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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. [ABSTRACT FROM AUTHOR]

Eosinophilic granulomatosis with polyangiitis (EGPA) and chronic eosinophilic pneumonia (CEP) are rare diseases. It has been reported that EGPA is an advanced stage of CEP and that EGPA develops subsequently in half of the CEP patients. In this context, two cases diagnosed with CEP and EGPA are presented with emphasis on their similarities and differences. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Lactate, as an indicator of hypoxia, may be useful in sleeprelated breathing disorders to identify higher risk groups and monitor the effectiveness of positive airway pressure (PAP) treatment. We aimed to investigate the change in arterial lactate level in blood after PAP treatment in patients with obstructive sleep apnea (OSA) and sleeprelated hypoventilation and hypoxemic syndromes and its applicability for monitoring this change regarding the effectiveness of the treatment. Materials and Methods: PAP titration was applied to 64 OSA patients diagnosed with polysomnography. Measurements included pulmonary function testing, overnight PAP titration, arterial blood gases, and analysis of arterial lactate before and after titration. Overnight lactate level change was calculated. Results: Of the 64 patients in the study, 49 were in the OSA group and 15 were in the Obesity Hypoventilation syndrome plus OSA group. No statistically significant difference was detected among the patients in terms of lactate levels before and after PAP treatment [1.97 (±0.7) - 1.98 (±0.6)] (p>0.05). In the OSA patient group, we detected an inverse relationship between Lactate and pre-treatment non-rapid eye movement 1-2% (r=-0.328, p=0.021), T 90% (r=-0.356, p=0.012), and total apnea hypopnea index (AHI) (r=-0.424, p=0.002). Lactate is found to be positively correlated with pre-treatment measured oxygen saturation (r=0.396, p=0.005), and with minimum oxygen saturation (r=0.361, p=0.011). Conclusion: Our study showed that there is a relationship between AHI, average and minimum oxygen saturation and T 90% and lactate difference, which are severity indicators for OSA. These results suggest that PAP treatment may prevent possible lactate increase. [ABSTRACT FROM AUTHOR]

Montelukast, a leukotriene receptor antagonist (LTRA) approved for the treatment of asthma and allergic rhinitis, is widely used, though real-world data on its application in asthma management remain limited. This registry-based study evaluated the use of montelukast in adult asthma patients, examining demographic and disease characteristics, asthma control status, asthma phenotypes, presence of atopy, and treatment regimens. Among 2053 patients analyzed, 61.76% (n = 1268; mean age: 46.2 ± 14.3 years), predominantly females (~76%), received montelukast. Montelukast users showed higher rates of allergic rhinitis (P < 0.001), hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) (P = 0.008), and chronic rhinosinusitis (P = 0.008). Montelukast group also had higher atopy and total IgE levels and tended to be more eosinophilic. Montelukast was commonly preferred in allergic, eosinophilic, NSAID-exacerbated respiratory disease, and severe asthma phenotypes (P < 0.001). Patients receiving Steps 4 and 5 treatments are more likely to be prescribed montelukast (P < 0.001). Montelukast usage was higher among patients with uncontrolled asthma [ACT< 20 (OR:1.29, 95%CI:1.052-1.582, P = 0.014)]. In addition, logistic regression analyses identified the main factors associated with increased montelukast use as; female gender (OR:1.33, 95%CI:1.041-1.713, P = 0.02), presence of atopy (OR:1.46, 95%CI:1.157-1.864, P = 0.002), comorbid allergic rhinitis (OR:2.12, 95%CI:1.679-2.293, P < 0.001), and severe asthma (OR:2.18, 95%CI:1.712-2.784, P < 0.001). These findings reveal that montelukast use is prevalent among asthma patients, particularly in females, middle-aged adults, and those with comorbid allergic rhinitis, uncontrolled asthma, or specific asthma phenotypes, underscoring the factors that influence its prescription in asthma management., Competing Interests: The authors have no conflict of interest to declare.