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.

Fever and Rheumatology

In all the patients with rheumatic diseases, fever should prompt an immediate and thorough evaluation. There are different disorders that can cause fever and arthritis. Fever that is thought to be due to active rheumatic disease is seen in over 50% of patients with SLE30. However, it can be also related to or a sequel of an infectious process. There are many infectious diseases with rheumatological manifestations. The aim of this chapter therefore is to address variable relationships of fever with patients with arthritis. Fever of unknown origin will be addressed as some systemic rheumatic disease may present with fever. It is always a dilemma when an established patient with arthritis presents with fever. What should you do? This issue is addressed with a suggested diagnostic approach that guides you in a stepwise manner until you reach to the definitive diagnosis.

FRI0491 IS THERE A RELATIONSHIP BETWEEN VOGT-KOYANAGI-HARADA AND INFLAMMATORY RHEUMATOLOGICAL DISEASES

Background:Vogt-Koyanagi-Harada Disease (VKHD) is a systemic autoimmune disease characterized by bilateral granulomatous panuveitis associated with systemic symptoms, including neurological, dermatological and audiovestibular systems. Due to its systemic nature, it may accompany with other autoimmune conditions. However, there is a considerably limited number of reports on the association of VKHD and rheumatologic diseases.Objectives:To investigate the relationship between VKHD and inflammatory rheumatological diseases.Methods:Patients who had bilateral granulomatous uveitis and fulfilled the 2001 revised diagnostic criteria for VKHD were included in our study. All patients were systematically reviewed in terms of the presence of any rheumatological manifestations including connective tissue diseases, spondyloarthritis (SpA), vasculitis, Behcet’s disease and sarcoidosis.Results:Demographic findings: There were fifteen patients in the study (86,7%,female), the mean age at diagnosis was 31,2 ± 11,1 years.Comorbidities: Six patients (4 hashimoto thyroiditis, 2 diabetes mellitus) had comorbid diseases.Rheumatological findings: Mechanical back pain in 4 patients, 1 patient had morning stiffness without any other SpA related features; 2 patients had inflammatory arthralgias in small joints, 4 patients had sicca symptoms, 1 patient had arthritis in knee joint, 3 patients had oral aphthae and 1 patient had photosensitivity.Laboratory tests and autoantibodies: The acute phase reactants were within normal ranges. The mean CRP value at the time of diagnosis was 2,7 ± 3,2 mg/L and ESR was 14,4 ± 9,2 mm/h. Two (15,3%) out of 13 patients had high serum ACE levels. RF, anti-CCP and anti-dsDNA were negative in all patients. ANA was positive (>1/160 titers) in 4 patients (28,6%) and 3 patients had a titer above 1/320. Anti-ENA profile was positive in 2 patients with anti-SS-B and anti-histone components. MPO-ANCA was positive in one patient.HLA test: HLA-B27 was negative in all patients. HLA-B51 and B18 were positive in 2 patients.Radiographic findings: One patient had heel enthesitis on X-ray, 4 patients had bilateral grade 1 and one patient had unilateral grade 2 sacroiliitis. None of them fulfilled the Modified New York criteria for radiographic sacroiliitis. Hand X-rays of all patients were normal. One patient had reticular density on chest X-ray.Pathergy: The pathergy test was negative in all patients.Capilleroscopy: Four patients had pathological capilleroscopy findings (3 patient tortuous loops, 1 patient tortuous loops and microhemorrhages).Conclusion:This study suggests that; 1) inflammatory arthralgias and sicca symptoms were the most common rheumatological findings, 2) the frequency of SpA related features were not increased in VKHD, 3) increased autoantibody frequency, particularly in high titers of ANA could be seen in VKHD possibly reflecting the autoimmune nature of the disease, 4) even though there were signs of rheumatic diseases, none of the patients were grouped into any rheumatologic diagnostic classification.Demographic findings and rheumatological manifestations in VKHD patientsVKHD patients (n=15)Females,n (%)13 (86,7)Age,yrs (mean ± std)34,6 ± 12,6Age of diagnosis, yrs (mean±std)31,2 ± 11,1CRP baseline (mean±std)2,7 ± 3,2 mg/LESR baseline (mean±std)14,4 ± 9,2 mm/HHigh ACE levels,n(%)2/13 (15,3)RF positivity,n(%)0/14 (0)Anti-CCP positivity,n (%)0/6 (0)ANA positivity,n(%)4/14 (28,6)ANA pattern,(n)Homogeneous (2)Nuclear (1)Homogeneous speckled (1)Anti-dsDNA positivity,n(%)0/11 (0)Anti-ENA profile positivity,n(%)2/14 (14,2)ANCA positivity,n(%)1/12 (8,3)Pelvis X-Ray abnormality,n(%)Sacroiliitis (n)5/12 (41,7)Bilateral grade 1 (4)Unilateral grade 2 (1)Capilleroscopy abnormality,n(%)4/9 (44,5)Pathergy,n (%)0/12 (0)Disclosure of Interests:None declared