Vasculitides Flashcards
What is the name given to vasculitis classification by vessel size?
Chapel-Hill classification
List the general clinical features associated with vasculitis.
- Fever, weight loss, myalgia, arthralgia
- Purpuric ulcers, livedo reticularis
- Nailbed infarcts, gangrene of digits
- Episcleritis, visual loss
- Epistaxis, naal crusting, stridor, deafness
- Haemoptysis, dyspnoea
- Angina or MI, HF, pericarditis
- Malabsorption
- HTN, haematuria, proteinuria, renal failure
List the subtypes of vasculitis and their classification.
Large
- Takayasu
- GCA
- PMR
Medium
- PAN
- Kawasaki
Small
- ANCA associated
- Immune complex associated
Mixed vessel
- Behcet’s
These are all primary types of vasculitis. Secondary causes include infection, malignancy, SLE and RhA, drugs (levamisole - contaminant of cocaine).
What investigations should be done in general for vasculitides?
- Urine dip and careful exam
- ANA
- ANCA
- Biopsy
- FDG-PET
What is mononeuritis multiplex and what is a common cause?
MNM = progressive motor and sensory deficits in the distribution of specific peripheral nerves
Causes: most commonly due to vasculitis, which may be either systemic or isolated to the nerves. Other causes include hypersensitivity reactions to drugs or infections, or direct viral or bacterial infection of nerves.
Why is Behcet’s termed a mixed vascultis?
Affects both veins and arteries and different vessel sizes
Most other vasculitides only affect the arteries
What is RS3PE?
Remitting seronegative symmetrical synovitis with pitting edema = a type of PMR onset RhA. Identified by symmetric polyarthritis, synovitis, acute pitting edema (swelling) of the back of the hands and/or feet, and a negative serum rheumatoid factor
What are the differentials for a purpuric rash?
Vascular - vasculitis e.g. HSP/IgA vasculitis
Infective - meningococcal sepsis
Autoimmune - SLE
Other
What are the main features of HSP?
- Purpuric rash
- Glomerulonephritis
- GI involvement
- Arthritis
- Usually in children
What medication and dose is first line for PMR?
15mg prednosolone daily
NB: methotrexate can be used as a steroid sparing agent in PMR
Which condition is associated with antibodies against proteinase 3 (PR3)
PR3 Abs have high specificity for granulomatosis with polyangiitis (Wegener’s)
What are the features of GPA?
Involvement of:
- Upper airway
- Lower airway
- Renal
What is GCA?
Temporal arteritis is large vessel vasculitis which overlaps with polymyalgia rheumatica (PMR). Histology shows changes that characteristically ‘skips’ certain sections of the affected artery whilst damaging others.
What are the clinical features of GCA?
- typically patient > 60 years old
- usually rapid onset (e.g. < 1 month)
- headache (found in 85%)
- jaw claudication (65%)
- visual disturbances
- tender, palpable temporal artery
- around 50% have features of PMR: aching, morning stiffness in proximal limb muscles (not weakness)
- also lethargy, depression, low-grade fever, anorexia, night sweats
What are the visual disturbances seen in GCA?
- amaurosis fugax
- blurring
- double vision
Vision testing is a key investigation in patients with suspected temporal arteritis
This is secondary to anterior ischemic optic neuropathy
Which arteries are most commonly affected in GCA?
- Temporal artery
- Masseter arteries - results in claudication
What investigations are done for GCA?
- ESR - >50mm/hr
- CRP- elevated
- USS of temporal and axillary arteries
- +/- Biopsy - skip lesions
NB: CK and EMG - normal
What is a major complication of GCA?
Ischaemic optic neuropathy due to involevement of the ophthalmic artery
What is the management of GCA?
URGENT high-dose steroids - Prednisolone 40mg daily
If there are eye symptoms –> IV methylprednisolone then give 60mg prednisolone daily + same day ophthal review
+/- bisphosphonates - for bone protection
+/- aspirin - sometimes given, little evidence
Which biological treatment may be used for GCA and what is its MOA?
Tocilizumab - anti-IL6
What is the prognosis with GCA?
There should be a dramatic response once steroids are started, if not the diagnosis should be reconsidered
Visual damage is often irreversible
Which areteries are scanned in GCA?
- Temporal artery
- Axillary artery to confirm diagnosis
What are the clinical features of Takayasu’s arteritis?
- upper and lower limb claudication on exertion
- systemic features of a vasculitis e.g. malaise, headache
- unequal blood pressure in the upper limbs - a difference in blood pressure of >10 mmHg on each arm may be significant
- carotid bruit and tenderness
- absent or weak peripheral pulsesaortic regurgitation (around 20%)
Who is most affected by Takayasu’s arteritis?
It is more common in younger females (e.g. 10-40 years) and Asian people
What investigation is used to diagnose Takayasu’s?
Acute phase markers elevated
Biopsy usually not feasible so requires imaging
CT, MRI vascular, angiography for diagnosis.
FDG-PET for inflammation
What is the management of Takayasu’s?
- Steroids - prednisolone suppresses inflammation
- +/- aspirin
- +/- immunosuppressants - methotrexate after steriod tapering
What is PMR associated with?
GCA - so always ask about headaches, visual symptoms and jaw claudication
What is PMR?
An inflammatory rheumatological syndrome that manifests as pain and morning stiffness involving the neck, shoulder girdle, and/or pelvic girdle in individuals older than age 50 years.
What similar condition should you exclude in PMR and how?
Polymyositis - pain and normal power. Elevated muscle enzymes with a positive ANA. Diagnosis confirmed with muscle biopsy.
What are the clinical features of PMR?
- typically patient > 60 years old
- usually rapid onset (e.g. < 1 month)
- aching, morning stiffness (>1hr) in proximal limb muscles
- mild polyarthralgia,
- lethargy,
- depression,
- low-grade fever,
- anorexia,
- night sweats
- weakness is not considered a symptom of polymyalgia rheumatica
Also ask for symptoms of GCA: unilateral temporal or occipital headaches, scalp tenderness, jaw claudication, or visual symptoms
What investigations are useful in PMR?
- raised inflammatory markers e.g. ESR > 40 mm/hr
- NB: CK and EMG normal
Other:
- FBC
- TSH
- RF
- Serum protein electrophoresis
- Anti-CCP
- US, MRI, FDG-PET - bursitis, tenosynovitis, synovitis, joint effusions, inflammation
What is the management of PMR?
- 15mg prednisolone - 12-24 months - patients typically respond dramatically to steroids, failure to do so should prompt consideration of an alternative diagnosis
- + calcium, vit D, bisphosphonate - bone protection
- +/- NSAID
- +/- methotrexate - steroid sparing agent
- +/- tocilizumab - anti-IL6
What is the prognosis with PMR? What % progress to GCA?
Response to treatment typically occurs within 24 to 72 hours but relapses or symptom exacerbations are common
10% progress to GCA
What is polyarteritis nodosa?
Necrotising inflammation of medium-sized or small arteries without glomerulonephritis or vasculitis in arterioles, capillaries, or venules
Which cause of PAN has become rare?
Hepatitis B - ince the introduction of effective immunisation programmes against the virus
What are the clinical features of PAN?
- fever, malaise, arthralgia
- weight loss
- hypertension
- mononeuritis multiplex, sensorimotor polyneuropathy
- testicular pain
- livedo reticularis
- haematuria, renal failure
- perinuclear-ANCA are found in around 20% of patients with ‘classic’ PAN
Who is most affected by PAN?
40-60yrs
Slight male predominance
What is seen in this renal angiogram in PAN?
Beading and numerous microaneurysms affecting the intrarenal vessels
Usually the liver is similarly affected
What investigations are useful in the diagnosis of PAN?
Bloods:
- FBC - anaemia due to chrnonic disease or GI bleeding
- CRP, ESR - raised
- Renal profile - raised Cr but no proteinuria
- LFTs - abnormal
- HBV serology - positive in 30%
- Low complement
- ANCA - if positive would suggest another type of vasculitis, such as GPA or MPA
Other:
- Angiography - MR or CT angiography, Doppler ultrasound, and chest x-ray all have their place in the diagnosis.
- Biopsy
What is the renal profile like in PAN?
Raised serum creatinine, typically without haematuria or proteinuria on urinalysis, may indicate renal ischaemia or infarction;
BUT, significant proteinuria or haematuria (especially red cell casts) would suggest glomerular disease, which is not a feature of PAN
What is the management of PAN?
- Prednisolone - up to 15mg/day for up to 18months
- and DMARD - cyclophosphamide + AZA/leflunomide/methotrexate
HBV-related PAN may require plasma exchange + lamivudine
What is the prognosis with PAN?
The 5-factor score predicts survival in PAN. The score consists of the following factors:
- Proteinuria >1 g/day
- Creatinine >120.5 mmol/L (>1.58 mg/dL)
- Cardiomyopathy
- Gastrointestinal (GI) symptoms
- Central nervous system (CNS) involvement.
The prognosis is improving because of earlier detection and more effective treatment. Around 10% relapse rate.
What is GPA?
GPA aka Wegener’s granulomatosis is a systemic vasculitis that typically involves small and medium vessels. Although any organ may be targeted
What is the triad of GPA?
- upper respiratory tract involvement
- lower respiratory tract involvement
- pauci-immune glomerulonephritis.
What are the clinical features of GPA?
- upper respiratory tract: epistaxis, sinusitis, nasal crusting
- lower respiratory tract: dyspnoea, haemoptysis (large nodules in lung which may bleed)
- rapidly progressive glomerulonephritis (‘pauci-immune’, 80% of patients)
- saddle-shape nose deformity
- also: vasculitic rash, eye involvement (e.g. proptosis), cranial nerve lesions
What type of glomerulonephritis is seen in GPA?
‘Pauci-immune’ or crescentic
What is seen on this CT of a patient with GPA?
2 large lung nodules, one of which has an air-fluid level
Which antibodies are present in GPA?
cANCA against proteinase 3
cANCA positive in > 90%, pANCA positive in 25%
What is the management of GPA?
- steroids
- cyclophosphamide (90% response) or methotrexate
- plasma exchange
What is the prognosis with GPA?
median survival = 8-9 years
Main causes of mortality are infection, cardiovascular disease, and active vasculitis
What is eGPA?
aka Churg-Strauss syndrome
A form of primary systemic autoimmune vasculitis characterised by inflammation of blood vessels. In EGPA, vasculitis is associated with asthma and eosinophilia.
What is the triad of eGPA?
eosinophilia, granulomatous inflammation, and vasculitis
What are the clinical features of eGPA?
- asthma, allergic rhinitis, sinusitis history
- blood eosinophilia (e.g. > 10%)
- paranasal sinusitis
- mononeuritis multiplex –> motor or sensory deficits e.g.foot drop
- skin nodules (granulomas)
- palpable purpura/petechiae
Which medications are linked to eGPA development?
- Macrolides
- Quinidine
- LTRA - although these may simply be unmasking disease
What investigations should be done for eGPA?
Bloods:
- FBC with WCC differential - eosinophilia >10% of the WBC count
- ANCA - typically p-ANCA, myeloperoxidase positive pattern
- IgE - raised
- ESR and CRP - raised
Imaging:
- CXR then CT if abnormalities seen
- Spirometry - obstructive pattern
- CT angiography of lungs
- EMG if mononeuritis multiplex
Sometimes organ biopsy.
What is the management of eGPA?
- Corticosteroids - to induce remission
- Methotrexate/AZA
- +/- mepolizumab - anti-IL-5
- +/- bone protection
- +/- asthma management - if asthma symptoms present
What is the prognosis in eGPA?
Calculated with the 5-factor score as for GPA.
Depends on extent and severity of organ involvement and 5 year survival ranges from 68% to 100%.
What are the clinical features of MPA?
- renal impairment: raised creatinine, haematuria, proteinuria
- fever
- other systemic symptoms: lethargy, myalgia, weight loss
- rash: palpable purpura
- cough, dyspnoea, haemoptysis
- mononeuritis multiplex
What is an indicator of relapse in MPA?
ANCA - often becomes positive before relapse
What are the types of small vessel immune complex associated vasculitis?
- IgA (HSP)
- Goodpastures
- Cryoglobulinaemia (ab to C1q)
