eMedicine Specialties > Emergency Medicine > Rheumatology
Rheumatic Fever
Updated: Jan 14, 2010
Introduction
Background
Rheumatic fever causes chronic progressive damage to the heart and its valves. 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 tropic areas.
However, research into the subtypes of streptococci has made it clear that differences among those types is also responsible for both the decline in overall US incidence and 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.
Pathophysiology
Acute rheumatic fever is a sequela of a previous group A streptococcal infection, usually of the upper respiratory tract. One beta-streptococcal serotype (eg, M types 3, 5, 18, 19, 24) is linked directly to acute rheumatic fever. Two vaccines—one that is 26-valent and likely to proceed into clinical trials—are based on the M protein characteristics of responsible subtypes.
Good evidence suggests that there is genetic susceptibility to development of the disease. Several recent studies have shed light on genetic predisposition.[1,2 ]
Non–group A streptococci has never been shown to cause this disease.
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.
Frequency
United States
Disease prevalence 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.[3 ]Consistent with earlier reports, most patients were children and most had carditis.
Acute rheumatic fever is common among American Samoans in Hawaii.[4 ]
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, acute rheumatic fever 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
Acute rheumatic fever (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 recent paper suggests the figure may be closer to 95%.
In those less developed nations, post ARF heart disease is the most commonly acquired heart disease in hospitalized children, adolescents, and young adults. 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.[5 ]
Wang et al reported on a possible acute rheumatic fever resurgence in Taiwan.[6 ]Authors in India and Turkey make a plea for more liberal application of the Jones criteria in order to avoid misdiagnosis.[7,8 ]Meira et al report on the high incidence in Brazil.[9 ]Others have reminded the medical community that good reporting of prevalence in underdeveloped nations is lacking.
Parks et al suggest that acute rheumatic fever is underdiagnosed in primary care clinics in the United Kingdom.[10 ]
Marijon et al believe that 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.[11 ]
Mortality/Morbidity
Morbidity from acute rheumatic fever (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.
- Those with carditis as part of the initial episode are at greater risk of developing recurrences and of sustaining further cardiac injury.
- Carapetis et al estimated that worldwide, approximately 60% of all patients with ARF will develop rheumatic heart disease.[12 ]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 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 2009, this is considered an unproven hypothesis.[13 ]
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.
Yee lists rheumatic pericarditis and myocarditis as cardiac emergencies in the first year of life.[14 ]
Clinical
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.
- If the initial abnormality is mild carditis, ARF may be insidious or subclinical.
- 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 used by the American Heart Association include major and minor criteria (ie, modified Jones criteria). In addition to evidence of a previous streptococcal infection, the diagnosis requires 2 major Jones criteria or 1 major plus 2 minor Jones criteria.
- Major criteria
- Carditis: This occurs in as many as 40% of patients and may include cardiomegaly, new murmur, congestive heart failure, and pericarditis, with or without a rub and valvular disease.
- Migratory polyarthritis: This condition occurs in 75% of patients and is polyarticular, fleeting, and involves the large joints. Note that one group of authors has suggested that atypical cases may only involve small joints.[7 ]
- Subcutaneous nodules (ie, Aschoff bodies): These nodules occur in 10% of patients and are edematous, fragmented collagen fibers. They are firm, painless nodules on the extensor surfaces of the wrists, elbows, and knees.
- Erythema marginatum: This condition occurs in about 5% of patients. The rash is serpiginous and long lasting.
- Chorea (also known as Sydenham chorea and "St Vitus dance"): This characteristic movement disorder occurs in 5-10% of cases. Sydenham chorea consists of rapid, purposeless movements of the face and upper extremities. Onset may be delayed for several months and may cease when the patient is asleep.
- Minor criteria
- Clinical findings include arthralgia, fever, and previous history of ARF.
- Laboratory findings include elevated acute-phase reactants (eg, erythrocyte sedimentation rate, C reactive protein), a prolonged PR interval, and supporting evidence of antecedent group A streptococcal infections (ie, positive throat culture or rapid streptococcal screen and an elevated or rising streptococcal antibody titer).
Note that the current Jones criteria are different than the original. Numerous authors have suggested that more changes 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.[15 ]They would like to see monoarthritis become a major criterion. These same authors suggest that the set point of fever at 38 º C might be too high. As mentioned above, at least one author reported on atypical cases in which arthritis involved small joints rather than large joints. Finally, Rayamajhi et al suggest that arthralgia be changed from a minor to a major Jones criterion.[16 ]
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.[11 ]
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 acute rheumatic fever in the United States. Note the suggestion by McDonald et al that pyoderma may be the cause in Aboriginal populations of Australia.[5 ]
- See discussion under Pathophysiology for reference to genetic predisposition.
Differential Diagnoses
| Aortic Regurgitation | Pediatrics, Scarlet Fever |
| Atrial Fibrillation | Pericarditis, Acute |
| Endocarditis | Reactive Arthritis |
| Huntington Chorea | Rheumatoid Arthritis |
| Lyme Disease | Scarlet Fever |
| Mitral Regurgitation | Systemic Lupus Erythematosus |
| Mitral Stenosis | |
| Myocarditis | |
| Pediatrics, Kawasaki Disease |
Other Problems to Be Considered
Leukemia
Juvenile rheumatoid arthritis
Workup
Laboratory Studies
- 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 streptococcal infection.
- The CDC has stated that a rapid antigen test in the appropriate clinical setting is sufficient to make the diagnosis of active GABHS infection and begin treatment.
- Isolate group A streptococci via throat culture. A significant percentage will result in a culture positive for group A beta-hemolytic Streptococcus (GABHS). However, a culture positive for GABHS does not definitively prove active infection. Some patients are carriers.
- Acute-phase reactants (eg, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP] in serum and leukocytosis) may show an increase in 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.
- 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.
- Chest radiography should be performed to determine 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) usually is preventable if antibiotics are initiated within 9 days of the onset of streptococcal infection. The Infectious Disease Society of America recommends that the diagnosis of GABHS infection be confirmed. In children and adolescents, a negative rapid antigen test (streptococcal screen) 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. Because of the low incidence of ARF in adults, a negative, properly performed rapid antigen test is considered acceptable evidence that streptococcal infection is not present.
- The best approach to treating the patient with pharyngitis is beyond the scope of this discussion. However, the number needed to treat to prevent one case of ARF is estimated to be 100.
Consultations
Because of the many clinical features of acute rheumatic fever (ARF), consider consulting a cardiologist, a rheumatologist, and a neurologist.
- Carditis is not only a major clinical finding, but it also is 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
Medical therapy for acute rheumatic fever involves the following 5 areas:
- Treat group A streptococcal infection regardless of organism detection.
- Steroids and salicylates are useful in the control of pain and inflammation.
- Heart failure may require digitalis, fluid and sodium restriction, diuretics, and oxygen.
- Administer prophylaxis against GABHS 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.
- Note that clinical trials for a 6-valent and a 26-valent vaccine are likely to take place in the near future. Phase I trials have been very promising.
Antimicrobials
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.
Dosing
Adult
2.4 million U IM once
Pediatric
Infants and children <60 lb (27kg): 600,000 U IM once
Children >60 lb (27 kg): 1.2 million U IM once
Combination of 900,000 U benzathine penicillin and 300,000 U procaine penicillin (Bicillin C-R) may be used in smaller children.
Interactions
Probenecid can increase penicillin effectiveness by decreasing its clearance; coadministration of tetracyclines can decrease penicillin effectiveness
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in impaired renal function
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.
Dosing
Adult
2.4 million U IM once
Pediatric
Infants and children <30 lb: 600,000 U IM
Children 30-60 lb: 900,000 to 1.2 million U IM
Interactions
Increases risk of bleeding when administered concurrently with warfarin; ethacrynic acid, aspirin, indomethacin, and furosemide may compete with penicillin G for renal tubular secretion increasing penicillin serum concentrations
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Never use IV route to administer penicillin G procaine; administer >10 d to eliminate organism and prevent complications, such as endocarditis and rheumatic fever; perform cultures after treatment to confirm streptococci eradication
Penicillin VK (Beepen-VK, Betapen-VK, Robicillin VK, Veetids)
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.
Dosing
Adult
500 mg PO q6h for 10 d
Pediatric
<12 years: 25-50 mg/kg/d PO divided tid/qid; not to exceed 3 g/d
>12 years: Administer as in adults
Interactions
Probenecid may increase effectiveness by decreasing clearance; tetracyclines are bacteriostatic, causing a decrease in the effectiveness of penicillins when administered concurrently
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in renal impairment
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.
Dosing
Adult
1 g/d PO divided bid for 10 d
Pediatric
30-50 mg/kg/d PO divided bid
Interactions
Coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin increases risk of rhabdomyolysis
Contraindications
Documented hypersensitivity; hepatic impairment
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in liver disease; estolate formulation may cause cholestatic jaundice; GI adverse effects are common (give doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur; macrolides can cause QT prolongation
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.
Dosing
Adult
500 mg on day 1 followed by 250 mg/d for 4 additional days
Pediatric
10 mg/kg on day 1 followed by 5 mg/kg/d for 4 additional days
Interactions
May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine
Contraindications
Documented hypersensitivity; hepatic impairment; do not administer with pimozide
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Site reactions can occur with IV route; bacterial or fungal overgrowth may result from prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function or prolonged QT intervals
Glucocorticoids
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.
Dosing
Adult
60-80 mg/d PO
Pediatric
2 mg/kg/d PO
Interactions
Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Contraindications
Documented hypersensitivity; viral, fungal, or tubercular skin infections
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use
Neuroleptic agents
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.
Dosing
Adult
0.5-2 mg PO bid/tid
Pediatric
<3 years: Not established
3-12 years: 0.05 mg/kg/d or 0.25-0.5 mg/d bid/tid; increase by 0.25-0.5 mg q5-7d
Maintenance dose: 0.05-0.15 mg/kg/d bid/tid; not to exceed 0.15 mg/kg/d
>12 years: Administer as in adults
Interactions
May increase tricyclic antidepressant serum concentrations and hypotensive action of antihypertensive agents; phenobarbital or carbamazepine may decrease effects; coadministration with anticholinergics may increase intraocular pressure; encephalopathylike syndrome associated with concurrent administration of lithium and haloperidol
Contraindications
Documented hypersensitivity; narrow-angle glaucoma; bone marrow suppression; severe cardiac and liver disease; severe hypotension; subcortical brain damage
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Severe neurotoxicity manifesting as rigidity, or inability to walk or talk may occur in patients with thyrotoxicosis also receiving antipsychotics; if IV/IM, watch for hypotension; caution in CNS depression or cardiac disease; if history of seizures, benefits must outweigh risks; significant increase in body temperature may indicate intolerance to antipsychotics (discontinue if this occurs)
Inotropic agents
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.
Dosing
Adult
0.125-0.375 mg PO qd
Pediatric
Digitalizing dose:
<2 years: Not established
2-5 years: 30-40 mcg/kg PO
5-10 years: 20-35 mcg/kg PO
>10 years: 10-15 mcg/kg PO
Maintenance dose: 25-35% of PO loading dose
Interactions
Medications that may increase digoxin levels include alprazolam, benzodiazepines, bepridil, captopril, cyclosporine, propafenone, propantheline, quinidine, diltiazem, aminoglycosides, oral amiodarone, anticholinergics, diphenoxylate, erythromycin, felodipine, flecainide, hydroxychloroquine, itraconazole, nifedipine, omeprazole, quinine, ibuprofen, indomethacin, esmolol, tetracycline, tolbutamide, and verapamil; medications that may decrease serum digoxin levels include aminoglutethimide, antihistamines, cholestyramine, neomycin, penicillamine, aminoglycosides, oral colestipol, hydantoins, hypoglycemic agents, antineoplastic treatment combinations (including carmustine, bleomycin, methotrexate, cytarabine, doxorubicin, cyclophosphamide, vincristine, procarbazine), aluminum or magnesium antacids, rifampin, sucralfate, sulfasalazine, barbiturates, kaolin/pectin, and aminosalicylic acid
Contraindications
Documented hypersensitivity; beriberi heart disease; idiopathic hypertrophic subaortic stenosis; constrictive pericarditis; carotid sinus syndrome
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Hypokalemia may reduce positive inotropic effect of digitalis; IV calcium may produce arrhythmias in digitalized patients; hypercalcemia predisposes patient to digitalis toxicity, and hypocalcemia can make digoxin ineffective until serum calcium levels are within reference range; magnesium replacement therapy must be instituted in patients with hypomagnesemia to prevent digitalis toxicity; patients with incomplete AV block may progress to complete block when treated with digoxin; exercise caution in hypothyroidism, hypoxia, and acute myocarditis
Anti-inflammatory agents
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.
Dosing
Adult
6-8 g/d PO for 2 mo or until ESR has returned to normal
Pediatric
80-100 mg/kg/d PO for 2 mo or until ESR has returned to normal
Interactions
Effects may decrease with antacids and urinary alkalinizers; corticosteroids decrease salicylate serum levels; additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants; may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; doses >2 g/d may potentiate glucose-lowering effect of sulfonylurea drugs
Contraindications
Documented hypersensitivity; liver damage; hypoprothrombinemia; vitamin K deficiency; bleeding disorders; asthma; because of association with Reye syndrome, do not use in children (<16 y) with flu
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause transient decrease in renal function and aggravate chronic kidney disease; avoid use in patients with severe anemia, in those with history of blood coagulation defects, or in those taking anticoagulants
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.
Dosing
Adult
250-500 mg PO bid; may increase to 1.5 g/d for limited periods
Pediatric
<2 years: Not established
>2 years: 2.5 mg/kg/dose PO; not to exceed 10 mg/kg/d
Interactions
Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Contraindications
Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia, and renal papillary necrosis may occur; patients with preexisting renal disease or compromised renal perfusion risk acute renal failure; leukopenia occurs rarely, is transient, and usually returns to normal during therapy; persistent leukopenia, granulocytopenia, or thrombocytopenia warrants further evaluation and may require discontinuation of drug
Follow-up
Further Inpatient Care
- 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.
Further Outpatient Care
- 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.
Transfer
- Transfer to an appropriate pediatric facility is essential.
Deterrence/Prevention
- Literature, much of it now dated, 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.[13 ]
- Lennon et al believe that ARF cases would decrease by 60% using a school or community clinic to treat streptococcal pharyngitis in New Zealand.[17 ]
- 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
- Carditis
- Mitral stenosis
- Mitral regurgitation
- Aortic stenosis
- Congestive heart failure (CHF)
Prognosis
- Sequelae are limited to the heart and are dependent upon the severity of the carditis during the acute attack.
Miscellaneous
Medicolegal Pitfalls
- Diagnosis of acute rheumatic fever (ARF) usually is evident if considered in the differential of a child with suggestive signs and symptoms. The primary medicolegal pitfall is not making the diagnosis in a timely fashion. Failure to diagnose translates into failure to treat. Complications may occur in any patient but are much more likely if treatment is delayed.
- Although rare, ARF has been diagnosed in adults who had never been diagnosed as children. Misdiagnosis in the population is probably more likely than in children.
- Concern also arises over failure to recognize and treat a streptococcal infection that eventually leads to ARF.
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Keywords
rheumatic fever, heart disease, rheumatic fever symptoms, rheumatic fever causes, rheumatic fever treatment, rheumatic fever rash, acute rheumatic fever, group A streptococcal infection, scarlet fever, streptococcal pharyngitis, congestive heart failure, CHF, myocarditis, carditis
Contributor Information and Disclosures
Author
Steven J Parrillo, DO, FACOEP, FACEP, Associate Professor, Emergency Medicine, Jefferson Medical College and Philadelphia College of Osteopathic Medicine; Medical Director, Department of Emergency Medicine, Einstein Elkins Park; Chair, Emergency Management Committee, Albert Einstein Healthcare Network; Medical Director, Disaster Medicine and Management Masters Program, Philadelphia University
Steven J Parrillo, DO, FACOEP, FACEP is a member of the following medical societies: American College of Emergency Physicians, American College of Osteopathic Emergency Physicians, American Osteopathic Association, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.
Coauthor(s)
Catherine V Parrillo, DO, FACOP, FAAP, Clinical Assistant Professor, Department of Pediatrics, Philadelphia College of Osteopathic Medicine
Catherine V Parrillo, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.
Medical Editor
Assaad J Sayah, MD, Chief, Department of Emergency Medicine, Cambridge Health Alliance
Assaad J Sayah, MD is a member of the following medical societies: National Association of EMS Physicians
Disclosure: Nothing to disclose.
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Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
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Gino A Farina, MD, Associate Professor of Clinical Emergency Medicine, Program Director, Department of Emergency Medicine, Long Island Jewish Medical Center, Albert Einstein College of Medicine
Gino A Farina, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.
CME Editor
John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
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Chief Editor
Robert E O'Connor, MD, MPH, Professor and Chair, Department of Emergency Medicine, University of Virginia Health System
Robert E O'Connor, MD, MPH is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Physician Executives, American Heart Association, American Medical Association, Medical Society of Delaware, National Association of EMS Physicians, Society for Academic Emergency Medicine, and Wilderness Medical Society
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