Lecture 8

Clinical Immunology
13-11-2022
Post-streptococcal autoimmune disorders
 I. Rheumatic fever:
• It is an inflammatory disease that may develop
after an infection with streptococcus bacteria
(like streptococcal tonsillitis or scarlet fever).
The disease can affect the heart, joints, skin,
and brain.
Throat and skin infection with group A
streptococcus which will release exotoxin, the
exotoxin causes the skin rash and strawberry
tongue
The rash does not appear on the face, but the
cheeks can look red. The redness may be harder
to see on brown and black skin.
On white skin the rash looks pink or red. It may
be harder to see on brown and black skin, but
you can still feel it.
A white coating also appears on the tongue. This peels, leaving
the tongue red, swollen and covered in little bumps (called
"strawberry tongue").
 Pathogenesis:
• Antibodies made against group A beta hemolytic
streptococci cross react (molecular mimicry)
human tissue like heart valves, brain, joints. It is
type II hypersensitivity reaction.
• RF mostly affects children ages 5 -18 years and
occurs approximately 20 days after sterp. throat
infection (tonsillitis) or scarlet fever.
 Symptoms:
• Symptoms:
1. Joints: arthritis presented with joint pain, swelling, inflamed.
2. Heart: valvular lesion, endocarditis, myocarditis,
pericarditis. The patient complaint is dyspnea, chest pain.
3. Skin: Erythema marginatum, Subcutaneous nodules
4. CNS: chorea
 Diagnosis:
1. Clinical examination reveals heart murmurs, arthritis,
2. Markers of inflammation: ESR elevated, CRP may be positive.
3. Feature of recent streptococcal infection:
a. anti-streptolysin antibodies (ASO) titer elevated. A positive test
usually is >200 units/mL, or if a rise in titer can be demonstrated in
paired blood samples taken days apart.
b. Detection of elevated Anti-DNase B antibodies. DNase B is an
enzyme produced by almost all strains of beta hemolytic Group A
and a few strains of Group C and G streptococci.
4. Chest X-ray, ECG (electrocardiogram)
 II.Sydenham’s chorea (SC)
• Sydenham’s chorea is a neurological disorder
characterized by jerking and twisting and
abnormal aimless movements of the limbs, trunk,
and facial muscles.
• These rapid movements cannot be controlled.
• Chorea is more common in girls and occurs more
often in children ages 5 to 15 years old.
•Sydenham’s chorea results from an auto-immune
reaction against a prolonged S. pyogenes infection,
where the body forms antibodies against antigens of
the bacteria known as epitopes. Similar epitopes are
found in the basal ganglia, an area in the brain which
controls movements.
Sydenham’s chorea (SC)
 III. Post streptococcal related myalgia
(PSM)
• Symptoms of myalgia include severe muscle
pain and tenderness.
•The diagnosis of PSM should be considered in children
presenting with acute myalgia and high
Anti-Streptolysin O titers.
 IV. PANDAS
• PANDAS stands for Pediatric Autoimmune Neuropsychiatric
Disorders Associated with Streptococcal infections.

• These disorders include obsessive-compulsive disorder (OCD) and

tic disorders that appear suddenly after strep throat or scarlet
fever. Symptoms include:

1. Motor tics (involuntary movements)

2. Vocal tics (involuntary sounds or words)

3. Obsessions and compulsions

4. Children may be moody, irritable, and experience anxiety attacks

 V. Acute post-streptococcal
glomerulonephritis:
• Poststreptococcal glomerulonephritis (PSGN) is
characterized by rapid deterioration of kidney
functions due to an inflammatory response (type
III hypersensitivity reaction) following
streptococcal infection.
Glomerulus is a network of small blood vessels
(capillaries) known as a tuft, located at the
beginning of a nephron in the kidney.
• This condition results mostly from specific
strains of group A beta-hemolytic streptococci
called nephrogenic streptococci.

• The disease affects the glomeruli and the small

blood vessels of the kidneys.
• It is not an infection, it is an immunologically
mediated glomerular injury triggered by an
infection.
• PSGN is a self-limited disease, especially in
children, but long-term follow-up studies indicate
persistent low-grade renal abnormalities in a
significant proportion of patients.
 Causes
• It is caused by an infection nephritogenic streptococcus.
• It is associated with a previous skin or throat infection
by group A streptococcus (Streptococcus pyogenes), or
occasionally groups C or G streptococcus.
• The infection does not occur in the kidneys, but in a
different part of the body, such as the skin or throat.
• The strep bacterial infection causes the tiny blood vessels
in the filtering units of the kidneys (glomeruli) to become
inflamed. This makes the kidneys less able to filter the
urine.
• The disorder may develop 1 to 2 weeks after an untreated
throat infection, or 3 to 4 weeks after a skin infection.
• It may occur in people of any age, but it most often occurs
in children ages 6 through 10.
 Pathogenesis:
• The disease is immunological; representing a
type III hypersensitivity reaction.

• The body responds to nephrogenic

streptococcal infection by forming immune
complexes containing the streptococcal antigen
with a human antibody.
• These immune complexes become deposited in
kidney glomeruli reaching the kindey through the
circulation. Immune complexes formation activates
complement pathway ending in the destruction of
renal glomeruli.
 Symptoms:
may include any of the following:
1. Decreased urine output: oliguria
2. Rust-colored urine
3. Visible blood in the urine (hematuria)
4. Swelling (edema), general swelling, swelling of the
abdomen, swelling of the face or eyes, swelling of the feet,
ankles, hands
5. Hypertension
6. Heart failure
7. Joint pain, stiffness, or swelling
Rust-colored urine
Macroscopical hematuria
 Diagnosis
1. Clinical features:

a. PSGN should be suspected in all children with

hypertension and heart failure.

b. Swelling (edema), especially in the face

 Diagnosis:
2. Laboratory investigation:
a. Evidence of a preceding streptococcal infection

Theis is determined by measuring

anti-streptolysin titer (ASO) which is elevated in
nearly 85% of PSGN, also anti-DNAse B may be
elevated.
b. Serum complement Levels (C3)
These are usually low due to its consumption in the
inflammatory reaction. Complement levels usually
return to normal levels in 6-8 weeks unless the case
is complicated.
 c. Urinalysis (General urine examination):

Urine analysis shows macroscopic or

microscopic hematuria, RBC casts, mild
proteinuria. Only 5% of patients with PSGN have
massive proteinuria that indicates nephrotic
syndrome. White blood cell casts, hyaline, and
cellular casts are usually present in the urine
analysis.
RBCs casts RBCs (dysmorphic RBCs)
Urinalysis