scholarly journals Nivolumab-associated DRESS in a genetic susceptible individual

2021 ◽  
Vol 9 (10) ◽  
pp. e002879
Author(s):  
Luoyan Ai ◽  
Jie Gao ◽  
Shihai Zhao ◽  
Qian Li ◽  
Yue-Hong Cui ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Human Leukocyte ◽  
Hla Typing ◽  
High Dose ◽  
Dress Syndrome ◽  
Th2 Response ◽  
Risk Alleles ◽  
Type Iv ◽  
Target Effect

The use of immune checkpoint inhibitors (ICIs) is rising exponentially in numerous cancers, but immune-related adverse events can occur. We report a rare case of high-grade drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome developed stepwise in a patient with gastric cancer after nivolumab treatment. Subclinical myocarditis was sensitively detected by cardiovascular magnetic resonance 3 weeks after initiating nivolumab. Eruption, eosinophilia, and interstitial pneumonitis occurred 1 week later. Corticosteroids were started and his condition improved. Four months later, when he was still on steroids tapering off, acute kidney injury and sequential herpes zoster virus activation developed. Severe acute tubulointerstitial nephritis (ATN) with an intense infiltration of lymphocytes was observed on renal biopsy. In blood, a substantial shift to Th2 response, an increase of Th17 cells, and strikingly enriched granzyme B+ and perforin+ CD8+ T cells were detected at ATN onset. Serum interleukin (IL)-5, IL-17, interferon gamma, and IL-6 levels were consistently elevated. Further molecular profiling identified a DRESS risk allele human leukocyte antigen (HLA)-A*31:01 in this patient. His ATN responded favorably to a high dose of corticosteroids. In parallel, complete antitumor response was observed during the clinical course of DRESS. This is the first ever case report of nivolumab-associated DRESS syndrome with exploration of the mechanisms from the histopathological, cellular and molecular aspects. Nivolumab-induced DRESS may result from type IV hypersensitivity-related ‘off-target effect’ and PD-1 block-mediated ‘on-target effect’. HLA risk alleles may constitute the genetic susceptible basis. HLA typing assay has the potential to screen susceptible individuals to avoid ICI-induced DRESS.

scholarly journals Development of Nivolumab/Ipilimumab-Associated Autoimmune Nephritis during Steroid Therapy

2021 ◽  
pp. 270-274
Author(s):  
Ellen Gebauer ◽  
Wibke Bechtel-Walz ◽  
Christoph Schell ◽  
Michelle Erbel ◽  
Gerd Walz ◽  
...  
Keyword(s):  
Steroid Therapy ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis ◽  
Oral Steroid ◽  
High Dose ◽  
Immune Mediated

Immunotherapy using immune checkpoint inhibitors revolutionized therapies for a variety of malignancies. Nivolumab, an antibody blocking programmed cell death 1 protein, and ipilimumab that blocks cytotoxic T-lymphocyte-associated protein 4 effectively target tumor cells by disinhibiting the endogenous immune response. At the same time, unrestrained T-cell activation may trigger a range of immune-mediated side effects including kidney injury. Steroid therapy constitutes the mainstay of treatment of these adverse events, but dosage, route of administration, and approach to nivolumab re-exposure remain unclear. Here, we report the case of a 72-year-old male patient who developed severe nivolumab/ipilimumab-associated acute kidney injury while on oral steroid therapy for immune-mediated colitis. Acute interstitial nephritis was confirmed by renal biopsy. Administration of high-dose intravenous steroid doses was required to revert declining renal function.

A case of immune-complex mediated glomerulonephritis associated with pembrolizumab

2021 ◽  
pp. 239936932110646
Author(s):  
Marco Bonilla ◽  
Vanesa Bijol ◽  
Antonio Gabriel De Leon Corona ◽  
Kevin M. Sullivan ◽  
Kenar D. Jhaveri
Keyword(s):  
Acute Kidney Injury ◽  
Immune Complex ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
High Dose ◽  
Dramatic Improvement ◽  
Pathologic Finding ◽  
Glomerular Injury ◽  
Metastatic Lung ◽  
Dose Prednisone

Introduction: Immune checkpoint inhibitors (ICI) are changing the way we treat cancer. However, these novel agents have various systemic adverse events that may preclude its use and cause poor patient outcomes. ICI-associated acute kidney injury is an emerging complication of this treatment. While tubulointerstitial disease is the most common pathologic finding of patients with ICI-associated AKI, there is sparse data in medical literature describing its association with glomerular disease. Case report: Here, we present a patient with metastatic lung adenocarcinoma who developed acute kidney injury and significant proteinuria after receiving pembrolizumab. The kidney biopsy revealed a membranoproliferative and diffuse segmental endocapillary proliferative pattern of glomerular injury. Management and outcome: Pembrolizumab was then held and high-dose prednisone was initiated, resulting in a rapid and dramatic improvement in kidney function and proteinuria. Discussion: We highlight a report of a patient diagnosed with immune-complex mediated glomerulonephritis associated with the use of pembrolizumab, who was successfully treated with drug withdrawal and corticosteroids.

scholarly journals Hypokalemic Paralysis Secondary to Immune Checkpoint Inhibitor Therapy

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Pragathi Balakrishna ◽  
Augusto Villegas
Keyword(s):  
Immune Checkpoint ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
High Serum ◽  
Admission Diagnosis ◽  
High Dose ◽  
Immune Mediated ◽  
History Of ◽  
Checkpoint Inhibitor Therapy

Introduction of immune checkpoint inhibitors (ICIs) has led to significant improvements in the treatment of multiple malignancies. Anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) are two essential ICIs that have been FDA approved since 2011. As the use of immunotherapy in melanoma and other malignancies increases, the potential of adverse events also increases. Overall, anti-PD-1 agents are well tolerated. In rare instances, colitis, endocrinopathies, skin, and renal toxicities have been observed. A 58-year-old male with a history of stage 4 cutaneous melanoma presented with quadriplegia while on nivolumab. Routine blood test revealed low potassium, low bicarbonate, and high serum creatinine. Admission diagnosis included hypokalemia, acute kidney injury, and renal tubal acidosis. The offending drug was discontinued, and the patient was started on high-dose corticosteroids. On discharge, paralysis was resolved. Renal function and potassium were normalized. Nivolumab was discontinued, and he was started on pembrolizumab. Literature suggests that, although rare, patients receiving ICE may develop immune-mediated nephritis and renal dysfunction. The mainstay of immune-related adverse event (irAE) management is immune suppression. Hence, given the increasing frequency of immunotherapy use, awareness should be raised in regard to irAEs and their appropriate management.

640 Characterizing severe acute kidney injury in patients treated with immune checkpoint inhibitors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A676-A676
Author(s):  
Chung-Jiah Chen ◽  
Lisa Kim ◽  
Ashley Weaver ◽  
Sandip Patel
Keyword(s):  
Acute Kidney Injury ◽  
Renal Biopsy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
University Of California ◽  
High Dose ◽  
Renal Ultrasound ◽  
The University

BackgroundRenal immune-related adverse events (irAEs), are relatively rare in patients treated with immune checkpoint inhibitors (ICIs). This retrospective analysis characterizes the etiology of severe acute kidney injury (AKI) in patients treated with ICIs at the University of California, San Diego.MethodsThe electronic medical record was used to identify all patients with an estimated glomerular filtration rate (eGFR) <15 mL/hr who received ipilimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, cemiplimab between 1/2000 and 1/2019. Patients with baseline eGFR < 15 mL/hr or who experienced an eGFR decline to <15 mL/hr prior to ICI initiation were excluded. Extracted data included serum creatinine, eGFR, ICI dose, urinalysis, renal ultrasound, clinical documentation of both ICI-related nephritis and other suspected causes of AKI. These data were analyzed to determine cause of AKI and possible relation to ICI.Results46 patients who received ICI therapy and subsequently developed an AKI with eGFR <15 mL/hr were identified. Three of these 46 patients (6.5%) had AKIs partially or predominately attributed by the clinician to ICI therapy (table 1). Characteristics of ICI-related AKI for these patients are summarized in (table 2). AKI onset occurred 32–110 days after ICI initiation. All three patients exhibited proteinuria, pyuria, and hematuria on urinalysis with negative urine cultures, but none underwent confirmatory renal biopsy. Only one patient had urine eosinophils checked, which was negative. Two (66%) of these patients received high-dose corticosteroids with subsequent complete eGFR recovery. Neither of these two patients required renal replacement therapy. One patient (33%) declined corticosteroid treatment due to concomitant multiorgan failure. An additional four (8.7%) patients developed multifactorial AKIs with other concurrent IRAEs that were treated with corticosteroids, but were not formally diagnosed with ICI-related AKI.Abstract 640 Table 1AKI etiologies in ICI-treated patientsAbstract 640 Table 2Patient characteristics in ICI-related AKIConclusionsIn our cohort, 6.5% of patients who develop AKI after receiving ICI therapy experienced immune-related nephritis. A further 8.7% of patients experienced other irAEs with AKI, suggesting that the true prevalence of immune-related nephritis is likely underdiagnosed. Notably, 84.8% of patients who develop AKI after ICI therapy have a non-ICI-related etiology, and no patient in our cohort of 46 patients underwent renal biopsy, highlighting the need for blood-based biomarker development for immune-related nephritis.Ethics ApprovalThe study was approved by the University of California San Diego’s Institutional Review Board, approval number 150348.

scholarly journals Renal Complications Related to Checkpoint Inhibitors: Diagnostic and Therapeutic Strategies

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1187
Author(s):  
Julie Belliere ◽  
Julien Mazieres ◽  
Nicolas Meyer ◽  
Leila Chebane ◽  
Fabien Despas
Keyword(s):  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Kidney Injury ◽  
Immunosuppressive Drugs ◽  
Peripheral Tolerance ◽  
Electrolyte Disorders ◽  
Glomerular Diseases ◽  
Renal Complications ◽  
Lower Baseline ◽  
Low Incidence

Immune checkpoint inhibitors (ICI) targeting CTLA-4 and the PD-1/PD-L1 axis have unprecedentedly improved global prognosis in several types of cancers. However, they are associated with the occurrence of immune-related adverse events. Despite their low incidence, renal complications can interfere with the oncologic strategy. The breaking of peripheral tolerance and the emergence of auto- or drug-reactive T-cells are the main pathophysiological hypotheses to explain renal complications after ICI exposure. ICIs can induce a large spectrum of renal symptoms with variable severity (from isolated electrolyte disorders to dialysis-dependent acute kidney injury (AKI)) and presentation (acute tubule-interstitial nephritis in >90% of cases and a minority of glomerular diseases). In this review, the current trends in diagnosis and treatment strategies are summarized. The diagnosis of ICI-related renal complications requires special steps to avoid confounding factors, identify known risk factors (lower baseline estimated glomerular filtration rate, proton pump inhibitor use, and combination ICI therapy), and prove ICI causality, even after long-term exposure (weeks to months). A kidney biopsy should be performed as soon as possible. The treatment strategies rely on ICI discontinuation as well as co-medications, corticosteroids for 2 months, and tailored immunosuppressive drugs when renal response is not achieved.

Acute kidney injury and nephrotic syndrome associated with eltrombopag therapy in chronic idiopathic thrombocytopenic purpura

2021 ◽  
Vol 14 (4) ◽  
pp. e241462
Author(s):  
Suchi Anindita Ghosh ◽  
Jean Patrick ◽  
Kyaw Zin Maw
Keyword(s):  
Acute Kidney Injury ◽  
Renal Failure ◽  
Nephrotic Syndrome ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Kidney Injury ◽  
High Dose ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Antibody Screen ◽  
Auto Antibody

A 77-year-old man was admitted with severe acute kidney injury and nephrotic syndrome. He was started on eltrombopag for chronic idiopathic thrombocytopenic purpura 6 weeks earlier. An ultrasound of the kidneys was normal and an auto-antibody screen was negative. The use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 5) between the patient’s development of acute renal failure and eltrombopag therapy. Literature review identified only one other case of nephrotic syndrome and acute kidney injury associated with eltrombopag therapy in which a kidney biopsy revealed focal segmental glomerulosclerosis. Due to the challenges faced during the prevailing SARS-CoV-2 pandemic and persistent low platelet counts a renal biopsy was not undertaken. On stopping eltrombopag, the patients renal function stabilised and he successfully went into remission following treatment with high dose corticosteroids and diuretics. This report of a serious case of reversible renal failure and nephrotic syndrome after treatment with eltrombopag may serve to inform clinicians about the possible severe renal adverse effects of eltrombopag before its commencement for future use.

scholarly journals Human leukocyte antigen B*0702 is protective against ocular Stevens–Johnson syndrome/toxic epidermal necrolysis in the UK population

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gibran F. Butt ◽  
Ali Hassan ◽  
Graham R. Wallace ◽  
Shigeru Kinoshita ◽  
Sajjad Ahmad ◽  
...  
Keyword(s):  
Human Leukocyte Antigen ◽  
Toxic Epidermal Necrolysis ◽  
Human Leukocyte ◽  
Stevens Johnson Syndrome ◽  
Ocular Complications ◽  
Leukocyte Antigen ◽  
Asian Populations ◽  
Risk Alleles ◽  
Johnson Syndrome ◽  
The Uk

AbstractStevens–Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN) are part of a disease continuum of vesiculobullous mucocutaneous reactions affecting the skin and mucous membranes including the ocular surface. Manifestations of disease range from mild dry eye to progressive conjunctival cicatrisation, limbal epithelial stem cell failure and corneal blindness. In Far Eastern and South East Asian populations where SJS/TEN is prevalent, numerous human leukocyte antigen (HLA) gene variants at the A, B and C loci have been identified as risk factors for developing SJS/TEN with severe ocular complications (SOC). By contrast, the incidence of SJS/TEN with SOC in European countries is relatively low. To date, ocular SJS/TEN risk altering alleles have not been widely investigated in European populations. In this study, we analysed the association of HLA -A, -B and -C alleles with SJS/TEN in 33 patients residing in the UK with age matched controls. The data showed statistically significant novel negative allele association with HLA-B*0702 and a trend with HLA-C*0702 in the patient group, indicating these alleles are protective. Further characterisation of protective and risk alleles in other ethnic groups is required to fully elucidate the putative role of these alleles in the susceptibility of SJS/TEN with or without severe ocular complications in patients in the UK.

scholarly journals Refractory constrictive pericarditis caused by an immune checkpoint inhibitor properly managed with infliximab: a case report

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Shohei Moriyama ◽  
Mitsuhiro Fukata ◽  
Ryoma Tatsumoto ◽  
Mihoko Kono
Keyword(s):  
Lung Cancer ◽  
Constrictive Pericarditis ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Rescue Therapy ◽  
Treatment Strategies ◽  
High Dose ◽  
Acute Pericarditis ◽  
Line Therapy ◽  
Steroid Refractory

Abstract Background Immune checkpoint inhibitors (ICIs) can cause cardiac immune-related adverse events (irAEs), including pericarditis. Cardiovascular events related to pericardial irAE are less frequent, but fulminant forms can be fatal. However, the diagnosis and treatment strategies for pericardial irAE have not established. Case summary A 58-year-old man was diagnosed with advanced non-small-cell lung cancer and nivolumab was administered as 5th-line therapy. Eighteen months after the initiation of nivolumab, the patient developed limb oedema and increased body weight. Although a favourable response of the cancer was observed, pericardial thickening and effusion were newly detected. He was diagnosed with irAE pericarditis after excluding other causes of pericarditis. Nivolumab was suspended and a high-dose corticosteroid was initiated. However, right heart failure (RHF) symptoms were exacerbated during the tapering of corticosteroid because acute pericarditis developed to steroid-refractory constrictive pericarditis. To suppress sustained inflammation of the pericardium, infliximab, a tumour necrosis factor-alfa inhibitor, was initiated. After the initiation of infliximab, the corticosteroid dose was tapered without deterioration of RHF. Exacerbation of lung cancer by irAE treatment including infliximab was not observed. Discussion IrAE should be considered when pericarditis develops after the administration of ICI even after a long period from its initiation. Infliximab rescue therapy may be considered as a 2nd-line therapy for steroid-refractory irAE pericarditis even with constrictive physiology.

scholarly journals Raltegravir-associated Drug-Reaction With Eosinophilia and Systemic Symptoms Syndrome in a Pediatric Patient Without Characteristic Human Leukocyte Antigen B*57:01 or B*53:01 alleles

2020 ◽  
Author(s):  
Sanya J Thomas ◽  
Jacob T Kilgore ◽  
Bradford A Becken ◽  
Coleen K Cunningham ◽  
Amelia B Thompson
Keyword(s):  
Drug Reaction ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
African American Female ◽  
Dress Syndrome ◽  
Leukocyte Antigen ◽  
Antigen B ◽  
Immunodeficiency Virus ◽  
Perinatally Acquired ◽  
Systemic Symptoms

Abstract We present the first published case of raltegravir-associated drug-reaction with eosinophilia and systemic symptoms (DRESS) syndrome in a child without characteristic human leukocyte antigen haplotypes HLA-B*57:01 or HLA-B*53:01. A 4-year-old African American female with perinatally acquired human immunodeficiency virus infection was hospitalized for DRESS after starting a raltegravir-based antiretroviral regimen.

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