Lymphadenopathy in the rheumatology practice: a pragmatic approach

Abstract

Lymphadenopathy is a common clinical finding and diagnostic challenge within general medicine and rheumatology practice. It may represent a primary manifestation of an underlying immune-mediated disease or indicate an infectious or neoplastic complication requiring differing management. Evaluating lymphadenopathy is of particular relevance in rheumatology, given that lymph node enlargement is a common finding within the clinical spectrum of several well-known rheumatologic disorders including RA, SLE and SS. In addition, lymphadenopathy represents a hallmark manifestation of rare immunological diseases such as Castleman disease and IgG4-related disease that must be considered in the differential diagnosis because effective targeted treatments can now impact the prognosis of these conditions. In this review we present an overview of the clinical significance of lymphadenopathy in common and rare rheumatologic diseases and propose a practical approach to lymphadenopathy in the rheumatology practice. Differential diagnosis of Castleman disease and therapeutic options for this condition of increasing rheumatologic interest will be discussed in detail.

Keywords: Castleman disease; IgG4-related disease; arthritis; connective tissue disease; lymph node enlargement; sarcoidosis; siltuximab.

Figure 1.

Morphological patterns in IgG4-related lymphadenopaty. (A–D) Follicular hyperplasia pattern, with preserved nodal architecture and IgG4+ plasma cells mainly distributed in germinal centres (GC); the IgG4+ to IgG+ ratio is >70%. (E–H) Castleman disease–like pattern with paracortical (PC) expansion and GCs showing regressive changes; IgG4+ plasma cells are mostly interfollicular and the IgG4+ to IgG+ ratio >70%. (A, B, E, F) Haematoxylin and eosin staining; (C, G) immunohistochemical staining for IgG; (D, H) immunohistochemical staining for IgG4

Figure 2.

Histological feature and patterns in Castleman disease. This research was originally published in Blood (Fajgenbaum DC et al. International, evidence-based consensus diagnostic criteria for HHV8–negative/idiopathic multicentric Castleman disease. Blood 2017;129:1646–57 [59]). © The American Society of Hematology. Hypervascular subtype is characterized by the presence of atretic germinal centres (A) predominantly composed by follicular dendritic cells (FDC) (B), whereas the plasmacytic subtype exhibits hyperplastic germinal centres (D) and profuse sheetlike plasmacytosis (E). Mixed subtype exhibits a combination of hypervascular and plasmacytic features. Prominent vascularity with blood vessels penetrating germinal centres (C) is frequently observed in iMCD, but can be seen with either subtype. Deidentified lymph node slides were obtained prestained with haematoxylin and eosin from Janssen Pharmaceuticals and scanned using an Aperio CS scanner (Leica Biosystems, Wetzlar, Germany) at 20×/0.75NA Plan Apochromat. Images were captured using an Aperio Imagescope and enhanced to 300 d.p.i. using Adobe Photoshop. Bars represent 60 μm (A, E), 200 μm (B–D). iMCD: idiopathic multicentric Castleman disease

Figure 3.

Flowchart for interpretation of lymphadenopathy in rheumatological diseases. Lymphadenopathy should be long-lasting and differential diagnosis with infectious and neoplastic aetiologies should always be exhaustive. KFD: Kikuchi Fujimoto disease; RDD: Rosai Dorfman disease; IgG4RD: IgG4-related disease; UCD: unicentric Castleman disease; MCD: multicentric Castleman disease