How Does Pregnancy and Type of Delivery Affect the Clinical Course of Hereditary Angioedema?

INTRODUCTION: Knowledge on the clinical course of hereditary angioedema (HAE) during pregnancy, delivery, and breastfeeding is very limited. In this study, we aimed to evaluate the course of HAE during these periods. METHODS: The HAE attacks C1-INH prophylaxis before and during pregnancy and during breastfeeding, and the delivery types were retrospectively determined. The severity of attacks was assessed by a 10-point Visual Analogue Scale (VAS). RESULTS: We evaluated 88 pregnancies in 48 HAE patients among whom 20 were primiparous. Among those who had a HAE diagnosis during pregnancy (n = 34), the median attack numbers before pregnancy, during pregnancy, breastfeeding, and after breastfeeding were 17, 39, 24, and 14 (before pregnancy vs. pregnancy, p < 0.001; during pregnancy vs. breastfeeding, p = 0.001). The mean VASs (SD) were 6.59 (1.82), 8.33 (1.58), 7.32 (1.66), and 6.95 (1.90) (before pregnancy vs. pregnancy, p < 0.001; during pregnancy vs. breastfeeding, p = 0.016), respectively. Among those who received a HAE diagnosis after pregnancy (n = 54), the number (59.3%) and the severity (60%) of HAE attacks were high in pregnancy. 47 of the deliveries were normal vaginal delivery (NVD). Regional anesthesia was applied in 8 NVDs. 20 of caesarean deliveries were performed under general anesthesia, and 21 were under spinal anesthesia. Lowest numbers of attacks were found in patients who did not receive anesthesia during NVD (p = 0.001). CONCLUSION: The course of HAE can be worse during pregnancy and breastfeeding. NVD is related to fewer HAE attacks and prophylaxis with C1-INH during NVD is not necessary to prevent a HAE attack.

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.

How important is patch testing with dental materials in real-life clinical practice?

Background: Allergy to dental materials in prostheses and implants that leads to dental device dysfunction is a challenging problem. Objective: In this prospective study, we aimed to investigate the diagnostic role and impact of dental patch test (DPT) results on the outcome of proceeding dental procedures with the collaboration of our allergy clinic and dental clinics. Methods: A total of 382 adult patients with oral or systemic signs or symptoms due to the applied dental materials were included. A DPT with 31 items was administered. The clinical findings after dental restoration according to the test results were assessed in the patients. Results: The most common positivity detected in the DPT was due to metals, among which nickel (29.1%) was the leading cause. The frequency of self-reported allergic diseases and metal allergy was significantly higher in patients with at least one positive result in the DPT (p = 0.004 and p < 0.001, respectively). Clinical improvement after the removal of dental restoration was seen in 82% of the patients who had a positive DPT result, whereas this rate was 54% among paatients with negative DPT results (p < 0.001). The only factor that predicted improvement after restoration was the positivity in the DPT result (odds ratio 3.96 [95% confidence interval, 0.21-7.09]; p < 0.001). Conclusion: Our study showed that a self-reported metal allergy was an important finding to predict allergic reactions to dental devices. Therefore, patients should be questioned for the presence of metal allergy-related signs and symptoms before exposure to the dental materials to prevent possible allergic reactions. Furthermore, DPT results are valuable to guide dental procedures in real life.

Comparison of 300 mg versus 600 mg daily maintenance doses of aspirin treatment after desensitization in N-ERD: A three-year multicentre experience.

Background: Aspirin treatment after desensitization (ATAD) is effective in preventing nasal polyps recurrence as well as respiratory symptoms in patients with nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory diseases (N-ERD). However, there is no consensus on effective daily maintenance doses in ATAD. Therefore, we aimed to compare the effects of two different maintenance doses of aspirin on clinical outcomes for 1-3 years of ATAD. Methods: This was a retrospective, multicenter study that involved four tertiary centers. The maintenance doses of daily aspirin were 300 mg in one center and 600 mg in the remaining three. The data of patients who were on ATAD for 1-3 years were included. Study outcomes (nasal surgeries, sinusitis, asthma attacks, hospitalization, oral corticosteroid use, and medication uses) were assessed in a standardized way and recorded from case files. Results: The study initially included 125 subjects, 38 and 87 were receiving 300 and 600 mg daily aspirin for ATAD, respectively. Number of nasal polyp surgeries decreased after 1 -3 years compared with before ATAD in both groups (group 1, baseline: 0.44 ± 0.07 versus first year: 0.08 ± 0.05; p < 0.001 and baseline: 0.44 ± 0.07 versus 3rd year: 0.01 ± 0.01; p < 0.001; and group 2, baseline 0.42 ± 0.03 versus first year: 0.02 ± 0.02; p < 0.001 and baseline: 0.42 ± 0.03 versus 3rd year: 0.07 ± 0.03; p < 0.001). Conclusion: Given the comparable effects of 300 mg and 600 mg aspirin daily as maintenance treatment of ATAD on both asthma and sinonasal outcomes in N-ERD, our results suggest using 300 mg of aspirin daily in ATAD owing to its better safety profile.

Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs in adults: Beyond current classification.

BACKGROUND: Hypersensitivity reactions (HSRs) to nonsteroidal anti-inflammatory drugs (NSAIDs) are a significant clinical issue. Several classifications have been proposed to categorize these reactions, including the current European Academy of Allergy and Clinical Immunology/European Network for Drug Allergy (EAACI/ENDA) classification. This study aimed to evaluate the applicability of this classification in a real-world clinical setting. METHODS: We conducted a national multicenter study involving patients from nine hospitals in four major urban centers in Turkey. All patients had a suggestive clinical history of hypersensitivity reactions to NSAIDs. Researchers collected data using a structured form and classified reactions based on the EAACI/ENDA classification. Oral provocation tests with several NSAIDs were performed using a single-blind challenge per EAACI/ENDA guidelines. RESULTS: Our retrospective study included 966 adult patients with a history of hypersensitivity to NSAIDs. The most common triggers were Acetylsalicylic Acid (ASA), paracetamol, and metamizole. The most prevalent acute NSAID hypersensitivity group was NSAID-induced urticaria/angioedema (NIUA) (34.3%). However, 17.3% of patients did not fit neatly into the current EAACI/ENDA classification. Notably, patients with underlying asthma or allergic rhinoconjunctivitis exhibited unusual reactions, such as urticaria and/or angioedema induced by multiple chemical groups of NSAIDs, blended mixed reactions, and isolated periorbital angioedema in response to multiple chemical groups of NSAIDs. CONCLUSIONS: While the EAACI/ENDA classification system stratifies NSAID-induced hypersensitivity reactions into five distinct endotypes or phenotypes, it may not fully capture the diversity of these reactions. Our findings suggest a need for further research to refine this classification system and better accommodate patients with atypical presentations.

Adherence to subcutaneous immunotherapy with aeroallergens in real-life practice during the COVID-19 pandemic.

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: A total of 104 (31.8%) patients (Group 3) were considered as nonadherent 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 with other groups (p < 0.001 for each comparison). Median VAS-QoL scores were the lowest in Group 3 compared with 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 encouraged to regularly adhere to SCIT injections since delays in SCIT administration can deteriorate clinical symptoms.

Relationship between Blastocystis spp. with Accompanying Food Hypersensitivity and Chronic Spontaneous Urticaria.

INTRODUCTION: The relationship between Blastocystis spp. and chronic spontaneous urticaria (CSU) is unclear. The aim of this study was to evaluate the role of this parasitic infection on CSU and to search for risky groups in CSU patients with this parasite. METHODS: Seventy adult CSU patients with Blastocystis spp. in their stool samples forming Group A and 70 CSU patients without any parasite as Group B were prospectively compared regarding urticaria activity score-7 (UAS7), medication scores (MS), and laboratory parameters. All patients received CSU treatment, and additionally, those in group A received an antiparasitic antibiotic. Eight months later, the same parameters were compared between the ones in remission (group A1) and those still having CSU symptoms (group A2) in group A. RESULTS: UAS7 and MS were lower in group A than in group B (p: 0.007, p < 0.001) 8 months later, while the initial scores were similar. The presence of food hypersensitivity reactions (FHRs) was higher in group A than in group B (p < 0.001) and was detected as a significant risk factor in the presence of Blastocystis spp. infection (p: 0.002, OR [CI] = 0.151 [0.045-0.502]). In group A, UAS7, MS, serum total IgE levels, and blood eosinophil counts decreased 8 months later (p < 0.001, p < 0.001, p: 0.003, p: 0.004, respectively). Additionally, total IgE levels and eosinophil counts decreased in group A1 (p: 0.033, p: 0.002) while they did not change in group A2. DISCUSSION/CONCLUSION: The eradication of Blastocystis spp. can improve the disease activity in CSU and the presence of FHRs seems to be risky in CSU patients with Blastocystis spp.

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.

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.

Clinical effects of intranasal corticosteroids on nasal symptoms in subjects with chronic rhinitis during COVID-19.

Background: The clinical effects of intranasal corticosteroids (INC) on nasal symptoms and the clinical course of coronavirus disease 2019 (COVID-19) in subjects with chronic rhinitis (CR) seem unclear. Objective: To evaluate the clinical effects of INCs on nasal symptoms in subjects with CR and with COVID-19. Methods: In subjects with CR and diagnosed with COVID-19 at four tertiary centers, quality of life and nasal symptoms were assessed by using the 22-item Sino-Nasal Outcome Test (SNOT-22) and the visual analog scale (VAS), respectively. In subjects with allergic rhinitis, nasal symptoms were also assessed on the total symptom score-6 (TSS-6) scale. The subjects were then allocated into two groups according to whether or not they used INCs while infected with the severe acute respiratory syndrome coronavirus 2 (group 1 and group 2, respectively). The subjects in group 2 were divided into two subgroups according to the use of antihistamines and/or leukotriene receptor antagonist or not (group 2a and group 2b, respectively). All the scores were compared before and during COVID-19 among the three groups. Results: A total of 71 subjects (21 in group 1, 24 in group 2a, and 26 in group 2b) were enrolled. The total scores of the SNOT-22 increased remarkably in all the groups during the infection when compared with the pre-COVID-19 scores (p < 0.001 in each group). However, the difference between the pre-COVID-19 and COVID-19 values revealed a lower decrease in the senses of smell and/or taste in group 1 than in group 2a and group 2b (p = 0.015, adjusted p = 0.045; and p = 0.001, adjusted p = 0.002, respectively). There were no significant differences in other COVID-19 findings, VAS, and TSS-6 scores among the groups (all p > 0.05). Conclusion: INCs in subjects with CR seemed protective against the decrease in smell and/or taste observed during COVID-19 and do not aggravate the clinical course of COVID-19.

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.

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.

Impact of anxiety, stress and depression related to COVID-19 pandemic on the course of hereditary angioedema with C1-inhibitor deficiency.

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 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) applied by the government. The 10-point visual analogue scale (VAS10) was used to define the severity of HAE attacks. Depression, Anxiety and Stress Scales-21 (DASS-21) and Fear of COVID-19 (FC-19) scale 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, and 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 cause 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.

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.

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.

Paucigranulocytic asthma: Do sputum macrophages matter?

Background: Although paucigranulocytic asthma (PGA) is the most common phenotype of stable asthma, its features have not been adequately studied. In this study, we aimed to display the characteristics of PGA. Method: A total of 116 non-smoking adult patients with asthma (80% women; mean ± standard deviation age, 39 ± 12.9 years) admitted to three tertiary centers were included. Their demographic and clinical features, allergy status, biochemical results, scores of Asthma Control Test (ACT), spirometry, and exhaled nitric oxide (FeNO) measurements were obtained. Induced sputum cytometry was performed. Results: Four phenotypes, according to induced sputum cell counts, were detected: eosinophilic asthma (EA) (22.4%), mixed granulocytic asthma (MGA) (6.9%), neutrophilic (NA) (7.8%), and PGA (62.9%). In the sputum, macrophages were higher in the PGA group compared with the other groups (PGA versus NA and PGA versus MGA, p < 0.001; and PGA versus EA, p =0 .030). The atopy rate between phenotypes was the same. Although the forced expiratory volume in the first second of expiration (FEV1) was similar in four groups, the ratio of FEV1 to the forced vital capacity ratio was higher (p = 0.013) and FEV1 reversibility was lower in the patients with PGA than the corresponding values in other phenotypes (p = 0.015). Low reversibility was comparable both in patients with PGA who were inhaled corticosteroid (ICS) naive and in patients on ICS treatment. Although insignificant, the FeNO values and blood eosinophil counts were higher in the MGA and EA groups, whereas these were the lowest in the PGA group. The uncontrolled asthma ratio was low in PGA (16%), whereas it was 11% for NA, 25% for MG, and 23% in EA. Conclusion: Macrophages are predominant in sputum of patients with PGA. Besides a lower uncontrolled asthma ratio, lower FEV1 reversibility is a prominent characteristic of this phenotype.

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.

Evaluation of the Potential Risk Factors for Drug-Induced Anaphylaxis in Adult Patients.

AIM: To investigate the potential risk factors in patients who have experienced anaphylaxis from drugs. METHOD: The study included 281 adult patients (median age 40 years; 76.5% female) who experienced immediate types of hypersensitivity reaction to a drug. The patients were divided into an anaphylaxis group and a nonanaphylaxis group. The anaphylaxis group was diagnosed according to the criteria of the World Allergy Organization. Skin testing with culprit drugs was performed. In the nonanaphylaxis group, drug provocation tests were performed with culprit drugs, including aspirin or diclofenac, to determine nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity. Atopy was determined by skin prick tests with the common inhalant allergens. Patients' demographics, clinical features, and baseline tryptase and total IgE levels were compared between the 2 groups. RESULTS: The median interval between the last reaction in the patient's history and the study evaluation was 7 months (range 1-120 months). In 52.3% of the patients, reactions were defined as anaphylaxis. The most common culprit drugs were NSAIDs (56.9%) and ß-lactams (34.7%). The culprit drugs were used parenterally in 13.2% of the patients. 34.9% of the patients had comorbid diseases and 24.6% used additional drugs, the most common being antihypertensives (10%). Atopy was determined in 28.8% and 28.1% of the patients were smokers. The median serum level of baseline tryptase and total IgE was 3.5 µg/L and 77 kU/L, respectively. In 46.3% of the patients, skin tests with culprit drugs were positive and the positivity ratio was higher in the anaphylaxis group (p = 0.002). Anapyhlaxis was more common in patients who were: hypertensive, atopic, using angio-tensin-converting enzyme inhibitors/angiotensin receptor blockers, and received the culprit drug parenterally (p = 0.034, p = 0.04, p = 0.03, p = 0.035, p = 0.013, and p < 0.001). In the multivariate analysis, it was observed that the parenteral usage of the drug and the presence of atopy were significantly higher in the anaphylaxis group (p < 0.001, odds ratio [OR] = 20.05, confidence interval [CI] 4.75-88.64; p = 0.012, OR = 2.1, CI 1.17-3.74). Age, smoking, family history, and serum levels of baseline tryptase and total IgE did not differ between groups. CONCLUSION: The parenteral route and atopy increase the risk of drug-induced anaphylaxis. IgE-mediated sensitivity to the culprit drug seems to facilitate anaphylaxis.

A practical 16-day desensitization protocol in lenalidomide-induced non-immediate hypersensitivity reactions.

BACKGROUND: Desensitization in immediate-type hypersensitivity reactions (HRs) caused by chemotherapeutics is well described and standardized for many drugs. However, there are no standardized protocols in non-immediate HRs. OBJECTIVE: To evaluate the effectiveness of a 16-day desensitization protocol in the non-immediate HRs induced by lenalidomide. METHODS: According to our previously published slow desensitization protocol, we desensitized patients who had experienced non-immediate HRs attributable to lenalidomide. The protocol was started with the 1/100 of the daily-prescribed dose in milligrams of the culprit drug; then the doses were slowly increased to complete the procedure in 16 days. Demographic and clinical features of the patients were further appraised. RESULTS: Ten patients (mean age was 64.7 ± 10.8 years; 7 male) were successfully desensitized to lenalidomide. The mean reaction time was 7.3 ± 3.9 days in the history, and the reaction types were delayed urticaria (n = 4), eczematous rash (n = 3), and maculopapular eruptions (n = 3). The desensitization was successfully completed in 16 days in 9 patients. In 1 patient, maculopapular eruptions developed on the 11th day, and the patient was treated with corticosteroids. We repeated the previous tolerated dose longer and completed with a slower dose increasement, and the targeted dose was achieved in 35 days. CONCLUSION: The 16-day desensitization protocol seemed to be safe and effective in the non-immediate type drug HRs caused by lenalidomide.

Proteomic Identification of Allergenic Proteins of Morus alba L. Pollenexacerbation.

BACKGROUND: Tree pollens are well-known aeroallergens all over the world. Little is known about the allergenicity of Morus alba (white mulberry) pollen. OBJECIVE: We aimed to explore the potential allergens of this pollen and its clinical relevance in tree pollen allergic patients living in Istanbul, Turkey. METHODS: Twenty three seasonal allergic rhinitis patients with a confirmed tree pollen allergy and 5 healthy control subjects underwent skin prick and nasal provocation tests with M.alba pollen extract. The pollen extract was then resolved by gel electrophoresis, and immunoblotted with sera from patients/control individuals to detect the potential allergenic proteins. The prevalent IgE binding proteins from 1D-gel were analyzed by MALDI-TOF/TOF. RESULTS: Eleven out of 23 patients were reactive to the extract with skin prick tests. Seven of those patients also reacted positively to the nasal provocation tests. The most common IgE-binding pollen proteins were detected between 55-100 kDa, and also at molecular weights lower than 30 kDa for some patients. Mass spectrometry analyses revealed that the principal IgE-binding protein was methionine synthase (5-methyltetrahydropteroyltriglutamate homocysteine methyltransferase), which is then proposed as a novel allergen in M.alba pollen. CONCLUSION: This study provides the first detailed information for the potential allergens of Morus alba pollen of Istanbul. Methionine synthase with an apparent molecular weight of 80 to 85 kDa has been recognized as one of the allergens in Morus alba pollen for the first time.