Collagenous colitis and atezolizumab therapy: an atypical case

Gallo, Antonella; Talerico, Rosa; Novello, L; Giustiniani, Maria Cristina; D’Argento, Ettore; Bria, Emilio; Montalto, Massimo

doi:10.1007/s12328-020-01276-4

Cited by 11 publications

(13 citation statements)

References 12 publications

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“…They found that most of the patients need steroid, while a minority of them required IFX or vedolizumab, regardless of whether in the initial or recurrent episode. Our analysis showed that 25% (8/32) of patients (36,41,43,46,48,54,57) had recurrent ICI-mediated colitis without ICI retreatment, which received subsequent therapy involving probiotics, antidiarrheal drugs, antiviral drugs, steroid, and immunosuppressants. Four cases with CIC finally did not improve or deteriorate after the second treatment (36,41,48,54).…”

Section: Rechallenge and Recurrencementioning

confidence: 87%

“…However, the atypical feature of microscopic colitis has also been reported, like crypt abscesses and neutrophilic cryptitis of active IBD (178). Gallo et al (41) reported a patient with lung cancer who received atezolizumab presented collagenous colitis along with acute neutrophilic inflammation. Besides, Choi et al (179) showed that patients with microscopic colitis induced by ICIs would have higher hospitalization rates and more aggressive course of disease and need more treatments like steroids and/or immunosuppressants than those without exposure to ICIs.…”

Section: Pathological Featuresmentioning

confidence: 99%

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Immune Checkpoint Inhibitor-Associated Colitis: From Mechanism to Management

et al. 2021

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Immune checkpoint inhibitors (ICIs), as one of the innovative types of immunotherapies, including programmed cell death-1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors, have obtained unprecedented benefit in multiple malignancies. However, the immune response activation in the body organs could arise immune-related adverse events (irAEs). Checkpoint inhibitor colitis (CIC) is the most widely reported irAEs. However, some obscure problems, such as the mechanism concerning gut microbiota, the confusing differential diagnosis with inflammatory bowel disease (IBD), the optimal steroid schedule, the reintroduction of ICIs, and the controversial prognosis features, influence the deep understanding and precise diagnosis and management of CIC. Herein, we based on these problems and comprehensively summarized the relevant studies of CIC in patients with NSCLC, further discussing the future research direction of this specific pattern of irAEs.

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Section: Rechallenge and Recurrencementioning

confidence: 87%

Section: Pathological Featuresmentioning

confidence: 99%

Immune Checkpoint Inhibitor-Associated Colitis: From Mechanism to Management

et al. 2021

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“…One case of an infliximab refractory colitis was also described in a patient treated with nivolumab; in follow up, the patient developed bowel perforation that required total colectomy with terminal ileostomy; the patient eventually died from sepsis 35 days after the colectomy was performed [36]. When speaking about ICI induced colitis, although the usual histologic and endoscopic findings resemble that of the IBD, there are also reports of some unusual cases such as collagenous colitis after pembrolizumab and atezolizumab therapy [37,38]. ePub ahead of printing A case of pseudomembranous colitis in a 57-year-old patient with hepatocellular carcinoma was reported, contributing to the constellation of different manifestations and endoscopic findings that can occur with anti PD-1 therapy [39].…”

Section: Discussionmentioning

confidence: 99%

“…While cases of severe colitis associated with anti CTLA-3 therapy are rather frequent, severe cases after anti PD-1 therapy are scarcely reported, with an incidence of only 0.4 % [36]. Some unusual cases of colitis were also described, such as collagenous [37,38], pseudomembranous [39], granulomatous [40], microscopic colitis [41] or even inflammatory bowel diseases (IBD) [42][43][44] due to different types of ICI.…”

Section: Gastrointestinal Tract Toxicitymentioning

confidence: 99%

Digestive Toxicities Secondary to Immune Checkpoint Inhibition Therapy – Reports of Rare Events. A Systematic Review

Radulescu

Crişan

Grapa

et al. 2021

JGLD

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Background and Aims: While immune checkpoint inhibitors therapy (ICI) is exceedingly effective, these drugs are associated with various immune-related adverse effects. As gastrointestinal, hepatic or pancreatic toxicity becomes more common, various reports of rare adverse effects have emerged, leading to a significant clinical and prognostic impact. We aimed to provide a systematic review of mainly case-reports on rare events, to help physicians to make an accurate and fast diagnosis. Methods: We performed a systematic review of the literature, using established MeSH terms: “immune checkpoint inhibitors”, “gastrointestinal tract”, “gastrointestinal diseases”, “liver”, “pancreas”, “nivolumab”, “ipilimumab”, the subheadings “adverse effects”, “toxicity” and the supplementary concepts “pembrolizumab”, “tremelimumab”, “atezolizumab”, “avelumab”, “durvalumab”, with defined inclusion criteria. Results: From 419 manuscripts initially selected, 74 reports of rare adverse events were included in our review. Special cases of neutrophilic gastritis, hemorrhagic gastritis, or even perforations were described at upper digestive tract. Different types of colitis were found secondary to ICI such as pseudomembranous, granulomatous, collagenous and microscopic colitis or even inflammatory bowel disease. In terms of liver toxicity, we found rare reports of cholangitis, granulomatous hepatitis, lipodystrophy and hepatic sinusoidal obstruction syndrome. Pancreas toxicity was rarely reported as severe pancreatitis, exocrine failure and diabetes mellitus. Conclusion: Although a complete check-up of every organ at every routine visit may not be practical, focus on symptoms, targeted laboratory and imaging testing may reveal rare organ damage. Raising awareness of the uncommon toxicities related to the immunotherapy is essential, as some rare events can lead to fatal outcomes.

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“…Immune-related adverse events, including colitis, are well-documented side effects of treatment with immune checkpoint inhibitors and some case reports have documented cases of MC following immune checkpoint inhibitor treatment. This suggests that immunomodulatory molecules play a key role in maintaining gut homeostasis (12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Patients With Microscopic Colitis Have Altered Levels of Inhibitory and Stimulatory Biomarkers in Colon Biopsies and Sera Compared to Non-inflamed Controls

et al. 2021

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Introduction: Microscopic colitis (MC) is an inflammatory bowel condition with two subtypes, lymphocytic colitis (LC) and collagenous colitis (CC). Unlike patients with ulcerative colitis (UC) and non-inflamed individuals, MC patients have reduced risk of developing colorectal cancer, possibly due to increased immune surveillance in MC patients.Aim: To examine differences in levels of immunomodulatory molecules, including those involved in immune checkpoint mechanisms, in sera from patients with MC and in colonic biopsies from patients with MC and UC compared with controls.Methods: Using Luminex, 23 analytes (4-1BB, 4-1BBL, APRIL, BAFF, BTLA, CD27, CD28, CD80, CTLA-4, E-cadherin, Galectin-3, GITR, HVEM, IDO, IL-2Rα, LAG-3, MICA, MICB, PD-1, PD-L1, PD-L2, sCD40L and TIM-3) were studied in serum from patients with active MC (n = 35) and controls (n = 23), and in colonic biopsies from patients with active LC (n = 9), active CC (n = 16) and MC in histological remission (LC n = 6, CC n = 6), active UC (n = 15) and UC in remission (n = 12) and controls (n = 58).Results: In serum, IDO, PD-1, TIM-3, 4-1BB, CD27, and CD80 were decreased whereas 4-1BBL and IL-2Rα were increased in MC patients compared with controls. In contrast, in biopsies, levels of PD-L2 and 4-1BB were increased in MC and UC patients with active disease. Furthermore, in biopsies from CC and UC but not LC patients with active disease, CTLA-4, PD-1, APRIL, BAFF, and IL-2Rα were increased compared with controls. PD-L1 was increased in CC but not UC or LC patients. CD27 and TIM-3 were decreased in biopsies from MC patients in comparison to controls whereas levels of MICB were decreased in patients with active UC compared with controls.Conclusions: Compared with non-inflamed controls, levels of soluble and membrane-bound immunomodulatory molecules were systemically and locally altered in MC and UC patients, with most analytes being decreased in serum but enhanced in colonic biopsies. These findings contribute to knowledge about checkpoint molecules and their role as biomarkers in MC and may also contribute to knowledge about possible mechanisms behind the seemingly protective effects of MC against colorectal cancer.

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Collagenous colitis and atezolizumab therapy: an atypical case

Cited by 11 publications

References 12 publications

Immune Checkpoint Inhibitor-Associated Colitis: From Mechanism to Management

Immune Checkpoint Inhibitor-Associated Colitis: From Mechanism to Management

Digestive Toxicities Secondary to Immune Checkpoint Inhibition Therapy – Reports of Rare Events. A Systematic Review

Patients With Microscopic Colitis Have Altered Levels of Inhibitory and Stimulatory Biomarkers in Colon Biopsies and Sera Compared to Non-inflamed Controls

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