Cyanosis differential diagnosis

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

Overview

Differential Diagnosis

Abbreviations: 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[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 - + + - +/- + -
Acute respiratory distress syndrome - + + +/- + - -
Pulmonary vascular disorders Massive pulmonary embolism[16] + - + +/- + - +/- 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[17][18][19] - + + - + + - 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 +
Chest wall disorders Flail chest[20] + - + - + - - Normal Normal ↓O2, ↑CO2 Normal - ≥3 adjacent ribs with segmental fractures, >5 adjacent rib fractures Normal - CXR Bruises over chest
Pneumothorax[21] + - + - + - - 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[22] +/- + + - +/- +/- - 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[23] - + +/- - +/- - - 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[24] - + +/- - +/- - - 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[25] - + + - + +/- - 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[26] - + + - +/- +/- - 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[27] - + + - +/- +/- - 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[28] - + +/- - +/- +/- - 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
Patent ductus arteriosus - +
Acquired disorders Heart failure[29] + - + +/- + - + 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[30] + - + - - - + Murmurs Schistocyte Normal Normal Hyperthyroidism Valve calcification - Valvular dysfunction in echocardiography Echocardiography Syncope, Palpitation
Myocardial infarction[31] - + + +/- + - - 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[32] +/- + + - - - + Muffled heart sound Anemia ↓O2, ↑CO2 Hyperkalemia ↓PaO2 in pulse oximetry Normal Normal Echocardiography  Clinical findings Tachypnea, Palpitation, Hypotension, Weak pulse
Cardiomyopathy - +
Heart tumors - +
Mitral Stenosis - +
Vascular disease Arterial disorders Acrocyanosis + -
Arterial embolism + -
Raynaud's Phenomenon + -
Venous disorders Superior vena cava obstruction + -
Venous stasis + -
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[33] - + + +/- + - - 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[34] + + + +/- +/- + - 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[35] - + + - +/- - - Wheezing Hypochromic microcytic anemia ↓O2 Hypocalcemia, Hypokalemia Iron deficiency Ruling out foreign body aspiration Normal EEG monitoring Clinical findings Fainting, Twitching muscles, Seizure
Seizure[36] - + + +/- - - - Normal Normal ↓O2, ↑CO2 Hyponatremia, Hypo/Hypercalcemia ↑CPK, ↑LDH, Normal Normal EEG EEG Fainting, Tonic-clonic movements
Coma[37] - + - - - - +/- Wheezing Normal ↓O2, ↑CO2 Normal - Underlying disease Underlying disease - Glasgow Coma Scale (GCS) Depressed brainstem reflexes, Agonal breathing
Head trauma[38] - + + - - - - Normal Normal ↓O2, ↑CO2 Normal - Skull fracture Intracranial hemorrhage MRI CT scan Nausea, Hypertension, Bradycardia,Tachypnea
Miscellaneous High altitude exposure +/- +
Septic shock[39] + - + + +/- - - 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[40] +/- + + - + - - 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[41] + - +/- - - - - Normal Leukopenia, ↑RBC ↓O2, ↑CO2, Metabolic acidosis Hypokalemia, Hypocalcemia Hyperglycemia, ↑CK Normal Normal - Clinical findings

References

  1. ↑ Cherry, James D. (2008). "Croup". New England Journal of Medicine. 358 (4): 384–391. doi:10.1056/NEJMcp072022. ISSN 0028-4793.
  2. ↑ Abdallah C (2012). "Acute epiglottitis: Trends, diagnosis and management". Saudi J Anaesth. 6 (3): 279–81. doi:10.4103/1658-354X.101222. PMC 3498669. PMID 23162404.
  3. ↑ Qureshi A, Behzadi A (2008). "Foreign-body aspiration in an adult". Can J Surg. 51 (3): E69–70. PMC 2496600. PMID 18682760.
  4. ↑ Liston SL, Gehrz RC, Siegel LG, Tilelli J (August 1983). "Bacterial tracheitis". Am. J. Dis. Child. 137 (8): 764–7. PMID 6869336.
  5. ↑ Spicuzza L, Caruso D, Di Maria G (2015). "Obstructive sleep apnoea syndrome and its management". Ther Adv Chronic Dis. 6 (5): 273–85. doi:10.1177/2040622315590318. PMC 4549693. PMID 26336596.
  6. ↑ Kim V, Criner GJ (2013). "Chronic bronchitis and chronic obstructive pulmonary disease". Am J Respir Crit Care Med. 187 (3): 228–37. doi:10.1164/rccm.201210-1843CI. PMC 4951627. PMID 23204254.
  7. ↑ Peroni DG, Boner AL (September 2000). "Atelectasis: mechanisms, diagnosis and management". Paediatr Respir Rev. 1 (3): 274–8. doi:10.1053/prrv.2000.0059. PMID 12531090.
  8. ↑ Lee JS, Im JG, Ahn JM, Kim YM, Han MC (August 1992). "Fibrosing alveolitis: prognostic implication of ground-glass attenuation at high-resolution CT". Radiology. 184 (2): 451–4. doi:10.1148/radiology.184.2.1620846. PMID 1620846.
  9. ↑ Simonetti AF, Viasus D, Garcia-Vidal C, Carratalà J (2014). "Management of community-acquired pneumonia in older adults". Ther Adv Infect Dis. 2 (1): 3–16. doi:10.1177/2049936113518041. PMC 4072047. PMID 25165554.
  10. ↑ Litonjua AA (June 2009). "Childhood asthma may be a consequence of vitamin D deficiency". Curr Opin Allergy Clin Immunol. 9 (3): 202–7. doi:10.1097/ACI.0b013e32832b36cd. PMID 19365260.
  11. ↑ "Cystic fibrosis - Genetics Home Reference".
  12. ↑ Qureshi H, Sharafkhaneh A, Hanania NA (2014). "Chronic obstructive pulmonary disease exacerbations: latest evidence and clinical implications". Ther Adv Chronic Dis. 5 (5): 212–27. doi:10.1177/2040622314532862. PMC 4131503. PMID 25177479.
  13. ↑ Olalekan, Adebimpe Wasiu; Oluwaseun, Faremi Ayodeji; Oladele, Hassan Abdul-Wasiu; Akeem, Adeyemi Damilare (2015). "Evaluation of electrolyte imbalance among tuberculosis patients receiving treatments in Southwestern Nigeria". Alexandria Journal of Medicine. 51 (3): 255–260. doi:10.1016/j.ajme.2014.10.003. ISSN 2090-5068.
  14. ↑ Shaw J, Marshall T, Morris H, Hayton C, Chaudhuri N (2017). "Idiopathic pulmonary fibrosis: a holistic approach to disease management in the antifibrotic age". J Thorac Dis. 9 (11): 4700–4707. doi:10.21037/jtd.2017.10.111. PMC 5721024. PMID 29268540.
  15. ↑ Yen CM, Lin CL, Lin MC, Chen HY, Lu NH, Kao CH (2016). "Pneumoconiosis increases the risk of congestive heart failure: A nationwide population-based cohort study". Medicine (Baltimore). 95 (25): e3972. doi:10.1097/MD.0000000000003972. PMC 4998335. PMID 27336897.
  16. ↑ Bĕlohlávek J, Dytrych V, Linhart A (2013). "Pulmonary embolism, part I: Epidemiology, risk factors and risk stratification, pathophysiology, clinical presentation, diagnosis and nonthrombotic pulmonary embolism". Exp Clin Cardiol. 18 (2): 129–38. PMC 3718593. PMID 23940438.
  17. ↑ Khurshid I, Downie GH (2002). "Pulmonary arteriovenous malformation". Postgrad Med J. 78 (918): 191–7. PMC 1742331. PMID 11930021.
  18. ↑ Doshi HM, Robinson S, Chalhoub T, Jack S, Denison A, Gibson G (2009). "Massive spontaneous hemothorax during the immediate postpartum period". Tex Heart Inst J. 36 (3): 247–9. PMC 2696501. PMID 19568398.
  19. ↑ Chanatry BJ (1992). "Acute hemothorax owing to pulmonary arteriovenous malformation in pregnancy". Anesth. Analg. 74 (4): 613–5. PMID 1554132.
  20. ↑ Pettiford BL, Luketich JD, Landreneau RJ (February 2007). "The management of flail chest". Thorac Surg Clin. 17 (1): 25–33. doi:10.1016/j.thorsurg.2007.02.005. PMID 17650694.
  21. ↑ Luh SP (2010). "Review: Diagnosis and treatment of primary spontaneous pneumothorax". J Zhejiang Univ Sci B. 11 (10): 735–44. doi:10.1631/jzus.B1000131. PMC 2950234. PMID 20872980.
  22. ↑ Macris MP, Ott DA, Cooley DA (1992). "Complete atrioventricular canal defect: surgical considerations". Tex Heart Inst J. 19 (3): 239–43. PMC 326195. PMID 15227445.
  23. ↑ Safi LM, Liberthson RR, Bhatt A (September 2016). "Current Management of Ebstein's Anomaly in the Adult". Curr Treat Options Cardiovasc Med. 18 (9): 56. doi:10.1007/s11936-016-0478-2. PMID 27439413.
  24. ↑ Bailliard F, Anderson RH (2009). "Tetralogy of Fallot". Orphanet J Rare Dis. 4: 2. doi:10.1186/1750-1172-4-2. PMC 2651859. PMID 19144126.
  25. ↑ Yoo BW, Park HK (2013). "Pulmonary stenosis and pulmonary regurgitation: both ends of the spectrum in residual hemodynamic impairment after tetralogy of Fallot repair". Korean J Pediatr. 56 (6): 235–41. doi:10.3345/kjp.2013.56.6.235. PMC 3693041. PMID 23807889.
  26. ↑ Stein P (March 2007). "Total anomalous pulmonary venous connection". AORN J. 85 (3): 509–20, quiz 521–4. doi:10.1016/S0001-2092(07)60123-9. PMID 17352891.
  27. ↑ Martins P, Castela E (2008). "Transposition of the great arteries". Orphanet J Rare Dis. 3: 27. doi:10.1186/1750-1172-3-27. PMC 2577629. PMID 18851735.
  28. ↑ Van Praagh R (1987). "Truncus arteriosus: what is it really and how should it be classified?". Eur J Cardiothorac Surg. 1 (2): 65–70. PMID 2856609.
  29. ↑ Inamdar AA, Inamdar AC (2016). "Heart Failure: Diagnosis, Management and Utilization". J Clin Med. 5 (7). doi:10.3390/jcm5070062. PMC 4961993. PMID 27367736.
  30. ↑ Maganti K, Rigolin VH, Sarano ME, Bonow RO (2010). "Valvular heart disease: diagnosis and management". Mayo Clin Proc. 85 (5): 483–500. doi:10.4065/mcp.2009.0706. PMC 2861980. PMID 20435842.
  31. ↑ "Myocardial Infarction (Heart Attack): Symptoms - National Library of Medicine - PubMed Health".
  32. ↑ Werdan K, Ruß M, Buerke M, Delle-Karth G, Geppert A, Schöndube FA; et al. (2012). "Cardiogenic shock due to myocardial infarction: diagnosis, monitoring and treatment: a German-Austrian S3 Guideline". Dtsch Arztebl Int. 109 (19): 343–51. doi:10.3238/arztebl.2012.0343. PMC 3364528. PMID 22675405.
  33. ↑ Ashurst J, Wasson M (July 2011). "Methemoglobinemia: a systematic review of the pathophysiology, detection, and treatment". Del Med J. 83 (7): 203–8. PMID 21954509.
  34. ↑ Spivak JL (February 2002). "The optimal management of polycythaemia vera". Br. J. Haematol. 116 (2): 243–54. PMID 11841424.
  35. ↑ Goldman RD (2015). "Breath-holding spells in infants". Can Fam Physician. 61 (2): 149–50. PMC 4325862. PMID 25676645.
  36. ↑ Goldenberg MM (2010). "Overview of drugs used for epilepsy and seizures: etiology, diagnosis, and treatment". P T. 35 (7): 392–415. PMC 2912003. PMID 20689626.
  37. ↑ Brown EN, Lydic R, Schiff ND (2010). "General anesthesia, sleep, and coma". N Engl J Med. 363 (27): 2638–50. doi:10.1056/NEJMra0808281. PMC 3162622. PMID 21190458.
  38. ↑ McAllister TW (2011). "Neurobiological consequences of traumatic brain injury". Dialogues Clin Neurosci. 13 (3): 287–300. PMC 3182015. PMID 22033563.
  39. ↑ Hotchkiss RS, Moldawer LL, Opal SM, Reinhart K, Turnbull IR, Vincent JL (2016). "Sepsis and septic shock". Nat Rev Dis Primers. 2: 16045. doi:10.1038/nrdp.2016.45. PMC 5538252. PMID 28117397.
  40. ↑ Rehberg S, Maybauer MO, Enkhbaatar P, Maybauer DM, Yamamoto Y, Traber DL (2009). "Pathophysiology, management and treatment of smoke inhalation injury". Expert Rev Respir Med. 3 (3): 283–297. doi:10.1586/ERS.09.21. PMC 2722076. PMID 20161170.
  41. ↑ Marriott, Bernadette (1996). Nutritional needs in cold and in high-altitude environments : applications for military personnel in field operations. Washington, D.C: National Academy Press. ISBN 0-309-05484-2.
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