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* [[Granulomatosis with polyangiitis|Granulomatosis with polyangitis]] ([[Wegener's granulomatosis|Wegner's granulomatosis]])
* [[Granulomatosis with polyangiitis|Granulomatosis with polyangitis]] ([[Wegener's granulomatosis|Wegner's granulomatosis]])
|
|
* [[Necrotizing]] [[granulomas]] ([[Nasopharynx]], [[lungs]], [[kidneys]])
* [[Necrotizing]] [[granulomas]] ([[lungs]], [[kidneys]])
* [[Conjunctivitis]]
* [[Conjunctivitis]]
* Ulceration of the [[cornea]]
* Corneal ulceration
* [[Episcleritis]]
* [[Episcleritis]]
* [[Peripheral neuropathy]]
* [[Peripheral neuropathy]]

Revision as of 18:07, 2 May 2018


Goodpasture syndrome Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Ali Poyan Mehr, M.D. [2]Associate Editor(s)-in-Chief: Krzysztof Wierzbicki M.D. [3]

Overview

Goodpasture syndrome should be differentiated from other diseases presenting as fever, hematuria and hemoptysis. It should also be differentiated from other causes of small vessel vasculitis.

Differential Diagnosis

Goodpasture syndrome should be differentiated from other diseases presenting as fever, hematuria, hemoptysis. It should also be differentiated from other causes of small vessel vasculitis. The differentials include the following:

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
Goodpasture syndrome or Anti-glomerular basement membrane disease[1] + +/- - - - - + - 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
Small-Vessel Vasculitis ANCA-associated vasculitis Granulomatosis with polyangiitis (Wegener’s)[2] + +/- +/- - - - - + 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 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
Gastrointestinal disease Acute mesenteric ischemia[5] - +/- - - - - - - 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[6] + + + - - - - + 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
Pulmonary disease Non-Small Cell Lung Cancer[7] - +/- + - - - - +/- 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[8] - +/- + - - - - +/- 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
Hematologic disease Hemolytic-Uremic Syndrome[9] + + - + - - + + 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)[10] + + + + +/- - - +/- 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[11] +/- +/- - - - - - - 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[12] + + + + +/- +/- +/- +/- 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[13] + + - +/- +/- - - +/- 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[14] +/- + - +/- - - + + 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[15] + +/- - + - - - + 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[16] + + + + - - - +/-  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[17] + + + + - - - +/- 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[18] + + + + - - + + 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
Relapsing polychondritis[19] - +/- +/- + + - - - - 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

Differentials Based On Renal Involvement

Goodpasture syndrome is associated with renal involvement in the form of rapidly progressive glomerulonephritis. The various types of glomerulonephritides should be differentiated from each other based on associations, presence of pitting edema, hemeturia, hypertension, hemoptysis, oliguria, peri-orbital edema, hyperlipidemia, type of antibodies, light and electron microscopic features. The following table differentiates between various types of glomerulonephritides:[20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43]

Glomerulonephritis Sub-entity Causes and associations History and Symtoms Laboratory Findings
Hyperlipidemia and hypercholesterolemia Nephrotic features Nephritic features ANCA Anti-glomerular basement membrane antibody (Anti-GBM antibody) Immune complex formation Light microscope Electron microscope Immunoflourescence pattern
History Pitting edema Hemeturia (pre-dominantly microscopic) Hypertension Hemoptysis Oliguria Peri-orbital edema
Non-proliferative Minimal change disease

+

-

-

-

+/-

-

+

+

-

-

-

-

  • Normal

-

Focal segmental glomerulosclerosis
  • Adults
 + - - - +/- - + + - - - - -
Membranous glomerulonephritis + - - - +/- - + + - - - + -
Proliferative IgA nephropathy +/- + + - + +/- - - + - - +
  • Crescent formation
 -
Rapidly progressive glomerulonephritis
  • Young adults
 +/- + + + + + - - + - + + + (Linear)
+/- + + + + + - - + - - + + (Granular)
+/- + + + + + - - + + (C-ANCA) - - - (pauci-immune) +/-
+/- + + + + + - - +

+ (C-ANCA)

- - - (pauci-immune) -
+/- + + + + + - - +

+ (P-ANCA)

- - - (pauci-immune) -
Membranoproliferative glomerulonephritis +/- + + + + + - + - - - + + (Granular)

References

  1. ↑ 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.
  2. ↑ 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.
  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. ↑ Sise MJ (February 2014). "Acute mesenteric ischemia". Surg. Clin. North Am. 94 (1): 165–81. doi:10.1016/j.suc.2013.10.012. PMID 24267504.
  6. ↑ 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.
  7. ↑ Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA (2008). "Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship". Mayo Clin Proc. 83 (5): 584–94. doi:10.4065/83.5.584. PMC 2718421. PMID 18452692.
  8. ↑ Jackman DM, Johnson BE (2005). "Small-cell lung cancer". Lancet. 366 (9494): 1385–96. doi:10.1016/S0140-6736(05)67569-1. PMID 16226617.
  9. ↑ Corrigan JJ, Boineau FG (November 2001). "Hemolytic-uremic syndrome". Pediatr Rev. 22 (11): 365–9. PMID 11691946.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ Lin RY (January 1986). "Serum sickness syndrome". Am Fam Physician. 33 (1): 157–62. PMID 2867672.
  14. ↑ Venugopal A (2014). "Disseminated intravascular coagulation". Indian J Anaesth. 58 (5): 603–8. doi:10.4103/0019-5049.144666. PMC 4260307. PMID 25535423.
  15. ↑ 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.
  16. ↑ 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.
  17. ↑ Murdoch DR (January 2003). "Diagnosis of Legionella infection". Clin. Infect. Dis. 36 (1): 64–9. doi:10.1086/345529. PMID 12491204.
  18. ↑ Tsokos, George C. (2011). "Systemic Lupus Erythematosus". New England Journal of Medicine. 365 (22): 2110–2121. doi:10.1056/NEJMra1100359. ISSN 0028-4793.
  19. ↑ Emmungil H, Aydın SZ (2015). "Relapsing polychondritis". Eur J Rheumatol. 2 (4): 155–159. doi:10.5152/eurjrheum.2015.0036. PMC 5047229. PMID 27708954.
  20. ↑ Saha TC, Singh H (November 2006). "Minimal change disease: a review". South. Med. J. 99 (11): 1264–70. doi:10.1097/01.smj.0000243183.87381.c2. PMID 17195422.
  21. ↑ Saleem MA, Kobayashi Y (2016). "Cell biology and genetics of minimal change disease". F1000Res. 5. doi:10.12688/f1000research.7300.1. PMC 4821284. PMID 27092244.
  22. ↑ Keskar V, Jamale TE, Kulkarni MJ, Kiggal Jagadish P, Fernandes G, Hase N (October 2013). "Minimal-change disease in adolescents and adults: epidemiology and therapeutic response". Clin Kidney J. 6 (5): 469–72. doi:10.1093/ckj/sft063. PMC 4438390. PMID 26064510.
  23. ↑ Chugh SS, Clement LC, Macé C (February 2012). "New insights into human minimal change disease: lessons from animal models". Am. J. Kidney Dis. 59 (2): 284–92. doi:10.1053/j.ajkd.2011.07.024. PMC 3253318. PMID 21974967.
  24. ↑ Rosenberg AZ, Kopp JB (March 2017). "Focal Segmental Glomerulosclerosis". Clin J Am Soc Nephrol. 12 (3): 502–517. doi:10.2215/CJN.05960616. PMC 5338705. PMID 28242845.
  25. ↑ Jefferson JA, Shankland SJ (September 2014). "The pathogenesis of focal segmental glomerulosclerosis". Adv Chronic Kidney Dis. 21 (5): 408–16. doi:10.1053/j.ackd.2014.05.009. PMC 4149756. PMID 25168829.
  26. ↑ Gephardt GN, Tubbs RR, Popowniak KL, McMahon JT (October 1986). "Focal and segmental glomerulosclerosis. Immunohistologic study of 20 renal biopsy specimens". Arch. Pathol. Lab. Med. 110 (10): 902–5. PMID 2429634.
  27. ↑ Lai WL, Yeh TH, Chen PM, Chan CK, Chiang WC, Chen YM, Wu KD, Tsai TJ (February 2015). "Membranous nephropathy: a review on the pathogenesis, diagnosis, and treatment". J. Formos. Med. Assoc. 114 (2): 102–11. doi:10.1016/j.jfma.2014.11.002. PMID 25558821.
  28. ↑ Wasserstein AG (April 1997). "Membranous glomerulonephritis". J. Am. Soc. Nephrol. 8 (4): 664–74. PMID 10495797.
  29. ↑ Suzuki H, Kiryluk K, Novak J, Moldoveanu Z, Herr AB, Renfrow MB, Wyatt RJ, Scolari F, Mestecky J, Gharavi AG, Julian BA (October 2011). "The pathophysiology of IgA nephropathy". J. Am. Soc. Nephrol. 22 (10): 1795–803. doi:10.1681/ASN.2011050464. PMC 3892742. PMID 21949093.
  30. ↑ Wyatt RJ, Julian BA (June 2013). "IgA nephropathy". N. Engl. J. Med. 368 (25): 2402–14. doi:10.1056/NEJMra1206793. PMID 23782179.
  31. ↑ He S, Wu Z (November 2011). "Gene-based Higher Criticism methods for large-scale exonic single-nucleotide polymorphism data". BMC Proc. 5 Suppl 9: S65. doi:10.1186/1753-6561-5-S9-S65. PMC 3287904. PMID 22373436.
  32. ↑ Higgins RM, Goldsmith DJ, Connolly J, Scoble JE, Hendry BM, Ackrill P, Venning MC (January 1996). "Vasculitis and rapidly progressive glomerulonephritis in the elderly". Postgrad Med J. 72 (843): 41–4. PMC 2398323. PMID 8746284.
  33. ↑ Jennette JC (March 2003). "Rapidly progressive crescentic glomerulonephritis". Kidney Int. 63 (3): 1164–77. doi:10.1046/j.1523-1755.2003.00843.x. PMID 12631105.
  34. ↑ Bolton WK (November 1996). "Goodpasture's syndrome". Kidney Int. 50 (5): 1753–66. PMID 8914046.
  35. ↑ Mathew TH, Hobbs JB, Kalowski S, Sutherland PW, Kincaid-Smith P (February 1975). "Goodpasture's syndrome: normal renal diagnostic findings". Ann. Intern. Med. 82 (2): 215–8. PMID 1090223.
  36. ↑ Renaudineau Y, Le Meur Y (October 2008). "Renal involvement in Wegener's granulomatosis". Clin Rev Allergy Immunol. 35 (1–2): 22–9. doi:10.1007/s12016-007-8066-6. PMID 18172777.
  37. ↑ Weiss MA, Crissman JD (October 1984). "Renal biopsy findings in Wegener's granulomatosis: segmental necrotizing glomerulonephritis with glomerular thrombosis". Hum. Pathol. 15 (10): 943–56. PMID 6384024.
  38. ↑ Sinico RA, Di Toma L, Maggiore U, Tosoni C, Bottero P, Sabadini E, Giammarresi G, Tumiati B, Gregorini G, Pesci A, Monti S, Balestrieri G, Garini G, Vecchio F, Buzio C (May 2006). "Renal involvement in Churg-Strauss syndrome". Am. J. Kidney Dis. 47 (5): 770–9. doi:10.1053/j.ajkd.2006.01.026. PMID 16632015.
  39. ↑ Cartin-Ceba R, Keogh KA, Specks U, Sethi S, Fervenza FC (September 2011). "Rituximab for the treatment of Churg-Strauss syndrome with renal involvement". Nephrol. Dial. Transplant. 26 (9): 2865–71. doi:10.1093/ndt/gfq852. PMC 3218640. PMID 21325353.
  40. ↑ Chung SA, Seo P (August 2010). "Microscopic polyangiitis". Rheum. Dis. Clin. North Am. 36 (3): 545–58. doi:10.1016/j.rdc.2010.04.003. PMC 2917831. PMID 20688249.
  41. ↑ Pagnoux C (March 2008). "[Wegener's granulomatosis and microscopic polyangiitis]". Rev Prat (in French). 58 (5): 522–32. PMID 18524109.
  42. ↑ Alchi B, Jayne D (August 2010). "Membranoproliferative glomerulonephritis". Pediatr. Nephrol. 25 (8): 1409–18. doi:10.1007/s00467-009-1322-7. PMC 2887509. PMID 19908070.
  43. ↑ Davis AE, Schneeberger EE, Grupe WE, McCluskey RT (May 1978). "Membranoproliferative glomerulonephritis (MPGN type I) and dense deposit disease (DDD) in children". Clin. Nephrol. 9 (5): 184–93. PMID 657595.

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