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CXR
MORNING REPORTDECEMBER 19TH 2008
BY: SIMA PATEL
ACUTE RHEUMATIC FEVER
DEFINITION
Rheumatic fever is an inflammatory process which can involve the joints, heart, skin and brain
It is caused by antibody cross reactivity and occurs 2-3 weeks after a Group A Streptococcal infection.
HISTORY
16th century: Baillou distinguishes acute arthritis from gout
17th century: Thomas Sydenham described chorea but did not associate it with other entities of Acute Rheumatic Heart Disease
1812: William Charles Wills made association of Rheumatism and carditis and described subcutaneous nodules
HISTORY
Jean-Baptiste Bouillard (1836) and Walter B Cheadle (1889) published many studies of rheumatic arthritis and carditis
1880: J.K. Fowler made association between sore throat and rheumatic fever
Early 1900’s: Bela Schick identified Acute Rheumatic Fever as a sequelae of scarlet fever
1904: Ludwig Aschoff: described specific rheumatic lesions in the myocardium
1930’s-1950’s: multiple studies identified Group A Streptococcus as the causative agent and development of antibiotic agents for primary and secondary prevention of rheumatic fever
EPIDEMIOLOGY
470,000 new cases of Acute Rheumatic Fever/year
233,000 deaths due to Rheumatic Fever/yearMajority of deaths occur in developing countriesIncidence in the US: 2-14 cases/100,000Historically, there is a temporal relationship
between epidemics of streptococcal pharyngitis and scarlet fever with the epidemics of acute rheumatic fever
No clear gender predilection overall, but mitral stenosis and syndenham’s chorea occur more in females than males.
BACKGROUND
Primarily affects children between ages 5-12Generally occurs 2-3 weeks after Group A
Streptococcal infection (strep throat or scarlet fever)
In the US, Rheumatic fever has become fairly rare due to use of antibiotics to treat streptococcal infections
Globally, 3% of those with an untreated streptococcal infection develop rheumatic fever
40% of those with Acute Rheumatic Fever develop mitral stenosis as adults
BACKGROUND
Cutaneous streptococcal infections have not been shown to initiate Acute Rheumatic Fever.
Strains of certain M serotypes/genotypes of streptococci have higher associations than other genotypes
Epidemics of Acute Rheumatic Fever in Trinidad and Chile showed that streptococci causing Acute Rheumatic Fever belonged to different serotypes than those that cause Acute Glomerulonephritis.
PATHOPHYSIOLOGY
Exact mechanism of how Group A streptococcal infection causes Acute Rheumatic Fever is unknown however it is believed to be caused by a cross reactivity of antibodies
Suggested Theories Toxic effects of streptococcal products (streptolysin S
or O) which then cause direct tissue injury Serum Sickness-like reaction mediated by antigen-
antibody complexes Autoimmune phenomenon
PATHOPHYSIOLOGY
More support for an autoimmune phenomenon (Type II hypersensitivity reaction)
During strep infection, antigen presenting cells present bacterial antigen to helper T cells. These helper T cells then activate B cells to induce production of antibodies against the Streptococcal cell wall. These antibodies can also interact with other cells in the body (for example, myocardium or joints, etc) producing the symptoms responsible with acute rheumatic fever
PATHOGENESIS
Most patient have elevated antibody titers to at least one streptococcal antibody Streptolysin O Hyaluronidase Streptokinase
PATHOPHYSIOLOGY (CARDIAC)
In early stages of disease there is fragmentation of collagen fibers, and a predominantly lymphocytic infiltration of tissues with fibrinoid deposition
Then, there is appearance of myocardial Aschoff Nodules (Bodies). These are areas with perivascular inflammation with an area of central necrosis surrounded by mononuclear and giant multinuclear cells. (“owl-eyed nucleus” or a “caterpillar” appearance)
Cardiac findings: pericarditis, myocarditis, endocarditis (usually involving the left side of the heart)
May have a thickened area in the left atrium (above the base of the posterior leaflet of the MV) called MacCullum’s Patch.
As time progresses these areas develop scarring leading to mitral valve deformities resulting in valvular stenosis or insufficiency.
PATHOPHYSIOLOGY (CARDIAC)
Aschoff nodule with owl-eyed shape in the cross section and catapillar-shaped
in the longitudinal section
PATHOPHYSIOLOGY (CARDIAC)
Thickened fused chordae of the mitral valve
PATHOPHYSIOLOGY (JOINTS)
Initially have fibrinous exudates over the synovial membrane with serous effusions.
Histology shows cellular infiltration and fibrinoid degeneration.
Usually show a central area of fibrinous necrosis surrounded by fibroblasts and histiocytes.
Just as in the heart, there is also perivascular changes with infiltration of lymphocytes and PMNs
CLINICAL MANIFESTATIONS
Latent period: time between preceding streptococcal pharyngitis and Acute Rheumatic fever is about 19 days (range 1-5 weeks)
If initial complaint is polyarthritis, disease generally has more abrupt onset compared to if initial presentation is with myocarditis.
Arthritis occurs in 75% of initial attacks, carditis in 40-50% and chorea in 15% with subcutaneous nodules and erythema marginatum in <10%
CLINICAL MANIFESTATIONS (CARDITIS)
Usually manifests within the first 3 weeks of Acute Rheumatic Fever
Signs: new heart murmur, cardiomegaly, CHF, perciardial friction rub, effusions
Chronic inflammatory changes may lead to development of rheumatic heart disease.
Characteristic murmur or Rheumatic heart disease: mitral regurgitation Low-pitched mid diastolic flow murmur at the apex (Carey
Coombs murmur Aortic regurgitation
Can also get AV conduction delays
CLINICAL MANIFESTATIONS (JOINTS)
Arthralgias and arthritis (may be migratory)Warm, swollen, tender jointsUsually involves the knees, ankles, elbows
and wristsLasts 2-3 weeks
CLINICAL MANIFESTATIONS
Subcutaneous Nodules: usually associated with severe carditis and occur several weeks after onset. Firm, painless nodules (up to 2cm) found over bony
surfaces and tendons Occur near elbows, knees, wrists, achilles tendon,
vertebral joints Usually persist for 1-2 weeks
SUBCUTANEOUS NODULES
CLINICAL MANIFESTATIONS
Erythema Marginatum: nonpruritic, painless erythematous rash on trunk and/or proximal extremities Macular lesions with raised margins and central clearing May last from weeks to months
Sydenham’s Chorea: neurologic disorder with muscular weakness, emotional lability and involuntary, uncoordinated, purposeless movements Disappear during sleep Mainly occur in hands, feet and face Sensation intact Lasts 2-4 months
ERYTHEMA MARGINATUM
DIFFERENTIAL DIAGNOSIS
Poststreptococcal reactive arthritis: is non-migratory
Rheumatoid ArthritisSLEInfective endocarditisSickle Cell diseaseDrug reactionsTBLyme DiseaseSerum Sickness
DIAGNOSIS
JONES CRITERIA Developed by Dr. T Duckett Jones in 1944 Need 2 major criteria or 1 major and 2 minor criteria
in the presence of a prior strep infection to make the diagnosis
Evidence of prior strep infection with positive throat culture or antigen test, elevated streptococcal antibody titer, or history of rheumatic fever/heart disease
MAJOR CRITERIA
Migratory Polyarthritis: migrating arthritis with inflammation involving the large joints (knees, ankles, elbows, wrists) and typically affects the leg joints first
Carditis: can manifest with new murmur, pericarditis, congestive heart failure
Subcutaneous Nodules: a form of aschoff bodies. Are painless nodules on the back of the wrists, elbows, knees
Erythema Marginatum: rash beginning on the arms or trunk and spreads outward. Lesion with ring with central clearing. Worsens with heat. Does not involve the face
Sydenham’s Chorea (St. Vitus’ Dance): purposeless movements of the face and arms. Late finding
MINOR CRITERIA
FeverArthralgia: joint pain without inflammationElevated CRP, ESR or leukocytosisEKG changes: primarily prolonged PR intervalEvidence of Group A Streptococcal infection
via elevated antistreptolysin O titer or DNAase
Prior history of rheumatic fever or heart disease
TREATMENT
Anti-inflammatory AgentsAntibioticsProphylaxis
ANTI-INFLAMMATORY AGENTS
Aspirin 4-8grams/day for adultsContinue anti-inflammatory therapy until ESR
or CRP are normalMay need steroids if there is cardiac
involvement to help prevent sequelae such as mitral stenosis
Corticosteroids, if indicated, are given at prednisone 2mg/kg/day for 2 weeks and then tapered
ANTIBIOTICS
Penicillin for at least 10 daysPenicillin 500mg BID-TIDCan use erythromycin for PCN allergic
patients (given at 40mg/kg/day given in 2-4 doses/day)
PROPHYLAXIS
Prophylaxis needed to prevent recurrence of Acute Rheumatic Fever
Start prophylaxis after acute episode resolvesCan use:
Penicillin V 250mg BID or, Sulfadiazine 1000mg daily, or Penicillin G 1.2 million units IM q4weeks For PCN allergic patients: erythromycin 250mg PO BID
Recurrence of disease generally occurs in the first couple years
PROPHYLAXIS
WHO GUIDELINES At least 5 years of prophylaxis or if child until age 18
if not cardiac involvement 10 years prophylaxis or if child until age 25 if has mild
mitral regurgitation Lifelong prophylaxis if has severe valve disease
PROGNOSIS/PREVENTION
Generally resolve over 12 weeks in 80% of patients
Prognosis depends on severity of cardiac involvement during acute attack
Primary Prevention: treatment of streptococcal infection (limitation is that 30% of streptococcal infections are subclinical)
Secondary Prevention: prevention of recurrent attacks of Rheumatic Fever with prophylactic antibiotics.
REFERENCES
Shulman, Stanford. Rheumatic Fever in America and Britain: A biological, epidemiological, and medical history. New England Journal of Medicine May 4, 2000; Volume 342: 1373-1374.
Mandell G, Bennett J, and Raphael Dolin. Principles and Practice of Infectious Disease, 6th Edition. Churchill Livingstone. Philadelphia, PA 2005.
Cohen J and William Powderly. Infectious Diseases, 2nd Edition. Harcourt Publishers. 2004.
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