Küttner's Tumor and Autoimmune Pancreatitis as Metachronous Manifestations of IgG4-Related Disease.

Immunoglobulin G4-related disease (IgG4-RD) is a multiorgan, fibro-inflammatory condition that presents with painless organ swelling, lymphoplasmacytic infiltration, and obliterative phlebitis, often showing a favorable response to corticosteroid therapy. The most affected organs include the pancreas, kidneys, retroperitoneum, lacrimal glands, and salivary glands. Diagnosis relies on serological, imaging, and histopathological findings, with glucocorticoids as the primary treatment. Despite its reversible nature and good prognosis in many cases, long-term complications such as organ dysfunction or malignancy can still occur. International collaborative efforts have enhanced the understanding, diagnosis, and management of IgG4-RD, emphasizing the importance of comprehensive diagnostic criteria and appropriate therapeutic strategies. Herein, we present an interesting case of a geriatric male who was referred to our clinic because of concern for pancreatic cancer. We diagnosed the patient with autoimmune pancreatitis, a manifestation of IgG4-RD. The patient experienced a dramatic response to steroid therapy and is currently on maintenance therapy.

IgG4-Related Autoimmune Pancreatitis Mimicking Pancreatic Cancer: A Report of Two Cases.

IgG4-related autoimmune pancreatitis (AIP) is a rare inflammatory condition characterized by elevated IgG4-positive plasma cells and lymphoplasmacytic infiltration in the pancreas. This disease responds to steroid therapy but can be challenging to differentiate from pancreatic cancer. In this paper, we present two cases of IgG4-related AIP presenting as pancreatic masses. Our aim is to highlight the diagnostic complexities of this condition and emphasize the need for a multidisciplinary approach to avoid unnecessary surgical interventions and ensure appropriate treatment.

A Case Report of a Prevertebral Mass in an Elderly Male Post Hodgkin's Lymphoma.

Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory autoimmune disease characterized by tissue infiltration by dense lymphoplasmacytic infiltrate composed of T cells, activated B-cells, and plasma cells expressing IgG4 and has varied presentations with similar histopathology. It can involve visceral organs, glands, aorta, lymph nodes, and retroperitoneal tissue. In our case, a 68-year-old male with a past history of Hodgkin's lymphoma and in remission presented for investigation of polyclonal gammopathy. Serum electrophoresis showed increased free kappa light chains, free lambda light chains, and kappa lambda ratio; immunoglobulin G (IgG) levels were also increased. A positron emission tomography (PET) scan and magnetic resonance imaging (MRI) thoracic spine suggested a hypermetabolic prevertebral soft tissue density. Biopsy of the mass suggested IgG4-related disease (IgG4-RD). He also had a compression fracture of the T7 vertebra. He was started on intravenous methylprednisolone and rituximab, following which he had a significant decrease in the size of the mass along with a decline in the levels of IgG, kappa, and lambda chains.

Blue-collar work is a risk factor for developing IgG4-related disease of the biliary tract and pancreas.

BACKGROUND & AIMS: Immunoglobulin G4-related disease (IgG4-RD) of the biliary tract and pancreas is a fibroinflammatory disease of unknown origin with striking male predominance. We aimed to investigate whether blue-collar work and occupational contaminant exposure are risk factors for IgG4-RD of the biliary tract and pancreas. METHOD: We performed an age-/sex-matched case-control study in the largest academic medical centers of the Netherlands. Occupational history was surveyed by questionnaires. The International Standard Classification of Occupations (ISCO88) was used to classify jobs. Job exposure matrices ALOHA and DOM were utilized to assess the years individuals were exposed to compounds. The disease control cohort consisted of patients from 6 equally sized groups. Conditional logistic regression was used to assess effects of blue-collar work and exposure to occupational contaminants on developing IgG4-RD of the biliary tract and pancreas. RESULTS: Overall, 101 patients with IgG4-RD of the biliary tract and pancreas were matched 1:3 to 303 controls. Patients with IgG4-RD had a lower level of education (p = 0.001). Individuals who at least once performed blue-collar work (>1 year), had higher odds of developing IgG4-RD than individuals that only performed white-collar work (odds ratio [OR] 3.66; CI 2.18-6.13; p <0.0001). Being ever exposed (>1 year) to industrial ALOHA (e.g. mineral dust; vapors-dust-gases-fumes) and DOM compounds (e.g. asbestos) resulted in higher odds of IgG4-RD (OR 2.14; 95% CI 1.26-3.16; p <0.001 and OR 2.95; 95% CI 1.78-4.90; p <0.001, respectively). CONCLUSION: Blue-collar work is a risk factor for developing IgG4-RD of the biliary tract and pancreas putatively driven by exposure to selected industrial compounds; this may explain the striking male predominance among patients. LAY SUMMARY: Immunoglobulin G4-related disease (IgG4-RD) causes tumor-like lesions and typically affects middle-aged to elderly men. The background and cause of this disease remain relatively unknown. In this study, we identified blue-collar work as a risk factor for developing IgG4-RD of the biliary tract and pancreas, which may explain the striking male predominance among patients. Furthermore, these results suggest that toxic exposure to occupational contaminants may drive autoimmunity in IgG4-RD of the biliary tract and pancreas.

European Guideline on IgG4-related digestive disease - UEG and SGF evidence-based recommendations.

The overall objective of these guidelines is to provide evidence-based recommendations for the diagnosis and management of immunoglobulin G4 (IgG4)-related digestive disease in adults and children. IgG4-related digestive disease can be diagnosed only with a comprehensive work-up that includes histology, organ morphology at imaging, serology, search for other organ involvement, and response to glucocorticoid treatment. Indications for treatment are symptomatic patients with obstructive jaundice, abdominal pain, posterior pancreatic pain, and involvement of extra-pancreatic digestive organs, including IgG4-related cholangitis. Treatment with glucocorticoids should be weight-based and initiated at a dose of 0.6-0.8 mg/kg body weight/day orally (typical starting dose 30-40 mg/day prednisone equivalent) for 1 month to induce remission and then be tapered within two additional months. Response to initial treatment should be assessed at week 2-4 with clinical, biochemical and morphological markers. Maintenance treatment with glucocorticoids should be considered in multi-organ disease or history of relapse. If there is no change in disease activity and burden within 3 months, the diagnosis should be reconsidered. If the disease relapsed during the 3 months of treatment, immunosuppressive drugs should be added.

Novel Autoantibody Signatures in Sera of Patients with Pancreatic Cancer, Chronic Pancreatitis and Autoimmune Pancreatitis: A Protein Microarray Profiling Approach.

Identification of disease-associated autoantibodies is of high importance. Their assessment could complement current diagnostic modalities and assist the clinical management of patients. We aimed at developing and validating high-throughput protein microarrays able to screen patients' sera to determine disease-specific autoantibody-signatures for pancreatic cancer (PDAC), chronic pancreatitis (CP), autoimmune pancreatitis and their subtypes (AIP-1 and AIP-2). In-house manufactured microarrays were used for autoantibody-profiling of IgG-enriched preoperative sera from PDAC-, CP-, AIP-1-, AIP-2-, other gastrointestinal disease (GID) patients and healthy controls. As a top-down strategy, three different fluorescence detection-based protein-microarrays were used: large with 6400, intermediate with 345, and small with 36 full-length human recombinant proteins. Large-scale analysis revealed 89 PDAC, 98 CP and 104 AIP immunogenic antigens. Narrowing the selection to 29 autoantigens using pooled sera first and individual sera afterwards allowed a discrimination of CP and AIP from PDAC. For validation, predictive models based on the identified antigens were generated which enabled discrimination between PDAC and AIP-1 or AIP-2 yielded high AUC values of 0.940 and 0.925, respectively. A new repertoire of autoantigens was identified and their assembly as a multiplex test will provide a fast and cost-effective tool for differential diagnosis of pancreatic diseases with high clinical relevance.

Distinct pathophysiological cytokine profiles for discrimination between autoimmune pancreatitis, chronic pancreatitis, and pancreatic ductal adenocarcinoma.

BACKGROUND: Discriminating between autoimmune pancreatitis (AIP), chronic pancreatitis (CP), and pancreatic ductal adenocarcinoma (PDAC) can be challenging. In this retrospective study, levels of serum and tissue cytokines were analyzed as part of the clinical strategy for the preoperative differentiation between AIP and PDAC. The identification of differential cytokine profiles may help to prevent unnecessary surgical resection and allow optimal treatment of these pathologies. METHODS: To compare the cytokine profiles of AIP, CP, and PDAC patients, serum and pancreatic tissue homogenates were subjected to multiplex analysis of 17 inflammatory mediators. In total, serum from 73 patients, composed of 29 AIP (14 AIP-1 and 15 AIP-2), 17 CP, and 27 PDAC, and pancreatic tissue from 36 patients, including 12 AIP (six AIP-1 and six AIP-2), 12 CP, and 12 PDAC, were analyzed. RESULTS: Comparing AIP and PDAC patients' serum, significantly higher concentrations were found in AIP for interleukins IL-1ß, IL-7, IL-13, and granulocyte colony-stimulating factor (G-CSF). G-CSF also allowed discrimination of AIP from CP. Furthermore, once AIP was divided into subtypes, significantly higher serum levels for IL-7 and G-CSF were measured in both subtypes of AIP and in AIP-2 for IL-1ß when compared to PDAC. G-CSF and TNF-α were also significantly differentially expressed in tissue homogenates between AIP-2 and PDAC. CONCLUSIONS: The cytokines IL-1ß, IL-7, and G-CSF can be routinely measured in patients' serum, providing an elegant and non-invasive approach for differential diagnosis. G-CSF is a good candidate to supplement the currently known serum markers in predictive tests for AIP and represents a basis for a combined blood test to differentiate AIP and particularly AIP-2 from PDAC, enhancing the possibility of appropriate treatment.

IgG4-related disease: a new kid on the block or an old aquaintance?

IgG4-related systemic disease is a recently recognized systemic condition characterized by unique pathological features that can affect a variety of organs. It includes a growing number of medical conditions which have the following features in common: diffuse organ swelling or focal mass formation, sclerosing storiforme (whirl-shaped) fibrosis with a lymphoplasmacytic infiltrate rich in IgG4-bearing plasma cells, as well as elevated levels of serum IgG4. It invariably responds to steroid treatment and is mostly diagnosed in elderly men. Well-known syndromes like Mikulicz's disease of the salivary or lacrimal gland, Küttner's tumour of the submandibular gland, Riedel's thyroiditis, or retroperitoneal fibrosis, as well as novel entities such as autoimmune pancreatitis type 1, are now regarded to be manifestations of this systemic disease. This article provides an overview of the epidemiology, concepts of pathogenesis, clinical presentation, proposed diagnostic approaches, treatment options, and differential diagnosis of IgG4-related disease.