Chronic Multifocal Osteomyelitis Due to Clostridium difficile in an Adolescent With Sickle Cell Anemia

Abstract

To The Editors: Patients with sickle cell anemia (SCA) are at risk for osteomyelitis and septic arthritis, mainly involving long bones, caused by Salmonella species, Staphylococcus aureus, and other Gram-negative enteric bacilli.1 We report a case of multifocal chronic osteomyelitis of long bones caused by Clostridium difficile in a patient with SCA. A 13-year-old boy from Cameroon with homozygous SS SCA was hospitalized in France in July 2000 for evaluation of osteomyelitis of both femora, right tibia and fibula, and left radius present since January 2000. At admission he appeared healthy and afebrile. Radiographs and CT scans demonstrated widespread and heterogeneous metaphysodiaphyseal centromedullary cavities surrounded by osteosclerotic margins and cortical destruction of the involved bones. Magnetic resonance imaging (MRI) showed signal abnormalities of medullary cavities, suggesting multifocal chronic osteomyelitis. Fine needle aspirations of metaphyses in both femora, right tibia and fibula, and left radius, resulted in growth of C. difficile. Histopathology was consistent with chronic and subacute osteomyelitis. Stool and blood cultures were negative for the bacterium. Treatment with amoxicillin/clavulanic acid and metronidazole, to which the bacterium was susceptible, was given. Multiple relapses occurred, treated with penicillins, metronidazole, and vancomycin. Numerous soft tissue and bone debridements, excision of both condyles and trochlea, curettage of tibial plateaus with the use of external fixators in the Ilizarov technique of skeletal reconstruction,2 and bone graft or cement were performed during the following years. Most intraoperative specimens taken from different sites identified C. difficile, but in 2002 and 2004 superinfection of tibial fistulae with Staphylococcus aureus occurred. The last debridement was done in December 2007 for persistent fistulae in the scars of both legs with C. difficile on bacteriologic analysis. The patient never complained of symptoms related to the gastrointestinal tract and search for C. difficile in stools was always negative. Rare extracolonic manifestations of C. difficile infections are bacteremia, cellulitis and soft tissue involvement, intra-abdominal abscesses, infection of implanted prosthetic devices, and rheumatologic manifestations such as reactive arthritis and osteomyelitis.3 The presence of C. difficile from isolates may be difficult to interpret, and may represent contamination of extraintestinal organs with fecal flora. The presence of the bacteria in pure growth on several occasions and at different sites is strong evidence for its responsibility in the infectious process.3 Two patients with SCA have been previously described with osteomyelitis caused by this pathogen. One patient was a 30-year-old woman who presented with 2 areas of frontal bone osteomyelitis suspected to be hematogenous and recovering with bifrontal craniectomy and chloramphenicol.4 The other was a 15-year-old girl who had tibial osteomyelitis associated with mild colitis suggesting an invasion from the intestinal flora, treated successfully with surgical irrigation and debridement, and vancomycin and metronidazole.5 Our patient had multifocal chronic osteomyelitis suggesting a hematogenous spread. The infection was probably associated with intestinal breaches secondary to ischemic mucosae. Diagnosis of chronic osteomyelitis caused by C. difficile may be difficult to establish requiring the identification of the bacterium and study of the strain since resistance to antibiotics has been reported.5 Its treatment relies on a multidisciplinary approach combining antibiotics and surgery.2 Unfortunately, successful eradication of infection was not achieved in our patient despite an aggressive approach. Claude Bachmeyer, MD François Lionnet, MD Service de Médecine Interne CHU Tenon Paris, France Mathieu Gibeault, MD Service de Radiologie CHU Tenon Paris, France Jean-Pierre Damsin, MD Service d’Orthopédie CHU Armand Trousseau Paris, France