ABSTRACT
Case Report: Protein losing enteropathy (PLE) occurs when proteins leak from the gastrointestinal (GI) system more rapidly than they are produced. Inflammation of the GI tract facilitates increased membrane permeability of gastric mucosa, leading to excess protein leakage. 1 PLE in children has been associated with CMV, rotavirus, COVID-19, HIV, C. difficile, and autoimmune diseases like Crohn's Disease. 2-6 Norovirus is a known cause of PLE in immunocompromised pediatric patients. 7-8 However, to our knowledge, there are no case reports about PLE precipitated by norovirus in immunocompetent pediatric patients. The purpose of this case report is to present a case of PLE precipitated by a norovirus infection in a 4- year-old previously healthy child. While the above gastrointestinal viruses have been proposed as precipitators for this disease, PLE precipitated by norovirus infection has not been well described. This case also highlights the importance of early diagnosis and management to avoid complications. Method(s): Our patient initially presented with two days of abdominal pain, diarrhea, emesis, reduced urine output, and swelling of the lower extremities. He was exposed to several sick family members-his sister had upper respiratory symptoms and his grandmother had gastrointestinal symptoms. Physical exam was notable for diminished breath sounds in the right lower lobe, abdominal distension with diffuse tenderness and dullness to percussion, significant scrotal and penile edema, and bilateral lower extremity pitting edema. Laboratory results revealed leukocytosis, hypoalbuminemia, hyponatremia, elevated aspartate aminotransferase (AST), and elevated serum alpha-1-antitrypsin, as well as low Immunoglobulins G and M. CD3 and CD4 levels were low reflecting cellular immune dysregulation seen in patients with PLE. IgA and Tissue Transglutaminase (TTF) were within normal limits. Ebstein Barr Virus and cytomegalovirus IgM antibodies were negative. COVID IgG was negative as well. His Polymerase chain reaction (PCR) gastrointestinal panel was positive for norovirus. A chest X-ray showed a large right pleural effusion. Abdominal CT revealed large ascites slightly more predominant in the upper abdomen, mesenteric lymphadenitis, and bilateral pleural effusions. Echocardiogram showed small anterior and apical pericardial effusions. Result(s): Based on the patient's elevated serum alpha-1 antitrypsin levels, hypoalbuminemia, low levels of immunoglobulins and lymphocytes, and clinical manifestations of ascites, bilateral pleural effusions, pericardial effusion, and dependent edema, along with a positive PCR for norovirus, the diagnosis of PLE secondary to Norovirus was made. Conclusion(s): This case demonstrates the importance of recognizing viruses like Norovirus as potential causes of PLE to avoid a delay in diagnosis and initiation of therapy, and to avoid unnecessary additional testing. Copyright © 2023 Southern Society for Clinical Investigation.
ABSTRACT
Background and Aims: Substantial practice variation exists in both the diagnostic criteria for and the post-diagnosis monitoring of celiac disease (CeD). Differences include standards for serological diagnosis, endoscopic practices, models of care, and long-term clinical monitoring, all confounded by the COVID-19 pandemic. With the exponential rise of gluten-related disorders, revised ESPGHAN guidelines and new healthcare barriers, it is helpful to explore practice patterns to inform updates to clinical guidelines and future research endeavors. The purpose of this survey was to understand the expertise and practice parameters of pediatric gastroenterology (GI) clinicians across North America for the diagnosis and management of children with celiac disease. Method(s): A 23-item survey designed by a working committee of the NASPGHAN Celiac Disease Special Interest Group was distributed electronically to NASPGHAN members, including attending physicians, fellows, and advanced practice providers from September to December 2021. Four themes were explored: 1) screening and diagnosis;2) monitoring;3) impact of the COVID-19 pandemic;and 4) education and training. The implementaion of the ESPGHAN non-biopsy serologic diagnosis (based on the 2020 guidelines: tissue transglutaminase IgA (TTG-IgA) 10x upper limit of normal and a second sample with a positive endomysial antibody) by providers was explored. Descriptive statistics were tabulated by region, clinical role and those who identified as working at a celiac center. Result(s): A total of 284 surveys were completed with a response rate of 11.1% (264/2552). The majority of respondents were from the United States (89%, n=235) and Canada (8%, n=22) with 2% (n=5) from Mexico. Serology-based diagnosis as per ESPGHAN 2020 guidelines was accepted by 54.5% (n=12/22) of Canadian respondents and 39.6% (n=93/235) from the U.S (p=0.17). Since the COVID-19 pandemic, 36% of respondents have increased their application of non-biopsy diagnosis. Canadian respondents reported offering the ESPGHAN non-biopsy approach to diagnosis more often during the COVID-19 pandemic (Canada 74% vs US 33%, <0.0001). A higher precentage of patients who lived in Canada (52%) with positive celiac serologies waited >1 month to be evaluated by GI than the US (30%);p=0.03. There was also a significant difference between access to endoscopy within a month between patients who lived in Canada and the US patients (Canada 77% >1 month, US 20% >1 month;p=<0.001). Investigations at follow-up which were completed most frequently by those who identified as working at a celiac center (n=108) included complete blood count, thyroid function tests, liver enzymes, iron profile, Vitamin D and TTG-IgA (Figure 1). Among these respondents, 49.1% (n=53/108) repeat family screening ranging every 1-5 years. Specialty training in CeD remains limited as only 25.7% (n=61/237) staff pediatric gastroenterologists had celiac-focused didactic lectures, and 23.3% (n=55/237) participated in a CeD specialty clinic during their fellowship. Conclusion(s): This survey revealed heterogeneity in current practices for the diagnosis and management of CeD in North America and the influence of the COVID-19 pandemic in increasing the use of the ESPGHAN no-biopsy approach to diagnosis. An education gap was identified for CeD in pediatric GI fellowship training. Further studies are needed to understand the impact of these variable practices and future research priorities and clinical guidelines should take this variation into consideration. (Figure Presented).
ABSTRACT
Celiac disease (CD) is a common immune-mediated disease of the gastrointestinal tract that results in small bowel damage from ingesting gluten in genetically susceptible patients. The SARS-CoV-2 (COVID-19) pandemic resulted in a nationwide healthcare lockdown, with the halting of elective medical procedures and tests. The potential consequence of the COVID-19 pandemic on the long-term risk of systemic and autoimmune disorders like CD is not yet clear. There is growing evidence that COVID-19 can cause a "cytokine storm" affecting epithelial cells like intestinal mucosal cells, which may increase the risk of celiac autoimmunity;defined as positive celiac serology like anti-tissue transglutaminase immunoglobulin A (TTG IgA). Many providers report observing an increased number of newly diagnosed autoimmune disorders such as the CD post-COVID-19 pandemic. It is not clear if this is a true increase in CD autoimmunity or due to overcompensation of diagnostic numbers after the lockdown. This study aims to evaluate the effect of the COVID-19 pandemic on the frequency of CD screening tests and the rate of celiac autoimmunity reflected by positive TTG IgA titers. Method(s): This retrospective cohort study used the Rochester Epidemiology Project (REP) electronic health records between January 2018 and December 2021. All subjects who underwent celiac serology screening testing (TTG IgA) during the study period were included. The REP 7-county core region includes Olmsted County and the following 6 counties: Wabasha, Waseca, Steele, Dodge, Freeborn, and Mower. We documented the total number of celiac serology screening (TTG IgA) tests ordered during the study period and compared the frequency of tests performed and the rate of positivity before and after COVID-19. We used January 2020 as a marker of the start of the COVID- 19 pandemic in the USA;referring to the first reported case by the CDC. All patients had active research authorization at the onset of the study before being included in the analysis. All data were stored and managed in compliance with the REP and Mayo Clinic IRB regulations. Result(s): A total of 15,443 (Mean=321.7, SD= 6.7, CI= 13.4) TTG IgA screening tests for CD were ordered from January 2018 till December 2021. As expected, the frequency of celiac screening tests ordered decreased sharply during the lockdown in early 2020 (March-May) (Mean= 202.7, SD=39.8, CI= 171.4)), but it picked rapidly by June 2020 with a 2.5% increase to the pre-pandemic testing frequency rate (Figure1). Despite this sharp decrease in celiac screening testing during the lockdown, the rate of celiac autoimmunity (positive TTG IgA) was higher during similar periods in pre and post-lock down years Figure1. Comparing the rate of positivity of celiac tests done during the months of March to May of the lockdown in 2020 (44/608;7.24%) to the same period during years 2018, 2019, and 2021, we found a statistical difference in the rate of positivity (p= 0.04, df= 3) figure2. There was no significant difference in the number of tests administered between pre-and post-COVID years (7625 vs. 7818, p = 0.09). Over the study period, the total number of positive screening tests was 655/15443 (4%). Using January 2020 as our cut-off, we compared the rate of screening test positivity pre and post COVID-19 to the total number of tests as demonstrated in figure1. Conclusion(s): Celiac screening and autoimmunity were stable over the study period, however, during the lockdown, the rate of celiac autoimmunity was significantly higher as compared to similar periods before and after the pandemic year. It is not clear if this is due to false-positive TTG IgA post-COVID, or true autoimmunity. We expect that follow-up studies with a longer follow-up period during and after the COVID-19 pandemic are needed to understand the true effect of COVID-19 on celiac autoimmunity. (Figure Presented).
ABSTRACT
Objective. No data are available on the effects of SARS-CoV2 infection in patients with celiac disease (CD) in terms of development of related symptoms and antibodies. We aimed to investigate the impact of SARS-CoV2 infection in CD. Design. During lockdown (March-May 2020), celiac patients living in Milano were interviewed about the development of COVID-19 resembling symptoms, adherence to an anti-virus lifestyle and gluten-free diet (GFD), and were asked to reply to a stress questionnaire. The development of anti SARSCoV2 IgG and IgA (anti RBD and N proteins) and the expression of duodenal ACE2 receptor were also investigated. Whenever available, duodenal histology, anti-tissue transglutaminase IgA (tTGA), immunologic comorbidities and GFD adherence were analyzed as possible risk factors. Results. 362 celiac patients have been interviewed and 42 (11%) reported COVID-19 resembling symptoms. The presence of symptoms was not influenced by positivity of tTGA, presence of duodenal atrophy or adherence to GFD. 37% of symptomatic patients showed anti SARS-CoV2 Immunoglobulins (Ig). Globally, 18% of celiac patients had anti SARS-CoV2 Ig vs 25% of non-celiac controls (p=0.18). Levels of anti RBD IgG/IgA and anti N IgG did not differ from non-celiac controls. Celiac patients had significantly lower levels of anti N IgA. ACE2 receptor was detected in the non-atrophic duodenal mucosa of celiac patients;atrophy was associated with a weaker expression of ACE2 receptor. Conclusion. CD patients show an anti SARS-CoV2 Ig positivity/profile similar to non-celiac controls, except for anti-N IgA. Main celiac biomarkers and adherence to the GFD do not influence the development of different antibody profiles.