Tuberculosis differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mashal Awais, M.D.[2]; Alejandro Lemor, M.D. [3]

Overview

Pulmonary tuberculosis should be distinguished from other diseases that cause cough, hemoptysis, fever, night sweat, and weight loss such as: bacterial pneumonia, atypical pneumonia, brucellosis, bronchogenic carcinoma, sarcoidosis, and Hodgkin lymphoma.

Differential Diagnosis

Pulmonary Tuberculosis

Disease	Findings
Bacterial pneumonia	Sudden onset of symptoms, such as high fever, cough, purulent sputum, chest pain, leukocytosis, chest X-ray shows consolidation.
Bronchogenic carcinoma	may be asymptomatic, usually at older ages (> 50 years old), cough, hemoptysis, weight loss
Brucellosis	Fever, anorexia, night sweats, malaise,back pain , headache, and depression. History of exposure to infected animal
Hodgkin lymphoma	Fever, night sweats, pruritus, painless adenopathy, mediastinal mass
Mycoplasmal pneumonia	Gradual onset of dry cough, headache, malaise, sore throat. Diffuse bilateral infiltrates on chest X-ray.
Sarcoidosis	Non-caseating granulomas in lungs and other organs, bilateral hilar lymphadenopathy, mostly in African American females.
Adapted from Mandell, Douglas, and Bennett's principles and practice of infectious diseases 2010

Extra-Pulmonary Tuberculosis

Extra-Pulmonary Location	Differential Diagnosis
Tuberculous Lymphadenitis	Lymphoma, squamous cell carcinoma, papillary thyroid cancer, pyogenic infection
Skeletal Tuberculosis	Multiple myeloma, bone metastasis, spinal cord abscess, osteoporosis
Tuberculous Arthrits	Bacterial septic arthritis, pseudogout
Central Nervous System Tuberculosis	Bacterial meningitis, viral meningitis, encephalitis
Tuberculosis Peritonitis	Bacterial peritonitis, chronic peritoneal dialysis
Adapted from Asian Spine J. Feb 2014; 8(1): 97–111; Handbook of Clinical Neurology; Circulation Dec 2005 vol.112 no.23 3608-3616; Am J Trop Med Hyg 2013 vol. 88 no. 1 54-64 Clin Infect Dis.(2011)53(6):555-562.

Causes of lung cavities	Differentiating Features	Differentiating radiological findings	Diagnosis confirmation
Malignancy (Primary lung cancer)	Elderly male or female Chronic smokers Presents with a low-grade fever, absence of leukocytosis, systemic complaints weight loss, fatigue Absence of factors that predispose to gastric content aspiration, no response to antibiotics within 10 days Hemoptysis is commonly associated with bronchogenic carcinoma	A coin-shaped lesion with thick wall(>15mm) is seen on CXR with less ground glass opacities Bronchoalveolar lavage cytology shows malignant cells	Biopsy of lung
Pulmonary Tuberculosis	Mostly in endemic areas Symptoms include productive cough,night sweats, fever and weight loss	CXR and CT demonstrates cavities in the upper lobe of the lung	Sputum smear-positive for acid-fast bacilli and nucleic acid amplification tests (NAAT) is used on sputum or any sterile fluid for rapid diagnosis and is positive for mycobacteria.
Necrotizing Pneumonia	Any age group Acute, fulminant life threating complication of prior infection >100.4F fever, with hemodynamic instability Worsening pneumonia-like symptoms	CXR demonstrates multiple cavitary lesions Pleural effusion and empyema are common findings	CBC is positive for the causative organism
Loculated empyema	Children and elderly are at risk Pleuritic chest pain, dry cough, fever with chills Dullness to percussion decreased breath sounds, and reduced vocal resonance on examination	Empyema appears lenticular in shape and has a thin wall with smooth luminal margins	Thoracocentesis
Granulomatosis with polyangiitis (Wegener's)	Women are more commonly effected than man. Kidneys are also involved Upper respiratory tract symptoms , perforation of nasal septum, chronic sinusitis, otitis media, mastoiditis. Lower respiratory tract symptoms, hemoptysis, cough, dyspnea. Renal symptoms, hematuria, red cell casts	Pulmonary nodules with cavities and infiltrates are a frequent manifestation of CXR	Positive for P-ANCA Biopsy of the affected tissue shows necrotizing granulomas
Rheumatoid nodule	Elderly females of 40-50 age group Manifestation of rheumatoid arthritis Presents with other systemic symptoms including symmetric arthritis of the small joints of the hands and feet and morning stiffness are common manifestations.	Pulmonary nodules with cavitation are present in the upper lobe (Caplan syndrome) on Xray.	Positive for both rheumatoid factor and anti-cyclic citrullinated peptide antibody.
Sarcoidosis	More common in African-American females Often asymptomatic except for enlarged lymph nodes Associated with restrictive lung disease Erythema nodosum Lupus pernio (skin lesions on face resembling lupus) Bell palsy Epithelioid granulomas containing microscopic Schaumann and asteroid bodies	On CXR bilateral adenopathy and coarse reticular opacities are seen. CT of the chest demonstrates extensive hilar and mediastinal adenopathy Additional findings on CT include fibrosis (honeycomb, linear, or associated with bronchial distortion), pleural thickening, and ground-glass opacities.	Biopsy of lung reveals non-caseating granuloma
Bronchiolitis obliterans (Cryptogenic organizing pneumonia)	Rare condition and mimics asthma, pneumonia and emphysema It is due to drug or toxin exposure, autoimmune diseases, viral infections, or radiation injury Individuals working in industries are at high risk Presents with fever, cough, wheezing and shortness of breath over weeks to months,	Common appearance on CT is patchy consolidation,often accompanied by ground-glass opacities and nodules.	Biopsy of the lung Pulmonary function tests demonstrate low fev1/fvc
Langerhans cell Histiocytosis	Exclusively occurs in smokers, with a peak age of onset 20-40 years. Clinical presentation is variable, but symptoms generally include months of dry cough, fever, night sweats and weight loss. Skin is involved in 80% of the cases, scaly erythematous rash is typical.	Thin-walled cystic cavities are the usual radiographic manifestation, observed in over 50% of patients by either CXR or CT scans.	Biopsy of the lung

Differentiating brain tuberculoma from other brain cystic lesions

Disease	Prominent clinical features	Lab findings	Radiological findings
Neurocysticercosis	Presenting symptoms vary based on the site of the cysticerci. Parenchymal neurocysticercosis causes all the symptoms and signs of space occupying lesions. Extraparenchymal neurocysticercosis causes manifestations of increased intracranial pressure if cysts are present in the subarachnoid space or in the ventricles, the clinical picture of spinal cord compression if present in the spinal cord or causes eye disease if cysts are present in the orbit.	CDC's immunoblot is based on detection of antibody to one or more of 7 lentil-lectin purified structural glycoprotein antigens from the larval cysts. It is 100% specific and has a sensitivity superior to that of any other test yet evaluated	Computerized tomography (CT) is superior to magnetic resonance imaging (MRI) for demonstrating small calcifications. However, MRI shows cysts in some locations (cerebral convexity, ventricular ependyma) better than CT, is more sensitive than CT to demonstrate surrounding edema, and may show internal changes indicating the death of cysticerci.
Brain abscess	Headaches are the most common symptom. Often, headaches occur on the same side of the abscess and tend to be severe (unresponsive to analgesics). Fever is not a reliable sign.	Lumbar puncture is contraindicated but when done, it was variable between patients. Culture from the CT-guided aspirated lesion helps in identifying the causative agent.	Contrast enhanced CT is useful for a rapid assessment of the size and number of the abscesses. MRI: Diffusion-weighted imaging (DWI) MRI can differentiate brain abscesses from cystic brain lesions with sensitivity and specificity of 96%.
Brain tumors	Most common presenting symptom is dull aching headache. Often, it is associated with other symptoms of increased intracranial pressure (ICP) as seizures, visual disturbances, nausea, and vomiting.		CT may be used in localizing the tumor and getting a rough estimate on the dimensions. MRI: Gadolinium-enhanced MRI is the preferred imaging modality for assessing the extension of the tumor and its exact location.
Brain tuberculoma	Brain tuberculomas has an insidious onset of symptoms as compared to tuberculous meningitis. Presentations are usually due to the pressure effect, not the T.B. bacilli. Presenting symptoms and signs in order of occurrence: Episodes of focal seizures Signs of increased intracranial pressure Focal neurologic deficits.	T.B. should be investigated everywhere else in the body (e.g. peripheral lymphadenopathy, sputum and blood culture)	CT: Contrast-enhanced CT scan shows a ring enhancing lesion surrounded by an area of hypodensity (cerebritis) and the resulting mass effect. MRI: Better than CT scan in assessing the site and size of the tuberculoma. Gadolinium-enhanced MRI reveals a ring-enhancing lesion between 1-5 cm in size (In NCC, the wall is thicker, calcifications are eccentric and the diameter is less than 2 cm)
Neurosarcoidosis	70% of the patients present with the neurological symptoms rather than the presentation of systemic disease. Common presentations include: Cranial nerve neuropathies: Facial palsy is the most common presentation. Meningeal involvement: diffuse meningeal inflammation can result in diffuse basilar polyneuropathy in 40% of the patients. with neurosarcoidosis. Inflammatory spinal cord disease: Inflammatory span is often more than 3 spinal cord segments that help to distinguish it from Multiple Sclerosis. Peripheral neuropathy: Asymmetric polyneuropathy or mononeuritis multiplex. It may also manifest as Guillain-Barré syndrome (GBS) like presentation. HPO axis involvement: may present as diabetes insipidus. More than 50% of the cases do not have any radiological signs.	Noninvasive tests have low sensitivity and specificity. Serum ACE levels are elevated in 25% of the cases Lumbar puncture shows elevated CSF proteins together with mild-moderate pleocytosis. It is usually accompanied by oligoclonal bands.	MRI with contrast shows enhancement of the inflamed areas (i.e. cranial nerves, meninges or HPO axis)

MRI brain showing brain abscess - Case courtesy of A.Prof Frank Gaillard, https://radiopaedia.org/ From the case https://radiopaedia.org/cases/4933"	MRI brain showing Glioblastoma multiforme - Case courtesy of A.Prof Frank Gaillard, <a href="https://radiopaedia.org/">Radiopaedia.org</a>. From the case <a href="https://radiopaedia.org/cases/28272">rID: 28272</a>	MRI brain showing tuberculoma - Case courtesy of Dr. G Balachandran, https://radiopaedia.org/ From the case https://radiopaedia.org/cases/5489"	MRI brain showing Neurosarcoidosis - Case courtesy of A.Prof Frank Gaillard, https://radiopaedia.org/ From the case https://radiopaedia.org/cases/4364S

Pulmonary tuberculosis must be distinguished from other cavitary lung lesions.

Differential Diagnosis

Pulmonary tuberculosis must be distinguished from other cavitary lung lesions.

Causes of lung cavities	Differentiating Features	Differentiating radiological findings	Diagnosis confirmation
Malignancy (Primary lung cancer)	Elderly male or female Chronic smokers Presents with a low-grade fever, absence of leukocytosis, systemic complaints weight loss, fatigue Absence of predisposing factors that lead to gastric content aspiration, no response to antibiotics within 10 days Hemoptysis is commonly associated with bronchogenic carcinoma	A coin-shaped lesion with thick wall(>15mm) is seen on CXR with less ground glass opacities Bronchoalveolar lavage cytology shows malignant cells	Biopsy of lung
Pulmonary Tuberculosis	Mostly in endemic areas Symptoms include productive cough, fever, night sweats, and weight loss	CXR and CT show cavities in the upper lobe of the lung	Sputum smear-positive for acid-fast bacilli and nucleic acid amplification tests (NAAT) are used on sputum or any sterile fluid for rapid diagnosis and is positive for mycobacteria.
Necrotizing Pneumonia	Any age group Acute, fulminant life threating complication of previous infection >100.4 °F fever, with hemodynamic instability Worsening pneumonia-like symptoms	CXR shows multiple cavitary lesions Pleural effusion and empyema are common findings	CBC is positive for the causative organism
Loculated empyema	Children and elderly are at high risk Pleuritic chest pain, dry cough, fever with chills Dullness to percussion decreased breath sounds, and reduced vocal resonance on examination	Empyema appears lenticular in shape and has a thin wall with smooth luminal margins	Thoracocentesis
Granulomatosis with polyangiitis (Wegener's)	Women are more commonly effected than men Kidneys are also involved Upper respiratory tract symptoms, perforation of nasal septum, chronic sinusitis, otitis media, mastoiditis. Lower respiratory tract symptoms (e.g. hemoptysis, cough, dyspnea) Renal symptoms, hematuria, red cell casts	Pulmonary nodules with cavities and infiltrates are common manifestations of CXR	Positive for P-ANCA Biopsy of the affected tissue reveals necrotizing granulomas
Rheumatoid nodule	Females of 40-50 age group Manifestation of rheumatoid arthritis Presents with other systemic symptoms including symmetric arthritis of the small joints of the hands and feet with morning stiffness are frequent manifestations	Pulmonary nodules with cavitation are present in the upper lobe (Caplan syndrome) on X-ray	Positive for both rheumatoid factor and anti-cyclic citrullinated peptide antibody.
Sarcoidosis	Occur more commonly in African-American females Usually asymptomatic except for enlarged lymph nodes Associated with restrictive lung disease Erythema nodosum Lupus pernio (skin lesions on face resembling lupus) Bell palsy Epithelioid granulomas containing microscopic Schaumann and asteroid bodies	On CXR bilateral adenopathy and coarse reticular opacities are seen CT of the chest demonstrates extensive hilar and mediastinal adenopathy Additional findings on CT include fibrosis (honeycomb, linear, or associated with bronchial distortion), pleural thickening, and ground-glass opacities.	Biopsy of lung shows non-caseating granuloma
Bronchiolitis obliterans (Cryptogenic organizing pneumonia)	Rare condition and resembles asthma, pneumonia and emphysema It is due to drug or toxin exposure, autoimmune diseases, viral infections, or radiation injury People working in industries are at high risk Presents with fever, cough, wheezing, and shortness of breath over weeks to months	CT shows patchy consolidation,usually associated with ground-glass opacities and nodules.	Biopsy of the lung Pulmonary function tests demonstrate low fev1/fvc
Langerhans cell Histiocytosis	Exclusively occurs in smokers, with a peak age of onset 20-40 years Clinical presentation is variable, but symptoms usually include months of dry cough, fever, night sweats, and weight loss Skin is involved in 80% of the cases, scaly erythematous rash is typical	Thin-walled cystic cavities are the common radiographic manifestation, seen in over 50% of patients on either CXR or CT scans.	Biopsy of the lung