Supervised by

Dr. Ragaa abd el-kader

Professor of Rheumatology
Alexandria University
CALSSIFICATION OF
VASCILITIS AND ITS
PATHOGENESIS
This part is made by:
Asmaa Ahmed Mahmoud Salem .(187)
1-calssicfation according
to cause
2-Classification according to
Vessel size :
3- classification according to
Pathogenesis:
4-calssicfation according
to Immunopathology
classification
Vasculitis is inflammation of blood vessels, often with
ischemia, necrosis, and occlusive changes
1ry
*Henoch-Schnlein purpura I
*diopathic cutaneous vasculitis
*Essential mixed cryoglobulinemia


*Wegener's granulomatosis
*PAN
*Churg stauss sundrome



*Giant cell arteritis
*Takayasu's arteritis

2ry
*Drug
*malignancy
*Infection
*Rheumatic dis.
classification according to cause:
classification according to vessle size :
calssification according to Pathogenesis:
Wegeners granulomatosis (WG)
Churg-Strass syndrome (CSS)
Microscopic polyangiitis (MPA)
Antibody
mediated
inflammation
Henoch Schlein purpura (HSP)
Cryoglobulinaemic vasculitis
Polyarteritis nodosa (PAN)
Immune complex-
mediated
inflammation
Giant cell arteritis
Takayasu arteritis
Cell-mediated
inflammation



Polyarteritis nodosa
Microscopic polyangiitis
Hypersensitivity
vasculitis (Leukocytoclastic vasculitis)
Henoch-Schonlein purpura
Immune
complex
mediated
vasculitis:

Giant cell arteritis
Takayasus arteritis
Churg-Strauss disease
Wegeners granulomatosis

Vasculitis
due to cellular
hypersensitivity
calssification according to Immuno pathology

1. Deposition of circulating antigen-antibody complex
within the vessel wall. This leads to complement activation and
chemotactic attraction of neutrophils by complement
components. Subsequent phagocytosis of such complexes with
Liberation of neutrophil granular products leads to vascular
damage.

2. Cell-mediated hypersensitivity: Antigenic exposure may
attract lymphocytes which liberate cytokines causing tissue
damage and further activation of macrophages and
lymphocytes.

3. Failure to clear the antigen may lead to persistent
inflammation and eventual formation of epithelioid cells and
giant cells, giving rise to a granulomatous tissue reaction.

The possible immunopathologic mechanism in
vasculitis are:



are Antibodies directed against certain
proteins in the cytoplasmic granules of
neutrophils and monocytes

ANCA Associated Diseases
Wegeners granulomatosis
Microscopic polyangiitis-70% positive
Churg-Strauss syndrome-about 50%
Renal limited (pauci-immune) vasculitis
Drug-induced ANCA-associated vasculitis
ANCA
C-ANCA P-ANCA
o cytoplasmic stain
o Antibody against proteinase 3
o Called PR3-ANCA
o Present in same granules and
lysosomes as P-ANCA
o More commonly detected in patients
with Wegeners Granulomatosis

o perinuclear stain
o Antibody against myeloperoxidase
o Called MPO-ANCA
o Present in primary granules of
neutrophils
Present in peroxidase positive
lysosomes of monocytes
o Predominates in pateitns with
microscopic polyangiitis and Churg-
Strauss Syndrome
PR3 MPO
o PR3 Cleaves elastase in the
extracellular matrix
o Release from granules of activated
neutrophils contribute to tissue
breakdown to allow more neutrophils
to enter
o PR3 Inhibited by Alpha 1-antitrypsin
o MPO released from granules of
activated neutrophils Promotes the
generation of bactericidal hypochlorite
molecules Leads to tissue breakdown
o Increases proteolytic activity of PR3
through enhancing the inactivation of
alpha-1 antitrypsin by ROS
Types
Giant-cell arteritis (GCA or temporal arteritis)

is an inflammatory disease of blood vessels most
commonly involving large and medium arteries of
the head.
The name (giant cell arteritis) reflects the type
of inflammatory cell involved as seen on a
biopsy.
It is also known as "Cranial arteritis" and
"Horton's disease."

Temporal Arteritis Risk Factors

Many serious complications may arise from Temporal Arteritis :
strokes can be just one of these.
Other dangerous health issues include :
blindness, paralysis and aortic aneurysm.
In worst cases, it may even lead to death.
It is because of the potentially serious
complications that Temporal Arteritis needs to be
treated as soon as it is diagnosed. Early treatment
prevents any serious physical damage and helps
the patient make a faster recovery. If you have
persistent headaches or any other symptoms
characteristic of Temporal Arteritis, it is necessary
that you begin the treatment immediately
Associated conditions

polymyalgia rheumatica (PMR): which is
characterized by sudden onset of pain and stiffness
in muscles (pelvis, shoulder) of the body and is seen
in the elderly.
Other diseases related with temporal arteritis are :
systemic lupus erythematosus,
rheumatoid arthritis
severe infections.

Symptoms:

It is more common in females than males by a
ratio of 3:1. The mean age of onset is about 70
years, and it is rare in those less than 50 years
of age.Patients present with:

New type of severe headache
fever
tenderness and sensitivity on the scalp
jaw claudication (pain in jaw when chewing)
tongue claudication (pain in tongue when chewing) and necrosis
reduced visual acuity (blurred vision)
acute visual loss (sudden blindness)
diplopia (double vision)
acute tinnitus (ringing in the ears)
Shoulder Pain
Cough:People with Temporal Arteritis can also suffer from a bad case of
dry cough.
The inflammation may affect blood supply to the eye and blurred vision
or sudden blindness may occur. In 76% of cases involving the eye, the
ophthalmic artery is involved causing anterior ischemic optic neuropathy
Loss of vision in both eyes may occur very abruptly and this disease is
therefore a medical emergency.

Complications:

Giant cell arteritis can cause the following
complications:

Blindness:
This is the most serious complication of GCA.
The swelling that occurs with giant cell arteritis
narrows your blood vessels, reducing the
amount of blood and therefore oxygen and
vital nutrients that reaches your body's
tissues. Diminished blood flow to your eyes can
cause sudden, painless vision loss in one or, in
rare cases, both eyes. Unfortunately, blindness
is usually permanent.

Complications:(cont.)

Aortic aneurysm. Having giant cell
arteritis increases your risk of aneurysm.
An aortic aneurysm is a serious condition
because it may burst, causing life-
threatening internal bleeding. Because it
may occur even years after the initial
diagnosis of GCA.

Stroke. In some cases, a blood clot may form in an
affected artery, obstructing blood flow completely,
depriving part of your brain of necessary oxygen
and nutrients, and causing stroke. This serious
condition is an uncommon complication of GCA.

Complications:(cont.)

Diagnosis
Physical exam
Laboratory
tests
Biopsy
Imaging studies
1-Physical exam:

Palpation of the head reveals prominent temporal
arteries with or without pulsation.
The temporal area may be tender.
Decreased pulses may be found throughout the
body.
Evidence of ischemia may be noted on fundal
exam.

2-Laboratory tests:

LFTs, liver function tests, are abnormal particularly
raised ALP- alkaline phosphatase
Erythrocyte sedimentation rate, an inflammatory
marker, >60 mm/hour (normal 1040 mm/hour), but
may be normal in approximately 20% of cases.
C-reactive protein, another inflammatory marker, is
also commonly elevated.
Platelets may also be elevated.

3-Biopsy:

The gold standard for diagnosing temporal
arteritis .
It involves removing a small part of the vessel and
examining it microscopically for giant cells infiltrating the
tissue.
Since the blood vessels are involved in a patchy pattern,
there may be unaffected areas on the vessel and the
biopsy might have been taken from these parts.
Unilateral biopsy of a 1.53 cm length is 85-90%
sensitive. So, a negative result does not definitely rule
out the diagnosis.

4-Imaging studies:

U.S: Radiological examination of the temporal
artery with ultrasound yields a halo sign.
Contrast enhanced brain MRI and CT :is generally
negative in this disorder.
Recent studies have shown that 3T MRI: using
super high resolution imaging and contrast injection
can non-invasively diagnose this disorder with high
specificity and sensitivity
corticosteroids
Temporal Arteritis
Natural Treatment:

Lifestyle and home
remedies:
Treatment:
Corticosteroids:
typically high-dose prednisone (4060 mg bd),
must be started as soon as the diagnosis is
suspected (even before the diagnosis is
confirmed by biopsy) to prevent irreversible
blindness secondary to ophthalmic artery
occlusion. Steroids do not prevent the diagnosis
from later being confirmed by biopsy. The dose
of prednisone is lowered after 24 weeks, and
slowly tapered over 912 months. Oral steroids
are at least as effective as intravenous
steroids,except in the treatment of acute visual
loss where intravenous steroids appear to offer
significant benefit over oral steroids

Temporal Arteritis Natural Treatment:

Physicians also advise patients to use some natural
remedies along with medicines for a faster recovery.
Vitamin D and Calcium supplements are very useful
in curing the condition. They are also effective in
counteracting the long-term effects of Corticosteroid
medicines.

Lifestyle and home remedies:
Eat a healthy diet. Eating well can help
prevent potential problems, such as ;
thinning bones, high blood pressure and
diabetes.
Emphasize fresh fruits and vegetables, whole
grains, and lean meats and fish.
limiting salt, sugar and alcohol.
Be sure to get adequate amounts of calcium
and vitamin D. Experts recommend between
1,000 and 1,500 milligrams of calcium and 800
international units (IU) of vitamin D a day.

Lifestyle and home remedies:(cont.)
Exercise regularly.
Regular aerobic exercise, such as walking, can
help prevent bone loss, high blood pressure and
diabetes.
It also benefits your heart and lungs.
many people find that exercise improves their
mood and overall sense of well-being.

Temporal Arteritis Prognosis:

For patients with Temporal Arteritis
recovery is usually complete.
People generally recover fully, though
treatment needs to be carried out for 1-2
years or a longer period of time. This
prevents any chance of Temporal Arteritis
recurrence. When properly treated, Giant
Cell Arteritis rarely makes a comeback.

.
Large vessel Small vessel
Medium
vessel
Takayasu`
s
arteritis
Giant cell
arteritis
First Description

The first case of
Takayasus arteritis was
described in 1908 by Dr.
Mikito Takayasu at the
Annual Meeting of the
Japan Ophthalmology
Society.
definition
Takayasu arteritis is a chronic
inflammation of the large blood vessel
(aorta).
Histopathology
Epidemiology
Incidence worldwide: rare disease 2-
3 cases per year per million head of
population.

affects women more frequently than
men with a 9:1 female:male ratio.

affects young adults up to the age of
40, but is most common in the age
range 15-20.

reported all over the world, but is most
common in Asia, particularly Japan.

Types of Involvement in Takayasus Arteritis

Classical
Takayasus
Pulmonary
Arteries
Descending
Aorta
Takayasus arteritis is
not known.
Some evidence
suggests that an
infection of some viral,
bacterial, or other
occurring in a person
with other predisposing
factors
Clinical picture
symptoms
Occlusive
stage
Systemic
stage
signs
Symptoms

Systemic stage
40-50%
Inflammation
Fever,fatigue,
weight loss.

Arthralgia and non-
specific pains.

Tndeness.

Symptoms
Occlusive
stage
50-60%
Ischaemic
phenomena
Vascular neurologic cardiac
pulmonary renal
Occlusive stage

Vascular

claudication of jaw or
extremities.
back pain (due to
involvement of the
aorta).
syncope (rare).
hypertension (the
commonest
presentation in
children).
Occlusive stage

Neurological

Dizziness
Headaches
TIAs
visual disturbance
Seizures
stroke
Occlusive stage

Cardiac :
angina
dyspnoea (from
congestive cardiac
failure - the primary
cause of death)

Pulmonary :
Haemoptysis
pleuritis
Occlusive stage
Gastrointestinal

abdominal pain

renal
haematuria

Dermatological

rashes including :
erythema multiforme
induratum
Signs

systolic BP difference >10 mmHg
between arms .
Peripheral pulses may not be
palpable.
Arterial bruits over any large
artery and bruit of aortic
regurgitation.
Hypertension in 50% due to renal
artery involvement.
Ophthalmoscopic changes.
Anaemia .
Muscle wasting.
Skin vasculitis .
Diagnostic criteria From the American College
of Rheumatology

3 of 6 of the following should be present:

1. Age at onset 40 years.
2. Claudication of the extremities.
3. Reduced pulsation of one or both brachial
arteries
4. >10 mmHg BP difference between arms
5. Bruit over one or both subclavians or the
abdominal aorta.
6. Arteriographic narrowing/occlusion of the
entire aorta, its primary branches or large
arteries in upper/lower limbs .
LAB
CBC: NN
Anaemia
Increase ESR
early
Hypoalbuminemi
a
RADIOGRAPHIC
MRA(non
invasive).
Angiography
CT &US
Investigations
(A) MRA patient with active TA at diagnosis. There is complete
occlusion of the left SCA at its origin (arrow) with numerous
collaterals evident and an ostial stenosis of the left common
carotid artery. (B) MRA image from the same patient in remission.
No significant progression of the lesions found on the baseline
MRA is seen.
3D
MRA
MRI
Angio
Management
Drugs

prednisolone, usually at a starting
dose 1 mg/kg/day.
Steroid sparing agents :
Cyclophosphamide.
Hypertension should be
aggressively managed .
Anticoagulant used to prevent
stroke .
Anti-tumour necrosis factor (anti -
TNF) has recently been used with
encouraging results .

Surgery

Surgical procedures are sometimes
required to increase the flow of
blood through an artery and
procedures undertaken include:

Angioplasty with stenting
Vascular bypass procedures
Aortic valve replacement
Suction thrombectomy of the
subclavian artery
Management
Complications

Complications occur as a result of narrowing or
occlusion of the arteries and may include:

Loss of vision
Hypertension
Stroke
Aortic regurgitation
Myocardial infarction
Pregnancy

Healthy baby
Prognosis
20% have self-limiting monophasic disease.
A picture however is emerging of long-term
disability and reliance on steroids to reduce the
remission rate.
The mortality rate is 2-35% over 5 years
Differential diagnosis
Acute lymphoblastic
leukemia
Behcet syndrome
Polyartheritis nodosa
Rheumatic fever
Giant cell arteritis
Buerger disease
Systemic lupus
erythematosis
juvenile rheumatoid
arthritis
Migraine
Malignancy
Takayasus arteritis
a rare disease :inflammation in the walls
of the largest arteries in the body: the
aorta and its major branches.
pulseless disease.
more common among young women
diagnosed by angiography & MRA
The problems caused by narrowed or
blocked arteries
treated with glucocorticoids (prednisone
and others)& other medications that
suppress the immune system.
Polyarteritis nodosa is an
autoimmune disease affecting
the medium sized arteries
Most cases of PAN occur in the
4th or 5th decade, although it
can occur at any age .
symptoms result from ischaemic
damage to affected organs, often
the skin, heart, kidneys, and
nervous system.
Generalised symptoms include fever,
fatigue, weakness, loss of appetite, and
weight loss. Muscle and joint aches are
common. The skin may show rashes, swelling,
ulcers.

Peripheral neuropathies are very common (50 to 70%). This
includes tingling, numbness and/or pain in the hands, arms,
feet, and legs.
Central nervous system (CNS) lesions may occur 2 to 3 years
after the
onset of PAN and may lead to
cognitive dysfunction, decreased
alertness, seizures and neurologic
deficits.
Skin affection include:
purpura,
livedo reticularis,
ulcers,
nodules
or gangrene.
Skin involvement occurs
most often on the legs and is
very painful
Renal artery vasculitis may lead to
impaired kidney function, and
renovascular hypertension.


Testicular infarction cause
testicular pain


.
affection of the mesenteric artery can cause
Abdominal pain, gastrointestinal bleeding
(occasionally is mistaken for inflammatory
bowel disease)
Hemorrhage, bowel infarction, and
perforation are rare, but very serious

1. Routine laboratory tests may provide important clues to
PAN, but there is no single blood test that is diagnostic
of this disease. Most patients with PAN have elevated
ESRs.
2. If there is skin or muscle/nerve involvement, a skin or
muscle/nerve biopsy can be extremely helpful in coming
to a definite diagnosis of PAN.
3. Nerve conduction studies are a non-invasive way of
identifying nerves that are involved by the inflammation.






4-An angiogram of the abdominal and
renal blood vessels may also be very
helpful in diagnosing PAN.
microaneurysms most often affect the
arteries leading to the kidneys, liver or
gastrointestinal tract.




1. Weight loss of > 4 kg since beginning of illness
2. Livedo reticularis
3. Testicular pain or tenderness
4. Myalgias, weakness, or leg tenderness
5. Mononeuropathy or polyneuropathy
6. Development of hypertension
7. Elevated BUN or creatinine unrelated to dehydration
or obstruction
8. Presence of hepatitis B surface antigen or antibody in
serum
9. Arteriogram demonstrating aneurysms or occlusions
of the visceral arteries
10. Biopsy of small or medium-sized artery containing
granulocytes
patients are treated with high doses
of corticosteroids. Other
immunosuppressive drugs are also
added for patients who are
especially ill. In most cases of PAN
now, if diagnosed early enough the
disease can be controlled, and often
cured.
Wagner Granulomatosis



BY
AsmaaHamed
191
Definition:

Wegener's granulomatosis (WG) is a chronic
granulomatous necrotizing vasculitis
predominantly affecting the upper and lower
respiratory tracts and the kidney.
Epidemiology:
The onset of Wegener's granulomatosis can
occur at any age, but it most often occurs
between the ages of 30 and 50.
Caucasians are most likely to develop Wegener's
granulomatosis.


Etiology:
The cause of Wegeners
Granulomatosis is not known.

Genetic
Factors
Environmental
factors
Pathophysiology:

Inflammation with granuloma
formation.

Anti-neutrophil cytoplasmic
antibodies (ANCAs) are
responsible for the inflammation in
Wegener's. This type of ANCA is
also known as cANCA, with the c
indicating cytoplasmic.

Clinical Picture:

SINUS SIGNS & SYMPTOMS

rhinorrhea.

Discolored nasal discharge

Bloody nasal discharge,
nose bleeding

Ulcerations of the mucous
membranes (sores or
crusting)

perforation of the nasal
septum may develop, and
collapse of the nasal bridge
(called saddle nose
deformity).
Respiratory SIGNS & SYMPTOMS

Pulmonary nodules

infiltrates

cavitary lesions

pulmonary hemorrhage
bronchial stenosis

subglottic stenosis

KIDNEY SIGNS & SYMPTOMS
Rapidly progressive segmental necrotizing
glomerulonephritis leading to chronic renal
failure.

MUSCULOSKELETAL SYSTEM
SIGNS & SYMPTOMS

Pain, joint swelling affects two-thirds of
patients.
It does not lead to permanent joint damage
or deformities

SKIN SIGNS & SYMPTOMS

Nearly half of people with
Wegener's
granulomatosis develop
skin lesions

Skin sores or rashes that
appear as small red or
purple patches, small
blister-like lesions,
ulcers or small nodules
EYES SIGNS & SYMPTOMS

Conjunctivitis, scleritis,
episcleritis, Uveitis
Weakened vision or double
vision.
Double vision or a
decrease in vision .
Oral Cavity
Strawberry gingivitis.
Bone destruction with
loosening of teeth.
Non-specific ulcerations
throughout oral mucosa.

Criteria:

In 1990, the American College of Rheumatology
accepted classification criteria for Wegener's.
Nasal or oral inflammation:
painful or painless oral ulcers or
purulent or bloody nasal discharge
Lungs: abnormal chest X-ray with:
nodules,
infiltrates or
cavities
Kidneys: urinary sediment with:
microhematuria or
red cell casts
Biopsy: granulomatous inflammation
within the arterial wall or
in the perivascular area

According to the Chapel Hill Consensus
Conference (CHCC) (1992):
a granulomatous inflammation involving
the respiratory tract, and
a vasculitis of small to medium-size
vessels.

Diagnosis:
Laboratory investigation
CBC
Anti-Neutrophil Cytoplasmic
Autoantibodies (ANCA)

Radiology
Lung X-ray show cavities or masses
,infiltrates, solid nodules.
A sinus X-ray or computed tomography
(CT) scan

TISSUE BIOPSY

The only sure way to confirm
a diagnosis of Wegener's
granulomatosis
Sites
nasal passages, airways,
or lungs
Finding
leukocytoclastic vasculitis
with necrotic changes and
granulomatous
inflammation (clumps of
typically arranged white
blood cells) on microscopy.
TREATMENT
A-DRUG THERAPY:

1-corticosteroids

2-Cyclophosphamide .
3-Methotrexate
4-Bactrim


5-Bisphosphonates (Fosamax)




6-Folic acid or folinic
acid
B-SURGERY:
Severe subglottic stenosis, tracheotomy
is required.
kidney transplant in cases of renal
failure

Prognosis:

Without treatment, people with this disease can die
within a few months.

With treatment, most people who receive
corticosteroids and cyclophosphamide get much
better.

However, the disease may return in about half of all
patients. In these cases, the disease usually comes
back within 2 years of stopping treatment.

Presented by: asmaa shaltot
Microscopic polyangiitis


Also known as "Microscopic polyarteritis,"
"Microscopic polyarteritis nodosa"
It is an ill-defined autoimmune disease characterized
by necrotizing, small-vessel vasculitis


The process is begun with an autoimmune process of
unknown etiology that triggers production of p-
ANCA( is usually directed against myeloperoxidase
(MPO).


Symptoms
and Signs
Skin
Respiratory
Ocular
GI
Neurologic
Renal
In the form of glomerulonephritis which causes
hematuria, proteinuria and RBC casts are
present.

Renal
About 1/3 of patients
have a purpuric rash .




Nail bed infarcts and
splinter hemorrhages
may occur.
Skin
Mild symptoms of rhinitis, epistaxis, and sinusitis
Alveolar hemorrhage
pulmonary fibrosis
chest x-ray
bilateral patchy infiltrates

Respiratory

Abdominal pain, nausea, vomiting, diarrhea, and
bloody stools.



Vasculitis peripheral neuritis and
mononeuritis multiplex.
Neurologic symptoms include numbness or tingling
in the arm, hand, leg, or foot.



GIT
Neurologic
Over time, muscle wasting that is secondary to
the nerve damage may result.









later, cerebral vasculitis cerebral hemorrhage,
infarction, seizures, or headache.

If the eyes are affected, episcleritis,
conjunctivitis and uveitis usually result.
The FIVE most common clinical
manifestations of MPA are:
Kidney inflammation (~ 80% of patients).
Weight loss (> 70%).
Skin lesions (> 60%).
Nerve damage (60%).
Fevers (55%).




Ocular
Diagnosis
Clinical
findings
laboratory
tests
Chest x-
ray
Biopsy
ANCA positive.






ESR and C-reactive protein levels are elevated.

laboratory
tests
CBC:WBC and platelet counts are
elevated
Anemia of chronic disease is
common.
An acute drop in Hct suggests
alveolar hemorrhage or hemorrhage in the
GI tract.

Serum creatinine should be measured
periodically to check for renal involvement.

Urinalysis: (to check for hematuria,
proteinuria, and cellular casts) should be
done.

Tissue biopsy may be needed to make the
diagnosis of MPA.

Biobsy
MPA PAN
BLOOD VESSEL SIZE Small to Medium Medium
BLOOD VESSEL TYPE Arterioles to venules Muscular Arteries
GRANULOMATOUS
INFLAMMATION
NO NO
LUNG SYMPTOMS YES
1
NO
GLOMERULONEPHRITIS YES(rapidely progressive) NO
RENAL HYPERTENSION NO YES
MONONEURITIS MULTIPLEXCOMMON COMMON
SKIN LESIONS YES
2
YES
2
GI SYMPTOMS NO YES
3
EYE SYMPTOMS YES
4
NO
ANCA-POSITIVITY 75%(P-ANCA) NO
MICROANEURYSMS RARELY TYPICAL
A steroid (usually prednisone) in combination with
a cytotoxic agent [cyclophosphamide (CYC)] is
typically the first combination of medications to be
prescribed.



Treatment
After control of the disease
CYC is then typically switched to azathioprine or
methotrexate .






Prednisone is usually discontinued after approximately 6
months.
Churg-Strauss Syndrome
Presented by: asmaa hassan 193
Churg-Strauss Syndrome
Defination
Churg-Strauss syndrome (CSS), or allergic
granulomatous angiitis, is a rare syndrome that
affects small- to medium- sized arteries and
veins. This disease was first described in 1951 by
Dr. Jacob Churg and Dr. Lotte Strauss as a
syndrome consisting of :
1. 1-Asthma
2. 2-eosinophilia
3. 3-fever
4. 4-vasculitis of various organ systems

Causes
Environmental
Genetics
Clinical Picture:
1-Type of the patient
-is a middle aged individual with a history of new-
onset or newly-worsened asthma.
-male=female

2-Classic symptoms and signs of Churg-
Strauss Syndrome
- is a highly variable illness
mild
symptoms
severe or life-threatening
complications
Stages of Churg-Strauss
syndrome
There are three stages, or phases, of Churg-
Strauss syndrome but not everyone develops
all three phases or in the same order
A)-Allergic stage
This is usually the first stage of Churg-Strauss
syndrome. It's marked by a number of allergic
reactions, including:
a-Asthma:
Asthma symptoms may begin long before the
onset of vasculitis
b-Hay fever (allergic rhinitis):
This affects the mucous membranes of the nose
causing runny nose
sneezing
itching

c-Sinus pain and inflammation (sinusitis):
there is facial pain and develop nasal polyps
(B)-Eosinophilic stage
An eosinophil is one subtypes of white blood cell.
Normally, eosinophils comprise 5% or less of the
total white blood cell count. In CSS, the
percentage of eosinophils may reach as high as
60%. In the picture below, the eosinophils are
shown by the dark pink stain.
Signs and symptoms of eosinophilia
may include:
* Fever
* Weight loss
* Asthma
* Fatigue
* Night sweats
* Cough
* Abdominal pain
* Gastrointestinal bleeding
(C)-Vasculitic stage
-the hallmark of this stage of Churg-Strauss
syndrome is severe blood vessel
inflammation (vasculitis).
-By narrowing blood vessels, inflammation
reduces blood flow to vital organs
and tissues throughout the body,
including the skin, heart,
peripheral nervous system,
muscles, bones
and digestive tract.


Nose
* Sinusitis,
* Nasal polyps

Lung
* Pulmonary infiltrates
* Bleeding into the lungs
* Diffuse interstitial lung
disease


Skin
Rashes
Palpable purpura
Nodules
often at sites of pressure,
such as the elbow





Kidney
Glomerulonephritis
Hypertension
Gastrointestinal
Heart
Granuloma sometimes
found in spleen
congestive heart failure or
a heart attack
Nerve
pain
numbness in extremities
Diagnosis:
1-abnormal blood tests (eosinophilia, in particular)
.
2-Elevated (ESR) and (CRP) levels
3-ANCA is present in approximately 40% of
patients
4-Elevated serum IgE levels
5-In addition to a detailed history and physical
examination, blood tests and imaging studies
6-nerve conduction tests, and tissue biopsies
(e.g., of lung, skin, or nerve)
The ACR selected 6 disease features
(criteria)
patient should have at least 4 of the 6 ACR criteria.
These criteria include:
1. asthma
2. eosinophilia [>10% on differential WBC count]
3. mononeuropathy
4. transient pulmonary infiltrates on chest X-rays
5. paranasal sinus abnormalities
6. biopsy containing a blood vessel with
extravascular eosinophils
Treatment
oral
intravenous
(usually methylprednisolone)
prednisone
2-immunosuppressive drugs, .
such as azathioprine
methotrexate,or cyclophosphamide
may be used
in addition to prednisone.

1-steroids
Immune Complex-Mediated
Small Vessel Vasculitis

There are four principal subtypes:
hypersensitivity vasculitis;
Cryoglobulinemic vasculitis;
HenochSchonlein purpura (HSP);
Hypocomplementemic urticarial
vasculitis.

Hypersensitivity cutaneous
Vasculitis:

Presented by :
Asmaa khairy beltagy 194
Hypersensitivity cutaneous Vasculitis:

Definition:
immune complex small-vessel vasculitis
that is restricted to the skin
not associated with any other form of
primary or secondary vasculitis.
not associated other organ involvement
(eg, the glomeruli or pulmonary capillaries)


cutaneous leukocytoclastic
angiitis
hypersensitivity vasculitis
leukocytoclastic vasculitis
cutaneous small-vessel
vasculitis
Epidemiology:

incidence 10-30 cases per million per
year.

Race

Sex

Age


Causes of hypersensitivity vasculitis:

half of patients no inciting
agent can be identified

Other causes:
Medications:


Infections:


Some malignancies:


Foods or food additives:

Pathogenesis:

Arthus reaction :


Immunegenecity:

Clinical findings:

Skin
palpable purpura , non palpable purpura,
papules,
vesicles, pustules,
urticaria, ulcers,
non palpable laisions (macules and patches)
splinter heamorrhage.
occur in symmetric fashion over dependent
regions, ie, the lower extremities or buttocks.
occur in cohorts or "crops" that are the same age.
may be asymptomatic or accompanied by a
burning or tingling sensation
Joints
Hypersensitivity vasculitis is sometimes
accompanied by arthralgias and even frank
arthritis, with a predominance for large joints.

Complications

residual hyperpigmentation

scars (in the case of ulcerated
lesions)

recurrent disease
Differential Diagnosis


Other vasculitides
Henoch-Schnlein purpura
Mixed cryoglobulinemia
Microscopic polyangiitis
Churg-Strauss syndrome
Wegener granulomatosis
Polyarteritis nodosa
Systemic autoimmune conditions
Systemic lupus erythematosus
Rheumatoid arthritis
Miscellaneous
Other types of drug eruptions
Thrombotic thrombocytopenic purpura.
Infective endocarditis.
Pregnancy associated purpura.

Diagnosis

1. ACR Criteria for Classification of
Hypersensitivity Vasculitis

2. Laboratory Findings and imaging

3. Biopsy

1. American College of Rheumatology 1990 Criteria for
the Classification of Hypersensitivity Vasculitis
1. Age at disease onset >16 years.
2. Offending medication at disease onset.
3. Palpable purpura.
4. Maculopapular rash.
5. Biopsy including arteriole and venule, showing neutrophils
perivascular
three of these five criteria has Sensitivity = 71%; specificity = 83.9%.
2.Laboratory Findings and imaging
Test Typical Result
Complete blood cell count, with differential Normal
Electrolytes Normal
Liver function tests Normal
Urinalysis with microscopy Normal
Erythrocyte sedimentation rate
/C-reactive protein
Mild to moderate
elevations in <50% of
patients
ANA Negative
Rheumatoid factor Negative
C3, C4 Normal
ANCA Negative
Antihepatitis B and C assays Negative
Cryoglobulins Negative
Chest radiography, CT and MRI Normal
3.Biopsy:

Light microscopy:
24 48 hours appearance of a lesion
from non ulcerated leision
If there are ulcers , it should be taken
from edges of the ulcer.
Cellular infiltrate of neutrophils and
lymphocytes (lymphocytes rich
infiltrates may be seen in new


Direct immuneflourescent microscopy (DIF)

this patient had a history of ventricular septal defect that was complicated
by streptococcal septicemia and was associated with IgA and IgM
vascular immunoglobulin deposition
Diagnostic algorithm :
Pesentation consistent with small vessel
vasculitis
History
Mdication
Infection e.g HCV
Connecive tissue
disease
Review of
systems and
physical ex. to
exclude extra
cutaneous
manifestation
Work-up
Skin biopsy
histoog
y
DIF
Blood work
radiology
CBC
ANA
ANCA
RF
Cryoglobulins
C3, C4
Treatment:

1. Elevation of the legs
2. or compression stockings
3. removal of the offending agent
4. Mild cases: NSAID
5. For persistent disease: colchicine,
hydroxychloroquine or dapsone
6. refractory or more severe cases:
immunosuppressive agents e.g glucocorticoids
or Azathioprine
Asmaa Samy Farag El Naggar
195


Cryoglobulinimic vasculitis (CV):
It is a systemic vasculitis secondary to
circulating immune complex deposition
in small blood vessels.

The name literally means cold antibody
in the blood

A. Brouet classification: based on cryoglobulin
composition

Classification of Cryoglobulins Composition of cryoprecipitates
Type I cryoglobulinemia monoclonal Ig, usually IgM or, less
frequently, IgG or IgA
Type II mixed cryoglobulinemia polyclonal IgGs + monoclonal IgM
Type III mixed
cryoglobulinemia
polyclonal IgGs + polyclonal IgMs
B. Classification based on the association of the
syndrome with an underlying disease:


1. Essential, or
idiopathic
2. Secondary
Distinct disorder;
it can be classified
among systemic
vasculitides.
lymphoproliferative
disorder,
autoimmune disease,
infectious disease


The prevalence varies from country to country(related to the
endemicity of HCV ).
No racial predilection.
female: male = 3:1.
Mean age = 42-52 ys.

Etiology of Mixed Cryoglobulinemia
1. There is frequent association between MC and HCV



2. However, the MC is also the result of concomitant
genetic and/or environmental factors, which remain
largely unknown.
A role for HBV < 5% .
HCV in MC patients 70% - 100% .

Etiopathogenesis of MC in HCV
HCV
hepato- and
lymphotropic virus
lymphoproliferation &
antibody production
Due to the shared
expression of CD81
receptors
HCV-dependent gene
translocation protects cells
against apoptosis Lowering
of the cell-activation
threshold
HCV syndrome

Meltzer triad: purpura, weakness, arthralgias
The common symptoms dt vasculitis
include:
Skin
Joints
Kidneys
Nerves
Lungs
Gastrointestin
al tract
Eyes
Brain
Blood
Sinuses
and nose
Type I cryoglobulinemia
acrocyanosis, retinal hemorrhage,
severe Raynaud phenomenon with
digital ulceration, livedo reticularis,
purpura, and arterial thrombosis
Specific clinical manifestations:
Types II & III
cryoglobulinemia
arthralgia, fatigue, myalgias, renal
disease, cutaneous vasculitis, and
peripheral neuropathy.
Specific clinical manifestations:

A. Isolated serum mixed cryoglobulins
B. Complete cryoglobulinemic syndrome
C. Incomplete mixed cryoglobulinemia
D.Typical cryoglobulinemic syndrome, but without serum
cryoglobulins

MC can represent a crossroads between some
autoimmune disorders and malignancies (B-cell
lymphomas, HCC). In only a minority of MC patients a
malignancy may develop, generally after a long lasting.
N.B

The main diagnostic parameter of MC is the presence of serum
mixed (IgG-IgM) cryoglobulins.

Laboratory Studies:
1. Evaluation for serum cryoglobulins
2. RF: RF is positive in types II and III.
3. Complement evaluation: hypocomplementemia
(esp. C4 ).
1. Liver function& hepatitis serology.
2. CBC: Leukocytosis &/or Anemia may be present.
3. Other

Imaging Studies:
1. Angiography
2. CT imaging may be
considered upon high
suspicion of underlying
malignancy.
3. Others according to clinical
manifestation
Tissue biopsy:
It may be required for diagnosis
when patients with vasculitis,
renal disease, or both are
evaluated.


criteria serological pathological clinical
major mixed
cryoglobulins
low C4
leukocytoclastic
vasculitis
purpura
minor Rheumatoid
factor +
HCV+
HBV +
clonal B-cell
infiltrates
(liver and/or
bone marrow)
chronic hepatitis
MPGN
peripheral
neuropathy
skin ulcers
Definite mixed cryoglobulinemia syndrome:
a. serum mixed cryoglobulins ( low C4) + purpura + leukocytoclastic vasculitis
b. serum mixed cryoglobulins ( low C4)+ 2 minor clinical symptoms
+ 2 minor serological/pathological findings

The goal of therapy is to:
1. Treat underlying conditions.
2. Limit the precipitant cryoglobulin and the resultant
inflammatory effects.

Asymptomatic cryoglobulinemia no treatment.
Secondary cryoglobulinemia treatment of
underlying or associated disease.

1. Nonsteroidal anti-inflammatory drugs.
2. Immunosuppressive medications (corticosteroid therapy
cyclophosphamide or azathioprine)

3. Plasmapheresis is indicated for severe
complications related to cryoprecipitation or
serum hyperviscosity.

4. Pegylated interferon alfa combined with
ribavirin.

5. Rituximab therapy
Treatment of HCV-associated Mixed
Cryoglobulinaemia
State of patient Proposed treatments
Asymptomatic none
Mild manifestations:
purpura, weakness ,arthralgias,
arthritis, peripheral sensory
neuropathy
LAC-diet, low dosage of steroids
other symptomatics
Severe manifestations:
nephropathy, skin ulcers, sensory-motor
neuropathy, widespread vasculitis,
active hepatitis
steroids, plasma exchange,
cyclophosphamide, alpha-interferon +
ribavirine
Cancer : B-cell NHL, HCC chemotherapy, surgery
Asmaa toto
196
HenochSchnlein purpura
HenochSchnlein purpura
Definision
also known as anaphylactoid purpura, rheumatica
,purpura
is a form of blood vessel inflammation or vasculitis.
HSP affects the small vessels called capillaries in
the skin and frequently the kidneys
Epidemiology

HSP occurs more often in children
than in adults, and usually follows an
upper respiratory tract infection.. It
occurs about twice as often in boys as
in girls
of HSP in children is about incidence The
20 per 100,000 children per year;
this makes it the most common vasculitis
in childhood
Etiology
The exact cause of HSP is unknown
HSP can develop after infections with
streptococci (-haemolytic, Lancefield
group A), hepatitis B, herpes simplex
virus, parvovirus B19
Drugs linked to HSP, usually as an idiosyncratic
reaction ,
and vancomycin include the antibiotics
- , anti captopril and enalapril ACE inhibitors
inflammatory agent
streptokinase and Diclofenac
Pathophysiology

Henoch-Schnlein purpura is a small-
vessel vasculitis in which complexes of
immunoglobulin A (IgA) and complement
component 3 (C3) are deposited on
arterioles, capillaries, and venules. As with
IgA nephropathy, serum levels of IgA are
high in HSP and there are identical
findings on renal biopsy; however, IgA
nephropathy has a prediliction for young
adults while HSP is more predominant
among children.
Signs and symptoms



are abdominal pain and arthritis , Purpura
known as the "classic triad" of Henoch
Schnlein purpura .
Purpura occurs in all cases, joint pains
and arthritis in 80 % and abdominal pain in 62 .%
as a gastrointestinal hemorrhage Some include
fourth criterion
this occurs in 33 % of cases may lead to
intussussception

Purpura
The purpura typically
appear on the legs
and
buttocks, but may
also be seen on the
arms, face and
trunk .
The abdominal pain
is colicky in character, and may be accompanied
by nausea, vomiting, constipation or diarrhea.
There may be blood or mucus in the stools.
, ankles The joints involved tend to be the
elbows , and knees ,
but arthritis in the hands and feet is
possible ;
the arthritis is nonerosive and hence
causes no permanent deformity .
kidney Forty percent have evidence of
involvement ,
(blood in the hematuria mainly in the form of
urine (
Problems in other organs
such as the central nervous system
(brain and spinal cord) and lungs
may occur, but is much less
common than in the skin, bowel and
kidneys .
(high blood pressure) may Hypertension
occur
Protein loss and high blood pressure ,
Symptoms usually last approximately a
month.
Recurrences are not frequent but do
occur.
Diagnosis
The diagnosis is based on the
combination of the symptoms, as very
few other diseases cause the same
symptoms together
Blood tests may show elevated creatinine
and urea levels (in kidney involvement)
raised IgA levels
The platelet count may be raised, and
distinguishes it from diseases where low
platelets are the cause of the purpura,
such as idiopathic thrombocytopenic
purpura

skin biopsy

The appearances are of
a hypersensitivity vasculitis
and immunofluorescence
demonstrates IgA and C3
in the blood vessel wall .
However, overall serum
complement levels are
normal
kidney biopsy
Main findings on kidney biopsy are
increased cells and Ig deposition in
the mesangium
Classification

the 2006 European League Against
Rheumatism (EULAR) and Pediatric
Rheumatology Society (PReS (
classification, include palpable purpura
as a mandatory criterion together with
at least one of the following findings :
diffuse abdominal pain, predominant IgA
deposition (confirmed on skin biopsy ( ,
acute arthritis in any joint, and renal
involvement
Treatment

Pain killers may be needed for the
abdominal and joint pains
Most patients do not receive therapy because
of the high spontaneous recovery rate.
are generally avoided Steroids .
However, if they are given early in the disease
episode ,
the duration of symptoms may be shortened ,
and abdominal pain can improve significantly .
Moreover, the chance of severe kidney problems
is reduced
Evidence of worsening kidney damage
Treatment may be indicated on the basis of
the appearance of the biopsy sample;
various treatments may be used, ranging
from oral steroids to a combination of
intravenous methylprednisolone (steroid),
cyclophosphamide and dipyridamole
followed by prednisone
(IVIG) is Intravenous immunoglobulin
occasionally used
Prognosis

Recovery and recurrence
Overall prognosis is good in most patients,
with one study showing recovery occurring
in 94 %and 89 %of children and adults,
respectively (some having needed
treatment).In children under ten, the
condition recurs in about a third of all
cases and usually within the first four
months after the initial attack. Recurrence
is more common in older children and
adults