Rheumatic fever is an inflammatory disease that can affect the heart, joints, brain and skin. It develops as an immune response 1-5 weeks after an untreated strep throat or scarlet fever infection caused by Group A Streptococcus bacteria. Symptoms include fever, painful joints, heart issues and involuntary movements. It most commonly affects children ages 5-15. Treatment involves antibiotics to treat the initial strep infection and prevent future episodes, while prevention focuses on treating strep throat infections early with antibiotics. The disease prevalence in rural Pakistan is estimated at 5.7 per 1000 people.

1. RHEUMATIC FEVER
KHAWAJA TAIMOOR SHAHID

2. Introduction
• Rheumatic fever (acute rheumatic fever) is a
disease that can affect the heart, joints, brain,
and skin. Rheumatic fever can develop if strep
throat and scarlet fever infections are not
treated properly. Early diagnosis of these
infections and treatment with antibiotics are
key to preventing rheumatic fever
(https://www.cdc.gov/groupastrep/diseases-
public/rheumatic-fever.html).

3. Causes
• Bacteria called group A Streptococcus (GAS) or
group A strep cause strep throat and scarlet fever.
It usually takes about 1 to 5 weeks after strep
throat or scarlet fever for rheumatic fever to
develop.
• Rheumatic fever is thought to be caused by a
response of the body’s defense system — the
immune system. The immune system responds to
the earlier strep throat or scarlet fever infection
and causes a generalized inflammatory response
(CDC).

5. Characteristics of Rheumatogenic
Strains
• Not all strains of group A Streptococcus (GAS) cause
acute rheumatic fever (ARF).
• In 1930s, it was noted that ARF was not reactivated by
certain strains representing certain M protein serotypes
(Coburn ans Pauli , 1935).
• By the 1950s, it was further reported that strains within
certain M types caused acute glomerulonephritis
(AGN) (Rammelkamp and Weaver, 1953).
• In the 1960s, it also became clear that the attenuated
strains responsible for streptococcal pharyngitis and
frequently carried in the throats of school children in
the United States did not cause ARF (Stollermanet
al.,1965).

6. The Molecular Biology and Genetics
of Well-Known Rheumatogenic GAS
• By 1979, the molecular structure of the M proteins of
epidemic rheumatogenic strains was defined by Edwin
Beachey, and by his associates, when they cleanly
separated the type-specific N-acetyl terminal peptide
from the proximal piece of the M molecule (Beachey et
al., 1977).
• The terminal type-specific epitope of the M molecule
was found to be nontoxic in human skin while still
antigenic in humans (Beachey et al., 1979).
• Since then, extensive studies of the molecular structure
of M protein in Memphis by James Dale and his
associates has led to the production of a recombinant
multivalent GAS vaccine (Dale, 1999).

7. • They further demonstrated that strains of GAS fell
into 2 main molecular classes based on
differences in theC repeat regions of the M
molecule.
• Class I molecules are characteristic of throat
strains, whereas class II molecules, containing a
much smaller and less antigenic M molecule, are
associated with streptococcal pyoderma
(impetigo). Indeed, an M antigen (so far
unidentified)has been detected in rheumatogenic
strains, and antibodies to this antigen have been
found in the blood of patients with RF.

8. • The M protein genes and those of hyaluronic
acid, streptolysin S, C5a peptidase,
erythrogenic toxins, and others have recently
been identified and now provide a genomic
approach to characterizing GAS strains. The
genes for expression and repression of the
capsule have opened investigation of the
conditions under which it is produced and
mutations in its repressor that may affect its
size and contribution to virulence.

9. • The “superantigen” portion of the M molecule
containing nonspecific epitopes, to which we become
progressively hypersensitized by repeated childhood
GAS infections, heightens immune responses to
streptococcal antigens, as is regularly observed in
patients with RF.
• Such immunologic stress may break immune tolerance
in susceptible hosts and account for the variety of
cross-reactive antibodies found in synovia, skin, basal
ganglia, heart valves, and so forth.
• Immune complexes may produce the non destructive
synovitis of the joints of patients with ARF and the
reversible reactions in the basal ganglia observed in
patients with Sydenham’s chorea, whereas
autoimmune, cell-mediated cytotoxic reactions may
destroy heart valves.

10. Is it Contagious or not?
• People cannot catch rheumatic fever from
someone else because it is an immune
response and not an infection.
• However, people with strep throat or scarlet
fever can spread group A strep to others,
primarily through respiratory droplets.
• So if your immune system is strong no matter
what you can get this germ inside your body
and also take proper medication.

11. Symptoms of rheumatic fever
• Fever and Fatigue
• Painful, tender joints (arthritis), most commonly in the
knees, ankles, elbows, and wrists
• Symptoms of congestive heart failure, including chest pain,
shortness of breath, fast heartbeat
• Jerky, uncontrollable body movements (called “chorea”)
• Painless lumps (nodules) under the skin near joints (this is a
rare symptom)
• Rash that appears as pink rings with a clear center (this is a
rare symptom)
• In addition, someone with rheumatic fever can have:
• A new heart murmur
• An enlarged heart
• Fluid around the heart

12. What kind of age and gender can
affect most?
• Children Most Often Affected
• It is more common in school-age children (5
through 15 years old).
• Crowded conditions can increase the risk of
getting strep throat or scarlet fever, and thus
rheumatic fever. These settings include:
– Schools
– Daycare centers
– Military training facilities
• Both gender can affect with same rate, but
females show proper hygienic measures so they
has little chance to get protected.

13. Diagnose Rheumatic Fever
• There is no single test used to diagnose
rheumatic fever. Instead, doctors can look for
signs of illness, and use many tests, including:
– A throat swab to look for a group A strep infection
– A blood test to look for antibodies that would show
if the patient recently had a group A strep infection
– A test of how well the heart is working
(electrocardiogram or EKG)
– A test that creates a movie of the heart muscle
working (echocardiography or echo)

14. Treatment and Prevention
• The main ways to prevent rheumatic fever are
to:
– Treat group A strep infections like strep throat and
scarlet fever with antibiotics
– Prevent group A strep infections in the first place
• Preventive antibiotics help protect people who
had rheumatic fever from getting it again.
Doctors also call this prophylaxis or
“secondary prevention.” Prophylaxis can
include daily antibiotics by mouth or a shot
into the muscle every few weeks.

15. Treatment
• Anti-TNF drugs that seem to delay or reduce joint
destruction in patients with rheumatoid synovitis
possibly might reduce valvular scarring in patients
with rheumatic carditis.
• The corticosteroids, symptomatically beneficial,
as they do not prevent valvular damage.
• The new COX-2–inhibiting NSAIDs may be
welcome to reduce the adverse gastrointestinal
effects of large doses of aspirin.

16. Status of rheumatic fever in pakistan
• The prevalence of reumatic heart disease
(RHD) in Rahim Yaar Khan subdistrict is 5.7 in
1000. Assuming that this is the rate of RHD
throughout the rural population of Pakistan
(88 million), there are more than 500 000
patients with RHD in rural Pakistan (NCBI,
2004,)(S.F Rizvi, 2004).

17. References
• Stollerman GH. Rheumatic fever. Lancet 1997; 349:935–42.
• Coburn AF, Pauli RH. Studies on the immune response of the
rheumatic subject and its relationship to activity of the rheumatic
process. IV. Characteristics of strains of hemolytic streptococci,
effective and non-effective in initiating rheumatic activity. J Clin
Invest 1935; 14:755–62.
• Rammelkamp CH Jr, Weaver RS. Acute glomerulonephritis: the
significance of the variations in the incidence of the disease. J Clin
Invest 1953; 32:345–58.
• Stollerman GH, Siegel AC, Johnson EE. Variable epidemiology of
streptococcal disease and the changing pattern of rheumatic fever.
Mod Concepts Cardiovascul Dis 1965; 34: 45–8.
• Beachey EH, Stollerman GH, Chiang EY, et al. Purification and
properties of M protein extracted from group A streptococci with
pepsin: covalent structure of the amino terminal region of type 24 M
antigen. J Exp Med 1977; 145:1469.

18. • Beachey EH, Stollerman GH, Johnson RH, Ofek I, Bisno
AL. Human immune response to immunization with a
structurally defined polypeptide fragment of
streptococcal M protein. J Exp Med 1979; 150:862–77.
• Dale JB. Group A streptococcal vaccines. Infect Dis Clin
North Am 1999; 13:227–43.
• Carreno-Manjarrez, R, Visvanathan K, Zibriskie JB.
Immunogenic and genetic factors in rheumatic fever.
Curr Infect Dis Rep 2000; 2:302–7.
• Veasy LG. Echocardiography for diagnosis and
management of rheumatic fever. JAMA 1993;269:2084.
• https://www.ncbi.nlm.nih.gov › articles › PMC1768176
• Researched by S.F Rizvi, NCBI. 2004.
References