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) CURB-65 Asthma (Late) − ✔ ✔ − ✔ ✔ in interstitial lung disease − End expiratory wheeze Absent wheeze and breath sounds in severe form ABG Eosinophilia IgE CXR to rule out other diagnosis complications like pneumonia, atelactasis HRCT Allergic bronchopulmonary aspergillosis Bronchiectasis Reversible obstructive disease Peak expiratory flow measurement is easy and very helpful GERD is a cause in case of refractory asthma. Triad of asthma, nasal polyps and rash is indicative of aspirin sensitivity. Cystic fibrosis ✔ − ✔ when infected ✔ ✔ − Wheeze or crackles Sputum stain and culture Sweat test Genetic test for CFTR (gene) CXR Hyperinflation Peribronchial thickening Nodules Bronchiectasis HRCT for detecting lung changes Sweat test Usually present since birth Recurrent pneumonia Recurrent wheezing Recurrent sinusitis Gastrointestinal manifestations Meconium ileus Pancreatic insufficiency COPD (Severe emphysema) ✔ − ✔ − ✔ − ✔ Reduced breath sounds Prolonged expiration Wheeze Inspiratory crackles Hematocrit ABG Sputum staining and culture Alpha 1-antitrypsin test CXR Elongated heart Flattening of diaphragms Prominent hilar vasculature HRCT Bullae HRCT Pulmonary hypertension Right heart failure Pulmonary vascular disorders Massive pulmonary embolism ✔ − ✔ ✔ ✔ − ✔ Reduced breath sounds Rales, crackles Loud P2 ABGs D-dimer EKG BNP CXR V/Q scan Spiral CT pulmonary angiogram Venous ultrasound for DVT Spiral CT pulmonary angiogram Tachycardia Shock Pulmonary hypertension can occur Pulmonary arterio-venous malformation − ✔ ✔ − ✔ ✔ − Pulmonary bruit CBC ABG CXR Round/oval mass lobulated well defined Connecting vessel in hilum Hemothorax Pulmonary angiography Contrast echocardiography Classic triad of dyspnea on exertion, cyanosis and clubbing Cerebral arteriovenous malformation Pregnancy can increase the size Chest wall disorders Flail chest − ✔ − − − Pneumothorax ✔ − ✔ − ✔ − − Decreased breath sounds Wheezing Cardiovascular Disease Peripheral Central Dyspnea Fever Chest pain Clubbing Peripheral edema Auscultation CB GB Electrolytes hert h ray- scanT t Other Gold standard Additional findings Atrioventricular canal defect ✔ + ± + CBC EKG Pulse oximetry CXR (Cardiac enlargement, Increased pulmonary vascular markings) Echocardiography MRI Cardiac catheterization Echocardiography Ebstein anomaly ✔ + ± + CBC EKG Pulse oximetry CXR (Cardiac enlargement, decreased pulmonary vascular markings) Echocardiography MRI Cardiac catheterization Echocardiography Tetralogy of Fallot ✔ + ± + (systolic) CBC EKG Pulse oximetry CXR (Boot shaped heart, decreased pulmonary vascular markings) Echocardiography MRI Cardiac catheterization Echocardiography Pulmonic stenosis ✔ + ± + (systolic) CBC EKG Pulse oximetry CXR (Cardiac enlargement, decreased pulmonary vascular markings) Echocardiography MRI Cardiac catheterization Echocardiography Total anomalous pulmonary venous connection ✔ + ± + (Systolic) CBC EKG Pulse oximetry CXR (normal heart size and venous congestion but in patients without obstruction have cardiomegaly and increased pulmonary blood flow.) Echocardiography MRI Cardiac catheterization Echocardiography Transposition of the great vessels ✔ + ± - CBC EKG Pulse oximetry CXR (Cardiac enlargement, increased pulmonary vascular markings) Echocardiography MRI Cardiac catheterization Echocardiography Truncus arteriosus ✔ + ± sys/±dias CBC EKG Pulse oximetry CXR (Cardiac enlargement, increased pulmonary vascular markings) Echocardiography MRI Cardiac catheterization Echocardiography Disease Peripheral Central Dyspnea Fever Chest pain Clubbing Peripheral edema Auscultation Lab Findings Imaging Gold standard Additional findings Heart failure ✔ ✔ + + + + (S3) CBC Complete metabolic profile Cardiac enzymes BNP Thyroid profile Renal function tests EKG Exercise stress test ABG's Lipid profile CXR Increase in heart size compared to the old film. Pleural fluid Interstitial edema Echocardiography Angiography Cardiac MRI Nuclear imaging Echocardiography Endomyocardial biopsy can be used when a specific diagnosis is suspected that would influence therapy in heart failure patients. Valvular heart disease ✔ ✔ ± − + + CBC Complete metabolic profile Cardiac enzymes BNP Thyroid profile Renal function tests EKG CXR To assess pulomary congestion or other lung pathology. Echocardiography Doppler echocardiography Angiography To assess the need for concomitant coronary artery bypass surgery in elderly people. Echocardiography Myocardial infarction ✔ ✔ − + + + [[CBC [[Complete metabolic profile [[Cardiac enzymes BNP Thyroid profile Renal function tests EKG Lipid profile CXR Normal or may show signs of CHF Echocardiography Angiography Central Nervous system Disease Peripheral Central Dyspnea Fever Chest pain Clubbing Peripheral edema Auscultation Lab Findings Imaging Gold standard Additional findings 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. Disease Peripheral Central Dyspnea Fever Chest pain Clubbing Peripheral edema Auscultation Lab Findings Imaging Gold standard Additional findings 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† − − − − −