Coexistence of Celiac Disease and Allergic Wheat Sensitivity: An Observational Study of Daily Clinical Practice.

INTRODUCTION: Although separate immunogenic mechanisms are involved, IgE-type sensitization to wheat and celiac disease (CD) may coexist. We observationally assessed the importance of this relationship in daily practice using CD and wheat sensitization screenings. METHODS: Celiac antibody (CA) screening and food prick tests (FPTs) were requested simultaneously from patients who presented to the Allergy Clinic between January 2022 and December 2023 and had any complaint accompanied by CD symptoms/findings (non-celiac group). Patients with positive CA (CA+) underwent endoscopy. As another group, FPT results were recorded for patients previously diagnosed with CD following a gluten-free diet (celiac group). RESULTS: In total, 169 patients (124 non-celiac and 45 celiac) were included in the study. Wheat prick positivity (WP+) was observed in 1 patient with CD. Among 65 WP+ patients without a CD diagnosis, 14 (20.3%) tested positive for CA+, and histopathology detected CD in 4 of these cases. Among the 59 WP- patients, 4 (8.8%) had CA+. The CA+ status of those with WP+ was significantly higher than those with WP- (p = 0.023). CONCLUSION: The 4 patients unaware of their CD exhibited WP+, with a higher rate of CA+ observed in the WP+ group. The association between WP+ and CA+ suggests that an impaired intestinal barrier may lead to simultaneous T helper 1 and 2 type inflammatory responses. Although different types of sensitization to the same food would not typically be expected, growing evidence indicates that this phenomenon does occur. Further studies are necessary to confirm these findings and to explore the underlying causes.

Drug Allergies in Older Adults: A Major Problem in a Specific Population.

INTRODUCTION: The use of medications in older adults is increasing due to the prevalence of chronic diseases. Data on the characteristics of drug allergies (DAs) in older adults are limited. This study investigated the prevalence and clinical characteristics of DAs in patients aged 65 years and older. METHODS: Patient records were examined retrospectively between January 2018 and December 2022. The study included 200 patients aged ≥18 years who met the criteria for diagnosis of type B drug reactions. The patients were divided into two groups: the adult group (18-64 years) and the older adult group (≥65 years). RESULTS: Advanced age was an independent risk factor for the development of anaphylaxis and immediate and delayed hypersensitivity reactions (odds ratio [OR] = 4.296; 95% confidence interval [CI] = 1.700-10.855; p = 0.002, OR = 3.800; 95% CI = 1.247-11.579; p = 0.019, OR = 3.028; 95% CI = 1.248-7.343; p = 0.014, respectively). Older adults had higher rates of comorbidities and polypharmacy (p < 0.001, p = 0.016, respectively), beta-lactam antibiotic allergy (p < 0.001), and hospitalization and intensive care unit (ICU) admission for DAs (p = 0.024, p = 0.045, respectively). CONCLUSION: Older age was an independent risk factor for anaphylaxis and both immediate and delayed reactions. Older adults had higher rates of comorbidities, polypharmacy, beta-lactam antibiotic triggers, and hospitalization and ICU admission.

The clinical and immunological characteristics of common variable immunodeficiency in adults and older adults.

OBJECTIVE: The aim of this study was to determine the clinical and immunological characteristics of older adults with common variable immunodeficiency (CVID). METHODS: Patients aged ≥18 years who were followed up with the diagnosis of CVID between 2015 and 2020 were included in the study. The patients were separated into two age groups according to the age at diagnosis: the adult group, aged 18-65 years (n=49) and the older adult group, aged ≥65 years (n=11). RESULTS: Splenomegaly (55.1% vs. 9.1%, p=0.006), bronchiectasis (53.0% vs. 9.1%, p=0.008), and autoimmunity (42.8% vs. 9.1%, p=0.036) were determined to be more common in the adult group than in the older adults. A similar frequency of malignancy was seen in both groups (6.1% vs. 9.1%, p=0.721). There were significantly more patients with no comorbidity in the older adult group than in the adult group (45.5% vs. 16.3%, p=0.034). Serum IgG and IgA levels were determined to be significantly higher in the older adult group than in the adult group (p=0.001 for all). The CD19+ B-cell count at the time of diagnosis was determined to be lower and the CD19+CD27+IgD- switched memory B-cells and CD16+CD56+ natural killer cell counts were higher in the older adults than in the adult group (p=0.016, p=0.032, p=0.044, respectively). CONCLUSION: Knowledge of clinical and immunological differences in older adult CVID patients may be of benefit in polyclinic follow-up and in respect of changes to be made to the treatment plan.

Impact of the COVID-19 Pandemic on Cockroach Allergy: A 4-Year Retrospective Study.

INTRODUCTION: Sensitivity to indoor allergens increases the risks of asthma and the emergence of allergic diseases. Indoor allergens include house dust mite (HDM), pet dander, cockroach (CR), and molds. We investigated how CR sensitivity was affected during the pandemic period. METHODS: This study included patients aged ≥18 years who visited the allergy unit of our clinic between March 2018 and March 2022 and who underwent skin prick tests (SPTs) for aeroallergens. Patients were divided into two groups: those of the prepandemic and pandemic periods, depending on the visit dates. RESULTS: In all, 7,687 patients were recruited; 5,074 individuals with negative SPT results were excluded. Among the 2,613 atopic patients, CR sensitivity was detected in 278 (10.6%). The prevalence of CR sensitivity was significantly higher in the pandemic group than in the prepandemic group (12% vs. 8.6%; p < 0.05). The frequency of asthma was higher in patients with CR sensitivity than in others (33.1% vs. 26%, p = 0.011). In addition, individuals with CR sensitivity were older than others (p = 0.001). CR sensitivity was more common in males than in females (44.2% vs. 37.7%, p = 0.034). Moreover, dog and HDM sensitivities were more common in individuals with CR sensitivity than in others (p = 0.004, p < 0.001, respectively). CONCLUSION: This study reveals an increased sensitivity to CR during the pandemic and establishes an association between such sensitivity and the frequency of asthma. Variability in terms of CR sensitivity across different countries is emphasized. In addition, HDM and dog sensitivities were more common in individuals with CR sensitivity.

Relationships between bronchiectasis and time to achieving target trough immunoglobulin G levels in patients with common variable immunodeficiency.

Background: The main treatment of common variable immunodeficiency (CVID) is to maintain immunoglobulin G (IgG) levels within the target range. However, trough IgG levels differ among patients with similar body mass index (BMI) and those receiving the same dose of immunoglobulin replacement therapy (IGRT). A crucial factor that underlies these differences is the presence of extensive bronchiectasis, which is associated with the immunoglobulin salvage pathway. Objective: We compared trough IgG levels in patients with CVID and with and in those without bronchiectasis who had received the same dose of IGRT for 2 years to determine the association of IgG level with infection frequency. Method: This retrospective cohort study included 61 patients with CVID, of whom 21 had bronchiectasis. We reviewed the electronic records for demographic variables, baseline immunoglobulin levels, mean trough IgG levels over 2 years, efficacy levels (trough IgG level - baseline IgG level), the time interval from treatment initiation to achieving the target trough IgG level (700 mg/dL), and the number of infections. Results: The median age of the patients was 39 years (IQR, 27-51), and 29 were women (47.5%). There were no significant differences between the groups in terms of age, age at diagnosis, delay in diagnosis, sex, BMI, IGRT type (subcutaneous or intravenous), and baseline immunoglobulin levels. Trough IgG and efficacy levels were lower (P < 0.001 and P = 0.016, respectively), the time required to achieve the target IgG level was longer in patients with bronchiectasis than in those without bronchiectasis, and this time interval was significantly associated with the infection frequency. Trough IgG and albumin levels were correlated (p = 0.007), with minor differences between the groups (p = 0.04). Conclusion: Bronchiectasis was significantly associated with a longer time to achieve the target IgG levels. These long-term differences between the patients with and those without bronchiectasis have significant clinical implications.

Evaluation of the Effectiveness of the 6 Warning Signs of the European Society for Immunodeficiencies for Primary Immunodeficiencies in Older Adults.

INTRODUCTION: Diagnostic delay in cases of primary immunodeficiency (PID) is a significant problem for clinicians, and most do not have sufficient awareness of this uncommon disorder. The European Society for Immunodeficiencies (ESID) has developed 6 warning signs to increase awareness of adult PIDs. The aim of this study was to determine the prevalence of PID in older adults regardless of the reason for presentation and to evaluate the effectiveness of the 6 warning signs of ESID in the diagnosis of PIDs. METHODS: The study included 1,331 patients aged ≥65 years who presented at our clinic for any reason and were questioned about the ESID 6 warning signs for PIDs. After the exclusion of reasons for secondary immunodeficiency (SID), all the patients underwent immunological evaluation for the diagnosis of potential underlying PIDs. RESULTS: After excluding 6 patients diagnosed with SID, PID was diagnosed in 16 (1.2%) of 1,325 older adults using ESID warning signs. The most common reasons for presentation were infection (69%) in the PID group and urticaria and/or angioedema (41.5%) in the non-PID group. The most common PID subgroup was common variable immunodeficiency (50%). In 12 of the patients diagnosed with PID, there was at least 1 positive ESID warning sign. In 4 patients, PID was determined despite negative ESID warning signs. The patients diagnosed with PID showed a significant, minimal level of agreement with questions 1 and 4 of the ESID warning signs (p < 0.001, ĸ = 0.204, p = 0.005, ĸ = 0.208, respectively). CONCLUSION: The ESID warning signs do not encompass all the symptoms and findings of PIDs. There is a need for more infection-centered questions to determine PIDs in older adults. Therefore, the ESID warning signs should be further developed.

Increasing Prevalence of Sensitization to Cat/Dog Allergens in the COVID-19 Pandemic.

INTRODUCTION: Cat and dog allergens are common indoor triggers for respiratory allergies such as allergic rhinitis and asthma. This study aims to evaluate the prevalence of cat and dog allergies in adults and analyze changes during the COVID-19 pandemic. METHODS: We retrospectively analyzed the medical records of 8,102 patients who visited an allergy clinic and underwent skin prick testing (SPT) from March 2018 to March 2022: 2 years before and 2 years during the pandemic. Demographic information, clinical attributes, and laboratory results were examined based on patient records. RESULTS: Of 8,102 SPTs performed, 400 (4.9%) were sensitized to cat allergen and 289 (3.6%) to dog allergen. Allergic rhinitis was the predominant clinical diagnosis in both groups. Of the 400 subjects exposed to cats, 240 (60%) experienced allergic symptoms, while of the 289 subjects exposed to dogs, 65 (22.5%) experienced allergic symptoms during exposure. Within the cat-sensitized group, anaphylaxis was observed in 5 patients (1.3%), while no cases of anaphylaxis were reported in the dog-sensitized group. Compared to the pre-pandemic period, patients presenting during the pandemic had higher rates of cat and dog sensitization (5.7% vs. 4.1%; p < 0.05, 5.2% vs. 1.7%; p < 0.05). CONCLUSION: During the COVID-19 pandemic, there was an increase in cat and dog allergies among adults. Increased exposure to pet antigens, both directly and indirectly, has resulted in more people becoming sensitized to cats or dogs.

Relationship between autoimmune diseases and serum basal immunoglobulin E levels in patients with common variable immunodeficiency.

Background: Autoimmune diseases can occur at any time in patients with common variable immunodeficiency (CVID). However, the relationship between low immunoglobulin E (IgE) levels and autoimmune diseases in patients with CVID remains poorly understood. Objective: We aimed to determine the relationship between autoimmunity and low IgE in patients with CVID. Methods: This retrospective cohort study was conducted by using data that had been collected from 62 adult patients with CVID between April 2012 and December 2021. Serum basal IgE levels were compared between patients with and patients without autoimmune disease. Results: Overall, 23 of the 62 patients with CVID (37.1%) had at least one autoimmune disease (CVID-O). Autoimmune cytopenias, mainly immune thrombocytopenic purpura, were observed in half of all the patients. Other autoimmune diseases present among the patients included rheumatological diseases, inflammatory bowel diseases, lymphoma, granulomatous lymphocytic interstitial lung disease, autoimmune hepatitis, alopecia, and multiple sclerosis. Serum IgE levels were measured at the time of diagnosis; IgE was undetectable (<2.5 IU/mL) in 82.6% of the patients with CVID-O (n = 19). The median (interquartile range) serum IgE value in the patients with CVID-O was 2 IU/mL (1-16 IU/mL), which was significantly lower than the median serum IgE value in patients with CVID and without autoimmune disease (p < 0.001). Low IgE levels in patients with CVID-O were an independent risk factor for the development of autoimmune disease in patients with CVID (odds ratio 3.081 [95% confidence interval, 1.222-7.771]; p = 0.017). Conclusion: Low serum IgE levels were associated with the development of autoimmune disease in patients with CVID. The monitoring of serum IgE levels in patients with CVID may be useful in the early diagnosis and treatment of autoimmune diseases.

Allergic Diseases as a Clinical Phenotype Marker in Patients with Common Variable Immunodeficiency.

INTRODUCTION: Patients with common variable immunodeficiency (CVID) have been shown to be more predisposed to develop allergic diseases because of mucosal immune defects and immune dysregulation. The aim of this study was to determine the prevalence, and clinical and laboratory characteristics of various allergic diseases in patients with CVID. METHODS: The study included patients aged ≥18 years who were followed up for a diagnosis of CVID. Patients were separated into 5 groups according to the clinical phenotypic characteristics of lymphoproliferation, autoimmunity, gastrointestinal diseases, allergic diseases, and malignancy. Atopic dermatitis (AD), drug hypersensitivity reaction (DHR), allergic rhinitis (AR), and asthma were accepted as allergic diseases. RESULTS: The most commonly seen clinical phenotypes were lymphoproliferation in 41 (48.8%) patients and allergic diseases in 31 (37%). AD was determined in 2 (2.4%) patient, DHR in 5 (6%), AR in 7 (8.3%), and asthma in 21 (25%). The delay in diagnosis of patients with allergic disease was determined to be shorter compared to those without allergic disease (p = 0.042). Serum total immunoglobulin E level, CD19+ B cell, switched memory B cell, and natural killer cell counts were determined to be higher in the CVID patients with allergic disease compared to those without (p = 0.007, p = 0.022, p = 0.023, p = 0.017, respectively). CONCLUSION: Allergic diseases should be considered as a marker of clinical phenotype in CVID because of the clinical and immunological differences. Early diagnosis and treatment of allergic diseases in patients with CVID can improve quality of life.

High digit ratio (2D:4D) is associated with attack frequency and severity in hereditary angioedema patients.

BACKGROUND: Hereditary angioedema (HAE) caused by a deficiency or dysfunction of the plasma protease C1-inhibitor is a rare autosomal-dominant disorder. We explored a possible correlation between the ratio of the second and fourth finger lengths (2D:4D) and the frequency of HEA attacks, and whether the ratio might predict laryngeal attack. METHOD: We evaluated 35 HEA patients aged 19 to 66 years; 3 were subsequently excluded. The 2D:4D ratio was calculated by dividing the length of the second finger by that of the fourth finger of both hands. A structured clinical questionnaire exploring HAE course and treatment over the prior year was administered. RESULTS: Of the 32 participants, 56.25 % (n = 18) were female. Of them, those with high 2D:4D ratios suffered significantly more laryngeal attacks than others; 93.3% of patients with high 2D:4D ratios experienced ≥5 attacks annually, significantly more than those with low ratios. Among type 2 HEA patients, 75 % of those experiencing ≥5 attacks annually had high 2D:4D ratios; all patients with low 2D:4D ratios reported <5 attacks annually. These significant effects were found for right-hand 2D:4D ratios and not left-hand 2D:4D ratios. CONCLUSION: The data suggest that intrauterine sex hormone exposure, which affects the 2D:4D ratio, is significantly associated with HEA attack frequency and severity, and laryngeal edema.

Anaphylaxis in older adult patients: a 10-year retrospective experience.

Background: Despite the worldwide increase in life expectancy and the elderly population, very little is known about the characteristics of anaphylaxis in older adults. Methods: A retrospective scan was made of the files of patients who presented at the Allergy Unit of our clinic between October 2011 and October 2021. The study included 971 patients aged ≥18 years who met the criteria for diagnosis of anaphylaxis. The patients were separated into 2 groups of adults (18-64 years) and older adults (≥65 years). Results: The adult group included 887 (91.3%) patients and the older adult group, 84 (8.7%) patients. Comorbid diseases were seen more frequently in the older adults than in the adult group (p < 0.001). Drugs were seen to be the most common trigger of anaphylaxis in both groups, and this was more common in the older adult group (p = 0.039). Food was a more common trigger of anaphylaxis in the adult group than in the older adult group (p = 0.017). In both groups, the skin was the organ most affected, and was less affected in the older adults than in the adults (p = 0.020). Cardiovascular symptoms were seen significantly more and respiratory symptoms significantly less in the older adult group (p < 0.001, p = 0.002, respectively). Admission to the hospital and the intensive care unit was more frequent in the older adult group and rates of adrenalin administration were higher compared to the adult group (p < 0.001 for all). Conclusion: Anaphylaxis in the older adults is generally caused by drugs. Older adults were found to have more cardiovascular symptoms and more frequent adrenalin injections, hospitalizations and intensive care unit admissions.

Evaluation of malnutrition risk and nutrition status in adult patients with common variable immunodeficiency.

BACKGROUND: The aim of this study is to determine the prevalence of malnutrition in outpatients with common variable immunodeficiency (CVID) and the utility of nutrition screening tools to detect malnutrition in these patients. METHODS: Fifty outpatients with CVID were included in the study. Nutrition risk for each patient was evaluated using four nutrition screening tools: Malnutrition Screening Tool (MST), Malnutrition Universal Screening Tool (MUST), Short Nutritional Assessment Questionnaire (SNAQ), and Nutritional Risk Screening 2002 (NRS-2002). RESULTS: According to MUST, MST, SNAQ, and NRS-2002, malnutrition risk was determined to be 48% (n = 24), 26% (n = 13), 20% (n = 10), and 20% (n = 10), respectively. Malnutrition was detected in 54% (n = 27) of the patients. It was found that MUST showed a better correlation in detecting malnutrition in outpatients with CVID (κ = 0.482, P = 0.001). MUST has a higher positive and negative predictive value than other nutrition screening tools (79% and 70%, respectively). In the multivariate logistic regression analysis, it was found that low serum immunoglobulin A (IgA) levels at diagnosis increased the risk of malnutrition by ∼15 times, and low CD19+ B-cell counts increased the risk by approximately eight times. CONCLUSION: The prevalence of malnutrition in patients with CVID was found to be quite high, and there was a strong correlation between malnutrition and low CD19+ B-cell counts and low serum IgA levels. Given the high rate of malnutrition in patients with CVID, nutrition assessment is recommended rather than starting with nutrition screening.

Memory B cells and serum immunoglobulins are associated with disease severity and mortality in patients with COVID-19.

PURPOSE OF THE STUDY: The aim of this study was to investigate the relationship of B cell-mediated immunity with disease severity and mortality in patients with COVID-19. STUDY DESIGN: In this retrospective cohort and single-centre study, 208 patients with laboratory-confirmed COVID-19 were recruited. A COVID-19 severity score, ranging from 0 to 10, was used to evaluate associations between various factors. Serum immunoglobulin levels and the number of cells in B lymphocyte subsets were measured and their association with disease severity and mortality in patients with COVID-19 examined. RESULTS: The median age of the patients was 50 (35-63) years and 88 (42%) were female. The number of deceased patients was 17. The median COVID-19 severity score was 8 (6-8) in deceased patients and 1 (0-2) in survivors. Deceased patients had significantly lower levels of total B lymphocytes, naive B cells, switched memory B cells, and serum IgA, IgG, IgG1 and IgG2 than recovered patients (all p<0.05). In addition, a significant negative correlation was found between the number of these parameters and COVID-19 severity scores. Decrease in the number of total B cells and switched memory B cells as well as lower serum IgA, IgG and IgG1 levels were independent risk factors for mortality in patients with COVID-19. CONCLUSION: In the present study, the prognosis of patients with COVID-19 was shown to be associated with the B cell subset and serum immunoglobulin levels.

Relationship between Selective IgA Deficiency and COVID-19 Prognosis.

The prevalence and mortality rates of coronavirus disease 2019 (COVID-19) widely vary among populations. Mucosal immunity is the first barrier to the pathogen's entry into the body. Immunoglobulin A (IgA) is the primary antibody responsible for mucosal immunity. We explored the relationship between selective IgA deficiency (SIgAD) and COVID-19 severity. We included 424 patients (203 women) with COVID-19. Eleven patients had SIgAD. Laboratory data of patients with SIgAD and normal IgA levels were compared. The relationship between SIgAD and severe COVID-19 infection was explored using logistic regression analysis. In the univariate logistic regression analysis, the risk of severe COVID-19 disease in patients with SIgAD was approximately 7.7-fold higher than that in other patients (odds ratio [OR], 7.789; 95% confidence interval [CI], 1.665-36.690, P = 0.008), while it was 4-fold (OR, 4.053; 95% CI, 1.182-13.903, P = 0.026) higher in the multivariate logistic regression analysis. Serum IgA levels were positively correlated with total lymphocyte counts and negatively correlated with C-reactive protein levels, which was a risk factor for severe COVID-19. In patients with SIgAD, the number of severe acute respiratory coronaviruses 2 that pass through mucosal membranes may be increased, leading to complications such as cytokine storm syndrome and acute respiratory distress syndrome.

Allergic diseases in the elderly population: a single-center experience.

BACKGROUND: Although allergic diseases are generally considered to be diseases of childhood and youth, the first symptoms of allergic diseases can be seen in old age sometimes. The aim of this study was to determine the prevalence and characteristics of allergic diseases in the elderly population admitted to the allergy unit on an outpatient basis. METHODS: The files of the patients who applied to our clinic's allergy unit during the 8-year period were retrospectively analyzed. The data of patients aged ≥ 65 years were obtained from the files of our allergy unit archive. RESULTS: A total of 1272 patients aged ≥ 65 years old were included in the study. The mean age was 70 years (range: 65-97 years). Most of the patients were female (n = 704, 55.3%). Of the patients, 887 (69.8%) presented with cutaneous symptoms, and urticaria was identified in 500 of them (56.3%). Drug hypersensitivity reactions were detected in 175 (13.7%) patients. A total of 71 (5.6%) patients had asthma, 65 (5.1%) had anaphylaxis, 48 (3.8%) had allergic rhinitis, 24 (1.9%) had hymenoptera venom allergy, and 18 (1.4%) had food allergies. Atopy history (OR = 2.323, 95% CI = 1.590-3.393, p < 0.001) and comorbidity (OR = 1.631, 95% CI = 1.050-2.533, p = 0.029) were found to be risk factors for drug hypersensitivity reactions. Male sex (OR = 3.462, 95% CI = 1.097-10.933, p = 0.034) and atopy history (OR = 14.877, 95% CI = 6.081-36.393, p < 0.001) were found to be risk factors for hymenoptera venom allergy. DISCUSSION: Diagnosis becomes difficult due to the perception that allergic diseases mainly affect young people. Clinical symptoms are not evident in the elderly and age-related difficulties are encountered in diagnostic tests. There is a need to develop specific guidelines for the diagnosis of allergic diseases in the elderly.