Uniparental Disomy of Chromosome 4: A Case of Whole Chromosome UPD Presenting with LRBA Deficiency.

PURPOSE: Lipopolysaccharide-responsive beige-like anchor protein (LRBA) encodes a widely expressed cytosolic protein that participates in polarized vesicle trafficking. Homozygous loss-of-function LRBA mutations can lead to immune deficiency due to the lack of immune regulation, classified as a part of Tregopathies. We present a case of a 49-year-old female, with polyarthralgia in metacarpophalangeal and proximal interphalangeal joints bilaterally, and morning stiffness, leading to the diagnosis of rheumatoid arthritis treated with pulse steroid therapy. She had experienced sepsis and in-depth scrutiny revealed panhypogammaglobulinemia. After being referred to the immunology clinic, she was followed under the diagnosis of common variable immunodeficiency (CVID)-like inborn errors of immunity (IEI). METHODS AND RESULTS: Physical examination and diagnostic follow-up revealed massive splenomegaly accompanied by portal hypertension, and ulcerations in the colon. She also presented with periodic hematuria and dysuria. Cystoscopic biopsy revealed mast cell-derived interstitial cystitis which has not been previously reported in LRBA deficiency in the literature to our knowledge. A multi-gene next-generation sequencing panel performed for immune deficiencies (264 genes and 524 amplicons), resulted in the identification of an apparently homozygous LRBA mutation (p.Arg722His) in the Beige and Chediak-Higashi (BEACH) domain. The SNP array showed copy neutral absence of heterozygosity of the entire chromosome 4, which is consistent with uniparental isodisomy of chromosome 4. CONCLUSION: In conclusion, this case study underscores the critical role of LRBA in immune regulation and highlights the clinical heterogeneity associated with LRBA deficiency. The patient's presentation with severe immune dysregulation, including massive splenomegaly, portal hypertension, and the novel finding of mast cell-derived interstitial cystitis, expands the clinical spectrum of LRBA mutations. The identification of an apparently homozygous LRBA mutation via next-generation sequencing further emphasizes the importance of genetic analysis in diagnosing monogenic defects manifested as CVID-like phenotype. This is the first reported case of LRBA deficiency due to whole chromosome UPD to our knowledge. Future research should focus on elucidating the full range of clinical manifestations and developing targeted therapies for patients with LRBA deficiency.

Early testing and grade of the reaction are affecting factors of skin test positivity in ß-Lactam allergies.

Background: ß-Lactams are the most widely used antibiotic family in the world. Nevertheless, they also stand out as the primary culprits for inducing drug hypersensitivity reactions (HSR). Methods: Between May 2018 and March 2023, patients with suspected HSRs to ß-lactams, who underwent skin tests (ST), were retrospectively screened. The determinants of allergenic penicillin (DAP) tests, which include penicillin minor and major determinants, clavulanic acid, and amoxicillin, along with ampicillin, sulbactam, the identified culprit drugs, and alternative cephalosporins, which include cefuroxime, ceftriaxone prick and/or intradermal tests, were administered. The analysis focused on identifying positive ST results and determining the true HSRs rates in this patient cohort. Results: Of the 147 patients, 78.9% (n = 116) were women and the median (minimum-maximum) age was 41 years (18-71 years). Mild HSRs (grades 1-2) were observed in 72.78% (n = 107), whereas 24.4% (n = 36) had severe reactions (grades 3-4) and 2.7% (n = 4) had an unknown grade. Of the patients, 64% (n = 94) experienced HSRs within the first hour after the last dose of the identified culprit drug. The overall positivity rate for all STs was 26.5% (n = 39). ST positivity rates were notably higher in individuals who had experienced HSRs within the past 6 months (p = 0.02) and those with severe anaphylaxis (p < 0.001). Conclusion: ß-Lactam ST positivity is higher, especially in those with grades 3-4 reactions and consulted a physician within the first 6 months after their HSRs.

Psychosocial Evaluation of Adults with Primary Immunodeficiency.

PURPOSE: Primary immunodeficiency disorder (PID) is a heterogeneous group of diseases characterized by immune dysregulation and increased susceptibility to infections, with various cognitive, emotional, behavioral, and social effects on patients. This study aimed to evaluate loneliness, social adaptation, anxiety, and depression and to identify associated factors in adults with immunodeficiency. METHODS: A cross-sectional study in Turkey (Feb-Aug 2022) obtained sociodemographic data from patient records. The Social Adaptation Self-Evaluation Scale (SASS), UCLA-Loneliness Scale (UCLA-LS), and Hospital Anxiety and Depression Scale (HADS) were administered in individual patient interviews. HADS-Anxiety (HADS-A) and HADS-Depression (HADS-D) scores were assessed using cut-offs of 10 and 7, respectively; SASS cut-offs for social imbalance and normalcy were < 25 and > 35, respectively. RESULTS: A total of 104 patients (60 women, 44 men) with a median age of 34 years (range: 18-89) were included in the study. Mean scores were SASS: 34.46 ± 8.11, UCLA-LS: 44.89 ± 12.66, HADS-A: 9.87 ± 4.77, and HADS-D: 9.12 ± 4.80. SASS score was negatively correlated with HADS-A, HADS-D, and UCLA-LS scores. There were positive correlations between UCLA-LS and HADS-A (r = -0.355, p < 0.01) and HADS-D (r = -0.614, p < 0.01) and between HADS-A and HADS-D (r = -0.454, p < 0.01). Low-income level was associated with higher HADS-A, HADS-D, and UCLA-LS scores and lower SASS score (p = 0.012, p = 0.041, p = 0.008, and p = 0.001, respectively). CONCLUSION: Adults with PID are at risk for depression and experience high levels of loneliness. Social maladjustment and loneliness contribute to anxiety and depression, and loneliness is correlated with impaired social functioning. These findings emphasize the importance of biopsychosocial evaluation of individuals diagnosed with PID.

Molecular prevalence of Pneumocystis jirovecii and Cryptosporidium in patients with asthma.

Asthma is characterized by chronic airway inflammation. In addition to allergens, microorganisms can affect the clinical course of asthma. It has been shown that some fungi play an important role in the progression of asthma. However, the effects of Pneumocystis jirovecii and Cryptosporidium spp., on the disease are little known. We investigated P. jirovecii and Cryptosporidium spp. in the sputum and stool sample of patients with asthma (n = 40) by microscopy and PCR compared to the healthy group (n = 40). P. jirovecii (12.5 %), and Cryptosporidium spp. (12.5 %) were detected in the sputum samples of only asthmatic patients (p = 0.029 and 0.029 respectively). However, Crpytosporidium spp. was detected equally in stool samples of both groups (p = 0.682). Our results indicate that P. jirovecii and Cryptosporidium spp. should be considered in patients with asthma and molecular screening of these neglected eukaryotes in respiratory tract samples may be beneficial in the clinical management of the disease.

CoronaVac/Sinovac COVID-19 Vaccine-Related Hypersensitivity Reactions and Second-Dose Vaccine Administration: Tertiary Allergy Center Experience.

INTRODUCTION: The COVID-19 pandemic has caused a global health crisis. To prevent the disease, the Ministry of Health of Turkey gained approval for the CoronaVac COVID-19 vaccine for emergency use as the first-line. This study aimed to evaluate patients who developed hypersensitivity reactions (HRs) due to the CoronoVac vaccine and to share our experience of administering the second dose of vaccine to these patients. METHODS: The study group included the patients who presented to the Ege University Allergy and Immunology Division between January and May 2021. Demographic data, atopic status, allergic reactions to the first dose of the COVID-19 vaccine and the route of second-dose vaccine administrations were recorded. RESULTS: A total of 7 patients (four healthcare professionals), 6 (86%) of whom were women, with an average age of 53.4 years, were included in the study. The rate of allergic reactions among Ege University health workers was 0.036% (2/5,558). Six of our patients had a history of additional allergic diseases and comorbid diseases. None had any allergic reactions to previous vaccinations and latex allergy. Reactions developed commonly on the skin, as generalized urticaria/angioedema and pruritus. The severity of the reactions was evaluated as mild in 2, moderate in 3, and severe in 2 cases. The second-dose CoronaVac was safely administered by using a gradually increase dose in a total of 6 patients. CONCLUSION: In patients with HRs due to Sinovac in the first dose, the second dose can be safely performed using a gradually increased dose.

Rapid Drug Desensitization with Chemotherapeutics (Platins, Taxanes, and Others): A Single-Center Retrospective Study.

BACKGROUND: Rapid drug desensitization (RDD) induces a temporary tolerance to chemotherapeutics that induce hypersensitivity reactions (HSRs). PURPOSE: Our objective is to report our experience with RDD to platins, taxanes, etoposide, doxorubicin, and irinotecan. METHODS: The study was conducted as a retrospective chart review of patients with symptoms of HSRs to chemotherapeutics. HSRs were classified as grade I, II, or III, based on their severity. Skin prick/intradermal tests were performed with implicated chemotherapeutics. A 12-step RDD protocol was used. RESULTS: The study consisted of 38 women and 3 men (mean age 53.3 ± 11.6 years). Patients had ovarian (n = 13, 31.8%), breast (n = 10, 24.4%), colon (n = 7, 17%), lung (n = 4, 9.8%), and other cancers (n = 7; endometrial sarcoma, testicular cancer, uterine cancer, ampulla of Vater tumor, choledochal tumor, peritonitis carcinomatosa, and Merkel cell carcinoma, n = 1, respectively). Twenty-two patients experienced HSRs to platins, 15 to taxanes, and 4 to other chemotherapeutics (doxorubicin, irinotecan, and etoposide). A total of 122 RDDs (47 to platins, 52 to taxanes, 23 to other chemotherapeutics) were performed. In 25 (61%) patients no reactions occurred during RDD, but breakthrough reactions developed in 16 patients (39%) with platins (n = 11), taxanes (n = 3), doxorubicin (n = 1), and irinotecan (n = 1). RDD procedures could not be completed in only 2 patients with grade II breakthrough reactions to carboplatin and oxaliplatin. CONCLUSION: In our experience, 98.3% of 122 RDDs were completed. We found that RDD was safe and effective in this the largest series of RDD with chemotherapeutics in our country.

Rapid Drug Desensitization with Biologics: A Single-Center Experience with Four Biologics.

BACKGROUND: Rapid drug desensitization (RDD) induces a temporary tolerance to biologics which induce hypersensitivity reactions (HSRs). Data are limited regarding the use of RDD outside the USA. Our purpose was to report our data on RDD to rituximab, infliximab, cetuximab, and trastuzumab. METHODS: The study was conducted as a retrospective chart review of patients with symptoms of HSRs to biologics. HSRs were classified as grades I, II, and III, based on their severity. Skin-prick tests/intradermal tests (IDTs) were performed with the implicated biologics. The 12-step RDD protocol was used. RESULTS: The study group comprised 11 women and 6 men (mean age: 47 ± 11.7 years). Fourteen patients experienced HSRs to rituximab; 3 had HSRs to cetuximab, infliximab, and trastuzumab, respectively. HSRs to cetuximab, infliximab, and trastuzumab occurred during the first infusion and were all grade III. Twelve of the 14 patients with rituximab hypersensitivity had a reaction during the first infusion; 10 patients had grade II reactions and 4 had grade III reactions. Respiratory symptoms were the most frequent presentation of HSR. Skin tests with rituximab were performed on 10 patients; only 3 resulted in positive IDTs (with 1:100 dilutions) and the other tests were negative as were those performed with the other biologics. Of 96 RDDs, 89 desensitizations were performed with rituximab, 5 with cetuximab, 1 with infliximab, and 1 with trastuzumab. There were 12 (13.5%) breakthrough reactions, all of which were associated with rituximab and were less severe than the initial reactions. CONCLUSION: RDD was found to be safe and effective in the largest case series of RDDs with biologics in our country, Turkey.