We describe two elderly patients evaluated at emergency departments for anosmia/dysgeusia in the absence of any other respiratory symptoms prior to or upon admission. In the current epidemiological context, clinical and biological work-up led to a diagnosis of COVID-19 infection. Unfortunately, one of the patients died during hospitalization, but the other recovered and was discharged.
Introduction: Idiosyncratic drug-induced neutropenia and agranulocytosis is seldom discussed in the literature, especially for new drugs such as biotherapies outside the context of oncology. In the present paper, we report and discuss the clinical data and management of this relatively rare disorder, with a focus on biotherapies used in autoimmune and auto-inflammatory diseases. Materials and methods: A review of the literature was carried out using the PubMed database of the US National Library of Medicine. We searched for articles published between January 2010 and May 2019 using the following key words or associations: “drug-induced neutropenia”, “drug-induced agranulocytosis”, and “idiosyncratic agranulocytosis”. We included specific searches on several biotherapies used outside the context of oncology, including: tumor necrosis factor (TNF)-alpha inhibitors, anti-CD20 agents, anti-C52 agents, interleukin (IL) 6 inhibitors, IL 1 inhibitors, and B-cell activating factor inhibitor. Results: Idiosyncratic neutropenia remains a potentially serious adverse event due to the frequency of severe sepsis with severe deep tissue infections (e.g., pneumonia), septicemia, and septic shock in approximately two-thirds of all hospitalized patients with grade 3 or 4 neutropenia (neutrophil count (NC) ≤ 0.5 × 109/L and ≤ 0.1 × 109/L, respectively). Over the last 20 years, several drugs have been strongly associated with the occurrence of idiosyncratic neutropenia, including antithyroid drugs, ticlopidine, clozapine, sulfasalazine, antibiotics such as trimethoprim-sulfamethoxazole, and deferiprone. Transient grade 1–2 neutropenia (absolute blood NC between 1.5 and 0.5 × 109/L) related to biotherapy is relatively common with these drugs. An approximate 10% prevalence of such neutropenia has been reported with several of these biotherapies (e.g., TNF-alpha inhibitors, IL6 inhibitors, and anti-CD52 agents). Grade 3–4 neutropenia or agranulocytosis and clinical manifestations related to sepsis are less common, with only a few case reports to date for most biotherapies. Special mention should be made of late onset and potentially severe neutropenia, especially following anti-CD52 agent therapy. During drug therapy, several prognostic factors have been identified that may be helpful when identifying ‘susceptible’ patients. Older age (>65 years), septicemia or shock, renal failure, and a neutrophil count ≤0.1 × 109/L have been identified as poor prognostic factors. Idiosyncratic neutropenia should be managed depending on clinical severity, with permanent/transient discontinuation or a lower dose of the drug, switching from one drug to another of the same or another class, broad-spectrum antibiotics in cases of sepsis, and hematopoietic growth factors (particularly G-CSF). Conclusion: Significant progress has been made in recent years in the field of idiosyncratic drug-induced neutropenia, leading to an improvement in their prognosis (currently, mortality rate between 5 and 10%). Clinicians must continue their efforts to improve their knowledge of these adverse events with new drugs as biotherapies.
We report a case of brainstem infarction following a C5–C6 cervical transforaminal injection, a rare and serious neurological complication of this procedure. Cervical transforaminal steroid injection is a common therapy for patients with persistent cervical radiculopathy not relieved by conservative treatment, and is effective in 65–70% of cases. Unfortunately, this procedure may lead to serious complications such as neurological damage. These complications are rare but potentially fatal, as reported in our case. Complications could be due to three mechanisms: the technique itself, the cervical vascular anatomy and the properties of the product (corticoids). The neurological complications can be diagnosed through brain MRI. This case report focuses on the importance of a risk/benefit evaluation when performing this medical procedure. LEARNING POINTS Physicians should be better informed about severe complications following cervical transforaminal epidural steroid injections and their strict indications. Severe adverse events are rare but they can be disastrous. Non-particulate corticosteroid should be used.
We report a case of ceftriaxone-induced encephalopathy correlated with high cerebrospinal fluid concentration. Neurotoxicity of cephalosporin is increasingly reported, especially regarding fourth-generation cephalosporins. The factors influencing the corticospinal fluid (CSF) concentration are plasma concentration, liposolubility, ionization, molecular weight, protein binding and efflux. In our patient, high levels of ceftriaxone (27.9 mg/l) were found in the CSF. β-lactam associated neurotoxicity is mainly related to similarities between GABA and β-lactam ring. Because of disparate CSF/plasma ratio and blood-brain barrier efflux among patients, plasmatic drug monitoring probably cannot be used as a surrogate of CSF concentration. This is, as we know, the first case of described ceftriaxone-induced encephalopathy associated with an objective excessive cerebrospinal concentration.
Boerhaave syndrome or spontaneous rupture of the oesophagus is a severe condition commonly misdiagnosed or unrecognized. Prognosis is poor even if the diagnosis is made promptly. We describe a case of Boerhaave syndrome diagnosed after the development of pneumomediastinum and cardiac arrest. Unfortunately, the patient died 48 hours after admission to the Intensive Care Unit. This entity requires a multidisciplinary management approach which may include conservative, surgical or endoscopic procedures. LEARNING POINTS • Boerhaave syndrome is a diagnostic and therapeutic challenge, and rapid diagnosis and management are crucial. • A thoraco-abdominal CT scan with oesophageal opacification is the gold standard investigation. • A multidisciplinary and individualized approach is needed in the management of this condition.
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