Arthritis as an Initial Presentation of Malignancy

Two Case Reports

Benjamin Sachdev Manjit Singh; Sharifah Aishah Wan; Yaw Kiet Cheong; Seow Lin Chuah; Cheng Lay The; Ahmad Tirmizi Jobli


J Med Case Reports. 2021;15(94) 

In This Article


In both patients described above, the symptoms of inflammatory arthritis preceded the detection of malignancy. Our first patient was a 65-year-old woman who presented with oligoarthritis of the ankle joints which was treated as SpA. The second patient presented with asymmetrical polyarthritis, which was treated as seronegative RA. Both our patients had poor clinical response to disease-modifying antirheumatic drugs (DMARDs) and were later found to have malignancy that was adenocarcinoma of the lung in the first patient and ovarian carcinoma in the second patient. In both patients, their arthritis resolved only after therapy for their malignancy was initiated.

Arthritis is a common symptom encountered by the rheumatologist, with a broad range of causes including RA, SpA, vasculitis, connective tissue diseases, crystal arthropathies and infections. It is however an uncommon presentation of paraneoplastic syndrome. Paraneoplastic syndromes, which include paraneoplastic arthritis, may precede or occur during the course of malignant disease.[2–4] They should not arise from direct tumor invasion or compression, and usually improve with treatment of the underlying malignancy.[3,4] Paraneoplastic arthritis itself is an inflammatory polyarthritis which may be seronegative.[5] It has a male predominance, with an average age of onset of 54 years.[5] The arthritis is typically asymmetrical, commonly affecting the lower extremity joints, and may occur about 8–12 months prior to malignancy development.[1,3–5] It is usually poorly responsive to the standard therapy of DMARDs, corticosteroids or nonsteroidal anti-inflammatory drugs (NSAIDs).[1,3–5] Malignancies associated with paraneoplastic arthritis include lung, breast, ovarian, laryngeal and gastrointestinal tumors.[2–4] The pathogenesis is not known, but mediators such as cytotoxic lymphocytes, antibodies, peptides, hormones and cytokines have been implicated[4,6]

According to Zupancic et al., paraneoplastic arthritis can be difficult to diagnose in the absence of a known malignancy.[4] This difficulty is illustrated by the two cases discussed above, where the symptoms of arthritis preceded the detection of malignancy. Similar to other reports, both our patients presented with symptoms suggestive of an inflammatory arthritis which were subsequently diagnosed and treated as rheumatic diseases.[4] In the first patient, the malignancy was found following and abnormal routine chest radiograph. Similarly, for the second patient, the malignancy only became apparent after the patient presented with abdominal pain requiring surgical intervention, resulting in the diagnosis of a stage IIIc ovarian carcinoma.

Finally, both our patients exhibited poor response to DMARDs and showed improvement after treatment of their underlying malignancy, leading to the suspicion of paraneoplastic arthritis. This poor response to DMARDs and improvement with antineoplastic therapy was described by both Briones et al. and Zupancic et al. in two different case reports.[3,4] Briones described a patient who presented with polyarthritis and responded poorly to glucocorticoid therapy and was subsequently diagnosed with lingual carcinoma. The patient was treated with antineoplastic therapy, leading to progressive resolution of the arthritis.[3] Similarly, Zupancic described a patient with a history of migratory inflammatory asymmetric polyarthritis which responded poorly to prednisolone. The patient was subsequently diagnosed with small cell lung carcinoma, and arthritis symptoms resolved with treatment of the malignancy.[4] Hence, it is important that occult malignancy be suspected as a cause of arthritis in a patient who responds poorly to DMARD therapy.