Cyanosis differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Differential Diagnosis of Central Cyanosis

• Abnormal hemoglobin
• Acute respiratory distress syndrome
• Alveolitis
• Atelectasis
• Atrial septal defect
• Bronchiectasis
• Central or peripheral respiratory paralysis
• Chronic bronchitis
• Congenital heart disease
• Decreased respiration with oversedation
• Double outlet right ventricle
• Emphysema
  
• Foreign-body aspiration
• High altitude exposure
• Hypersensitivity pneumonitis
• Intoxication
• Intrapulmonary arteriovenous aneurysms
• Lung cancer
• Mediastinitis
• Patent ductus arteriosus
• Pickwickian syndrome
• Pleural Effusions
• Pneumoconiosis
• Poliomyelitis
• Polyneuropathy
• Primary alveolar hypoventilation
• Pulmonary arteriovenous fistulas
• Pulmonary edema
• Pulmonary embolism
• Pulmonary fibrosis
• Pulmonary hypertension
• Severe chronic obstructive pulmonary disease (COPD) or asthma
• Severe pneumonia
• Single ventricle
• Sleep apnea
• Tension pneumothorax
• Tetralogy of Fallot
• Toxins/poisons
  
• Transposition of the great vessels
• Tuberculosis
• Ventricular septal defect

Differential Diagnosis of Peripheral Cyanosis

• Acrocyanosis
• Arterial embolism
• Arrhythmia
• Cardiomyopathy
• Cold exposure
• Congenital Heart Disease
• Congestive Heart Failure
• Endomyocardial fibrosis
• Heart tumors
• Hypertensive heart disease
• Mitral Stenosis
• Pericardial effusion
• Polycythemia vera
• Raynaud's Phenomenon
• Shock
• Superior vena cava obstruction
• Valvular disease
• Venous hypertension
• Venous stasis

Differential diagnosis

Abbreviations: AP= Anteroposterior, CXR= Chest X-ray, CT= Computed tomography, ABG= Arterial blood gas, V/Q= Ventilation/perfusion scan , EKG= Electrocardiogram, COPD= Chronic obstructive pulmonary disease, BNP= Brain natriuretic peptide, DVT= Deep vein thrombosis, HRCT= High Resolution CT, IgE= Immunoglobulin E

Diseases Cyanosis Clinical manifestations Para-clinical findings Gold standard Additional findings Symptoms Physical examination Lab Findings Imaging Peripheral Central Dyspnea Fever Chest pain Clubbing Peripheral edema Auscultation CBC ABG Electrolytes Other X-ray CT scan Other Pulmonary diseases Airway disorder Severe croup + - + +/- - - - Stridor Lymphocytosis Normal Normal - Steeple sign - Distended hypopharynx during inspiration Clinical findings Intercostal and subcostal retraction, Barking cough Epiglottitis + - + + - - - Stridor Leukocytosis with neutrophilia Normal Normal - Thumb sign - - Laryngoscopy Muffled voice, Drooling Foreign body aspiration + - + - +/- - - Decreased breath sounds, Wheezing Normal Normal Normal - Hyperinflation, Atelectasis, Objects Foreign body entrapment with edema or granulation tissue - Bronchoscopy Mediastinitis Bacterial tracheitis + - + + + - - Inspiratory stridor Leukocytosis Normal Normal Blood culture, Gram stain Irregular tracheal margin - Steeple sign (confusing) Laryngotracheobronchoscopy Brassy cough, Hoarseness Parenchymal disorder Pneumonia - + + + + +/- - Rales, crackles, Wheeze, Pleural friction rub Leukocytosis, Pancytopenia Normal Hyponatremia - Entire lobe consolidated, Air bronchograms Focal ground-glass opacity - HRCT Tachycardia, Bradycardia (Legionella) Asthma (Late) - + + - +/- +/- - End expiratory wheeze Eosinophilia ↓O2, ↑CO2 Normal ↑ IgE Atelectasis Allergic bronchopulmonary aspergillosis, Bronchiectasis - Spirometry before and after bronchodilator Triad of asthma, nasal polyps, and rash is indicative of aspirin sensitivity. Cystic fibrosis + - +/- +/- + - Wheeze, Crackles Normal ↓O2, ↑CO2 Increased sweat chloride Sweat chloride test Hyperinflation, Nodules Peribronchial thickening, Bronchiectasis - Sweat chloride test Absent vas deferens COPD (Severe emphysema) + - + +/- + +/- +/- Reduced breath sounds, Wheeze, Inspiratory crackles Polycythemia ↓O2, ↑CO2 Normal Alpha 1-antitrypsin test Elongated heart, Flattened diaphragms, Prominent hilar vasculature Bullae - HRCT Pulmonary hypertension, Right heart failure Pulmonary vascular disorders Massive pulmonary embolism + - + +/- + - +/- Reduced breath sounds, Crackles, Loud P2 Leukocytosis ↓O2, ↑CO2, Respiratory acidosis Normal D-dimer, BNP Fleischner sign, Hampton hump, Westermark sign, Pleural effusion  Filling defects in the pulmonary vasculature Spiral CT pulmonary angiogram Spiral CT pulmonary angiogram Tachycardia, Shock, Pulmonary hypertension Pulmonary arterio-venous malformation - + + - + + - Pulmonary bruit Normal ↓O2, ↑CO2, Respiratory acidosis Normal - One or more rounded or multilobular opacities Connecting vessel in hilum Magnetic resonance angiography, Echocardiography Contrast enhanced magnetic resonance angiography  Cerebral arteriovenous malformation Chest wall disorders Flail chest + - + - + - - Normal Normal ↓O2, ↑CO2 Normal - ≥3 adjacent ribs with segmental fractures, >5 adjacent rib fractures - - CXR Bruises over chest Pneumothorax + - + - + - - Diminished breath sounds Normal ↓O2, ↑CO2 Normal - No lung marking on one side, Collapsed lung Loculated air in thoracic cavity M-mode ultrasonography Chest CT scan Tachypnea Disease Peripheral Central Dyspnea Fever Chest pain Clubbing Peripheral edema Auscultation CBC ABG Electrolytes Other X-ray CT scan Other Gold standard Additional findings Cardiovascular diseases Congenital disorders Atrioventricular canal defect +/- + + - +/- +/- - Wheezing,Holosystolic or systolic ejection murmur Normal Normal Normal Pulse oximetry Cardiomegaly, Increased pulmonary vascular markings Normal Echocardiography, MRI Echocardiography Tachypnea, Lack of appetite, Pale skin color, Excessive sweating Ebstein anomaly - + +/- - +/- - - Loud S1 Normal Normal Normal Pulse oximetry Cardiomegaly, "Box shape" heart Apical displacement of the septal and posterior leaflets of the tricuspid valve "Atrialisation" of the right ventricle in MRI, Tricuspid regurgitation in echocardiography Echocardiography Fatigue, Palpitations Tetralogy of Fallot - + +/- - +/- - - Harsh systolic murmur Normal Normal Normal Pulse oximetry "Boot-shaped" heart with an upturned cardiac apex Aortopulmonary collateral vessels Peripheral pulmonary stenosis and atresia in echocardiography Echocardiography Fainting, Palpitation Pulmonic stenosis - + + - + +/- - Crescendo-decrescendo ejection murmur Schistocyte ↓O2 Normal Pulse oximetry Right ventricular hypertrophy, Dilated main pulmonary artery Stenotic segment, Post stenotic dilatation Severity of the stenosis by velocity encoded phase contrast (VEC) cine sequences Echocardiography Fainting, Palpitation Total anomalous pulmonary venous connection - + + - +/- +/- - Systolic murmur over the pulmonary area Normal ↓O2 Normal Pulse oximetry Snowman sign Anomalous venous return Blind ended left atrium with no connecting veins in echocardiography Echocardiography Pounding heart, Weak pulse, Extreme sleepiness Transposition of the great vessels - + + - +/- +/- - Diastolic and Systolic murmur Normal ↓O2 Normal Pulse oximetry Cardiomegaly with narrow superior mediastinum (egg on a string sign) Abnormal great vessel anatomy Flow dynamics on Steady-state free precession (SSFP) MRI Echocardiography Lack of appetite, Poor weight gain Truncus arteriosus - + +/- - +/- +/- - Holosystolic or ejection type murmur Normal ↓O2 Normal Pulse oximetry Moderate cardiomegaly, pulmonary plethora, Widened mediastinum Single cardiac trunk Anomalous anatomy in MRI Echocardiography Fatigue, Sweating, Pale or cool skin Acquired disorder Heart failure + - + +/- + - + Coarse crackles, S3 Anemia ↓O2, ↑CO2 Hyponatremia, Hypokalemia, Hypomagnesemia Elevated BNP Pleural effusion, Cardiomegaly Kerley B lines - Radioisotope scan Echocardiography Generalized edema, Hepatomegaly Valvular heart disease + - + - - - + Murmurs Schistocyte Normal Normal Hyperthyroidism Valve calcification - Valvular dysfunction in echocardiography Echocardiography Syncope, Palpitation Myocardial infarction - + + +/- + - - S3 and S4 Normal Normal Hyponatremia, Hypokalemia Elevated troponin I and CKMB Rolling out other causes Coronary luminal narrowing in CT perfusion scan Wall motion abnormality in echocardiography Cardiac troponin I Dizziness, Fatigue, Lightheadedness, Cold sweat Disease Peripheral Central Dyspnea Fever Chest pain Clubbing Peripheral edema Auscultation CBC ABG Electrolytes Other X-ray CT scan Other Gold standard Additional findings Central Nervous system Methemoglobinemia ✔ + + + CBC Peripheral smear Complete metabolic profile Hemoglobin electrophoresis Serum nitrite levels Pulse oximetry ABG's Drug screen LDH CXR EKG Family history of methemoglobinemia or glucose-6-phosphate dehydrogenase (G6PD) deficiency is important to determine. Polycythemia ✔ + + CBC Raised all cell lines in primary and only raised erythrocytes in secondary polycythemia Pulse oximetry Erythropoietin levels (EPO) Ferritin levels ABG's Increased leukocyte alkaline phosphatase B12 levels JAK 2 mutation CXR EKG Tenderness in the sternum may indicate transformation to acute myeloid leukemia and should be properly investigated. Breath holding spells ✔ No confirmatory study CBC Serum ferritin Blood lead level video-EEG monitoring can be use in non diagnostic cases. Cyanotic breath-holding spells most commonly occur around 1 year of age with a range of six months to four years. Iron deficiency anemia is more prevalent in children with breath-holding spells. Miscellaneous Shock ✔ + + (septic shock) + + (Cardiogenic shock) Complete metabolic profile CBC Cardiac enzymes ABG's Lactate BNP Renal function tests Coagulation studies and D-dimer level Echocardiography Chest radiography Angiography Smoke inhalation + + + CBC Electrolytes BUN and CR, Lactate levels Toxicology screen CO-oximetry CXR ECG Serial cardiac enzymes (in patients with chest pain)\ Pulmonary function testing Direct laryngoscopy and fiberoptic bronchoscopy CO toxicity should be suspected in any patient who presents following smoke inhalation unless co-oximetry shows normal carboxyhemoglobin. Cold exposure ✔ − − − − − − Fingerstick glucose (Hyperglycemia) Electrocardiogram (ECG) may show J wave, sinus bradycardia and prolongation of all ECG intervals. Serum electrolytes (including potassium and calcium) BUN and creatinine Serum hemoglobin, white blood cell, and platelet counts ( Raised HCT due to volume contraction) Coagulation profile acidosis) Creatine kinase (Rhabdomylosis) Arterial blood gas CXR Mild hypothermia: core temperature 32 to 35°C ; patient presents with confusion, tachycardia, and increased shivering. Moderate hypothermia: 28 to 32°C patient presents with lethargy, bradycardia and arrhythmia and decreased shivering. Severe hypothermia: below 28°C patient presents with coma, hypotension, arrhythmia, pulmonary edema, and rigidity.

Causes of cyanosis Cyanosis Clinical manifestations/association Diagnosis Additional findings Symptoms Signs Peripheral Central Dyspnea Fever Chest pain Clubbing Peripheral edema Auscultation Lab Findings Imaging Gold standard Respiratory Airway disorder Severe croup ✔ − ✔ ✔ − − − Audible stridor at rest Lymphocytosis AP Neck X ray for soft tissues: Steeple sign Lateral neck X ray: Distended hypopharynx during inspiration Clinical diagnosis Croupy cough and stridor Intercostal, subcostal retractions Epiglottitis ✔ − ✔ ✔ − − − Stridor Leukocytosis with neutrophilia Blood cultures Throat culture in intubated patients Lateral neck X ray Thumbprint sign (swollen epiglottis) Laryngoscopy Sore Throat Dysphagia Odynophagia Muffled voice Drooling Coma ✔ Seizures ✔ Head trauma ✔ Breath holding spells ✔ Miscellaneous Shock ✔ Smoke inhalation ✔ + + + Cold exposure ✔ − − − − − − − CBC Fingerstick glucose (Hyperglycemia) EKG- J wave Sinus bradycardia Prolongation of all ECG intervals. Serum electrolytes -K+ and calcium BUN and creatinine PT, PTT S. lactate ABG Mild hypothermia: core temperature 32 to 35°C ; Confusion Tachycardia Increased shivering. Moderate hypothermia: 28 to 32°C Lethargy Bradycardia Arrhythmia Decreased shivering. Severe hypothermia: <28°C Coma Hypotension Arrhythmia Pulmonary edema Rigidity Drugs† − − − − −