Vasculitis

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Vasculitis

• Dr. Andy Thompson
• Assistant Professor of Medicine
• Division of Rheumatology
• University of Western Ontario

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Objectives

• Gain a basic understanding of Vasculitis
• Understand potential organ involvement with
  vasculitis
• Understand the current classification system for
  Vasculitis
• Understand useful investigations for the patient
  suspected of having vasculitis
• Understand the basics of Giant-Cell arteritis and
  Wegeners Granulomatosis

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WAY TOO MUCH INFORMATION

• Vasculitis is a HUGE Topic
• Cannot be completely covered in a short period of
  time
• Other References American Family Physician
• An Approach to Diagnosis and Initial Management
  of Systemic Vasculitis
• http//www.aafp.org/afp/991001ap/1421.html
• ANCAAssociated Small-Vessel Vasculitis
• http//www.aafp.org/afp/20020415/1615.html
• Johns Hopkins Vasculitis Center
• http//vasculitis.med.jhu.edu/index.html

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Case 1

• JH is a 35 year old man married with 2 children
• Works as a material planning specialist at Fort
  Canada
• He has no known medical problems, takes no
  medications, and has no known medication allergies

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Case 1

• 2001
• Mild ankle swelling pain
• Preceded by mild diarrhea
• Rash over the ankles
• Non-Pruritic (not-itchy)
• Non-Blanchable (doesnt turn white when you push
  on it)
• Non-Painful (this ones obvious)
• Resolved in 7 days

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Case 1

• 2001-2003
• Yearly attacks of ankle swelling accompanied by
  this rash
• 2004
• Attacks now coming once monthly
• Lasting 7 days
• Associated arthralgias in knees
• Occasional chills

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Case 1
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Case 1
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What is going on?

• Leukocytoclastic Vasculitis
• Recurrent episodes of a dependent purpuric rash
  associated with ankle swelling and arthralgia

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What is Vasculitis?

• A general term for a group of diseases that
  involve inflammation of the blood vessel
• Inflammation
• Swelling, pain, warmth
• All blood vessels can be affected from the
  largest (Aorta) to the smallest blood vessels in
  the skin (capillaries)

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What is Vasculitis
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What is Vasculitis?
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Types of Vasculitis

• There are over 20 different disorders that are
  classified as vasculitis
• Different types of vasculitis have characteristic
  (localized) patterns of blood vessel involvement
• The symptoms depend on the type of blood vessel
  that is affected

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Symptoms

• Vasculitis is a systemic illness
• Patients with vasculitis feel sick
• Often have fevers, weight loss, fatigue, a rapid
  pulse, and diffuse aches and pains that are
  difficult to pinpoint

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Symptoms

• Vasculitis is a hurting disease, because it is
  so commonly associated with pain of one type or
  another
• Pain from nerve infarction
• Pain from sore joints
• Pain from leg ulcers
• Pain from insufficient blood flow to the GI tract
• Vasculitis may involve virtually every organ
  system in the body

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What Causes the Symptoms?

• Inflammation Of the blood vessel itself
• Inflammation Of other tissues in the body
• Ischemia From lack of blood flow through the
  swollen blood vessel
• Damage From longstanding lack of blood flow or
  inflammation

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Inflammation of the Blood Vessel
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Inflammation of the Blood Vessel
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Inflammation of Other Tissues
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Inflammation of Other Tissues
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Inflammation of Other Tissues
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Ischemia
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Ischemia
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Remember - Vasculitis

• Inflammation of the Blood Vessel Itself
• Inflammation in other tissues
• Ischemia from poor blood flow
• Permanent damage from long-standing
  ischemia/inflammation

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Organ Systems Affected
Brain
Sinuses, nose, Ears
Eyes
Lungs
GI Tract
Heart
Kidneys
Joints
Nerves

• Skin

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Skin A Variety of Rashes

• Palpable Purpura Most common rash
• Begin as non-palpable petechiae or purpura which
  coalesce with time
• Vary in size and usually found on the lower limbs
  (dependent)
• Become palpable with time
• Do not blanche
• May heal with pigmentation

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Palpable Purpura
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Purpura
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Other Rashes

• Urticaria (Hives)
• Skin Ulcers
• Skin Blisters
• Skin Nodules
• Erythematous plaques

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Joints

• Arthritis Full blown swelling of the joints
• Arthralgia Aching and pain in the joints with
  little swelling

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Swollen Hand
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Nerves

• Can affect the blood supply to nerves and result
  in a
• Mononeuritis Damage to a single nerve
• Mononeuritis-Multiplex Damage to many single
  nerves (i.e. Ulnar, Sural, peroneal etc)

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Nerves
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Lungs

• Cough
• Shortness of breath
• Hemoptysis
• Infiltrates in the lungs (inflammatory)
• Cavities in the lungs from necrosis or
  inflammation

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Lung Infiltrates
Inflitrates in the lungs which represent bleeding
from damaged capillaries NOT infection
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Lung Infiltrates
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Heart

• Inflammation of coronary blood vessels
• Ischemia/Infarction
• Inflammation of other tissues
• Pericarditis
• Pancarditis
• myocarditis

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Normal CXR
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Pericarditis with Effusion
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Kidneys

• Inflammation of the kidney glomeruli may lead to
• Protein in the urine
• Blood in the urine
• Red Blood Cell Casts in the urine
• Renal failure with rising creatinine
• Can be very severe and rapid

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Inflammation in the Kidney
Inflammatory Cells
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Gastrointestinal Tract

• Inflammation of the blood vessels supplying the
  GI Tract leads to ischemia and
• Abdominal pain
• Bloody diarrhea
• Sometimes the bowel perforates

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Gastrointestinal Tract
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Blood

• Anemia Normochromic Normocytic
• Elevated WBC
• Elevated Platelets (Reactive Thrombocytosis)

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Sinuses, Nose, Ears

• Inflammation of the organs or the blood vessels
  supplying the organs
• Chronic sinus infections with nosebleeds
• Inflammation of the nasal septum saddle nose
  deformity
• Hearing loss
• Inflammation of the ears

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Inflammation of Nose
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Inflammation of Ears
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Eyes

• Blood vessels going to the eyes
• Sudden loss of vision
• Blood vessels within the eye
• Retinal vasculitis
• Thinning of the sclera (white part of the eye)
• Inflammation in other chambers (iritis)
• Conjuctivitis (pink-eye)

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Brain

• Headaches
• Strokes
• Changes in mental status
• Difficulty with coordination

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Brain Hemorrhage
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Diagnosis of Vasculitis

• Can be very difficult as it can take years to
  progress and the symptoms can be non-specific
  (i.e. fatigue)
• Usually need a biopsy of affected tissue
• Vasculitis has many mimickers
• Treatments have significant risk and diagnosis
  should be confirmed

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Diagnosis of Vasculitis

• Blood tests, Xrays, and other studies may
  suggest the diagnosis of vasculitis
• Often the only way to clinch the diagnosis is to
  biopsy an involved tissue
• The trick to diagnosing vasculitis is to figure
  out the least invasive method of accomplishing
  this task.

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Diagnosis of Vasculitis

• Places to Biopsy
• Skin Underlying Nodules
• Kidneys
• Nerves (Sural nerve Sensory only)
• Temporal Artery
• Lung Biopsy
• Brain Biopsy

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Diagnosis of Vasculitis

• Inflammation in the Blood
• Elevated Erythrocyte Sedimenation Rate (ESR)
• Elevated C-Reactive Protein (CRP)
• Normochromic Normocytic Anemia
• Reactive thrombocytosis (Elevated platelets)
• Low albumin (more chronic)

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Diagnosis of Vasculitis

• Organ Involvement
• CBC Look for Inflammation
• Cr Urinalysis Look for renal involvement
• CXR Infiltrates
• Infection Screening
• Liver Enzymes Look for evidence of hepatitis
• Hepatitis B C Serology
• HIV

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Diagnosis of Vasculitis

• Connective Tissue Disease
• RF
• ANA, ds-DNA, ENA
• Vasculitis Other Screening
• ANCA p c
• Cryoglobulins
• Immunoglobulins
• C3, C4, CH50
• Serum Protein Electrophoresis

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Classification of Vasculitis

• Vasculitis may be classified by
• The size and type of vessel involvement
• The histopathologic features (leukocytoclastic,
  granulomatous vasculitis, etc.)
• The pattern of clinical features

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Classification of Vasculitis

• Important to classify the vasculitis since some
  types may be self-limited while others may be
  chronic
• However, initially it is important to determine
  the amount and extent of organ system involvement

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Approach to Vasculitis

• History Physical Examination
• Determines the type and extent of organ system
  involvement
• Determines a pattern which may be helpful in
  classification
• Laboratory Investigations
• Determines blood involvement
• Can help determine type and extent of organ
  involvement
• Antibodies can help with classification

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Large Blood Vessels

• Giant-Cell or Temporal Arteritis
• Takayasu Arteritis

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Medium Blood Vessels

• Polyarteritis Nodosa
• Kawasaki Disease

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Small Blood Vessels

• ANCA Related
• Wegeners, MPA, Churg-Strauss
• Immune Complex Related
• Hypersensitivity Vasculitis
• Cryoglobulinemic Vasculitis
• Connective Tissue Diseases
• Henoch Schonlein Purpura (IgA)
• Miscellaneous
• Malignancy
• Behcets Disease
• Inflammatory Bowel Disease

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CLASSIFICATION TREE
Vasculitis
Small Blood Vessel

• Large Blood Vessel
• Temporal Arteritis
• Takayasu Arteritis

• Medium Blood Vessel
• Polyarteritis Nodosa
• Kawasakis Disease

Non-ANCA Associated

• ANCA Associated
• Wegeners Granulomatosis
• Churg-Strauss Vasculitis
• Microscopic Polyangiitis
• Drug Induced

• Immune Complex
• Hypersensitivity Vasculitis
• Cryoglobulinemic Vasculitis
• CTD related Vasculitis
• Henoch Schonlein Purpura
• Behcets

• Miscellaneous
• Paraneoplastic Vasculitis
• Inflammatory Bowel Disease

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Temporal (Giant-Cell) Arteritis

• Chronic granulomatous vasculitis affecting large
  arteries in older people
• Most are gt60 years of age (average 72)
• Inflammation of the walls of large arteries
• Cranial arteritis (most common) Temporal,
  occipital, ophthalmic
• Subclavian, iliac/femoral
• Aorta

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Temporal (Giant-Cell) Arteritis

• Significant Fatigue
• Pain Stiffness Around shoulders and hips
  (polymyalgia rheumatica) 15
• Fever Can sometimes present with Fever of
  Unknown Origin (FUO)

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Temporal (Giant-Cell) Arteritis

• Cranial Arteritis (most common)
• Headache
• Temporal tenderness/pain
• Jaw claudication
• Tongue claudication
• Diplopia (double vision)
• Loss of vision
• Strokes

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Temporal (Giant-Cell) Arteritis

• Physical Examination
• Very tender over temples
• Swollen, rope like temporal artery
• Optic disc swelling due to ischemia

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Temporal (Giant-Cell) Arteritis
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Temporal (Giant-Cell) Arteritis

• Physical Examination
• Very tender over temples
• Swollen, rope like temporal artery
• Optic disc swelling due to ischemia

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Temporal (Giant-Cell) Arteritis

• Investigations
• Complete Blood Count (CBC)
• Normochromic, normocytic anemia
• Reactive thrombocytosis
• WBC is usually normal
• Erythrocyte Sedimentation Rate (ESR)
• Significantly elevated
• C-Reactive Protein (CRP)
• Significantly elevated

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What to do?

• Relative EMERGENCY as patient can lose vision
• Urgent temporal artery biopsy (get the tissue) to
  confirm the diagnosis
• Initiate high-dose corticosteroids (40-60 mg per
  day)
• Low dose ASA can be considered

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Temporal Artery Biopsy
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Temporal Artery Biopsy
Inflammation
Multi-Nucleated Giant Cell
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Wegeners Granulomatosis

• A Necrotizing (caseating) Granulomatous
  Vasculitis affecting small blood vessels
• Characteristic Pattern of
• Upper Airway Involvement
• Lower Airway Involvement
• Renal Involvement
• Joint Involvement

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What is a Granuloma?

• An imprecise term applied to
• (1) Any small nodular delimited aggregation of
  mononuclear inflammatory cells, or
• (2) Such a collection of modified macrophages
  resembling epithelial cells, usually surrounded
  by a rim of lymphocytes, often with
  multinucleated giant cells.
• Some granulomas contain eosinophils and plasma
  cells, and fibrosis is commonly seen around the
  lesion.

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What is a Granuloma?

• Granuloma formation represents a chronic
  inflammatory response initiated by various
  infectious and noninfectious agents.
• An important aspect of granulomas is whether they
  are caseating or not.
• Caseation (literally turning to cheese) is a
  form of necrosis at the centre of a granuloma

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Wegeners Granulomatosis

• Upper Respiratory Tract
• Chronic sinusitis with/without hematochezia
• Oral/nasal ulcers
• Otitis media/hearing loss
• Hoarseness of the voice
• Lower Respiratory Tract
• Cough, Shortness of Breath
• Pulmonary Infiltrates or Nodules that may
  cavitate
• Renal
• Glomerulonephritis (Rapidly Progressive)
• Joints
• Arthritis

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Anti-Neutrophil Cytoplasmic Antibody (ANCA)

• A collection of antibodies directed against
  components of granules inside the neutrophil
• Detected in the laboratory by Immunofluorescence
  Assay and by ELISA methods for specific antibodies

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Anti-Neutrophil Cytoplasmic Antibody
Immunofluorescence

• 2 patterns possible
• Cytoplasmic
• Perinuclear - artifact of the laboratory test

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Anti-Neutrophil Cytoplasmic Antibody
Immunofluorescence
c-ANCA
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Anti-Neutrophil Cytoplasmic Antibody
Immunofluorescence
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Anti-Neutrophil Cytoplasmic Antibody
Immunofluorescence
p-ANCA
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Anti-Neutrophil Cytoplasmic Antibody
Immunofluorescence
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Anti-Neutrophil Cytoplasmic Antibody
Immunofluorescence - Disease Associations

• Wegeners Granulomatosis
• c-ANCA 75-80, p-ANCA 10-15,
• Negative 5-10
• Microscopic Polyangiitis (MPA)
• c-ANCA 25-35, p-ANCA 50-60,
• Negative 5-10
• Churg Strauss Syndrome (CSS)
• c-ANCA 25-30, p-ANCA 25-30
• Negative 40-50

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Anti-Neutrophil Cytoplasmic Antibody
Immunofluorescence Antibodies

• c-ANCAs
• Anti-Proteinase 3 (PR3)
• p-ANCA
• Anti-Myeloperoxidase (MPO)

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Anti-Neutrophil Cytoplasmic Antibody Disease
Associations

• Strong ANCA activity is a good surrogate marker
  of small vessel vasculitides (svv)
• It must fit into good clinical context
• Diagnosis should be confirmed by histopathologic
  findings on biopsy

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Saddle Nose Deformity
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Wegeners Granulomatosis
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Wegeners Granulomatosis
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Wegeners Granulomatosis
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Small Vessel Vasculitis

• Factor Five Score
• Proteinuria gt 1 gram/24 hrs
• Renal Insufficiency Cr gt 140
• Cardiac Involvement
• Gastrointestinal Tract Involvement
• CNS Involvement
• Mortality
• FFS0 (12), FFS1(26), FFS2(46)

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Wegeners Granulomatosis

• Treatment
• High Dose Corticosteroids
• Immunosuppressive Therapy
• Cyclophosphamide
• Azathioprine

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Vasculitis Causes .

• Patients to feel systemically unwell
• Inflammation of blood vessels
• Inflammation of other organs
• Damage to the body
• Can result in Death

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Vasculitis is ...

• Frustrating as signs and symptoms may be
  non-specific
• Worrisome as it can result in death
• Incredibly interesting (from a certain point of
  view)

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Vasculitis can be horrible
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Thank-you