Goodpasture syndrome differential diagnosis

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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
Small-Vessel Vasculitis	ANCA-associated vasculitis	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
	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, 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	-	+/-	-	-	-	-	-	-	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	+	+	+	-	-	-	-	+	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	-	+/-	+	-	-	-	-	+/-	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	-	+/-	+	-	-	-	-	+/-	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	+	+	-	+	-	-	+	+	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)	+	+	+	+	+/-	-	-	+/-	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	+/-	+/-	-	-	-	-	-	-	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	+	+	+	+	+/-	+/-	+/-	+/-	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	+	+	-	+/-	+/-	-	-	+/-	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	+/-	+	-	+/-	-	-	+	+	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	+	+/-	-	+	-	-	-	+	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	+	+	+	+	-	-	-	+/-	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	+	+	+	+	-	-	-	+/-	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	+	+	+	+	-	-	+	+	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	-	+/-	+/-	+	+	-	-	-	-	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