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Ferrata Storti Foundation
Haematologica 2019 Volume 104(3):444-455
IgG4-relateddisease: whatahematologist needs to know
Luke Y.C. Chen,1 Andre Mattman,2 Michael A. Seidman2,3 and Mollie N. Carruthers3
1Division of Hematology, Department of Medicine, University of British Columbia; 2Department of Pathology and Laboratory Medicine, St. Paul’s Hospital and 3Division of Rheumatology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada
ABSTRACT
IgG4-related disease is a fibro-inflammatory condition that can affect nearly any organ system. Common presentations include major sali- vary and lacrimal gland enlargement, orbital disease, autoimmune pancreatitis, retroperitoneal fibrosis and tubulointerstitial nephritis. This review focuses on the hematologic manifestations of IgG4-related dis- ease, including lymphadenopathy, eosinophilia, and polyclonal hyper- gammaglobulinemia. The disease can easily be missed by unsuspecting hematologists, as patients may present with clinical problems that mimic disorders such as multicentric Castleman disease, lymphoma, plasma cell neoplasms and hypereosinophilic syndromes. When IgG4-related disease is suspected, serum protein electrophoresis and IgG subclasses are helpful as initial tests but a firm histological diagnosis is essential both to confirm the diagnosis and to rule out mimickers. The central histopathological features are a dense, polyclonal, lymphoplasmacytic infiltrate enriched with IgG4-positive plasma cells (with an IgG4/IgG ratio >40%), stori- form fibrosis, and obliterative phlebitis. Importantly for hematologists, the latter two features are seen in all tissues except bone marrow and lymph nodes, making these two sites suboptimal for histological confir- mation. Many patients follow an indolent course and respond well to treatment, but a significant proportion may have highly morbid or fatal complications such as peri-aortitis, severe retroperitoneal fibrosis or pachymeningitis. Corticosteroids are effective but cause new or worsen- ing diabetes in about 40% of patients. Initial response rates to rituximab are high but durable remissions are rare. More intensive lymphoma chemotherapy regimens may be required in rare cases of severe, refrac- tory disease, and targeted therapy against plasmablasts, IgE and other dis- ease biomarkers warrant further exploration.
Example case
An 80-year old Korean man was referred for evaluation of chronic lymphadenopathy, eosinophilia and polyclonal hypergammaglobulinemia. He had had abdominal pain since the 1970s and was initially thought to have Crohn disease, subsequently complicated by idiopathic common bile duct narrowing. In the 1990s, he was found to have a kidney mass on computed tomography which was suspected to be lymphoma, but after the mass was resected, the histology was in keeping with multifocal fibrosclerosis. At the time of referral, his physical examination revealed a low, firm, slightly enlarged, left submandibular gland, no lacrimal gland swelling, and multiple 2 cm or smaller soft inguinal lymph nodes bilaterally. His white blood cell count was 8.3x109/L, eosinophil count 2.0x109/L (normal values <0.7x109/L), creatinine concentration 140 μmol/L, total protein 87 g/L (normal values <82 g/L), with a polyclonal increase in gamma globulins on serum protein electrophoresis of 20.5 g/L (normal values <14 g/L), and total IgG of 28.9 g/L (normal values <18.5 g/dL).
Correspondence:
LUKE Y.C. CHEN
lchen2@bccancer.bc.ca
Received: October 23, 2018. Accepted: January 7, 2019. Pre-published: January 31, 2019.
doi:10.3324/haematol.2018.205526
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/3/444
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