Background and Aims Common variable immunodeficiency (CVID) can affect quality of life (QoL) which can be better assessed with validated scales. Our goal was to validate the Turkish version of the Italian CVID-QoL questionnaire. Methods International recommendations for cultural adaptation and translation process of original scale was followed. CVID patients completed Turkish CVID-QoL questionnaire between October 2019 and January 2020. The Short Form Health Survey (SF-36) was used as a comparative questionnaire. Reliability, reproducibility, factor analysis, content validity, convergent validity and discriminant validity were analysed. Results 50 CVID patients were included in the study. 64 % of patients (n=32), the mean age of the patients was 36.68 ± 13.2 years, the median duration of disease was 52.5 months. The instrument had good internal consistency in 50 patients [Cronbach’s alpha: 0.92, emotional functioning (EF): 0.91, relational functioning (RF): 0.77]. It also revealed high reproducibility in 26 patients QoL global, intraclass correlation coefficient (ICC)= 0.80 (95 % CI 0.56 - 0.91); EF, ICC = 0.78 (95 % CI 0.51- 0.90); RF, ICC = 0.82 (95 % CI 0.59-0.92); Gastrointestinal and skin symptoms (GSS), ICC = 0.89 (95 % CI 0.76-0.95); (p <0.001, p <0.001, p <0.001, p <0.001). QoL global, EF and RF scores showed good convergent validity with similar subscales of SF-36. The number of infections within last 3 months had a significant impact on QoL global, EF and RF (p=0.038, p=0.045, p=0.028). Conclusions The Turkish version of CVID QoL scale has appropriate validity and reliability among Turkish patients with CVID.

Backgrounds: 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 is to validate CG as a screening test in 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 1.5 to 2.5 mg/dl 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 <600 mg/dl as a screening test was determined as <2.0 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 <0.7. In the retrospective analysis, 37 of 47 patients (78.7%) with PAD had a CG value of <2.0 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 <0.7. Conclusion: The determined CG cut-off value of <2.0 can be used as a screening test in Turkish adult patients.

Low and high IgE is linked to improvement and worsening of chronic urticaria during pregnancy, respectively Kocatürk E, Thomsen SF, Al-Ahmad M, Gimenez-Arnau A, Conlon N, Savk E, Criado RF, Danilycheva I, Fomina D, Khoshkhui M, Gelincik A, Degirmentepe EN, Demir S, Ensina LF, Kasperska-Zajac A, Rudenko M, Bauer A, Medina I, Maurer M.1 Urticaria Center of Reference and Excellence (UCARE), Dept. of Dermatology, Koç University School of Medicine, Istanbul, Turkey [email protected] Urticaria Center of Reference and Excellence (UCARE), Center of Reference and Excellence (UCARE), Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark [email protected] Urticaria Center of Reference and Excellence (UCARE), Microbiology Department, Faculty of Medicine, Kuwait University, Safat, Kuwait [email protected] Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology, Hospital del Mar, IMIM, Universitat Autònoma, Barcelona, Spain [email protected] Urticaria Center of Reference and Excellence (UCARE), Dermatology, and Immunology, St James’s Hospital, Dublin, Ireland [email protected] Aydın Adnan Menderes University, Aydın, Turkey [email protected] Urticaria Center of Reference and Excellence (UCARE), Faculdade de Medicina do ABC (FMABC), Santo André, Brazil [email protected] Urticaria Center of Reference and Excellence (UCARE), NRC Institute of Immunology FMBA of Russia, Moscow, Russia [email protected] Urticaria Center of Reference and Excellence (UCARE), First Moscow State Medical University, Moscow Center of Allergy and Immunology , Clinical Hospital 52 , Ministry of Moscow Healthcare, Moscow, Russia [email protected] Urticaria Center of Reference and Excellence (UCARE), Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran [email protected] Urticaria Center of Reference and Excellence (UCARE), Istanbul Faculty of Medicine Istanbul University, Istanbul, Turkey [email protected] Urticaria Center of Reference and Excellence (UCARE), Okmeydani Training and Research Hospital, Istanbul, Turkey [email protected] Urticaria Center of Reference and Excellence (UCARE), Istanbul Faculty of Medicine Istanbul University, Istanbul, Turkey [email protected] Urticaria Center of Reference and Excellence (UCARE), Federal University of São Paulo, Sao Paulo, Brazil [email protected] Urticaria Center of Reference and Excellence (UCARE), European Center for Diagnosis and Treatment of Urticaria (GA2LEN UCARE Network) Medical University of Silesia in Katowice, Poland [email protected] Urticaria Center of Reference and Excellence (UCARE), The London Allergy & Immunology Centre, London, United Kingdom [email protected] Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology, University Allergy Center, University Hospital Carl Gustav Carus, Technical University Dresden, Germany. [email protected] Urticaria Center of Reference and Excellence (UCARE), the Centro Médico Vitae, Buenos Aires, Argentina [email protected] Urticaria Center of Reference and Excellence (UCARE), Dermatological Allergology, Allergie-Centrum-Charité, Dept. of Dermatology and Allergy, Charité – Universitätsmedizin Berlin, Germany [email protected] Editor,PREG-CU, the recent study on pregnancy and chronic urticaria (CU) by the Urticaria Centers of Reference and Excellence (UCAREs), showed that CU improves in half (51.1%) of patients during pregnancy, whereas 28.9% and 20% of patients, respectively, experienced worsening and no change. Low disease activity, no angioedema, and no treatment before pregnancy were risk factors for worsening during pregnancy (1).We hypothesized that patients with chronic spontaneous urticaria (CSU) that worsens during pregnancy are more likely to have type I autoimmune CSU, also called autoallergic CSU. We also hypothesized that patients who improve during pregnancy are more likely to have type IIb autoimmune CSU (2). This hypothesis is supported by the immunological changes observed during pregnancy, i.e., decreased Th1 and Th17 immunity and a switch to a Th2-type cytokine profile (3).To test this hypothesis, we retrieved total IgE levels of CSU patients who gave consent to be included in the PREG-CU study (1). Elevated IgE levels have been reported to be linked to autoallergic CSU, whereas low IgE is a marker of type IIb autoimmune CSU (4).Total IgE blood levels were available for 115 of the 218 CSU patients not treated with omalizumab enrolled in PREG-CU. The median IgE level was 106 (range: 3-1664 IU/mL), more than half of patients (51.3%) had elevated IgE (≥100 IU/mL), and 17.4% had low IgE (<40 IU/mL). Most patients with mild disease (51%) or moderate disease (61%), but only one in four patients with severe disease (26%) had elevated IgE levels (≥100 IU/mL). IgE levels were lower in patients with severe disease (68 IU/mL) vs mild (112 IU/mL; p=0.009) or moderate disease (128 IU/mL; p=0.018), and low IgE levels (<40 IU/mL) were more frequent in patients with severe than mild disease (36.8 vs 11.6%; p=0.034).CSU patients who got worse during pregnancy had higher IgE levels (154 vs. 82.2 IU/mL; p=0.033) and numerically higher rates of elevated IgE (57.5 vs. 46%) compared to patients who got better during pregnancy. In contrast, patients who improved during pregnancy more often had low IgE levels than patients who deteriorated (22 vs. 12.5%), but this was not statistically significant. One in three of our patients (34.9%) had elevated anti-TPO, another marker of type IIb autoimmune CSU, but this was not linked to improvement during pregnancy.Worsening of CSU during pregnancy in patients with high IgE levels may be explained, in part, by the role that IgE and Th2 immunity play in the pathogenesis of their CSU. High IgE, in CSU, has been linked, in some studies, to autoallergy, characterized by the presence of IgE autoantibodies (5). Pregnancy skews immunity towards Th2 responses and patients with Th2-driven diseases, including allergies, often experience worsening of their disease during pregnancy (3). Improvement of CSU during pregnancy in patients with low IgE may point to a role of Th1 and Th17 cytokines in the pathogenesis of their disease. Low IgE is a type IIb autoimmune CSU marker, which is linked to Th1 and Th17 autoimmunity (6). Pregnancy decreases Th1/Th17 immunity, and patients with TH1/TH17-driven autoimmune diseases often experience improvement during pregnancy (3). Our finding that elevated IgG-anti-TPO, another marker of type IIb autoimmune CSU, is not linked to CSU improvement during pregnancy remains unexplained. Many CSU patients with IgG-anti-TPO also have IgE-anti-TPO and vice versa, which could point to both autoallergic and autoimmune drivers of their CSU. Better biomarkers are needed to identify which patients have autoallergic CSU, autoimmune CSU, both or none of these.Our findings support the notion that CSU is a heterogeneous disease, with at least two endotypes, i.e., autoallergic and autoimmune. Further studies are needed to better characterize the course of disease during and after pregnancy, in patients with autoallergic CSU and with autoimmune CSU. IgE levels may help to predict which CSU patients get worse and which improve when they get pregnant.

Background: The success of subcutaneous immunotherapy (SCIT) mostly depends on regular injections. Our aim was to investigate adherence to SCIT with aeroallergens during the COVID-19 pandemic and demonstrate clinical consequences of treatment disruptions in real-life. Methods: Visual analogue scale for quality of life (VAS-QoL), VAS for symptom scores (VAS-symptom), medication scores (MSs) and total symptom scores (TSS-6) were recorded during the pandemic in 327 adult allergic rhinitis and/or asthmatic patients receiving maintenance SCIT and these scores were compared with the pre-pandemic data. Patients were grouped according to SCIT administration intervals; no delay (Group 1), <2 months (Group 2), and ≥2 month intervals (Group 3). Results: 104 (31.8%) patients (Group 3) were considered as non-adherent which was mostly related to receiving SCIT with HDMs and using public transportation for reaching the hospital. Median MS, VAS-symptom and TSS-6 scores of Group 3 patients during the pandemic were higher than the pre-pandemic scores (p=0.005, p<0.001, p<0.001, respectively) whereas median VAS-QoL scores of Group 3 during the pandemic were lower than the pre-pandemic scores (p<0.001). Median TSS-6 and VAS-symptom scores were the highest in Group 3 compared to other groups (p<0.001 for each comparison). Median VAS-QoL scores were the lowest in Group 3 compared to Group 1 and Group 2 (p<0.001, p=0.043, respectively). Conclusion: When precautions in allergy clinics are carefully applied, adherence to SCIT can be high during a pandemic. Patients must be warned about adhering to SCIT injections since delays in SCIT administration can deteriorate clinical symptoms.

Background: Hereditary angioedema (HAE) attacks can be provoked with psychological factors. The aim of this study was to assess the effects of anxiety, depression and stress related to COVID-19 pandemic on disease activity of HAE patients during the quarantine period (QP) and the return to normal period (RTNP). Methods: This prospective study was conducted between March 2020 and September 2020 in four allergy centres. Demographic, clinical features and mental health status were evaluated in QP (from March to the beginning of June) and RTNP (from June to the beginning of September) was applied by the government. The 10-point visual analogue scale (VAS10) was used to define the severity of HAE attacks. Depression-Anxiety- Stress Scale-21 (DASS-21) and Fear of Covid-19 (FC-19) scales were performed to assess mental health status. Results: 139 HAE patients were included in the study. In QP, median attack numbers and median VAS10 scores were 5 (min-max: 0-45) and 6 (min-max: 0-10), respectively. HAE attack numbers, DASS-21 stress, anxiety, depression and total DASS-21 scores, as well as FC-19 scores were higher in QP than RTNP (p= 0.001, p <0,001, p = 0,001, p <0,001, p <0.001, p<0.001, respectively). However, there was no difference in attack severity scores between the two periods (p>0.05). Conclusions: This study revealed that the restriction measures during Covid-19 outbreak causes an increase in the number of HAE attacks in relation to anxiety, depression, stress and fear of Covid-19 pandemic. Therefore, it is important to provide psychological support to HAE patients during the pandemic.

Background: Knowledge on endothelial dysfunction and its relation to atherosclerosis in mastocytosis is limited. Aim: To investigate the endothelial function in mastocytosis by flow mediated dilatation (FMD) and biomarkers related to vascular endothelia, the presence of subclinical atherosclerosis by carotid intima media thickness (CIMT). Method: Forty-nine patients with mastocytosis and 25 healthy controls (HCs) were included. FMD and CIMT during transthoracic echocardiography, biomarkers including endocan, endothelin-1 (ET-1), vascular endothelial growth factor (VEGF) were measured in sera of participants. Tumor necrosis factor-alpha (TNF-α), interleukine-6 (IL-6) and high sensitive c-reactive protein (hsCRP) were determined as inflammatory biomarkers. Result: The mean FMD% was lower in the patients than HCs (11.26±5.85% vs 17.84±5.27% p<0.001) and was the lowest in the advSM and SSM group among the patients (p=0.03). The median value of VEGF was significantly higher in patients than HCs. [73.30 pg/mL; min-max (32.46-295.29) pg/mL vs (46.64 pg/mL; min-max 11.09-99.86 pg/mL; p:0.001] and it was the highest in the advSM and SSM group (p:0.01). FMD was inversely correlated with endocan (r:-.390, p:0.006), ET-1 (r:-.363, p:0.01) and VEGF (r:-.402, p:0.004) but there were no correlations between FMD and TNF-α, IL-6, and hsCRP. 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. Keywords: CIMT, Endocan, Endothelial function, Endothelin-1, FMD, VEGF