Rare Adverse Effect Research Articles

Current and emerging medications for the management of obesity in adults.

Current and emerging medications for the management of obesity in adults.

A Rare Adverse Effect Following Prolonged Linezolid Therapy.

A Rare Adverse Effect Following Prolonged Linezolid Therapy.

SARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunity

mRNA-based vaccines dramatically reduce the occurrence and severity of COVID-19, but are associated with rare vaccine-related adverse effects. These toxicities, coupled with observations that SARS-CoV-2 infection is associated with autoantibody development, raise questions whether COVID-19 vaccines may also promote the development of autoantibodies, particularly in autoimmune patients. Here we used Rapid Extracellular Antigen Profiling to characterize self- and viral-directed humoral responses after SARS-CoV-2 mRNA vaccination in 145 healthy individuals, 38 patients with autoimmune diseases, and 8 patients with mRNA vaccine-associated myocarditis. We confirm that most individuals generated robust virus-specific antibody responses post vaccination, but that the quality of this response is impaired in autoimmune patients on certain modes of immunosuppression. Autoantibody dynamics are remarkably stable in all vaccinated patients compared to COVID-19 patients that exhibit an increased prevalence of new autoantibody reactivities. Patients with vaccine-associated myocarditis do not have increased autoantibody reactivities relative to controls. In summary, our findings indicate that mRNA vaccines decouple SARS-CoV-2 immunity from autoantibody responses observed during acute COVID-19.

Role of spontaneous reporting in investigating the relationship between mRNA COVID-19 vaccines and myocarditis: The French perspective

Post-mRNA coronavirus diseases 2019 (COVID-19) vaccines myocarditis emerged as a rare adverse effect, particularly in adolescents and young adults, and was labeled as such for both vaccines in the summer of 2021. This study aims to summarize the timeline and process of signal detection, substantiation, and quantification of myocarditis cases related to mRNA vaccines in France. The intensive monitoring plan for COVID-19 vaccine safety was based on case-by-case analysis of all cases collected in the French spontaneous reporting database (Base nationale de pharmacovigilance, BNPV). Cases were evaluated by drug safety medical professionals and discussed at a national level for signal detection purposes. Reported cases were compared to the number of vaccine-exposed persons up to September 30th, 2021. Reporting rates (Rr) of myocarditis per 100,000 injections were calculated and stratified according to age, gender, and injection rank of BNT162b2 and mRNA-1273 vaccines. Poisson distribution was used to compute Rrs 95% Confidence Interval (95% CI). The case-by-case analysis detected a possible cluster of myocarditis in April 2021 (5 cases, 4 after the 2nd injection). In June 2021, the signal was substantiated with 12 cases (9 related to BNT162b2, and 3 to mRNA-1273). As of September 2021, almost 73 million BNT162b2 and 10 million mRNA-1273 doses had been injected. The Rr per 100,000 injections was 0.5 (0.5-0.6) for BNT162b2 and 1.1 (95% CI 0.9-1.3) for mRNA-1273. The difference among vaccines was more pronounced after the second injection, particularly in men aged 18-24 years (4.3 [3.4-5.5] for BNT162b2 vs. 13.9 [9.2-20.1] for mRNA-1273) and aged 25-29 years (1.9 [1.2-2.9] vs. 7.0 [3.4-12.9]). The study highlighted the role of the spontaneous reporting system in the detection, assessment, and quantification of myocarditis related to m-RNA vaccines. It suggested from September 2021 that mRNA-1273 was reasonably related to a higher risk of myocarditis than BNT162b2 in people under 30, particularly after the second injection.

Donepezil-induced psychosis: a cautionary report of a rare adverse reaction

IntroductionDonepezil is an acetylcholinesterase inhibitor approved by the Food and Drug Administration for the treatment of dementia in Alzheimer’s disease. While it is not curative for Alzheimer’s disease, donepezil has been shown to improve symptoms and slow disease progression; however, cases of rare psychiatric adverse effects, including hallucinations, mania, and increased confusion, have been reported. This report presents a case of donepezil-induced psychosis, which quickly resolved following cessation of the offending medication.ObjectivesTo illustrate a unique case of donepezil-induced psychosisMethodsThe patient is an 81-year-old male with a history of late-onset Alzheimer’s disease, mild depression, hypertension, hyperlipidemia, gastroesophageal reflux disease, and myocardial infarction. The patient was prescribed oral donepezil 10mg twice daily to manage his late-onset Alzheimer’s disease. Subsequently, he began developing persecutory delusions, increased agitation toward his family, and auditory hallucinations. His symptoms were worse at night after taking the donepezil, and he regularly requested to have a firearm for self-defense in the late hours of the night. His symptoms progressed for several weeks before his family brought him into the geriatric psychiatry clinic to address his psychosis. The family recognized that these new symptoms started shortly after the patient began taking donepezil and had already started decreasing the dose to half of what was originally prescribed.ResultsThis patient experienced symptom remission from psychosis immediately upon discontinuation of donepezil. The patient and his family reported significant improvement with no continuation of hallucinations or paranoia. There was also reported improvement in mood and irritability, and the patient appeared significantly better upon follow-up with geriatric psychiatry. Due to this immediate improvement, the suspected causative factor in the precipitation of psychosis in this patient is the anticholinesterase activity of the donepezil. Although the prescribing information of donepezil details inadequate data proving an association between donepezil and psychotic symptoms, two other published case reports (Yorston GA et al. J Psychopharmacol 2000;14:303-4, Pozzi FE et al. Case Rep Neurol 2022; 14:359-365), along with this one, provide evidence of a causal relationship between the two. The patient was switched to memantine therapy and has remained free of psychotic symptoms thus far.ConclusionsThis case demonstrates the caution required among clinicians when prescribing donepezil for the treatment of Alzheimer’s disease. There needs to be a more focused risk evaluation of potential psychiatric adverse effects in patients treated with donepezil.Disclosure of InterestNone Declared

Evaluation of Jaw Osteonecrosis Following Intra-Ligament Anesthesia in Zoledronate-Treated Rats: a Histological Evaluation.

One of the rare adverse effects in patients who take bisphosphonates is the osteonecrosis of the jaw in the oral cavity following any trauma such as tooth extraction. The aim of this study is the histopathological evaluation of the jaw following intra-ligament anesthesia injection in Zoledronate-treated rats. In this descriptive-experimental study, rats weighing 200-250 g were divided into 2 groups. The first group received a 0.6 mg/kg dose of zoledronate and the second group received normal saline. Five injections with a 28-day interval were performed. At the end of the injection, the animals were sacrificed. Then, five-micrometer histological slides were prepared from the first maxillary molars and the surrounding tissues. Hematoxylin and eosin staining was performed to evaluate osteonecrosis, infiltration of inflammatory cells, fibrosis, and root and bone resorption. There was no difference between the macroscopic and clinical features in both groups and no evidence of osteonecrosis of the jaw was observed in the samples. From the histological point of view, all the samples had normal tissues and none of them showed any evidence of inflammation, tissue fibrosis, disorder, or pathological root resorption. According to the histological findings, the periodontal ligament space, the bone adjacent to the roots, and the dental pulp conditions were similar in both groups. Osteonecrosis of the jaw did not develop in the rats that took bisphosphonates after intraligamental injection.

Abstract Number ‐ 233: Vaccine‐Induced Thrombotic Thrombocytopenia presenting as Massive Stroke: Case Report and Literature Review

Introduction Vaccines have been pivotal for the COVID‐19 pandemic. Rare adverse effects of the vaccines such as thrombosis have been observed. Here we report a case of an acute malignant ischemic stroke in a young healthy patient caused by thrombosis due to Vaccine‐Induced Thrombotic Thrombocytopenia (VITT). Methods Electronic chart review for a case report. Results A 43‐year‐old Caucasian female with a medical history of hypertension was found unresponsive on the morning of presentation. Her Last known normal was the night before. On arrival in the emergency department, she was globally aphasic, with left eye deviation, right‐sided neglect, right facial droop, and right‐side hemiplegia. Pupils were equal and reactive to light. NIHSS was 23. Head CT showed large left middle cerebral artery and anterior cerebral artery strokes with significant cerebral edema and midline shift. Head and neck CTA showed left ICA and left MCA occlusions. She was taken for decompressive craniectomy immediately. Ten days prior to the stroke, she received her first COVID vaccination. She smoked but did not take oral contraceptives. She did not have a family history of hypercoagulability. Stroke workup showed LDL 141, A1C 4.8%, and a negative COVID test. She had normal white and red blood cell counts but low platelet counts at 73,000, which was 233,000 one month prior. 2D echocardiogram showed an ejection fraction of 54% and no patent foramen ovale or thrombus. Lower extremity doppler showed deep vein thrombosis. Because of arterial and venous thrombosis with new thrombocytopenia, hematology was consulted. She was found to have positive anti–PF4–heparin antibody, leading to a VITT diagnosis. She received IVIG, rituximab, and steroid treatments, and her platelets gradually returned to the baseline. She was later transferred to a rehabilitation facility. Conclusions VITT is characterized by thrombosis and thrombocytopenia with positive PF4 antibodies after a median of 14 days post‐vaccination. It was reported in COVID vaccines from all manufacturers. The mechanism remains unclear. The current hypothesis describes a two‐hit process through which the vaccine triggers neoantigen formation (the first hit) followed by a systemic inflammatory response (the second hit). Incidence of VITT from COVID vaccinations is unknown but the reported cases were rare. VITT‐caused acute stroke, especially malignant strokes, is even rarer.Although the COVID vaccines can cause rare life‐threatening adverse events, they are essential for controlling the pandemic. When encountering an ischemic stroke patient with thrombocytopenia, we should consider VITT. Further study with post‐vaccination registration and monitoring is warranted.

Rare adverse effects of Electro Convulsive Therapy

IntroductionECT’s most common side effects are headache, memory impairment, and cardiovascular changes [1]. We report the unusual case of unilateral eyelid swelling and cheek flushing as a side effect of ECT in a depressed but otherwise healthy patient.ObjectivesThe patient is a 53-year-old woman with a recurrent depressive disorder for 15 years with a current major depressive episode without psychotic symptoms. With therapy resistance to mirtazapine (60 mg/d) and lithium (675 mg/d; 0.75 mmol/l), an ECT series with a total of seven sessions were performed. Treatment was performed with right unilateral electrode placement according to d’Elia (RUL).MethodsAfter the first session (Thymatron IV; energy: 20%; pulse width: 0.5; EEG: 45 s), marked hemifacial erythema and supraorbital lid swelling on the right side were evident. After each of the total seven sessions with adequate seizures in the EEG between 45 to 68 s, hemifacial erythema and supraorbital eyelid swelling were evident on the right side.ResultsBoth supraorbital eyelid edema occurred immediately after seizure onset, and hemifacial erythema resolved spontaneously and entirely within 10 minutes after the termination of the respective seizure.ConclusionsThe right side of the face appeared normal before ECT and had no injuries or abnormalities. Trauma, allergic reactions to the anesthetic, or complications of manual ventilation were excluded. In the literature, only one case report with supraorbital eyelid edema [2] and one case report with hemifacial redness of the face [3] after ECT have been described so far. We evaluate the eyelid edema and erythema that occurred in our case as isolated benign complications, most likely due to autonomic activation of facial nerves due to electrical stimulation in RUL.Disclosure of InterestNone Declared

Clinical features, risk factors, diagnosis, and treatment of trimethoprim-sulfamethoxazole-induced hypoglycemia.

Hypoglycemia is a sporadic and serious adverse reaction of trimethoprim-sulfamethoxazole (TMP-SMX) due to its sulfonylurea-like effect. This study explored the clinical characteristics, risk factors, treatment, and prognosis of TMP-SMX-induced hypoglycemia. Case reports and series of TMP-SMX-induced hypoglycemia were systematically searched using Chinese and English databases. Primary patient and clinical information were extracted for analysis. A total of 34 patients were reported from 31 studies (16 males and 18 females). The patients had a median age of 64 years (range 0.4-91), and 75.8% had renal dysfunction. The median duration of a hypoglycemic episode was six days (range 1-20), and the median minimum glucose was 28.8 mg/dL (range 12-60). Thirty-two patients (97.0%) showed neuroglycopenic symptoms, with consciousness disturbance (30.3%) and seizure (24.2%), sweating (18.2%), confusion (15.2%), asthenia (12.1%) being the most common symptoms. Fifteen patients (44.1%) had elevated serum insulin levels, with a median of 31.8 μU/mL (range 3-115.3). C-peptide increased in 13 patients (38.2%), with a median of 7.7 ng/mL (range 2.2-20). Complete recovery from symptoms occurred in 88.2% of patients without sequelae. The duration of hypoglycemia symptoms was 8 hours to 47 days after the intervention. Interventions included discontinuation of TMP-SMX, intravenous glucose, glucagon, and octreotide. Hypoglycemia is a rare and serious adverse effect of TMP-SMX. Physicians should be aware of this potential adverse effect, especially in patients with renal insufficiency, increased drug doses, and malnutrition.

A RARE CASE OF ANTI-TUBERCULAR DRUG INDUCED CARDIOMYOPATHY

Anti-tubercular drugs are associated with some common and some rare adverse effects. We describe a case of a rare side effect- cardiomyopathy. In literature, none of the antituberculosis drugs are commonly mentioned among the drugs known to cause myocardial injury and cardiomyopathy. There have been only a handful of cases of anti-tuberculosis drug induced cardiomyopathy reported before. It is very important to recognize and treat this condition in a timely fashion which can otherwise be fatal as is shown in this case.

COVID-19 vaccines adverse events: potential molecular mechanisms.

COVID-19 is an infectious disease caused by a single-stranded RNA (ssRNA) virus, known as SARS-CoV-2. The disease, since its first outbreak in Wuhan, China, in December 2019, has led to a global pandemic. The pharmaceutical industry has developed several vaccines, of different vector technologies, against the virus. Of note, among these vaccines, seven have been fully approved by WHO. However, despite the benefits of COVID-19 vaccination, some rare adverse effects have been reported and have been associated with the use of the vaccines developed against SARS-CoV-2, especially those based on mRNA and non-replicating viral vector technology. Rare adverse events reported include allergic and anaphylactic reactions, thrombosis and thrombocytopenia, myocarditis, Bell's palsy, transient myelitis, Guillen-Barre syndrome, recurrences of herpes-zoster, autoimmunity flares, epilepsy, and tachycardia. In this review, we discuss the potential molecular mechanisms leading to these rare adverse events of interest and we also attempt an association with the various vaccine components and platforms. A better understanding of the underlying mechanisms, according to which the vaccines cause side effects, in conjunction with the identification of the vaccine components and/or platforms that are responsible for these reactions, in terms of pharmacovigilance, could probably enable the improvement of future vaccines against COVID-19 and/or even other pathological conditions.

Mirtazapine-induced Acute Pancreatitis in Patients With Depression: A Systematic Review.

Antidepressant-induced pancreatitis is a rare, albeit serious, adverse effect, with a frequency of occurrence that is not equally distributed among antidepressant drugs. The goal of this study was to investigate the association and causal relationship between mirtazapine treatment of patients with depression and pancreatitis. The study was designed as a systematic review of the literature, accompanied by the description of a new case of mirtazapine-associated acute pancreatitis. Nine cases of mirtazapine-associated pancreatitis have been reported, involving 7 female patients and 2 male patients with a mean age of 46.4 years (range: 26 to 83y of age). All of the patients were hospitalized, with an average length of stay of 16.2 days (range: 3 to 34d). In 6 cases, "de-challenge" followed by improvement was reported. The patients for whom the outcome was reported (7 of 9) recovered completely. Although a rare adverse effect, mirtazapine-induced pancreatitis should be considered when patients taking mirtazapine report abdominal discomfort.

Approach to acute psychosis in older adults.

Approach to acute psychosis in older adults.

A study on management of hemorrhoids: Comparison between conservative management and injection sclerotherapy

Background: Hemorrhoidal disease is one of the most common anorectal conditions encountered in daily practice for centuries. Conservative management of hemorrhoids (with oral diosmin, calcium dobesilate cream local application) and injection sclerotherapy with 3% polidocanol-both are very commonly practiced, cost effective, and outpatient department-based management of hemorrhoids which bear rare adverse effects. Comparative efficacy of injection sclerotherapy and conservative management in cases of hemorrhoids is still confusing and contradictory to each other according to different studies. Aims and Objectives: This study was conducted to compare the effectiveness between conservative management of hemorrhoids and injection sclerotherapy. Materials and Methods: This institution-based experimental study done over 74 patients of first- and second-degree internal hemorrhoids. Thirty-seven patients were randomly selected and managed with conservative management, and the rest with injection sclerotherapy. Treatment responses were assessed after 3 weeks and in unsatisfactory responses, treatment was repeated for another 3 weeks. Reassessment was done after 6 weeks and 6 months. Results: This study demonstrated that both injection sclerotherapy and conservative management had improved per rectal bleeding after 3 and 6 weeks of treatment, but the former had a significant edge over the counterpart after 6 months of treatment (56.8% vs. 35.1%, P = 0.002). In case of reduction of hemorrhoidal mass – injection sclerotherapy had significantly better outcome in all the follow-up visits, that is, 3 weeks (54.1% vs. 13.5%, P = 0.001), 6 weeks (70.3% vs. 35.1%, P = 0.008) and 6 months (59.5% vs. 27.0%, P = 0.003). Injection sclerotherapy had superior overall treatment outcome after 6 weeks of treatment (73% vs. 45.9%, P = 0.04) and long-term periods (56.85% vs. 27%, P < 0.01). Conclusion: Injection sclerotherapy shows significantly better and long-lasting improvement in symptomatic hemorrhoids in comparison to conservative management which is mainly able to limit per rectal bleeding only for a short period of time.

Rare adverse effects of anti tuberculous therapy − a case series

Tuberculosis is prevalent throughout the world and is a major public health problem in most developing countries. Standardized and directly observed treatment under NTEP (National Tuberculosis Elimination Programme) is currently recommended for drug-sensitive pulmonary tuberculosis in India. It is generally well tolerated, with few minor side effects. Severe side effects necessitating discontinuation of therapy are rare with standard TB treatment regimens. Drug-resistant tuberculosis (DR-TB) has become more common in recent years, posing a challenge to global efforts to control the disease. Therapy for DR-TB has been associated with many adverse effects. Therefore, close monitoring of patients on DR-TB therapy is necessary to ensure that adverse effects of drugs are recognized early by healthcare personnel and treated accordingly. This will improve drug compliance and, hence, treatment goals. Here we report three cases of tuberculosis who had unusual adverse effects while receiving anti-tuberculous medication, prompting drug discontinuation.

Vaccine-Associated Rubella Caused by the RA 27/3 Strain

Vaccine-associated rubella is a very rare adverse effect after rubella vaccination; we report the characteristics of a young women who, after a vaccination campaign where she received three different vaccines against influenza, tetanus/diphtheria, and measles/rubella, developed a fever and rash consistent with rubella disease that was confirmed by sequencing of the virus. The evolution was favorable. The woman had two close contacts who did not develop the disease. Follow-up of the patient and her contacts was important to detect complications and for epidemiology surveillance.

Ponesimod: An Oral Second-Generation Selective Sphingosine 1-Phosphate Receptor Modulator for the Treatment of Multiple Sclerosis.

To describe the safety, efficacy, and potential role in therapy of ponesimod, which was recently approved by the Food and Drug Administration (FDA) as a therapeutic option for the treatment of multiple sclerosis (MS). A PubMed literature search using the following terms: ponesimod and MS (January 1, 2012-October 31, 2022). FDA product labeling was also reviewed for pertinent data sources. All relevant English-language articles examining efficacy and/or safety of ponesimod were considered for inclusion. Ponesimod is an orally administered second-generation sphingosine 1-phospate (S1-P) receptor modulator classified as a disease modifying treatment (DMT) for MS. Clinical studies have shown that ponesimod prevents relapse in patients with relapsing-remitting MS (RRMS) and has superior efficacy compared with teriflunomide. Nasopharyngitis, upper respiratory tract infections, headache, high blood pressure, and liver dysfunction were some of the common adverse effects associated with ponesimod. Dyspnea, bradyarrhythmias, atrioventricular conduction delays, and macular edema were some of the rare but serious adverse effects associated with ponesimod. Some advantages of ponesimod over other S1-P receptor modulators approved for RRMS include selectivity for the S1-P1 receptor and short half-life, which allows for quick reversal of immunosuppressive effects. However, data from long-term efficacy and safety studies and more direct comparison studies with other DMTs are required. Currently available data suggest that ponesimod is a useful addition to other high-efficacy DMTs available to treat patients with MS.

Nephrotic-range proteinuria and membranoproliferative glomerulonephritis-like pattern caused by interferon-β1b in a patient with multiple sclerosis.

Interferon-beta (IFN-β) subtypes are widely used as immunomodulatory agents for relapsing-remitting multiple sclerosis (MS). Although generally well tolerated, a growing number of reports have recently shown association of long-term IFN-β therapy with several types of glomerulonephritis. Here, we present the case of a 42-year-old woman with MS who developed nephrotic-range proteinuria after taking IFN-β1b for nine years. Initially, due to the presence of histological features consistent with immunoglobulin A (IgA) nephropathy (granular IgA deposits in mesangial lesions), a tonsillectomy plus steroid pulse therapy was performed. However, proteinuria did not significantly decrease after these treatments. Therefore, a second renal biopsy was performed after three years, revealing a membranoproliferative glomerulonephritis-like pattern without immune complex. Further immunofluorescence analysis showed attenuated IgA staining. Consequently, IFN-β1b was replaced with dimethyl fumarate, resulting in complete remission, with proteinuria decreasing to the level of 0.2g/day. Although it is a rare adverse effect, physicians should pay careful attention to the symptoms and findings of nephritis during the follow-up of patients under treatment with this agent.

Checkpoint inhibitor-induced myocarditis

Immunological checkpoint inhibitors have been revolutionary in the treatment of cancer. A rare but serious adverse effect is the development of heart muscle inflammation (myocarditis). The prevalence of this type of myocarditis is increasing as more cancer patients receive treatment with immune checkpoint inhibitors. Knowledge of immune checkpoint inhibitor-induced myocarditis isimportant to enable early diagnosis and initiation of treatment. In this article we provide a clinical review of this.

SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19 Morbidities and Therapeutics and for Vaccine Adverse Effects

Experimental findings for SARS-CoV-2 related to the glycan biochemistry of coronaviruses indicate that attachments from spike protein to glycoconjugates on the surfaces of red blood cells (RBCs), other blood cells and endothelial cells are key to the infectivity and morbidity of COVID-19. To provide further insight into these glycan attachments and their potential clinical relevance, the classic hemagglutination (HA) assay was applied using spike protein from the Wuhan, Alpha, Delta and Omicron B.1.1.529 lineages of SARS-CoV-2 mixed with human RBCs. The electrostatic potential of the central region of spike protein from these four lineages was studied through molecular modeling simulations. Inhibition of spike protein-induced HA was tested using the macrocyclic lactone ivermectin (IVM), which is indicated to bind strongly to SARS-CoV-2 spike protein glycan sites. The results of these experiments were, first, that spike protein from these four lineages of SARS-CoV-2 induced HA. Omicron induced HA at a significantly lower threshold concentration of spike protein than the three prior lineages and was much more electropositive on its central spike protein region. IVM blocked HA when added to RBCs prior to spike protein and reversed HA when added afterward. These results validate and extend prior findings on the role of glycan bindings of viral spike protein in COVID-19. They furthermore suggest therapeutic options using competitive glycan-binding agents such as IVM and may help elucidate rare serious adverse effects (AEs) associated with COVID-19 mRNA vaccines, which use spike protein as the generated antigen.