A Case-Control Study Comparing the General Characteristics of Patients with Symptomatic Dermographism and Chronic Spontaneous Urticaria: Is Atopy a Risk Factor for Symptomatic Dermographism?

INTRODUCTION: Symptomatic dermographism (SDerm) is the most common chronic inducible urticaria (CIndU) subtype. There is still limited information in the literature about clinical features, triggering factors, and accompanying comorbidities of SDerm. The aim of this study was to compare the clinical features and laboratory data of patients with SDerm and chronic spontaneous urticaria (CSU). METHODS: The clinical features and laboratory data of patients with SDerm and CSU were compared retrospectively. The laboratory data and general characteristic features of the patients were obtained from the medical records. RESULTS: The study included a total of 361 patients (CSU: 220, SDerm: 141). The rates of asthma (odds ratio [OR]: 1.79, p = 0.036), allergic rhinitis (OR: 6.03, p < 0.001), and thyroid disease (OR: 1.78, p = 0.039) were higher in patients with SDerm. The disease duration (median 12 months, p < 0.001) and regular antihistamine use (OR: 0.31, p < 0.001) were lower in patients with SDerm. Total IgE level (median: 193, p < 0.001), thyroid antibody positivity (OR: 1.93, p = 0.039), and atopy (OR: 8.81, p < 0.001) were higher in patients with SDerm. Dermatophagoides pteronyssinus (OR: 17.72, p < 0.001), Dermatophagoides farinae (OR: 17.20, p < 0.001), grass pollen (OR: 2.50, p < 0.026), cat epithelium (OR: 3.68, p < 0.023), and cockroach (OR: 4.93, p < 0.009) allergen positivity rates were higher in patients with SDerm. CONCLUSION: Atopic diseases such as asthma and allergic rhinitis and the sensitization rate to aeroallergens seem to be higher in patients with SDerm than in patients with CSU. The results of this study should be supported by multicenter studies of patients from different geographical regions.

Comparison of the General Characteristics of Patients with Severe Asthma Who Switched from Omalizumab to Mepolizumab versus Patients Who Responded to Omalizumab Treatment: A Real-Life Study.

INTRODUCTION: Severe asthma is characterized by frequent recurrent airway symptoms and exacerbations, and these affect the quality of life. Biological agents can be used in the treatment of patients with severe asthma if the disease cannot be controlled with standard controller treatment. The aim of this study was to compare the clinical characteristics and laboratory data of patients with severe asthma who were switched from omalizumab to mepolizumab and patients with severe asthma who responded to omalizumab. METHODS: The clinical characteristics and laboratory data of patients with severe asthma who responded to omalizumab and switched from omalizumab to mepolizumab were compared retrospectively. RESULTS: Evaluation was made of a total of 79 patients, including 64 omalizumab responders and 15 who switched to mepolizumab from omalizumab. After omalizumab and mepolizumab treatment, the annual number of asthma attacks, the use of oral corticosteroid (OCS), the annual number of hospitalizations, and the eosinophil count significantly decreased (omalizumab: p < 0.001, p < 0.001, p < 0.001, p < 0.001, respectively; mepolizumab: p = 0.001, p = 0.001, p = 0.002, p = 0.001, respectively). After omalizumab treatment, the increase in forced expiratory volume in 1 s (FEV1) (%) and asthma control test (ACT) score were determined to be statistically significant (p < 0.001, p < 0.001, respectively). After mepolizumab treatment, the increase in ACT score was significant (p = 0.003). Drug allergy, chronic sinusitis with nasal polyps (CRSwNP), regular use of OCS, and high baseline eosinophil count (cells/µL) were associated with poor response to omalizumab treatment (odds ratio [OR] = 7.86, p = 0.003; OR = 52.92, p < 0.001; OR = 10.16, p = 0.004; OR = 0.99, p = 0.004, respectively). House dust mite sensitivity and high baseline FEV1 (%) were associated with good response to omalizumab treatment (OR = 0.29, p = 0.041; OR = 1.06, p = 0.03, respectively). The blood eosinophil count had diagnostic value in predicting the nonresponsiveness to omalizumab treatment (area under the curve [AUC]: 0.967, p < 0.001, cut-off: 510). CONCLUSION: A high pretreatment eosinophil count, concomitant CRSwNP, a history of drug allergy, and regular OCS use may be associated with poor response to omalizumab treatment in patients with severe asthma. Depending on the treatment response, treatment switching can be applied between biological agents. The results of the current study should be supported by multicenter studies.

Long-term use of omalizumab in patients with allergic bronchopulmonary aspergillosis: a tertiary-level care center experience.

INTRODUCTION: Allergic bronchopulmonary aspergillosis (ABPA) is a lung disease caused by a hypersensitivity reaction to antigens of Aspergillus fumigatus. OBJECTIVE: The aim of this study was to evaluate the long-term clinical outcomes of omalizumab use in patients with ABPA. METHODS: In this retrospective study, 12 patients diagnosed with ABPA and receiving omalizumab for at least 2 years, and 32 patients diagnosed with severe allergic asthma and receiving omalizumab for at least 2 years (control group) were evaluated. RESULTS: Evaluation was made of a total of 44 participants, comprising 11 (25%) males and 33 (75%) females, who received omalizumab for at least 2 years with the diagnosis of the control group (n = 32) and ABPA (n = 12). The increase in asthma control test (ACT) score after omalizumab was significant at 12 months and at 24 months in patients with ABPA. After omalizumab, the use of oral corticosteroid (OCS), the annual number of asthma attacks and hospitalizations were significantly decreased at 12 months and at 24 months in patients with ABPA. The increase in forced expiratory volume in 1 s (FEV1) (%) and ACT score after omalizumab were significant at 12 months and at 24 months in the control group. After omalizumab, the use of OCS, annual number of asthma attacks and hospitalizations were significantly decreased at 12 months and at 24 months in the control group. CONCLUSION: Long-term omalizumab use in patients with ABPA seems to be an effective treatment for improving pulmonary function and reducing asthma exacerbations and hospitalizations.

Comparison of Omalizumab Treatment Response in Patients with Chronic Spontaneous Urticaria and Symptomatic Dermographism: A Single-Center Retrospective Study.

INTRODUCTION: Omalizumab is a humanized anti-IgE monoclonal antibody, which is effective in the treatment in patients with chronic spontaneous urticaria (CSU) who are unresponsive to antihistamine therapy. There are few studies in the literature evaluating omalizumab treatment response in patients with symptomatic dermographism (SDerm). The aim of this study was to compare the response to omalizu-mab treatment in patients with CSU and SDerm. METHODS: Patients treated with omalizumab for the diagnosis of CSU and SDerm were evaluated retrospectively. Treatment response to omalizumab was evaluated with the urticaria control test (UCT). Quality of life was evaluated with the dermatology quality of life questionnaire (DLQI). Baseline UCT and DLQI were compared with UCT and DLQI after omalizumab treatment. RESULTS: Evaluation was made of a total of 116 patients (CSU: 92, SDerm: 24), comprising 36 (31%) males and 80 (69%) females with a mean age of 38.95 ± 13.64 years. The most common accompanying comorbid disease was allergic rhinitis (n = 40, 34.5%). There was no statistically significant difference between patients with CSU and SDerm in respect of response to omalizumab treatment (p = 0.890). After omalizumab treatment, the increase in UCT and decrease in DLQI was statistically significant in all patient groups (p < 0.001; p < 0.001, respectively), patients with CSU (p < 0.001; p < 0.001, respectively) and SDerm (p < 0.001; p < 0.001, respectively). There was no statistically significant difference between baseline (before omalizumab treatment) UCT (p = 0.804) and UCT after omalizumab treatment (p = 0.933) between patients with CSU and patients with SDerm. There was no statistically significant difference between baseline (before omalizumab treatment) DLQI (p = 0.356) and DLQI after omalizumab treatment (p = 0.145) between patients with CSU and patients with SDerm. CONCLUSION: Omalizumab treatment improved disease control and quality of life in patients with SDerm. The findings of this study should be supported by randomized placebo-controlled studies.

Evaluation of the Clinical Features and Laboratory Data of Patients with Severe Eosinophilic Asthma Classified as Super-Responders, Partial Responders, or Nonresponders to Mepolizumab Treatment: A Real-Life Study.

INTRODUCTION: Mepolizumab is a treatment option in patients with severe eosinophilic asthma, which inhibits interleukin-5. The aim of this study was to evaluate the clinical features and laboratory data of patients with severe eosinophilic asthma who were classified as super-responders, partial responders, or nonresponders to mepolizumab treatment. METHODS: In this retrospective real-life study, the clinical features and laboratory data were compared between groups of patients with severe eosinophilic asthma who were classified as super-responders, partial responders, or nonresponders to mepolizumab treatment. RESULTS: Evaluation was made of a total of 55 patients, comprising 17 (30.9%) males and 38 (69.1%) females with a mean age of 51.28 ± 14.32 years. All the patients were receiving mepolizumab treatment for severe eosinophilic asthma, with 17 (30.9%) patients evaluated as super-responders, 26 (47.3%) as partial responders, and 12 (21.8%) as nonresponders. After mepolizumab treatment, there was a statistically significant decrease in asthma exacerbations, the number of oral corticosteroids (OCSs) used, the rate of hospitalization due to asthma attacks, and the eosinophil count (cells/µL) (p < 0.001, p < 0.001, p < 0.001, and <0.001, respectively). A statistically significant increase was determined in the forced expiratory volume in 1 s (FEV1) value (p = 0.010) and asthma control test (ACT) score (p < 0.001) after mepolizumab treatment. The baseline eosinophil count, eosinophil/lymphocyte ratio and FEV1 (%) values were significantly higher in the super-responder and partial responder groups (p < 0.001, p = 0.002, and p = 0.002, respectively). The baseline ACT score and the rate of chronic sinusitis with nasal polyps were significantly higher in the partial responder group (p = 0.004, p = 0.015, respectively). The rate of regular OCS use before mepolizumab treatment was significantly higher in the nonresponder group (p = 0.049). As a result of the receiver operating characteristics curve analysis, the blood eosinophil count (area under the curve [AUC]: 0.967, p < 0.001), eosinophil/lymphocyte ratio (AUC: 0.921, p < 0.001), and FEV1 (%) (AUC: 0.828, p = 0.002) were found to have diagnostic value in predicting the response to mepolizumab treatment in patients with severe eosinophilic asthma. CONCLUSION: Baseline eosinophil count, eosinophil/lymphocyte ratio, and FEV1 (%) were found to be important predictors of response to mepolizumab treatment. Further studies are needed to define the characterization of mepolizumab responders in the real world.

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.

Evaluation of the clinical features and laboratory data of patients with severe asthma classified as super-responder or non super-responder to omalizumab treatment: a single-center real-life study.

INTRODUCTION: Omalizumab is used for the treatment of severe allergic asthma. OBJECTIVE: The aim of this study was to evaluate the clinical features and laboratory data of patients with severe allergic asthma classified as super-responder or non super-responder to omalizumab. METHODS: Comparisons were made of the laboratory data and clinical features of patients with severe allergic asthma. Patients who had no asthma exacerbation, no oral corticosteroid (OCS) use, asthma control test (ACT) score >20 and forced expiratory volume in 1 s (FEV1) >80% were considered super-responder after omalizumab. RESULTS: A total of 90 patients were included in the study, comprising 19 (21.1%) males. The age at onset of asthma, allergic rhinitis rate, number of endoscopic sinus surgeries (ESS), intranasal corticosteroid (INS) use, baseline FEV 1 (%) and ACT score were significantly higher in the omalizumab super-responder group (p = 0.013, p = 0.015, p = 0.002, p = 0.001, p = 0.001 and p < 0.001, respectively). The duration of asthma, rate of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), regular use of OCS, baseline eosinophil count and eosinophil-to-lymphocyte ratio were significantly higher in the omalizumab non super-responder group (p = 0.015, p < 0.001, p = 0.004, p < 0.001 and p < 0.001, respectively). Blood eosinophil count (AUC: 0.187, p < 0.001), eosinophil-to-lymphocyte ratio (AUC: 0.150, p < 0.001) and FEV1 (%) (AUC:0.779, p = 0.001) were determined to have diagnostic value in predicting the treatment response to omalizumab of patients with severe allergic asthma. CONCLUSION: High-blood eosinophil levels, CRSwNP and low pretreatment lung capacity may affect omalizumab treatment response in patients with severe allergic asthma. These results should be supported by further multicenter real-life studies.

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.

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.

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.

Positive perception of COVID-19 vaccination in HAE: No significant impact of vaccination on disease course.

Background: There are some adverse effects with coronavirus disease 2019 (COVID-19) vaccines, but the impact of COVID-19 vaccination on attacks in hereditary angioedema (HAE) is not well defined. Objective: We aimed to investigate the influence of COVID-19 vaccination on the course of HAE. Method: The COVID-19 vaccination status was determined in 140 adult patients with HAE. The number and severity of attacks recorded from patients' diaries were evaluated at four different periods, comprising 1 month before the first dose, the period between the first and the second doses of COVID-19 vaccine in all the patients, the period between the second dose and the third doses in those who received three doses, and 1 month after the last vaccination dose. The disease and attack severities were assessed with the disease severity score (DSS) and 10-point visual analog scale, respectively. The patients were divided into two main groups as group 1 (those who had at least two doses of COVID-19 vaccines [n = 114]) and group 2 (those who had no vaccination [n = 26]). Only Sinovac and Biontech, which were only approved in Turkey. Results: The mean ± standard deviation DSS was significantly higher in the patients who experienced an attack after vaccination within 48 hours (6.61 ± 1.88 versus 4.14 ± 1.69; p < 0.001). Long-term prophylaxis was less common in the patients with an increased number of attacks (n = 5 (27.8%) versus n = 54 (56.3%); p = 0.027). The number of patients with less than a high school education was higher in group 2 (n = 23 [88.5%]) than in group 1 (n = 26 [3.1%]) (p < 0.001). The number of patients who had concerns about the triggering of a vaccine-induced HAE attack or about the possible vaccine adverse effects was higher in group 2 (n = 26 [100%]) than in group 1 (n = 74 [64.9%]). Conclusion: It seems that COVID-19 vaccination does not increase HAE attacks regardless of the type of the vaccines. We recommend that HAE activity should be under control before COVID-19 vaccination, and the patients should be well informed about the safety of the vaccines.

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.

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.

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.

Immunosuppressive Treatment in C3 Glomerulopathy: Is it Really Effective?

BACKGROUND: C3 glomerulopathy (C3GP) is a recently identified and described disease that has a high risk of progressing into end-stage renal disease. We aimed to evaluate the effects of various immunosuppressive regimens on C3GP progression because there are conflicting data on the treatment modalities. METHODS: In this retrospective study of 66 patients with C3GP, 27 patients received mycophenolate mofetil (MMF)-based treatment, 23 received non-MMF-based treatment (prednisolone or cyclophosphamide), and 16 received conservative care. The study groups were compared with each other with specific focus on primary outcomes defined as (1) kidney failure and (2) estimated glomerular filtration rate (eGFR) decline ≥50% from the baseline value. RESULTS: Overall, 17 (25.8%) patients reached the primary outcome after a median period of 28 months. The number of patients who reached the primary outcome were similar among the study groups (MMF-based: 8/27 [29.6%], non-MMF-based: 4/23 [17.4%], and conservative care: 5/16 [31.3%], p = 0.520). In the Cox regression analysis, age (HR 0.912, p = 0.006), eGFR (HR 0.945, p = 0.001), and proteinuria levels (HR 1.418, p = 0.015) at the time of biopsy, percentage of crescentic (HR 1.035, p = 0.001) and sclerotic glomeruli (HR 1.041, p = 0.006), severity of interstitial fibrosis (HR 1.981, p = 0.048), as well as no remission of proteinuria (HR 2.418, p = 0.002) predicted the primary outcome. CONCLUSION: Although patients receiving immunosuppressive treatments had higher proteinuria and lower serum albumin at baseline, there were no differences between these patients and those receiving conservative care alone in proteinuria remission or in the decline of renal function. Younger age, higher proteinuria, lower eGFR, and the presence of crescentic and sclerotic glomeruli, severity of interstitial fibrosis, and no remission of proteinuria predicted the progression of kidney disease.

The Clinical Significance of Uric Acid and Complement Activation in the Progression of IgA Nephropathy.

BACKGROUND/AIMS: The aim of this study is to investigate the utility of clinical [age, gender, mean arterial pressure (MAP)] and laboratory parameters [eGFR, hemoglobin (Hgb), serum levels of creatinine, uric acid, albumin, proteinuria, hematuria] and also histopathological lesions (Oxford classification parameters, crescents, intensity and pattern of staining for C3, C1Q, IgA, IgG, IgM) as progression markers in patients with IgA Nephropathy (IgAN). METHODS: A total of 111 IgAN patients with a follow-up period >1 year or who reached kidney failure [GFR category G5 chronic kidney disease (CKD)] <1 year were investigated. Primary endpoint was the development of kidney failure or eGFR decline ≥50% from the baseline. Kaplan-Meier and Cox proportional hazards analyses were performed. RESULTS: Mean follow-up period was 33±29 months. Thirty-seven (33.3%) patients progressed to kidney failure and 4 (3.6%) patients developed eGFR decline ≥50% from the baseline after a median of 23 and 65 months, respectively. In multivariate Cox regression analysis, baseline levels of Hgb (HR:0.782, 95% CI 0.559-0.973, p=0.037), serum uric acid (HR:1.293, 95% CI 1.023-1.621, p=0.046), eGFR (HR:0.966, 95% CI 0.947-0.984, p=0.004) and intensity of C3 staining (HR:1.550, 95% CI 1.198-1.976, p=0.049) predicted primary endpoint. Serum uric acid level was associated independently with T score (ß=0.303, p=0.005) in patients with eGFR>30 ml/min/m2. CONCLUSIONS: Hyperuricemia and the deposition of C3 are independent risk factors for IgAN progression.

Test Panel of Hidden Allergens for "Idiopathic Anaphylaxis" Reveals Wheat Allergy Dependent on Augmentation Factors as Common Final Diagnosis.

BACKGROUND: Idiopathic anaphylaxis (IA) is an unresolved concern. Hidden allergens may be relevant in IA and in nonsteroidal anti-inflammatory drug hypersensitivity (NSAID-HS). OBJECTIVE: To identify hidden elicitors for IA and NSAID-HS by a skin prick test (SPT) (13 allergens) and allergen-specific IgE (sIgE) panel (12 allergens) and to determine the value of each tested allergen. METHODS: We retrospectively included all patients from 2018 to 2021 referred with a suspicion of IA or NSAID-HS by history in whom SPT and/or sIgE to allergens of the IA panel were performed. Patient characteristics from patients' records included comorbidities, history and symptoms of anaphylaxis, serum baseline tryptase level, total IgE level, SPT, sIgE, challenge results, and final diagnoses. RESULTS: A total of 134 patients (77 female, mean age 39.7 ± 14.6 years) were included. Median serum baseline tryptase and total IgE levels were 4.23 µg/L and 133.5 kU/L, respectively. Allergologic workup with the IA panel resulted in positive SPT and sIgE in 61 (47%) and 66 (60%) patients, respectively. In those, confirmation or exclusion of allergy, mostly by challenge, led to a definitive diagnosis in 61 of 134 patients (46%). Skin prick test was most frequently positive to gluten (22.4%) and sIgE to ω5-gliadin (21.6%), which correlated with the history (r = 0.310, P < .001; and r = 0.407, P < .001, respectively). In 28 of 134 patients (21%) with initially suspected IA or NSAID-HS, challenges confirmed occult food allergy in which wheat allergy dependent on augmentation factors was the most frequent cause of anaphylaxis (19%). CONCLUSIONS: Wheat allergy dependent on augmentation factors should be considered in all patients with anaphylaxis of unknown cause or after NSAID intake.