Rheumatic fever: causes, symptoms, diagnosis, treatment, complications, prognosis

By Cristiano Antonino On Jul 8, 2022

Rheumatic fever (or ‘acute joint rheumatism’; hence the acronym ‘RF’, or ‘acute rheumatic fever’, hence the acronym ‘ARF’) is an acute inflammatory disease that can involve the heart, joints, skin and brain

The disease usually develops two to four weeks after a streptococcal throat infection

The heart is involved in about half of the cases. Damage to the heart valves, known as rheumatic heart disease (hence the acronym ‘RHD’), usually occurs after repeated attacks, but can sometimes occur after only one.

Damaged valves can cause heart failure, atrial fibrillation and valve infection.

Rheumatic fever can occur following an infection of the throat by the bacterium streptococcus pyogenes (‘group A β-haemolytic streptococcus’)

If the infection goes untreated, rheumatic fever occurs in up to 3% of people.

It is believed that the underlying mechanism involves the production of ‘self’ antibodies, i.e. mistakenly directed against certain tissues of the body (autoimmune disease).

The diagnosis of RF is often based on the presence of signs and symptoms in combination with evidence of a recent streptococcal infection.

Treating people with streptococcus with antibiotics, such as penicillin, reduces the risk of developing rheumatic fever.

To avoid misuse of antibiotics, it is important to be certain of the bacteria in the airways.

Other preventive measures include improved hygiene conditions.

In those with rheumatic fever and rheumatic heart disease, prolonged periods of antibiotics are sometimes recommended.

After an attack, there may be a gradual return to normal activities.

Once rheumatic heart disease develops, treatment becomes more difficult.

Occasionally, valve replacement surgery or valve repair is required.

Rheumatic fever is so called because its symptoms are similar to those of some rheumatic disorders

It is believed that the first descriptions of a disease similar to rheumatic fever date back to at least the 5th century BC in the writings of Hippocrates.

Rheumatic fever was certainly the most widespread rheumatic disease until the end of World War II.

Later, thanks to the spread of antibiotics and the improvement of social and economic conditions in Western countries, its occurrence decreased considerably.

In the second half of the 20th century, the incidence was one case per 1000 inhabitants per year.

Rheumatic fever occurs in about 325,000 children every year and about 33.4 million people currently suffer from rheumatic heart disease

Those who develop rheumatic fever are most often between the ages of 5 and 14, with 20% of first attacks occurring in adults.

It affects both sexes indiscriminately.

The disease is most common in developing countries and among indigenous populations in the developed world, where it is still a public health problem and where the incidence is as high as 100 cases per 100,000, while in places such as Australia or Eastern European states it usually exceeds 10 cases per 100,000.

In 2015, it caused 319,400 deaths compared to 374,000 in 1990.

Most deaths occur in developing countries, where up to 12.5 per cent of those affected can die each year.

Currently in Italy, thanks to increased socio-economic wellbeing, the occurrence of this disease has decreased greatly to 1 case per 100,000 people.

Causes of rheumatic fever

The origin of the disease lies in a pathogen localised in the throat that causes pharyngo-tonsillitis: group A β-haemolytic streptococcus.

If this is not adequately treated, the risk of contracting the disease increases.

There is also a greater familial predisposition in some individuals.

The manifestations of the disease are due to inflammation of the valve tissue, which leads to a decrease in the capacity of the heart valve (valve insufficiency) and an increase in the chemotaxis of lymphocytes towards it.

The causes are to be found in an autoimmune type disorder: recurrent and frequent conditions of pharyngo-tonsillitis lead to sensitisation of the subject against antigenic molecules carried by Streptococcus, which leads to a cross-reaction against common epitopes, of the self, at cardiac, joint and blood vessel localisation.

That is, antibodies, especially IgG produced against antigens carried by the bacterium also interact with molecules that are structurally similar to the bacterial antigens, causing even irreversible damage.

Risk factors

Due to their genetics, some people are more likely to contract the disease when exposed to the bacteria than others.

Other risk factors, besides familiarity, include:

low socio-economic status,
malnutrition by default,
low hygiene,
poverty,
frequent respiratory infections.

Symptoms and signs

Signs and symptoms include fever, multiple painful joints, involuntary muscle movements and occasionally a characteristic non-itchy rash known as ‘erythema marginata’.

Other symptoms include drowsiness, fatigue, abdominal pain, anorexia and epistaxis (‘nosebleeds’ found in 4% of children).

The data on symptoms and clinical signs were first compiled in 1944 by Jones TD, and were subsequently reviewed by other groups.

Thus, major and minor criteria necessary for making diagnoses were developed, which must support either 2 major criteria or one major and 2 minor criteria in order to be valid; in the latter possibility, these criteria must be accompanied by the demonstration of either a recent streptococcal infection, which can also be demonstrated by a pharyngeal swab, or a positive antistreptolysin titre.

Major criteria

Rheumatic cardiopathy (endocarditis, myocarditis, pericarditis, identifiable in 50% of cases) very often associated with the appearance of heart murmurs (for aortic insufficiency and mitral insufficiency), with various forms, in the most severe of which it can lead to the death of the patient.
Sydenham’s chorea (10% in children), once called St. Vitus’ dance, occurs late, even months after the onset of the disease, and leads the patient to make involuntary movements.
Erythema marginata, which rarely occurs on the trunk and is not itchy.
Polyarthritis, an arthritis with a migratory character that mostly affects the large joints (knees, ankles, shoulders, etc.), which is the most common manifestation (70%). It responds well to salicylates but prolongs its duration for a couple of weeks if left untreated.
Subcutaneous nodules (or Meynet’s rheumatic nodules), small (varying in volume from a lentil to a hazelnut), which are localised at the extensor surfaces of the joints, are mobile, non-painful and transitory.
The acronym J.O.N.E.S. is used to recall these criteria and derives from the initials of the English words: Joints (joints, polyarthritis), O (where the ‘O’ represents the heart, thus indicating carditis), Nodules (cutaneous nodules), Erythema marginatum (erythema marginata), Sydenham’s Chorea (Sydenham’s chorea).

Minor criteria

fever,
arthralgia,
elevated ESR,
PCR positivity,
PR tract lengthening on ECG,
previous episode of rheumatic fever.

Rheumatic fever, diagnosis

Jones’ major criteria still remain valid, although they are changed and updated very often.

The useful tests for diagosis are:

blood tests, where the ESR appears elevated;
electrocardiogram, where certain arrhythmias or conduction blocks (first-degree atrio-ventricular block) are found;
chest X-ray;
echocardiography with colordoppler, showing insufficiency of one of the heart valves, especially the mitral and aortic;
endomyocardial biopsy;
pharyngeal swab (showing infection with group A beta haemolytic streptococcus);
search for antibodies to streptococcal antigens (antistreptolysin titre).

The differential diagnosis arises in relation to:

infective endocarditis;
rheumatoid arthritis;
septic arthritis;
hepatitis B;
rubella.

Therapies

The management of rheumatic fever is directed at reducing inflammation with anti-inflammatory drugs such as aspirin or corticosteroids.

In addition to enforced rest and controlled diet in the case of carditis, drug therapy and, in severe cases, surgical therapy are also provided.

To combat the infection, penicillin V or G is used, which must be taken for at least 10 days.

Primary prophylaxis serves to avoid complications of pharyngotonsillitis and prevent rheumatic disease.

Other drugs:

erythromycin, 250 mg, every 6 hours, always for 10 days
prednisone, 40-60 mg (if carditis is present)
Penicillin: phenoxymethylpenicillin 250 mg (to be administered every 6 hours).

Only in certain cases, the most serious, is surgical valve replacement necessary, while reparative surgery does not always provide positive results.

Vaccine

No vaccine is currently available to protect against S. pyogenes infection, although research is underway to develop one.

Difficulties in developing a vaccine include the wide variety of S. pyogenes strains present in the environment and the large amount of time and people that will be required for appropriate testing for vaccine safety and efficacy.

Complications

Some patients develop significant carditis that manifests as congestive heart failure.

This requires the usual treatment for heart failure: ACE inhibitors, diuretics, beta-blockers and digoxin. Unlike typical heart failure, rheumatic heart failure responds well to corticosteroids.