6

ACUTE RHEUMATIC FEVER + INFECTIVE ENDOCARDITIS

Malak Abu-aqulah & Rahaf Hasan

ACUTE RHEUMATIC FEVER

PS. At least there will be 6 questions about these two lectures in the exam

In the past there were a lot of children have tonsillitis, their parents may give them poached eggs or lemon or whatever and after a period of time the child will develop joint pain, it was very common (rheumatic fever), but now when the child have fever they give him good antibiotic so the rheumatic fever significantly decreased especially in Jordan.

Rheumatic fever is an acute systemic immune disease, when

bacteria attack the throat specifically tonsils the body start to form antibodies against those bacteria and the result will be immune complex, this immune complex has many complications, the most important is pancarditis.

Page 2

The bacteria that is responsible to cause rheumatic fever is Group A beta- hemolytic Streptococcal infection in the pharynx mainly in tonsils, the same bacteria may attack the skin and cause scarlet fever and skin lesions but it will not cause rheumatic fever, it must be in the throat. There was a question about this point last year Rheumatic fever with its immune complex has many complications the most important one affects the heart, also another complications on joints, skin, subcutaneous tissue and brain. In sum the immune complex form nodules called aschoff nodules it depends where these nodules reach then it will cause symptoms. At the beginning the child have sore throat, tonsillitis and fever, after a period of time there will be joint pain, joint pain usually not important although it may develop to acute mono-arthritis it does not leave any deformities in the bone, just we are concern about knowing that it is rheumatic fever to prevent pancarditis. The incubation period for this disease about 2-3 weeks, the child might have sore throat and tonsillitis and it will be subsided after taking simple antibiotic, after 2-3 weeks incubation period joint pain may reveal with the symptoms of rheumatic fever. The most common ages affected by rheumatic fever are the children between 5-15 years old, so its peak incidence 5-15 yrs old, rarely we see patients pre to this period < 4 or after 40 yrs old.
Page 3

Question: Why 5-15 yrs old is the most common ages to develop rheumatic fever? First of all we have to know that rheumatic fever cause destruction to the main mitral (tricuspid) valve in the heart. Answer: There are many theories to explain that, one of them said that the structure of the mitral valve between 5-15 yrs old exactly similar to the structure of the bacteria!, so the antibodies attack against the bacteria and the heart. Before 4 yrs old and after 40 yrs old the structure is different; the structure of the tricuspid valve is different from the structure of the bacteria. Another theory said that the immune complex end to have fibrin and anti-inflammatory cells over it which will form aschoff nodules which will cause many things that we will see later on. It is not necessary that everyone have infection in beta hemolytic anemia will develop rheumatic fever, it is just up to 3% even now it is less than that. Question: Does every patient or child come to us with sore throat or tonsillitis and a little joint pain mean that he has rheumatic fever? Answer: no it doesnt. We have criteria help establishing rheumatic fever called modified JONES CRITERIA *We have major and minor, minor criteria are not important but if we have two major it is rheumatic fever

Page 4

MODIFIED JONES CRITERIA Major criteria Polyarthritis Carditis Chorea Subcutaneous nodules Erythema marginatum

Polyarthritis usually happens on large joints like ankle and knee, but it will not lead to any deformity, migratory; patient has pain in left knee and after 2-3 days it will subside and begin in the right ankle. Carditis it may cause pancarditis, patient might come with severe heart failure and it may lead to death. Chorea involuntary coarse movement: the name refers to monk his name is SYDENHAM CHOREA who had his own dance with strange random movements difficult to describe and dont have any specific characteristics. Subcutaneous nodules: which are the aschoffs nodules composed of immune complex with collagen, fibrin and inflammatory cells, might be subcutaneous and we can feel it. Erythema marginatum: redness in the skin which will expand and the center of it will disappear and improve eventually forming a ring and the center of it will be normal skin.

Page 5

Minor criteria Fever Polyarthralgia Previous rheumatic fever or heart disease

Prolongation in P-R interval Increase in ESR Positive ASO Positive throat culture

Fever, anyone with infection will have fever. Polyarthralgia, joint pain.

Previous rheumatic fever or heart disease, if we do ECG for the patient, the PQR complex between P-R interval should be less than 0.2 or less than large square on the ECG paper. But with patient has rheumatic fever as a result of infection there will be an effect on AV node which is responsible in controlling heart rate, may cause elongation in P-R interval. ESR: as a dentist you have to do it, any patient complain from anything with high ESR, this is significant, so means that if ESR high there is something wrong.

Page 6

If ESR above 100 it is alarm sign, because most of malignancies associated with ESR above 100. *So 40, 60 or 80 it is normal. How do we perform the ESR test? ESR: elimination sedimentation rate, we put a sample of blood in a tube in the laboratory and then we see during the first hour how much there is separation between RBCs and plasma, it is measured by milliliter. ASO anti-streptolysin O if it positive that means there is infection Positive throat culture; we take swap culture from throat, it will give streptococcal antigen, rarely we do it because the mouth full of flora, so with normal patient it may give positive culture.

*DR return to the major criteria.

Polyarthritis it is migratory may be sever bone for example at

day one there is severe knee pain and in the second day in the ankle and the third day in the wrist, so it is called flitting and fleeting; means it will not lead to any effect. It affects mainly large joints not small ones like fingers.
*rheumatoid arthritis is another disease affect small joints like in fingers not large ones and cause deformity*

Page 7

It affect large joints sequentially as we said 2-3 days pain in the right ankle then disappears completely and develop again in the left ankle. Usually affect just a single joint in adults 25-30 yrs old just knee pain or ankle pain. Pain last for 1-5 weeks then it will be disappeared there Is no more joint pain. Happens with 75% of patients who have rheumatoid arthritis (I think it is rheumatic fever) If we have 2 major criteria or more with some minor then we can say that it is rheumatic fever. (but may we have rheumatic fever without any arthritis) It subsided without any residual deformity leaving normal joints. If there is sever joint pain, Rheumatic response to aspirin and non steroidal so the pain will completely disappear.

Carditis
Most likely happened in children, above 80 yrs old rheumatic fever is not as harmful as it happens in the childhood, because the structure of the valve and the myocardium differ from the that of bacteria. It is a difficult issue to say this myocarditis or pancarditis as simple as that.
Page 8

It happens in one third of cases while polyarthritis happens in 75% of case two thirds or more, here (carditis) less than polyarthritis. We have to have one of these: Mitral regurg MR or aortic regurg AR murmur (normal valve but dilated ventricle) As we know each ventricle connected by two valves (mitral valve in the left ventricle and tricuspid valve in the right ventricle, aortic valve from the left ventricle, and pulmonary valve from the right. The normal blood circulation we have to know about it. Any new murmur (abnormal heart sound) due to dilated ventricle lead to dilated valve and mitral or tricuspid regurg, may we have short diastolic murmur, means there are more blood flow during the valve it may be due to high volume state or due to mitral regurg itself. Change in quality of heart sound (just you have to know about it but not to practice it), you cannot gauge this is abnormal heart sound even practitioner cannot know if it diastolic or systolic murmur in some cases. Tachycardia even at rest. The normal heart rate between 60100 if we have heart rate more than 100 this is tachycardia, below 60 this is bradycardia. Cardiomegaly on chest X-ray or on echo (echo-cardiogram). Pericarditis, picture of pericarditis (retrosternal chest pain, increase the respiration associated with diffuse ST changes in the ECG, it is acute pericarditis and pericardial effusion.
Page 9

 ECG changes, changes in contour of P wave due to depolarization and contraction of both atria (p wave means atrial contraction), if we have dilated ventricle, mitral regurg and tricuspid regurg may we have dilated atria and the P wave will be changed in shape and size. Inversion of T-waves (it must be positive and must go with the QRS direction, but in this case we may have inverted T wave). Prolonged PR interval as we said before.

SYDENHAMS CHOREA
Involuntary choreo- athetoid movements (like ballet dance he move one hand alone then he start to move the other). It exists in 50% of patients. So as we said the most common is polyarthritis 75%, pancarditis or cadiac involvement in one third, and here (Sydenhams chorea) in 50% of cases. Girls affected more frequently than males. *And as we said all these manifestations are rare in adult patients

Erythema Marginatum
There is ring enlarges slowly and there is pale area in the center, may be raised over the skin and can feel it, most likely it is transient means after a period it will disappear but in some cases it may be persistent and continue to be there.
Page 10

Subcutaneous Nodule
Feel it on the external joints like elbow, wrist or knee. Small fair nontender , rarely see it in adults it is childhood disease, it is not painful important point, attached to fascia or tendon sheaths over bony prominences so it can move, where there is prominence bone over the joints we see nodules ,it may persist for days or weeks, recurrent may disappear and come back again. Indistinguishable from rheumatoid nodules, there is another disease rheumatoid arthritis it affects the small joints and share some manifestations with rheumatic fever and one of these is subcutaneous nodules.

To reach a diagnosis we have to have two major criteria or one major with two minor

Differential diagnosis
Rheumatoid arthritis involving the small joints with deformities, patients affected by it cannot do anything by their hands Osteomyelitis

Endocarditis Chronic meningococcemia SLE systemic lupus erethromatosus, very bad disease

Page 11

 Lyme disease Sickle cell disease Surgical abdomen The question about them in the exam may come as : All of the following is considered as differential diagnoses except You dont have to know the details about them just know them by name ^_^

Treatment
The most important thing is to eradicate the bacteria from the pharynx, otherwise accordingly if the patient has pancarditis we do bed rest, give him non-steroidal or steroids. Polyarthritis: non-steroidal or high dose aspirin, their action like a magic with it.

But again the most important thing to prevent rheumatic fever and to prevent another attack, each attack take more risk to have complications, because of that children with documented rheumatic fever we should give them Benzathene penicillin 1.2 million units, sometimes in two weeks or monthly for at least 5 years after the last attack or till age of 18 yrs old and in some cases till 25 yrs old (monthly needle injection till 25 yrs old).

Page 12

*If the patient has penicillin allergy we give him erythromycin or oral penicillin not important point

If we leave the patient without any treatment the sequence will not affect the joint but it will destroy the heart valves. As a result if we dont make a good treatment with good antibiotic we may have rheumatic heart disease. Rheumatic heart disease: destruction of the heart valves, the bacteria beta-hemolytic streptococcus eventually the immune complex will destruct mainly the mitral valve (between the left atrium and the left ventricle). In majority of case 50% mitral valve alone involved, but mitral + aortic in 25% of cases. Pure aortic uncommon, to have patients with pure aortic stenosis due to rheumatic fever it is rare. If we have patient 35 yrs old with mitral stenosis always we ask about history of rheumatic fever or history of recurrent tonsillitis. Patient presented with sever mitral stenosis or mitral regurg, in about 60% they remember that they had some joint pain or tonsillitis or recurrent tonsillitis while he/she was a child.

Page 13

Let me sum up with you the main points in the lecture: Rheumatic fever is an acute systemic immune disease, affect the pharynx Caused by Group A beta- hemolytic Streptococcus bacteria Most important complication is pancarditis cause of formation of aschoff nodules Incubation period is 2-3 weeks Peak incidence 5-15 yrs old, rare <4 and >40 3% of people develop rheumatic fever MODIFIED JONES CRITERIA-major criteria Polyarthrits affect 75%, pain last for 1-5 weeks, 2-3 days migratory between large joints Carditis affect 1/3 of cases, MR or AR, tachycardia, cardiomegaly, abnormal heart sounds, pericarditis, changes in contour of P wave, inversion of T wave, prolonged P-R interval SYDENHAMS CHOREA, affect 50% of cases Subcutaneous Nodule, affect external joints, non painful, nontender, recurrent, indistinguishable from those of rheumatoid arthritis nodules Erythema marginatum MODIFIED JONES CRITERIA-minor criteria Fever Polyarthralgia Previous rheumatic fever or heart disease Prolongation in P-R interval Increase in ESR, above 100 Positive ASO Positive throat culture, not commonly do it To reach a diagnosis we have to have two major criteria or one major with two minor

Refer to page 11 to know the Differential diagnosis

Treatment, Benzathene penicillin 1.2 million units, at least for 5 years End of part 1
Page 14

Infective Endocarditis

As we said One of the causes of Infectious Endocarditis is RHEUMATIC FEVER, when there is a destructive valve now, let's start :

Infectious Endocarditis (IE): an infection of the hearts endocardial surface There are many Classification of Infectious Endocarditis firstly, We Classify IE into four groups: i. ii. iii. iv.

Native Valve IE Prosthetic Valve IE Intravenous drug abuse (IVDA) IE, as Addiction on heroin Nosocomial IE

Why were classified in this way?

There are different bacteria organisms

1-The patients with IV drug uses have Staphylococci auras with destructive tricuspid valve. 2- The patient with mitral valve rarely seen severe Infectious Endocarditis.

Page 15

3-The patient with Prosthetic Valve IE have vegetation prosthesis. 4-Patients in Nosocomial IE have very aggressive bacteria usually MRSA. Further Classification: i. Acute IE ii. Sub-acute IE How to differentiate between Acute IE and Sub-acute IE?

Sub acute IE often affects damaged heart valves with RF , mitral stenosis , mitral leakages thicken valve Acute IE affects normal heart valves Commonly Staph. Rapidly destructive valve If not treated, usually fatal within 6 weeks Be careful Rarely , we seen patient with Acute IE when they are already taken available antibiotics like Ampicillin, Amoxicillin, Zinnate Etiology( Important)::

*Native valve Endocarditis- Streptococcus viridians, Staphylococci, HACEK* *Prosthetic Valve Endocarditis- Coagulase negative Staphylococci, S.Aureus (very bad bacteria as when we make gastric band patient will died from S .Aurous pneumonia exposure) *IV Drug abuse endocarditis:- Tricuspid valve ,MRSA

Page 16

 *Nosocomial- we see in patient with Infectious Endocarditis in hospital , pacemaker lead- and/or implanted defibrillator associated endocarditis , also in depleted patient (long time central line patient ) 5-15% may be culture negative?? Although blood culture is a majors criteria to say its Infectious Endocardia because of prior antibiotic exposure and there's a special organism like HACEK group need special media to growth. Pathophysiology:

Which patient susceptibility more to have Infectious Endocarditis?

Turbulent blood flow, when we have mitral stenosis, calcified mitral valve or mitral leakage the blood flow from atrium to ventricles or from ventricle to aortic will have bad way which lead injury to valve if we have wound it will form a clot why this clot isnt inside a vessel? To prevent bacteria to catch the internal part of vessel, also injury to valve turbulent blood flow make a good area to colonization a bacteria. Bacteremia, the most important sources of Bacteremia a tooth brush, mouth bacteria that go inside blood stream if theres no suitable area to attack, it will go to spleen and destructed. ,but if have suitable area to attack like (mitral ring, aortic ring ),it will adhesive and form vegetation with bacteria, fibrin, inflammatory cell ,WBC SO we have amass called vegetation with Eventual invasion of the valvular leaflets
Page 17

So,, Pathophysiology :

We have Turbulent blood flow disrupts the endocardium making it sticky Bacteremia delivers the organisms to the endocardial surface Adherence of the organisms to the endocardial surface Eventual invasion of the valvular leaflets

As the result Turbulent blood flow causes endothelial injury- direct infection theres OR Nonbacterial thrombotic endocarditic s as in- platelet fibrin thrombus which seen in some cases of vegetation without endocarditic mainly in CLE patient Epidemiology Much more common in males than in females May occur in persons of any age and increasingly common in elderly Mortality ranges from 20-30% Risk Factors

Page 18

Intravenous drug abuse, with recurrent skin infection and destructive tricuspid valve Artificial heart valves , (prostheses valve ) and pacemakers Acquired heart defects, especially with Turbulent blood flow and injury to intimae of the valve Calcific aortic stenosis Mitral valve prolapsed with regurgitation up to 50% Congenital heart defects, patient with VCD more common associated with Infectious Endocarditic while patient with ACD must associated with other Congenital heart defects to cause Infectious Endocarditis Intravascular catheters Symptoms: Symptoms of infection fever, myalgia, Abdominal pain, joint pain, back pain, Leukocytosis without obvious source, the onset of symptoms is usually ~2 weeks or less from the initiating bacteremia, and not responding to antibiotic

Signs (the doctor search it)

Page 19

-Fever -Clubbing -Splenomegaly -Neurological manifestations -Heart murmur abnormal heart sound -Peripheral manifestationsOslers nodes, Subungual hemorrhage, Janeway lesions - Leukocytosis

-Anemia ,it a chronic process with more than 2 week fever for unknown origin so we chick Infectious Endocarditis -Microscopic hematuria -Elevated ESR, CRP -Decreased serum complement -Immune complexes -Rheumatoid factor in patient with RHEUMATIC ARTHRITIS will be positive while in patient with Infectious Endocarditic it will be positive due to Immune complexes

Cardiac Manifestations -New regurgitant murmurs -CHF- valvular damage (aortic), myocarditis -Perivalvular abscess -Fistulae connection between cardiac chambers right and left -Pericarditis -Heart block/ MI due to embolic phenomena

Page 20

in chest x ray Septic Pulmonary Emboli with some infraction in lung

Non cardiac manifestations In general in asystemic dieses when there are vegetation with abesses in heart and showing Emboli ,they will go to brain with nurigical manifestations, to lung with abscess and cause ischemic toes subungual hemorrhage Janeway noduls and glomunthrits in kidney(if it immune complex or vegetation)

Petechiae Nonspecific (without any causes ) Often located on extremities or mucous membranes mainly hard palate ,skin, congigtiva Splinter Hemorrhages Nonspecific Non blanching, dont disappear while we presses Linear reddish-brown lesions found under the nail bed Usually do NOT extend the entire length of the nail

Page 21

Mechanism: -Vessel damage from swelling of the blood vessels (vacuities) from immune complex -Tiny clots that damage the small capillaries (micro emboli) from vegetation (source infection).

Oslers Nodes More specific rarely seen with other dieses so if we have mostly associated with Infectious Endocarditis Painful and erythematous nodules Located on pulp of fingers and toes More common in subacute IE Mechanism :: immune complex Janeway Lesions More specific Erythematous, blanching macules painful Located on palms and soles -Mechanism: micro abscess of the dermis with marked necrosis and inflammatory infiltrate not involving the epidermis ( vegetation) **Roth Spots mainly seen in the retina of the eyes
Page 22

The Essential Blood Test Blood Cultures -Minimum of three separate blood cultures -Three separate venipuncture sites (not in same syringe and then disrupted in bottles) - At least 1 hour apart- over 24 hours from certain person from hospital they can deal with it (you have to have sterile gloves, gown, and bottles aerobic or non-aerobic with specific media for bacteria) -Serology- bacteria dont deal with them Imaging *Chest x-ray as we said, more commonly, the chest x-ray may reveal septic pulmonary emboli in a patient *ECG Rarely diagnostic prosthetic valve but if we have complete heart block or bradycardiain in infectious Endocarditic may a signe of abbesses (infection) spread to AV node so may have bradycardiain or tachycardia arrhythmias *Echocardiography Indications for Echocardiography *Transthoracic echocardiography (TTE): simple, non invasion, cheap test , TTE has superior sensitivity, especially in detecting native valve vegetations no need to further test , while in the
Page 23

prosthetic valve vegetation with echogenicity have a difficulty to judge normal or not because of their artificial prosthetic valve so we do what called Trans-esophageal echocardiography (TEE) *Trans-esophageal echocardiography (TEE) : - High risk patients, we have highly subspecialty of prosthetic valve but in Trans-esophageal Echocardiograph there no more important information -Intra-cardiac complications, we can't say never ever this is abbesses, fistulaetc. If there is any suspicion of IE, get a TTE. -Inadequate TTE if we have patient with long standing smoking, inflated lung (difficulty in window), obesity >100 kg -Fungal or S.aureus or bacteremia , in Fungal infection there's a difficulty in differentiation between thrombus and vegetations, he saw thrombus with 4x4 cm so if I have fever or suspicion Infectious Endocarditic, I can't say its thrombus or Fungal infection with larger vegetation so we need Transthoracic echocardiography(TTE) to judge .

Modified Duke Criteria (important) These criteria are sensitive and specific and very rarely reject a true endocarditis: *Definite IE

Page 24

-Microorganism (via culture or histology) in a valvular vegetation, embolized vegetation, or intra-cardiac abscess -Histologic evidence of vegetation or intra-cardiac abscess 2 Major 1 Major + 3 minors 5 Minor *Possible IE 1 major and 1 minor 3 minor Treatment -parenteral antibiotics for 6 weeks (long stay in hospital) -Prolonged treatment to kill dormant bacteria clustered in vegetation (broad spectrum) -Costly ** So you need to be accurate in Infectious Endocarditis

Poor Prognostic Factors Female, more aggressive in male than female-. S.aureus ,you will have small abscess with very aggressive bacteria Vegetation size, when you have just 0.8 cm it easier to deal with more than when we have multiple vegetation valves. Aortic valve, more dangerous than mitral and tricuspid valve because its out flow tract so the blood will take fewer bacteria to the body to brain.

Page 25

 Prosthetic valve because there's no blood flow in Prosthetic valve so most likely we need to put another prostheses with a result increasing in mortality rate Low serum albumen they happen with liver problem , Diabetes, can't even eat patient Paravalvular abscess, as a rule if we have abcsses and give antibiotic we will never cure we need to drain it, so in Paravalvular abscess when the abscess between valve and wall most likely to do incision. Embolic events Older age

Good luck ^_^ Malak Abu-aqulah Rahaf Hasan

Page 26