Clinical Case Summary

A 23-year-old female presented with abdominal distension, diarrhea and nausea for a month, which worsened recently and led to hospitalization. Genetic testing confirmed a mutation in her MT-TL1 gene (m.3243A>G), consistent with the diagnosis of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. The patient had been experiencing chronic intestinal pseudo-obstruction(CIPO) for three years. Previous gastroenteroscopy showed no abnormality. She suffered from prolonged fasting and gastrointestinal decompression. Physical examination revealed significant emaciation, abdominal distension, without palpable mass. Abdominal CT showed severe gastric dilatation and decompression tube can be observed in the pelvic cavity (Fig.1-2). MELAS is a maternally inherited mitochondrial disease characterized by mitochondrial dysfunction and impaired energy production. Currently, there is no specific treatment. The patient was treated with L-carnitine and coenzyme Q10, which significantly alleviated the symptoms. Subsequently, she gradually accepted liquid food and had the gastrointestinal decompression removed. During the three-month follow-up, she no longer experienced abdominal discomfort. In this case, we demonstrate an unusual CIPO with the diagnosis of MELAS syndrome. Indeed, CIPO had been reported as a rare complication of MELAS syndrome. The intestinal obstruction complicated by this disease is characterized by diffuse obstruction of the whole digestive tract. In most previous cases, the main manifestations were lower digestive tract dilation and megacolon. However, the CT graphs of this patient shows the untypical severe gastric dilatation into the pelvis, which supplementing the complex manifestations of this rare complication.
Fig 1: Abdominal CT image from sagittal view
Fig 2(a,b,c,d): 4 CT images from coronal view at different levels

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.

Clinical Case Summary

Immunotherapy with checkpoint inhibitors (CPI) has transformed oncology management, achieving durable remissions. However, its widespread has also led to significant immune-mediated side effects, whose treatment is a challenge in today's medicine.
We present the case of a 59-year-old man diagnosed with non-small-cell lung cancer who started treatment with Nivolumab(anti-PD1). After 6 months, the patient was admitted for 3 weeks diarrhoea(4 liquid stools/day).
A colonoscopy was done, identifying severe pancolitis with oedema, erythema, nodularity and superficial ulcers. PA revealed diffuse non-specific colitis with CMV IHC -. Given the suspicion of immune-mediated colitis vs de novo IBD, treatment was started with iv GCC, with no improvement.
Given the contraindication of long-term use of anti-TNF in IBD patients with active malignancies, induction with IV Ustekinumab (anti-IL12/23) was decided. Ustekinumab 390 mg iv was given, after which the patient showed clinical improvement until complete resolution. He continued with Ustekinumab 90 mg/8 weeks. A follow-up colonoscopy showed pancolic scarring with pseudopolyps and no inflammatory activity. Given these findings Ustekinumab was discontinued after 1 year, with the patient remaining asymptomatic and without oncologic progression.
Immune-mediated colitis is a common side effect, being mild in most cases. When severe cases occur, CPI should be discontinued indefinitely, and high-dose iv GCC (up to 2 mg/kg) should be initiated. Up to one-third of GCC-treated patients don't respond and are candidates for immunosuppressive therapy with biologic drugs.
Although clinical guidelines recommend Infliximab/Vedolizumab for induction as 2º line treatment, the therapeutic decision should be individualized, as they are contraindicated in IBD patients with active malignancies. Therefore, in this context of complex differential diagnosis, Ustekinumab (with lower rate of oncological side effects) appears to be an effective option.

References

Photo 1: Initial colonoscopy: severe pancolitis with erythema, oedema, superficial ulcers and mucosal nodularity.
Photo 2: Abdominal CT: Diffuse thickening of the colon with increased uptake of the wall.
Photo 3: Follow-up colonoscopy: Chronic scar changes without signs of acute activity.

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

Patients with inflammatory bowel disease (IBD) are at increased risk of reduced bone mineral density (BMD), often linked to chronic inflammation, corticosteroid use, biologics, and vitamin D deficiency. 25-hydroxyvitamin D (25(OH)D) is a fat-soluble vitamin essential for calcium and phosphorus homeostasis, and its deficiency is common in IBD due to malabsorption, dietary, altered metabolism, or impaired VDR signaling.

Aims & Methods

This cross-sectional study aimed to evaluate the relationship between serum 25(OH)D levels, BMD, and body composition in IBD patients. A total of 73 outpatients with IBD (38 ulcerative colitis, 35 Crohn’s disease) were assessed. Body composition was evaluated using BMI and bioelectrical impedance analysis (BIA). BMD was measured using whole-body dual-energy X-ray absorptiometry (DEXA), and vitamin D status was assessed by serum 25(OH)D concentration. Statistical analysis included descriptive and comparative tests (Chi-square and t-test).

Results

Participants had a mean age of 45.27±11.37 years, with 67.1% being female and a mean disease duration of 10.22±7.54 years. Most patients (93.15%) were in clinical and endoscopic remission. The average BMI was 26.85±4.51 kg/m², with 39.7% classified as overweight. DEXA revealed a high prevalence of osteopenia (39.7%) and osteoporosis (19.0%). Mean BMD Z-scores were whole body -1.32±1.13, spine -0.92±1.19, and femoral neck -0.34±1.02. Mean serum 25(OH)D level was 31.20±8.78 ng/mL; 52.1% had insufficient levels and 47.9% were sufficient. Vitamin D insufficiency was significantly associated with osteopenia/osteoporosis (p=0.0144) and with overweight/obesity (p=0.0265). No significant associations were observed between vitamin D levels and age (p=0.6476), sex (p=0.4565), lean mass (p=0.2941), fat mass (p=0.1218), phase angle (p=0.3154), or regional BMD (total body p=0.5001; spine p=0.3067; femoral neck p=0.2364).

Conclusion

IBD patients are vulnerable to low serum vitamin D levels and present a high prevalence of low BMD. Vitamin D insufficiency was associated with altered BMI and increased risk of osteopenia/osteoporosis, though not with other body composition metrics. Further studies are needed with larger and more clinically heterogeneous samples to confirm these associations and guide screening and supplementation strategies.

References

Khan, ZAW, Shetty, S., Pai, GC, Acharya, KKV, & Nagaraja, R. (2020). Prevalence of low bone mineral density in inflammatory bowel disease and factors associated with it. Indian journal of gastroenterology: official journal of the Indian Society of Gastroenterology, 39(4), 346–353. https://doi.org/10.1007/s12664-020-01048-5
Kuo, YW, Kuo, CJ, Le, PH, Chang, ML, Lin, CY, Hsu, CM, Lin, WP, Chen, CW, Lin, WR, Ho, YP, Su, MY, and Chiu, CT (2025). Risk factors and awareness of bone fragility in inflammatory bowel disease in Taiwan: a cross-sectional study. Biomedicines, 13(3), 638. https://doi.org/10.3390/biomedicines13030638
Chauhan, G., & Rieder, F. (2025). The Pathogenesis of Inflammatory Bowel Diseases. Surgical Clinics of North America, 105(2), 201–215. https://doi.org/10.1016/j.suc.2024.10.008
Kärnsund, S., Lo, B., Bendtsen, F., Holm, J., & Burisch, J. (2020). Systematic review of the prevalence and development of osteoporosis or low bone mineral density and its risk factors in patients with inflammatory bowel disease. World Journal of Gastroenterology, 26(35), 5362–5374. https://doi.org/10.3748/wjg.v26.i35.5362
Aaseth, JO, Finnes, TE, Askim, M., & Alexander, J. (2024). The importance of vitamin K and the combination of vitamins K and D for calcium metabolism and bone health: a review. Nutrients, 16(15), 2420. https://doi.org/10.3390/nu16152420