ORTHOPAEDIC

Haematogenous osteomyelitis
Malcolm F Macnicol Adam C Watts

Presentation
Children usually present early before any radiological abnormalities are evident. Symptoms may be muted or covert; beware of the child who is unwell with indeterminate symptoms, often with a history of mild trauma. Subdued infection (particularly within the confines of a joint) will leave destructive and irreversible change if treatment is delayed. Infection may mimic neoplasia and infiltrative disorders of the skeleton.

Osteomyelitis is an inflammatory reaction of bone to an infecting organism and can be classified as: exogenous (e.g. from a compound fracture or from surgical intervention) haematogenous (from a bacteraemia). Haematogenous osteomyelitis is more common in children than adults because of the: higher incidence of bacteraemia rich blood supply of the metaphysis and thick periosteum. The incidence of osteomyelitis of long bone is decreasing due to improving standards of living. Early referral and a more educated population ensure that chronic disease is rarely encountered in the developed world.

Principles of treatment
The principles of treatment are to: reduce the bacterial load by the use of antibiotics drain pus (if present) preserve articular function and normal bone growth. Reconstructive surgery for the late sequelae of bone and joint infection (although infrequent) merits specialist attention.

Classification
Osteomyelitis is classified according to the: route of entry of the infecting organism clinical presentation (i.e. acute, subacute, chronic). Chronic osteomyelitis in the adult may be further classified by anatomical pattern, as described by Cierney and Mader (Figure 1).

Malcolm F Macnicol is a Consultant Orthopaedic Surgeon at the Royal Hospital for Sick Children, Edinburgh, and a part-time Senior Lecturer in Orthopaedic Surgery at the Royal Infirmary, Edinburgh, UK. Adam C Watts is a Specialist Registrar in Orthopaedic Surgery on the South-East Scotland rotation.

Aetiology
Haematogenous osteomyelitis is more common in patients with: compromised immunity chronic illness

Cierny and Mader anatomical classification

Skin Soft tisue Pus Cortex Medulla

Medullary

Superficial

Localized 1

Diffuse

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malnutrition specific immunodeficiency. Children and adults may have deficiency in humoral or cellular immunity that may be congenital, acquired or induced by drugs. There is little evidence for familial predisposition to osteomyelitis. The haematogenous source may be a: minor skin abrasion dental procedure cannulation catheterization. The source can seed into any bone, although the vertebral bodies are most commonly affected. In children, there is a bimodal distribution, the most commonly affected being aged: under two years from 8 years to 12 years. The preferential focus is the metaphysis of long bones, although the pelvis, vertebrae and smaller bones (e.g. patella, calcaneum) are increasingly involved. Three biological factors predispose the metaphysis or cancellous bone to infection. Vascular anatomy In the infant, many epiphyses are entirely cartilaginous. The metaphyseal end-arteries are tortuous (Figure 2) and the blood flow is sluggish, allowing sedimentation of bacteria, which may then spread: subperiosteally along the medullary cavity into the adjacent joint if the metaphysis is intra-articular (Figure 3). In children, the physis usually acts as a barrier to infection, but in infants some microvessels may cross the growth plate, allowing

direct transgression to the joint. There is no such barrier in adults. Thus, septic arthritis is usually seen only in infants and adults. Preferential chemi-adsorption to cartilage The glycocalyx of the bacterial wall may preferentially adsorb to the chondrocytes and cartilage matrix of the growth plate. This chemi-adsorption is not seen with the trabeculum of bone. Systemic and local immunodeficiency Poor phagocytosis, deficient fixed-cell immunity and a lack of reticulo-endothelial cells within the metaphysis of bone are common factors in all patients with osteomyelitis. Also, children may have specific immunodeficiencies, e.g. in prematurity: the absence of breast-milk feeding in the neonate chronic granulomatous disease of childhood the lazy leukocyte syndrome hypogammaglobulinaemia IgA deficiency HIV.

Course of the disease

Five pathological phases characterize haematogenous osteomyelitis. Inflammation There is an acute inflammatory phase with exudation of fluid and ingress of polymorphonuclear lymphocytes (resulting in an increase in intra-osseous pressure) causing extreme pain and local tenderness. Suppuration Pus formation occurs over 4872 hours. With increasing pressure, pus is forced along the Volkmann canals to the surface of the bone, stripping the periosteum. The pus may then burst through the periosteum into the surrounding soft tissue (eventually forming a sinus to the skin) or into a joint (resulting in septic arthritis). Pus may travel along along the medullary canal of the diaphysis. Vertebral infection may spread through the end plate into the intervertebral disc (discitis, see below). Necrosis The increase in intra-osseous pressure may imperil the endosteal blood supply and, with stripping of the periosteum, osteonecrosis will occur. The result is a segment of dead bone (sequestrum) surrounded by pus, denuded of its blood supply. The physis may be irreparably damaged in infants. Avascular necrosis of the epiphysis may occur, and this is seen most commonly in the proximal femur and humerus.

Change in vascular anatomy of the metaphysis of long bones with age

Epiphysis Physis

Metaphysis Nutrient artery

Child <1 year

Child >1 year

Formation of new bone At 1014 days, the periosteum starts to lay down new bone from mesenchymal stem cells. A honeycomb of new bone will form an involucrum, ensheathing the sequestrum. Resolution Resolution will occur if this process is interrupted by antibiotic therapy and the release of pressure through surgical drainage. Delay in treatment may result in permanent deformity.

Bacteria may seed in this region

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Routes of spread of pus from the metaphysis

Proximal tibia Epiphysis Physis Pus Metaphysis Periosteum Joint capsule Metaphysis Proximal femur Epiphysis Joint space

Along medulla

To bone surface, lifting the periosteum

Into joint if metaphysis is intra-articular

Bacteriology
Staphylococcus aureus is the most common organism responsible for musculoskeletal infection. Although Staphylococcus aureus is implicated in up to 80% of cases, it is important to search for unusual bacteria or fungi. Haemophilus influenzae affects the infant or pre-school child (although it is much less common with the advent of vaccination). In the newborn, group B streptococcus or Escherichia coli should be considered if a staphylococcal isolate is absent. Other organisms commonly identified are: Streptococcus pyogenes proteus salmonella Serratia marcescens Clostridium welchii neisseria bacteroides Paracolon bacillus. Gram-negative bacteria may produce vertebral osteomyelitis. Pseudomonas or bacteroides are common isolates in users of intravenous drugs. Fungal infections may affect chronically ill patients on long-term antibiotic therapy. Salmonella may infect the diaphysis of long bones in patients with sickle cell disease. Management of infection Initial antibiotic treatment should be broad spectrum (i.v.), to cover the most likely organisms. This should be delayed (if possible) to obtain aspirates for culture. Antibiotics specific to the organism cultured should be used after microbiology specimens have been obtained. For adults or older children, flucloxacillin and fucidic acid (in preference to benzylpenicillin, due to better penetrance of bone) should be started initially. A third-generation cephalosporin is

recommended to cover Staphylococcus aureus and Gram-negative organisms for children aged <5 years. Patients with sickle cell disease should be treated initially with chloramphenicol or co-amoxiclav. Heroin addicts are prone to infections at unusual sites and with unusual organisms. Initial treatment is with a third-generation cephalosporin or with gentamycin and flucloxacillin.

Investigations
Imaging Radiographs: one must obtain preliminary radiographs at 90 projection to each other because osseous changes are not seen on radiographs in the first 710 days of infection. Soft tissue swelling, joint effusions and other pathological conditions may be identified. Ultrasound is more sensitive if osteomyelitis has been detected early, showing periosteal lift-off in osteomyelitis and increased fluid in an affected joint. MRI is nearly 100% sensitive and detects lesions in the spine, pelvis and limbs well before radiographic changes become apparent. Isotope bone scanning is rarely needed, but can help to differentiate multifocal from unifocal infection. In one review, multifocal lesions were found in 13% of 90 patients presenting with symptoms and signs of localized osteomyelitis. CT scanning has a role in preoperative planning of reconstructive surgery for the long-term sequelae of infection. Biochemistry Routine blood tests are of value, particularly elevation of C-reactive protein and white cell count (although the latter is less sensitive).

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In health, the white cell count for adults ranges from 4.0 to 11.0 109/l. In children, the normal reference range changes with age (Figure 4). The erythrocyte sedimentation rate is less helpful because it is frequently raised in simple inflammatory conditions. Blood cultures should be performed although, when negative, they do not exclude infection.

Acute osteomyelitis
Presentation Osteomyelitis of the long bone may be masked at the extremes of age or in the immunocompromised. Suspicion should be raised by: bone tenderness limp muscle spasm pyrexia and malaise (possible). Treatment Initial treatment is aimed at resuscitation, rehydration, analgesia, and splintage of the affected limb. The need for surgical drainage and the frequency of complications have lessened over the last few decades in the UK because most cases of osteomyelitis are referred early. If the metaphyseal abscess ruptures into the subperiosteal space, release from the periosteum or more superficially is indicated. Identify the physis to avoid injury at the time of surgery because it may lead to a physeal arrest and growth disturbance. Indications for surgery are: failure to respond to antibiotics after 4872 hours frank pus on aspiration intra-articular suppuration sequestered abscess. The incision should be extensile, avoiding subcutaneous skeletal sites. Antibiotics are given intravenously for seven days and continued orally for 56 weeks. Serial measurements of C-reactive protein guide treatment.

100,000 children per year in the UK, and is greater in younger children or those with: cachexia neoplasia inflammatory arthritis haematological disorders (e.g. haemophilia, HIV infection). The hip and shoulder may become infected by secondary spread from the proximal metaphysis of the femur and humerus which are intracapsular, but transphyseal vessels may carry organisms from the metaphysis into the joint until these are obliterated (usually by the age of one year). Presentation The child (particularly the premature infant) may present with pseudoparalysis due to a joint painfully distended by pus. The differential diagnosis between transient synovitis and septic arthritis is difficult to make acutely. In general, the child will be unwell, with a pyrexia of >38C and an erythrocyte sedimentation rate of >20 mm in the first hour. The affected joint is usually tender and swollen, with movement restricted by muscle spasm. Straight leg raise is often possible with an irritable hip. The child will continue to limp and will not be able to bear weight. A raised white cell count and haematocrit are also more likely with sepsis, but delay in drainage and antibiotic therapy will crucially affect outcome, so the index of suspicion should be high (even at the risk of opening uninfected joints). Treatment Ultrasound scanning cannot distinguish between a sterile effusion and infection because neither the volume nor the echogenicity of the effusion are diagnostic. When turbid fluid is aspirated from a joint, drainage by arthrotomy or arthroscopy is mandated. A white cell count >50 000/mm3 in the aspirate is an indication for washout of a joint (even in the absence of positive cultures). Complications Complications are dislocation, joint stiffness, and limb shortening.

Subacute osteomyelitis Septic arthritis

Septic arthritis is a surgical emergency whether it is primary or secondary to metaphyseal infection; the complications that result from delay in treatment are profound. It is most common in the larger joints (e.g. knee, hip, shoulder). The incidence is 510 per Presentation Subacute osteomyelitis presents after a long history (usually at least two weeks). The patient is rarely systemically unwell, but local tenderness is evident and radiographic changes are characteristic. The classic Brodies abscess (Figure 5) seen in young adults involves the proximal tibia, producing: sclerotic margination central bone absorption sequestration of necrotic bone fragments (possible). Subacute osteomyelitis less commonly involves the femur, tarsus, forearm bones and humerus. Unusual sites include the spine, clavicle, pelvis and even the patella. The level of C-reactive protein and erthythrocyte sedimentation rate may be raised, but the white cell count and blood cultures are likely to be negative. Biopsy (for microbiology and histology) and curettage are advised because neoplasia or infiltrative disorders cannot be excluded. Culture results in no bacterial growth in 3040% of cases in the UK.

Typical white cell count reference ranges in children

Age Birth 2 weeks 2 months 1 year 2 6 years 612 years White cell count (x 109/l) 10.026.0 6.021.0 6.018.0 6.017.5 5.017.0 4.514.5

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Treatment Antibiotic therapy should cover the probability of staphylococcal infection and recovery is slow but progressive. Complications of acute osteomyelitis are septic arthritis and chronic osteomyelitis.

One must monitor any discrepancy in leg length because a limblength equalization (preferably by contralateral epiphysiodesis) is often effective.

Discitis Chronic osteomyelitis

Chronic osteomyelitis is rare in developed countries, but may develop if: host defences are compromised there is circulatory impairment the organism is resistant to the antibiotics used. Presentation Chronic osteomyelitis is characterized by the development of a sequestrum of dead bone surrounded by a sleeve of involucrum produced by the surrounding periosteum. However, these are late developments and represent delayed or inadequate treatment. Treatment Surgical extirpation is the only effective remedy, although suppression of the disease may be all that is possible. The condition can usually be considered cured if recurrence is prevented over a five-year period. Complications If chronic osteomyelitis persists in the child, the following may develop: arrest of the growth plate, with shortening or angular deformity of the limb stimulation of the growth plate pathological fracture avascular necrosis septicaemia amyloidosis cachexia. The cause of discitis is poorly understood. Viral or bacterial infection, inflammatory disorders, and trauma have been suggested. Children of all age groups may be affected. In the neonate, intraosseous, vertebral arteries anastomose within the adjoining disc through the vertebral end plate. The disc loses its vascularity as the child matures. Presentation Presentation may be delayed and includes: a limp (or refusal to walk) back pain and stiffness psoas spasm causing hip flexion or pain referred to the hip Fever and abdominal pain (more common in older children). Blood cultures may be positive in up to 67% of cases, but diagnosis and localization are best achieved with MRI. Treatment The condition is usually self-limiting and treated with bed rest. Surgical decompression is warranted if the following are seen on MRI scan: protrusion of the nucleus pulposus nerve root compression abscess formation. Antibiotic therapy (i.v.) may shorten the duration of discitis. The intervertebral space may fuse in up to 40% of cases.

Tuberculosis
The prevalence in developed countries is very low (about 1000 cases reported annually in the UK), secondary to improvements in living standards and health care (including nationwide vaccination programmes). However, it is increasing, due mainly to immigration and immunodeficiency. The most common infective organisms are Mycobacterium tuberculosis or Mycobacterium bovis. Tuberculosis is spread by droplets and is therefore associated with overcrowding. It may also be contracted from ingestion of infected milk products or through the skin (rare). The primary complex is typically a sub-pleural Gohn focus and mediastinal lymphadenopathy. Haematogenous miliary spread occurs to bones, joint, lungs or meninges. Tuberculosis may lie dormant and reactivate during adolescence or adulthood (post-primary tuberculosis). Presentation Presentation is typically with fever, chills, a cough, pleuritic pain, weight loss or fatigue. There is respiratory involvement in 50% of cases of osseous tuberculosis. Acute mycobacterial arthritis most commonly affects the hips or knees. It is usually a monoarthropathy with preservation of the joint space and periarticular osteopenia radiologically. If the spine is the focus, there may be segmental collapse and gibbus formation (Potts disease), leading to neurological impairment. Fusion of joints or vertebrae may occur.

a b c d

5 Plain radiograph of the left knee (anteroposterior view) showing: a epiphysis b physis c metaphysis d Brodies abscess (Image courtesy of Mr J E Robb).

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Investigations Biochemical investigations reveal a normochromic normocytic anaemia or thrombocytopenia. The white cell count is often normal and the erythrocyte sedimentation rate may be normal or raised. Isotope bone scans or gallium scans are very sensitive in the detection of tuberculosis infection, but not very specific. MRI or CT may guide attempts at obtaining tissue samples for: microscopy ZiehlNeelsen staining culture. The presence of acid-fast bacilli is diagnostic. Samples should be transported in LowensteinJensen medium. Treatment The majority of patients can be treated conservatively with rest, chemotherapy and rehabilitation. Chemotherapy may be needed for 612 months and multiply-resistant strains have been identified. Patient contacts should also be treated. Surgery may involve: drainage of abscess arthrotomy and biopsy curettage and bone grafting of extra-articular lesions resection of joints or bones arthrodesis amputation.

Primary and secondary tumours of bone

Robert J Grimer

Presentation
A bone tumour usually presents with non-specific pain that is usually worse at night and which initially may have many features of non-mechanical pain (i.e. similar to toothache). However, the pain may become more mechanical and related to activity. The use of the involved limb may become restricted and a swelling may develop. Some will present with a pathological fracture which may be the first sign of an abnormality in the underlying bone.

Investigation of a suspicious lesion of bone (Figure 1)

The presence of any of the following on plain radiograph should alert the clinician to possible underlying bone pathology: bone destruction new formation of bone swelling of soft tissue periosteal elevation. These features are not specific for a bone tumour (the differential diagnoses are listed in Figure 2). However, further investigation is needed and should follow a series of steps (Figure 3).

Differential diagnoses
Chronic sclerosing osteomyelitis of Garre This non-suppurative condition is characterized by marked sclerosis and cortical thickening. Radiographs reveal no abscess cavity (although the medulla of long bones may eventually be obliterated). Gradually, a segment of bone enlarges and becomes tender. The clavicle, humerus, radius, femur, tibia and mandible may be involved (sometimes multifocally), with elevation of the level of C-reactive protein or erythrocyte sedimentation rate during the more active phase. The process may resolve for periods, only to become symptomatic again over a number of years. The prognosis is usually satisfactory. Arthropathy and limb-length discrepancy occur rarely. Symptoms can be relieved by intermittent administration of NSAIDs. Bacterial culture is infrequently achieved because biopsy or excision of the affected segment is not indicated. Chronic recurrent multifocal osteomyelitis Chronic recurrent multifocal osteomyelitis is a benign, self-limiting, inflammatory, (apparently non-pyogenic) skeletal disorder. The clavicle, limbs, spine, thorax and pelvis may be involved, usually between the ages of four and fifteen years. Antibiotic treatment is unnecessary unless the diagnosis is in doubt. Anti-inflammatory medication and radiographical follow-up are adequate. The SAPHO syndrome (synovitis, acne, palmoplantar pustulosis, hyperostosis and osteiitis) and plasmacellular osteomyelitis should be distinguished from chronic recurrent multifocal osteomyelitis, preferably with the help of a microbiologist. u

1 Plain radiograph of the knee (anteroposterior view) of a 45-yearold male showing a destructive lesion in the upper tibia (arrow). How would you investigate? Non-Hodgkins lymphoma was diagnosed.

Robert J Grimer is a Consultant Orthopaedic Surgeon at the Royal Orthopaedic Hospital, Birmingham, UK.

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