Characterizing IgG4-related disease with ¹⁸F-FDG PET/CT: a prospective cohort study

Jingjing Zhang, Hua Chen, Yanru Ma, Yu Xiao, Na Niu, Wei Lin, Xinwei Wang, Zhiyong Liang, Fengchun Zhang, Fang Li, Wen Zhang, Zhaohui Zhu, Jingjing Zhang, Hua Chen, Yanru Ma, Yu Xiao, Na Niu, Wei Lin, Xinwei Wang, Zhiyong Liang, Fengchun Zhang, Fang Li, Wen Zhang, Zhaohui Zhu

Abstract

Purpose: IgG4-related disease (IgG4-RD) is an increasingly recognized clinicopathological disorder with immune-mediated inflammatory lesions mimicking malignancies. A cohort study was prospectively designed to investigate the value of (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in characterizing IgG4-RD.

Methods: Thirty-five patients diagnosed with IgG4-RD according to the consensus criteria were enrolled with informed consent. All patients underwent baseline (18)F-FDG PET/CT evaluation. Among them, 29 patients underwent a second (18)F-FDG PET/CT scan after 2 to 4 weeks of steroid-based therapy.

Results: All 35 patients were found with (18)F-FDG-avid hypermetabolic lesion(s); 97.1% (34/35) of these patients showed multi-organ involvement. Among the 35 patients, 71.4% (25/35) patients were found with more organ involvement on (18)F-FDG PET/CT than conventional evaluations including physical examination, ultrasonography, and computed tomography (CT). (18)F-FDG PET/CT demonstrated specific image characteristics and pattern of IgG4-RD, including diffusely elevated (18)F-FDG uptake in the pancreas and salivary glands, patchy lesions in the retroperitoneal region and vascular wall, and multi-organ involvement that cannot be interpreted as metastasis. Comprehensive understanding of all involvement aided the biopsy-site selection in seven patients and the recanalization of ureteral obstruction in five patients. After 2 to 4 weeks of steroid-based therapy at 40 mg to 50 mg prednisone per day, 72.4% (21/29) of the patients showed complete remission, whereas the others exhibited > 81.8% decrease in (18)F-FDG uptake.

Conclusion: F-FDG PET/CT is a useful tool for assessing organ involvement, monitoring therapeutic response, and guiding interventional treatment of IgG4-RD. The image pattern is suggested to be updated into the consensus diagnostic criteria for IgG4-RD.

Trial registration: ClinicalTrials.gov NCT01665196.

Figures

Fig. 1
Fig. 1
List of involved organs/tissues in the 35 IgG4-RD patients in descending order and the contribution of 18F-FDG PET/CT to the detection of involvement. Blue bar: total number of cases with the organs/tissues involved; Red Bar: the amount of involvement additionally detected by 18F-FDG PET/CT
Fig. 2
Fig. 2
A 54-year-old man with IgG4-related disease showed multi-organ involvement (a whole-body view; b salivary glands; c pancreas; d prostate), significant response after two weeks of steroid-based treatment (e–h), and characteristic immunohistochemical stains of submandibular gland specimen (i HE stain; j CD38-positive plasma cells; k IgG-positive cells; l IgG4-positive cells. The IgG4-positive cells were > 60 % of the IgG-positive cells)
Fig. 3
Fig. 3
18F-FDG PET/CT guided the timely ureter recanalization in an IgG4-RD patient with retroperitoneal fibrosis and aorta involvement. The enlarged right renal pelvis with radioactive urine retention indicated severe ureteral obstruction, whereas the left side without radioactivity indicated complete obstruction (a and b). After D-J tube cannulation, the renal function was recovered bilaterally (c and d); the intense-uptake lesions were smaller and the intensity was significantly lower in response to the steroid treatment. The arrows show the aorta involvement beside the retroperitoneal fibrosis (e, f), which has a complete response to steroid-based treatment (g, h)
Fig. 4
Fig. 4
Changes in total lesion glycolysis (TLG) demonstrated by 18F-FDG PET/CT (a) were more remarkable than the changes in serum IgG4 level (b) after 2 to 4 weeks of steroid-based treatment

References

    1. Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med. 2012;366:539–51. doi: 10.1056/NEJMra1104650.
    1. Khosroshahi A, Stone JH. A clinical overview of IgG4-related systemic disease. Curr Opin Rheumatol. 2011;23:57–66. doi: 10.1097/BOR.0b013e3283418057.
    1. Carruthers MN, Stone JH, Khosroshahi A. The latest on IgG4-RD: a rapidly emerging disease. Curr Opin Rheumatol. 2012;24:60–9. doi: 10.1097/BOR.0b013e32834ddb4a.
    1. Stone JH, Khosroshahi A, Deshpande V, Chan JK, Heathcote JG, Aalberse R, et al. Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations. Arthritis Rheum. 2012;64:3061–7. doi: 10.1002/art.34593.
    1. Watanabe T, Yamashita K, Fujikawa S, Sakurai T, Kudo M, Shiokawa M, et al. Involvement of activation of toll-like receptors and nucleotide-binding oligomerization domain-like receptors in enhanced IgG4 responses in autoimmune pancreatitis. Arthritis Rheum. 2012;64:914–24. doi: 10.1002/art.33386.
    1. Tanaka A, Moriyama M, Nakashima H, Miyake K, Hayashida JN, Maehara T, et al. Th2 and regulatory immune reactions contribute to IgG4 production and the initiation of Mikulicz disease. Arthritis Rheum. 2012;64:254–63. doi: 10.1002/art.33320.
    1. Kamisawa T, Funata N, Hayashi Y. A new clinicopathological entity of IgG4-related autoimmune disease. J Gastroenterol. 2003;38:982–4. doi: 10.1007/s00535-003-1175-y.
    1. Kamisawa T, Egawa N, Nakajima H. Autoimmune pancreatitis is a systemic autoimmune disease. Am J Gastroenterol. 2003;98:2811–2. doi: 10.1111/j.1572-0241.2003.08758.x.
    1. Hamano H, Arakura N, Muraki T, Ozaki Y, Kiyosawa K, Kawa S, et al. Prevalence and distribution of extrapancreatic lesions complicating autoimmune pancreatitis. J Gastroenterol. 2006;41:1197–205. doi: 10.1007/s00535-006-1908-9.
    1. Masaki Y, Sugai S, Umehara H. IgG4-related diseases including Mikulicz’s disease and sclerosing pancreatitis: diagnostic insights. J Rheum. 2010;37:1380–5. doi: 10.3899/jrheum.091153.
    1. Stone JH, Khosroshahi A, Hilgenberg A, Spooner A, Isselbacher EM, Stone JR. IgG4-related systemic disease and lymphoplasmacytic aortitis. Arthritis Rheum. 2009;60:3139–45. doi: 10.1002/art.24798.
    1. Kamisawa T, Okamoto A. Autoimmune pancreatitis: proposal of IgG4-related sclerosing disease. J Gastroenterol. 2006;41:613–25. doi: 10.1007/s00535-006-1862-6.
    1. Masaki Y, Dong L, Kurose N, Kitagawa K, Morikawa Y, Yamamoto M, et al. Proposal for a new clinical entity, IgG4-positive multiorgan lymphoproliferative syndrome: analysis of 64 cases of IgG4-related disorders. Ann Rheum Dis. 2009;68:1310–5. doi: 10.1136/ard.2008.089169.
    1. Abraham SC, Wilentz RE, Yeo CJ, Sohn TA, Cameron JL, Boitnott JK, et al. Pancreaticoduodenectomy (Whipple resections) in patients without malignancy: are they all 'chronic pancreatitis'? Am J Surg Pathol. 2003;27:110–20. doi: 10.1097/00000478-200301000-00012.
    1. Gardner TB, Levy MJ, Takahashi N, Smyrk TC, Chari ST. Misdiagnosis of autoimmune pancreatitis: a caution to clinicians. Am J Gastroenterol. 2009;104:1620–3. doi: 10.1038/ajg.2008.89.
    1. Maldonado A, González-Alenda FJ, Alonso M, Sierra JM. PET-CT in clinical oncology. Clin Transl Oncol. 2007;9:494–505. doi: 10.1007/s12094-007-0093-5.
    1. Haroon A, Zumla A, Bomanji J. Role of fluorine 18 fluorodeoxyglucose positron emission tomography-computed tomography in focal and generalized infectious and inflammatory disorders. Clin Infect Dis. 2012;54:1333–41. doi: 10.1093/cid/cis193.
    1. Ebbo M, Grados A, Guedj E, Gobert D, Colavolpe C, Zaidan M, et al. 18F-FDG PET/CT for staging and evaluation of treatment response in IgG4-related disease: a retrospective multicenter study. Arthritis Care Res (Hoboken). 2014;66:86–96. doi: 10.1002/acr.22058.
    1. Kitada M, Matuda Y, Hayashi S, Ishibashi K, Oikawa K, Miyokawa N, et al. IgG4-related lung disease showing high standardized uptake values on FDG-PET: report of two cases. J Cardiothorac Surg. 2013;8:160. doi: 10.1186/1749-8090-8-160.
    1. Taniguchi Y, Ogata K, Inoue K, Terada Y. Clinical implication of FDG-PET/CT in monitoring disease activity in IgG4-related disease. Rheumatology (Oxford) 2013;52:1508. doi: 10.1093/rheumatology/ket182.
    1. Nakatani K, Nakamoto Y, Togashi K. Utility of FDG PET/CT in IgG4-related systemic disease. Clin Radiol. 2012;67:297–305. doi: 10.1016/j.crad.2011.10.011.
    1. Suga K, Kawakami Y, Hiyama A, Hori K, Takeuchi M. F-18 FDG PET-CT findings in Mikulicz disease and systemic involvement of IgG4-related lesions. Clin Nucl Med. 2009;34:164–7. doi: 10.1097/RLU.0b013e3181967568.
    1. Matsubayashi H, Furukawa H, Maeda A, Matsunaga K, Kanemoto H, Uesaka K, et al. Usefulness of positron emission tomography in the evaluation of distribution and activity of systemic lesions associated with autoimmune pancreatitis. Pancreatology. 2009;9(5):694–9. doi: 10.1159/000199439.
    1. Ozaki Y, Oguchi K, Hamano H, Arakura N, Muraki T, Kiyosawa K, et al. Differentiation of autoimmune pancreatitis from suspected pancreatic cancer by fluorine-18 fluorodeoxyglucose positron emission tomography. J Gastroenterol. 2008;43:144–51. doi: 10.1007/s00535-007-2132-y.
    1. 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;34:2088–95. doi: 10.1007/s00259-007-0562-7.
    1. Umehara H, Okazaki K, Masaki Y. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol. 2012;22:21–30. doi: 10.3109/s10165-011-0571-z.
    1. Deshpande V, Zen Y, Chan JK, Yi EE, Sato Y, Yoshino T, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012;25:1181–92. doi: 10.1038/modpathol.2012.72.
    1. Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumours. J Nucl Med. 2009;50:122–50. doi: 10.2967/jnumed.108.057307.
    1. Okazaki K, Umehara H. Are classification criteria for IgG4-RD now possible? The concept of IgG4-related disease and proposal of comprehensive diagnostic criteria in Japan. Int J Rheumatol. 2012;2012:357071. doi: 10.1155/2012/357071.
    1. Yamamoto M, Tabeya T, Naishiro Y, Yajima H, Ishigami K, Shimizu Y, et al. Value of serum IgG4 in the diagnosis of IgG4-related disease and in differentiation from rheumatic diseases and other diseases. Mod Rheumatol. 2012;22:419–25. doi: 10.3109/s10165-011-0532-6.
    1. Ryu JH, Horie R, Sekiguchi H, Peikert T, Yi ES. Spectrum of disorders associated with elevated serum IgG4 levels encountered in clinical practice. Int J Rheumatol. 2012;2012:232960. doi: 10.1155/2012/232960.
    1. Vaglio A, Strehl DJ, Manger B, Maritati F, Alberici F, Beyer C, et al. IgG4 immune response in Churg–Strauss syndrome. Ann Rheum Dis. 2012;71:390–3. doi: 10.1136/ard.2011.155382.
    1. Horger M, Lamprecht HG, Bares R, Spira D, Schmalzing M, Claussen CD, et al. Systemic IgG4-related sclerosing disease: spectrum of imaging findings and differential diagnosis. AJR Am J Roentgenol. 2012;199:W276. doi: 10.2214/AJR.11.8321.
    1. Nguyen VX, De Petris G, Nguyen BD. Usefulness of PET/CT imaging in systemic IgG4-related sclerosing disease. A report of three cases. JOP. 2011;12:297–305.
    1. Kamisawa T, Okazaki K, Kawa S, Shimosegawa T, Tanaka M, Research Committee for Intractable Pancreatic D et al. Japanese consensus guidelines for management of autoimmune pancreatitis: III. Treatment and prognosis of AIP. J Gastroenterol. 2010;45:471–7. doi: 10.1007/s00535-010-0221-9.
    1. Agaimy A, Weyand M, Strecker T. Inflammatory thoracic aortic aneurysm (lymphoplasmacytic thoracic aortitis): a 13-year-experience at a German Heart Center with emphasis on possible role of IgG4. Int J Clin Exp Pathol. 2013;6:1713–22.
    1. Holubec T, Laco J, Holubcova Z, Vojacek J, Dominik J, Steiner I, et al. Repair of thoracic aortic aneurysm due to noninfectious aortitis. J Card Surg. 2012;27:199–204. doi: 10.1111/j.1540-8191.2011.01399.x.
    1. Moroni G, Castellani M, Balzani A, Dore R, Bonelli N, Longhi S, et al. The value of (18)F-FDG PET/CT in the assessment of active idiopathic retroperitoneal fibrosis. Eur J Nucl Med Mol Imaging. 2012;39:1635–42. doi: 10.1007/s00259-012-2144-6.
    1. Kiyama K, Kawabata D, Hosono Y, Kitagori K, Yukawa N, Yoshifuji H, et al. Serum BAFF and APRIL levels in patients with IgG4-related disease and their clinical significance. Arthritis Res Ther. 2012;14:R86. doi: 10.1186/ar3810.
    1. Carruthers MN, Stone JH, Deshpande V, Khosroshahi A. Development of an IgG4-RD responder index. Int J Rheumatol. 2012;2012:259408. doi: 10.1155/2012/259408.
    1. 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;62:1755–62. doi: 10.1002/art.27435.
    1. Liu Y, Chen L, Li F. Predominant IgG4 disease and concurrent early-stage rectal cancer. Clin Nucl Med. 2011;36:1135–6. doi: 10.1097/RLU.0b013e3182336247.
    1. Yamamoto M, Takahashi H, Tabeya T, Suzuki C, Naishiro Y, Ishigami K, et al. Risk of malignancies in IgG4-related disease. Mod Rheumatol. 2012;22:414–8. doi: 10.3109/s10165-011-0520-x.

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