Case 1: Multifocal bone lesions in a teenager

A 15-year-old healthy female of East Indian decent presented with a two-day history of nontraumatic left ankle pain, swelling, erythema and fever, with a temperature up to 40°C. There was no other joint involvement, rashes, lethargy, weight or appetite loss, or night sweats. There was no history of recent travel, sick contacts or sexual activity. She took acetaminophen and ibuprofen for both pain and fever, but was on no other medications. Family history was negative for autoimmune conditions, inflammatory bowel disease and malignancy. Two years before she had presented with a one-week history of bilateral ankle pain followed by a four-day history of right ankle pain, swelling and erythema and a two-week history of daily fever, reduced energy and a 2.3 kg weight loss. At that time, her erythrocyte sedimentation rate (ESR) was 76 mm/h (normal 1 mm/h to 10 mm/h). Serology was negative for Epstein-Barr virus, varicella, Bartonella, Coxiella burnetii and toxoplasmosis. A malaria screen, and blood and urine cultures were negative. The joint was not aspirated at this time. Antinuclear antibody (ANA)/antineutrophil cytoplasmic antibody (ANCA) were negative and both complement component 3 and 4 were in the normal range. A bone scan (Figure 1A) showed multi-focal areas of increased activity in the right radius, right femur, and left and right tibia. She was treated with naproxen with complete resolution of her symptoms. Although there were no known tuberculosis (TB) contacts, she had a TB-positive skin test and a recent travel history to India so was treated with isoniazid for nine months for latent TB. Her ESR normalized after six months. Figure 1) Bone scans at initial presentation (A) and at admission, approximately two years later (B). X-rays of her tibia and fibula approximately one month later showed no abnormalities, other than generalized osteopenia. On current admission, she had a heart rate of 120 beats/min with a respiratory rate of 20 breaths/min and a temperature of 39.2°C. Physical examination revealed left ankle swelling and erythema, with an overall limited range of passive and active movement. Examination of her other joints was normal. The remainder of her examination was unremarkable. Twenty-four hours after presentation, despite complete resolution of her symptoms, she continued to spike fevers with temperatures >39°C. Her C-reactive protein was 20.5 mg/L (range 0 mg/L to 8 mg/L), ESR was 31 mm/h, white blood cell count was 2.9×109/L (normal 4×109/L to 10×109/L), neutrophils were 1.26×109/L (normal 2×109/L to 7.5×109/L), haemoglobin was 115 g/L (normal 120 g/L to 153 g/L) and her platelet count was were 173×109/L (normal 150×109/L to 400×109/L). Blood cultures were negative. Bone biopsy showed chronic inflammation with focal clusters of plasma cells. No malignant cells were noted. To rule out malignancy, given the low white blood cell count and boney lesions, a bone marrow aspirate was performed; it showed no increased blasts or malignant cells. Bone biopsy and bone marrow cultures were both negative for TB, bacteria and fungi. A bone scan (Figure 1B) showed intense tracer uptake in the distal left tibial metaphysis, right and left femoral meta-physis, symphysis pubis and both superior rami. X-rays of her clavicles appeared normal. She also underwent magnetic resonance imaging (MRI) of her lower extremities, which showed increased signal intensity in the left tibia and minimal joint effusion.

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