Long-term nivolumab treatment possibly associated with aseptic meningitis.

Nivolumab is a programmed death-1 receptor blocker within the family of medications called immune checkpoint inhibitors (ICIs). Although generally well tolerated, cases of immune-related adverse events (irAEs) have been reported. We present a case of a man being treated with nivolumab for renal cell carcinoma who presented to the emergency department with problems of headache, fever and disorientation. After extensive evaluation, a diagnosis of immunotherapy-induced aseptic meningitis was considered more probable than infectious. Due to stable clinical status, no treatment was initiated, and the patient's condition improved spontaneously. The patient was discharged home. To date, only a handful of prior cases of nivolumab-induced meningitis have been reported. Our case demonstrates that irAEs can occur years after the initiation of ICIs. This was a milder presentation of a neurological irAE that resolved spontaneously with watchful waiting, showing that irAEs are likely an evolving spectrum of disease for which clinicians should be aware.

Drug-induced aseptic meningitis after an interlaminar lumbar epidural steroid injection.

BACKGROUND: This case report describes a rare instance of drug-induced aseptic meningitis after an interlaminar lumbar epidural steroid injection. CASE PRESENTATION: A 74 year-old female patient presented to the ED post-procedure day three after an L4-L5 interlaminar lumbar epidural steroid injection with fever, nausea, and vomiting. The patient had previously undergone numerous lumbar epidurals without complications and used identical medications, which included 1% lidocaine, iohexol contrast, methylprednisolone (Depo-medrol), and normal saline. Pertinent labs included a WBC of 15,000 cells/µL. Lumbar MRI revealed L4-S1 aseptic arachnoiditis. Two bone scans with Gallium and T-99 confirmed no infectious process. The patient then had a second admission months later with similar presenting symptoms and hospital course after repeating the lumbar epidural steroid injection. Lumbar MRI and CSF studies confirmed aseptic meningitis. CONCLUSION: This patient's repeated admissions from aseptic meningitis were likely caused by irritation of the meningeal layers from a medication used during the procedure.

Sulfasalazine-Induced Delayed Hypersensitivity Reaction Presenting as Fever, Aseptic Meningitis, and Mesenteric Panniculitis in a Patient with Seronegative Arthritis.

BACKGROUND An 82-year-old woman presented with acute pyrexial illness and mesenteric panniculitis and developed biochemical aseptic meningitis (cerebrospinal fluid pleocytosis with no identifiable pathogen). Investigation determined her illness was likely a delayed hypersensitivity reaction caused by sulfasalazine. Sulfasalazine-induced aseptic meningitis is a rare condition often diagnosed late in a patient's admission owing to initial non-specific illness symptomatology requiring the exclusion of more common "red flag" etiologies, such as infection and malignancy. CASE REPORT An 82-year-old woman with a history of recurrent urinary tract infections and seronegative arthritis presented with a 3-day history of fatigue, headache, dyspnea, and lassitude. On admission, she was treated as presumed sepsis of uncertain source owing to pyrexia and tachycardia. Brain computer tomography (CT) revealed no acute intracranial abnormality. Furthermore, CT of the chest, abdomen, and pelvis did not reveal any source of sepsis or features of malignancy. After excluding infective etiologies with serological and cerebrospinal fluid testing, sulfasalazine-induced aseptic meningitis (SIAM) was diagnosed. The patient was then commenced on intravenous steroids, resulting in immediate defervescence and symptom resolution. CONCLUSIONS SIAM remains a diagnostic challenge since patients present with non-specific signs and symptoms, such as pyrexia, headaches, and lassitude. These patients require a thorough investigative battery starting with anamnesis, physical examination, biochemical testing, and radiologic imaging. This case illustrates the need for a high suspicion index of drug-induced hypersensitivity reaction in a rheumatological patient with pyrexial illness where infective etiologies have been confidently excluded. Prompt initiation of intravenous steroids in SIAM provides a dramatic recovery and resolution of symptoms.

Aseptic Meningitis after BNT-162b2 COVID-19 Vaccination: Case Report and Literature Review.

We encountered a-27-year-old female patient who developed refractory severe headache and photophobia after the first dose of COVID-19 vaccine. Despite her prior history of migraine, we diagnosed COVID-19 vaccine-induced aseptic meningitis. Symptoms were significantly resolved after methylprednisolone therapy. On reviewing the literature, we could find only nine similar cases, with over half of them affecting women aged 20-40 years. Although uncommon, aseptic meningitis should be suspected in patients with persistent or delayed onset of headache following COVID-19 vaccination.

Amoxicillin-induced aseptic meningitis: clinical features, diagnosis and management.

OBJECTIVES: The clinical features of aseptic meningitis associated with amoxicillin are unknown. The main objective of this study was to investigate the clinical characteristics of amoxicillin-induced aseptic meningitis (AIAM) and provide a reference for clinical diagnosis and treatment. METHODS: AIAM-related studies were collected by searching the relevant databases from inception to October 31, 2022. RESULTS: AIAM usually occurred 3 h to 7 days after amoxicillin administration in 13 males and 9 females. Twenty-one patients (95.5%) had recurrent AIAM with a total of 62 episodes. Fever (19 cases, 86.4%) and headache (18 cases, 81.8%) were the most common symptoms. Typical cerebrospinal fluid (CSF) findings were leukocytosis (100%) with lymphocytic predominance (14 cases, 63.6%), elevated protein (20 cases, 90.1%), normal glucose (21 cases, 95.5%) and negative culture (21 cases, 100%). Brain magnetic resonance imaging showed mild meningeal enhancement in one patient. The symptoms resolved mainly within 1-4 days after drug discontinuation in all patients. CONCLUSION: Clinical attention should be given to the adverse effects of AIAM. The medication history of patients with suspected meningitis should be investigated to avoid unnecessary examination and antibiotic treatment.

Drug-induced aseptic meningitis. / Legemiddelindusert aseptisk meningitt.

Drug-induced aseptic meningitis is a rare but serious condition that should be suspected in patients with meningitis who test negative for a microbiological agent. The medical history is presented here of a woman with recurrent urinary tract infections where meningitis symptoms arose after repeated exposure to a frequently prescribed drug.

Trimethoprim-sulfamethoxazole induced aseptic meningitis case report.

RATIONALE: Drug-induced aseptic meningitis (DIAM) is an uncommon meningitis and trimethoprim with or without sulfamethoxazole is the most involved antibiotic. Although DIAM is easily treated with the discontinuation of the causative drug, the diagnosis is a big challenge for physicians, as it remains a diagnosis of exclusion. Here, we present a case report of trimethoprim-sulfamethoxazole induced aseptic meningitis in a woman with acute osteomyelitis. PATIENT CONCERNS: A 52-year-old woman was admitted to the hospital for septic shock and acute osteomyelitis of the right homerus. She was started on antibiotic therapy with oxacillin and daptomycin, then oxacillin was replaced with cotrimoxazole, due to its excellent tissue penetration, including bone tissue. During cotrimoxazole therapy, the patient developed a fluent aphasia with ideomotor apraxia and muscle hypertonus. DIAGNOSIS AND INTERVENTIONS: Having excluded infectious, epileptic and vascular causes of the acute neurologic syndrome of our patient, given the improvement and full recovery after discontinuation of cotrimoxazole, we hypothesized a DIAM. OUTCOMES: After discontinuation of cotrimoxazole, in 48 hours the patient had a full recovery. LESSONS: Although DIAM can be easily managed with the withdrawal of the causative drug, it can be difficult to recognize if it is not included in the differential diagnosis. An antimicrobial stewardship program with a strict monitoring of patients by infectious disease specialists is essential, not only to optimize the appropriate use of antimicrobials, but also to improve patient outcomes and reduce the likelihood of adverse events.

Immune-related aseptic meningitis and strategies to manage immune checkpoint inhibitor therapy: a systematic review.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) can induce adverse neurological effects. Due to its rarity as an adverse effect, meningitis has been poorly described. Therefore, meningitis diagnosis and management can be challenging for specialists. Moreover, meningitis can be an obstacle to resuming immunotherapy. Given the lack of alternatives, the possibility of reintroducing immunotherapy should be discussed on an individual basis. Here, we present a comprehensive systematic review of meningitis related to ICIs. REVIEW: We performed a search for articles regarding immune-related meningitis published in PubMed up to November 2021 with the MeSH terms "meningitis" and "immune checkpoint" using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. We summarized the studies not only by category but also based on whether it was a primary article or case report to provide a systematic overview of the subject. We reviewed a total of 38 studies and herein report the clinical experiences, pharmacovigilance data and group knowledge from these studies. CONCLUSION: This review summarizes the existing information on immune-related meningitis and the possibility of reintroducing immunotherapy after the development of central neurological side effects. To the best of our knowledge, there is little information in the literature to guide clinicians on decisions regarding whether immunotherapy should be continued after a neurological adverse event occurs, especially meningeal events. This review emphasizes the necessity of systematic examinations, steroid treatment (as a cornerstone of management) and the need for further exploratory studies to obtain a clearer understanding of how to better manage patients who experience these side effects. The findings summarized in this review can help provide guidance to practitioners who face this clinical situation.

Aseptic meningitis following AZD1222 COVID-19 vaccination.

The AZD1222 is one of the vaccines used against coronavirus disease 2019 (COVID-19), which is currently being used in many countries worldwide. Some important neurological side effects have been reported in association with this vaccine, but aseptic meningitis has not yet been reported. Herein, we report a case of aseptic meningitis in a 26-year-old health care worker, following the first dose of the AZD1222 vaccine.

Case Report: A Variety of Immune-Related Adverse Events Triggered by Immune Checkpoint Inhibitors in a Subject With Malignant Melanoma: Destructive Thyroiditis, Aseptic Meningitis and Isolated ACTH Deficiency.

Recently, immune checkpoint inhibitors have been drawing much attention as cancer immunotherapy, but it has been shown that various immune-related adverse events (irAEs) are induced by immune checkpoint inhibitors in various organs, which has become one of the serious issues at present. A 58-year-old Japanese male with malignant melanoma was treated with nivolumab and/or ipilimumab. During the period of treatment, he suffered from various irAEs. Firstly, about 1 month after starting nivolumab monotherapy, destructive thyroiditis was induced, and so we started replacement therapy with levothyroxine. Secondly, about 1 month after starting nivolumab and ipilimumab combination therapy, aseptic meningitis was induced. We stopped both drugs and started steroid therapy with prednisolone. Finally, about 9 months after restarting nivolumab, isolated adrenocorticotropic hormone (ACTH) deficiency was induced, and so we started replacement therapy with hydrocortisone. Taken together, we should bear in mind the possibility of a variety of irAEs when we use immune checkpoint inhibitors.

Aseptic meningitis, hepatitis and cholestasis induced by trimethoprim/sulfamethoxazole: a case report.

BACKGROUND: Drug-induced aseptic meningitis is a rare, but challenging diagnosis, most commonly reported with nonsteoroidal anti-inflammatory drugs (NSAIDs) and antibiotics. Trimethoprim/sulfamethoxazole (TMP/SMX) is a sulfonamide that is widely used in clinical practice for the treatment and prophylaxis of various infections. The most common side effects associated with TMP/SMX are generally mild and self-limited, but serious side effects have been reported, including liver injury and aseptic meningitis. CASE PRESENTATION: We report a 2,5 year old Dutch girl with both drug-induced aseptic meningitis and drug-induced liver injury while using TMP/SMX prophylaxis. Ursodeoxycholic acid was started because of cholestatic injury. After cessation of TMP/SMX, full convalescence was reached within weeks. CONCLUSIONS: This is the first report of a young patient with both aseptic meningitis and drug-induced liver injury caused by TMP/SMX. Drug-induced aseptic meningitis and cholestatic hepatitis constitute a considerable diagnostic challenge to clinicians. In addition to a thorough evaluation for infectious causes, clinicians should be aware of drug-induced aseptic meningitis and cholestatic hepatitis.

Neurological Immunotoxicity from Cancer Treatment.

The emergence of immune-based treatments for cancer has led to a growing field dedicated to understanding and managing iatrogenic immunotoxicities that arise from these agents. Immune-related adverse events (irAEs) can develop as isolated events or as toxicities affecting multiple body systems. In particular, this review details the neurological irAEs from immune checkpoint inhibitors (ICI) and chimeric antigen receptor (CAR) T cell immunotherapies. The recognition and treatment of neurological irAEs has variable success, depending on the severity and nature of the neurological involvement. Understanding the involved mechanisms, predicting those at higher risk for irAEs, and establishing safety parameters for resuming cancer immunotherapies after irAEs are all important fields of ongoing research.

A Case Report of Antibiotic-Induced Aseptic Meningitis in Psoriasis.

Although frequently prescribed, certain antibiotics such as trimethoprim-sulfamethoxazole carry the risk of a rare yet life-threatening adverse effect, termed drug-induced aseptic meningitis. Morbidity can be avoided if the medication is identified and discontinued. Patients in reported cases tend to be female and have an autoimmune disease or prior adverse reaction to the offending agent. As a rare and poorly characterized condition, the subset of patients using antibiotics at risk for aseptic meningitis remains unclear; hence, cataloging these adverse events remains critical for better elucidating the disease. Here, we report a 62-year-old man with psoriasis and no prior history of sulfa allergy, who presented with a sudden onset of fever, chills, vomiting, and muscle aches 5 hours after taking single doses of trimethoprim-sulfamethoxazole and ciprofloxacin. Common infectious causes were ruled out, and his medications were discontinued. Despite initial symptom resolution with discontinuation, the patient neurologically deteriorated over the next two days before eventually recovering with supportive care. This case highlights the variable presentation of drug-induced aseptic meningitis. In contrast to previous reports of drug-induced aseptic meningitis, our patient was male, older than the median age of 40 years, and did not have a prior adverse reaction to the antibiotic. Furthermore, to the best of our knowledge, we report a possible case of antibiotic-induced aseptic meningitis in a patient with psoriasis. Lastly, the case emphasizes not only the value of a thorough medication history but also the importance of recognizing that patients may deteriorate in the first 48 hours before resolution.

Aseptic Meningitis-retention Syndrome Associated with Tocilizumab in a Patient with Idiopathic Multicentric Castleman Disease.

This is the first report of tocilizumab-associated meningitis-retention syndrome in a patient with idiopathic multicentric Castleman disease. A 57-year-old man presented with headache, nuchal rigidity, impaired consciousness, pyramidal tract signs and urinary retention. A cerebrospinal fluid examination revealed increased cell counts and protein levels. These symptoms were improved by intravenous methylprednisolone. Tocilizumab-associated meningoencephalitis has been reported in patients with rheumatoid arthritis and juvenile idiopathic arthritis but not with multicentric Castleman disease. This case presents evidence of the increased probability of meningitis as a neurological complication of tocilizumab administration.

A case report of intracranial hypertension and aseptic meningitis: anti-tumor necrosis factor associated or juvenile idiopathic arthritis related.

BACKGROUND: The adverse effects of tumor necrosis factor alpha inhibitors (TNFi) are well characterized but rare adverse events are increasing day by day. CASE: We presented an 18-year-old girl with rheumatoid factor positive polyarticular juvenile idiopathic arthritis (JIA) who developed fever, headache, and nausea after the second dose of adalimumab. In addition to her suspicious complaints for meningitis, she had bilateral papilledema and partial abducens nerve palsy. Leptomeningeal contrast enhancement was noted in magnetic resonance imaging (MRI) of the brain. Brain MRI venography was normal. The cerebrospinal fluid (CSF) opening pressure was high but CSF analysis was normal. She was diagnosed with non-infectious subacute meningitis. Since brain biopsy was not performed, no definite distinction could be made between TNFi related aseptic meningitis or cerebral involvement of JIA. Due to the onset of neurological complaints after initiation of adalimumab treatment and rare cerebral involvement in JIA, the drug-associated aseptic meningitis was likely to be responsible in our patient. Adalimumab was discontinued and methylprednisolone followed by methotrexate treatment were initiated. Her symptoms resolved and control brain MRI was normal. CONCLUSION: Pediatric rheumatologists should be aware of this potentially severe side effect of anti-TNF treatment.