Introduction

Crohn’s Disease (CD) is a chronic disease in which inflammation is sustained by continuous influx of inflammatory leukocytes into gut mucosa and may affect all segments of the gastrointestinal tract. Immune cell trafficking is regulated via chemokine gradients and adhesion molecules such as integrins. Here we explored the expression profile of gut-specific integrin and chemokine axes in different regions of the gut to identify possible targets for treating CD patients with different disease location or phenotype.

Aims & Methods

This study used transcriptomic data from gut tissue biopsies of the large and small intestine of 611 CD and 315 UC patients enrolled in a multicentred longitudinal Study of a Prospective Adult Research Cohort with IBD (SPARC IBD) obtained from the IBD Plexus program of the Crohn’s and Colitis Foundation. We mapped the expression of selected chemokine receptors and their ligands as well as gut-specific integrins onto the different segments of the intestine. Expression data were then linked to available clinical disease phenotypes, as well as genotype information.

Results

In both CD and UC patients, ITGA4 and ITGB7, the targets for Vedolizumab, and their endothelial ligand MADCAM1 were ubiquitously present in all regions of the gut. GPR15 and its ligand C10orf99 were predominantly expressed in colonic biopsies. On the contrary, expression of CCR9 and its ligand CCL25 were specific to the terminal ileum with only minimal transcriptional activity in the colon. Expression of CCL25 was significantly increased in patients with penetrating and/or stricturing CD, a disease feature associated with ileal CD that has high impact for patients and is currently an unmet for IBD patients. Further, we identified an expression quantitative trait loci (eQTL) upstream of the CCL25 promoter linked to small bowel expression of CCL25.

Conclusion

Our data highlight the potential for targeting the CCR9/CCL25 axis as a treatment for small bowel Crohn’s Disease which may have been incompletely targeted to date by small molecule inhibitors.

Disclosure

All authors were employees of AstraZeneca during the conduct of the study and hold AstraZeneca stocks or stock options.

Introduction

Celiac disease (CD) is an autoimmune enteropathy induced by the ingestion of gluten in genetically predisposed individuals. Although its clinical expression is most often digestive, extra-digestive manifestations can occur, among which thromboembolic complications, although rare, deserve particular attention.
The aim of this study is to describe the profiles of coeliac patients with thromboembolic complications, analyze their clinical, paraclinical and etiological characteristics, and discuss the underlying pathophysiological mechanisms.

Aims & Methods

This is a retrospective, descriptive, monocentric study conducted in the hepato-gastroenterology department of Ibn Sina Hospital in Rabat over a 30-year period, from 1995 to 2025. The records of 344 patients followed for celiac disease were reviewed. Patients with one or more documented thromboembolic complications during follow-up were included in the study. Clinical, biological, endoscopic and histological data were collected and analyzed.

Results

Of a total of 344 patients followed for celiac disease in the department, 5.5% (n=19) developed a thromboembolic complication during follow-up. The population concerned was predominantly female, with 89.5% women (n=17) versus only 10.5% men (n=2). The mean age at the time of complication was 39.6 years, with a median of 35.5 years, and extremes ranging from 18 to 62 years.
Endoscopic exploration (oesogastro duodenal fibroscopy) in these patients showed lesions suggestive of celiac disease in 68.4% (n=12), while it was non-specific in 31.6% (n=6), and normal in 5.3% (n=1). Histologically, villous atrophy was found in all patients, with 78.9% (n=15) showing total atrophy (Marsh IIIc) and 21.1% (n=4) subtotal atrophy (Marsh IIIb).
As regards thromboembolic manifestations, portal vein thrombosis was the most frequent complication, observed in 57.9% of cases (n=11). It was followed by deep vein thrombosis of the lower limbs, reported in 15.8% of cases (n=3), and ischemic stroke in 10.5% (n=2). Isolated cases of thrombosis of the inferior vena cava, axillary vein and femoral vein were recorded, each accounting for 5.3% of cases (n=1).
The etiological study revealed hyperhomocysteinemia in 36.8% of patients (n=7) and protein C and/or S deficiency in 21.1% (n=4). In the remaining 42.1% of patients (n=8), the thrombophilia work-up was normal, suggesting that celiac disease itself was the cause of the thrombotic event.
Therapeutically, all patients were treated with oral anticoagulation. One patient required a vena cava filter because of the risk of bleeding on anticoagulation, and another underwent surgical treatment for axillary thrombosis. The outcome was favorable in all cases, with no recurrence or major complication during follow-up.

Conclusion

Thromboembolic complications in celiac disease are rare but potentially serious. This study highlights the predominance of women, the diversity of thrombotic localizations, and the possible involvement of hyperhomocysteinemia and C/S protein deficiencies. In almost half the cases, no thrombophilic cause has been identified, suggesting a role for celiac disease in the genesis of these events. Clinical vigilance is essential, particularly in cases of late diagnosis or poor compliance with the gluten-free diet.

Introduction

Celiac disease (CD) is a chronic autoimmune enteropathy triggered by gluten ingestion in genetically predisposed individuals. While isolated hypertransaminasemia is the most frequent hepatic manifestation of CD, its association with portal hypertension (PHT) remains rare and poorly understood.

Aims & Methods

This study aims to describe this association and evaluate the impact of a gluten-free diet (GFD) on the progression of PHT-related complications.
We conducted a 30-year retrospective study including 20 patients with both histologically and serologically confirmed CD and PHT, among a total cohort of 344 CD patients. Clinical, biological, endoscopic, imaging, and histological data were analyzed.

Results

Among the 20 patients (75% female, F/M ratio 3; mean age 34.2 years), the most frequent symptoms were abdominal pain and weight loss (45% each), followed by ascites (35%), malabsorptive diarrhea (30%), atypical diarrhea (20%), and vomiting (15%). One patient presented with upper gastrointestinal bleeding. Splenomegaly was observed in 70%, and collateral venous circulation in 30%. Liver was clinically normal in 80%, cirrhotic in 20%. Imaging showed a regular liver in 65%, nodular in 35%, with 25% having portal cavernoma and one patient with focal IVC thrombosis.
Liver biopsy findings included porto-sinusoidal vascular disease (40%), celiac cirrhosis (20%), granulomatous hepatitis (15%), and normal histology (25%). Upper endoscopy revealed esophageal varices in 55%. PHT led to the diagnosis of CD in 4 patients. In non-adherent patients, progression of varices and cirrhosis occurred in 20% over 5 years.

Conclusion

The CD–PHT association is rare (5.8% in our series) but clinically significant. Various mechanisms may underlie this link, highlighting the importance of screening for CD in unexplained PHT. GFD adherence appears to slow hepatic deterioration and variceal progression, reinforcing its therapeutic value.

Introduction

Celiac disease (CD) is an autoimmune enteropathy triggered by gluten in genetically predisposed individuals. Both hereditary and acquired factors may increase thrombotic risk in CD. Anti-phospholipid antibodies (aPL), including anti-cardiolipin (aCL) and anti-β2 glycoprotein I (β2GPI), are known markers of thrombophilia.

Aims & Methods

This study aimed to evaluate the frequency of these antibodies in CD patients and investigate any correlation with gluten-free diet (GFD) adherence.
This prospective, descriptive study was conducted over four years and included 42 patients diagnosed with CD based on clinical, serological, and histological criteria. Anti-cardiolipin IgG (aCL) and anti-β2GPI IgG antibodies were tested by ELISA, and lupus anticoagulant (LA) was assessed via coagulation assay.

Results

Among 42 CD patients, aPL results were available for 9 (22%). The mean age was 35.5 years (range 18–58), with a female-to-male ratio of 2. All patients were prescribed a GFD with regular follow-up.
aCL IgG antibodies were positive in 3/9 patients (15.2%), β2GPI IgG antibodies were positive in 1/9 (5%), and LA was negative in all patients. No correlation was found between the presence of aPL and disease activity or adherence to GFD. Additionally, aPL presence was not associated with disease duration or thrombotic events.

Conclusion

In our cohort, we did not observe a high prevalence of anti-phospholipid antibodies among CD patients. aCL IgG was the most frequently detected antibody (15.2%) under strict GFD. The clinical significance and pathogenic role of these antibodies in CD remain unclear and warrant further large-scale prospective studies.

Introduction

Coeliac disease (CD) is a chronic small intestinal immune-mediated enteropathy which occurs in genetically predisposed individuals by exposure to ingested gluten, globally about 1% of the world’s population. CD mainly affects the gastrointestinal tract but may also affect other organs. CD may therefore present with a wide range of symptoms and signs. Diagnosing CD involves assessment of symptoms, clinical findings, serology, and endoscopy with duodenal biopsies. In children and adolescents, endoscopy with biopsies can be omitted if serology is conclusive, but this is controversial in adults. Endoscopy can have an additional yield by diagnosing other non-CD related findings, including premalignant and malignant lesions of the upper gastrointestinal tract.

Aims & Methods

The aim of this study was to assess the additional non-CD related findings at the diagnostic endoscopy for CD in an adult population screened for CD. The study was based on the fourth Trøndelag Health Study (HUNT4), a population-based study of adults above 20 years of age in Norway (1). Serum samples of 54,505 participants were analysed using a dual anti-transglutaminase 2 immunoglobulin A and G assay, and the 1107 seropositive individuals were invited to upper gastrointestinal endoscopy with duodenal biopsies. CD was confirmed if histological findings corresponding to Marsh grade 3 were found. At the diagnostic investigation performed by specialists in gastroenterology, additional endoscopic findings were recorded systematically. Multivariable logistic regression analysis was used to estimate the risk of additional findings at the diagnostic endoscopy for CD. The risk was adjusted for sex, age, and use of medications (non-steroid anti-inflammatory drugs/acetylsalicylic acid and proton pump inhibitors/histamine-2 receptor antagonists).

Results

In the present study, 476 individuals with confirmed CD were included. Median age was 55 years and 54.6% were women. The proportion of additional non-CD related endoscopic findings increased with increasing age, especially above 50 years of age. Seven Barrett’s oesophagus and one duodenal adenoma with low grade dysplasia were found, all among participants above 50 years of age. No malignant lesions were found. The risk of additional endoscopic findings increased with advancing age and was higher among men and those using proton pump inhibitors or histamine-2 receptor antagonists.

Conclusion

This study suggests that diagnosing CD without endoscopy will not result in missing clinically significant additional findings in the younger adult population below 50 years of age. However, with advancing age above 50 years, the risk of non-CD related premalignant lesions increases. These lesions can be detected at the diagnostic endoscopy for CD and treated or included in surveillance programs to prevent sinister outcomes.

References

1. Lukina P, Andersen IL, Eggen PT, Mjones PG, Ronne E, Bolstad N, et al. Coeliac disease in the Trondelag Health Study (HUNT), Norway, a population-based cohort of coeliac disease patients. BMJ Open. 2024;14(1):e077131.

Clinical Case Summary

Diseases damaging the enteric mucosa cause malabsorption that may trigger neurologic symptoms, both by immune-related processes and impaired absorption of essential vitamins.
Celiac disease (CD) is found in patients presented with nonhereditary ataxia. In these patients, abnormalities referred to as “gluten ataxia”, are probably the result of immunologic damage to the CNS and peripheral nerves.
B1 is an essential vitamin which its deficiency has broad clinical spectrum; thus, its diagnosis is challenging, and a sensitized clinician is needed to prompt identification. The encephalopathic form of adult thiamine deficiency is called Wernicke-Korsakoff syndrome.
A 40-y/o/w, G4P2, suffered from severe hyperemesis gravidarum resistant to antiemetics during trimester 1.
On 13^th week of pregnancy, she went to the ER, d/t confusion & extensive weakness. Her lab tests showed severe electrolytes deficiencies with transaminitis and elevated CPK levels. She was diagnosed with rhabdomyolysis secondary to her continuous vomiting. On her neurological examination psychomotor slowness and ataxia were found. Thus, Wernicke encephalopathy was suspected and her B1 level was tested and found low: 12 ug/L. She was hospitalized in the ICU to get electrolytes replacement and intravenous thiamine. To confirm the diagnosis, brain MRI was performed and demonstrated a classic picture of Wernicke encephalopathy (1).
6m later she gave birth, but her neurological deficits got worse. TTG level was tested and found positive. Gastroscopy showed duodenal scalloping (2) and Marsh 3C on biopsy (3). She started GFD and neurological rehabilitation. On repeated anamnesis she had abdominal pain before the pregnancy, but her investigation was negative.
This case illustrates a rare herald of CD and increases the awareness of possible manifestation of B1 def.
Points to discuss:

1. Two-hit theory of B1 def. (hyperemesis gravidarum and CD)
2. Neurologic manifestation of CD & B1 def.
3. Vitamins’ malabsorption in CD

References

1. Brain MRI with classic picture of Wernicke encephalopathy
2. Endoscopic picture of duodenal scalloping
3. H&E staining that demonstrates Marsh 3C in duodenal biopsy

Introduction

Celiac disease (CD) is a chronic autoimmune enteropathy triggered by gluten ingestion in genetically predisposed individuals. Diagnosis is based on clinical, biological, serological, and especially histological criteria, including villous atrophy and intraepithelial lymphocytic infiltration (>30%).

Aims & Methods

The aim of this study is to highlight the importance of clinical presentation, biological markers, and histology in the diagnosis of seronegative CD, particularly since serological testing often guides biopsy decisions.
We conducted a retrospective descriptive study over a 30-year period, from January 1995 to March 2025, including all patients with histologically confirmed CD based on jejunal biopsy and clinical response to a gluten-free diet (GFD), but with negative anti-transglutaminase IgA and/or anti-endomysial antibodies. All seropositive patients were excluded.

Results

Out of 344 patients diagnosed with CD in our department, 74 (21.3%) were seronegative. The mean age was 65 years (range: 20–65), with a female-to-male ratio of 3.1.
From a clinical standpoint, nutritional deficiency syndromes were present in 95.9% (n=71), malabsorptive chronic diarrhea in 77% (n=57), diffuse abdominal pain in 71.6% (n=53), weight loss in 54% (n=40), and chronic evacuation constipation in 6.7% (n=5). Clinical examination showed anemia in 70.3% (n=52) and neurological signs in 25.6% (n=19).
Endoscopic findings were suggestive of CD in 43.2% of cases, including duodenal fold reduction in 37.8% (n=28), and a 'scalloping' appearance in 5.4% (n=4). Duodenal mucosa and folds appeared normal in 44.6% (n=33).
Histological analysis of jejunal biopsies in all patients revealed intraepithelial lymphocytosis >30%. Severe villous atrophy (Marsh stage IIIc) was found in 71.5% (n=53), and partial atrophy (Marsh IIIa) in 10.8% (n=8).

Conclusion

In our study, seronegative CD represented 21.3% of all celiac patients. These patients had more severe clinical presentations and more advanced villous atrophy (Marsh stage III), despite negative serology. This underlines the importance of histology and clinical judgment in diagnosing CD in seronegative individuals.