Infectious (Septic) Arthritis
Viral (Immune Complex) Arthritis
Bone and joint infections are serious infections because destruction of bone or cartilage can lead to significant disability. Osteomyelitis and infectious arthritis are caused primarily by bacteria or fungi. In these diseases, the organisms directly infect the bone and joint. In contrast, immune complex arthritis, reactive arthritis, and rheumatic fever are caused by immune reactions to either bacteria or viruses, and organisms are not found in the joints.
The clinical diagnosis of infectious arthritis often involves an analysis of joint fluid. Radiologic studies of joints and bone contribute important information. Microbiologic diagnosis of osteomyelitis and infectious arthritis is typically made by culturing either a bone specimen or joint fluid. Antimicrobial therapy is typically given for long periods (i.e., weeks to months).
Osteomyelitis is an infection of the bone. The term osteo refers to bone, and myelo refers to the bone marrow. Osteomyelitis is classified as either acute or chronic.
The most common mode by which organisms reach the bone is by hematogenous spread (i.e., either bacteremia or fungemia) from a distant site. Acute bacterial osteomyelitis often arises from a pyogenic skin infection such as a boil, but many sources are undetected. Mycobacterial and fungal osteomyelitis often arise from the initial site of infection in the lung.
In children, hematogenous spread tends to result in osteomyelitis located at the end of long bones (at the metaphyses) that are richly endowed with blood vessels. In adults, hematogenous spread results most commonly in vertebral osteomyelitis and discitis, not osteomyelitis of the long bones.
Osteomyelitis also occurs by direct extension from an infected contiguous site such as a skin or soft tissue infection. It also can occur following trauma that results in an open fracture and direct contamination of the bone.
Chronic osteomyelitis tends to occur in the lower extremity, especially in diabetics who often have vascular insufficiency. They are predisposed to skin and soft tissue infections that extend into the bone.
The most characteristic clinical manifestations are bone pain and localized tenderness at the site of infection. Most (but not all) patients also have constitutional symptoms such as fever, night sweats, and fatigue. Limited range of motion of an affected extremity is seen. In vertebral osteomyelitis, the lumbar region is affected more often than the cervical or thoracic regions (Figure 70–1).
FIGURE 70–1 Vertebral osteomyelitis. Arrow indicates site of vertebral lesion. (Reproduced with permission from McKean SC et al. Principles and Practice of Hospital Medicine. New York: McGraw-Hill, 2012. Copyright © 2012 by The McGraw-Hill Companies, Inc.)
In acute osteomyelitis, the symptoms occur abruptly and progress rapidly, whereas in chronic osteomyelitis, the course is more indolent. In chronic osteomyelitis, necrosis of the bone occurs, and a sequestrum (an avascular piece of infected bone) can form at the site of the lesion (Figure 70–2). Relapses tend to occur in chronic osteomyelitis more than in acute osteomyelitis, and surgical debridement, especially to remove sequestra, is important to minimize the risk of relapse.
FIGURE 70–2 Chronic osteomyelitis. A. White arrow points to draining fistula at site of chronic osteomyelitis. B. White arrow points to necrotic bone caused by chronic osteomyelitis. (From Kemp WL, Burns DK, Brown TG: Pathology: The Big Picture. New York, McGraw-Hill, 2008. Copyright © 2008 by The McGraw-Hill Companies, Inc.)
The most common bacterial cause of acute osteomyelitis in both children and adults is Staphylococcus aureus (Table 70–1). However, vertebral osteomyelitis in adults may be caused by Mycobacterium tuberculosis (Pott’s disease). Osteomyelitis in patients with hip or knee prostheses is likely to be caused by Staphylococcus epidermidis or other skin flora. When osteomyelitis occurs in an intravenous drug user, it is most often caused by S. aureus; however, gram-negative rods, such as Pseudomonas and Serratia, and yeasts, such as Candida species, are also important causes. Osteomyelitis following a puncture wound of the foot through a sneaker is often caused by Pseudomonas aeruginosa, and osteomyelitis associated with a cat bite is likely to be caused by Pasteurella multocida. Patients with sickle cell anemia are predisposed to osteomyelitis cause by Salmonella species.
TABLE 70–1 Organisms Causing Osteomyelitis with Various Predisposing Factors
Fungal osteomyelitis is most often caused by either Coccidioides immitis or Histoplasma capsulatum. Living in areas where these fungi are endemic is an important predisposing factor. Viruses do not cause osteomyelitis.
A microbiologic diagnosis of acute osteomyelitis is most consistently made by culture of a specimen of the bone lesion. Blood cultures are positive in approximately half of cases.
The typical radiologic finding in acute osteomyelitis is a defect in the bone accompanied by periosteal elevation (Figure 70–3). Early in the disease, X-rays and even computed tomography (CT) scans may be negative. Magnetic resonance imaging (MRI) scans are the most sensitive radiologic test for diagnosis of osteomyelitis.
FIGURE 70–3 Periosteal elevation (arrow) in acute osteomyelitis of the tibia. (Reproduced with permission from Longo DL et al (eds). Harrison’s Principles of Internal Medicine. 18th ed. New York: McGraw-Hill, 2012. Copyright © 2012 by The McGraw-Hill Companies, Inc.)
Empiric therapy for acute osteomyelitis should include drugs that are bactericidal, penetrate well into bone, and include coverage for S. aureus. Vancomycin, nafcillin, or cephalexin administered parenterally can be used. Vancomycin is often used until the culture results and the sensitivity of the organism are known. The duration of therapy ranges from 3 to 6 weeks or longer. Surgical debridement of chronic osteomyelitis lesions is often necessary.
There is no vaccine effective against the common causes of osteomyelitis, and chemoprophylaxis is typically not employed. Proper foot care in diabetics can prevent osteomyelitis.
INFECTIOUS (SEPTIC) ARTHRITIS
Infectious (septic) arthritis is an infection of the joints. The terms infectious and septic are used to distinguish these infections from immune-mediated arthritis, such as rheumatoid arthritis. Bacteria, especially S. aureus, cause the vast majority of cases of infectious (septic) arthritis. Monoarticular involvement of a large weight-bearing joint, such as the hip or knee, is the most common presentation.
Synovial Fluid Analysis
Analysis of synovial fluid aspirated from a swollen joint plays an important role in the diagnosis of arthritis. Table 70–2 shows the findings in the fluid aspirated from an infected joint compared to normal synovial fluid. Synovial fluid from an infected joint may appear cloudy, has at least 20,000 neutrophils/μL, and has a low glucose concentration. Analysis of the fluid from the joints of those with rheumatoid arthritis and those who have a traumatic injury to the joint is included for comparison.
TABLE 70–2 Synovial Fluid Findings in Arthritis
Organisms typically reach the joint via the bloodstream from a skin site. Less frequently, organisms enter the joints through penetrating trauma, medical procedures such as arthroscopy, or a contiguous osteomyelitis.
Patients with long-standing rheumatoid arthritis and those with prosthetic hips and knees are predisposed to infectious arthritis.
The acute onset of an inflamed joint, typically a large weight-bearing joint such as the hip or knee, is the typical manifestation (Figure 70–4). Fever is often present. On physical examination, the affected joint is red, warm, and swollen, and a joint effusion is typically present. Reluctance to use a joint, especially in a child, may be a sign of infectious arthritis.
FIGURE 70–4 Septic arthritis of knee. Note swollen and inflamed left knee. (From the clinical slide collection on Rheumatic Diseases, 1991, 1995. Used by permission of the American College of Rheumatology.)
The most common cause of infectious arthritis overall is S. aureus (Table 70–3). In young sexually active adults, Neisseria gonorrhoeae is the most common cause. Patients with a prosthetic hip or knee joint are predisposed to infectious arthritis caused by S. epidermidis. S. aureus and P. aeruginosa are the most common causes in intravenous drug users. Borrelia burgdorferi, the cause of Lyme disease, should also be mentioned as the cause of inflamed joints that resemble those seen in infectious arthritis. However, organisms are not recovered from the affected joints in Lyme disease.
TABLE 70–3 Organisms Causing Infectious Arthritis with Various Predisposing Factors
Visualization of the organisms in the Gram stain of joint fluid is used to guide empiric therapy. A microbiologic diagnosis of infectious arthritis is typically made by culture of a specimen of the joint fluid. Blood cultures are positive in less than 30% of cases.
The typical radiologic finding in infectious arthritis is soft tissue swelling. Evidence of joint destruction can be seen if the infection progresses.
Untreated infectious arthritis can lead to joint destruction and loss of mobility, so prompt antibiotic treatment is required for optimal recovery. Empiric therapy for infectious arthritis should include drugs such as vancomycin, nafcillin, or cefazolin that are bactericidal against S. aureus. Ceftriaxone should be used if there is evidence that Neisseria gonorrhoeae is the cause. Removal of joint fluid via arthrocentesis and/or surgical drainage is an important adjunct to antibiotics.
There is no vaccine effective against the common causes of infectious arthritis, and chemoprophylaxis is typically not employed.
VIRAL (IMMUNE COMPLEX) ARTHRITIS
Viral arthritis is often called immune complex arthritis because the virus does not infect the joint but rather forms immune complexes with antiviral antibody that is deposited in joints and elicits an inflammatory response.
The clinical features of viral arthritis consist of either arthralgia (painful joints but without visible inflammation) or frank arthritis in which inflammation is apparent. Most cases of viral arthritis are of short duration and resolve spontaneously, but chronic arthritis may occur. The small joints of the hands are most often affected, but large joints can also be involved.
Viral arthritis occurs during the course of infection by several viruses. Rubella virus, either from the natural infection or from the immunization, is a well-recognized cause. Parvovirus B19 is an important cause in that the lesions resemble those of rheumatoid arthritis. The joint lesions of chronic hepatitis C also resemble rheumatoid arthritis. Arthralgia and arthritis occur in the prodromal period of hepatitis B infection. Several arboviruses also cause severe arthralgia, the most common of which is dengue virus. There is no antiviral treatment for viral arthritis.
Reactive arthritis is the term used to describe arthritis that occurs following infection by several bacteria that infect the gastrointestinal or genitourinary tract. The bacteria do not infect the joints. Rather, the arthritis is a result of the immune response to the bacterial infection. People who are HLA-B27 positive are predisposed to reactive arthritis. The bacteria commonly associated with this arthritis are Campylobacter, Shigella, Salmonella, Yersinia, and Chlamydia.
The main clinical manifestation is an asymmetric arthritis of the knee or ankle accompanied by fever. It typically resolves within a few days or weeks, but chronic arthritis may occur. Recurrences are common. Culture of synovial fluid is negative. Reactive arthritis accompanied by conjunctivitis and urethritis is called Reiter’s syndrome. Nonsteroidal anti-inflammatory drugs are considered first-line therapy. Antibiotics have no effect on reactive arthritis.
Rheumatic fever is an immune-mediated, poststreptococcal disease that affects the joints, heart, brain, and skin. It follows pharyngitis caused by Streptococcus pyogenes (group A β-hemolytic Streptococcus). It typically occurs in children ages 5 to 15 years. It is rare in the United States today probably because streptococcal pharyngitis is treated promptly.
Rheumatic fever typically begins with a migratory polyarthritis involving the large joints approximately 2 to 3 weeks after the pharyngitis. Carditis often occurs and is the main, life-threatening component of rheumatic fever. The carditis is a pancarditis (i.e., endocarditis, myocarditis, and pericarditis occur, often resulting in congestive heart failure). The mitral valve is most frequently involved. Chorea consisting of involuntary athetoid movements also occurs but is a rare manifestation. Skin involvement consists of erythema marginatum and subcutaneous nodules.
There is no diagnostic test for rheumatic fever. Table 70–4 shows the Jones criteria that are used as a guideline to establish the diagnosis. Two major manifestations or one major plus two minor manifestations suggest the diagnosis. In addition, laboratory evidence of prior infection by S. pyogenes is needed. This consists of either (1) a positive throat culture or positive rapid streptococcal antigen test or (2) a rising anti–streptolysin O antibody titer.
TABLE 70–4 Jones Guidelines for the Diagnosis of Acute Rheumatic Fever
The drug of choice is aspirin to reduce the inflammation. Antibiotics such as penicillin G have no effect on the course of the disease but can be given to reduce carriage of streptococci in the pharynx. Prevention of rheumatic fever involves prompt diagnosis and treatment of strep throat with penicillin G or oral penicillin V. In patients with residual heart disease, prevention of additional damage to heart valves by preventing subsequent episodes of streptococcal pharyngitis is very important. This is achieved by monthly administration of benzathine penicillin G, a depot preparation. This should continue until the patient is at least 20 years old or for 10 years after the last attack.