Rheumatic fever – diagnosis and treatment

At a glance

1. Rheumatic fever is an autoimmune illness that follows group A streptococcal pharyngitis by 2 to 4 weeks and inflames the heart, joints, brain and skin. Its heart disease is covered in acute rheumatic fever; this page is about making the diagnosis and treating the whole patient.
2. A child or young adult with fever and arthritis has a long differential diagnosis. A single hot, swollen joint is aspirated first, and leukaemia is excluded before any steroid is given.
3. The 2015 Jones criteria need evidence of a recent streptococcal infection with two major manifestations, or one major and two minor. They are stricter in low-risk populations, such as most of Europe, where only polyarthritis counts as a major joint criterion.
4. The arthritis migrates between large joints, is very painful and settles within a day or two of aspirin or an NSAID; if it does not, the diagnosis is doubtful. Post-streptococcal reactive arthritis is persistent and responds poorly.
5. Sydenham chorea, which comes months later, is enough on its own for the diagnosis. Erythema marginatum and subcutaneous nodules are rare and go with carditis.
6. Treatment clears the streptococcus with penicillin, treats the arthritis with an NSAID or aspirin, and treats severe chorea with carbamazepine. No drug has been shown to stop the valve damage.
7. Secondary prophylaxis with benzathine benzylpenicillin every 4 weeks, for years, is what protects the heart, and keeping patients on it is the hardest part of care.

01Definition and overview

Rheumatic fever is a non-suppurative complication of pharyngitis with group A streptococcus (Streptococcus pyogenes): an autoimmune inflammation of the heart, the joints, the brain and the skin, in which no organism is found in the tissues. It is the same disease as acute rheumatic fever, whose page covers carditis and the valve disease it leaves. This page looks at it as a rheumatologist meets it: a young patient with fever and painful joints, or with chorea, in whom the diagnosis has to be made, other diseases excluded and every manifestation treated.

Rheumatic fever is described as a first episode or a recurrence, and as definite or, in some guidelines, probable or possible when the criteria are only nearly met in a high-risk setting. The diagnosis matters well beyond the attack: it commits the patient to years of penicillin injections.

02Etiology and pathophysiology

Only a small minority of untreated streptococcal sore throats are followed by rheumatic fever, about 0.3 per cent in the community and up to 3 per cent in epidemics. Susceptibility runs in families and twin studies suggest a large inherited part. Poverty, overcrowding and poor access to care bring the repeated streptococcal infections that lead to it. In some high-risk populations, streptococcal skin infection may also contribute.

The immune response to the streptococcus cross-reacts with human proteins, by molecular mimicry: the steps from the sore throat to the valve are set out in acute rheumatic fever. The other organs are affected differently:

• The joints: the synovitis is transient, with a sterile inflammatory effusion and probably immune complexes. There are no erosions, so the joints heal without damage.
• The brain: antibodies raised against the group A carbohydrate cross-react with neurons of the basal ganglia, binding lysoganglioside, tubulin and dopamine receptors, and increase dopamine release. This is why chorea can occur on its own; why it comes months after the infection is not fully explained.
• The skin: subcutaneous nodules show fibrinoid necrosis surrounded by histiocytes, like the granulomas of the heart, which is why they go with carditis. The cause of erythema marginatum is unknown.

03Clinical features

The illness begins with fever and malaise, typically 2 to 4 weeks after the sore throat, which many patients do not remember. Arthritis is the commonest presenting complaint, and the commoner and more severe the older the patient; carditis is commoner in young children.

The joints

Rheumatic arthritis occurs in 35 to 66 per cent of patients. It has a recognisable pattern:

• large joints: knees, ankles, elbows and wrists; the hips, the small joints of the hands and feet and the spine less often;
• migratory: each joint is inflamed for a few days, rarely more than a week, as the next one starts, so that the attack overlaps and lasts 2 to 4 weeks in all if untreated;
• painful out of proportion to the signs: a joint that looks only mildly swollen may be too tender to bear the bedclothes;
• dramatically responsive: aspirin or an NSAID settles it within 24 to 72 hours;
• benign: it never leaves damage. After many attacks, a rare Jaccoud arthropathy can follow, with ulnar deviation of the fingers that the patient can correct, because it lies in the capsule and tendons, not the bone.

In high-risk populations the arthritis can be in one joint only (aseptic monoarthritis), or there may be pain without swelling (polyarthralgia), which is why the Jones criteria count these as major there.

Chorea

Sydenham chorea occurs in 10 to 30 per cent, mostly in girls and in children, 1 to 6 months or more after the sore throat, and often alone:

• quick, jerky, purposeless movements of the face, hands and feet that vanish in sleep, sometimes on one side only (hemichorea);
• motor impersistence: a grip that squeezes and relaxes (milkmaid's grip), a tongue that darts in and out when held out, and arms that pronate when held above the head;
• weakness and low tone, clumsiness, untidy handwriting and slurred, explosive speech;
• emotional lability, anxiety and obsessive-compulsive symptoms, which can come before the movements and outlast them.

Because chorea comes late, inflammatory markers and even the streptococcal antibodies may be normal. Other causes are excluded first: lupus and the antiphospholipid syndrome, drugs, thyrotoxicosis, Wilson disease, tics and, in an adult, Huntington disease.

The skin

• Erythema marginatum, in under 6 per cent: pink rings with pale centres and spreading edges on the trunk and the upper arms and thighs, never the face, which come and go within hours and appear with heat. It does not itch and is easily missed, especially on dark skin.
• Subcutaneous nodules, in up to 10 per cent: firm, painless, pea-sized nodules over the extensor surfaces of the elbows, knees and wrists, the occiput and the spinous processes, appearing weeks into the illness and lasting a week or two. They are felt more than seen.

The heart and the minor features

Carditis, in 50 to 70 per cent when echocardiography is used, is often silent; its signs and management are in acute rheumatic fever. The minor manifestations are fever, joint pain without arthritis, raised ESR or CRP and a prolonged PR interval.

04Diagnosis and management

Fever with arthritis in a child or young adult

Rheumatic fever is one of many causes, and in Europe one of the rarer ones.

Tests

• Evidence of a recent streptococcal infection: a raised or rising antistreptolysin O titre, peaking 3 to 6 weeks after the infection, or anti-DNase B, peaking at 6 to 8 weeks. The normal range rises with age through childhood, so the laboratory's age-adjusted upper limit is used, and a second sample 10 to 14 days later can show a rise. A throat culture or rapid antigen test is often negative by the time of the fever.
• ESR and CRP, which are high in arthritis and carditis but may be normal in chorea.
• A blood count and film, and blood cultures if there is a murmur or a single hot joint.
• Synovial fluid from any single swollen joint: in rheumatic fever, sterile and inflammatory.
• An ECG for the PR interval, and echocardiography with Doppler in every suspected case, repeated during the illness.

The Jones criteria, 2015

A low-risk population has 2 or fewer cases per 100,000 school-aged children a year, or a prevalence of rheumatic heart disease of 1 per 1000 or less; a patient from a high-risk population, such as a recent migrant, is judged by the high-risk column even when living in Europe. With evidence of a recent group A streptococcal infection:

• a first episode needs two major manifestations, or one major and two minor;
• a recurrence needs two major, one major and two minor, or three minor once other causes are excluded.

Chorea alone, once other causes are excluded, and carditis found late, after a slow onset, need no evidence of a recent infection. The same joint findings cannot count twice: polyarthritis as a major manifestation excludes polyarthralgia as a minor one. The WHO's 2024 guideline recommends the Jones criteria for diagnosis in children, adolescents and adults.

Rheumatic fever or post-streptococcal reactive arthritis

In a moderate- or high-risk population, an arthritis after a streptococcal infection is treated as rheumatic fever, because there monoarthritis and polyarthralgia meet the Jones criteria, and missing rheumatic fever costs a heart valve.

Treating the attack

Patients are usually admitted for diagnosis, echocardiography and the start of prophylaxis; the 2025 Australian guideline allows some to be managed outside hospital with specialist advice. Activity is limited while the joints are inflamed and for longer if there is heart failure; long bed rest is no longer advised.

Australian guidance, since 2020, prefers naproxen or ibuprofen to aspirin for the arthritis, because aspirin at these doses causes tinnitus, gastric bleeding and, in children with influenza or chickenpox, Reye syndrome. The WHO's 2024 guideline made no recommendation for or against aspirin, NSAIDs, steroids or immunoglobulin to prevent rheumatic heart disease: the evidence is too poor to say that any of them does.

Secondary prophylaxis in practice

Recurrences come with new streptococcal infections, are most likely in the first year and the first five years after an attack, and cause most rheumatic heart disease. Every patient with rheumatic fever or rheumatic heart disease is given prophylaxis.

The duration, by American guidance:

The WHO's 2024 guideline adds:

• children and adolescents found on echocardiographic screening to meet the criteria for rheumatic heart disease are given prophylaxis too;
• intramuscular benzathine benzylpenicillin is the preferred prophylaxis, and oral penicillin is an acceptable alternative where injections are not possible, are refused or cannot be delivered;
• the evidence on duration is limited, so national guidelines decide it;
• patients with no history of penicillin allergy are not skin-tested; those with a mild past reaction, without anaphylaxis, angioedema or a severe skin reaction, may be given an oral test dose before the first injection;
• a local anaesthetic, lidocaine, may be added to the injection to reduce pain;
• every patient on prophylaxis should be supported to keep to it.

Keeping a teenager on injections every four weeks for a decade is the real challenge. Programmes that work keep a register of patients with recall reminders, give the injection at home or school by a familiar nurse, explain to the family why it matters, and make it hurt less: the vial at room temperature, lidocaine in the diluent, a slow injection, pressure or cold on the site beforehand and distraction. In registers, receiving more than 80 per cent of scheduled injections goes with lower mortality from rheumatic heart disease. Every missed injection is followed up within days.

Primary prevention

Treating streptococcal pharyngitis with penicillin prevents rheumatic fever, and the WHO recommends penicillin, by injection or by mouth, as the first-line treatment where the infection is confirmed, or suspected in children and adolescents in moderate- and high-risk populations without access to testing. In low-risk countries, sore throat guidance spares antibiotics for most patients, because rheumatic fever is now so rare. Vaccines against group A streptococcus are still in development.

05Epidemiology

First attacks peak between 5 and 15 years and are rare under 3 and over 30. The WHO's 2024 guideline puts rheumatic heart disease at about 55 million people and 360,000 deaths in 2021, almost all in low- and middle-income countries and in marginalised groups of richer ones, such as Indigenous Australians and Māori and Pacific peoples in New Zealand.

In most of Europe, rheumatic fever is now rare, with an incidence well below the low-risk threshold, and a European rheumatologist is more likely to see post-streptococcal reactive arthritis. The cases that do occur are often in migrants and refugees from high-risk countries, in deprived communities, and occasionally in clusters when streptococcal infections surge. Chorea is commoner in girls, and after puberty is seen mostly in women.

06Prognosis

The attack usually lasts up to three months. The arthritis always heals without damage. Chorea settles in most patients within weeks to a few months, but can last up to two years, recurs in a substantial minority, more often when prophylaxis lapses, and can come back in pregnancy or with oestrogen-containing contraceptives; some patients keep anxiety or obsessive-compulsive symptoms. Nodules and erythema marginatum leave no trace.

The heart decides the long-term outcome: about half of patients with carditis develop chronic rheumatic heart disease. Recurrences tend to repeat the pattern of the first attack, so a patient who had carditis is likely to have it again. Adherence to prophylaxis is the strongest influence on what happens next: with it, mild valve lesions often regress, and without it each recurrence adds damage. In children with isolated mild mitral or aortic regurgitation, which often regresses, the WHO considers it reasonable to stop prophylaxis after one to two years if the echocardiogram has returned to normal.

Post-streptococcal reactive arthritis heals without joint damage, though it can last months; whether it carries a real risk of later valve disease is uncertain.

Check yourselfAnswer, then say how sure you were: a lucky guess still counts as a weak point.

1A 12-year-old boy born and raised in Denmark has a fever of 38.6 °C and a single swollen, hot knee three weeks after a sore throat. His ASO titre is raised and his CRP is 9 mg/dL. The echocardiogram is normal. How do the 2015 Jones criteria count the knee?

As a major criterion, because any arthritis countsAs a minor criterion, polyarthralgiaIt cannot count as a major criterion, because only polyarthritis is major in a low-risk populationAs subclinical carditis

2A 14-year-old with suspected rheumatic fever has migratory arthritis of the ankles and knees. Five days after starting full-dose naproxen, the joints are no better. What should this prompt?

A switch to aspirin, which works better in rheumatic feverA higher dose of naproxen for another two weeksOral prednisolone for the arthritisA search for another diagnosis

3A 7-year-old girl has fever, pain in several joints, pallor and a few bruises. Her ASO titre is mildly raised. Why must a blood film be examined before any corticosteroid is given?

Acute leukaemia can present with fever and bone and joint pain, and steroids can mask it and harm its later treatmentSteroids interfere with the ASO titreSteroids cause choreaThe blood film is needed to measure the ESR

4A 15-year-old girl with Sydenham chorea is so restless that she cannot write, feed herself or walk safely. Which drug is usually chosen first?

Sodium valproateCarbamazepineHaloperidolAspirin

5A 17-year-old receiving benzathine benzylpenicillin every 4 weeks after rheumatic fever has started missing injections because of the pain. Which measure does the WHO 2024 guideline support?

Stopping prophylaxis, because the risk of recurrence is low at 17Giving the injection every 8 weeks insteadAdding a local anaesthetic such as lidocaine to the injection, with support to keep to the scheduleChanging to a single injection every year