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)
Vasculitis
Vasculitisisisinflammation
inflammationofofblood
bloodvessels,
vessels,often
oftenwith
with
ischemia,
ischemia,necrosis,
necrosis,and
andocclusive
occlusivechanges
changes
classification according to cause:
classification according to vessle size :
calssification according to Pathogenesis:
                
                                              

calssification according to  Immuno pathology

The possible immunopathologic mechanism in
vasculitis are:
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.
 ANCA

are Antibodies directed against certain

proteins in the cytoplasmic granules of
neutrophils and monocytes

 ANCA Associated Diseases

•Wegener’s granulomatosis
•Microscopic polyangiitis-70% positive
•Churg-Strauss syndrome-about 50%
•Renal limited (pauci-immune) vasculitis
•Drug-induced ANCA-associated vasculitis
Types
 ri t i s
A rt e
or a l
e m p
T
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 7
years, and it is rare in those less than 50 year
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.
Complications:(cont.)
• 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.
 Physical exam

Laboratory
Biopsy Diagnosis tests

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 10–40 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 1.5–3 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
:Tr
ea
tm
en
t
Treatment:
Corticosteroids:
typically high-dose prednisone (40–60 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 2–4 weeks, and
slowly tapered over 9–12 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.
 Medium
Large vessel Small vessel
vessel

Takayasu`
s
arteritis
Giant cell
arteritis
First Description
The first case of
Takayasu’s 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 Takayasu’s Arteritis

Classical
Takayasu’s
Pulmonary
Arteries

Descending
Aorta
Takayasu’s 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

Systemic stage
40-50% Inflammation

 Fever,fatigue,
weight loss.

 Arthralgia and non-

specific pains.

 Tndeness.
Symptoms
Occlusive
stage Ischaemic
50-60% phenomena
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 .
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 .
Management
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
 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  Buerger disease
leukemia  Systemic lupus
Behcet syndrome erythematosis
Polyartheritis nodosa  juvenile rheumatoid
Rheumatic fever arthritis
Giant cell arteritis  Migraine
 Malignancy
Takayasu’s arteritis
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

he problems caused by narrowed or

blocked arteries

reated 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 Wegener’s
Granulomatosis is not known.
Pathophysiology:
• Inflammation with granuloma
formation.

• Anti-neutrophil cytoplasmic antibo

dies
(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

. Cyclophosphamide-2

Methotrexate-3
4-Bactrim

5-Bisphosphonates (Fosamax)

Folic acid or folinic-6

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.
Microscopic polyangiitis
• Presented by: asmaa shaltot
 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).
Renal
In the form of glomerulonephritis which causes
hematuria, proteinuria and RBC casts are
present.
 Skin
 About 1/3 of patients
have a purpuric rash .

 Nail bed infarcts and

splinter hemorrhages
may occur.
 Respiratory

 Mild symptoms of rhinitis, epistaxis, and sinusitis

 Alveolar hemorrhage
pulmonary fibrosis
 chest x-ray
bilateral patchy infiltrates
 GIT

 Abdominal pain, nausea, vomiting, diarrhea, and

bloody stools.

Neurologic

 Vasculitis peripheral neuritis and

mononeuritis multiplex.
 Neurologic symptoms include numbness or tingli
in the arm, hand, leg, or foot.
 Over time, muscle wasting that is secondary to
the nerve damage may result.

 later, cerebral vasculitis cerebral hemorrhage,

infarction, seizures, or headache.
Ocular

 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%).
 laboratory
tests

 ANCA positive.

 ESR and C-reactive protein levels are elevated.

 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.
Biobsy
Tissue biopsy may be needed to make the
diagnosis of MPA.
Treatment
A steroid (usually prednisone) in combination with
a cytotoxic agent [cyclophosphamide (CYC)] is
typically the first combination of medications to be
prescribed.
After control of the disease
 CYC is then typically switched to azathioprine or
methotrexate .

 Prednisone is usually discontinued after approxima

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

Genetics Environmental
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
mild
symptoms
is a highly variable illness -

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 Granuloma sometimes
found in spleen

Heart congestive heart failure or

a heart attack

pain
Nerve
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 prednisone
steroids-1 intravenous
)usually methylprednisolone(

. ,immunosuppressive drugs-2
such as azathioprine
methotrexate,or cyclophosphamide
may be used
in addition to prednisone.
 Immune Complex-Mediated
Small Vessel Vasculitis
There are four principal subtypes:
• hypersensitivity vasculitis;
• Cryoglobulinemic vasculitis;
• Henoch–Schonlein 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)
hypersensitivity vasculitis

cutaneous leukocytoclastic
angiitis

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-Schönlein 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
Typical Result Test
Normal Complete blood cell count, with differential

Normal Electrolytes
Normal Liver function tests
Normal Urinalysis with microscopy
Mild to moderate Erythrocyte sedimentation rate
elevations in <50% of /C-reactive protein
patients
Negative ANA
Negative Rheumatoid factor
Normal C3, C4
Negative ANCA
Negative Antihepatitis B and C assays
Negative Cryoglobulins
Normal Chest radiography, CT and MRI
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 Review of
Mdication systems and
Infection e.g HCV physical ex. to
Connecive tissue exclude extra
disease cutaneous
manifestation
Work-up

Skin biopsy Blood work

CBC
ANA
radiology ANCA
histoog RF
DIF Cryoglobulins
y
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
By
Asmaa Samy Farag El Naggar 
195
Definition
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”
Classification of
Cryoglobulinemia
A. Brouet classification: based on cryoglobulin
composition

Composition of cryoprecipitates Classification of Cryoglobulins

monoclonal Ig, usually IgM or, less Type I cryoglobulinemia

frequently, IgG or IgA
polyclonal IgGs + monoclonal IgM Type II mixed cryoglobulinemia

polyclonal IgGs + polyclonal IgMs Type III mixed

cryoglobulinemia
B. Classification based on the association of the
syndrome with an underlying disease:
 

Essential, or .1 Secondary .2
idiopathic

Distinct disorder;  lymphoproliferative

it can be classified disorder,
among systemic  autoimmune disease,
vasculitides.  infectious disease
Epidemiology
 The prevalence varies from country to country(related to
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

 A role for HBV < 5% .

 HCV in MC patients 70% - 100% .

2. However, the MC is also the result of concomitant genetic

and/or environmental factors, which remain largely
unknown.
 Etiopathogenesis of MC in HCV
HCV

hepato- and lymphoproliferation &

lymphotropic virus antibody production

Due to the shared HCV-dependent gene

expression of CD81 translocation protects cells
receptors against apoptosis Lowering
of the cell-activation
threshold

HCV syndrome
Clinical description
Meltzer triad: purpura, weakness, arthralgias
The common symptoms dt
vasculitis include:
Specific clinical manifestations:
Specific clinical manifestations:
 Types of presentations:
A. Isolated serum mixed cryoglobulins
B. Complete cryoglobulinemic syndrome
C. Incomplete mixed cryoglobulinemia
D.Typical cryoglobulinemic syndrome, but without serum
cryoglobulins

N. MC can represent a crossroads between some

autoimmune disorders and malignancies (B-cell
B
lymphomas, HCC). In only a minority of MC patients a
malignancy may develop, generally after a long lasting.
 Diagnostic methods
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.
 Diagnosic criteria
clinical pathological  serological criteria
  purpura  leukocytoclastic mixed major 
  vasculitis cryoglobulins
low C4
chronic hepatitis clonal B-cell Rheumatoid minor
MPGN infiltrates  factor +
peripheral (liver and/or HCV+
neuropathy bone marrow) HBV + 
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
Treatment
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.
Treatment modalities
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
Proposed treatments State of patient
none Asymptomatic

LAC-diet, low dosage of steroids Mild manifestations:

other symptomatics purpura, weakness ,arthralgias,
arthritis,  peripheral sensory
neuropathy

steroids,   plasma exchange, Severe manifestations:

cyclophosphamide, alpha-interferon + nephropathy, skin ulcers, sensory-
ribavirine motor neuropathy, widespread
vasculitis, active hepatitis

chemotherapy, surgery Cancer : B-cell NHL, HCC

Henoch–Schönlein purpura

Asmaa toto
196
Henoch–Schönlein 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

The incidence of HSP in children is about

;per 100,000 children per year 20
this makes it the most common vasculitis
in childhood
Etiology
• The exact cause of HSP is unknown
• HSP can develop after infections with
streptococci (
β-haemolytic, Lancefield group A),
hepatitis B, herpes simplex virus,
parvovirus B19
Drugs linked to HSP, usually as an idiosyncratic
,reaction
include the antibiotics vancomycin and
and captopril, anti- enalapril ACE inhibitors
inflammatory agent
Diclofenac and streptokinase
Pathophysiology
• Henoch-Schönlein 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.
Purpura, arthritis and abdominal pain are
known as the "classic triad" of Henoch–
.Schönlein purpura

Purpura occurs in all cases, joint pains

and arthritis in 80%and abdominal pain in 62%.
Some include gastrointestinal hemorrhage as a
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.
The joints involved tend to be the ankles,
,knees, and elbows
but arthritis in the hands and feet is
;possible
the arthritis is nonerosive and hence
.causes no permanent deformity
Forty percent have evidence of kidney
,involvement
mainly in the form of hematuria (blood in the
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.
Hypertension (high blood pressure) may
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.
.Steroids are generally avoided

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
Intravenous immunoglobulin (IVIG) is 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