Rheumatic Heart Disease
Gbemiga Sofowora
INTRODUCTION
Acute rheumatic fever and rheumatic heart disease remain prevalent in the developing world although their incidence has declined substantially in Western countries, except in certain pockets, because of improved health care services, hygiene, and accommodation.1,2 Developing countries are cognizant of the need for progress in preventing and treating acute rheumatic fever and its sequelae. In Africa, the Addis Ababa communique was launched to put forth recommendations to assist with the eradication of rheumatic heart disease, particularly in hyperendemic areas.3 Reports of successful implementation are not yet available, but this may serve as a template for future programs in other similarly hyperendemic areas.4
Epidemiology
The global burden of group A streptococcus is estimated to be at least 18.1 million cases with 1.78 million cases yearly,4 and the greatest burden is due to rheumatic heart disease, with a prevalence of 15.6 million cases and an estimated 282,000 new cases occurring yearly. These cases occur disproportionately in developing countries and among migrants and socioeconomically disadvantaged populations, as well as indigenous populations in high-income countries. Widespread availability of penicillin G, better housing and hygiene, and the health care access that exists in the United States and Western Europe have contributed to the decline in these regions, although variations in population susceptibility to disease have also been proposed.5
The mean incidence of first attack of acute rheumatic fever per annum ranged from 5 to 51 per 100,000 with a mean of 19 per 100,000 (95% confidence interval [CI]: 9 to 30 per 100,000) in a study,6 with the highest mean annual incidences found in India (51 per 100,000) and the Maori community in New Zealand (>80 per 100,000). Low incidence rates (≤10/100,000) were found in the United States and Western Europe and higher rates in Asia, Australasia, and the Middle East. It must be noted that accurate figures are hard to come by in regions of sub-Saharan Africa and Asia.
In 2015, the age-standardized prevalence of rheumatic heart disease was estimated to be approximately 444 per 100,000 in countries that showed an endemic pattern versus 3.4 per 100,000 in countries that did not show an endemic pattern. The endemic pattern in the study was defined as “having a high mortality and prevalence among children” versus the nonendemic pattern with low mortality and prevalence mostly among adults. This prevalence was highest in Oceania, central sub-Saharan Africa, and South Asia.7 Most epidemiologic estimates of disease come from clinical data. Comparing clinical data with the use of echocardiographic data, Marijon et al.7 showed that echocardiography was 10 times more sensitive in picking up cases of rheumatic heart disease in Cambodia and Mozambique than clinical data alone. This suggests that our estimates of the global burden of this disease may be grossly underestimated.
More recent figures show the largest numbers of deaths in 2015 because of rheumatic heart disease in India (119,100), China (72,600), and Pakistan (18,900),8 although statistics are somewhat skewed by such large populations. The highest estimated age-standardized death rates because of rheumatic heart disease occurred in the Central African Republic and Lesotho in Africa, the Solomon Islands, Pakistan, Papua New Guinea, Kiribati, Vanuatu, Fiji, India, the Federated States of Micronesia, and the Marshall Islands.
PATHOGENESIS
Acute rheumatic fever is preceded by infection with rheumatogenic strains of Lancefield group A β-hemolytic streptococci (Streptococcus pyogenes) usually in the form of pharyngitis. There is exception in Australia among the aboriginal people who have one of the highest rates of acute rheumatic fever and rheumatic heart disease in the world, and colonization of the throat with group A streptococcus and symptomatic pharyngitis are uncommon. In this community, group A streptococcus infections of the skin (pyoderma) and group C and G streptococci are thought to account for the higher incidence, suggesting that epidemiology may vary from region to region.9
In populations exposed to rheumatogenic strains of S. pyogenes, the cumulative incidence of acute rheumatic fever is between 3% and 6%, implicating host susceptibility as a factor in the transmission of this disease. That genetic factors may also play a part in the susceptibility to acute rheumatic fever was highlighted by the fact that, in a meta-analysis of 175 monozygotic twins and 260 dizygotic twins,10 concordance between monozygotic twins was six times that of dizygotic twins. The major histocompatibility complex human leukocyte antigen (HLA) molecules are attractive candidates that may determine susceptibility, and research in this area is still ongoing.11 Early findings using genome-wide association studies point to HLA-DQA1-HLA-DQB2 regions as well as the immunoglobulin heavy chain locus on chromosome 14.12
After pharyngeal infection with Lancefield group A β-hemolytic streptococci, approximately 3% to 6% of the population will develop acute rheumatic fever, which generally occurs 2 to 5 weeks after onset of the pharyngitis and may indicate development of antibodies against host tissues. The antibodies formed are specific to the M moiety on the bacteria, which confer it with the ability to attach to host tissues. These M proteins are similar in structure to cardiac myosin, tropomyosin, actin, and laminin, so that repeated infection leads to development of autoantibodies against these structures on valves. In support of this fact, the vast majority of patients with acute rheumatic fever have elevated titers of antibodies to streptococcal antigens including antistreptolysin O (ASO), anti-DNase B, and anti-group A carbohydrate. Although much is still unknown about its pathogenesis, it is thought that there is ultimately autoantibody-mediated injury, leading to destruction and scarring of the valves. These autoantibodies also lead to inflammation of the joints, brain, and subcutaneous tissues, contributing to the features of acute rheumatic fever. Repeated or ongoing infections possibly drive the inflammation of the heart valves over subsequent years, leading to rheumatic heart disease.
Natural History
Following infection with Lancefield group A streptococcus, 3% to 6% of patients will develop acute rheumatic fever.13 The most common age group is 5 to 15 years with no gender predominance. Most persons with acute rheumatic fever present with polyarthritis, which is usually migratory, symmetrical, and tends to involve the larger joints, mainly the knees, ankles, wrist, elbows, and shoulders. Carditis occurs in fewer patients than arthritis, whereas Sydenham chorea occurs in only about a quarter of patients with acute rheumatic fever and tends to be predominantly female. The skin features of erythema marginatum (Figure 9.1) and subcutaneous nodules occur less frequently than the other symptoms, and the subcutaneous nodules may not be present at all. These cardinal symptoms if left untreated usually resolve within 3 months. Years later, in some cases up to decades, the features of rheumatic heart disease appear with predominant mitral valve involvement.
 FIGURE 9.1 A,B: The rash of erythema marginatum begins as a serpiginous area of erythema, and the margins of the rash progress as the center clears. It primarily occurs over the trunk and proximal extremities. A: Erythema marginatum in an adult with rheumatic fever. B: Closer view of rash. (Courtesy of P. Witman, Mayo Clinic. Used with permission of Mayo Foundation for Medical Education and Research. All rights reserved.) |
CLINICAL PRESENTATION
Acute rheumatic fever may present with the following features:
Arthritis occurs in most people with acute rheumatic fever and is usually described as a migratory, symmetric, aseptic polyarthritis, which most commonly affects the knees, ankles, wrists, elbows, and shoulder joints. Symptoms of pain and swelling are generally present and last about 5 to 7 days before affecting another joint. Aspiration of a joint typically does not yield bacteria. In select hyperendemic communities, however, a monoarthritis has been described,14 and a revision of the Jones Criteria recommends “at present, consideration that monoarthritis may be part of the acute rheumatic fever spectrum should be limited to patients from moderate to high risk populations (Class 1; Level of Evidence C).”15
Carditis usually described as a pancarditis affects mainly the valves and is better described as a valvulitis. The mitral valve is the most commonly affected, and mitral regurgitation is the most common valve lesion seen. If severe, the patient may present with signs and symptoms of congestive heart failure with shortness of breath with exertion, paroxysmal nocturnal dyspnea and orthopnea with rales and edema on examination as well as tachycardia, and a third heart sound on auscultation. Murmurs include a holosystolic murmur of mitral regurgitation heard at the apex that radiates to the axilla, an apical mid-diastolic flow murmur (Carey Coombs murmur), and an aortic diastolic murmur heard at the base and radiating down the left sternal border.
Pericarditis with a pericardial rub best heard over the second or third interspace and a pericardial effusion may be noted on echocardiography.
Sydenham chorea (St Vitus dance, St Johannis’ chorea) may be due to the effect of autoantibodies on the basal ganglia and occurs in 26% of patients with acute rheumatic fever.16 Patients with Sydenham chorea are usually female and between 5 and 15 years. St Vitus dance is characterized by jerky, involuntary, semi-purposeful movements involving the face and limbs with emotional lability and personality disorders. These movement disorders tend to abate during sleep. The chorea presents as gait changes, a tendency to drop objects, and bursts of dysarthric speech (Sydenham speech).
Psychological features range from emotional lability and anxiety to frank obsessive compulsive disorder and tend to precede the movement disorders by 2 to 4 weeks.
Muscle weakness typically characterized by the inability of the patient to sustain a muscle contraction (milkmaid’s grip) usually resolves within a few months with no permanent sequelae.
Erythema marginatum (Figure 9.1) is a nonpruritic, serpiginous rash that is usually located over the trunk and proximal limbs and appears intermittently over weeks to months as transient macules that tend to heal in the center while advancing at the margins. The appearance of this rash may be induced by heat, and the macules blanche with pressure.
TABLE 9.1 Revised Jones Criteria
A. For all patient populations with evidence of preceding GAS infection
Diagnosis: initial ARF
Two major manifestations or one major plus two minor manifestations
Diagnosis: recurrent ARF
Two major or one major and two minor or three minor
B. Major criteria
Low-risk populationsa
Moderate- and high-risk populations
Carditisb (clinical or subclinical)
Carditis (clinical or subclinical)
Arthritis (polyarthritis only)
Arthritis (monoarthritis, polyarthritis or polyarthralgia)c
Chorea
Chorea
Erythema marginatum
Erythema marginatum
Subcutaneous nodules
Subcutaneous nodules
C. Minor criteria
Low-risk populationsa
Moderate- and high-risk populations
Polyarthralgia
Monoarthralgia
Fever (≥38.5 °C)
Fever (≥38 °C)
Prolonged PR interval, after accounting for age variability (unless carditis is a major criterion)
Prolonged PR interval, after accounting for age variability (unless carditis is a major criterion)
ARF, acute rheumatic fever; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; GAS, group A streptococcal infection.
a Low-risk populations are those with ARF incidence ≤2 per 100,000 school-aged children or all-age rheumatic heart disease prevalence of ≤1 per 1000 population per year.
b Subclinical carditis indicates echocardiographic valvulitis as defined in Table.9.4.
c Polyarthralgia should only be considered as a major manifestation in moderate- to high-risk populations after exclusion of other causes. As in past versions of the criteria, erythema marginatum and subcutaneous nodules are rarely “stand-alone” major criteria. Additionally, joint manifestations can only be considered in either the major or minor categories but not both in the same patient.
d CRP value must be greater than upper limit of normal for laboratory. Also, because ESR may evolve during the course of ARF, peak ESR values should be used.
Reprinted with permission from Gewitz MH, Baltimore RS, Tani LY, et al; American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young. Revision of the Jones Criteria for the diagnosis of acute rheumatic fever in the era of Doppler echocardiography: a scientific statement from the American Heart Association. Circulation. 2015;131(20):1806-1818. Copyright © 2015 American Heart Association, Inc.
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