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Management of Acute Rheumatic Fever
INTRODUCTION
Initial management of acute rheumatic fever (ARF) is based on establishing the diagnosis, eradication of the streptococcal organism, curtailment of normal physical activities, management of fever, joint manifestations, carditis and heart failure, and Sydenham chorea. Long-term care involves the commencement of prophylaxis against ARF and infective endocarditis, as well as patient/family/community education and public health measures ( Table 4.1 ).
Table 4.1
Management Protocol for Acute Rheumatic Fever.
| Diagnosis |
|
| Eradication of GAS |
|
| Arthritis/arthralgia and symptomatic treatment |
|
| Carditis/heart failure |
|
| Chorea |
|
| Discharge procedure |
|
ACEI, angiotensin-converting enzyme inhibitor; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; GAS, group A streptococcal; NSAIDs, nonsteroidal antiinflammatory drugs.
a Also known as phenoxymethylpenicillin or penicillin V potassium (PVK)
Recommendations for the management of ARF have been sourced predominantly from the Indian Academy of Pediatrics (2008), as well as the Australian (2012) and New Zealand (2014) consensus guidelines. These are based mainly on expert opinion, supported by various levels of evidence. There are few randomized controlled trials on the management of ARF and these do not cover all aspects of management. It is important to note that no treatment for ARF has been proven to slow the progression of valvular disease.
A medication summary ( Table 4.2 ) with dosage regimens is provided based on these recommendations. In addition, patients should be monitored regularly for response to treatment and physicians should be mindful of contraindications to medications and drug allergies.
Establishing the Diagnosis
In most instances, admission to hospital is recommended as establishing the diagnosis takes time, requiring laboratory and echocardiographic evidence. The consequences of under- and overdiagnosis cannot be overstated. The diagnosis and differential diagnosis of ARF are discussed in detail in Chapter 3 .
Hospitalization also allows the opportunity for repeated education about ARF and the need for secondary prophylaxis.
Eradication of the Group A Streptococcus
Penicillin is the most important medical treatment of ARF. Its introduction during the acute phase of ARF should eradicate the Group A Streptococcus (GAS) infection, which if persistent can induce chronic or relapsing autoimmune reactions. Although penicillin is considered mandatory, this treatment has not been shown to alter the cardiac outcome after 1 year in controlled studies.
Following hospital admission, oral penicillin V ( Table 4.2 ) should be commenced in all cases whilst the diagnosis of ARF is being established . Ordinarily, oral treatment should last for 10 days to reliably eradicate GAS . However, once the diagnosis of ARF is established and providing that the patient is not in severe heart failure, the first dose of benzathine penicillin G (BPG) should also be started in hospital, at which point the oral penicillin is stopped . BPG administration in these circumstances serves the dual purpose of eradication of GAS whilst also acting as the first dose of secondary prophylaxis. Education on the importance of secondary prophylaxis should also be provided at the same time . Intravenous penicillin is not indicated.
Table 4.2
Medication Table for Acute Rheumatic Fever.
| Australian Guidelines, 2012 | New Zealand Guidelines, 2014 | Other Recommendations | |
|---|---|---|---|
| Antibiotics | |||
| To treat the initial streptococcal infection | |||
| Phenoxymethylpenicillin (Penicillin V), orally a | Child : 250 mg bd (for 10 days). Adolescents and Adult : 500 mg bd (for 10 days). |
Children <20 kg : 250 mg 2–3 × daily (for 10 days). Children and adults ≥20 kg : 500 mg 2–3 × daily (for 10 days). |
Children : 250 mg 2–3 × daily. Adolescents or adults : 250 mg 3–4 × daily, or 500 mg bd. |
| Amoxicillin , orally a | – | Once daily (for 10 days) : 50 mg/kg (maximum dose 1000 mg daily). OR : Weight <30 kg: 750 mg once daily. Weight ≥30 kg: 1000 mg once daily. Twice daily (for 10 days) : 25 mg/kg bd (maximum dose 1000 mg daily). |
25–50 mg/kg/day tds.
Total adult dose is 750–1500 mg/day × 10 days. |
| Erythromycin ethyl succinate b , orally. Used in those with penicillin allergy | Child : 20 mg/kg (maximum dose 800 mg) bd (for 10 days). Adult : 800 mg bd (for 10 days). |
Children and adults : 40 mg/kg/day in 2–3 divided doses (for 10 days). Maximum dose 1600 mg daily. |
- |
| Benzathine penicillin G by IM injection (Once the first dose is given, oral penicillin is stopped) |
<20 kg (single dose): 450 mg (600,000 units) ≥20 kg (single dose): 900 mg (1.2 million units) |
Children <30 kg (single dose) : 450 mg (600,000 units). Adults and children ≥30 kg (single dose) : 900 mg (1.2 million units). |
1.2 million units IM, 600 000 units For children <27 kg. |
| Analgesics | |||
| Antiinflammatory drugs | |||
| Paracetamol , orally. For fever and mild arthralgia or until diagnosis is confirmed. Duration: until symptoms are relieved or NSAIDs are started. | 60 mg/kg/day given in 4–6 doses/day. Can increase to 90 mg/kg/day, if needed, under medical supervision. Maximum 4 grams daily. | 60 mg/kg/day in 4–6 doses. Can increase to 90 mg/kg/day if required under medical supervision. Maximum 4 grams daily. | - |
| Naproxen , orally. For arthritis, or severe arthralgia (when ARF diagnosis is confirmed), until joint symptoms are relieved. Safer alternative to aspirin. |
10–20 mg/kg/day (maximum 1250 mg/day), divided q12h. | 10–20 mg/kg/day, divided q12h (maximum 1000 mg/day) until pain is relieved, then taper dose. | - |
| Ibuprofen , orally. Use as for naproxen. No data to support its use in ARF |
30 mg/kg/day (maximum 1600 mg daily), divided tds. | 5–10 mg/kg/dose 8 hourly until pain is relieved, then taper dose. Maximum 400 mg per dose. |
- |
| Aspirin, orally. Use as for naproxen. |
Begin with 50–60 mg/kg/day, increasing if needed to 80–100 mg/kg/day (4–8 g/day in adults) given in 4–5 divided doses/day. If higher doses are required, reduce to 50–60 mg/kg/day when symptoms improve, and cease when symptom free for 1–2 weeks. Consider stopping in presence of acute viral illness, and it is recommended that children receiving aspirin during the influenza season (autumn/winter) also receive the influenza vaccine. |
Not recommended due to concern about Reye's Syndrome. | - |
| Heart failure drug s | |||
| Diuretics | |||
| Furosemide , orally or IV (can also be given IM). For heart failure signs and symptoms. Duration: until heart failure is controlled and carditis improved. |
Child : 1–2 mg/kg stat, then 0.5–1 mg/kg/dose 6–24 hourly (maximum 6 mg/kg/day). Adult : 20–40 mg/dose, 6–24 hourly, up to 250–500 mg/day. |
Orally in children: 1 month–12 years: 0.5–2 mg/kg 2–3 times daily. Medium dose is 1 mg/kg bd. Maximum 6 mg/kg daily, not to exceed 80 mg/day. 12–18 years: 20–40 mg daily (increase to 80–120 mg daily in resistant oedema). Slow intravenous injection in children: 1 month–12 years: 0.5–1 mg/kg every 8 h as necessary. Maximum 2 mg/kg (40 mg) every 8 h. 12–18 years: 20–40 mg every 8 h as necessary (resistant cases may require higher doses). Adults : 20–40 mg/dose 12–24 hourly up to a maximum dose of 250–500 mg/day. |
- |
| Spironolactone, orally. Duration as for furosemide. Round dose to multiple of 6.25 mg (quarter of a 25 mg tablet) if liquid form not available |
1–3 mg/kg/day (maximum 100–200 mg/day) in 1–3 divided doses. | Orally in children: 1 month–12 years: 1–3 mg/kg/day (maximum 100–200 mg/day) in 1–2 divided doses. 12-18 years: 50–100 mg daily in 1–2 divided doses. |
- |
| ACE inhibitor s | |||
| Enalapril, orally. Duration as for furosemide. | Child: 0.1 mg/kg/day in 1-2 doses, increased gradually over 2 weeks. Adult: Initially 2.5 mg daily. Maintenance 10–20 mg daily. Maximum 40 mg daily. |
Children: 0.1 mg/kg/day in 1–2 doses increased gradually over 2 weeks. Adults: Initially 2.5 mg daily. Maintenance 10–20 mg daily. Maximum 40 mg daily. |
- |
| Captopril, orally. Duration as for furosemide. | Child: Initial dose 0.1 mg/kg/dose. Beware of hypotension. Increase gradually over 2 weeks to 0.5–1 mg/kg/dose 8 hourly (maximum 2 mg/kg/dose 8 hourly). Adult : Initial dose 2.5–5 mg. Maintenance dose 25–50 mg 8 hourly. |
Children: 0.1–0.2 mg/kg/dose 8 hourly increasing in increments to 1–1.5 mg/kg/dose 8 hourly. 12 – 18 years: 12.5–25 mg 2–3 times a day increasing to a maximum of 150 mg daily in divided doses. Adults: Up to 50 mg 8 hourly. |
- |
| Lisinopril, orally. Duration as for furosemide. | Child: 0.1–0.2 mg/kg once daily, up to 1 mg/kg/dose. Adult: 2.5–20 mg once daily (maximum 40 mg/day). |
Children: Initially 70 mcg/kg (maximum 5 mg) once daily, increased in intervals of 1–2 weeks to a maximum of 600 mcg/kg (or 40 mg) once daily. Adults : 2.5–20 mg once daily Maximum of 40 mg daily. Monitor blood pressure during initiation of therapy. |
- |
| Additional Heart Failure Medicines | |||
| Digoxin, orally or IV. For heart failure/atrial fibrillation Seek advice from specialist regarding duration of use. Intravenous use in children rarely indicated |
Child: 15 mcg/kg initially, then 5 mcg/kg after 6 h, then 3–5 mcg/kg/dose (maximum 125 mcg) 12 hourly. Adult 125–250 mcg daily. Check serum levels. |
Children: 15 mcg/kg oral stat and then 5 mcg/kg after 6 h, then 3–5 mcg/kg/dose 12 hourly. Maximum dose 125 mcg 12 hourly. Adults: 62.5–500 mcg daily. Check serum levels. |
- |
| Prednisolone or prednisone , orally. For severe carditis, heart failure, or pericarditis with effusion (if acute heart surgery is not indicated) . Not evidence based and not shown to alter long-term outcome. Usual duration: 1–3 weeks. |
1–2 mg/kg/day (maximum 80 mg). If used >1 week, taper by 20%–25% per week. | 1–2 mg/kg/day. If used >1 week, taper by 20%–25% per week. Maximum dose: 60 mg daily. |
Regime I Prednisolone: 2 mg/kg/day, maximum 80 mg/day till ESR normalizes—usually 2 weeks. Taper over 2–4 weeks, reduce dose by 2.5–5 mg every 3rd day. Start aspirin: 50–75 mg/kg/day simultaneously, to complete total 12 weeks. (Level of evidence: class I) Regime II Prednisolone: same doses × 3–4 weeks. Taper slowly to cover total period of 10–12 weeks. (Level of evidence: class IIb) |
| Methylprednisolone sodium succinate ("Solu-Medrol"), IV If no response to oral steroids. |
– | – | Children 1–18 years: 10–30 mg/kg/day, in 2 divided doses (maximum dose 1000 mg/day) c Adults: initial dose 10–40 mg over several minutes; for high-dose therapy, 30 mg/kg, may repeat every 4–6 hours c |
| Sydenham Chorea | |||
| Carbamazapine, orally. For severe chorea. Continue until chorea controlled for several weeks then trial off medication. |
7–20 mg/kg/day (7–10 mg/kg/day usually sufficient) in divided doses, given 3 × daily. | 7–20 mg/kg/day (7–10 mg/kg/day usually sufficient), given in divided doses tds. | - |
| Valproic acid, orally. For refractory chorea (hepatotoxic). Avoid in women of childbearing potential as teratogenic. Duration as for carbamazepine |
15–20 mg/kg/day (can increase to 30 mg/kg/day) given In divided doses tds. | 15–20 mg/kg/day (can increase to 30 mg/kg/day), given in divided doses tds. | - |
| Haloperidol | – | – | Start 0.025 mg/kg/day, increasing slowly monitoring effect to a maximum of 0.15 mg/kg/day. |
| Prednisone | – | – | 2 mg/kg/day for 4 weeks and then taper. |
| Intravenous immunoglobulins (IVIG) | – | – | 1 g/kg/day × 2 days. |
ARF, Acute Rheumatic Fever; bd , bis die (twice daily); BPG benzathine penicillin G; ESR , erythrocyte sedimentation rate; IM, intramuscular; IV, intravenously; mcg, micrograms; NSAID, nonsteroidal antiinflammatory drug; po , per oral; stat , statum (Latin word for immediately). tds , ter die sumendum (three times daily);
a Both Penicillin V and amoxicillin are equally effective in eradicating GAS. Oral penicillin V is best absorbed on an empty stomach whereas amoxicillin can be taken with food and is relatively palatable.
b There are other erythromycins available with different dosing regimens to erythromycin ethyl succinate. Check dosing with your local pharmacist.
c Administer by slow intravenous infusion over at least 30 min. Therapy should be continued only until the patient's condition has stablised, usually not longer than 48–72 hours.
There is emerging evidence that impetigo (skin sores) may play a role in the pathogenesis of ARF. As such, bacterial cultures of impetigo should be taken and treatment of impetigo undertaken.
Rashes following previous antibiotic administration may lead to patients erroneously being labeled as allergic to penicillin (the vast majority are not). Penicillin allergy can be investigated by skin testing, preferably with input from an allergist. If this is unavailable and following careful investigation to ensure that it is safe to do so, an empiric course of penicillin should be given in hospital with close observation and treatment for anaphylaxis as required (see Chapter 11 for further discussion on anaphylaxis and assessment of possible penicillin allergy ) . Erythromycin orally is the treatment of choice in those proven to have penicillin allergy (see Table 4.2 ).
General Measures and Symptomatic Relief
Salicylates (aspirin) and nonsteroidal antiinflammatory drugs (NSAIDs) have been recommended for fever and joint pain but do not affect the prevalence or severity of clinical valve sequelae in the long term.
Fever
Paracetamol can be prescribed in several circumstances: for fever and mild arthralgia; until the diagnosis of ARF is confirmed (see Arthritis and/or Arthralgia, below); until symptoms are relieved; or concomitantly when NSAIDs are started.
Bed Rest and Diet
Most patients with suspected ARF should be admitted to hospital, which has benefits beyond establishing the diagnosis. If there is evidence of carditis, hospitalization also ensures that bed rest is adhered to (which may not be feasible in a home environment, particularly in poorly-resourced countries). Resting allows reduction of workload on the heart and may prevent progression of the inflammatory process. Hospitalization also provides an ideal opportunity to educate patients and families about ARF. Further education by primary healthcare staff, using culturally appropriate educational materials, should be continued once the patient has returned home.
In the prepenicillin era there was evidence that bed rest was associated with a shorter duration of carditis and fewer relapses. In the postpenicillin era, no randomized controlled trials have been undertaken to assess the effect of bed rest objectively. If mild, the mitral regurgitation in patients with carditis can diminish or disappear with bed rest. If the patient continues to exercise and the patient does not receive penicillin, rheumatic activity may persist and mitral regurgitation can worsen. The excessive workload on the heart of a patient with severe rheumatic mitral regurgitation produces a situation analogous to that of a child with active carditis and a mild valve lesion being forced to exercise continuously. Severe mitral regurgitation, with its associated hemodynamic overload, can aggravate rheumatic activity. This concept is supported by the observation of rapid resolution of rheumatic activity postoperatively. The correction of the valve lesion results in removal of the excessive cardiac workload caused by the regurgitation.
Although most patients with ARF need bed rest early in their illness, gradual mobilization is recommended once the initial symptoms have begun to resolve. In those with heart failure or acute severe valve lesions, mobilisation should occur gradually over the first 4 weeks or until normalisation of the C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) has normalised or dramatically reduced.
In summary, in the absence of evidence, expert-based recommendation supports a role for bed rest initially, with the length of bed rest largely determined by the severity of carditis. In the absence of carditis, the patient can be mobilized once arthritis settles. No dietary restrictions are required except if the patient is in heart failure, then fluid and salt intake should be limited. Many patients with ARF are malnourished (pointing to rheumatic recurrence or an acute-on chronic or indolent presentation) and their diet should be optimized with the help of a dietician and improvements should be monitored with weekly weight checks during their hospitalization.
Major Manifestations
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