Background/Purpose: IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory disease of unclear etiology.  Studies have suggested that patients with IgG4-RD may be at increased risk of malignancy when followed prospectively.  We have observed a frequent history of malignancy preceding the onset of IgG4-RD.  If true, this may inform our understanding of the pathogenesis.  We therefore evaluated this further in a well-described cohort of 125 patients by comparing the prevalence of malignancy to the general US population as well as that of age- and sex-matched controls from our Center. 

Methods:

We reviewed the electronic medical records of the first 125 patients with IgG4-RD evaluated in our Center, all of whom were diagnosed by strict clinicopathologic criteria. We identified those with a history of invasive malignancy and collected details from the electronic medical record, confirming details with the patients. The indirect standardization method was used to compare the rate of malignancy between our cohort and that of the US population using the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute (NCI).  Furthermore, up to 5 age- and gender- matched controls were selected among patients with either osteoarthritis or fibromyalgia evaluated in the MGH Division of Rheumatology, Allergy, and Immunology (DRAI) and identified using the Research Patient Data Registry (RPDR) at Partners HealthCare. The age of control patients at their first visit in DRAI was matched to the age of cases at the onset of findings or symptoms attributed to IgG4-RD. Patients with immune-mediated conditions (e.g., SLE, RA) were excluded because of the putatively increased risk of malignancy in some of those patient subsets. Conditional logistic regression was used to compare the rate of malignancy between our cohort and that of the matched controls evaluated in DRAI. 

Results: 

Of the125 patients with IgG4-RD included, 60.8% was male and the average age of onset was 50.3+/-14.9 years. The mean number of organs involved was 2.3 +/-1.3.  Twenty patients (16%) had been diagnosed with 21 malignancies before the onset of IgG4-RD. Malignancy was diagnosed an average of 6.9 years (range 1-22) prior to the diagnosis of IgG4-RD. Prostate cancer (n=7) and lymphoma (n=4) were the most common malignancies. Compared to the general US population, the observed prevalence of malignancy in patients with IgG4-RD is 2.5 times higher than expected (95% CI: 1.1-3.6). Compared to patients evaluated in the MGH DRAI, patients with IgG4-RD had a significantly higher prevalence of malignancy than age- and gender-matched controls (OR 2.9, 95% CI 1.5-5.9). 

Conclusion: Our findings, derived from two separate comparison groups, suggest that patients with IgG4-RD more often have a history of malignancy prior to their diagnosis. The reason(s) for this finding remains under investigation, but potential explanations include shared risk factors for the respective diagnoses and increase in the risk of IgG4-RD resulting from the treatment of cancer.  Future studies may investigate potential pathogenetic, clinical, and prognostic differences between patients with and without a history of malignancy.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/malignancy-prevalence-is-increased-among-patients-before-the-onset-of-igg4-related-disease/