| IgG4-related disease (IRD) is a syndrome characterized by raised serum IgG4 levels. Clinically, tumor-like enlargements are |
| observed, often in the retroperitoneal area or in one or more exocrine glands, most commonly in the pancreas, biliary tract, |
| with more submandibular gland and lacrimal gland. The pathology involves a massive polyclonal lymphoplasmacytic |
| Infiltration more than 30% of the plasma cells staining for IgG4, and fibrosis with a typical star-like or storiform appearance. |
| The lymphocytes are mostly T helper cells, which presumably are follicular Th cells [28], and relatively few B cells. |
| Furthermore, extensive neutrophil infiltration is absent in IRD. Manifestations of IRD are manifold. Descriptions of the |
| full clinical and pathological spectrum of IRD can be found, for instance, in the reviews by Umehara [1] and by |
|
Khosroshahi and Stone [29]. An illustration of the scope of the spectrum is the finding that IRD is involved in many cases of |
| retroperitoneal fibrosis, which may cause severe, potentially fatal, aortic pathology, including aortic aneurism [30]. |
| The pancreatic variant of IRD is often referred to as autoimmune pancreatitis (AIP) type 1, which should be distinguished |
| from the classical duct-destructive AIP, nowadays called AIP type 2 [31]. In AIP type 1, the glandular ducts are typically |
| not infiltrated. |
| Similarly, if salivary and tear glands are affected, their secretion is less affected than in Sjögren’s syndrome, |
| because the ducts remain relatively undamaged. Extensive neutrophil infiltration is absent in IRD. Lymph nodes may be |
| involved in IRD, raising suspicion of IL-6-hypersecreting multicentric Castleman’s disease (MCD). However, IgG4-RD |
| cases have been found to be negative for the herps virus associated with MCD, and IgG4-RD is not associated with fever. |
| The complex connection between IRD and lymphadenopathy is well discussed by Sato et al. [32]. The emphasis in this |
| opinion is on the pancreas and related tissues (biliary tree, salivary glands, and tear glands). In other locations, some aspects |
| of the histopathology may differ, particularly the extent of the fibrosis. |
