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Q1: What are the differential diagnoses of the arthritis?
Migratory arthritis among children typically is described in acute rheumatic fever. Generally multiple joints are involved in an asymmetric pattern and the arthritis often subsides within a few days only to reappear in other joints over the next few days or weeks. If single joints are involved for more than a few days or weeks, other possible causes of arthritis, such as the systemic form of juvenile chronic arthritis (JCA), systemic lupus erythematosus, and septic arthritis should be considered. In our patient, even though the site and the migratory nature of the joint involvement are typical of rheumatic fever, the relatively prolonged joint symptoms are unusual for rheumatic fever. Moreover, the marked anaemia, negative antistreptolysin O antibodies and absence of carditis, chorea, or subcutaneous nodules make this diagnosis less likely. The patient's fever, generalised lymphadenopathy, hepatosplenomegaly, and anaemia are consistent for systemic onset JCA (Still's disease) or acute leukaemia. On the contrary, in systemic JCA there is characteristically thrombocytosis and leucocytosis with a neutrophilic predominance and thus the initial thrombocytopenia would be against this diagnosis. In our patient, the normal white cell count, thrombocytopenia and a poor response to conventional antirheumatic treatment have cast considerable doubt upon the diagnosis of Still's disease. Arthritis is a known manifestation of acute leukaemia but has rarely been described with a migratory pattern.
Q2: What do the peripheral blood and bone marrow smears show?
Microscopic examination of the peripheral blood smears (fig 1A, see p 717) shows prominent leucoerythroblastosis with presence of 30% lymphoblasts and severe thrombocytopenia. The bone marrow (fig 1B, see p 717) is heavily infiltrated by lymphoblasts constituting 95% of nucleated cells and immunophenotyping study confirmed the diagnosis of precursor B cell acute lymphoblastic leukaemia.
The patient received induction treatment with vincristine, daunorubicin, L-asparaginase, and prednisolone that resulted in complete haematological remission. The joint symptom settled rapidly after initiation of antileukaemic therapy and did not recur.
Children with a diverse group of malignancies including leukaemia, may first present to the paediatric rheumatologist
Although uncommon, arthritis may be the first symptom of leukaemia in children
Acute leukaemia remains an important differential diagnosis in children presenting with musculoskeletal pain and/or arthritis as delayed diagnosis and treatment could have a deleterious impact on prognosis.
Acute leukaemia is a great mimic of many diseases
Bone marrow study should be considered in all patients with unexplained anaemia and thrombocytopenia even in the absence of blasts in the peripheral blood
Although this is an interesting and previously recognised association of arthritis and leukaemia, most children with leukaemia do not present in this way, and conversely most children with a referral diagnosis of JCA probably have this diagnosis or a related connective tissue or vasculitic disorder, or possibly chronic fatigue syndrome, rather than leukaemia. Nevertheless, the multifarious presentations of malignant disorders in children should always be borne in mind, and in this case the initial thrombocytopenia is a key finding. Hence, leukaemia and other childhood malignancies remain important differential diagnoses in children presenting with musculoskeletal pain and/or arthritis. When it is the sole clinical finding, the diagnosis of JCA may be made initially and hence delay diagnosis of the underlying malignancy. In one study, three of 30 children (10%) referred for JCA had leukaemia (two had acute lymphoblastic leukaemia and one acute myeloblastic leukaemia),1 although this would not be as common in most series. All three patients had slight anaemia, normal to slightly reduced platelet count, mild neutropenia, and absence of blasts in the peripheral blood. In another study, nine (11.6%) of the 77 children studied in an orthopaedic clinic presented with the chief complaint of a limp and no history of trauma and were subsequently diagnosed with leukaemia.2 Raised erythrocyte sedimentation rate, anaemia, neutropenia, lymphocytosis, and thrombocytopenia were frequent manifestations among the patients. In general, initial articular and extra-articular symptoms are not helpful in differentiating leukaemic arthropathy from JCA. However, distinctive features suggesting a paraneoplastic arthritis were prominent thrombocytopenia, absence of neutrophilia, early significant osteopenia, and lytic bone lesions. The exact mechanism of development of arthritis in acute leukaemia is unknown. Leukaemic cells have been detected in the synovial fluid and histologic examination revealed proliferation into the synovium. Interleukin-1β secreted in great amounts by leukaemic B cells appears to be the major cytokine that mediates joint destruction in leukaemic arthritis. Human T cell leukaemia virus type 1, initially found as a causative agent for adult T cell leukaemia, has been lately proposed as a causative virus for several autoimmune disorders. The relationship between arthritis and this virus was clearly proved by epidemiological study. The transactivating gene of this virus, tax, is responsible for proliferation of synovial cells.3
Although arthritis is a known manifestation of haematological malignancies but migratory polyarthritis is unusual. Apart from this patient there have been only two reported cases of migratory polyarthritis subsequent to T cell lymphoma4 and myelofibrosis.5
Precursor B cell acute lymphoblastic leukaemia.
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