Pneumonia differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hamid Qazi, MD, BSc [2], Priyamvada Singh, M.D. [3] Syed Hassan A. Kazmi BSc, MD [4]

Overview

Pneumonia should be differentiated from other conditions that cause cough, fever, shortness of breath and tachypnea, such as asthma, COPD, CHF, cancer, GERD, pulmonary emboli.

Differentiating Pneumonia from other Diseases

Differential Diagnosis of Pneumonia

Disease	Findings
Acute bronchitis	No infiltrates seen on the chest X-ray.
Asthma	Past medical history, no infiltrates seen on chest X-ray.
Bronchiolitis obliterans	Should be suspected in patients with pneumonia who do not respond to antibiotics treatment.
Congestive heart failure	Bilateral pulmonary edema, shortness of breath.
COPD	Past medical history, no infiltrates on chest X-ray, fever is uncommon.
Empyema	CXR showing features of pleural effusion, inflammatory markers on thoracocentesis.
Endocarditis	Finding of septic pulmonary emboli
Gastroesophageal reflux disease (GERD)	Normal chest X-ray, symptoms are worse during night and associated with meals.
Lung abscess	Chest X-ray shows signs of lung abscess.
Lung cancer	Weight loss, clear sputum. CT scan and biopsy are helpful in ruling out malignancy.
Pertussis	Productive cough for weeks, nasopharyngeal aspirate aids in diagnosis.
Pulmonary embolus	A high degree of suspicion should be kept for pulmonary embolus. Chest X-ray may be normal.
Sinusitis	Sinus tenderness, post nasal drip.
Vasculitis	Systemic manifestations of collagen vascular disease may be seen.

Differential diagnosis

Causes of Lung Cavities	Differentiating Features	Differentiating Radiological Findings	Diagnosis Confirmation
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 and nucleic acid amplification tests (NAAT) is used on sputum or any sterile fluid for rapid diagnosis and is positive for mycobacteria.
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
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
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

Table 1: Differentiating psittacosis from other diseases

Clinical feature	Cough	Sputum	Dyspnea	Sore throat	Headache	Confusion	Diarrhea	Chest radiograph changes	Hyponatremia	Leukopenia	Abnormal Liver function tests	Treatment
Psittacosis	++	-	+	-	+++	+	Minimal	No changes seen	-	+	-	Doxycycline
C.pneumoniae pneumonia	+	+	+	+++	++	+	-	Minimal changes observed	-	-	-	Doxycycline, Azithromycin
M. pneumoniae pneumonia	++	++	++	-	-	-	-	Bronchial wall thickening Centrilobular nodules Ground-glass attenuation Consolidation	-	-	+	Doxycycline
L. Pneumophila infection	+	+++	+++	-	+	++	+	Often Multifocal	++	+	++	Doxycycline
Influenza	++	++	++	++	++	+/-	+/-	Bi-basal air-space opacities Perihilar reticular and alveolar infiltrates	-	-	-	zanamivir, oseltamivir,
Endocarditis	++	++	+	-	-	-	-	Hazy opacities at lung bases bilaterally	-	+/-	+/-	Vancomycin
Coxiella burnetii infection	++	-	+	+/-	-	+/-	Minimal	Segmental or lobar opacification Occasional pleural effusions	-	+/-	=/-	Doxycycline
Leptospirosis	++	+	++	+	+	++	-	Multiple ill-defined nodules in both lungs.	+++			Doxycycline, azithromycin, amoxicillin
Brucellosis	++	-	+	-	++	+	-	Soft miliary mottling Parenchymal nodules Consolidation Chronic diffuse changes Hilar or paratracheal lymphadenopathy Pneumothorax.	-/+	+/-	+/-	Doxycycline, rifampin

Key;

+, occurs in some cases

++, occurs in many cases,

+++, occurs frequently

Pnemonia must be differentiated from other diseases that cause atypical pneumonia such as Q fever and legionella pneumonia:

Disease	Prominent clinical features	Lab findings	Chest X-ray
Q fever	Q fever is characterized by abrupt onset of fever, myalgia, headache, and other constitutional symptoms. Cough is the most prominent respiratory symptom and it is usually dry. Cough is associated with dyspnea and pleuritic chest pain.	Antibody detection using indirect immunofluorescence (IIF) is the preferred method for diagnosis. PCR can be used if IIF is negative, or very early once disease is suspected. C. burnetii does not grow on ordinary blood cultures, but can be cultivated on special media such as embryonated eggs or cell culture. A two-to-three fold increase in AST and ALT is seen in most patients.	Q fever pneumonia - - Case courtesy of Royal Melbourne Hospital Respiratory, Radiopaedia.org, rID 21993
Mycoplasma pneumonia	Mycoplasma pneumonia can be asymptomatic. Headache, nausea, and malaise usually precede the onset of symptoms. Cough is intractable and nonproductive.	Postitve Coombs test Leukocytosis Thrombocytosis	Mycoplasma pneumonia - Case courtesy of Dr Alborz Jahangiri, Radiopaedia.org, rID 45781
Legionellosis	Legionellosis is characterized by cough that is slightly productive. Constitutional symptoms such as chills, myalgia, and arthralgia. Gastrointestinal symptoms such as diarrhea, nausea, and vomiting.	Labs are nonspecific for diagnosing legionellosis Renal and hepatic dysfunction Thrombocytopenia and leukocytosis Hyponatremia	Legionella pneumonia - Case courtesy of Dr Henry Knipe, Radiopaedia.org, rID 31816
Chlamydia pneumonia	There are no specific clinical features of chlamydia pneumonia. Symptoms appear gradually. Chlamydia infection is usually associated with upper respiratory tract symptoms (pharyngitis, sinusitis, etc). It might be associated with extrapulmonary maifestations such as meningitis and Guillain-Barre syndrome.	Chlamydia pneumonia is usually associated with normal WBC count. Diagnosed with the presence of antichlamydial antibody (through complement fixation or direct immunofluoroscence) or direct antigen detection.	Chlamydia-pneumonia - Case courtesy of Dr Andrew Dixon, Radiopaedia.org, rID 14567

Other differentials

Pneumonia should be differentiated from other diseases presenting with cough, fever, shortness of breath and tachypnea. The differentials include the following:

Diseases	Diagnostic tests			Physical Examination			Symptoms							Past medical history	Other Findings
	CT scan and MRI	EKG	Chest X-ray	Tachypnea	Tachycardia	Fever	Chest Pain	Hemoptysis	Dyspnea on Exertion	Wheezing	Chest Tenderness	Nasalopharyngeal Ulceration	Carotid Bruit
Pulmonary embolism	On CT angiography: Intra-luminal filling defect On MRI: Narrowing of involved vessel No contrast seen distal to obstruction Polo-mint sign (partial filling defect surrounded by contrast)	S1Q3T3 pattern representing acute right heart strain	Fleischner sign (enlarged pulmonary artery), Hampton hump, Westermark's sign	✔	✔	✔ (Low grade)	✔	✔ (In case of massive PE)	✔	-	-	-	-	Hypercoagulating conditions (Factor V Leiden, thrombophilia, deep vein thrombosis, immobilization, malignancy, pregnancy)	May be associated with metabolic alkalosis and syncope
Congestive heart failure	On CT scan: Mediastinal lymphadenopathy Hazy mediastinal fat On MRI: Abnormality of cardiac chambers (hypertrophy, dilation) Delayed enhancement MRI may help characterize the myocardial tissue (fibrosis) Late enhancement of contrast in conditions such as myocarditis, sarcoidosis, amyloidosis, Anderson-Fabry's disease, Chagas disease)	Goldberg's criteria may aid in diagnosis of left ventricular dysfunction: (High specificity) SV1 or SV2 + RV5 or RV6 ≥3.5 mV Total QRS amplitude in each of the limb leads ≤0.8 mV R/S ratio <1 in lead V4	Cardiomegaly	✔	✔	✔	-	-	✔	-	-	-	-	Previous myocardial infarction Hypertension (systemic and pulmonary) Cardiac arrythmias Viral infections (myocarditis) Congenital heart defects	Right heart failure associated with: Hepatomegaly Positive hepato-jugular reflex Increased jugular venous pressure Peripheral edema Left heart failure associated with: Pulmonary edema Eventual right heart failure
Percarditis	On contrast enhanced CT scan: Enhancement of the pericardium (due to inflammation) Pericardial effusion Pericardial calcification On gadolinium-enhanced fat-saturated T1-weighted MRI: Pericardial enhancement (due to inflammation) Pericardial effusion	ST elevation PR depression	Large collection of fluid inside the pericardial sac (pericardial effusion) Calcification of pericardial sac	✔	✔	✔ (Low grade)	✔ (Relieved by sitting up and leaning forward)	-	✔	-	-	-	-	Infections: Viral (Coxsackie virus, Herpes virus, Mumps virus, HIV) Bacteria (Mycobacterium tuberculosis-common in developing countries) Fungal (Histoplasmosis) Idiopathic in a large number of cases Autoimmune Uremia Malignancy Previous myocardial infarction	May be clinically classified into: Acute (< 6 weeks) Sub-acute (6 weeks - 6 months) Chronic (> 6 months)
Pneumonia	On CT scan: (not generally indicated) Consolidation (alveolar/lobar pneumonia) Peribronchial nodules (bronchopneumonia) Ground-glass opacity (GGO) Abscess Pleural effusion On MRI: Not indicated	Prolonged PR interval Transient T wave inversions	Consolidation (alveolar/lobar pneumonia) Peribronchial nodules (bronchopneumonia) Ground-glass opacity (GGO)	✔	✔	✔	✔	-	✔	✔	-	-	-	Ill-contact Travelling Smoking Diabetic Recent hospitalization Chronic obstructive pulmonary disease	Requires sputum stain and culture for diagnosis Empiric management usually started before culture results
Vasculitis	On CT scan: (Takayasu arteritis) Vessel wall thickening Luminal narrowing of pulmonary artery Masses or nodules (ANCA-associated granulomatous vasculitis) On MRI: Homogeneous, circumferential vessel wall swelling	Right or left bundle-branch block (Churg-Strauss syndrome) Atrial fibrillation (Churg-Strauss syndrome) Non-specific ST segment and T wave changes	Nodules Cavitation	✔	✔	✔	✔	✔	✔	-	✔	✔	✔	Takayasu arteritis usually found in persons aged 4-60 years with a mean of 30 Giant-cell arteritis usually occurrs in persons aged > 60 years Churg-Strauss syndrome may present with asthma, sinusitis, transient pulmonary infiltrates and neuropathy alongwith cardiac involvement Granulomatous vasculitides may present with nephritis and upper airway (nasopharyngeal) destruction
Chronic obstructive pulmonary disease (COPD)	On CT scan: Chronic bronchitis may show bronchial wall thickening, scarring with bronchovascular irregularity, fibrosis Emphysema may show alveolar septal destruction and airspace enlargement (Centrilobular- upper lobe, panlobular- lower lobe) Giant bubbles On MRI: Increased diameter of pulmonary arteries Peripheral pulmonary vasculature attentuation Loss of retrosternal airspace due to right ventricular enlargement Hyperpolarized Helium MRI may show progressively poor ventilation and destruction of lung	Multifocal atrial tachycardia (atleast 3 distinct P wave morphologies)	Enlarged lung shadows (emphysema) Flattening of diaphragm (emphysema)	✔	✔	-	-	-	✔	✔	-	-	-	Smoking Alpha-1 antitrypsin deficiency Increased sputum production (chronic bronchitis) Cough	Alpha 1 antitrypsin deficiency may be associated with hepatomegaly

References