Therapeutic modalities and clinical outcomes in a large cohort with LRBA deficiency and CTLA4 insufficiency.

BACKGROUND: LPS-responsive beige-like anchor (LRBA) deficiency (LRBA-/-) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) insufficiency (CTLA4+/-) are mechanistically overlapped diseases presenting with recurrent infections and autoimmunity. The effectiveness of different treatment regimens remains unknown. OBJECTIVE: Our aim was to determine the comparative efficacy and long-term outcome of therapy with immunosuppressants, CTLA4-immunoglobulin (abatacept), and hematopoietic stem cell transplantation (HSCT) in a single-country multicenter cohort of 98 patients with a 5-year median follow-up. METHODS: The 98 patients (63 LRBA-/- and 35 CTLA4+/-) were followed and evaluated at baseline and every 6 months for clinical manifestations and response to the respective therapies. RESULTS: The LRBA-/- patients exhibited a more severe disease course than did the CTLA4+/- patients, requiring more immunosuppressants, abatacept, and HSCT to control their symptoms. Among the 58 patients who received abatacept as either a primary or rescue therapy, sustained complete control was achieved in 46 (79.3%) without severe side effects. In contrast, most patients who received immunosuppressants as primary therapy (n = 61) showed either partial or no disease control (72.1%), necessitating additional immunosuppressants, abatacept, or transplantation. Patients with partial or no response to abatacept (n = 12) had longer disease activity before abatacept therapy, with higher organ involvement and poorer disease outcomes than those with a complete response. HSCT was performed in 14 LRBA-/- patients; 9 patients (64.2%) showed complete remission, and 3 (21.3%) continued to receive immunosuppressants after transplantation. HSCT and abatacept therapy gave rise to similar probabilities of survival. CONCLUSIONS: Abatacept is superior to immunosuppressants in controlling disease manifestations over the long term, especially when started early, and it may provide a safe and effective therapeutic alternative to transplantation.

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

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

COVID-19 infection during pregnancy: A retrospective study in a city in the Southeastern region of Turkey.

OBJECTIVES: To evaluate the maternal and fetal clinical outcomes in SARS-CoV-2 infected pregnant women during the whole period of the pandemic in a single province in the southeast of Turkey. METHODS: This retrospective study included patients who were screened from the medical registration system and found to be infected with SARS-CoV-2 virus during pregnancy. The demographic, clinical, laboratory, and radiological features of all the patients were obtained and compared between groups classified as severe-critical and mild-moderate disease severity. RESULTS: The mean age of all the cases was 29.0±5.3 years in the mild-moderate cases, and 30.1±5.5 years in the severe-critical cases. The rates of 3rd trimester, cesarean and premature birth, high body mass index (BMI), symptoms of cough and dyspnea, the presence of comorbidities, and hypothyroidism were significantly higher in the severe-critical cases than in the mild-moderate group. In the univariate analyses, BMI, dyspnea, cough, maternal complication rate, the neutrophil/lymphocyte ratio, the values of white blood cells, procalcitonin, high-sensitive C-reactive protein, D-dimer, ferritin, aspartate aminotransferase, and alanine aminotransferase were detected as significant risk factors. In the multivariate analysis, only procalcitonin was a significant factor. CONCLUSION: In the 3rd trimester of pregnancy, obesity and hypothyroidism were found to be risk factors for severe-critical cases of COVID-19 infection, and the clinical course was more severe with a higher rate of mortality in the recent period of the pandemic.

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

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

Topical cyclosporine versus allergen specific immunotherapy in perennial allergic conjunctivitis.

PURPOSE: Symptom control in the long-term with less side effects is important in perennial allergic conjunctivitis, since would improve quality of life. This study aimed to assess the clinical efficacies of topical cyclosporin A and subcutaneous allergen immunotherapy (SCIT) in terms of sign control in perennial allergic conjunctivitis. METHODS: This retrospective study included 20 adult patients with perennial allergic conjunctivitis and confirmed sensitization to house dust mites with skin prick test. Patients were assigned to either topical cyclosporine A treatment or SCIT. The participants were followed for 6 months, and signs scores were recorded at 1, 3 and 6 months. RESULTS: Overall, both cyclosporine and immunotherapy groups showed significant improvements in papillary reaction (p = 0.011 and 0.003, respectively), limbal involvement (p = 0.031 and 0.001), and conjunctival hyperemia (p = 0.001 and p < 0.001) scores during the 6-month follow-up. However, only cyclosporine group showed a significant improvement in corneal involvement scores (p = 0.015) during the study period. When scores at different time points were compared, significant improvement in conjunctival hyperemia was evident at 6 months in both groups when compared to baseline (cyclosporine group, 0.7 ± 0.68 vs. 2.4 ± 0.84, 70.8% decrease, p = 0.01; immunotherapy group, 0.3 ± 0.48 vs. 2.3 ± 0.95, 87.0% decrease, p = 0.004), whereas for limbal involvement such an improvement was only evident in the immunotherapy group (0.1 ± 0.32 vs. 1.3 ± 0.95, 92.3% decrease, p = 0.01). CONCLUSIONS: Allergen immunotherapy and cyclosporin A treatment may provide effective sign relief in perennial allergic conjunctivitis. It may represent an encouraging treatment option particularly for cases with perennial allergic conjunctivitis refractive to other treatments and positive skin prick test to a specific allergen (house dust in the present study). Long-term relief by SCIT would reduce the side effects of polypharmacotherapy. Larger studies with longer follow-up are warranted to confirm our findings.

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.

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.

Evaluation of the Autoimmunity and Preexisting Risky Conditions for Hypersensitivity Reactions to COVID-19 Vaccines.

INTRODUCTION: The role of autoimmunity and other preexisting risky conditions in hypersensitivity reactions (HSRs) to COVID-19 vaccines seems unclear. The aim of the study was to investigate the autoimmunity and preexisting risky conditions in HSRs to COVID-19 vaccines. METHODS: The patients aged ≥18 years with a history of HSR to CoronaVac or Pfizer-BioNTech COVID-19 vaccines within 24 h in 2 tertiary centers were assessed. The patients were divided according to the type of vaccine which they showed immediate-type (<4 h) HSR to (group A1 for CoronaVac and group B1 for Pfizer-BioNTech). Equal number of subjects who did not show HSR to two doses of either CoronaVac or Pfizer-BioNTech was recruited into the study as control groups (group A2 for CoronaVac and group B2 for Pfizer-BioNTech). The autologous serum skin test (ASST) was performed on patient and control groups. Later, the demographic, clinical, and laboratory features were compared between groups. RESULTS: A total number of 27 patients were included in the study. Subjects with chronic spontaneous urticaria (CSU) were more frequent in group B1 than in group B2 (p:0.041). In addition to CSU, the presence of HSRs to drugs was higher in group A1 than in A2 (both p:0.007). The presence of autoimmunity and autoimmune diseases, positivity of antithyroid peroxidase antibody, and ASST were less in group A2 than in A1 (p:0.015, p:0.048, p:0.048, and p:0.037). Additionally, COVID-19 infection history was less in group A2 than in A1 (p:0.037). DISCUSSION/CONCLUSION: Type IIb autoimmunity seems to play a role in immediate type HSRs to the CoronaVac vaccine as previously shown in autoimmune CSU and multidrug hypersensitivity.

Clinical Effects of BNT162b2 Vaccine on the Short-Term Course of Chronic Spontaneous Urticaria Patients.

Background: The clinical effects of Pfizer-BioNTech coronavirus disease 2019 (COVID-19; BNT162b2) vaccine on the clinical course of chronic spontaneous urticaria (CSU) is unclear. Aims and Objectives: To evaluate the clinical effects of BNT162b2 vaccine on the clinical course of CSU. Methods: In this study, 90 CSU patients vaccinated with one or two repeated doses of BNT162b2 vaccine were included. Urticaria Activity Score over 28 days (UAS28), Urticaria Control Test (UCT), Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL), and Medication Scores (MSs) were obtained before the vaccination, 28 days after the first and, if available, after the second dose of BNT162b2 vaccine. The demographic, clinical, and laboratory features were compared between the subjects with exacerbated (group A) and non-exacerbated (group B) disease activity. Results: Among the 90 study participants, 14 (15.5%) experienced exacerbations in their urticarial activity after the first or repeated doses of BNT162b2 vaccinations. The demographic, clinical, and laboratory features were similar between the exacerbated and non-exacerbated CSU patients. However, the rate of adverse reactions within 48 hours, such as hives, injection site reactions and wheals lasting <1 hour, were significantly higher in group A than in group B (P = 0.004, P < 0.001, P = 0.001, P = 0.018). Conclusions: BNT162b2 vaccination caused an exacerbation in 15.5% of CSU patients during the short-term follow-up. The long-term evaluation can be informative about the lasting effects of BNT162b2 vaccine on the clinical course of CSU patients.

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.

The role of mean platelet volume in nonalcoholic fatty liver disease without cardiovascular comorbidities, obesity and diabetes mellitus.

BACKGROUND: While the relation of mean platelet volume (MPV) with inflammatory diseases is obvious, its role in nonalcoholic fatty liver disease (NAFLD) without cardiovascular comorbidities, obesity and diabetes mellitus is not clear. METHODS: A total of 249 patients (nonobese, nondiabetic and not having cardiac diseases) who underwent an abdominal ultrasonography assessment were enrolled. They were divided according to the absence (group 1) or presence (group 2) of hepatic steatosis. The patients with steatosis were further divided according to the severity of steatosis as group 2a (grade 1), 2b (grade 2) and 2c (grade 3). The demographic and laboratory features were compared between groups. RESULTS: Hepatic steatosis was absent in 120 patients and detected in 129 patients (grade 1, 2, 3 hepatic steatosis in 75, 49 and 5 patients, respectively). BMI, aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio and serum AST, ALT, triglyceride levels were significantly higher in group 2 than in group 1 (P < 0.001, P < 0.001, P < 0.001, P = 0.005, P < 0.001, respectively). BMI, serum AST and triglyceride levels were significant factors for NAFLD (P < 0.001, P = 0.018, P = 0.001). MPV was neither different between groups (P > 0.05) nor a predictor factor for NAFLD (P > 0.05). CONCLUSION: MPV is a useless parameter to detect NAFLD without cardiovascular comorbidities, obesity and diabetes mellitus.