A boy of early school-age with a painful foot

A previously healthy boy of early school-age was brought by one of his parents to his general practitioner (GP) with pain in his right forefoot, after a trauma to the foot six days earlier. A plain radiograph revealed no sign of skeletal injury, and the pain was treated symptomatically with over-the-counter analgesics.

Six weeks later, the boy was referred urgently from the out-of-hours primary healthcare service to a paediatric outpatient clinic owing to suspected juvenile idiopathic arthritis. The suspicion was based on several weeks of increasing pain, swelling and warmth in the right knee, which had become noticeably worse over the past four days. Clinical examination revealed warmth and erythema over the patella, as well as an extension deficit. Blood tests showed haemoglobin 14.0 g/dL (reference range 11.6–14.0), platelets 245 × 10⁹/L (210–590 × 10⁹), leukocytes 4.9 × 10⁹/L (3.5–14.0 × 10⁹) and CRP 1 mg/L (<5). Tests for ANA, ANA Hep2, rheumatoid factor and anti-CCP were negative. The patient was assessed the same day by a rheumatologist, who performed an ultrasound scan of the knee. This showed signs of increased prepatellar vascularisation in the absence of any obvious effusion. Prepatellar bursitis was considered the most likely diagnosis, and symptomatic treatment was initiated with ibuprofen (400 mg orally up to three times a day).

A further six weeks later, and twelve weeks after symptom onset, the boy attended a scheduled outpatient appointment in the paediatric department. The pain and swelling in his knee had resolved, but he now had pain on the medial side of his right ankle. No swelling, warmth, or restriction of movement were seen in the ankle or any other joint. His gait was normal, with no sign of a limp, and he had no fever or nocturnal pain. Arthritis and other systemic diseases were therefore considered unlikely. No further blood samples were taken, and no diagnostic imaging of the ankle was performed. The ankle pain was attributed to fallen arches and possibly incorrect loading of the joint as a result of the bursitis.

In parallel with the follow-up by the paediatric department, and eleven weeks after symptom onset, the boy attended his GP surgery along with his mother due to swelling and a feeling of heaviness in the right hemiscrotum. The swelling had developed gradually over several days, and the boy noted a sensation of pressure in the scrotum while running. He had little pain and no urinary symptoms. On examination, the GP found painless swelling of the right hemiscrotum, but no warmth or erythema. The scrotal swelling was not discussed at the paediatric outpatient clinic.

The gradual onset of symptoms and absence of pain meant that testicular torsion was considered unlikely. The patient received a fast-track referral from his GP for an ultrasound scan, which was performed a week later. This revealed normal-sized testicles with preserved blood flow, but a markedly enlarged, hyperemic caput epididymis, as well as 180-degree rotation of the distal spermatic cord. The GP contacted the on-call surgeon, and an additional ultrasound scan and clinical assessment were arranged with the surgeon for two weeks' time.

The second ultrasound showed similar findings, and at the surgical outpatient clinic, the gradually increasing but painless right-sided hemiscrotal swelling was confirmed. Fifteen weeks had now passed since the boy first reported pain in his foot, and about four weeks since the onset of the scrotal symptoms. After consultation with a paediatric surgeon at the university hospital, it was decided that the swelling was most likely due to torsion-detorsion, and surgical exploration and orchiopexy were scheduled for the next day. During the operation, no signs of torsion were found, but the radiological findings of normal-sized testicles and a greatly enlarged right caput epididymis were confirmed. The orchiopexy was performed as planned.

Just under two weeks after the orchiopexy, and 17 weeks after symptom onset, the boy sustained an elbow trauma. A plain radiograph showed the anterior fat pad sign, suggesting a possible fracture. The injury was treated conservatively with a sling at the orthopaedic outpatient clinic. While at the clinic, the boy again reported pain in his right foot, and he was referred for assessment by a paediatrician the next day. The paediatrician noted pain upon weight-bearing, but no obvious swelling or warmth. Rheumatic disease was still considered unlikely, and the boy was advised to continue with his existing symptomatic treatment. No further diagnostic testing was performed.

A little over a month later, and now 22 weeks after symptom onset, the boy presented at the out-of-hours primary healthcare service with his mother with a 3-day history of worsening pain in his foot upon weight-bearing and nocturnal pain. He was referred for urgent assessment at the paediatric outpatient clinic. Examination revealed erythema and tenderness to palpation over the medial tarsal bones. The boy also had noticeable swelling under both eyes. Blood tests revealed haemoglobin 13.7 g/dL, platelets 350 × 10⁹/L, leukocytes 7.0 × 10⁹/L, CRP 10 mg/L and a sedimentation rate of 9 mm/h (<5). Urine dipstick analysis was negative. A plain radiograph of the ankle was considered normal, and the patient was initially sent home. However, when an experienced radiologist scrutinised the images later that evening, s/he noticed that one of the cuneiform bones had an uneven structure, with a small area in the centre that appeared slightly more lucent than the surrounding areas (Figure 1). The patient was therefore admitted for further testing the next day. An MRI scan showed widespread bone marrow oedema in the bones of the foot as well as two suspected abscesses in the cuneiform bones (Figures 2 and 3). Infectious osteomyelitis with abscess formation was considered the most likely diagnosis. Empirical antibiotic therapy was initiated with intravenous clindamycin (10 mg/kg four times daily). An urgent needle biopsy of bone tissue and abscess drainage under general anaesthesia were also scheduled.

No pus or signs of bacterial infection were observed perioperatively. Chronic recurrent multifocal osteomyelitis was therefore considered a more likely diagnosis. The patient remained in hospital and antibiotic treatment was continued pending the biopsy and culture results. Analgesia in the form of naproxen (250 mg twice daily) and paracetamol (500 mg up to four times daily as required) was also initiated, as recommended for the treatment of chronic recurrent multifocal osteomyelitis.

Six days after surgery, the biopsy results from the suspected abscess revealed massive infiltration of B lymphoblasts. The boy was transferred to the university hospital the same day to undergo testing for lymphoma and leukaemia. On examination, his general condition was found to be good. He had swelling under both eyes with small, hard, palpable infiltrates bilaterally and a small cutaneous lesion ventrally on the left side of the thorax. Palpation revealed both testicles to be pathologically enlarged, to 6 cm and 3 cm on the right and left sides, respectively. There was no hepatosplenomegaly or generalised lymphadenopathy. Flow cytometric analysis of the bone marrow showed 35 % immature B lymphoblasts from the right iliac crest and 14 % from the left iliac crest. The boy was diagnosed with pre-B acute lymphoblastic leukaemia (ALL).

Induction therapy for pre-B acute lymphoblastic leukaemia was started in accordance with the ALLTogether protocol, a large multinational research and treatment study for children and young adults aged 1–45 years with acute lymphoblastic leukaemia (clinicaltrials.gov: NCT04307576). The study is based in part on the earlier Nordic NOPHO ALL-2008 protocol (1). The boy showed a good clinical response to the induction therapy. After a few days, the pain in his foot had significantly decreased, the cutaneous infiltrates underneath his eyes had disappeared, and his testicles had decreased in size.

Upon evaluation of minimal residual disease in the bone marrow on day 29 after the start of induction therapy, the boy was found to be in complete remission with no evidence of disease. He continues to receive treatment in line with the standard risk arm of the ALLTogether study protocol and has been informed that his prognosis is good.