Case Report: Fulminant Celiac Disease With Combination Immune Checkpoint Therapy

Falade, Ayo; Reynolds, Kerry L.; Zubiri, Leyre; Fintelmann, Florian J.; Dougan, Michael; Mooradian, Meghan J.

doi:10.3389/fimmu.2022.871452

Cited by 9 publications

(8 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Budesonide is not effective as prophylactic therapy for gastrointestinal irAEs as has been demonstrated in a randomized controlled trial 50 . The second group of patients who do not require systemic glucocorticoids are those with ICI‐associated Celiac disease 33,34,51 . These patients represent a small fraction of gastrointestinal irAEs (around 2%) but are important to identify because they will respond to a gluten‐free diet 33 .…”

Section: Current Treatments For Gastrointestinal Iraesmentioning

confidence: 99%

Gastrointestinal mucosal toxicities from immune checkpoint inhibitors: Current understanding and future directions

Dougan

2023

Immunological Reviews

Self Cite

View full text Add to dashboard Cite

SummaryImmune checkpoint inhibitor (ICI) therapy has revolutionized the field of oncology over the past decade, leading to durable remissions in some patients but also producing a wide spectrum of treatment‐limiting inflammatory toxicities that are referred to as immune‐related adverse events (irAEs). Although irAEs can involve any organ system in the body, they most commonly affect the barrier tissues, including the gastrointestinal tract with colitis and enterocolitis affecting a significant fraction of patients on ICIs. We are beginning to understand the mechanisms that drive ICI colitis, with early experiments indicating a role for CD8+ resident memory T cells (TRMs) in the gut, which become activated and differentiate into cytotoxic cells in response to ICI therapy. The risk factors that define who will develop ICI colitis are not understood and substantial efforts are underway to identify potential biomarkers for risk of this and other toxicities. Optimal management of ICI colitis is also an area of active investigation. Current standard treatments are based largely on small, retrospective analyses, and while drugs like systemic glucocorticoids or the TNFα inhibitor infliximab do appear to be highly active in ICI colitis, the impact of these therapies on antitumor responses is poorly understood. As discussed in this review, future work will have to define the immune mechanisms driving ICI colitis in more detail and in comparison to antitumor responses in order to identify candidate pathways that can be targeted to improve ICI colitis without interfering in antitumor immunity. Studying these interventions will require randomized, controlled trials with both tumor and colitis endpoints, a goal that will necessitate collaboration across institutions and funding agencies. We are at a point where such collaborative trials are feasible, and have the potential to greatly improve the care of patients with ICI colitis as well as other irAEs.

show abstract

Section: Current Treatments For Gastrointestinal Iraesmentioning

confidence: 99%

Gastrointestinal mucosal toxicities from immune checkpoint inhibitors: Current understanding and future directions

Dougan

2023

Immunological Reviews

Self Cite

View full text Add to dashboard Cite

show abstract

“…Further, ICI-related gastrointestinal disease includes standard ICI-related enterocolitis, ICI-related microscopic colitis (lymphocytic inflammation in the colon in the absence of macroscopic signs of inflammation) [ 32 ••], and ICI-related celiac disease [ 33 •]. Indeed, celiac disease is an important confounding diagnosis [ 33 •, 34 ]. Patients may have either an underlying diagnosis of celiac disease that was previously missed or treatment related breach in tolerance leading to new celiac disease.…”

Section: Diagnosticsmentioning

confidence: 99%

“…ICI-related celiac disease is another important subpopulation of patients with ICI gastrointestinal toxicity, whose disease may present with symptoms that overlap with irEC including life threatening presentations [34] . ICI-related celiac disease should be treated with a gluten free diet.…”

Section: Therapiesmentioning

confidence: 99%

See 1 more Smart Citation

Update on Immune Checkpoint Inhibitor Enterocolitis

Kelly-Goss

Badran

Dougan

2022

Curr Gastroenterol Rep

View full text Add to dashboard Cite

Purpose of Review Immune checkpoint inhibitor (ICI) therapy revolutionized the treatment of multiple solid and hematologic malignancies. Yet, with it came profound inflammatory toxicities that mimic autoimmune diseases, termed immune-related adverse events (irAEs). Prominent among these is gastrointestinal inflammation, including a spectrum of gastritis, enteritis, and colitis. Here we synthesize an approach to immune checkpoint related enterocolitis (irEC) – including diagnostics and therapeutics – underpinned by new insights into the mechanism behind these phenomena. Recent Findings This review presents updated insights on how to approach irEC, including novel approaches to selective immunosuppressive therapy, the role of fecal microbiota transplant, and the underlying cellular mechanisms of irEC. Summary This review provides an update on irEC diagnosis and therapy, with considerations of new therapies and special patient populations. The field of gastrointestinal irAEs requires additional investigation, which will ultimately provide the tools required for patients to continue to receive life-saving ICI therapy.

show abstract

“…The blistering mostly affects elbows, knees and buttocks ( 2 ). CD is a chronic, small-intestinal T-cell-mediated enteropathy, caused by reaction to dietary gluten and presenting with diarrhoea, unexpected weight lost and vague abdominal discomfort ( 3 , 4 ). The disease typically occurs in genetically predisposed persons ( HLA-DQ2 or- DQ8 ) with frequent onset in childhood, while is has also been described as an immune therapy-related adverse event ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

Primate liver tissue substrate in indirect immunofluorescence diagnostics for patients with dermatitis herpetiformis and celiac disease

et al. 2023

View full text Add to dashboard Cite

IntroductionDermatitis herpetiformis (DH) is a rare autoimmune, polymorphous blistering disorder, characterized by severe itch or burning sensation, which represents the cutaneous manifestation of celiac disease (CD). The current estimation of DH versus CD is around 1:8 and the affected individuals have a genetic predisposition. Pathogenetically, IgA autoantibodies against the epidermal transglutaminase, an essential constituent of the epidermis, cause DH and are reported to develop through cross-reaction with the tissue transglutaminase, with IgA auto-antibodies causing CD. Immunofluorescence techniques allow for a rapid diagnostics of the disease using patient sera. Evaluation of IgA endomysial deposition with indirect immunofluorescence on monkey oesophagus is highly specific, but moderately sensitive, with some operator-dependent variability. Recently, indirect immunofluorescence with monkey liver as a substrate has been proposed as an alternative, well-functioning diagnostic approach with higher sensitivity in CD.MethodsThe objective of our study was to evaluate whether monkey oesophagus or liver tissue shows advantage for diagnostics in patients with DH, compared to CD. To that end, sera of 103 patients with DH (n=16), CD (n=67) and 20 controls ere compared by 4 blinded experienced raters.ResultsFor DH, we found a sensitivity of 94.2% for monkey liver (ML) compared to 96.2% in monkey oesophagus (ME), while specificity in ML was superior (91.6% versus 75%) to ME. In CD, ML had a sensitivity of 76.9% (ME 89.1%) and specificity of 98.3% (ME 94.1%).DiscussionOur data show that ML substrate is well suitable for DH diagnostics.

show abstract

Case Report: Fulminant Celiac Disease With Combination Immune Checkpoint Therapy

Cited by 9 publications

References 8 publications

Gastrointestinal mucosal toxicities from immune checkpoint inhibitors: Current understanding and future directions

Gastrointestinal mucosal toxicities from immune checkpoint inhibitors: Current understanding and future directions

Update on Immune Checkpoint Inhibitor Enterocolitis

Primate liver tissue substrate in indirect immunofluorescence diagnostics for patients with dermatitis herpetiformis and celiac disease

Contact Info

Product

Resources

About