Differentials
Granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis)
SIGNS / SYMPTOMS
Granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and Churg-Strauss syndrome (CSS) are forms of anti-neutrophil cytoplasmic (ANCA) -associated small-vessel vasculitis, whereas polyarteritis nodosa (PAN) affects only medium-sized vessels (i.e., small- and medium-sized arteries).
Commonly presents with signs and/or symptoms involving the upper or lower respiratory tract.
Glomerulonephritis and pulmonary capillaritis are features of ANCA-associated vasculitis conditions but are not found in PAN.
INVESTIGATIONS
ANCA: cANCA (cytoplasmic pattern on immunofluorescence testing) combined with positive proteinase 3 antibody testing by enzyme immunoassay (EIA); pANCA (perinuclear pattern on immunofluorescence testing) combined with positive myeloperoxidase antibody testing by EIA. ANCA is not associated with PAN.
Urinalysis: may show haematuria, proteinuria; dysmorphic red blood cells, RBC casts.
Pulmonary function testing: typically be normal or may show evidence of extrathoracic airway obstruction in cases of subglottic stenosis.
CT chest: lung nodules (which may cavitate); infiltrates.
Tissue biopsy (skin, lung, kidney): granulomatous inflammation, necrosis and vasculitis; minimal/absent immune deposits on immunofluorescence and electron microscopy.
Microscopic polyangiitis
SIGNS / SYMPTOMS
Granulomatosis with polyangiitis (GPA, formerly known as Wegener's granulomatosis), microscopic polyangiitis (MPA), and Churg-Strauss syndrome (CSS) are forms of ANCA-associated small-vessel vasculitis, whereas polyarteritis nodosa (PAN) affects only medium-sized vessels (i.e., small- and medium-sized arteries).
MPA and GPA seem to be part of a clinical spectrum. However, the upper respiratory tract is not involved in MPA.
Glomerulonephritis and pulmonary capillaritis are features of ANCA-associated vasculitis conditions but are not found in PAN.
INVESTIGATIONS
ANCA: positive pANCA (perinuclear) more common than cANCA (cytoplasmic). ANCA is not associated with PAN.
Urinalysis: may show haematuria, proteinuria; dysmorphic red blood cells, RBC casts.
CT chest: alveolar haemorrhage.
Tissue biopsy (skin, lung, kidney): absence of granulomatous inflammation.
Churg-Strauss syndrome
SIGNS / SYMPTOMS
Granulomatosis with polyangiitis (GPA, formerly known as Wegener's granulomatosis), microscopic polyangiitis (MPA), and Churg-Strauss syndrome (CSS) are forms of ANCA-associated small-vessel vasculitis, whereas polyarteritis nodosa (PAN) affects only medium-sized vessels (i.e., small- and medium-sized arteries).
Patients typically present with a history of asthma, allergic rhinitis, or sinusitis.
Peripheral neuropathy (typically mononeuritis multiplex) is the most common vasculitic manifestation.
Glomerulonephritis and pulmonary capillaritis are features of ANCA-associated vasculitis conditions but are not found in PAN.
INVESTIGATIONS
FBC: significant (>10% of peripheral WBC count) peripheral eosinophilia.
Urinalysis: may show haematuria, proteinuria; dysmorphic red blood cells, RBC casts.
ANCA: usually pANCA (perinuclear). ANCA is not associated with PAN.
Tissue biopsy (sural nerve, skin): granulomatous inflammation, may have extravasated eosinophils.
Deficiency of adenosine deaminase 2 (DADA2)
SIGNS / SYMPTOMS
DADA2 is a monogenic vasculitis syndrome that can present in an identical way to idiopathic PAN. It is an autosomal recessive disorder that can present in children and young adults. DADA2 should be considered in the differential diagnosis of a patient presenting with features of PAN if there is a history of recurrent or prolonged PAN-like vasculitis, early-onset stroke, and/or a family history of vasculitic syndromes. Haematological manifestations include hypogammaglobulinaemia, pure red cell aplasia, thrombocytopenia and neutropenia.
INVESTIGATIONS
Genetic testing for lack of function mutations in the adenosine deaminase 2 gene (previously called the CECR1 gene). Immunoglobulins may be low in a subgroup of patients with DADA2. FBC may show anaemia with low reticulocyte count (representing red cell aplasia), thrombocytopenia or neutropenia.
Giant cell arteritis (GCA)
SIGNS / SYMPTOMS
Giant cell arteritis (GCA) does not usually present with mononeuritis multiplex, orchitis, or coronary vasculitis, nor does it involve the skin or affect the renal arteries.
GCA is predominantly a large- and medium-sized vessel vasculitis with a predilection for the cranial arteries. It is associated with temporal arteritis, though the temporal artery can also be involved in PAN, and PAN can cause ischaemic optic neuropathy similar to that seen in GCA.
INVESTIGATIONS
Magnetic resonance, CT, or conventional angiography shows affected medium-sized cranial vessels, especially the temporal artery. GCA also affects extracranial large vessels, such as the aorta and the carotid arteries, but extra-cranial medium-sized arteritis is more likely to be due to PAN.
Infection
SIGNS / SYMPTOMS
Endovascular bacterial infection is an important vasculitis mimic that needs to be excluded before immunosuppressive therapy can be started.
HIV and hepatitis C virus (HCV) are associated with vasculitis.[45] HCV-related vasculitis is usually in the form of a cryoglobulinaemia.
Epstein-Barr virus, cytomegalovirus, parvovirus, and many other viruses are implicated in causing vasculitis or can cause symptoms that mimic vasculitis.[45]
INVESTIGATIONS
Blood cultures to detect bacteraemia. HIV serology, HCV serology, or other viral serology when clinically appropriate to detect infection. The presence of cryoglobulins suggests an HCV-related vasculitis.
Rheumatoid arthritis
SIGNS / SYMPTOMS
This can present with similar symptoms to those of PAN or cause a secondary vasculitis. A presentation with mainly arthritis should lead to investigations for rheumatoid arthritis.
INVESTIGATIONS
Rheumatoid factor and antibodies to cyclic citrullinated peptides (anti-CCP antibodies) are positive in rheumatoid arthritis.
Systemic lupus erythematosus (SLE)
SIGNS / SYMPTOMS
SLE can present with similar symptoms to those of PAN or cause a secondary vasculitis. A malar rash, alopecia, oral ulcers, or serositis, especially in a young woman, should trigger investigation for SLE.
INVESTIGATIONS
ANA is positive in SLE. Anti-double-stranded DNA antibodies (anti-dsDNA) can be useful to make a diagnosis of SLE if the clinical manifestations fit with this diagnosis.
Malignancy
SIGNS / SYMPTOMS
Fever, weight loss, fatigue, myalgia, and arthralgia may be due to cancer. In the absence of organ involvement characteristic of vasculitis, a thorough evaluation for malignancy should be performed.
Vasculitis can occur as a paraneoplastic phenomenon, particularly with haematological malignancies.[46]
INVESTIGATIONS
Investigation for malignancy should be guided by specifics of history and examination. This may involve checking tumour markers, imaging of chest/abdomen/pelvis, and other investigations as clinically appropriate.
Fibromuscular dysplasia (FMD)
SIGNS / SYMPTOMS
FMD can affect the renal, carotid, mesenteric, and other visceral arteries. Ischaemic symptoms, depending on the arterial system involved, result from luminal narrowing. However, FMD does not cause fever, weight loss, arthritis, skin lesions, or mononeuritis multiplex.
INVESTIGATIONS
Biopsy is usually difficult, so imaging (with conventional digital subtraction angiography or magnetic resonance angiography [MRA]) remains the best method of diagnosis. Angiography shows a 'string of beads' with aneurysms and stenosis. MRA may reveal thickening of the vessel wall.[47]
Inflammatory markers (CRP or erythrocyte sedimentation rate [ESR]) are not raised in FMD.
Atheroma
SIGNS / SYMPTOMS
Atherosclerosis is the most common cause of organ ischaemia. Symptoms and signs depend on the arterial systems involved. Atheroma formation is accelerated in inflammatory diseases, including PAN, in which a combination of inflammation and ischaemia may both be present, making it difficult to differentiate between atherosclerotic disease and vasculitis.
INVESTIGATIONS
Conventional digital subtraction angiography is the best test; the absence of microaneurysms in purely atherosclerotic disease is the main discriminating factor.
CRP and ESR are not usually raised in patients with atherosclerosis alone.
Cholesterol emboli
SIGNS / SYMPTOMS
Usually presents with distal ischaemia, hypertension, and renal impairment, but can manifest itself with any ischaemic symptom, including mononeuropathy.[48]
Typically occurs after a vascular interventional procedure causing mechanical disruption of an atheromatous plaque. Small cholesterol crystals shower downstream, or large plaques break off and occlude larger vessels. In the first scenario, the crystals induce an inflammatory reaction in small vessels, resulting in fibrosis and eventually tissue ischaemia.[49]
INVESTIGATIONS
Biopsy of affected organ shows microcrystals of cholesterol.
Atrial myxoma
SIGNS / SYMPTOMS
Can cause recurrent emboli to multiple organs, resulting in tissue ischaemia and infarction. Symptoms may mimic vasculitis. In some cases, this embolus is purely thrombus; in others, a combination of thrombus and tumour material.[50]
INVESTIGATIONS
Echocardiography reveals the atrial mass.
Catastrophic antiphospholipid syndrome
SIGNS / SYMPTOMS
A rare disorder with pathological overlap to antiphospholipid syndrome. It presents with multiorgan infarction from microthrombi over a period of days to weeks. Preceding infection is a risk factor.[51]
INVESTIGATIONS
IgG anticardiolipin antibodies (IgG) and beta-2 glycoprotein are elevated.
Lupus anticoagulant may be present.
FBC may show a low platelet count, and the partial thromboplastin time may be raised.
Buerger's disease (thromboangiitis obliterans)
SIGNS / SYMPTOMS
Typically occurs in men aged 20 to 40 years who are heavy smokers, but can occur in women and at older ages. Presents with claudication, ischaemic pain at rest, Raynaud's phenomenon, or gangrene of the extremities.
INVESTIGATIONS
Pathologically, there is vasculitis affecting the small- and medium-sized vessels of the hands and feet. Angiogram of extremities and renal or mesenteric arteries shows occluded vessels distal to the elbow or knee, with a corkscrew appearance of collateral vessels. Differentiated from PAN by the absence of visceral vessel involvement.[52]
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