A Summary of the Rare Reports of Osteonecrosis of the Jaw Associated With Tumor Necrosis-α Inhibitors in the United States Food and Drug Administration's Adverse Event Reporting System Database.

PURPOSE: Recent case reports highlight an association between osteonecrosis of the jaw (ONJ) and antitumor necrosis factor (anti-TNF) medications. Our study reviewed and described reports of anti-TNF associated ONJ reported to the United States of America's Food and Drug Administration Adverse Event Reporting System to explore this potential adverse drug reaction further. METHODS: Using the Food and Drug Administration Adverse Event Reporting System database, we identified reported cases of ONJ between 2010 and 2021. Cases were included in our study if they reported any prior or concomitant anti-TNF medication use. Additionally, only adults (age 18+) and reports from health-care professionals were included. Cases lacking subject age or gender were excluded. After duplicates were removed, a dataset was created and demographics were described including age, gender, and indication for use. Naranjo scoring was conducted to assess adverse drug reaction probability. Subject demographics were then separately described for cases without reported denosumab or bisphosphonate therapy history and compared to those with reported history or concomitant denosumab or bisphosphonate therapy. RESULTS: Over twenty thousand cases of ONJ were reported. Forty-four potential cases (0.22%) of anti-TNF medication-associated ONJ were identified and reviewed. Of these, female gender comprised 77.3% (35 cases) and there was an average age of 61.3 years ± 13.7 years. Twenty cases (45.5%) had no prior/concomitant bisphosphonate or denosumab therapy. Of these, 55% (11 cases) were female and the average age was 54.5 ± 17.3 years. Rheumatoid arthritis was the most frequent indication for use (5 cases, 25%) followed by inflammatory bowel disease (IBD) and psoriatic arthritis (4 cases each, 20%) in this cohort. CONCLUSIONS: Twenty potential cases of anti-TNF-associated ONJ without prior or concomitant medications known to be associated with ONJ were identified and described. Interestingly, male gender was more frequent and subjects were younger in these cases compared to those with prior/concomitant bisphosphonates or denosumab therapy. Naranjo scoring indicated a probable interaction for three cases. Further studies are needed to clarify the association of ONJ and anti-TNF therapy, including investigating potential mechanisms and reporting future cases with sufficient detail to assess possible confounding factors.

A Case of Jejuno-Jejunal Intussusception Caused by Underlying Metastatic Melanoma.

Intussusception in adults is a rare finding with a majority of cases occurring in the pediatric population. It occurs infrequently and its presentation, etiology, and treatment differ from childhood intussusception. When discovered in adults, it raises suspicion for a neoplastic process serving as the pathological lead point. Cross-sectional imaging is the primary study of choice for diagnosis, but at times, a more invasive approach involving an exploratory laparotomy is required posing an increased risk for morbidity and mortality. Here we present a 64-year-old male who was found to have jejunal-jejunal intussusception that was surgically removed with pathology revealing metastatic melanoma as the lead point. This case highlights a unique presentation of a melanoma that was previously eradicated with immunotherapy and now had metastasized to the intestine many years later.

A Unique Case of Acute Respiratory Distress Syndrome Secondary to Rheumatoid Lung Disease With Administration of Anti-Tumor Necrosis Factor Alpha (TNFα) Agent.

Patients with rheumatoid arthritis (RA) may experience complications directly from the disease process or from immune-modulating agents used to treat RA. Adalimumab is a recombinant human monoclonal antibody directed against tumor necrosis factor alpha (TNFα) which has been increasingly used in the management of inflammatory and autoimmune diseases. Acute lung injury has been associated with the use of anti-TNFα agents, but the association with adalimumab is rare. Here we present a case of a patient with RA-associated lung disease who developed acute respiratory distress syndrome while being treated with adalimumab. Adalimumab-related lung injury is less common than lung injury associated with other anti-TNFα drugs, thus clinicians should be aware of this condition, as prompt recognition and supportive management can help prevent worsening outcomes.

Multiple Autoimmune Complications After a Single Dose of Pembrolizumab.

Pembrolizumab, a monoclonal antibody that inhibits programmed cell death protein-1 (PD-1), is an important treatment for various malignancies. Unfortunately, it has also been associated with a wide array of immune-related adverse events. We present a unique case of a patient who received a single dose of pembrolizumab and subsequently developed multiple immune-mediated complications, including dermatitis, hepatitis, myositis, myocarditis, and myasthenia gravis.

Medication-induced osteonecrosis of the jaw: a review of cases from the Food and Drug Administration Adverse Event Reporting System (FAERS).

BACKGROUND: Osteonecrosis of the jaw (ONJ) is a rare but serious adverse drug reaction (ADR) commonly associated with bisphosphonate and denosumab therapy. Prior research utilized an online, public FDA Adverse Event Reporting System (FAERS) Database to explore this ADR. This data identified and described several novel medications associated with ONJ. Our study aims to build upon the prior findings, reporting trends of medication induced ONJ over time and identifying newly described medications. METHODS: We searched the FAERS database for all reported cases of medication related osteonecrosis of the jaw (MRONJ) from 2010 to 2021. Cases lacking patient age or gender were excluded. Only adults (18 +) and reports from Healthcare Professions were included. Duplicate cases were removed. The top 20 medications were identified and described for April 2010-December 2014 and April 2015-January 2021. RESULTS: Nineteen thousand six hundred sixty-eight cases of ONJ were reported to the FAERS database from 2010-2021. 8,908 cases met inclusion criteria. 3,132 cases were from 2010-2014 and 5,776 cases from 2015-2021. Within the cases from 2010-2014, 64.7% were female and 35.3% were male, and the average age was 66.1 ± 11.1 years. Between 2015-2021, 64.3% were female and 35.7% were male, and the average age was 69.2 ± 11.5 years. Review of the 2010-2014 data identified several medications and drug classes associated with ONJ not previously described. They include lenalidomide, corticosteroids (prednisolone and dexamethasone), docetaxel and paclitaxel, letrozole, methotrexate, imatinib, and teriparatide. Novel drugs and classes described between 2015-2021 include palbociclib, pomalidomide, radium 223, nivolumab, and cabozantinib. DISCUSSION: While stricter inclusion criteria and removal of duplicate cases led to fewer overall identified cases of MRONJ when compared to prior research, our data represents a more reliable analysis of MRONJ reports to the FAERS database. Denosumab was the most frequently reported medication associated with ONJ. While unable to imply incidence rates from our data due to the nature of the FAERS database, our findings provide further description of the various medications associated with ONJ and elucidate patient demographics associated with the ADR. Additionally, our study identifies cases of several newly described drugs and drug classes that have not been previously described in literature.

Acute Myeloid Leukemia Masquerading as Decompensated Cirrhosis.

Patients with known cirrhosis who present with anemia, thrombocytopenia, acute renal failure, and confusion are usually presenting with decompensated cirrhosis. We present a patient with known alcoholic cirrhosis presenting with the above abnormalities, initially thought to be decompensated cirrhosis but found to have acute myeloid leukemia (AML) with acute blast crisis. This case was presented as a poster at the American College of Gastroenterology Annual Scientific Meeting held on October 22-27, 2021. A 59-year-old male with a history of compensated alcoholic cirrhosis presented with unresponsiveness. On physical exam, vitals were normal, he appeared lethargic with generalized pallor, and rectal exam demonstrated an empty rectal vault with no blood or stool noted. Labs were notable for hemoglobin 3.1 g/dL, platelet count 41,000/µL, creatinine 5.2mg/dL, aspartate aminotransferase (AST) 242 U/L, alanine aminotransferase (ALT) 138 U/L, bilirubin 0.8 mg/dL, lactic acid 8.5 mmol/L, international normalized ratio (INR) 1.8, ammonia 51µmol/L. Imaging with CT head was unremarkable and CT abdomen demonstrated cirrhotic morphology of the liver with a small amount of ascites. Upper endoscopy was performed with no evidence of varices. Paracentesis demonstrated a high serum-ascites albumin gradient with low total protein consistent with portal hypertension. He was intubated for airway protection due to worsening encephalopathy. A peripheral smear was performed which showed myeloblasts with no signs of hemolysis. Bone marrow biopsy was subsequently performed which revealed 38% myeloblasts and features of myelodysplastic syndrome suggestive of secondary AML. Chemotherapy was not initiated as he was acutely critically ill and he expired shortly thereafter.  AML can present with symptomatic anemia, bleeding, mental status changes due to central nervous system involvement, organomegaly, and renal insufficiency. Diagnosing AML in the setting of decompensated liver cirrhosis can be difficult as the clinical presentations can be similar at times. Thus, hematological causes should be considered when there is profound anemia with no acute blood loss early in the course.