Differences in Clinical Characteristics of IgG4-Related Disease Across Age Groups

A Prospective Study of 737 Patients

Hui Lu; Fei Teng; Panpan Zhang; Yunyun Fei; Linyi Peng; Jiaxin Zhou; Mu Wang; Xiaowei Liu; Liang Zhu; Liwen Wang; Xuan Luo; Zheng Liu; Jieqiong Li; Yan Zhao; Wen Zhang; Xiaofeng Zeng


Rheumatology. 2021;60(6):2635-2646. 

In This Article

Abstract and Introduction


Objective: The aim of this study was to compare the clinical characteristics of IgG4-related disease (IgG4-RD) among different age groups.

Methods: We conducted a prospective study of 737 patients who were newly diagnosed with IgG4-RD and compared detailed demographic features, organ involvements, laboratory tests, treatments and outcomes across age groups. The patients were divided into five groups according to their age at diagnosis: ≤39, 40–49, 50–59, 60–69 and ≥70 years. The clinical characteristics of paediatric patients were also described.

Results: Sex ratio, disease duration, allergy history and clinical symptoms were significantly different across age groups. Besides, the proportions of superficial organ involvement (lacrimal gland and sinus) decreased with age, while the proportions of internal organ involvement (pancreas, biliary tract, retroperitoneal tissue, lung and prostate) increased with age, which was more prominent in male patients. Mikulicz's disease was the most common manifestation (70%) in paediatric IgG4-RD patients. Multiple Cox analysis identified that age ≤56 years at diagnosis was an independent risk factor of relapse.

Conclusion: We revealed the impact of age on clinical characteristics of IgG4-RD, which indicated that different management might be required among different age groups.


IgG4-related disease (IgG4-RD) is an immune-mediated condition associated with fibroinflammatory lesions that can involve almost all organs in human body, with salivary gland, lacrimal gland, pancreas, biliary tract and lymph nodes the most commonly affected sites.[1–3] Typical patients are middle-aged to elderly men.[1,4] It features a series of pathological characteristics such as dense lymphoplasmacytic infiltration, storiform pattern of fibrosis and massive IgG4 positive plasma cells infiltrating in the affected tissues with or without serum IgG4 elevation.[5] Glucocorticoid (GC) is the first-line therapy of IgG4-RD, and is effective in most of the patients.[6,7] Immunosuppressants (IM) are often required in combination with GC since the relapse rate of GC monotherapy is 38.5~50% in the process of GC tapering and withdrawal stages.[8–10]

With progressive advancements in medical science and health care system, the proportion of elderly people continues to rise. Previous studies have demonstrated that ageing remains the single largest risk factor for various diseases, such as cardiovascular disease, stroke, cancers and infections.[11] Besides, immunosenescence and inflammaging have been considered one of the sources of chronic inflammatory disorders and autoimmune diseases.[12,13] In rheumatoid arthritis (RA), the proportion of ACPA negative patients, level of acute phase reactants, experience of constitutional symptoms, disease severity, choice of pharmacological treatment and prognosis were associated with age.[14–17] In SLE, clinical manifestations such as arthritis, serositis, malar rash, renal disease and 10-year survival rates were different across age groups.[18–20] In terms of IgG4-RD, younger age has been implicated as a risk factor for disease relapse.[21–23] Besides, Yamamoto et al.[24] have revealed laboratory differences between the elderly (>70) and non-elderly (≤70) in IgG4-related dacryoadenitis and sialadenitis. Although these studies have partly demonstrated the association between age and relapse or age and laboratory tests, to our knowledge, age disparities in clinical manifestations, disease severity and treatment agents in full-spectrum IgG4-RD have not been studied in detail before. Hence, based on our data of 737 patients from our cohort, we focused on the clinical characteristics and treatment outcomes among age groups. Moreover, paediatric patients were also described in order to illustrate the broad range of manifestations and emphasize awareness of IgG4-RD in paediatrics.