Budesonide-Related Iatrogenic Cushing's Syndrome in Microscopic Colitis

Tripathi, Kartikeya; Dunzendorfer, Thomas

doi:10.14309/crj.2017.5

Cited by 8 publications

(6 citation statements)

References 11 publications

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“…No new safety signals were noted in the study with longest follow up (28). Despite inconsistent data in literature suggesting long-term treatment with budesonide in MC patients may lead to adverse effects (38,39), there is currently no solid evidence for an increased risk of adverse events in long-term treatment with low-dose budesonide. Interventions such as immunomodulatory agents (thiopurines, methotrexate, biologics) are used to maintain remission in ulcerative colitis and Crohn`s disease has yielded mixed results in microscopic colitis (40,41,42) although there are no placebo-controlled trails in this setting.…”

Section: Discussionmentioning

confidence: 88%

Budesonide treatment for microscopic colitis: systematic review and meta-analysis

Sebastian

Wilhelm²,

Lisle

et al. 2019

European Journal of Gastroenterology &Amp; Hepatology

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Microscopic colitis, encompassing lymphocytic and collagenous colitis, is a common cause for chronic non-bloody diarrhoea, which impacts significantly on the quality of life for patients. Despite increasing awareness of the condition and its treatment, there is considerable variation in therapeutic approaches.To conduct a systematic review and meta-analysis on the efficacy and safety of budesonide in the treatment of microscopic colitis.We searched MEDLINE, EMBASE and CENTRAL databases using predefined search methodology for randomised trials using budesonide in the treatment of microscopic colitis.We extracted data, on the efficacy and safety of budesonide, from studies identified that met the feasibility for analysis criteria. These data were pooled with a fixed effects model.Nine studies met the inclusion criteria for analysis. The pooled odds ratios (OR) for response to budesonide therapy at induction and maintenance were 7.34 (95% CI 4.08 to 13.19) and 8.35 (95% CI 4.14 to 16.85) respectively. Histological response rates were superior in budesonide-treated patients compared to placebo following induction (OR 11.52, 95% CI 5.67 to23.40) and maintenance treatment (OR 5.88, 95% CI 1.90 to 18.17). There was no difference in adverse events. Significant relapse rates (>50%) were observed following treatment cessation with no difference noted between the budesonide or the placebo-treated patients Budesonide is an effective treatment option for microscopic colitis for achieving induction and maintenance of both clinical and histological response. High relapse rates on treatment cessation were observed.

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Section: Discussionmentioning

confidence: 88%

Budesonide treatment for microscopic colitis: systematic review and meta-analysis

Sebastian

Wilhelm²,

Lisle

et al. 2019

European Journal of Gastroenterology &Amp; Hepatology

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“…Studies show that there is a small change in systemic cortisol levels, but classic steroid-related side effects are not seen with these drugs. There are case reports of steroid-related side effects with oral budesonide when used in high doses for long term 30…”

Section: Mild-to-moderate Diseasementioning

confidence: 99%

New developments in ulcerative colitis: latest evidence on management, treatment, and maintenance

Tripathi¹,

Feuerstein²

2019

DIC

Self Cite

110

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Ulcerative colitis (UC) is a chronic idiopathic inflammatory disorder that involves any part of the colon starting in the rectum in a continuous fashion presenting typically with symptoms such as bloody diarrhea, abdominal pain, and rectal urgency. UC is diagnosed based on clinical presentation and endoscopic evidence of inflammation in the colon starting in the rectum and extending proximally in the colon. The clinical presentation of the disease usually dictates the choice of pharmacologic therapy, where the goal is to first induce remission and then maintain a corticosteroid-free remission. There are multiple classes of drugs that are available and are used based on the clinical severity of the disease. For mild-to-moderate disease, oral or rectal formulations of 5-aminosalicylic acid are used. In moderate-to-severe UC, corticosteroids are usually used in induction of remission with or without another class of medications such as thiopurines or biologics including anti-tumor necrosis factor, anti-integrins, or Janus kinase inhibitors for maintenance of remission. Up to 15% of the patients may require surgery as they fail to respond to medications and have risk of developing dysplasia secondary to longstanding colitis.

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“… 3 However, relapse after discontinuation of budesonide is common, and patients can become steroid-dependent or treatment-refractory. 4 , 5 Thus, specific anti-diarrhoeal drugs are an unmet clinical need.…”

Section: Introductionmentioning

confidence: 99%

The Water Channel Aquaporin 8 is a Critical Regulator of Intestinal Fluid Homeostasis in Collagenous Colitis

Escudero-Hernández

Münch

Østvik

et al. 2020

Journal of Crohn's and Colitis

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Background and Aims Diarrhoea is a common, debilitating symptom of gastrointestinal disorders. Pathomechanisms probably involve defects in trans-epithelial water transport, but the role of aquaporin [AQP] family water channels in diarrhoea-predominant diseases is unknown. We investigated the involvement of AQPs in the pathobiology of collagenous colitis [CC], which features chronic, watery diarrhoea despite overtly normal intestinal epithelial cells [IECs]. Methods We assessed the expression of all AQP family members in mucosal samples of CC patients before and during treatment with the corticosteroid drug budesonide, steroid-refractory CC patients and healthy controls. Samples were analysed by genome-wide mRNA sequencing [RNA-seq] and quantitative real-time PCR [qPCR]. In some patients, we performed tissue microdissection followed by RNA-seq to explore the IEC-specific CC transcriptome. We determined changes in the protein levels of the lead candidates in IEC by confocal microscopy. Finally, we investigated the regulation of AQP expression by corticosteroids in model cell lines. Results Using qPCR and RNA-seq, we identified loss of AQP8 expression as a hallmark of active CC, which was reverted by budesonide treatment in steroid-responsive but not refractory patients. Consistently, decreased AQP8 mRNA and protein levels were observed in IECs of patients with active CC, and steroid drugs increased AQP8 expression in model IECs. Moreover, low APQ8 expression was strongly associated with higher stool frequency in CC patients. Conclusion Down-regulation of epithelial AQP8 may impair water resorption in active CC, resulting in watery diarrhoea. Our results suggest that AQP8 is a potential drug target for the treatment of diarrhoeal disorders.

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Budesonide-Related Iatrogenic Cushing's Syndrome in Microscopic Colitis

Cited by 8 publications

References 11 publications

Budesonide treatment for microscopic colitis: systematic review and meta-analysis

Budesonide treatment for microscopic colitis: systematic review and meta-analysis

New developments in ulcerative colitis: latest evidence on management, treatment, and maintenance

The Water Channel Aquaporin 8 is a Critical Regulator of Intestinal Fluid Homeostasis in Collagenous Colitis

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