Rheumatic Fever in Emergency Medicine

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 its 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 regions where the incidence is significant, especially in sub-Saharan Africa, the Middle East, Central and South Asia, the South Pacific, and in indigenous people of Australia and New Zealand.  This is likely related to circulating subtypes of streptococci and genetic characteristics of the host populations.[2, 3, 4]

 

Acute rheumatic fever (ARF) is the sequela of a previous group A streptococcal infection, usually of the upper respiratory tract. The clinical entity appears to be a result of molecular mimicry by the bacteria, plus autoimmune and inflammatory responses and genetic predisposition in the host. This autoimmune response occurs around 1-5 weeks after the initial infection

During the initial infection, alpha-helical M proteins (M8 and M13) on the surface of the streptococcus bind type IV collagen in the host, and this interaction can trigger auto-antibody formation. Additionally, a streptococcal carbohydrate epitope, N-acetyl glucosamine (GlcNAc), mimics host proteins myosin, keratin, tropomyosin, vimentin and laminin. This mimicry triggers B- and T-cell immune responses directed against the heart, joints, central nervous system (CNS), skin, and subcutaneous tissues where those proteins are found. When ARF develops, exudative and proliferative inflammatory lesions can appear in connective tissues of the joints, blood vessels, and subcutaneous tissue, but they are especially detrimental in cardiac tissue, where structural changes can occur, resulting in rheumatic heart disease (RHD).[5, 6, 7, 8]

Pro-inflammatory cytokines and chemokines also appear to contribute to ARF and RHD. Elevated levels of interleukin-6 (IL-6), IL-8/CXCL8, and tumor necrosis factor alpha (TNFα) have been detected in these patients. Histologic studies of affected valve tissue implicates T-helper 1 (Th1) and Th17- associated pro-inflammatory cytokines, chemokine CXCL9, and transforming growth factor beta (TGF-β; the fibrosis-associated cytokine) in the damaging cycle of inflammation and fibrotic repair. Immune molecules appear to contribute to the acute inflammatory disease stage of ARF, as well as cardiac remodeling, stenosis, and ultimately valve dysfunction in RHD.[9, 10] ​

Individual genetics have been thought to play a part in susceptibility to disease progression from ARF to RHD since the 1980s and 1990s. Early research demonstrated that the human leukocyte antigen (HLA) locus on chromosome 6 is associated with susceptibility.

Additional candidate regions were implicated in the early 2000s, and current areas of genetic research include the use of genome-wide association studies (GWAS) to analyze associations among millions of variants across thousands of individuals with rheumatic fever.[11] This new approach has demonstrated involvement of the HLA-DQA1 to HLA-DQB1 region, as well as the locus that codes immunoglobulin heavy chain in chromosome 14, specifically the IGHV4-61 gene segment.[12] ​[10, 13] The RhEumatiC Heart diseAse Genetics (RECHARGE) study is currently underway in Rwanda, where approximately 1000 participants are undergoing next-generation genetic sequencing. It is expected to be completed in 2024.[14]

 

 

 

Acute rheumatic fever (ARF) has been linked definitively with a preceding streptococcal infection, usually of the upper respiratory tract. The M protein in certain streptococcal subtypes is responsible for antigenicity, with additional antigenic effects of the carbohydrate epitope N-acetyl glucosamine (GlcNAc), and possibly bacterial DNA and other proteins. These can all trigger the autoimmune response in the host.[6]

Although streptococcal skin infections were not historically linked with ARF, there is increasing evidence that group A streptococcal skin infections, including impetigo, can trigger ARF.[15]  Maori and Pacific Islanders demonstrate particular vulnerability to this progression.[16, 17]

See discussion under Pathophysiology for reference to genetic predisposition.

Frequency

United States

The prevalence of acute rheumatic fever (ARF) in the United States is a function of socioeconomic status, with higher frequency in elderly individuals, in areas of crowding, and in immigrant communities.  The national annual incidence is based on estimates, since the disease is no longer reportable.  The incidence is low in most parts of the country but varies by state.There is also a seasonal component, with higher prevalence in the colder months of the year, when school-aged children are more likely to transmit streptococcal pharyngitis.[1]

In a study published in 2006, Martin and Barbadora showed that the disease remained a problem in western Pennsylvania, with 121 new cases from 1994-2003.[18] Consistent with earlier reports, most patients were children and most had carditis.  ARF is also more common in American Samoa and Hawaii. A 2011-2012 study in American Samoa demonstrated rates about 10 times higher than in the continental United States. Hawaii's higher rates were also associted with populations of American Samoans living on the islands.[19]

Overall the incidence of rheumatic fever in North America and Europe has declined significantly in the past 4-6 decades.[20]

International

ARF remains prevalent in sub-Saharan Africa, the Middle East, Central and South Asia, the South Pacific, and among populations of immigrants, older adults, and indigenous peoples in higher-income countries.[21] Worldwide, its sequela of rheumatic heart disease (RHD) is the most common acquired heart disease in people under age 25.[22]  An estimated 40 million people suffer from RHD, with 300,000 deaths annually, although the numbers may be much higher due to under-reporting and missed diagnoses.[2] Since RHD occurs twice as commonly in women, there is also a significant association with maternal and infant morbidity and mortality related to RHD in pregnancy.[16, 23]

Since rheumatic fever is highly treatable, and the sequela of RHD is preventable, targeted public health measures should help ameliorate the burden of disease. In 2018 the World Health Assembly adopted a resolution calling upon the World Health Organization (WHO) to coordinate a global response against rheumatic fever and RHD. This involves standardizations of clinical guidelines for prevention and treatment, as well as long-term plans to help people already living with RHD.[22] The WHO Road Map for Access to Medicines, Vaccines, and Other Health Products 2019-2023 also devotes specific attention to the importance of a safe and available supply of benzathine penicillin for treatment of rheumatic fever.[24]

Demographics

No sex predilection for rheumatic fever exists, except that Sydenham chorea occurs more often in females than in males.[25]  Progression to RHD occurs twice as frequently in women.[23]

Although individuals of any age group may be affected, most cases are reported in school-aged children from 5-15 years-old. Paulo et al report that ARF can be found in children younger than 5 years with no significant difference in the frequency and severity of clinical signs.[26] Yee lists rheumatic pericarditis and myocarditis as cardiac emergencies in the first year of life.[27]

Over the past two decades, new attention has been focused on the racial and ethnic disparities that result in a higher disease burden among indigenous peoples, especially in Australia and New Zealand. Whether those rates are related to genetic predisposition, socioeconomic factors, or a combination remains an area of active investigation.[2, 12, 28, 29]

Sequelae are limited to the heart and depend on the severity of the carditis during the acute attack. Infections that are not treated adequately are most likely to cause the major sequelae noted in the list of Jones criteria in Presentation/Physical Examination. Morbidity is related to the care that the patient receives.[1, 30]

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 and its sequela are a major cause of death and disability in children and adolescents.

Most cases of uncomplicated acute rheumatic fever resolve with proper treatment within 3 months.[1]

 

Acute rheumatic fever (ARF) is associated with 2 distinct patterns of presentation. The first pattern is sudden onset, which 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.[31]

According to the revised Jones Criteria, the requirements 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 as follows:

• Two major manifestations or
• One major and two minor manifestations or
• Three minor manifestations

Major manifestations of ARF are the same across all populations, regardless of risk. Minor manifestations vary between low-risk populations and moderate- and high-risk populations. A low-risk population is defined as having an ARF incidence of < 2 per 100,000 school-aged children or all-age rheumatic heart disease prevalence of ≤1 per 1000 population per year. Patients who are not from a low-risk population are defined as being at moderate or high risk depending on their reference population.[20, 1]

Major manifestations comprise the following:

• Carditis, clinical and/or subclinical (i.\e., 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 for the joint pain 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) ^{[1, 20, 32]}

Carditis

Carditis usually presents as chest discomfort, shortness of breath, fatigue, and possibly palpitations; yet not all patients with carditis will have clinical symptoms. The realization that subclinical carditis could be identified with Doppler echocardiography prompted the revision of the historic Jones criteria to ensure that this major manifestitation and its associated morbidity and mortality do not go unrecognized.[20]

Polyarthritis

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. Symptoms may be migratory. The arthritis is transient and self-limited, with no long-term sequelae.[1, 30]

Sydenham chorea

Sydenham chorea is characterized by neuropsychiatric changes that may present suddenly or gradually. Specific symptoms include dyspraxia or coordination problems, ataxia, dysarthria, weakness, involuntary muscle movements, emotional lability, anxiety, depression, problems with concentration, and even obsessive-compulsive behaviors.

Sydenham chorea can occur as an isolated entity (separate from ARF) up to 6 months after the intial group A streptococcal (GAS) infection. Regardless of time of onset, symptoms usually resolve within 3 to 6 weeks; however, some children may experience symptoms lasting months. In addition, some children may experience a recurrence within the next 1.5-2.5 years.[25, 33]

Erythema marginatum

Erythema marginatum is an annular erythematous lesion that occurs in about 10% of pediatric ARF cases and may be difficult to identify in darker-skinned individuals. If present, it is usually found on the trunk and proximal extremities. It spares the face, hands, and feet. The rash begins as a red or pink macule or papule that spreads outward. The center clears, and the edges become raised and erythematous. The rash is neither painful nor pruritic. The lesions may fade and reappear, and they can last for months.[34] ​

Subcutaneous nodules

Subcutaneous nodules appear about 4-6 weeks after the initial GAS infection. The painless lesions affect extensor surfaces, elbows, knees, dorsal surfaces of the hands and feet, scalp, and vertebral prominences. They are uncommon, occurring in less than 2% of cases, but they are invariably associated with carditis. The nodules usually resolve within one month, but may persist for longer.[35, 34]

Patients with carditis as part of the initial episode are at greater risk of developing recurrent ARF and of sustaining further cardiac injury. Those without carditis during the initial episode have a relatively low risk of developing carditis during recurrences. Approximately 10% of patients with ARF will develop heart failure, and recurrent rheumatic fever can trigger heart failure even in the absence of valvular disease. Isolated heart failure, without valvular dysfunction, is reversible with proper treatment.[36, 30]

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 by the cycle of inflammation and fibrosis. Those valves then become stenotic and dysfunctional, which may lead to left ventricular dilation and congestive heart failure, sometimes decades later. Oftentimes women are unaware of their RHD until they become pregnant and the cardiovascular changes of pregnancy lead to accelerated RHD and cardiac dysfunction. RHD is a leading cause of infant and maternal morbidity and mortality in high burden regions.[23]  

Vegetations may develop on damaged valves and become infected, leading to infective endocarditis. A retrospective study at a single center in Auckland, New Zealand from 2016-2018 concluded that "patients with RHD experienced infective endocarditis at a younger age, had a higher incidence of prosthetic valve endocarditis and a prior history of infective endocarditis." Mortality in the RHD patients was almost exclusively as a result of infective endocarditis.[37]

Although cardiac complications are very well described, the understanding of neurologic involvement and persistent morbidity is still evolving. Literature began to appear in 1998 suggesting that ARF might be associated with PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections).[38] Sydenham chorea is a result of antineuronal autoantibodies attacking the dopamine receptors in the basal ganglia; symptoms of Sydenham chorea usually resolve without long-term sequelae.[6]

In PANDAS, the autoimmune response is also triggered by molecular mimicry, but the clinical entity presents differently. The antibodies responsible for PANDAS bind to a different subtype of dopamine receptors and/or lysoganglioside antigens, and result in persistence of clinical neuropsychaitric symptoms. Research is ongoing, but as Cunningham and Cox note, "Sydenham chorea may be a prototype for other group A streptococcal or infection-related movement and neuropsychiatric conditions​."[39]

The best approach to evaluating and treating the patient with group A streptococcal (GAS) pharyngitis is beyond the scope of this discussion (see Pharyngitis), but since the diagnosis of acute rheumatic fever (ARF) is dependent upon a preceding GAS infection, it warrants discussion. While the need to treat all cases of streptococcal pharyngitis remains controversial, it is clear that antibiotic treatment of GAS does prevent ARF. The number needed to treat to prevent one case of ARF is estimated to be 100.[40, 41]

The diagnosis of GAS pharyngitis can be confirmed with a rapid antigen detection test or a throat culture, with throat culture considered the gold standard during acute infection. Note that the Centers 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 ARF is very rare in those age groups in the United States. 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, 42]

Similarly, the Infectious Disease Society of America and the American Heart Association (AHA) recommend that the diagnosis of GABHS infection be confirmed with testing. 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.[43] A culture positive for GABHS does not definitively prove active infection, however, as some patients are carriers.  

Of course, access to rapid antigen tests, molecular assays, and microbiological cultures is limited in lower socioeconomic areas. They are costly, and storage can be challenging. Increasing accessibility to diagnostic tools as a primary prevention strategy is a cornerstone of the AHA's Call to Action for Reducing the Global Burden of Rheumatic Heart Disease.[44] ​ 

The AHA further suggests that ARF diagnostic criteria may be applied differently, depending on the rate of ARF or 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.[20]

Diagnosis of ARF therefore requires a high index of suspicion. The modified Jones Criteria and clinical guidelines from the AHA include major and minor criteria, which are described in the Presentation/Physical Examination. Laboratory evidence of a preceding GAS infection is preferred 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.[20]

No specific confirmatory laboratory tests exist for acute rheumatic fever. However, several laboratory findings indicate continuing rheumatic inflammation, and some are part of the minor Jones criteria. Confirmation of a preceding group A strep infection is strongly preferred, but not always possible.

According to a statement by the American Heart Association, evidence of prior GAS infection can be demostrated by an increased or rising anti-streptolysin O titer or other streptococcal antibodies; a positive throat culture for GABHS, or a positive rapid GAS test in a child with a high pre-test probability of GAS pharyngitis.[43]  Routine testing for streptococcal skin infections is not yet recommened, but may be beneficial in some cases.[17]

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.[45, 22]

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.[46]

In patients with arthritis, synovial fluid analysis may demonstrate an elevated white blood cell count with no crystals or organisms.[47]

Current research is focused on identifying novel biomarker profiles associated with ARF that could become the basis of reliable point-of-care testing in regions with a high disease burden. This research could also yield targets for new immunomodulatory therapies.[2, 44, 48]

Echocardiography has shown to be extremely effective in diagnosis carditis and valvular dysfunction in ARF, and it can be used to diagnose latent RHD in asymptomatic children.[49] Its use has revolutionized screening in remote areas with limited healthcare access and will likely contribute to earlier identification and treatment of RHD in high disease burden areas.[20, 2]

Chest radiography should be performed to determine the presence of cardiomegaly and congestive heart failure in ARF.[2, 12]

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.

Most patients with acute rheumatic fever (ARF) will be managed as inpatients by a multidisciplinary team of pediatricians, internists, cardiologists, infectious disease specialists, and rheumatologists. Transfer to an appropriate pediatric facility is essential. The emergency medicine physician's primary responsibilities are to suspect the diagnosis, initiate the diagnostic work-up, administer antibiotics, and treat symptoms. 

Individual medications are discussed in the Medication section.

Anti-inflammatory agents are used to control the arthritis, fever, and other acute symptoms. ARF arthritis is very responsive to non-steroidal anti-inflammatory drug (NSAID) treatment.[50] Historically, high-dose aspirin was used, but naproxen and ibuprofen demonstrate similar efficacy with fewer toxic effects.[51, 52]

Sydenham chorea varies in its severity and degree of discomfort or impaired functionality. Some patients may benefit from valproic acid or carbamazepine. Those agents have similar efficacy and minimal adverse effects. For severe Sydenham chorea, corticosteroids can reduce time to remission.[2] There are also case reports showing improvement with levetiracetam, olanzapine, and risperidone.[53]

Symptoms of carditis can be managed with corticosteroids. A meta-analysis did not demonstrate clear benefit; nevertheless, it is still a consensus expert recommendation.[54, 55]

The use of intravenous immunoglobulin is not recommended, as it did not demostrate any benefit in cardiac disease at one year after treatment.[54] A small case series reported 2 cases of carditis treated with hydroxychloroquine, but the specific mechanism of action and in vivo effect is unclear.[56] Furthermore, QTc prolongation is often seen in early stages of ARF, so the use of hydroxychloroquine, which can further prolong the QTc and put the patient at risk for dysrhythmia, must be done with caution.[57]

Heart failure is managed with nitrates and diuretics, and pressors or mechanical support as needed.

 

 

 

Consultations for patients with ARF are as follows:

• A pediatric consult for admission or transfer is usually required.
• A cardiology consult is essential, since carditis is a major clinical finding and also the cause of most morbidity and mortality.
• Consider consulting rheumatology, neurology, and infectious disease, especially if the diagnosis is uncertain.

Although surgical intervention is rarely needed in ARF, patients who sustain significant damage and stenosis of their mitral and/or aortic valves may require valve replacement or repair at some point. As surgical techniques evolve, valve repair has become the preferred intervention. Valve replacement can be performed surgically or via catheter.[14]

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 treatment of GABHS infection in most cases is not needed because most people will not progress from GAS to ARF.

At least one third of ARF episodes occur after inapparent streptococcal infections, making prevention in that group impossible.[43]

Lennon et al proposed that in New Zealand, ARF cases would decrease by 60% using a school or community clinic to treat streptococcal pharyngitis.[58]

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 test [RADT] or formal culture) and advise antibiotic therapy when streptococci are 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.[59]

Several secondary prevention antibiotic regimens exist to prevent recurrences. Duration of antibiotic 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.

Children 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 and after 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.[24, 22]

 

The development of a vaccine against GAS remains a topic of intense research and clinical interest. The earliest efforts, 100 years ago, were ineffective, and vaccine trials were paused from the 1970's-2000's due to safety concerns. The past two decades of molecular research have provided new targets,[60] but a lack of financial investment hindered meaningful progress.

In 2018, the World Health Organization published the Group A Streptococcal Vaccine Research and Development Roadmap, and in 2019, a Strep A Vaccine Consortium was formed.[61] A small number of vaccine candidates are currently under development; however, only one has reached a phase II trial. No major pharmaceutical companies are working on GAS vaccines.[14, 24, 61]

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

• Eradication of group A streptococcal infection
• Management of arthritis pain and inflammation with NSAIDs or salicylate
• Treatment of carditis with glucocorticoids
• Control of chorea
• Prophylaxis against group A beta-hemolytic Streptococcus infections in patients who have developed ARF

 

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, monthly injection is widely accepted as the treatment of choice for prophylaxis.

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.

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)

Penicillin VK is the oral formulation of penicillin and an alternative treatment of rheumatic fever.

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. 

Clindamycin (Clindamax, Cleocin, Cleocin Pediatric)

Antibiotic treatment alternative for patients allergic to penicillin.  

Binds 23S RNA of 50S ribosome subunit to inhibit bacterial protein synthesis.

 

 

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

Antibiotic treatment alternative 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)

Antibiotic treatment alternative for 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.

Biaxin (DSC), Clarithromycin

Antibiotic treatment alternative for patients allergic to penicillin.  

Reversibly binds 50S ribosomal subunit and inhibits RNA-dependent protein synthesis in susceptible organisms.

Cephalexin (Keflex, Panixine Disperdose)

Antibiotic treatment alternative for patients allergic to penicillin.  

Binds penicillin binding proteins in actively dividing bacteral cells; inhibits bacterial cell-wall synthesis.

 

 

Class Summary

These agents possess anti-inflammatory (ie, glucocorticoid) and salt-retaining (ie, mineralocorticoid) properties. These agents modify the body's immune response to diverse stimuli.   Indicated in carditis and severe Sydenham chorea.

Prednisone (Deltasone, Sterapred)

Decrease inflammation contributing to carditis.  Also useful in severe Sydenham chorea.

Class Summary

Reduce the pain and inflammation of arthritis.

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.

Class Summary

Help manage Sydenham chorea.

Carbamazepine (Carbamazepine CR, Carbamazepine Chewtabs, Carbatrol)

Stabilizes inactivated state of sodium channels, making neurons less excitable.

Valproic acid (Depacon (DSC), Depakene (DSC), Stavzor (DSC))

May increase GABA concentration in the central nervous system.

Class Summary

Used to manage heart failure symptoms in ARF.

Furosemide (Lasix, Furoscix)

Inhibits reabsorption of Na+ and Cl- at proximal and distal tubules and Loop of Henle.

Spironolactone (Aldactone, CaroSpir)

Increases Na+, Cl-, and water excretion, but conserves K+, H+.

Class Summary

Used to manage heart failure symptoms in ARF.

Nitroglycerin IV (Glyceryl trinitrate IV, IV Nitroglycerin, NitroBid IV)

Enters vascular smooth muscle and is converted to nitric oxide, which induces cGMP synthesis and vasodilation; decreases preload.

Nitroglycerin PO (Glyceryl trinitrate PO)

Enters vascular smooth muscle and is converted to nitric oxide, which induces cGMP synthesis and vasodilation; decreases preload.

Hydroxychloroquine sulfate (Plaquenil)

Mechanism unclear. May provide some benefit in carditis based on in vitro studies and a small case report, but must be used with caution due to risk of QTc prolongation.

Class Summary

May provide some relief of neuropsychiatric symptoms from Sydenham chorea

Olanzapine (Zyprexa, Zyprexa Relprevv, Zyprexa Zydis)

Atypical antipsychotic.  Dopamine and serotonin receptor antagonist.

Risperidone (Risperdal, Perseris, Risperdal Consta)

Atypical antipsychotic.  Dopamine and serotonin receptor antagonist.

Class Summary

May provide some relief of neuropsychiatric symptoms from Sydenham chorea

Levetiracetam (Keppra, Elepsia, Keppra XR)

Modulates neurotransmitter release by binding to the synaptic vesicle protein SV2A.