Differentiating vasculitis from other diseases

Vasculitis
Overview
Classification Large-sized vessel vasculitis Takayasu's Arteritis Temporal Arteritis Medium-sized vessel vasculitis Kawasaki's Disease Polyarteritis Nodosa Small-sized vessel vasculitis Churg-Strauss Syndrome Cutaneous leukocytoclastic vasculitis Essential cryoglobulinemic vasculitis Henoch-Schonlein Purpura Microscopic polyangiitis Wegener's Granulomatosis Variable-sized vessel vasculitis Sjogren syndrome Cogan syndrome Single organ vasculitis Primary central nervous system angiitis
Causes
Differential Diagnosis

gsEditor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief:

Differential Diagnosis

Abbreviations: ABG= Arterial blood gas, ANP= Atrial natriuretic peptide, BNP= Brain natriuretic peptide, CBC= Complete blood count, COPD= Chronic obstructive pulmonary disease, CRP= C-reactive protein, CT= Computed tomography, CXR= Chest X-ray, DVT= Deep vein thrombosis, ESR= Erythrocyte sedimentation rate, HRCT= High Resolution CT, IgE= Immunoglobulin E, LDH= Lactate dehydrogenase, PCWP= Pulmonary capillary wedge pressure.

Diseases			Clinical manifestations								Para-clinical findings									Gold standard	Additional findings
			Symptoms					Physical examination
											Lab Findings				Imaging				Histopathology
			Headache	Fever	Weight loss	Arthralgia	Claudication	Bruit	HTN	Focal neurological disorder	Biomarker	CBC	ESR	Other	CT scan	Angiography	Ultrasound/ Echocardiography	Other
Large-Vessel Vasculitis	Takayasu arteritis		+	+/-	+	-	+	+	+/-	+/-	MMP-3 and MMP-9	Leukocytosis, Anemia	↑	↑CRP	Aneurysmal dilatation of the aorta	Blood vessel stenosis	Circumferential thickening of the arterial wall (Macaroni sign)	PET-scan, Cardiac CT	Granulomatous inflammation of arteries	Arteriography	Coronary aneurysm
	Giant cell arteritis		+	-	+	+/-	-	-	-	+/-	Pentraxin 3 (PTX3)	Normal	↑	↑CRP	Stenosis, Occlusion, Dilatation	Aneurysm	-	Mural inflammation in MRA	Granulomatous inflammation of arteries	Biopsy	Jaw pain and claudication
	Neurological disease	Cerebral aneurysm	+	-	-	-	-	-	+/-	+	-	Normal	Normal	-	Well-defined round, slightly hyperattenuating lesion	Bulging out of the main lumen	-	Heterogeneous signal intensity in MRA	Layers of smooth muscle cells, Intact endothelium	Digital subtraction angiography (DSA)	Nausea, Vomiting
		Neurofibromatosis type 1	+/-	-	+/-	-	-	-	+	+	NF1 mutated gene	Normal	Normal	Neurofibromin gene	Bone abnormalities	Optical coherence tomography angiography (OCTA)	-	Optic nerve gliomas in MRI	Elongated spindle-shaped cells in neurofibromas	NIH diagnostic criteria	Cafe au Lait spot
		Neurofibromatosis type 2	+/-	-	+/-	-	+/-	-	-	+	NF2 mutated gene	Normal	Normal	Schwannomin	Meningioma, Schwannoma, Ependymoma	Fluorescein angiography showed retinal hamartoma	Localized schwannomas in nerve ultrasound	Schwannoma in MRI	Encapsulated biphasic nerve sheath tumor	NIH diagnostic criteria	Hearing loss, Vision loss
	Systemic disease	Fibromuscular dysplasia	+	-	+/-	+	+	+	+	+/-	Transforming growth factor β (TGF-β)	Normal	↑	↑ Cr or BUN	Alternating stenosis and dilatations in CT angiography	Stenosis in the renal arteries	Luminal narrowing alternating with dilatation (Beads sign)	Focal concentric, long-segment tubular stenosis or outpouching in MRA	Fibrodysplastic changes, Collagen deposition	Digital subtraction angiography (DSA)	Spontaneous coronary artery dissection (SCAD)
		Ehlers-Danlos syndrome	-	-	-	+	+/-	+/-	-	+/-	TGF-β	Normal	Normal	Cultured skin fibroblasts	Multiple vascular segments with aneurysms and dissections	Dissection of the posterolateral branch of the left circumflex coronary artery (LCx)	Visceral arteries abnormality	Vascular abnormalities in MRA	Thin and rare collagen bundles in the dermis	History and physical examination	Bleeding, Bruisability, Heart murmur
		Polymyalgia rheumatica (PMR)	+	-	+/-	+	-	-	-	-	Plasma fibrinogen	Normocytic, normochromic anemia	↑	CRP	Periodontoid localization of calcification	Vessel wall thickening, Increased mural contrast enhancement	Subacromial or subdeltoid bursitis	High F-FDG accumulation around the joints in FDG PET-CT	Small angular fibers, Pyknotic nuclear clumps, or target-targetoid fibers	-	Joint stiffness, Fatigue
		Amyloidosis	+/-	-	-	+/-	+/-	-	+	+	Immunoglobulin light chain(Amyloid)	Anemia	Normal	↑ Cr or BUN, ↑ ALT or AST	Diffusely hypoattenuating and enlarged liver	Amyloid deposition in the media and adventitia of small arteries	Solid organs increased echogenicity	Tc-DPD for cardiac amyloid deposits	Extracellular deposition of fibrillar proteins	Biopsy	Cardiomegaly, Dyspnea
Diseases			Headache	Fever	Weight loss	Arthralgia	Claudication	Bruit	HTN	Focal neurological disorder	Biomarker	CBC	ESR	Other	CT scan	Angiography	Ultrasound/ Echocardiography	Other	Histopathology	Gold standard	Additional findings
Medium-Vessel Vasculitis	Polyarteritis nodosa		+	+	+	+	+	+	+/-	+/-	LAMP-2 protein autoantibodies	Leukocytosis, Normochromic anemia, Thrombocytosis	↑	↑ Cr or BUN, ↑ ALT or AST, Proteinuria	Focal regions of infarction or hemorrhage	Multiple microaneurysms, Hemorrhage due to focal rupture, Occlusion	Aneurysms and renal arteriovenous fistula in color Doppler sonography	-	Necrotizing inflammatory lesions	Angiography	Sudden weight loss, Abdominal pain
	Hepatitis B virus-associated polyarteritis nodosa		+/-	+/-	+	+	+/-	+/-	+	-	HBsAg	Leukocytosis, Normochromic anemia, Thrombocytosis	↑	↑ ALT or AST	Focal regions of infarction or hemorrhage	Microaneurysms in mesenteric artery	Aneurysms and renal arteriovenous fistula in color Doppler sonography	-	Necrotizing inflammatory lesions	Angiography	Peripheral neuropathy, Livedo reticularis
	Kawasaki disease		-	+	+/-	+	+	-	+/-	-	NT-proBNP, Meprin A, Filamin C	Normochromic anemia, ↑WBC with a left shift, Thrombocytosis	↑	Acute-phase reactants, ↓Cholesterol, ↓HDL, ↓ApolipoA	Coronary artery calcifications	Coronary artery aneurysms, stenosis or occlusion	Coronary artery anomaly in echocardiography	Electron beam CT (EBCT)	Acute destruction of the media by neutrophils, with loss of elastic fibers	History and physical examination	Diarrhea, Vomiting
	Infectious disease	Parvovirus B19 infection	+	+	+	+	-	-	-	+/-	B19 DNA, ↓Reticulocyte count	Anemia	↑	anti–parvovirus B19 IgM	-	-	Hydrops in fetal ultrasonography	-	-	B19 DNA	Purpuric rash, Erythema multiforme
		Scarlet fever	+	+	+/-	+	-	-	-	-	Antistreptolysin-O (ASO) titers	Leukocytosis	↑	↑CRP	Thickened pulmonary markings if pneumonia	-	-	-	Sparse neutrophilic perivascular infiltrate	History and physical examination	Sand-paper rashes, Sore throat
		Toxic shock syndrome	+	+	+	+	-	-	-	+/-	Procalcitonin	Leukocytosis with left shift	↑	Myoglobinuria, Sterile pyuria	Acute respiratory distress syndrome	-	-	-	Necrolysis of keratinocytes in epidermis, Perivascular lymphocytic infiltrate	Clinical criteria	Peeling or rashes, Organ dysfunction
		Mononucleosis	+	+	+	+	-	-	-	-	EBV DNA	Atypical lymphocyte	↑	Heterophile antibodies	CNS involvement	-	Splenomegaly	Encephalitis in MRI	Lymphoproliferative response in oropharynx, Lymphocytic infiltration in spleen	Heterophile antibody test	Splenomegaly, Palatal petechiae
		Leptospirosis	+	+	+	+	+/-	-	-	-	IL-6, IL-8 and IL-10	Anemia	-	↑Cr or BUN, ↑ALT or AST, Proteinuria	Diffuse alveolar hemorrhage	-	-	-	Toxin-mediated break down of endothelial cell membranes of capillaries	Culture and the microscopic agglutination test	Red eyes, Skin rash
		Lyme Disease	+/-	+	+/-	+	+/-	-	-	-	CXCL9 (MIG), CXCL10 (IP-10) and CCL19 (MIP3B)	Leukopenia, Thrombocytopenia	-	Microscopic hematuria, Proteinuria, ↑ALT or AST	Punctate lesions in periventricular white matter in brain SPECT	-	-	-	Acrodermatitis chronica atrophicans	Serologic tests	Erythema migrans
		Measles	+/-	+	+/-	+	-	-	-	-	Measles IgM	Leukopenia, Lymphocytosis, Thrombocytopenia	-	↑ALT or AST	Pneumonia	-	-	CXR	Spongiosis and vesiculation in the epidermis with scattered dyskeratotic keratinocytes	PCR	Generalized rash, Cough, Coryza, or Conjunctivitis
		Rocky Mountain Spotted Fever	+	+	+	+	-	-	-	-	R rickettsii serology	Thrombocytopenia, Anemia	-	↑ALT or AST, Hyponatremia	Infarction, edema, and meningeal enhancement	-	Myocardial or conduction abnormalities in echocardiography	-	Immunofluorescent or immunoperoxidase staining of R rickettsii	Clinical criteria and tick exposure	Rash on the palms and soles
		Staphylococcal Scalded Skin Syndrome	+	+	+	+	-	-	+/-	+/-	Anti exfoliatin and anti alpha-toxin antibodies	Leukocytosis with left shift	↑	Blood culture	Pneumonia	-	-	-	Intraepidermal blister, dense superficial perivascular lymphohistiocytic infiltrate	Blood culture and clinical findings	Widespread skin erythema, fluid-filled blisters
		Toxic Epidermal Necrolysis	-	+	+	-	-	-	-	+/-	MicroRNA-124	Normochromic normocytic anemia, Eosinophilia	↑	Fluid loss and electrolyte abnormalities	Tracheobronchial inflammation	-	-	-	Necrotic keratinocytes with full-thickness epithelial necrosis	Histopathology and clinical findings	Erythematous macular rash with purpuric centers
	Cardiovascular disease	Atrial Myxoma	-	-	+/-	-	-	-	-	+/-	Calretinin	Mild anemia, Leukocytosis	↑	↑IL-6	Atrial filling defect larger than a thrombus	-	Tumor location, size, attachment, and mobility in echocardiography	Size, shape, and surface characteristics in MRI	Lipidic cells embedded in a vascular myxoid stroma	Echocardiography	Dyspnea on exertion, Syncope
		Cholesterol Embolism	+/-	+/-	-	-	+	-	-	+	IL-5	Eosinophilia, Leukocytosis	↑	Eosinophiluria	Thoracic and abdominal aortic sources of embolism	Atheroembolism in abdominal aorta and the lower extremity arteries	Excluding an intracardiac source of embolism with echocardiography	-	Birefringent crystals or biconvex needle-shaped ghostly clefts within the arterial lumen	Angiography	Livedo reticularis, Ischemic patches
		Segmental arterial mediolysis	+	-	-	-	+	+	+	+/-	-	Leukocytosis	-	-	Visceral artery aneurysm in CT angiography	Alternating aneurysms and stenoses (beading)	Retroperitoneal hematoma	-	Disruption of the smooth muscle in the media	Angiography	Hematuria, Ischemic colitis
	Systemic disease	Antiphospholipid Syndrome	+	+	-	-	-	-	-	+/-	Antiphospholipid antibodies	Thrombocytopenia, Hemolytic anemia	-	Lupus anticoagulant (LA)	Stroke, Pulmonary embolism, Budd-Chiari syndrome	Thrombus in major vessels	Valve thickening, vegetations, or insufficiency in echocardiography	-	Noninflammatory bland thrombosis without perivascular inflammation	Hx of thrombosis and antiphospholipid antibodies	Miscarriage, Pulmonary hypertension
		Juvenile Idiopathic Arthritis	-	-	-	+	+/-	-	-	-	Rheumatoid factor (RF), S100A12	Lymphocytosis, Thrombocytopenia	↑	Myeloid-related proteins 8/14 (MRP8/14)	Synovial hypertrophy, Joint effusions	Cerebral vasculitis	Inflamed synovium	Bone scanning	Vascular congestion, RBC extravasation, Venular lumen occlusion	Conventional radiography	Evanescent rash, Dactylitis
Diseases			Headache	Fever	Weight loss	Arthralgia	Claudication	Bruit	HTN	Focal neurological disorder	Biomarker	CBC	ESR	Other	CT scan	Angiography	Ultrasound/ Echocardiography	Other	Histopathology	Gold standard	Additional findings
Small-Vessel Vasculitis	ANCA-associated vasculitis	Microscopic polyangiitis	+	-	-	+/-	-	-	-	+	Anti-PR3 antibody (C-ANCA) (40%), Anti-MPO antibody (P-ANCA) (60%)	Leukocytosis, Normocytic anemia	↑	Proteinuria, Erythrocyte casts	Suspected pancreatitis	Mesenteric angiography for differentiating from polyarteritis nodosa	-	Bilateral nodular, and patchy opacities in CXR	Glomerulonephritis with focal necrosis, crescent formation, and lack or paucity of immunoglobulin deposits	Histological confirmation	Rash, Hemoptysis
		Granulomatosis with polyangiitis (Wegener’s)	+	+/-	+/-	-	-	-	-	+	Anti-PR3 antibody (C-ANCA) (90%), Anti-MPO antibody (P-ANCA) (10%)	Leukocytosis, Normochromic normocytic anemia	↑	↑Cr or BUN, Hypoalbuminemia	Consolidation, Patchy or diffuse ground-glass opacities	Occlusion or stenosis of LAD and RCA in coronary angiography	-	Single or multiple nodules and masses with cavitation in CXR	Parenchymal necrosis, Granulomatous inflammation	Histological confirmation	Conjunctivitis, Episcleritis, Uveitis, Optic nerve vasculitis
		Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)	+/-	-	-	+	-	-	-	+	Anti-MPO antibody (P-ANCA) (40%), Eotaxin-3	Eosinophilia, Anemia	↑	↑Cr or BUN, Proteinuria, Erythrocyte casts, ↑IgE levels	Significant enlargement of peripheral pulmonary arteries	Myocardial ischemia and infarction in coronary angiography	Congestive heart failure (CHF) in echocardiography	Extensive air-space opacities in CXR	Small necrotizing granulomas with eosinophilic core surrounded by macrophages and epithelioid giant cells	Histological confirmation	Allergic rhinitis, Asthma, Urticarial rash
		Hydralazine-associated ANCA-associated vasculitis	-	-	-	+	-	-	-	+/-	Anti-MPO antibody (P-ANCA), Anti-histone antibodies	Anemia	-	↑Cr or BUN, Hypoalbuminemia	Bilateral pulmonary infiltrates	Aneurysms or occlusions of the visceral arteries	-	-	Pauci-immune necrotizing and crescentic glomerulonephritis	Histological confirmation	Sinusitis, Hemoptysis
	Immune complex small-vessel vasculitis	Anti-glomerular basement membrane disease	+	+/-	-	-	-	-	+	-	Anti-GBM antibodies	Hypochromic microcytic anemia, Thrombocytopenia	-	↓C3 level	Pulmonary hemorrhage	-	Normal kidneys	Alveolar infiltrates spreading from the hilum in CXR	Cellular crescents in the glomeruli, Intra-alveolar hemorrhages	Anti-GBM antibodies	Hemoptysis, Hematuria
		Cryoglobulinemic vasculitis	+/-	+/-	-	+	+/-	-	-	-	C4 component	Leukocytosis, Anemia	↑	ANA, hypocomplementemia	R/O underlying malignancy	Stenosis or occlusions of the visceral arteries	Bacterial endocarditis in echocardiography	Interstitial involvement or pleural effusions in CXR	HCV-associated proteins in vasculitic skin, Intraluminal cryoglobulin deposits	Histological confirmation	Acrocyanosis, Retinal hemorrhage, Purpura
		Hepatitis C virus-associated cryoglobulinemic vasculitis	+/-	+/-	+	+	-	-	+	+/-	HCV RNA			↓Serum C4, Positive RF							Palpable purpura, Microscopic hematuria
		IgA vasculitis (Henoch-Schönlein purpura)	-	-	+	+	-	-	-	-											Hematuria
		Hypocomplementemic urticarial vasculitis (anti-C1q vasculitis)	-	-	+/-	+	-	-	-	-
	Gastrointestinal disease	Acute mesenteric ischemia	-	+/-	-	-	-	-	-	-
	Cardiovascular disease	Infective Endocarditis	+	+	+	-	-	-	-	+
		Leukocytoclastic Vasculitis	+	-	-	+	-	-	-	+
	Pulmonary disease	Langerhans Cell Histiocytosis	+/-	-	-	+	-	-	-	-
		Lung Abscess	-	+	+	-	-	-	-	-
		Non-Small Cell Lung Cancer	-	+/-	+	-	-	-	-	+/-
		Small Cell Lung Cancer	-	+/-	+	-	-	-	-	+/-
		Asthma	-	+	+	-	-	-	-	-
		Pulmonary Infarction	+/-	-	-	-	-	-	+	-
	Renal disease	Acute Poststreptococcal Glomerulonephritis	-	-	-	+	-	-	+	+/-
	Hematologic disease	Hemolytic-Uremic Syndrome	+	+	-	+	-	-	+	+
		Chronic Lymphocytic Leukemia (CLL)	+	+	+	+	+/-	-	-	+/-
		Multiple Myeloma	+	-	+	+	+	+	+/-	+/-
		Hypereosinophilic Syndrome	+/-	+/-	-	-	-	-	-	-
		Non-Hodgkin Lymphoma	+	+	+	+	+/-	+/-	+/-	+/-
		Serum Sickness	+	+	-	+/-	+/-	-	-	+/-
		Disseminated Intravascular Coagulation	+/-	+	-	+/-	-	-	+	+
		Idiopathic Thrombocytopenic Purpura	+	+/-	-	+	-	-	-	+
		B cell lymphoproliferative disorder	+	+	+	+	+/-	-	-	+
	Systemic disease	Sarcoidosis	+	+	+	+	-	-	-	+/-
		Legionella Infection	+	+	+	+	-	-	-	+/-
		Systemic lupus erythematosus	+	+	+	+	-	-	+	+
		Rheumatoid arthritis	-	-	+	+	+	+	-	-
		Relapsing polychondritis	-	+/-	+/-	+	+	-	-	-
Diseases			Headache	Fever	Weight loss	Arthralgia	Claudication	Bruit	HTN	Focal neurological disorder	Biomarker	CBC	ESR	Other	CT scan	Angiography	Ultrasound/ Echocardiography	Other	Histopathology	Gold standard	Additional findings
Variable-vessel vasculitis	Behçet’s syndrome		-	-	-	+	-	-	+/-	-
	Cogan's syndrome		+/-	-	-	+/-	-	-	-	+											Red eye, Hearing loss, Vertigo
	Gastrointestinal disease	Inflammatory Bowel Disease	+/-	+	+	+	+	-	-	-
		Whipple's disease	+	+/-	+	+	+	+	+	+
		Sjögren's syndrome	-	-	+/-	+	-	-	-	-
Single-organ vasculitis	Primary central nervous system vasculitis		+	+	+	-	+	-	+	+	von Willebrand factor antigen (vWF)
	Infectious disease	Aspergillosis	+	+	+	-	-	-	-	+
		Histoplasmosis	+	+	+	+	+	-	-	+
		Herpes Simplex Encephalitis	+	+	-	-	-	-	-	+
	Systemic disease	Eclampsia	+	+	-	+	-	-	+	+
		Fibromuscular dysplasia	+	-	+/-	+	+	+	+	+/-	Transforming growth factor β (TGF-β)	Normal	↑	↑ Cr or BUN	Alternating stenosis and dilatations in CT angiography	Stenosis in the renal arteries	Luminal narrowing alternating with dilatation (Beads sign)	Focal concentric, long-segment tubular stenosis or outpouching in MRA	Fibrodysplastic changes, Collagen deposition	Digital subtraction angiography (DSA)	Spontaneous coronary artery dissection (SCAD)