Celiac disease (CD) can present solely with atypical extra-intestinal symptoms. We describe a 33-year-old woman hospitalized for a one-month history of fever, myalgias, and tachycardia. Extensive infectious, autoimmune, and malignancy investigations were unrevealing. However, hypochromic anemia and elevated CRP prompted serologic testing, revealing positive anti-transglutaminase IgA. Duodenal biopsy confirmed CD with Marsh IIIa villous atrophy. This case illustrates CD as a rare etiology of fever of unknown origin (FUO), emphasizing the importance of celiac serology in the differential diagnosis of prolonged unexplained fever.

Esophageal squamous cell carcinoma (ESCC) usually affects the upper or middle esophagus and is strongly associated with tobacco and alcohol use. We report a 28-year-old woman with longstanding celiac disease who presented with progressive dysphagia, weight loss, retrosternal pain, and melena. Endoscopy showed a partially obstructing distal esophageal mass; biopsy confirmed moderately differentiated keratinizing ESCC, while duodenal biopsy showed active celiac disease. CT and PET imaging revealed regional lymphadenopathy without distant metastasis. She underwent feeding jejunostomy, nutritional support, and neoadjuvant chemoradiotherapy, but follow-up imaging showed interval disease progression. The patient's young age, squamous cell histology in a distal esophagus, and the absence of conventional risk factors make this an unusual presentation. This case emphasizes the need for high clinical suspicion and early endoscopic evaluation in young patients with celiac disease presenting with alarming symptoms, even in the absence of classic risk factors for esophageal cancer.

Double-balloon enteroscopy (DBE) is an essential diagnostic and therapeutic modality for small-bowel disorders. Most prior studies on age-related differences in DBE involved limited age groups and small cohorts. We evaluated age-specific differences in the indications, findings, therapeutic interventions, and complications of DBE in a large single-center cohort. We retrospectively analyzed 817 patients who underwent 1101 DBE procedures between January 2006 and January 2023 at a tertiary center. The patients were grouped as young (18-44 years), middle-aged (45-64 years), and elderly (≥65 years). Demographics, indications, endoscopic and pathological findings, interventions, and complications were compared among groups. Bleeding was the most frequent indication in elderly patients, whereas diarrhea, abdominal pain, inflammatory bowel disease, and polyposis syndromes were more common in younger patients. Inflammatory lesions and polyps predominated in younger patients, whereas vascular lesions and tumors were more frequent in elderly patients (P < .05). Diagnostic interventions predominated in young and middle-aged patients, whereas therapeutic interventions were more common in the elderly (P < .001). Benign and malignant neoplasms were more common in the elderly, whereas celiac disease and polyposis syndrome were more common in younger individuals (P < .05). The overall complication rate was 2.6%, with a higher but nonsignificant rate of anesthesia-related complications in the elderly (P = .11). DBE is safe and effective in all age groups. Age was significantly associated with clinical indications and endoscopic findings, and recognizing these patterns can guide more targeted use of DBE and improve diagnostic accuracy.

Celiac disease (CeD) is driven by pathogenic CD4[+] T cell responses, primarily targeting four HLA-DQ2.5-restricted immunodominant epitopes derived from α-gliadin and ω-gliadin. While gliadin-specific CD4[+] T cells have been investigated, how transcriptional and effector phenotypes in CeD vary across distinct epitope specificities remains unclear, as do the signature TCR motifs governing gliadin epitope specificity and cross-reactivity. Single-cell transcriptomic and TCR profiling of gliadin epitope-specific peripheral blood CD4[+] T cells from patients with CeD after gluten challenge revealed T cells with an activated TH1 effector, conventional regulatory T cell (Treg cell) or cytotoxic phenotypes across specificities, with no evidence of functional specialization driven by specific epitopes. Moreover, we identified core TCR motifs that dictate gliadin epitope specificity and cross-reactivity and elucidated the structural basis of their cognate pMHC recognition. These motifs enabled accurate prediction of gliadin specificity from unassigned TCRs. Collectively, these findings advance our understanding of immune responses in CeD and provide a foundation for tracking disease-relevant T cells.

X-linked agammaglobulinemia (XLA) is an inborn error of immunity caused by BTK gene mutations, characterized by hypogammaglobulinemia and recurrent infections. This study evaluates a long-term pediatric cohort to assess clinical spectrum, therapeutic outcomes, and molecular findings. We retrospectively reviewed clinical, immunological, treatment, and genetic data for 11 male XLA patients followed over 20 years at our center. Median age at symptom onset was 12.7 months (range: 3-60), while median age at diagnosis was 4.5 years (range: 1-10), revealing marked diagnostic delays in patients without family history. Severe complications included bronchiectasis, septic arthritis, and immune dysregulation (e.g., juvenile idiopathic arthritis, autoimmune hepatitis, pancytopenia, celiac disease). Immunoglobulin replacement and antibiotic prophylaxis significantly reduced median annual infections from 16.9 to 2.09. Six distinct BTK variants were identified, including three novel mutations: c.90del, c.1922_1924delGTC, and c.1589dup. Inter-sibling phenotypic heterogeneity was notable. In the absence of functional expression studies, pathogenic contributions of novel variants remain exploratory. XLA extends beyond recurrent infections to encompass significant immune dysregulation and phenotypic variability. Early diagnosis, family screening, genetic testing, and tailored immunoglobulin therapy are vital to improve long-term outcomes. Larger multicenter cohorts with functional testing are needed to validate genotype-phenotype associations.

Coeliac disease (CeD) and immunoglobulin A deficiency (IgAD) frequently co-occur and share a genetic background within the HLA-DQ2 region. Although this has been known for decades, the underlying mechanisms linking the two conditions remain unclear. We conducted a scoping review to evaluate the prevalence, clinical characteristics, diagnostic challenges and histopathological features of IgAD in patients with CeD. Thirty-one studies published between 1985 and 2024 were included. IgAD was more prevalent among individuals with CeD, 1.4%-4.8% than in the general population, and CeD occurred in 5.9%-14.1% of patients with IgAD. Most patients presented with gastrointestinal symptoms, although selection bias was common. IgG-based serology remains essential for diagnosis and monitoring, but its reliability during follow-up is limited by the slow decline of antibodies. Histological findings indicate compensatory IgM and IgG responses and persistent mucosal immune activation. Improved strategies for diagnosis and long-term monitoring of patients with both conditions are warranted.

Tuberculosis (TB) remains a major global health concern, particularly among immunologically and nutritionally vulnerable individuals. Although celiac disease (CD) has been associated with an increased risk of TB, extensive and complicated forms remain rarely reported. We report the case of a 27-year-old man with CD, poor adherence to a gluten-free- diet (GFD), schizophrenia, and substance use disorders, who presented with extensive cavitary pulmonary TB (PT) complicated by pyopneumothorax and severe undernutrition. Concerns were raised regarding anti-TB drug absorption. In the absence of injectable anti-TB agents, standard oral treatment was initiated alongside a strict GFD, nutritional rehabilitation, and cessation of substance use. The patient showed very gradual general health improvement and required prolonged chest drainage, ultimately resulting in clinical recovery with residual pleuroparenchymal sequelae. This case highlights that PT in active CD can achieve recovery with oral anti-TB therapy when associated malabsorption is strictly managed.

Unaccompanied minor refugees (UMRs), particularly from regions like Syria, Eritrea, and Iraq, face significant healthcare challenges in the Netherlands. Their unique medical and psychosocial needs necessitate a culturally sensitive diagnostic approach and coordinated care. Chronic conditions linked to nutritional deficiencies, such as celiac disease, are of particular concern. Celiac disease is an immune-mediated disorder triggered by gluten, leading to inflammation and malabsorption in the intestines. We present a case of a 16-year-old Eritrean UMR who, after a lengthy migration, arrived with anemia, gastrointestinal issues, and nutritional deficiencies. Diagnostic tests revealed anemia, intramedullary hemolysis, and vitamin B12 deficiency, with endoscopy confirming celiac disease and chronic gastritis. Treatment included a blood transfusion, vitamin B12 supplementation, a gluten-free diet, and multidisciplinary follow-up, resulting in significant clinical improvement within weeks. This case highlights the necessity of culturally sensitive, comprehensive care for chronic conditions in UMRs.