The earliest manifestations of leukaemia often include rheumatic signs and symptoms. Arthritis is a well recognised complication of leukaemia in children, but acute and chronic leukaemia may also cause arthritis in adults. Leukaemic arthritis may occur at any time during the course of leukaemia and may be the presenting manifestation. It should therefore be considered in the differential diagnosis of both childhood and adult rheumatic disease. We present an adult patient presenting with arthritis due to acute leukaemia.
- synovial fluid analysis
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A significant number of patients with leukaemia have bone or joint symptoms as a part of their disease.1 However, arthritis as an initial manifestation of leukaemia is extremely rare.2 Leukaemic arthritis (LA) may be defined as joint pain and swelling in association with peripheral blood or bone marrow leukaemia after other causes of arthritis have been excluded.3 Early in the course of the disease there may be difficulty in arriving at the correct diagnosis when studies of peripheral blood are not diagnostic.
We report an adult patient presenting with arthritis whose peripheral smear was normal. However, examination of synovial fluid and bone marrow revealed LA and acute lymphoblastic leukaemia (ALL).
A 22-year-old man was referred to our hospital with complaints of pain and swelling of his ankles for the last 3 months. On initial evaluation, he was conscious and fully oriented. Body temperature, blood pressure, pulse rate were 38.3°C, 130/80 mmHg, and 86 beats/min, respectively. On physical examination there was diffuse swelling and tenderness with erythema and discharge in both ankles. Other physical findings were within the normal range. Haematological studies revealed a haemoglobin level of 9.6 g/dl, leukocytes 10.3 × 109/l (55% neutrophils, 22% lymphocytes, 19% monocytes, 4% eosinophils), platelets 310 × 109/l, with an erythrocyte sedimentation rate of 103 mm/h. Blood biochemical values were normal. Serum uric acid was 5.4 mg/dl (normal range 3.5–8.5 mg/dl). Antinuclear antibody, rheumatoid factor, and serological tests for hepatitis B were negative. Anti-DNA and serum complement level were within normal limits. Radiographs of the ankles showed soft tissue swelling and joint effusion (figure 1). The synovial fluid could not be aspirated during the first arthroscopy. The patient was prescribed indomethacin and colchicum for the pain, but during the following 2 weeks there was no benefit and the patient's symptoms increased, with complaints of pain and swelling of knees. Arthroscopy was repeated and cytologic examination revealed immature blastic cells (figure 2). Flow cytometric analysis of synovial fluid revealed CD19 58%, CD20 70%, and HLA-DR 91%. A bone marrow aspiration and biopsy was performed. Infiltration of leukaemic cells was seen on bone marrow aspiration (figure 3), and a diagnosis of ALL (L2, B-cell origin) was made. Mitoxantrone, vincristine and prednisolone were started immediately. However, his overall condition deteriorated and he died of neutropenia and sepsis on the seventh day of chemotherapy.
The leukaemias are a heterogenous group of neoplasms arising from the malignant transformation of haematopoietic cells. Leukaemic cells proliferate primarily in the bone marrow and lymphoid tissues where they interfere with normal haematopoiesis and immunity. Leukaemias are classified according to the cell types primarily involved (myeloid or lymphoid) and as acute or chronic based upon the natural history of the disease. Acute leukaemia can be identified and classified on the basis of morphology, immunologic phenotype, and cytochemistry (table). It is critical to distinguish ALL from acute myeloid leukaemia (AML) since these two diseases differ considerably in their clinical behaviour, prognosis, and response to therapy.4
In addition to suppressing normal marrow function, leukaemic cells can infiltrate normal organs. In general, this occurs more commonly in ALL than AML.4 LA, an uncommon complication of acute leukaemias, develops due to infiltration of synovial membrane by leukaemic cells. Childhood leukaemias (especially ALL) are complicated by arthritis more frequently than adult leukaemias. It has been reported that LA occurs in 12% of cases of childhood leukaemia,5 but leukaemia presenting with arthritis in an adult patient has been reported only in occasional case reports.6
Arthritis can occur at any time during the course of leukaemia and may rarely be the initial manifestation of the disease.7Proposed pathogenic mechanisms for arthritis in leukaemia include infiltration of leukaemic cells into synovial tissue, haemorrhage into the joint from thrombocytopenia, synovial reaction to periosteal or capsular infiltration, and immune-complex-induced synovitis. However, synovial infiltration appears to be the predominant mechanism.7 8 In acute leukaemias, arthritis usually presents early in the course of disease, whereas in chronic leukaemias it presents later and more symmetrically. Large joints, most commonly the knees, are usually affected, although involvement of the ankle, wrist, elbow, shoulder, and hip have been described.7-9
Involved joints are usually warm, swollen, and tender on palpation. Effusions, if present, are small; most swelling is due to synovial hypertrophy. Fever may accompany joint swelling.7-9 The diagnosis of LA may be difficult as it can mimic other rheumatic diseases, especially juvenile arthritis.10 In some cases of LA, the peripheral blood smear and complete blood count show nonspecific findings such as anaemia or mild leukocytosis, and bone marrow aspirate or biopsy is necessary to make the diagnosis. One method of diagnosing LA is direct pathological demonstration of synovial membrane infiltration by leukaemic cells. Leukaemic blasts may be present in specimens of synovial fluid, as in our patient.
leukaemia must be remembered in the differential diagnosis of arthritis of unknown aetiology which is resistant to palliative therapy
cytologic examination of synovial fluid and bone marrow examination can confirm the diagnosis in such patients
In conclusion, arthritis is a well recognised complication of leukaemia in children, but acute and chronic leukaemia may also cause arthritis in adults. LA may present before, after, or at the same time as the underlying disease. Because the leukaemia may not be obvious, another cause of the arthritis may be considered. As early diagnosis is one of the most important prognostic factors in leukaemia, this possibility must be remembered in the differential diagnosis of arthritis of unknown aetiology which is also resistant to palliative therapies. In such patients, cytologic examination of synovial fluid and bone marrow examination can be important diagnostic procedures.