Vasculitis, as the name implies, is inflammation of blood vessels. However, there are numerous types of vasculitis, affecting different sizes of vessels. As a result, we can classify them as either small, medium and large vasculitis. Within these 3 types there numerous conditions that cause vasculitis (these are known as the vasculitides).
It is worth noting that drug-induced vasculitis is the most common form of vasculitis.
🔢 Classification and nomenclature of vasculitides
Large-vessel vasculitis
Affecting the large vessels such as the aorta and its branches.
- Giant cell arteritis (GCA)
- Takayasu’s arteritis
Variable-vessel vasculitis
This was recognised by the Chapel Hill Consensus Conference and includes 2 vasculitides.
- Behcet’s disease
- Cogan syndrome
Medium-vessel vasculitis
It affects the visceral arteries and their subsequent branches.
- Polyarteritis nodosa
- Kawasaki’s disease
Small-vessel vasculitis
This includes arterioles, capillaries and venules within the skin and other organs
- Henoch Schonlein Purpura (HSP)
- ANCA-associated small vessel vasculitides
- Eosinophilic granulomatosis with polyangiits (Churg-Strauss syndrome)
- Granulomatosis with polyangiitis (Wegener’s disease)
- Microscopic polyangiitis
😷 Presentation
This of course refers to the common features seen across the vasculitides as they all differ in certain aspects.
- Purpura - these are purple-coloured, non-blanching spots that form as a result of blood leakage from vessels that lie below the skin. It is more prominent in small vessel vasculitis.
- Joint and muscle pain
- Renal impairment
- GI disturbances - such as diarrhoea, abdominal pain and bleeding.
- Anterior uveitis and scleritis
- Hypertension - due to blood vessel inflammation as well as due to renal impairment.
- Peripheral neuropathy
Other, more generic/systemic features of vasculitides include:
- Anorexia
- Weight loss
- Anaemia
- Fatigue
- Fever
🔍 Investigations
- CRP/ESR - raised as a result of the inflammation.
CRP peaks at about 48 hours after the inflammation and then rapidly declines. It is a more direct measure of inflammation.
ESR, on the other hand, rises at a slower rate and then can take weeks after the inflammation has subsided to return to the baseline level.
- Anti neutrophil cytoplasmic antibodies (ANCA) - these are a group of antibodies that target neutrophils. There are 2 distinct types of ANCAs to consider:
- Perinuclear ANCA (p-ANCA) - targeting the myeloperoxidase protein (MPO protein). It is associated with Churg-Strauss syndrome. and microscopic polyangiitis.
- Circular ANCA (c-ANCA) - targets the PR3 protein (proteinase 3) which is associated with granulomatosis with polyangiitis (GPA).
Below is a table describing some instances where p-ANCA and c-ANCA may be found:
p-ANCA | c-ANCA | |
Target | Myeloperoxidase (MPO) | Serine proteinase 3 (PR3) |
Granulomatosis with polyangiits | 25% | 90% |
Eosinophilic granulomatosis with polyangiits | 50% | Low |
Microscopic polyangiits | 75% | 40% |
Other associated conditions | Ulcerative colitis
Primary sclerosing cholangitis
Anti-GBM disease
Crohn’s disease | |
Usefulness in monitoring disease activity | Not useful in monitoring disease activity | Some correlation between c-ANCA levels and disease activity |
🧰 Management
The general management for vasculitides (with the exception of Kawasaki’s disease and HSP) follows the same principles of immunosuppression and anti-inflammation (with steroids):
- Oral - e.g. prednisolone
- IV - e.g. hydrocortisone
- Nasal - for nasal symptoms
- Inhaled - for example in Churg-Strauss syndrome which has lung involvement.
Some immunosuppressants used include:
- Cyclophosphamide
- Methotrexate
- Azathioprine
- Rituximab and other MABs.
Vasculitides
Giant cell arteritis (GCA), also known as temporal arteritis is a medium to large-vessel vasculitis, particularly affecting the temporal arteries. The lining of the extracranial branches of the carotid artery (such as the temporal arteries) become inflamed. This inflammation leads to swelling in the affected arteries, which thereby narrows the artery. Subsequently, there is a reduction in the amount of blood and oxygen that is able to reach the tissues typically perfused by these arteries, like the masseter, or jaw muscles.
It is most prominent in individuals >50 years and older.
😷 Presentation It can have an acute or insidious onset. With the following symptoms:
- Temporal headache - an elderly person with a temporal headache should always be considered for GCA.
- Jaw claudication - pain associated with chewing.
- Amaurosis fugax - due to the ophthalmic artery being affected. It is a true ophthalmic emergency as it can lead to permanent vision loss.
- Thickened & tender temporal arteries - they may also be pulseless.
- Polymyalgia rheumatica - it does not lead to PMR, but it is strongly linked with it and so we may often see its manifestations as well such as symmetrical proximal muscle weakness and oligoarthritis (swelling and inflammation of 2-4 joints).
- Stroke - this is another serious complication that may occur.
🔍 Investigations
- 🥇 ESR - GCA is unlikely if ESR is not elevated
- 🥇 Vascular ultrasound - a non-compressible halo sign is the finding that most indicates GCA.
- FBC - normocytic, normochromic anaemia (similar to all ACDs).
- LFTs - deranged in 1/3rd of patients.
- 🏆 Temporal artery biopsy - a diagnostic procedure. However, GCA has skip lesions and so a negative biopsy does not rule out GCA.
🧰 Management
It is a medical emergency.
- It requires high dose steroids:
- Oral prednisolone - 60mg OD. The dose is reduced slowly over several months as treatment is needed for 1-2 years which can cause tolerance and lack of production endogenously (may lead to Addisonian crisis if stopped suddenly).
- If weaning off the steroids will be problematic, give azathioprine instead.
- Acute or intermittent vision loss
- IV glucocorticoid (hydrocortisone) is first line.
- Oral prednisolone - 60-100mg for 3 consecutive days.
- Aspirin may be given to reduce the risk of stroke and amaurosis fugax.
❗️ With long-term steroid use we need to protect against osteoporosis and ulcers ❗️
→ Bisphosphonates, calcium and vitamin D
→ PPI
Takayasu’s arteritis (TA) is a chronic, granulomatous large vessel vasculitis that primarily affects aorta and the branches of the aorta as well as the pulmonary artery. It leads to inflammation and aneurysm formation or to narrowing of the artery which can lead to a weak pulse or loss of pulses. For this reason it is also known as pulseless disease.
It mostly occurs in females (80-90%), especially in Far East Asia and subcontinental Asia.
😷 Presentation
The systemic manifestations of vasculitis are present - fatigue, malaise, night sweats and arthritis.
- Unequal BP within upper limbs - a >10mmHg discrepancy between both sides usually.
- Carotid bruits and tenderness
- Absent/weak peripheral pulses
- Upper and lower limb claudication
- Aortic regurgitation
- Renal impairment - due to renal artery stenosis.
🔍 Investigations
🔢 Classification
Based on the angiographic findings, we can classify Takayasu’s arteritis into 5 types.
- Type I - branches of the aortic arch.
- Type IIa - ascending aorta, aortic arch and branches of the aortic arch.
- Type IIb - ascending aorta, aortic arch, branches of the aortic arch, thoracic descending aorta.
- Type III - thoracic, descending aorta, abdominal aorta and/or renal arteries.
- Type IV - abdominal aorta and/or renal arteries.
- Type V - features of type IIb and type IV.
🧰 Management
- 🥇 Steroids
- Bisphosphonates, calcium and vitamin D should also be given to protect against osteoporosis.
Polyarteritis nodosa (PAN) is a rare medium vessel vasculitis. It is defined as transmural necrotising vasculitis of medium and small arteries.
The medium-sized vessels that it affects are those in the skin, GI tract, kidneys and heart which leads to the associated symptoms in those systems.
It, however, does not include the pulmonary vessels and is not associated with ANCA (unlike many other vasculitides).
⚠️ Risk factors
- Middle-aged men
- Hepatitis B infection - subsequently become rare after the introduction of HepB vaccination schemes.
😷 Presentation
It presents with symptoms of ischaemia as well as features of the affected organ system:
- Kidneys - renal failure, haematuria
- Heart - IHD, acute MI
- GI - abdominal pain, nausea and melaena
- MSK - arthritis, myalgia, arthralgia
- Skin - livedo reticularis (also discussed in antiphospholipid syndrome)
- Nervous system - mononeuritis multiplex (a type of peripheral neuropathy that happens when there is damage to at least two different areas of the peripheral nervous system), sensorimotor polyneuropathy.
- Fever, weight loss, general malaise
🔍 Investigations
Diagnosis can be made through clinical history, physical examination, laboratory testing and if possible a biopsy may be done.
Lab tests that may be done include
- CRP
- Serum creatinine
- ANCA
- ANA
- HBV serology
- HCV serology
🧰 Management
For non-HBV related PAN → immunosuppression with corticosteroids and cyclophosphamide
HBV-related PAN → corticosteroids as well as antiviral treatment (lamivudine) as well as plasma exchange.
HSP is an IgA-mediated small vessel vasculitis that is the most common form of vasculitis in childhood with IgA deposition in the kidneys, joints and gut.
😷 Presentation
It has a clinical triad of:
- Palpable purpuric rash on the extensor surfaces (legs and buttocks)
- Abdominal pain
- Arthritis
Other symptoms include: haematuria and renal failure.
🔍 Investigations
It is a clinical diagnosis that can be confirmed by the presence of IgA and C3 in the skin with immunofluorescence. Renal biopsy will show similar findings to IgA nephropathy (IgA deposits in the mesangium).
🧰 Management
- Arthralgia → analgesia
- Nephropathy/enteropathy → corticosteroids
Prognosis is usually very good as it is usually self-limiting, especially in children who do not have renal involvement. Only about 1/3rd of patients will relapse.
Churg-Strauss syndrome is a rare, granulomatous small and medium vessel vasculitis. It has a triad of eosinophilia, granulomatous inflammation and vasculitis.
It too is an ANCA associated vasculitis, and the antibody involved is p-ANCA (anti-MPO) which is found in 60% of patients.
The most commonly affected organs include lung and skin.
😷 Presentation
- Severe asthma
- Eosinophilia (>10% in peripheral blood)
- Paranasal sinusitis
- Mononeuritis multiplex/polyneuropathy
- Palpable pupura
🔍 Investigations
- ANCA - positive.
- FBC - eosinophilia.
- CRP/ESR - raised.
- Pulmonary function tests - may indicate obstructive pattern consistent with asthma.
- CXR - may indicate interstitial lung infiltrates.
🧰 Management
- We start off by inducing remission with corticosteroids (prednisolone).
- If it is severe we can add an immunosuppressant (cyclophosphamide or rituximab).
- Maintenance - there are a couple options available, including low-dose prednisolone, methotrexate, azathioprine, mycophenolate.
- We also can treat the asthma with inhaled corticosteroids as it aids tapering off the oral corticosteroid, but standard asthma treatment may also be given.
Wegener’s disease is a systemic vasculitis that involves the small and medium vessels. It classically affects the upper and lower respiratory tract as well as kidneys (known as pauci-immune crescentic glomerulonephritis [PICGN]).
It may also affect the skin, eyes, musculoskeletal system and peripheral nervous system.
It is also an ANCA-associated vasculitis, and the associated antibody is c-ANCA (anti-PR3) which is found in 90% of cases.
The median survival time after diagnosis is 8-9 years.
😷 Presentation
- Upper resipiratory tract symptoms
- Chronic sinusitis
- Epistaxis
- Crusty nasal secretions
- Saddle nose deformity
- Hearing loss
- Lower respiratory tract symptoms
- Cough
- Haemoptysis
- Pleuritis
- Kidney (PICGN) symptoms
- Haematuria
- Proteinuria
🔍 Investigations
- 🥇 ANCA - cANCA positive in >90& and pANC positive in 25%. This is the first-line investigation.
- CXR - bilateral nodular and cavity lesions (may look similar to pneumonia leading to misdiagnosis)
- Renal biopsy - epithelial crescents in Bowman’s capsule (similar to rapidly progressing glomerulonephritis)
- U&Es and urinalysis - assessing kidney function with creatinine and proteinuria on urinalysis.
- CRP/ESR
🧰 Management
- 🥇 Steroid (prednisolone) as well as immunosuppression (cyclophosphamide) as well as supportive therapy.
Dear future Sarmad,
Please remember to add in section on Bechet’s disease.
Kind regards
Sarmad (23/01/2023)