Looking around he met the gaze of the Cardiology Registrar who was clearly waiting to make eye contact before launching into “the patient’s story”!
…“I have a patient in her early twenties who came in with a fever and a rash, but over the last few days she has started to go into heart failure”.
The Registrar had been in the Microbiologist’s teaching session early in the week, and had clearly “swotted up” after being asked questions he didn’t know the answers too.
The Cardiology Registrar then delivered the “piece de resistance” and declared “I think this might be Rheumatic Fever”.
“Have you done a throat swab and an ASOT?” asked the Microbiologist.
“Yes I’ve done a throat swab but …what’s at Ascot?” asked the Registrar looking slightly puzzled, “…other than …a race course...are “they” processing our throat swabs now?!”
The Microbiologist sighed… it had all been going so well up until then… it’s clear these “Any Qualified Provider (AQP) initiatives” are certainly changing medicine…
What is Rheumatic Fever?
Rheumatic Fever (RF) is a condition thought to occur as a result of infection with Streptococcus pyogenes (Group A beta-haemolytic streptococcus) in the upper respiratory tract which then causes “molecular mimicry”. Molecular mimicry is a form of autoimmune disease where the infection initiates a reaction away from the main expected source; in RF Streptococcus pyogenes, in the throat, triggers an immune response (antibodies and T cells) which cross-reacts to a normally unaffected part of the body, the heart. The immune system is essentially “tricked” into attacking the normal tissue causing the symptoms distant to the original infection.
RF is estimated to affect 500,000 people around the World every year and is the leading cause of cardiovascular death within the first 50 years of life. RF is primarily a disease of poverty and overcrowding which both support more efficient transmission of the infection, however cases do occur in developed and more affluent countries.
Who gets RF?
There are two components as to who gets RF. The first is the bacterium S. pyogenes itself, the second is the patient.
Streptococcus pyogenes – only certain types of S. pyogenes cause RF. These particular types are the ones that cause upper respiratory tract infections (URTI) such as pharyngitis and tonsillitis. Other types that cause skin infections or necrotising fasciitis do not cause RF. This specificity is thought to be due to the upper respiratory S. pyogenes having the correct antigens on its cell wall to cross-react with the normal body tissues involved in RF, added to this there is lots of lymphoid tissue in the upper respiratory tract where autoimmune reactions can develop. However, even with the right bacterium in the right place, only 3% of cases of S. pyogenes upper respiratory tract infections cause RF; the rest is down to the other component - the patient.
The patient – there is thought to be a genetic predisposition to RF, as not everyone infected with the type of S. pyogenes capable of causing RF actually develops the disease. It is thought that only certain people have the right targets on their body tissues for the cross-reacting antibodies and T cells to attack. Without this genetic predisposition the autoimmune reaction wouldn’t occur even if antibodies and T cells with the potential to cross-react were produced as a result of S. pyogenes; there is just no target for them. It’s the genetic predisposition that is the important bit.
What are the symptoms of RF?
The symptoms, which are included in the criteria used to diagnose RF known as the Jones criteria, usually occur 1-5 weeks after tonsillitis or URTI. The criteria are called the Jones criteria because they were first developed in 1944 by an American Cardiologist called T. Duckett Jones. They have been revised a number of times since then to bring them in line with the availability of modern investigations like blood tests and electrocardiograms (ECG). NB Weird to think of a time when blood tests and ECGs did not exist!
The Jones Criteria
I think “Duckett’s Criteria” or even “ducks in buckets” is better than boring “Jones Criteria”… Anyhow, I digress… The diagnosis of RF requires evidence of preceding S. pyogenes infection by positive culture or elevated / rising Anti-Streptolysin O Titre (ASOT) PLUS 2 major OR 1 major and 2 minor criteria.
ASOT is an antibody produced in response to infection with S. pyogenes that starts to rise about 10 days after the initial infection, and which returns to zero within 2-3 months. NB Ascot is a town in Berkshire with a horse racecourse frequented by the Queen and no, it does not process throat swabs! (correct at time of blogging!)
- Carditis – inflammation of all areas of the heart, but especially the heart valves. The left heart valves (mitral > aortic) are predominantly affected leading to the valves leaking (regurgitation), which if severe can result in heart failure. Heart valve damage usually persists into later life and can result in rheumatic heart disease from valve failure 10-20 years later.
- Arthritis – inflammation of joints, primarily the knees, ankles, elbows and wrists. Different joints are affected over time as the inflammation spreads and so this is often known as a migratory arthritis. Joint pain usually settles within 4 weeks and there is no long-term damage.
- Chorea – also known as St. Vitus dance and Sydenham’s chorea, this is an abrupt, writhing, non-rhythmic, involuntary movement which usually affects one side of the body. The movement stops when the person is asleep. The face can also be affected leading to involuntary frowns, grimaces and grins, as well as a “bag of worms” wriggling appearance to the tongue. It is extremely distressing to the person but does normally settle within 6 weeks, with a few people having problems up to 6 months. Longer term affects are rare but can occur.
- Erythema marginatum – this is a pink or red, non-itchy, rash that occurs on the trunk and limbs but spares the face. The rash spreads by clearing in the middle (hence the term “marginatum” describing the edge like appearance). The rash eventually disappears completely over a few days to weeks.
- Subcutaneous nodules – these are painless lumps up to 2cm in diameter which appear over bony surfaces or tendons. They are often symmetrical and the elbow is the most common site to be affected. They eventually disappear over a few days to weeks.
- Arthralgia – pain in the joints without inflammation
- Fever – temperature >38.5oC
- Elevated CRP or ESR – these are blood tests and markers of acute inflammation
- Prolonged PR interval – this is the period on the ECG that represents electrical conduction in the heart between the atria and the ventricles, and when prolonged it means the conduction is delayed and the patient’s heart is not beating properly
How is RF treated?
There is no specific treatment for RF. The goals of treatment are to provide symptomatic relief, eradicate the S. pyogenes from the upper respiratory tract and prevent further recurrence with prophylaxis.
- Joint pain and fever are treated with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) such as Ibuprofen or Naproxen. Fever can be controlled using Paracetamol.
- Eradication of S. pyogenes from the upper respiratory tract using beta-lactam antibiotics such as Phenoxymethylpenicillin, Amoxicillin or an oral cephalosporin. If the patient is allergic to beta-lactams, then a macrolide such as Erythromycin or Clarithromycin can be used.
- Patients who have had one episode of rheumatic fever should be given long-term antibiotics to prevent further cases as these can lead to progressive cardiac damage.
1st Line PO Penicillin V 250-500mg BD
2nd Line PO Erythromycin 250-500mg OD