There were 94 cases of IgG4-RD in three medical college-affiliated hospitals during the 10.5- years study period. In our study, there were only 1-5 new cases per year within the first 6 years. However, it increased to more than 10 cases per year with the last 4 years. This finding showed that the diagnosis of IgG4-RD made by clinicians is increasing, and more cases of IgG4-RD may be reported in Korea, with consideration of the incidence of IgG4-RD (0.28 – 1.08 per 100,000) and the newly diagnosed patients each year of IgG4-RD (336 – 1300 patients) in Japan.[17]
The clinical features of IgG4-RD in our study were similar to those of previous studies in terms of sex, age, and organs involved.10-13,15 Our study differed from previous studies. First, the initial clinical symptoms vary based on organ involvement. However, the most common symptoms in previous studies were salivary gland swelling, lacrimal gland swelling, and nonspecific abdominal pain.10,12,16,17 By contrast, in our study, the most common symptom was flank pain, and all patients were initially diagnosed with retroperitoneal fibrosis (RPF) with hydronephrosis. RPF can occur due to several etiologies, and it is categorized as idiopathic and secondary based on the medications used, autoimmune disease, and malignancy. This study showed the role of IgG4-RD in the development RPF. Second, 10 (10.6%) patients were incidentally diagnosed via imaging studies during health screenings. If patients who incidentally found azotemia were included, 15 (16.0%) patients were not symptomatic at the time of IgG4-RD diagnosis. Third, in our cohort, unlike previous studies, pancreas involvement was significantly less common. The pancreas is frequently involved in IgG4-RD. The prevalence rate is approximately 25 ~ 60%, and that in our cohort is 8.5%.12,13,16-18 Forth, in previous studies, allergic disease was commonly observed, and eosinophilia was frequently noted particularly among Japanese, Chinese and Caucasian.10,12,16,17 However, in our cohort, only one patient had bronchial asthma, which was treated with steroid inhaler, prior to IgG4-RD diagnosis. The incidence of eosinophilia was relatively lower in this study than in previous studies.11,12
In our study, 38 and 56 patients presented with single and multiple organ involvement, respectively. Since IgG4-RD is a systemic disease, whether the clinical features and prognosis differed based on the number of organs involved was evaluated. Results showed no significant difference in clinical features and outcomes between patients with single and those with multiple organ involvement, except those with high serum IgG4 concentration and relapse in multiple organ involvement. These results were similar to those of previous studies.11,16,17,19,20 Although patients had a higher serum IgG4 concentration and relapse rate in multiple organ involvement, the response to treatment and the rate of complete remission did not differ between patient with single and those with multiple organ involvement.
The kidney is one of the relatively common organs involved in IgG4-RD. However, only few studies have investigated the differences in clinical characteristics in patients with or without IgG4-RKD.11,21 Thus, we compared the clinical features and outcomes between these patients. Results showed that patients with IgG4-RKD were older and had a higher incidence of hypertension. The association between renal and retroperitoneal involvement was not observed in our cohort. This finding may indicate that retroperitoneal involvement is not a secondary reaction to IgG4-RKD. In terms of renal histopathological findings, all patients had TIN. Glomerular changes were observed in one tissue. However, an accurate diagnosis could not be obtained due to 86% of global glomerular sclerosis. All glomerular and tubulointerstitial disease including TIN, membranous nephropathy, immunoglobulin A nephropathy, mesangial proliferative and membranous proliferative glomerulonephritis can be noted in histopathological findings, and TIN is known as the most common finding.22,23 Lymphoplasmacytic infiltration with storiform fibrosis was the most common finding in our cohort. However, there were specific histological features that can be used to distinguish IgG4-RKD from other TIN in previous studies.24,25 Hypocomplementemia was an important laboratory finding, particularly in IgG4-RKD, and this finding is in accordance with previous studies.4,9,26 In general, serum IgG4 does not to bind to complement component 1q and does not activate the classical complement pathway.5 Thus, the other IgG subtypes, such as IgG1 and IgG3, may be associated with the pathogenesis of IgG4-RD, with consideration of the incidence of hypocomplementemia.
GCs therapy is the gold standard for treatment. However, there is no the international standard guideline for treatment. IgG4-RD responds well to GCs therapy symptomatically, radiologically, and serologically.5,6 The most common treatment was according to GCs-based therapy in our cohort. The rate of response to GCs-based therapy was 85.3%. However, the relapse rate was 21.3% when GCs therapy is discontinued or the minimal dose of GCs is maintained, and this is in accordance with a previous report.27 In addition, approximately 10% of patients received the wait-and-see treatment. Among them, one-third had spontaneous remission based on a previous report.27 In general, GCs therapy is the gold standard treatment. However, it is not curative. In addition, with consideration of spontaneous remission cases, further studies about the pathophysiology of IgG4-RD have to be conducted.
Our study had several limitations. First, this was a retrospective observational study. Second, the diagnosis and treatment strategy for IgG4-RD were inconsistent. Third, because the follow-up duration was short and there was a lack of standard tool for the assessment of disease outcome, some data about treatment response and outcomes were missing. Despite these limitations, the biopsy rate was 78.7%. Moreover, the serum IgG4 concentration of most patients was measured, and all patients underwent imaging studies for IgG4-RD diagnosis.
In conclusion, kidney or other organ involvement is not significantly associated with clinical outcomes. Since IgG4-RD has different clinical features, it should be accurately diagnosed, and all physicians must actively diagnose and treat the condition. Hence, it is necessary to establish international diagnostic criteria and treatment guidelines.