Paraneoplastic Arthropathies Of Solid Tumours

2.1. Cancer Arthritis

Occult malignancy is a rare cause of polyarthritis and its prevalence is unknown, although it seems to be similar to that of hypertrophic osteoarthritis (HOA) and dermatomyositis [1]. Cancer arthritis is a distinct entity not to be confused with HOA or with metastatic implants. The clinical manifestations of cancer arthritis are extremely varied, making it sometimes difficult to distinguish this disease from rheumatoid arthritis. The same is true with adult Still's disease when associated with unexplained fever or reflex sympathetic dystrophy syndrome, particularly two of its clinical variants (shoulder-hand syndrome and the syndrome of palmar fasciitis and polyarthritis).

The pathogenesis of paraneoplastic symptoms remains to be elucidated. One of the distinct mechanisms might be the deposition of immune complexes consisting of tumour antigens and host antibodies within the joint [2]. Cytotoxic lymphocytes may be produced by normal immune system against the host tumour, and an immune response to a target antigen within the joint might play a role in the cancer arthritis [3] An activated cytokine network is the third proposed mechanism. Elevated concentrations of interleukin-(IL)-lra, IL-6 [4] and IL-1 [5] in patients with malignant diseases and arthritis were described.

In a series of 18 patients with arthritis and cancer, 8 had typical rheumatoid arthritis while the other 10 had atypical features including an explosive onset, asymmetry and predominate lower limb involvement with sparing of the hands; only one of this latter group was rheumatoid factor positive. The arthropathy antedated the discovery of the tumour by a mean 10 months. In 8 of 11 patients, in whom the tumour could be treated, the arthritis improved, and relapsed in 2 of 3 cases with tumour recurrence [1]. In another series, 26 patients were described whose inflammatory arthropathy began within 2 years of discovery of a tumour. Four of these patients met the American Rheumatism Association's (ARA) criteria for definite rheumatoid arthritis, while 7 of the remaining 22 were rheumatoid factor positive and 3 had bone erosions. No consistent relationship between successful treatment of the ma lignancy and remission were found and in addition no correlation was noted between tumour location and development of arthritis. However, breast cancer was by far the most common cause of an asymmetrical arthritis in women [6]. Analysis of an additional 12 cases revealed symmetric arthritis and a positive rheumatoid factor in 10 and 6 patients, respectively. Therapy of the tumour resulted in complete disappearance of the joint symptoms in 9 of the 12 patients and amelioration was achieved in the remaining 3 patients. The arthropathy antedated discovery of the tumour from 15 days to 18 months. Although the late age at onset of arthritis was suggested as a typical feature of cancer arthritis, in this series of 12 patients the youngest was a 36-year-old man who suffered from testicular seminoma [7]. Another case of a 21-year-old man was reported in which symmetric polyarthritis antedate a discovery of a malignant fibrous histiocytoma of the heart by 5 months [8]. Besides the late age at the onset of arthritis, a predominant lower extremity involvement with sparing of wrists and small joints of hands was proposed as another typical feature of cancer arthritis. However, two cases were recently reported in which these two typical features were not observed. The first was 50-year-old man who presented with seronegative arthritis of the left elbow, wrists, metacarpophalangeal and proximal interphalangeal joints of both hands. Eleven months later laryngeal carcinoma was diagnosed [9]. The second case was a 49-year-old woman with a fever, seronegative symmetrical polyarthritis and erythematous rash. Six weeks after the onset of symptoms, a metastatic breast cancer was found [4].

The clinical course of a cancer arthritis usually parallels that of the tumour. Cure or significant remission of cancer usually but not invariably results in regression of the arthritis.

2.2. Palmar Fasciitis and Polyarthritis

Palmar fasciitis and polyarthritis (PFA) are considered as an atypical form of the reflex sympathetic dystrophy syndrome (RSDS). It differs from typical cases of RSDS in that the fasciitis is more severe, arthritis is more inflammatory and both are more rapidly progressive [10]. The association between PFA and the underlying malignant neoplasm was first described in an ovarian carcinoma. Six postmenopausal women

(aged 50-65 years old) developed PFA 5-25 months before the diagnose of ovarian adenocarcinoma was established. All had bilateral pain and a limitation of motion of the shoulders and hands, as well as prominent palmar fasciitis and polyarthritis. A nonresectable tumour with ascites and peritoneal metastatic seeding was found in all patients [11], In another series 5 patients, 3 women and 2 men were reported. The neoplasm with PFA in this study included chronic myelogenous leukaemia, adenocarcinoma of the pancreas, squamous cell carcinoma of unknown origin, and Hodgkin's lymphoma.

Rheumatologic symptoms occurred in close temporal relation to the discovery of malignancy in all patients. Arthritis involving joints in the upper extremities was seen in all patients, as well as a flexion contratures of the small joints of the hands resulting in Claw hand. Two patients exhibited also arthritis of the lower extremities, palmar and plantar faciitis [10], It is important to emphasise the aggressive fibrosing nature of the upper extremity lesions. Several patients described [10, 11] were initially misdiagnosed as having scleroderma, idiopathic fibromatosis or a fibrosing syndrome of unknown aetiology. Recently a patient with PFA associated with breast cancer was reported

[12]. The PFA syndrome has also been noted in a patient suffering from endometrial benign ovarian cyst

Rheumatologic symptoms are usually reluctant to nonsteroidal anti-inflammatory agents, corticosteroids, ganglion blockade or physical therapy but chemotherapy may offer some improvement [10]. Successful removal of a tumour may also be followed by a dramatic improvement in pain and vasomotor disturbances, but predictably, contractures improve at a slower rate [14].

2.3. Hypertrophic Osteoarthropathy

The syndrome of hypertrophic osteoarthropathy (HOA) is a well recognised complication of malignancy [15], It is characterised by digital clubbing, periostosis of the tubular bones and oligosynovitis or poly synovitis [16]. As a minimum digital clubbing and periostosis of the tubular bones must be present to diagnose HOA, it may be classified as either primary, which is usually hereditary, or secondary [17], The latter most commonly occurs in the setting of nonsmall cell lung cancer and lung metastases [15, 18]. Rarely the syndrome is also seen with lymphomas, hepatic, oesophageal and colon carcinoma as well as with some non malignant diseases. This is especially true with chronic infections, cystic fibrosis, pulmonary fibrosis, cyanotic congenial heart disease and liver cirrhosis [16].

The pathogenesis of HOA is uncertain, with neural involvement suggested by rapid response to vagotomy and atropine [19], Platelet-endothelial interaction with the production of von Willebrand factor antigen has been implicated in the pathogenesis of HOA [20]. It was also proposed that clubbing and HOA are the result of the peripheral impaction of megakaryocytes and platelet clumps in the fingers and toes, to which this particular matter has passed in an axial stream [21].

Synovial effusions, usually with an insidious onset, most often involves knees, ankles, wrists, and metacarpophalangeal joints. It is often associated with tenderness over adjacent bones. Synovial fluid from affected joints is typically noninflammatory [22], An isotopic bone scan may demonstrate a pericortical, linear concentration of nuclide along the shafts of affected bones and so permit an early diagnosis before periostal new bone formation is apparent on plain X-ray images [23]. The bone scan may be positive prior to the development of symptoms [16],

The treatment of HOA is rather disappointing. Successful treatment of the underlying diseases is usually associated with a rapid resolution of the problem. However, in most cases with lung cancer, the disease is often in the advanced state, making successful treatment difficult. Although nonsteroidal anti-inflammatory drugs and colchicine might be successful in pain relieving, many times, however, the symptoms do not respond to therapy [24].

2.4. Jaccoud's Type Arthropathy

Jaccouds arthropathy, characterised by a rapidly developing, nonerosive, deforming, painless arthropathy, has been associated with a variety of medical conditions (rheumatic fever, SLE, eosinophilic fasciitis, myocardial infarction, chronic obstructive lung disease and tuberculosis, and in otherwise apparently healthy patients). But it may be also an initial manifestation of metastatic lung carcinoma [25],

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