Pancreatitis in Patients with Cancer Receiving Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) occasionally cause immune-related adverse events (AEs), which pose challenges to the continuation of treatment. Although ICIs are widely used in patients with cancer, studies reporting immune-mediated pancreatitis remain scarce. OBJECTIVES: We performed a systematic review and meta-analysis to address current knowledge gaps and provide clinical guidance for ICI-associated pancreatitis and lipase elevation. PATIENTS AND METHODS: We searched PubMed/Medline, Embase, and Web of Science for phase 3 randomized controlled trials (RCTs) evaluating ICIs. The incidence of any-grade and grade 3-5 pancreatitis/lipase elevation was calculated. Then, we performed a random-effect model meta-analysis to pool the odds ratios (ORs) of these outcomes using RCTs evaluating the addition of an ICI to systemic therapy to assess the effect of ICIs on pancreatic AEs. A systematic review of the treatment of ICI-related pancreatitis was also conducted. RESULTS: The incidence analysis included 81 articles (79 RCTs) comprising 36,871 patients. The incidence of treatment-related pancreatitis was 0.68% (any-grade) and 0.32% (grade 3-5). Meta-analysis revealed that the addition of ICI therapy significantly increased any-grade (OR 2.12, 95% confidence interval [CI] 1.45-3.11, p < 0.001) and grade 3-5 pancreatitis (OR 1.76, 95% CI 1.01-3.08, p < 0.05) with low heterogeneity among ICI subtype subgroups (any-grade: I2 = 0%, p = 0.99; grade 3-5: I2 = 0%, p = 0.63). In analysis of treatment outcome among 146 patients from 53 articles, glucocorticoids were used in 80.6% (n = 108/134) and ICIs were discontinued in 76.5% (n = 101/132; permanent discontinuation: 62.5% [n = 35/56]). CONCLUSIONS: The overall rate of pancreatitis appears low, but the addition of ICI therapy significantly increased the incidence of pancreatitis. These findings provide insight into the incidence and treatment of pancreatitis associated with ICIs.

Uncommon Presentation of IgM Monoclonal Gammopathy of Undetermined Significance (MGUS) and Anti-Myelin-Associated Glycoprotein (MAG)-Associated Demyelinating Peripheral Neuropathy as Respiratory Failure: A Case Report.

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant clonal plasma cell disorder characterized by monoclonal immunoglobulins and/or an abnormal free immunoglobulin light chain ratio. MGUS can be associated with immune-mediated neuropathies, including chronic inflammatory demyelinating neuropathy and its variants. Here, we report the case of a 76-year-old male who presented with progressive weakness, initially in the lower extremities and later including the upper extremities. Serum protein electrophoresis and immunofixation identified an IgM kappa monoclonal protein and further testing confirmed high titers of anti-myelin-associated glycoprotein (MAG) antibodies, leading to a diagnosis of anti-MAG-associated demyelinating peripheral neuropathy. The coexistence of MGUS and anti-MAG antibodies requires meticulous diagnosis and management, especially in patients who present with atypical symptoms of the disease.

Extremely Late Diagnosis of Hereditary Angioedema Type I in an Elderly Female.

This case presents an instance of an extremely delayed diagnosis of hereditary angioedema (HAE) type I in an elderly female with no significant past medical history. The patient had a prolonged history of recurrent lip swelling and itchiness dating back to her teenage years, leading to multiple visits to the emergency room (ER). These recurrent episodes were characterized by random onset and accompanied by generalized pruritus and urticaria. During these ER visits, the patient would be inappropriately treated for presumed hypersensitivity reaction due to her confounding environmental allergies presenting with urticaria, complicating and significantly delaying her diagnosis. The patient was adopted, and the family history was unknown. There was no history of medication use suggestive of acquired angioedema. At the time of the visit, she had signs of chronic lip changes and atopy. After an extensive workup, it showed severely low levels of C1 esterase inhibitor and borderline low to normal C4 and C1q, consistent with the diagnosis of HAE type I. Initial treatment with an on-demand C1 esterase inhibitor reduced the recurrence of lip swelling and transitioned to long-term prophylaxis use. Overall, the treatment outcome was generally successful, with less recurrence of lip swelling and ER visits.

Trichinellosis-Induced Eosinophilic Myocarditis Mimicking Hypereosinophilic Syndrome.

Trichinella spiralisis an uncommon parasitic disease contracted through the consumption of undercooked pork. We report the case of a 59-year-old man with a history of bicuspid aortic valve with recent travel to the Philippines and consumption of raw pork presenting with progressive myalgia and hypereosinophilia (nadir 12,940/uL) in profound cardiogenic shock in the setting of critical aortic stenosis. He underwent emergent balloon valvuloplasty, which was complicated by aortic insufficiency. This necessitated a transcatheter aortic valve replacement. However, despite hemodynamic stabilization, he developed catastrophic eosinophilic myocarditis, complicated by cardiac arrest from ventricular tachycardia. A rectus femoris muscle biopsy confirmed the diagnosis, showing a T. spiralis parasite and significant eosinophilic infiltration. Empiric treatment with albendazole, ivermectin, and methylprednisolone resulted in the significant resolution of symptoms and the liberalization of critical illness. This case highlights the challenges of diagnosing the underlying etiologies of hypereosinophilia and/or eosinophilic myocarditis, underscoring the importance of considering parasitic etiologies, particularly in endemic regions or in patients who have a significant travel history to such areas. Prompt diagnosis and treatment are essential to prevent morbidity and mortality.

Steroid-Responsive Encephalopathy Associated With Autoimmune Thyroiditis Masquerading Sepsis.

A 72-year-old male presented with a fever and altered mental status. While initially diagnosed with sepsis due to cholangitis, he continued to decline and had seizures that complicated the course. After extensive workup, he was found to have anti-thyroid peroxidase antibodies and diagnosed with steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT). He showed remarkable improvement with glucocorticoids and intravenous immunoglobulins. SREAT is a rare autoimmune encephalopathy characterized by elevated serum titers of antithyroid antibodies. SREAT needs to be listed as a differential diagnosis in a patient with encephalopathy of unclear causes, and the presence of antithyroid antibodies is a hallmark of the entity.