New clues to the nature of immunoglobulin G4-related disease: a retrospective Japanese multicenter study of baseline clinical features of 334 cases

Abstract

BackgroundThe aim was to further characterize immunoglobulin G4-related disease (IgG4-RD) by a large-scale multicenter study of its clinical and laboratory features conducted by multidisciplinary physicians of IgG4-RD in Japan.MethodsVarious specialists retrospectively evaluated IgG4-RD patients diagnosed between 1996 and 2015 in five hospitals by analyzing their baseline clinical features, laboratory, imaging, and pathological test findings, and treatment.ResultsOf the 334 patients listed, 205 were male and median age at diagnosis was 65 years. The mean number of organs involved was 3.2 at diagnosis. The most frequently affected organs were the salivary glands, followed by the lacrimal glands, lymph nodes, pancreas, retroperitoneum/periaorta, kidneys, and lungs. The mean serum level of IgG4 was 755 mg/dl, and more than 95% of patients had elevated serum IgG4 levels. The median serum level of C-reactive protein (CRP) was 0.1 mg/dl and the level was less than 1 mg/dl in 90% of patients. A total of 34.7% of patients had low serum levels of C3. Serum levels of C3 and non-IgG4 IgG, calculated as the total IgG minus IgG4, showed an inverse correlation in patients with kidney lesions, while serum IgG4 levels were not correlated with serum C3 levels. Corticosteroid was administered in 78.0% of patients, and was effective in all.ConclusionsThe serum CRP level is generally low and the serum IgG4 level is elevated in most Japanese IgG4-RD patients, in contrast to western patients. These original findings suggest that these two parameters in IgG4-RD differ in some interesting ways from those hitherto reported in western populations. Additional studies, especially international comparative ones, are needed to elucidate the extent and significance of these differences between populations. Attention will also have to be paid to whether the existence of such differences requires consideration when devising international classification criteria.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1467-x) contains supplementary material, which is available to authorized users.

Identifying clinical subgroups in IgG4-related disease patients using cluster analysis and IgG4-RD composite score

“…Wallace et al [27] identified four distinctive IgG4-RD phenotypes according to organ involvement using latent class analysis. Regarding the heterogeneity in serology, one of the major characteristics of IgG4-RD is elevation of serum IgG4, and studies have generally attached crucial importance to serum IgG4 concentrations, which is also used to assess disease activity [4,5,[28][29][30]. However, serum elevation of IgG4 is the lack of specificity, and normal serum IgG4 concentrations are described even in the setting of active, biopsy-proven disease [3,31,32].…”

“…However, serum elevation of IgG4 is the lack of specificity, and normal serum IgG4 concentrations are described even in the setting of active, biopsy-proven disease [3,31,32]. Furthermore, a high percentage of eosinophil; high levels of IgG, IgE, ESR, and CRP; and hypocomplementemia have been frequently reported in IgG4-RD and have been related to outcomes [15,18,29,33], but without excellent specificity. Herein, we proposed clinical patterns in IgG4-RD using cluster analysis based on various baseline blood tests.…”

IgG4-related respiratory disease

“…Although the frequency of intrathoracic lesions in IgG4- RD has not yet been accurately determined, an assessment of 125 patients with IgG4-RD found lung involvement in 22 (17.6%) [7]. Similarly, lung involvement was reported in 78 (23.4%) of 334 patients with IgG4-RD [8]. Because lung involvement in these studies was defined as clinically or radiographically detectable manifestations in the bilateral pulmonary area, the rate of lung involvement may be higher when mediastinal/bronchial manifestations are included (see Image findings).…”

“…Patients with IgG4-RD have been reported to be at high risk of malignancy, especially within one year after onset, suggesting that IgG4-RD is a para-neoplastic syndrome [42]. An analysis of 334 patients found 67 malignancies in 57 patients, with lung cancer being the most frequent, being present in 12 patients [8]. Additionally, an analysis of 294 patients with non-small cell lung cancer who underwent surgical resection found >20 IgG4þ plasma cells per high power field in 35 patients, with six of these 35 patients having an IgG4/IgG ratio >40% [43].…”

IgG4-related periaortitis/periarteritis: An under-recognized condition that is potentially life-threatening

“…Both studies included patients primarily diagnosed with IgG4-related disease in non-vascular organs. More recently, Yamada et al reported that among 334 patients diagnosed with IgG4-related disease on the basis of either by Comprehensive Diagnostic Criteria (CDC) or organ-specific diagnostic criteria, 83 (25%) were found to have lesions in the retroperitoneum or periaorta [40].…”