Chest pain differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Associate Editor(s)-in-Chief: Iqra Qamar M.D.[2] Amresh Kumar MD [3]

An expert algorithm to assist in the diagnosis of Chest pain can be found here.

To go back to the main page on Unstable angina, click here.

Overview

There are several life-threatening causes of chest pain which need to be evaluated for first, which include; myocardial infarction, aortic dissection, esophageal rupture, pulmonary embolism, and tension pneumothorax. The other possible causes of chest pain can be determined by carefully assessing the nature of the pain, and obtaining a thorough patient history.

2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines^[1]

Recommendation for Evaluation of Acute Chest Pain With Suspected Noncardiac Causes


Class I
"1. Patients with acute chest pain should be evaluated for noncardiac causes if they have persistent or recurring symptoms despite a negative stress test or anatomic cardiac evaluation, or a low-risk designation by a CDP. (Level of Evidence: C-EO)"

Differential Diagnosis of Chest Pain

5 Life Threatening Diseases to Exclude Immediately

The frequency of conditions exclusive of acute myocardial infarction in a decreasing order is:^[10]

Gastroesophageal disease
Ischemic heart disease (angina)
Chest wall syndromes

Differential Diagnosis of Non-Cardiac Chest pain
Respiratory Pulmonary embolism Pneumothorax Hemothorax Pneumomediastinum Pneumonia Bronchitis Pleural irritation Malignancy
Gastrointestinal Cholecystitis Pancreatitis Hiatal hernia Gastroesophageal reflux disease, gastritis, esophagitis Peptic ulcer disease Esophageal spasm Dyspepsia
Chest wall Costochondritis Chest wall trauma, inflammation Herpes Zoster (shingles Cervical radiculopathy Breast disease Rib fracture Musculoskeletal injury, spasm
Psychological Panic disorder Anxiety Clinical depression Somatization disorder Hypochondria
Other Hyperventilation syndrome Carbon monoxide poisoning Sarcoidosis Lead poisoning Prolapsed intervertebral disc Thoracic outlet syndrome Side effect of medications (5-fluorouracil) Sickle cell crisis

The above table adopted from 2021 AHA/ACC/ASE Guideline^[11]

Differentiating the Life-Threatening and Ischemic Causes of Chest Pain from other Disorders

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

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

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

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

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

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

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

To review the differential diagnosis of chest pain, cough, and weight loss, click here.

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

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

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

The following table outlines the major differential diagnoses of chest pain:^[12]^[13]^[14]^[15]^[16]^[17]^[18]^[19]^[20]^[21]^[22]^[23]^[24]^[25]^[26]^[27]^[28]^[29]^[30]^[31]^[32]^[33]^[34]^[35]^[36]^[37]^[38]^[39]^[40]^[41]^[42]^[43]^[44]^[45]^[46]^[47]

Abbreviations: ABG (arterial blood gas); ACE (angiotensin converting enzyme); BMI (body mass index); CBC (complete blood count); CSF (cerebrospinal fluid); CXR (chest X-ray); 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); Coronary CT angiography (CCTA); multidetector row scanners (MDCT); Cardiovascular magnetic resonance — CMRI; Myocardial perfusion imaging (MPI); single-photon emission CT (SPECT); Positron emission tomography (PET) scanning; Magnetic resonance (MR) angiography, Computed tomographic (CT) angiography, and Transesophageal echocardiography (TEE), late gadolinium enhancement (LGE); right ventricular hypertrophy (RVH), right atrial enlargement (RAE), functional tricuspid regurgitation (TR), Pulmonary artery systolic pressure (PASP; adenosine deaminase (ADA); Serum amyloid A (SAA), soluble interleukin-2 receptor (sIL2R); High-resolution CT (HRCT) scanning

Differentials on the Basis of Etiology	Disease	Clinical Manifestations										Diagnosis
		Symptoms								Risk Factors	Physical Exam	Lab Findings	EKG	Imaging	Gold Standard
		Onset	Duration	Quality of Pain	Cough	Fever	Dyspnea	Weight Loss	Associated Features	Risk Factors	Physical Exam	Lab Findings	EKG	Imaging	Gold Standard
	Stable Angina^[48]	Sudden (acute)	2-10 minutes	Heaviness/pressure/ tightness/squeezing/ burning (Levine's sign) Retrosternal or left sided chest pain	-	-	+/-	-	Nausea and vomiting Diaphoresis	Dyslipidemia, hypertension, smoking, family history of premature disease, and diabetes	Transient third heart sound (S3 - ventricular filling sound) and fourth heart sound (S4 - atrial filling sound)	Cardiac enzymes normal	Exercise EKG: ST-segment depression	Exercise Stress Testing: Decreased myocardial perfusion Transthoracic echocardiography: Ejection fraction <50 percent	Coronary angiography
	COVID-19-associated myocardial infarction^[49]	Sudden (acute)	Commonly > 20 minutes	Retrosternal or left sided chest pain Same as stable angina but often more severe	+/-	+/-	+/-	-	Nausea and vomiting Diaphoresis	Dyslipidemia, hypertension, smoking, family history of premature disease, and diabetes	Transient third heart sound (S3 - ventricular filling sound) and fourth heart sound (S4 - atrial filling sound)	Cardiac enzymes elevated	ST elevation MI (STEMI) Non-ST elevation MI (NSTEMI) or Non Q wave	Exercise Stress Testing: Decreased myocardial perfusion Transthoracic echocardiography: Localized wall motion abnormalities Diffuse hypokinesia Left ventricular ejection fraction was lower than 50% in about 61% of the individuals	Coronary angiography
	Unstable Angina^[50]^[51]^[52]	Acute	10-20 minutes	Same as stable angina but often more severe	-	-	+	-	Nausea and vomiting Diaphoresis Presyncope Palpitations	Dyslipidemia, hypertension, smoking, family history of premature disease, and diabetes	Reverse splitting of the second heart sound Rales or crackles Elevated jugular venous pressure	Cardiac biomarkers [Cardiac troponin I, cardiac troponin T and MB isoenzyme of creatine kinase (CK-MB)] normal	ST-depression New T wave inversions Transient ST-elevation	Echocardiography: Ejection fraction <50 percent Exercise Stress Testing: Decreased myocardial perfusion	Invasive coronary angiography
	Myocardial Infarction^[12]^[13]^[14]^[15]	Acute	Commonly > 20 minutes	Same as stable angina but often more severe	-	-	+	-	Nausea and vomiting Diaphoresis Presyncope Palpitations Lateral displacement of the apical impulse	Dyslipidemia, hypertension, smoking, family history of premature disease, and diabetes	Hypotension Tachycardia S4 gallop Paradoxical splitting of S2 Mitral regurgitation murmur	Elevated cardiac enzymes ↑B-Type Natriuretic Peptide	ST elevation MI (STEMI) Non-ST elevation MI (NSTEMI) or Non Q wave	Echocardiography: ↓ EF CCTA: Coronory artery stenosis CMRI: Coronory vessels stenosis MPI on SPECT or PET scanning: Decreased myocardial perfusion.	CCTA combined with MPI
Cardiac	Vasospastic/ Prinzmetal/ Variant Angina^[53]^[54]	Gradual in onset and offset	Episodic, gradual in onset and offset	Chest discomfort described as squeezing, tightness, pressure, constriction, strangling, burning, heart burn, fullness in the chest, a band-like sensation, knot in the center of the chest, lump in the throat, ache, and heavy weight on chest	-	-	+	-	Nausea, diaphoresis, dizziness, dyspnea, and palpitations Associated with other vasospastic disorders, such as Raynaud's phenomenon and migraine headache	Multiple drugs (ephedrine-based products, cocaine, marijuana, alcohol, butane, sumatriptan, and amphetamines) Food-born botulism Guide wire or balloon dilatation while doing PCI Magnesium deficiency	Tachycardia, hypertension, diaphoresis, and a gallop rhythm	Urine drug screen may be positive for cocaine or other drugs	Transient (less than 15 minutes) ischemic ST changes in multiple leads A tall and broad R wave, Disappearance of the S wave A taller T wave Negative U waves	Stress testing: normal noninvasive stress test, exercise-induced spasm with ST-segment elevation, Stress echocardiography with ergonovine provocation: Vasospasm of coronory vessels Coronary arteriography: Epicardial spasm	Coronary arteriography
	Aortic Dissection^[55]^[56]	Sudden severe progressive pain (common) or chronic (rare)	Variable	Tearing, ripping sensation, knife like	-	-	+	-	Focal neurologic deficit Hypotension	Hypertension Genetically mediated collagen disorders Preexisting aortic aneurysm Bicuspid aortic valve Aortic coarctation Turner syndrome Vasculitis (giant cell arteritis, Takayasu arteritis, rheumatoid arthritis, syphilitic aortitis)	Pulse deficit New diastolic murmur Diastolic decrescendo murmur Focal neurologic deficit Hypotension	D-dimer <500 ng/mL rules out aortic dissection ↑Soluble ST2 (sST2) Measurements of soluble elastin fragments, smooth muscle myosin heavy chain, high-sensitivity C-reactive protein, fibrinogen, and fibrillin fragments	Nonspecific ST and T wave changes	CXR: Mediastinal and/or aortic widening CTA: A compressed true lumen MRA: Detects differential flow between the true and false lumens, widening of the aorta with a thickened wall TEE: Intimal dissection flaps, true and false lumens, thrombosis in the false lumen Aortography: Distortion of the normal contrast column, Flow reversal or stasis into a false channel, Failure of major branches to fill, and Aortic valvular regurgitation	CT angiography Digital subtraction aortography (if high suspicion)
	Pericarditis^[57]^[58]^[59]	Acute or subacute	May last for hours to days	Sharp & localized retrosternal pain	+	+	+	-	Pericardial friction rub	HIV TB Immunosuppression Acute trauma	Pericardial friction rub heard with the diaphragm of stethoscope	Leukocytosis ↑Troponin level ↑Erythrocyte sedimentation rate ↑C-reactive protein level	EKG changes (typically widespread ST segment elevation or PR depressions)	Chest x-ray typically normal Echocardiogram: normal or pericardial effusion CT scan: Noncalcified pericardial thickening with pericardial effusion CMR: inflamed pericardium and myocarditis	Pericardiocentesis Pericardial biopsy
	Pericardial Tamponade^[60]^[61]	Acute or subacute	May last for hours to days	Sharp and stabbing retrosternal pain	+/-	+	+	-	Pulsus paradoxus Pericardial rub	HIV TB Immunosuppression Acute trauma	Kussmaul sign Beck triad Pulsus paradoxus	Creatine kinase and isoenzymes Abnormal LFTs Antinuclear antibody assay, erythrocyte sedimentation rate and rheumatoid factor HIV testing	EKG findings: Sinus tachycardia Low QRS voltage Electrical alternans	CXR: enlarged cardiac silhouette with clear lung fields Echocardiography: Chamber collapse, Respiratory variation in volumes and flows, IVC plethora Swan-Ganz Catheterization: Equilibration of average intracardiac diastolic pressures (usually between 10 and 30 mmHg)	Echocardiography
	Myocarditis^[62]^[63]^[64]	Acute or subacute	Variable	Sharp & localized retrosternal pain reflects associated pericarditis	+/-	+	+	-	Heart failure Sudden cardiac death Arrythmias	Ischemic heart disease Valvular heart disease	S3 and S4 gallop Cardiac murmurs Pericardial friction rub	Serum cardiac troponin levels ↑ BNP or NT-proBNP level	Nonspecific ST changes, single atrial or ventricular ectopic beats, complex ventricular arrhythmias	CXR: Normal to enlarged with or without pulmonary vascular congestion and pleural effusions Echo: Left ventricular dilation, changes in left ventricular geometry (eg, development of a more spheroid shape), and wall motion abnormalities CMR: T1 and T2 signal intensity consistent with edema, presence of LGE consistent with necrosis or scar Radionuclide ventriculography: ↓ EF Cardiac catheterization: Assessment of hemodynamic status	Endomyocardial biopsy
	Hypertrophic cardiomyopathy^[65]^[66]^[67]	Acute or subacute	Variable	Typical or atypical chest pain	-	-	+	-	HF Arrhythmias Syncope Acute hemodynamic collapse	Positive family history of sudden cardiac death Genetic mutation	S4 Systolic murmurs LV apical impulse Brisk carotid pulse ↑ JVP A parasternal lift	Non-specific	Prominent abnormal Q waves P wave abnormalities Left axis deviation Deeply inverted T waves	Echocardiography: LV hypertrophy Systolic anterior motion of the mitral valve, LVOT obstruction Cardiac catheterization Pressure gradient Augmentation of the gradient Aortic pressure Left ventricular pressure Left atrial or pulmonary capillary wedge pressure Coronary angiography Obstructive epicardial coronary artery disease Genetic testing for HCM: Sarcomere mutation in an athlete with a maximal LV wall thickness in the "grey zone"	Genetic testing for HCM
	Stress (takotsubo) Cardiomyopathy^[68]^[69]^[70]^[71]	Acute	Commonly > 20 minutes	Substernal heaviness or tightness	-	-	+	-	Setting of physical or emotional stress or critical illness	Stress	Murmurs and rales may be present on auscultation in the setting of acute pulmonary edema	Catecholamines transiently elevated ↑TnT level ↑BNP level	ST segment elevation ST depression QT interval prolongation, T wave inversion, abnormal Q waves	Radionuclide myocardial perfusion imaging: Transient perfusion abnormalities in the left ventricular apex	Ventriculography and invasive coronary angiography
	Aortic Stenosis^[72]^[73]^[74]	Acute, recurrent episodes of angina	2-10 minutes	Heaviness/pressure/ tightness/squeezing/ burning (Levine's sign) Retrosternal	-	-	+	-	Dyspnea and decreased exercise tolerance Dizziness and syncope Angina pectoris	HTN Old age	S2 is soft, single and paradoxically split A2 delayed and tends to occur simultaneously with P2 Aortic ejection click Fourth heart sound (S4) can also be heard Crescendo–decrescendo murmur	Schistiocytes on peripheral blood smear	Non specific (the voltage of the QRS complex is increased showing the presence of left ventricular hypertrophy)	Echocardiography: aortic leaflets thickened and calcified, ↑ pulmonary artery pressure) CMR: Myocardial fibrosis, evaluation of aortic anatomy and size MDCT: Degree of aortic valve calcification PET: Measures active mineralization which correlates with stenosis severity	Echocardiography
	Heart Failure^[75]^[76]^[77]	Subacute or chronic	Variable	Dull Left sided chest pain	+	+/-	+	+	Orthopnea Peripheral edema Hemoptysis	Dyslipidemia, hypertension, smoking, family history of premature disease, and diabetes	S3 Elevated JVP Peripheral edema	Hyponatremia Hypoalbuminemia ↑ Serum brain natriuretic peptide (BNP) or NT-proBNP level A mild elevation in serum bilirubin (total bilirubin <3 mg/dL)	EKG findings are specific according to each cause of heart failure Q waves, ST and T wave abnormalities in patients with prior MI New onset arrhythmias (atrial fibrillation and ventricular tachycardia)	CXR: Cardiomegaly Echocardiography: ↓ EF Right heart catheterization: Pulmonary capillary wedge pressure >20 mmHg, right atrial pressure ≥12 mmHg) and/or decreased cardiac index (≤2.2 L/min/m2	Echocardiography
Differentials on the Basis of Etiology	Disease	Clinical Manifestations										Diagnosis
		Symptoms								Risk Factors	Physical Exam	Lab Findings	EKG	Imaging	Gold Standard
		Onset	Duration	Quality of Pain	Cough	Fever	Dyspnea	Weight Loss	Associated Features	Risk Factors	Physical Exam	Lab Findings	EKG	Imaging	Gold Standard
Pulmonary	Pulmonary Embolism^[78]^[79]	Acute	May last minutes to hours	Sharp or knifelike or pleuritic pain Localized to side of lesion	+	+/-	+	-	Hemoptysis History of venous thromboembolism or coagulation abnormalities.	Hormone replacement therapy Cancer Oral contraceptive pills Stroke Pregnancy Postpartum Prior history of VTE Thrombophilia	S3 or S4 gallop Low grade fever Tachycardia Tachypnea Hypoxia	↑D-dimer ≥500 ng/mL Arterial blood gases (Respiratory alkalosis) ↑Troponin levels Hypercoagulation workup	Tachycardia and nonspecific ST-segment and T-wave changes (70 percent) S1Q3T3 pattern New right bundle branch block Inferior Q-waves (leads II, III, and aVF)	Duplex Ultrasonography: DVT CXR: Westermark sign, Hampton hump, Palla's sign Echocardiography: RV dilation (ratio of apical 4-chamber RV diameter to left ventricle (LV) diameter > 0.9) RV systolic dysfunction Ventilation-Perfusion Scanning: High probability	CT pulmonary angiography
	Spontaneous Pneumothorax^[80]^[81]	Acute	May last minutes to hours	Sharp Localized pleuritic	-	-	+	-	Respiratory distress Tachypnea Asymmetric lung expansion Hyperresonance on percussion Decreased tactile fremitus Tachycardia Cardiac apical displacement	Smoking Positive family history Marfan syndrome Homocystinuria Thoracic endometriosis.	Decreased breath sounds on involved side Lung sounds transmitted from the unaffected hemithorax are minimal with auscultation at the midaxillary line Adventitious lung sounds (crackles, wheeze; an ipsilateral finding) Pulsus paradoxus	Respiratory alkalosis on ABGs	Rightward shift in the mean electrical axis Loss of precordial R waves Diminution of the QRS voltage Precordial T wave inversions	CXR: White visceral pleural line on the chest radiograph CT: small amounts of intrapleural gas, atypical collections of pleural gas, and loculated pneumothoraces	CT scan
	Tension Pneumothorax^[82]^[83]	Acute	May last minutes to hours	Sharp Pleuritic	-	-	+	-	Hypotension Jugular venous distention Respiratory distress	Trauma	Decreased breath sounds on involved side Lung sounds transmitted from the unaffected hemithorax are minimal with auscultation at the midaxillary line Adventitious lung sounds (crackles, wheeze; an ipsilateral finding) Pulsus paradoxus	Respiratory alkalosis on ABGs	Significant elevation of the ST-T segment from leads V1 to V4	CXR: A distinct shift of the mediastinum to the contralateral side, collapse of the ipsilateral lung, and flattening or inversion of the ipsilateral hemidiaphragm	CT scan
	Pneumonia^[84]^[85]^[86]	Acute or chronic	Variable	Dull Localized to side of lesion	+	+	+	+/-	Altered mental status Tachycardia Rust-colored sputum Green sputum Red currant-jelly sputum Central cyanosis	Long hospital stay Ill contact exposure Aspiration	Wheezing Rhonchi Rales Decreased breath sounds Pleural friction rub	Arterial blood gas : Hypoxia, hypoxemia ↑ Procalcitonin Leukocytosis Sputum evaluation Positive blood cultures	Sinus tachycardia Nonspecific ST-segment or T-wave changes	CXR: Interstitial infiltrates, lobar consolidation, cavitation	CXR
	Tracheitis/ Bronchitis^[87]^[88]^[89]^[90]	Acute	Variable	Dull Substernal	+	+	+	-	Tachypnea Respiratory distress Hoarseness Dyspnea Cyanosis Sore throat Odynophagia Dysphonia	Aspiration Pneumonia	Inspiratory stridor (with or without expiratory stridor) Nasal flaring Wheezing	Gram stain of exudates: Neutrophils	Peaked P-wave	Radiography of the neck: Steeple sign Laryngotracheobronchoscopy: a normal epiglottis with subglottic narrowing, thick and purulent secretions in the trachea, pseudomembranes	Endoscopy
	Pleuritis	Acute or subacute or chronic	May last minutes to hours	Sharp Localized pleuritic	+	+	+	-	Sharp chest pain with breathing Itching in sites on the back Dizziness	Autoimmune conditions Infections	Tachypnea Tachycardia Pleural Rubs Decreased breath sounds	Leukocytosis Arterial blood gas (ABG): Hypoxia Thoracocentesis	EKG done to rule out other causes in differential diagnoses	Chest X Ray: Pleural fluid on one or both sides Computerized tomography (CT) scan: Pleural effusions	CXR
	Pulmonary Hypertension^[91]^[92]^[93]	Acute or subacute or chronic	Variable	Substernal pressure like	+	-	+	-	Dyspnea Symptoms of right heart failure (edema) Past history of heart murmur Deep venous thrombosis (DVT) Arthritis or arthralgias Rash	Smoking HF Heavy snoring Morbid obesity	The intensity of the pulmonic component of the second heart sound (P2) may be increased and the P2 may demonstrate fixed or paradoxical splitting. Systolic ejection murmur A right-sided fourth heart sound (S4) with a left parasternal heave	Abnormal Arterial blood gas Antinuclear antibody (ANA) levels Antineutrophil cytoplasmic antibody (ANCA) Brain natriuretic peptide (BNP of NT-proBNP) HIV testing Iron deficiency Pulmonary Function Testing Polysomnography	Right axis deviation An R wave/S wave ratio greater than one in lead V1 Incomplete or complete right bundle branch block Increased P wave amplitude in lead II (P pulmonale) due to right atrial enlargement	Chest Radiography: Oligemic lung fields Echocardiography: PASP is >50 and the TRV is >3.4 Ventilation-Perfusion (V/Q) Lung Scanning: Abnormal Right-sided cardiac catheterization: Mean PCWP >15 mmHg,	Cardiac catheterization
	Pleural Effusion^[94]^[95]^[96]	Acute or subacute or chronic	Variable	Dull Pleuritic pain	+	+/-	+	+/-	Increasing lower extremity edema Orthopnea Paroxysmal nocturnal dyspnea Night sweats Hemoptysis	Pneumonia	Diminished or inaudible breath sounds Pleural friction rub Egophony (known as "E-to-A" changes)	Pleural fluid LDH levels above 1000 IU/L Nucleated cells - Lymphocytosis - Eosinophilia - Mesothelial cells Pleural fluid culture and cytology Pleural fluid antinuclear antibody and rheumatoid factor	Typically not indicated	Chest X Ray: Pleural fluid on one or both sides Computerized tomography (CT) scan: Detects small pleural effusions, ie, less than 10 mL and possibly as little as 2 mL of liquid in the pleural space, Thickening of the visceral and parietal pleura MRI: Characterize the content of pleural effusions	Computed tomography
	Asthma & COPD^[97]^[98]^[99]^[100]	Acute or subacute or chronic	Variable	Tightness	+	+/-	+	+/-	Cyanosis	Smoking HF HTN	Elevated jugular venous pulse (JVP) Hyperinflation (barrel chest) Peripheral edema Clubbing Wheezing Rhonchi Diffusely decreased breath sounds Coarse crackles beginning with inspiration	Leukocytosis Eosinophilia Respiratory alkalosis	Peaked P-wave Reduced amplitude of the QRS complexes Multifocal atrial tachycardia (MAT)	CXR: Hyperinflation Spirometry: ↓ FEV1, PEF, ↓ FEV1/FVC	Spirometry
	Pulmonary Malignancy^[101]^[102]^[103]^[104]	Chronic	Variable	Dull aching	+	+/-	+	+	Bone pain Fatigue Neurologic dysfunction Superior vena cava (SVC) obstruction Hoarseness Hemidiaphragm paralysis Dysphagia Paraneoplastic syndromes Hypercalcemia	Smoking Metastasis	Wheeze Crackles Depending upon complications caused by the spread of cancer	Hypercalcemia	EKG may be performed before cancer treatment to identify any pre-existing conditions, or during treatment to check for possible heart damage	CXR and CT scan: Mass lesion, hilar lymphadenopathy Spirometry: ↓Vt, ↑RV Bronchoscopy: Biopsy	Bronchoscopy
	Sarcoidosis^[105]^[106]^[107]^[108]	Chronic	Days to week	Chest fullness	+	-	+	+	Löfgren syndrome (fever, bilateral hilar lymphadenopathy (BHL), and polyarthralgias) Uveitis Heart block Lymphocytic meningitis Diabetes insipidus Fatigue Hypercalciuria	Black population Autoimmune diseases	Diminished respiratory sounds	↑ ACE level, adenosine deaminase, SAA, sIL2R Hypercalciuria Elevated 1,25-dihydroxyvitamin D levels	AV block Prolongation of the PR interval (first-degree AV block) Ventricular arrhythmias (sustained or nonsustained ventricular tachycardia and ventricular premature beats [VPBs]) Supraventricular arrhythmias	Chest radiograph: Bilateral hilar adenopathy High-resolution CT (HRCT) scanning of the chest: Ground glass opacification, Hilar and mediastinal lymphadenopathy, Bronchial wall thickening	Lung Biopsy
	Acute chest syndrome (Sickle cell anemia)^[109]^[110]^[111]	Acute	May last minutes to hours	Chest tightness	+	+/-	+	-	Sickle cell anemia Vaso-occlusive crisis Pain crises	↑ WBC ↑ Hb levels ↓ fetal hemoglobin levels Smoking Vaso-occlusive pain events	Systolic murmur may be heard over the entire precordium	↑Erythrocyte sedimentation rate Peripheral blood smears: Schistiocytes ↑ Reticulocyte count	EKG typically not indicated	Plain radiography of the extremities: Avascular necrosis	---
Differentials on the Basis of Etiology	Disease	Clinical Manifestations										Diagnosis
		Symptoms								Risk Factors	Physical Exam	Lab Findings	EKG	Imaging	Gold Standard
		Onset	Duration	Quality of Pain	Cough	Fever	Dyspnea	Weight Loss	Associated Features	Risk Factors	Physical Exam	Lab Findings	EKG	Imaging	Gold Standard
Gastrointestinal	GERD, Peptic Ulcer^[112]^[113]^[114]	Acute	Minutes to hours (gastroesophageal reflux) Prolonged (peptic ulcer) 5 to 60 minutes	Burning Substernal Epigastric	+/-	-	-	+/-	Visceral, substernal, worse with recumbency, no radiation, relief with food, antacids Hematemesis or melena resulting from gastrointestinal bleeding Dyspepsia	Prolonged NSAIDs intake Smoking Alcohol abuse Spicy foods H-pylori infection	Not any auscultatory findings associated with this disease Enamel erosion or other dental manifestations	↑Serum Gastrin Level Secretin Stimulation Test H-Pylori testing	EKG usually normal but may show T wave inversions in leads V2 through V4 consistent with myocardial ischemia in patients with peptic ulcer perforation	Upper Gastrointestinal Endoscopy: Biopsy Esophageal Manometry: To exclude an esophageal motility disorder Esophageal impedance pH testing: Monitors esophageal pH	Upper Gastrointestinal Endoscopy
	Diffuse Esophageal Spasm^[115]^[116]^[117]^[118]	Acute	Minutes to hours 5 to 60 minutes	Burning Pressure Visceral, spontaneous, substernal	+	-	+/-	+/-	Associated with cold liquids Relief with nitroglycerin	---	---	Barium swallow: Multiple areas of spasm throughout the length of the esophagus Impedance testing: Higher amplitudes and better transit of swallowed boluses	No ECG findings associated with DES, but ECG is done to exclude variant angina due to higher concurrent association of variant angina with DES	Esophageal manometry : ≥20 percent premature contractions (distal latency <4.5 seconds)	Esophageal manometry
	Esophagitis^[119]^[120]^[121]	Acute	Variable	Burning Epigastric	+	+	-	+/-	Heartburn Abdominal pain	HIV Immunosuppression	No auscultatory finding	Troponin or other cardiac markers Leukopenia ↓CD4 count Human immunodeficiency virus (HIV) test	ECG is done to rule out acute coronary syndrome	Double-contrast esophageal barium study (esophagography) Endoscopy: Biopsy	Endoscopy
	Eosinophilic Esophagitis^[122]^[123]^[124]^[125]^[126]^[127]	Chronic	Variable	Burning Retrosternal Abdominal	+	-	-	-	Dysphagia Food impaction GERD	Allergic diseases Asthma Rinitis Eczema	No auscultatory finding in the this disease	Elevated IgE (>114,000 units/L) Elevated peripheral eosinophils	Typically no finding on EKG	Barium studies: Strictures and a ringed esophagus Endoscopy: Stacked circular rings ("feline" esophagus) ●Strictures ●Linear furrows ●Whitish papules Esophageal biopsy: More than 15 eosinophils per high-power field	Esophageal biopsy
	Esophageal Perforation^[17]	Acute	Minutes to hours	Burning Upper abdominal	-	+/-	+	-	Eating disorders such as bulimia Repeated episodes of retching and vomiting with either recent excessive dietary or alcohol intake Subcutaneous emphysema	Instrumentation/surgery Penetrating or blunt trauma Medications, other ingestions, foreign body Violent retching/vomiting Hernia/intestinal volvulus/obstruction Inflammatory bowel disease Appendicitis Peptic ulcer disease	Mild tachycardia or hypothermia Hamman crunch (crackling sound upon chest auscultation occurs due to pneumomediastinum)	↑Serum amylase ↑C-reactive protein levels	EKG may be indicated to assess for myocardial ischemia due to acute gastrointestinal bleeding, especially if there is coexisting:Cardiovascular disease, significant anemia and advanced age	Plain chest films or chest CT: Pneumomediastinum, Free air under the diaphragm, •Pleural effusion •Pneumothorax (Macklin effect). •Subcutaneous emphysema Plain abdominal films (or abdominal CT scout film):The appearance of pneumoperitoneum -Free air under the diaphragm -Cupola sign (inverted cup) -Rigler sign (double-wall sign) -Psoas sign -Urachus sign	Confirmed by water-soluble contrast esophagram
	Mediastinitis^[128]^[129]^[130]^[131]	Acute, Chronic	Variable	Retrosternal irritation	+/-	+	+	-	Nonspecific	Infection Esophageal perforation Post operative complication	Dysphagia Dysphonia Stridor Hamman sign	Positive organisms in sternal culture Leukocytosis Positive blood cultures	Diffuse ST elevation	CT: Localize the infection and extent of spread MRI: Assesses vascular involvement and complications	CT scan
	Cholelithiasis^[132]^[133]^[134]^[135]	Acute, subacute	Minutes to hours	Burning Colicky Right upper abdomen Substernal epigastric	-	+/-	-	-	Obesity Fertile females in 40's	The presence of a common bile duct stone on transabdominal ultrasound •Clinical acute cholangitis •A serum bilirubin greater than 4 mg/dL (68 micromol/L)	Murphy sign negative Jaundice	↑ALT ↑AST ↑Amylase levels ↑ALP	Typically not indicated	Transabdominal ultrasound (TAUS): shows gallstones EUS: Detects biliary sludge MRCP: Detects stones >6mm Endoscopic Retrograde Cholangiopancreatography (ERCP): Diagnostic and therapeutic removal of stones	Endoscopic ultrasound and MECP
	Pancreatitis^[136]^[137]^[138]^[139]^[140]	Acute, Chronic	Variable	Epigastric Upper left side of the abdomen Pressure like	-	+	+	+/-	Primary cirrhosis Primary sclerosing cholangitis Cystic fibrosis Autoimmune diseases	Alcohol abuse Smoking Genetic predisposition	Tachypnea Hypoxemia Hypotension Cullen's sign Grey Turner sign	↑Amylase levels ↑Lipase levels ↑ALT ↑ALP Leukocytosis	T-wave inversion ST-segment depression ST-segment elevation rarely Q-waves	CT: focal or diffuse enlargement of the pancreas MRI: Pancreatic enlargement	CT Scan
	Sliding Hiatal Hernia^[141]^[142]^[143]	Acute	Variable	Epigastric Burning	+	-	+	-	Obstruction Cameron ulcers GERD Dysphagia	Trauma Iatrogenic Congenital malformation	Bowel sounds may be heard in the chest	Non specific	T wave inversion in anterior lead.	Barium swallow: At least three rugal folds traversing the diaphragm Upper endoscopy: A greater than 2-cm separation between the squamocolumnar junction and the diaphragmatic impression High resolution manometry: The separation of the crural diaphragm from the lower esophageal sphincter (LES) by a pressure trough	Upper endoscopy High resolution manometry (for smaller hernias)
Musculoskeletal	Costosternal syndromes (costochondritis)^[144]^[145]^[146]^[147]	Acute, subacute	Days to weeks	Pressure like on anterior part of chest wall	-	+	-	-	History of repeated minor trauma or unaccustomed activity (eg, painting, moving furniture)	Trauma	Pain by palpation of tender areas Maneuvers, such as the "crowing rooster" and horizontal arm flexion maneuver	Non specific	EKG is done to rule out other cardiovascular causes	CXR: To rule out fracture	Pain by palpation of tender areas
	Lower rib pain syndromes^[148]	Chronic	Variable	Aching Lower chest Upper abdomen	-	-	+	-	Common in women with a mean age in the mid-40s	---	Hooking maneuver Reproduces pain by pressing a tender spot on the costal margin	Non specific The workup is done for excluding cardiac disorders and other causes of chest pain	EKG is done to rule out other cardiovascular causes	CXR: To rule out fracture	---
	Sternalis syndrome	Chronic	Variable	Pressure like pain Over the body of sternum Sternalis muscle Left or middle side of the chest wall	-	-	-	-	Cardiac diseases	Daily activities Emotional distress Anxiety	Localized tenderness is found directly over the body of the sternum or overlying sternalis muscle	No specific diagnostic test for this disease The workup is done for excluding cardiac disorders and other causes of chest pain	EKG is done to rule out other cardiovascular causes	X-ray : To rule out fracture	Physical exam
	Tietze's syndrome^[149]	Acute	Weeks	Pressure like pain over Costosternal joint Sternoclavicular joint Costochondral joint Second and third ribs	-	-	-	-	Most often involve the areas of 2nd and 3rd ribs More common in young adults Sternocostoclavicular hyperostosis Ankylosing spondylitis	Upper respiratory infections Excessive coughing	Painful and localized swelling of the costosternal, sternoclavicular, or costochondral joints most often involving 2nd and 3rd ribs	No specific diagnostic test for this disease The workup is done for excluding cardiac disorders and other causes of chest pain	EKG is done to rule out other cardiovascular causes	X-ray: To rule out fracture	Tests are done to rule out other diseases
	Xiphoidalgia^[150]	Acute	Variable	Pressure like pain over Over the xiphoid process Sternum Xiphisternal joint	-	-	-	-	Symptoms are aggravated by twisting and bending movements	Cough Heavy work	Provocative test	No specific diagnostic test for this disease The workup is done for excluding cardiac disorders and other causes of chest pain	EKG is done to rule out other cardiovascular causes	X-ray: To rule out fracture	Tests are done to rule out other diseases
	Spontaneous sternoclavicular subluxation^[151]	Acute, Chronic	Variable	Aching pain over Sternoclavicular joint	-	-	-	-	More common in middle age women Occurs in dominant hands with repetitive tasks of heavy or moderate quality	Trauma	Palpation of tender areas	No specific diagnostic test for this disease The workup is done for excluding cardiac disorders and other causes of chest pain	EKG is done to rule out other cardiovascular causes	X-ray: Sclerosis of the medial clavicle	X-ray
Differentials on the Basis of Etiology	Disease	Clinical Manifestations										Diagnosis
		Symptoms								Risk Factors	Physical Exam	Lab Findings	EKG	Imaging	Gold Standard
		Onset	Duration	Quality of Pain	Cough	Fever	Dyspnea	Weight loss	Associated Features	Risk Factors	Physical Exam	Lab Findings	EKG	Imaging	Gold Standard
Rheumatic	Fibromyalgia^[152]^[153]^[154]	Chronic	Variable	Raynaud phenomenon (RP) Deep ache and burning pain on Shoulders Back of the Neck Chest Lower Back Elbows Hips Shin Knees	-	-	+	-	Somatization Depression IBS	---	Presence of tenderness in soft-tissue anatomic locations	Non specific Normal Blood and urine test (mandatory to rule out other diseases)	P-wave dispersions (Pd)	---	---
	Rheumatoid arthritis^[155]	Chronic	Years	Symmetrical joint pain in Wrist Fingers Knees Feet Ankles	-	+	-	+	Extra-articular involvement of other organ systems Carpal tunnel syndrome Tarsal tunnel syndrome	Old age Smoking Autoimmune conditions	Reduced grip strength Rheumatoid nodules	Positive Rheumatic Factor Anti-CCP body Synovial fluid analysis: WBC between 1500 and 25,000/cubicmm, low glucose, low C3 and C4 complement level. Thrombocytosis Anemia Mild leukocytosis	ECG is done rule out the heart failure as RA is one of the causes of heart failure	Plain film radiography: periarticular osteopenia, joint space narrowing, and bone erosions MRI: Bone erosions Ultrasonography: Degree of inflammation and the volume of inflamed tissue	---
	Ankylosing spondylitis^[156]^[157]^[158]^[159]	Chronic	Years	Intermittent pain in Spine joint Sacroiliac joint	-	-	-	-	Patients with HLA-27 variant Extra-articular joint involvements Restrictive pulmonary disease Acute coronary syndromes (ACS), strokes, venous thromboembolism, conduction abnormalities	Genetics (Monozygotic twins)	Tenderness of the SI Limited spinal ROM Schober test	↑ESR ↑CRP ↑ALP ↑IgA Antigen HLA-27 positive Negative Rheumatic Factor	ECG is done to rule out conductions defects and aortic insufficiency	Plain radiography: Erosions, ankylosis, changes in joint width, or sclerosis. Magnetic resonance imaging (MRI): Osteitis" or "bone marrow edema" (BME)	Plain films of the sacroiliac joints
	Psoriatic arthritis^[158]	Chronic	Years	Asymmetrical intermittent pain in Interphalangeal joints Nails Wrist Knees Ankles Lower Back	-	-	-	-	Psoriasis Enthesitis Tenosynovitis Dactylitis	Psoriasis HLA-B*27 positive	Dactylitis with sausage digits Onycholysis Pitting edema Ocular involvement	Non specific	Longer PR interval	X-ray: "pencil-in-cup" deformity, erosive changes and new bone formation, lysis of the terminal phalanges; fluffy periostitis MRI: Detects articular, periarticular, and soft-tissue inflammation, enthesitis	X-ray
	Sternocostoclavicular hyperostosis (SAPHO syndrome)^[158]^[160]^[161]^[162]^[163]	Chronic	Years	Recurrent and multifocal pain in Sternoclavicular joint	-	+	-	-	Palmoplantar pustulosis (PPP)	Positive family history of: Spondyloarthritis IBD Psoriasis Rheumatoid arthritis Other autoimmune/autoinflammatory disease	Hyperostosis Osteitis Synovitis Pustular eruptions Inflammatory nodules or plaques	Serologic testing to exclude other diseases Non specific	ECG is done to rule out conductions defects and aortic insufficiency	Plain radiography: Hyperostotic changes (thickening of periosteum, cortex, and endosteum), sclerotic lesions, osteolysis, periosteal reaction, and osteoproliferation Bone scan: "bull's head" change Magnetic resonance imaging: Osteitis and soft tissue involvement Fluorodeoxyglucose positron emission tomography (FDG-PET)/CT: Differentiates active versus inactive lesions	Bone scan
	Systemic lupus erythematosus^[164] ^[165]^[166]	Chronic	Years	Skin Joints (fingers, wrist, knees) Kidneys SLE can affect any organ of the body	+/-	+	+	+	HLA-genetic mutations Female gender Being younger than 50	Autoimmune conditions Genetic predisposition Positive family history	Malar rash Photosensitive rash Discoid rash Arthritis of the proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints of the hands Pleuro-pericardial friction rubs Systolic murmurs	Elevation of autoantibodies (ANA, anti-dsDNA, anti-SM, antiphospholipid) Complement levels decreased Anemia	Sinus tachycardia, ST segment changes, and ventricular conduction disturbances	Related to specific organ involvent	Anti-dsDNA antibody test
	Relapsing polychondritis^[167]	Chronic	Years	Intermittent pain in: Tissues that cover the end of the joints Cartilage of costal rib	+	+	+	+	Hodkin's lymphoma Myelodysplastic syndromes Gastrointestinal disorders Type 1 Diabetes mellitus Auricular chondritis	Autoimmune diseases	Physical examinations findings are seen related to nasal chondritis, ocular inflammation, cardiovascular disease, skin disease, CNS and pulmonary system	Negative rheumatoid factor Anti-type II collagen antibodies Antineutrophil cytoplasmic antibodies	ECG is done to rule out the cardiovascular complications of this disease	Non specific Related to specific organ involvent	No gold standard test for this disease
Psychiatric	Panic attack/ Disorder^[168]^[18]^[169]	Acute or subacute or chronic	Variable	Variable	+	-	+	-	History of Depression Panic attacks Agoraphobia	Psychiatric disorders	Anxious Tachypneic	Thyroid function tests Complete blood count Chemistry panel	Sinus Tachycardia	No any specific radiographic test is done	---
Others	Substance abuse (Cocaine)^[170]^[171]^[172]	Acute (hours)	Minutes to hours	Pressure like pain in the center of chest	+	+	+	+	Anxiety Dyspnea Nausea Palpitations	Psychiatric disorders	Signs of injection drug use Signs of drug inhalation Poor personal hygiene	Serum biomarkers (Troponin I, Troponin T) Toxicologic tests or drug screens of bodily fluids (blood, urine, saliva) and hairs	QT prolongation Sinus Tachycardia Arrhythmias Cardiac conduction abnormalities	---	Gold standard test depends on the type of substance is abuse
Others	Herpes Zoster^[173]^[174]^[175]	Acute or Chronic	Variable	Burning pain on Chest Upper back Lower back	-	+	-	-	People who had chickenpox	Immunosuppression	Painful grouped herpetiform vesicles on an erythematous base distributed in a single dermatome	Viral culture Direct immunofluorescence testing, Polymerase chain reaction assay (PCR)	ECG is done to rule out other cardiovascular causes of chest pain	Magnetic resonance imaging (MRI): To rule out encephalitis	Viral tissue culture

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