scholarly journals Myasthenia Gravis as an Immune-Mediated Side Effect of Checkpoint Inhibitors

Cureus ◽  
2021 ◽  
Author(s):  
Caio T Heleno ◽  
Ala Mustafa ◽  
Nico A Gotera ◽  
Amy Tesar
Keyword(s):  
Myasthenia Gravis ◽  
Side Effect ◽  
Checkpoint Inhibitors ◽  
Immune Mediated

Late-onset double-seronegative myasthenia gravis syndrome and myasthenic crisis due to nivolumab use for Hodgkin’s lymphoma

2020 ◽  
pp. 107815522097679
Author(s):  
Thai Dang ◽  
Samir Macwan ◽  
Constantin A Dasanu
Keyword(s):  
Myasthenia Gravis ◽  
Late Onset ◽  
Checkpoint Inhibitors ◽  
Myasthenic Crisis ◽  
Immune Mediated ◽  
Seronegative Myasthenia Gravis ◽  
Programmed Cell Death 1 ◽  
Bulbar Symptoms ◽  
Checkpoint Inhibitor Therapy ◽  
Grade 3

Introduction Insofar, use of programmed cell death-1 (PD-1) immune checkpoint inhibitors in oncology has been linked with several immune-mediated neurologic effects. However, grade 3 to 4 adverse events such as myasthenic crisis have been vanishingly rare. Case presentation: We present herein a unique patient with Hodgkin lymphoma who developed late-onset double-seronegative myasthenia gravis syndrome followed by myasthenic crisis after 16 weeks of therapy with nivolumab. One day prior to this event, she developed ptosis, diplopia, bulbar symptoms of dysphagia, dysarthria, orthopnea as well as extremity weakness. She required intubation, mechanical ventilation, plasmapheresis and steroid therapy. Management and outcome: She gradually achieved a near-complete resolution of neurologic symptoms over the next several weeks. On a follow-up visit eight weeks later, she only has some residual diplopia. Restaging scans showed a continued decrease in size of the mediastinal mass, without abnormal uptake. She remains on prednisone 10 mg orally daily. Discussion Prompt recognition of this rare phenomenon, immediate discontinuation of checkpoint inhibitor therapy and subsequent management with immunosuppressive therapy are necessary steps in order to minimize the considerable rates of morbidity and mortality.

scholarly journals Hyponatremia and Fever in a Patient on Ipilimumab and Nivolumab (Immune Checkpoint Inhibitors): A Case Report

2021 ◽  
Vol 9 ◽  
pp. 232470962110452
Author(s):  
Sumit S. Patel ◽  
Sasmit Roy ◽  
Mytri Pokal ◽  
Vijay Gayam ◽  
Sreedhar Adapa ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Side Effect ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Interesting Case ◽  
Volume Depletion ◽  
Urine Sodium ◽  
Immune Mediated ◽  
Systemic Side Effects ◽  
Hemodynamic Disturbance

Immune checkpoint inhibitors (ICIs) are novel anticancer therapy approved in multiple tumors and their use is rapidly increasing. They are associated with various systemic side effects that are immune-mediated and clinically coined as “immune-related adverse effects” (irAE). Hyponatremia is a possible side effect in patients receiving ICIs. Fever is another side effect that is mostly non-infectious. There are different mechanisms leading to hyponatremia in patients on ICIs, which could be (1) hypovolemic hyponatremia due to hemodynamic disturbance secondary to volume depletion (eg, from irAE like colitis and enteritis) or hypervolemia due to congestive heart failure, cirrhosis, or nephrosis; (2) syndrome of inappropriate antidiuretic hormone (SIADH) secretion (especially from underlying lung cancer or neurological irAE like encephalitis and meningitis) with elevated urine sodium and urine osmolarity; and (3) irAE-related endocrinopathies such as hypophysitis, adrenal insufficiency, and hypothyroidism leading to euvolemic hyponatremia. We describe an interesting case of hyponatremia and fever in a patient receiving Ipilimumab and Nivolumab. The possible etiology of hyponatremia, in this case, was hypovolemia and volume depletion secondary to fever.

scholarly journals Durable Metastatic Melanoma Remission Following Pembrolizumab and Radiotherapy: A Case Report of Prophylactic Immunosuppression in a Patient with Myasthenia Gravis and Immune-Mediated Colitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Luke A. Moradi ◽  
Curtis A. Clark ◽  
Craig S. Schneider ◽  
Alok S. Deshane ◽  
Michael C. Dobelbower
Keyword(s):  
Myasthenia Gravis ◽  
Metastatic Melanoma ◽  
Tumor Regression ◽  
Checkpoint Inhibitors ◽  
Small Subset ◽  
Tumor Microenvironments ◽  
Mixed Response ◽  
Immune Mediated ◽  
Anti Cancer ◽  
Autoimmune Conditions

Immune checkpoint inhibitors (ICIs) and radiotherapy (RT) combinations for various metastatic cancers are increasingly utilized, yet the augmentation of anti-cancer immunity including distant tumor responses by RT remains ill-characterized. Immunosuppressive tumor microenvironments and defective anti-tumor immune activation including immune-related adverse events (irAEs) likely limit dramatic immuno-radiotherapy combinations, though it remains unclear which immune characteristics mediate dramatic systemic tumor regression in only a small subset of patients. Moreover, the efficacy of ICI treatment in patients receiving immunosuppressive therapies for autoimmune conditions or irAEs is convoluted, yet clinically valuable. Here, we report a case of a 75-year-old man with myasthenia gravis and metastatic melanoma who experienced complete and durable systemic regression after receiving pembrolizumab and single-lesion RT while on prednisone for myasthenia gravis prophylaxis and vedolizumab for immune-mediated colitis after previously experiencing mixed response on pembrolizumab monotherapy. We discuss the potential paradoxical effects and clinical considerations of immunosuppressive regimens in patients with underlying autoimmune disease or adverse immune reactions while receiving immuno-radiotherapy combinations.

scholarly journals COVID-19 lung injury as a primer for immune checkpoint inhibitors (ICIs)-related pneumonia in a patient affected by squamous head and neck carcinoma treated with PD-L1 blockade: a case report

2021 ◽  
Vol 9 (2) ◽  
pp. e001870
Author(s):  
Angelo Dipasquale ◽  
Pasquale Persico ◽  
Elena Lorenzi ◽  
Daoud Rahal ◽  
Armando Santoro ◽  
...  
Keyword(s):  
Lung Injury ◽  
Head And Neck ◽  
Checkpoint Inhibitors ◽  
Experimental Therapy ◽  
Common Mechanism ◽  
Nasopharyngeal Swab ◽  
Immune Mediated ◽  
Diagnostic Work ◽  
Work Up ◽  
Diagnostic Work Up

By the beginning of the global pandemic, SARS-CoV-2 infection has dramatically impacted on oncology daily practice. In the current oncological landscape, where immunotherapy has revolutionized the treatment of several malignancies, distinguishing between COVID-19 and immune-mediated pneumonitis can be hard because of shared clinical, radiological and pathological features. Indeed, their common mechanism of aberrant inflammation could lead to a mutual and amplifying interaction.We describe the case of a 65–year-old patient affected by metastatic squamous head and neck cancer and candidate to an experimental therapy including an anti-PD-L1 agent. COVID-19 ground-glass opacities under resolution were an incidental finding during screening procedures and worsened after starting immunotherapy. The diagnostic work-up was consistent with ICIs-related pneumonia and it is conceivable that lung injury by SARS-CoV-2 has acted as an inflammatory primer for the development of the immune-related adverse event.Patients recovered from COVID-19 starting ICIs could be at greater risk of recall immune-mediated pneumonitis. Nasopharyngeal swab and chest CT scan are recommended before starting immunotherapy. The awareness of the phenomenon could allow an easier interpretation of radiological changes under treatment and a faster diagnostic work-up to resume ICIs. In the presence of clinical benefit, for asymptomatic ICIs-related pneumonia a watchful-waiting approach and immunotherapy prosecution are suggested.

scholarly journals Presynaptic Paraneoplastic Disorders of the Neuromuscular Junction: An Update

2021 ◽  
Vol 11 (8) ◽  
pp. 1035
Author(s):  
Maria Pia Giannoccaro ◽  
Patrizia Avoni ◽  
Rocco Liguori
Keyword(s):  
Potassium Channels ◽  
Neuromuscular Junction ◽  
Calcium Channels ◽  
Myasthenia Gravis ◽  
Neuromuscular Transmission ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Immune Mediated ◽  
Recent Developments ◽  
Myasthenic Syndrome

The neuromuscular junction (NMJ) is the target of a variety of immune-mediated disorders, usually classified as presynaptic and postsynaptic, according to the site of the antigenic target and consequently of the neuromuscular transmission alteration. Although less common than the classical autoimmune postsynaptic myasthenia gravis, presynaptic disorders are important to recognize due to the frequent association with cancer. Lambert Eaton myasthenic syndrome is due to a presynaptic failure to release acetylcholine, caused by antibodies to the presynaptic voltage-gated calcium channels. Acquired neuromyotonia is a condition characterized by nerve hyperexcitability often due to the presence of antibodies against proteins associated with voltage-gated potassium channels. This review will focus on the recent developments in the autoimmune presynaptic disorders of the NMJ.

scholarly journals When steroids are not enough in immune-related hepatitis: current clinical challenges discussed on the basis of a case report

2020 ◽  
Vol 8 (2) ◽  
pp. e001322 ◽  
Author(s):  
Dimitrios C Ziogas ◽  
Aikaterini Gkoufa ◽  
Evangelos Cholongitas ◽  
Panagiotis Diamantopoulos ◽  
Amalia Anastasopoulou ◽  
...  
Keyword(s):  
Immune Checkpoint Inhibitors ◽  
Liver Toxicity ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Phase Iii ◽  
Steroid Resistant ◽  
Immune Mediated ◽  
Cancer Types ◽  
Clinical Considerations ◽  
Steroid Refractory

Unleashing adaptive immunity via immune checkpoint inhibitors (ICPIs) in many cancer types led to durable antitumor responses and prolonged survivals and also added some new immune-related adverse events (irAEs) to the ‘old-fashioned’ safety profile of chemotherapy. Among bowel and endocrine irAEs, immune-mediated hepatotoxicity/hepatitis is a less common and far less well-studied toxicity, which, however, could develop into a serious complication, especially when it becomes persistent or refractory to steroids. Its incidence, onset and severity vary widely, depending on the type of underlying treated cancer, the class, the dosage and the duration of immunotherapy as well as the way of its administration (as a single agent or in combination with other ICPI or chemotherapy). In this study, we present a patient with metastatic melanoma who developed severe steroid-resistant ir-hepatitis after treatment with ipilimumab and required triple concurrent immunosuppression with prednisolone, mycofenolate mofetil and tacrolimus in order for his liver toxicity to be resolved. Intrigued by this case, we focused further on melanoma, as the disease-paradigm of immunotherapy in cancer, reviewed the reported incidence of hepatotoxicity among phase III ICPIs-containing trials on melanoma and discussed the main clinical considerations regarding the diagnosis and the management of persistent/steroid-refractory ir-hepatitis. As more clinical experience is gradually gained on this challenging topic, better answers are provided to questions about the appropriate diagnostic workup, the necessity of liver biopsy, the available immunosuppressive options beyond corticosteroids (their combinations and/or their sequence) as well as the correct decision on withdrawing or resuming immunotherapy. Nonetheless, a thorough multidisciplinary discussion is still required to individualize the overall approach in each case after failure of steroids.

Immune-mediated rippling muscle disease and myasthenia gravis

2016 ◽  
Vol 299 ◽  
pp. 59-61 ◽  
Author(s):  
Mariela Bettini ◽  
Hernan Gonorazky ◽  
Marcelo Chaves ◽  
Ernesto Fulgenzi ◽  
Alejandra Figueredo ◽  
...  
Keyword(s):  
Myasthenia Gravis ◽  
Muscle Disease ◽  
Immune Mediated

scholarly journals Zytux in Refractory Myasthenia Gravis: A Multicenter, Open-Labeled, Clinical Trial Study of Effectiveness and Safety of a Rituximab Biosimilar

2021 ◽  
Vol 12 ◽  
Author(s):  
Farzad Fatehi ◽  
Kamyar Moradi ◽  
Ali Asghar Okhovat ◽  
Ghazaleh Shojatalab ◽  
Behnaz Sedighi ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Clinical Trial ◽  
Myasthenia Gravis ◽  
Clinical Status ◽  
Neuromuscular Disorder ◽  
Clinical Trial Registration ◽  
Prednisolone Dose ◽  
Immune Mediated ◽  
Post Infusion

Objectives: Myasthenia gravis (MG) is an immune-mediated neuromuscular disorder responsive to immunomodulatory treatments. 10–20% of MGs are not responsive to conventional first-line therapies. Here, we sought to investigate the efficacy and safety of rituximab therapy in the treatment of patients with refractory MG.Methods: In a 48-week, multicenter, open-labeled, prospective cohort setting, 34 participants with refractory MG were assigned to receive infusions of Zytux, which is a rituximab biosimilar, according to a validated protocol. Clinical, functional, and quality of life (QoL) measurements were recorded at baseline, and seven further visits using the Myasthenia Gravis Foundation of America (MGFA), Myasthenia Gravis Composite (MGC), Myasthenia Gravis Activities of Daily Living profile (MG-ADL), and Myasthenia Gravis Quality of Life (MGQoL-15) scales. Besides, the post-infusion side effects were systematically assessed throughout the study.Results: The correlation analysis performed by generalized estimating equations analysis represented a significant reduction of MGC, MG-ADL, and MGQoL-15 scores across the trial period. The subgroup analysis based on the patients' clinical status indicated a significant effect for the interaction between time and MGFA subtypes on MG-ADL score, MGC score, and pyridostigmine prednisolone dose, reflecting that the worse clinical condition was associated with a better response to rituximab. Finally, no serious adverse event was documented.Conclusions: Rituximab therapy could improve clinical, functional, and QoL in patients with refractory MG in a safe setting. Further investigations with larger sample size and a more extended follow-up period are warranted to confirm this finding.Clinical Trial Registration: The study was registered by the Iranian Registry of Clinical Trials (IRCT) (Code No: IRCT20150303021315N18).

scholarly journals A Case of COVID-19 Vaccine Associated New Diagnosis Myasthenia Gravis

2021 ◽  
Vol 12 ◽  
pp. 215013272110519
Author(s):  
Augustine Chavez ◽  
Charlotte Pougnier
Keyword(s):  
Myasthenia Gravis ◽  
Late Onset ◽  
Severe Exacerbation ◽  
Presenting Symptoms ◽  
Immune Mediated ◽  
Peg Tube ◽  
New Diagnosis

An 82-year-old man presented with intermittent episodes of slurred speech during his evening meals after receiving the BNT162b2 COVID-19 vaccine. Thorough evaluation was conducted including lab work and EMG confirming a new diagnosis of late-onset myasthenia gravis. Despite treatment, the patient progressed rapidly to severe exacerbation requiring intubation and placement of a PEG tube. Infections provoking new diagnosis and exacerbations of myasthenia gravis have been reported. New diagnosis of myasthenia gravis associated with the COVID-19 vaccine is rarely reported. This case highlights the need for clinicians to be aware of the uncommon presenting symptoms in late-onset myasthenia gravis and the possibility of vaccine provoked diagnoses of immune mediated diseases.

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