IgG4-Related Lung Disease



Pulmonary involvement in IgG4-related disease can manifest in any intrathoracic compartment including the lung parenchyma, airways, lymph nodes, mediastinum, and pleura. Although most patients with IgG4-related lung disease have extrapulmonary manifestations, some patients present with isolated pulmonary disease and may be difficult to diagnose. Approximately one-half of those with IgG4-related lung disease have respiratory symptoms at presentation. The most common form of intrathoracic involvement is mediastinal and/or hilar lymphadenopathy. Parenchymal manifestations of IgG4-related lung disease include single or multiple rounded opacities and interstitial lung disease. Airway disease can cause airway narrowing and asthma-like symptoms. Aside from mediastinal lymphadenopathy, IgG4-related fibrosing mediastinitis has also been reported. Pleural manifestations include pleural masses and pleural effusions. These patterns of intrathoracic disease are best characterized by CT (including high-resolution images of the lung parenchyma). Diagnostic confirmation of IgG4-related lung disease may require bronchoscopic or surgical biopsy, partly depending on the site of involvement. Histopathologic findings associated with IgG4-related lung disease are similar to those seen in extrapulmonary organs, but characteristic storiform fibrosis is not as apparent in lung biopsies. IgG4-related lung disease generally responds well to corticosteroid therapy.


Idiopathic Pulmonary Fibrosis Interstitial Lung Disease Serum IgG4 Level Idiopathic Interstitial Pneumonia Hilar Lymphadenopathy 


  1. 1.
    Zen Y, Nakanuma Y. IgG4-related disease: a cross-sectional study of 114 cases. Am J Surg Pathol. 2010;34(12):1812–19.PubMedCrossRefGoogle Scholar
  2. 2.
    Tsushima K, Tanabe T, Yamamoto H, et al. Pulmonary involvement of autoimmune pancreatitis. Eur J Clin Invest. 2009;39(8):714–22.PubMedCrossRefGoogle Scholar
  3. 3.
    Shrestha B, Sekiguchi H, Colby TV, et al. Distinctive pulmonary histopathology with increased IgG4-positive plasma cells in patients with autoimmune pancreatitis: report of 6 and 12 cases with similar histopathology. Am J Surg Pathol. 2009;33(10):1450–62.PubMedCrossRefGoogle Scholar
  4. 4.
    Zen Y, Inoue D, Kitao A, et al. IgG4-related lung and pleural disease: a clinicopathologic study of 21 cases. Am J Surg Pathol. 2009;33(12):1886–93.PubMedCrossRefGoogle Scholar
  5. 5.
    Shigemitsu H, Koss MN. IgG4-related interstitial lung disease: a new and evolving concept. Curr Opin Pulm Med. 2009;15(5):513–16.PubMedCrossRefGoogle Scholar
  6. 6.
    Inoue D, Zen Y, Abo H, et al. Immunoglobulin G4-related lung disease: CT findings with pathologic correlations. Radiology. 2009;251(1):260–70.PubMedCrossRefGoogle Scholar
  7. 7.
    Khosroshahi A, Stone JH. A clinical overview of IgG4-related systemic disease. Curr Opin Rheumatol. 2011;23(1):57–66.PubMedCrossRefGoogle Scholar
  8. 8.
    Yamashita K, Haga H, Kobashi Y, Miyagawa-Hayashino A, Yoshizawa A, Manabe T. Lung involvement in IgG4-related lymphoplasmacytic vasculitis and interstitial fibrosis: report of 3 cases and review of the literature. Am J Surg Pathol. 2008;32(11):1620–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Zen Y, Kitagawa S, Minato H, et al. IgG4-positive plasma cells in inflammatory pseudotumor (plasma cell granuloma) of the lung. Hum Pathol. 2005;36(7):710–17.PubMedCrossRefGoogle Scholar
  10. 10.
    Taniguchi T, Ko M, Seko S, et al. Interstitial pneumonia associated with autoimmune pancreatitis [comment]. Gut. 2004;53(5):770; author reply 770–1.PubMedGoogle Scholar
  11. 11.
    Kobayashi H, Shimokawaji T, Kanoh S, Motoyoshi K, Aida S. IgG4-positive pulmonary disease. J Thorac Imaging. 2007;22(4):360–2.PubMedCrossRefGoogle Scholar
  12. 12.
    Hirano K, Kawabe T, Komatsu Y, et al. High-rate pulmonary involvement in autoimmune pancreatitis. Intern Med J. 2006;36(1):58–61.PubMedCrossRefGoogle Scholar
  13. 13.
    Taniguchi T, Hamasaki A, Okamoto M. A case of suspected lymphocytic hypophysitis and organizing pneumonia during maintenance therapy for autoimmune pancreatitis associated with autoimmune thrombocytopenia. Endocr J. 2006;53(4):563–6.PubMedCrossRefGoogle Scholar
  14. 14.
    Ohara H, Nakazawa T, Sano H, et al. Systemic extrapancreatic lesions associated with autoimmune pancreatitis. Pancreas. 2005;31(3):232–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Duvic C, Desrame J, et al. Retroperitoneal fibrosis, sclerosing pancreatitis and bronchiolitis obliterans with organizing pneumonia. Nephrol Dial Transplant. 2004;19(9):2397–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Ito M, Yasuo M, Yamamoto H, et al. Central airway stenosis in a patient with autoimmune pancreatitis. Eur Respir J. 2009;33(3):680–3.PubMedCrossRefGoogle Scholar
  17. 17.
    Inoue M, Nose N, Nishikawa H, Takahashi M, Zen Y, Kawaguchi M. Successful treatment of sclerosing mediastinitis with a high serum IgG4 level. Gen Thorac Cardiovasc Surg. 2007;55(10):431–3.PubMedCrossRefGoogle Scholar
  18. 18.
    Naitoh I, Nakazawa T, Ohara H, et al. Clinical significance of extrapancreatic lesions in autoimmune pancreatitis. Pancreas. 2010;39(1):e1–5.PubMedCrossRefGoogle Scholar
  19. 19.
    Cheuk W, Yuen HKL, Chu SYY, Chiu EKW, Lam LK, Chan JKC. Lymphadenopathy of IgG4-related sclerosing disease. Am J Surg Pathol. 2008;32(5):671–81.PubMedCrossRefGoogle Scholar
  20. 20.
    Hamano H, Arakura N, Muraki T, Ozaki Y, Kiyosawa K, Kawa S. Prevalence and distribution of extrapancreatic lesions complicating autoimmune pancreatitis. J Gastroenterol. 2006;41(12):1197–205.PubMedCrossRefGoogle Scholar
  21. 21.
    Nakajo M, Jinnouchi S, Fukukura Y, Tanabe H, Tateno R, Nakajo M. The efficacy of whole-body FDG-PET or PET/CT for autoimmune pancreatitis and associated extrapancreatic autoimmune lesions. Eur J Nucl Med Mol Imaging. 2007;34(12):2088–95.PubMedCrossRefGoogle Scholar
  22. 22.
    Hamed G, Tsushima K, Yasuo M, et al. Inflammatory lesions of the lung, submandibular gland, bile duct and prostate in a patient with IgG4-associated multifocal systemic fibrosclerosis. Respirology. 2007;12(3):455–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Smyrk TC. Pathological features of IgG4-related sclerosing disease. Curr Opin Rheumatol. 2011;23(1):74–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Takato H, Yasui M, Ichikawa Y, et al. Nonspecific interstitial pneumonia with abundant IgG4-positive cells infiltration, which was thought as pulmonary involvement of IgG4-related autoimmune disease. Intern Med. 2008;47(4):291–4.PubMedCrossRefGoogle Scholar
  25. 25.
    Saegusa H, Momose M, Kawa S, et al. Hilar and pancreatic gallium-67 accumulation is characteristic feature of autoimmune pancreatitis. Pancreas. 2003;27(1):20–5.PubMedCrossRefGoogle Scholar
  26. 26.
    Yokoyama A, Kondo K, Nakajima M, et al. Prognostic value of circulating KL-6 in idiopathic pulmonary fibrosis. Respirology. 2006;11(2):164–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Al-Salmi QA, Walter JN, Colasurdo GN, et al. Serum KL-6 and surfactant proteins A and D in pediatric interstitial lung disease. Chest. 2005;127(1):403–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Kinoshita F, Hamano H, Harada H, et al. Role of KL-6 in evaluating the disease severity of rheumatoid lung disease: comparison with HRCT. Respir Med. 2004;98(11):1131–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Kamisawa T, Shimosegawa T, Okazaki K, et al. Standard steroid treatment for autoimmune pancreatitis. Gut. 2009;58(11):1504–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Khan ML, Colby TV, Viggiano RW, Fonseca R. Treatment with bortezomib of a patient having hyper IgG4 disease. Clin Lymphoma Myeloma Leuk. 2010;10(3):217–19.PubMedCrossRefGoogle Scholar
  31. 31.
    Ghazale A, Chari ST, Zhang L, et al. Immunoglobulin G4-associated cholangitis: clinical profile and response to therapy. Gastroenterology. 2008;134(3):706–15.PubMedCrossRefGoogle Scholar
  32. 32.
    Khosroshahi A, Bloch DB, Deshpande V, Stone JH. Rituximab therapy leads to rapid decline of serum IgG4 levels and prompt clinical improvement in IgG4-related systemic disease. Arthritis Rheum. 2010;62(6):1755–62.PubMedCrossRefGoogle Scholar
  33. 33.
    Takahashi N, Ghazale AH, Smyrk TC, Mandrekar JN, Chari ST. Possible association between IgG4-associated systemic disease with or without autoimmune pancreatitis and non-Hodgkin lymphoma. Pancreas. 2009;38(5):523–6.PubMedCrossRefGoogle Scholar
  34. 34.
    Fukui T, Mitsuyama T, Takaoka M, Uchida K, Matsushita M, Okazaki K. Pancreatic cancer associated with autoimmune pancreatitis in remission. Intern Med. 2008;47(3):151–5.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Division of Pulmonary and Critical Care MedicineMayo Clinic College of MedicineRochesterUSA
  2. 2.Division of Pulmonary and Critical Care MedicineMayo Clinic RochesterRochesterUSA
  3. 3.Department of Laboratory Medicine and PathologyMayo ClinicRochesterUSA

Personalised recommendations