Pulmonary hypertension differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Assistant Editor(s)-in-Chief: Ralph Matar, Rim Halaby

Overview

One of the most common initial presentations of patients with pulmonary hypertension is dyspnea; therefore, the differential diagnosis is very broad. As the disease progresses with time, more symptoms related to right ventricular hypertrophy and failure occur; which further narrows down the differential diagnosis.

Differential Diagnosis

Differentiating Pulmonary Arterial Hypertension from Other Diseases

Major entities in the differential diagnosis of pulmonary arterial hypertension are:[1]

Differentiating Shortness of Breath or Dyspnea from other Diseases

Diseases that cause shortness of breath have to be differentiated upon the following table[2]

To review the differential diagnosis of dyspnea and fever, click here.

To review the differential diagnosis of dyspnea and chest pain, click here.

To review the differential diagnosis of dyspnea and cough, click here.

To review the differential diagnosis of dyspnea and jugular vein distention, click here.

To review the differential diagnosis of dyspnea and cyanosis or clubbing, click here.

To review the differential diagnosis of dyspnea and loss of consciousness or agitation, click here.

To review the differential diagnosis of dyspnea with normal auscultation, click here.

To review the differential diagnosis of dyspnea with stridor, click here.

To review the differential diagnosis of dyspnea with wheezing, click here.

To review the differential diagnosis of dyspnea with crackle, click here.

To review the differential diagnosis of dyspnea with rhonchi, click here.

To review the differential diagnosis of dyspnea, fever, and cough, click here.

To review the differential diagnosis of dyspnea, fever, and chest pain, click here.

To review the differential diagnosis of dyspnea, cough, and cyanosis or clubbing click here.

To review the differential diagnosis of dyspnea, fever, chest pain, cough, and cyanosis or clubbing click here.

Abbreviations: ABG (arterial blood gas); ACE (angiotensin converting enzyme); BMI (body mass index); CBC (complete blood count); CSF (cerebrospinal fluid); CXR (chest X-ray); DOE (dyspnea on exercise); ECG (electrocardiogram); FEF (forced expiratory flow rate); FEV1 (forced expiratory volume); FVC (forced vital capacity); JVD (jugular vein distention); MCV (mean corpuscular volume); Plt (platelet); RV (residual volume); SIADH (syndrome of inappropriate antidiuretic hormone); TSH (thyroid stimulating hormone); Vt (tidal volume); WBC (white blood cell);

Organ system Diseases Clinical manifestations Diagnosis Other features
Symptoms Physical exam
Loss of consciousness Agitation Weight loss Fever Chest pain Cough Orthopnea DOE Cyanosis Clubbing JVD Peripheral edema Auscultation CBC ABG Imaging Spirometry Gold standard
Acute Dyspnea Respiratory system Head and Neck,

Upper airway

Angioedema[3] - - - - - +/- + - - +/- - + Normal Normal ↓O2, ↑CO2 Normal N/A Physical exam Generalized edema
Anaphylaxis[4] +/- + - +/- - - - - +/- - - - Scattered wheezing Normal Normal Normal N/A Vital sign Type 1 hypersensitivity
Aspiration[5] - + - - +/- + - - + - - - Diminished breath sounds Normal Normal Atelectasis ↓Vt, ↑RV Bronchoscopy Choking
Croup[6] - + - +/- - + - - + - - - Stridor ↑WBC Normal Steeple sign Normal Physical exam Barking cough
Epiglottitis[7] - + - + - + - - - - - - Stridor ↑WBC Normal Thumb sign Normal Laryngoscopy Drooling
Rhinosinusitis[8] - - - + - +/- - - - - - - Normal ↑WBC Normal Air fluid level Normal Physical exam Headache
Vocal cord dysfunction[9] - - - - - +/- - - - - - - Stridor Normal Normal Normal ↓ FVC Laryngoscopy Choking sensation
Chest and Pleura,

Lower airway

Asthma attack[10] - + - - +/- + - - + - - - Wheeze ↑ Eosinophil Respiratory alkalosis Normal ↓ FEV1, PEF Physical exam and

Spirometry

Chest pain
Atelectasis - - - +/- +/- +/- - - +/- - - - Diminished breath sounds, Wheeze Normal ↓O2, Normal/↓CO2 Collapsed lung lobe, fissuresdisplacement ↓ FVC Chest CT scan Surgical procedure, Aspiration,

Mechanical ventilation

Bronchitis[11] - - - + + + - - - - - - Rhonchi  ↑WBC Normal Normal Normal Physical exam Rhonchi relieved by cough
Bronchospasm[12] +/- + - - + +/- - - + - - - Wheeze Normal ↓O2, ↑CO2 Normal ↓Vt, ↑RV Physical exam Allergic reaction
Bronchiolitis[13] - - - + +/- + - - - - - - Wheeze and Crackles ↑WBC Normal Bronchovascular markings ↓Vt Clinical assessment Respiratory syncytial virus (RSV)
COPD exacerbation[14] - + - + + + + - + +/- +/- +/- Wheeze, Rhonchi, and Crackles ↑WBC, ↑RBC Respiratory alkalosis Hyperexpansion ↓ FEV1/FVC Clinical assessment Acute exacerbations of chronic bronchitis (AECB)
Lung carcinoma[15] - - + - - + - - + + - - Wheeze and Crackles Normal Normal Mass lesion, hilar lymphadenopathy ↓Vt, ↑RV Bronchoscopy  Paraneoplastic syndromes, such as SIADH and Lambert-Eaton
Pneumonia[16] - - - + + + - - - - - - Wheeze, Rhonchi, and Crackles ↑WBC, neutrophilia Normal Lobar consolidation Normal Chest X-ray and CT Scan productive cough
Pneumothorax[17] - - - - + - - - - - +/- - Diminished breath sounds Normal ↓O2, ↑CO2 Radiolucency without lung marking ↓Vt CXR and Chest CT scan Tracheal deviation
Pulmonary embolism[18] - - - - + - - +/- - - - - Normal Normal Respiratory alkalosis Normal Normal Pulmonary CT angiography Pleuritic chest pain
Rib fractures (flail chest)[19] - + - - + - - - - - - - Normal Normal Respiratory acidosis Fracture marks Normal Chest X-ray Pneumothorax
Cardiovascular system Acute myocardial ischemia[20] +/- + - +/- + - + + - - - - Normal Normal Normal Normal Normal Cardiac troponin I Nausea and vomiting, Positive pertinent risk factors, such as hypertension, diabetes, and smoking
Acute heart failure[21] +/- + - - +/- + +/- + + - + + S3 Normal Respiratory alkalosis ↑ Cardiothoracic ratio ↓Vt B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) Excessive sweating, high blood pressure
Pericardial tamponade[22] +/- - - - + - +/- +/- - - + - Muffled heart sounds Normal Normal Water bottle appearance enlarged heart Normal Echocardiography Fluid accumulation in pericardium
Tachyarrhythmia[20] +/- + - - +/- - - - - - - - High pulse rate Normal Normal Normal Normal ECG Palpitation
Pulmonary edema[23] +/- + - + + + + + + + + + Basal crackle Normal Respiratory alkalosis Bat wing pattern, air bronchograms ↓Vt, ↑RV Cardiac Catheterization Tachypnea
Central nervous system Stroke + - - +/- - - - - - - - - Normal Normal Normal Intracranial infarct or hemorrhage Normal Brain MRI Paralysis or paresthesia
Encephalitis[24] + + - + - - - - - - - - Normal ↑WBC, neutrophilia Normal Normal Normal CSF PCR Confusion
Traumatic brain injury[25] + +/- - - - - - - - - - - Normal Normal Respiratory acidosis Intracerebral hemorrhage Normal Brain CT scan Lucid interval
Toxic/Metabolic Organophosphate poisoning[26] + - - + - - - - - - - - Wheeze Normal ↓O2, ↑CO2 Normal Normal Blood test Salivation, Lacrimation, Emesis, Miosis
Salicylate poisoning[27] + - - - - - - - + - - - Normal Normal Metabolic acidosis, Respiratory alkalosis Normal Normal Blood test Vomiting, Tinnitus, Confusion, Hyperthermia
Carbon monoxide poisoning[28] + - - - + + - - + - - - Wheeze Carboxyhemoglobin ↓O2, ↑CO2 Normal N/A Carboxyhemoglobin (HbCO) level Headache, Dizziness, Weakness, Vomiting, Confusion
Diabetic ketoacidosis[29] + +/- - - - - - - - - - - Scattered wheeze, Kussmaul's respiration ↑WBC Metabolic acidosis Normal Normal Blood test (acidosis, hyperglycemia, ketonemia) Vomiting, Abdominal pain, Weakness, Confusion
Systemic Panic attack[30] +/- + - - - - - - - - - - Normal Normal Normal Normal Normal Clinical assessment Severe anxiety
Pregnancy[31] - - - - +/- - - - - - - + Normal ↑WBC, RBC ↓O2, ↑CO2 Normal ↓Vt, ↑RV βhCG Missed period, Hyperemesis
Sepsis[32] +/- - - + - - - - - - - - Normal ↑WBC, neutrophilia ↓O2, ↑CO2 Normal Normal SIRS criteria Chills, Confusion
Organ system Diseases Clinical manifestations Diagnosis Other features
Symptoms Physical exam
Loss of consciousness Agitation Weight loss Fever Chest pain Cough Orthopnea DOE Cyanosis Clubbing JVD Peripheral edema Auscultation CBC ABG Imaging Spirometry Gold standard
Chronic Dyspnea Respiratory system Head and Neck,

Upper airway

Goiter[33] - - - - - - - - - - - + Normal Normal Normal Normal Normal Blood test (TSH, T4) Weight gain
Laryngeal adenocarcinoma[34] - - + - - +/- - - - - - - Stridor Normal ↓O2, ↑CO2 Retropharyngeal tissue thickness Normal Laryngoscopy Choking sensation
Vocal cord paralysis[9] - - - - - +/- - - - - - - Stridor Normal Normal Pharyngeal constrictor muscles thinning, uvular deviation Normal Laryngoscopy Choking sensation
Tracheal stenosis[35] - - - - +/- +/- - - + + - - Stridor, Stertorous Normal ↓O2, ↑CO2 Soft tissue thickening internal to normal-appearing tracheal cartilage Normal Bronchoscopy Respiratory distress
Chest and Pleura,

Lower airway

Bronchial asthma[10] - + +/- - +/- + - - + + - - Wheeze ↑ Eosinophil Respiratory alkalosis, Metabolic acidosis Pulmonary hyperinflation,

Bronchial wall thickening

↓ FEV1/FVC Spirometry before and after bronchodilator Paroxysmal respiratory distress
Bronchiectasis[11] - - - + + + - - + + - - Rhonchi, Wheezing, Crackles ↑WBC, neutrophilia ↓O2, ↑CO2 Tram-track opacities ↑ FEV1/FVC High resolution computed tomography (HRCT) Chronic productive cough
COPD[14] - - +/- - - + + + + + + +/- Expiratory wheeze ↑ RBC Respiratory alkalosis, Metabolic acidosis ↑ Bronchovascular markings, Cardiomegaly ↓ FEV1/FVC Physical exam and

Spirometry

Heavy smoking history
Emphysema[36] - - - - - +/- - - + + - - Expiratory wheeze, Hyperinflation Normal Respiratory alkalosis, Metabolic acidosis Flattening of diaphragm, vertical heart ↓ FEV1/FVC Physical exam and

Spirometry

Barrel chest
Pulmonary hypertension[37] - - - - +/- +/- - - +/- +/- + + Accentuated S2 Normal Hypoxia and acidosis Enlarged pulmonary arteries ↑Physiologic RV Cardiac catheterization Syncope,

Ascites, Pleural effusion

Interstitial lung disease[38] - - - - + + - - + + - - Rhonchi, Wheezing, Crackles Normal ↓O2, ↑CO2 Peripheral pulmonary infiltrative opacification ↑ FEV1/FVC High resolution computed tomography (HRCT) Pneumoconiosis
Sarcoidosis[39] - - +/- - +/- + - - + - - - Crackles Normal ↓O2, ↑CO2 Hilar adenopathy ↑ FEV1/FVC High resolution computed tomography (HRCT) Hypercalcemia, high ACE
Alveolitis[40] - - - + + + - - - - - - Basal crackle ↑WBC, neutrophilia Normal  Basal reticulonodular opacification   ↑ FEV1/FVC High resolution computed tomography (HRCT) Dry cough
Bronchiolitis obliterans[13] - - - + + + - - + + - - Expiratory wheeze ↑WBC ↓O2, ↑CO2 Hyperinflation, Reticulonodular opacities ↓ FEV1/FVC Lung biopsy Complication of allogeneic hematopoietic stem cell transplantation
Cystic fibrosis[41] - - + + - +/- - - + + - - Rhonchi, Wheezing, Crackles Normal Metabolic alkalosis Thick-walled bronchiectasis ↓ FEF75%/FVC Sweat test Absent vas deferens
Pleural effusion[42] - +/- + - + - +/- - - - +/- +/- Egophony ("E-to-A" change) Normal Normal Blunting of the costophrenic and cardiophrenic angle ↓Vt, ↑RV Light's criteria ↓Tactile fremitus, Asymmetrical chest expansion
Pulmonary right-to-left shunt[43] - - - - +/- + - - + + - - Diminished breath sounds Normal ↓O2, ↑CO2, Respiratory acidosis Normal ↓Vt, ↑RV

(physiological)

Pulmonary CT angiography Chronic hypoxemia
Diaphragmatic paralysis[44] - - - +/- +/- +/- - - - - - - Normal Normal Normal Unilateral or bilateral diaphragmatic flattening ↓Vt, ↑RV

(anatomical)

CXR confirmed by fluoroscopic sniff test Respiratory insufficiency
Tuberculosis[45] - - + + + + - - +/- - - - Rhonchi, Wheezing, Crackles ↑WBC ↓O2, ↑CO2 Patchy consolidation or poorly defined linear and nodular opacities Restrictive, obstructive, or mixed IFN-γ release assay (IGRA)

Acid-fast staining

Night sweat
Cardiovascular system Constrictive pericarditis[22] - - - - + - + + - - + - Muffled heart sounds Normal Normal Calcifications  Normal Chest CT scan Syncope
Restrictive cardiomyopathy[46] - - - - + - + + - - - +/- Normal Normal Normal Dilatation of the inferior vena cava and right atrium Normal Right ventricular biopsy Weight gain,

Nausea

Valvular heart disease[20] - - - - + - +/- + - - - - Cardiac murmur Normal Normal Dilatation of heart chambers Normal Echocardiography Syncope, Palpitation
Bradyarrhythmia[47] - - - - - - - - - - - - Normal Normal Normal Normal Normal ECG Syncope, Palpitation
Pericardial effusion[48] - - - +/- + + +/- +/- - - + - Muffled heart sounds Normal Normal Fluid density around the heart Normal M-mode and 2-dimensional Doppler echocardiography Hoarseness, Palpitation
Coronary heart disease[20] - +/- - - + - + + - - - - Normal Normal ↓O2 Normal Normal Cardiac troponin I Nausea, Lightheadedness, Sweating
Intracardiac shunt[49] - - - - +/- - +/- + + + - - Cardiac continuous murmur Normal ↓O2 Dilatation of heart chambers Normal Echocardiography Syncope, Palpitation
Neuromuscular disease Amyotrophic lateral sclerosis[50] +/- - +/- - - - - - - - - - Normal ↑WBC Normal Normal ↓Vt, ↑RV Revised El Escorial criteria (clinical) Muscle weakness, Dysphagia
Polymyositis/dermatomyositis[51] - - +/- - + - - - - - - +/- Normal ↑WBC Normal Normal ↓Vt, ↑RV Muscle biopsy Muscle weakness, Heliotrope
Mitochondrial diseases[52] - - +/- - - - - - - - - - Wheeze ↓WBC, Plt Normal Normal ↓Vt, ↑RV Muscle biopsy Muscle pain
Glycolytic enzyme defects (e.g., McArdle)[53] +/- - - - - - - - - - - +/- Normal Normal Normal Normal ↓Vt, ↑RV Muscle biopsy (ragged red fibers) Myoglobinuria,

Muscle weakness

Toxic/Metabolic Metabolic acidosis[54] - - + - - - - - - - - - Normal Normal Metabolic acidosis, Respiratory alkalosis Normal Normal ABG Confusion, Vomiting
Renal failure[55] - - + - - - + + - - - + Normal ↓ RBC Metabolic acidosis Normal Normal Cr Nausea, Vomiting, Oliguria
Systemic Anemia[56] - - + - - - - +/- - - - - Normal ↓ RBC ↓O2 Normal Normal HGB, MCV Weakness, Fatigue
Anxiety[57] + + + - +/- +/- - - - - - - Normal Normal Normal Normal Normal Psychological interview Sweating, Palpitation
Ascites[58] - - - - - - - - - - - - Normal Normal Normal Peritoneal fluid accumulation ↓Vt, ↑RV Abdominal ultrasound Abdominal distention
Depression[59] - + + - - - - - - - - - Normal Normal Normal Normal Normal Psychological interview Depressed mood, fatigue
Kyphoscoliosis[60] - - - - - - - - - - - - Wheeze Normal Normal Deviated vertebral column ↓Vt, ↑RV

(anatomical)

Standing lateral spine radiograph Low back pain
Obesity[61] - - - - - - - - - - - - Normal Normal ↓O2 Normal ↓Vt, ↑RV

(anatomical)

BMI Low stamina,

Sweating

Autoimmune Churg-Strauss syndrome[62] - - - - - + - - - - - - Scattered wheezing Normal Normal Areas of parenchymal opacification ↓Vt, ↑RV Biopsy  Fatigue,Numbness
Microscopic polyangiitis[63] - - +/- + + - - - - - - +/- Scattered wheezing ↑WBC ↓O2, ↑CO2 Normal ↓Vt, ↑RV Histological confirmation Skin lesions, Nerve damage
Wegener's granulomatosis[64] - - +/- - - + - - - - - - Wheezing, Crackles ↓ RBC ↓O2, ↑CO2 Cavitate nodules, ground-glass opacity ↓ FEV1/FVC Biopsy demonstrating a granulomatous vasculitis Chronic rhinosinusitis
Goodpasture's disease[65] - - - - - + - - - - - -  Bilateral coarse crepitations ↓ RBC, HGB, HCT Normal  Like pulmonary edema Normal Kidney biopsy Hematuria,

Hemoptysis

References

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