Elsevier

Autoimmunity Reviews

Volume 13, Issue 12, December 2014, Pages 1203-1210
Autoimmunity Reviews

Review
The clinical spectrum of IgG4-related disease

https://doi.org/10.1016/j.autrev.2014.08.013Get rights and content

Abstract

IgG4-related disease (IgG4-RD) is an emerging immune-mediated disease with the capability of involving essentially any organ. The epidemiology of this disease has not been explored in detail. A majority of patients reported in the literature to date are from Japan, but the condition has been described all across the world and there is no strong evidence to suggest a predilection for Asian populations. The mean age at diagnosis is approximately 60 years and there is a decided male predominance for many clinical features, with an overall male:female ratio of 8:3. A cardinal feature of IgG4-RD is single or multiple organ swelling that often raises concern for malignancy. IgG4-RD should be suspected in patients presenting with unexplained enlargement or swelling of one or more organs. Presenting features vary substantially according to the specialty to which patients present first; in addition, the disease can be diagnosed unexpectedly in pathological specimens or identified incidentally on radiology studies. Involvement of major organs is common and IgG4-RD may lead to organ failure, particularly in the pancreas, liver and biliary tree, kidneys, thyroid gland, lungs, and aorta. The diagnosis of IgG4-RD relies on the coexistence of various clinical, laboratory and histopathological findings, although none is pathognomonic by itself.

Section snippets

Historical overview and definition

IgG4-related disease (IgG4-RD) is a systemic immune-mediated disease described in Japan in the first years of the 21st century [1]. The disease is characterized pathologically by the infiltration of IgG4-bearing plasma cells into involved organs [1]. IgG4-RD is not a new disease because many previously-recognized single- and even multi-organ conditions, once regarded as entirely separate disorders, are now known to comprise parts of the IgG4-RD spectrum. Such conditions include “Mikulicz

Geoepidemiology of IgG4-RD

IgG4-RD is generally regarded as an uncommon disorder but it is likely that substantial under-recognition of the disease exists because many physicians remain unfamiliar with this diagnosis. A recent study estimated that approximately 8000 patients had IgG4-RD in Japan in 2009 [8], representing an estimated prevalence in the Japanese population of 6 cases per 100,000 people. Fig. 1 summarizes the geographic origin of 3482 reported cases (MEDLINE search of articles published through March 24,

Pancreas

The pancreas was the first organ reported in the context of IgG4-RD [2], [3] and perhaps as a result this organ has been reported most frequently in the literature. Type I autoimmune pancreatitis was described in 345/840 (41%) systemic cases reported (Table 1). Eight studies including 1245 patients have focused on IgG4-related pancreatitis [10], [12], [13], [14], [15], [16], [17], [18]. Four studies [10], [12], [15], [18] have detailed the main presenting symptoms, which included jaundice in

Conclusions

IgG4-RD is an increasingly-recognized condition in adults, with a heterogeneous clinical presentation affecting a wide range of organ systems. This review shows that clinical studies have a low level of evidence, especially with respect to the lack of a homogeneous diagnostic approach. The body of evidence relies predominantly on series including a range of 10–50 patients in 80% of selected studies. Although a long list of features involving the majority of organs and systems has been reported

Take-home messages

  • IgG4-related disease is a systemic immune-mediated disease described in the 21st century

  • The disease is characterized by the infiltration of IgG4-bearing plasma cells and raised IgG4 levels

  • The cardinal clinical feature of IgG4-RD is single or multiple organ swelling

  • Nearly 75% of cases have been reported in Japan

  • More than 40 different organs have been reported to be involved in IgG4-RD

  • The organs more frequently involved are the pancreas, salivary/lacrimal glands, biliary tree, kidneys, thyroid

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    Supported by the Josep Font Research Fellow Award, Hospital Clinic, Barcelona, Spain.

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