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==Overview==
==Overview==
Vasculitis means [[inflammation]] of a [[blood vessel]]. Vasculitis is classified based on the size of vessels which are involved. Large sized-vessel vasculitis mostly happens in major vessels of the body, such as [[Takayasu's Arteritis]] and [[Temporal arteritis|temporal Arteritis]]. Medium sized-vessel vasculitis includes [[Kawasaki's Disease]] and [[Polyarteritis Nodosa]]. Small sized-vessel vasculitis commonly manifests as skin lesions and includes [[Churg-Strauss Syndrome]], [[leukocytoclastic vasculitis]], [[Henoch-Schonlein Purpura]], and [[Wegener's Granulomatosis]]. Variable sized-vessel vasculitis are [[Sjogren syndrome]] and [[Cogan syndrome]]. Single organ vasculitis is basically primary [[central nervous system]] angiitis. As the affected vessels are vary in size.
Vasculitis means [[inflammation]] of a [[blood vessel]]. Vasculitis is classified based on the size of vessels which are involved. Large sized-vessel vasculitis mostly happens in major vessels of the body, such as [[Takayasu's Arteritis]] and [[Temporal arteritis|temporal Arteritis]]. Medium sized-vessel vasculitis includes [[Kawasaki's Disease]] and [[Polyarteritis Nodosa]]. Small sized-vessel vasculitis commonly manifests as skin lesions and includes [[Churg-Strauss Syndrome]], [[leukocytoclastic vasculitis]], [[Henoch-Schonlein Purpura]], and [[Wegener's Granulomatosis]]. Variable sized-vessel vasculitis are [[Sjogren syndrome]] and [[Cogan syndrome]]. Single organ vasculitis is basically primary [[central nervous system]] angiitis. As the affected vessels are vary in size, the affected organs could be different among patients which leads to different disease presentation and severities. This spectrum of diseases could be primary or secondary to another conditions like [[sepsis]]. A high degree of level of suspicious is necessary when encounter a patients with appropriate clinical manifestation to lead to final diagnosis. Diagnosis is based on a combination of clinical scenario, lab findings, and imaging findings. Although the definite diagnostic modality is tissue biopsy and microscopic findings. The diseases course could be acute although they usually presents with constitutional symptoms and chronic progression .
==Classification ==
== Classification ==
=== '''Large-sized vessel''' vasculitis ===
=== '''Large-sized vessel''' vasculitis ===
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Eiman Ghaffarpasand, M.D. [2]
Overview
Vasculitis means inflammation of a blood vessel . Vasculitis is classified based on the size of vessels which are involved. Large sized-vessel vasculitis mostly happens in major vessels of the body, such as Takayasu's Arteritis and temporal Arteritis . Medium sized-vessel vasculitis includes Kawasaki's Disease and Polyarteritis Nodosa . Small sized-vessel vasculitis commonly manifests as skin lesions and includes Churg-Strauss Syndrome , leukocytoclastic vasculitis , Henoch-Schonlein Purpura , and Wegener's Granulomatosis . Variable sized-vessel vasculitis are Sjogren syndrome and Cogan syndrome . Single organ vasculitis is basically primary central nervous system angiitis. As the affected vessels are vary in size, the affected organs could be different among patients which leads to different disease presentation and severities. This spectrum of diseases could be primary or secondary to another conditions like sepsis . A high degree of level of suspicious is necessary when encounter a patients with appropriate clinical manifestation to lead to final diagnosis. Diagnosis is based on a combination of clinical scenario, lab findings, and imaging findings. Although the definite diagnostic modality is tissue biopsy and microscopic findings. The diseases course could be acute although they usually presents with constitutional symptoms and chronic progression.
Classification
Large-sized vessel vasculitis
Medium-sized vessel vasculitis
Small-sized vessel vasculitis
Variable-sized vessel vasculitis
Single organ vasculitis
Causes in Alphabetical Order
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3
Differentiating Vasculitis from Other Diseases
As vasculitis manifests in a variety of clinical forms, differentiation must be established in accordance with the particular subtype.
To review the differential diagnosis of large-sized vessel vasculitis, click here .
To review the differential diagnosis of large-sized vessel vasculitis with weight loss, click here .
To review the differential diagnosis of large-sized vessel vasculitis with arthralgia, click here .
To review the differential diagnosis of large-sized vessel vasculitis with claudication, click here .
To review the differential diagnosis of large-sized vessel vasculitis with hypertension, click here .
To review the differential diagnosis of medium-sized vessel vasculitis, click here .
To review the differential diagnosis of medium-sized vessel vasculitis with headache, click here .
To review the differential diagnosis of medium-sized vessel vasculitis with fever, click here .
To review the differential diagnosis of medium-sized vessel vasculitis with weight loss, click here .
To review the differential diagnosis of medium-sized vessel vasculitis with arthralgia, click here .
To review the differential diagnosis of medium-sized vessel vasculitis with claudication, click here .
To review the differential diagnosis of medium-sized vessel vasculitis with bruit, click here .
To review the differential diagnosis of medium-sized vessel vasculitis with hypertension, click here .
To review the differential diagnosis of medium-sized vessel vasculitis with focal neurological sign, click here .
To review the differential diagnosis of medium-sized vessel vasculitis with headache, fever, and focal neurological sign, click here .
To review the differential diagnosis of medium-sized vessel vasculitis with headache, fever, weight loss, and arthralgia, click here .
To review the differential diagnosis of medium-sized vessel vasculitis with headache, fever, weight loss, arthralgia, claudication, bruit, and hypertension, click here .
To review the differential diagnosis of small-sized vessel vasculitis, click here .
To review the differential diagnosis of small-sized vessel vasculitis with headache, click here .
To review the differential diagnosis of small-sized vessel vasculitis with fever, click here .
To review the differential diagnosis of small-sized vessel vasculitis with weight loss, click here .
To review the differential diagnosis of small-sized vessel vasculitis with arthralgia, click here .
To review the differential diagnosis of small-sized vessel vasculitis with claudication, click here .
To review the differential diagnosis of small-sized vessel vasculitis with hypertension, click here .
To review the differential diagnosis of small-sized vessel vasculitis with focal neurological sign, click here .
To review the differential diagnosis of small-sized vessel vasculitis with fever and headache, click here .
To review the differential diagnosis of small-sized vessel vasculitis with fever and weight loss, click here .
To review the differential diagnosis of small-sized vessel vasculitis with fever and arthralgia, click here .
To review the differential diagnosis of small-sized vessel vasculitis with fever and claudication, click here .
To review the differential diagnosis of small-sized vessel vasculitis with fever and focal neurological sign, click here .
To review the differential diagnosis of small-sized vessel vasculitis with fever, weight loss, and arthralgia, click here .
To review the differential diagnosis of small-sized vessel vasculitis with fever, weight loss, and focal neurological sign, click here .
To review the differential diagnosis of small-sized vessel vasculitis with fever, headache, weight loss, arthralgia, and claudication, click here .
To review the differential diagnosis of small-sized vessel vasculitis with fever, headache,weight loss, arthralgia, claudication, hypertension, and focal neurological sign, click here .
To review the differential diagnosis of variable-sized vessel vasculitis, click here .
To review the differential diagnosis of single organ vasculitis, click here .
Abbreviations:
ABG= Arterial blood gas , ANA= Antinuclear antibody , ANP= Atrial natriuretic peptide , ASO= Antistreptolysin O antibody , 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 , PCR= Polymerase chain reaction , PFT= Pulmonary function test .
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 rhinitis , Asthma , 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
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 [34]
+/-
+/-
+
+
-
-
+
+/-
HCV RNA , Cryoglobulins
Leukocytosis , Anemia
↑
↓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 valve in 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 [42]
-
+/-
+
-
-
-
-
+/-
p53 , Thyroid transcription factor-1 (TTF1)
Anemia
↑
Hyponatremia
Large hilar mass with bulky mediastinal adenopathy
-
Endobronchial ultrasound (EBUS)
Standard staging
Spindled cells with dark nuclei , scant cytoplasm , and fine, granular nuclear chromatin
High resolution CT-scan
Cough , Hemoptysis
Pulmonary Infarction [43]
+/-
-
-
-
-
-
+
-
D-dimer
Mild leukocytosis , Mild anemia
-
Hypoxemia , Hypocarbia or Hypercarbia , Respiratory alkalosis
Pulmonary embolism
Low-density filling defect within the pulmonary artery
Pericardial effusion in echocardiography
Pulmonary infiltrates, atelectasis , and pleural effusions in CXR
Infarct induced apoptosis
Pulmonary artery angiography
Cough , Hemoptysis
Renal disease
Acute Poststreptococcal Glomerulonephritis [44]
-
-
-
+
-
-
+
+/-
Antistreptolysin-O (ASO) titers
Leukocytosis
↑
Hypocomplementemia
-
-
Normal to slightly enlarged kidneys
Central venous congestion in a hilar pattern in CXR
Hypercellularity of endothelial and mesangial cells , Infiltration of the glomerular tuft with polymorphonuclear cells
Histological confirmation
Hematuria
Hematologic disease
Hemolytic-Uremic Syndrome [45]
+
+
-
+
-
-
+
+
C5b-9 , ADAMTS13
Anemia , Thrombocytopenia , Reticulocytosis
↑
↑Lactate dehydrogenase (LDH) , Hypercalcemia
Thalami , brainstem , or cerebellum abnormality
Cerebral microangiopathy or hypertension
Hypoechoic kidney
Abnormal hyperintensity in the brain cisterns in MRI
Microthromboses include fibrin thrombi that may occlude the glomerular tuft
Clinical findings coupled with laboratory abnormalities
Hematuria , Proteinuria
Chronic Lymphocytic Leukemia (CLL) [46]
+
+
+
+
+/-
-
-
+/-
CD5 , CD19 , CD20 , IgVH
Absolute lymphocytosis , Smudge cells
↑
Flow cytometry
Staging
-
-
-
Large atypical cells , cleaved cells, and prolymphocytes
Chromosomal and genetic testing
Easy bruising
Multiple Myeloma [47]
+
-
+
+
+
+
+/-
+/-
Ig light chain
Anemia , Thrombocytopenia , Leukopenia
↑
Bone marrow aspiration and biopsy , ↑Cr
Osseous involvement and lytic lesions
Peripheral zone of increased vascularity in lesions
-
Punched-out lesion in skull X-ray
Clonal proliferation of plasma cells
Protein electrophoresis plus conventional X-rays
Constipation
Hypereosinophilic Syndrome [48]
+/-
+/-
-
-
-
-
-
-
IgE , CD117 with CD2
Eosinophilia
-
↑Serum tryptase
Lymphadenopathy and splenomegaly
-
Intracardiac thrombi in echocardiography
-
Reticulin stain for myelofibrosis and tryptase staining for mast cells
Clinical findings coupled with laboratory abnormalities
Splinter hemorrhages , Raynaud phenomenon
Non-Hodgkin Lymphoma [49]
+
+
+
+
+/-
+/-
+/-
+/-
MYC , BCL2 , BCL6 , and TP53
Lymphocytosis , Anemia , Thrombocytopenia
↑
↑Lactate dehydrogenase (LDH) , Hypercalcemia
Enlarged lymph nodes , Hepatosplenomegaly , Filling defects in the liver and spleen
-
Hepatosplenomegaly
Mediastinal lymphadenopathy
Small cleaved or noncleaved, intermediate, or large cell with a follicular or diffuse pattern
Surgically excised tissue biopsy
Easy bruising , Testicular mass , Skin lesion
Serum Sickness [50]
+
+
-
+/-
+/-
-
-
+/-
IL-1 , IL-6 , TNF
Leukopenia
↑
Polyclonal gammopathy , ↑Cr , Cryoglobulinemia
-
-
-
-
Arteritic lesions are focal, necrotizing , and inflammatory involving all layers of the artery
Clinical findings coupled with laboratory abnormalities
Hematuria , Skin rash
Disseminated Intravascular Coagulation [51]
+/-
+
-
+/-
-
-
+
+
Fibrin degradation product (FDP)
Thrombocytopenia , Schistocytes
↑
↑D-dimer , aPTT and PT
Intracranial hemorrhage
-
-
-
Ischemia and necrosis due to fibrin deposition in small and medium-sized vessels
Clinical findings coupled with laboratory abnormalities
Acral cyanosis , Hemorrhagic skin infarctions
Idiopathic Thrombocytopenic Purpura [52]
+
+/-
-
+
-
-
-
+
FC gamma receptors (FCGR) IIb
Anemia , Thrombocytopenia
-
HIV , ANA
R/O other causes
-
R/O splenomegaly
-
Increased number of normal morphologic megakaryocytes
Clinical findings coupled with thrombocytopenia
Easy bruising , Purpura
Systemic disease
Sarcoidosis [53]
+
+
+
+
-
-
-
+/-
IL-2 and IFN-γ
Mild anemia
↑
↑ACE , ↑1, 25-dihydroxyvitamin D
Active alveolitis or fibrosis
-
Hepatosplenomegaly
Bilateral hilar adenopathy
Noncaseating granulomas (NCGs)
Histological confirmation
Heart block , Ocular lesion
Legionella Infection [54]
+
+
+
+
-
-
-
+/-
Inflammatory cytokines
Leukocytosis with left shift , Thrombocytosis
↑
↑D-dimer , FDP , Hyponatremia
Pleural effusion
-
-
Nonspecific and indistinguishable CXR
Intra-alveolar inflammation , Microabscesses in the parenchyma
Sputum culture
Cough , Diarrhea
Systemic lupus erythematosus [55]
+
+
+
+
-
-
+
+
Anti dsDNA , ANA
Leukopenia , Lymphopenia , Anemia , Thrombocytopenia
↑
↑Cr or BUN ,
↑ALT or AST , Proteinuria
Interstitial lung disease, Pneumonitis , Pulmonary emboli , Alveolar hemorrhage
Aneurysms
Pericardial effusion , pulmonary hypertension , or verrucous Libman-Sacks endocarditis in echocardiography
Central nervous system (CNS) lupus white-matter changes in MRI
Staging lupus nephritis
Anti-dsDNA antibody test
Skin rashes or photosensitivity
Rheumatoid arthritis [56]
-
-
+
+
+
+
-
-
RF , Anti-CCP antibody
Anemia
↑
↑Cr or BUN ,
↑ALT or AST , ANA
Microfractures
Aneurysms
Effusions in joints
Basilar invagination with cranial migration of an eroded odontoid peg in MRI
Influx of inflammatory cells into the synovial membrane , with angiogenesis , proliferation of chronic inflammatory cells
Clinical findings coupled anti-CCP antibody
Rheumatoid nodules
Relapsing polychondritis [57]
-
+/-
+/-
+
+
-
-
-
-
Leukocytosis , Anemia
-
Cryoglobulins , ANA , C-ANCA
Calcification of cartilaginous structures
Aortic root dilatation
Aortic root dilatation and degree of aortic regurgitation in echocardiography
Tracheal stenosis in CXR
Chondrolysis, Chondritis , Perichondritis
Clinical findings coupled with imaging
Ear pain and redness, Polyarthritis
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 [58]
-
-
-
+
-
-
+/-
-
CXCL1
Mild anemia , Neutrophilia
↑
Factor V Leiden
Focal CNS lesions
Aneurysm formation and thrombosis areas
Valve vegetations and ventricular thrombi in echocardiography
Meningoencephalitis in MRI
Lymphocytic and plasma cell invasion in the prickle cell layer of the epidermis
Clinical criteria
Genital ulcerations , Oral ulceration
Cogan's syndrome [59]
+/-
-
-
+/-
-
-
-
+
Anti-Hsp70 antibodies
Anemia , Thrombocytosis
↑
RF , ANA
Thickening and enhancement of both posterior sclera
Stenosis , thrombosis or more lesions in aortic root
Aortic insufficiency in echocardiography
Early interstitial keratitis by slit lamp
Muscle necrosis and atrophy resembling myositis
-
Red eye , Hearing loss , Vertigo
Gastrointestinal disease
Inflammatory Bowel Disease [60]
+/-
+
+
+
+
-
-
-
Anti-Saccharomyces cerevisiae antibody (ASCA), P-ANCA
Leukocytosis , Anemia
↑
Iron or vitamin deficiency , Stool OB
Mesenteric fat stranding, bowel wall enhancement, increased vascularity (comb sign)
-
Fistulas , Abscesses , Stenosis
Grossly denuded mucosa with active bleeding in colonoscopy
Crypt abscesses and mucosal ulceration , Granulomas
Endoscopy
GI bleeding
Whipple's disease [61]
+
+/-
+
+
+
+
+
+
CCR6 , Gut-homing marker integrin β7-chain , T whippelii DNA
Mild anemia , Neutrophilia
↑
72-hour fecal fat determination
Nonspecific malabsorption
-
Hepatosplenomegaly
-
Periodic acid-Schiff –positive macrophages infiltration in lamina propria of the small bowel
Broad-spectrum PCR amplifications
Cachexia ,
Glossitis
Sjögren's syndrome [62]
-
-
+/-
+
-
-
-
-
Anti-Ro and Anti-La, Anti-alpha-fodrin antibody
Anemia ,
Leukopenia ,
Eosinophilia
↑
Hypergammaglobulinemia , Low bicarbonate level, Hypokalemia
Salt and pepper or honeycomb appearance in parotid glands
-
Multicystic or reticular pattern in atrophic salivary gland
R/O obstructions or strictures with Sialography
Focal aggregates of lymphocytes
Schirmer test
Keratoconjunctivitis , Gingival inflammation
Single-organ vasculitis
Primary central nervous system vasculitis [63]
+
+
+
-
+
-
+
+
von Willebrand factor antigen (vWF)
Normal
-
CSF pleocytosis , predominantly lymphocytes
Cerebral infarcts or hemorrhages with mass effect , or hydrocephalus
Aneurysm in circle of Willis
-
Progression of the disease or response to therapy in MRI
Chronic granulomatous inflammation and giant cells
Histological confirmation
Skin rash , Purpura
Infectious disease
Aspergillosis [64]
+
+
+
-
-
-
-
+
Aspergillus nucleic acid in blood , Galactomannan
Eosinophilia
↑
↑Serum IgE
Aspergilloma mass within a cavity
Mass effect stenosis
-
Aspergilloma mass within the brain in MRI
Septate hyphae , branching at acute angles, and tissue necrosis with granulomata and blood vessel invasion
Histological confirmation
Hemoptysis , Aspergilloma
Histoplasmosis [65]
+
+
+
+
+
-
-
+
-
Mild anemia
↑
↑ALP , ↑LDH
Cerebral histoplasmosis
-
Valvular involvement in echocardiography
PFT
Presence of yeast forms in tissue through hematoxylin and eosin staining
Sputum cultures
Pneumonia , Mediastinitis
Herpes Simplex Encephalitis [66]
+
+
-
-
-
-
-
+
HSV DNA
Mild lymphocytosis
↑
CSF pleocytosis
Low-density lesions in the temporal and/or frontal lobe
-
-
Hemorrhagic lesion in white matter
Multinuclear giant cells
PCR or brain biopsy
Seizures ,
Vomiting
Systemic disease
Eclampsia [67]
+
+
-
+
-
-
+
+
VEGF , PlGF , Soluble FLT-1
Anemia , Thrombocytopenia , Schistocytes
-
↑Bilirubin , ↓Haptoglobin , ↑LDH , ↑Cr
Cortical hypodense areas in the occipital lobes , Diffuse cerebral edema
-
Poor fetal growth , Oligohydramnios , Abnormal umbilical artery
Increased signal at the gray-white matter junction in MRI
-
24-hour urine study
Seizure , Edema
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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