IgG4-related disease: patient group characterization and rituximab therapy

Sedyshev S.Kh.

NII revmatologii RAMN

Vasiliev V.I.

Laboratory of Intensive Therapeutic Techniques, Federal state budgetary institution 'V.A. Nasonova Research Institute of Rheumatology', Russian Academy of Medical Sciences

Kovrigina A.M.

Nauchno-klinicheskoe otdelenie gematologicheskoĭ khirurgii Gematologicheskogo nauchnogo tsentra Minzdrava RF, Moskva

Logvinenko O.A.

NII revmatologii RAMN

Rodionova E.B.

Polyclinical Department Federal state budgetary scientific institution «V.A. Nasonova Research Institute of Rheumatology», Moscow, Russia

Safonova T.N.

FGBU "NII glaznykh bolezneĭ" RAMN, Moskva

Gaiduk I.V.

Department of Oral Surgery Stomatological Faculty Moscow State University of Medicine and Dentistry named after A.I. Evdokimov Russian Ministry of Health

Silin A.Yu.

Research and Practical Clinical Center of Diagnostics and Telemedicine Technologies, Department of Health Care of Moscow, Moscow, Russia

Komov D.V.

Rossiĭskiĭ onkologicheskiĭ nauchnyĭ tsentr im. N.N. Blokhina RAMN, Moskva

Nasonov E.L.

"Research Institute of rheumatology n. a. V. A. Nasonova"

IgG4-related disease: patient group characterization and rituximab therapy

Authors:

Sedyshev S.Kh., Vasiliev V.I., Kovrigina A.M., Logvinenko O.A., Rodionova E.B., Safonova T.N., Gaiduk I.V., Silin A.Yu., Komov D.V., Nasonov E.L.

More about the authors

Journal: Therapeutic Archive. 2013;85(2): 48‑53

Downloaded: 897

Download PDF (RU)

Contact the author

Table of contents

To cite this article:

Sedyshev SKh, Vasiliev VI, Kovrigina AM, et al. . IgG4-related disease: patient group characterization and rituximab therapy. Therapeutic Archive. 2013;85(2):48‑53. (In Russ.)

Close metadata

Aim. To characterize a group of patients with IgG4-related disease (IgG4-RD) in a Russian population and to evaluate the efficiency of rituximab therapy. Subjects and methods. In 2009 to 2011, at the Research Institute of Rheumatology, Russian Academy of Medical Sciences, 30 patients (16 men and 14 women; mean age 44 years) were diagnosed with IgG4-RD that was confirmed by determination of serum IgG4 levels and immunohistochemical study of biopsy samples stained for IgG4-positive plasma cells. Seven patients received rituximab therapy. Results. It was assumed at baseline that there were different types of neoplasias in 12 (40%), non-Hodgkin's and Hodgkin's lymphomas in 10 (33.3%), Sjögren's syndrome in 5 (16.7%), and Wegener's granulomatosis in 3 (10%). When 2 or more locations were involved, the condition was regarded as multifocal fibrosclerosis (33.3%). Localized forms were revealed in 20 (66.7%) patients. Among them, the largest number of patients was those who had orbital pseudotumor, Mikulicz's disease, or retroperitoneal fibrosclerosis. The most common sites of involvement were orbits (66.7%), salivary glands (70%) and lymph nodes (36.7%). Comparison of serum IgG4 levels in 28 patients with IgG4-RD, 22 patients with Sjögren's disease, salivary and lacrimal gland lymphomas, and 10 healthy controls showed that the concentration of IgG4 was significantly higher in Group 1 (median 2.6 g/l; IQR 1.22-4.65 (p<0.001). Tissue IgG4/IgG ratio varied from 25 to 50% and averaged 38%. A moiré-like pattern of varying fibrosis was noted in 83% of cases. Analysis of laboratory data revealed elevated C-reactive protein concentrations (46.7% with a mean of 39.5 mg/l; normal values <5.0 mg/ l), increased erythrocyte sedimentation rate (60% with a mean of 37.6 mm/h), hypergammaglobulinemia (30% with a mean of 29.4%; normal range 13-22%), and rheumatoid factor (23.3%). After rituximab therapy, all the patients showed a decrease of IgG4 levels to the normal levels and positive changes evidenced by visualization techniques (computed tomography, magnetic resonance imaging). Conclusion. IgG4-RD is a novel problem in modern medicine, which requires a multidisciplinary approach and further study. Rituximab therapy is a promising treatment.

Keywords:

IgG4

IgG4-related disease

multifocal fibrosclerosis

Mikulicz's disease

rituximab

Authors:

Sedyshev S.Kh.

NII revmatologii RAMN

Vasiliev V.I.

Laboratory of Intensive Therapeutic Techniques, Federal state budgetary institution 'V.A. Nasonova Research Institute of Rheumatology', Russian Academy of Medical Sciences

Kovrigina A.M.

Nauchno-klinicheskoe otdelenie gematologicheskoĭ khirurgii Gematologicheskogo nauchnogo tsentra Minzdrava RF, Moskva

Logvinenko O.A.

NII revmatologii RAMN

Rodionova E.B.

Polyclinical Department Federal state budgetary scientific institution «V.A. Nasonova Research Institute of Rheumatology», Moscow, Russia

Safonova T.N.

FGBU "NII glaznykh bolezneĭ" RAMN, Moskva

Gaiduk I.V.

Department of Oral Surgery Stomatological Faculty Moscow State University of Medicine and Dentistry named after A.I. Evdokimov Russian Ministry of Health

Silin A.Yu.

Research and Practical Clinical Center of Diagnostics and Telemedicine Technologies, Department of Health Care of Moscow, Moscow, Russia

Komov D.V.

Rossiĭskiĭ onkologicheskiĭ nauchnyĭ tsentr im. N.N. Blokhina RAMN, Moskva

Nasonov E.L.

"Research Institute of rheumatology n. a. V. A. Nasonova"

List of references:

Zhang L., Smyrk T.C. Autoimmune pancreatitis and IgG4-related systemic diseases. Int J Clin Exp Pathol 2010; 3: 491-504.
Comings D., Skubi K., Van Eyes J., Motulsky A. Familial multifocal fibrosclerosis. Findings suggesting that retroperitoneal fibrosis, mediastinal fibrosis, sclerosing cholangitis, Riedel's thyroiditis, and pseudotumor of the orbit may be different manifestations of a single disease. Ann Intern Med 1967; 66: 884-892.
Yoshida K., Toki F., Takeuchi N., Watanabe S. Chronic pancreatitis caused by autimmune abnormality. Proposal of the concept of autoimmune pancreatitis. Dig Dis Sci 1995; 40: 1561-1568.
Hamano H., Kawa S., Horiuchi A., Unno H. et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med 2001; 344: 732-738.
Zamboni G., Luttges J., Capelli P., Frulloni L. Histopathological features of diagnostic and clinical relevanct in autoimmune pancreatitis: a study of 53 resection specimens and 9 biopsy specimens. Virchows Arch 2004; 445 (6): 552-563.
Kamisawa T., Nakajima H., Egawa N. et al. IgG4-related sclerosing disease incorporating sclerosing pancreatitis, cholangitis, sialadenitis and retroperitoneal fibrosis with lymphadenopathy. Pancreatology 2006; 6: 132-137.
Zen Y., Sawazaki A., Miyayama S. et al. A case of retroperitoneal fibrosis exhibiting elevated levels of IgG4 in the absence of sclerosing pancreatitis (autoimmune pancreatitis). Hum Pathol 2006; 37: 239-243.
Kitagawa S., Zen Y., Harada K. et al. Abundant IgG4-positive plasma cell infiltrationcharacterizes chronic sclerosing sialadenitis (Kuttner's tumor). Am J Surg Pathol 2005; 29: 783-791.
Hamano H., Arakura N., Muraki T. et al. Prevalence and distribution of extrapancreatic lesions complicating autoimmune pancreatitis. J Gastroenterol 2006; 41: 1197-1205.
Kamisawa T., Funata N., Hayashi Y. et al. Close relationship between autoimmune pancreatitis and multifocal fibrosclerosis. Gut 2003; 52: 683-687.
Kamisawa T., Funata N., Hayashi Y. et al. A new clinicopathologicalentity of IgG4-related autoimmune disease. J Gastroenterol 2003; 38: 982-984.
Okazaki K., Uchida K., Koyabu M. et al. Recent advances in the concept and diagnosis of autoimmune pancreatitis and IgG4-related disease. J Gastroenterol 2011; 46 (3): 277-288.
Mikulicz J. Uber eine eigenartige symmetrische erkrankung der thraä nen- und undspeicheldrüsen. In: Billroth T. (ed). Beiträge zur chirurgie festschrift gewidmet. Stuttgart: Ferdinand Enke 1892; 610-630.
Simonova M.V., Vasil'ev V.I., Kornilova N.N. i dr. Differentsial'naya diagnostika bolezni Mikulicha i bolezni Shegrena. Stomatologiya 1988; 3: 71-73.
Vasil'ev V.I., Simonova M.V., Safonova T.N. Kriterii diagnoza bolezni i sindroma Shegrena. Izbrannye lektsii po klinicheskoi revmatologii. Pod red. V.A. Nasonovoi i N.V. Bunchuka. M: Meditsina 2001: 112-132.
Tsubota K., Fujita H., Tsuzaka K., Takeuchi T. Mikulicz's disease and Sjögren's syndrome. Invest Ophthalmol Vis Sci 2000; 41 (7): 1666-1673.
Yamamoto M., Ohara M., Suzuki C. et al. Elevated IgG4 concentrations in serum of patients with Mikulicz's disease. Scand J Rheumatol 2004; 33:32-433.
Löhr J.M., Faissner R., Koczan D. et al. Autoantibodies against the exocrine pancreas in autoimmune pancreatitis: gene and protein expression profILing and immunoassays identify pancreatic enzymes as a major target of the inflammatory process. Am J Gastroenterol 2010; 105: 2060-2071.
Zen Y., Fujii T., Harada K. et al. Th2 and regulatory immune reactions are increased in immunoglobin G4-related sclerosing pancreatitis and cholangitis. Hepatology 2007; 45 (6): 1538-1546.
Koyabu M., Uchida K., Miyoshi H. et al. Analysis of regulatory T cells and IgG4-positive plasma cells among patients of IgG4-related sclerosing cholangitis and autoimmune liver diseases. J Gastroenterol 2010; 45: 732-741.
Kamisawa T., Anjiki H., Egawa N., Kubota N. Allergic manifestations in autoimmune pancreatitis. Eur J Gastroenterol Hepatol 2009; 21: 1136-1139.
Dhall D., Suriawinata A.A., Tang L.H. et al. Use of immunohistochemistry for IgG4 in the distinction of autoimmune pancreatitis from peritumoral pancreatitis. Human Pathol 2010; 41: 643-652.
Smyrk T.C. Pathological features of IgG4-related sclerosing disease. Cur Opin Rheumatol 2010; 23 (1): 74-79.
Kamisawa T., Okazaki K., Kawa S. et al. Japanese consensus guidelines for management of autoimmune pancreatitis: III. Treatment and prognosis of AIP. J Gastroenterol 2010; 45: 471-477.
Cheuk W., Yuen H.K.L., Chan A.C.L. et al. Ocular adnexal lymphoma associated with IgG4+ chronic sclerosing dacryoadenitis: A previously undescribed complication of IgG4-related sclerosing disease. Am J Surg Pathol 2008; 32: 1159-1167.
Ochoa E.R., Harris N.L., Pilch B.Z. Marginal zone B-cell lymphoma of the salivary gland arising in chronic sclerosing sialadenitis (Kuttner tumor). Am J Surg Pathol 2001; 25: 1546-1550.
Sato Y., Takata K., Ichimura K. et al. IgG4-producing marginal zone B-cell lymphoma. Int J Hematol 2008; 88: 428-433.
Vasil'ev V.I., Pal'shina S.G., Simonova M.V. i dr. Pervyi opyt ispol'zovaniya RTMa v terapii bolezni Mikulicha. Ter arkh 2010; 6: 62-66.
Khosroshahi A., Bloch D.B., Deshpande V., Stone J.H. Rituximab therapy leads to rapid decline of serum IgG4 levels and prompt clinical improvement in IgG4-related systemic disease. Arthritis Rheum 2010; 62: 1755-1762.
Khan M.L., Colby T.V., Viggiano R.W., Fonseca R. Treatment with bortezomib of a patient having hyper IgG4 disease. Clin Lymphoma Myeloma Leuk 2010; 10: 217-219.

Close metadata