الفهرس 
RHEUMATOLOGICAL MANIFESTATIONS OF MALIGNANCIESOnly 14 pages are availabe for public view
 |  | from | 171 |  |  |
| | | from | 171 | | |
Abstract
T
here is a complex relationship between different malignancies and rheumatic diseases. Many studies have revealed common manifestations between different malignancies and many rheumatic diseases. Malignancies can be associated with a wide variety of rheumatological manifestations, this may be either due to direct tumor invasion into the joints / bones or it is cytokine mediated paraneoplastic syndrome through altered immune surveillance or they are possible side effects of different chemotherapeutic regimens.
In some patients, the rheumatic symptoms are the main presenting feature of the disease. More interestingly, the musculoskeletal and vascular immune-mediated manifestations that may occur in association with different malignancies remit with treatment of these malignancies.
Immune checkpoint inhibitors are a breakthrough in cancer therapy that allows the self-immune system to fight against the evolving malignant cells. They are cancer immunotherapy that works by blocking certain immunological checkpoints that cause negative regulation of T cells. This allows for the unopposed activation of T cells.
Consequently, as off-target effects of these drugs are the well-known immune-related adverse events that can affect a wide range of tissue organs, among these are different rheumatic and musculoskeletal adverse events: inflammatory arthritis, sicca syndrome, myositis, vasculitis, psoriatic arthritis, and polymyalgia rheumatica and rheumatoid like arthritis.
The aim of this study was to investigate and record the rheumatic manifestations of different malignancies with or without immune modulation therapy.
This study was conducted on two groups of patients. The first group included 25 patients with hematological malignancies confirmed by bone marrow examination and/or lymph node biopsy. The second group included 25 patients with solid malignancies confirmed by tissue biopsy.
All patients were recruited from Oncology, Hematology and Rheumatology inpatient departments and outpatient clinics at Ain Shams University Hospitals and Ain Shams University Specialized Hospital.
All patients were subjected to full medical history taking, full clinical examination including musculoskeletal examination. Also, laboratory assessment was done to all patients.
As regards the rheumatological manifestations among total number of patients, our study showed that joint manifestations (arthritis or arthralgia) were the most common rheumatological manifestations and were found in 36 patients (72%).
On comparing the hematological and solid malignancies groups, we found a statistically significant difference as regards the age of patients with hematological malignancies, (mean 43.68 ± 16.04) which was younger than the patients with solid malignancies (mean 53.6 ± 14.29) (p= 0.025). We also found a statistically significant difference between both groups as regards sex with a higher ratio of F:M (7.3:1) in the solid group compared to F:M ratio (1.5:1) in hematological group with (p = 0.024).
Our results showed a statistically highly significant difference between both groups as regards the first presentation in which the rheumatological symptoms preceded the malignancy in most of hematological malignancies group (60%) while in the solid group the rheumatological symptoms appeared after the onset of malignancy in most patients (80%) with (p =0.004).
In our study, there was no statistically significant difference between both groups as regards all rheumatological manifestations which could be explained by the small sample size.
As regards laboratory assessment in our study, we found a statistically significant difference between both groups as regards the total leucocytic count (TLC) being lower in solid malignancies group compared to hematological malignancies group (p= 0.045). We also found a statistically significant difference as regards uric acid level between both groups being higher in hematological malignancies compared to solid malignancies (p= 0.026).
However, we did not find any statistically significant difference regarding the autoimmune markers between both groups of patients.
Regarding the relation of rheumatic manifestations to the onset of treatment in patients with different malignancies in the present study, comparison between patients who received treatment for cancer and those who did not receive treatment yet, showed a statistically significant difference in rheumatological manifestations as regards dry eye, oral/genital ulcers and Raynaud`s phenomenon being higher in patients who received treatment (p= 0.03, 0.014 and 0.03 respectively).
We also found a statistically significant difference between the patients who received chemotherapy and those who did not as regards arthritis as a joint manifestation being more in the group who did not receive chemotherapy yet, with ratio 64.7% compared to those who received chemotherapy with ratio 14.3% (p=0.025).
As regards the immune checkpoint inhibitors, we found a statistically significant difference between the patients who received checkpoint inhibitors and those who did not as regards polymyalgia rheumatica which was more evident in patients who received checkpoint inhibitors with ratio (25% vs. 0%) (p =0.03).
Regarding the relation of arthritis/arthralgia to laboratory parameters and autoimmune markers among our studied patients, anticardiolipin antibodies were found to be significantly higher in patients with malignancies who did not have arthritis/arthralgia (p= 0.021).
In conclusion, all rheumatic disease patients, regardless of age, should get a thorough cancer screening, especially during the first two years after diagnosis. Important extra-articular symptoms include muscle weakness, skin rash, weight loss, and fever. Anti-CCP can help patients with early arthritis distinguish between RA and patients who also have arthritis and a tumor. Larger prospective investigations are required to confirm these findings because our study was only a pilot study.
Patients who develop musculoskeletal symptoms after immunotherapy are frequently not referred to rheumatologists for a variety of reasons. First of all, since oncologists lack a questionnaire for accurately identifying these issues, they are frequently missed. Another explanation is that corticosteroid therapy that the patient might receive for other side effects—especially if they started earlier—alleviates the symptoms. Due to the existence of numerous symptoms associated with neoplasia, another issue is that patients do not specifically mention rheumatic pain.
There are a lot of questions in the subject of IRAEs that remain unresolved. Rheumatologists must carefully assess these patients at the outset and monitor them over time because of the variety of inflammatory arthritis symptoms, including the types of joints affected, the presence or lack of autoantibodies, and the presence or absence of erosive disease. Without meticulously categorizing these patients, it will be impossible to comprehend the complex phenotypes. To determine the prevalence of rheumatic IRAEs, additional research is required. So that the frequency of rheumatic symptoms may be known and the risk of these events can be properly given to patients, the denominator of patients treated with ICIs should be carefully studied. Last but not least, the rheumatologist’s recommendations regarding the therapy of rheumatic IRAEs should be made in cooperation with oncologists.
RECOMMENDATIONS
M
alignancies can present with rheumatic manifestations so close monitoring of patients presented with rheumatic manifestations and not fulfilling a full rheumatological disease picture is recommended as there might be an underlying malignancy preceding malignancy symptoms.
Collaboration between oncologists and rheumatologists is a must for early detection and control of rheumatological adverse effects occurring with anti cancer therapy.
We also recommend that further studies should be done to investigate the rheumatological manifestations occurring with patients receiving targeted therapy for cancer and immune checkpoint inhibitors.