4th Year Rheumatology Lecture The systemic rheumatic diseases Vasculitis

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4th Year RheumatologyLecture The systemic
rheumatic diseasesVasculitis
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Aims and objectives

• Overview of the systemic vasculitides
• 1. Classification
• 2. Epidemiology
• 3. Clinical features
• 4. Investigations
• 5. Therapy
• 6. Prognosis.

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Definitions of vasculitis

• A group of conditions characterised by
• 1. Inflammatory cell infiltrate and necrosis of
  the blood vessel wall with impairment of blood
  flow and sometimes damage to vessel integrity
• 2. Present usually as multisystem diseases
• 3. Symptoms depend on the size and site of blood
  vessel involved
• 4. Remitting and relapsing course

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One approach to classification

• Primary vasculitis
• Large artery Takayasus, Giant cell arteritis
• Medium artery Polyarteritis nodosa, Kawasaki
• Medium/small artery Wegeners granulomatosis,
• Churg-Strauss, Behcets
• Microscopic polyangiitis,
• Small vessel Henoch- Schonlein purpura,
  Leucocytoclastic vasculitis
• Secondary vasculitis
• Connective tissue disease RA, SLE, Sjogrens
• Infection, drugs, malignancy essential to exclude

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These are rare diseases - epidemiology

• Incidence
• overall 43 / 106
• Systemic rheumatoid vasculitis 12.5 /106
• Wegeners granulomatosus 8.5 /106
• Microscopic polyangiitis 2.4 /106
• Polyarteritis nodosa 2.4 /106
• Age 60 years (16-82)
• Sex male female 1.31

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History Multisystem disease

• Onset may be acute or grumbling
• Systemic upset
• fever, anorexia, weight loss
• Skin
• vasculitic rash
• digital infarction/gangrene

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• Eyes red /- pain /- photophobia
• ENT epistaxis, crusting, sinusitis, hoarse voice

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Vasculitis history continued

• CVS/RS
• pain, SOB, haemoptysis, asthma
• GI
• abdominal pain, diarrhoea /- blood loss
• NS
• numbness, weakness

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Musculoskeletal history

• arthralgia (pain /- tenderness/swelling)
• myalgia (pain)
• loss of muscle bulk /- weakness

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Clinical signs in vasculitic diseases

• General features
• Pyrexia
• Muscle wasting

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Inflammatory arthritis- often asymmetrical,
oligoarthritis
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Skin signs

• purpuric rash nodules
• digital infarction ulceration or
  gangrene

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Mucous membranes

• Oro-genital ulcers
• mouth ulcers
• nasal ulcers
• genital ulcers
• Red eyes
• uveitis

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Uveitis with hypopyon
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• Episcleritis
• Scleritis
• scleromalacia

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ENTsigns Nasal collapse
Stridor from laryngeal disease
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RS/CVS signshaemoptysiscrackleswheezeper
icarditis
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Vasculitis neurological signs include

• peripheral neuropathy- glove and stocking
• mononeuropathy
• mononeuritis multiplex

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Neurological signs

• Neuropathy
• vasculitic (motor-sensory)
• peripheral entrapment
• sensory neuropathy
• Cervical spine involvement in RA
• subluxation of cervical vertebrae
• cervical myelopathy
• local pressure on nerve roots

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Abdominal signs

• Tenderness eg liver, gall bladder
• intestinal (obstruction)
• peritonitis (local, generalised)

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Some examples of primary vasculitis
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Investigations to consider in a patient with
suspected vasculitis

• Urinalysis
• Renal function
• urea, creatinine,
• creatinine clearance
• 24 hr protein excretion
• Other biochemistry
• LFT CRP

• Haematology
• FBC, eosinophils ESR
• Immunology
• Anti-neutrophil cytoplasmic antibody (ANCA)
• RhF ANA

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Investigations II

• Microbiology
• blood, sputum culture
• MSU, stool culture
• virology Hep B/C
• Radiology
• CXR, sinus XR
• CT scan, MRI, Angiography

• 2D Echo
• (to look for SBE/myxoma)
• Biopsy (often needed to confirm diagnosis)
• skin, nose, lung, kidney, rectum, nerve, muscle,

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A little bit on ANCA testing

• IgG ANCA detected using indirect IF or ELISA
• ethanol fixed neutrophils express intracellular
  granules on cell surface
• ANCA against proteinase 3 (weak cationic) has a
  cytoplasmic or cANCA pattern
• ANCA against myeloperoxidase (strongly cationic)
  has a perinuclear or pANCA pattern
• Other ANCA against elastase, cathepsin G,
  Azurocidin, lactoferrin also exist

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Relevance of ANCA tests

• Anti-neutrophil cytoplasmic antibody (ANCA) test
  has been found to be positive in
• Vasculitis
• Inflammatory bowel disease
• Autoimmune liver disease SLE
• Infections
• Malignancies

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ANCA in vasculitis

• cANCA ve in
• 90 Wegeners patients
• may reflect disease activity
• may predict relapse
• pANCA ve in
• 15 WG (MPO/elastase)
• 60 MPA
• 50 CSS (MPO/PR3)
• ? 10 PAN

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Serious complications resulting from vasculitic
diseases (preventable?)

• Gangrene or infarction of skin or a digit
• Nasal collapse and subglottic stenosis
• Pulmonary haemorrhage
• Coronary arteritis
• Neuropathy (mononeuropathy or multifocal
  neuropathy)
• Renal failure (acute/chronic)

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The differential diagnosis may be wide

• Infection chronic, atypical, SBE
• Connective tissue disease eg SLE
• Malignancy
• Pseudovasculitis cholesterol emboli,
• atrial myxoma
• Sarcoidosis
• HIV

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Therapy to suppress disease activity and then to
maintain remission

• Remission induction
• steroid /- cyclophosphamide (continuous oral or
  pulse)
• Maintenance therapy
• azathioprine, methotrexate, septrin
• Adjuvant therapy
• IVIG, pulse iv steroid, plasma exchange
• Relapse
• combination of above

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Prognosis is improved by 1. early recognition
of disease activity and 2. introduction of
appropriate therapy

• 2 year survival no therapy 10
• cyclophosphamide 80
• Remission induced in 90 Wegeners patients with
  cyclophosphamide
• Relapse occurs in 50 Wegeners but
• lt 10 PAN
• Prognosis good for small vessel vasculitis