mycophenolic-acid and Myocarditis

Clinical heterogeneity, unpredictable course and flares are characteristics of systemic lupus erythematosus (SLE). Although SLE is-by and large-a systemic disease, occasionally it can be organ-dominant, posing diagnostic challenges. To date, diagnosis of SLE remains clinical with a few cases being negative for serologic tests. Diagnostic criteria are not available and classification criteria are often used for diagnosis, yet with significant caveats. Newer sets of criteria (European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019) enable earlier and more accurate classification of SLE. Several disease endotypes have been recognised over the years. There is increased recognition of milder cases at presentation, but almost half of them progress overtime to more severe disease. Approximately 70% of patients follow a relapsing-remitting course, the remaining divided equally between a prolonged remission and a persistently active disease. Treatment goals include long-term patient survival, prevention of flares and organ damage, and optimisation of health-related quality of life. For organ-threatening or life-threatening SLE, treatment usually includes an initial period of high-intensity immunosuppressive therapy to control disease activity, followed by a longer period of less intensive therapy to consolidate response and prevent relapses. Management of disease-related and treatment-related comorbidities, especially infections and atherosclerosis, is of paramount importance. New disease-modifying conventional and biologic agents-used alone, in combination or sequentially-have improved rates of achieving both short-term and long-term treatment goals, including minimisation of glucocorticoid use.

Topics: Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal, Humanized; Autoantibodies; Azathioprine; Calcineurin Inhibitors; Cardiovascular Diseases; Cyclophosphamide; Disease Management; Female; Glucocorticoids; Heart Valve Diseases; Humans; Hydroxychloroquine; Hypertension, Pulmonary; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lupus Nephritis; Lupus Vasculitis, Central Nervous System; Macrophage Activation Syndrome; Methotrexate; Mycophenolic Acid; Myocarditis; Outcome Assessment, Health Care; Pericarditis; Phenotype; Pregnancy; Pregnancy Complications; Prognosis; Purpura, Thrombocytopenic, Idiopathic; Quality of Life; Recurrence; Rituximab; Severity of Illness Index; Survival Rate; Uterine Cervical Neoplasms

A 45-year-old male with cardiac sarcoidosis verified by cardiac biopsy presented with multiple coexisting arrhythmias, including ventricular tachycardia of more than 1000 episodes per 24 h, paroxysmal atrial fibrillation, and third-degree atrioventricular block. He did not respond to corticosteroids dose of 20-60 mg once daily and mycophenolate mofetil dose of 1 g twice daily for 6 months. Cardiac magnetic resonance (CMR) demonstrated inflammation and late gadolinium enhancement on right ventricular wall and interventricular septum. Positron emission tomography-computed tomography (PET-CT) showed multifocal

Topics: Adalimumab; Arrhythmias, Cardiac; Atrioventricular Block; Cardiomyopathies; Contrast Media; Fluorodeoxyglucose F18; Gadolinium; Humans; Inflammation; Male; Middle Aged; Mycophenolic Acid; Myocarditis; Positron Emission Tomography Computed Tomography; Sarcoidosis

Novel immune-modulating anticancer drugs are being used with increasing frequency. With increased use, there are more frequent cases of toxicities caused by these drugs, termed immune-related adverse events (irAEs). We present a case in which we successfully treated a case of severe, steroid-refractory, nivolumab-induced myocarditis with therapeutic plasma exchange (TPE). Nivolumab is an immune checkpoint inhibitor (ICI) which blocks programmed death receptor-1 (PD-1). This blockade allows for enhanced T-cell function and increased anti-tumor response. The patient presented with signs and symptoms of heart failure and was found to have a significantly depressed cardiac ejection fraction. Over the course of her five TPE procedures, she improved clinically and was discharged home with improved left ventricular ejection function. This case suggests an emerging role of TPE in the management of severe ICI-induced toxicity, such as myocarditis.

Topics: Abatacept; Adrenal Cortex Hormones; Adrenal Gland Neoplasms; Aged; Antineoplastic Agents; Carcinoma, Renal Cell; Female; Humans; Immune Checkpoint Inhibitors; Immune System; Mycophenolic Acid; Myocarditis; Neoplasms; Nivolumab; Plasma Exchange; Programmed Cell Death 1 Receptor; Steroids

Anti-Ku is a rare antibody which can be positive in some rheumatic diseases and it might be related to cardiac involvement. Polymyositis is an inflammatory myopathy, and its cardiac involvement seldom presents as myopericarditis and anti-Ku positive.. In this case, we report a mid-aged woman with chest pain, upper limbs weakness and fever unrelated with infection. The diagnosis of this case was unquestionably myopericarditis supported by ECG, cardiac MRI and negative findings in coronary arteries. Diagnosis of polymyositis was further clarified by the evidence of persistently increased CK, degeneration of proximal muscle in MRI, muscular dystrophy with lymphocytes infiltration in muscle biopsy. In the analysis of autoantibodies, we surprisingly discovered positive anti-Ku. Glucocorticoid and mycophenolate mofetil were then prescribed for polymyositis. Patient follow-up indicated remission of both myopericarditis and polymyositis. We finally clarified this rare case as a positive anti-Ku polymyositis with myopericarditis as cardiac involvement.. This report presents a rare case with anti-Ku positive polymyositis and the cardiac involvement of polymyositis was manifested as myopericarditis. Therefore, positive anti-Ku might explain the myopericarditis as cardiac involvement in polymyositis. More cases and longer duration of follow-up is required for the comprehensive understanding of the disease.

Topics: Autoantibodies; Chest Pain; Creatine Kinase; Electrocardiography; Female; Fever; Glucocorticoids; Humans; Ku Autoantigen; Magnetic Resonance Imaging; Middle Aged; Muscular Dystrophies; Mycophenolic Acid; Myocarditis; Polymyositis

virus-negative lymphocytic myocarditis (VNLM) is a severe inflammatory heart disease with elusive therapies. We aimed to assess the efficacy of mycophenolate-mofetil (MMF) in patients with VNLM.. patients were enrolled in this prospective cohort study and were treated with MMF, as the initial treatment in case of concomitant systemic immune diseases (SIDs), or as rescue therapy in isolated myocarditis intolerant/resistant to azathioprine. All were initially evaluated for endomyocardial biopsy; ECG, 24-h Holter, echocardiography, troponin T and NT-proBNP were obtained in all patients at baseline and after 6 months. The primary end-point was the change in left-ventricular ejection-fraction (LVEF) on echocardiogram after 6 months.. decrease in serum NT-proBNP and troponin-T levels, reduction of LV end-diastolic-volume (LVEDV), amelioration of regional wall motion abnormalities (RWMA), and modification of clinical status.. 20 patients (10 females, median age at diagnosis 32 [41-59] years) were enrolled. Baseline echocardiography revealed a reduced LVEF (<55%) in 11 patients (55%) and a median LV-EF of 53.5 [44-60.5]%. Baseline median troponin T and NT-proBNP were 50.5 (14.4-288.5)ng/L and 257.0 (90.5-912.0)pg/ml, respectively. After 6 months, the median LVEF significantly improved (57 [50-61]%,p = 0.016), irrespective of concomitant steroid dose. Consistently, after 6 months LVEDV decreased from 135 ± 50 ml to 114 ± 38 ml (p < 0.001), and only 6 patients had RWMA, compared to 14 at baseline (p = 0.016). The amelioration of cardiac function was paralleled by a reduction of median troponin T (12.0 [10.0-24.0],p = 0.02) and NT-proBNP(79.5 [74.5-223-2],p = 0.007) and by a reduction in the number of patients with dyspnea NYHA class II-III(p = 0.02). None of the patients required drug discontinuation.. MMF migh be a safe and effective therapeutic option in VNLM, both as first-line agent and as a rescue therapy.

Topics: Adult; Azathioprine; Cohort Studies; Female; Humans; Lymphocytes; Male; Middle Aged; Mycophenolic Acid; Myocarditis; Prospective Studies; Stroke Volume; Troponin T; Ventricular Function, Left

Myocarditis is an uncommon manifestation of systemic lupus erythematosus in which the clinical presentation can range from subclinical to life-threatening. We report cases of two patients who presented to our hospital with myocarditis as an initial manifestation of systemic lupus erythematosus despite negative results of extensive workup that excluded other diagnoses. The mainstays of treatment are corticosteroids, immunosuppressive agents, and anti-heart failure medications, with use of the latter being case-specific. Mycophenolate mofetil was the cornerstone of the proposed treatment for induction of remission, although it is well known to be used as a maintenance therapy in lupus myocarditis.. Both Emirati patients described satisfied the diagnostic criteria for mixed connective tissue disease (systemic lupus predominant) and systemic lupus erythematous. Other differential diagnoses of myocarditis were excluded. The patients were started on pulsed steroid followed by oral steroid, with hydroxychloroquine, mycophenolate mofetil, and anti-heart failure medications used as needed. Dramatic responses were noted in the first few weeks in terms of symptoms.. Early recognition and treatment of lupus myocarditis is needed to avoid fatal consequences.

Topics: Adrenal Cortex Hormones; Adult; Female; Humans; Hydroxychloroquine; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Mycophenolic Acid; Myocarditis; Treatment Outcome

Topics: Adult; Female; Fertilization in Vitro; Heart Transplantation; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Mycophenolic Acid; Myocarditis; Sirolimus; Surrogate Mothers; TOR Serine-Threonine Kinases; Treatment Outcome; Troponin T

A 59-year-old man with a history of giant cell myocarditis was admitted to our hospital with recurrent giant cell myocarditis triggered by a 1 mg/day taper in his prednisolone dose. During the initial episode, he had undergone rescue implantation of a temporary left ventricular assist device followed by the administration of dual immunosuppressive therapy with prednisolone and concomitant cyclosporine. Triple combination immunosuppressive therapy maintained with additional mycophenolate mofetil successfully controlled recurrent myocarditis, enabled a reduction in the prednisolone dose, and achieved the functional recovery of the left ventricle.

Topics: Combined Modality Therapy; Cyclosporine; Drug Therapy, Combination; Giant Cells; Heart-Assist Devices; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Myocarditis; Prednisolone; Treatment Outcome

Cardiac involvement during systemic lupus erythematosus (SLE) may include the pericardium, myocardium, valvular tissue, and coronary arteries. The aim of this study was to describe the clinical, biological, and radiological presentation of lupus myocarditis (LM) as well as the treatment response and longterm outcomes.. We conducted a multicentric retrospective study of LM from January 2000 to May 2014.. Twenty-nine patients (3 men and 26 women) fulfilled the inclusion criteria (median age at the diagnosis of SLE: 30 yrs, range 16-57). Myocarditis was the first sign of SLE in 17/29 cases (58.6%). Troponin was elevated in 20/25 cases. Electrocardiogram results were abnormal in 25/28 cases. Echocardiography revealed low (≤ 45%) left ventricular ejection fraction (LVEF; 19/29, 66%) and pericardium effusion (20/29, 69%). Cardiac magnetic resonance imaging revealed delayed gadolinium enhancement in 9/13 patients (69%). Patients were treated with corticosteroids (n = 28), cyclophosphamide (CYC; n = 16), intravenous immunoglobulins (n = 8), and/or mycophenolate mofetil (n = 2). The median followup was 37 months. One month after the beginning of the treatment, 10/23 patients (43%) who had undergone echocardiography had an LVEF ≥ 55%. At the end of followup, 21/26 patients (81%) exhibited an LVEF ≥ 55%. Three patients died during followup, and 2 died from LM.. LM is a severe manifestation of SLE. It can be the first manifestation of the disease or it can occur during followup, in particular in untreated patients. However, the longterm prognosis is typically positive. Patients with less severe disease exhibited good LVEF recovery without CYC.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Cyclophosphamide; Echocardiography; Female; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Magnetic Resonance Imaging; Male; Middle Aged; Mycophenolic Acid; Myocarditis; Retrospective Studies; Symptom Assessment; Treatment Outcome; Young Adult

Topics: Acute Disease; Antiviral Agents; Child, Preschool; Female; Humans; Immunosuppressive Agents; Interferon-beta; Male; Methylprednisolone; Mycophenolic Acid; Myocarditis; Parvoviridae Infections; Stroke Volume

Topics: Antilymphocyte Serum; Extracorporeal Membrane Oxygenation; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Myocarditis; Treatment Outcome

Topics: Adult; Arthralgia; Cyclosporine; Diagnosis, Differential; Female; Humans; Hypotension; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Mycophenolic Acid; Myocarditis; Treatment Outcome

Experimental autoimmune myocarditis (EAM) is characterized by the appearance of multinucleated giant cells. EAM leads to severe myocardial damage and is a useful model of human giant cell myocarditis. We investigated whether mycophenolate mofetil (MMF), which is a potent immunosuppressant, prevents the development of myocarditis in a rat EAM model, and focused on the role of osteopontin (OPN) in the pathogenesis of this disorder. Adult Lewis rats were immunized with porcine cardiac myosin to establish EAM. The early MMF treatment completely prevented the development of EAM, and the late MMF treatment was also effective even against established EAM. Echocardiogram demonstrated that left ventricular function was also improved by the treatment with MMF. Real-time RT-PCR analysis showed that both early and late MMF treatments significantly inhibited myocarditis-induced OPN mRNA expression in the heart. Immunohistochemistry revealed that OPN expression was prominent in the myocardium on day 14, whereas expression was observed in the infiltrated macrophages on day 21. Mycophenolic acid (MPA) did inhibit agonist-induced OPN expression in cultured cardiomyocytes. These results show the therapeutic potential of MMF for autoimmune myocarditis and provide new insights into the pathogenesis of this disease.

Topics: Animals; Animals, Newborn; Autoimmune Diseases; Body Weight; Cells, Cultured; Disease Models, Animal; Echocardiography; Heart Ventricles; Immunohistochemistry; Immunosuppressive Agents; Male; Mycophenolic Acid; Myocarditis; Myocardium; Myocytes, Cardiac; Organ Size; Osteopontin; Rats; Rats, Inbred Lew; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sialoglycoproteins; Time Factors

Viral replication as well as an immunopathological component are assumed to be involved in the development of coxsackie B virus (CBV)-induced myocarditis. We observed that mycophenolic acid (MPA), the active metabolite of the immunosuppressive agent mycophenolate mofetil (MMF), inhibits coxsackie B3 virus (CBV3) replication in primary Human myocardial fibroblasts. We therefore studied whether MMF, which is thus endowed with a direct antiviral as well as immunosuppressive effect, may prevent CBV-induced myocarditis in a murine model.. Four week old C3H-mice were infected with CBV3 and received twice daily, for 7 consecutive days (from one day before to 5 days post-virus inoculation) treatment with MMF via oral gavage. Treatment with MMF resulted in a significant reduction in the development of CBV-induced myocarditis as assessed by morphometric analysis, i.e. 78% reduction when MMF was administered at 300 mg/kg/day (p < 0.001), 65% reduction at 200 mg/kg/day (p < 0.001), and 52% reduction at 100 mg/kg/day (p = 0.001). The beneficial effect could not be ascribed to inhibition of viral replication since titers of infectious virus and viral RNA in heart tissue were increased in MMF-treated animals as compared to untreated animals.. The immunosuppressive agent MMF results in an important reduction of CBV3-induced myocarditis in a murine model.

Topics: Animals; Cells, Cultured; Chlorocebus aethiops; Dose-Response Relationship, Drug; Enterovirus B, Human; Enterovirus Infections; Humans; Immunosuppressive Agents; Male; Mice; Mice, Inbred C3H; Mice, Inbred Strains; Mycophenolic Acid; Myocarditis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Viral; Vero Cells; Virus Replication

"Panel Reactive Antibody" (PRA) testing is commonly used to assess the pretransplant antibody status in order to estimate the risk of an adverse humoral response following transplantation. We report on a female patient with end-stage cardiac failure suffering from acute myocarditis who underwent implantation of a left-ventricular assist device (Novacor, Baxter Healthcare Corp. Oakland, CA). During evaluation for heart transplantation, a PRA level of 50-70% was detected. After treatment with mycophenolate mofetil at a dosage of 2 g daily, PRA levels declined within one week to 0-5%, and remained low after discontinuation of the immunosuppressive drug. We feel that pretreatment of patients with elevated PRA levels with mycophenolate mofetil is well justified.

Topics: Acute Disease; Adult; Antibodies, Monoclonal; Antibody Formation; Anticoagulants; Female; Follow-Up Studies; Heart Failure; Heart Transplantation; Heart-Assist Devices; Humans; Immunosuppressive Agents; Mycophenolic Acid; Myocarditis; Preoperative Care; Thrombophlebitis