Immunome Research
Open Access

The Role of Autoimmune and Infectious Triggers of Giant Cell Myocarditis and its Clinical Management

Lucas Davis^{* *}Correspondence: Lucas Davis, Department of Immunology, University of Sydney, Sydney, Australia, Email:

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Description

Immune system dysregulation can lead to various autoimmune and inflammatory conditions, one of which is Giant Cell Myocarditis (GCM). This rare and severe form of myocarditis involves inflammation of the heart muscle, often associated with giant cells in the myocardium. GCM is primarily caused by an immune-mediated response, which leads to the destruction of the heart muscle. The most common cause is autoimmune dysregulation, where the body’s immune system mistakenly targets its own tissues, specifically the heart. This immune response may be triggered by viral infections, such as those caused by coxsackievirus, adenovirus and human herpesvirus. These infections can induce a cascade of immune responses, leading to inflammation of the heart muscle. Other potential causes of GCM include drug reactions, specifically from medications like checkpoint inhibitors used in cancer immunotherapy, which can alter immune responses. Genetic predispositions and other environmental factors may also contribute to an increased risk of GCM in susceptible individuals.

Mechanism of immune system dysregulation in GCM

The immune system dysregulation in GCM involves both cellular and humoral components of immunity. Initially, the infection or immune stimulus leads to the activation of immune cells, including T-cells, macrophages and dendritic cells. These immune cells migrate to the myocardium, where they promote inflammation.

One key feature of GCM is the formation of multinucleated giant cells, which are large, abnormal cells created by the fusion of individual macrophages. These cells play a critical role in the inflammatory response, as they release pro-inflammatory cytokines and other immune mediators that exacerbate the tissue damage in the myocardium. The chronic inflammation leads to cardiomyocyte injury, fibrosis and ultimately, heart dysfunction.

In addition to giant cells, T-cells play a significant role in GCM pathogenesis. Specifically, CD8+ cytotoxic T-cells are implicated in the direct destruction of heart muscle cells. The abnormal activation of these immune cells results in severe inflammation and damage to the myocardium, disrupting normal heart function.

Source and treatment of GCM

The primary source of GCM lies in the immune system’s response to external triggers, such as infections, drugs, or autoimmunity. Although viral infections are among the most common sources, there is also evidence that genetic factors can predispose individuals to immune dysregulation. Certain autoimmune diseases, such as systemic lupus erythematosus and inflammatory bowel disease, may increase the risk of developing GCM.

Moreover, GCM has been observed following the administration of immune checkpoint inhibitors used in cancer treatment. These drugs, such as nivolumab and pembrolizumab, can lead to the activation of autoreactive T-cells, triggering inflammation in various organs, including the heart.

The treatment of GCM is challenging, as it requires a multifaceted approach involving immunosuppressive therapy, supportive care and, in some cases, heart transplantation. The main goal of treatment is to control the inflammatory response, prevent further damage to the myocardium and improve the patient's cardiac function.

Immunosuppressive therapy

The foundation of treatment for GCM is the use of immunosuppressive drugs to reduce the activity of the immune system. Steroids such as prednisone are typically used to control inflammation. However, due to the severe and progressive nature of GCM, additional immunosuppressive agents may be required, including azathioprine, mycophenolate mofetil and cyclophosphamide. These drugs help suppress the immune response, reducing the number of immune cells attacking the myocardium.

Antiviral and antimicrobial therapy: In cases where a viral infection is suspected to be the trigger, antiviral or antimicrobial treatment may be initiated. However, the use of these agents remains controversial, as not all cases of GCM are directly caused by infections.

Heart failure management: Supportive treatments for heart failure are also crucial. Medications such as Angiotensin- Converting Enzyme (ACE) inhibitors, beta-blockers and diuretics may be used to alleviate symptoms of heart failure and improve the heart’s ability to pump blood.

Heart transplantation: In cases where the heart failure is refractory to treatment and the patient’s condition continues to deteriorate, heart transplantation may be considered. This is typically a last resort for individuals with end-stage GCM who do not respond to other therapies.

Immunotherapy for drug-induced GCM

For patients whose GCM is triggered by immune checkpoint inhibitors or other drugs, stopping the offending drug is essential. Additionally, immunotherapy may be required to manage the immune-mediated inflammation.

GCM is a severe inflammatory condition characterized by immune system dysregulation and destruction of the heart muscle. The causes are multifactorial, with viral infections, drug reactions and autoimmune conditions being the primary contributors. The pathogenesis of GCM involves the activation of immune cells, particularly T-cells and giant cells, leading to inflammation and cardiomyocyte injury. Treatment involves immunosuppressive therapy, heart failure management and, in some cases, heart transplantation. Early diagnosis and intervention are important to improving outcomes for individuals with GCM.