Pathology of Bone & Joint InfectionsDoç. 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 Osteomyelitis2- Osteomyelitis from a Contiguous Infection3- 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 blood-borne 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

Etiology• Infectious agents:– 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, coagulase-negative 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)

• RememberInfection 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 in-utero (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