Whole-exome sequencing for genetic diagnosis of idiopathic liver injury in children.

Genome-wide approaches, such as whole-exome sequencing (WES), are widely used to decipher the genetic mechanisms underlying inter-individual variability in disease susceptibility. We aimed to dissect inborn monogenic determinants of idiopathic liver injury in otherwise healthy children. We thus performed WES for 20 patients presented with paediatric-onset recurrent elevated transaminases (rELT) or acute liver failure (ALF) of unknown aetiology. A stringent variant screening was undertaken on a manually-curated panel of 380 genes predisposing to inherited human diseases with hepatobiliary involvement in the OMIM database. We identified rare nonsynonymous variants in nine genes in six patients (five rELT and one ALF). We next performed a case-level evaluation to assess the causal concordance between the gene mutated and clinical symptoms of the affected patient. A genetic diagnosis was confirmed in four rELT patients (40%), among whom two carried novel mutations in ACOX2 or PYGL, and two had previously-reported morbid variants in ABCB4 or PHKA2. We also detected rare variants with uncertain clinical significance in CDAN1, JAG1, PCK2, SLC27A5 or VPS33B in rELT or ALF patients. In conclusion, implementation of WES improves diagnostic yield and enables precision management in paediatric cases of liver injury with unknown aetiology, in particular recurrent hypertransaminasemia.

Circulating Pentraxin-3 and its association with C-reactive protein levels and disease activity in patients with chronic spontaneous urticaria.

INTRODUCTION: Pentraxin-3 (PTX3) is a soluble long pentraxin molecule that regulates inflammatory responses. This study aimed to determine the plasma levels of plasma PTX-3 as an inflammation marker in chronic spontaneous urticaria (CSU) and whether the PTX3 levels correlate with disease activity and other clinical parameters, including acute phase reactants and biomarkers. METHODS: The study included 70 CSU patients and 30 healthy controls. Plasma PTX3 levels were measured by ELISA. CSU disease activity was evaluated with the urticaria activity score summed over 7 days. Complete blood count, C-reactive protein (CRP), transaminases, total IgE, antinuclear antibody, anti-thyroid peroxidase, anti-thyroglobulin, and D-dimer levels were recorded. RESULTS: Of the 70 patients, 52 (74.3%) were female, with a mean age of 37.51 ± 11.80 years. Disease activity was severe in 43, moderate in 15, and mild in 12 patients. Mean PTX3 levels were elevated in CSU patients compared to healthy controls (0.81 vs. 0.55 ng/mL, p = 0.031). The mean CRP levels were higher in patients than in the controls (4.26 vs. 1.57 mg/L, p = 0.023). Patients also had higher D-dimer levels than the controls (5.96 vs. 0.59 mg/L, p < 0.001). A significant positive correlation was found between PTX3 and CRP levels (r = 0.508, p < 0.001) and between D-dimer levels and UAS7 (r = 0.338, p = 0.004) and CRP (r = 0.213, p = 0.034) levels. A multivariable stepwise regression analysis showed that the one-unit increase in the CRP level increased to 38.19 units in the PTX3 level (95% confidence interval [17.40-58.98], p < 0.001). CONCLUSION: Circulating levels of CRP and PTX3, two members of the pentraxin family, are significantly correlated and elevated in CSU patients with increasing disease activity, indicating their utility as inflammatory markers in CSU.

Calculated Globulin Is Clinically Useful as a Screening Test for Antibody Deficiency in Turkish Adult Patients.

INTRODUCTION: Heterogeneous clinical features of antibody deficiency (AD) may cause diagnostic delays. Calculated globulin (CG) (total protein minus albumin) has been proposed as a screening test to prevent morbidity due to diagnostic delays in AD. Our aim was to validate CG as a screening test for AD in Turkish adult patients by comparing its role with gamma globulin analysis in protein electrophoresis. METHODS: Fifty serum samples were randomly collected for each level of CG from 15 to 25 g/L and tested for serum IgG, IgA, IgM levels and protein electrophoresis. Cut-off values predicting low IgG levels were calculated for electrophoretically determined gamma globulin and CG. Additionally, the data of 47 patients followed up in our clinic with a diagnosis of primary antibody deficiency (PAD) were retrospectively analyzed. RESULTS: A total of 550 adult patients were included in the study. The CG value predicting patients with IgG <6 g/L as a screening test was determined as <20 g/L with 83.8% sensitivity and 74.9% specificity. The gamma globulin value which predicted patients with the same IgG value of 89.0% sensitivity and 89.4% specificity was determined as <7 g/L. In the retrospective analysis, 37 of 47 patients (78.7%) with PAD had a CG value of <20 g/L at the time of the diagnosis and all 13 patients (100%) whose gamma globulin values were measured at the time of the diagnosis had a gamma globulin value of <7 g/L. CONCLUSION: The determined CG cut-off value of <20 g/L can be used as a screening test in Turkish adult patients.

Common but neglected problem in chronic spontaneous urticaria: Sleep disturbance.

Background: Association of chronic spontaneous urticaria (CSU) with sleep disturbance has not been evaluated in studies that involve a large number of patients. Objective: In this study, we aimed to evaluate the sleep attitude and circadian rhythm in patients with CSU. Methods: As the patient group, recently diagnosed 100 patients with CSU, 100 patients with allergic rhinitis (AR) as the patient control group, and 100 healthy controls (HCs) were included. The Pittsburgh Sleep Quality Index (PSQI) questionnaire, sleep hygiene index (SHI), Epworth Sleepiness Scale (ESS) questionnaire, and the morningness-eveningness questionnaire (MEQ) were filled to assess sleep quality and circadian rhythm. CSU disease activity was evaluated by urticaria activity score-7 (UAS-7). Patients with concomitant diseases, e.g., psychiatric illnesses, that possibly affect sleep status or those who use related medications and at moderate or high risk of obstructive sleep apnea according to the STOP-Bang questionnaire were excluded from the study. Results: PSQI, SHI, and ESS scores were higher, and the MEQ score was lower in patients with CSU and patients with AR than those in the HCs (p < 0.001, for each score). However, the scores were not different among the patients with CSU and the patients with AR. UAS-7 was only correlated with PSQI scores (r = 0.402, p < 0.001). In addition, blood eosinophil counts and the serum C Reactive Protein (CRP) level were correlated with sleep quality (p = 0.02). Conclusion: The poor sleep quality, impaired sleep hygiene, increased daytime sleepiness, and intermediate type of circadian rhythm were observed in the patients with CSU and the patients with AR. Physicians should be aware of sleep problems in patients with CSU that might affect their quality of life and the success of their treatment.

Picturing asthma in Turkey: results from the Turkish adult asthma registry.

INTRODUCTION: National data on asthma characteristics and the factors associated with uncontrolled asthma seem to be necessary for every country. For this purpose, we developed the Turkish Adult Asthma Registry for patients with asthma aiming to take a snapshot of our patients, thereby assigning the unmet needs and niche areas of intervention. METHODS: Case entries were performed between March 2018 and March 2022. A web-based application was used to record data. Study outcomes were demographic features, disease characteristics, asthma control levels, and phenotypes. RESULTS: The registry included 2053 patients from 36 study centers in Turkey. Female subjects dominated the group (n = 1535, 74.8%). The majority of the patients had allergic (n = 1158, 65.3%) and eosinophilic (n = 1174, 57.2%) asthma. Six hundred nineteen (32.2%) of the patients had obese asthma. Severe asthma existed in 670 (32.6%) patients. Majority of cases were on step 3-5 treatment (n: 1525; 88.1%). Uncontrolled asthma was associated with low educational level, severe asthma attacks in the last year, low FEV1, existence of chronic rhinosinusitis and living in particular regions. CONCLUSION: The picture of this registry showed a dominancy of middle-aged obese women with moderate-to-severe asthma. We also determined particular strategic targets such as low educational level, severe asthma attacks, low FEV1, and chronic rhinosinusitis to decrease uncontrolled asthma in our country. Moreover, some regional strategies may also be needed as uncontrolled asthma is higher in certain regions. We believe that these data will guide authorities to reestablish national asthma programs to improve asthma service delivery.

Impact of COVID-19 pandemic on the course of refractory chronic spontaneous urticaria under omalizumab treatment.

BACKGROUND: The course of chronic spontaneous urticaria (CSU) can be influenced by infections, depression, and stress. OBJECTIVE: Our aim was to investigate the impact of the COVID-19 pandemic on the course of refractory CSU together with patient adherence to omalizumab and treatment adjustments. METHODS: Urticaria Activity Score (UAS7) was used to assess disease activity. Fear of COVID-19 Scale (FC-19s), and Depression Anxiety Stress Scale (DASS-21s) were performed to assess mental health status. All scales were performed during the Quarantine Period (QP) and Return to the Normal Period (RTNP). UAS7 Before Pandemic (BP) was recorded from the patients medical records. RESULTS: The authors evaluated 104 omalizumab-receiving CSU patients. UAS7 scores during QP were significantly higher than those in RTNP and BP (p < 0.01). DASS-21 and FC-19 scores were significantly higher during QP compared to RTNP (p < 0.01). Nineteen (18.2%) patients ceased omalizumab, 9 patients prolonged the intervals between subsequent doses during the pandemic. UAS7 scores in QP were significantly higher in patients who ceased omalizumab than in those who continued (p < 0.001). Among patients who continued omalizumab, 22.4% had an increase in urticaria activity and higher FC-19 scores in comparison with those with stable disease activity (p = 0.008). STUDY LIMITATIONS: The small sample size of patients with prolonged intervals of omalizumab and the lack of mental health evaluation with the same tools prior to the study. CONCLUSION: Fear induced by COVID-19 can determine an increase in disease activity. Therefore, patients on omalizumab should continue their treatment and prolonged interval without omalizumab can be considered in patients with good urticaria control.

Plasma levels of oxysterols 7-ketocholesterol and cholestane-3ß, 5α, 6ß-triol in patients with allergic asthma.

The prevalence of allergic asthma is increasing on a global scale, reflecting changes in air pollution, climatic changes, and other environmental stimulants. In allergic conditions, oxidative stress occurs as a result of immune system activation. Oxidation of cholesterol leads to the formation of oxysterols. The main purpose of the study was to compare plasma levels of two oxysterols, namely 7-ketocholesterol (7-KC) and cholestane-3ß, 5α, 6ß-triol (C-triol), and a lipid peroxidation product, malondialdehyde (MDA) in allergic asthma patients with those of healthy controls, in order to provide information about the involvement of lipid peroxidation in allergic asthma.Oxysterols were quantified by LC-MS/MS in plasma samples of 120 asthma patients (90 females + 30 males) and 120 healthy controls (matched by age and sex). Plasma MDA level was analyzed by a spectrophotometric method.Plasma 7-KC (39.45 ± 20.37 ng/mL) and C-triol (25.61 ± 10.13 ng/mL) levels in patients were significantly higher than in healthy subjects (17.84 ± 4.26 ng/mL and 10.00 ± 3.90 ng/mL, respectively) (P < 0.001). Plasma MDA levels were also higher in asthmatic patients (4.98 ± 1.77 nmol/mL) than in healthy controls (1.14 ± 0.31 nmol/mL) (P < 0.001). All data support that lipid peroxidation products are involved in allergic asthma.Oxysterols were quantified for the first time in allergic asthma. Since the high plasma 7-KC and C-triol levels of allergic asthma patients correlate with high IgE levels, detection of these oxysterols by LC-MS/MS may be helpful in the clinical monitoring of allergic asthma. Current data may also lead to new approaches for the prevention, diagnosis, and treatment of the disease.Supplemental data for this article is available online at at.

Anaphylaxis in Risky Populations.

Anaphylaxis should be clinically diagnosed with immediate recognition, whereas, despite advances in the field of allergy, the symptoms of anaphylaxis remain to be under-recognized, diagnosis is often missed, and treatment is often delayed. Anaphylaxis presents with symptoms in a spectrum of severity, ranging from mild objective breathing problems to circulatory shock and/or collapse. Indeed, anaphylaxis management frequently relies on a 'one-size-fits-all approach' rather than a precision medicine care model, despite the evidence that anaphylaxis is a heterogeneous condition with differences in causative agents, clinical presentation, and host susceptibility. The key important risk factors for severe anaphylaxis and mortality are certain age groups or certain stages of life (infants, elderly and pregnant women), augmenting factors (physical exercise, alcohol consumption, menstruation, acute infections), concurrent use of some medications (beta-adrenergic blockers (ß-blockers) and angiotensin-converting enzyme (ACE) inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), and proton pump inhibitors (PPIs), and concomitant diseases (i.e. asthma, cardiovascular disease, mastocytosis). The present review aims to collectively address the patient groups who are at high risk of having anaphylaxis, those who have a more severe course, those that are difficult to diagnose, and require a special approach in treatment. Therefore, the risky populations like the elderly, pregnant women, patients receiving ß- blockers or ACE inhibitors, those with concomitant cardiovascular diseases, asthma, and mastocytosis, or those having higher baseline serum tryptase levels are discussed, including their clinical presentations and treatment strategies. Additionally, anaphylaxis during the perioperative period is addressed.

Predictive factors of recurrence after omalizumab cessation in the elderly with urticaria: A real-life study.

Background: There are no well-defined data that help predict the recurrence risk of urticaria after omalizumab cessation in elderly patients with chronic spontaneous urticaria (CSU). Objective: We aimed to evaluate the effectiveness and safety of omalizumab and to determine the possible predictive factors for recurrence after omalizumab cessation in the elderly with CSU. Methods: A total of 193 patients with CSU treated with omalizumab were included and divided into two groups according to age: group 1, ages 18-64 years (n = 127), and group 2, ages ≥ 65 years (n = 66). Demographics, clinical features, immunoglobulin G (IgG) anti-thyroid peroxidase antibody (anti-TPO), serum total IgE were analyzed. The IgG anti-TPO/total IgE ratio was calculated. Pretreatment 7-day urticaria activity scores, medication scores, and urticaria control test results were compared with those after treatment periods. Adverse effects were also evaluated. Results: The most common adverse effect of omalizumab treatment was injection-site reactions (4.7%) in both groups. Omalizumab was ceased after 24 weeks in 40.9% and in 73.1% in group 1 and group 2, respectively (p < 0.001). CSU recurred after omalizumab discontinuation in 9 and 15 patients in group 1 and in group 2, respectively (p < 0.001). The median baseline IgG anti-TPO was higher in patients with recurrent CSU in group 2 than in those in group 1 (p = 0.002). In group 2, the cutoff values of IgG anti-TPO and the IgG anti-TPO/total IgE ratio were 54.83 IU/mL and 0.45 for recurrence, respectively. Conclusion: Omalizumab is effective and safe in elderly patients with CSU. The serum baseline IgG anti-TPO level and the IgG anti-TPO/total IgE ratio could serve as predictors of recurrence in CSU after omalizumab cessation in elderly patients.

Psychiatric comorbidity and quality of life in patients with drug hypersensitivity.

Background: Compared with advances in a drug hypersensitivity diagnosis and management, little is known about the mental health status of patients with drug hypersensitivity and the impact of this psychological distress on their quality of life (QoL). Objective: The objectives were to evaluate anxiety, depression, and QoL levels in patients with drug hypersensitivity, assess how some related factors may affect them, and determine the impact of disease on their QoL. Methods: A total of 203 patients with drug hypersensitivity and 80 healthy controls were evaluated with the Beck Anxiety (BAI) and the Depression Inventory (BDI), and the short version of the World Health Organization Quality of Life (WHOQOL-BREF) scale. Results: The mean ± standard deviation (SD) BAI scores of the patients and the controls were 13.46 ± 11.78 and 1.94 ± 1.93, respectively (p < 0.0001). The mean ± SD BDI scores were higher in the patient group (9.23 ± 6.36) than in the control group (2.18 ± 2.02) (p < 0.0001). The patients had significantly increased risk of anxiety versus the controls (48.8% versus 7.5%) (odds ratio [OR] 11.74 [95% confidence {CI}, 4.88-28.20]; p < 0.0001) and depression versus the controls (31.5% versus 6.2%) (OR 6.90 [95% CI, 2.66-17.90]; p = 0.0001). The comparison of patients' BAI and BDI scores showed that those with more severe reactions had higher scores than those with moderate and mild reactions. A negative correlation was found among all WHOQOL-BREF scale domain scores and the BAI and BDI scores. Conclusion: Anxiety and depressive symptoms have a high prevalence in patients with confirmed drug hypersensitivity, which leads to a notable decrease in QoL. Self-administered psychological questionnaires were shown to be useful in the psychological examination and management of patients with drug hypersensitivity. Therefore, we found that psychological support is critical to reducing the negative outcomes of hypersensitivity reactions in patients.

How satisfactory is on-demand icatibant from the patients' perspective in real life?

Background: Patients' satisfaction is important for the success of the management of chronic diseases. Objective: Our aim was to evaluate the satisfaction level of the patients with hereditary angioedema (HAE) for icatibant treatment. Methods: Patients with HAE C1 esterase inhibitor (C1-INH) were evaluated by using a questionnaire that included details of their icatibant-treated attacks. Patients' demographic and clinical features were collected from their medical records and personal attack diaries. The visual analog scale was used for determining the attack severity. Results: Of the total 161 patients with HAE C1-INH, 91% had HAE type I and were included in the study. Patients reported a median (interquartile range [IQR]) attacks of 2 (0.5-3) per month and 16 (4.5-36) attacks per year. The median (IQR) frequency of attacks treated with icatibant was 6 (0-20) per year. The mean ± standard deviation (SD) duration of treatment with icatibant was 3 ± 2.3 years. The self-administration rate was 91.3%. The mean ± SD time to administration and time to onset of symptom resolution were 1.6 ± 1.1 hours and 1.7 ± 1.3 hours, respectively. There was a correlation between the time to administration and time to onset of symptom resolution (r = 0.566; p < 0.0001). A total of 125 patients (77%) reported that they were very satisfied or satisfied with icatibant. No correlation was observed between the satisfaction level and the attack sites; however, the patients with more severe attacks were more satisfied with icatibant (p < 0.0001). A total of 52 patients reported 74 mild local reactions. Systemic reactions were not observed. Conclusion: The current real-life study showed that icatibant was safe and effective. Moreover, the patients' satisfaction level with icatibant was high. We believe that the availability of icatibant should be encouraged during HAE attacks because it enables patients to be more involved in their disease management.

Evaluation of oxidative stress biomarkers and antioxidant parameters in allergic asthma patients with different level of asthma control.

OBJECTIVE: There is evidence that reactive oxygen species, especially free radicals, produced during the immune and inflammatory response may play important roles in the development of asthma.We aimed to evaluate the levels of certain oxidative stress biomarkers and antioxidant capacity in asthma patients with different asthma control levels in comparison to healthy subjects. METHODS: A total of 120 adult allergic asthma patients and 120 healthy individuals were included in this study. Using spectrophotometric methods, we analyzed two oxidative stress markers, levels of malondialdehyde (MDA) and protein carbonyls (PC), as well as reduced glutathione (GSH), total antioxidant capacity (FRAP) and catalase activity as critical antioxidant defense parameters in the blood samples of allergic asthma patients and healthy controls. The patients were divided into 3 subgroups according to asthma control test (ACT) results: totally controlled (TCG), partially controlled (PCG) and uncontrolled (UCG) subgroups. All biomarkers were compared between the three patient subgroups, as well as between total asthma patients and control subjects. RESULTS: There were remarkable differences between the control group and the combined patient group for all parameters. A significant increase in MDA and PC, especially in the UCG (p < 0.01 and p < 0.05, respectively) was detected in comparison to other subgroups. Additionally, increased MDA and PC levels, as well as decreased GSH levels were observed in all subgroups individually in comparison to the control (p < 0.001). CONCLUSIONS: This research demonstrates the presence of severe oxidative stress, considering the increase in lipid peroxidation and protein oxidation, in patients with allergic asthma, even under controlled conditions.

Increased serum nesfatin-1 levels in patients with inflammatory bowel diseases.

BACKGROUND: Adipokines are adipose tissue-derived secreted molecules that can exert anti-inflammatory or proinflammatory activities. Altered expression of adipokines has been described in various inflammatory diseases, including inflammatory bowel diseases (IBDs) such as Crohn's disease (CD) and ulcerative colitis (UC). Little is known about nesfatin-1, a recently identified adipokine, in IBD. The aim of this study was to investigate serum nesfatin-1 levels in patients with IBD. METHODS: This study included a total of 52 adult individuals (17 patients with CD, 18 patients with UC and 17 healthy volunteers) with similar age and body mass index. Serum nesfatin-1 levels were measured by ELISA in healthy individuals and patients with IBD in their active and remission periods. Blood inflammation markers including C reactive protein (CRP), erythrocyte sedimentation (ESR) and white cell count (WCC) were also measured in patients. RESULTS: We found significantly elevated levels of serum nesfatin-1 in the active disease period in both patients with CD (p=0.00003) and patients with UC (p=0.00001), compared with healthy individuals. Serum nesfatin-1 levels moderately decreased in the remission period; however, they were still significantly higher than that of healthy individuals. Receiver operating characteristic curve analyses indicated serum nesfatin-1 with an excellent diagnostic value for IBD. Finally, patients had significantly high CRP, ESR and WCC in the active IBD; however, we found the nesfatin-1 strongly correlated only with ESR in the active CD. CONCLUSION: This is the first study investigating the circulating levels of nesfatin-1 in patients with IBD. Serum nesfatin-1 may serve as an additional inflammatory marker for diagnosis of IBD in affected individuals.

Evaluation of skin test indications for general anesthetics in real life: a prospective cohort study.

BACKGROUND: In daily practice, atopic patients and those who have other drug allergies are referred to allergy clinics for evaluation of possible general anesthetic allergy despite the fact that it is not recommended in recent guidelines. OBJECTIVE: The aim of this prospective study is to determine the negative predictive value of skin tests for common general anesthetic drugs prior to general anesthesia in atopic patients and in patients who had drug allergies by including the data of those who had previously tolerated or reacted to general anesthesia. METHODS: A database program was constituted to collect the preoperative skin test data of patients referred to our clinic between 2013 and 2018. Demographic and clinical history, medications implemented during perioperative period, reactions, and results of skin tests performed with anesthetic drugs and latex were evaluated. RESULTS: Four hundred fifty-nine out of the total 1167 patients referred fulfilled the inclusion criteria for further evaluation. Nearly 75% of the patients were female and mean age was 46.3 ±â€¯14.3 years. History of hypersensitivity reactions (HRs) due to NSAIDs and/or antibiotics, radiocontrast agents, local anesthetics, and food were present in the 53.1%, 4.1%, 1.5%, and 2.0%, respectively. The negative predictive values of skin tests for general anesthetics were in the range of 80-100%. Only 4 patients (0,87%) experienced HRs during operation. CONCLUSION: These real-life data reveal high rates of negative predictive value of skin tests with general anesthetic drugs and a low reaction rate in atopic patients and in patients with allergy to other drugs.

Impact of mental health on disease activity in mastocytosis during COVID-19 pandemic.

BACKGROUND: Mast cell-related symptoms might be influenced by mental health status in mastocytosis. In this study, we aimed to investigate the influence of mental health problems developed during the COVID-19 pandemic on the course of mastocytosis. METHODS: Mental health status in 60 adult patients with mastocytosis was prospectively evaluated with the total Depression-Anxiety-Stress Scale (tDASS-21) and Fear of COVID-19 Scale (FCV-19S) in the lockdown period (LP) and the return to normal period (RTNP) during the pandemic. The disease course was assessed from emergency and outpatient medical reports, including Scoring Mastocytosis (SCORMA) index and serum baseline tryptase levels, by telephone interviews and clinical visits. RESULTS: The mean FCV-19S and median tDASS-21 scores were significantly higher in LP than RTNP (p < 0.001) and there was a positive correlation between FCV-19S and tDASS-21 in LP (r = 0.820, p < 0.001) and in RTNP (r = 0.572 p= <0.001). Disease-related symptoms including skin lesions, flushing and anaphylaxis attacks increased in 22 patients in LP, and in this group, mean FCV-19S and median tDASS-21 were higher than those without symptom exacerbation (p < 0.001). During the study period, four (6.7%) patients who experienced COVID-19 recovered without any requirement for hospitalization and had not experienced symptom exacerbation. CONCLUSIONS: Fear of COVID-19 can be a reason for mental health changes, including depression, anxiety and stress which may further increase mast cell-related symptoms. Therefore, psychological support is important to control the severity of mast cell-related symptoms in mastocytosis during a pandemic.

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.

Psychological burden of COVID-19 on mild and moderate chronic spontaneous urticaria

Background: The impact of coronavirus disease 2019 (COVID-19) related mental health status on chronic spontaneous urticaria (CSU) has not been addressed before. Objective: The aim of this study was to evaluate the depression, anxiety and stress levels, and the fear of COVID-19 in patients with mild-to-moderate CSU and to determine their impact on urticaria activity during the pandemic. Methods: A total of 509 patients with mild-to-moderate CSU were prospectively evaluated with validated scales, the Depression Anxiety Stress Scale 21 (DASS-21) and the Fear of COVID-19 Scale (FCV-19S) during the lockdown period (LP) and the return to normal period (RTNP). CSU activity was determined with the urticaria activity score summed over 7 days (UAS7) and medication scores (MS). UAS7 and MS before the pandemic were retrospectively collected from medical records. Results: The median UAS7 and MS were both significantly higher in the LP than in the median of related scores during the prepandemic period (p < 0.0001) and the RTNP (p < 0.0001). The mean FCV-19S and DASS-21 scores were both significantly higher in the LP than in the RTNP (p < 0.0001). The FCV-19S and the DASS-21 anxiety and stress subscales were significantly higher in women. The UAS7s were positively correlated with the FCV-19S and depression, anxiety, and stress subscale scores. Conclusion: Fear of COVID-19, anxiety, depression, and stress during the COVID-19 pandemic, especially when strict isolation measures are taken, have a significant impact on mental health and urticaria activity in patients with mild-to-moderate CSU, even though they are not infected. Psychological support for patients with CSU seems to be important to control disease activity during the pandemic.

Impaired endothelial function irrespective of systemic inflammation or atherosclerosis in mastocytosis.

BACKGROUND: Knowledge on endothelial dysfunction and its relation to atherosclerosis in mastocytosis is limited. OBJECTIVE: To investigate the endothelial function in mastocytosis by flow-mediated dilatation (FMD) and biomarkers related to vascular endothelia and to evaluate its relationship with the presence of subclinical atherosclerosis by carotid intima media thickness (CIMT). METHODS: A total of 49 patients with mastocytosis and 25 healthy controls (HCs) were included. The FMD and CIMT during transthoracic echocardiography biomarkers including endocan, endothelin-1, and vascular endothelial growth factor (VEGF) were measured in the sera of participants. Tumor necrosis factor-alpha, interleukin 6, and high-sensitive C-reactive protein were determined as inflammatory biomarkers. RESULTS: The mean FMD % was lower in the patients than HCs (11.26% ± 5.85% vs 17.84% ± 5.27% P < .001) and was the lowest in the advanced systemic mastocytosis and smoldering systemic mastocytosis group among the patients (P = .03). The median value of VEGF was considerably higher in patients than HCs (73.30 pg/mL; minimum-maximum 32.46-295.29 pg/mL vs 46.64 pg/mL; minimum-maximum, 11.09-99.86 pg/mL; P = .001) and it was the highest in the advanced systemic mastocytosis and smoldering systemic mastocytosis group (P = .01). The FMD was inversely correlated with endocan (r = -0.390; P = .006), endothelin-1 (r = -0.363; P = .01) and VEGF (r = -0.402; P = .004) but there were no correlations between FMD and tumor necrosis factor-alpha, interleukin 6, and high-sensitive C-reactive protein. No differences in CIMT values between patients and HCs and no correlation between CIMT and the biomarkers were observed. CONCLUSION: Endothelial dysfunction in mastocytosis becomes evident with decreased FMD and elevated serum VEGF in the absence of atherosclerosis or systemic inflammation and is related to disease severity.

Diagnostic workup including CD203c-based basophil activation test in immediate hypersensitivity due to metronidazole and ornidazole and evaluation of cross-reactivity in between.

BACKGROUND: Little is known about the diagnostic approaches for immediate hypersensitivity reactions (IHRs) due to 5-nitroimidazole antibiotics. The aim was to evaluate the usefulness of in vivo tests and basophil activation test (BAT) for the diagnosis of IHRs due to metronidazole and ornidazole and to determine possible cross-reactivity in between. METHODS: Forty-nine patients with a clear history of IHRs due to these drugs and 20 healthy subjects who were known to tolerate these drugs were included. Skin tests (STs) and single-blind placebo-controlled drug provocation tests (SBPCDPTs) were performed with both drugs whereas BAT was applied only with the culprit drug. RESULTS: The most and least common reaction types were urticaria/angioedema (34.7%) and anaphylaxis (14.3%), respectively. SBPCDPTs were positive in 15 out of 47 patients, and only 7 had positive STs. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of STs for metronidazole/ornidazole were 33.3%/16.6%, 94.2%/97.3%, 60%/50%, and 84.6%/88.1%, respectively. BAT was positive in 12 out of 15 patients and negative in 10 control subjects, giving a sensitivity rate of 71.4% (CI, 29.0%-96.3%) for metronidazole and 83.3% (CI, 35.8%-99.5%) for ornidazole. The optimal concentration of both drugs for BAT was determined as 5 mg/mL. No cross-reactivity among two drugs was observed according to in vivo tests. CONCLUSIONS: Our study showed that SBPCDPT and BAT are both useful diagnostic tools for IHRs due to 5-nitroimidazole antibiotics and can be used as supplementary to each other. No cross-reactivity between metronidazole and ornidazole in IHRs exists.