Granulomatosis with polyangiitis differential diagnosis

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

Granulomatosis with polyangiitis must be differentiated from other diseases that cause purpura, alveolar hemorrhage, fever, arthralgia, myalgia, necrotizing extra-capillary glomerulonephritis, such as Microscopic polyangiitis and Eosinophilic granulomatosis with polyangiitis.

Differentiating Granulomatosis with polyangiits from other Diseases

Granulomatosis with polyangiitis must be differentiated from other diseases that cause purpura, alveolar hemorrhage, necrotizing extra-capillary glomerulonephritis, such as Microscopic polyangiitis and Eosinophilic granulomatosis with polyangiitis.

Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis serological findings
	Eosinophilic granulomatosis with polyangiitis	Granulomatosis with polyangiitis	Microscopic polyangiitis
Cytoplasmic ANCA (cANCA)		90% positive
Perinuclear ANCA (pANCA)	30 to 40% positive		60 to 80% positive
Myeloperoxidase antigen	40% sensitivity	10% sensitivity	30% sensitivity
Proteinase 3 antigen	<5% sensitivity	70-80% sensitivity	60% sensitivity

Differentiating Granulomatosis with polyangiitis from other diseases

Granulomatosis with polyangiitis must be differentiated from other diseases that cause purpura, alveolar hemorrhage, fever, arthralgia, myalgia, necrotizing extra-capillary glomerulonephritis and include:

• mononeuritis multiplex
• venous thrombosis
• necrotizing vasculitis of small-sized vessels
• ear nose throat involvement

Differential diagnosis

Causes of lung cavities	Differentiating Features	Differentiating radiological findings	Diagnosis confirmation
Granulomatosis with polyangiitis (Wegener's)	Women are more commonly effected than man. Kidneys are also involved Upper respiratory tract symptoms , perforation of nasal septum, chronic sinusitis, otitis media, mastoiditis. Lower respiratory tract symptoms, hemoptysis, cough, dyspnea. Renal symptoms, hematuria, red cell casts	Pulmonary nodules with cavities and infiltrates are a frequent manifestation on CXR	Positive for P-ANCA Biopsy of the tissue involved shows necrotizing granulomas
Malignancy (Primary lung cancer)	Elderly male or female Chronic smokers Presents with a low-grade fever, absence of leukocytosis, systemic complaints weight loss, fatigue Absence of factors that predispose to gastric content aspiration, no response to antibiotics within 10 days Hemoptysis is commonly associated with bronchogenic carcinoma	A coin-shaped lesion with thick wall(>15mm) is seen on CXR with less ground glass opacities Bronchoalveolar lavage cytology shows malignant cells	Biopsy of lung
Pulmonary Tuberculosis	Mostly in endemic areas Symptoms include productive cough,night sweats, fever and weight loss	CXR and CT demonstrates cavities in the upper lobe of the lung	Sputum smear positive for acid-fast bacilli Nucleic acid amplification tests (NAAT) is used on sputum or any sterile fluid .
Necrotizing Pneumonia	Any age group Acute, fulminant life threating complication of prior infection >100.4F fever, with hemodynamic instability Worsening pneumonia-like symptoms	CXR demonstrates multiple cavitary lesions Pleural effusion and empyema are common findings	CBC is positive for causative organism
Loculated empyema	Children and elderly are at risk Pleuritic chest pain, dry cough, fever with chills Dullness to percussion decreased breath sounds, and reduced vocal resonance on examination	Empyema appears lenticular in shape and has a thin wall with smooth luminal margins	Thoracocentesis
Rheumatoid nodule	Elderly females of 40-50 age group Manifestation of rheumatoid arthritis Presents with other systemic symptoms including symmetric arthritis of the small joints of the hands and feet with morning stiffness are common manifestations.	Pulmonary nodules with cavitation are located in the upper lobe (Caplan syndrome) on Xray.	Positive for both rheumatoid factor and anticyclic citrullinated peptide antibody.
Sarcoidosis	More common in African-American females Often asymptomatic except for enlarged lymph nodes Associated with restrictive lung disease Erythema nodosum Lupus pernio (skin lesions on face resembling lupus) Bell palsy Epithelioid granulomas containing microscopic Schaumann and asteroid bodies	On CXR, bilateral adenopathy and coarse reticular opacities are seen. CT of the chest demonstrates extensive hilar and mediastinal adenopathy Additional findings on CT include fibrosis (honeycomb, linear, or associated with bronchial distortion), pleural thickening, and ground-glass opacities.	Biopsy of lung shows non-caseating granuloma
Bronchiolitis obliterans (Cryptogenic organizing pneumonia)	Rare condition and mimics asthma, pneumonia and emphysema It is caused by drug or toxin exposure, autoimmune diseases, viral infections, or radiation injury People working in industries are at high risk Presents with fever, cough, wheezing and shortness of breath over weeks to months,	Common appearance on CT is patchy consolidation,often accompanied by ground-glass opacities and nodules.	Biopsy of the lung Pulmonary function tests demonstrate low FEV1/FVC
Langerhans cell Histiocytosis	Exclusively afflicts smokers, with a peak age of onset of between 20 and 40 years. Clinical presentation varies, but symptoms generally include months of dry cough, fever, night sweats and weight loss. Skin is involved in 80% of the cases, scaly erythematous rash is typical.	Thin-walled cystic cavities are the usual radiographic manifestation, observed in over 50% of patients by either CXR or CT scans.	Biopsy of the lung