Idiopathic pulmonary fibrosis differential diagnosis

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

Overview

Idiopathic pulmonary fibrosis must be differentiated from other causes of interstitial lung diseases which may cause fibrosis as well. Other diseases may include acute interstitial pneumonia, hypersensitivity pneumonia, occupational lung diseases, and pulmonary hemorrhage diseases.

Differentiating Interstitial Lung Disease from other Diseases

To review the complete differential diagnosis of dyspnea, click here.

To review the complete differential diagnosis of hemoptysis, click here.

To review the complete differential diagnosis of restrictive lung disease, click here.

Abbreviations: ABG: Arterial blood gas, BAL: Bronchoalveolar lavage, ESR: Erythrocyte sedimentation rate, CRP: C–reactive protein, FVC: Forced vital capacity, RV: Residual volume, FEV1: Forced expiratory volume during the 1st second, DLCO: Diffusing capacity of the lungs for carbon monoxide, O2: Oxygen, TLC: Total lung capacity, PaO2: Arterial partial pressure of oxygen, FiO2: Fraction of inspired oxygen, LDH: Lactate dehydrogenase, CEA: Carcinoembryonic antigen, Anti-GBM antibody: Anti-glomerular basement membrane antibody, A−a gradient: Alveolar-arterial gradient, PAS: Periodic acid-Schiff stain, LAM: Lymphangiomyomatosis, IgE: Immunoglobulin E, ANCA: Anti-neutrophil cytoplasmic antibody, RBC: Red blood cell, ACE: Angiotensin-converting enzyme

Disease Clinical manifestation Investigations
History Symptoms Physical examination Lab findings Imaging Pulmonary function test Bronchoscopy and BAL Gold standard
Duration Age Gender Family history Smoking history Environmental exposure HIV Dyspnea Cough Wheezing Chest pain Tachypnea   Auscultation Cyanosis Clubbing Spirometry ABG
Idiopathic pulmonary fibrosis[1] Chronic 60−70 years old Men + + ± + Dry + + + +
  • Bibasilar, peripheral reticular abnormalities
  • Focal honeycomb cyst formation
  • Traction bronchiectasis
  • Diagnosis of exclusion 
  • Lung biopsy
Idiopathic nonspecific interstitial pneumonia[2] Acute/Chronic 50−60 years old Female + + + + + + ±
  • Normal
  • Nonspecific
  • Lung biopsy and multidisciplinary approach
Cryptogenic organising pneumonia[3] Acute/subacute 50−60 years old Both ± + Dry
Disease History Symptoms Physical examination Lab findings Imaging Pulmonary function test Bronchoscopy and BAL Gold standard
Duration Age Gender Family history Smoking history Environmental exposure HIV Dyspnea Cough Wheezing Chest pain Tachypnea   Auscultation Cyanosis Clubbing Spirometry ABG
Acute interstitial pneumonia (Hamman−Rich syndrome)[4] Acute 50−60 years old Both + + +
  • N/A
Lymphocytic interstitial pneumonia[5] Subacute 30−40 years old Female ± + + + + +
Respiratory bronchiolitis−interstitial lung disease[6] Subacute 30−40 years old Both + + Dry +
  • Inspiratory high−pitched rhonchi
  • Fine, bibasilar end−inspiratory crackles
  • Nonspecific 
  • Diffuse or patchy ground glass opacities in a mosaic pattern 
  • Fine nodules 
  • Air trapping
  • Clinical evaluation and investigations
Desquamative interstitial pneumonia[7][8] Chronic 40−50 years old Both + + Dry +
  • Fine, bibasilar end−inspiratory crackles
  • Nonspecific 
  • Ground glass opacities without the peripheral reticular and reticulonodular opacities
Disease History Symptoms Physical examination Lab findings Imaging Pulmonary function test Bronchoscopy and BAL Gold standard
Duration Age Gender Family history Smoking history Environmental exposure HIV Dyspnea Cough Wheezing Chest pain Tachypnea   Auscultation Cyanosis Clubbing Spirometry ABG
Pulmonary Langerhans cell granulomatosis[9] Chronic 20−40 years old Both + + ± Dry + +
  • Unremarkable
  • Nonspecific 
  • Normal
Pulmonary alveolar proteinosis[10][11] Acute/chronic 40−50 years old Male + + + + + + + +
  • Bbilateral perihilar and basilar alveolar opacities without air−bronchograms
  • "Bat wing" distribution
  • Intralobular thickening
  • Diffuse ground−glass opacities
Pulmonary lymphangioleiomyomatosis[12] Acute/chronic 30−40 years old Female + + + Bloody + + +
Eosinophilic pneumonia[13] Acute/chronic 20−40 years old Male + Dry + + +
  • Clinical evaluation and investigations
Hypersensitivity pneumonitis[14] Acute/subacute/chronic 40−60 years old Both ± + + Dry/productive + + + +
  • Centrilobular ground−glass or nodular opacities of mid−to−upper zone 
  • Air−trapping
Disease History Symptoms Physical examination Lab findings Imaging Pulmonary function test Bronchoscopy and BAL Gold standard
Duration Age Gender Family history Smoking history Environmental exposure HIV Dyspnea Cough Wheezing Chest pain Tachypnea   Auscultation Cyanosis Clubbing Spirometry ABG
Occupational lung disease[15] Chronic Elderly Male + + + ± + + + + Peripheral/central +
  • Mineral dust +
  • History of environmental exposure and imaging
  • Lung biopsy not required
Radiation−induced lung injury[16] Subacute/chronic Any age Both + + Dry + + + +
  • Nonspecific
  • History of irradiation and clinical presentation
Pulmonary hemorrhage syndromes Goodpasture syndrome[17] Chronic All ages Male + ± ± Bloody ±
  • Pulmonary infiltrates
  • Normal
  • NA
Idiopathic pulmonary hemosiderosis[18] Acute/subacute/chronic Children − 10 years old Both + ± + Bloody + +
  • O2
  • ↓ CO2
  • Clinical evaluation and investigations
Isolated pulmonary capillaritis[19] Chronic 40−60 years old Both + ± + Bloody + + +
  • Diagnosis of exclusion
Disease History Symptoms Physical examination Lab findings Imaging Pulmonary function test Bronchoscopy and BAL Gold standard
Duration Age Gender Family history Smoking history Environmental exposure HIV Dyspnea Cough Wheezing Chest pain Tachypnea   Auscultation Cyanosis Clubbing Spirometry ABG
Sarcoidosis[20] Acute/subacute/chronic 20−40 years old Female + ± ± + + ± +
  • Clinical evaluation and investigations
Granulomatous vasculitides Granulomatosis with polyangiitis (Wegener)[21] Chronic Elderly Both + + + + ±
  • Alveolar hemorrhage
Eosinophilic granulomatosis with polyangiitis (Churg Strauss)[22] Chronic 40−50 years old Both + + +
  • Areas of parenchymal opacification
  • Mixed interstitial patchy alveolar opacities
  • Normal
Bronchocentric granulomatosis[23] Chronic 30−70 years old Both ± ± + ±
  • Normal
Pulmonary lymphomatoid granulomatosis[24] Chronic 30−50 years old Male + + + +
  • Normal
  • Mid to lower zone multiple poorly defined nodules
  • Diffuse reticular abnormalities
  • Normal
  • Normal
Amyloidosis[25][26] Subacute/chronic 50−70 years old Male + Bloody +
  • Congophilia with apple−green birefringence under polarized light
  • Normal
Disease History Symptoms Physical examination Lab findings Imaging Pulmonary function test Bronchoscopy and BAL Gold standard
Duration Age Gender Family history Smoking history Environmental exposure HIV Dyspnea Cough Wheezing Chest pain Tachypnea   Auscultation Cyanosis Clubbing Spirometry ABG

References

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  2. Travis, William D.; Hunninghake, Gary; King, Talmadge E.; Lynch, David A.; Colby, Thomas V.; Galvin, Jeffrey R.; Brown, Kevin K.; Chung, Man Pyo; Cordier, Jean-François; du Bois, Roland M.; Flaherty, Kevin R.; Franks, Teri J.; Hansell, David M.; Hartman, Thomas E.; Kazerooni, Ella A.; Kim, Dong Soon; Kitaichi, Masanori; Koyama, Takashi; Martinez, Fernando J.; Nagai, Sonoko; Midthun, David E.; Müller, Nestor L.; Nicholson, Andrew G.; Raghu, Ganesh; Selman, Moisés; Wells, Athol (2008). "Idiopathic Nonspecific Interstitial Pneumonia". American Journal of Respiratory and Critical Care Medicine. 177 (12): 1338–1347. doi:10.1164/rccm.200611-1685OC. ISSN 1073-449X.
  3. Mehrian, P.; Doroudinia, A.; Rashti, A.; Aloosh, O.; Dorudinia, A. (2017). "High-resolution computed tomography findings in chronic eosinophilic vs. cryptogenic organising pneumonia". The International Journal of Tuberculosis and Lung Disease. 21 (11): 1181–1186. doi:10.5588/ijtld.16.0723. ISSN 1027-3719.
  4. Parambil, Joseph; Mukhopadhyay, Sanjay (2012). "Acute Interstitial Pneumonia (AIP): Relationship to Hamman-Rich Syndrome, Diffuse Alveolar Damage (DAD), and Acute Respiratory Distress Syndrome (ARDS)". Seminars in Respiratory and Critical Care Medicine. 33 (05): 476–485. doi:10.1055/s-0032-1325158. ISSN 1069-3424.
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  9. Blakley, Matthew P.; Dutcher, Janice P.; Wiernik, Peter H. (2018). "Pulmonary Langerhans cell histiocytosis, acute myeloid leukemia, and myelofibrosis in a large family and review of the literature". Leukemia Research. 67: 39–44. doi:10.1016/j.leukres.2018.01.011. ISSN 0145-2126.
  10. Carrington JM, Hershberger DM. PMID 29493933. Missing or empty |title= (help)
  11. Kiani, Arda; Parsa, Tahereh; Adimi Naghan, Parisa; Dutau, Hervé; Razavi, Fatemeh; Farzanegan, Behrooz; Pourabdollah Tootkaboni, Mahsa; Abedini, Atefeh (2018). "An eleven-year retrospective cross-sectional study on pulmonary alveolar proteinosis". Advances in Respiratory Medicine. 86 (1): 7–12. doi:10.5603/ARM.2018.0003. ISSN 2543-6031.
  12. Xu, Kai-Feng; Lo, Bee Hong (2014). "Lymphangioleiomyomatosis: differential diagnosis and optimal management". Therapeutics and Clinical Risk Management: 691. doi:10.2147/TCRM.S50784. ISSN 1178-203X.
  13. Bernheim, Adam; McLoud, Theresa (2017). "A Review of Clinical and Imaging Findings in Eosinophilic Lung Diseases". American Journal of Roentgenology. 208 (5): 1002–1010. doi:10.2214/AJR.16.17315. ISSN 0361-803X.
  14. Miller, Ross; Allen, Timothy Craig; Barrios, Roberto J.; Beasley, Mary Beth; Burke, Louise; Cagle, Philip T.; Capelozzi, Vera Luiza; Ge, Yimin; Hariri, Lida P.; Kerr, Keith M.; Khoor, Andras; Larsen, Brandon T.; Mark, Eugene J.; Matsubara, Osamu; Mehrad, Mitra; Mino-Kenudson, Mari; Raparia, Kirtee; Roden, Anja Christiane; Russell, Prudence; Schneider, Frank; Sholl, Lynette M.; Smith, Maxwell Lawrence (2018). "Hypersensitivity Pneumonitis A Perspective From Members of the Pulmonary Pathology Society". Archives of Pathology & Laboratory Medicine. 142 (1): 120–126. doi:10.5858/arpa.2017-0138-SA. ISSN 0003-9985.
  15. Sirajuddin, Arlene; Kanne, Jeffrey P. (2009). "Occupational Lung Disease". Journal of Thoracic Imaging. 24 (4): 310–320. doi:10.1097/RTI.0b013e3181c1a9b3. ISSN 0883-5993.
  16. Giridhar P, Mallick S, Rath GK, Julka PK (2015). "Radiation induced lung injury: prediction, assessment and management". Asian Pac. J. Cancer Prev. 16 (7): 2613–7. PMID 25854336.
  17. DeVrieze BW, Hurley JA. PMID 29083697. Missing or empty |title= (help)
  18. Khorashadi, L.; Wu, C.C.; Betancourt, S.L.; Carter, B.W. (2015). "Idiopathic pulmonary haemosiderosis: spectrum of thoracic imaging findings in the adult patient". Clinical Radiology. 70 (5): 459–465. doi:10.1016/j.crad.2014.11.007. ISSN 0009-9260.
  19. Thompson, Gwen; Klecka, Mary; Roden, Anja C.; Specks, Ulrich; Cartin-Ceba, Rodrigo (2016). "Biopsy-proven pulmonary capillaritis: A retrospective study of aetiologies including an in-depth look at isolated pulmonary capillaritis". Respirology. 21 (4): 734–738. doi:10.1111/resp.12738. ISSN 1323-7799.
  20. Li, Cheng-Wei; Tao, Ru-Jia; Zou, Dan-Feng; Li, Man-Hui; Xu, Xin; Cao, Wei-Jun (2018). "Pulmonary sarcoidosis with and without extrapulmonary involvement: a cross-sectional and observational study in China". BMJ Open. 8 (2): e018865. doi:10.1136/bmjopen-2017-018865. ISSN 2044-6055.
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  22. Greco A, Rizzo MI, De Virgilio A, Gallo A, Fusconi M, Ruoppolo G, Altissimi G, De Vincentiis M (April 2015). "Churg-Strauss syndrome". Autoimmun Rev. 14 (4): 341–8. doi:10.1016/j.autrev.2014.12.004. PMID 25500434.
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  24. Ankita, Grover; Shashi, Dhawan (2016). "Pulmonary Lymphomatoid Granulomatosis- a Case Report with Review of Literature". Indian Journal of Surgical Oncology. 7 (4): 484–487. doi:10.1007/s13193-016-0525-1. ISSN 0975-7651.
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