Pre-existing Autoimmune Conditions Research Articles

12337 Nivolumab Induced Secondary Adrenal Insufficiency And Hypothyroidism In A Patient With Graves’ Disease: A Case Report

Abstract Disclosure: F. Sajid: None. J. Kaur: None. A. Zatsepina: None. M. Khan: None. C.A. Resta: None. Introduction: We present a case of a patient with Graves’ disease who developed concurrent secondary adrenal insufficiency (SAI) and primary hypothyroidism while undergoing treatment with nivolumab for non-small cell lung cancer (NSCLC). This case sheds light on the immune-related adverse events (irAEs) associated with immune checkpoint inhibitor (ICI) therapy. Case Presentation: A 63-year-old woman with a history of Graves’ disease and NSCLC undergoing neoadjuvant chemoimmunotherapy was admitted with hyponatremia. She was diagnosed with Graves’ disease a year before and was treated with methimazole (MMI). When she was diagnosed with Graves’ disease, her TSI was 1.64 IU/L (<0.55). Before starting nivolumab, TSH had normalized at 0.5 MCIU/mL on MMI therapy. She started nivolumab 3 months before admission. One month after starting nivolumab, her TSH was <0.01. By the time she was admitted, she had severe hypothyroidism and SAI with sodium 116 mmol/L (135-149), TSH 40.34 mIU/mL (0.39-4.08), free T4 <0.25 ng/dL (0.8-1.8), TSI 21.2 IU/L (0.00-0.55) Total Cortisol 0.4 ug/dL (6.7-27.6), AM Cortisol 0.6 ug/dL, ACTH <1.5 pg/mL (7.2-63.3), LH 75.5 IU/L (7.7-58.5), and FSH 179 IU/L (25.8-134.8). MMI was discontinued due to hypothyroidism. She was started on replacement therapy with levothyroxine and hydrocortisone. Subsequent sodium levels normalized. Discussion: Nivolumab has emerged as a promising immunotherapy for NSCLC. Our patient developed irAEs following nivolumab treatment. Notably, this case represents only the third documented case to our knowledge of both primary hypothyroidism and secondary adrenal insufficiency occurring post-nivolumab treatment. Workup for our patient revealed two irAE’s. She developed primary hypothyroidism and isolated ACTH deficiency with other pituitary function remaining normal. The pattern of thyroid profile over time was consistent with thyroiditis due to ICI therapy. TSI increased, ruling out remission from Graves’ disease. Even after discontinuing methimazole, she remained hypothyroid. Hence, in this case, ICI effectively acted as definitive therapy for her Graves’ disease. Conclusion: This case sheds light on the intricate interplay between nivolumab therapy, pre-existing autoimmune conditions such as Graves’ Disease, and the emergence of irAEs. This case underscores the importance of vigilant monitoring of serum sodium levels, and thyroid and pituitary function tests in patients undergoing immunotherapy. Presentation: 6/1/2024

Autoimmune manifestations following COVID-19 infection in two individuals with primary immunodeficiency

Background: Due to widespread vaccination efforts worldwide, the mortality rates linked to COVID-19 have been decreasing. Nevertheless, there persists a notable level of morbidity, marked by increased occurrences of post-COVID-19 conditions. This includes the development of new autoimmune and inflammatory diseases in individuals who have recovered from COVID-19. A more severe progression of COVID-19 has been correlated with an increased probability of newly diagnosed autoimmune disease, and among individuals with pre-existing autoimmune conditions, COVID-19 increased the risk of developing another autoimmune disease. Methods: Our patients’ medical records were analyzed retrospectively, including their medical history. Results: We present two cases of primary immunodeficiency patients. One of them experienced the onset of new autoimmune symptoms, while the other had a worsening of her autoimmune condition following COVID-19 infection. Conclusion: Recognizing the potential connection between COVID-19 and autoimmune conditions is crucial for identifying symptoms promptly in primary immunodeficiency patients and ensuring timely treatment. Further research is required to comprehensively grasp the relationship between COVID-19 and the development of autoimmunity in this particular patient group. Statement of novelty: In this paper, we present a novel exploration into the emergence of autoimmune manifestations in primary immunodeficiency patients subsequent to COVID-19 infection, through an analysis of two distinct case reports.

Graves Disease - A Comprehensive Review

Graves Disease (GD) is an inflammatory disorder that often results in hyperthyroidism. GD is particularly prone to affecting women, African Americans, individuals with pre-existing autoimmune conditions, and first-degree relatives of those with GD. GD presents through a breakdown of immune tolerance against thyroid antigens. This occurs through a multifactorial autoimmune dysfunction of environmental and mainly genetic contribution. Hereditary predisposition accounts for 79% of the GD risk and increases susceptibility to dysfunction by environmental risk factors such as smoking, vitamin D deficiency, and stressful life events. GD is caused by a disruption of the thyroid gland on a molecular level. The disease is characterized by an overstimulation of the thyroid gland causing hyperthyroidism. This issue is caused by thyroid-stimulating immunoglobulin (TSI) synthesized by B cells. These immunoglobulins bind to the TSH receptors on the thyroid gland, activating it and producing an abundance of the thyroid hormones, levothyroxine (T4) and triiodothyronine (T3). The clinical presentation of GD encompasses a diverse array of signs and symptoms, from common manifestations such as palpitations, weight reduction, and exophthalmos, to less conventional presentations like cardiac complications and cholestatic hepatic injury. There are many methods of diagnosis that are used for GD including the gold standard, which tests for TSI and antibodies against the TSH receptor. Other methods include radioactive iodine uptake and CT scans that test for thyroid enlargement and are used to substitute radioactive iodine uptake tests for pregnant women. The three classical treatments for GD are antithyroid drugs, radioiodine treatment, and thyroidectomy. Additional treatments include corticosteroids which are used to decrease exophthalmos. Beta-adrenergic blockers are used for tachycardia, palpitations, and also blocking the peripheral conversion of T4 to T3. Immunotherapies, such as Mycophenolate mofetil and Azathioprine show promise as potential treatments are currently being investigated. This comprehensive review provides an up-to-date compact analysis of literature pertinent to the epidemiology, etiology, risk factors, genetics, pathophysiology, classifications, clinical presentation, diagnosis, and treatments of GD.

A comprehensive review of oral microenvironment changes and orofacial adverse reactions after COVID-19 vaccination: The good, the bad, and the ugly.

Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have the potential to alter several biological systems concurrently with remolding the immune system, most of which are related to immunization, while some others are known as adverse effects. This review aims to explore the potential effects of vaccination on the oral microenvironment and classifies them as good, bad, or ugly, with a brief review of facial diseases following coronavirus disease 2019 (COVID-19) vaccination. This study was a comprehensive review conducted through searching related articles in Medline, Scopus, and Google Scholar databases. On one side, the "Good" impacts of vaccination on the oro-nasal mucosa are explained as if the mucosal immune responses followed by SARS-CoV-2 vaccines are enough to provide immunity. On the other side, the possible "Bad" and "Ugly" effects of the vaccine, which manifest as orofacial adverse events and autoimmune reactivations, respectively, should be noted. Exacerbation of pre-existing autoimmune conditions such as lichen planus, pemphigus vulgaris, bullous pemphigoid, and Stevens-Johnson syndrome have been reported. COVID-19 vaccines could affect different biological systems alongside stimulating the immune system, and some of these effects are referred to as adverse effects. Nonetheless, these adverse effects are treatable, and healthcare professionals should not prevent patients from taking the first available vaccination.

Risk of severe immune-related adverse events in cancer patients with pre-existing autoimmunity receiving immune checkpoint inhibitor therapy.

To evaluate the frequency and severity of irAEs in patients with pre-existing autoimmunity, including irAE-related morbidity and mortality, irAE-related management and resolution, and outcome of ICI rechallenge, to better understand the treatment options for this vulnerable patient population. We designed a retrospective, single-center, case-control study at a large, academic medical center to evaluate the incidence and severity of irAEs in patients with pre-existing autoimmunity compared to controls. Controls were matched 2:1 for age, sex, cancer histology, and ICI class. Patients were identified with ICD 9 and 10 codes followed by manual chart extraction. Cases were defined as patients with pre-existing, systemic autoimmunity. The primary outcome was severe irAE (Grade 3 or higher by Common Terminology Criteria for Adverse Events) within 6 months of ICI therapy. Secondary outcomes included response to ICIs, resolution of the irAE, ICI rechallenge success, and survival. Statistical analyses were performed by Chi-square, Fishers exact, Mann-Whitney, and Log-rank tests. Of 3,130 patients treated with ICIs from 2015-2021, 28 cases with pre-existing autoimmune disease were identified and were matched with 56 controls. Pre-existing autoimmune conditions included antiphospholipid syndrome, inflammatory polyarthritis, juvenile rheumatoid arthritis, multiple sclerosis, psoriatic arthritis, rheumatoid arthritis, and type I diabetes. Multiple cancer histologies, including genitourinary, gynecologic, head & neck, hepatobiliary, lung, melanoma, and pancreatic, were represented. Six of 28 cases (21.4%) experienced severe irAEs compared to 9/56 (16.1%) controls; the odds of developing a severe irAE were not significantly different (OR 0.43, 95% CI 0.083-2.33, p = 0.627, ns). Moreover, there were no significant differences in overall survival or tumor response between the two groups. The majority of irAEs resolved without long-term sequelae (66.7% of cases, 55.6% of controls). The majority of patients who were rechallenged with ICIs were successful in continuing therapy (66.7% of cases, 100% of controls). Our study suggests that patients with pre-existing autoimmune disease can be treated with ICI cancer therapies and experience rates of severe irAEs and overall survival that are similar to those of the general population. These data can aid oncologists in discussing risks and benefits of ICIs when treating patients with pre-existing autoimmunity and solid tumors.

Multisystem Inflammatory Syndrome in a Patient with SLE

Coronavirus disease 2019 (COVID-19) was one of the most important infections in the past few years. Although most cases of COVID-19 are mild, serious complications may arise. The multisystem inflammatory syndrome (MIS) is a rare but severe, yet poorly understood complication of COVID-19. It was first described in childhood patients with COVID-19 (MIS-C) but is increasingly reported in adults. MIS-A may lead to diagnostic and therapeutic dilemma as its manifestations may mimic a flare of the underlying disease and the use of immunosuppressive therapy may further increase the risk of other infective complications in these patients. However, MIS-A has rarely been reported in patients with pre-existing autoimmune conditions. We hereby present a patient with systemic lupus erythematosus who developed severe MIS-A 6 weeks after a recent SARS-CoV-2 infection.

Single-cell multi-omics analysis of COVID-19 patients with pre-existing autoimmune diseases shows aberrant immune responses to infection.

In COVID-19, hyperinflammatory and dysregulated immune responses contribute to severity. Patients with pre-existing autoimmune conditions can therefore be at increased risk of severe COVID-19 and/or associated sequelae, yet SARS-CoV-2 infection in this group has been little studied. Here, we performed single-cell analysis of peripheral blood mononuclear cells from patients with three major autoimmune diseases (rheumatoid arthritis, psoriasis, or multiple sclerosis) during SARS-CoV-2 infection. We observed compositional differences between the autoimmune disease groups coupled with altered patterns of gene expression, transcription factor activity, and cell-cell communication that substantially shape the immune response under SARS-CoV-2 infection. While enrichment of HLA-DRlow CD14+ monocytes was observed in all three autoimmune disease groups, type-I interferon signaling as well as inflammatory T cell and monocyte responses varied widely between the three groups of patients. Our results reveal disturbed immune responses to SARS-CoV-2 in patients with pre-existing autoimmunity, highlighting important considerations for disease treatment and follow-up.

Clinical and Etiological Profile of Acute Undifferentiated Fever With Thrombocytopenia in an Emergency Department.

Acute undifferentiated fever with thrombocytopenia is a common and challenging clinical presentation encountered in the emergency departments of tertiary care centers, particularly in tropical regions, often requiring prompt evaluation and management. The study aimed to explore the clinical and etiological profile of acute undifferentiated fever with thrombocytopenia in the Emergency Department of Indira Gandhi Institute of Medical Sciences, Patna. It investigates factors associated with patient outcomes and compares platelet transfusion requirements among different etiological groups. In this cross-sectional observational study, 350 patients with acute undifferentiated fever with thrombocytopenia were analyzed for one year from October '21 to September '22. Pre-existing chronic infectious diseases, liver cirrhosis, and autoimmune conditions were excluded. Thrombocytopenia was observed in all patients, with 65% having platelet counts below 50,000/µL. Associations were found between the degree of thrombocytopenia and organ dysfunction, shock, and third space loss. Logistic regression analysis identified thrombocytopenia, organ dysfunction, and platelet transfusion requirement as significant predictors of the overall outcome. Etiological group comparisons revealed higher platelet transfusion requirements in the bacterial group. Prompt recognition and management of thrombocytopenia in acute undifferentiated fever are vital. Thrombocytopenia, along with organ dysfunction and shock, significantly influence patient outcomes. Tailored interventions based on etiological factors are crucial. Further research should focus on specific viral aetiologies in acute undifferentiated fever with thrombocytopenia.

Autoimmune gastritis as an unexpected cause of diarrhea in a young adult with type I diabetes: a case report

BackgroundType 1 diabetes mellitus (T1DM) is a lifelong diagnosis that involves immune-mediated damage of pancreatic beta cells and subsequent hyperglycemia, manifesting as: polyuria, polydipsia, polyphagia, and weight loss. Treatment of type 1 diabetes centers on insulin administration to replace or supplement the body's own insulin with the goal of achieving euglycemia and preventing or minimizing complications. Patients with T1DM are at risk for developing other autoimmune conditions, most commonly thyroid or celiac disease.Case presentationA 20-year-old African American female with T1DM was referred by her endocrinologist to pediatric gastroenterology for 2 months of nocturnal, non-bloody diarrhea, left lower quadrant pain, and nausea; she was also being followed by neurology for complaints of lower extremity paresthesias and pain. The patient’s initial lab-workup was remarkable for a low total Immunoglobulin A (IgA) level of < 6.7 mg/dL. As IgA deficiency is associated with an increased risk of celiac disease, the patient underwent upper and lower endoscopy, which was grossly unremarkable; however, histology revealed a pattern consistent with autoimmune gastritis. Subsequent serum evaluation was remarkable for an elevated fasting gastrin level and an elevated parietal cell antibody level without macrocytic anemia, iron deficiency, or vitamin B12 depletion. The patient was diagnosed with autoimmune gastritis (AIG) and subsequently initiated on parenteral B12 supplementation therapy with improvement in her neurologic and gastrointestinal symptoms.ConclusionThis case illustrates the importance of recognition of red flag findings in a patient with known autoimmune disease. Following well-established health maintenance recommendations for individuals with T1DM ensures that common comorbidities will be detected. Autoimmune gastritis, while a rarer pathology in the pediatric population, deserves consideration in patients with pre-existing autoimmune conditions and new gastrointestinal or neurologic symptoms, as AIG can be associated with poor outcomes and risk of malignancy. Initial lab findings associated with an eventual diagnosis of AIG typically include anemia, iron deficiency, or Vitamin B12 deficiency. However, as demonstrated in this case, symptoms of AIG can rarely present before anemia or Vitamin B12 deficiency develops. To prevent permanent neurological damage, parenteral Vitamin B12 therapy must be considered even in the absence of Vitamin B12 deficiency, especially in those patients already experiencing neurological symptoms.

Incidence, outcomes, and risk factors of acute immune checkpoint inhibitor (ICI) pneumonitis post-chemoradiation with durvalumab for patients with locally advanced non-small cell lung cancer (LA-NSCLC): A population-based multicenter study.

8561 Background: The PACIFIC trial has drastically changed the LA-NSCLC treatment paradigm and improved survival outcomes with consolidation durvalumab post-chemoradiotherapy. Despite these promising results, real-world practice has demonstrated that ICI pneumonitis can have significant clinical complications and terminate consolidation therapy prematurely. This study aimed to identify clinical predictors, outcomes, and healthcare utilization in ICI pneumonitis in LA-NSCLC patients who received consolidation durvalumab in real-world practice. Methods: Using the Alberta Immunotherapy Database, we retrospectively evaluated all NSCLC patients who received durvalumab in Alberta, Canada from January 2018 to December 2021. Pneumonitis cases were identified based on radiographic changes and oncologists’ clinical assessments. We examined incidence and predictive values of severe pneumonitis (≥grade 3), with secondary outcomes of overall survival (OS) and time-to-treatment failure (TTF). Exploratory multivariate analyses were performed to identify predictive values to developing severe pneumonitis and worse OS/TTF. Results: Of 189 total patients, most were ECOG 0-1 (91%) and had partial response from chemoradiation (85%) prior to durvalumab. 49% received full year of therapy (n = 93). Median TTF was 11.2 months, and median OS of 19.7 months with 1-year OS 64% (n = 121). 26% (n = 49) developed any grade of pneumonitis. 9% (n = 17) had severe pneumonitis. Corticosteroids were administered to 86% of the pneumonitis patients (n = 42); 53% (n = 26) required admission. 13% (n = 9) of deaths were attributed to pneumonitis. Male gender and pre-existing autoimmune condition were associated with severe pneumonitis whereas V20 (percentage of irradiated lung volume ≥20Gy) was associated with developing any grade pneumonitis. In multivariable analysis, male gender and V20 was significantly associated with worse OS whereas older age, smoking status, pneumonitis, and male gender with lower TTF. Pneumonitis development was found to be an independent risk factor for worse OS (p = 0.038) and TTF (p = 0.007). Conclusions: We report a pneumonitis incidence comparable to prior retrospective studies and higher rate of severe pneumonitis compared to PACIFIC trial. Our results corroborate that V20, a previously established risk factor for durvalumab associated pneumonitis, is a significant predictor for developing pneumonitis and worse OS. In contrast to smaller retrospective studies, we observed male gender and pre-existing autoimmune conditions appear to predict severe durvalumab associated ICI pneumonitis. These results affirm the importance of careful patient selection for safe completion of consolidation durvalumab in real-world LA-NSCLC population.

Physician Views on the Provision of Information on Immune Checkpoint Inhibitor Therapy to Patients with Cancer and Pre-Existing Autoimmune Disease: A Qualitative Study.

Immune checkpoint inhibitors (ICIs) have improved cancer outcomes but can cause severe immune-related adverse events (irAEs) and flares of autoimmune conditions in cancer patients with pre-existing autoimmune disease. The objective of this study was to identify the information physicians perceived as most useful for these patients when discussing treatment initiation with ICIs. Twenty physicians at a cancer institution with experience in the treatment of irAEs were interviewed. Qualitative thematic analysis was performed to organize and interpret data. The physicians were 11 medical oncologists and 9 non-oncology specialists. The following themes were identified: (1) current methods used by physicians to provide information to patients and delivery options; (2) factors to make decisions about whether or not to start ICIs in patients who have cancer and pre-existing autoimmune conditions; (3) learning points for patients to understand; (4) preferences for the delivery of ICI information; and (5) barriers to the implementation of ICI information in clinics. Regarding points to discuss with patients, physicians agreed that the benefits of ICIs, the probability of irAEs, and risks of underlying autoimmune condition flares with the use of ICIs were most important. Non-oncologists were additionally concerned about how ICIs affect the autoimmune disease (e.g., impact on disease activity, need for changes in medications for the autoimmune disease, and monitoring of autoimmune conditions).

Coronavirus disease 2019 (COVID-19) in pediatric patients with autoimmune disorders.

In this review, we sought to evaluate the currently available literature on the impact of autoimmune disease and its related therapeutic approaches on the COVID-19 infection course of disease in children and reflect on the gaps in the evidence and the need for further research in this field. • The majority of children infected with COVID-19 demonstrate mild to moderate clinical manifestations compared to adults, whereas those children with pre-existing autoimmune conditions are at a greater risk for severe symptoms. •There is currently limited understanding of the pathophysiology and clinicaloutcomes of COVID-19 in pediatric patients with autoimmune disorders due to scattered reports and inadequateevidence. • Generally, children with autoimmune disorders have more unfavorable outcomes than healthy children; yet, the severity is not extreme, and is highly dependent on their autoimmune disease type and severity, as well as the medication they are taking.

PSUN42 New-Onset Rheumatoid Arthritis After Surgical Treatment of Cushing Syndrome

Abstract Background Cushing syndrome (CS) is a rare endocrinopathy resulting from prolonged exposure to endogenous or exogenous glucocorticoids. CS can be subclinical or can present with an array of overt signs and symptoms. The goal of treatment in CS is to reestablish normal cortisol levels in the body by eliminating the source of excess cortisol. Autoimmune diseases are often treated successfully with exogenous glucocorticoids. There are several case reports/series in the literature describing patients who developed autoimmune diseases, or experienced recrudescence of otherwise quiescent autoimmune processes, after the withdrawal of glucocorticoids. Such diseases include rheumatoid arthritis, Graves disease, Hashimoto's thyroiditis, systemic lupus erythematosus, psoriasis, and myasthenia gravis. Below we share a case of rheumatoid arthritis that presented after unilateral adrenalectomy for CS. Clinical case A 55 year old female with a history of Graves disease status post radioactive iodine ablation many years ago with post-ablative hypothyroidism was found to have a left adrenal mass on CT in 2016. An MRI in February 2021 showed interval growth from 3.8×2.9×3.6cm to 5.1×3.5×4.8cm. ACTH was suppressed to &amp;lt;1.5 pg/mL (7.2-63.3 pg/mL), 24 hour urine free cortisol was elevated to 256 ug/24hr (10-34 ug/24hr), midnight salivary cortisol was elevated to 219 ng/dL then 430 ng/dL on repeat (n&amp;lt;100 ng/dL), and AM cortisol was 13.7 ug/dL (6.0-18.4 ug/dL) after 1mg overnight dexamethasone administration. This biochemical testing was supportive of the diagnosis of ACTH-independent adrenal CS. Our patient underwent successful left adrenalectomy in March 2021 and was started on hydrocortisone postoperatively given long-standing suppression of her hypothalamic-pituitary-adrenal axis. Within three months, she developed muscle aches and pain in bilateral hands, ankles and feet with stiffness and swelling. These symptoms worsened with glucocorticoid taper. She was found to have a rheumatoid factor of 32 IU/mL (0-13 IU/mL) and was diagnosed with rheumatoid arthritis, for which she was started on hydroxychloroquine and briefly switched from hydrocortisone to prednisone. She has since been tapered off steroids with resolution of adrenal insufficiency. Her rheumatoid arthritis symptoms remain adequately controlled on hydroxychloroquine. Conclusions While it is known that withdrawal of exogenous chronic steroids can result in exacerbation of pre-existing autoimmune disease, the emergence of new autoimmune disease upon withdrawal of endogenous steroid production after treatment of pituitary ACTH-dependent or adrenal ACTH-independent CS is extremely rare. Of special interest, our patient described above had a history of Graves disease years before her CS diagnosis was made, suggesting an underlying proclivity towards autoimmunity. Further study may reveal the need for higher vigilance in postoperative monitoring in patients with preexisting autoimmune conditions. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

S3677 Tissue Is the Issue: A Rare Case of Collagenous Gastritis

Introduction: Collagenous gastritis (CG), collagenous sprue, and collagenous colitis are rare forms of collagenous gastroenteritides marked by subepithelial collagen deposition of more than 10 mm and inflammatory infiltrate in the lamina propria. CG was first identified in 1989. It's a rare disease, with just 100 cases reported so far. Here, we present a distinct case of collagenous gastritis. Case Description/Methods: 52-year-old female with no chronic medical conditions presented with symptoms of mild reflux, epigastric pain, and intermittent diarrhea up to 5 times per day. She had sporadic Ibuprofen use for headaches. Her mother was diagnosed with lupus and a half-sister with a history of mixed connective tissue disorder. Initial upper endoscopy revealed grade B esophagitis and gastritis, biopsies showed CG. Colonoscopy with random biopsies showed no evidence of collagenous colitis. She was treated with high dose proton pump inhibitor (PPI) and repeat endoscopy in 4 weeks with biopsies via Sydney protocol was performed. Additional blood work was normal including normal thyroid panel, celiac screen (anti-transglutaminase IgA: < 1.0 U/ml, IgA: 2.34 g/L) and IgG4 titer (0.27 g/L.) Repeat EGD with biopsies per Sydney protocol confirmed CG in all gastric quadrants, except fundus. After stopping NSAIDs and continuing on PPI, her symptoms resolved with a plan for surveillance endoscopy in 6 months (Figure 1). Discussion: In our patient, the diagnosis of CG led to further investigations to rule out possible associated autoimmune diseases. The occasional ibuprofen may have been contributory, but the repeat biopsies on the second endoscopy confirmed the presence of CG despite cessation. The only contributing factor in her case is positive family history. There are very few cases reported in the literature with the possible association of lupus with CG. This distinctive case of CG is an important contribution to the limited pool of existing cases as the patient herself did not have any preexisting allergic or autoimmune conditions and it appears that this process occurred idiopathically. Given the rarity of the condition and limited literature available, we emphasize the importance of delineated medical guidelines for appropriate screening and surveillance.Figure 1.: Endoscopic appearance of collagenous gastritis. A, B. body, C. Antrum D. fundus ; E, F: Histology of collagenous gastritis characterized by thickening of sub epithelial basement membrane accompanied by diffuse superficial lymphoplasmacytic infiltrates and surface epithelial degeneration. Table 1. - Summary of Collagenous gastritis (CG) COLLAGENOUS GASTRITIS (CG) - Characterized by marked sub epithelial collagen deposition with associated inflammatory infiltrate. EPIDEMIOLOGY - Female Preponderance - All age groups but primarily affects adults. ETIOLOGY - The etiology is unknown - Stancu et al. outlined three pathogenic mechanisms that may lead to collagen deposition in cases of CG: (1) Chronic inflammation (2) Fibroblast sheath abnormality (3) Leakage of plasma proteins and fibrinogen ASSOCIATIONS - Intestinal and autoimmune disorders, including celiac disease. collagenous enteritis, collagenous colitis, sjogren syndrome, SLE, juvenile arthritis, RA, Hashimoto's thyroiditis, Grave's disease, Diabetes mellitus type 1, and CVID. - Medications such as Olmesartan, Venlafaxine SYMPTOMS AND SIGNS - Epigastric and or abdominal pain, anemia , gastrointestinal bleeding, diarrhea, nausea and vomiting, perforated ulcer, weight loss, abdominal distension, fatigue, dyspepsia, retrosternal pain, constipation and dysphagia. DIAGNOSIS - EGD with biopsy TREATMENT - Anti-secretory agents including PPIs, and H2 receptor antagonists, steroids, iron supplementation and hypoallergenic diets have been tried with limited success. - Other treatment modalities , such as sucralfate, mesalazine, bismuth subsalicylate, furazolidone, sulfasalazine, azathioprine, and parenteral nutrition have also been tested.

Psoriasis, inflammatory bowel disease, and uveitis as paradoxical adverse effects induced by TNF inhibitors in patients with immune-inflammatory rheumatic conditions

Despite their known benefits, tumor necrosis factor alpha inhibitors (TNFi) may cause certain unexpected side effects, such as the aggravation of pre-existing autoimmune conditions or inducing the onset of new inflammatory conditions, these reactions being called “paradoxical adverse effects’’ (PAEs). The spectrum of TNFi-induced PAEs is vast and may include dermatological disease (frequently - psoriasiform skin reactions), gastroenterological disease (inflammatory bowel disease), ophthalmological disease (uveitis) and other autoimmune conditions (lupus-like reactions, vasculitis). PAEs are characterized by complex physio-pathological mechanisms which remain a matter of further research and may significantly impact the patients’ evolution and quality of life. Importantly, a large number of patients require the cessation of TNFi treatment, as well as other types of therapeutic interventions. The present review aimed to analyze recent findings regarding certain paradoxical adverse effects (psoriasis, inflammatory bowel disease, and uveitis) in patients with RA, ankylosing spondylitis (AS), and PsA treated with TNFi.

Challenging Dermatologic Considerations Associated with Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors have emerged as a new paradigm in oncologic care for many malignancies. However, nonspecific immune activation has led to "collateral damage" in the form of immune-related adverse events, with skin being a commonly affected organ. Cutaneous immune-related adverse events include a wide spectrum of clinical presentations and challenging considerations, often necessitating dermatology referral to support diagnosis and management, particularly for atypical presentations or more severe, cutaneous immune-related adverse events that may require specialized dermatologic evaluations including biopsy and histopathology. Close collaborations between oncologists and dermatologists may optimize clinical decision making in the following challenging management settings: non-steroidal therapies for corticosteroid-refractory, cutaneous immune-related adverse events, immune checkpoint inhibitor rechallenge, balancing cutaneous immune-related adverse events and treatments, and immune checkpoint inhibitors in patients with pre-existing autoimmune disease, skin conditions, and organ transplants. These complex clinical decisions that often lack rigorous data should be made in close collaboration with dermatologists to minimize unnecessary morbidity and mortality. This article provides a review of approaches to challenging dermatologic considerations associated with immune checkpoint inhibitor therapies.

Outcomes of Anti-PD1 Treatment for Relapsed/Refractory Hodgkin Lymphoma: A German Hodgkin Study Group (GHSG) Multi-Center Real-World Analysis

Outcomes of Anti-PD1 Treatment for Relapsed/Refractory Hodgkin Lymphoma: A German Hodgkin Study Group (GHSG) Multi-Center Real-World Analysis

EYES WIDE SHUT: AN UNUSUAL CAUSE OF PTOSIS

TOPIC: Lung Cancer TYPE: Medical Student/Resident Case Reports INTRODUCTION: Pembrolizumab is an immune checkpoint inhibitor (ICI) known to cause a variety of side effects. Here is a case of a lung cancer patient on pembrolizumab presented with dyspnea and chest pain and was found to have a rare side effect. CASE PRESENTATION: A 74-year-old female, with stage IV adenocarcinoma of the lung, presented to the hospital with chest pain & shortness of breath. She admitted to fatigue, new-onset left-sided ptosis for 2 weeks and RUE weakness. Patient was admitted the day before her 3rd treatment. She required supplemental O2 due to hypoxia. Physical exam was significant for ptosis (L > R), UE weakness (L > R), otherwise unremarkable. Labs were significant for AKI, elevated CK and CRP, with a borderline high leukocytosis. Imaging ruled out stroke and PE. Her mass was stable radiographically. Cardiac causes were ruled out. Despite initial treatment for post-obstructive pneumonia, she remained symptomatic and desaturated with exertion, requiring non-invasive ventilation at times. Diaphragmatic paralysis, neuromuscular weakness or paraneoplastic syndromes were considered as possible etiologies. Serologies for myasthenia gravis (MG), Lambert-Eaton and myositis were ordered. Hemi-diaphragmatic paralysis was ruled out. ABG showed evidence of hypercapnia and sitting and supine spirometry demonstrated a drop in FVC >20%, suggesting neuromuscular weakness. Anti-AChR Ab was positive, while anti-MUSK Ab, anti-voltage-gated Ab and auto-antibodies for myositis were all negative. She was diagnosed with MG induced by pemrolizumab and was started on prednisone, pyridostigmine and IVIG. On follow-up, she noted slow improvement and her chemotherapy remained on hold due to her high steroid dose. DISCUSSION: Most ICI-induced MG (iciMG) cases were from melanoma patients, it is rare to see them in lung cancer patients, especially with adenocarcinoma. iciMG can present as exacerbation or new-onset disease. The cause for our patient's respiratory distress was confounded by possible post-obstruction pneumonia. There was also uncertainty on the functioning of her diaphragm, which could result from ICI-induced myositis. To differentiate the two, Sekiguchi et al. recommended using ultrasound over needle EMG to assess for diaphragm dysfunction to avoid pneumothorax. The current recommendation is to treat with plasmapheresis and pulse-dose steroids. ICI can trigger underlying autoimmune diseases. However, pre-existing autoimmune conditions should not be considered as contraindications to ICI therapy, as there was a report on a patient tolerating a re-challenge despite having iciMG. Thus, limiting therapeutic options based on adverse events should be decided on a case-by-case basis. CONCLUSIONS: Pembrolizumab can cause de novo myasthenia gravis. These symptoms tend to develop within the first few cycles of treatment. Physicians should consider this as a differential when encountering similar patients. REFERENCE #1: Hibino M, Maeda K, Horiuchi S, Fukuda M, Kondo T. Pembrolizumab-induced myasthenia gravis with myositis in a patient with lung cancer. Respirol Case Rep. 2018;6(7):e00355. Published 2018 Aug 7. doi:10.1002/rcr2.355 REFERENCE #2: Sekiguchi K, Hashimoto R, Noda Y, et al. Diaphragm involvement in immune checkpoint inhibitor-related myositis. Muscle Nerve. 2019;60(4):E23-E25. doi:10.1002/mus.26640 REFERENCE #3: Tedbirt B, De Pontville M, Branger P, et al. Rechallenge of immune checkpoint inhibitor after pembrolizumab-induced myasthenia gravis. Eur J Cancer. 2019;113:72-74. doi:10.1016/j.ejca.2019.03.006 DISCLOSURES: No relevant relationships by Rumon Chakravarty, source=Web Response No relevant relationships by Vernon Chan, source=Web Response

Interleukin-6 blockade for prophylaxis and management of immune-related adverse events in cancer immunotherapy

BackgroundImmune checkpoint inhibitors (ICIs) have activity across many tumor types, but activation of the immune system may also lead to significant, often steroid-refractory immune-related adverse events (irAEs). We sought to determine the activity of tocilizumab, an anti-interleukin-6 receptor monoclonal antibody, in treatment or prevention of auto-immune irAE in ICI-treated patients. MethodsInstitutional databases from 2 melanoma centers were reviewed for patients treated with ICIs and tocilizumab. Longitudinal assessment of C-reactive protein (CRP) and assessment of clinical improvement or prevention of flare of pre-existing auto-immune conditions were utilised to evaluate the benefit of tocilizumab. ResultsTwenty-two patients were identified. Two were treated prophylactically. Twenty were treated for management of irAEs. Median time to irAE onset from ICI start was 48 days (range 8–786) and from irAE onset to tocilizumab 32 days (range 1–192). Median time to irAE resolution from tocilizumab was 6.5 days (range 1–93). Clinical improvement/benefit was demonstrated in 21/22 patients. Median CRP prior to ICI administration was 32 mg/l (range 0.3–99), at the onset of irAE 49.5 mg/L (range 0.3–251, P = 0.047) and after tocilizumab 18 mg/L (range 0.3–18, P = 0.0011). Tocilizumab was well tolerated with self-limiting and transient toxicities in 11 (50%) patients. From start of ICI, median progression-free survival was 6 months (range 3.9–18.8) and median overall survival was not reached. ConclusionsTocilizumab was a well-tolerated and effective steroid-sparing treatment for both management of irAEs, as well as prevention of flare of pre-existing auto-immune disorders. Prospective trials to evaluate its efficacy and impact on cancer outcomes compared with standard strategies are required.

Use of immune checkpoint inhibitors in patients with solid tumors and pre-existing autoimmune or inflammatory disease: real-world data.

Aim:Immune checkpoint inhibitors (ICIs) are a cornerstone in cancer treatment but they can induce immune-related adverse events (irAEs). Furthermore, patients with pre-existing autoimmune and/or inflammatory disease (AID) have been excluded from clinical trials. The objective of this study is to evaluate the efficacy and safety of ICIs in patients with cancer and AID.Materials & methods:This is an observational, retrospective study carried out at the Medical Oncology Department of Hospital Universitario Puerta de Hierro, Majadahonda, Madrid between January 2016 and December 2018.Results:A total of 202 cancer patients treated with ICIs were included, 15 (7, 4%) of them had pre-existing autoimmune diseases. The most frequent pre-existing AID were thyroid diseases (33.3%): autoimmune hypothyroidism, Graves–Basedow disease and Hashimoto’s thyroiditis. Three patients had psoriasis, two antinuclear antiboides + polyarthritis, one rheumatoid arthritis, another latent autoimmune diabetes in adults, another systemic lupus erythematosus and the last one, a polymyalgia rheumatica. In this series, the majority of patients (73.33%) did not experience any flare up of their autoimmune disease. In patients who had AID flare up, this was treated with corticosteroids. The most frequent cause of immunotherapy discontinuation was tumor progression (40%). A total of 20% of patients had to discontinue immunotherapy due to toxicity.Conclusion:In our series, AID flare ups or irAEs in patients with pre-existing AID who receive immunotherapy are not very common and can often be controlled without interrupting treatment. Prospective studies are needed to establish the incidence of irAEs in patients with pre-existing autoimmune conditions, evaluate risk–benefit and elaborate management clinical guidelines in this population.