Clinical Case Summary

Case: A 23-year-old female patient presented with non-bloody diarrhea, abdominal pain, flatulence, postprandial fullness, bloating, nausea, anal pain and itching, and low back pain. Three years prior, a minor trauma led to an X-ray revealing a compression fracture of two lumbar vertebrae. A densitometric exam of bone tissue showed osteopenia (T-score = -1.2). The patient reported no harmful habits and no relevant family medical history. Physical exam revealed abdominal tenderness in the right and left pelvic regions. Laboratory abnormalities included CRP at 6.78 mg/L, fecal calprotectin >1000 µg/g, total IgA at 1.91 g/L, and Anti-tTG IgA at 406.1 RU/mL. Tests for intestinal infections were negative. An abdominal CT scan revealed terminal ileitis with mesenteric lymphadenopathy. Endoscopy showed multiple erosive lesions in the stomach (Helicobacter pylori negative), as well as multiple erosive lesions with fibrin coating in the ileum. Isolated erosive lesions were also noted in the transverse, descending, and sigmoid colons, and the lower ampullary section of the rectum. Histological patterns were consistent with both Crohn's disease (Montreal classification: A2, L3 + L4, B1p) and Celiac disease (Marsh classification: III B). The therapeutic approach was tailored to the patient’s condition: biological therapy (Infliximab), a gluten-free diet, bisphosphonates, calcium, and vitamin D supplementation.
Conclusion: Both Crohn’s and Celiac disease are primarily considered gastrointestinal (GI) disorders, but they are systemic conditions that may present with a broad range of extraintestinal manifestations. These may develop earlier than, or in the absence of, classic GI symptoms and may be the only indication of the underlying condition. Patients presenting with osteopenia, osteoporosis, or fractures may initially be evaluated for metabolic bone disorders, while underlying Crohn’s or Celiac disease remains undiagnosed and/or alters both diagnostic and therapeutic pathways.

References

1. Chong, K. W., & Ananthakrishnan, A. N. (2018). Extraintestinal manifestations of inflammatory bowel disease. World Journal of Gastroenterology, 24(42), 4757-4767.
2. Lebwohl, B., Sanders, D. S., & Green, P. H. (2018). Celiac disease. The Lancet, 391(10115), 70-81.
3. Aro, P., & Mustalahti, K. (2010). Extra-intestinal manifestations of celiac disease. Celiac Disease: From Pathogenesis to Treatment, 11-27.
4. O’Mahony, S., et al. (2012). Extra-intestinal manifestations of Crohn’s disease. World Journal of Gastroenterology, 18(32), 4091-4098.

Introduction

Incidental inflammation of the terminal ileum is not uncommon in individuals who are submitted to screening colonoscopy. It is mostly mild and considered to have a benign course without the need for immunosuppressive therapy used for moderate Crohn’s disease. In the light of recent literature highlighting the effectiveness of early treatment of Crohn’s Disease we sought to determine the natural course of asymptomatic terminal ileitis in our pool of individuals who underwent screening (ileo)colonoscopy, and in particular which patients ended up being treated with biologics in real life , as well as any baseline factors.

Aims & Methods

We included individuals from the endoscopic database with asymptomatic terminal (Crohn’s) ileitis in the last 5 years: we only included those with recorded endoscopic images available for endoscopic assessment with the SES-CD score and biopsies compatible with Inflammatory Bowel Disease (IBD) without a history of significant NSAID consumption. We recorded baseline characteristics (age, gender, smoking status, IBD family history, extra-intestinal autoimmunity), endoscopic severity, degree of histologic inflammation and biomarkers of inflammation (C-RP, Fecal Calprotectin). Finally we went through the Greek Prescription Database to find out the ones that were prescribed with biologics, steroids or had IBD-related surgery or hospitalization. We used point-biserial correlation, Pearson correlation, chi-square test to establish any variable correlations.

Results

We included 46 individuals : 28 women, 18 men with a median age of 55.8 years and a median follow up of 46.8 months. Nine of them were smokers (19.5%) and 10 (21.7%) had elevated C-RP (>0.5 mg/dL) and/or Fecal Calprotectin (>250 μg/mg). Steroids were used in 11 patients (23.9%) and only 1 had IBD-related surgery. Patients that received biologic therapy at some time-point amounted to 15 (32.6%): 9 with adalimumab (60%), 5 with ustekinumab (33.3%) and 1 patient received upadacitinib (concomitant rheumatoid arthritis). No factor other than an initial SES-CD score > 4 displayed statistically significant correlation with the future use of biologic therapy (p-bc=0,4214, p=0,0032). Interestingly enough most of the patients to eventually receive biologic therapy showed some kind of endoscopically visible ileocecal valve inflammation.

Conclusion

In this carefully selected but with a real life follow up group of patients with incidental asymptomatic terminal (Crohn’s) ileitis a rather surprising one third of patients was eventually treated with biologic therapy during a median period of a 4-year follow up. Only baseline endoscopic severity (SES CD score >4) predicted the use of biologic therapy (mostly adalimumab or ustekinumab). All those patients had moderate disease and uneventful disease course. We need more studies to determine the (endoscopic?) threshold for biologic therapy or the right non-invasive tool (intestinal ultrasound?) to monitor these individuals in order to prevent over (or under)treatment.

References

Jellyana Peraza, Marco Emilio Kaper, Andre Bargas, Iris Kim, Manasi Agrawal, Lone Larsen, Henrik Albaek Jacobsen, Tine Jess, Jean-Frederic Colombel, Joana Torres, Ryan C. Ungaro, Ashwin N. Ananthakrishnan. A Simple Endoscopic Score for Crohn's Disease (SES-CD) ≥ 7 Predicts Disease Progression. Alimentary Pharmacology and Therapeutics 2025. Mar;61(6):1011-1018. doi: 10.1111/apt.18492. Epub 2025 Jan 5.PMID: 39757503.

Introduction

The estimated global prevalence of biopsy-confirmed celiac disease (CeD) is 0.7% and sero-positive prevalence is 1.4%. Differences in definitions of CeD cases and at-risk populations, as well as underdiagnosis, may affect accurate estimation of the size of the diagnosed CeD population. In this study, we calculated the 10-year prevalence of diagnosed CeD in the USA using different CeD case definitions and at-risk populations.

Aims & Methods

A prevalence analysis of CeD cases was conducted using data collected from the Optum Clinformatics^® Data Mart, a US claims database. Prevalence calculations were based on two different definitions of CeD cases. Case definition 1 included any of the following: 1) International Classification of Diseases (ICD)-9/-10 diagnostic codes for CeD (≥ 1 inpatient or ≥ 2 outpatient codes), 2) tissue transglutaminase immunoglobulin A (tTG-IgA) positive serology or 3) biopsy-confirmed CeD (defined as esophagogastroduodenoscopy [EGD] followed by an ICD diagnostic code for CeD used as proxy). Case definition 2 was defined as the first ever positive tTG-IgA test followed by biopsy-confirmed CeD. The prevalence of diagnosed CeD was estimated for each study year from 2013 to 2022. Prevalence estimations were age- and sex-standardized using 2022 US Census data.

Results

The total population (denominator) comprised ~81 million individuals; of whom, 110,140 had ≥ 1 inpatient or ≥ 2 outpatient diagnostic codes for CeD, 41,184 had ≥ 1 positive tTG-IgA test and 44,641 had biopsy-confirmed CeD. Among all individuals that were tested for tTG2-IgA, 0.85% (95% confidence interval [CI]: 0.82, 0.89) were positive for CeD. The age- and sex-standardized prevalence of diagnosed CeD according to case definition 1 modestly increased from 0.27% (95% CI: 0.27, 0.27) in 2013 to 0.35% (0.34, 0.35) in 2022. Over the same time period, the age- and sex-standardized prevalence of diagnosed CeD according to case definition 2 increased from 0.01% (0.01, 0.01) to 0.03% (0.03, 0.03), respectively.

Conclusion

The overall prevalence of diagnosed CeD in the USA modestly increased from 2013 to 2022. During this same time period, the proportion of patients who underwent an EGD after a positive tTG-IgA test steadily rose. Validation of the CeD case definitions used in this study will be important to enable these results to be replicated or refuted. Furthermore, a standardized and validated CeD case definition will support comparisons between studies and inform better clinical care/disease management.

Disclosure

MA, SM, NC, KG and DAL are employees of Takeda Development Center Americas, Inc. and receive stock or stock options.