out. MAIN OUTCOME MEASURES: Not applicable. RESULTS: Although the percentage of E. coli phagocytizing neutrophils was not different between groups, the MIF value of absorbed E. coli was significantly lower in patients with SCI than in controls (P<.05). The MIF value of ROI production by neutrophils with both stimulator of phorbol 12-myristate 13-acetate and E. coli was significantly higher in patients with SCI (P<.05). CONCLUSIONS: In patients with SCI, decreased phagocytic activity of neutrophils may be a result of a regulatory mechanism to minimize the deleterious effects of increased neutrophil burst activity.

Desensitization effect of preseasonal seven-injection allergoid immunotherapy with olive pollen on basophil activation: the efficacy of olive pollen-specific preseasonal allergoid immunotherapy on basophils.

BACKGROUND: It has previously been demonstrated that subcutaneous immunotherapy with allergoids positively affects clinical and immunological parameters even after 7 preseasonal injections. However, its effect on basophil activation remains unclear. We investigated the effect of preseasonal allergoid immunotherapy on basophils and concomitantly assessed its clinical and immunological efficacy in olive pollen-monosensitized patients. METHODS: This study enrolled 437 consecutive patients with respiratory allergy and positive skin prick tests (SPTs); 212 (48.5%) patients were sensitized to olive pollen, and 33 (7.5%) patients were sensitized to olive pollen only. Of these patients, 23 received preseasonal immunotherapy with an olive pollen allergoid. The olive pollen-specific basophil activation, the titrated nasal provocation test, the nasal symptom score, and olive pollen-specific IgE, IgG1 and IgG4 levels were evaluated before immunotherapy and 8 months after the end of immunotherapy in the follow-up visit. RESULTS: In comparison to baseline evaluation, 7 preseasonal injections of an allergoid resulted in a significant decrease in the percentage of basophils expressing CD63 (29 vs. 7%, respectively, p < 0.0001) and a significant increase in the titrated nasal provocative dose (1/10 vs. 1/1, respectively, p < 0.01). SPT induration diameters caused by an olive pollen extract decreased (12 mm at baseline vs. 5.5 mm at follow-up, p < 0.005), as did nasal symptom score (7 at baseline vs. 3 at follow-up, p < 0.01). Olive pollen-specific IgE (17.5 vs. 50 kU/l, p < 0.012), IgG1 (0.16 vs. 2.9 µg/ml, p < 0.0001) and IgG4 (0.07 vs. 1.92 µg/ml, p < 0.0001) levels significantly increased. CONCLUSIONS: Immunotherapy with 7 preseasonal injections of an olive pollen allergoid decreases olive pollen-specific basophil activation over 8 months, an effect observed in vitro and in vivo.

Diagnostic value of specific IgE analysis in latex allergy.

BACKGROUND: The precision of the methods used to diagnose latex allergy is of great importance due to false-positive results. Neither the skin prick test (SPT) nor the latex-specific IgE assay has 100% diagnostic accuracy. We analysed the diagnostic value of latex-specific IgE by the first-ever concomitant use of the SPT and nasal provocation test (NPT). METHODS: Twenty-seven latex-sensitive patients (group 1), 46 aeroallergen-sensitive patients (group 2a) and 33 healthy subjects (group 2b) participated in the study. All groups underwent an SPT with latex and aeroallergens and an NPT with latex. Latex-specific IgE and total IgE levels were measured by the ImmunoCAP assay. RESULTS: Latex-specific IgE was positive in 92.6, 30.4 and 9.1% of groups 1, 2a and 2b, respectively. The 11 aeroallergen-sensitive patients in group 1 and all of the patients in group 2a were predominantly sensitised to pollens (grass, weed and tree) and reacted to a lesser degree to house dust mite, moulds and animal dander. Combined pollinosis was remarkably more prevalent in patients with positive latex-specific IgE in group 2a than in those with negative latex-specific IgE (p = 0.001). The NPT was positive in 84.6% of group 1 and negative in all control subjects. The sensitivity, specificity, negative predictive value and positive predictive value of the latex-specific IgE assay were 90.9, 72.2, 96.3 and 50%, respectively. CONCLUSION: The high rate of false-positive results for latex-specific IgE by ImmunoCAP should be taken into account when making a diagnosis of latex allergy in patients with pollinosis, especially in those sensitised to more than one pollen species.

The Turkish Hereditary Angioedema Pilot Study (TURHAPS): the first Turkish series of hereditary angioedema.

BACKGROUND: No published data presently exist concerning hereditary angioedema (HAE) in Turkey. The aim of the study was to initiate a preliminary multicentric evaluation about HAE and to determine the genetic properties of Turkish patients. METHODS: Based on records drawn from four medical centers we identified a total of 70 subjects, belonging to 60 unrelated families, fulfilling clinical and laboratory criteria for diagnosis of HAE with C1 inhibitor deficiency. Ten type I patients, and their first-degree relatives, underwent genetic analysis for HAE. RESULTS: The majority of patients were female (60%), the mean age was 37.7 ± 14.1 years. The mean age at the time of first angioedema symptom was 12.5 ± 9.2 years. Mean time lag between first symptom and diagnosis was 26 ± 14.4 years. All but 3 subjects had HAE type I. Family history of angioedema was present in 75.7% of the cases. Cutaneous swelling was reported by 87.1% of the patients, facial edema by 65%, abdominal symptoms by 74.3% and approximately one half (55.7%) had experienced one or more laryngeal attack. Genetic analysis of 10 families demonstrated that 5 carried a mutation that had never been previously described. CONCLUSION: We found that the clinical features of Turkish HAE patients were consistent with previously described patterns of this rare disease. The most noteworthy feature identified in the study was a significantly long duration between the first symptom appearance and final diagnosis. Our detection of different mutations in 10 patients confirms the allelic heterogeneity of the disease.

Vitamin D deficiency in the absence of enteropathy in three cases with common variable immunodeficiency.

BACKGROUND: Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia and a defect in antibody production. Herein we describe 3 patients diagnosed with CVID in whom vitamin D deficiency was detected in the absence of enteropathy. METHODS: Biochemical and immunological analysis, serum osteocalcin, parathyroid hormone, 25-OH vitamin D, 1,25(OH)(2) vitamin D, vitamin A, vitamin E, urinary calcium, and deoxypyridinoline measurements were carried out. Vitamin D receptor (VDR) expression was examined in the peripheral blood mononuclear cells and hair follicles by reverse transcriptase polymerase chain reaction. VDR gene polymorphism was evaluated by high-performance liquid chromatography. RESULTS: None of the patients presented nutrient deficiencies other than vitamin D. Two of them were free of osteomalacia-related symptoms. VDR expression was found to be lower in the peripheral blood mononuclear cells and hair follicles when compared to the control group. CONCLUSIONS: Patients with CVID may present asymptomatic vitamin D deficiency. Vitamin D and VDRs play an important role in the innate immune system and modulate Toll-like receptor-related responses. Delay in diagnosis may predispose these patients not only to irreparable bone loss but also to infections, and autoimmune and malignant disorders, thus emphasizing the importance of prompt intervention.

The effects of short term statin treatment on left ventricular function and inflammatory markers in patients with chronic heart failure.

BACKGROUND: Statins may provide additional benefits in patients with cardiac failure due to their pleiotropic effects besides their cholesterol-lowering actions. In this study, we aimed to evaluate the impact of 12-week fluvastatin therapy on the inflammatory cytokines and the ventricular performance markers in patients with heart failure. METHODS AND RESULTS: Fourty chronic heart failure patients, twenty with idiopathic dilated cardiomyopathy (DCM group) and 20 with ischemic cardiomyopathy (ICM group), for whom statin treatment was indicated according to Adult Treatment Panel III were included to this open label and prospective study. After a 12-week treatment with fluvastatin 80 mg/day; clinical functional capacity, echocardiographic indices of cardiac performance and inflammatory markers were evaluated. After the treatment, functional capacity (in DCM group: 2.05+/-0.4 versus 1.65+/-0.6, p=0.005; in ICM group: 2.25+/-0.5 versus 1.8+/-0.6, p=0.003), left ventricular ejection fraction, LVEF (from 30+/-5% to 33+/-5%, p=0.001 in DCM and 29+/-4% to 31+/-5%, p=0.001 in ICM group) and tissue Doppler mitral annular systolic velocity, Sm (5.8+/-1 cm/s to 7+/-1 cm/s, p=0.001 in DCM and 5.4+/-0.8 cm/s to 7+/-1 cm/s, p=0.001 in ICM group) improved. Tumor necrosis factor-alpha and interleukin-6 levels decreased, but no significant changes in high sensitive C-reactive protein and brain natriuretic peptide levels were detected with the fluvastatin treatment in both groups. CONCLUSION: Fluvastatin improved cardiac functions and the clinical symptoms in HF patients with either idiopathic dilated or ischemic etiology. This positive effect of fluvastatin which might be secondary to inflammatory modulation was more marked in patients with ischemic etiology. Statins in HF deserves special attention by means of further large-scale trials.

Common variable immunodeficiency (CVID) presenting with malabsorption due to giardiasis.

Common variable immunodeficiency is characterized with B-cell and T-cell dysfunction and hypogammaglobulinemia. Recurrent bacterial infections, such as otitis media, chronic sinusitis and recurrent pneumonia due to diminished immunoglobulin (Ig) levels and impaired antibody production are frequently observed in common variable immunodeficiency. Almost half of the patients with common variable immunodeficiency have problems related to the gastrointestinal system. A 39-year-old woman was referred to our department with the complaint of chronic diarrhea. She had experienced diarrhea without mucus or blood in the last year and had lost 30 kg. In her medical history, she had suffered from recurrent upper and lower respiratory infections like sinusitis, otitis media and pneumonia since childhood. Serum immunoglobulin levels were low. There were no parasites or ova in her stool examinations. Esophagogastroduodenoscopy detected widespread macroscopic nodular appearance on duodenum, and biopsies from the duodenum revealed giardiasis invading the tissue. She was diagnosed as common variable immunodeficiency. After metronidazole therapy and intravenous immunoglobulin infusion was started, her diarrhea attacks ceased and she regained her normal weight. Common gastrointestinal system problems in patients with common variable immunodeficiency are lactose intolerance, lymphoid hyperplasia/diffuse lymphoid infiltration, loss of villi and infection, especially with Giardia lamblia. Giardiasis may lead to severe mucosal flattening and sometimes to lymphoid hyperplasia at the lamina propria of the duodenum. Medical history should be evaluated carefully regarding recurrent respiratory infections. In such cases with chronic diarrhea, common variable immunodeficiency should be kept in mind as a possible cause.

Chlamydia pneumoniae arthritis in a patient with common variable immunodeficiency.

BACKGROUND: Arthritis is an important and sometimes life-threatening complication in patients with common variable immunodeficiency (CVID). OBJECTIVE: To describe a patient with CVID and arthritis due to Chlamydia pneumoniae, which is usually regarded as a respiratory tract pathogen and has not previously been detected in the synovial fluid by cell culture technique. METHODS: Routine bacteriologic, virologic, mycologic, and tuberculosis cultures were performed. The patient's synovial fluid was examined for fastidious organisms that might be causative pathogens of arthritis, such as chlamydiae, and special cell culture methods were used. Serologic tests were performed to determine viral and bacteriologic etiology. RESULTS: The patient had a history of recurrent respiratory tract infections, and the latest exacerbation was followed by arthritis. Cytologic examination of the fluid yielded abundant lymphocytes. Chlamydia pneumoniae was detected in synovial fluid specimens by cell culture technique. Her nasopharyngeal swab and sputum culture specimens were also positive for this pathogen. She was diagnosed as having arthritis caused by C pneumoniae and was given antibiotherapy. CONCLUSION: Chlamydia pneumoniae should be kept in mind as a causative pathogen in patients with CVID and arthritis, especially when effusion fluid is full of lymphocytes rather than polymorphonuclear cells and no organism is grown on routine cultures.