Introduction

Acute rheumatic fever (ARF) results from an autoimmune inflammatory process seen after a Streptococcus pyogenes (group A streptococcus) infection.

When you have a patient with features suggestive of Rheumatic fever (RF), you will have to categorise him under one of these categories for long-term management. Therefore, it is important to make a definitive diagnosis before you commence treatment.

1. No Rheumatic fever – There are no criteria to diagnose RF, and it is not considered
2. Possible Rheumatic fever – There are no criteria to diagnose RF, diagnosis of ARF is uncertain, but considered
3. Probable Rheumatic fever – There are no criteria to diagnose RF, but the diagnosis of ARF is more likely
4. Definite Acute Rheumatic fever without cardiac involvement – Criteria fulfilled
5. Definite Acute Rheumatic fever with cardiac involvement – Criteria fulfilled
6. Borderline Rheumatic heart disease – There is no history of ARF, but there is borderline evidence of RHD on Echocardiogram

Initial History and Examination

Take a relevant history on

• History of a sore throat (for aetiology)
• Joint symptoms – to differentiate from other forms of arthritis (joints involved, migratory type, swelling, duration, course and response to Aspirin. Arthralgia in ARF responds very well to Aspirin)
• Features of carditis (to decide on prophylaxis)
• Previous treatment with NSAIDs, antibiotics (as it can mask investigation results and course of the disease)
• Living conditions of the patient (to decide on the risk of recurrence)
• Family history of Rheumatic heart disease
• Risk of exposure to future Streptococcus infections

Examine to look for

• Features of a sore throat
• Joint involvement
• Carditis
• Chorea
• Subcutaneous nodules – Firm nodules over hard bony surfaces such as the elbows, wrists, shins, knees, ankles, vertebral column, and occiput
• Erythema marginatum
• Features of any other infection or inflammatory disorder (Chikungunya, Rheumatoid arthritis etc)

Investigations to be performed during the initial period

• FBC (to look for anaemia and leucocytosis)
• ESR (generally very high in RF)
• CRP
• Throat swab (for Group A Beta Haemolytic Streptococcus)
• ASOT repeat after 2 weeks to look for a 4-fold rise
• Chest x-Ray (to look for cardiomegaly, look for other chest infections)
• ECG (prolonged PR interval)
• Echocardiogram – to look for subclinical carditis and to evaluate the degree of RHD if there is clinical carditis
• Blood culture if Endocarditis or other infection is suspected on clinical grounds

Diagnosis

Diagnosis is made through application of modified Duket-Jones’ criteria (2015). The patient should fit into one of the six categories mentioned above.

Major criteria		Incidence at 1st episode of RF
Low risk population*	Moderate and high-risk populations**
Arthritis Polyarthritis only	Arthritis • Monoarthritis or polyarthritis   • Polyarthralgia	35-66%
Carditis*** – Clinical or subclinical		50-70%
Chorea		10-30%
Erythema marginatum		<6%
Subcutaneous nodules		0-10%

Minor criteria
Low-risk population	Moderate- and high-risk populations
Polyarthralgia	Monoarthralgia
Fever (≥38.5°C)	Fever (≥38°C)
ESR ≥60 mm/h and/or CRP ≥3.0 mg/dL	ESR ≥30 mm/h and/or CRP ≥3.0 mg/dL
Prolonged PR interval (unless carditis is a major criterion)

*Low Risk Population: Rheumatic fever incidence of <2/100,000 in school going children; RHD prevalence <1/1000)

**Moderate or High-Risk Population: Rheumatic fever incidence of > 2/100,000 in school going children; RHD prevalence >1/1000

***Evidence of carditis:

Clinical: Tachycardia (which is out of proportion to fever) – measure sleeping pulse

Significant murmurs. The commonest is due to MR; AR is relatively rare

Evidence of heart failure (combination of tachycardia, tachypnoea and tender hepatomegaly)

Evidence of pericarditis (Pericardial rub or effusion on echo or USS)

Cardiomegaly

Subclinical: Echocardiographic evidence of Rheumatic carditis

Criteria needed to diagnose during the 1^st Episode of suspected Rheumatic fever

Definite ARF

if the patient meets the following criteria

• 2 major manifestations + evidence of preceding Strep A infection or
• 1 major + 2 minor manifestations + evidence of preceding Strep A infection

“Probable” or “Possible” ARF?

When the clinical presentation is more in favour of ARF but there is only

1. One major or one minor manifestation or
2. There is no evidence of preceding Streptococcal infection (ASOT not measured or falls within normal limits)

Criteria needed to diagnose a recurrence of Rheumatic fever

Recurrence of Rheumatic Fever is diagnosed if the patient fulfils the following criteria, with evidence of a preceding group A streptococcal infection

• 2 major criteria or
• 1 major + 2 minor criteria or
• 3 minor criteria

* However, if the patient presents with Chorea or Indolent Carditis, there is no need for evidence of Group A Streptococcal infection

Management of the acute phase

Main objectives include

1. Suppress the inflammatory response in order to

1. Manage heart failure
2. provide symptomatic relief

2. Eradicate pharyngeal streptococcal infection to

1. Prevent the spread of the disease to others
2. Minimise the antigenic stimulation from Streptococcus
3. Eliminate the carrier state

Address the following areas during the management of a patient with ARF

1. Rest

Restrict activity during the acute phase (until ESR/CRP returns to normal)

Strict bed rest is not required in most cases

2. Eradicate Streptococcal infection

2.1 Penicillin V – Oral Phenoxymethylpenicillin

1. <30kg 250 mg 6-hourly oral for 10 days (or 15mg/kg up to 500mg)
2. >30kg 500 mg 6hourly oral for 10days

Or

2.2   Benzathine penicillin G – IM Benzathine penicillin

1. <27 kg: 600,000 units
2. ≥27 kg: 1.2 million units IM injection Once

Or

2.3   Oral Erythromycin for 10 days if allergic to penicillin

3. Treatment of arthritis and arthralgia

Do not start anti-inflammatory drugs until the diagnosis of ARF is complete. If it is only a single joint involvement, wait till it migrates to another joint. Use paracetamol for pain relief during this period

3.1 Aspirin

• Starting dose: 50-60mg/kg/day
  • Maximum dose: 80-100mg/kg/day (Adults 4-8g/day)
  • Give in 4-5 divided doses
  • Duration of treatment
    • It is based on clinical response and ESR/CRP results
    • Many patients need it only for 1-2 weeks
    • Some with persistent symptoms may need it for 6 weeks
      • May taper off if there is gradual improvement
    • If there is a rebound when tapering off, step up the dose again
      • Rebound does not indicate a recurrence of RF

3.2 Naproxen and Ibuprofen

Can be used if intolerant to Aspirin

4. Treatment of carditis

4.1 Mild to moderate carditis (without features of cardiac failure)

Specific pharmacological treatment is not indicated

4.2 Carditis (with features of heart failure)

4.2.1 Urgent investigations

• CxR
• Echocardiogram

4.2.2 Initial treatment

Rest

Evidence from the pre-penicillin era shows that prolonged bed rest is associated with shorter duration of carditis, fewer relapses and less cardiomegaly

• Strict bed rest is not necessary
• Gradual mobilisation as tolerated by the patient during the first 4 weeks
• ESR and CRP can be used as a guide to determine the need for rest
• If there is only mild or no carditis, rest is only to manage other symptoms like joint pain

Diuretics

• Furosemide 0.5 – 2 mg/kg/day

Corticosteroids

Studies performed during the pre-echo era failed to suggest any benefit of corticosteroids in reducing the risk of long-term heart disease

Many clinicians believe that the use of corticosteroids

• lead to rapid resolution of carditis and can be lifesaving in certain situations with severe acute carditis and
• are beneficial in carditis with pericardial effusions, advanced AV block and significant cardiomegaly

Dose

• Prednisolone 1-2mg/kg/day to a maximum of 80mg per day

• IV methylprednisolone may be given in very severe cases

• Duration: Usually <3 weeks
  • Tapering off
    • If less than one week, it can be stopped with improvement of CRP/ESR and when heart failure is controlled
    • If the duration is longer – decrease the dose by 20-25% every week
    • Can overlap with Aspirin, depending on the need for a longer period of anti-inflammatory therapy

ACE inhibitors

• Used especially for those who have AR or MR to reduce afterload
• Captopril or Enalapril can be used

 Cardiac surgery

Surgery for valve disease is not advisable during the acute phase unless there is refractory heart failure

Long term management

Main objectives include

• Prevention of recurrences through
  • Penicillin prophylaxis
  • improved living conditions and healthy lifestyle
• Follow-up for cardiac sequelae    

Categorisation and Duration of Prophylaxis

Possible ARF with no cardiac involvement

Normal Echocardiogram and normal ECG throughout

• Duration of prophylaxis – 12 months
  • At the end of 12 months after the initial episode, if there are no signs and symptoms of ARF and if the echocardiogram is normal, can discontinue prophylaxis
• **However, some experts believe close observation without penicillin prophylaxis is adequate for this category. You may use your judgment based on clinical features and patient factors
• Repeat Echocardiogram one year after discontinuing prophylaxis

Probable ARF

ARF is highly likely, but the criteria are incomplete, and the Echocardiogram is normal

Duration of prophylaxis

• Minimum of 5 years after the most recent episode of probable ARF or
• Until 21 years of age (whichever is longer)

Prophylaxis can be discontinued only if there are no probable or definite episodes of ARF within the previous 5 years and the echocardiogram is normal.

Repeat echocardiogram after one, three and five years from the date of cessation of prophylaxis to look for any new features to suggest that the patient had breakthrough attacks after cessation of prophylaxis.

Definite ARF without cardiac involvement

Diagnosis of ARF can be made based on criteria, but the echocardiogram and ECG remain normal throughout the episode

Duration of prophylaxis – same as probable ARF

Criteria for cessation of prophylaxis – same as probable ARF

Timing of echocardiography after cessation of prophylaxis – same as probable ARF

Definite ARF with cardiac involvement

Diagnosis of ARF can be made based on criteria, and there are echocardiogram and ECG changes to indicate cardiac involvement.

Duration of prophylaxis depends on the severity of heart disease.        

• Mild RHD
  • Mild regurgitation or stenosis of a single valve or prolonged PR interval on ECG during ARF
  • Duration of prophylaxis
    • Those with a documented history of ARF
      • Minimum of 10 years after the most recent episode of ARF or
      • Until 21 years of age (whichever is longer)
    • Those without a documented history of ARF and age <35 years
      • Minimum of 5 years after the most recent episode of ARF or
      • Until 21 years of age (whichever is longer)
  • Prophylaxis can be discontinued if there are no probable or definite episodes of ARF within the previous 10 years and the echocardiographic features remain stable without any progression of RHD.
  • Repeat echocardiogram after one, three and five years from the date of cessation of prophylaxis to look for any new features to suggest that the patient had breakthrough attacks after cessation of prophylaxis.
• Moderate to severe RHD
  • Moderate to severe valve involvement (stenosis or regurgitation) due to RHD
  • Duration of prophylaxis
    • Those with a documented history of ARF
      • Minimum of 10 years after the most recent episode of ARF or
      • Until 40 years of age (whichever is longer)
    • Those without a documented history of ARF
    • Minimum of 5 years after the most recent episode of ARF or
    • Until 40 years of age (whichever is longer)
  • Criteria for cessation of prophylaxis – can be considered if they have stable valve disease and cardiac function for more than 3 years, or if the patient or family decides based on advancing age or end-of-life care.
  • Timing of echocardiography after cessation of prophylaxis – every 6 months

Drugs recommended for prophylaxis

The following drugs can be used as prophylaxis against Group A beta haemolytic streptococcus infection

• IM Benzathine penicillin G
  • Dose
    • <20 kg: 600,000 units
    • ≥20 kg: 1.2 million units IM
  • Frequency
    • Once every 3 weeks for those with valvular heart disease
    • Once every 4 weeks for those without valvular heart disease
• Oral Penicillin V: 250mg BD
• Sulphadiazine, sulfisoxazole, sulfadoxine: 500mg BD in adults, 500mg OD in children < 30 kg
• Erythromycin: 250mg BD

Other Important points to note when managing patients with Rheumatic fever

• Always try to use IM Benzathine Penicillin as the Risk of recurrence* of Rheumatic fever is much higher with oral penicillin and other alternative antibiotics.

*Risk of recurrence with

            Benzathine penicillin: 0.4-0.6/100 Pt Yr

            Oral Sulfonamide: 2.8/100 Pt Yr

            Oral Penicillin: 5.5/100 Pt Yr (nearly 10 times more compared to IM B. Penicillin)

The duration of secondary prophylaxis must be adapted to each patient, depending on the risk of RF recurrence. Please consider the following fact when you decide on the duration of prophylaxis.

1. Age of the patient
2. Presence of RHD
3. Time elapsed from the last attack
4. Number of previous attacks
5. Degree of crowding in the family
6. Family history of RF/RHD
7. Socioeconomic and educational status of the individual
8. Risk of streptococcal infection in the area
9. Whether the patient is willing to receive injections
10. Occupation and place of employment of the patient
    1. (school teachers, physicians, employees in crowded areas)

Emphasise hygienic practices, prevention of overcrowding, good ventilation and sunlight at home, etc, in addition to the need for antibiotic prophylaxis to prevent recurrences.