Appendicular Infection

Etiology

Bacteria are the most common cause of osteomyelitis. The bacterial pathogens vary with age and also with certain groups of patients ( eTable 65-1 ). However, the predominant cause of osteomyelitis is Staphylococcus aureus , in all age groups. Methicillin-resistant S. aureus (MRSA), in the last decade, has become a common causative agent. The majority of the MRSA carries the gene Panton-Valentine leukocidin, which produces a cytotoxin that destroys leucocytes. Infection with this strain is associated with more severe disease presentation and complications, which frequently require surgical intervention.

Group B streptococcus is the next most common cause of osteomyelitis in children. Haemophilus influenza infection has significantly reduced recently with the widespread use of vaccination. Gram-negative bacteria, such as Escherichia coli and anaerobes, are uncommon and more frequently found in adult and diabetic cases. Staphylococcus epidermidis osteomyelitis is common in intravenous drug abusers and those with joint implants. Salmonella osteomyelitis is frequently seen in patients with sickle cell disease, although S. aureus is still the most common cause in this group.

S. aureus adheres to bone by expressing receptors (adhesins) for components of bone matrix (fibronectin, laminin, collagen, and bone sialoglycoprotein) and cartilage. It also elaborates fibronectin-binding adhesins, which enable it to attach to surgically implanted devices in bone.

Prevalence and Epidemiology

Acute hematogenous osteomyelitis is predominantly a disease of children (85% of cases occur in children), whereas the posttraumatic or contiguous-focus type of osteomyelitis is more common in adults and adolescents. Contiguous-focus osteomyelitis forms about half of all cases of osteomyelitis.

According to the literature, the incidence of acute osteomyelitis in the developed world is 1 case per 5000 children. Data on the incidence or prevalence of acute and chronic osteomyelitis in adults are not available. The incidence is thought to be much lower with widespread use of antibiotics.

The risk of chronic osteomyelitis after an episode of acute osteomyelitis is 5% to 25%.

Appendicular osteomyelitis is predominantly a disease of the lower limbs, accounting for about 90% of cases, and the remaining 10% occur in the upper limbs. The most common bones affected are the tibia (50%) and the femur (30%).

Clinical Presentation

The main factors that determine clinical presentation are virulence of the infective pathogen, the dose of the inoculum, and the immune status of the host. Traditionally, osteomyelitis has been subdivided into acute, subacute, and chronic, on the basis of speed of onset and course of the infection.

Acute osteomyelitis commonly occurs in children, with approximately half of the cases occurring in children younger than 5 years. It is rapid in onset and may present as systemic toxicity. This is especially seen in children in the bacteremic phase of the infection. Nonetheless, almost 50% of cases may not manifest any of the acute systemic features. The bones most commonly affected are the tibia, the femur, and the humerus. Other sites affected are the metaphyseal equivalents, such as apophyses of long bones and synchondroses of pelvis, particularly in older children. Multifocal infections are also seen. This is more common in neonates (22%) than in children (7%).

The patient presents with pain and unwillingness to use the affected limb and as an unwell and irritable child. Toddlers may present with a limp. Redness, swelling, and warmth due to acute inflammatory response may be seen in the affected part. However, this is also seen in bone tumors. The laboratory results may indicate an elevated white blood cell count and increased levels of inflammatory markers, such as erythrocyte sedimentation rate (ESR) and C-reactive protein, but the absence of such changes does not exclude the diagnosis. The blood cultures are positive in only 50% of cases.

The presentation of subacute osteomyelitis or Brodie abscess is more insidious. This may be secondary to inadequate treatment or low virulence of the organism. The disease may have been present for several months. Indolent pain is the predominant presentation, which may be worse after activity. Swelling may be present, but redness is normally not seen. Effusion in the adjacent joint and some atrophy of the muscles may be noted. Systemic toxicity is conspicuously absent. Subacute osteomyelitis is more common in adolescent boys, with the knee and ankle being the sites of predilection.

Subacute osteomyelitis may progress to chronic osteomyelitis, which generally presents as recurrent attacks of acute inflammation over a period of more than 6 weeks to many years. Pain is the predominant presenting symptom. On occasion, a discharging sinus may be the presenting complaint in an otherwise asymptomatic patient. On examination, the bone may feel thickened, and a number of skin scars from old healed sinuses may be seen. Anemia and generalized malnourishment may be noticed in long-standing cases. A previous history of acute osteomyelitis, trauma, or orthopedic implants that were complicated by infection is often present.

Pathophysiology

The infection of bone can occur by one of four main routes: hematogenous, spread from contiguous source, direct implantation, and postoperative infections.

The infection has a predilection for growing ends of appendicular bones. The infective pathogen tends to lodge at the metaphyseal vessels in acute hematogenous infection. These metaphyseal vessels have slow but turbulent flow of blood, reduced leukocytes, as well as impaired phagocytic ability, which are conducive to proliferation of infective organisms.

Anatomy

The anatomy of the vasculature of the appendicular long bones varies with age. The metaphyseal and epiphyseal vessels are distinct and separated by the growth plate in children, but communication is present in infants and adults after the fusion of the growth plate. Therefore, infection can easily extend into the epiphyseal region in the infants and adults. Infection in the epiphyseal region can potentially spread to the joint, causing septic arthritis. In some joints, such as the hip or shoulder, where the metaphysis lies within the capsule, septic arthritis can occur from a breach of the metaphyseal cortex.

Pathology

Acute hematogenous osteomyelitis commonly affects children and is relatively uncommon in healthy adults, but it can occur in immunocompromised individuals or intravenous drug abusers. The metaphyses, especially around the knee, are sites of predilection. These are sites of rapid growth and are also more prone to trauma in children. The onset of infection triggers the inflammatory response with influx of leukocytes and exudate formation. The intraosseous pressure is raised due to edema within the rigid medullary cavity, producing thrombosis of vessels. This further exacerbates and spreads the infective process. Ultimately, the exudates track through the haversian canals of the cortex, which is particularly thin at the metaphysis. The spread of inflammatory exudates to the subperiosteal region elevates the periosteum. This causes periosteal vessel thrombosis, leading to cortical necrosis. The enzymes released by the bacteria, polymorphonuclear cells, and dying tissues further contribute to the local bone marrow and cortical necrosis.

The elevation of the periosteum also triggers the osteoblasts to produce new bone, which manifests as periosteal reaction. This response is earlier and more florid in children but is delayed and somewhat patchy in adults. In children, the periosteum is loosely attached and, therefore, can be easily peeled off, manifesting as an early periosteal reaction, whereas, in adults, it is more firmly attached. This periosteal new bone formation is seen radiographically but better and earlier noted when using MRI and ultrasonography.

Necrotic bone fragment bereft of vascularization is dense relative to vascularized bone. The vascularized bone undergoes demineralization due to the inflammatory response. Areas of infected bone also undergo destruction due to osteoclastic action. These are seen as patchy osteopenic areas on plain radiographs, whereas the devascularized bone fragment, which is referred to as sequestrum, stands out as a dense bony fragment within patchy osteopenia on radiographs and CT. The sequestrum is of low signal intensity on all pulse sequences on MRI (see Fig. 65-1 ). The dead sequestrum can harbor infective organisms. These may be difficult to eradicate, unless the sequestrum is removed and the infective area is thoroughly cleaned and débrided. Therefore, the presence of sequestrum has the potential to make the infection chronic with risk of future acute exacerbations.

The periosteal new bone formation that takes place is referred to as involucrum and attempts to contain the infection. This tends to surround the infected area and has pathologically a soft spongy texture. If the infection is controlled, then the involucrum undergoes remodeling and bridges the gap in the cortex.

If the infection is not adequately controlled, then the infective exudates may breach through the involucrum, producing an opening called cloaca. The pus may then accumulate in the soft tissues to form abscesses before tracking through the soft tissues to break through the skin as a sinus. The cloaca may be seen on plain radiographs but is difficult to detect, unless a sinogram is performed before the examination. The sinogram can delineate the soft tissue track of the sinus and abscesses as well as indicate the sites of the cloacae ( eFig. 65-1 ). Sinography is now less frequently undertaken because the cloaca and soft tissue abscesses and fistulous track may be exquisitely seen on MRI ( eFig. 65-2 ). CT can delineate the cloacae and abscesses in the soft tissues as rim-enhancing collections.

When the infection is adequately controlled and healing has taken place, the infected marrow undergoes cystic changes with fatty infiltration, and the bony cortex undergoes remodeling.

Biomechanics

The biomechanical significance of osteomyelitis is that the infected bone is not strong and is prone to pathologic fractures. This is a particular problem of long-standing chronic osteomyelitis.

Imaging Techniques

Osteomyelitis is a potentially treatable disease, but early diagnosis is critical to avoid extensive damage and morbidity. Although clinical findings combined with laboratory results and imaging findings are unambiguous in most cases, there are a significant number of cases in which the diagnosis may not be clear, especially in children. In addition, the differentiation from other conditions, such as tumors and fractures that have completely different management pathways, means that the imaging has to be tailored with close cooperation between various disciplines.