Therapeutic options for CTLA-4 insufficiency.

BACKGROUND: Heterozygous germline mutations in cytotoxic T lymphocyte-associated antigen-4 (CTLA4) impair the immunomodulatory function of regulatory T cells. Affected individuals are prone to life-threatening autoimmune and lymphoproliferative complications. A number of therapeutic options are currently being used with variable effectiveness. OBJECTIVE: Our aim was to characterize the responsiveness of patients with CTLA-4 insufficiency to specific therapies and provide recommendations for the diagnostic workup and therapy at an organ-specific level. METHODS: Clinical features, laboratory findings, and response to treatment were reviewed retrospectively in an international cohort of 173 carriers of CTLA4 mutation. Patients were followed between 2014 and 2020 for a total of 2624 months from diagnosis. Clinical manifestations were grouped on the basis of organ-specific involvement. Medication use and response were recorded and evaluated. RESULTS: Among the 173 CTLA4 mutation carriers, 123 (71%) had been treated for immune complications. Abatacept, rituximab, sirolimus, and corticosteroids ameliorated disease severity, especially in cases of cytopenias and lymphocytic organ infiltration of the gut, lungs, and central nervous system. Immunoglobulin replacement was effective in prevention of infection. Only 4 of 16 patients (25%) with cytopenia who underwent splenectomy had a sustained clinical response. Cure was achieved with stem cell transplantation in 13 of 18 patients (72%). As a result of the aforementioned methods, organ-specific treatment pathways were developed. CONCLUSION: Systemic immunosuppressants and abatacept may provide partial control but require ongoing administration. Allogeneic hematopoietic stem cell transplantation offers a possible cure for patients with CTLA-4 insufficiency.

The COVID-19 Pandemic: Fears and Overprotection in Pediatric Patients with Inflammatory Bowel Disease and Their Families.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has influenced the lives of people worldwide. Little is known about the effects of the COVID-19 pandemic on the behavior and fears of pediatric patients with inflammatory bowel disease (IBD) and their families. We conducted a survey to determine the COVID-19 exposure, related perceptions, and information sources; medication compliance; and patients' and parents' behaviors, fears, and physician contact. METHODS: An anonymous cross-sectional survey of pediatric patients with IBD and their parents at one pediatric gastroenterology unit of a university medical center was performed. RESULTS: A total of 46 pediatric patients with IBD and 44 parents completed the survey. Parents of pediatric patients with IBD had high fear of their children becoming infected with severe acute respiratory syndrome coronavirus 2. They perceived schools as the most hazardous environment, whereas the children did not. Half the pediatric patients with IBD feared infection. Patients and parents felt sufficiently informed about COVID-19. The primary source of guidance for pediatric patients was their parents (43%), followed by television and social media, whereas the parents mainly consulted internet news websites (52.2%), television, and public health institutes. Pediatric patients with IBD adhered to their prescribed medication. They also showed cautious behavior by enhancing hand hygiene (84%) and leaving the house less frequently than before. However, in-person medical visits remained favored over video consultations. CONCLUSION: Although parents expressed overprotective concerns, both parents and pediatric patients with IBD are coping well with the COVID-19 pandemic. IBD-relevant information should be actively conveyed.

Abdominal symptoms in cystic fibrosis and their relation to genotype, history, clinical and laboratory findings.

BACKGROUND & AIMS: Abdominal symptoms (AS) are a hallmark of the multiorgan-disease cystic fibrosis (CF). However, the abdominal involvement in CF is insufficiently understood and, compared to the pulmonary manifestation, still receives little scientific attention. Aims were to assess and quantify AS and to relate them to laboratory parameters, clinical findings, and medical history. METHODS: A total of 131 patients with CF of all ages were assessed with a new CF-specific questionnaire (JenAbdomen-CF score 1.0) on abdominal pain and non-pain symptoms, disorders of appetite, eating, and bowel movements as well as symptom-related quality of life. Results were metrically dimensioned and related to abdominal manifestations, history of surgery, P. aeruginosa and S. aureus colonization, genotype, liver enzymes, antibiotic therapy, lung function, and nutritional status. RESULTS: AS during the preceding 3 months were reported by all of our patients. Most common were lack of appetite (130/131) and loss of taste (119/131) followed by abdominal pain (104/131), flatulence (102/131), and distention (83/131). Significantly increased AS were found in patients with history of rectal prolapse (p = 0.013), distal intestinal obstruction syndrome (p = 0.013), laparotomy (p = 0.022), meconium ileus (p = 0.037), pancreas insufficiency (p = 0.042), or small bowel resection (p = 0.048) as well as in patients who have been intermittently colonized with P. aeruginosa (p = 0.006) compared to patients without history of these events. In contrast, no statistically significant associations were found to CF-associated liver disease, chronic pathogen colonization, lung function, CF-related diabetes, and nutritional status. CONCLUSION: As the complex abdominal involvement in CF is still not fully understood, the assessment of the common AS is of major interest. In this regard, symptom questionnaires like the herein presented are meaningful and practical tools facilitating a wider understanding of the abdominal symptoms in CF. Furthermore, they render to evaluate possible abdominal effects of novel modulators of the underlying cystic fibrosis transmembrane (conductance) regulator (CFTR) defect.

Magnetic resonance imaging in children and adolescents with chronic inflammatory bowel disease.

Inflammatory bowel diseases (IBD) represent challenges, both from a diagnostic, and therapeutic point of view. Deep-seated anatomic structures are difficult to assess by ultrasound technique alone. As radiation-free alternative cross-sectional imaging method, magnetic resonance imaging of the intestinal structures is costly and time-consuming. Examination of pediatric patients imply additional considerations: reduction of body motions in younger children and consideration of the most appropriate preparation, and examination technique. The demanding Sellink technique is the only means for appropriately distending the lesser intestine in order to detect small bowel strictures. Oral intake of contrast medium (CM) alone shows its limitations regarding distensibility. The need for intravenous contrast media application needs to be considered, too. Active inflammation of both intestinal wall, and mesentery can be demonstrated accurately. Nevertheless, viable alternatives to CM application is desirable, considering non-negligible adverse reactions. Recent data suggest diffusion weighted imaging might fill this diagnostic gap. Irrespective of sequence technique chosen, bowel movement remains a major obstacle. Antispasmolytics in their function as smooth muscle relaxants help in improving image quality, however, their use in children might be off-label. Optimal preparation for the examination and appropriate imaging technique allow for diagnosing typical patterns of changes in IBD, such as bowel wall thickening, ulcers, mural stratification, strictures, creeping fat, and comb sign, and lymphadenopathy. The article gives a detailed overview of current significance of magnetic resonance imaging pediatric patients suffering from IBD, considering indications, limitations, and safety aspects.