Rheumatic fever which valve

In severe cases, treatment may include surgery to replace or repair a badly damaged valve. The best treatment is to prevent rheumatic fever. Antibiotics can usually treat strep infections and keep rheumatic fever from developing. Anti-inflammatory drugs may be used to reduce inflammation and lower the risk of heart damage. Other medicines may be needed to manage heart failure. People who have had rheumatic fever are often given daily or monthly antibiotic treatments, possibly for life, to prevent recurrent infections and lower the risk of further heart damage.

To reduce inflammation, aspirin, steroids, or non-steroidal medicines may be given. Heart failure. This can occur from either a severely narrowed or leaking heart valve. Bacterial endocarditis. This is an infection of the inner lining of the heart, and may occur when rheumatic fever has damaged the heart valves. Complications of pregnancy and delivery due to heart damage. Women with rheumatic heart disease should discuss their condition with their healthcare provider before getting pregnant.

Ruptured heart valve. This is a medical emergency that must be treated with surgery to replace or repair the heart valve. Rheumatic heart disease can be prevented by preventing strep infections or treating them with antibiotics when they do occur. You will need to have ongoing follow-up with your healthcare provider to check the condition of your heart. Depending on the amount of heart damage, you may have some activity restrictions. As general pathomorphological findings, mitral valve specimens from patients at end state disease are thick and stiff due to a high degree of fibrosis Figures 1A,B.

As this process stretches over decades, different morphological changes dominate the various phases. While leaflets are usually minimally fibrose and pliable in three quarters of patients younger than 30 years of age, they are scared and ridged in two thirds of patients older than 40 years.

Different morphological manifestations also lead to different clinical symptoms. In most late cases, the valve commissures are fused and often endothelium surface erosion is observed. Chordae tendineae show fusion and shortening Figure 1B , which may reduce subvalvular chordal space 12 , Accumulating studies had shown that lipids may trigger vascular calcification associated with atherosclerosis.

Therefore, it is possible that RHVD patients who develop valve calcification have altered cholesterol profile. It still remains a gap of knowledge in RHVD research. Figure 1. Gross pathology and histological aspects of rheumatic mitral valve at the end stage of RHVD. A,B Atrial and ventricular sides of mitral valves excised from female, 49 year-old patient, showing thick leaflets with retraction.

C Mitral valve excised from male, 61 year-old, showing calcification. D Representative Hematoxylin and Eosin staining of anterior mitral valve leaflet showing presence of nodular calcification. Figure 2. Histological comparison between normal mitral valves and rheumatic mitral valves. A Masson trichrome staining showing focal fibrosis and thickening of rheumatic mitral valves. Representative images are shown.

C Picrosirius red staining showing uneven collagen deposition. Mitral valves are populated by two major types of cells: valvular endothelial cells VEC , covering the leaflets, on both atrial and ventricular sites; and valvular interstitial cells VIC , quiescent fibroblast-like cells, which are important in the homeostatic remodeling of matrix constituents 16 — In disease state, cell composition shifts toward contractile and collagen-producing myofibroblast-like cells leading to fibrotic changes and stiffness of leaflets Figure 2A Mitral valve is composed of three layers of specialized connective tissue between the two endothelial layers and its architecture substantially changes during RHVD progression.

Anatomical features of mitral valve can be associated with its preferential involvement in this disorder. However, the underlying mechanisms of mitral valve predominant involvement in RHVD are unknown.

Although more than five decades passed after the pioneering studies on the pathogenesis of RHVD, little progress has been made in respect of the cellular and molecular aspects, which lead to the destruction of the valve tissue. In RHVD patients, the generation of an antibacterial immune response starts in the pharyngeal epithelium by innate immune components such as neutrophils, macrophages, and dendritic cells.

These cells recognize and process bacterial antigens and present them to B lymphocytes, culminating in the production of immunoglobulins that are able to recognize epitopes in several host sites and activate T cells. Still a mystery the mechanisms involved in the loss of self-tolerance in RHVD and how immune system target heart valvular tissue, especially mitral valve.

Autoimmune valvular carditis are mainly described in literature as associated with human rheumatic conditions, however, it is possible that autoreactive antibodies can be associated with pathology of other HVD, including CAVD. Ectopic calcification and autoimmunity has been also explored in atherosclerosis 21 , Multiple bacterial antigens are involved in RHVD damage.

These molecules share structural similarity with host cardiac myosin, laminin, vimentin, and tropomyosin. Many studies point to M protein as the most virulent protein 23 , Although myosin is present in the myocardium but not in the valvular tissue, anti-myosin antibodies respond against GlcNac epitope due to similar structures of common alpha-helical sequences and glycosylated proteins It is assumed that myosin is an intracellular protein and therefore immunologically inaccessible, and thus does not participate as the initial target of cross-reactive antibodies.

However, after initial mild endothelial breakdown, intracellular epitopes may contribute to robust amplification of the immune response due to increased availability of binding sites for anti-myosin antibodies. Investigations have highlighted an important participation of GlcNac antigens in RHVD pathogenesis, since persistent levels of anti-GAS antibodies were correlated with valvulitis. It is also observed that after valve replacement the serum levels of anti-GAS were reduced 23 , In non-rheumatic valve disease, the triggering factors leading to cardiovascular calcification, as in CAVD are still under investigation Although pan-carditis occurs in the early disease stages, it is reversible, and only the valvular damage is permanent, especially in mitral valve.

Mitral valve damage is initiated by circulating autoantibodies that bind to the endothelial surface of the valves, leading to increased expression of vascular cell adhesion protein 1 VCAM The activated endothelium facilitates the infiltration of T lymphocytes into the valvular subendothelium at the endocardium site, leading to edema and elongation of the chordae tendinae 28 , Due to tissue injury, components of ECM are exposed and anti-collagen antibodies are produced.

These antibodies can deposit in the valve contributing to pro-inflammatory environment. All these changes cause the heart valves to be a vulnerable immune-privileged site for injury. The role of anti-collagen antibodies will be addressed in more details below. It is important to comment that typically the first streptococcus throat infection does not trigger an episode of rheumatic fever.

Recent studies have shown that continuous infections maintain the germinal center reaction and affinity for antibody maturation 30 , As such, preexisting immune complexes would capture more immunoglobulin leading to amplification of the immune response, which further favors the recognition of several self-antigens and propagate tissue damage.

Thus, repeated infections feed the disease onset To date, no evidence exists that the isolated presence of valve-reactive antibodies in the serum of RHVD patients is sufficient to produce the valve lesion, suggesting the importance of cellular response besides humoral components.

In addition, autoantibodies are often found in patients after uncomplicated streptococcal pharyngitis and in healthy individuals. Humoral and cellular response acts together in autoimmune diseases. It is known that women produce more immunoglobulin than men, and the X chromosome contains over 1, genes, while the Y chromosome only has about a Immune cells express estrogen and androgen receptors, and engagement of these receptors affects lymphocyte responses Thus, is likely that endogenous hormones are key mediators of disease progression.

Overexpressed X-linked immune genes and estradiol probably act in a synergistic manner, leading to a greater female-biased predisposition in RHVD. These data support that T cells are sufficient to induce inflammation, not requiring the presence of cross-reactive antibodies to trigger valvulitis Although some studies showed that the presence of antibodies is not crucial in triggering RHVD pathogenesis, it is important to emphasize that the ability of antibodies to become self-reactive will depend on the combination of factors such as genetic background, recurrence of infections, and strain virulence.

These variables make it even more challenging to fully understand the mechanisms associated with the development of valve lesions. The inflammatory infiltrate described in the rheumatic mitral valve of patients in the end state of disease are predominantly composed of mononuclear cells Figure 3C , mainly helper Th - CD4, and cytotoxic—T CD8 lymphocytes, macrophages and B cells 37 , The effector function and therefore the contribution of these cells in the pathogenesis of RHVD is largely associated with the profile of cytokines and other soluble mediators produced by them that lead to differentiation of VICs to activated collagen-producing myofibroblast Figure 3.

Schematic representation of the mechanisms of the pathogenesis of rheumatic heart valve disease. Activated B cells produce antibodies that are able to recognize epitopes in several sites in the host and also activate T lymphocytes.

In the heart, cross reactive T cell clones and antibodies act against heart valve constituents leading to an intense inflammatory process culminating in valve dysfunction. In addition, these cells are able to differentiate into various repertoires of subpopulations producing diverse cytokines leading to the development of different degrees of cross-reactivity 40 — Th1 cytokines are pro-inflammatory soluble mediators involved in host defense and also crucial to autoimmunity.

In the RHVD context, some studies have evaluated the expression of different inflammatory cytokines in the valvular tissue, however cell sources of these cytokines and contributions of each cellular subpopulation to the cytokine production remain unknown.

IL-1 is a key cytokine in autoimmune disease and has also been shown to be associated with inflammatory damage, especially in the acute phase of rheumatic disease 46 , IL-2 is an essential cytokine initiating generation of regulatory T cells Tregs , which play a vital role in the maintenance of immune tolerance.

Low levels of IL-2 and deficiency of circulating Tregs were associated with rheumatic mitral valve disease 44 , 52 , Moreover, patients who presented multiple valve impairment showed a greater deficiency in the number of Tregs This cell subset plays opposite roles as compared to Tregs in autoimmune diseases.

In the context of RHVD, it was shown to be associated with progression of the disease toward chronic state in an experimental model Peripheral blood cells from patients with rheumatic mitral valve disease showed an increased number of Th17 cells and high serum levels of IL as compared to healthy individuals The onset of rheumatic fever usually occurs about two to four weeks after a strep throat infection.

Rheumatic fever signs and symptoms — which result from inflammation in the heart, joints, skin or central nervous system — can include:. Proper treatment of strep throat can prevent rheumatic fever. Also, have your child see a doctor if he or she shows other indications of rheumatic fever.

Rheumatic fever can occur after a throat infection from a bacteria called group A streptococcus. Group A streptococcus infections of the throat cause strep throat or, less commonly, scarlet fever. Group A streptococcus infections of the skin or other parts of the body rarely trigger rheumatic fever.

The link between strep infection and rheumatic fever isn't clear, but it appears that the bacteria trick the immune system. The strep bacteria contain a protein similar to one found in certain tissues of the body. The body's immune system, which normally targets infection-causing bacteria, attacks its own tissue, particularly tissues of the heart, joints, skin and central nervous system. This immune system reaction results in swelling of the tissues inflammation. If your child receives prompt treatment with an antibiotic to eliminate strep bacteria and takes all medication as prescribed, there's little chance of developing rheumatic fever.

If your child has one or more episodes of strep throat or scarlet fever that aren't treated or aren't treated completely, he or she might develop rheumatic fever. Inflammation caused by rheumatic fever can last a few weeks to several months. In some cases, the inflammation causes long-term complications. Rheumatic fever can cause permanent damage to the heart rheumatic heart disease. Rheumatic fever is caused by certain strains of streptococcal bacteria.

A strep throat infection that isn't properly treated can trigger rheumatic fever. Rheumatic fever can damage heart muscle and heart valves. Not all people who have rheumatic fever develop rheumatic heart disease. This infection causes swelling and muscle damage to the heart.

It can also damage the heart valves in a way that keeps the blood from moving through the heart normally. The infection can cause heart valve leaflets to stick together, which narrows the valve opening. Also, the infection can scar the valves. This keeps the valves from closing tightly, so blood leaks backward in the heart. If the aortic valve is narrowed, this problem is called aortic valve stenosis. If the mitral valve is narrowed, this problem is called mitral valve stenosis.