Introduction

Autoimmune pancreatitis (AiP) is a rare form of chronic pancreatitis. Studies from Japan and Germany suggest that AiP patients may have a higher incidence of malignancies compared to the general population. However, reliable data in this regard are still lacking.

Aims & Methods

We initiated a retrospective, multicenter observational study within the Pancreas 2000 framework to investigate the incidence of malignancy in AiP Patients.In our global multicenter retrospective observational trial, we are currently collecting data from patients with AiP diagnosed after 2005, including type 1, type 2, and not-otherwise-specified (NOS) AIP, regardless of the diagnostic criteria used. Patients with less than 12 months of follow-up after AIP diagnosis and those with immune checkpoint inhibitor-induced pancreatitis are excluded. Our primary outcome is to determine the occurrence of the first invasive cancer in AiP patients. The secondary outcome is to evaluate the characteristics of AiP patients with distinct pancreatic and/or extrapancreatic cancers and the prevalence of all cancer diagnoses within 12 months prior to AiP diagnosis. The standardized incidence ratio of any first invasive cancer after AiP diagnosis will be compared to age-grouped and gender-matched controls in the general population. The expected number of cancers in the general population will be determined using the Cancer Incidence in Five Continents Volume XI (CI5XI) registry.

Results

We will present the current status of recruitment and preliminary data. To date, 16 centers from Europe and America have entered 321 cases. Ethics submissions have already been applied for in an additional 45 centers across four continents (Europe, Asia, America, and Oceania).

Conclusion

To the best of our knowledge, this is the first global observational trial analyzing the risk of developing cancer in patients with AiP.

Introduction

Nutritional deficiencies, including fat-soluble vitamins, water-soluble vitamins and minerals have been studied in the setting many autoimmune diseases, including those involving the digestive system. However, despite the well-known pancreatic involvement in IgG4-related diseases, nutritional deficiencies in autoimmune pancreatitis (AIP) have not been examined so far.

Aims & Methods

The aim of the present study was to determine the prevalence of micronutrient deficiencies in patients with AIP as well as to investigate their relationship with relapse. We retrospectively analysed medical records of patients followed up for AIP at our Pancreas Outpatient Clinic between January 2001 and March 2022. Demographic and clinical data were collected. The primary outcome was the prevalence of micronutrient deficiencies during AIP follow-up. The secondary outcome was the prevalence of AIP relapse, with exposure defined as micronutrient deficiency occurring at any time during follow-up. Micronutrient variables were solely described categorically as deficient or normal, according to the reference values at the time of each test. However, the cut-off value for vitamin D deficiency was set to below 25 nmol/L since levels between 25-50 nmol/L solely indicate an insufficiency.

Results

One hundred patients were included in the final analysis. The male-to-female ratio was 2.5:1; median age at diagnosis was 57 years (range 19-85). Median follow-up was 53 months, and during this time, 38% of patients suffered from at least one micronutrient deficiency. The most prevalent micronutrient deficiencies were vitamin D (16.1%) and zinc (25.5%). There were no statistically significant differences in prevalence of micronutrient deficiency stratified by AIP subtype. The prevalence of PEI and of at least one relapse were significantly higher in patients with micronutrient deficiencies than in those without (92.1% vs 69.4%, p = 0.01 for PEI, and 52.6% versus 27.4%, p = 0.02 for relapse). Interestingly, the prevalence of pancreatic enzyme replacement therapy (PERT) was also higher in patients with any micronutrient deficiency compared to in patients with no deficiencies 34 (89.5%) vs 40 (64.5%), p=0.01. Relapse was observed in 37% of the AIP patients. The odds for relapse were 2.9 (1.26-6.86, p=0.02), 2.71(1.36-5.41, p=0.006) and 3.38 (1.09-10.55, p=0.04) times higher in patients with any deficiency, zinc deficiency and vitamin D deficiency, respectively, compared to in non-deficient patients. However, after stratifying for AIP type 1 and adjusting for PEI and elevated IgG4 levels, this association ceased to be statistically significant.

Conclusion

Zinc and vitamin D deficiencies may be common in patients with AIP indicating that these micronutrients might play a role in the natural course of AIP probably as a result of delicate interplay between disease burden, disease severity and the consequent destruction of the gland. Importantly, any micronutrient deficiency may be prevalent even in the light of treated PEI which emphasizes the potential of micronutrients as an additional tool in the workup and follow-up of AIP patients. More studies are warranted to ascertain our findings.

References

Wessels I, Rink L. Micronutrients in autoimmune diseases: possible therapeutic benefits of zinc and vitamin D. J Nutr Biochem. 2020;77:108240.
Löhr JM, Vujasinovic M, Rosendahl J, Stone JH, Beuers U. IgG4-related diseases of the digestive tract. Nat Rev Gastroenterol Hepatol. 2022;19(3):185-97.
Sanna A, Firinu D, Zavattari P, Valera P. Zinc Status and Autoimmunity: A Systematic Review and Meta-Analysis. Nutrients. 2018;10(1)