A Case of Ocular Myasthenia Gravis Seen by Rheumatology as Suspected Mononeuritis Multiplex in an Adult Male Shortly after Pfizerbiontech Sars-Cov-2 Vaccination

Background/Aims Myasthenia gravis (MG) is an antibody-mediated autoimmune disease targeting proteins at the postsynaptic membrane of the neuromuscular junction. MG is thought to occur in genetically susceptible individuals following an environmental trigger. SARS-CoV-2 infection has been associated with new-onset autoimmune disease, new-onset MG, and exacerbations of pre-existing MG, with molecular mimicry between SARS-CoV-2 epitopes and autoantigen-induced autoreactivity thought to be part of the underlying mechanism. We report a case of newonset ocular MG following first dose Pfizer-BioNTech BNT162b2 SARS-COV2 vaccination which was referred to rheumatology as suspected mononeuritis multiplex. Methods A 53-year-old man of East Asian ethnicity presented to the emergency department (ED) with sudden onset diplopia and left lateral gaze restriction 7 days after receiving his first dose of the Pfizer-BioNTech BNT162b2 SARS-COV2 vaccination. He had longstanding myopia and dry eyes but no other medical history, no regular medications or significant family history. He was a current smoker, with a 50-pack year history. He did not drink alcohol or use any recreational drugs. He was found to have an isolated left VI cranial nerve (CN) palsy with an otherwise normal ocular and physical examination. Blood tests were unremarkable apart from raised cholesterol, and he was discharged with a suspected self-limiting microvascular CN lesion. Three weeks later he presented to ED with worsening diplopia, increasingly restricted eye movements, headache, nausea, vomiting and blurred vision. Ophthalmology assessment noted new right sided CN III and VI palsy, persistent left CN VI palsy, and vertical diplopia in all fields of gaze. Neurological and physical examination were normal. Bloods including an autoimmune screen were unremarkable. SARS-CoV-2 Spike antibodies were positive consistent with SARS-CoV-2 vaccination but not infection. Intracranial and thoracic imaging were unremarkable. He was referred to and seen by both rheumatology and neurology as a case of suspected mononeuritis multiplex. Results A diagnosis of ocular MG was confirmed with positive serum acetylcholine receptor antibodies, and he was started on prednisolone, and pyridostigmine to good effect. Daily forced vital capacity (FVC) showed no respiratory muscle involvement, and nerve conduction studies and electromyography were normal, excluding secondary generalisation. Conclusion A review of the literature found 14 reported cases of new-onset MG all within 4 weeks following SARS-CoV-2 vaccine. Whilst these cases provide interesting insights into the pathogenesis of autoimmune conditions such as MG, they are not epidemiological studies to inform vaccine safety. Ultimately, current evidence suggests that the risks of SARS-COV-2 infection outweigh the risk of vaccine-related adverse events, therefore we suggest clinicians should be aware of potential new-onset autoimmune conditions, but support the safety of SARSCOV2 vaccination. Further, research into possible immunological mechanisms behind this phenomenon, including identifying potential epitopes inducing molecular mimicry, could help establish the likelihood of a causative link.

Toxicity patterns associated with chronic ketamine exposure

Introduction: Synthesized in 1962, ketamine is used as a sedative, antidepressant and for the management of complex chronic pain. More recently, besides its therapeutic use, ketamine has been increasingly used as a recreational drug among young adults. As a result, an increasing number of reports have described side effects associated with its chronic exposure. This review aims to present the current evidence on the toxicity associated with chronic ketamine exposure. Method(s): Considering the limited literature on the topic, Pubmed and Embase were searched and all types of articles were considered, including systematic reviews, retrospective studies, case series and animal studies. Evidence: Chronic ketamine exposure is associated with urological toxicity manifesting mainly by lower urinary tract symptoms with features of ulcerative cystitis. More severe forms with upper urinary tract involvement can require multiple line treatments, including surgery. There are reports of gastrointestinal toxicity with abdominal pain, liver function test derangement and cholangiopathy. More recently, reports have described the association between prolonged ketamine sedation during covid-19 outbreak and cholangiopathies. Development of tolerance, brain and psychiatric changes have been described. These can manifest in cognitive impairment and psychiatric disorders, with schizophrenia-like symptoms. Possible cardiovascular alterations have been described in few reports. Whereas supportive treatment can offer transient relief, ketamine cessation remains the cornerstone of the treatment. Conclusion(s): There is evidence of toxicity associated with chronic ketamine exposure on the different systems studied in this review. Nevertheless, due to the limitation of the studies more prospective studies would be required to clarify those findings.Copyright © 2023 Societe Francaise de Toxicologie Analytique

CULTURAL BARRIERS AND PANDEMIC RESTRICTIONS RESULT IN A DELAYED DIAGNOSIS OF DRUG INDUCED LUPUS (DIL) AND SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

CASE: A 58-year-old female with a history of hypertension, type 2 diabetes and hyperlipidemia presented with a two- week history of abdominal pain and fevers. Per the patient, family history was unremarkable, and she denied alcohol, tobacco, or recreational drug use. She denied recent travel or sexual activity and had moved to the U.S. in the 1970s from Cambodia. Medications included amlodipine, atorvastatin, dapagliflozin, lisinopril, metformin and sitagliptin. Physical exam was notable for bilateral axillary lymphadenopathy, hepatomegaly, and right sided abdominal tenderness. Laboratory data was notable for microcytic anemia, thrombocytopenia, and elevated transaminases, D-dimer, and C- reactive protein. Urinalysis demonstrated microscopic hematuria and proteinuria. Imaging showed diffuse lymphadenopathy and hepatomegaly. Autoimmune work-up was strongly positive for ANA, anti-histone, and anti DS DNA. Kidney biopsy was suggestive of glomerulonephritis. Liver biopsy was suggestive of drug induced liver injury or autoimmune hepatitis. A diagnosis of DIL and SLE was not reached until additional historical data from the patient's son was provided on hospital day 4;namely that the patient had a 30-lb unintentional weight loss, took unknown herbal supplements and had a daughter who passed away from complications of lupus. IMPACT/DISCUSSION: DIL is a rare adverse reaction to many drugs that generally manifests with mild systemic symptoms such as low-grade fevers, anorexia, and fatigue and rarely involves classic symptoms of SLE such as skin findings and major organ involvement. Notably, DIL can unmask clinically silent SLE and thereby lead to lupus like syndromes. This patient presented with mild symptoms and underwent an extensive workup due to missing key historical data which led to a delayed diagnosis. Due to COVID-19 restrictions on visitation, it was not until hospital day 4 when the patient's son visited that the team became aware of an unintentional 30-lb weight loss, unknown herbal supplement use, and a family history of SLE. The lack of such critical information stemmed from the fact that we did not ask about the use of supplements properly and never revisited it in a different manner. The patient did not share the cause of her daughter's passing as she was unaware of it, which may speak to cultural limitations in sharing health information among family members. It is imperative that as clinicians we constantly revisit the history and diversify our questions. A more complete history would optimize our workup and limit unnecessary testing, including blood draws and painful biopsies, which unfortunately occurred in this patient. CONCLUSION: A thorough history is important to achieving a timely diagnosis and to avoid excessive testing and procedures. Revisiting the history is necessary to finding key information and clinicians should consider incorporating available family members early in the diagnostic work up, especially if the diagnosis is unclear.

The influence of the COVID19 pandemic in the patterns of acute poisoning presenting to an emergency department in Spain

Objective: COVID-19 has left no healthcare system untouched. Adjustments to accommodate COVID-19 pandemic needs resulted in widespread deferment of non-COVID19 scheduled healthcare activities, added to a general patient's reluctance to visit healthcare settings. This study is aimed to analyse retrospectively demographic and clinical characteristics of patients with acute poisoning attended at the Emergency Department (ED) in three different pandemic periods of time. Material and/or methods: We carried out an observational and retrospective study in which we included all the patients who visited the Emergency Department at Hospital Son Espases due to acute poisoning during three different periods of time from June to July in 2019 (pre pandemic), same period in 2020 (right after the strict confinement in Spain) and in 2021 (post-pandemic). This study was approved by the Research Ethics Committee of the Balearic Islands. Results: All cases of acute poisoning were included (n = 1182). Patients with acute poisoning presenting to the ED decreased significantly during the pandemic (2019: 1.9%, 2020: 1.5%;p < 0.01). The ratio male/female and the mean age of the patients increased during the pandemic (2 vs. 1.4, p = 0.02, and 31.4 vs. 41.3 years, p < 0.001, respectively). The roll of poisoning in suicide attempts increased substantially during the pandemic (2019: 8.71%, 2020: 21%;p < 0.01), mostly driven by the increase in poisoning due to commercially available drugs (2019: 14.20%;2020: 28.76%, p < 0.01), while recreational drug poisoning decreased (2019: 76.1%, 2020: 62%;p < 0.01), while in 2021, figures tended to return to prior patterns. Conclusions: This study found significant changes in some clinical patterns in patients attending the ED due to acute poisoning in the context of COVID19, in line with the already described impact of the pandemic in other areas of the healthcare system.

Pre- and post-COVID-19 pandemic: acute poisoning among patients in an Emergency Department

Objective: The COVID-19 pandemic has affected daily life in unprecedented ways. Many studies have found dramatic changes in individuals' physical activity, sleep and mental health [1]. This study aimed to analyze retrospectively demographic and clinical characteristics of patients with acute poisoning presenting to the Emergency Department (ED) [2] in three different periods of time (June-July): pre-pandemic (2019), after strict confinement of the Spanish population (2020) and post-pandemic (2021) [3]. Methods: All cases of poisoning in the study periods were reviewed. Demographic variables and the type of intoxication were studied. A comparison was made between the three periods. Results: All cases of acute poisoning were included (n=1182, 528 in June-July 2019;299 in June-July 2020, 355 in June-July 2021). Patients with acute poisoning presenting to the ED decreased during the pandemic (2019: 1.9%, 2020: 1.5%;p<0.01). The ratio male/female increased during the pandemic (2 versus 1.4, p=0,02). The mean age of the patients increased during the pandemic (2019: 31.4, 2020: 41.3, p<0,001), this tendency was maintained in 2021 (38.3). Poisoning in suicide attempts increased during the pandemic (2019: 8.71%, 2020: 21%;p<0.01), as well as poisoning due to commercialized drugs (2019: 14.20%;2020: 28.76%, p<0.01), while recreational drug poisoning decreased (2019: 76.1%, 2020: 62%;p<0.01), in 2021 these increased again (69%, p 0.07). Conclusion: This study has found significant changes in some clinical patterns in patients attending the ED due to acute poisoning in the context of COVID-19, in line with the already described psychological impact of the pandemic.

A rare and early skin reaction after the third dose of comirnaty vaccine

Introduction: In December 2019, many cases of atypical pneumonia with unknown etiology were reported in China. Later on, a new coronavirus was identified, named SARS-Cov2. In December 2020, FDA, EMA and AIFA issued emergency use authorizations for Pfizer/SARS-Cov2 vaccine (Comirnaty). In this case report we describe a serious early large local reaction after the third dose Comirnaty. Case clinic: A 66 year-old white female with cutaneous reaction after inoculation Comirnaty arrived at the Dermatology Service. She reported six hours ago had received the third dose of the vaccine. The patient was lucid, oriented and cooperative. She reported no history of allergy no medical history and took no drugs. The blood pressure was 125/75 with sinus rhythm with pulse 75 bpm, apyretic, SpO2 98% on ambient air. The physical examination showed a large wheal reaction the left arm at the injection site. She complained of heat pain and difficulty in moving the limb. The chest examination and ABG were normal. She was submitted to therapy based on antihistamine and topical steroids. After a week she presented complete resolution of the symptoms. Conclusions: In many COVID-19 studies the incidence of cutaneous reaction after messenger RNA based COVID-19 vaccines have been reported but are not well characterized. The peculiarity of this case-report is given by the rare (after third dose) serious and early cutaneous manifestation in the absence of history of allergy, drugs smoke tobacco or use recreational drugs. This suggests that others processes not yet defined are involved in the skin reaction.

GRAVE DANGER: RARE CASE OF COMPLETE HEART BLOCK SECONDARY TO GRAVES DISEASE

Background: Complete heart block (CHB) is a cardiac conduction disorder commonly due to age-related degeneration of the conduction system. Other etiologies include hypothyroidism, Lyme disease or COVID-19, infiltrative cardiomyopathy, myocarditis, and atrioventricular (AV) nodal blocking agents. Hyperthyroidism is an extremely rare cause of CHB. Case: We present the case of a 40-year-old previously healthy male who presented after two syncopal episodes. He denied any home medications, recreational drug use, or prior syncopal episodes. He did endorse worsening palpitations, heat intolerance, anxiety, insomnia and diarrhea for one month. Initial EKG was normal. Labs revealed an undetectable thyroid stimulating hormone (TSH), and high T4 of 3.26 ng/dL. Potassium was 3.1 mMol/L which was replaced to normal levels. In the emergency department, he had another syncopal episode. Telemetry showed a 20 second episode of CHB. Patient was admitted and started on methimazole. Decision-making: Labs showed positive TSH receptor antibodies and thyroid stimulating immunoglobulins, confirming a diagnosis of Graves’ disease. COVID-19 IgG antibodies were positive with negative COVID-19 PCR, indicative of remote COVID 19 infection. Cardiac MRI did not show any myocarditis or infiltrative disease, and otherwise revealed a structurally normal heart. Lyme disease antibodies were negative. Toxicology screen was negative. Thyroid ultrasound showed diffuse heterogeneity of the gland. 72 hour telemetry monitoring revealed no further conduction abnormalities. At this point, CHB wes attributed to hyperthyroidism. As this was reversible, and CHB resolved after initiation of methimazole, a permanent pacemaker was not placed. He was discharged with a 30-day event monitor which did not show any conduction abnormalities. Conclusion: This case highlights a rare sequela of hyperthyroidism induced CHB. Although the pathophysiology is not well understood, a proposed mechanism is the direct toxic effect of T3 leading to focal inflammation of the AV node. Further studies are needed to evaluate the pathophysiology and chronicity of this process, which will assist in the decision to implant a permanent pacemaker.

An early complication in patient with CoViD19 pneumonia

Background: In December 2019, many cases of atypical pneumonia with unknown etiology were reported in China. Later on, a new coronavirus was identified, named SARS-CoV-2. We present a case of SARS-CoV-2 pneumonia complicated by spontaneous pneumomediastinum (SPM), pneumothorax (PNX) and subcutaneous emphysema (SCE) without the use of an invasive or noninvasive positive pressure ventilator. Presentation of the case: A 42-year-old man with moderate dyspnea arrived at the DEA. He reported infection with SARS-CoV-2 from a week. He reported no medical history. At the entrance the patient was lucid, oriented and cooperative. The B.P. was 125/75 with sinus rhythm with pulse 75 bpm, apyretic, SpO2 88% on A.A. To DEA showed examinations: D-Dimer 549, fibrinogen 850, VES 75, PCR 8.33, LDH 295. The EGA (Reservoir 90%) detected: pO2 60.7 mmHg, pCO2 36.3, pH 7.47, SpO2 92% and P/F 67,4. The Rx thorax showed multiple hazy parenchymal opacities in the lower lobar seat bilaterally. He was submitted to therapy based on dexamethasone, fluid therapy, antibiotics, enoxaparin. After 36 hours, he presented progressive deterioration of respiratory function and chest CT showed: SPM, PNX, SCE. After two days he died. Conclusions: In many CoViD-19 studies the incidence of SPM, PNX, SCE is rare. The peculiarity of this case report is given by the serious SPM, PNX, SCE as an early complication in the absence of lung comorbidities, cough, consume alcohol, smoke tobacco or use recreational drugs. This suggests that others processes related to CoViD-19 might be the mechanism of air leak that progress to SPM, PNX, SCE.