Simon, 4-years-old, complained to his mother that his leg was sore. That night he did not eat his evening meal with his usual enthusiasm. In the early hours of the morning, he awoke crying, and complaining that his leg still hurt. Later in the day his mother saw that he was reluctant to run around. She felt he was warm. In the afternoon, she took him to the doctor, who asked him to point to where his leg hurt and he indicated just below the knee on the inner side of the leg. When the doctor pressed at that spot, Simon said ‘Ouch’. The skin was not discoloured. Lymph nodes in his groin were not palpable. Although he was reluctant to walk for the doctor, his knee joint range of movement was normal. His body temperature was elevated at 38.5°C. The doctor did not find any other abnormal clinical signs and made a provisional diagnosis of acute osteomyelitis of the tibia.

Once infection is established, it is the outcome of the host and parasite contest that determines the effect of the infection. Microorganisms may:

• be repelled and eradicated, with restitution of the tissues to their normal state

• cause such tissue damage that the host is unable to survive

• be eradicated by the host but tissue destruction and inflammation lead to the formation of repair tissue that leaves a fibrous scar at the site of invasion (the most common outcome)

• remain dormant in the tissues but there is ‘clinical resolution’ of the disease.

The ‘clinical outcome’ is the recovery of function in the host and is determined by the tissue responses. Those responses may be modified by effective treatment, tipping the balance between microorganism and host in favour of the host.

The mere presence of microorganisms is not sufficient to produce disease. They must demonstrate an ability to invade the host tissues, to enter, multiply, spread and produce toxic substances. The body has defences against invasiveness and toxigenicity. The ability to produce a disease is known as pathogenicity. The comparative pathogenicity of various organisms is known as virulence. Very small numbers of virulent bacteria produce disease, whereas larger numbers are required of less virulent organisms. The invasiveness of microorganisms relates not only to the toxins that they produce, but also to enzymes, which may allow them to spread by tissue dissolution and protect them from host phagocytes.

Portals of entry

In order to produce diseases of the musculoskeletal system in man, organisms must gain access to those tissues. There are several ways in which this may occur:

• haematogenous spread by bacteraemia or septicaemia from a primary site of colonization (skin, mouth, gut) if barriers to spread have been breached

• direct access by puncture of the skin and deeper tissues following injury, with organisms carried in by the penetrating instrument

• direct access at the time of elective surgery or following surgery for open injury

• local spread from infected adjacent tissues.

Interesting associations

Certain clinical observations are useful in trying to understand the basis for musculoskeletal infections. The common sites of infections in infants and children are in the lower limbs, both bones and joints, whereas the spine is the bone site most commonly affected by haematogenous infection in adults. This probably reflects the larger vascular beds or the nature of blood flow in the vessels in those sites. Acute haematogenous osteomyelitis and septic arthritis are more common in boys than girls; however, the reason for this is unclear.

The organisms involved are not randomly distributed. Staphylococcus aureus is a common cause of bone and joint infections in all age groups, but in the past 40 years it has been recognized that Haemophilus influenzae was a not infrequent cause of septic arthritis in children between the ages of 6 months and 2 years. This may represent a modification of the immune competence of children in that age group. Salmonella has a predilection for black-skinned races with sickle cell disease. The site of infection in adults is usually the diaphysis of a long bone, while the common site of infection in children, as in Simon, is metaphyseal.

Host defences against infection

The host, for its part in the host–parasite relationship, has a resistance to invasion by microorganisms and the effects of their toxins that can be assessed in terms of non-specific and specific factors.

Non-specific factors are those acting against a variety of microorganisms:

• physiological, physical and chemical barriers at the portal of entry (skin or mucous membrane)

• phagocytosis (intracellular killing of microorganisms)

• the reticuloendothelial system

• the inflammatory response.

The specific factors are those that confer resistance against a specific infectious agent and come under the heading of immunity. Such immunity may be natural (not acquired through previous contact with the infecting agent), or acquired (passively or actively). Passive acquired immunity is a state of relative temporary insusceptibility to an infectious agent that has been induced by the administration of antibodies that were formed in another host, rather than formed by the individual person. Monoclonal antibodies, or polyvalent antisera, are examples. Tetanus immune globulin is a product of autologous human serum that contains antibodies against tetanus toxin. Active immunity is a state of resistance built up in an individual following effective contact with the foreign antigens; that is the microorganisms or their products. Active immunization against tetanus requires injection of deactivated tetanus toxin. The antibodies are manufactured by the host. Adaptive or acquired resistance to infection requires a specific response by the host to enable it to eradicate a particular infection.

The resistance of acquired immunity is a complex subject, but as reviewed in Chapter 1, there are two major subgroups:

1. humoral immunity, or the active production of antibodies; and

2. cellular immunity, in which certain lymphoid cells recognize material as foreign and initiate a chain of responses that permit them to destroy intracellular organisms.

Humoral immunity involves the production and secretion of special protein molecules called antibodies by cells of the lymphoid system. The antibodies circulate in the blood and body fluids, having been stimulated to appear by the presence of antigens. Antibodies may induce resistance to infection because they:

• neutralize toxins or cellular enzymes

• have direct bactericidal or lytic effect

• block the infective ability of microorganisms

• agglutinate microorganisms, making them more susceptible to phagocytosis

• opsonize microorganisms and therefore aid phagocytosis.

Cell-mediated immunity depends on the ability of sensitized lymphocytes to kill foreign cells by direct contact. Lymphocytes are found in lymphoid tissue (bone marrow, thymus, spleen, lymph nodes and lymph) and in the blood. In Chapter 1 we described how humoral immunity is mediated by B lymphocytes derived from stem cells in the bone marrow. These are stimulated by antigen to divide and form plasma cells, which then secrete antibodies against the antigen concerned. The other lymphocyte population, the T lymphocytes, are responsible for cellular immunity.

The presence of antibodies, and their amount, can sometimes be used to determine whether or not a person has had contact with an antigen; this is useful in the diagnosis of some infections and in determining a person’s response to treatment. Similarly, the ability of T cells to respond to challenge by some antigens can be used as a diagnostic technique.

The tissues that are regularly in contact with the external environment, such as skin, mucous membrane and cornea, have adaptations that resist invasion by microorganisms, and it is usually only at times when the continuity of the tissue surface is breached that infection occurs. The deeper tissues such as bone and joint do not have the same natural barriers to infection. Muscle is also a deeper tissue, but has a lower incidence of primary infection than bones or joints, for unknown reasons.

Also important are alterations in function of one or more organ systems in the host. The normal ecological balance of symbiotic organisms resident on the host may be upset by burns, trauma, surgery, hospitalization or antibiotic therapy. Disrupted anatomical barriers consequent on burns, trauma, bites, other infections, ischaemia or the presence of foreign materials (including implanted prostheses) alter normal relations. If the person has diabetes, renal failure, diseases of the haematopoietic system or is taking immunosuppressive drugs, the normally protective inflammatory response may be altered. Diseases of the lymphoreticular system, cancer, debilitating diseases, malnutrition and cigarette smoking have an effect on the way the body meets challenges from microorganisms.

Blood supply of bone

The clinical patterns of acute osteomyelitis are different in infants, children and adults. The most likely explanation is that the blood supply and structure of bone in the three age groups is different (Fig. 11.1). You will recall from Chapter 5 that children have a well-defined growth plate (physis), while adults do not have a growth plate. In infants, a growth plate is present, but it is less well defined, and has some vessels that penetrate it and thereby connect the epiphysis and metaphysis of the bone. The physis is cartilaginous, and therefore capable of being ‘expanded’ by dividing and growing cells, whereas adult bone can only grow by apposition on its surface. At the junction of metaphysis and physis, small blood vessels are open-ended, growing towards the physis. At that point, the contents of the lumen can escape and lie adjacent to physeal cartilage. If an embolus of bacteria (septicaemia or bacteraemia) escapes from such a vessel, and the size of the inoculum is sufficient to cause an infection (a measure of virulence), and there is a tropism (attraction) of the pathogenic bacteria for cartilage, then an infection may be initiated.

Fig. 11.1 The anatomy of bone and joint in a child. The terms used to describe the parts of the bone are shown. Note the relationship of the site of initiation of a metaphyseal abscess to the blood supply and junction of dead cartilage and forming bone adjacent to the physis.

Case 11.1 Acute osteomyelitis: 2

Case note: Aetiology

The doctor made a diagnosis of acute haematogenous osteomyelitis. Osteomyelitis is inflammation (-itis) of bone (osteo-) and bone marrow (myel-), and is normally due to infection. Some books call it osteitis but it is not possible to distinguish if bone can be infected without the marrow component. The primary infection is usually blood-borne in infants and children and the first site of lodgement of the bacterial embolus is in small blood vessels within the medullary (marrow) cavity of the bone.

Once a metaphyseal infection is initiated, cell death occurs and an inflammatory process follows. Intramedullary (within the marrow cavity) inflammation in the metaphysis of a long bone further impairs the circulation to the bone and ischaemia occurs around the initial septic focus or abscess. Because the direction of flow of blood in bone is dependent on pressure differences in capillaries, the nutrition of the cortical bone of the metaphysis may be secondarily impaired. The ischaemic necrosis of bone allows pus (the consequence of infective inflammation) to spread from the initial focus within the cancellous bone of the metaphysis through the bone cortex, and through the medullary cavity.

Acute infection of bone and joints

Diagnosis of acute bone infection

The absolute diagnosis of infection in bone requires that microorganisms be detected at a site in bone. The simplest way to confirm bone infection is to put a needle at the site of tenderness and to aspirate for pus. Any material collected should then be subjected to Gram staining and microbiological culture. However, this is not always possible and other investigations are usually necessary.

Case 11.1 Acute osteomyelitis: 3

Case note: Relating clinical features to pathology

The fact that Simon pointed to the metaphyseal region of his tibia as his site of pain, and the doctor found tenderness at precisely that site links the anatomy of the region to the pathology and observed clinical picture. In adults, metaphyseal osteomyelitis is uncommon, and haematogenous osteomyelitis is less common than direct invasion of bone. When haematogenous in adults, osteomyelitis is most frequent in the vertebrae.

Had Simon been examined when he first complained of his leg being sore, the doctor may not have found tenderness at the tibial metaphysis. However, the pathological sequela of the infectious process in the intervening hours, then untreated, leads to purulent oedema fluid collecting beneath the periosteum of the bone cortex, providing a critical clinical sign—finger point tenderness at the metaphysis of a long bone in a child. If this sign is found, acute osteomyelitis should be considered the most likely diagnosis until proven otherwise.

Although bone is an easy tissue to image, changes in bone on plain radiographs, characteristic of infection, do not appear for several days after the infection has started. When present, the most typical change is the laying down of thin layers of bone on the periosteal surface (Fig. 11.2). By the time that occurs, the infective process may be well established and difficult to abort by treatment. Nevertheless, plain radiography should always be performed as it may show an alternative diagnosis. The best investigation to perform is ultrasound imaging. It is non-invasive, not painful, and shows an image of the tissues in real time. An anechoic zone adjacent to bone (that is, under the periosteum) means a collection of liquid and in the clinical setting confirms a diagnosis of osteomyelitis (Fig. 11.3). Furthermore, an aspirating needle can be guided by the ultrasound image to enter the liquid for the collection of a sample.