Infectious Agents

From WiserWiki

[edit] Infectious Agents

Bernard ZimmermannIII

Edward V. Lally

Nancy Y.N. Liu

Musculoskeletal infections constitute an important group of illnesses for which patients often seek primary care.Acute inflammation of a joint, bursa, or tendon must be identified as either infectious or noninfectious to institute proper treatment.The most common bacterial infections that affect the musculoskeletal system include septic arthritis, septic bursitis, and osteomyelitis.In addition, viral arthritis, HIV-associated musculoskeletal syndromes, and Lyme disease are associated disorders.

[edit] SEPTIC ARTHRITIS

[edit] Epidemiology and Etiology

Acute bacterial septic arthritis is an urgent medical emergency because of the potential for joint destruction and mortality if the diagnosis and treatment are delayed or overlooked.The most common presentation of septic arthritis is an acutely painful and swollen joint in the patient with preexisting arthritis.Septic arthritis is usually caused by the hematogenous spread of bacteria to a joint previously damaged by arthritis or injury.Host factors that increase the risk of septic arthritis include older age, chronic illnesses with immunodeficiency, and preexisting arthritis.A large prospective study showed that age over 80 years, diabetes mellitus, rheumatoid arthritis (RA), prosthetic joint surgery, and skin infections were important independent risk factors predisposing to the development of septic arthritis in patients with arthritis.^[1] Skin flora are the most common sources of infection, but upper respiratory, gastrointestinal, and genitourinary portals of entry are also found.Rarely, septic arthritis may follow a penetrating injury or may be related to contiguous osteomyelitis, especially in children.The knee is the joint most often affected by septic arthritis, followed by, in decreasing order of frequency, the shoulder, hip, elbow, wrist, ankle, and small joints of the hands and feet.Infections of deep joints (e.g., sacroiliac) are uncommon, and the correct diagnosis often depends on the results of appropriate imaging studies.^[2]

From 75% to 80% of cases of nongonococcal bacterial septic arthritis in adults are caused by gram-positive bacteria, usually Staphylococcus or Streptococcus, and 15% to 20% of these infections are caused by gram-negative organisms (Table 141-1).The incidence of gram-negative septic arthritis, particularly Escherichia coli, has risen in the past 25 years.These infections occur notably in elderly debilitated patients, injection drug users, and young children.^[3] Septic arthritis caused by Haemophilus influenzae may be decreasing with the advent of vaccination of children for this organism.^[4] Anaerobic joint infections, although still rare, have also increased in frequency and are most often found in association with postoperative wound infections, especially after total joint replacement.^[5] A variety of unusual organisms, including fungi and mycobacteria, have been reported tocause septic arthritis.These usually present as chronic insidious monoarticular inflammation.

Table 141-1 Microbiology of Bacterial Septic Arthritis Related to Age of Patient✢

✢Percentages compiled from several studies.

[edit] Patient Evaluation

The patient usually complains of several days of progressive pain and swelling in one or more joints.Fever, sweats, or shaking chills may indicate systemic infection, and cough or dysuria may suggest an extraarticular source of bacteremia.Acute migratory polyarthritis with tenosynovitis in a young, sexually active adult suggests septic arthritis from disseminated gonococcal infection.

Physical examination may yield findings of a source of infection, such as pneumonia, otitis, pharyngitis, or cutaneous abscess.A synovial effusion is invariably present but may be difficult to discern in the obese patient.There is swelling, erythema, warmth, and limited range of motion of the affected joint.A complete musculoskeletal examination should be performed to investigate the possibility of polyarticular septic arthritis, which may be found in 20% of patients.

[edit] Laboratory Studies and Differential Diagnosis

The definitive diagnosis of septic arthritis depends on the analysis of synovial fluid obtained by arthrocentesis (Box 141-1).Septic synovial fluid appears cloudy or purulent.Gram's stain demonstrates bacteria in 50% to 75% of cases of nongonococcal bacterial septic arthritis and should be used to guide the initial choice of antibiotic therapy.Synovial fluid white blood cell (WBC) counts greater than 50,000 cells/mm³with more than 80% polymorphonuclear neutrophil leukocytes (PMNs) signify a high probability of infection, although gout and acute flares of RA may produce this degree of inflammation.Bacterial septic arthritis may occasionally present with a synovial fluid WBC count less than 50,000 cells/mm³, particularly in gonococcal septic arthritis.Radiographs of the affected joints should be obtained to assess underlying arthritis, investigate for contiguous osteomyelitis, and establish a baseline for future comparison.Blood cultures are also necessary to determine the presence of bacteremia.Extraarticular sources of infection should be pursued with appropriate diagnostic studies.

The differential diagnosis includes crystalline arthritis, acute viral arthritis, and nonseptic inflammatory arthritis.The patient with preexisting RA or another chronic inflammatory arthritis presents a particular diagnostic challenge, since septic arthritis may initially be mistaken for a flare of the underlying disease.A history of pain and swelling in one joint out of proportion to the others or the presence of fever or systemic signs should suggest joint infection.The presence of monosodium urate or calcium pyrophosphate crystals on polarized microscopy establishes the diagnosis of acute crystalline arthritis in the appropriate clinical setting but does not rule out coexistent bacterial arthritis.

[edit] Gonococcal Arthritis

Disseminated gonococcal infection may present with manifestations of acute septic arthritis.The dermatitis-arthritis syndrome is usually seen in sexually active adults, often in females within 1 week of menstruation or in the postpartum period.Many skin and joint manifestations of the syndrome are mediated by circulating immune complexes rather than direct microbial infection.^[6] The emergence of penicillin-resistant strains of gonococci requires third-generation cephalosporins in geographic areas where resistance is common (see Chapter 27 ).Two thirds of patients have tenosynovitis that affects the tendon sheaths of the wrists, fingers, ankles, and toes.Approximately 50% of patients have frank arthritis that is usually monoarticular but may progress to migratory or additive polyarthritis.Skin involvement occurs in as many as two thirds of patients with disseminated gonococcal infection.Cutaneous papules or pustules with anerythematous base are usually noted on the extremities and may have a necrotic center.The diagnosis must often be made on clinical grounds, since the synovial fluid WBC counts are lower than with nongonococcal bacterial infections (30,000 to 60,000 cells/mm³), Gram's stain is often nondiagnostic, and even careful cultures plated on chocolate agar are positive in only 25% of cases.To increase the yield of positive cultures, urethral, cervical, blood, and, when appropriate, pharyngeal and rectal cultures should be performed if disseminated gonococcal infection is suspected.Studies with polymerase chain reaction (PCR) analysis have demonstrated bacterial deoxyribonucleic acid (DNA) in synovial fluid, which may be diagnostically useful.^[7]

[edit] Management

The treatment of nongonococcal bacterial septic arthritis requires hospitalization for intravenous (IV) antibiotic therapy and joint drainage.Table 141-2 presents recommendations for the initial choice of antibiotics for adults based on the Gram's stain and clinical setting.Results of culture and sensitivity analysis determine the final antibiotic selection (Table 141-3).To remove inflammatory cells producing proteolytic enzymes, the joint must be thoroughly drained to minimize permanent joint damage.There are no prospective studies of the optimum method of drainage of the infected joint.^[8] In many cases, such as uncomplicated knee infections, satisfactory drainage may be achieved by daily needlearthrocentesis.The hip is usually treated with arthrotomy because daily needle aspiration is difficult.When arthrocentesis does not achieve a good clinical response, as indicated by a rising WBC count and persistent culture positivity despite several days of antibiotic treatment, more invasive methods of drainage (e.g., arthroscopy, open arthrotomy) should be employed.

Table 141-2 Antibiotic Therapy of Presumed Bacterial Arthritis in Adults (Pathogen Unknown)

Table 141-3 Antibiotic Therapy of Acute Bacterial Arthritis in Adults (Known Pathogen)

When the inflammation subsides, physical therapy with passive mobilization followed by active strengthening of periarticular structures helps to prevent joint contracture.Parenteral antibiotic therapy should continue for at least 3 to 4 weeks to ensure complete eradication of bacteria and prevent recurrence.Home IV therapy may be an effective alternative to prolonged hospitalization, particularly in the patient with infection in a non-weight-bearing joint who has responded to antibiotics and drainage.

[edit] Prognosis

The outcome of treatment for septic arthritis depends on many variables, including duration of the infection, virulence of the organism, and age and comorbidities of the patient.Virtually all patients with gonococcal arthritis recover completely, and 70% to 85% with group A streptococcal infections have a good outcome.However, up to 50% of patients who have septic arthritis from Staphylococcus aureus or gram-negative infections have residual joint damage.Patients with RA who develop polyarticular infection have less than a 50% chance of survival.

[edit] SEPTIC BURSITIS

Septic bursitis is a common soft tissue infection seen in outpatients.Features of the history and examination readily distinguish septic bursitis from other causes of periarticular inflammation, such as septic arthritis, traumatic bursitis, and tendinitis.The diagnosis is confirmed by bursal fluid analysis and culture.Treatment with oral antibiotics and appropriate drainage usually results in a good functional outcome.

[edit] Pathophysiology

The pathophysiology of septic bursitis differs from septic arthritis in that bacterial seeding is almost always through the transcutaneous route and is rarely associated with bacteremia.The subcutaneous olecranon and prepatellar bursae, located in the superficial tissue overlying the olecranon process and the patella, respectively, are the most frequently infected bursae.Local trauma may lead to superficial lacerations and abrasions, resulting in local cellulitis and bursal infection (Box 141-2).Infections of deep bursae (e.g., subacromial, iliopectineal) have been reported but are usually found with infection of the contiguous joint.

The vast majority (80% to 100%) of cases of septic bursitis are caused by gram-positive organisms, most often S.aureus. Streptococcal organisms, especially β-hemolytic streptococcus, account for 5% to 30% of infections.Case reports have described a variety of gram-negative, anaerobic, and fungal infections, but these are rare.^[9]

[edit] Patient Evaluation

The presenting symptoms of septic bursitis are usually gradually progressive pain, warmth, and swelling around the elbow or knee.A history of acute or chronic antecedent trauma is often present.Fever, chills, or systemic symptoms should suggest a more serious infection.The physical examination often reveals discrete tenderness and swelling of the bursal sac, but extensive erythema and cellulitis may obscure the source of the infection.The absence of joint involvement can be inferred if there is a full passive range of joint motion.Articular fluid, if present, should be investigated for septic arthritis, but arthrocentesis may demonstrate a sterile sympathetic effusion.

[edit] Laboratory Studies and Differential Diagnosis

Needle aspiration of the inflamed bursal fluid provides both diagnostic information and relief of symptoms.The technique employs a large-bore (18-or 20-gauge) needle inserted into the bursal sac parallel to the long axis of the extremity with the joint extended.The insertion point should be away from the apex of the bursa in an area of more normal skin, if possible, to avoid poor wound healing and a chronic draining sinus tract (Fig.141-1).Aspirated fluid should be sent for a WBC count with differential, Gram's stain, and crystal analysis.Superficial septic bursitis is often less inflammatory than septic arthritis.The bursal fluid WBC count is less than 20,000 cells/mm³in 50% of patients, but the range may be as high as 100,000 cells/mm³.Gram's stain reveals organisms in approximately 75% of patients, which serves to direct initial antibiotic treatment while culture results are pending.As in the diagnosis of the inflamed joint, the presence of intrabursal crystals does not rule out a coexistent infection.

Figure 141-1 Technique for aspirating olecranon bursa.

[edit] Management

Treatment of septic bursitis includes appropriate antibiotic therapy, bursal drainage, and local care.An oral penicillinase-resistant antibiotic (e.g., dicloxacillin) or first-generation cephalosporin (e.g., cephalexin, 500 mg every 6 hours, or clindamycin, 300 mg every 6 hours) treats the most common pathogens and penetrates well into the inflamed bursa.A 2-week course of antibiotics is usually sufficient, but patients with extensive cellulitis require prolonged therapy.Daily needle aspiration should be performed until the fluid is sterile and no longer reaccumulating.Patients who require hospitalization for IV antibiotic therapy include those with extensive cellulitis (Fig.141-2), a debilitated or immunocompromised state, or evidence of systemic infection.Some authors recommend inpatient therapy for all cases of septic prepatellar bursitis because of the difficulty of eradicating organisms in the thick skin overlying the knee.^[10] In patients with recurrent or resistant infection, surgical consultation is advised to obtain open drainage and to consider bursectomy for definitive therapy.

Figure 141-2 Septic olecranon bursitis with extensive surrounding cellulitis.

The outcome of therapy for septic bursitis is generally favorable.Some patients have recurrent infections, however, especially if the behavior leading to the local trauma in the predisposed area is not modified.

[edit] OSTEOMYELITIS

The clinical spectrum of osteomyelitis varies considerably depending on age of the patient, duration of infection, anatomic location of bone involvement, host factors, rapidity of diagnosis, and adequacy of initial treatment.The ability to diagnose and adequately treat bone infections is a difficult exercise at best, but a clearer understanding of this disease has emerged in recent years.

[edit] Pathophysiology

Osteomyelitis is generally divided into adult and pediatric categories and is considered in acute, subacute, and chronic forms (Table 141-4).Furthermore, vertebral osteomyelitis is a distinctly different entity from infections of the nonaxial skeleton.

Table 141-4 Osteomyelitis in Adult and Pediatric Age Groups

In neonates and children, hematogenous osteomyelitis most often results from a bacteremia or septicemia.In adults, hematogenous osteomyelitis is much less common and occurs most often in the vertebrae, particularly in the lumbar region.An apparent focus of infection at another site or a history of injection drug use is usually present.In the adult the arterial blood supply to the vertebrae ends at the vertebral end plate, and thus vertebral osteomyelitis is confined to the vertebral body and involves the disk only secondarily.Adult osteomyelitis most often develops secondary to trauma, contiguous infection, or surgical instrumentation.Bacteria are directly seeded into the bone at the level of the periosteum or medullary canal and produce an acute inflammatory reaction that often becomes subacute or chronic.

The microbiology of osteomyelitis varies with the mode of transmission.Aerobic bacteria or fungi are most often associated with hematogenous osteomyelitis.A single pathogen is usually responsible in both pediatric and adult patients. S.aureus is the most common organism in all age groups.In adult hematogenous osteomyelitis, aerobic gram-negative rods and fungal species are frequently causative, particularly in elderly patients with an extraosseous focus of infection and in injection drug users.

In contrast to the single pathogens responsible for hematogenous osteomyelitis, patients with trauma-related osteomyelitis or contiguous infection are typically infected with mixed microbial species, although S.aureus and S.epidermidis are often seen.Aerobic gram-negative bacilli and anaerobic organisms are frequently isolated from these mixed microbial infections.Unique pathogens are found under certain clinical circumstances. Pseudomonas species are often found in drug addicts.Osteomyelitis in patients with SC (sickle cell–hemoglobin C disease) and SS (sickle cell anemia) hemoglobinopathies is often caused by Salmonella. In immunocompromised patients, fungal species may be the causal agents, particularly Candida.

[edit] Patient Evaluation

The symptoms of osteomyelitis may reflect an acute localized infection of abrupt onset or a smoldering infectious process that is poorly localized and is associated with a paucity of systemic symptoms.Osteomyelitis is categorized as acute,subacute, or chronic based on duration of relevant symptoms.Overall, acute osteomyelitis is the most common form of the disease.The presentation is that of an acute febrile illness of a few days' duration.Localized pain in the axial or appendicular skeleton, accompanied by symptoms of acute infection, is the most common history obtained in adult osteomyelitis.Subacute or chronic osteomyelitis is usually a result of traumatic inoculation or transmission from a contiguous focus of infection.Pain is usually of longer duration, is less well localized, and frequently is not associated with systemic signs of infection.

The physical examination of acute osteomyelitis reveals signs of infection, including fever and warmth, erythema, swelling, and tenderness over the affected site.The clinical picture may be confused with cellulitis, but the localized nature of bony tenderness should suggest underlying osteomyelitis.With vertebral involvement the spine is often rigid, with localized tenderness of involved vertebrae.Signs are frequently lacking in subacute or chronic osteomyelitis.Tenderness in the axial or appendicular skeleton is often poorly localized.In cases associated with trauma or contiguous soft tissue infection, signs of osteomyelitis may be obscured by overlying inflammation.Patients with osteomyelitis contiguous with a joint may show evidence of acute septic arthritis.Careful neurologic examination should be performed, since patients with sensory peripheral neuropathies may have impaired pain perception.

[edit] Laboratory and Radiologic Studies

The ability to diagnose osteomyelitis depends on the host's ability to mount an appropriate localizing response to the osseous infection, as well as the physician's index of suspicion.An accurate diagnosis requires the documentation of a microbial species from a culture of blood or infected bone.In acute, untreated hematogenous osteomyelitis, blood cultures are positive in approximately 50% of cases, but the offending organism can be cultured from involved tissue in a much higher percentage.In chronic osteomyelitis it is usually necessary to obtain bone tissue for culture, since blood cultures are usually negative.

Radiographic abnormalities may support a diagnosis of osteomyelitis but are usually not conclusive.Plain radiographs in acute osteomyelitis usually demonstrate no bony pathology.Subacute osteomyelitis may require 2 to 3 weeks for x-ray changes to appear.These include periosteal elevation, cortical erosions, or large lytic areas.

Radionuclide imaging has been advocated as an adjunctive method to assist in the diagnosis.^[11] Technetium 99m, gallium Ga 67 citrate, or indium In 111 chloride scans may become positive within 48 to 72 hours of infection, but false-positive and false-negative results are common.It is particularly difficult to interpret such scans in the presence of overlying soft tissue infection or adjacent inflammatory arthritis.The In 111–labeled leukocyte scan has significant discriminatory capacity for osteomyelitis, particularly in diabetic patients and those with overlying soft tissue infection.^[12] Computed tomography (CT) and magnetic resonance imaging (MRI) are often useful to define areas of osteomyelitis more accurately.

The standard method of diagnosing osteomyelitis demands a positive culture result from a tissue specimen involved with infection; arriving at a diagnosis using any other method is presumptive.Practically, it is often difficult to make a culture-proven diagnosis, and management strategies are developed based on a high diagnostic probability for osteomyelitis.Culture of a single pathogen from blood or an overlying soft tissue infection combined with high-probability radionuclide or plain x-ray imaging studies may warrant presumptive antibiotic therapy.Less specific therapy results when diagnostic data are inconclusive.Whenever possible, a surgical or radiographically directed needle biopsy specimen of involved bone should be obtained for culture and sensitivity before initiating antibiotic therapy.

[edit] Management

Optimal treatment for osteomyelitis results from the early detection of bone infection and the isolation of a specific pathogen with known antibiotic sensitivities.In early acute osteomyelitis, IV antibiotics can be administered for a few days, then switching to oral antibiotics for up to 6 weeks.As initial therapy, antibiotics directed at S.aureus and β-hemolytic streptococci should be administered pending the results of culture sensitivities.Oxacillin (100 to 200 mg/kg/day), nafcillin, or benzylpenicillin (1 to 4 million U/day) are reasonable choices.Penicillin-allergic patients should receive a third-or fourth-generation cephalosporin.If the diagnosis of acute osteomyelitis is delayed for up to 2 weeks after symptoms are noted, or if the patient has chronic osteomyelitis, drainage of pus and debridement of infected bone are essential adjuncts to antibiotic therapy.Treatment of overlying soft tissue infection or removal of prosthetic devices is also necessary in most cases to eradicate infection.

Chronic osteomyelitis requires antibiotic therapy directed at identified organisms with appropriate sensitivities.In blood culture–positive adult osteomyelitis, IV antibiotics should be administered for at least 2 weeks and usually for 4 to 6 weeks.In osteomyelitis secondary to contiguous infection, broad- spectrum antibiotics that target gram-positive cocci, aerobic gram-negative organisms, and anaerobic or fungal species as appropriate should be administered.

Chronic osteomyelitis is now treated with oral antibiotics after an initial phase of parenteral medication.This approach is advocated largely because of the availability of newer antibiotics, especially the fluoroquinolones (e.g., ciprofloxacin, ofloxacin), which achieve excellent bone penetration and inhibit most strains of bacteria that cause osteomyelitis.Many patients with osteomyelitis may be treated entirely with prolonged oral courses of such agents.^[13] Exceptions include patients with diabetes mellitus and severe peripheral vascular disease.Such oral therapy depends on the ability to isolate the microbial pathogen (with appropriate antibiotic sensitivities) and to achieve a complete surgical debridement or excision of necrotic tissue.Most patients with chronic osteomyelitis, however, probably should be treated with IV antibiotics for at least 2 weeks before considering oral antibiotics.For patients with unknown or uncertain bacteriology, a full course of broad-spectrum IV antibiotics is still recommended.

[edit] VIRAL ARTHRITIS

[edit] Pathophysiology

Acute viremia is often associated with severe myalgias and arthralgias, regardless of the causative viral species.Much less often, frank arthritis or tenosynovitis is associated with an acute viral infection.Acute viral arthritis may be caused by direct viral replication in the joint or synovial tissue or, more frequently, by promoting an immune complex formation that initiates an inflammatory cascade within the joint.The vastmajority of acute articular syndromes (arthralgias and arthritis) are of short duration and do not lead to chronic arthritis or joint damage.However, certain viruses (e.g., human parvovirus B19) often produce polyarthritis that is subacute or chronic.A variety of viruses have been implicated in causing viral arthritis (Box 141-3).

[edit] Patient Evaluation

Patients who develop viral arthritis initially have features of a typical viral syndrome: fever, headache, malaise, myalgias, arthralgias, nausea, pharyngitis, or coryza.Such viral symptoms may occur sporadically or in association with a defined outbreak.Historically, generalized arthralgias are associated with viremia from diverse viral species.Joint swelling, severe stiffness, and redness should suggest frank arthritis.In many viral syndromes, polyarthralgias may be the only prodromal symptom.In viruses associated with characteristic rashes, articular symptoms frequently appear at or near the time of the viral exanthem.Concomitant findings associated with arthralgias include rash, oral ulcers, swollen glands, and cough.

Physical examination of patients with viral arthritis frequently reveals signs of an acute viral infection, including rash, pharyngitis, lymphadenopathy, hepatosplenomegaly, and oral ulcers.Viral arthritis may be monoarticular or oligoarticular, but it is most often symmetric and polyarticular.Most viruses lead to an arthropathy that involves large and small joints, which develops in an additive or migratory fashion.With all the viruses, involvement of the small finger joints and knees is most common.Joints in the wrists, ankles, feet, elbows, and shoulders are also frequently involved.Some viruses (e.g., hepatitis B, rubella) may involve the tendon sheath and produce tenosynovitis with swelling, erythema, and tenderness across the joint (typically the wrist or ankle), corresponding to the distribution of extensor tendons.

[edit] Specific Musculoskeletal Viruses

The three viruses that most often cause frank arthritis are human parvovirus B19, hepatitis B virus, and rubella virus.

Human parvovirus B19, a DNA virus, is the causal agent of erythema infectiosum (fifth disease of childhood).Parvovirus is a ubiquitous virus, with 30% to 40% of adults having serologic evidence of prior exposure.In children, parvovirus infection is characterized by an evanescent rash (often a slapped-face appearance) with low-grade fever and occasional mild arthralgias (Fig.141-3).In adults the rash is not a prominent feature of the illness.Arthralgias occur in up to 77% of patients.^[14] Joints most often affected include the small finger joints, wrists, and knees, although the ankles, feet, and elbows may also be affected.The arthritis may resemble acute RA, although rheumatoid factor is usually not detected.Unlike most other forms of viral arthritis, parvovirus-associated arthritis may persist for months or even years.No evidence of chronic erosive arthritis or permanent joint damage has been documented.Parvovirus arthritis is usually documented by the identification of immunoglobulin M (IgM) anti-B19 antibodies for up to several weeks after the initial exposure.

Figure 141-3 Slapped-cheeks appearance of fifth disease.

Hepatitis B virus(HBV) is a well-known cause of articular syndromes, particularly during the prodromal phase of the illness.The incubation period for HBV is 40 to 180 days.Several features of the illness are mediated by hepatitis B surface antigen (HBsAg) and the humoral response to this agent.Prodromal symptoms include fever, headaches, malaise, anorexia, nausea, vomiting, and abdominal pain.These symptoms precede the icteric phase by 2 to 14 days.Articular symptoms are a common feature of the clinical prodrome, occurring in 10% to 25% of cases.Immune complexes with HBsAg and HBV antibody are thought to mediate this process.Arthralgia or arthritis usually precedes clinical jaundice by days to weeks and resolves before the icteric phase of HBV infection.Joint symptoms are often associated with urticarial, petechial, or maculopapular skin rashes, usually on the lower extremities.Tenosynovitis of the wrist or ankle may be noted on physical examination.Articular involvement is usually symmetric and additive and involves the large and small joints.Arthritis usually resolves completely by the onset of jaundice but persists in 5% of patients with HBV infection.

Rubella virus infection produces a characteristic maculopapular eruption and lymphadenopathy.Children have no typical prodrome.In adults, however, sore throat, headache, fever, swollen glands, and myalgias may precede the rash by1 to 5 days.Adult patients with rubella infection who develop joint symptoms tend to be women between ages 20 and 40.About 30% of women and 6% of men with rubella infection manifest joint symptoms.Articular symptoms may develop before or after the appearance of the rash.Polyarthralgias develop most often, but frank arthritis may occur.The joint involvement is usually bilaterally symmetric, with small and large joints affected in an additive or migratory fashion.Arthritis and arthralgias usually evolve over 7 to 10 days and most often are short-lived with complete resolution.A similar articular syndrome has been associated with rubella vaccine virus, and again, women are predominantly affected.Severe arthralgias with stiffness, particularly of the hands and knees, usually develop approximately 2 weeks after the vaccination.Unlike the articular symptoms associated with natural rubella infection, those seen with the vaccine virus may recur, but permanent joint damage does not develop.

[edit] Diagnosis

The diagnosis of viral arthritis is usually presumptive.Confirmatory tests include the demonstration of acute and convalescent viral antibody titers of the IgM and IgG classes.Accurate identification of the offending virus is usually not necessary, since the course of the joint disease is usually self-limited, and specific antiviral treatment is not indicated.Synovial fluid from joints involved with viral arthritis usually has a mild leukocytosis, although synovial fluid WBCs have a wide range, typically with a mononuclear cell predominance.

[edit] Management

The treatment of viral arthritis includes standard supportive treatment for the acute viral syndrome.Inflamed joints and tendons should be splinted in the acute setting.If arthritis persists after the resolution of the viral infection, a short course of nonsteroidal antiinflammatory drugs (NSAIDs) is indicated.More intense treatment with second-line antirheumatic drugs is rarely necessary.

[edit] Prognosis

The prognosis of viral arthritis is usually excellent.In genetically predisposed individuals a viral infection may trigger an immune response that leads to chronic arthritis.The details of such a mechanism have not been elucidated.In such patients, treatment is directed at the suppression of chronic joint inflammation.

[edit] HIV-ASSOCIATED MUSCULOSKELETAL SYNDROMES

Since 1987 a variety of rheumatic syndromes has been reported in association with human immunodeficiency virus (HIV) infection (Table 141-5).It is still not established that HIV is directly responsible for the association of these syndromes or even that HIV has a statistically significant association with these conditions (see Chapter 32 ).

Table 141-5 Rheumatic Syndromes Associated With Human Immunodeficiency Virus (HIV) Infection

[edit] Epidemiology and Pathogenesis

The incidence and prevalence of musculoskeletal syndromes in the HIV-infected population are unknown.Studies attempting to establish these figures suffer from ascertainment bias.Estimates vary depending on the gender, ethnicity, and risk profile of the population studied as well as the clinical stage of the HIV infection.The most common rheumatic manifestations of HIV infection probably are polyarthralgias and bone pain, which occur in up to one third of patients.Frank arthritis is noted during the infection in approximately 5% to 10% of patients.True Reiter's syndrome or psoriatic arthritis probably occurs in fewer than 5%.Sporadic cases of septic arthritis, osteomyelitis, vasculitis, Sjögren's-like syndrome, and inflammatory myopathy have been described, but incidence figures are indeterminate.^[15]

Several possible mechanisms may explain the relationship between HIV infection and rheumatic disease.During a phase of viremia, HIV could produce polyarthralgias and bone pain as do other viral infections.HIV may produce a direct viral synovitis, which would explain arthritis syndrome associated with acquired immunodeficiency syndrome (AIDS).HIV has been isolated from synovial fluid, but this does not confirm an etiologic role in arthritis.Immune complexes can be found in HIV-infected individuals, but whether or not these mediate arthritis (as with HBV) is unknown.HIV infection may lead to an enhanced role for CD8 cytotoxic T cells, which have a potential pathogenetic role in the seronegative spondyloarthropathies^[16](see Chapter 137 ).

[edit] Patient Evaluation

When obtaining a history from an individual with known or suspected HIV infection and musculoskeletal symptoms, the physician must consider the spectrum of multisystemic rheumatic disease.In addition to symptoms of joint pain and swelling, patients with HIV should be questioned about low back and heel pain, rashes, genital ulcers, ocular inflammation, dry eyes, dry mouth, and muscle weakness.

Physical examination should include inspection for signs of ocular inflammation, lymphadenopathy, oral ulcers, skin rashes, mucocutaneous and genital ulcers, and nail changes.In addition to signs of arthritis, patients with seronegative spondyloarthropathies may have dactylitis (swelling and tenderness along an entire digit, or sausage digits).Evidence of inflammation at the entheses (points of ligamentous attachment to bones) may be particularly apparent in the heels, plantar surface of the foot, and pelvic brim.Signs of sacroiliac inflammation should also be sought on physical examination.

[edit] Diagnosis

The diagnosis of rheumatic syndromes in AIDS patients requires documentation of HIV infection.Most rheumatic syndromes are diagnosed on the basis of clinical findings.Analysis of synovial fluid obtained from involved joints demonstrates a mild to moderate inflammatory reaction with a monocytic predominance.Rheumatoid factor and antinuclear antibodies (ANAs) are typically not found in these patients and do not help to establish a specific diagnosis.

[edit] Management

The treatment of the rheumatic manifestations of AIDS requires treatment of the underlying infections.Some of the rheumatic syndromes (arthralgias, AIDS-associated arthritis) may be transient and require only analgesic medications.Syndromes associated with frank arthritis (Reiter's syndrome, psoriatic arthritis, AIDS-associated arthritis) usually require NSAIDs.Physical therapy measures may also be helpful.When these modalities are ineffective, sulfasalazine may be used for chronic arthritis.Caution should be exercised in the use of methotrexate or other immunosuppressive agents for Reiter's syndrome or psoriatic arthritis associated with AIDS,since this form of treatment may convert AIDS-related complex or mild AIDS to a fulminant syndrome, including malignant transformation.Septic arthritis and osteomyelitis are treated as in non-AIDS patients.

[edit] Prognosis

The prognosis of AIDS-related rheumatic syndrome is directly related to the underlying disease.Reiter's syndrome may lead to chronic arthritis with deformity and disability.Cases with long-term data are insufficient to evaluate the natural history of these conditions.

[edit] LYME DISEASE

Lyme disease is a multisystem spirochetal infection secondary to Borrelia burgdorferi. The organism is transmitted to humans from infected deer and white-footed mice by the tick vector Ixodes scapularis in the northeast and north-central United States or Ixodes pacificus in the Pacific Northwest.These are the most endemic areas, although nearly every state has reported cases of Lyme disease.

[edit] Pathophysiology and Patient Evaluation

The clinical manifestations of Lyme disease have been divided into three stages: early localized, early disseminated, and late or persistent infection^[17](Box 141-4).Initial infection usually occurs in the late spring or early summer, when the nymphal tick is 1 to 2 mm in size.Thus the tick or tick bite may not be detected until the symptoms of early localized infection occur, usually within 3 to 32 days.Fever, malaise, myalgias, arthralgias, headache, and localized lymphadenopathy may mimic viral infections. Erythema migrans(EM), the classic skin lesion that develops at the site of a tick bite, occurs in 60% to 80% of patients.^[18] Characteristically it is an erythematous macule or papule with expanding borders, reaching a mean size of 15 cm and often accompanied by central clearing (Fig.141-4).The lesion resolves spontaneously without antibiotic therapy.

Figure 141-4 Primary erythema migrans (EM) lesion of Lyme disease behind the knee, with multiple secondary lesions. (Courtesy Howard Keller, MD, Infectious Disease Division, Massachusetts General Hospital.)

The early disseminated stage, representing the hematogenous spread of the spirochete, develops days to weeks after infection.Secondary skin lesions may develop and are typically smaller than the initial EM lesion.Neurologic manifestations are common (15% to 20%) and include aseptic meningitis, encephalitis, Bell's palsy (often bilateral), and radiculoneuritis that can be sensory, motor, or mixed.Cardiac involvement occurs in 4% to 8% and manifests as fluctuating degrees of atrioventricular (AV) block or myopericarditis.Migratory arthralgias in large and small joints may accompany these symptoms.

Late or persistent infection may present months to years after the initial infection.The spirochete appears to persist in the central nervous system, joints, and rarely the skin, heart, and eyes.Neurologic disease includes chronic sensorimotor polyradiculopathy, subacute encephalopathy, and rarely a meningoencephalomyelitis.The encephalopathy is characterized by cognitive abnormalities, headache, and fatigue.Cerebrospinal fluid (CSF) analysis may reveal mild pleocytosis, elevated protein, and intrathecal production of antibodies to B.burgdorferi.

Joint disease occurs in 62% of untreated patients and manifests as inflammatory monoarticular or oligoarticular arthritis of the knees, ankles, and elbows.The small joints and bursae are rarely affected.Temporomandibular joint, hip, shoulder, back, and neck pain are common.Initially the pattern of joint inflammation is intermittent, lasting days to several weeks.Chronic arthritis, defined as persistent inflammation for 1 year or more, develops in 10% of untreated patients.Joint effusions may be massive; synovial fluid WBCs range from 10,000 to 20,000/mm³with predominantly PMNs.Cultures are usually negative.

[edit] Laboratory Studies and Diagnostic Procedures

Cultures of punch biopsies taken from the edges of EM lesions yield B.burgdorferi in 60% to 80% of cases, but cultures of blood, synovial fluid, and CSF are rarely successful.The diagnosis of Lyme disease is based on the clinical manifestations and serologic studies that detect antibodies to B.burgdorferi. The IgM response occurs 2 to 4 weeks after infection, whereas IgG is rarely detected before 4 to 8 weeks.The enzyme-linked immunosorbent assay (ELISA) is used most often; however, its sensitivity and specificity vary widely due to the lack of standardization among commercial laboratories, as well as the patient population tested.False-negative results occur because serum was obtained too early in the disease course or the patient had prior antibiotic therapy, which can abort the immune response.False-positive results may be seen in healthy individuals, autoimmune diseases, and other spirochetal and viral infections.Immunoblotting (Western blot) is useful in borderline cases or to distinguish true from false-positive results.PCR and T-cell proliferative assays are reported to be highly specific but have low sensitivity and remain primarily research techniques.

The American College of Physicians has published guidelines for laboratory evaluation in the diagnosis of Lyme disease.^[19] Recommendations are based on the probability that an individual patient has Lyme disease.If probability is low, and especially if the patient has nonspecific symptoms of myalgias, arthralgias, or fatigue, then no testing should be done.When a rash typical of EM is present and a history of tick bite (high probability), empiric therapy is recommended without need for antibody testing.All other patients with objective clinical signs should be evaluated by two-step testing with ELISA or immunofluorescence assay followed by Western blot if results are indeterminate.

Other tests that may support the diagnosis of Lyme disease include synovial fluid analysis, lumbar puncture with CSF analysis and antibody studies, and electromyography and nerve conduction tests.MRI may show nonspecific abnormalitiesin 25% of patients.Neuropsychiatric testing is useful to differentiate subtle encephalopathy from depression.

[edit] Management

Antibiotics are the major treatment for Lyme disease (Table 141-6).Currently, prophylactic therapy for tick bites is not indicated unless the patient is pregnant.Oral antibiotic therapy is adequate for early disease and arthritis.Doxycycline is contraindicated in children and in pregnant or lactating women.Parenteral antibiotics are recommended for meningitis, carditis, arthritis unresponsive to oral antibiotics, and other neurologic manifestations.Patients with early neurologic symptoms improve quickly, whereas late neurologic symptoms improve slowly over months.^[20]

Table 141-6 Recommendations for Treatment of Lyme Disease

✢May be less effective than other oral regimens.

In addition to antibiotics, management of high-degree AV block may require a temporary pacemaker.Joint aspiration and corticosteroid injections for chronic arthritis are effective but should be performed only after antibiotic therapy.Surgical synovectomy is often successful in chronic arthritis.

A minority of patients may not respond to antibiotic therapy.Patients with treated Lyme disease may have persistent fatigue or fibromyalgia symptoms that remain unresponsive to repeated courses of antibiotics.In patients with fatigue, headaches, or cognitive deficits, other useful modalities include tricyclic antidepressants, antiinflamma tory medications, cognitive retraining, and behavioral modifications.

[edit] Prevention

Vaccines made of recombinant B.burgdorferi outer surface lipoprotein A (OspA) are now available.Effective immunity against symptomatic infections is provided after a series of three doses.The first two are given 1 month apart in the months just before nymphs are active, followed by the third dose 1 year later.Whether the third dose can be given a month after the second dose and be effective remains to be demonstrated.Side effects are minor and include local injection site irritation and influenza-like illness in a small percentage of patients.The duration of immunity and indications for vaccination have yet to be defined.

Prevention of Lyme disease should be stressed to patients traveling to endemic areas.Since most experts believe that the spirochete is not transmitted until 36 to 48 hours after tick attachment, a daily body check for ticks is crucial.If a tick is found, gentle pulling with tweezers in a steady fashion is best.In addition, wearing long sleeves, tucking pants into socks, and using insect repellent containing diethyltoluamide (deet) are effective measures against tick attachment.

[edit] REFERENCES