A Pitfall in Suspected (refractory) Celiac Disease: Losartan-Induced Enteropathy

Gils, Tom van; Robijn, R. J.; Bouma, Gerd; Neefjes-Borst, E. Andra; Mulder, Chris J.

doi:10.1038/ajg.2017.281

Cited by 7 publications

(18 citation statements)

References 4 publications

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“…p < 0.05 were considered statistically significant. Ninety-four were case reports or case series of enteropathy due to ARBs (86 case reports or case series with less than five patients and eight case series with five or more patients 5,11,[99][100][101][102][103][104] ) corresponding to a total of 183 patients (101 F, mean age at diagnosis 69 ± 10 years) published between 2012 and 2023, with most cases being reported in Europe (93 cases) 11,13,17,18,20,21,23,24,26,27,[30][31][32][33][34]40,44,45,50,51,[55][56][57][61][62][63][64]67,68,70,73,75,77,80,[83][84][85][89][90][91]…”

Section: Discussionmentioning

confidence: 99%

Systematic review: Clinical phenotypes, histopathological features and prognosis of enteropathy due to angiotensin II receptor blockers

Schiepatti,

Minerba,

Puricelli

et al. 2024

Aliment Pharmacol Ther

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SummaryBackgroundAlthough enteropathy due to angiotensin II receptor blockers (ARBs) has been known for over 10 years, clinicians' awareness of this condition is still low.AimsTo systematically review the literature about clinical phenotypes, distribution of mucosal changes throughout the gastrointestinal tract and prognosis of enteropathy due to ARBs.MethodsAccording to PRISMA guidelines, we searched PubMed and Embase for relevant articles up to November 6, 2023. We included full‐text papers, letters, case reports and case series describing enteropathy due to ARBs. Patients were classified into subgroups based on endoscopic and histological findings of different regions of the gastrointestinal tract. The protocol was registered with Open Science Framework (https://doi.org/10.17605/OSF.IO/TK67C).ResultsWe included 94 articles reporting 183 cases (101 female, mean age at diagnosis 69 ± 10 years). The clinical picture at diagnosis was characterised by severe diarrhoea (97%) and weight loss (84%, median −13 kg), leading to hospital admission in 167 (95%) patients. Olmesartan (90%) was most frequently implicated. Villous atrophy (VA) was reported in 164/183 (89%) patients. One hundred and nine had only VA, 12 had pan‐gastrointestinal involvement, 23 had VA and gastric involvement and 19 had VA and colon involvement (predominantly microscopic colitis). Outcomes were reported for 178/183 (97%) patients, who all recovered clinically on ARBs withdrawal. Histological recovery occurred in all 96 patients with VA at baseline who underwent follow‐up duodenal biopsy.ConclusionsEnteropathy due to ARBs is characterised by severe malabsorption often requiring hospital admission and can involve the entire gastrointestinal tract. Clinician awareness can lead to prompt diagnosis and excellent prognosis.

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Section: Discussionmentioning

confidence: 99%

Systematic review: Clinical phenotypes, histopathological features and prognosis of enteropathy due to angiotensin II receptor blockers

Schiepatti,

Minerba,

Puricelli

et al. 2024

Aliment Pharmacol Ther

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“… 10 , 11 There is an increased number of CD8+‐positive T cells and granzyme‐positive B cells resulting in destruction of the lamina propria and epithelial layer. 2 , 10 , 12 Previous studies have demonstrated an increased number of CD8+‐positive T cells which express interleukin 15 and 15R resulting in the disruption of tight junction complexes such as in refractory celiac sprue. 10 , 12 Given some of the known histopathology overlap observed in celiac disease and ARB‐induced sprue‐like enteropathy, a cutaneous manifestation is not unexpected, although the cutaneous manifestations may differ.…”

Section: Discussionmentioning

confidence: 99%

“… 2 , 10 , 12 Previous studies have demonstrated an increased number of CD8+‐positive T cells which express interleukin 15 and 15R resulting in the disruption of tight junction complexes such as in refractory celiac sprue. 10 , 12 Given some of the known histopathology overlap observed in celiac disease and ARB‐induced sprue‐like enteropathy, a cutaneous manifestation is not unexpected, although the cutaneous manifestations may differ. 13 , 14 Celiac disease is associated with dermatitis herpetiformis whereas ARB‐induced sprue enteropathy may cause ulcerative lesions.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have demonstrated that many of the common pathogenic pathways seen in celiac disease are also present within that of ARB‐induced sprue‐like enteropathy 10,11 . There is an increased number of CD8+‐positive T cells and granzyme‐positive B cells resulting in destruction of the lamina propria and epithelial layer 2,10,12 . Previous studies have demonstrated an increased number of CD8+‐positive T cells which express interleukin 15 and 15R resulting in the disruption of tight junction complexes such as in refractory celiac sprue 10,12 .…”

Section: Discussionmentioning

confidence: 99%

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Cutaneous ulcers in association with sprue‐like enteropathy secondary to Losartan

Essien

Juakiem

Tate

et al. 2021

Clinical Case Reports

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“…Since then, a host of publications have appeared both confirming this ARB-e as a new clinical entity [2][3][4][5][6][7][8][9] but also implicating other ARBs, though perhaps not as severe as olmesartan, but nonetheless demonstrating a class effect. [10][11][12][13][14][15][16] Many patients with an initial diagnosis of 'serology negative' CD were reclassified as having an ARB-e. 11,12,[17][18][19][20][21] While the risk of developing ARB-e in individuals taking ARB medication is extremely low, 22,23 the prevalence of ARB-e is likely to be underreported. 17 The pathophysiology of ARB-e and indeed the exact cause of mucosal injury remains largely unexplained.…”

Section: Introductionmentioning

confidence: 99%

Coeliac disease enteropathy and symptoms may be aggravated by angiotensin receptor blockers in patients on a gluten‐free diet

et al. 2021

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Background: Angiotensin receptor blocker-associated enteropathy (ARB-e) is an increasingly recognised clinical entity with symptoms and histological findings identical to coeliac disease (CD). There is evidence to suggest immune-mediated mucosal injury in ARB-e with a high prevalence of DQ2/DQ8; however, as IgA anti-tissue transglutaminase (anti-TTG) is usually negative, an insult other than TTG-mediated injury is suspected. The impact of ARBs on disease activity in patients with CD is not known.Objective: To assess the effect of ARB exposure on patients with established CD. Methods: A patient record search of 1142 individual patients attending a dedicated coeliac clinic from 2010 to the present identified 59 patients treated with ARB.Those with CD confirmed by serology (TTG + ve/EMA + ve) and histopathology (Marsh criteria) were included (n = 40, 0.52%). Data collected included disease duration, compliance with gluten-free diet (GFD), reported symptoms (diarrhoea, weight loss and abdominal pain), surrogate markers of absorption (Vitamin D, Iron, Calcium and Haemoglobin), in addition to anti-TTG titre and histological grade at last follow up. Patients were age and sex-matched in a 1:2 ratio with CD patients not taking ARBs (controls), with comparable rates of disease duration and compliance with GFD. Results:The ARB and control groups were matched in terms of age (mean 66.2 years) and gender (female 63%). Strict compliance with GFD was reported in 55% and 56%, respectively. Persistent symptoms were reported in 10/40 (25%) of the ARB group compared with 7/82 (9%) of controls (p = 0.0181). There were lower rates of mucosal healing (Marsh grade 0) in the ARB group (36% n = 11) compared to controls (55%, n = 33). There was no significant difference in anti-TTG titres.Surrogate markers of absorption were comparable across the groups, except for Vitamin D which was lower in those taking olmesartan (p = 0.0015).This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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A Pitfall in Suspected (refractory) Celiac Disease: Losartan-Induced Enteropathy

Cited by 7 publications

References 4 publications

Systematic review: Clinical phenotypes, histopathological features and prognosis of enteropathy due to angiotensin II receptor blockers

Systematic review: Clinical phenotypes, histopathological features and prognosis of enteropathy due to angiotensin II receptor blockers

Cutaneous ulcers in association with sprue‐like enteropathy secondary to Losartan

Coeliac disease enteropathy and symptoms may be aggravated by angiotensin receptor blockers in patients on a gluten‐free diet

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