eMedicine Specialties > Rheumatology > Miscellaneous Inflammatory Arthritis
Acute Rheumatic Fever: Treatment & Medication
Updated: Jul 31, 2009
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Treatment
Medical Care
Treatment strategies can be divided into management of an acute rheumatic fever (ARF) attack, management of the current infection, and prevention of further infection and attacks.
- The primary goal of treating an ARF attack is to eradicate streptococcal organisms and bacterial antigens from the pharyngeal region.
- Penicillin is the drug of choice in persons who are not at risk of allergic reaction.
- A single parenteral injection of benzathine benzylpenicillin can ensure compliance.
- Oral cephalosporins, rather than erythromycin, are recommended as an alternative in patients who are allergic to penicillin. However, be cautious of the 20% cross-reactivity of the cephalosporins with penicillin.
- By promptly treating streptococcal pharyngitis in susceptible hosts, repetitive exposure to pathologically reactive antigens can be avoided. However, management of the current infection will probably not affect the course of the current attack.
- Antimicrobial therapy does not alter the course, frequency, or severity of cardiac involvement.
- Analgesia is optimally achieved with high doses of salicylates, often inducing dramatic clinical improvement.
- A lower dose may be required to avert symptoms of nausea and vomiting.
- When salicylates are used as therapy, the dosage should be increased until the drug produces either a clinical effect or systemic toxicity characterized by tinnitus, headache, or hyperpnea.
- Corticosteroids should be reserved for the treatment of severe carditis.
- After 2-3 weeks, the dosage may be tapered, reduced by 25% each week.
- Overlap with high-dose salicylate therapy is recommended as the dosage of the prednisone is tapered over a 2-week period to avoid poststeroid rebound. In extreme cases, intravenous methylprednisolone may be used.
- Mild heart failure usually responds to rest and corticosteroid therapy.
- Digoxin can be useful in patients with severe carditis, but its use should be monitored closely because of the possibility of heart block.
- Nocturnal tachycardia may be a sign of cardiac involvement that may be responsive to digoxin. Vasodilators and diuretics also may be used.
- Protracted Sydenham chorea has responded to haloperidol.
- Chorea requires long-term antimicrobial prophylaxis, even if no other manifestations of rheumatic fever evolve.
- The signs and symptoms of chorea usually do not respond well to treatment with antirheumatic agents.
- Complete physical and mental rest is essential because the manifestations of chorea may be exaggerated by emotional trauma.
- Glucocorticoids or salicylates have little or no effect on chorea.
- Because chorea disappears with sleep, adequate sedation should be provided.
- Prevention has been successful in developed societies. The recommended approach can be divided into primary and secondary prevention.
- Primary prevention: Eradicate Streptococcus from the pharynx, which generally entails administering a single intramuscular injection of benzathine benzylpenicillin.
- Secondary prevention: The AHA Committee on Acute Rheumatic Fever recommends a regimen consisting of benzathine benzylpenicillin at 1.2 million units intramuscularly every 4 weeks. However, in high-risk situations, administration every 3 weeks is justified and advised. High-risk situations include patients with heart disease who are at risk of repetitive exposure.
- Oral prophylaxis, which is less reliable, consists of phenoxymethylpenicillin (penicillin V) or sulfadiazine. These can be used in compliant patients.
- If penicillin allergy is suspected, oral cephalosporins should be used.
- Although no consensus on the required duration of antibacterial prophylaxis has been reached, the AHA recommends that prophylaxis be continued for at least 10 years after the last episode of rheumatic fever or until patients are well into adulthood. For those with heart disease who are at risk of repetitive exposures, prophylaxis should be continued for a longer duration, probably indefinitely. However, discontinuing prophylaxis may be reasonable in patients in their third decade of life in whom more than 5 years have passed since their last attack and who are free from rheumatic heart disease. The principles of treatment include the following:
- The risk of rheumatic fever recurrence is greatest during the first 3-5 years following the attack.
- Prophylaxis must continue indefinitely in patients with established heart disease or in those frequently exposed to streptococci.
- Treatment for an indefinite period is required among patients with frequent exposure to streptococci or for those who are difficult to monitor.
- In underdeveloped countries, prophylaxis should be continued as follows:
- Continue for 5 years after the first attack.
- Continue indefinitely in patients with established heart disease.
- Continue indefinitely in patients who are frequently exposed to streptococci, are less than optimal, and are difficult to monitor.
- The decision to withdraw the antibacterial drugs should be individualized after carefully assessing the risk of repetitive exposures.
Surgical Care
- Valve replacement should be considered in patients with active carditis, especially in cases that are refractory to medical care or require high doses of vasodilators and diuretics.
- Regurgitant lesions respond to valve replacement, while pure stenotic lesions may benefit from more conservative balloon mitral commissurotomy.
Consultations
- Primary care physicians should be considered the patient's advocate and guide to medical resources.
- Rheumatologists usually assist in diagnosis in the face of a substantial differential. Then, they can advise on the therapy plan.
- A cardiologist should be consulted when cardiac involvement is present.
- A neurologist may offer interventions to help manage chorea.
Diet
- No dietary factors are known.
Activity
- All patients should be restricted to bed rest and monitored closely for carditis.
- Aggressive use of acutely inflamed joints or other exercise may cause permanent joint injury to acutely inflamed joints.
- When carditis has been documented, a 4-week period of bed rest is recommended. As soon as the signs of acute inflammation subside, patients should resume active ambulation as tolerated.
- Most patients can be treated safely in an outpatient setting.
Medication
Treatment and prevention may involve multiple fields of discipline, including infectious diseases, cardiology, and neurology. For this reason, several different classes of medications are used. These include antibiotic, neuroleptic, and cardiac medications.
Antibiotics
Antibiotics are the initial pharmacotherapy for prevention and treatment of rheumatic fever.
Penicillin G procaine (Crysticillin)
Long-acting parenteral penicillin indicated in the treatment of moderately severe infections caused by microorganisms sensitive to penicillin G. IM administration only.
Adults: Deep IM injection into the upper outer quadrant of the buttock only.
Infants and small children: IM injection into midlateral aspect of the thigh is suggested.
Some authors prefer 10 d of therapy.
Adult
2.4 million U IM once
Pediatric
<30 lb: 600,000 U IM once
30-60 lb: 900,000-1,200,000 U IM once
Increases risk of bleeding when administered concurrently with warfarin; ethacrynic acid, aspirin, indomethacin, and furosemide may compete with penicillin G for renal tubular secretion, thereby increasing penicillin serum concentrations
Documented hypersensitivity
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 for more than 10 d to eliminate the organism and prevent complications such as endocarditis and rheumatic fever; perform cultures after treatment to confirm streptococci eradication
Penicillin G benzathine (Bicillin L-A)
Interferes with synthesis of cell wall mucopeptides during active multiplication, which results in bactericidal activity. Long-acting depot form of penicillin G. Because of its prolonged blood level, several authors believe this to be the DOC. Others prefer daily injections with short-acting penicillin.
Adult
2.4 million U IM once
Pediatric
<30 lb: 600,000 U IM once
30-60 lb: 900,000-1,200,000 U IM once
Probenecid can increase penicillin effectiveness by decreasing clearance; tetracyclines are bacteriostatic, possibly decreasing penicillin effect
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in renal dysfunction (adjust dose accordingly)
Penicillin VK (Beepen-VK, Betapen-VK, Robicillin VK, Veetids)
Inhibits biosynthesis of cell wall mucopeptide and is effective during stage of active multiplication. Inadequate concentrations may produce only bacteriostatic effects. PO alternative.
Adult
500 mg PO q6h for 10 d
Pediatric
<12 years: 25-50 mg/kg/d PO divided tid/qid, not to exceed to 3 g/d
>12 years: Administer as in adults
Probenecid can increase effects of penicillin by decreasing clearance; coadministration of tetracyclines can decrease effects of penicillin
Documented hypersensitivity
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 (adjust dose accordingly)
Erythromycin (EES, E-Mycin, Ery-Tab, Erythrocin)
Alternative for patients allergic to penicillin (although not the DOC).
Drug may inhibit RNA-dependent protein synthesis by stimulating the dissociation of peptidyl t-RNA from ribosomes. Inhibits bacterial growth.
In children, age, weight, and the severity of infection determine proper dosage. When bid dosing is desired, half-total daily dose may be taken every 12 h. For more severe infections, dose may be doubled.
Adult
250 mg erythromycin stearate, base, or estolate salts (or 400 mg ethylsuccinate) PO q6h or 500 mg PO q12h for 10 d; not to exceed 1 g/d; alternatively, 333 mg (as the base) q8h
Pediatric
30-50 mg/kg/d (base or ethylsuccinate) PO divided q6-8h; not to exceed 1 g/d
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; inhibits CYP1A2 CYP3A4 isoenzymes
Documented hypersensitivity, severe hepatic impairment
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); adverse GI effects are common; discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur
Anti-inflammatory agents
These agents inhibit inflammation to prevent destruction in the joints and heart.
Aspirin (Ascriptin, Bayer Buffered Aspirin, Ecotrin)
For treatment of mild to moderate pain and headache. Considered the first DOC for the treatment of arthritis due to acute rheumatic fever (ARF).
Adult
6-8 g/d PO for 2 mo or until ESR has returned to normal, adjust dose according to serum levels
Pediatric
80-100 mg/kg/d PO for 2 mo or until ESR has returned to normal, adjust dose according to serum levels
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; serum levels of 20-30 mg/100 dL required to control inflammatory response; high doses may cause gastric irritation or salicylate toxicity (ie, serum levels >20 mg/100 dL) and require dose reduction or alternative treatment with corticosteroids
Documented hypersensitivity; liver damage; hypoprothrombinemia; vitamin K deficiency; bleeding disorders; aspirin-sensitive asthma; because of association with Reye syndrome, do not use in children <16 y who have influenza or varicella infections
Pregnancy
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 with severe anemia or blood coagulation defects
Glucocorticosteroids
These agents demonstrate anti-inflammatory (glucocorticoid) and salt-retaining (mineralocorticoid) properties. Glucocorticoids produce profound and varied metabolic effects. These agents also modify the body's immune response to diverse stimuli.
Prednisone (Deltasone, Liquid-Pred, Meticorten, Orasone, Sterapred)
Patients with carditis require prednisone. The goal is to decrease myocardial inflammation. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. After 2-3 wk, dosage may be tapered, reduced 25% each week.
Adult
1-2 mg/kg/d PO for 2-3 wk initially; then discontinue by gradual taper over 3 wk; not to exceed 80 mg/d
Pediatric
0.05-2 mg/kg/d PO for 2-3 wk initially; then discontinue by gradual taper over 3 wk
May cause water and salt retention, thereby exacerbating hypertension and increasing requirement for antihypertensive drugs in patients with hypertension; may aggravate hyperglycemia, thereby increasing requirement for hypoglycemic agents in patients with diabetes; coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (adjust dose); hypokalemia may occur with coadministration of diuretics
Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI disease
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; may cause hyperglycemia, edema, weight gain, osteonecrosis, myopathy, dyspepsia, peptic ulcer, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, cataracts, glaucoma, and infections
Neuroleptic agents
These agents are used for chorea associated with ARF.
Haloperidol (Haldol)
Dopamine receptor blocker used for irregular spasmodic movements of the limbs or facial muscles.
Adult
0.5-2 mg PO bid/tid
Pediatric
<3 years: Not established
3-12 years
Initial: 0.05 mg/kg/d or 0.25-0.5 mg/d PO divided bid/tid, may increase by 0.25-0.5 mg/d PO q5-7d
Maintenance: 0.05-0.15 mg/kg/d PO in 2-3 divided doses; not to exceed 0.15 mg/kg/d
>12 years: Administer as in adults
May increase tricyclic antidepressant serum concentrations; may increase 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
Documented hypersensitivity; narrow-angle glaucoma; bone marrow suppression; severe cardiac or liver disease; severe hypotension; subcortical brain damage
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; monitor for hypotension with parenteral administration; caution in diagnosed 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 it occurs)
Positive inotropic agents
Digoxin may be indicated for patients with congestive heart failure.
Digoxin (Lanoxin)
Acts directly on cardiac muscle, increasing myocardial systolic contractions. Its indirect actions result in increased carotid sinus nerve activity and enhanced sympathetic withdrawal for any given increase in mean arterial pressure.
Adult
0.125-0.375 mg PO qd
Pediatric
Digitalizing dose (administer in divided doses over 24 h)
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
<10 years: 25-35% of PO loading doses divided bid
>10 years: 25-35% of PO loading dose qd
Medications that may increase 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; drugs that may decrease serum levels include aminoglutethimide, antihistamines, cholestyramine, neomycin, d-penicillamine, aminoglycosides, oral colestipol, hydantoins, hypoglycemic agents, antineoplastic treatment combinations (including carmustine, bleomycin, methotrexate, cytarabine, doxorubicin, cyclophosphamide, vincristine, and procarbazine), aluminum or magnesium antacids, rifampin, sucralfate, sulfasalazine, barbiturates, kaolin/pectin, and aminosalicylic acid
Documented hypersensitivity; beriberi heart disease; idiopathic hypertrophic subaortic stenosis; constrictive pericarditis; carotid sinus syndrome
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 normal; magnesium replacement therapy must be instituted in patients with hypomagnesemia to prevent digitalis toxicity; patients diagnosed with incomplete AV block may progress to complete block when treated with digoxin; exercise caution in hypothyroidism, hypoxia, and acute myocarditis
More on Acute Rheumatic Fever |
| Overview: Acute Rheumatic Fever |
| Differential Diagnoses & Workup: Acute Rheumatic Fever |
 Treatment & Medication: Acute Rheumatic Fever |
| Follow-up: Acute Rheumatic Fever |
| Multimedia: Acute Rheumatic Fever |
| References |
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Further Reading
Keywords
acute rheumatic fever, ARF, group A streptococcal pharyngitis, streptococcal pharyngitis, Sydenham chorea, painful migratory arthritis, rheumatic heart disease, chorea, erythema marginatum, subcutaneous nodules, antistreptococcal antibodies, antistreptolysin O, ASO, Aschoff nodules, carditis, Jones criteria, valvular murmurs, streptococcal infection, migratory polyarthritis
