Clinical and Pathologic Features
Pyogenic (septic) arthritis is usually (80% to 90%) monoarticular with predilection for large weight-bearing joints, such as the knee or hip. The clinical signs and symptoms depend on the site and extent of involvement as well as the specific infectious organism. Although most cases of septic arthritis are caused by Staphylococcus aureus, Escherichia coli, and Neisseria gonorrhoeae, other pathogens—including Pseudomonas aeruginosa, Enterobacter cloacae, Klebsiella pneumoniae, Candida albicans, and Serratia marcescens—are being encountered with increasing frequency in joint infections in drug users caused by the contamination of injected drugs or needles. New strains of Staphylococcus aureus may be methicillin (MRSA) or vancomycin resistant. MRSA’s secretion of the necrotizing toxin Panton-Valentine leukocidin results in more invasive infection and higher complication rates. Any large or small joint can be affected by septic arthritis, and hematogenous spread in drug addicts is characterized by unusual locations of the lesion, such as the spine (vertebrae and intervertebral disks), sacroiliac joints, sternoclavicular and acromioclavicular articulations, and pubic symphysis. Furthermore, with the increased usage of biologics and immunosuppressive drugs, clinicians should always keep in mind the possibility that an autoimmune disease has become complicated by an infection. This statement is particularly valid for the patients with rheumatoid arthritis who underwent surgery.
Figure 9.2 ▪ Entry routes of an infectious organism into a joint. The routes of infection in infectious arthritis are similar to those of osteomyelitis, which itself may be a source of spread.
The classic clinical presentation of septic arthritis is an abrupt, acute onset of joint pain accompanied by swelling and warm sensation. The joint becomes tender to palpation, and there is marked restriction of both active and passive motion. Fever is encountered in about 60% to 80% of cases. Some patients may experience chills. Laboratory findings include elevation of white blood cell (WBC) count, elevation of erythrocyte sedimentation rate, and positive blood cultures. Pathologic findings include progressive and increasing neutrophilic infiltrate of the synovium, associated with vascular dilatation and congestion, and increased number of type A and B synoviocytes. This is followed by cartilage necrosis and subchondral bone erosion. Infiltrates of polymorphonuclear leukocytes on the articular cartilage surface are a common finding (Fig. 9.3
). Synovial fluid appears opaque or frankly purulent. The nucleated cell count is very high, up to 50,000 cells per mm3
(see also discussion in Chapter 1
). Percutaneous aspiration and US-guided, CT-guided, or fluoroscopy-guided biopsy of a suspected focus of infection may be performed in the radiology suite. It can rapidly confirm a suspected diagnosis of infection and reveal the causative organism. For bacteriologic examination, synovial fluid should be placed into an empty sterile container (not carrying any media) and taken immediately to the laboratory for gram staining
and plating on appropriate media. Chocolate agar (CHOC), Thayer-Martin, or Transgrow media should be used when gonococcal arthritis is considered; Löwenstein-Jensen media, when tuberculous arthritis is suspected; Mannitol salt agar, for staphylococcus infection; and potato dextrose agar or Sabouraud agar for fungi infection.
▪ Pathology of infectious arthritis.
Photomicrograph of a portion of articular cartilage obtained from an acutely inflamed joint shows polymorphonuclear leukocytes on the cartilage surface and underlying erosion of the cartilage (H&E, original magnification ×25). (From Bullough PG. Atlas of Orthopedic Pathology with Clinical and Radiologic Correlation
. 2nd ed. New York, NY: Gower Medical Publishing; 1992. Fig. 4.20, p. 4.11
Figure 9.4 ▪ Infectious arthritis. A: A 48-year-old diabetic man presented with pain and soft tissue swelling of the right great toe for the past 3 months. Anteroposterior radiograph shows destruction of the first metatarsophalangeal joint associated with soft tissue swelling and edema typical for septic joint. B: In another patient, a 45-year-old HIV-positive man, who presented with a history of right hip pain for several months, anteroposterior radiograph shows extensive destruction of the right femoral head and right acetabulum. Hip joint aspiration and culture revealed methicillin-resistant Staphylococcus aureus (MARSA) infection.
In most instances, conventional radiography is sufficient to demonstrate the pertinent features of a bone or joint infection, particularly with the advantage of digital radiography and newest technology of PACS (Picture Archive and Communication System) allowing filmless high-resolution image-display format. Most infectious arthritides demonstrate a very similar radiographic picture, including joint effusion and destruction of cartilage and subchondral bone with consequent joint space narrowing (Fig. 9.4
, see also Fig. 3.19
). However, certain radiographic features are characteristic of individual infectious processes as demonstrated at various target sites (Table 9.2
) and may be helpful in arriving at the correct diagnosis. Generally, a single joint is affected, most commonly a weight-bearing joint like the knee or hip. The early stage of joint infection may be seen simply as joint effusion, soft tissue swelling, and periarticular osteoporosis, but “radiographic” joint space is usually preserved (Fig. 9.5
). In the later phase of pyogenic arthritis, articular cartilage is destroyed; characteristically, both subarticular plates are involved and the joint space narrows (Figs. 9.6
Scintigraphy has a very prominent role in diagnosing musculoskeletal infections, including infectious arthritis. In cases of suspected infection, radionuclide bone scan using
Tc) phosphonates is routinely used, because there is an accumulation of tracer in the infected areas (see Fig. 2.54
). A three- or four-phase technique is particularly useful for distinguishing infected joint from infected periarticular soft tissues if radiography is not diagnostic. With cellulitis, diffuse increased uptake is present in the first two phases, but there is no significant increase in uptake in the bone in the third and fourth delayed phases (see Fig. 2.53
). Conversely, osteomyelitis causes focally increased uptake in all four phases. The fourphase bone scan can also be useful in diagnosing septic arthritis in situ or with extension into the adjacent bone.
Table 9.2 CLINICAL AND IMAGING HALLMARKS OF INFECTIOUS ARTHRITIS AT VARIOUS TARGET SITES
Radionuclide bone scan (early)
Standard views specific for site of involvement
Destruction of subchondral bone (on both sides of joint)
Aspiration and arthrography
Narrowing of disk space
Loss of definition of vertebral end plate
Anteroposterior and lateral views
Partial or complete obstruction of intrathecal contrast flow
Destruction of disk
Diskogram and aspiration
Monoarticular involvement (similar to rheumatoid arthritis)
Radionuclide bone scan
“Kissing” sequestra (knee)
Sclerotic changes in subchondral bone
Anteroposterior and lateral views
Lytic lesion in vertebral body
Destruction of disk
Diskogram and aspiration
Soft tissue abscess (“cold” abscess)
Obstruction of intrathecal contrast flow
Narrowing of femoropatellar compartment
Edematous changes in infrapatellar fat pad
* In IV drug users, unusual sites of infection are encountered, including the vertebra; the sacroiliac, sternoclavicular, and acromioclavicular joints; and the pubic symphysis. The radiologic techniques used to evaluate infections at these sites, as well as the crucial radiographic abnormalities, are the same as those for the more common sites.
Figure 9.5 ▪ Infectious arthritis. Anteroposterior (A) and lateral (B) radiographs of the left knee of a 4-year-old child demonstrate a significant degree of periarticular osteoporosis and a large joint effusion. Note the small erosions of the distal epiphysis of the femur and the preservation of the joint space. Aspiration revealed hematogenous spread of a staphylococcal urinary tract infection.
Figure 9.6 ▪ Infectious arthritis. Anteroposterior (A) and lateral (B) radiographs of the right knee of an 80-year-old man show destruction of articular cartilage of all three joint compartments, erosions of the subchondral bone, posterolateral subluxation, and a large joint effusion.
Figure 9.7 ▪ Infectious arthritis. Anteroposterior (A) and lateral (B) radiographs of the left knee of a 66-year-old man show destruction of the articular cartilage of all three joint compartments, large erosions of the subchondral bone, posterolateral subluxation, large joint effusion, and soft tissue swelling.
Figure 9.8 ▪ Infectious arthritis. Oblique (A) and lateral (B) radiographs of the right ankle of a 31-year-old man show destruction of the articular cartilage of the medial malleolus, anterior tibia, and dorsal aspect of the talus, associated with ankle joint effusion.
Figure 9.9 ▪ Infectious arthritis. Radiograph of the toes of a 53-year-old woman shows destruction of the fifth metatarsophalangeal joint associated with a soft tissue swelling and edema.
Once the bone sustains an injury, such as surgery, fracture, or neuropathic osteoarthropathy, that causes increased bone turnover, routine scintigraphy with technetium-labeled phosphonate becomes less specific for infection. However, radionuclide studies using gallium (a ferric analog) and indium are more specific in these instances. There is still no general agreement on the exact mechanism of gallium localization in infected tissues. After intravenous injections of gallium, more than 99% is bound to various plasma proteins, including transferrin, haptoglobin, lactoferrin, albumin, and ferritin. At least five mechanisms of gallium transfer from the plasma into inflammatory exudates and cells have been suggested. These include direct leukocyte uptake, direct bacteria uptake, the protein-bound tissue uptake, increased vascularity, and increased bone turnover. Because gallium binds to the iron-binding molecule transferrin, the mechanism of gallium uptake in infectious processes is best explained by hyperemia and elevated permeability that increase delivery of
the protein-bound tracer transferrin into the area of inflammation. Cells associated with the inflammatory response, particularly polymorphonuclear white cells in which lactoferrin is carried within intracytoplasmic granules, deposit iron-binding proteins extracellularly at the site of inflammation, serving to combat the infection by sequestering needed iron from bacteria. Lactoferrin, which has a high binding affinity for iron, takes the gallium away from the transferrin.
The other tracer used in infections is indium. Because indium-labeled white blood cells are usually not incorporated into areas of increased bone turnover, scintigraphy with indium-111 (111
In) oxine-labeled leukocytes is used as a sensitive and specific test in the general diagnosis of infection of the musculoskeletal system and in specific instances when infection complicates previous fracture or surgery. Like other imaging procedures in nuclear medicine, this test monitors the internal distribution of a tracer agent to provide diagnostic information. The inherent ability of white blood cells to accumulate at sites of inflammation makes their use in this test particularly effective in the diagnosis of infections (Fig. 9.10
, see also Fig. 2.62
). Merkel reported the sensitivity of indium scintigraphy in detecting infections to be 83%,
with a specificity of 94% and an accuracy of 88%. It must be stressed, however, that because the 111
In-labeled leukocytes also accumulate in active bone marrow, the sensitivity for the detection of chronic osteomyelitis is reduced. To improve the diagnostic ability of this technique, a combined 99m
Tc-sulfur colloid bone marrow/111
In-labeled leukocyte study is advocated. A particularly difficult problem is the patient with diabetic foot neuropathy in whom superimposed infection is suspected. In this circumstance, radiography and even MRI are not very specific. Although soft tissue infection can be detected by the latter technique, early changes of osteomyelitis and septic arthritis may be missed. Often, no single imaging method can provide the correct diagnosis, and a combination of several imaging techniques should be used. The traditional sequential use of 67
Ga citrate in conjunction with the 99m
Tc-methylene diphosphonate (MDP) bone scan as an aid to diagnose osteomyelitis and infectious arthritis in the diabetic foot has been supplanted in recent years by the use of 111
In-labeled leukocytes. The drawback of this technique is that there remain difficulties in differentiating infection in the bone (osteomyelitis) from that in the adjacent tissue (cellulitis). A more recent attempt to improve this situation is the use of a combined 99m
In-labeled leukocyte study to determine whether the leukocyte collection is in the bone or in the soft tissue. A new challenger to 111
In leukocyte scanning is the 99m
Tc-hexamethylpropylene amino oxine (HMPAO)-labeled leukocyte scan. At the time of this writing, other methods are being tested, namely, isotope-labeled (99m
In, or 123
I) monoclonal antigranulocyte antibodies, isotope-labeled polyclonal IgG, isotope-labeled monocytes, isotope-labeled chemotactic polypeptide analogs, and isotope-labeled specific antibodies against bacteria.
Figure 9.10 ▪ Scintigraphy and MRI of infectious arthritis. A: Anteroposterior radiograph of the left shoulder of a 20-year-old woman shows moderate periarticular osteoporosis, osteolytic ill-defined lesions in the glenoid and proximal humerus, and periosteal reaction at the lateral aspect of the humeral shaft. B: 111In oxine-labeled white blood cell scintigraphy shows increased uptake of the radiopharmaceutical agent in the right shoulder (arrow). Coronal (C) and axial (D) T1-weighted fat-suppressed MR images obtained after administration of gadolinium show significant enhancement of the bones and surrounding soft tissues. The aspiration/biopsy followed by bacteriologic examination revealed Bacteroides fragilis.
Over the past decade, FDG-PET/CT has emerged as a rapidly evolving diagnostic tool for evaluation of infections. In particular, recent studies by Diaz and collaborators using a combination of [124I] FIAU-positron emission tomography and CT demonstrated positive signals at the site of infection at two hours after administration of 2mCi (74 MBq) of radiopharmaceutical agent. FIAU [1-(2′-deoxy-2″fluoro-beta-D-arabinofuranosyl)-5-iodouracil], a nucleoside analog that freely enters and exits cells, is a substrate for the native thymidine kinase (TK) from a wide variety of bacteria. Once phosphorylated by TK, [124 I] FIAU becomes trapped within bacteria and can be detected with PET/CT.
Figure 9.11 ▪ CT of osteomyelitis and infectious arthritis. Axial (A), coronal reformatted (B), and sagittal reformatted (C) CT images of the left foot of a 72-year-old diabetic man demonstrate an active osteomyelitis of calcaneus and infection of the subtalar joint. Note several sclerotic osseous fragments representing sequestra (arrows).
Arthrography has rather limited application in the diagnosis of joint infections. This radiologic technique, which is often performed after aspiration of the joint to obtain a fluid specimen for bacteriologic examination, helps determine the extent of joint destruction and demonstrate the presence of synovitis (see Fig. 2.30
). CT plays a determining role in demonstrating the extent of infection in bones and joints (Figs. 9.11
). Ultrasound (US) can occasionally be used in diagnosing soft tissue and joint infections, as well as osteomyelitis. This modality has the advantage of being easily accessible and available at relatively reasonable cost. In addition, this technique does not expose the patient to ionizing radiation. Real-time capability of US is unique in providing a means to evaluate structures under dynamic conditions. Furthermore, US plays an important role in the guidance of percutaneous biopsy and aspiration of infectious lesions, as well as the therapeutic drainage of abscesses.
At the present time, MRI established its place in the evaluation of musculoskeletal infections. As several studies have indicated, osteomyelitis, soft tissue abscesses, joint and tendon sheath effusions, and various forms of cellulitis are well depicted by this modality. MRI is as sensitive as 99m
Tc-MDP in demonstrating osteomyelitis and infectious arthritis and more sensitive and more specific than other scintigraphic
techniques in demonstrating soft tissue infections, primarily because of its superior spatial resolution. The proper evaluation of musculoskeletal infections with MRI requires both T1- and T2-weighted images in at least two imaging planes. In anatomically complex areas such as the pelvis, spine, foot, and hand, three planes may be necessary. MRI manifestations of pyogenic arthritis include joint effusion with surrounding soft tissue edema and bone marrow edema (Figs. 9.13
). In more advanced stages, cartilage and bone destruction may be seen, due to associated osteomyelitis (Figs. 9.15
, see also Fig. 9.4
). “Lamellated” joint effusion demonstrated with MRI has been described as a reliable sign of septic arthritis.
Figure 9.12 ▪ CT of infectious arthritis. A 31-year-old IV drug abuser presented with anterior chest pain and fever. A: Lateral radiograph of the chest shows a large soft tissue swelling anteriorly to the upper sternum (arrow). B: Sagittal CT image of the chest demonstrates erosive changes of the manubriosternal joint (arrow). C: Coronal reformatted CT image shows more clearly the joint erosions (arrows).
Figure 9.13 ▪ MRI of septic arthritis. Coronal T2-weighted MRI of the right hip in a 12-year-old boy demonstrates a joint effusion with capsular distension (arrow). There is edema of the surrounding muscles. There are no signs of osteomyelitis. The arthrocentesis and bacteriologic studies of the obtained fluid confirmed the presence of joint infection.
Figure 9.14 ▪ MRI of septic arthritis. A: Radiograph of the index finger of a 22-year-old man shows narrowing of the proximal interphalangeal joint, periarticular osteoporosis, and soft tissue swelling. B: Axial T1-weighted MR image shows low-intensity signal of the bone marrow and surrounding soft tissues of the index finger (compare with normal middle and ring fingers). Axial (C) and coronal (D) T1-weighted fat-suppressed MR images obtained after intravenous administration of gadolinium show significant enhancement consistent with infectious synovitis, cellulitis, and osteomyelitis.
Figure 9.15 ▪ MRI of septic arthritis. A: Dorsovolar radiograph of the right wrist of a 43-year-old man shows destruction of the radiocarpal joint and erosive changes of the distal radius, distal ulna, lunate, and scaphoid bones. Note also involvement of the carpometacarpal articulation. There is periosteal reaction of the distal radius and ulna and soft tissue swelling. B: Coronal 3D GRE fat-suppressed and coronal proton density-weighted fat-suppressed MR images demonstrate an erosion of the distal ulna (arrow) with a radiocarpal joint effusion extending to the distal radioulnar joint through a complete tear of the triangular fibrocartilage complex. Note the intermediate-to-low signal intensity of most of the effusion and mild surrounding soft tissue edema (arrowheads) consistent with synovitis due to septic arthritis.
Figure 9.16 ▪ MRI of septic arthritis. A: Dorsoplantar radiograph of the right forefoot of a 52-year-old man shows destruction of the first metatarsophalangeal joint, erosions of the head of the first metatarsal bone, and a large soft tissue swelling. Short-axis (B) and sagittal (C) T1-weighted MR images show low-intensity signal of partially destroyed head of the first metatarsal bone and surrounding soft tissues (arrows). Short-axis (D) and sagittal (E) T1-weighted fat-suppressed MR images obtained after administration of gadolinium show enhancement within the joint and bone marrow (arrows) indicative of joint infection and osteomyelitis.