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.

Clinical Case Summary

An 18-year-old female was diagnosed with very early-onset Crohn’s disease (CD) in 2008. Due to steroid dependence, adalimumab 40 mg biweekly was initiated in 2019, with escalation to 40 mg weekly in February 2023 following secondary loss of response. In November 2023, despite clinical and biochemical remission (CRP <0.5 mg/L, fecal calprotectin <50 µg/g), the patient developed painful purpuric and ulcerated lesions on both lower limbs. Histological examination of a skin biopsy confirmed leukocytoclastic vasculitis (LCV), revealing perivascular neutrophilic infiltrates, nuclear debris, and fibrinoid necrosis in post-capillary venules. Infectious and autoimmune screening, including ANA, antiphospholipid antibodies, p-ANCA, and c-ANCA, were negative. Following consultation with an immunologist, adalimumab was discontinued, and oral prednisone 25 mg/day was initiated. However, the clinical course was complicated by a skin abscess, which was treated with oral amoxicillin/clavulanate (1 g three times daily for 3 days). As vasculitic lesions worsened, the patient was hospitalized, and prednisone was increased to 50 mg/day. Intravenous cefazolin (2 g every 8 hours for 5 days) was also administered, resulting in stabilization and partial clinical improvement. A multidisciplinary team, including a gastroenterologist, immunologist, and dermatologist, opted to initiate off-label treatment with upadacitinib 30 mg/day, a selective Janus kinase 1 (JAK1) inhibitor. After four weeks, the patient showed improvement in the vasculitic lesions, and corticosteroid therapy was tapered. At the six-month follow-up, the patient remained on upadacitinib monotherapy, with sustained clinical and biochemical remission of both CD and LCV, without any adverse events. This case highlights the potential of JAK1 inhibition as an effective and safe therapeutic option for leukocytoclastic vasculitis in patients with Crohn’s disease.

References

Photographic documentation of the clinical case:
1. Images showing the initial presentation of petechial and purpuric lesions on the lower limbs.
2. Images of severe vasculitis characterized by confluent and ulcerated lesions.
3. Images documenting cutaneous healing following upadacitinib treatment.

Clinical Case Summary

Introduction: PSC is closely associated with IBD and affects up to 3.6% of Crohn's disease patients, while AIH is also more prevalent in IBD patients, in up to 16% of patients.
Case report: We report a female patient who, at the age of 14, presented with right hypochondrial pain and abnormal liver biochemistry (SGOT: 44 U/l, SGPT: 145 U/l, γ-GT: 300 U/l, ALP: 421 U/l, TBL: 1 mg/dL). The patient underwent MRCP (Figure A) which revealed local strictures with prostenotic dilatation in both intrahepatic and extrahepatic bile ducts, suggestive of PSC. One year later the patient presented with severe abdominal pain and bloody diarrhea. Ileocolonoscopy showed terminal ileitis (Figure B) and segmental colitis. Histological evaluation (Figure C) showed disruption of the architecture, focal erosions of the epithelium, mild mucopenia, inflammatory infiltrate in the dermis, sites of cryptitis and focal formation of crypt abscesses with extension of inflammation to the muscularis mucosae, suggestive of Crohn’s Disease. Two years later, in a regular laboratory test, the patient had abnormal liver function tests (SGOT: 211 U/l, SGPT: 603 U/l, γ-GT: 54 U/l, ALP: 105 U/l, TBL: 0.9 mg/dl). Further evaluation with immunoassay revealed ANA (+) 1/80, AMA (-), SMA (+) 1/160, + F-actin, anti-LKM (-), anti-LC (-), anti-LM (-), p ANCA (+) 1/80, so the patient underwent percutaneous liver biopsy with findings of portal spaces with presence of waxy-containing macrophages, thin fibrous septa, parenchyma with centrolobular necrosis with aggregates of inflammatory cells and waxy macrophages, suggestive of Autoimmune Hepatitis. Today, the patient is in clinical remission under treatment with Ursodeoxycholic acid, Ustekinumab and Mycophenolate Mofetil.
Conclusion: The association of IBD with PSC, AIH and variant forms is now known, however the complexity of the diseases presents a challenge for the clinician and the provision of individualized care.

References

1. Ballotin VR, Bigarella LG, Riva F, Onzi G, Balbinot RA, Balbinot SS, Soldera J. Primary sclerosing cholangitis and autoimmune hepatitis overlap syndrome associated with inflammatory bowel disease: A case report and systematic review. World J Clin Cases. 2020 Sep 26;8(18):4075-4093.
2. Saich R, Chapman R. Primary sclerosing cholangitis, autoimmune hepatitis and overlap syndromes in inflammatory bowel disease. World J Gastroenterol. 2008 Jan 21;14(3):331-7.
3. Rocha HC, Vilela EG. Clinical aspects and prognosis of patients with inflammatory bowel disease associated with autoimmune liver diseases. Gastroenterol Hepatol. 2022 Feb;45(2):83-90. English, Spanish.
4. Malik T, A, Gutierrez A, M, McGuire B, Zarzour J, G, Mukhtar F, Bloomer J: Autoimmune Hepatitis-Primary Sclerosing Cholangitis Overlap Syndrome Complicated by Crohn’s Disease. Digestion 2010;82:24-26.

Clinical Case Summary

Splenic granulomas are a rare extraintestinal manifestation of Crohn’s disease (CD). In previously reported cases, the diagnosis was confirmed by biopsy. However, due to the increased risk of complications associated with biopsy, confirmation by imaging is desirable.
52-year-old male patient presented with a previously diagnosed, currently untreated CD.
Symptoms:

• Abdominal pain in the right lower quadrant for several weeks, postprandial
• Bowel movements: 4-6 times/day for a few weeks, liquid consistency
• No fever or weight loss
• Palpation: tenderness in the lower right abdomen

Findings:

• C-reactive protein and leukocytes: not elevated
• Calprotectin: 184ug/g. Stool culture and intestinal cytomegaly virus PCR biopsy negative
• Tuberculosis interferon-g release assay: negative
• Colonoscopy and magnetic resonance enterography (MRE): ileitis of terminal Ileum (Fig. 1)
• MRE: multiple T2w-hyperintense splenic lesions, increased in number since last imaging 2024 (Fig. 2)
• B-mode ultrasound: splenomegaly, round nodules of mixed echogenicity (Fig. 3)
• Contrast-enhanced ultrasound (CEUS): 1,5ml contrasting agent (sulphur hexafluoride microbubbles): arterial isoenhancement and late phase hypoenhancement of nodules (Fig. 3), atypical for haemangiomas
• 18-Fluorodeoxyglucose positron emission tomography with computed tomography: no uptake in the spleen (Fig. 4)

After excluding malignancy, abscesses, sarcoidosis, and infectious causes, the splenic granulomatous lesions represented an extraintestinal manifestation of CD. The patient was started on prednisolone, 60mg/day, resulting in marked clinical improvement in 4 days; with reduced abdominal pain and decreased stool frequency. Patient declined recommended maintenance therapy with ustekinumab.
This CEUS pattern is novel to CD and resembles previously reported enhancement patterns of inflammatory lesions. This is a rare reported case of splenic granulomas as an extraintestinal manifestation of CD diagnosed non-invasively by CEUS.

References

Figure 1: Colonoscopy shows 2-4mm aphthous ulcers in the terminal Ileum
Figure 2: (A)T2-Haste and (B)T2-STIR MRE depicting multiple hyperintense splenic lesions
Figure 3: B-mode (left) and CEUS (right) of the splenic lesions. (A) Nodules appear mixed in echogenicity, nodules show isoenhancement during the arterial phase. (B) Nodules exhibit hypoenhancement in the late phase
Figure 4: 18F-Fluorodeoxyglucose (FDG) positron emission tomography with computed tomography shows no uptake of FDG in the spleen
1. Castellani L, Sartini A, Marocchi M, Balbi T, Belluzzi A. Splenic granulomas in a patient with severe Crohn's disease associated with multiple extraintestinal manifestations. Inflamm Bowel Dis. 2011 Jun;17(6):E35-7. doi: 10.1002/ibd.21665. Epub 2011 Feb 11. PMID: 21319276.
2. Schulz C, von Arnim U, Kuester D, Fischbach F, Malfertheiner P. Milzbefall - seltene extraintestinale Manifestation bei Morbus Crohn [Splenic granulomas - rare extraintestinal manifestation of Crohn's disease]. Z Gastroenterol. 2010 Dec;48(12):1367-70. German. doi: 10.1055/s-0029-1245562. Epub 2010 Dec 1. PMID: 21125512
3. Safai Zadeh E, Prosch H, Ba-Ssalamah A, Findeisen H, Alhyari A, Raab N, Görg C. Contrast-enhanced ultrasound of the liver: basics and interpretation of common focal lesions. Rofo. 2024 Aug;196(8):807-818. English, German. doi: 10.1055/a-2219-4726. Epub 2024 Jan 4. PMID: 38176437

Disclosure

Travel grant from Johnson & Johnson

Clinical Case Summary

Introduction: Eosinophilic enteritis (EoEo) is a rare condition characterized by eosinophilic infiltration of the intestinal wall without an identifiable secondary cause. Clinical presentation varies depending on the affected intestinal segment and layer. While mucosal involvement causes digestive symptoms, muscular involvement may lead to obstruction, and serosal involvement—least common—can present with eosinophilic ascites.
Case Report: A 15-year-old male presented with epigastric pain, vomiting, and oral intolerance. Laboratory tests revealed marked eosinophilia (>5,000/μL). Abdominal CT showed free fluid and ileocecal wall thickening. Diagnostic paracentesis revealed ascitic fluid with a high leukocyte count and eosinophil predominance. Endoscopic studies revealed ileitis, typhlitis, and duodenitis. Biopsies confirmed eosinophilic infiltration of the intestinal wall. Other causes of eosinophilia, including infections and malignancy, were ruled out. The patient was treated with intravenous corticosteroids, with good clinical response, and discharged on oral budesonide. A relapse occurred after tapering steroids, prompting initiation of azathioprine for maintenance. The patient remains clinically stable without further hospitalizations.
Discussion: EoEo with eosinophilic ascites is rare and should be considered in the differential diagnosis of unexplained ascites, particularly in patients with peripheral eosinophilia. Key diagnostic findings include eosinophil-predominant ascitic fluid and GI tract biopsies with eosinophilic infiltration. Early recognition and treatment are essential to prevent complications. It is crucial to rule out parasitic and infectious causes before initiating corticosteroid therapy to avoid worsening an undiagnosed infection.