Primary Sternal Osteomyelitis in Children With Sickle Cell Disease

Sternal osteomyelitis is rare and occurs usually poststernotomy for open heart surgery. Primary sternal osteomyelitis has rarely been described in those with intravenous drug abuse, immunodeficiency, acne fulminans, palmoplantar pustulosis, SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis and osteomyelitis) and vascular access infection.1, 2 We report five cases of primary sternal osteomyelitis in children with sickle cell hemoglobinopathy. Because sickle cell disease (SCD) has not been previously described as a risk factor, we report the clinical presentation, the bacteriologic results and the outcome from therapy of these cases. Methods. All patients <15 years of age diagnosed with primary acute hematogenous sternal osteomyelitis from 1987 through 1997 were included in this retrospective review. All medical records and results of bacteriologic, radiologic and radionuclide bone scan were reviewed. Cases that occurred after surgery, trauma or primary bone pathology were excluded. Osteomyelitis was confirmed by the presence of pus aspirated from bone or the presence of bacteria in blood or bone aspirate culture coupled with suggestive symptoms and signs of bone infection or by radiologic findings consistent with osteomyelitis. Results. During the study period five patients (four male) had acute sternal osteomyelitis. Their mean age was 2.2 years (range, 0.8 to 3.6 years). All had had previous bone vasoocclusive crisis related to SCD. None had a history suggestive of immunodeficiency, HIV exposure, diabetes mellitus, indwelling catheter, chest trauma, cardiopulmonary resuscitation, diagnostic sternal bone marrow aspirate, recent history of varicella or other cutaneous bacterial infection, intravenous, drug abuse, acne fulminans, palmoplantar pustulosis, SAPHO syndrome, descending necrotizing mediastinitis or hemodialysis. One week before the diagnosis of osteomyelitis, one patient developed Salmonella C1 enteritis and bacteremia, with a temperature 40°C and toxicity; the peripheral white blood cell count and differential were normal. Despite intravenous ceftriaxone therapy to which the organism was susceptible (100 mg/kg/24 h), fever persisted and the findings of osteomyelitis appeared 5 days later. The mean duration of symptoms before diagnosis was 4 days (range, 1 to 7). All five patients had fever, sternal swelling, tenderness and fluctuation. None had another focus of bone infection or mediastinitis. The mean values for leukocyte count were 24.8 × 109/l (range, 15 to 53), absolute neutrophil count 16.6 × 109/l (range, 8 to 32), absolute band count 0.6 × 109/l (range, 0 to 3) and erythrocyte sedimentation rate 63 mm/h (range, 15 to 140). The serum immunoglobulin values were normal for age, and skin tuberculin testing was negative in all. Hemoglobin electrophoresis with agar at acid pH (6.1 to 6.2) showed the presence of sickle cell hemoglobinopathy in all five patients. Four patients had homozygous SCD with elevated hemoglobin (Hb) F, a common variant in Saudi Arabia: their mean HbS concentration was 64.3% (range, 61 to 67%), mean HbF 34.5% (range, 32 to 37%). One child had HbS-beta-plus thalassemia (HbS 63%, HbF 19%, HbA 18%). None of these 5 children was splenectomized or had symptoms of gallstones. During the same period another 20 patients developed acute osteomyelitis in sites other than the sternum; 9 had SCD of whom 5 had Salmonella as the causative organism. Sternal osteomyelitis constituted 20% of all cases of osteomyelitis and 37.5% of cases osteomyelitis in children with SCD. Roentgenography of the sternum showed soft tissue swelling (5 patients), demineralization (2), destructive bone changes (2) and sequestrum (1). Computed tomography with contrast was performed in three patients and showed soft tissue swelling (3 patients), irregular sternal contour (1) and small loculations in the parasternal area with inflammatory changes (1). None had mediastinal extension. [99mTc]Technetium methylene diphosphonate bone scan showed decreased uptake in the two patients on whom it was carried out early in the course of the disease. [67Ga]Gallium citrate bone scan was performed on one patient and showed increased uptake. Salmonella species were responsible for all five cases: type B (2); type C1 (2); and type D (1). Salmonella were identified in the culture from bone aspirates of all five cases and in three of the five blood cultures. All patients received a total of 6 weeks of antibiotic therapy that included ceftriaxone in all, followed after 2 weeks by oral ampicillin in one and oral cefaclor in another patient. Three children required surgical drainage. All five patients made a full recovery. No residual sternal or chest wall deformities were seen at up to 5 years of follow-up. Discussion. Primary sternal osteomyelitis is rare in childhood.1 Review of large series of osteomyelitis in Nigeria and Saudi Arabia, totaling 359 children, revealed only 2 cases of sternal osteomyelitis, both in children with SCD.3-9 Our 5 patients are the largest pediatric series reported to date. The condition represented 20% of all cases of osteomyelitis in our center and 35.7% of those that occurred in children with SCD. Although Staphylococcus aureus, Pseudomonas aeruginosa, mycobacteria and Aspergillus fumigatus were responsible in previously reported cases, Salmonella species was the causative organism in our patients, all of whom had SCD, where this organism is known to cause bone infection.3, 6 Previous studies have shown a decrease in the incidence and severity of complications in SCD with elevated fetal hemoglobin, caused by either persistently high levels of fetal hemoglobin or to association with the alpha-thalassemia gene. For reasons that are unclear, sternal osteomyelitis developed in our patients with SCD despite an elevated fetal hemoglobin. Patients with SCD are susceptible to Salmonella species and to encapsulated organisms, as a result of splenic dysfunction, defect in the alternative complement pathway and abnormalities in opsonization and phagocytosis. Gastrointestinal carriage of Salmonella has been suggested as a factor for Salmonella infections in patients with SCD. Vasoocclusive ischemic episodes of the digestive tract may lead to mucosal barrier breakdown, predisposing to repeated episodes of bacteremia with intraluminal Salmonella.6 This may explain the occurrence of Salmonella sternal osteomyelitis in one patient a few days after an episode of enteritis and bacteremia caused by the same organism. Although no routine stool cultures were performed in the other four patients, who did not have gastrointestinal symptoms, previous studies in the United States did not show an increased rate of Salmonella carriage in patients with SCD.10 No similar studies of Salmonella carriage in patients with SCD have been conducted in Saudi Arabia, but as reported by the Epidemiology Unit in our company (unpublished data), the incidence rates of Salmonella infections between 1983 and 1993 were similar in Saudi Arabs (220 × 105) and North American workers (199 × 105) (P = 0.24), making it unlikely that the Salmonella carriage in our population of Saudi patients with SCD would be different from the North American study. Although gallstones are common in patients with SCD and increase the risk of biliary carriage of Salmonella, our patients were asymptomatic for gallstones and those are uncommon before 10 years of age. Sternal avascular necrosis is rarely seen in patients with SCD before adolescence. Although all patients had a history of vasoocclusive crisis, none had any episode of bone infarction. The characteristics of the sternal bone may explain its susceptibility to infection with Salmonella organisms. It is porous, with extensive Volkmann's canals and haversian system but with fewer reticuloendothelial cells to fight organisms. The abundant amount of red marrow in its medullary cavity is especially susceptible to Salmonella infection, which can persist at that site for a long time. Given the brief duration of symptoms, the finding of destructive bone changes in two children is surprising, especially that they were not younger, nor was the duration of symptoms longer than in the other children. It is possible that the infection may have started at a low grade, with progressive bone destruction before the inflammatory symptoms and signs became clinically apparent later. Although increased bone up-take on radionuclide studies is suggestive of osteomyelitis and decreased uptake is more commonly seen in bone infarction, two patients had decreased uptake early in the course of the disease, which may potentially have misled physicians into diagnosing bone infarction instead of infection. A possible explanation for that unusual finding may be that bone infarction might have occurred first and predisposed to the infection. Primary sternal osteomyelitis is a rare condition and should be considered in children presenting with fever, anterior sternal pain, redness, tenderness and swelling over the sternal area. Other conditions, such as cellulitis, soft tissue abscess and tumors, also should be considered, as well as aseptic bone infarction in those who also have SCD. Diagnosis should be confirmed by bacteriologic studies of pus aspirated from bone. Radiologic or bone scintigraphic studies may not be required. Early treatment with appropriately chosen antibiotics is required, with an antistaphylococcal agent and an antibiotic with activity against Salmonella for children who have SCD, adjusted later according to the culture findings. Surgical drainage involves a limited resection of the anterior sternal periosteum and infected bone, leaving intact the posterior periosteum, if not infected, to maintain the integrity of the mediastinum. Our experience illustrates the good outcome with this approach and that SCD should be added to the list of risk factors for primary sternal osteomyelitis. Hassib Narchi, F.R.C.P.