Vasculitis - overview
Last edited on : 23/09/2024
Vasculitis refers to a group of disorders characterized by inflammatory involvement of blood vessels, leading to structural changes in their walls. All types of vessels can be affected, and clinical manifestations are very heterogeneous.
Vasculitis can be classified into secondary vasculitis (++ infectious origin), which are common, and primary vasculitis, which are rare. However, it's worth noting that aside from vasculitis considered secondary to autoimmune diseases, most "primary vasculitis" exhibit high rates of association with various autoimmune conditions.
Classification
Primary Vasculitis
| Preferentially affected vessel types | Disease |
|---|---|
| All calibers | Behçet's disease (predominantly affects small vessels) |
| Large vessels | Giant cell arteritis
Takayasu arteritis |
| Medium vessels | Polyarteritis nodosa (PAN)
Kawasaki disease Buerger's disease |
| Small vessels | Granulomatosis with polyangiitis (Wegener's)
Churg-Strauss syndrome |
In addition to these well-defined syndromes, one may encounter primary vasculitis that is either multisystemic or confined to a single organ, not fitting into any specific nosology.
Secondary Vasculitis
More common than primary vasculitis, they are probably underdiagnosed (especially those secondary to sepsis).
- Infections: streptococci, HBV, syphilis, borreliosis, tuberculosis, HIV… common during severe sepsis of any origin
- Autoimmune diseases: rheumatoid arthritis, collagenoses, sarcoidosis, primary biliary cirrhosis, autoimmune hepatitis, Crohn's disease…
- Neoplasms: leukemias, lymphomas, multiple myeloma, solid tumors…
- Medications: antibiotics, cytostatics, D-penicillamine, non-steroidal anti-inflammatory drugs (NSAIDs), gold salts…
Clinical Clues
When to Suspect Vasculitis
The clinical presentations of vasculitis are highly variable and non-specific. Vasculitis should be particularly suspected when several of these symptoms or signs are associated without an obvious explanation:
- General: unexplained fever, weight loss, weakness, fatigue
- Musculoskeletal: arthralgia, myalgia, arthritis
- Cutaneous: palpable purpura, nodules, urticaria, livedo reticularis, superficial/deep phlebitis, ischemic/necrotic lesions
- Neurological: headaches, repeated or atypical strokes, mono and polyneuropathies
- Head and neck: sinusitis, chondritis, otitis, iridocyclitis
- Renal: glomerulonephritis, renal infarction, hypertension
- Pulmonary: alveolar hemorrhage, hemoptysis, cavities, nodules, infiltrates
The presence of just one of these signs or symptoms should also raise suspicion of vasculitis in certain contexts (see secondary vasculitis etiologies). Some signs are also very suggestive on their own outside of any context (palpable purpura, glomerulonephritis, recurrent oligoarthritis, polyneuropathies, recurring ischemic or necrotic skin lesions) in the absence of an obvious explanation.
Clinical Features Suggesting a Specific Primary Vasculitis
Pediatric Vasculitis
A suspicion of vasculitis in a child immediately points towards Henoch-Schönlein purpura or Kawasaki disease (almost ruled out if no fever > 40°C).
Association with New-Onset Asthma
The presence of asthma during the active phase suggests Churg-Strauss syndrome.
Polyneuropathies
Rapidly progressing polyneuropathy suggests PAN.
Predominantly Cutaneous or Dermo-Renal Syndrome
A clinical picture dominated by skin involvement (± renal involvement, always to be investigated - renal function and proteinuria) should first suggest small vessel vasculitis (++ Henoch-Schönlein purpura and essential mixed cryoglobulinemia) or PAN.
Small Vessel Vasculitis
Can be confined to the skin. 90% of cases are isolated (spontaneous resolution within a few weeks), 10% will develop a recurrent form (flares separated by several months/years). Infiltrated purpura suggests small vessel vasculitis… but it is very nonspecific, and its differential diagnosis includes most primary or secondary vasculitis.
Isolated cutaneous involvement should always raise suspicion of a drug-related cause (~10% of cases, generally 1-3 weeks after drug exposure). A dermo-renal syndrome should always suggest Henoch-Schönlein purpura and essential mixed cryoglobulinemia.
Cutanous PAN
A limited and "benign" form of PAN. Painful cutaneous nodules, livedo reticularis, ulcers, muscle pain, arthralgia, paresthesias, increased ESR, absence of systemic signs. Skin lesion biopsy shows panarteritis of small and medium-caliber arteries with focal panniculitis.
Aortic Arch Syndrome
Clinical signs suggestive of aortic arch and supra-aortic vessel involvement should raise suspicion of large vessel disease (Horton, Takayasu) and PAN.
Giant Cell Arteritis (= temporal arteritis = Horton disease)
Signs of polymyalgia rheumatica (associated in 50% of cases), asthenia, malaise, fever, headaches, jaw claudication, scalp tenderness, visual disturbances, tongue necrosis… ± anemia, increased ESR… ++ in those > 50 years old.
If temporal artery is tender, tortuous, or thickened: start corticosteroids immediately after temporal artery biopsy. If biopsy is normal → repeat biopsy and preserve long segments → if negative: biopsy of the contralateral artery → if still negative: aortic angiography.
Visual disturbances suggest involvement of the ophthalmic artery with a high risk of rapid permanent blindness, requiring urgent corticosteroid therapy.
NB: PAN can also affect the temporal artery and should also be considered in patients presenting with systemic symptoms (fever, asthenia, weight loss, nonspecific inflammatory syndrome,…)
Takayasu Arteritis
+++ women, +++ < 40 years old.
Generally accompanied by fever, sweating, asthenia, arthralgia, myalgia… may evolve over several years before presenting signs of ischemia: loss of peripheral pulses, vascular bruits, symptoms depending on the affected artery (amaurosis, headaches, claudication, hypertension, angina,…). May mimic renovascular hypertension.
± moderate anemia, increased ESR. An aortic angiography should be performed to look for proximal occlusions, stenoses, and aneurysms.
Pulmonary-Renal Syndrome
These are life-threatening situations → diagnosis and treatment are relative emergencies. Unfortunately, its differential diagnosis includes a large number of primary or secondary vasculitis and non-vasculitic etiologies. In the face of a pulmonary-renal syndrome, the two primary diagnostic considerations should be small vessel vasculitis (++ Churg-Strauss, Wegener’s and MPA) and Goodpasture syndrome (anti-glomerular basement membrane antibody disease).
Renal biopsy (or pulmonary biopsy, with higher morbidity) with immunofluorescence and serology is the diagnostic gold standard. However, it may not always identify certain ANCA-associated microvasculitis that can present such a picture. Other clues to look for are: ANCA +, poor response to corticosteroids, development of upper airway lesions, cavitated pulmonary lesions.
Additional Diagnostic Tests
Initial investigations may include some or all of the following:
- Biology: complete blood count, ESR, C-reactive protein, fibrinogen, renal function, serology for HBV/HCV/HIV, antinuclear antibodies, anti-DNA antibodies, ANCA, cryoglobulin, complement levels and fractions C3 and C4, rheumatoid factor, anti-basement membrane antibodies
- Urinalysis: dipstick, urinary sediment, 24-hour proteinuria, CK, troponins
- Chest X-ray ± sinus X-ray
- ECG
- Electromyography and nerve conduction studies
- Blood cultures
- Skin biopsy of clinically affected tissues
... keeping in mind that, except for ANCA, the specificity and sensitivity of isolated results are very low. The need for biopsy should be assessed based on the clinical situation and results from less invasive tests. Thus, a patient suspected of having vasculitis with active nephritis and acute kidney injury should promptly undergo renal biopsy. In a patient with jaw claudication and polymyalgia rheumatica, one might settle for an ESR and complete blood count before performing a temporal biopsy.
Vasculitis associated with ANCA presence includes:
- Microscopic polyangiitis (60%, p-ANCA +++)
- Wegener's (90%, c-ANCA +++)
- Churg-Strauss (60%, p-ANCA +++)
- (PAN: p-ANCA, rarely present)
An increase in serum IgA is present in 50% of cases of Henoch-Schönlein purpura.
Differential Diagnosis
The differential diagnosis mainly depends on the clinical manifestations, which are highly variable. Generally, one should systematically consider major groups of systemic diseases (Still’s disease, hereditary periodic fevers and related conditions, sarcoidosis, rheumatoid arthritis, ankylosing spondylitis, Sjögren's syndrome, systemic lupus erythematosus, antiphospholipid syndrome,…).