Bone Pain in a 4-year-old Boy with Chronic Granulomatous Disease and History of Aspergillus pneumonia.

Abstract

CASE A 4-year-old boy with chronic granulomatous disease, status post autologous peripheral stem cell rescue 6 months prior, presented to our clinic with a 3-week history of right leg and ankle pain progressing to a limp in the preceding 2 days. He was afebrile and had no other complaints. One week before the onset of right leg pain, he had fallen and twisted his ankle while running but recovered from the fall and continued to walk normally. He had been diagnosed with chronic granulomatous disease at age 20 months and was status post 2 attempts at allogeneic peripheral stem cell transplant with failure to engraft, followed by autologous peripheral stem cell rescue with engraftment. He developed Aspergilluspneumonia during the first transplant, 7 months before the onset of leg pain. This was treated with caspofungin, voriconazole and subsequently, a right upper lung lobectomy due to progression of lesions despite medical therapy. Caspofungin was discontinued after 3 months. His medication list was as follows: cefdinir suspension (13 mg/kg/day in 2 divided doses) for antibacterial prophylaxis, voriconazole suspension (200 mg twice daily or 26 mg/kg/day) for continued treatment of Aspergillus pneumonia and dapsone suspension (4 mg/kg/week) for Pneumocystis jirovecii pneumonia prophylaxis (he had a recent history of elevated transaminases which coincided with initiation of trimethoprim/sulfamethoxazole prompting its replacement with dapsone). On physical examination, he was a well-appearing, playful boy in no acute distress. His vital signs were as follows: temperature of 36.2°C, blood pressure of 100/60 mm Hg, pulse rate of 108 beats per minute, weight of 15.2 kg, height of 102 cm and BMI of 14.6 kg/m2. Musculoskeletal examination was significant for tenderness to palpation along the anterior surface of the right tibia, from about 4 cm below the knee to the ankle. He also had discomfort when the right calf was palpated. There was no erythema or swelling of the right leg, knee or ankle. The rest of the physical examination was normal. A complete blood count showed a leukocyte count of 5.6 × 109/L (with 44% neutrophils, 38% lymphocytes, 12% monocytes and 5% eosinophils), hemoglobin of 11.5g/dL and platelet count of 236 × 109/L. The peripheral smear was normal. The erythrocyte sedimentation rate was 16 mm/h and C-reactive protein was 5.5 mg/L (reference: ≤8 mg/L). Chemistries were as follows: alkaline phosphatase 385 U/L (reference: 93–309 U/L), alanine aminotransferase 62 (reference: 7–55 U/L), creatine phosphokinase 56 U/L (reference: 0–249 U/L), uric acid 3.9 mg/dL (reference: 2–5.5 mg/dL), creatinine 0.3 mg/dL (reference: 0.1–0.5 mg/dL), calcium 9.7 mg/dL (reference: 9.6–10.6 mg/dL), phosphorus 5.2 mg/dL (reference: 3.6–5.2 mg/dL), total 25-hydroxy vitamin D 47 ng/mL (reference: 20–50 ng/mL), parathyroid hormone 19 pg/mL (reference: 15–65 pg/mL) and lactate dehydrogenase of 234 U/L (reference: 120–345 U/L). The most recent voriconazole trough serum concentration was 2.5 mcg/mL (reference: 1–5.5 mcg/mL). Radiographs of both lower extremities including the hip and ankle joints showed no significant abnormalities besides mild bilateral genu valgum and growth recovery lines at the ends of long bones with no evidence of rickets. Magnetic resonance imaging of the lower extremities with and without intravenous contrast (shown in Fig. 1A, B) revealed a homogenously enhancing, elongated focal area of abnormally increased T2 signal within the bone marrow of the distal right tibial diaphysis 4 cm above the distal growth plate extending for a length of 2.5 cm. There was periosteal reaction with mild edema and enhancement in the adjacent posterior lateral myofascial planes. There was also a faint smaller focal area of abnormal T1 and T2 signal in the proximal right tibial shaft measuring 1.2 cm. A similar but larger area of abnormal signal was identified in the proximal left tibial shaft. The symmetric nature of these abnormalities was thought to represent a chronic osteitis, osteomyelitis or tibial stress reaction.FIGURE 1: Magnetic resonance imaging of the lower extremity with and without intravenous contrast revealing a homogenously enhancing, elongated focal area of abnormal increased T2 signal within the bone marrow of the distal right tibial diaphysis and periosteal reaction with mild edema and enhancement in the adjacent posterior lateral myofascial planes. A) Contrast MRI of the right tibia showing an elongated focal area of abnormal increased T2 signal within the bone marrow of the diaphysis. B) Contrast MRI showing a focal area of abnormal increased T2 signal within the bone marrow of the proximal left tibial diaphysis.Additional blood tests led to the diagnosis.