Immune checkpoint inhibitors-related pancreatitis with fulminant type 1 diabetes mellitus: case report and literature review
Ontology highlight
ABSTRACT:
SUBMITTER: Fang W
PROVIDER: S-EPMC10569069 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:ObjectiveTo better define the rare adverse event (AE) of diabetes mellitus associated with immune checkpoint inhibitors (ICIs).Design and methodsWe report the case of a lung cancer patient with diabetic ketoacidosis (DKA) and autoimmune thyroiditis during pembrolizumab treatment. We provide a systematic review of all published cases (PubMed/Web of Science/Cochrane, through November 2018) of autoimmune diabetes mellitus related to blockade of the cytotoxic T-lymphocyte antigen 4 (CTLA-4)-, programmed cell death 1 (PD-1) receptor or its ligand (PD-L1) or combination (ICI) therapy.ResultsOur literature search identified 90 patient cases (our case excluded). Most patients were treated with anti-PD-1 or anti-PD-L1 as monotherapy (79%) or in combination with CTLA-4 blockade (15%). On average, diabetes mellitus was diagnosed after 4.5 cycles; earlier for combination ICI at 2.7 cycles. Early-onset diabetes mellitus (after one or two cycles) was observed during all treatment regimens. Diabetic ketoacidosis was present in 71%, while elevated lipase levels were detected in 52% (13/25). Islet autoantibodies were positive in 53% of patients with a predominance of glutamic acid decarboxylase antibodies. Susceptible HLA genotypes were present in 65% (mostly DR4). Thyroid dysfunction was the most frequent other endocrine AE at 24% incidence in this patient population.ConclusionICI-related diabetes mellitus is a rare but often life-threatening metabolic urgency of which health-care professionals and patients should be aware. Close monitoring of blood glucose and prompt endocrine investigation in case of hyperglycemia is advisable. Predisposing factors such as HLA genotype might explain why some individuals are at risk.
| S-EPMC6709545 | biostudies-literature
Project description:BackgroundPregnancy-associated fulminant type 1 diabetes (PF) occurs during pregnancy or within 2 weeks of delivery. Although it occurs infrequently, it is associated with high fetal mortality rate. Few studies have examined whether PF is associated with gestational diabetes mellitus (GDM).Case descriptionA 29-year-old woman diagnosed with GDM at 24 weeks of gestation developed a fever, sore throat, nausea and vomiting at 29 weeks of gestation. Ketoacidosis was considered based on her blood ketone and glucose levels and the results of a blood gas analysis. Since the patient's islet function declined rapidly, fluid replacement, insulin therapy, and other treatments were administered. The patient was ultimately diagnosed with PF, and has required ongoing insulin therapy. She delivered a healthy baby girl by elective cesarean section at 37-week gestation. Her blood glucose has been satisfactorily controlled over the 12 months since her acute presentation.ConclusionsPF is characterized by poor maternal and infant outcomes and a high stillbirth rate. Blood glucose should be regularly monitored in pregnant women with GDM. A sudden increase in blood glucose may indicate the possibility of PF, which needs to be managed in a timely manner to avoid adverse pregnancy outcomes.
| S-EPMC11292075 | biostudies-literature
Project description:Treatment with immune checkpoint inhibitors (ICIs) is steadily becoming the standard of care for hepatocellular carcinoma (HCC), with an increasing number of immune-related adverse events (irAEs). However, only a small number of reports on the occurrence of diabetes mellitus (DM) in patients with HCC treated with ICIs have been published. In the present study, the clinical manifestations, laboratory findings, treatment and prognosis of three patients with advanced HCC were reported, who suffered immune-related DM when receiving treatment with ICIs. Furthermore, the relevant literature was reviewed in order to summarize clinical manifestations, possible mechanisms, diagnosis, prognosis of rechallenge and recommended management options, as well as clinical treatment suggestions. ICI-induced diabetes is rare but irAEs are potentially fatal, as diabetic ketoacidosis (DKA) is often the first manifestation. The incidence of immune-related DM is 0.86% and among those cases, the incidence of DKA is 59%. The combination of two ICIs markedly increases the risk. The human leukocyte antigen genotype, islet autoantibodies and autoreactive T cell-mediated β-cell destruction may be linked to the occurrence of immune-related DM. Patient education and clinicians' awareness of ICI-related DM are good management options. Adequate clinical judgment, close monitoring and early detection are also needed to decide whether to continue immunotherapy or to rechallenge it, so as to achieve the maximum benefit of clinical treatment.
| S-EPMC10966655 | biostudies-literature
Project description:Immune checkpoint inhibitors (ICIs) have now emerged as a mainstay of treatment for various cancer. Along with the development of ICIs, immune-related adverse effects (irAEs) have been the subject of wide attention. The cardiac irAE, a rare but potentially fatal and fulminant effect, have been reported recently. This article retrospectively reviewed 10 cases from our hospital with cardiac irAEs, with severity ranging from asymptomatic troponin-I elevations to cardiac conduction abnormalities and even fulminant myocarditis. In our series, all the cases were solid tumors and lung cancer was the most frequent cancer type (4,40%). In total, three (30.0%) patients experienced more than one type of life-threatening complication. A systemic corticosteroid was given to nine patients (90.0%). The majority of cases (7, 70%) were performed at an initial dose of 1-2 mg/kg/day. Two (20.0%) patients were admitted to ICU, three (30.0%) patients were put on mechanical ventilation, two (20.0%) patients received the plasma exchange therapy, and one patient was implanted with a pacemaker. Two (20.0%) of the patients succumbed and died, with a median duration of 7.5 days (IQR5.0-10.0) from diagnosis of cardiac irAE to death. Based on these results, we recommend that clinicians be alert to cardiac irAEs, including performing cardiovascular examinations before ICI treatment to accurately diagnose suspected myocarditis, enabling immediate initiation of immunosuppressive therapy to improve prognosis.
| S-EPMC8685438 | biostudies-literature
Project description:Gastric hepatoid adenocarcinoma (GHAC) is a highly aggressive histological subtype of gastric cancer (GC) with similar tissue morphology to hepatocellular carcinoma. GHAC frequently produces alpha-fetoprotein (AFP) and has a poor prognosis; however, standardized treatment remains elusive. We report a male patient in his early 60s with GHAC who received immunotherapy, and the curative effect was evaluated. He was admitted because of progressive fatigue and dizziness for 2 months. He had experienced spontaneous epigastric pain with muscular defense of the epigastrium and accompanying tenderness 1 year earlier and underwent radical gastrectomy. Immunohistochemistry showed that hepatocyte-specific marker (Hep) was highly-expressed, indicating probable GHAC. Additionally, imaging suggested GC recurrence or gastric stump cancer. Radioimmunoassay indicated an AFP level of >1210.00 µg/L, and liver biopsy was performed following abdominal contrast-enhanced computed tomography. Pathology showed a few hepatocytes and proliferative fibrous connective tissue. The patient received three cycles of chemotherapy, with no obvious improvement. The possibility of surgical treatment was excluded, and immunotherapy or palliative treatment was selected. He received 11 cycles of a programed death-1 (PD-1) monoclonal antibody, and the effect of treatment was satisfactory. The mechanism of action of immunotherapy in GHAC warrants further investigation.
| S-EPMC9087251 | biostudies-literature
Project description:BackgroundImmune checkpoint inhibitors (ICIs) are a class of cancer immunotherapy with growing indications for treatment of various malignancies. Immune checkpoint inhibitors are monoclonal antibodies that block inhibitory pathways in immune cells, including cytotoxic T lymphocyte antigen-4 (CTLA4), programmed death 1 receptor (PD1), and programmed cell death ligand-1 (PDL1), to activate the immune system. However, these agents can disrupt self-tolerance and lead to immune-related adverse events. Fulminant myocarditis, a feared complication of ICIs, can be highly fatal, and there is a need for effective treatment options.Case summaryA 70-year-old patient with recurrent metastatic disease of urothelial carcinoma subsequently developed fulminant myocarditis after receiving eight cycles of pembrolizumab. He developed cardiogenic shock and required inotropes and a percutaneous microaxial flow pump placement for temporary mechanical circulatory support. He received methylprednisolone initially and then was started on second-line immunosuppression agents, ruxolitinib and abatacept, for steroid-refractory myocarditis. Abatacept is thought to inhibit activation of T-cell CTLA4 and PD1/PDL1 pathways and reverse ICI-activated pathways. Ruxolitinib is a Janus kinase inhibitor that impairs immune activation through suppressing cytokine sensing and production and T-cell activation. After these treatments, the patient subsequently clinically improved and his myocarditis resolved.DiscussionThis case highlights ICI myocarditis refractory to corticosteroids leading to treatment with second-line immunosuppression. As immunotherapies are increasingly applied to a broader range of cancers, further research is needed to evaluate the optimal treatment strategy for ICI-related myocarditis and other immune-related adverse events.
| S-EPMC11831032 | biostudies-literature
Project description:A case of fulminant type 1 diabetes mellitus secondary to administration of pembrolizumab in a patient with urothelial carcinoma is presented. Eight days after the third infusion of pembrolizumab, the patient presented with complaints of malaise and anorexia. The patient's laboratory data showed a blood glucose level of 1092mg/dl with ketonuria and negative for glutamic acid decarboxylase antibody. As leaving ketoacidosis by insulin therapy, pembrolizumab therapy was continued without delay. After administration of another eight infusions of pembrolizumab, the patient's disease was stable without new severe side effects.
| S-EPMC6562295 | biostudies-literature
Project description:Background: Fulminant type 1 diabetes mellitus (FT1DM) is a new subtype of type 1 diabetes, first proposed by Japanese scholars in 2000. Herein, the functions of the islets are rapidly destroyed. Its pathogenesis is related to viral infection. Most people have been infected with Epstein-Barr virus (EBV), and many people have also suffered from drug hypersensitivity, however, few cases of FT1DM which were caused by both of the two conditions have been reported. Thus, below, we describe one such valuable case. Case Summary: The plasma glucose levels of a 73-year-old man diagnosed with drug-induced dermatitis showed a sudden increase (42 mmol/L) during methylprednisolone therapy. The urine ketone test was positive. The glycated hemoglobin level was 7%, endogenous insulin secretion decreased significantly, and the islet-related autoantibodies were negative. The patient was diagnosed with FT1DM. The lymphocyte EBV-DNA showed high copies numbers. The general condition of the patient improved after symptomatic treatment with insulin. However, the systemic allergic reaction aggravated after the use of iodinated contrast agents, prednisone, and thymic pentapeptide. The re-test for EBV-DNA showed significantly high relative levels, thus indicating the presence of EBV infection. We think that drug hypersensitivity and EBV infection together led to FT1DM in this case. After an indication for multiple daily insulin therapy, the patient's blood glucose was quickly controlled and he was discharged on the 38th-day post-admission. Conclusion: FT1DM is a rare case, however, drug hypersensitivity and EBV infection are not rare in the population. This is a rare case of FT1DM caused by drug hypersensitivity reaction and EBV infection. Through this case report, we emphasize the importance of the relationship between drug hypersensitivity, EBV infection and FT1DM and vigilance for the occurrence of FT1DM among hypersensitive individuals in clinical practice.
| S-EPMC9305474 | biostudies-literature
Project description:Immune checkpoint inhibitors (ICIs), including anti-programmed cell death protein 1 (PD-1), anti-programmed cell death protein ligand 1 (PD-L1) and anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibodies, are novel therapeutic agents widely used in numerous malignancies. They are known to cause multiple immune-related endocrine adverse events (irAEs); however, anterior pituitary hypophysitis with secondary hypopituitarism is the most frequently reported irAE, especially in patients receiving anti-CTLA-4 treatment. By contrast, posterior pituitary involvement, such as central diabetes insipidus (CDI), is relatively rare and only few case reports have been published. The present report describes the case of a 53-year-old woman with metastatic melanoma treated with nivolumab an anti-PD-L1 monoclonal antibody. At 6 months after the initiation of nivolumab treatment, the patient was diagnosed with deficiency of the corticotrope and thyreotrope axes and in the following 2 months the patient was diagnosed with progressive development of polyuria-polydipsia syndrome. The diagnosis of partial CDI was retained based on plasma and urinary osmolalities, the water deprivation test and baseline copeptin levels as well as on the absence of the bright spot in the posterior pituitary in magnetic resonance imaging. Systematic research of the literature revealed a total of 13 cases reports (including 14 patients) presenting with CDI treated with monotherapy with CTLA-4 (n=5) or PD-1/PD-L1 Abs (n=6) or combined treatments (n=3). The improved understanding of the mechanisms of ICI action along with their extensive use should contribute to the early recognition of irAE symptoms. We hypothesized that clinicians should be aware of this clinical entity and its symptoms and treat it appropriately.
| S-EPMC9748697 | biostudies-literature
Project description:Lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency is a subtype of common variable immune deficiency (CVID). Numerous case reports and cohort studies have described a broad spectrum of clinical manifestations and variable disease phenotypes, including immune dysregulation, enteropathy, and recurrent infections. Although LRBA deficiency is an autosomal recessive primary immunodeficiency resulting in a phenotype similar to CVID, it is a monogenic disease and separate from CVID. Recently, in a report of monogenic primary immunodeficiency disorder associated with CVID and autoimmunity, the most common mutated gene was LRBA. We report the case of a girl who presented with fulminant type 1 diabetes at age 7 months. She later experienced recurrent bacterial infections with neutropenia and idiopathic thrombocytopenic purpura. Clinical genome sequencing revealed compound heterozygosity of the LRBA gene, which bore two novel mutations. A genetic basis should be considered in the differential diagnosis for very young patients with fulminant autoimmunity, and the diagnostic work-up should include evaluation of markers of immunodeficiency.
| S-EPMC8072023 | biostudies-literature