Rheumatological Adverse Events Following Immunotherapy for Cancer

Background and Objectives: The occurrence of rheumatological side effects in a patient after receiving immunotherapy for cancer is becoming increasingly common. Oncologists often fail to diagnose and refer affected patients to rheumatologists. This paper presents the various rheumatological adverse events that occur after immunotherapy in patients as well as their treatment and evolution. Materials and Methods: A total of 36 patients were monitored between November 2018 and March 2020. The oncologist monitoring the immunotherapy-treated patients identified the occurrence of musculoskeletal side effects. The grading of toxicities was performed by both the oncologist and the rheumatologist using common terminology criteria for adverse events (CTCAE). Rheumatological treatment was administered, and for some patients, immunotherapy was discontinued. Results: The clinical presentations of the patients varied. Mild side effects (grade 1–2) were reported in a higher proportion than severe side effects (grade 3–5). Therefore, thirty-one patients had mild-to-moderate side effects, and five patients had severe side effects. Adverse reactions occurred, on average, 10 weeks after the initiation of immunotherapy; this indicated that the severity of the toxicity was dose dependent. Patients were treated with NSAIDs or prednisone, depending on the severity of the side effects, and for patients with severe manifestations, immunotherapy was discontinued. The remission of rheumatic manifestations varied depending on the grade of the manifestations. Conclusions: The clinical, biological, and ultrasound presentations of the patients with adverse events followed by cancer treatments differed from classic rheumatological manifestations. Thorough examinations of these patients by both oncologists and rheumatologists are needed in order to correctly diagnose and treat rheumatological adverse events. Multiple studies that include a larger number of participants are needed in order to better understand the pathogenesis and clinical evolution of these patients under different treatment conditions.

Current issues in the management of patients with HIV infection and rheumatic diseases

According to experts, the human immunodeficiency virus (HIV) epidemic has a steady downward trend, but the attention of the medical community to this problem is not waning. Before the introduction of highly active antiretroviral therapy, the prevalence of rheumatic manifestations in HIV-infected patients ranged from 3 to 71% and was associated with late stages of infection and severe immunosuppression. HIV-associated arthritis, reactive arthritis, psoriatic arthritis, arthralgias and diffuse infiltrative lymphocytosis syndrome are the most common rheumatic pathologies in HIV. Most people with HIV and musculoskeletal inflammatory disease respond well to NSAIDs, opioids, and basic anti-inflammatory drugs. In cases that are torpid to the abovementioned treatment, the use of biologic disease-modifying antirheumatic drugs may be required.The lecture summarizes modern data on the features of the course and treatment of immunoinflammatory rheumatic diseases in HIV infection.

Rheumatic Manifestations and Diseases From Immune Checkpoint Inhibitors in Cancer Immunotherapy

Immune checkpoint inhibitors (ICIs), which can enhance antitumor immunity and inhibit cancer growth, have revolutionized the treatment of multiple cancers and dramatically decreased mortality. However, treatment with ICIs is directly associated with immune-related adverse events (irAEs) because of inflammation in off-target organs and autoimmunity resulting from non-specific immune activation. These irAEs can cause rheumatic diseases and manifestations such as inflammatory arthritis, polymyalgia rheumatica, myositis, vasculitis, Sicca and Sjogen's syndrome, and systemic lupus erythematosus. Early diagnosis and treatment of these adverse events will improve outcomes and quality of life for cancer patients. The treatment of rheumatic diseases induced by ICIs requires multidisciplinary cooperation among physicians. Furthermore, the underlying mechanisms are not fully understood and it is difficult to predict and evaluate these side effects precisely. In this review, we summarize available studies and findings about rheumatic irAEs, focusing mainly on the clinical manifestations, epidemiology, possible mechanisms, and guiding principles for treating these irAEs.

Impact of frailty on elderly patients with infective endocarditis

Introduction Frailty studies focused on patients with infective endocarditis (IE) are scarce and its potential impact on patient outcomes is not well known. The aim of this study is to describe the clinical profile and prognosis of elderly patients with IE, comparing patients who met the frailty criteria versus those who did not. Methods A total of 121 cases of confirmed IE were consecutively collected in three tertiary hospitals between 2017 and 2019. The patients were classified into two groups: Group I (n=49), patients with IE who met the Frail criteria for frailty, and Group II (n=72), those patients without frailty by this scale. Results The median age of our cohort was 77 years (69–82), and 62.8% were men. Frail patients were older than those in Group II, as shown in Table 1. Regarding comorbidity, chronic anemia (40.8% vs 25%; p<0.060) was more common in Group I, as well as rheumatic manifestations at admission (12.2% vs 1.4%; p=0.014). The most frequently isolated microorganisms were S. aureus (n=25), coagulase negative staphylococci (n=25), viridans group streptococci (n=14), and enterococci (n=14). Enterococci (16.3% vs 8.3%, p=0.177) and non-viridans streptococci (10.2% vs 2.8%); p=0.086) were more frequent in frail patients. Vegetation (79.6% vs 80.6%; p=0.896) and periannular complications (24.5% vs 29.2%; p=0.571) were similar in both groups. No significant differences were found regarding the location of the infection. The incidence of in-hospital complications was similar between both groups. Frail patients underwent surgery less frequently than those in Group II, and had higher predicted mortality on surgical risk scale scores. However, the percentage of patients who met the surgical criteria and were considered inoperable was similar (33.3% vs 26.2%; p=0.415). In-hospital mortality was similar in both groups. When analyzing in-hospital mortality according to the therapeutic strategy in Group I, a mortality of 34.5% was observed in frail patients with conservative medical treatment, compared to 47.1% in those patients who underwent surgery in the same group. One third of our patients received outpatient antibiotic treatment, being significantly more frequent in Group I (39.6% vs 29.0%; p=0.232). Conclusions The elderly patients with IE and frailty criteria were older and more frequently had rheumatic symptoms at admission. Enterococci and non-viridans streptococci were isolated more frequently than in non-frailty patients. Surgery was less performed among frail patients, who had a higher predicted surgical risk. Although complications and in-hospital mortality were similar between both groups, in the group of frail patients, those with conservative management showed lower mortality compared to surgery. FUNDunding Acknowledgement Type of funding sources: None.

An Elderly Gentleman with Acute Lupus Pneumonitis as the Initial Manifestation of Systemic Lupus Erythematosus

Systemic lupus erythematosus is a systemic autoimmune disease, with presentations that vary within a population and across the lifespan of an individual. The disease afflicts childbearing women more than men and uncommonly presents in the geriatric population. Lupus pneumonitis is rare, with a reported incidence of 1–4%. Herein, we discuss the case report of an elderly gentleman with biopsy-proven acute lupus pneumonitis (ALP) as an initial presentation of lupus. After starting high-dose steroids, the patient initially improved, though unfortunately endured a non-ST elevation myocardial infarction and recurrent gastrointestinal bleeding. Despite multiple interventions and a prolonged hospital course, his gastrointestinal bleeding persisted. He elected to go on home hospice and ultimately passed away due to ongoing gastrointestinal bleeding. As with our patient, elderly patients can pose a diagnostic dilemma with regard to late-onset lupus; multiple comorbidities and growing evidence that late-onset lupus may manifest with distinct clinical patterns from younger cohorts complicate diagnosis in these patients. It is critical to maintain a broad differential, which includes unusual rheumatic manifestations when management of common comorbidities fails to alleviate symptoms for an elderly patient. Failure to do so may result in delayed diagnosis of rheumatic disease and increased side effects related to treatment. Additionally, this case serves as a reminder that due to the complexity of rheumatic disease and the additional challenge of older patients with baseline comorbidities, sometimes palliative care options may be appropriate.

Significance of genotyping in the diagnosis of arthritis associated with C-viral hepatitis

To date, a number of studies have been conducted on the relationship of HCV genotypes with complications such as liver cirrhosis, hepatocellular carcinoma, but research on the correlation of the genotype with extrahepatic clinical manifestations associated with HCV, especially rheumatic manifestations, is insufficient. The purpose of the study is to analyze the most common genotypes of viral hepatitis C in the Republic of Uzbekistan and study their correlation with rheumatic manifestations of HCV. Methods: This study involved 88 patients with HCV infection who received inpatient and subsequent ambulatornoe treatment in Scientific Research Institute of Epidemiology, Microbiology and Infectious diseases of the Republic of Uzbekistan. Diagnostics procedures at the initial level included a set of studies, i. e. clinical, rheumatological and laboratory studies, ultrasound of the joint. In addition, 88 samples of RNA - positive serum from patients diagnosed with HCV were genotyped. Results: the Results showed that genotype 1 of HCV (subtype 1b) is the main genetic variant of HCV in Uzbekistan. Based on the results obtained, the genotypic features of viruses can be markers of the development of extrahepatic clinical manifestations. There is a reliable direct correlation between the incidence and severity of associated arthritis in patients with chronic viral hepatitis C with genotype 1b of the virus according to our research. Conclusions: The results of the study can be provided to help the doctor of the polyclinic service as recommendations that patients with the 1b genotype of the virus have a greater adherence to associated arthritis, and in this case, timely targeted consultation of a specialist is necessary.

POS1224 RHEUMATIC MANIFESTATIONS IN COVID-19 PATIENTS - SINGLE-CENTER EXPERIENCE AMIDST THE PANDEMIC

Background:Recently evolved from a monochromic flu-like disease to a polysyndromic “spectrum of disease”, our understanding of coronavirus disease 2019 (COVID-19) is still far from being complete [1]. Hyperinflammation involving not only the lungs but also the musculoskeletal system, skin, cardiovascular, genitourinary systems is immune-mediated resembling the flares of a full-blown rheumatic disease [2,3].Objectives:To describe the prevalence and type of rheumatic manifestations in a cohort of COVID-19 patients hospitalized in the COVID-19 rheumatology department in University Hospital St. Marina, Varna, Bulgaria.Methods:In the present single-center cohort study, а retrospective database analysis was performed among all COVID-19 patients hospitalized from 1 Dec 2020 to 22 Jan 2021. All 243 patients (age 19 - 93 years) were treated for moderate or severe SARS-CoV-2 infection confirmed by laboratory tests, including positive polymerase chain reaction (PCR) test, and imaging modality. Inpatient treatment included antibiotics, dexamethasone, anticoagulants, and antiviral drug remdesevir (optional). Detailed disease history and clinical examination were carried out by a fully certified rheumatologist and/or specialist in internal medicine.Results:Among all 243 COVID-19 patients, those with prominent self-reported myalgia and arthralgia were 26% (n = 63) and 21.3 (n = 52), respectively. We had 4 (1.6%) cases of newly developed cutaneous vasculitis and 2 (0.8%) cases of severe Raynaud’s phenomenon after SARS-CoV-2 infection onset. Two patients experienced severe muscle weakness, had elevated creatine phosphokinase, and were diagnosed with inflammatory myopathy secondary to COVID-19. Lupus-like syndrome was observed in 2 (0.8%) patients.Conclusion:Rheumatic manifestations are part of the heterogeneous spectrum of COVID-19 disease. Amidst the COVID-19 crisis, each newly onset rheumatic manifestation warrants exclusion of SARS-CoV-2 infection. Therefore, a rheumatologist should be a part of a multidisciplinary approach towards the COVID-19 treatment.References:[1]Misra DP, Agarwal V, Gasparyan AY, Zimba O. Rheumatologists’ perspective on coronavirus disease 19 (COVID-19) and potential therapeutic targets. Clin Rheumatol. 2020;39(7):2055-2062[2]Georgiev T, Angelov AK. Complexities of diagnosis and management of COVID-19 in autoimmune diseases: Potential benefits and detriments of immunosuppression. World J Clin Cases. 2020;8(17):3669-3678[3]Ciaffi J, Meliconi R, Ruscitti P, Berardicurti O, Giacomelli R, Ursini F. Rheumatic manifestations of COVID-19: a systematic review and meta-analysis. BMC rheumatology. 2020 Dec;4(1):1-5.Disclosure of Interests:None declared

POS1270 MUSCULOSKELETAL MANIFESTATIONS IN A COHORT OF 234 INFLAMMATORY BOWEL DISEASE PATIENTS

Background:Musculoskeletal symptoms represent the most common extraintestinal manifestations of inflammatory bowel disease (IBD) and a major cause of impaired quality of life in these patients. Spondyloarthritis (SpA) is classically associated with IBD, but other rheumatic manifestations may occur.Objectives:To characterize musculoskeletal symptoms and rheumatic diseases in an IBD cohort.Methods:Retrospective monocentric descriptive study including all the patients with IBD consecutively reffered from Gastroenterology to the Rheumatology Department between January of 2013 and December 2020 in a tertiary university hospital. Demographic and clinical data and musculoskeletal symptoms were collected at the time of the first visit in the Rheumatology outpatient center and the rheumatic diseases diagnosed during the entire follow-up were registered.Results:A total of 234 patients were included, 136 (58.1%) females, 20 (8.5%) smokers. At the first Rheumatology consultation the mean age was 43.6 (±13.7) years and the mean IBD duration was 11.7 (±9.7) years. Concerning IBD: 172 (73.5%) had Crohn’s disease and 62 (26.5%) had ulcerative colitis; azathioprine (39.7%), infliximab (28.2%) and mesalazine (26.5%) were the most frequently used drugs; eleven patients (4.7%) were taking glucocorticoids and 106 (45.3%) had already been treated with glucocorticoids.Regarding musculoskeletal symptoms: 76 (32.5%) patients had peripheral symptoms and 98 (41.9%) had axial symptoms (Table 1).Table 1.Characterization of peripheral and axial musculoskeletal symptoms in patients with Inflammatory Bowel Disease.N (%)Peripheral symptomsNo158 (67.5%)Arthritis / “inflammatory” joint pain24 (10.3%)“Mixed” rhythm joint pain15 (6.4%)“Mechanical” joint pain29 (12.4%)Enthesopathy8 (3.4%)Axial symptomsNo136 (58.1%)“Inflammatory” back pain46 (19.7%)“Mixed” rhythm back pain35 (14.9%)“Mechanical” back pain17 (7.3%)Total234 (100%)Twenty-six (11.1%) patients had radiographic sacroiliitis, 14 (6.0%) had sacroiliitis in computed tomography and 9 (3.8%) in magnetic resonance. Forty-four (18.8%) patients fulfilled Assessment of SpondyloArthritis international Society (ASAS) criteria for axial SpA and 5 (2.1%) for peripheral SpA. Also of note, 16 (6.8%) patients had a previous diagnosis of psoriasis and 5 (2.1%) had uveitis in the past.Concerning other rheumatic diagnosis, we observed: osteoarthritis in 64 (27.3%), osteoporosis in 16 (6.9%), diffuse idiopathic skeletal hyperostosis in 6 (2.6%), systemic lupus erythematosus in 4 (1.7%), rotator cuff tendinopathy in 2 (0.9%), rheumatoid arthritis, gout, calcium pyrophosphate deposition disease, fibromyalgia, drug-induced lupus, osteitis condensans ilii, Dupuytren’s contracture and avascular necrosis of the femoral head in 1 (0.4%), each.Conclusion:Our results demonstrate a high prevalence of musculoskeletal symptoms and rheumatic diseases in patients with IBD. These diagnoses are not limited to the group of SpA and osteoporosis, emphasizing the importance of rheumatologists being alert to other rheumatic diagnoses in patients with IBD.Disclosure of Interests:None declared

P653 Rheumatic extraintestinal manifestations in ulcerative colitis : Prevalence and predictive factors

Background Ulcerative colitis (UC) are an inflammatory condition affecting the gastrointestinal tract. They are considered as chronic disease with complex genetic, immune and environmental components. UC are not exclusive to the gastrointestinal system as they have been identified to be associated with extraintestinal manifestations (EIM) that encompass every other organ in the human body including musculoskeletal system. The aim of this study was to evaluate the prevalence and predictive factors of rheumatic EIM among patients with UC. Methods We carried out a retrospective study from January 2000 to December 2018 including all patients with UC. A complete rheumatologic examination, osteodensitometry,lumbosacral and sacroiliac X-rays were performed.The variables retrospectively analyzed were: gender, age,habits, location and extension of the disease, biochemical markers, other EIM, and previous immunosuppressive therapy. We investigated associations between rheumatic manifestations and clinical and biological criteria. Results Seventy eight patients were included in our study with an average age of 47,56 years [24–85 years]. Sex ratio M/F 0,85. Rheumatic manifestations of any type were present in 42,3%(33 of 78). Peripheral arthritis were observed in 3,8%. Axial involvement including sacroiliitis (SI), with or without spondylitis was noticed in 8,97%. Bone mineral loss was present in 25,6% with 13 cases of osteopenia and 7 cases of osteoporosis. Three patients (3,8%) had an association of SI and osteoporosis. No cases of enthesopathy have been reported. Otherwise, univariate and multivariate logistic regression methods testing for each predictor and their possible association with rheumatic manifestations among UC had shown a decreased risk for rheumatic manifestations with an age over 40 years (p=0,018), an hepatobiliary disorders such as the presence of hepatic cytolysis (p=0,034) and cholestasis (p=0,017) , the coexistence of dermatologic EIM (p=0,048). Forms complicated with an acute severe ulcerative colitis are likely to be correlated with rheumatologic manifestations (p=0,039) but location and extension of the disease had not shown any significant association. And finally, patients who underwent systemic corticosteroid treatment were highly associated with a decreased risk for rheumatic manifestations (p=0,044). Conclusion Predictive factors involved in the occurrence of rheumatic manifestations are: an advanced age, presence of other EIM, severe forms and the use of steroid. Regular screening for EIM and early use of biological therapies may prevent the development of musculoskeletal involvement . Medical care for patients with UC should be multidisciplinary involving the coordination between rheumatologists and gastroenterologists .

COVID-19: An Emerging Culprit of Inflammatory Arthritis

Arthralgia is one of the most common symptoms that occur in patients with COVID-19. About 15% of patients present with arthralgia at some point. Although COVID-19 seems to attack the musculoskeletal system (muscles and joints) in its infective and postinfective stage causing inflammatory arthritis, not much is known about the rheumatic manifestations of this infection. In this case series of 5 patients, we discuss the occurrence of bilaterally symmetrical polyarthritis in patients, previously free from any rheumatic disease, after encountering COVID-19 infection. The musculoskeletal manifestations in these patients phenotypically resembled rheumatoid arthritis. These patients were treated successfully with low-dose glucocorticoids and disease-modifying antirheumatic drugs (DMARDs).