Novel anti-psoriasis agent-associated cardiotoxicity, analysis of the FDA adverse event reporting system (FAERS).

INTRODUCTION: Psoriasis is a chronic skin condition characterized by hyperproliferation of epidermal keratinocytes, resulting in erythematous and scaling lesions. The US Food and Drug Administration (FDA) has approved nine biologic agents to address the burden of psoriasis, but their cardiovascular risks remain poorly studied. METHODS: This retrospective pharmacovigilance study utilized the FDA Adverse Event Reporting System (FAERS) database to analyze adverse events associated with newly approved therapeutic agents for psoriasis. We employed disproportionally signal analysis, calculating the reporting odds ratio (ROR) with a 95% confidence interval. RESULTS: Among the vast FAERS database, which contained >25 million adverse events, a total of 334,399 events were associated with newly approved therapeutic agents for psoriasis. Cardiac adverse events accounted for 3852 cases, including pericarditis, atrial fibrillation, and coronary artery disease. Secukinumab had the highest number of reported adverse events, followed by brodalumab, while tildrakizumab had the lowest. Coronary artery disease was the most reported adverse event (1438 cases), followed by pericarditis (572 cases) and atrial fibrillation (384 cases). Secukinumab had the highest incidence of coronary artery disease, pericarditis, and atrial fibrillation. Risankizumab was significantly associated with an increased risk of coronary artery disease and atrial fibrillation, while tildrakizumab and Ixekizumab were associated with atrial fibrillation. Secukinumab was associated with an elevated risk of pericarditis. CONCLUSIONS: The study uncovers the cardiovascular adverse effects related to biologic agents used in psoriasis treatment. These findings emphasize the importance of monitoring and evaluating the cardiovascular safety profiles of biological agents used in psoriasis treatment.

Adult-onset Still's disease with concurrent thrombotic microangiopathy: Observations from pooled analysis for an uncommon finding.

BACKGROUND: Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder that is characterized by quotidian fevers, arthritis, and an evanescent rash. Occurrence of concurrent thrombotic microangiopathy (TMA) in AOSD is rare. The treatment aspects of TMA in AOSD are actively being debated. METHODS: Medline search using MeSH terms and snowballing yielded a total of 29 articles with co-occurrence of AOSD and thrombotic thrombocytopenic purpura (TTP) including our own. Pooled data were synthesized for descriptive analysis. RESULTS: Median age was 35 years with a majority of females (68.96%). A majority of these studies/patients were either Asian (34.48%) or Caucasian (31.03%). Concurrent TMA at the time of AOSD diagnosis was seen in 65.51% patients. Only 3/29 patients had ADAMTS13 level less than 10%, consistent with TTP and 3/29 were diagnosed with hemolytic uremic syndrome (HUS). The remainder were diagnosed clinically. Complication rate was high, and 15/29 (51.72%) patients died or had permanent neurological/renal/vision/gangrenous complications. Median and mean ferritin peak was observed to be higher (7458 and 12 349, respectively) in patients who either died/had partial remission, compared to those who had complete response (3257 and 10 899, respectively), p = .829. CONCLUSIONS: A majority of patients with AOSD-associated TMA either died or had permanent complications. TMA was diagnosed alongside AOSD in 65% patients, while the rest developed TMA during the course of their disease. Blurred vision may precede TMA and could help risk-stratify high-risk AOSD patients clinically. Glycosylated ferritin remains low several weeks to months after disease remission and may be used to monitor severity of disease process. Further studies are necessary to confirm the existing vascular endothelial growth factor hypothesis in AOSD-associated TMA.

Esophageal squamous cell carcinoma at the site of tracheo-esophageal fistula repair in a patient with cystic fibrosis.

With increasing survival in patients with cystic fibrosis (CF), complications such as gastrointestinal (GI) malignancies are becoming more apparent, especially in transplanted patients. In patients with CF, these malignancies are most commonly found in the small bowel, colon, biliary tract and pancreas. We describe a patient with esophageal squamous cell cancer at the site of trachea-esophageal fistula repair in the setting of long-standing CF. Many factors such as low expression of CF transmembrane conductance regulator gene, inflammation and resulting metaplasia, bacterial dysbiosis, dysregulation of Wnt/ß-catenin signalling, immune cell infiltration, disruption of intestinal stem cell homeostasis and intestinal barrier integrity have all been implicated in the causation of GI malignancy in patients with CF. Based on shared decision-making in high-risk transplanted individuals, esophagogastroduodenoscopy can be considered alongside colon cancer screening which is currently recommended starting at age 30-35 years.

Unusual case of pernicious anaemia masquerading as thrombotic thrombocytopenic purpura in the setting of multiple normal vitamin B12 deficiency parameters: preventing anchoring and overdiagnosis.

BACKGROUND: Pseudo-thrombotic microangiopathy (pseudo- thrombotic microangiopathy (TMA)) is a rare presentation of B12 deficiency. Overlapping features like elevated LDH/total bilirubin with low haemoglobin/haptoglobin/platelets could deceivingly suggest thrombotic thrombocytopenic purpura (TTP) resulting in avoidable procedures/treatments. CASE PRESENTATION: A 36-year-old female with hypothyroidism initially presented to clinic with fatigue, palpitations, lightheadedness, and dyspnoea over a 3-month duration and was found to have a haemoglobin of 5.7 g/dL. She received two packed red blood cell units in the emergency room and subsequently discharged with outpatient follow-up and empiric oral iron. During her follow-up visit, she was found to have easy bruisability, gum bleeding, and generalized weakness from hemolytic anaemia (mean corpuscular volume (MCV) 90 fL, haptoglobin <8 mg/dL, LDH >4,000 U/L and schistocytosis on CBC) and thrombocytopenia of 52 K/uL. Due to PLASMIC score of 6 and suspicion for TTP, she was transferred to our facility and tr eated with three cycles of plasma exchange and prednisone but were discontinued when ADAMTS13 levels returned normal. While the patient had normal B12 levels, further testing revealed positive intrinsic factor antibodies (IF-Ab) and an elevated MMA level of 1.56 umol/L. Replacement with cobalamin led to normalization of labs and symptoms. CONCLUSIONS: Timely diagnosis of pseudo-TMA was exceptionally challenging due to several overlapping features with TTP including normal B12 and normal MCV. B12 levels may falsely appear normal in pernicious anemia due to IF-Ab interference with chemiluminescent immunoassay. Schistocytes lower the MCV in automated cell counters. Lower reticulocyte index (<2%), presence of immature/large platelets and teardrop cells, elevated MMA and a higher LDH (>2500) are indicative of B12 deficiency.

Vancomycin- and piperacillin-induced acute interstitial nephritis in a patient with lupus: A case report showcasing rapid decline in renal function.

Drug-induced acute interstitial nephritis (AIN) presents as acute kidney injury (AKI) with the use of certain offending drugs. Antibiotics, such as ß-lactams, trimethoprim-sulfamethoxazole, fluoroquinolones, and rifampin, account for up to 50% of drug-induced AIN cases. The onset of drug-induced AIN following drug exposure usually ranges from few days to several weeks or months. We present a patient with lupus who had rapid decline in renal function with a single dose of vancomycin and piperacillin-tazobactam (VPT) administration, termed as the "workhorse" regimen at many institutions. In addition, she did not exhibit many clinical and laboratory signs of AIN, making diagnosis challenging. Prompt kidney biopsy and early steroid therapy had a critical role in recovery of the patient's renal function. The median duration for renal impairment in vancomycin-induced AIN is 26 days. Onset of AKI is usually rapid from VPT, within 3 - 5 days of drug exposure. However, the severity of AKI is often low, in contrast to this patient whose AKI reached a stage 3 (AKIN/KDIGO) within 2 days from drug exposure. This study highlights the nephrotoxic potential of piperacillin, especially when used along with vancomycin, concurrent with recent evidence. Within rising antibiotic usage rates, is important to consider AIN in the differential diagnosis of rapidly declining AKI, especially with the combined use of VPT.

De novo monocytic-M5b AML with t(8;16) (p11.2; p13.3) KAT6A/CREBBP fusion and FLT3-TKD mutation complicated by chemotherapy-induced Takotsubo cardiomyopathy.

Acute myeloid leukemia (AML) with t(8;16) is a rare cytogenetic abnormality that presents unique characteristics such as hemophagocytosis, disseminated intravascular coagulation, leukemia cutis and varying levels of CD45 expression. It is more common in women and usually associated with prior cytotoxic therapies, accounting for <0.5% of all AML cases. We present a case of de novo t(8;16) AML with FLT3-TKD mutation who relapsed after initial induction and consolidation. Mitelman database analysis reveals only 175 cases with this translocation, majority of which are M5 (54.3%) and M4 (21.1%) AML. Our review reveals very poor prognosis with overall survival ranging from 4.7 to 18.2 months. She also developed Takotsubo cardiomyopathy after receiving 7+3 induction regimen. Our patient died in 6 months from the date of diagnosis. Although a rare occurrence, it has been discussed in literature to identify t(8;16) as a separate subtype of AML due to unique characteristics.

Cardiovascular complications of modern multiple myeloma therapy: A pharmacovigilance study.

AIMS: Multiple myeloma accounts for over 10-15% of haematological malignancies. Continued molecular advances have resulted in the development of new drugs for treatment of multiple myeloma. Four drugs were approved by the Food and Drug Administration (FDA) in 2015, but their safety is not well defined. The aim of this study is to delineate the cardiovascular adverse events of these drugs. METHODS: We reviewed the adverse cardiac events of newly approved FDA drugs since 2015 using the US FDA Adverse Events Reporting System (FAERS) database. We calculated the reporting odds ratio (ROR) with 95% confidence interval (CIs) for the drugs that have the highest incidence of cardiovascular adverse events. RESULTS: Among the medications that have approved for multiple myeloma between 2015 and 2020, 4 novel drugs showed the highest incidence of cardiotoxicity. ROR (95% CI) for atrial fibrillation due to elotuzumab, ixazomib, daratumumab and panobinostat compared to other FAERS drugs was 5.8 (4.4-7.7), 1.9 (1.5-2.3), 4.8 (4.2-5.6) and 5.7 (4.1-8.1), respectively. The ROR (95% CI) for cardiac failure was 8.2 (6.4-10.5), 4.7 (4.1-5.4), 5.8 (4.9-6.7) and 5.6 (3.8-8.1) and ROR (95% CI) for coronary disease was 2.7 (1.9-3.9), 2.7 (2.3-3.2), 2.3 (1.9-2.8) and 4.6 (3.2-6.6) due to elotuzumab, ixazomib, daratumumab and panobinostat compared to all other drugs in FAERS. CONCLUSION: Our results demonstrated that certain newly approved antimyeloma therapies are significantly associated with previously unknown cardiotoxicity. These results warrant further studies and highlight the importance of considering the cardiac history of patients with multiple myeloma when utilizing these novel agents.