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 is inflammation of blood vessels, often with ischemia, necrosis, and occlusive changes

classification according to cause:

classification according to vessle size :

calssification according to Pathogenesis:

                                                              

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 complementcomponents. Subsequent phagocytosis of such complexes with 

Liberation of neutrophil granular products leads to vasculardamage.  

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•Wegener’s granulomatosis•Microscopic polyangiitis-70% positive•Churg-Strauss syndrome-about 50%•Renal limited (pauci-immune) vasculitis•Drug-induced ANCA-associated vasculitis

ANCA

Types

Temporal Arteritis

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 fevertenderness and sensitivity on the scalpjaw claudication (pain in jaw when chewing)tongue claudication (pain in tongue when chewing) and necrosisreduced visual acuity (blurred vision)acute visual loss (sudden blindness)diplopia (double vision)acute tinnitus (ringing in the ears) Shoulder PainCough: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 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

Trea

tmen

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.

Large vessel Small vesselMedium vessel

Takayasu`s

arteritisGiant cell arteritis

First DescriptionThe first case of Takayasu’s arteritis was described in 1908 by Dr. Mikito Takayasu at the Annual Meeting of the Japan Ophthalmology Society.

definitionTakayasu 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

DescendingAorta

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 stage40-50% Inflammation

Fever,fatigue, weight loss.

Arthralgia and non-specific pains.

Tndeness.

SymptomsOcclusive stage50-60%

Ischaemic 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

DizzinessHeadachesTIAsvisual disturbanceSeizuresstroke

Occlusive stage

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

Pulmonary :Haemoptysispleuritis

Occlusive stageGastrointestinal 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

ManagementDrugs

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 .

SurgerySurgical 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

Prognosis20% 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 syndromePolyartheritis nodosaRheumatic fever Giant cell arteritis

Buerger disease Systemic lupus

erythematosis juvenile rheumatoid

arthritis Migraine Malignancy

Takayasu’s arteritisa

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

BYAsmaaHamed

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 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 & SYMPTOMSConjunctivitis, scleritis,

episcleritis, Uveitis Weakened vision or double

vision. Double vision or a

decrease in vision .

Oral CavityStrawberry 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 CytoplasmicAutoantibodies (ANCA)

RadiologyLung 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).

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

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

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-eosinophiliaeosinophilia3. 3-fever4. 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) levels3-ANCA is present in approximately 40% of

patients4-Elevated serum IgE levels 5-In addition to a detailed history and physical

examination, blood tests and imaging studies6-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.

11--steroidssteroids

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)

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-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.

Diagnosis1. 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 imagingTestTypical Result

Complete blood cell count, with differentialNormal

ElectrolytesNormalLiver function testsNormalUrinalysis with microscopyNormalErythrocyte sedimentation rate/C-reactive protein

Mild to moderate elevations in <50% of patients

ANANegativeRheumatoid factorNegativeC3, C4NormalANCANegativeAntihepatitis B and C assaysNegativeCryoglobulinsNegativeChest radiography, CT and MRINormal

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

HistoryMdication

Infection e.g HCVConnecive tissue

disease

Review of systems and

physical ex. to exclude extra

cutaneous manifestation

Work-up

Skin biopsy

histoogy DIF

Blood work

radiologyCBC ANA

ANCARF

CryoglobulinsC3, C4

Treatment:1. Elevation of the legs2. or compression stockings3. removal of the offending agent4. Mild cases: NSAID5. For persistent disease: colchicine,

hydroxychloroquine or dapsone 6. refractory or more severe cases:

immunosuppressive agents e.g glucocorticoids or Azathioprine

ByAsmaa Samy Farag El Naggar 195

DefinitionCryoglobulinimic 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 CryoglobulinemiaA. Brouet classification: based on cryoglobulin

composition

Classification of CryoglobulinsComposition of cryoprecipitates

Type I cryoglobulinemia monoclonal Ig, usually IgM or, less frequently, IgG or IgA

Type II mixed cryoglobulinemiapolyclonal 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

Epidemiology 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 Cryoglobulinemia1. 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

Clinical descriptionMeltzer 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

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

Diagnostic methodsThe main diagnostic parameter of MC is the presence of serum

mixed (IgG-IgM) cryoglobulins.

Laboratory Studies:1. Evaluation for serum cryoglobulins2. 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 criteriacriteria serologicalpathologicalclinicalmajor mixed

cryoglobulins low C4

 leukocytoclastic  vasculitis

  purpura

minorRheumatoid 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

TreatmentThe 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 modalities1. 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 patientProposed treatmentsAsymptomaticnone

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, HCCchemotherapy, surgery

Asmaa toto196

Henoch–Schönlein purpura

Henoch–Schönlein purpuraDefinision also known as anaphylactoid purpura, rheumatica , purpurais 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 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 (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 ACE inhibitors enalapril and captopril, anti-

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.

Signs and symptoms

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 criterionthis 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 occurProtein 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