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Small-sized vessel vasculitis with fever and headache


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Eiman Ghaffarpasand, M.D. [2]

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
Small-Vessel Vasculitis ANCA-associated vasculitis Granulomatosis with polyangiitis (Wegener’s)[1] + +/- +/- – – – – + 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

Immune complex small-vessel vasculitis Anti-glomerular basement membrane disease[2] + +/- – – – – + – 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[3] +/- +/- – + +/- – – – 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[4] +/- +/- + + – – + +/- 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
Cardiovascular disease Infective Endocarditis[5] + + + – – – – + 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
Hematologic disease Hemolytic-Uremic Syndrome[6] + + – + – – + + 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)[7] + + + + +/- – – +/- CD5, CD19, CD20, IgVH Absolute lymphocytosis, Smudge cells ↑ Flow cytometry Staging – – – Large atypical cells, cleaved cells, and prolymphocytes  Chromosomal and genetic testing Easy bruising
Hypereosinophilic Syndrome[8] +/- +/- – – – – – – 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[9] + + + + +/- +/- +/- +/- 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[10] + + – +/- +/- – – +/- 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[11] +/- + – +/- – – + + 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[12] + +/- – + – – – + 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[13] + + + + – – – +/-  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[14] + + + + – – – +/- 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[15] + + + + – – + + 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

References

  1. ↑ Kubaisi B, Abu Samra K, Foster CS (2016). “Granulomatosis with polyangiitis (Wegener’s disease): An updated review of ocular disease manifestations”. Intractable Rare Dis Res. 5 (2): 61–9. doi:10.5582/irdr.2016.01014. PMC 4869584. PMID 27195187.
  2. ↑ McAdoo SP, Pusey CD (July 2017). “Anti-Glomerular Basement Membrane Disease”. Clin J Am Soc Nephrol. 12 (7): 1162–1172. doi:10.2215/CJN.01380217. PMID 28515156.
  3. ↑ Ferri C, Mascia MT (January 2006). “Cryoglobulinemic vasculitis”. Curr Opin Rheumatol. 18 (1): 54–63. PMID 16344620.
  4. ↑ Guo QY, Wu M, Wang YW, Sun GD (2017). “Hepatitis C virus-associated cryoglobulinemia with membrano-proliferative glomerulonephritis treated with prednisolone and interferon: A case report”. Exp Ther Med. 14 (2): 1395–1398. doi:10.3892/etm.2017.4671. PMC 5525644. PMID 28810602.
  5. ↑ McDonald JR (2009). “Acute infective endocarditis”. Infect Dis Clin North Am. 23 (3): 643–64. doi:10.1016/j.idc.2009.04.013. PMC 2726828. PMID 19665088.
  6. ↑ Corrigan JJ, Boineau FG (November 2001). “Hemolytic-uremic syndrome”. Pediatr Rev. 22 (11): 365–9. PMID 11691946.
  7. ↑ Byrd JC, Stilgenbauer S, Flinn IW (2004). “Chronic lymphocytic leukemia”. Hematology Am Soc Hematol Educ Program: 163–83. doi:10.1182/asheducation-2004.1.163. PMID 15561682.
  8. ↑ Klion A (2009). “Hypereosinophilic syndrome: current approach to diagnosis and treatment”. Annu. Rev. Med. 60: 293–306. doi:10.1146/annurev.med.60.062107.090340. PMID 19630574.
  9. ↑ Shankland KR, Armitage JO, Hancock BW (September 2012). “Non-Hodgkin lymphoma”. Lancet. 380 (9844): 848–57. doi:10.1016/S0140-6736(12)60605-9. PMID 22835603.
  10. ↑ Lin RY (January 1986). “Serum sickness syndrome”. Am Fam Physician. 33 (1): 157–62. PMID 2867672.
  11. ↑ Venugopal A (2014). “Disseminated intravascular coagulation”. Indian J Anaesth. 58 (5): 603–8. doi:10.4103/0019-5049.144666. PMC 4260307. PMID 25535423.
  12. ↑ Nomura S (2016). “Advances in Diagnosis and Treatments for Immune Thrombocytopenia”. Clin Med Insights Blood Disord. 9: 15–22. doi:10.4137/CMBD.S39643. PMC 4948655. PMID 27441004.
  13. ↑ Chiarchiaro J, Chen BB, Gibson KF (2016). “New molecular targets for the treatment of sarcoidosis”. Curr Opin Pulm Med. 22 (5): 515–21. doi:10.1097/MCP.0000000000000304. PMC 5152532. PMID 27454074.
  14. ↑ Murdoch DR (January 2003). “Diagnosis of Legionella infection”. Clin. Infect. Dis. 36 (1): 64–9. doi:10.1086/345529. PMID 12491204.
  15. ↑ Tsokos, George C. (2011). “Systemic Lupus Erythematosus”. New England Journal of Medicine. 365 (22): 2110–2121. doi:10.1056/NEJMra1100359. ISSN 0028-4793.

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