Differentiating vasculitis from other diseases

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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:

Overview

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[1] + +/- + - + + +/- +/- 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[2] + - + +/- - - - +/- 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[3] + - - - - - +/- + - 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[4] +/- - +/- - - - + + 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[5] +/- - +/- - +/- - - + 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[6] + - +/- + + + + +/- 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[7] - - - + +/- +/- - +/- 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)[8] + - +/- + - - - - 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[9] +/- - - +/- +/- - + + 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[10] + + + + + + +/- +/- 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[11] +/- +/- + + +/- +/- + - 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[12] - + +/- + + - +/- - 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[13] + + + + - - - +/- B19 DNA, ↓Reticulocyte count Anemia anti–parvovirus B19 IgM - - Hydrops in fetal ultrasonography - - B19 DNA Purpuric rash, Erythema multiforme
Scarlet fever[14] + + +/- + - - - - 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[15] + + + + - - - +/- 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[16] + + + + - - - - 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[17] + + + + +/- - - - 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[18] +/- + +/- + +/- - - - 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[19] +/- + +/- + - - - - 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[20] + + + + - - - - 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[21] + + + + - - +/- +/- 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[22] - + + - - - - +/- 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[23] - - +/- - - - - +/- 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[24] +/- +/- - - + - - + 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[25] + - - - + + + +/- - 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[26] + + - - - - - +/- 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[27] - - - + +/- - - - 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[28] + - - +/- - - - + 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)[29] + +/- +/- - - - - + 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)[30]

+/- - - + - - - + 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 rhinitisAsthma, Urticarial rash
Hydralazine-associated ANCA-associated vasculitis[31] - - - + - - - +/- 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[32] + +/- - - - - + - 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[33] +/- +/- - + +/- - - - C4 component LeukocytosisAnemia 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[34] +/- +/- + + - - + +/- HCV RNA, Cryoglobulins LeukocytosisAnemia Serum C4, Positive RF Increased hepatic echogenicity - Hepatomegaly, Splenomegaly Increased hepatic echogenicity in MRI Vasculitic skin, Antigen infilteration in lesions HCV RNA, Histological confirmation Palpable purpura, Microscopic hematuria
IgA vasculitis (Henoch-Schönlein purpura)[35] - - + + - - - - IgA Normochromic anemia, Leukocytosis  Stool OB, ↓C3, ↓C4 - - Increased bowel wall thickness, hematomas, peritoneal fluid, and intussusception Dilated loops of bowel consistent in abdominal X-ray Leukocytoclastic vasculitis in postcapillary venules with IgA deposition History and physical examination Hematuria, Palpable purpura
Hypocomplementemic urticarial vasculitis (anti-C1q vasculitis)[36] - - +/- + - - - - C1q Mild anemia ANA, ↓C1q, ↓C3, ↓C4 - - Hepatomegaly, Splenomegaly - Deposits of immunoglobulins, complement, or fibrin around blood vessels Urticaria,

Histological confirmation

Urticaria, Hematuria
Gastrointestinal disease Acute mesenteric ischemia[37] - +/- - - - - - - I-FABP, Alpha-GST, Ischemia-modified albumin (IMA) Leukocytosis, ↑HCT -  ↑Amylase Bowel wall thickening, Intestinal pneumatosis, Portomesenteric thrombosis Mesenteric venous thrombosis  Arterial stenosis or occlusion of the celiac or superior mesenteric arteries in duplex ultrasound Ileus with distended loops of bowel, Bowel wall thickening in abdominal X-ray Superficial mucosal hemorrhage, edema and necrosis History and physical examination Abdominal pain, Distension, Absent bowel sounds
Cardiovascular disease Infective Endocarditis[38] + + + - - - - + NT-proBNP Normochromic-normocytic anemia Hyperglobulinemia, Cryoglobulinemia Metastatic infections, such as splenic infarct, renal infarcts, or psoas abscess - Vegetation, abscess, or new dehiscence of a prosthetic valvein echocardiography Vertebral osteomyelitis in MRI Vegetation or intracardiac abscess demonstrating active endocarditis Echocardiography (TTE) Janeway lesions, Osler nodes, Roth spots, Vertebral osteomyelitis
Leukocytoclastic Vasculitis[39] + - - + - - - + IgM, IgA, IgG Leukocytosis, Anemia Hypocomplementemia - Vascular stenosis and obstruction in visceral angiography - - Perivascular inflammatory infiltrate of neutrophils with leukocytoclasia (releasing nuclear debris) Histological confirmation Palpable purpura, Petechiae 
Pulmonary disease Langerhans Cell Histiocytosis[40] +/- - - + - - - - CD1a, CD207,BRAF-V600E Anemia Hypercalcemia Pulmonary cysts and nodules, Bone lytic lesions - Hepatomegaly, Splenomegaly Cerebellum and pons hyperintensity in MRI Birbeck granules by electron microscopy Histological confirmation Brown to purplish papules, Eczematous rash
Non-Small Cell Lung Cancer[41] - +/- + - - - - +/- EGFR, ROS1, EML4-ALK,  PD-L1 Leukocytosis, Anemia Hypercalcemia, Hyponatremia Pulmonary lesion or mass - Pulmonary marginal lesions Staging and response to treatment in PET-CT Adenocarcinoma, Squamous cell carcinoma High resolution CT-scan Cough, Hemoptysis
Small Cell Lung Cancer - +/- + - - - - +/- Hyponatremia Large hilar mass with bulky mediastinal adenopathy Cough, Hemoptysis
Asthma - + + - - - - -
Pulmonary Infarction +/- - - - - - + -
Renal disease Acute Poststreptococcal Glomerulonephritis - - - + - - + +/-
Hematologic disease Hemolytic-Uremic Syndrome + + - + - - + +
Chronic Lymphocytic Leukemia (CLL) + + + + +/- - - +/-
Multiple Myeloma + - + + + + +/- +/- Ig light chain
Hypereosinophilic Syndrome +/- +/- - - - - - - IgE
Non-Hodgkin Lymphoma + + + + +/- +/- +/- +/-
Serum Sickness + + - +/- +/- - - +/-
Disseminated Intravascular Coagulation +/- + - +/- - - + +
Idiopathic Thrombocytopenic Purpura + +/- - + - - - +
B cell lymphoproliferative disorder + + + + +/- - - +
Systemic disease Sarcoidosis + + + + - - - +/- e
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[6] + - +/- + + + + +/- 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)

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