The risk of malignancy in patients with IgG4-related disease: a systematic review and meta-analysis

Abstract

Background The relationship between IgG4-related disease (IgG4-RD) and the risk of malignancy is still controversial. This article focused on assessing the risk of cancer in patients with IgG4-RD by meta-analysis. Methods We conducted a systematic review of the literature and meta-analysis characterizing the associated risk of overall malignancy and four site-specific malignancies (pancreas, lung, gastric and lymphoma) in patients with IgG4-RD. A search from 2003 to 2020 was performed using specified terms from PubMed, Embase, Web of Science and SinoMed. Random-effects model analysis was used to pool standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were conducted to clarify the heterogeneity of the included studies. Begg’s funnel plot and Egger’s linear regression test were used to evaluate the bias of the meta-analysis. A P value < 0.05 indicated the existence of publication bias. Results A total of 10 studies were included in the article. The overall SIR estimates suggested an increased risk of overall cancer in IgG4-RD patients (SIR 2.57 95% CI 1.72–3.84) compared with the general population. The specific SIRs for pancreas and lymphoma were higher than those of the general population in IgG4-RD patients (SIR 4.07 95% CI 1.04–15.92, SIR 69.17 95% CI 3.91–1223.04, respectively). No significant associations were revealed in respiratory and gastric cancer (SIR 2.14 95% CI 0.97–4.75, SIR 0.95 95% CI 0.24–3.95, respectively). Four studies were found to be the major sources of heterogeneity by sensitivity analysis. There was no evidence of publication bias via Egger’s test. Conclusion Compared with the general population, patients with IgG4-RD appear to have a higher risk of overall cancer, especially pancreatic and lymphoma. The risk of lung and gastric cancer was not different between IgG4-RD patients and the general population.

Immunoglobulin G4-related ophthalmic disease presenting as a steroid-resistant choroidal mass: a case report

“…Disease progression in the left eye was rapid despite high-dose oral steroid. Although malignant lymphoma was a differential diagnosis and IgG4-RD is associated with an increased risk of lymphoma, 14 the patient did not have any B symptoms (fever, night sweats, and loss of >10% of body weight over 6 months) and the diagnosis of lymphoma was not supported by histological findings. The involvement of the fellow right eye was treated promptly with rituximab and second-line immunosuppressants, which led to resolution of scleritis and choroidal mass.…”

Gastric linitis plastica with autoimmune pancreatitis diagnosed by an endoscopic ultrasonography-guided fine-needle biopsy: A case report

“…One possibility is carcinogenesis due to chronic inflammation. In patients with IgG4-RD, it has been suggested that stimulation from chronic inflammation may trigger carcinogenesis, and one such pathway involves interleukin-33, which plays a role in the pathogenesis of IgG4-RD and is also associated with malignancy[ 5 - 7 ]. Tumor secretion of hormones, peptides, and cytokines or immune cross-reactivity promote the onset of autoimmune disease, widely known as paraneoplastic syndrome[ 25 ], which is separate from the carcinogenic pathway due to chronic inflammation.…”

“…However, IgG4-RD is also known to be associated with malignant tumors, and some have reported that chronic inflammatory stimulation was involved, although the exact mechanism has not been elucidated[ 5 ]. One pathway, involving interleukin-33, which plays a role in the pathogenesis of IgG4-RD, has also been reported to be associated with the development of malignancy[ 6 , 7 ].…”

Comment on “The risk of malignancy in patients with IgG4-related disease: a systematic review and meta-analysis” by Yu et al.

“…With great interest, we have read the recent article “The risk of malignancy in patients with IgG4-related disease: a systematic review and meta-analysis” by Yu et al [ 1 ]. published in Arthritis Research and Therapy.…”