Theme :
1. Acute rheumatic fever in children. Etiology, pathogenesis, clinical classification, treatment, prognosis, prophylaxis.
2. Juvenile rheumatoid arthritis and reactive arthropathies. Etiology, pathogenesis, clinical classification, treatment, prognosis.
Rheumatic fever (acute rheumatic fever or ARF) is an autoimmune disease that may occur after a group A streptococcal throat infection that causes inflammatory lesions in connective tissue, especially that of the heart, joints, blood vessels, and subcutaneous tissue.
The disease has been described since the 1500s, but the association between a throat infection and rheumatic fever symptom development was not described until the 1880s. It was associated with scarlet fever (rash caused by streptococcal exotoxins) in the 1900s. Prior to the broad availability of penicillin, rheumatic fever was a leading cause of death in children and one of the leading causes of acquired heart disease in adults. The disease has many symptoms and can affect different parts of the body, including the heart, joints, skin, and brain. There is no simple diagnostic test for rheumatic fever, so the American Heart Association’s modified Jones criteria (first published in 1944 and listed below) are used to assist the physician in making the proper diagnosis.
The average annual incidence of acute rheumatic fever in children aged 5-15 years is 15.2 cases per 100,000 population in
Causes
Rheumatic fever is common worldwide and is responsible for many cases of damaged heart valves. It is not common in the
Rheumatic fever mainly affects children ages 5 -15, and occurs approximately 14-28 days after strep throat or scarlet fever.
When a streptococcal throat infection goes untreated, most patients recover without complications. Approximately 1 percent, however, develop rheumatic fever. The onset of the disease is most often characterized by the sudden occurrence of fever and joint pain and inflammation several days to six weeks after the streptococcal infection. Signs of cardiac involvement include heart murmurs, increased heartbeat rate, and heart enlargement. Inflammation of the heart muscle and supporting structures may lead to a permanent scarring and contracture of the heart valves and a marked decrease in life expectancy.
Other symptoms of rheumatic fever include nodules beneath the skin and skin rashes, the most typical of which is erythema marginatum; Sydenham chorea, a nervous system manifestation marked by emotional instability and purposeless, involuntary movements of the arms and legs; abdominal pain; nosebleeds; weakness; and loss of appetite and body weight. Generally the clinical symptoms, severity, and aftereffects of an attack of rheumatic fever are highly variable, ranging from a condition so mild as to go unnoticed to a severe acute attack associated with cardiac failure and death.
During the course of rheumatic fever, the streptococcal organism may no longer be demonstrable in cultures of the throat or other infected body areas, but blood titres of antibodies against the streptococcus, such as antistreptolysin O, are high. All the numerous types of group A beta-hemolytic Streptococcus appear capable of inducing rheumatic fever in susceptible individuals; infection with one type confers no immunity against the others, and individuals who have experienced one attack of rheumatic fever are especially prone to subsequent attacks. Both the initial and recurrent attacks can be effectively prevented with penicillin. Symptomatic treatment of the condition includes the use of salicylates such as aspirin or one of the steroid hormones. Surgery may be advocated to relieve the narrowing of the openings of the heart valves. Rheumatic fever patients must receive antibiotics on a regular basis for the remainder of their lives because their damaged heart valves predispose them to the development of bacterial endocarditis.
The exact cause of rheumatic fever is not clear, although most authorities favour the theory that the disease results from an autoimmune reaction, involving the production of antibodies that attack the body’s own tissues. The autoimmune reaction is believed to be triggered by components of the streptococci (antigens) whose structure resembles that of molecules found in human tissue (“self antigens”). Because of this resemblance, the antibodies that recognize streptococcal antigens may mistakenly react with similarly shaped antigens of certain cells of the body—such as those of the heart. By binding to these self antigens, the antibodies cause the tissue damage characteristic of rheumatic fever.
Since the mid-20th century the incidence and severity of rheumatic fever and other streptococcal infections, such as scarlet fever, have declined precipitously in the developed countries. This decline has occurred independently of the use of penicillin and other drugs and may simply signal the gradual dying out of the disease. However, in many other parts of the world rheumatic fever remains a serious and prevalent disease.
ETIOPATHOGENESIS:
Disease follows 1-5 weeks after pharyngeal infection by Group A beta -Hemolytic Streptococcus.
There is raised Anti-streptolysin-O titre (ASO titre) in blood.
Hence, the disease is thought to be due to cross-reaction between “Antibodies to streptococcal antigen” and “Cardiac tissue antigen” (which is similar to streptococcal antigen).
The initiating beta-hemolytic streptococcal infection of the throat, introduces the streptococcal antigens into the body and may also activate cytotoxic T-cells.
These antigens lead to the production of antibodies to various antigenic components of the streptococcus, which can cross react with certain cardiac antigens, including those from the myocyte sarcoplasma and from the glycoproteins of the valves.
This may be the mechanism for the production of the acute inflammation of the heart in acute rheumatic fever that involves all cardiac layers (endocarditis, myocarditis, and pericarditis).
This inflammation becomes apparent after a latent period of 2 to 3 weeks.
This may progress to chronic stenosis or insufficiency of the valves.
Clinically, the patients give the history of fever, sore throat followed by recovery.
After about two weeks, there is appearance of the symptoms of cardiac involvement and/ or migratory large joint polyarthritis, skin involvement (erythema marginatum) and subcutaneous nodule.
Some patients may develop Sydenham chorea, a neurologic disorder with rapid, involuntary, purposeless movement.
Repeated attacks or severe first attack causes chronic rheumatic heart disease leading to congestive cardiac failure.
Pathology:
Lesion develops in three stages:
1. Stage of exudation (edema with inflammatory cells) with fibrinoid necrosis.
2. Stage of cellular proliferation with formation of Aschoff body.
3. Stage of healing by fibrosis.
Aschoff body:
It is the characteristic lesion of the Rheumatic disease.
It consists of:
1. Cental fibrinoid necrosis ;
2. Surrounded by inflammatory cells and large, mono or multinucleated cells with transverse chromatin (Caterpillar cell or Anitschkow myocyte) ;
3. Fibroblasts encircling the above elements.
Aschoff bodies are situated on one side of the small arteries and are characteristically seen in the myocardium.
Jones criteria are guidelines decided on by the American Heart Association to help doctors clinically diagnose rheumatic fever.
Lesions :
– Extracardiac Rheumatic Lesions:
1. Joints – Larger joints are involved. Example: knee, ankle, elbow, wrist, shoulder and hip joints.
Aschoff bodies are formed in the synovial membrane, capsule, ligament etc. with serofibrinous effusion.
2. Serous membranes with effusion.
3. Skin- Erythema marginatum.
4. Subcutaneous tissue -Rheumatic nodule mainly seen over the bony prominences. Example: mastoid, knuckle, elbow, patella, scapular margin etc.
– Cardiac Rheumatic Lesions:
Heart (Pancarditis) – involves pericardium, myocardium and endocardium (valvular and mural).
Pericardium:
Grossly, due to acute fibrinous inflammation, pericardium loses its shiny, glossy appearance and becomes rough.
Sticky fibrinous exudate binds two layers of pericardium and on separation the rough surface shows “bread & butter” appearance.
Occasionally, there is a small amount of serofibrinous exudate in the pericardial sac.
Microscopic appearance :
Loss of endothelium with deposition of inflammatory cells – lymphocytes, plasma cells and occasionally polymorphs.
An occasional subpericardial Aschoff body may be present.
Fate:
1. Complete resolution
2. Organization with:
– Adhesion between two layers of pericardium (Adhesive pericarditis).
– Adhesive pericarditis with adhesion to mediastinal structures (Adhesive mediastino-pericarditis).
– Milk spot on the anterior surface of the left ventricle.
It is an unresolved patch of rheumatic pericarditis healed by organization.
Myocardium:
Aschoff bodies the characteristic lesion of rheumatic disease, is typically seen in the loose connective tissue of the myocardium, located characteristically near a small blood vessel.
Myocardial fibers are separated by edema and infiltrated with inflammatory cells .
In acute phase of exudation, heart is enlarged with functional disorder.
Later, Aschoff bodies are formed as minute white specks under endocardium, particularly in the left side of the heart at the base of the interventricular septum.
Aschoff bodies are present in the connective tissue between the muscle fibres and cause secondary degeneration of the muscles.
Aschoff bodies are healed up by fibrosis and myocardium is riddled with scarred areas resulting in myocardial failure.
Endocardium:
1. Mural endocardium, particularly in the posterior wall of the left atrium, just above the mitral valve, become rough, thick and later on scarred (MacCallum’s patch).
This is due to subendocardial aggregation of Aschoff bodies followed by fibrosis.
2. Valvular endocardium:
Most harmful effect of rheumatic disease is due to involvement of cardiac valves.
Mitral valve is most commonly affected, mainly in women, followed by aortic valve, mainly in men.
Tricuspid valve is rarely affected.
Pulmonary valve is practically never affected.
Inflammed valve cusps become edematous, thickened and there is formation of Aschoff bodies in the subendothelial connective tissue.
Continued work of the inflamed valves causes loss of endothelium due to trauma along the line of contact (a few millimeters above the free margin of the cusps).
On this raw surface platelets and fibrin are deposited forming minute, pale thrombi called rheumatic vegetations.
In course of time vegetations are organized and covered by the growth of the adjacent endothelium.
Rheumatic Vegetations:
1. Tiny (size of a pin’s head), sessile arranged in a row and firmly fixed with the underlying tissue, hence there is no embolism.
2. These are situated in the valve cusp, a few millimeters away from the free margin (this is the most traumatized area).
3. Vegetations may be situated on the auricular surface of mitral valve and ventricular surface of the aortic valve.
4. These are organized and endothelialized pale thrombi.
Aschoff bodies are also found in the chordae tendineae, which become fibrosed and shortened.
During acute stage, inflamed edges of cusps adhere together and later become fibrosed causing narrowing or stenosis.
Repeated attack of rheumatic fever causes repeated injury to valves and chordae tendineae, which become fibrosed, thickened and shortened.
Valve cusps appear as diaphragm with a central slit called ‘button hole’ type of mitral stenosis, commonly seen in adults.
Fusion of cusps with shortening of chordae tendineae produce ‘funnel shaped’ mitral stenosis with oval orifice at the apex of the funnel.
This is commonly seen in children.
CLASSIFICATION OF RHEUMATIC FEVER
|
Criteria |
Clinical-anatomical characteristics of the damages
|
Course of a disease |
Blood circulation insufficiency |
|
|
Heart |
Other systems and organs |
|||
|
Active activity: I, II, III stages |
1) primary rheumatic carditis 2)recurrent rheumatic carditis (without valvulas defects, with defects) 3)without visual heart changes |
Polyarthritis, serousitis (pleuritis, peritonitis, abdominal syndrome), chorea, meningoencephalitis, cerebdal vasculitis, nephritis, hepatitis, pneumonia, dental problems, iritis, iridocyclitis, thy roiditis |
Acute, subacute, prolonged, recurrent, remittent |
CI 0 – absent CI1 – I stage CI 2 – II stage CI 3 – III stage |
|
Not active |
1) heart defect ( what one) 2) rheumatic myocardiosclerosis |
Consequences and remaining effects after the main rheumatic process
|
|
|
|
If it possible, there is a necessity to point the main damage localization ( myocarditis, pericarditis , pancarditis, coronaritis) and to stress the numbers of attacks |
||||
Cryteria activity of the process
I stage
|
Leukocytosis |
less than 8х109 in |
|
Erythrocyte sedimentation rate |
less than 20 mm/hour |
|
C-reactive protein |
“-” or”+” |
|
Diphenilamine (DFA |
less 0,250 |
|
Serrummucoid |
0,30 |
|
Antistreptolysin 0 |
less than 330 |
II stage
|
Leukocytosis |
8- l0xl09nl 1 |
|
Erythrocyte sedimentation rate |
less than 20-30 mm/hour |
|
C-reactive protein |
“+”or”++” |
|
Diphenilamine (DFA |
less 0,250-0,330 |
|
Serrummucoid |
0,30-0,60 |
|
Antistreptolysin 0 |
less than 330 – 660 |
Ill stage
|
Leukocytosis |
more than l0xl09 1 1 |
|
Erythrocyte sedimentation rate |
more than 30 mm/hour |
|
C-reactive protein |
“+++”or”++++” |
|
Diphenilamine (DFA |
more than-0,3 30 |
|
Serrummucoid |
more than 0,60 |
|
Antistreptolysin 0 |
more than 660 |
The presence of 2 major criteria or of one major and two minor criteria indicates a high probability of the presence of rheumatic fever.
THE MAJOR CRITERIA for diagnosis include
· arthritis in several joints (polyarthritis), or migratory polyarthritis (joint inflammation), which usually presents first and occurs in 45% of patients and most commonly affects the large joints such as the knees
· heart inflammation (carditis), (inflammation of the heart), which occurs in 60% of patients is the most severe symptom of ARF and can result in permanent damage to the heart valves, and can be life threatening;
· nodules under the skin (subcutaneous nodules or Aschoff bodies), which are firm, painless lumps most frequently found around the wrists, elbows and knees. These are present in only 2% of patients
· rapid, jerky movements (Sydenham’s chorea), occurs in 30% of patients and is a movement disorder comprising of purposeless volatile movements of the face and arms. This was also called St. Vitus’ dance, which was named after the patron saint of the “mania dancers” of the middle ages
· skin rash (erythema marginatum), which occurs in 5% of patients and often described as a “serpiginous” with a wavy and snakelike appearance which has distinct erythematous (red) borders or “margins”
THE MINOR CRITERIA include
· fever, is often present during the acute infection with group A strep and is present during the initial phase of rheumatic fever.
· high ESR (erythrocyte sedimentation rate, an laboratory sign of inflammation),
· joint pain (arthralgia),
· ECG changes (electrocardiogram), and
other laboratory findings (elevated C-reactive protein, elevated or rising streptococcal antigen test).
Two major criteria or one major and two minor plus a history of a streptococcal throat infection are required to make the diagnosis of rheumatic fever.
Acute rheumatic myocarditis is a disease that occurs in a large percentage of patients with acute rheumatic fever with carditis. Can occur independently, rarely, or associated with acute rheumatic endocarditis, or pericarditis.According to some, in any acute rheumatic heart disease myocarditis is discrete or easily shaped.
Symptoms and diagnosis
Clinical symptoms and diagnosis can be clearly expressed, under expressed or almost non-existent.
Start can be acute with fever, migratory poliarthritis, weakness, sweating, dyspnea at movement, abdominal pain, swelling around the ankles, palpitations. Physical examination may determine that the apex of the heart is moved laterally from medioclavicular lines, diffuse. There is tachycardia and during the day and during sleep of patients and occurs in more severe and is usually a bad prognostic sign.
Heart sounds are muffled. You can hear the rhythm of the gallop (gallop protodiastolic).
http://www.youtube.com/watch?v=D6DSKN3jsKE
Extrasystolic arrhythmias are common, especially during physical activity.
Atrial fibrillation is rarely seen.
Phlebography jugular vein may show a pronounced wave of Berheimovog effect of the right ventricle, and pronounced v wave due to functional insufficiency trikuspidalnih valve when the heart is considerably enlarged.
About 5% of these patients will stagnans and heart failure. These are the most severe forms of acute rheumatic fever with carditis. More frequent in patients in whom acute rheumatic fever began gradually, with low temperatures and arthralgia for several weeks, but the children in which the disease started acutely with high fever and stiff joints.
The most common symptoms are: fatigue, sweating, loss of appetite, shortness of breath, coughing, chest pain, palpitation and epigastric pain. Physical signs vary and depend on the degree and duration of heart failure. The initial sign may be tachypnea. However, if it is a child, and if receiving salicylates, which can cause tachypnea, should be careful in assessing tachypnea as a sign of heart failure. In the lungs can be heard bronchogeny, wet litter in lung bases. Auscultation of the heart, in addition to tachycardia, hear the muffled tones and protodiastolic gallop.
The veins in the neck may be swollen, and there is tenderness in the right hypochondrium due to an enlarged liver that can tap under your upper abdomen. Sometimes there is a light facial fullness and swelling leg.
Radiological signs of
At radiological examination the heart is increased, more or less as a whole.
Due to Brake heart failure is very pronounced hilus patterns. In pulmonary edema there confluent, inhomogeneous shadow in the upper and middle lung outside.
ECG signs of
The most common finding was prolonged PR interval, and occurs in about 25% of patients with acute rheumatic myocarditis.
As the prolonged PR interval (or degree AV block) happiness in other pathological conditions, it should not be understood as a specific manifestation of rheumatic. Clinical symptoms and diagnosis of acute rheumatic fever, are in favor of acute rheumatic myocarditis.
Rarely are observed: AV dissociation,
complete AV block
nodal (Junctional) rhythm.
QT interval (electric systole) was extended, but it caot be taken as a sure indicator of acute carditis, or is in direct correlation with inflammatory changes in the myocardium.
Functional signs
Acute changes in diffuse inflammatory nature in the myocardium lead to less or more pronounced heart failure and delays. Cardiac output is reduced, there are signs of a halt to the lungs and in the field of large hollow veins.The patient was because of this and because of changes in the joints forced to lie in bed. If stagnans heart failure patients is more pronounced orthopnea and takes spolusjedeći iil sitting spoložaj.
If acute rheumatic myocarditis associated with endocarditis and pericarditis (pankarditis), signs of impaired hemodynamics are most pronounced.
Laboratory signs of
SE is accelerated. There is anemia, leukocytosis, increased alpha-2 globulin and fibrinogen in plasma. There is a C-reactive protein. In some patients leads to increased SGOT (AST) and SGPT (ALT) and lactic dehydrogenase increased (LDH), and alpha-1 glyco-iproteina.
Bacteriological and immunological findings
Group A beta-hemolytic streptococci are rarely isolated from throat swab culture. ASTO titer increased.Imunoelectroforesis shows is an increase of IgA globulin in about 70% of cases. The first days and weeks, and increased serum complement. Special techniques and methods of examination can be detected in the serum, circulating antibodies directed against heart tissue.
The minimal diagnostic program
Symptoms and diagnosis of acute rheumatic myocarditis is on the basis of data on the recent history of acute tonsillopharyngitis, acute migratory polyartritis interventions that mainly large joints, appears systolic functional character of forests at the top, tachycardia, gallop rhythm, tone muklih, rapidly, ASTO titer increases in serum , increase in alpha-2 globulin electrophoregram, extending PR and QT intervals, appears isorytmic dissociation or nodal rhythm on ECG and cardiac enlargement on X-ray shadow-in.
In some children the clinical picture is rarely seen. The child is usually pale, no appetite, cheerless, with arthralgia and myalgia, pronounced weakness, tachycardia, quiet heart sounds, gallop rhythm, functional sistolmm trees at the top, rapidly, anemia, leukocytosis, elevated ASTO titers, increased concentration of fibrinogen in plasma, and increased alpha-2 globulins in the electrophoregram. Rtg: cardiac shadow is enlarged, there is sometimes a delay in the hilum and the lung.
ECG: may be prolonged PR and QT interval, and the happiness and isorytmic dissociation and nodal rhythm.
Forecast
Acute rheumatic myocarditis leads to scars in the myocardium.
In some cases these changes are not so diffuse as to be in other cases. You, the easiest cases, clinical not show almost no signs of acute myocardial rheumatoid rniokarditisa. Sometimes it is just possible to see easily prolonged PR interval on ECG.
In other patients there is a diffuse change, enlargement of the heart and the occurrence of heart failure Brake. Aschoffovi nodules, which develop in the myocardium of patients and in 25% of these are clinically inactive cases, show signs of morphological evolution. This suggests that certain patients may evolute that subclinical, and the prognosis is poor in them. These patients should be under the constant, regular, controlled by doctors.
The prognosis of patients with acute rheumatic myocarditis is even worse if the clinical manifestations of myocarditis are more pronounced and more difficult of the first attack of acute rheumatic fever with carditis.
COMPLICATIONS
Inflammation caused by rheumatic fever may last for a few weeks to several months. In some cases, the inflammation may cause long-term complications.
Rheumatic heart disease is permanent damage to the heart caused by the inflammation of rheumatic fever. Problems are most common with the valve between the two left chambers of the heart (mitral valve), but the other valves may be affected. The damage may result in one of the following conditions:
Valve stenosis. This condition is a narrowing of the valve, which results in decreased blood flow.
Mitral valve stenosis symptoms — which may resemble those of other heart or heart valve conditions — may appear or worsen anytime you increase your heart rate, such as during exercise. An episode of rapid heartbeats also may accompany these symptoms. Or they may also be triggered by pregnancy or other stress on your body, such as an infection.
Mitral valve stenosis symptoms usually include those of heart failure. In mitral valve stenosis, pressure that builds up in the heart is then sent back to the lungs, resulting in fluid buildup (congestion) and shortness of breath.
Symptoms of mitral valve stenosis most often appear in your 40s and 50s, but they can occur at any age — even during infancy. Depending on the amount of narrowing, an infant or a child with mitral valve stenosis may have no symptoms, may tire easily or may have shortness of breath with vigorous physical activity.
Mitral valve stenosis may also produce a number of signs that only your doctor will be able to find. These may include:
– Heart murmur
http://www.youtube.com/watch?v=L5DEqvgS_xs
– Lung congestion
–
– Irregular heart rhythms (arrhythmias)
– Pulmonary hypertension
– Blood clots
Aortic stenosis is the abnormal narrowing of the aortic valve, which restricts the flow of blood from the ventricle into the aorta. Normally, blood carrying oxygen (oxygenated) enters the left upper chamber (atrium) of the heart. It is then pumped into the lower left chamber (ventricle). The aortic valve opens when the heart contracts to pump blood from the left ventricle into the aorta, the body’s main artery. When the left ventricle relaxes, the aortic valve closes because there is a higher blood pressure within the aorta compared to the ventricle.
Aortic stenosis creates high blood pressure inside the left ventricle. This is because the narrowed valve restricts blood flow. In response to the extra workload, the muscle of the left ventricle thickens (concentric hypertrophy) and the chamber itself may eventually balloon out. The heart can no longer pump blood efficiently. Without treatment, death from congestive heart failure is possible. Around four in every 1,000 people are thought to have aortic stenosis.
Symptoms of aortic stenosis
Aortic stenosis may have no symptoms (asymptomatic) for many years. This is why the condition, which may have been congenital (present from before birth), is often diagnosed during teenage years. Symptoms may appear later in life after decades of gradual progressive narrowing. The onset of symptoms may be gradual or abrupt with:
– Breathlessness
– Breathing problems worsened by physical activity
– Coughing at night when lying down in bed
– Fainting
– Heart palpitations
– Pains in the chest, from the heart (angina)
– Fatigue
– Visual problems.
Valve regurgitation. This condition is a leak in the valve, which allows blood to flow in the wrong direction.
Damage to heart muscle. The inflammation associated with rheumatic fever can weaken the heart muscle, resulting in poor pumping function.
Damage to the mitral valve, other heart valves or other heart tissues can cause problems with the heart later in life. Resulting conditions may include:
Atrial fibrillation, an irregular and chaotic beating of the upper chambers of the heart (atria)
Heart failure, an inability of the heart to pump enough blood to the body
TREATMENT :
Aims of treatment-
1. Eradication of initiating streptococcal infection by a therapeutic course of penicillin.
2. Treatment of acute carditis
3. Treatment of extracardiac manifestations
4. Specific treatment of congestive cardiac failure
Eradication of initiating streptococcal infection by a therapeutic course of penicillin-
The patient with acute rheumatic fever with whatever manifestations should be given a therapeutic course of antibiotic to eradicate residual streptococci which may be difficult to isolate.
A ten day course of oral penicillin or Inj Benzathine penicillin in single IM inj 1,20,000 IU in children above 60kg and 600,000 IU in children below 60kg. If patient is sensitive to penicillin – oral erythromycin 20mg/kg/day in three divided dose can be given for 10 days. Tetracyclines and sulphonamides are not used.
Bed rest –
Recommended duration and strictness of bed rest is variable. Reason for bed rest is to reduce cardiac work and to avoid use of involved joints.
In those patients with only arthritis 3 weeks, bed rest is advised. Generally patients with polyarthritis or arthralgia become asymptomatic by 2nd or 3rd week and also if at all carditis is going to develop it develops within 3 weeks. After three weeks, ambulatory bed rest is given.
In those patients with murmur of mitral &/or aortic regurgitant murmur but without cardiomegaly or CHF- two weeks complete bed rest and next two weeks gradual ambulatory bed rest is given.
In those patients with murmur and cardiomegaly without CHF, 4 weeks strict bed rest followed by 2 weeks ambulatory bed rest is given.
In those patients with murmur, cardiomegaly and CHF, strict bed rest is given until CHF is completely controlled and ambulatory bed rest is given for 4 weeks after anti-inflammatory therapy has been stopped.
Anti-inflammatory drugs –
Aspirin and steroids are the two anti-inflammatory agents of choice for treatment of acute rheumatic fever. Both drugs suppress inflammation, joint manifestations as well as acute phase reactions. There is a little or doubtful effect on erythema marginatum, subcutaneous nodules, chorea as well as on long term complication of arthritis. Aspirin is effective for arthritis but steroids are far superior to aspirin in case of severe carditis.
Why aspirin is not given in severe carditis?
· High dosage aspirin increases O2 consumption of myocardium and increases workload on heart and so precipitates CHF.
· It has been shown that if only aspirin is used in carditis, during the course of aspirin the patient can develop pericardial rub which never happens during steroid course.
· Aspirin exerts no specific effect on lesion of acute rheumatic process at any site but produces excellent symptomatic relief of arthritis and fever.
· There is not yet proven evidence that steroids reduce incidence and severity of residual rheumatic heart disease but there is definite impression that death during acute attack of carditis is prevented.
Duration of treatment:
With either drug, duration is 6 weeks or until patient’s clinical condition improves and ESR has returned to normal. Both drugs should be given for 4 weeks and then tapered off slowly iext 2 weeks. To avoid or minimize rebounds addition of aspirin towards the end of steroid treatment is quite useful.
Occasionally, it is necessary to continue the steroid treatment for longer periods of time especially in patients who remain in heart failure with other decongestive measures. If the patient remain in CHF beyond 3 – 4 months of steroid and other decongestive measurers one should seriously think of surgery.
In very severe CHF, methyl prednisolone parenterally should be used followed by oral prednisolone.
Aspirin : 100 – 120 mg/kg/day.
Prednisolone: 2 – 3 mg/kg/day
( maximum 60mg/day. )
Congestive heart failure In patients who present with heart failure, digitalis and diuretics are considered. Digitalis i.e. digoxin was previously contraindicated since some patients are extremely sensitive to the glycoside. It can be used if one remains on low dosage schedule.
Chorea – Isolated chorea is treated symptomatically since neither aspirior steroids have any effect on the course. The combination of phenobarbitone and chlorpromazine works well, if not haloperidol can be used.
Prophylaxis :
The story of rheumatic fever does not end with the completion of anti-inflammatory treatment and normalization of acute phase reactants. Every patient of acute rheumatic fever is a candidate for continuous prophylaxis as risk of recurrent attack of acute rheumatic fever continue.
The method of choice is monthly intramuscular injection of 1.2 mega units of benzathine penicillin and at times every three weeks. In case of genuine penicillin allergy, sulfonamides (0.5gm/daily <
The point of confusion is when to stop prophylaxis. If a patient presents with severe carditis or with recurrent episodes of Acute Rheumatic Fever, prophylaxis is considered for life. For moderate carditis, prophylaxis till 16 years and for mild or no carditis for 3 years from last episode should be given.
Primary Prevention of Rheumatic Fever
Group A streptococcus (GAS) infections of the pharynx are the precipitating cause of rheumatic fever. Proper diagnosis and adequate antibiotic treatment of GAS infections can prevent acute rheumatic fever in most cases.
DIAGNOSIS OF STREPTOCOCCAL PHARYNGITIS
Acute pharyngitis is caused much more often by viruses than by bacteria. However, differentiation of GAS pharyngitis from other causes of acute pharyngitis is often difficult because none of the clinical findings suggestive of GAS infection is specific enough on its own for diagnosis. A history of recent exposure is helpful in making the diagnosis, as is an awareness of the prevalence of GAS infections in the community.
If clinical and epidemiologic findings suggest GAS infection, microbiologic confirmation with a throat culture or rapid antigen detection test (RADT) is required. The diagnosis of GAS pharyngitis is more easily excluded than confirmed, so testing usually is unnecessary in patients with findings suggestive of a viral origin. Treatment is indicated for patients with acute pharyngitis who have a positive throat culture or RADT. However, because of the low sensitivity of many RADTs, a negative test does not exclude GAS infection, and a throat culture usually should be performed. The exception is in adults, in whom the incidence of GAS pharyngitis and the risk of acute rheumatic fever are low. In this population, diagnosis of GAS pharyngitis can be made on the basis of an RADT alone, without confirmation of negative results by a throat culture.
Antistreptococcal antibody titers reflect past—not present—immunologic events and therefore cannot be used to determine whether a patient with pharyngitis and GAS in the pharynx is truly infected or merely a streptococcal carrier. When present, elevated or increasing antistreptococcal titers can confirm a recent GAS infection and are valuable in identifying a preceding GAS infection in a patient suspected of having rheumatic fever.
TREATMENT OF STREPTOCOCCAL PHARYNGITIS
Primary prevention of rheumatic fever requires adequate therapy for GAS pharyngitis. In selecting a treatment regimen, physicians should consider bacteriologic and clinical effectiveness, ease of adherence to the recommended regimen (i.e., dosing frequency, duration of therapy, and palatability), cost, spectrum of activity of the selected agent, and potential adverse effects.
Intramuscular penicillin G benzathine, oral penicillin V potassium, and oral amoxicillin are the recommended antimicrobial agents for the treatment of GAS pharyngitis in persons without penicillin allergy (Table 2). GAS resistance to penicillin has never been documented, and penicillin prevents primary attacks of rheumatic fever even when started nine days after illness onset. Patients are no longer considered contagious after 24 hours of antibiotic therapy.
Penicillin V potassium is preferred over penicillin G benzathine because it is more resistant to gastric acid. However, penicillin G benzathine should be considered in patients who are unlikely to complete a 10-day course of oral therapy, in those with personal or family histories of rheumatic fever or rheumatic heart failure, and in those with environmental factors that put them at risk for rheumatic fever (e.g., crowded living conditions, low socioeconomic status).
OTHER RECOMMENDATIONS
Because most patients with GAS pharyngitis respond well to antimicrobial therapy, posttreatment throat cultures are indicated only in those who remain symptomatic, who have recurrent symptoms, or who have had rheumatic fever previously.
With the exception of persons who have had or whose family members have had rheumatic fever, repeated courses of antibiotics are typically not indicated in asymptomatic persons who continue to harbor GAS after appropriate therapy.
Although acute infections with group B and C beta-hemolytic streptococci can appear similar to GAS pharyngitis, rheumatic fever has not been documented as a complication of these infections.
Secondary Prevention of Rheumatic Fever
Recurrent rheumatic fever is associated with worsening or development of rheumatic heart disease. Prevention of recurrent GAS pharyngitis is the most effective method of preventing severe rheumatic heart disease. However, a GAS infection does not have to be symptomatic to trigger a recurrence, and rheumatic fever can recur even when a symptomatic infection is treated optimally. Therefore, prevention of recurrent rheumatic fever requires continuous antimicrobial prophylaxis rather than recognition and treatment of acute episodes of GAS pharyngitis.
SECONDARY PROPHYLAXIS
Continuous prophylaxis is recommended in patients with well-documented histories of rheumatic fever and in those with evidence of rheumatic heart disease (Tables 3 and 4). Prophylaxis should be initiated as soon as acute rheumatic fever or rheumatic heart disease is diagnosed. To eradicate residual GAS, a full course of penicillin should be given to patients with acute rheumatic fever, even if a throat culture is negative.
Continuous antimicrobial prophylaxis provides the most effective protection from recurrences of rheumatic fever. Because the risk of recurrence depends on many factors, physicians should determine the appropriate duration of prophylaxis on a case-by-case basis while also considering the presence of rheumatic heart disease. Patients who have had rheumatic carditis, with or without valvular disease, are at high risk of recurrences and are likely to have increasingly severe cardiac involvement with each episode. These patients should receive long-term antibiotic prophylaxis well into adulthood, and perhaps for life. Patients with persistent valvular disease should receive prophylaxis for 10 years after the last episode of acute rheumatic fever or until 40 years of age, whichever is longer. At that time, the severity of valvular disease and the potential for exposure to GAS should be determined, and continued prophylaxis (possibly lifelong) should be considered in high-risk patients.
In the
Successful oral prophylaxis depends on patient adherence to the prescribed regimen. Patients should be given careful, repeated instructions about the importance of compliance to the dosing regimen. Even with optimal patient compliance, the risk of recurrence is higher in patients receiving oral prophylaxis than in those receiving injections of penicillin G benzathine. Therefore, oral regimens are more appropriate for patients at lower risk of recurrent rheumatic fever.
Bacterial Endocarditis
The AHA no longer recommends prophylaxis for infective endocarditis in most patients with rheumatic heart disease. The exceptions are patients with prosthetic valves or valves repaired with prosthetic material, patients with previous endocarditis or specific forms of congenital heart disease, and cardiac transplant recipients who develop cardiac valvulopathy. In these patients, an agent other than penicillin should be used to prevent infective endocarditis, because alpha-hemolytic streptococci have likely developed resistance to penicillin.
Poststreptococcal Reactive Arthritis
Poststreptococcal reactive arthritis (PSRA) may occur after an episode of GAS pharyngitis in patients who do not have any other major criteria of acute rheumatic fever. PSRA generally follows a symptom-free interval of about 10 days after the GAS pharyngitis, is cumulative and persistent, involves the large and small joints and the axial skeleton, and does not respond to aspirin therapy. In contrast, arthritis associated with rheumatic fever occurs two to three weeks after an episode of GAS pharyngitis, is migratory and transient, involves only the large joints, and responds rapidly to aspirin therapy.
Although all patients with PSRA have serologic evidence of a recent GAS infection, GAS is isolated io more than one half of these patients who have a throat culture. Because valvular heart disease can develop in patients with PSRA, secondary prophylaxis should be administered for up to one year after symptom onset, and these patients should be observed for several months for clinical evidence of carditis. If such evidence is not observed, prophylaxis can be discontinued. However, if valvular disease is detected, the patient should be classified as having had acute rheumatic fever, and secondary prophylaxis should be continued.
Differential diagnosis
1) rheumatoid arthritis
2) systemic lupus erythematosus
3) chronic tonsyllogenic intoxication
4) nonrheumatic cardities
5) infectious arthritis and
Juvenile rheumatoid arthritis and reactive arthropathies. Etiology, pathogenesis, clinical classification, treatment, prognosis.
Juvenile rheumatoid arthritis is the most common form of arthritis in children. It may be a mild condition that causes few problems over time, but it can be much more persistent and cause joint and tissue damage in other children. JRA can produce serious complications in more severe cases. Arthritis is best described by four major changes in the joints that may develop. The most common features of JRA are: joint inflammation, joint contracture (stiff, bent joint), joint damage and/or alteration or change in growth.
The signs and symptoms of JRA vary from child to child, and even from day to day in the same child! This is an important fact for parents, caretakers and teachers (especially gym teachers) to keep in mind when working with children who have JRA.
Diagnostic criteria of JRA:
Clinical signs:
1.Arthritis more than 3 months (in Europe), more than 6 weeks (in
2.Next joint arthritis in 3 months and more after the first joint affection
3.Symmetrical affection of small joints
4.Effusion in joint cavity (under the capsule)
5.Joint contracture.
6.Tendosynovitis or bursitis.
7.Muscular atrophy.
8.Morning stiffness of joints.
X-ray signs:
1.Osteoporosis.
2.Articular cavities narrowing
3.Bone growth disturbances
There is no single test to diagnose JRA. The diagnosis is made when there has been persistent arthritis in one or more joints for at least 6 weeks after other possible illnesses have been ruled out. Sometimes, a variety of tests may be necessary to come to a firm diagnosis. Once your child’s physician suspects or makes this diagnosis, your child may be referred to a pediatric rheumatologist. This is a physician who specializes in the diagnosis and treatment of children with arthritis and arthritis-related conditions.
The type of arthritis is usually determined based on the symptoms your child has had during the first 6 months of the illness. The 3 major types of JRA are: pauciarticular which affects 4 or fewer joints; polyarticular JRA which affects 5 or more joints; and systemic onset JRA which affects at least one joint but causes inflammation of internal organs as well.
Types of Juvenile Rheumatoid Arthritis
Pauciarticular JRA
Pauciarticular means “few joints.” This form of JRA affects 4 or fewer joints. About 50% of all children with JRA have this type. Usually, large joints (knees, ankles or elbows) are most often involved. Other joints such as wrists, spine and even small finger or toe joints can also be affected but less commonly. Pauciarticular JRA often affects a particular joint on one side of the body rather than both sides at the same time (both sides involved is called “symmetrical arthritis”).
There are two different types of pauciarticular JRA: one type usually affects little girls under age 7 and is associated with the development of eye inflammation (chronic iridocyclitis or uveitis) in about 1/3 of these children.
These children should be tested for antinuclear antibodies (ANA). This tells the rheumatologist and the ophthalmologist (eye doctor) whether your child has a higher risk of developing uveitis (when the ANA is positive the risk is higher). Unfortunately, this eye condition is silent so only proper monitoring by an eye doctor who is familiar with this complication of JRA may find the changes in the eyes.
The second type of pauciarticular JRA usually affects boys who are somewhat older, typically after age 8 and tends to involve the lower spine (sacroiliac joints), hips, knees, ankles and tendons. Sometimes, the spots at which tendons and ligaments attach to bones are also inflamed (enthesitis). These children may also develop eye problems, but this is usually acute uveitis (rather than chronic uveitis) and often causes redness and pain in the eyes. This type of JRA may be the first sign of another arthritis-related condition, such as one of the spondyloarthropathies. This group of diseases usually affects the spine, tendons, and eyes, and is associated with a genetic factor, HLA-B27 in some people.
Long-term problems due to pauciarticular JRA are seen in some of the children affected. Many children have no long-term consequences due to this illness. However, chronic damage can occur in the eyes and the eye problems may be much more persistent than any joint problems. On the other hand, some children develop chronic joint problems. This can include: decreased range of motion of a joint, shortening or lengthening of a limb or digit, damaged cartilage and/or enlargement of a joint. In some children, the arthritis spreads to other joints. These children are said to have “extended pauciarticular JRA” which is similar to polyarticular JRA. Speak to your doctor if you have questions or concerns about any of these issues.
Polyarticular JRA
Polyarticular means many joints; this form of arthritis affects five or more joints. Girls are affected by polyarticular JRA more frequently than boys. When polyarticular JRA affects teenagers, it often resembles RA.
Polyarticular arthritis usually affects the small joints of the fingers and hands; it can also affect weight-bearing joints (including the knees, hips and ankles) as well as the neck and jaw. Polyarticular JRA often affects the same joints on both sides of the body (symmetrical arthritis). Other possible symptoms might include: low grade fever, a positive blood test for rheumatoid factor (RF), and/or nodules (bumps on an elbow or other point of the body that receives a lot of pressure from chairs, shoes or other objects). Less often, inflammation of internal organs may occur. Anemia (low red blood cell count) is a common problem for these children.
Children with polyarticular JRA, especially the younger girls with a positive ANA, are at risk to develop chronic uveitis just like those with pauciarticular disease. Ophthalmologists should evaluate these children too.
Children with polyarticular JRA may develop damage to some of their joints. For example, slower growth may occur in the jaw due to arthritis in the TMJ (temporomandibular joint). This may cause jaw pain and discomfort with chewing. It may also affect dental care and eating habits. This may affect how well your child grows.
In the spine, neck stiffness and difficulty turning the head side to side may occur. Special x-rays can help your doctor determine if arthritis has developed in these areas.
Since polyarticular JRA affects many more joints than is seen with pauciarticular JRA, your doctor may need to use several different medications (often taken together) to treat your child successfully.
Systemic Onset JRA
A systemic illness is one that affects the entire person or body systems. This is the least common form of JRA. Boys and girls are equally likely to have systemic onset JRA. This type of JRA is associated with high fevers, a rash, arthritis and, in some children, inflammation of internal organs. For some children the systemic symptoms of the disease and the fever may go away completely after the first few months of the illness, although the joint-related symptoms of arthritis may remain for a longer period of time.
Symptoms of systemic onset JRA usually include: daily high spiking fevers (103 degrees or higher) that may last for weeks or even months; a rash of pale red or pink spots that appear on the child’s chest, thighs and sometimes other parts of the body (the rash may accompany the fever and may come and go for many days in a row); joint pain and inflammation that may accompany the fever or begin weeks or months later. Joint problems can become a major long-term symptom. Other possible features of this form of arthritis include inflammation of the outer lining of the heart (pericarditis) or the lungs (pleuritis); anemia and high white blood cells and platelets (cells that help with clotting); and enlarged lymph nodes, liver or spleen. Blood work is usually checked frequently in the first few weeks and months of this illness to watch your child closely.
In about half the children with systemic JRA, the illness seems to disappear within 1 year of onset. Flare-ups, or a return of the illness, can happen without warning or after some viral infections (mononucleosis and chicken pox, for example). In most children with systemic JRA, medications must be used for months to years to control both parts of this illness – the systemic part (fever, rash, anemia, etc.) as well as the arthritis.
Long term problems due to systemic JRA are similar to polyarticular JRA. Uveitis, however, is uncommon, so the eyes only need to be checked only once a year in these children.
Diagnosis.
Physician may have to go through many steps to find out if a type of juvenile arthritis or a related condition is present. Other possible diagnoses are reviewed in detailed pamphlets available through the Arthritis Foundation. The main processes involved in making a diagnosis usually include:
· A complete health history to help determine the length of time symptoms have been present, to rule out other possible causes such as viral infections, and to find out if other family members may have had a form of arthritis that possibly could have been inherited (family history).
· A physical examination to look for joint inflammation, rashes, nodules, signs of internal organ inflammation and/or eye problems that may suggest the presence of juvenile arthritis.
· Laboratory tests to help rule out other diseases. These may include erythrocyte sedimentation (sed) rate (ESR), ANA, RF, HLA-B27 typing, hemoglobin and blood count testing and urinalysis (UA).
· X-rays or other specialized x-ray procedures of joints, bones and organs to check for infections, tumors or fractures.
· Tests of joint, blood and tissue fluids to check for infections or inflammation.
For example, an illness such as systemic lupus erythematosus may be similar to JRA in its symptoms (fever, rash arthritis) or fibromyalgia may seem similar, too (joint and muscle pain, fatigue). Further testing will help exclude these and other diagnoses.
Treatment of JRA.
Early diagnosis and appropriate treatment provides children with the best possible opportunity for a favorable outcome. Your child’s treatment will be based on the kind of arthritis he/she has and on their specific symptoms.
The goals of any treatment program for juvenile arthritis are: control inflammation, relieve pain, prevent or control joint damage and maximize joint and body function.
Sick child’s treatment program will usually include medication, exercise, eye care, dental care and healthy eating practices. Treatments such as surgery may be necessary for special long-term problems. Some physicians have also found that pain can be lessened by combining medical treatment with techniques such as progressive muscle relaxation, meditative breathing and guided imagery.
Because so many techniques are used to treat children with JRA, the ideal type of care is sometimes called team care or coordinated care. Your child’s health-care team will include many different specialists who work together to offer your child a complete treatment program. These may include a pediatric rheumatologist, nurse clinician, physical or occupational therapist, dietitian, ophthalmologist, psychologist, nephrologist, neurologist, gastroenterologist, cardiologist, pulmonologist, dentist, social worker or orthopaedic surgeon.
Pediatric rheumatology centers in many major medical centers offer this care in one location. If you do not live near a pediatric rheumatology center, your child’s physician will refer you to the specialists he/she needs.
Medications
The immediate goal of drug therapy is to reduce inflammation, relieve pain and swelling, and maximize function. Long-range goals are to alter the progress of the disease and the prevent damage to bone, cartilage and soft tissues such as muscles, tendons and joint capsules. It must be remembered that medication dosages in children must be carefully calculated based on their weight and body size. Medication doses should be adjusted regularly as the child grows to make sure the proper dosages are used. In addition, it is well known that children metabolize some medications differently than do adults. Therefore, drug dosages may be much higher than one would expect based just on the child’s smaller body size. Side effects may be different in children, or occur rarely compared to adults taking the same medication.
The following medications may be used to treat children with arthritis and related conditions.
NSAIDs
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first line of medication used in juvenile arthritis and are the mainstay of the initial therapy. NSAIDs must be taken for at least three to four weeks to tell whether they are helping control pain and inflammation. Laboratory tests may be done a few times a year to monitor medication side effects. These medications come in liquid or pill form and are taken from one to four times per day, depending on the drug prescribed. Some common NSAIDs on the market approved for children include: ibuprofen, naproxen, tolmentin, aspirin, choline magnesium trisalicylate and indomethacin.
Possible side effects of NSAIDs include: occasional stomach pain, nausea and vomiting; anemia; headache; and uncommonly, blood in the urine; fluid retention; thinning and scarring of the skin (especially with naproxen); difficulty concentrating; and rarely, stomach ulcer.
Aspirin
Aspirin is a rarely prescribed NSAID these days. If chosen by your doctor, it may be used to control joint pain and swelling and to reduce fever just like the other NSAIDs. It is prescribed in large amounts and is given three or four times a day. Young children should not suck or chew on the aspirin because this may damage the chewing surfaces of the teeth and irritate the gums. Instead, try crushing the dose and having the child swallow it in a small amount of a favorite food such as applesauce or yogurt.
Possible side effects of aspirin include stomach pains or stomach bleeding; toxic reactions can occur from too a high dose built up in your child’s system (rapid or deep breathing, ringing in the ears, decrease in hearing, drowsiness, nausea, vomiting, irritability, unusual behavior and black stools). A rare complication called Reye’s syndrome can occur in children who have the chicken pox or the flu and are taking aspirin. Symptoms include frequent vomiting, very painful headaches, unusual behavior, extreme tiredness and confusion. The different NSAIDs should never be combined together without your doctor’s instructions.
Slow Acting Anti-Inflammatory Drugs
These drugs do not relieve pain or inflammation right away; instead, they are given to change the progress of joint disease (such as joint erosions or cartilage and bone destruction) weeks to months after therapy is begun. Therefore, they are referred to as slow-acting anti-rheumatic drugs (SAARDs) or disease modifying anti-rheumatic drugs (DMARDs). These drugs are often used in combination with NSAIDs. Because they are more powerful medications, children will need to have more frequent laboratory tests for monitoring of possible side effects. Some of these medications are described below.
Hydroxychloroquine
Hydroxychloroquine (Plaquenil) is a pill used to control joint pain and swelling. It may take 3 to 6 months to work. While not helpful in all cases, it may be useful when methotrexate or gold have not been completely effective and can be used alone or in combination with other drugs.
Side effects of hydroychloroquine include upset stomach, skin rash and a rare complication, eye damage. A child who takes this drug should have his/her eyes examined at least every six months by an ophthalmologist familiar with this medication.
Sulfasalazine
Sulfasalazine (Azulfadine) is given in pill form. This medication helps the joint pain, stiffness and swelling. It can sometimes have more side effects in children with systemic onset JRA, so should be used with caution in this type of JRA. It takes 6-12 weeks to work.
Side effects may include stomach upset, achiness, diarrhea, dizziness, headache, light sensitivity, itching, appetite loss, liver abnormalities, lowered blood count, nausea, vomiting or rash. Blood work is checked within a few weeks of starting this medication then every few months to check for these changes.
Gold Compounds
Gold compounds (Auranofin, Ridaura, Myochrysine and Solganol) are used to ease morning stiffness and control joint swelling and pain. The oral form is taken daily. Injections are usually given every week for five or six months, then one or twice a month for as long as necessary. These medications are only occasionally used in JRA any more. They take 3-6 months to work.
Side effects may include skin rash, mouth sores, kidney problems, a low blood count or anemia. Blood and urine tests are checked every 1 to 4 weeks while taking gold compounds.
Penicillamine
Penicillamine (DePen and Cuprimine) is given in pill form. This medication is rarely used for JRA but more often for scleroderma, an arthritis-related condition. It takes up to 6 months to work.
Side effects include diarrhea, skin rash, hives or itching, low blood counts, mouth sores, nausea or vomiting, stomach pain, loss of taste or appetite, swollen glands, unusual bleeding or bruising, or weakness.
Immune System Medications
Methotrexate
Methotrexate (Rbeumatrex) is given weekly either orally as a liquid or in pill form, or by injection. It is one of the most commonly prescribed SAARDs for children with JRA. It can help the arthritis as well as the systemic illness in many children. It can help control uveitis in more severe cases. It takes 4-8 weeks to work.
Few side effects have been reported at the low doses at which methotrexate is usually prescribed (typically 7.5 to 25 mg a week), but regular laboratory monitoring is still important. Blood tests are usually checked every month at first then every 6-8 weeks later on. This is also a cancer chemotherapy drug but the dosages used in children with JRA are much lower. Therefore, the side effects are less frequent.
Side effects may include nausea, mouth sores, moodiness, diarrhea, low white blood cell count, lung irritation, infections and liver irritation. Avoid all alcohol intake and smoking while on this medication.
Azathioprine
Azathioprine (Imuran) is given in pill form. This is an immune system suppressing medication. It is not commonly used to treat JRA. It is saved for children that have failed or cannot take methotrexate. It takes about 3 months to work.
Side effects can include cough, fever and chills, loss of appetite, nausea or vomiting, skin rash, unusual bleeding or bruising, unusual tiredness or weakness, or possibly, sterility.
Cyclophosphamide
Cyclophosphamide (Cytoxan) is given in pill form daily or intravenously in a single dose, usually monthly. This drug is rarely used for JRA but often given in children with systemic lupus erythematosus, an arthritis-related condition. It may take several months to work.
Side effects include blood in the urine or burning on urination, confusion or agitation, cough, dizziness, fever and chills, infertility, loss of appetite, nausea or vomiting, unusual bleeding or bruising, unusual tiredness or weakness, and an increased risk for cancer.
Cyclosporine
Cyclosporine (Sandimmune) is given in liquid or pill form. This drug helps the joint inflammation as well as the systemic symptoms of systemic onset JRA. It may take a 1-2 months to work. Blood levels are often checked to determine the best dosage for your child.
Side effects include bleeding, tender or enlarged gums; fluid retention; high blood pressure; increased hair growth; kidney problems; loss of appetite; or trembling or shaking of hands.
Biologic Agents
Biological agents are a new class of medications made of synthetic proteins. These drugs may be made of antibodies that block high levels of inflammatory proteins in patients with arthritis. The drugs available include etanercept (Enbrel) which blocks the protein TNF, and was approved in 1998 by the FDA for RA treatment in adults, and in 1999 for the treatment of JRA. Infliximab (Remicade) is another anti-TNF medication that is approved to treat RA and has begun testing in JRA.
Intravenous immunoglobulin (IVIG) is used to treat several childhood rheumatic diseases. It is usually given intravenously once a month. It is sometimes used as part of the treatment of systemic JRA. Side effects include the risk of allergic reactions, headaches, stomachache and flu-like symptoms.
Researchers are developing other experimental biologic therapies that are aimed at specific proteins to control a variety of different diseases.
Glucocorticoid Drugs
Glucocorticoid medications (Dexamethasone, Methylprednisolone, Cortef, Prednisolone and Prednisone) are the most potent anti-inflammatory agents. These drugs are used to treat a variety of rheumatic diseases when the disease is severe or has not responded to other drugs. Sometimes glucocorticoids are used for a few weeks until other slower medications can become effective in controlling the arthritis.
Because of their many side effects, glucocorticoids must be used with caution. If these drugs are prescribed, the lowest possible dose should be used for the shortest length of time. Usually the drug is given by mouth as a pill or liquid. It can also be given as an injection into the joint itself, or into a muscle, or vein (IV).
Possible side effects of these medications include high blood pressure, osteoporosis (brittle bones), Cushing’s syndrome (weight gain, moon face, thin skin, muscle weakness) cataracts, slowed growth rate, reduced resistance to infection, sudden mood swings, increased appetite and weight gain, or increased risk for ulcers. Many of these side effects occur only when the dose is more than 7.5 to 10 mg a day (dose for an average size adult who is taking prednisone).
Glucocorticoids should never be stopped suddenly if they have been taken for more than a month. Your child’s owatural gluco-corticoids may not be produced enough after using these drugs for a month or more. A schedule to slowly discontinue or taper these medications will be given to you by your doctor and will prevent this problem. A child taking glucocorticoids should wear a medical alert bracelet or necklace. This will alert emergency medical personnel to give extra medication if the child has surgery or is seriously injured.
Analgesics
Analgesics (acetaminophen [Tylenol, Panadol], tramadol [Ultram]) do not relieve inflammation, but provide pain relief. They should be taken only under a physician’s advice in conjunction with other medications. Acetaminophen has few side effects when taken in small doses; very high doses (overdoses) can cause liver damage. Side effects of tramadol may include dizziness, nausea, constipation, headache and sleepiness.
Exercise
Exercise is a very important part of treatment for juvenile arthritis. For children with arthritis, exercise helps keep joints mobile; keep muscles strong; regain lost motion or strength in a joint or muscle; make everyday activities like walking or dressing easier; and improve general fitness and endurance.
Therapeutic Exercise
While medications reduce pain and inflammation, only therapeutic exercise can restore lost motion in a joint. These exercises can make it easier for children to walk and perform other activities of daily living such as walking, eating and writing.
Range-of-motion exercises keep joints flexible and are especially important for children who have lost motion in a joint, or whose joints have become fixed in a bent position. Strengthening exercises build muscles.
A physical or occupational therapist will teach the child how to perform these exercises at home. Most of these must be done daily. The therapist will show to the child how to use hot baths, hot packs and/or cold treatments before exercise to make the therapy easier.
Sports and Recreational Activities
Recreational activities help to the sick child exercise joints and muscles, develop important social skills and have fun. But remember that recreational activities cannot take the place of therapeutic exercise.
Participating in sports and recreational activities helps children with arthritis develop confidence in their physical abilities. Encourage activities that exercise the joints and muscles without putting too much stress on them, like swimming.
Strong muscles and joint protection are the keys to participating in sports. Although contact sports are never recommended, even aggressive sports like soccer and basketball may not be off-limits for sick child. Special exercises and protective equipment can further reduce the risk of injury, and help to the child play sports she likes.
Splints
Splints help keep joints in the correct position and relieve pain. If a joint is developing a contraction (bent in the wrong position), a splint may help stretch that joint gradually back to its normal position. Commonly used splints include knee extension splints, wrist extension splints and ring splints for the fingers.
An occupational or physical therapist usually makes the splint. Arm and hand splints are made from plastic; leg splints are sometimes made of cast material. The therapist custom-makes the splint for your child and can adjust the splint as your child grows, or as the joint position changes.
Morning Stiffness Relief
Many children experience a period of stiffness when they get up each day. This morning stiffness can be one of the best measures of disease activity; the longer the stiffness lasts, the more active the disease. Taking a hot bath or shower, sleeping in a sleeping bag or warm bed, doing range-of-motion exercises, or using a hot or cold pack can help relieve it. Although most children do better with warmth, there are a few who respond to cold treatments (a plastic bag filled with ice or frozen vegetables works well).
Surgery
Surgery is rarely used to treat juvenile arthritis in the early course of the disease. However, surgery can be used to relieve pain, release joint contractures and replace a damaged joint.
In joint replacement surgery, the entire joint is replaced with an artificial joint. This procedure is used mainly in older children whose growth is complete or almost complete and whose joints are badly damaged by arthritis. This operation is usually used to replace the hip, knee or jaw joints. It can reduce pain and improve function.
Soft tissue release may sometimes help to improve the position of a joint which has pulled out of line by a contracture. In this operation, the surgeon cuts and repairs the tight tissues that caused the contracture, allowing the joint to return to a normal position.
Eye Care
Several forms of eye inflammation are associated with various forms of juvenile arthritis. However, frequent eye exams can identify inflammatory problems early and reduce the potential for serious eye complications.
Chronic iridocyclitis occurs most commonly in young girls with pauciarticular JRA whose blood contains an antibody protein called the ANA. This inflammation of the eyes may occur without obvious signs or symptoms. Therefore, it is important for all children with JRA to have their eyes checked by an ophthalmologist as soon as the diagnosis is suspected. This allows the doctor to detect any eye problems early and to begin proper treatment to avoid serious problems. Children diagnosed before 7 years old with pauciarticular JRA and a positive ANA are at the greatest risk of developing chronic uveitis. Their eyes should be checked every 3 months for several years. Acute or sudden onset of eye inflammation is called iritis. This may occur particularly in the spondyloarthropathies.
The ophthalmologist will give to the child a complete medical eye evaluation, including a slit lamp test. This simple and painless procedure can spot problems before symptoms are present. Children should continue to get periodic eye exams, since eye inflammation may occur when the joint disease is inactive. The frequency of eye exams will depend on sick child’s risk for developing eye problems.
Dental Care
Children with arthritis may have limited jaw movement, which can make brushing and flossing their teeth difficult. Your child’s dentist may suggest various toothbrush handles, electric toothbrushes, floss holders, toothpicks and rinses that will help your child maintain healthy teeth and gums.
Medications may also affect your child’s oral health and development. Always inform your dentist about the status of your child’s disease and the medications she is taking. The dentist will consider these when planning any treatment, general anesthesia, sedation or oral surgery. Older children who have had joint replacements may require an antibiotic before dental treatment.
The joint in front of the ears, where the lower jaw connects to the base of the skull, is called the temporomandibular joint (TMJ). Arthritis may affect this joint in the same way it does others, by causing pain, stiffness and altered growth. Jaw exercises and therapy may be recommended for the pain and stiffness. If the lower jaw does not develop properly, it may create an overbite. Your child’s dentist may recommend an early consultation with an orthodontist if this occurs. Surgery is also sometimes necessary for this condition.
A child with active arthritis may not always have the stamina for even routine dental work. If possible, schedule appointments when your child has the most stamina, or schedule shorter appointments.
Diet
Children with arthritis sometimes have poor appetites, leading to weight loss and poor growth; medication side effects may cause excessive weight gain.
Chronic disease places increased demands on a child’s body and creates a need for additional calorie intake. Children may have little appetite when they feel ill, or may have a difficult time eating when they have painful joints or limited mobility. Some children with arthritis might feel too sick or too tired to eat. Encourage him/her to eat a well-balanced diet at regular meal times and include planned snacks even when he/she may not feel like eating. Try to reduce the amount of food he/she needs to eat by increasing the nutrient content of each bite of food or drink. For example, add melted cheese, gravies, margarine and dips to foods, and offer whole milk. This can help prevent weight loss and poor growth.
At the opposite end of the spectrum, children with arthritis may gain too much weight due to medication side effects or limited activity. Excess weight puts more stress on joints such as knees, hips and ankles. Appropriate exercise combined with eating a well-balanced diet based on the basic four food groups can help your child keep a normal body weight. A registered dietitian can teach you ways to improve your child’s diet.
Many children with arthritis need additional calcium and vitamin D to help strengthen their bones. Giving your child a multivitamin with breakfast is usually worth the effort.
