Uncommon Adverse Reaction Research Articles

Rapid cycling bipolar disorder and atypical anorexia nervosa: changes in drug metabolism

IntroductionBipolar disorder (BD) is a complex mental illness described by recurrent episodes of mania and depression. One subtype of the illness is rapid cycling BD, characterized by experiencing four or more extreme mood swings within a year. Diagnosing and treating BD can be complicated by comorbid conditions, such as atypical anorexia nervosa (AAN), marked by disordered eating and disturbing weight-related thoughts.ObjectivesTo discuss the diagnosis and treatment plan of a patient with rapid cycling BD, who experienced adverse effects from prescribed medication and later was diagnosed with comorbid AAN.Methods We present a case of a 21 year-old man initially presenting with anxiety, low mood, and obsessive weight-related thoughts, ultimately diagnosed with major depression and mixed anxiety disorder.Results21 year-old man was diagnosed with major depression and mixed anxiety disorder, initially treated with mirtazapine and fluoxetine (limited success), later attempting escitalopram and bupropion combination (partial remission). After 2 years the patient discontinued the treatment due to feeling “euphoric”, subsequently experiencing depression and manic episodes – the initial diagnosis was rapid cycling BD. The treatment was changed to sodium valproate (up to 1500 mg/day) and aripiprazole (up to 10 mg/day), however extremely rare adverse medication effects (nosebleeds, diarrhea with blood admixture, “high-frequency sounds”) were reported. Throughout valproate treatment, the patient experienced persistent diarrhea. During hospitalization for treatment adjustment lithium carbonate was introduced at a starting dose of 900 mg/day, maintaining blood lithium levels between 0.4 mmol/l and 0.49 mmol/l. Later the dose was adjusted and a therapeutic lithium blood level was reached with 1575 mg/day of lithium carbonate. Additionally, risperidone was prescribed, however, the patient experienced an uncommon adverse reaction – nasal congestion. Subsequently, amisulpride was introduced, which provoked severe anxiety and fear, resulting in medication discontinuation. During the latest outpatient visit, fluoxetine was added to the treatment due to observed depressive symptoms. Throughout the treatment, the patient episodically intermittently starved, had persistent distressing thoughts about weight and was diagnosed with AAN. While planning further treatment it was hypothesized that comorbid AAN might affect drug metabolism and the patient was referred to a specialized inpatient facility for eating disorder management.ConclusionsThis case report highlights the complexity of psychiatric disorders and the importance of monitoring and adjusting treatment based on patient response and side effects. Additionally, it emphasizes comorbid conditions significance in influencing the primary disorder’s dynamics as well as the metabolism and effectiveness of psychiatric medications.Disclosure of InterestNone Declared

Retrospective Analysis of Risk Factors for Cefoperazone/Sulbactam-Induced Thrombocytopenia in Adult Chinese Patients: A Six-Year Real-World Study.

Drug-induced thrombocytopenia is a rare adverse reaction of drug therapy and usually underdiagnosed. Cefoperazone/sulbactam is a compound preparation composed of the third generation of cephalosporin and β-lactamase inhibitor, of which thrombocytopenia is an uncommon but serious adverse reaction. However, the existing literature on cefoperazone/sulbactam-induced thrombocytopenia remains limited, and the specific risk factors associated with this adverse effect have not been thoroughly elucidated. Consequently, this study aims to investigate the clinical characteristics and identify the risk factors for thrombocytopenia in adult patients undergoing cefoperazone/sulbactam therapy. In this retrospective study, we reviewed patients treated with cefoperazone/sulbactam at Beijing Hospital between January 2017 and June 2023. Patients were categorized into two groups based on the presence or absence of thrombocytopenia: the thrombocytopenia group and the non-thrombocytopenia group. We collected data on demographic features, clinical characteristics, laboratory parameters, treatments, and outcomes. Subsequently, univariate and multivariate logistic regression analyses were performed to identify potential risk factors for cefoperazone/sulbactam-induced thrombocytopenia. In total, 6489 patients were included in this study, and 2.4% (155/6489) developed thrombocytopenia. The results of multivariate analysis showed that cefoperazone/sulbactam therapy duration (d) >14, PLT (109/L) <200, daily dose of cefoperazone/sulbactam (g) ≥6, TBil (μmoL/L) >21, AST (U/L) >35, and use of non-invasive ventilator were risk factors for cefoperazone/sulbactam-induced thrombocytopenia. Despite the low incidence (2.4%), cefoperazone/sulbactam could cause serious thrombocytopenia sometimes accompanied with hemorrhage. In clinical therapy, clinicians should be vigilant in monitoring platelet count, especially for patients with risk factors of cefoperazone/sulbactam-induced thrombocytopenia.

General dermatology and dermatology in primary healthcare.

Heparin-induced bullous haemorrhagic dermatosis is an uncommon cutaneous adverse reaction to heparin, thought to be under-reported owing to its relatively asymptomatic presentation and favourable prognosis. This vesiculobullous condition is largely self-limiting and tends to resolve spontaneously despite continued anticoagulant therapy. Correct identification can reassure clinicians and patients alike.

Drug-Induced Parotitis—A Rarity?

Abstract Unilateral parotitis is due to ductal obstruction. Bilateral parotitis occurs due to viral infections such as mumps, bacterial infections, Sjögren syndrome, and ductal obstruction. Drug-induced parotitis is a relatively uncommon adverse reaction, and it can be unilateral and bilateral. Unilateral causes of drug-induced parotitis can be due to clozapine, chlorpromazine, l-asparaginase, and α-methyldopa, whereas bilateral causes can be due to thioridazine, sulfadiazine, phenylbutazone, oxyphenylbutazone, nitrofurantoin, and valproic acid. Adverse reactions to sulfonamide are rare and manifest as rashes or urticaria. Herein, we report a case of acute unilateral parotitis occurring as a result of cotrimoxazole that resolved within 48 hours after discontinuation of therapy, which highlights that sulfonamide therapy can cause parotitis. Early clinical suspicion and discontinuation of therapy help in the prompt resolution of the allergic reaction to cotrimoxazole.

Alopecia associated with dimethyl fumarate treatment for multiple sclerosis.

After 2weeks of treatment, awoman with multiple sclerosis treated with dimethyl fumarate developed alopecia. Considering the adverse events, the therapy was discontinued, leading to alopecia regression during the next 3months. Although the precise mechanism has not been completely elucidated, glutathione depletion or downregulation of aerobic glycolysis are considered to be potential reasons for hair loss induction. The incidence and mechanism of this uncommon adverse reaction to dimethyl fumarate should be further investigated.

Anti-TNF-α induced paradoxical psoriasis in patients with ankylosing spondylitis: a systematic review.

The approval of TNF-a inhibitors (TNFi) was a breakthrough in the treatment of ankylosing spondylitis (AS). Although also effective in psoriasis, drug-related adverse events of onset of psoriasiform skin lesions - paradoxical psoriasis (PP) under TNFi have been reported. We performed an electronic data search in MEDLINE via Pubmed and Cochrane library scientific databases from inception to January 2023, following the PRISMA guidelines. We assessed the distinct characteristics and frequency of risks for PP appearance in AS patients treated with different TNFi. PP was found in 0.5-1% of TNFi-treated AS patients and the latency period was 2-11 months. The safest TNFi in terms of PP induction was certolizumab, whereas the one most commonly associated with PP was infliximab. PP is an uncommon adverse reaction to TNFi treatment in AS patients and responds well to drug withdrawal. More large data studies need to be conducted though, to shed light on PP nature and management.

Intravenous Immunoglobulin-Induced Aseptic Meningitis—A Narrative Review of the Diagnostic Process, Pathogenesis, Preventative Measures and Treatment

Intravenous immunoglobulins (IVIGs) are widely used in the treatment of numerous diseases in both adult and pediatric populations. Higher doses of IVIGs usually serve as an immunomodulatory factor, common in therapy of children with immune thrombocytopenic purpura. Considering the broad range of IgG applications, the incidence of side effects in the course of treatment is inevitable. Aseptic meningitis, an uncommon but significant adverse reaction of IVIG therapy, can prove a diagnostic obstacle. As of April 2022, forty-four cases of intravenous immunoglobulin-induced aseptic meningitis have been reported in the English-language literature. This review aims to provide a thorough overview of the diagnostic process, pathophysiology, possible preventative measures and adequate treatment of IVIG-induced aseptic meningitis.

Global prevalence and clinical manifestations of cutaneous adverse reactions following COVID-19 vaccination: A systematic review and meta-analysis.

Although vaccination is widely accepted as an effective method of preventing and controlling the COVID‐19 pandemic, many people are concerned about possible cutaneous side‐effects, which can delay or prevent them from being vaccinated. The objectives of this systematic review were to assess the global prevalence and clinical manifestations of cutaneous adverse reactions following COVID‐19 vaccination. PubMed and Scopus databases were searched for articles published from 1 January 2019 to 31 December 2021, and reference lists for each selected article were screened. Case reports, case series, observational studies and randomized controlled trials that provided information on cutaneous adverse reactions following COVID‐19 vaccines were included. A total of 300 studies were included in a systematic review of which 32 studies with 946 366 participants were included in the meta‐analysis. The pooled prevalence of cutaneous manifestations following COVID‐19 vaccination was 3.8% (95% CI, 2.7%–5.3%). COVID‐19 vaccines based on the mRNA platform had a higher prevalence than other platforms at 6.9% (95% CI, 3.8%–12.3%). Various cutaneous manifestations have been reported from injection site reactions, which were the most common (72.16%) to uncommon adverse reactions such as delayed inflammatory reactions to tissue filler (0.07%) and flares of pre‐existing dermatoses (0.07%). Severe cutaneous reactions such as anaphylaxis have also been reported, but in rare cases (0.05%). In conclusion, cutaneous adverse reactions are common, especially in those receiving mRNA vaccines. Most reactions are mild and are not contraindications to subsequent vaccination except for anaphylaxis, which rarely occurs. COVID‐19 vaccination may also be associated with flares of pre‐existing dermatoses and delayed inflammatory reactions to tissue filler. Patients with a history of allergies, pre‐existing skin conditions or scheduled for filler injections should receive additional precounselling and monitoring. A better understanding of potential side‐effects may strengthen public confidence in those wary of new vaccine technologies.

403 Acute myopericarditis after mRNA COVID-19 vaccine

AimsCases of myocarditis and myopericarditis after mRNA COVID-19 vaccines have been reported, especially after the second dose and in young males. Their course is generally benign, with symptoms onset after 24–72 h from the dose.Methods and resultsWe report two cases of myopericarditis after the second dose of the mRNA-1273 COVID-19 vaccine in two young males, 20-years old and 21-years old. Both the patients were administered the vaccine on the same day. They both experienced fever on the same day of the vaccine and symptoms consistent with myopericarditis three days after the dose, which was confirmed by cardiac magnetic resonance. Figure 1 summarizes the main non-invasive findings that suggested and confirmed the diagnosis of acute myopericarditis. The disease course was benign in both patients, and only one patient presented rare ventricular arrhythmias on the admission day. They were both discharged on the 9th day of the in-hospital stay.ConclusionsMyopericarditis is usually considered an uncommon adverse reaction after various vaccinations, reported also after the mRNA COVID-19 vaccine. Several explanations have been proposed, including an abnormal activation of the immune system leading to a pro-inflammatory cascade responsible for myocarditis development. The temporal aspect of these case reports is rather peculiar and it is useful to underscore that both vaccines belonged to the same batch of vaccines. However, despite these cases, vaccination against COVID-19 far outweighs the risk linked to COVID-19 infection and remains the best option to overcome this disease. 403 Figure

Drug triggered pruritus, rash, papules, and blisters \u2013 is AGEP a clash of an altered sphingolipid-metabolism and lysosomotropism of drugs accumulating in the skin?

Rash, photosensitivity, erythema multiforme, and the acute generalized exanthematous pustulosis (AGEP) are relatively uncommon adverse reactions of drugs. To date, the etiology is not well understood and individual susceptibility still remains unknown. Amiodarone, chlorpromazine, amitriptyline, and trimipramine are classified lysosomotropic as well as photosensitizing, however, they fail to trigger rash and pruritic papules in all individuals. Lysosomotropism is a common charcteristic of various drugs, but independent of individuals. There is evidence that the individual ability to respond to external oxidative stress is crosslinked with the elongation of long-chain fatty acids to very long-chain fatty acids by ELOVLs. ELOVL6 and ELOVL7 are sensitive to ROS induced depletion of cellular NADPH and insufficient regeneration via the pentose phosphate pathway and mitochondrial fatty acid oxidation. Deficiency of NADPH in presence of lysosomotropic drugs promotes the synthesis of C16-ceramide in lysosomes and may contribute to emerging pruritic papules of AGEP. However, independently from a lysosomomotropic drug, severe depletion of ATP and NAD(P)H, e.g., by UV radiation or a potent photosensitizer can trigger likewise the collapse of the lysosomal transmembrane proton gradient resulting in lysosomal C16-ceramide synthesis and pruritic papules. This kind of papules are equally present in polymorphous light eruption (PMLE/PLE) and acne aestivalis (Mallorca acne). The suggested model of a compartmentalized ceramide metabolism provides a more sophisticated explanation of cutaneous drug adverse effects and the individual sensitivity to UV radiation. Parameters such as pKa and ClogP of the triggering drug, cutaneous fatty acid profile, and ceramide profile enables new concepts in risk assessment and scoring of AGEP as well as prophylaxis outcome.

A Case of Priapism After Intrathecal Morphine Injection

BACKGROUND: Data on the frequency of priapism after spinal injections is lacking. Priapism may occur as a rare complication following intrathecal narcotic administration. This report describes an uncommon adverse reaction to intrathecal morphine injection uniquely without concurrent local anesthetic. CASE REPORT: A 74-year-old male presented to the pain management office for a scheduled intrathecal bolus trial to monitor for response prior to permanent placement of an intrathecal pump. Following an intrathecal injection of a bolus dose of 100 mcg of morphine, the patient noted the development of an erection lasting 8 hours. A diagnosis of intrathecal morphine-induced priapism was made. CONCLUSION: This report presents the first case in the literature of priapism induced by noncontinuous intrathecal morphine injection in the context of an intrathecal pump trial. A specific mechanism has not yet been defined; however, we believe multiple factors play a role in the body’s response to morphine. KEY WORDS: Case report, chronic pain, intrathecal drug delivery, morphine, priapism

Cephalexin Induced Breast Necrosis: A Case Report

This is a brief case-report, describing an extensive area of skin necrosis due to a rare condition. In literature, cases of warfarin-induced skin necrosis have been reported, but to the best of our knowledge, there is no report of skin necrosis following therapeutic dose of cephalexin. Here we highlight the potentially serious, yet uncommon adverse reactions associated with the use of cephalexin.

German S3-Guideline on the treatment of Psoriasis vulgaris, adapted from EuroGuiDerm - Part 2: Treatment monitoring and specific clinical or comorbid situations.

German S3-Guideline on the treatment of Psoriasis vulgaris, adapted from EuroGuiDerm - Part 2: Treatment monitoring and specific clinical or comorbid situations.

Oxidative Stress in Drug-Induced Liver Injury (DILI): From Mechanisms to Biomarkers for Use in Clinical Practice.

Idiosyncratic drug-induced liver injury (DILI) is a type of hepatic injury caused by an uncommon drug adverse reaction that can develop to conditions spanning from asymptomatic liver laboratory abnormalities to acute liver failure (ALF) and death. The cellular and molecular mechanisms involved in DILI are poorly understood. Hepatocyte damage can be caused by the metabolic activation of chemically active intermediate metabolites that covalently bind to macromolecules (e.g., proteins, DNA), forming protein adducts—neoantigens—that lead to the generation of oxidative stress, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress, which can eventually lead to cell death. In parallel, damage-associated molecular patterns (DAMPs) stimulate the immune response, whereby inflammasomes play a pivotal role, and neoantigen presentation on specific human leukocyte antigen (HLA) molecules trigger the adaptive immune response. A wide array of antioxidant mechanisms exists to counterbalance the effect of oxidants, including glutathione (GSH), superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX), which are pivotal in detoxification. These get compromised during DILI, triggering an imbalance between oxidants and antioxidants defense systems, generating oxidative stress. As a result of exacerbated oxidative stress, several danger signals, including mitochondrial damage, cell death, and inflammatory markers, and microRNAs (miRNAs) related to extracellular vesicles (EVs) have already been reported as mechanistic biomarkers. Here, the status quo and the future directions in DILI are thoroughly discussed, with a special focus on the role of oxidative stress and the development of new biomarkers.

Cutaneous drug eruptions including serum sickness-like reaction, symmetrical drug-related intertriginous and flexural exanthema, and drug-induced lupus

Cutaneous manifestations of drug reactions are common yet vary widely in their appearance and degree of internal organ involvement. Serum sickness-–like reactions, symmetrical drug-related intertriginous and flexural exanthem, granulomatous drug eruption, pseudolymphoma, and drug-induced lupus are medication-induced conditions with dermatologic presentations. Many of the conditions discussed are relatively rare but nonetheless demand our attention and understanding. Some of the conditions presented may be more likely encountered in the hospital setting, as is the case with serum sickness–like reactions and drug-induced lupus, whereas others may present to outpatient clinic for diagnosis. Given the similarities in clinical history of patients presenting with these conditions, an understanding of the clinical presentation, pathophysiology, culprit medications, histologic appearance, and serologic characteristics is warranted to correctly diagnose and manage these uncommon adverse reactions. We also discuss how to differentiate some of these conditions from more serious mimickers, as in the case of pseudolymphoma drug reaction mimicking a true lymphoma and drug-induced lupus mimicking acute systemic lupus erythematosus.

Nicolau Syndrome Following Metamizole Injection: A Case Report

Abstract Introduction: Nicolau syndrome is a rare complication following intramuscular injections of various drugs. It is characterized by severe pain, skin and sometimes muscle necrosis after drug injection. However the pathogenesis of Nicolau syndrome remains unclear. Here, we report a case of Nicolau syndrome following metamizole injection. Case presentation: A 35-year-old female presented with an painful necrotic ulcer who developed Nicolau syndrome after an intramuscular injection of metamizole in her right thigh due to reccurent episodes of back pain. This reaction is typical for Nicolau syndrome. Discussion: The most common finding of Nicolau syndrome in the early period was severe pain at the injection site. Other common findings were skin discoloration, tenderness, and swelling; indurated livedoid plaques; and erythematous, ecchymotic and purpuric patches. The histopathological results of the case with Nicolau syndrome showed formation of ulceration and fat necrosis. Conclusion: Although Nicolau syndrome is an uncommon cutaneous adverse reaction, clinicians should be aware of this complication to prevent or minimize the severity of Nicolau syndrome.

Chorea as an Uncommon Adverse Reaction to Ertapenem (4961)

Chorea as an Uncommon Adverse Reaction to Ertapenem (4961)

A Systematic Review and Meta-analysis of the Adverse Effects of Levonorgestrel Emergency Oral Contraceptive.

The levonorgestrel oral emergency contraceptive is well tolerated and effective, however its use is still limited, mainly due to safety concerns. This systematic review and meta-analysis aimed to summarize current evidence regarding the adverse events, and their prevalence, reported during the use of oral levonorgestrel emergency contraceptives. Four electronic databases and the US FDA Adverse Event Reporting System (FAERS) Public Dashboard were searched. Studies that reported or investigated safety outcomes or adverse reactions during the use of levonorgestrel as an emergency oral contraceptive were included. Data on study design, demographics of levonorgestrel and the control cohort, and reported adverse effects were extracted. A total of 47 articles were included in this systematic review, from which it was shown that most of the adverse reactions were common and not serious. Uncommon adverse reactions identified included anorexia, ectopic pregnancy, exanthema, chloasma, miscarriage, and weight gain. Multiple serious adverse events, including convulsion, ectopic pregnancy, febrile neutropenia, stroke, abdominal hernia, anaphylaxis, cancer, ovarian cyst rupture, serious infections, and suicidal ideation, were reported. In addition, the prevalence of adverse events after a levonorgestrel 0.75mg two-dose regimen and a levonorgestrel 1.5mg single-dose regimen were not statistically different (p > 0.05). The most common adverse effects of levonorgestrel were not serious. This systematic review shows that data regarding the adverse reactions of repeated use of levonorgestrel are scarce. Studies on the multiple uses of levonorgestrel emergency contraception are still required to ensure its safety.

Efficacy upon 12-weeks after achievement of maximal dose and tolerability of lacosamide as an adjunctive therapy in epilepsy: Real world clinical experience

Lacosamide (LCM) is a new generation antiepileptic drug. It has only been available in Asia in recent years. A retrospective study at two hospitals in Hong Kong was performed to investigate the post-marketing efficacy and tolerability of the drug. A total of 81 subjects were recruited, among which 88% had drug-resistant epilepsy. The most common type of epilepsy was focal with unknown etiology. All patients used LCM as adjunctive therapy. The 50% responder rate was 42% at 12 weeks after achievement of maximal dose of LCM. No specific factor correlated with responsiveness including concomitant enzyme-inducing or sodium channel blocking anticonvulsants. Withdrawal rate within first 12 weeks after drug initiation was 14% while that at any time upon follow-up was 23%. Two cases of uncommon adverse reaction of myoclonus were also reported. The mechanism was postulated to be the sodium channel inhibiting action of LCM. Our study has shown LCM to have comparable efficacy and tolerability in post-marketing experience when compared with the landmark randomized controlled trials.

Incomplete Vaccination Among Children With Special Health Care Needs in Zhejiang, China: Analysis of Retrospective Data.

Objective: There is a lack of data relating to vaccination of children with special health care needs (CSHCN) and its influencing factors in China. We investigated the disease spectrum of CSHCN at the Vaccination Consultation Clinic in Zhejiang province as well as the underlying factors of vaccination recommendations of these children.Methods: In this study, we retrospectively analyzed the data of 4,525 CSHCN, who visited to our clinic for a vaccination consultation from January 1, 2016 to May 30, 2018. Descriptive data were presented as mean ± standard deviation (SD) and percentages. Multivariate analysis was performed with non-conditional bivariate logistic regression to identify the underlying factors of vaccination recommendations. Subsequent information regarding the following vaccination and the occurrence of AEFI were also collected and analyzed.Results: The main diseases consulted were those relating to the circulatory and nervous systems as well as neonatal diseases. The distribution of diseases varied by age: 53.6% infants under 12 months were counseled for circulatory system diseases, while 44.6% children aged 12~24 months and 54.7% children over 25 months were counseled for nervous system diseases. According to the evaluation reports issued by the consultation clinic, 75.0% of CSHCN were recommended to be vaccinated normally, 21.2% were recommended to defer specific vaccination, while only 3.8% were recommended to defer all vaccinations. In logistic regression analysis, age, history of adverse events following immunization (AEFI) and the number of diseases combined were all strong correlative factors for vaccination recommendations. Children who were aged over 25-month-old (OR = 1.34, 95%CI: 1.11–1.61) or had a history of AEFI (OR = 3.77, 95%CI: 2.83~5.01) or those who had numerous diseases combined (OR = 2.00, 95%CI: 1.46~2.75) tended to have a higher rate of deferred vaccination recommendation. Among those CSHCN who received nationally-recommended vaccines, the estimated AEFI rate was 24.29/100 000. No uncommon or rare serious adverse reactions were detected.Conclusion: Age, history of AEFI, and the number of diseases combined were important factors that affected the vaccination recommendations of CSHCN. Most CSHCN can be safely vaccinated according to the nationally-recommended schedule.