Rheumatic Fever in Emergency Medicine 

Updated: Feb 02, 2018
Author: Steven J Parrillo, DO, FACOEP, FACEP; Chief Editor: Barry E Brenner, MD, PhD, FACEP 

Overview

Practice Essentials

Acute rheumatic fever (ARF) is a sequela of a previous group A streptococcal infection, usually of the upper respiratory tract. Group A strep pharyngitis is most common in children 5-15 years of age, but can occur in persons of any age. Children with confirmed group A strep pharyngitis should be treated with antibiotics to reduce risk of developing ARF.[1]

Major manifestations of ARF comprise the following (see Presentation):

  • Carditis, clinical and/or subclinical (ie, detected by echocardiography)
  • Arthritis
  • Chorea
  • Erythema marginatum
  • Subcutaneous nodules

In the emergency department, treatment includes measures to relieve pain and inflammation, ameliorate heart failure, and control chorea (see Treatment and Medication).

Background

Rheumatic fever causes chronic progressive damage to the heart and its valves and is the most common cause of pediatric heart disease in the world. Until 1960, it was a leading cause of death in children and a common cause of structural heart disease. The disease has been known for many centuries. Baillou (1538-1616) first distinguished acute arthritis from gout. Sydenham (1624-1668) described chorea but did not associate it with acute rheumatic fever (ARF). In 1812, Charles Wells associated rheumatism with carditis and provided the first description of the subcutaneous nodules. In 1836, Jean-Baptiste Bouillaud and, in 1889, Walter Cheadle published classic works on the subject.

The association between sore throat and rheumatic fever was not made until 1880. The connection with scarlet fever was made in the early 1900s. In 1944, the Jones criteria were formulated to assist disease identification. These criteria, with some modification, remain in use today. The introduction of antibiotics in the late 1940s allowed for the development of treatment and preventive strategies. Dramatic declines in the incidence of rheumatic fever are thought to be largely due to antibiotic treatment of streptococcal infection. However, there are pockets where the incidence is significant, especially in tropical areas.

Research into the subtypes of streptococci has made it clear that differences among those types are also responsible for both the decline in the overall incidence of ARF, as well as of isolated outbreaks.

The most recent advance is the recognition that there is genetic predisposition to development of acute rheumatic fever, though the exact reason is still a matter of research.[2, 3]

Pathophysiology

Acute rheumatic fever is a sequela of a previous group A streptococcal infection, usually of the upper respiratory tract. This is an autoimmune response secondary to molecular mimicry following group A streptococcal pharyngitis. One beta-streptococcal serotype (eg, M types 3, 5, 18, 19, 24) is linked directly to acute rheumatic fever. Non–group A streptococci have never been shown to cause this disease.

Good evidence suggests that there is genetic susceptibility to development of the disease. Several studies have shed light on genetic predisposition.[2, 3] Susceptibility studies have focused on human leukocyte antigens, B-cell alloantigens, and cytokine genes. Study results, however, often conflict.[2]

Some have questioned the possibility that viruses may also be implicated as a correlating cause; however, most studies have shown no correlation, with the single exception of Epstein-Barr virus. In that setting, one author found DNA positivity in acute cases but not in controls.[4]

The disease involves the heart, joints, central nervous system (CNS), skin, and subcutaneous tissues. It is characterized by an exudative and proliferative inflammatory lesion of the connective tissue, especially that of the heart, joints, blood vessels, and subcutaneous tissue.

Epidemiology

Frequency

United States

The prevalence of acute rheumatic fever (ARD) in the United States is a function of socioeconomic status, with higher frequency in areas of crowding. The United States had experienced a resurgence of rheumatic fever in the last 2 decades, with many of the reported cases involving persons in upper socioeconomic groups. The reason for this disparity is unclear but may be caused by the emergence of more virulent strains of group A streptococci. The overall incidence has been declining in developed nations but is still rampant in less developed ones.

The incidence is low in most parts of the country but is variable. In a study published in 2006, Martin and Barbadora showed that the disease remains a problem in western Pennsylvania with 121 new cases from 1994-2003.[5] Consistent with earlier reports, most patients were children and most had carditis. Curiously, most studies report that rheumatic fever is very unusual if not rare in developed countries, but remains a major problem in developing nations.[6, 7]

ARF is common among American Samoans in Hawaii.[8]

Frequency of streptococcal infection, virulence of the bacterial strain, and M protein subtypes determine the incidence of rheumatic fever in the population.

As a sequela of beta-streptococcal exposure, ARF occurs during the school-aged years when streptococcal pharyngitis is most prevalent. Similarly, prevalence is higher in the colder months of the year when streptococcal pharyngitis is most likely to occur.

International

ARF is a major problem in the high-risk areas of the tropics, in countries with limited resources, and in communities with minority indigenous populations. Although older literature estimates that 25-40% of cases worldwide appear in those nations, a more recent paper suggests the figure may be closer to 95%.[9]

In those less developed nations, post ARF heart disease is the most commonly acquired heart disease in hospitalized children, adolescents, and young adults.[6] ARF is clearly still a major problem is less developed areas of the world.[10] In some areas, the incidence of this entity exceeds that of congenital heart disease. Some studies point out the association with heart failure and death in pregnant women. McDonald et al have suggested that in Aboriginal communities of central and northern Australia, group A streptococcal pyoderma is much more likely to cause acute rheumatic fever than is streptococcal pharyngitis.[11]

Wang et al reported on a possible ARF resurgence in Taiwan.[12] Authors in India and Turkey make a plea for more liberal application of the Jones criteria in order to avoid misdiagnosis.[13, 14, 15] Similarly, Steer et al found a significant pocket of cases on the island of Fiji when clinicians liberally applied diagnostic criteria and followed with echocardiography.[16] Meira et al report on the high incidence in Brazil.[17] Others have reminded the medical community that good reporting of prevalence in underdeveloped nations is lacking.

Parks et al suggest that ARF is underdiagnosed in primary care clinics in the United Kingdom.[18] Other authors continue to report the problem of ARF in underdeveloped countries and in the indigenous populations of developed countries.[10]

Pastore et al studied cases in Trieste, Italy and report that ARF still occurs in industrialized countries.[19]

Marijon et al believe that the World Health Organization echocardiographic criteria for making the diagnosis in subclinical cases are inadequate. The group advocates for criteria that include valves with morphological changes consistent with rheumatic disease but without pathological regurgitation.[20]

Mortality/Morbidity

Morbidity from ARF is directly proportional to the rate of streptococcal infections. Infections that are not treated adequately are most likely to cause the major sequelae noted in the list of Jones criteria in Physical. Morbidity also is related to the care that the patient receives.

The mortality rate has declined steadily over the last 3 decades. A partial explanation for the decrease in mortality rate may be the increase in antibiotic use. In developing nations and lower socioeconomic areas where rheumatic fever is more prevalent, acute rheumatic fever is a major cause of death and disability in children and adolescents.

Cardiac involvement is the major cause of long-term morbidity. ARF causes inflammation of valvular endocardium. One or more valves (most commonly the mitral valve) may be permanently deformed. Those valves are then dysfunctional and may lead to problems including left ventricular dilation and congestive heart failure, sometimes decades later. Vegetations may develop on damaged valves and become infected leading to endocarditis. Myocarditis is present but is not the direct cause of heart failure.

Carapetis et al estimated that worldwide, approximately 60% of all patients with ARF will develop rheumatic heart disease.[21] Further, they estimate a world burden of 2.4 million children aged 5-14 years affected or a total population of 15-20 million living with rheumatic heart disease.

Patients with carditis as part of the initial episode are at greater risk of developing recurrences and of sustaining further cardiac injury. Those without carditis during the initial episode have a relatively low risk of developing carditis during recurrences, although scattered case reports of carditis occurring only during a recurrence exist.

Migratory polyarthritis occurs early in the disease course and is a common complaint for patients with rheumatic fever. Joint involvement ranges from arthralgia without objective findings to overt arthritis with warmth, swelling, redness, and exquisite tenderness. The larger joints such as the knees, ankles, elbows, and wrists are involved most frequently. An inverse relationship between severity of joint involvement and risk of carditis appears to exist.

In approximately 75% of cases, the acute attack lasts only 6 weeks. Ninety percent of cases resolve in 12 weeks or less. Fewer than 5% of patients have symptoms that persist for 6 months or more.

Literature began to appear in 1998 suggesting that acute rheumatic fever might be another disorder associated with PANDAS — pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. As of 2015, this is considered an unproven hypothesis.[22]

Race

In the United States, the attack rate is more a function of crowding than race, though the socioeconomic realities of those crowded conditions is no doubt a factor.

Sex

No sex predilection exists, except that mitral valve prolapse and Sydenham chorea occur more often in females than in males.

Age

Although individuals of any age group may be affected, most cases are reported in persons aged 5-15 years. Paulo et al report that acute rheumatic fever can be found in children younger than 5 years with no significant difference in the frequency and severity of clinical signs.[23]

Yee lists rheumatic pericarditis and myocarditis as cardiac emergencies in the first year of life.[24]

 

Presentation

History

Acute rheumatic fever (ARF) is associated with 2 distinct patterns of presentation. The first pattern of presentation is sudden onset. It typically begins as polyarthritis 2-6 weeks after streptococcal pharyngitis and is usually characterized by fever and toxicity. The second pattern is insidious or subclinical onset, which may occur if the initial abnormality is mild carditis.

Age at onset influences the order of complications. Younger children tend to develop carditis first, whereas older patients tend to develop arthritis first.

Physical

Diagnosis of acute rheumatic fever (ARF) requires a high index of suspicion. Guidelines of diagnosis from the American Heart Association (AHA) include major and minor criteria (ie, modified Jones criteria), which were updated in 2015. Laboratory evidence of a preceding group A streptococcal infection is needed whenever possible. Without it, the diagnosis of ARF is in doubt, except in patients with chorea, which may be the sole initial manifestation of ARF, and rarely in patients with indolent rheumatic carditis with insidious onset and slow progression.[25]

The AHA suggests that diagnostic criteria may be applied differently, depending on the rate of ARF or rheumatic heart disease (RHD) in the local population. This can help avoid overdiagnosis in low-incidence populations and underdiagnosis in high-risk ones. The AHA defines low risk as an ARF incidence of < 2 per 100,000 school-aged children (usually 5–14 years old) per year or an all-age prevalence of RHD of ≤1 per 1000 population per year. Children not clearly from a low-risk population are at moderate to high risk, depending on their reference population.[25]

Criteria for the diagnosis of initial ARF are the presence of two major manifestations or one major and two minor manifestations. For recurrent ARF, the criteria are two major manifestations, one major and two minor manifestations, or three minor manifestations.[25]

Major manifestations comprise the following:

  • Carditis, clinical and/or subclinical (ie, detected by echocardiography)
  • Arthritis
  • Chorea
  • Erythema marginatum
  • Subcutaneous nodules

In patients from low-risk populations, arthritis must be polyarthritis. For patients from moderate- and high-risk populations, either monoarthritis or polyarthritis qualifies; polyarthralgia may qualify if other causes have been excluded.

Minor manifestations in low-risk populations comprise the following:

  • Polyarthralgia
  • Fever ≥38.5°C
  • Acute phase reactions: Erythrocyte sedimentation rate (ESR) ≥60 mm in the first hour and/or C-reactive protein (CRP) level ≥3.0 mg/L
  • Prolonged PR interval, after accounting for age variability (unless carditis is a major criterion)

Minor manifestations in moderate- and high-risk populations comprise the following:

  • Monoarthralgia
  • Fever ≥38°C
  • ESR ≥30 mm/h and/or CRP ≥3.0 mg/dL
  • Prolonged PR interval, after accounting for age variability (unless carditis is a major criterion)

Numerous authors have suggested that changes to the Jones Criteria may be in order. For example, some have suggested that echocardiography be performed in all suspected cases in order to avoid both underdiagnosis and overdiagnosis. Carapetis and Currie suggest that cases are missed because some patients have only monoarthritis and not polyarthritis.[26] They would like to see monoarthritis become a major criterion. The same authors suggest that the set point of fever at 38ºC might be too high. Rayamajhi et al suggest that arthralgia be changed from a minor to a major Jones criterion.[27]

As mentioned above, there are authorities who suggest that less stringent echocardiographic criteria for the diagnosis of rheumatic valvular disease will increase the number of cases diagnosed.[20]

Karacan et al found several asymptomatic rhythm disturbances in children with ARF. Those without carditis often had accelerated junctional rhythm. Those with carditis often had premature contractions. The group suggests a role for 24-hour electrocardiography.[28]

Causes

Acute rheumatic fever (ARF) has been linked definitively with a preceding streptococcal infection, usually of the upper respiratory tract. Evidence is very strong that the M protein in certain streptococci subtypes is responsible for antigenicity.

Although streptococcal skin infections also are extremely common, they have not been linked with ARF in the United States. Note the suggestion by McDonald et al that pyoderma may be the cause in Aboriginal populations of Australia.[11]

See discussion under Pathophysiology for reference to genetic predisposition.

 

DDx

 

Workup

Laboratory Studies

 

The diagnosis of group A strep pharyngitis can be confirmed with a rapid antigen detection test or a throat culture, with throat culture considered the gold standard. Note that the Center for Disease Control and Prevention (CDC) advises that testing for group A beta-hemolytic Streptococcus (GABHS) pharyngitis is not routinely indicated for children younger than 3 years of age or for adults, since acute rheumatic fever (ARF) is very rare in those age groups. In children older than 3 years of age, the CDC recommends confirming the diagnosis of GABHS pharyngitis, which can be done with a positive rapid test. In a child with a negative rapid test, however, a follow-up throat culture should be performed.[1]

Similarly, the Infectious Disease Society of America and the American Heart Association recommend that the diagnosis of GABHS infection be confirmed. In children and adolescents, a negative rapid antigen test result should be followed by culture unless the physician has determined that in his or her own practice the rapid antigen test is comparable to a throat culture.[29] However, a culture positive for GABHS does not definitively prove active infection; some patients are carriers.

No specific confirmatory laboratory tests exist for acute rheumatic fever. However, several laboratory findings indicate continuing rheumatic inflammation. Some are part of the Jones minor criteria. Streptococcal antibody tests disclose preceding but not current streptococcal infection.

Acute-phase reactants (eg, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]) may show an increase, as may serum complement, mucoproteins, alpha-2, and gamma globulins. Anemia is usually caused by suppression of erythropoiesis.

PR-interval prolongation is present in approximately 25% of all cases and is neither specific for nor diagnostic of acute rheumatic fever.

Although there are a few small studies that show the contrary, troponins have not been shown to be helpful in making the diagnosis because ischemia and necrosis are not the major cardiac problems.[15]

In patients with arthritis, synovial fluid analysis may demonstrate an elevated white blood cell count with no crystals or organisms.

Differences exist among nations in terms of diagnosing and treating GABHS pharyngitis. Most North American, French, and Finnish guidelines consider diagnosis of streptococcal infection essential (with either rapid antigen detection or with formal culture) and advise antibiotic therapy when streptococci is detected. Several European guidelines consider streptococcal infection a self-limited disease and do not recommend antibiotics.

Imaging Studies

Echocardiography may be helpful in establishing carditis. Some suggest it be performed in all suspected cases.[14]

Chest radiography should be performed to determine the presence of cardiomegaly and congestive heart failure.

 

Treatment

Prehospital Care

Although no specific prehospital interventions exist for those with acute rheumatic fever, the patient's presentation may warrant establishment of intravenous access and placement of a cardiac monitor.

Emergency Department Care

The emergency medicine physician's primary responsibilities are to suspect the diagnosis and to treat complications. Consider early administration of antibiotics.

Acute rheumatic fever (ARF) is usually preventable if antibiotics are initiated within 9 days of the onset of streptococcal infection. Remember, however, that most patients are not susceptible to developing ARF, even when infected with group A beta-hemolytic streptococci (GABHS).

The best approach to treating the patient with pharyngitis is beyond the scope of this discussion (see Pharyngitis).  However, the number needed to treat to prevent one case of ARF is estimated to be 100.

The controversy regarding the need to treat all cases of streptococcal pharyngitis is acknowledged. However, it remains true that appropriate treatment of such infection can and does prevent ARF.[30, 31]

Consultations

Consider consulting a cardiologist, a rheumatologist, and a neurologist, for the following reasons:

  • Carditis is not only a major clinical finding, but is also the cause of much of the disability.

  • Arthritis is one of the major manifestations.

  • Movement disorders associated with acute rheumatic fever may be difficult to differentiate from those of other clinical problems.

 

Medication

Medication Summary

Medical therapy for acute rheumatic fever (ARF) involves the following areas:

  • Treat group A streptococcal infection regardless of organism detection.

  • Steroids and salicylates are useful in the control of pain and inflammation; naproxen is an alternative to aspirin for ARF arthritis[32]

  • Heart failure may require digoxin, fluid and sodium restriction, diuretics, and oxygen.

  • Administer prophylaxis against group A beta-hemolytic Streptococcus infections to patients who have developed ARF. Most authorities suggest that prophylaxis be given for 5 years. For those who have rheumatic carditis, some authorities suggest lifelong prophylaxis.

  • Phenobarbital and haloperidol may be helpful in controlling chorea.

The development of a vaccine against group A streptococci remains a topic of intense interest, but has been hampered by the significant antigenic strain variation in the pathogen and the importance of avoiding autoimmune reactions.[33]

Antimicrobials

Class Summary

Because of the direct link between ARF and group A beta-streptococcal infection, the first step in treatment is the eradication of the organism.

Antibiotic regimens used for prevention of recurrence are mentioned briefly under Further Outpatient Care.

Penicillin G benzathine (Bicillin LA, Bicillin C-R)

Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible bacteria.

Because of its prolonged blood level, several authors believe this to be the DOC. Others prefer daily injections.

Penicillin G procaine (Crysticillin, Wycillin)

Long-acting parenteral penicillin (IM only) indicated in the treatment of moderately severe infections caused by penicillin G–sensitive microorganisms.

Some prefer 10-d therapy.

Administer by deep IM injection only into the upper outer quadrant of the buttock. In infants and small children, the midlateral aspect of the thigh may be the best site for administration.

Penicillin VK (Beepen-VK, Betapen-VK, Robicillin VK, Veetids)

Amoxicillin

Inhibits the biosynthesis of the cell-wall mucopeptide and is effective during the stage of active multiplication. Inadequate concentrations may produce only bacteriostatic effects. Penicillin VK is the oral alternative for the treatment of rheumatic fever.

Some authors suggest that once-daily amoxicillin is as effective and can be recommended as an alternative because compliance is likely to be better.

Erythromycin (EES, E-Mycin, Ery-Tab, Erythrocin)

DOC for patients allergic to penicillin; inhibits RNA-dependent protein synthesis, possibly by stimulating the dissociation of peptidyl tRNA from ribosomes, which inhibits bacterial growth.

In children, age, weight, and severity of infection determine the proper dosage. When bid dosing is desired, one-half the daily dose may be administered q12h. For more severe infections, the dose may be doubled.

Azithromycin (Zithromax)

Alternate antibiotic for treating GAS pharyngitis in patients allergic to penicillin.

Acts by binding to 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Nucleic acid synthesis is not affected.

Concentrates in phagocytes and fibroblasts as demonstrated by in vitro incubation techniques. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues.

Treats mild-to-moderate microbial infections.

Plasma concentrations are very low, but tissue concentrations are much higher, giving it value in treating intracellular organisms. Has a long tissue half-life.

Glucocorticoids

Class Summary

These agents possess anti-inflammatory (ie, glucocorticoid) and salt-retaining (ie, mineralocorticoid) properties. Glucocorticoids cause profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli.

Prednisone (Deltasone, Sterapred)

Patients with carditis require prednisone instead of aspirin. The goal is to decrease myocardial inflammation. Some authors suggest that carditis without associated cardiomegaly or congestive heart failure be treated with aspirin instead of glucocorticoids.

Glucocorticoids are useful in treatment of inflammatory and autoimmune disorders. Reversing increased capillary permeability and suppressing PMN activity may decrease inflammation.

Neuroleptic agents

Class Summary

These agents may help to control the chorea associated with ARF.

Haloperidol (Haldol)

A dopamine receptor blocker useful in the treatment of irregular spasmodic movements of limbs or facial muscles.

Inotropic agents

Class Summary

Some believe that digoxin may be helpful in congestive heart failure.

Digoxin (Lanoxin)

Cardiac glycoside with direct inotropic effects and indirect effects on the cardiovascular system.

Effects on the myocardium involve a direct action on cardiac muscle that increases myocardial systolic contractions and indirect actions that result in increased carotid sinus nerve activity and enhanced sympathetic withdrawal for any given increase in mean arterial pressure.

Anti-inflammatory agents

Class Summary

Reduce the inflammation associated with the disease process. Joints and heart are the targets of inflammation, but carditis is treated with glucocorticoids as noted above.

Aspirin (Ascriptin, Bayer Buffered Aspirin, Ecotrin)

Treats mild to moderate pain. Inhibits prostaglandin synthesis, which prevents formation of platelet-aggregating thromboxane A2.

Naproxen (Anaprox, Naprelan, Naprosyn)

For relief of mild to moderate pain; inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which is responsible for prostaglandin synthesis.

NSAIDs decrease intraglomerular pressure and decrease proteinuria.

 

Follow-up

Further Outpatient Care

See the list below:

  • Several regimens exist to prevent recurrences—"secondary prevention."

    • Duration of prophylaxis is determined by the number of previous attacks, time since last attack, the risk of exposure to streptococcal infections, patient age, and—very importantly—presence or absence of cardiac involvement. Although the emergency medicine physician is not likely to be the prescriber of such a regimen, it is worth knowing what our colleagues may prescribe.

    • Penicillin is still the drug of choice and may be given daily by mouth or monthly by intramuscular injection. Macrolides are acceptable in penicillin-allergic patients.

    • Those who have had carditis should be treated well into adulthood and may require lifelong prophylaxis.

    • Those without carditis may be treated until they reach their 20s andafter at least 5 years have elapsed since the past episode. Duration may increase if patients in this group are at risk for exposure to streptococcal infection.

Further Inpatient Care

See the list below:

  • Most patients with acute rheumatic fever (ARF) will be managed as inpatients by a multidisciplinary team of pediatrics, internal medicine, cardiology, infectious disease, and rheumatology specialists.

Transfer

See the list below:

  • Transfer to an appropriate pediatric facility is essential.

Deterrence/Prevention

See the list below:

  • The literature reports that acute rheumatic fever (ARF) can effectively be prevented if appropriate antibiotics are given within 9 days of symptom onset. Though somewhat controversial, most authorities believe this to be a valid conclusion. Others believe that GABHS infection in most cases is not needed because most people are not genetically susceptible.

  • At least one third of acute rheumatic fever episodes occur after inapparent streptococcal infections making prevention in that group impossible.[29]

  • Lennon et al believe that ARF cases would decrease by 60% using a school or community clinic to treat streptococcal pharyngitis in New Zealand.[34]

  • The CDC believes that, in most cases, the Centor criteria are adequate to rule in or rule out streptococcal pharyngitis. Culture is not needed. Infectious disease specialists argue that culture is still the standard. Use of the Centor criteria is more practical in the ED.

  • Differences exist among nations in terms of diagnosing and treating GABHS pharyngitis. Most North American, French, and Finnish guidelines consider diagnosis of streptococcal infection essential (with either rapid antigen detection or with formal culture) and advise antibiotic therapy when streptococci is detected. Several European guidelines consider streptococcal infection a self-limited disease and do not recommend antibiotics. The North American guidelines refer primarily to North American studies. European guidelines did not reference North American studies as frequently.

Complications

See the list below:

  • Carditis

  • Mitral stenosis

  • Mitral regurgitation

  • Aortic stenosis

  • Congestive heart failure (CHF)

Prognosis

See the list below:

  • Sequelae are limited to the heart and are dependent upon the severity of the carditis during the acute attack.