Cyanosis differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Eiman Ghaffarpasand, M.D. [2]

Overview

The underlying causes of cyanosis are classified based on the type of cyanosis (central or peripheral cyanosis), which they may cause. Different causes of cyanosis include pulmonary, cardiovascular, hematological, neurological, and vascular diseases.

Differential Diagnosis of Cyanosis

Differential Diagnosis of Central Cyanosis

To review the differential diagnosis of central cyanosis, click here.

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

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

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

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

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

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

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

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

To review the differential diagnosis of central cyanosis, fever, and clubbing, click here.

To review the differential diagnosis of central cyanosis, chest pain, and clubbing, click here.

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

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

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

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

Differential Diagnosis of Peripheral Cyanosis

To review the differential diagnosis of peripheral cyanosis, click here.

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

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

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

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

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

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

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

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

To review the differential diagnosis of peripheral cyanosis, fever, and clubbing, click here.

To review the differential diagnosis of peripheral cyanosis, chest pain, and clubbing, click here.

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

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

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

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

Abbreviations: ABG= Arterial blood gas, ANP= Atrial natriuretic peptide, BNP= Brain natriuretic peptide, CBC= Complete blood count, COPD= Chronic obstructive pulmonary disease, CRP= C-reactive protein, CT= Computed tomography, CXR= Chest X-ray, DVT= Deep vein thrombosis, ESR= Erythrocyte sedimentation rate, HRCT= High Resolution CT, IgE= Immunoglobulin E, LDH= Lactate dehydrogenase, PCWP= Pulmonary capillary wedge pressure.

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[1] + - + +/- - - - Stridor Lymphocytosis Normal Normal - Steeple sign Normal Distended hypopharynx during inspiration Clinical findings Intercostal and subcostal retraction, Barking cough
Epiglottitis[2] + - + + - - - Stridor Leukocytosis with neutrophilia Normal Normal - Thumb sign Normal - Laryngoscopy Muffled voice, Drooling
Foreign body aspiration[3] + - + - +/- - - Decreased breath sounds, Wheezing Normal Normal Normal - Hyperinflation, Atelectasis, Objects Foreign body entrapment with edema or granulation tissue - Bronchoscopy Mediastinitis
Bacterial tracheitis[4] + - + + + - - Inspiratory stridor Leukocytosis Normal Normal Blood culture, Gram stain Irregular tracheal margin Normal Steeple sign (confusing) Laryngotracheobronchoscopy Brassy cough, Hoarseness
Sleep apnea[5] - + + - - - - Normal Polycythemia O2, ↑CO2 Normal - Normal Normal Polysomnography Polysomnography Nightmares, Snoring
Chronic bronchitis[6] - + + +/- +/- + - Rales, crackles, Wheeze Leukocytosis O2, ↑CO2, Respiratory acidosis Hypokalemia, Hypernatremia Gram stain of sputum Elongated heart, Flattened diaphragms, Prominent hilar vasculature Bronchial wall thickening with increased bronchovascular markings - HRCT Productive cough, Chest tightness
Atelectasis[7] - + + - + - - Localized diminished breath sounds, Wheeze Leukocytosis O2, ↑CO2, Respiratory acidosis Normal - Localized increased opacity, Deviation toward the atelectasis Local crowding of pulmonary vessels and bronchi MRI for distinguishing obstructive from non-obstructive HRCT Cough, Shallow breathing
Parenchymal disorder Alveolitis[8] +/- + + + + +/- - Wheeze, Crackles Leukocytosis, Eosinophilia O2, ↑CO2 Normal ESR, ↑CRP Scattered opacities, Fine reticulation Homogeneous ground-glass opacity - HRCT PLUS Clinical findings Malaise, Chills, Headache
Pneumonia[9] - + + + + +/- - Rales, Crackles, Wheeze, Pleural friction rub Leukocytosis with neutrophilia Normal Hyponatremia - Entire lobe consolidated, Air bronchograms Focal ground-glass opacity - HRCT Tachycardia, Bradycardia (Legionella)
Asthma (Late)[10] - + + - +/- +/- - 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[11] + - +/- +/- + - 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)[12]

+ - + +/- + +/- +/- 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
Tuberculosis[13] - + + + + +/- - Reduced breath sounds, Wheeze, Inspiratory crackles Leukocytosis, ↑Lymphocyte O2, ↑CO2 Hyponatremia, Hyperkalemia, Hypochloremia PPD, interferon-gamma release assay (IGRA) Dense, homogeneous parenchymal consolidation Nodules with low-density centers and rim enhancement Fluorodeoxyglucose positron emission tomography/CT (FDG PET/CT) Sputum culture, QuantiFERON-TB Gold (QFT) Loss of appetite, Night sweats
Pulmonary fibrosis[14] - + + - + + - Inspiratory crackles Anemia O2, ↑CO2 Normal Matrix metalloproteinases (MMPs) Honeycombing Traction bronchiectasis,

Interlobular septal thickening

HRCT HRCT Fatigue, Weight loss
Pneumoconiosis[15] - + + - +/- +/- - End expiratory wheeze Leukocytosis, Anemia O2, ↑CO2, Respiratory acidosis Hyper/Hypocalcemia,

Hypermagnesemia

- Small to large round nodular opacities Diffuse distribution of small nodules MRI and PET-CT scan CT/HRCT scan Tightness in the chest
Lung cancer[16] - + + - +/- + - Absence of breath sounds, Stridor, Wheezing Leukocytosis, Anemia O2, ↑CO2 Hyponatremia CRP, ↑ESR Pulmonary nodule or mass,

Mediastinal widening

Hilar lymphadenopathy

Massive lymphadenopathy, Direct mediastinal invasion MRI, PET-CT scan, Bronchoscopy Low dose computed tomography scan (LDCT) Weight loss, Loss of appetite
Acute respiratory distress syndrome[17] - + + +/- + - - Inspiratory crackles Leukopenia/Leukocytosis O2, ↓CO2, Respiratory alkalosis Hyponatremia, Hyperkalemia BNP, ↑Von Willebrand factor (VWF) Bilateral pulmonary infiltrates (patchy to diffuse) Emphysema, Pneumothorax and pneumomediastinum, Mediastinal lymphadenopathy Invasive Hemodynamic Monitoring (PCWP), Bronchoscopy Chest CT scan Tachypnea, Muscle weakness
Pulmonary vascular disorders Massive pulmonary embolism[18] + - + +/- + - +/- 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[19][20][21] - + + - + + - 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
Pulmonary hypertension[22] - + + - +/- +/- - Tricuspid regurgitation murmur, Pulmonic insufficiency murmur Mild anemia O2, ↑CO2 Hypernatremia BNP, ↑ANP Right deviated cardiac apex,

Prominent pulmonary artery

Ill-defined nodules, Interlobular septal thickening CT pulmonary angiography (CTPA), MRA Cardiac catheterization (PCWP) Fatigue, Inability to exercise
Chest wall disorders Flail chest[23] + - + - + - - Normal Normal O2, ↑CO2 Normal - ≥3 adjacent ribs with segmental fractures, >5 adjacent rib fractures Normal - CXR Bruises over chest
Pneumothorax[24] + - + - + - - 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
Cardiac diseases Congenital disorders Atrioventricular canal defect[25] +/- + + - +/- +/- - 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[26] - + +/- - +/- - - 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[27] - + +/- - +/- - - 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[28] - + + - + +/- - 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[29] - + + - +/- +/- - 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[30] - + + - +/- +/- - 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[31] - + +/- - +/- +/- - Holosystolic or ejection type murmur Normal O2 Normal Pulse oximetry Moderate cardiomegalypulmonary plethoraWidened mediastinum Single cardiac trunk Anomalous anatomy in MRI Echocardiography Fatigue, Sweating, Pale or cool skin
Patent ductus arteriosus[32] - + +/- - +/- +/- - Continuous machinery murmur Normal O2, ↑CO2 Normal Pulse oximetry Cardiomegaly, Aortopulmonary window obsecuration Tortuous morphology of ductus (Krichenko classification) Spiral CT pulmonary angiogram Echocardiography Failure to thrive, Respiratory distress
Acquired disorders Heart failure[33] + - + +/- + - + Coarse crackles, S3 Anemia O2, ↑CO2 Hyponatremia, Hypokalemia, Hypomagnesemia Elevated BNP Pleural effusion, Cardiomegaly Kerley B lines Normal Radioisotope scan Echocardiography Generalized edema, Hepatomegaly
Valvular heart disease[34] + - + - - - + Murmurs Schistocyte Normal Normal Hyperthyroidism Valve calcification Normal Valvular dysfunction in echocardiography Echocardiography Syncope, Palpitation
Myocardial infarction[35] - + + +/- + - - 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
Cardiogenic shock[36] +/- + + - - - + Muffled heart sound Anemia O2, ↑CO2 Hyperkalemia PaO2 in pulse oximetry Normal Normal Echocardiography  Clinical findings Tachypnea, Palpitation, Hypotension, Weak pulse
Cardiomyopathy[37] - + + - + + + S3 and S4 Lymphocytosis O2, ↑CO2 Normal PaO2 in pulse oximetry Enlarged left ventricle and atria, Pulmonary edema Normal MRI Endomyocardial biopsy Arrhythmia, Bloating
Heart tumors[38] - + + - +/- +/- +/- Early diastolic tumor plop Normal Normal Normal Mild ↓PaO2 in pulse oximetry Calcification in lateral view Intracardiac mass Echocardiography  Histologic diagnosis (biopsy) Syncope, Weight loss
Mitral Stenosis[39] - + + - +/- +/- +/- Diastolic murmur Normal Normal Normal Mild ↓PaO2 in pulse oximetry Left atrial enlargement, Mitral annular calcification Secondary pulmonary hemosiderosis Velocity-encoded cine-magnetic resonance imaging (VEC-MRI) Echocardiography Dizziness, Hemoptysis
Vascular disease Arterial disorders Acrocyanosis[40] + - +/- - - + - Normal Anemia, Leukocytosis O2, ↑CO2 Hypercalcemia PaO2 in pulse oximetry Normal Normal - Clinical findings Brittle nails, Telangiectasia
Arterial embolism[41] + - + - + +/- - Normal Normal Normal Hyperkalemia PaO2 in pulse oximetry Normal Normal Transesophageal echocardiography (TEE) Clinical findings Headache, Decreased sensation
Raynaud's Phenomenon[42] + - - - - + - Normal Polycythemia O2 Normal Mild ↓PaO2 in pulse oximetry Normal Normal - Clinical findings Sensitivity to cold, Decreased sensation
Venous disorders Superior vena cava obstruction[43] + - +/- - +/- +/- + Normal Polycythemia O2 Normal PaO2 in pulse oximetry Superior mediastinal widening, Right hilar prominence  Thrombosis, Mediastinal mass or lymphadenopathy, Associated lung mass - Chest CT scan Headache,

Facial swelling

Venous stasis[44] + - - - - +/- + Normal Polycythemia O2 Hypercalcemia Normal Normal Normal Color-flow duplex ultrasound Color-flow duplex ultrasound Leg swelling, Pain during walking,

Leg ulcers

Disease Peripheral Central Dyspnea Fever Chest pain Clubbing Peripheral edema Auscultation CBC ABG Electrolytes Other X-ray CT scan Other Gold standard Additional findings
Hematologic diseases Methemoglobinemia[45] - + + +/- + - - Wheezing Anemia, Methemoglobinemia Normal PaO2, ↑SaO2, "Saturation gap" Normal SaO2 in pulse oximetry Normal Normal Echocardiography for ruling out other causes Co-oximetry, ABG paired with pulse oximetry. Serum methemoglobin levels Headache, Altered mental status, Delirium, Seizure, Coma
Polycythemia[46] + + + +/- +/- + - Normal RBC, ↑WBC, ↑HGB, ↑Plt O2 Hyperkalemia Leukocyte alkaline phosphatase, ↑Ferritin, ↑Erythropoietin AVM, COPD, pulmonary hypertension Normal Abdominal ultrasound or renal vascular studies for ruling out renal artery stenosis RBC mass (RCM) and plasma volume measurement Itchiness, Headache. Dizziness. Blurred vision
Neurological disease Breath-holding spells[47] - + + - +/- - - Wheezing Hypochromic microcytic anemia O2 Hypocalcemia, Hypokalemia Iron deficiency Ruling out foreign body aspiration Normal EEG monitoring Clinical findings Fainting, Twitching muscles, Seizure
Seizure[48] - + + +/- - - - Normal Normal O2, ↑CO2 Hyponatremia, Hypo/Hypercalcemia CPK, ↑LDH, Normal Normal EEG EEG Fainting, Tonic-clonic movements
Coma[49] - + - - - - +/- Wheezing Normal O2, ↑CO2 Normal - Underlying disease Underlying disease - Glasgow Coma Scale (GCS) Depressed brainstem reflexes, Agonal breathing
Head trauma[50] - + + - - - - Normal Normal O2, ↑CO2 Normal - Skull fracture Intracranial hemorrhage MRI CT scan Nausea, Hypertension, Bradycardia,Tachypnea
Miscellaneous High altitude exposure[51] +/- + + - +/- + - Wheezing Polycythemia O2, ↓CO2, Respiratory alkalosis Hyperphosphatemia, Hypercalcemia, Hyponatremia, Hypokalemia, Hypomagnesemia Decreased bicarbonate Central interstitial edema Pulmonary consolidation - Hypoxic challenge test Dizziness, Coma, Death
Septic shock[52] + - + + +/- - - Rales, crackles, Wheeze, Pleural friction rub Leukocytosis with neutrophilia O2, ↑CO2, Metabolic acidosis Hyperkalemia ESR, ↑CRP Consolidation Pulmonary infiltration Echocardiography Blood culture Chills, Hypothermia, Loss of consciousness
Smoke inhalation[53] +/- + + - + - - Wheezing Anemia, Carboxyhemoglobin O2, ↑CO2, Respiratory acidosis Normal CO-oximetry Diffuse opacities Pulmonary infiltration Pulmonary function testing Bronchoscopy Cough, Hoarseness, Hemoptysis, Headache, Fainting
Cold exposure[54] + - +/- - - - - Normal Leukopenia, ↑RBC O2, ↑CO2, Metabolic acidosis Hypokalemia, Hypocalcemia Hyperglycemia, ↑CK Normal Normal - Clinical findings Confusion, Tachycardia/Bradycardia, Coma

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