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Our observations and those of other authors support the opinion that children with sickle cell disease have a predisposition to osteomyelitis and that there is a tendency for Salmonella organisms to be the infecting agents. Of the eight cases of Salmonella osteomyelitis complicating sickle cell disease now fully described, six were in children 1 to 4 years of age and two were in children 14 years old. This suggests that this combination of diseases occurs chiefly in young children. There is a marked disposition to multiple bony involvement in this syndrome. Roentgenograms of affected bones have a characteristic appearance. Changes include irregular destructive areas, periosteal proliferation, cortical fissuring and in some instances pathologic fractures. Although chloramphenicol is generally the most effective antibiotic in Salmonella osteomyelitis, it is difficult to eradicate completely the offending agent. Perhaps this is partly due to the extensiveness of the pathologic process with involvement of many bones. Perhaps it is related to local abnormalities in the bones of these patients with sickle cell disease. Owing to repeated thrombosis of vessels in bones, an inherent aspect of sickle cell disease, it may be more difficult to achieve high concentrations of antibiotic in the infected areas. Osteomyelitis should be considered as a possibility in children with sickle cell disease who have pain or swelling in one or more extremities, or who seem unusually irritable when moved. The fact that these manifestations are usually due to vascular thromboses should not blind the clinician to the possibility of bone infection. Cultures of the blood and stool should be obtained. If pathogenic bacteria are isolated their antibiotic vulnerability should be determined. As Salmonella organisms and hemolytic staphylococcus aureus are the chief organisms so far reported to cause osteomyelitis in children with sickle cell disease, when bone infection is present but results of cultures and sensitivity tests are not yet known chloramphenicol and erythromycin would appear to be the logical combination of antibiotics.