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Pathology of Bone & Joint Infections Doç. Dr. Işın Doğan Ekici • The term osteomyelitis formally designates inflammation of the bone and marrow cavity; as commonly used, however, it almost always implies infection. • Osteomyelitis can be a complication of systemic infection but more frequently occurs as an isolated focus of disease; it can be an acute process or a chronic, debilitating illness. • Although any microorganism can cause osteomyelitis, the most common etiologic agents are pyogenic bacteria and Mycobacterium tuberculosis. • Spread to bone by one of three routes: – Hematogenous spread – Direct extension from a contiguous site of infection – Direct introduction • The most serious bone infections are pyogenic osteomyelitis and tuberculosis • The clinical course of osteomyelitis depends on – the characteristics of the causative organism – the route of the infection – the age of the patient • Osteomyelitis can be occured as; • Acute • Subacute • Chronic Acute (Pyogenic) Osteomyelitis 1- Hematogenous Osteomyelitis 2- Osteomyelitis from a Contiguous Infection 3- Osteomyelitis from an Introduced Infection Hematogenous (Pyogenic) Osteomyelitis • Acute hematogenous osteomyelitis • Predominately in children and before the age of epiphysial closure (<21 y), • Typically originates in the metaphysis of long bones: – the lower end of the femur, – the upper end of the tibia and humerus, – the radius. • Sometimes results from the bloodborne spread to bone of an extraskeletal focus of infection. Etiology of Hematogeneous osteomyelitis • In children: – S. aureus (60-90%) – Group B streptococci and E. Coli (in neonates) – Salmonella osteomyelitis (Children with sickle cell disease) • In adults: – S. aureus (55%) – Gram-negative bacteria – Streptococci Hematogeneous osteomyelitis of children usually begins in the metaphysis of long bones: The blood-borne bacteria are carried to the marrow space by way of the nutrient artery Hematogenous osteomyelitis in adults: – Vertebrae – Long bones (rarely) • The hematogenous spread of infection: – by way of the nutrient branches of the spinal artery or – by flow from the pelvic veins to the lumbar veins • The vertebral infection is usually secondary to a primary bacteremia caused by – genitourinary tract infection – soft tissue and respiratory infections – iv drug abusers • The complications of vertebral osteomyelitis: – extension of the infection to the adjacent disk space – extension to retropharyngeal, mediastinal, peritoneal, and meningeal sites depending on the vertebrae involved Pathology • Fulminant acute inflammation of the marrow space • An exudation of polymorphonuclear leukocytes • The presence of an inflammatory exudate within the rigid limits of the marrow space causes: – – – – an increase in intramedullary pressure reduced blood flow local vascular occlusion thrombosis • Local ischemic injury cell necrosis (marrow and osseous tissue) • The bacteria, pus material, and necrotic debris comprise a septic focus of purulent inflammation Exudation of polymorphonuclear leukocytes • The infection may then spread rapidly by way of vascular channels through the medullary cavity • The bone cortex which is thin in the region of the metaphysis and provides easy access to the periosteum • The purulent material may elevate the periosteum and form abscesses beneath it or penetrate the periosteum (subperiostal abscess) • Sinus tracts which drain into the soft tissue or extend to the skin surface (fistula or cloaca) Sinus tracts which drain into the soft tissue or extend to the skin surface (fistula or cloaca) • Impaired the blood supply to the cortical and medullary bone ischemic bone tissue necrosis • After several days a sizeable portion of the necrotic bone tissue may separate from the viable bone as an avascular bone fragment termed a sequestrum – the formation of an involucrum (coffin) • With continuation of the bone infection, – chronic inflammatory cells (lymphocytes, histiocytes, plasma cells), – proliferating fibroblasts, – reactive new bone formation contribute to the microscopic picture of chronic osteomyelitis. Osteomyelitis from a Contiguous Infection • The adjoining sites of microbial infection that may spread to bone: – – – – – Burns Sinus disease Periodontal infections of jaws Soft tissue infection Skin ulcers caused by peripheral vascular disease • Arteriosclerosis • Diabetes • Vasculitis • The pathological and radiological changes are similar to those seen in chronic hematogenous osteomyelitis • The treatment usually requires surgical intervention (debridement of necrotic tissue, drainage of abscesses, etc.) combined with bacteriological cultures and appropriate antimicrobial therapy • Blood cultures are positive in about 10% of cases. Osteomyelitis from an Introduced Infection • Penetrating wounds • Compound fractures • Simple fractures treated surgically with open reduction and internal fixation • Prosthetic joint replacements • Other orthopedic appliances (plates, nails, screws, pins) The pathological changes in the involved bone (as occur in hematogenous osteomyelitis): • suppurative inflammation • ischemic necrosis • fibrosis • reactive new-bone formation Subacute osteomyelitis Subacute osteomyelitis (Brodie abscess) • A Brodie abscess is a subacute osteomyelitis with a predilection for the ends of long bones and the carpals and tarsals – may mimic various benign and malignant conditions, resulting in delayed diagnosis and treatment • Infectious agents: Etiology – Subacute osteomyelitis is one of the many clinical presentations of hematogenous osteomyelitis – The causative organism usually is Staphylococci (30-60%) • Others:Streptococcus, Pseudomonas, Haemophilus influenzae, coagulasenegative Staphylococcus, and Kingella kingae (a gram-negative coccobacillus). – The organisms reach the bone from a disrupted site • skin pustule • furuncles • impetigo • infected blisters and burns – Infection has even been suggested to be the outcome of common events such as normally harmless daily teeth brushing. • Site of infection – The lower limb is affected much more often than the upper limb. • tibia is affected relatively more often than is the femur – Involve the epiphysis and metaphysis • Radiographic findings: • a localized destructive lesion of bone • with a surrounding sclerosis in the metaphysis • and a variable degree of periosteal new-bone formation Histologic Findings • The surrounding bone is usually sclerotic • Granulation tissue lines the abscess cavity • Fibroblastic response, remnant of necrotic bone, and new bone formation • Pus is a rare finding • Inflammatory infiltration consisting of polymorphonuclears, lymphocytes and plasma cells (mixed) Chronic osteomyelitis • Garrè’s sclerosing osteomyelitis • Chronic suppurative osteomyelitis • Chronic recurrent multifocal osteomyelitis • Specific forms of chronic osteomyelitis (Tbc,Syph) • SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis) • The disease may result from – – – – (1) inadequately treated acute osteomyelitis (2) a hematogenous type of osteomyelitis (3) trauma (4) iatrogenic causes such as joint replacements and the internal fixation of fractures – (5) compound fractures – (6) infection with organisms, such as Mycobacterium tuberculosis and Treponema species (syphilis) – (7) contiguous spread from soft tissues, as in diabetic ulcers or ulcers in peripheral vascular disease Infective process • Chronic osteomyelitis results when the inflammatory process continues over time, leading to bone sclerosis and deformity • The ends of long bones are the most common locus of infection, and Staphylococcus aureus is the most common infective organism involved ( chronic suppurative osteomyelitis) • Remember Infection increase of intramedullary pressure (due to inflammatory exudate) strips the periosteum leading to vascular thrombosis bone necrosis formation of sequestra • These sequestra with infected material are surrounded by sclerotic bone that is relatively avascular. • Antibiotics cannot penetrate these relatively avascular tissues and are hence ineffective in clearing the infection. Chronic osteomyelitis Sclerosing osteomyelitis of Garré – Mandible: a sclerotic nonpurulent form of osteomyelitis Complications of Chronic Osteomyelitis (1) arthritis (2) skeletal deformations (3) malignant transformation (eg, Marjolin ulcer [squamous cell carcinoma], SCC of the sinus tract) (4) secondary amyloidosis (5) pathologic fractures Specific forms of chronic osteomyelitis • Tuberculous osteomyelitis • Syphilis (congenital and acquired) • Actinomycotic osteomyelitis Tuberculous osteomyelitis • Bone Tuberculosis • Hematogenous spread of organisms from an active focus of tuberculosis : – – – – lung (common) mediastinal or aortic lymph nodes kidney bowel • Most common in children&youngs • The vertebrae and the long bones of the extremities are most frequently involved • In many cases the infection also spreads to contiguous joints such as the hip, knee, and intervertebral joints Pathology • The onset of tuberculous osteomyelitis is usually insidious. • The infection is unrelenting, necrotizing, and destructive of bone, cartilage, and soft tissue. • The tuberculous exudation and the inflammatory necrosis may extend through the medullary and cortical bone, penetrate through the periosteum, and progress through the epiphysial and articular cartilage. • Tunneling sinuses may extend into the adjoining soft tissue and drain to the skin surface. • Sequestration and the formation of an involucrum are uncommon. Tuberculosis of the spine (Pott's disease)** • The thoracic and lumbar vertebrae • The infection often begins in the anterior part of the vertebral body and extends into the intervertebral disc: - Destruction and collapse of the vertebral bodies and discs – Kyphosis – Kyphoscoliosis Pott's disease The tuberculous exudate: • may spread through sinuses in the soft tissue • dissect along fascial planes and muscle sheaths • present at a more remote site as a "cold" abscess. – In this way, tuberculous exudation from the thoracolumbar spine may spread along paravertebral muscles and the psoas muscle sheath and localize in the inguinal region (psoas abscess). • Microscopically, tuberculosis of bone and joint is characterized, as are all tuberculous lesions, by the presence of – epithelioid granulomas (tubercles) – with central caseous necrosis and – Langhans' multinucleate giant cells Epithelioid granulomas & Langhans' multinucleate giant cells Bone Syphilis • Syphilitic infection may be acquired inutero (congenital syphilis) or postnatally (acquired syphilis) • Hematogenous spread of Treponema pallidum • In congenital syphilis, the infection is spread to the fetus by way of the placenta – The spirochetes localize at active sites of endochondral ossification in the metaphysis of long tubular bones • The two chief bone lesions of congenital syphilis are: • osteochondritis • periostitis Actinomycotic osteomyelitis • Actinomyces israelii : Actinomycosis is a chronic granulomatous disease • Two-thirds of all cases occur in the cervicofacial region • Microorganisms occur as normal flora of the oral cavity, • Remain localized in the soft tissues or invade the jaw bones. • The patient exhibits swelling, pain, fever and trismus. • If the lesion progresses slowly, little suppuration takes place; however • If it breaks down, abscesses are formed that discharge pus containing yellow granules (nicknamed sulfur granules) through multiple sinuses • The more aggressive lesion resembles chronic suppurative osteomyelitis Arthritis (Synovitis) Changes in synovial fluid in diseases of joints S. aureus (common), S.pyogenes, S.pneumoniae, N.gonorrhoeae, and H. influenzae.; Leukocytosis. ------------------------------------------------Knee, hip, or wrist: - culture of joint fluid - examination of a synovial biopsy specimen