Supervised by Dr. Ragaa abd el-kaderProfessor 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

Deposition of circulating antigen-antibody complexwithin the vessel wall. This leads to complement activation andchemotactic 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 immunopathologicmechanism in vasculitis are:

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

ANCA Associated DiseasesWegeners granulomatosisMicroscopic polyangiitis-70% positiveChurg-Strauss syndrome-about 50%Renal limited (pauci-immune) vasculitisDrug-induced ANCA-associated vasculitis

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.)

DiagnosisPhysical examLaboratory testsBiopsyImaging 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 phosphataseErythrocyte sedimentation rate, an inflammatory marker, >60mm/hour (normal 1040mm/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 1.53cm 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

Treatment:

Corticosteroids: typically high-dose prednisone (4060mg 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.

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.

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 Takayasus Arteritis

Classical TakayasusPulmonary ArteriesDescendingAorta

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

Inflammation Fever,fatigue, weight loss.

Arthralgia and non-specific pains.

Tndeness.

SymptomsIschaemic 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:

Age at onset 40 years. Claudication of the extremities. Reduced pulsation of one or both brachial arteries >10 mmHg BP difference between arms Bruit over one or both subclavians or the abdominal aorta. Arteriographic narrowing/occlusion of the entire aorta, its primary branches or large arteries in upper/lower limbs .

Investigations

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 .

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

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 arteritisBuerger disease Systemic lupus erythematosis juvenile rheumatoid arthritisMigraine Malignancy

Polyarteritis nodosa is an autoimmune disease affecting the medium sized arteriesMost 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

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. 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. 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.

Weight loss of > 4 kg since beginning of illness Livedo reticularis Testicular pain or tenderness Myalgias, weakness, or leg tenderness Mononeuropathy or polyneuropathy Development of hypertension Elevated BUN or creatinine unrelated to dehydration or obstruction Presence of hepatitis B surface antigen or antibody in serum Arteriogram demonstrating aneurysms or occlusions of the visceral arteries 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

BYAsmaaHamed191

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.

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 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 investigationCBC 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 shaltotMicroscopic 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.

About 1/3 of patients have a purpuric rash .

Nail bed infarcts and splinter hemorrhages may occur.

Mild symptoms of rhinitis, epistaxis, and sinusitis Alveolar hemorrhage pulmonary fibrosischest x-ray bilateral patchy infiltrates

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.

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%).

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.

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

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 approximately 6 months.

Churg-Strauss Syndrome Presented by: asmaa hassan 193

Churg-Strauss Syndrome DefinationChurg-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-Asthma 2-eosinophilia3-fever4-vasculitis of various organ systems

CausesEnvironmental 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 Nervepain 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. 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 vasculitisleukocytoclastic vasculitiscutaneous 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:

Skinpalpable 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 vasculitidesHenoch-Schnlein purpuraMixed cryoglobulinemiaMicroscopic polyangiitisChurg-Strauss syndromeWegener granulomatosisPolyarteritis nodosaSystemic autoimmune conditionsSystemic lupus erythematosusRheumatoid arthritisMiscellaneousOther types of drug eruptionsThrombotic thrombocytopenic purpura.Infective endocarditis.Pregnancy associated purpura.

Diagnosis

ACR Criteria for Classification of Hypersensitivity Vasculitis

Laboratory Findings and imaging

Biopsy

three of these five criteria has Sensitivity = 71%; specificity = 83.9%.

1. American College of Rheumatology 1990 Criteria for the Classification of Hypersensitivity Vasculitis

Age at disease onset >16 years.Offending medication at disease onset.Palpable purpura.Maculopapular rash.Biopsy including arteriole and venule, showing neutrophils perivascular

2.Laboratory Findings and imaging

TestTypical ResultComplete blood cell count, with differentialNormalElectrolytesNormalLiver function testsNormalUrinalysis with microscopyNormalErythrocyte sedimentation rate/C-reactive proteinMild to moderate elevations in

3.Biopsy:

Light microscopy:24 48 hours appearance of a lesionfrom non ulcerated leisionIf 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 vasculitisHistoryMdication Infection e.g HCVConnecive tissue diseaseReview of systems and physical ex. to exclude extra cutaneous manifestationWork-upSkin biopsyhistoogyDIFBlood workradiologyCBC ANAANCARFCryoglobulinsC3, C4

Treatment:

Elevation of the legs or compression stockingsremoval of the offending agentMild cases: NSAIDFor persistent disease: colchicine, hydroxychloroquine or dapsone refractory or more severe cases: immunosuppressive agents e.g glucocorticoids or Azathioprine

ByAsmaa Samy Farag El Naggar195

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 CryoglobulinemiaBrouet classification: based on cryoglobulin composition

Classification of CryoglobulinsComposition of cryoprecipitatesType I cryoglobulinemia monoclonal Ig, usually IgM or, less frequently, IgG or IgA Type II mixed cryoglobulinemiapolyclonal IgGs + monoclonal IgMType III mixed cryoglobulinemiapolyclonal IgGs + polyclonal IgMs

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

EpidemiologyThe 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

However, the MC is also the result of concomitant genetic and/or environmental factors, which remain largely unknown.

Etiopathogenesis of MC in HCV

Clinical description

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.

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

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

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

Diagnosic criteria

criteriaserologicalpathologicalclinicalmajormixed cryoglobulins low C4leukocytoclastic vasculitis purpuraminorRheumatoid 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:Treat underlying conditions.Limit the precipitant cryoglobulin and the resultant inflammatory effects.

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

Treatment modalitiesNonsteroidal anti-inflammatory drugs. 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 treatmentsAsymptomaticnoneMild manifestations: purpura, weakness ,arthralgias, arthritis, peripheral sensory neuropathyLAC-diet, low dosage of steroids other symptomaticsSevere manifestations: nephropathy, skin ulcers, sensory-motor neuropathy, widespread vasculitis, active hepatitissteroids, plasma exchange, cyclophosphamide, alpha-interferon + ribavirineCancer : B-cell NHL, HCCchemotherapy, surgery

Asmaa toto196HenochSchnlein purpura

HenochSchnlein 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 girlsThe 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 unknownHSP 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, include the antibiotics vancomycin and ACE inhibitors enalapril and captopril, anti-inflammatory agent Diclofenac and streptokinase

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

Purpura, arthritis and abdominal pain are known as the "classic triad" of HenochSchnlein 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.

DiagnosisThe diagnosis is based on the combination of the symptoms, as very few other diseases cause the same symptoms togetherBlood 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 vasculitisand immunofluorescence demonstrates IgA and C3 in the blood vessel wall. However, overall serum complement levels are normal

kidney biopsyMain 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 damageTreatment 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 recurrenceOverall 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

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