Pancreatic fallout: autoimmune pancreatitis post-mRNA COVID-19 vaccination

Autoimmune pancreatitis (AIP) is a distinct and rare form of pancreatitis, typically presenting with obstructive jaundice, weight loss and abdominal pain. Diagnosis is based on clinical evaluation, biochemical and radiological investigations, histological findings and, in some instances, the response to glucocorticoids.¹

During the COVID-19 pandemic, New Zealand began vaccinating at-risk groups with the Pfizer-BioNTech Comirnaty mRNA vaccine in February 2021. Although phase-II/III trials (~44,000 participants) demonstrated safety, very rare effects were unable to be excluded and may only come to light during post-marketing surveillance.²

Emerging case reports and small series suggest a temporal association between this mRNA vaccine and new-onset autoimmune manifestations.^3,4

We describe the first Australasian case of autoimmune pancreatitis developing shortly after a second Pfizer vaccine dose.

Case report

A 42-year-old previously healthy female healthcare worker received a second Pfizer mRNA COVID-19 vaccine in April 2021. Four days later, she developed abdominal pain and malaise. After multiple primary care visits, she presented to the emergency department in May 2021 with 6 weeks of worsening pain, early satiety and weight loss.

An abdominal computed tomography (CT) scan showed inflammatory changes of the pancreatic head in keeping with focal pancreatitis (Figure 1). Biochemical results were remarkable for serum lipase 212U/L (0–70U/L), AST 237U/L (10–50U/L), ALT 249U/L (0–30U/L), CRP 26mg/L (<5mg/L). Serum bilirubin, ALP and electrolytes were within normal limits. SARS-CoV-2 RNA real-time PCR was negative.

View Figure 1–2.

Endoscopic ultrasound (EUS) in June 2021 showed a diffusely bulky, inflamed pancreas without ductal dilatation. EUS-guided fine needle biopsy revealed lymphoplasmacytic infiltrate and perilobular fibrosis with no malignancy. IgG4 staining was negative.

High-dose corticosteroids were initiated with rapid symptom relief. Follow-up imaging and blood tests confirmed complete radiological and biochemical remission, fulfilling international AIP diagnostic criteria.¹ A likely aetiology was the Pfizer-BioNTech Comirnaty mRNA vaccine due to temporal association and absence of other concomitant autoimmune disease or infectious triggers, including COVID-19 infection.

Discussion

AIP after COVID-19 vaccination is rare but increasingly recognised. To our knowledge, only eight similar cases have been published to date. Among these, Patel et al. describe a 63-year-old man who developed type 1 AIP, 2 months after mRNA-based COVID-19 vaccination.⁵ The patient presented with weight loss, fatigue and insulin-dependent diabetes. Treatment with glucocorticoids led to complete clinical and radiological remission after 6 weeks of therapy.

Rodrigues et al. report a case of a 65-year-old man who developed seronegative type 1 AIP 2 weeks following Pfizer-BioNTech COVID-19 vaccination.⁶ Despite normal serum IgG4 levels, the patient exhibited extra-pancreatic manifestations and achieved complete biochemical and radiological remission within 6 weeks of initiating glucocorticoid therapy.

Surveillance data suggests COVID-19 vaccine-associated autoimmune events occur in ~1.5 per 100,000 vaccine recipients.⁷ Given its rarity, it is unsurprising that only isolated case reports have temporally associated AIP to COVID-19 vaccination.

The presumed mechanism is molecular mimicry combined with the immune response triggered by the vaccine.^4,8 Structural similarities between the SARS-CoV-2 spike protein (expressed after mRNA vaccination) and host peptides may activate T cells and B cells, reducing tolerance to self-antigens and triggering organ-specific inflammation.^8,9 A COVID-19 mRNA vaccination may therefore deliver a potent innate stimulus for spike antigen, promoting the pathogenesis of autoimmune pancreatitis.

This mechanism mirrors reports of AIP after natural SARS-CoV-2 infection,³ lending biological plausibility to a shared pathway between infection and vaccination in autoimmune disease.

Certain HLA genotypes are associated with AIP, both in the Japanese and Caucasian population.¹⁰ However, genetic susceptibility for vaccine-associated AIP is unknown.

Conclusion

This case adds to the small amount of data demonstrating a temporal association between new onset AIP and COVID-19 vaccination. Clinicians should remain aware of this potential association in order to facilitate earlier diagnosis and management. Continued surveillance and detailed case reporting are essential to better understand the epidemiology and potential mechanisms of vaccine-associated autoimmune conditions.