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Pathology
Pathology
C. G. Woods
Introduction
as causes of bone infection, now have to be sought if the patient is to be treated adequately. Although infection may be a focal abnormality the response involves the whole patient. The particular problems of neonates, the old and debilitated, and diabetics are well-known. Sickle cell disease and salmonella infection are an established association. Immunodeficiency and immuno-suppressant drugs predispose to infection. Whether the acquired immunodeficiency syndrome will be a significant factor in bone and joint infection remains to be seen. In this connection the skeletal infection occurring in intravenous drug abusers is of interest.5 Changes in infected bone always include loss of bone tissue (Fig. 1). Much of this bone loss is due to cells or their products in the inflammatory or reparative reactions, but disuse in a painful immobile limb will also lead to osteoporosis. Altered stresses in bone are a probable cause of some of the increase in bone which may occur around osteomyelitis. Inflammatory reactions are, as previously stated, categorised according to the cellular pattern observed in the tissue examined. In fact, if the observations on reactions to mycobacterial infections in experimental animals can be applied to human infections, the early stages of all infections involve a polymorphonuclear leucocyte response, which is soon totally replaced by the reaction which is regarded as characteristic of the disease. Some infections may provoke either a persistent pyogenic response or a granulomatous reaction, for reasons which are not clear. Brucella and fungal infections have this potential. The condition described as chronic recurrent multifocal osteomyelitis, which is of unknown aetiology, can produce a pyogenic, granulomatous or an almost purely lymphocytic response.6
Histopathological features of infective lesions are not adequately described by the terms ‘acute’, ‘subacute’ and ‘chronic’ without further qualification, although such terms may be a reasonable indication of the clinical course. It is necessary, for a complete pathological description, to specify the histological appearances as ‘pyogenic’, ‘non-specific’, ‘granulomatous’ as appropriate. There are accounts of the pathology of specific types of osteomyelitis in monographs of skeletal pathology with good illustrations. lP3 Rather than regurgitate those descriptions and present illustrations which are merely variations of wellknown images, this account will present some information about the subcellular components of the inflammatory and reparative processes of osteomyelitis and septic arthritis and relate them to the microscopic and macroscopic features. There is an excellent review by Smith on the biochemical aspects of inflammation and tissue repair, about which there is a considerable amount of information, but which does not yet fully explain the processes.” Descriptions of osteomyelitis and arthritis are based on the assumption that the tissues were normal before they became infected. Whilst this is reasonable, it is becoming more common to encounter infection superimposed on tissue which is already abnormal. Fractures and sites of implants are examples of such situations and the latter cause complex cellular reactions if plastic materials are used as components or as methods of fixation. The other consequences of previous trauma and endoprostheses is that organisms which were previously uncommon, or even unknown, C. G. Woods, Consultant Pathologist, The Nuffield Centre, Headington, Oxford OX3 7LD.
Orthopaedic
Current Orthopaedrcs (1988) 2, 7&79 IE 1988 Longman
Croup UK
Ltd
76
CURRENT
Fig. l-Lateral spine radiograph in acute pyogenic osteomyelitis. There has been destruction of disc and contiguous parts of adjacent vertebrae.
Acutepyogenic injammation The response to infection is initiated by tissue damage resulting from the action of products of the infecting organism, bacterial or fungal. Several of the substances released from damaged or dead cells and their role in the subsequent events have been identified. Vascular changes caused by cell degradation products result in exudation of fluid and cells; this is then followed by stasis. A combination of toxins from organisms and vascular stasis is responsible for death of bone which leads to sequestrum formation. The polymorphonuclear leucocyte infiltration is induced by chemotactic substances from both organisms and dead tissue. The primary function of these cells is to ingest organisms and debris, an activity facilitated by the digestive enzymes, including collagenase, contained in the lysosomes. Collagenase is probably the cause of the digestion and dissolution of cartilage which occurs in joint and bone infections and is a characteristic and serious consequence of pyogenic arthritis and osteomyelitis. Release of lysosomal enzymes is thought to be initiated by lipid peroxidation.
ORTHOPAEDICS
77
The next phase of the reaction is the attraction of macrophages and lymphocytes to the site. Interleukin I is a polypeptide product of macrophages which stimulates proliferation of lymphocytes and activated complement on the surface of macrophages is a chemoattractant of lymphocytes. Phagocytic activity by macrophages is an essential part of the debris clearing which is required to allow repair to occur, a process which includes the removal of dead bone. Both B and T lymphocytes are present. The major function of the former is probably the production of antibodies, In addition to their general functions as ‘helper’ and ‘suppressor’ cells, T ‘helper’ lymphocytes produce, by interaction with macrophages, a lymphokine which activates osteoclasts (osteoclast activating factor). Increased osteoclastic activity further assists in the removal of dead bone and is also responsible for resorption of viable bone at the periphery of the infection site. Repair begins when the infection is contained. New blood vessels are formed and fibroblasts migrate into and multiply within the area of repair. Products of the initial inflammatory response have an influence on fibroblastic proliferation and function. Histamine is a depressor of fibroblastic proliferation. Serotonin, bradykinin and catecholamines stimulate growth of fibroblasts and serotonin stimulates collagen production. Growth factors for both endothelial cells and fibroblasts are produced by monocytes (macrophages). Endothelial cells can stimulate fibroblast growth and are in turn influenced in their differentiation and organisation by the type of collagen produced by the fibroblast. New bone formation also occurs in repair following both osteomyelitis and arthritis. Two types of bone are formed. Metaplasia within fibrous scar tissue produces immature, ephemeral, bone. Apposition of lamellar bone on pre-existing bone surfaces leads to the sclerotic appearance at the periphery of pyogenic infections. What induces fibroblasts to transform to osteoblasts within the reparative tissue is not clear; prostaglandins, which are produced by most cells involved in inflammation and repair, have been observed to have an effect on both osteoclastic and osteoblastic differentiation and function during repair.. Appositional bone formation occurs frequently in parts of the bone which are not infiltrated by inflammatory cells. In these locations the cause of the osteoblastic activity is probably a change in the loading through the trabeculae around an area from which bone has been lost. New bone formation under the periosteum (the involucrum) occurs because the periosteum is elevated by acute inflammatory exudate and is not part of the repair process (Fig. 2). It may protect against pathological fracture, but is probably not primarily induced as a response to change in stresses. If the periosteum is infected it will be killed, together with the underlying cortex and a cloaca may be formed. Perfect restoration of bone to its previous state is
78
PATHOLOGY
clear leucocytes, lymphocytes, plasma cells and macrophages are admixed in varying proportions, but in which there is no predominant cell type. Pyogenic infections which have been incompletely or inadequately controlled by antimicrobials are a common cause, but it also occurs with untreated infections. Brucella and salmonella infections may induce this type of reaction. Brodie’s abscess commonly contains this type of inflammatory tissue. There is more than one pathogenesis of this lesion; infection by an organism of low virulence, a small number of organisms, inadequately treated virulent infection and high level of host resistance have all been advanced as explanations. A major problem preventing full understanding of this condition is that an infecting organism has not been identified in a majority of cases. Fig. 2-Lateral radiograph of lower humerus showing periosteal new bone formation (the involverum) formed as a result of elevation of the periosteum by the inflammatory exudate.
rarely achieved after infection is eliminated. The bones of children, which are still actively growing and modelling, will be more effectively repaired than those of adults where remodelling activity is at a relatively low level. Immature cartilage has the possibility to repair if some of the proliferative cells escape damage. Mature articular and intervertebral cartilage which is destroyed is never restored; at best it may be replaced by fibrocartilage which is a poor substitute. Apart from the endogenous factors, which have a complex role in the response to injury, exogenous factors also play a part. Vitamin C may limit the amount of tissue damage in the initial stages by inhibiting peroxidation. It is also necessary for the hydroxylation of proline and collagen synthesis. Vitamin D deficiency inhibits mineralisation of bone. Deficiencies of Vitamins A, E and some of the B’s lead to delay in healing. Probably the only clinical implication here is that the patient should have a physiological intake of nutrients. Therapeutic doses of indomethacin and corticosteroids inhibit bone healing; the former is an inhibitor of prostaglandin production. Pathological fracture, recurrent infection and ankylosis are consequences of pyogenic infection which can be predicted. Amyloid deposition may be anticipated if there is a continuous production of high levels of circulating antibody in the presence of persistent infection. Malignant transformation in either the epidermis at a sinus orifice or at the scar tissue within the bone occurs in a very small proportion of patients who have recurrences of infection over a period of 10 years and more. Repeated stimulation of cellular proliferation is a factor in neoplastic transformation, together with other, unknown causes. Chronic pyogenic inflammation
This type of inflammatory response is composed of vascular granulation tissue in which polymorphonu-
Chronic non-specijic inflammation
Chronic non-specific inflammation differs from a chronic pyogenic reaction in containing virtually no pus cells and being relatively poorly vascularised. Some forms of this reaction are predominantly lymphocytic. Congenital syphilis causes this type of infiltrate, characteristically in the metaphysis. The normal tissue of the metaphysis is replaced by the infiltrate and there is neither resorption of the calcified growth cartilage nor new bone formation, as a result of which the cartilage becomes deeper than normal and may be detached from the metaphysis. There is no necrosis of tissue resulting directly from the infection or the cellular reaction. Periosteal elevation and new bone formation are also features of congenital syphilis and may be due to either an inflammatory infiltrate or to mechanical displacement associated with growth cartilage detachment. As previously mentioned, chronic recurrent multifocal osteomyelitis can present an almost purely lymphocytic reaction. Non-specific inflammatory reactions in synovium are extremely common; they are rarely due to infection. Viral infections are sometimes followed by transient synovial reactions. Whether viral particles are present in the synovium is not known. Possible viral infections of bone also present the problem of proof.* Granulomatous inflammation
The characteristic of this pattern of cellular response is the presence of focal collections of histiocytic-type cells (the granuloma) scattered in a cellular reaction which consists of macrophages, lymphocytes and plasma cells. Some of the granulomata will include one or more multinucleate giant cells. The centre of a granuloma may be necrotic. What regulates this form of reaction is unknown. Presumably the products of the inflammatory cells are much the same as those produced by similar cells appearing after pyogenic infection. The essential difference is probably the mode of formation and delivery of antibody against, and the development of
CURRENT
hypersensitivity to, organisms which cause a granulomatous response. Whilst the granuloma is the diagnostic histological feature it is the diffuse cellular reaction and the tissue necrosis which have greater significance for the evolution of the lesion. The advancing front contains a large proportion of macrophages and resorption of, usually viable, bone occurs between the inflammatory cells. If the tissue within the lesion becomes necrotic, included bone remains. Unlike the necrosis which occurs in pyogenic infection, the dead tissue is not liquefied and has to be removed by phagocytosis and presents a considerable barrier to repair. Onset of repair varies considerably, usually not until the late stages of treatment of a tuberculous lesion, and sometimes relatively early in the tertiary lesions of treponemal infections (syphilis and yaws). The cause of caseous necrosis is not absolutely certain : tissue hypersensitivity is one possibility and avascularity resulting from obliterative endarteritis is another. Because of the paucity of reparative reaction, foci of tuberculous osteomyelitis seldom present sclerotic features on a radiograph. By contrast, the lesions due to acquired yaws usually and those due to tertiary syphilis commonly, are both sclerotic and exosteophytic and may have a radiographic appearance resembling an osteoblastic tumour. On the other hand syphilitic lesions may be predominantly bone-destroying and cause perforations through flat bones. Granulomatous reactions occur following some fungal and some brucella infections as well as M tuberculosis and treponemal infections. Fungal infections may cause a response which is histologically indistinguishable from that of a tuberculous lesion. Brucella infections tend not to be associated with extensive tissue necrosis. Joints are commonly infected by M tuberculosis, and much less commonly by brucella. Direct implantation of fungi may involve joints as commonly as bones. Tuberculosis arthritis can be extensively destructive if not treated at an early stage, and especially if there is a combined infection of both synovium and subchondral bone. In this situation the articular cartilage will be killed, probably because it cannot obtain nutrients from either the joint space or the subchondral bone, and will become detached from the subchondral bone, often in large fragments. The joint space will also contain caseous debris, and repair is
ORTHOPAEDICS
79
seriously impeded. A totally destroyed, unstable, joint is the consequence. Pathological fracture can be expected if there has been much bone resorption and when this occurs in the spine it may cause cord compression. Serious neurological deficit can also result from endarteritis and cord necrosis in the absence of fracture. Granulomatous lesions are not complicated by malignant transformation, nor by amyloid deposition. M leprae rarely infects bone and, when it does, a ‘lepromatous’ type of reaction, histiocytic and nongranulomatous, results. Peripheral sensory deficit resulting from ‘tuberculoid leprosy’ is frequently complicated by direct infection by other organisms and by bone and joint destruction. Atypical mycobacteria also cause a non-granulomatous reaction which may be polymorphonuclear and histiocytic and is commonly found to have a very large number of organisms in the lesion. Infestations
Parasitic lesions of bone are virtually always due to echinococcus. Usually several cysts develop in close proximity and enlarge, bone being resorbed by ‘pressure atrophy’. Whilst the cysts remain intact there is very little, if any, inflammatory reaction. Should the cysts rupture, for example if there is a pathological fracture, the cyst wall fragments become surrounded by a foreign body giant cell reaction. Traumatic rupture of bone cysts did not, in the two cases known to me, cause any constitutional upset. References I. Jaffe H L 1972 Metabolic, 2. 3. 4. 5. 6.
7.
8.
degenerative and inflammatory diseases of bones and joints. Lea and Febiger Philadelphia Revel1 PA 1986 Pathologyof bone. Springer-Verlag Berlin Bullough P G. Vigerita V J 1984 Atlas oforthopaedic Pathology. Butterworths, London Smith R 1985 Recovery and tissue repair. British Medical Bulletin 41: 295-301 Rota R P, Yoshikawa T T 1979 Primary skeletal infections in heroin users. Clinical Orthopaedics 144: 2388248 Biorksten B. Boauist L 1980 Histooatholoeical asuects of chronic recurrent multifocal osteomyelitis. Journal of Bone and Joint Surgery 62B : 376380 Dekel S, Lenthall G, Francis M J 0 1981 Release of prostaglandins from bone and muscle after tibia1 fracture. Journal of Bone and Joint Surgery 63B : 185-l 89 Cochran W. Connolly J H, Thompson I D 1963 Bone involvement after vaccination against smallpox. British Medical Journal II : 285-287
C. G. Woods
Introduction
as causes of bone infection, now have to be sought if the patient is to be treated adequately. Although infection may be a focal abnormality the response involves the whole patient. The particular problems of neonates, the old and debilitated, and diabetics are well-known. Sickle cell disease and salmonella infection are an established association. Immunodeficiency and immuno-suppressant drugs predispose to infection. Whether the acquired immunodeficiency syndrome will be a significant factor in bone and joint infection remains to be seen. In this connection the skeletal infection occurring in intravenous drug abusers is of interest.5 Changes in infected bone always include loss of bone tissue (Fig. 1). Much of this bone loss is due to cells or their products in the inflammatory or reparative reactions, but disuse in a painful immobile limb will also lead to osteoporosis. Altered stresses in bone are a probable cause of some of the increase in bone which may occur around osteomyelitis. Inflammatory reactions are, as previously stated, categorised according to the cellular pattern observed in the tissue examined. In fact, if the observations on reactions to mycobacterial infections in experimental animals can be applied to human infections, the early stages of all infections involve a polymorphonuclear leucocyte response, which is soon totally replaced by the reaction which is regarded as characteristic of the disease. Some infections may provoke either a persistent pyogenic response or a granulomatous reaction, for reasons which are not clear. Brucella and fungal infections have this potential. The condition described as chronic recurrent multifocal osteomyelitis, which is of unknown aetiology, can produce a pyogenic, granulomatous or an almost purely lymphocytic response.6
Histopathological features of infective lesions are not adequately described by the terms ‘acute’, ‘subacute’ and ‘chronic’ without further qualification, although such terms may be a reasonable indication of the clinical course. It is necessary, for a complete pathological description, to specify the histological appearances as ‘pyogenic’, ‘non-specific’, ‘granulomatous’ as appropriate. There are accounts of the pathology of specific types of osteomyelitis in monographs of skeletal pathology with good illustrations. lP3 Rather than regurgitate those descriptions and present illustrations which are merely variations of wellknown images, this account will present some information about the subcellular components of the inflammatory and reparative processes of osteomyelitis and septic arthritis and relate them to the microscopic and macroscopic features. There is an excellent review by Smith on the biochemical aspects of inflammation and tissue repair, about which there is a considerable amount of information, but which does not yet fully explain the processes.” Descriptions of osteomyelitis and arthritis are based on the assumption that the tissues were normal before they became infected. Whilst this is reasonable, it is becoming more common to encounter infection superimposed on tissue which is already abnormal. Fractures and sites of implants are examples of such situations and the latter cause complex cellular reactions if plastic materials are used as components or as methods of fixation. The other consequences of previous trauma and endoprostheses is that organisms which were previously uncommon, or even unknown, C. G. Woods, Consultant Pathologist, The Nuffield Centre, Headington, Oxford OX3 7LD.
Orthopaedic
Current Orthopaedrcs (1988) 2, 7&79 IE 1988 Longman
Croup UK
Ltd
76
CURRENT
Fig. l-Lateral spine radiograph in acute pyogenic osteomyelitis. There has been destruction of disc and contiguous parts of adjacent vertebrae.
Acutepyogenic injammation The response to infection is initiated by tissue damage resulting from the action of products of the infecting organism, bacterial or fungal. Several of the substances released from damaged or dead cells and their role in the subsequent events have been identified. Vascular changes caused by cell degradation products result in exudation of fluid and cells; this is then followed by stasis. A combination of toxins from organisms and vascular stasis is responsible for death of bone which leads to sequestrum formation. The polymorphonuclear leucocyte infiltration is induced by chemotactic substances from both organisms and dead tissue. The primary function of these cells is to ingest organisms and debris, an activity facilitated by the digestive enzymes, including collagenase, contained in the lysosomes. Collagenase is probably the cause of the digestion and dissolution of cartilage which occurs in joint and bone infections and is a characteristic and serious consequence of pyogenic arthritis and osteomyelitis. Release of lysosomal enzymes is thought to be initiated by lipid peroxidation.
ORTHOPAEDICS
77
The next phase of the reaction is the attraction of macrophages and lymphocytes to the site. Interleukin I is a polypeptide product of macrophages which stimulates proliferation of lymphocytes and activated complement on the surface of macrophages is a chemoattractant of lymphocytes. Phagocytic activity by macrophages is an essential part of the debris clearing which is required to allow repair to occur, a process which includes the removal of dead bone. Both B and T lymphocytes are present. The major function of the former is probably the production of antibodies, In addition to their general functions as ‘helper’ and ‘suppressor’ cells, T ‘helper’ lymphocytes produce, by interaction with macrophages, a lymphokine which activates osteoclasts (osteoclast activating factor). Increased osteoclastic activity further assists in the removal of dead bone and is also responsible for resorption of viable bone at the periphery of the infection site. Repair begins when the infection is contained. New blood vessels are formed and fibroblasts migrate into and multiply within the area of repair. Products of the initial inflammatory response have an influence on fibroblastic proliferation and function. Histamine is a depressor of fibroblastic proliferation. Serotonin, bradykinin and catecholamines stimulate growth of fibroblasts and serotonin stimulates collagen production. Growth factors for both endothelial cells and fibroblasts are produced by monocytes (macrophages). Endothelial cells can stimulate fibroblast growth and are in turn influenced in their differentiation and organisation by the type of collagen produced by the fibroblast. New bone formation also occurs in repair following both osteomyelitis and arthritis. Two types of bone are formed. Metaplasia within fibrous scar tissue produces immature, ephemeral, bone. Apposition of lamellar bone on pre-existing bone surfaces leads to the sclerotic appearance at the periphery of pyogenic infections. What induces fibroblasts to transform to osteoblasts within the reparative tissue is not clear; prostaglandins, which are produced by most cells involved in inflammation and repair, have been observed to have an effect on both osteoclastic and osteoblastic differentiation and function during repair.. Appositional bone formation occurs frequently in parts of the bone which are not infiltrated by inflammatory cells. In these locations the cause of the osteoblastic activity is probably a change in the loading through the trabeculae around an area from which bone has been lost. New bone formation under the periosteum (the involucrum) occurs because the periosteum is elevated by acute inflammatory exudate and is not part of the repair process (Fig. 2). It may protect against pathological fracture, but is probably not primarily induced as a response to change in stresses. If the periosteum is infected it will be killed, together with the underlying cortex and a cloaca may be formed. Perfect restoration of bone to its previous state is
78
PATHOLOGY
clear leucocytes, lymphocytes, plasma cells and macrophages are admixed in varying proportions, but in which there is no predominant cell type. Pyogenic infections which have been incompletely or inadequately controlled by antimicrobials are a common cause, but it also occurs with untreated infections. Brucella and salmonella infections may induce this type of reaction. Brodie’s abscess commonly contains this type of inflammatory tissue. There is more than one pathogenesis of this lesion; infection by an organism of low virulence, a small number of organisms, inadequately treated virulent infection and high level of host resistance have all been advanced as explanations. A major problem preventing full understanding of this condition is that an infecting organism has not been identified in a majority of cases. Fig. 2-Lateral radiograph of lower humerus showing periosteal new bone formation (the involverum) formed as a result of elevation of the periosteum by the inflammatory exudate.
rarely achieved after infection is eliminated. The bones of children, which are still actively growing and modelling, will be more effectively repaired than those of adults where remodelling activity is at a relatively low level. Immature cartilage has the possibility to repair if some of the proliferative cells escape damage. Mature articular and intervertebral cartilage which is destroyed is never restored; at best it may be replaced by fibrocartilage which is a poor substitute. Apart from the endogenous factors, which have a complex role in the response to injury, exogenous factors also play a part. Vitamin C may limit the amount of tissue damage in the initial stages by inhibiting peroxidation. It is also necessary for the hydroxylation of proline and collagen synthesis. Vitamin D deficiency inhibits mineralisation of bone. Deficiencies of Vitamins A, E and some of the B’s lead to delay in healing. Probably the only clinical implication here is that the patient should have a physiological intake of nutrients. Therapeutic doses of indomethacin and corticosteroids inhibit bone healing; the former is an inhibitor of prostaglandin production. Pathological fracture, recurrent infection and ankylosis are consequences of pyogenic infection which can be predicted. Amyloid deposition may be anticipated if there is a continuous production of high levels of circulating antibody in the presence of persistent infection. Malignant transformation in either the epidermis at a sinus orifice or at the scar tissue within the bone occurs in a very small proportion of patients who have recurrences of infection over a period of 10 years and more. Repeated stimulation of cellular proliferation is a factor in neoplastic transformation, together with other, unknown causes. Chronic pyogenic inflammation
This type of inflammatory response is composed of vascular granulation tissue in which polymorphonu-
Chronic non-specijic inflammation
Chronic non-specific inflammation differs from a chronic pyogenic reaction in containing virtually no pus cells and being relatively poorly vascularised. Some forms of this reaction are predominantly lymphocytic. Congenital syphilis causes this type of infiltrate, characteristically in the metaphysis. The normal tissue of the metaphysis is replaced by the infiltrate and there is neither resorption of the calcified growth cartilage nor new bone formation, as a result of which the cartilage becomes deeper than normal and may be detached from the metaphysis. There is no necrosis of tissue resulting directly from the infection or the cellular reaction. Periosteal elevation and new bone formation are also features of congenital syphilis and may be due to either an inflammatory infiltrate or to mechanical displacement associated with growth cartilage detachment. As previously mentioned, chronic recurrent multifocal osteomyelitis can present an almost purely lymphocytic reaction. Non-specific inflammatory reactions in synovium are extremely common; they are rarely due to infection. Viral infections are sometimes followed by transient synovial reactions. Whether viral particles are present in the synovium is not known. Possible viral infections of bone also present the problem of proof.* Granulomatous inflammation
The characteristic of this pattern of cellular response is the presence of focal collections of histiocytic-type cells (the granuloma) scattered in a cellular reaction which consists of macrophages, lymphocytes and plasma cells. Some of the granulomata will include one or more multinucleate giant cells. The centre of a granuloma may be necrotic. What regulates this form of reaction is unknown. Presumably the products of the inflammatory cells are much the same as those produced by similar cells appearing after pyogenic infection. The essential difference is probably the mode of formation and delivery of antibody against, and the development of
CURRENT
hypersensitivity to, organisms which cause a granulomatous response. Whilst the granuloma is the diagnostic histological feature it is the diffuse cellular reaction and the tissue necrosis which have greater significance for the evolution of the lesion. The advancing front contains a large proportion of macrophages and resorption of, usually viable, bone occurs between the inflammatory cells. If the tissue within the lesion becomes necrotic, included bone remains. Unlike the necrosis which occurs in pyogenic infection, the dead tissue is not liquefied and has to be removed by phagocytosis and presents a considerable barrier to repair. Onset of repair varies considerably, usually not until the late stages of treatment of a tuberculous lesion, and sometimes relatively early in the tertiary lesions of treponemal infections (syphilis and yaws). The cause of caseous necrosis is not absolutely certain : tissue hypersensitivity is one possibility and avascularity resulting from obliterative endarteritis is another. Because of the paucity of reparative reaction, foci of tuberculous osteomyelitis seldom present sclerotic features on a radiograph. By contrast, the lesions due to acquired yaws usually and those due to tertiary syphilis commonly, are both sclerotic and exosteophytic and may have a radiographic appearance resembling an osteoblastic tumour. On the other hand syphilitic lesions may be predominantly bone-destroying and cause perforations through flat bones. Granulomatous reactions occur following some fungal and some brucella infections as well as M tuberculosis and treponemal infections. Fungal infections may cause a response which is histologically indistinguishable from that of a tuberculous lesion. Brucella infections tend not to be associated with extensive tissue necrosis. Joints are commonly infected by M tuberculosis, and much less commonly by brucella. Direct implantation of fungi may involve joints as commonly as bones. Tuberculosis arthritis can be extensively destructive if not treated at an early stage, and especially if there is a combined infection of both synovium and subchondral bone. In this situation the articular cartilage will be killed, probably because it cannot obtain nutrients from either the joint space or the subchondral bone, and will become detached from the subchondral bone, often in large fragments. The joint space will also contain caseous debris, and repair is
ORTHOPAEDICS
79
seriously impeded. A totally destroyed, unstable, joint is the consequence. Pathological fracture can be expected if there has been much bone resorption and when this occurs in the spine it may cause cord compression. Serious neurological deficit can also result from endarteritis and cord necrosis in the absence of fracture. Granulomatous lesions are not complicated by malignant transformation, nor by amyloid deposition. M leprae rarely infects bone and, when it does, a ‘lepromatous’ type of reaction, histiocytic and nongranulomatous, results. Peripheral sensory deficit resulting from ‘tuberculoid leprosy’ is frequently complicated by direct infection by other organisms and by bone and joint destruction. Atypical mycobacteria also cause a non-granulomatous reaction which may be polymorphonuclear and histiocytic and is commonly found to have a very large number of organisms in the lesion. Infestations
Parasitic lesions of bone are virtually always due to echinococcus. Usually several cysts develop in close proximity and enlarge, bone being resorbed by ‘pressure atrophy’. Whilst the cysts remain intact there is very little, if any, inflammatory reaction. Should the cysts rupture, for example if there is a pathological fracture, the cyst wall fragments become surrounded by a foreign body giant cell reaction. Traumatic rupture of bone cysts did not, in the two cases known to me, cause any constitutional upset. References I. Jaffe H L 1972 Metabolic, 2. 3. 4. 5. 6.
7.
8.
degenerative and inflammatory diseases of bones and joints. Lea and Febiger Philadelphia Revel1 PA 1986 Pathologyof bone. Springer-Verlag Berlin Bullough P G. Vigerita V J 1984 Atlas oforthopaedic Pathology. Butterworths, London Smith R 1985 Recovery and tissue repair. British Medical Bulletin 41: 295-301 Rota R P, Yoshikawa T T 1979 Primary skeletal infections in heroin users. Clinical Orthopaedics 144: 2388248 Biorksten B. Boauist L 1980 Histooatholoeical asuects of chronic recurrent multifocal osteomyelitis. Journal of Bone and Joint Surgery 62B : 376380 Dekel S, Lenthall G, Francis M J 0 1981 Release of prostaglandins from bone and muscle after tibia1 fracture. Journal of Bone and Joint Surgery 63B : 185-l 89 Cochran W. Connolly J H, Thompson I D 1963 Bone involvement after vaccination against smallpox. British Medical Journal II : 285-287