Administration Of High-dose Corticosteroids Research Articles

High-Dose Hydrocortisone Treatment Does Not Affect Serum C-Reactive Protein (CRP) Concentrations in Healthy Dogs.

Measuring C-reactive protein (CRP) in serum is a useful surrogate marker for assessing disease progression and treatment response in dogs with autoinflammatory diseases. Affected dogs often receive high-dose glucocorticoid treatment, but the effect of such treatment alone on serum CRP concentrations is unknown. We evaluated serum CRP concentrations via immunoassay (sandwich enzyme-linked immunosorbent assay and particle-enhanced turbidimetric immunoassay) in 12 healthy beagle dogs administered high-dose hydrocortisone (8 mg/kg q12 h) per os vs. placebo over 28 days (days 0, 1, 5, and 28) in a randomized parallel study design. Serum CRP concentrations slightly decreased during treatment or placebo but without a significant association with hydrocortisone administration (p = 0.761). Compared to baseline, serum CRP concentrations were decreased by >2.7-fold (minimum critical difference) in three hydrocortisone-treated dogs and two dogs in the placebo group on day 28, whereas an increase to >2.7-fold was seen in one dog receiving placebo. These results suggest a lack of confounding effects of high-dose hydrocortisone administration on serum CRP concentrations in healthy dogs. This might also hold in dogs with autoinflammatory conditions and/or administration of other high-dose corticosteroids, suggesting that CRP presents a suitable biomarker to monitor inflammatory disease processes. However, this needs confirmation by further studies evaluating corticosteroid-induced cellular (e.g., hepatic) transcriptome and proteome changes.

Computed Tomography Provides Improved Quantification of Trabecular Lumbar Spine Bone Loss Compared to Dual-Energy X-Ray Absorptiometry in Ovariectomized Sheep.

Early detection of osteoporosis using advanced imaging is imperative to the successful treatment and prevention of high morbidity fractures in aging patients. In this preclinical study, we aimed to compare dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) to quantify bone mineral density (BMD) changes in the sheep lumbar spine. We also aimed to determine the relationship of BMD to microarchitecture in the same animals as an estimate of imaging modality precision. Osteoporosis was induced in 10 ewes via laparoscopic ovariectomy and administration of high-dose corticosteroids. We performed DXA and QCT imaging to measure areal BMD (aBMD) and trabecular volumetric BMD (Tb.vBMD)/cortical vBMD (Ct.vBMD), respectively, at baseline (before ovariectomy) and at 3, 6, 9, and 12 months after ovariectomy. Iliac crest bone biopsies were collected at each time point for micro-computed tomography (microCT) analysis; bone volume fraction (BV/TV), trabecular number (Tb.N), thickness (Tb.Th), and spacing (Tb.Sp) were reported. aBMD and Tb.vBMD both decreased significantly by 3 and 6 months (p < 0.05) compared with baseline, whereas no changes to Ct.vBMD were observed. Combined (Tb. and Ct.) vBMD was significantly correlated with aBMD at all time points (all p < 0.05). Additionally, greater significant correlations were found between BV/TV and Tb.vBMD at all five time points (R 2 = 0.54, 0.57, 0.66, 0.46, and 0.56, respectively) than with aBMD values (R 2 = 0.23, 0.55, 0.41, 0.20, and 0.19, respectively). The higher correlation of microCT values with QCT than with DXA indicates that QCT provides additional detailed information regarding bone mineral density changes in preclinical settings. Because trabecular bone is susceptible to rapid density loss and structural changes during osteoporosis, QCT can capture these subtle changes more precisely than DXA in a large animal preclinical model. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Role of Thalidomide in the management of complicated Tuberculous Meningitis (S25.005)

<h3>Objective:</h3> The optimal management of TBM complications like opto-chiasmatic arachnoiditis, spinal arachnoiditis, vasculitic infarcts, tuberculomas (esp. paradoxical as well as persisting lesions), and hydrocephalus remains to be defined. These patients are managed by the continuation of ATT and administration of high-dose systemic corticosteroids. Some authors suggest more aggressive immunomodulation. <h3>Background:</h3> To study the role of Thalidomide in managing complications in patients of Tuberculous meningitis (TBM) despite being on the best medical therapy <h3>Design/Methods:</h3> The present study included 59 patients of Opto-chiasmatic arachnoiditis, 33 patients of spinal arachnoiditis with myelitis, and 27 patients with a paradoxical increase in the size of tuberculomas on follow-up despite being on full dose anti-tubercular drugs (ATT) and steroids. Imaging (Baseline MRI and follow-up MRI at 3 months and 1 year of treatment) was done in all patients. <h3>Results:</h3> The mean duration of appearance of vision loss despite being on treatment varied from 4 weeks to 9 months. The patients with spinal arachnoiditis with myelitis showed worsening from 2 weeks to 6 months, and a paradoxical response was observed as late as 8 months in a few patients. All these patients were treated with Thalidomide at the dose of 2–3 mg/ kg body weight (Range of 50–150 mg/ day), which was continued for an average of 6 months duration. Of 59 patients with vision loss, 39 patients showed clinical improvement in visual acuity, while 21 out of 33 patients with spinal arachnoiditis showed clinical improvement, and 18 out of 27 patients showed either reduction or healing of tuberculomas after starting this immunomodulation. Baseline MRI in most patients (&gt;95%) showed abnormalities in the form of arachnoiditis, tuberculomas, etc., which on 2–3-month follow-up Imaging showed worsening of radiological features and responded well after starting Thalidomide. <h3>Conclusions:</h3> Thalidomide is a promising immunomodulator, especially in complicated TBM cases due to worsening arachnoiditis and tuberculomas. <b>Disclosure:</b> Dr. Modi has nothing to disclose. Dr. Shree has nothing to disclose. Dr. Kakkar has nothing to disclose. Manoj Goyal has nothing to disclose. Kusum Sharma has nothing to disclose.

Case Report] Challenging Detection of Latent Tuberculosis in a Patient Undergoing High-Dose Corticosteroid Therapy for Acute Hemolytic Anemia and Rhupus Arthropathy

Acute autoimmune hemolytic anemia requires rapid stabilization, typically through the administration of high-dose corticosteroids. However, it is important to consider reactivation of latent infection and how immune suppression can interfere with molecular screening tools. In this case report, we present a patient with Rheumatoid Arthritis/Systemic Lupus Erythematosus experiencing severe autoimmune hemolytic anemia complicated by an unknown latent tuberculosis infection.

Case Report] Challenging Detection of Latent Tuberculosis in a Patient Undergoing High-Dose Corticosteroid Therapy for Acute Hemolytic Anemia and Rhupus Arthropathy

Acute autoimmune hemolytic anemia requires rapid stabilization, typically through the administration of high-dose corticosteroids. However, it is important to consider reactivation of latent infection and how immune suppression can interfere with molecular screening tools. In this case report, we present a patient with Rheumatoid Arthritis/Systemic Lupus Erythematosus experiencing severe autoimmune hemolytic anemia complicated by an unknown latent tuberculosis infection.

Causal relationship between the administration of high-dose corticosteroids and the appearance of maniform-type psychopathology

IntroductionTo present a clinical case that reflects the causal relationship between the administration of high-dose corticosteroids and the appearance of maniform-type psychopathology.ObjectivesDescriptive study of a case report and literature review on the subject.Methods32-year-old woman with alcohol abuse detected, added Antabus 250 mg / day to her treatment.ResultsAfter 2 months of treatment, she was admitted to the Digestive Service due to acute hepatitis. After a liver biopsy and autoimmunity study was diagnosed as Autoimmune Hepatitis. Treatment with Antabus was withdrawn, and Prednisone 60 mg/day was prescribed. Seven days after starting treatment with corticosteroids, she presented maniform symptoms (psychomotor restlessness, expansive mood, dysphoria, megalomanic delusions, alteration of biological rhythms with decreased need for sleep and risk behaviors), and she was admitted in a psychiatric hospitalization unit. After considering various differential diagnoses she is diagnosed with Substance-Induced (corticosteroids) Mood Disorder with manic features. Psychiatry agrees with the Digestive Service to start treatment with Paliperidone and progressively lower the dose of corticosteroids until suspending it and prescribe an immunosuppressant. Finally, the maniform symptoms that led to admission remitted completely and control and outpatient treatment were continued.ConclusionsIts important to always keep in mind the great risk of the appearance of psychiatric disorders that treatment with high doses of corticosteroids entails, especially in susceptible patients or with a psychiatric history or genetic susceptibility. It is necessary to know the possible appearance of these neuropsychiatric adverse effects in order to prevent them, and if it appear, to assess, if possible, the suspension or reduction of corticosteroid treatment.Disclosure of InterestNone Declared

Analysis of Factors Associated with Charcot Neuroarthropathy following Pancreatic Transplantation

Charcot neuroarthropathy (CN) is a progressive neuropathic complication of diabetes mellitus. Patients undergoing pancreatic transplantation are at risk of developing CN, and CN is known to be a poor prognostic factor for graft loss and patient death. This study aimed to investigate the factors associated with CN in patients who had undergone pancreatic transplantation. We analyzed the data of 61 patients who underwent pancreatic transplantations to investigate the relationship between patient background, nerve conduction velocity tests prior to transplantation, and CN onset. Of these patients, six developed CN. The cumulative incidence rates at 1, 3, and 5 years after transplantation were 3.3, 6.9, and 9.0%, respectively. Sensory neuropathy was severe in six patients with CN, with no sural nerve waveform detected. CN development was not observed when the sural nerve waveforms were visualized. However, when no sural nerve waveforms were observed, the incidence of CN significantly increased due to high-dose corticosteroid administration (p = 0.036). High-dose corticosteroids are associated with the development of CN in the presence of severe neuropathy. Corticosteroid administration is associated with bone metabolism; therefore, appropriate therapeutic intervention is required.

Mineralocorticoids induce polyuria by reducing apical aquaporin-2 expression of the kidney in partial vasopressin deficiency.

The symptoms of diabetes insipidus may be masked by the concurrence of adrenal insufficiency and emerge after the administration of hydrocortisone, occasionally at high doses. To elucidate the mechanism underlying polyuria induced by the administration of high-dose corticosteroids in the deficiency of arginine vasopressin (AVP), we first examined the secretion of AVP in three patients in whom polyuria was observed only after the administration of high-dose corticosteroids. Next, we examined the effects of dexamethasone or aldosterone on water balance in wild-type and familial neurohypophyseal diabetes insipidus (FNDI) model mice. A hypertonic saline test showed that AVP secretion was partially impaired in all patients. In one patient, there were no apparent changes in AVP secretion before and after the administration of high-dose corticosteroids. In FNDI mice, unlike dexamethasone, the administration of aldosterone increased urine volumes and decreased urine osmolality. Immunohistochemical analyses showed that, after the administration of aldosterone in FNDI mice, aquaporin-2 expression was decreased in the apical membrane and increased in the basolateral membrane in the collecting duct. These changes were not observed in wild-type mice. The present data suggest that treatment with mineralocorticoids induces polyuria by reducing aquaporin-2 expression in the apical membrane of the kidney in partial AVP deficiency.

Drug-related immune-mediated myelopathies.

Iatrogenic immune-mediated inflammatory disorders of the spinal cord are an uncommon but potentially severe complication of drug therapy for several human diseases. Particularly the introduction of novel biological agents in the treatment of systemic inflammatory disorders and cancer immunotherapy have led to a significant increase in immune-related adverse events of the central nervous system (CNS). The use of Tumor necrosis factor alpha (TNF-alpha) inhibitors in rheumatic and inflammatory bowel diseases has been associated with demyelinating and other inflammatory CNS conditions, including myelitis. The introduction of immune checkpoint inhibitors in the treatment of several human malignancies has led to an increase in drug-induced immune-related adverse events including in the CNS. Other drugs that have been associated with immune-mediated myelitis include tyrosine-kinase inhibitors and chimeric antigen receptor (CAR) T Cell therapy. A high degree of suspicion is necessary when diagnosing these conditions, as early diagnosis and treatment is crucial in preventing further neurological damage and disability. The treatment of drug-induced inflammatory myelitis typically involves administration of high-dose intravenous corticosteroids, however additional immunosuppressive agents may be required in severe or refractory cases. While most cases are monophasic and remit following discontinuation of the offending agent, chronic immunosuppressive therapy may be indicated in cases with a progressive or relapsing disease course or when a diagnosis of a specific underlying neuro-inflammatory disorder is made. Outcomes are generally favorable, however depend on the specific therapeutic agent used, the clinical presentation and patient factors. In this review we aim to describe the clinical characteristics, imaging findings and management for the most common forms of iatrogenic immune-mediated myelopathies.

Challenges and Pitfalls in the Management of Rhino-Orbital Mucormycosis in Ophthalmology: A Highlighted Problem in the COVID-19 Era.

Secondary infections in hospitalized and ill patients with coronavirus disease 2019 (COVID-19) are common. One of these life-threatening infectious diseases is rhino-orbital mucormycosis, which made an outbreak recently. This outbreak was mainly caused by the administration of high-dose corticosteroids in patients with COVID-19, especially those with diabetes mellitus. The increased incidence of rhino-orbital mucormycosis in the COVID-19 era presents different challenges for healthcare providers including ophthalmologists who are directly involved in disease management. We summarized the main challenges and recommendations for ophthalmologists on the management of rhino-orbital mucormycosis.

Benefits of High-Dose Corticosteroid and Antiviral Agent Combination Therapy in the Treatment of House-Brackman Grade VI Ramsay Hunt Syndrome.

Few large-scale investigations have been conducted on treatment of House-Brackmann grade VI (HB grade VI) Ramsay Hunt syndrome (RHS) patients. We compared recovery rates among patients receiving a normal-dose corticosteroid (prednisolone [PSL] 60 mg/d) or high-dose corticosteroid (PSL 200 mg/d), both with or without an antiviral agents. Recovery rates were also examined based on the order of presentation of herpetic vesicles versus facial palsy. Retrospective case review. Tertiary referral center. A total of 128 patients with HB grade VI RHS were treated in our department between 1995 and 2017. These patients were divided into four treatment groups based on corticosteroid dosage and use of an antiviral agent. We assessed treatment outcomes for HB grade VI patients together with logistic regression analysis to investigate factors that can impact treatment outcomes, that is, sex, age, days to start of treatment, PSL dosage, and antiviral agent administration. Recovery rates were best in the high-dose corticosteroid group with an antiviral agent (71.1%) in comparison with the normal-dose corticosteroid group with an antiviral agent (60.0%) or high-dose corticosteroid alone (57.1%). Significant factors for treatment outcomes were high-dose corticosteroid administration and early initiation of treatment. A better recovery rate was also found when the herpetic vesicles appeared before facial palsy. We showed that a combination of a high-dose corticosteroid and antiviral agent produced the best outcomes for patients with HB grade VI RHS. However, our results were not statistically significant because of small sample size.

A case of repeated focal motor seizures as expression of an inflammatory cerebral process with suspected dysimmune etiology.

Autoimmune encephalitis (AE) is a condition of severe brain inflammation with a complex differential diagnosis. The identification of a specific neuronal antibody (NA) is not mandatory to diagnose AE. Moreover, even when a NA is detected, the clinical picture can be inconsequential (i.e., GAD-65) and not disease-specific (i.e., LGI1). Peculiar clinical manifestations and specific alterations of conventional tests as cerebral spinal fluid (CSF) and magnetic resonance imaging (MRI) can be sufficient to confirm the diagnostic suspicion of AE. New-onset seizures may be the first manifestation of AE and require immediate treatment. We report the case of a 19-year-old woman with sudden onset of focal motor seizures with unimpaired awareness, resistant to different intravenous antiseizure medications (ASMs). Ancillary tests (MRI, CSF analysis and electroencephalogram) were pathological and compatible with an autoimmune disorder of the brain. A weak positivity of GluR-3 antibody was detected in low serum dilution along with very high levels of angiotensin-converting enzyme in serum. After administration of high-dose corticosteroids, electro-clinical and neuroradiological pictures progressively normalized. This case report suggests that, even without a definite NA positivity, an inflammatory brain disorder of suspected autoimmune etiology should be considered based on clinical assessment and suggestive ancillary tests.

Проблема диагностики приобретенных гемолитических анемий в детском возрасте

Аутоиммунная гемолитическая анемия (АИГА) — это группа заболеваний, в основе которых лежит декомпенсированный приобретенный гемолиз. АИГА у детей чаще всего наблюдается после вирусного заболевания. Это достаточно редкое состояние с частотой менее 0,2 случая на 100 000 педиатрического населения. Целью статьи было представить клинический случай больного АИГА. Представлен случай гемолитической анемии у ребенка 4 лет на фоне острой вирусной инфекции с пневмонией и диспептическим синдромом. Во время пребывания в больнице состояние мальчика резко ухудшилось за счет быстрого нарастания слабости и бледности кожных покровов. Общий анализ крови выявил прогрессирующую гемолитическую анемию (Hb 57 г/л, эритроциты 2,58 × 1012/л, Ht 0,16, лейкоциты 13,88 × 109/л, СОЭ 69 мм/ч, тромбоциты 400 × 109/л). Наблюдалось умеренное повышение билирубина за счет неконъюгированной фракции (31,3 и 21,2 мкмоль/л соответственно). В связи с критическим нарастанием анемического синдрома встал вопрос о необходимости гемотрансфузии, но в результате теста на индивидуальную совместимость 20 пакетов крови одной группы было отклонено из-за несовместимости. Интенсивная иммуносупрессивная терапия (комплексное введение высоких доз кортикостероидов в сочетании с внутривенными иммуноглобулинами в дозе 2 г/кг/день) позволила остановить гемолиз и улучшить состояние пациента, вопрос о переливании крови был отклонен. Особенностью представленного случая было критическое нарастание анемии при отсутствии классических признаков гемолиза, невозможность проведения гемотрансфузии и положительная динамика при назначении высоких доз кортикостероидов и иммуноглобулина. Осведомленность об АИГА должна присутствовать у педиатров, и важно расширить их знания о правильном алгоритме диагностики в таких случаях. Препаратами выбора для лечения АИГА являются внутривенные иммуноглобулины в иммуносупрессивных дозах и глюкокортикоиды коротким курсом. В случаях резистентности к такому лечению показано переливание перфторана.

Prognostic Impact of Early Treatment Interruption of Nivolumab Plus Ipilimumab Due to Immune-Related Adverse Events as First-Line Therapy for Metastatic Renal Cell Carcinoma: A Multi-Institution Retrospective Study.

It remains unclear how early treatment interruption of nivolumab plus ipilimumab due to immune-related adverse events affects the outcome of previously untreated metastatic renal cell carcinoma (mRCC). To investigate the prognostic impact of the early interruption of nivolumab plus ipilimumab, used as first-line therapy for mRCC. We retrospectively evaluated 59 intermediate- or poor-risk mRCC patients who received nivolumab plus ipilimumab as first-line therapy. Based on whether early treatment interruption was implemented within the initial four treatment cycles (i.e., 3 months) or not, progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were compared. The prognostic association was further compared with that of 186 patients treated with tyrosine kinase inhibitors (TKIs) as first-line therapy. Twenty-three of the 59 patients (39%) experienced interruption of nivolumab plus ipilimumab therapy. The patients with interruption had longer PFS (p = 0.0055), similar OS (p = 0.366), and likely higher ORR (p = 0.0660) than those without interruption. Of the patients treated with TKIs, 60 of 186 (32%) experienced interruption, with shorter PFS (p = 0.0121), similar OS (p = 0.378), and similar ORR (p = 0.738) than those without interruption. In the 23 patients with nivolumab plus ipilimumab interruption, high-dose corticosteroids were administered in seven patients (30%). PFS (p = 0.638), OS (p = 0.968), or ORR (p = 0.760) did not differ based on corticosteroid administration. Early treatment interruption, which exerted a negative effect for TKIs, was a preferable event for nivolumab plus ipilimumab when considering PFS. Furthermore, early administration of high-dose corticosteroids did not diminish the anti-tumor effect of nivolumab plus ipilimumab.

Effect of high-dose corticosteroid use on efficacy of immune checkpoint inhibitors in patients with renal cell carcinoma (RCC).

4583 Background: The use of High-Dose Corticosteroids (HDC) has been linked to poor outcomes in patients with lung cancer treated with immune checkpoint inhibitors (ICIs) (Ricciuti B, JCO, 2019). There is no data on the effect of HDC on renal cell carcinoma patients (RCC) treated with immunotherapy. We hypothesized that HDC use would be associated with worse outcomes in RCC patients receiving ICIs. Methods: This study evaluated a retrospective cohort of patients with RCC at Dana-Farber Cancer Institute in Boston, MA. Clinical information including demographics, IMDC risk score, RCC histology, steroid administration, ICI regimen, line of therapy, time to treatment failure (TTF) and overall survival (OS) were collected. Patients were divided into those receiving HDC (prednisone ≥10 mg or equivalent for ≥ 1 week, HDC group) or not receiving HDC (No-HDC group). HDC administration was evaluated in relation to TTF and OS in a univariate analysis (Log-rank test) and a multivariate analysis (Cox regression). Results: 190 patients with RCC receiving ICIs were included, with a median age of 59 years. HDC were administered to 56 patients and 134 patients received no (N= 116) or only low-dose (N=18) steroids. In the HDC group, 40 patients received steroids for immune-related adverse events, 8 for other cancer-related indications, and 8 for non-oncological indications. There was no difference in TTF between the HDC and No-HDC groups (12-mo TTF rate: 34.8 vs. 32.3%, respectively; log-rank p=0.65). Similarly, there was no difference in OS between the HDC and No-HDC groups (36-mo OS rate: 56.7 vs. 62.4%, respectively; log-rank p=0.97). After adjusting for IMDC risk group, RCC histology, ICI regimen type, and line of therapy, TTF and OS did not differ in the HDC group as compared to No-HDC group (HR=1.14 [95%CI: 0.80-1.62], p=0.44 and HR=1.17 [95%CI: 0.65-2.11], p=0.59, respectively). Conclusions: In this retrospective study of patients with RCC treated with ICIs, administration of high-dose corticosteroids was not associated with worse outcomes.[Table: see text]

Immune Checkpoint Inhibitors: Cardiotoxicity in Pre-clinical Models and Clinical Studies.

Since the approval of the first immune checkpoint inhibitor (ICI) 9 years ago, ICI-therapy have revolutionized cancer treatment. Lately, antibodies blocking the interaction of programmed cell death protein (PD-1) and ligand (PD-L1) are gaining momentum as a cancer treatment, with multiple agents and cancer types being recently approved for treatment by the US Food and Drug Administration (FDA). Unfortunately, immunotherapy often leads to a wide range of immune related adverse events (IRAEs), including several severe cardiac effects and most notably myocarditis. While increased attention has been drawn to these side effects, including publication of multiple clinical observational data, the underlying mechanisms are unknown. In the event of IRAEs, the most widely utilized clinical solution is administration of high dose corticosteroids and in severe cases, discontinuation of these ICIs. This is detrimental as these therapies are often the last line of treatment options for many types of advanced cancer. In this review, we have systematically described the pathophysiology of the PD-1/PD-L1 axis (including a historical perspective) and cardiac effects in pre-clinical models, clinical trials, autoimmune mechanisms, and immunotherapy in combination with other cancer treatments. We have also reviewed the current challenges in the diagnosis of cardiac events and future directions in the field. In conclusion, this review will delve into this expanding field of cancer immunotherapy and the emerging adverse effects that should be quickly detected and prevented.

Case Report of Lambert Eaton Myasthenic Syndrome in a Patient with Small Cell Lung Cancer on Immune Checkpoint Inhibitor Therapy

Lambert Eaton myasthenic syndrome (LEMS) is a rare autoimmune neuromuscular junction disorder involving loss of functional pre-synaptic P/Q-type voltage-gated calcium channels. Many cases occur as a paraneoplastic disorder, often in small cell lung cancer (SCLC). Recently, immune checkpoint inhibitors (ICI) have emerged as treatment of choice for various malignancies. While generally well tolerated, certain ICI-treated patients experience neurologic immune-related adverse events (irAEs). Here, we explore therapeutic and diagnostic conundrums from the unclear etiology (paraneoplastic vs. irAE) of a case of LEMS in a patient with SCLC treated with ICI therapy. A 62-year-old female patient with SCLC was referred to EMG laboratory with 7 weeks of progressive weakness, shortness of breath and dysphagia. Due to tumor progression, immunotherapy with pembrolizumab was initiated five months prior to presentation. On examination, she had mild non-fatigable right-sided ptosis and diplopia, normal bulbar strength, and proximal greater than distal weakness of lower greater than upper extremities. Her reflexes were 2-/4 throughout, with left biceps reflex facilitating after 30 seconds of exercise. On nerve conduction studies (NCS), there was an amplitude increase in multiple nerves including the left median nerve (160%) and left ulnar nerve (370%) after 10 seconds of exercise. Paraneoplastic panel came back with elevated LEMS-related anti-P/Q-type voltage gated calcium channel antibodies at 0.19nmol/L (normal: ≤0.02nmol/L). This case illustrates the diagnostic and therapeutic challenges that surround LEMS in SCLC patients on immunotherapy. Diagnosis hinges on clinical presentation, motor NCS, and antibody testing while determination of the etiology (paraneoplastic vs ICI related LEMS) is more complex and may affect selection of the correct treatment. Therapy for ICI-related neuromuscular irAEs depends on symptom severity, but typically should include holding immunotherapy and administration of high dose corticosteroids as first line treatment with possible addition of IVIg and plasmapheresis. This differs from the common first line treatment for paraneoplastic LEMS, highlighting the importance of understanding of the etiology. Further research is needed to better understand optimal management.

Case Report of Lambert Eaton Myasthenic Syndrome in a Patient with Small Cell Lung Cancer on Immune Checkpoint Inhibitor Therapy

Lambert Eaton myasthenic syndrome (LEMS) is a rare autoimmune neuromuscular junction disorder involving loss of functional pre-synaptic P/Q-type voltage-gated calcium channels. Many cases occur as a paraneoplastic disorder, often in small cell lung cancer (SCLC). Recently, immune checkpoint inhibitors (ICI) have emerged as treatment of choice for various malignancies. While generally well tolerated, certain ICI-treated patients experience neurologic immune-related adverse events (irAEs). Here, we explore therapeutic and diagnostic conundrums from the unclear etiology (paraneoplastic vs. irAE) of a case of LEMS in a patient with SCLC treated with ICI therapy. A 62-year-old female patient with SCLC was referred to EMG laboratory with 7 weeks of progressive weakness, shortness of breath and dysphagia. Due to tumor progression, immunotherapy with pembrolizumab was initiated five months prior to presentation. On examination, she had mild non-fatigable right-sided ptosis and diplopia, normal bulbar strength, and proximal greater than distal weakness of lower greater than upper extremities. Her reflexes were 2-/4 throughout, with left biceps reflex facilitating after 30 seconds of exercise. On nerve conduction studies (NCS), there was an amplitude increase in multiple nerves including the left median nerve (160%) and left ulnar nerve (370%) after 10 seconds of exercise. Paraneoplastic panel came back with elevated LEMS-related anti-P/Q-type voltage gated calcium channel antibodies at 0.19nmol/L (normal: ≤0.02nmol/L). This case illustrates the diagnostic and therapeutic challenges that surround LEMS in SCLC patients on immunotherapy. Diagnosis hinges on clinical presentation, motor NCS, and antibody testing while determination of the etiology (paraneoplastic vs ICI related LEMS) is more complex and may affect selection of the correct treatment. Therapy for ICI-related neuromuscular irAEs depends on symptom severity, but typically should include holding immunotherapy and administration of high dose corticosteroids as first line treatment with possible addition of IVIg and plasmapheresis. This differs from the common first line treatment for paraneoplastic LEMS, highlighting the importance of understanding of the etiology. Further research is needed to better understand optimal management.

The Successful Treatment of Combined Local and Systemic Steroids in a Patient with Brachial Plexus Neuritis: A Case report

Brachial plexus neuritis (BPN), also known as Parsonage-Turner syndrome, is an uncommon neurological disorder that can manifest with acute extreme upper arm pain followed by patchy muscle paralysis. There is no evidence supporting any recommended treatments for BPN from randomized trials. Non-randomized studies have supported the effectiveness of early administration of high-dose oral corticosteroids during the painful phase. We present a case of a 41-year-old-female with a history of acute left lateral shoulder pain and shoulder girdle weakness who was diagnosed with acute BPN. To reduce the risk of complications arising from high-dose oral steroid administration, we used an ultrasound-guided brachial plexus blockade combined with low-dose oral steroids. The combined treatment approach successfully restored shoulder function and effectively alleviated pain while avoiding complications associated with systemic steroid administration. Keywords: Brachial plexus neuritis; Interventional ultrasonography; Steroid

13955 Recalcitrant lower-extremity ulcerations: Importance of rebiopsy

Lower-extremity ulcerations have an estimated prevalence of 1%-2% in the United States and are a common cause of inpatient hospitalization. A systematic approach beginning with the most frequent etiologies is essential to avoiding misdiagnosis and excessive health care expenditure, as more than 90% of cases may be explained by chronic arterial or venous disease alone. The differential diagnosis for the remaining minority of non-healing leg ulcers is extraordinarily broad and includes infection, panniculitis, calciphylaxis, vasculitis or other immune-mediated etiologies (eg, neutrophilic dermatoses such as pyoderma gangrenosum or Behçet disease), and malignancy, among numerous other causes. Herein, we present the case of a 36-year-old woman with a several year history of bilateral lower extremity erythema nodosum (previously responsive to prednisone tapers and hydroxychloroquine) and bilateral leg ulcerations secondary to thrombotic vasculopathy (confirmed on skin biopsy), known chronic venous insufficiency, steroid-induced diabetes mellitus, and obesity was admitted to our hospital with acute on chronic worsening of longstanding leg ulcerations. Physical examination was notable for two large bilateral lower extremity ulcerations accompanied by faintly erythematous, blanching macules and papules coalescing into patches and plaques on the bilateral thighs as well as oral and genital ulcerations. Laboratory evaluation was notable for leukocytosis of unclear significance in the setting of high-dose systemic corticosteroid administration. A repeat skin biopsy revealed an intravascular lymphoid infiltrate ultimately consistent with T-cell prolymphocytic leukemia (T-PLL). Our case demonstrates the importance of repeat skin biopsy in cases of atypically presenting, recalcitrant to therapy, or acutely worsened lower extremity ulcerations.