Affected Joints

The joints of the lower extremities are the most common sites of infection, and knees, hips, ankles, and elbows account for 90% of infected joints in children. Septic arthritis affecting the small joints of the hands or feet is rare ( Table 41-3 ). Pyogenic sacroiliac joint disease can occur.

Multiple Infected Joints

Although septic arthritis is most often a monoarthritis, two or more joints are infected simultaneously or during the course of the same illness in a few children. In the large clinical experience reported by Fink and Nelson, septic arthritis was monoarticular in 93.4% of patients but affected two joints in 4.4%, three in 1.7%, and four in 0.5%. Multijoint septic arthritis is usually part of generalized septicemia such as with staphylococcus aureus.

Geographical variation exists with up to 24% multisite involvement reported in some studies. Certain immune deficiencies, such as chronic granulomatous disease or acquired immunodeficiency syndrome (AIDS), may predispose to septic arthritis in multiple joints.

Synovial Fluid Analysis

The characteristics of the synovial fluid depend somewhat on the duration and severity of the disease and previous administration of antibiotics. Synovial fluid may appear normal, turbid, or grayish green with bloody streaks. The synovial fluid white blood cell (WBC) count is often markedly elevated, with 90% polymorphonuclear leukocytes (PMN) leukocytes. Speiser and colleagues reported that synovial WBC counts in septic arthritis were less than 50,000/mm ³ (50 × 10 ⁹ /L) in 15% of children; 50,000 to 100,000/mm ³ (50 × 10 ⁹ to 100 × 10 ⁹ /L) in 34%, and more than 100,000/mm ³ (100 × 10 ⁹ /L) in 51%. Fink and Nelson found a relatively low WBC count (less than 25,000/mm ³ or 25 × 10 ⁹ ) in one third of their patients.

The protein content is high (more than 2.5 g/dL) in septic arthritis and the glucose concentration, compared with plasma glucose, is usually low, although it may be normal. A Gram stain identifies the organism in half of untreated patients but in only one fifth of those who have received antibiotics. A Gram stain provides rapid confirmation of bacterial infection and tentative identification of the organism (if the findings are positive), permitting rational antibiotic therapy. Special procedures such as counterimmunoelectrophoresis, latex agglutination, or evaluation by PCR may sometimes identify bacterial antigens in a culture-negative fluid (i.e., blood, urine, or cerebrospinal fluid). These techniques have the advantage of providing antigenic identification much more rapidly than cultures, but they do not provide antibiotic sensitivities. Use of real-time PCR to identify Kingella kingae toxin substantially increases the detection of this organism not identified in routine culture.

Blood Studies

At least two blood cultures should always be performed for a child suspected of having septic arthritis. An elevated WBC count with a predominance of PMNs and bands and a markedly elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) level, although of limited help in specific diagnosis, provide a baseline whereby the efficacy of subsequent treatment can be judged. CRP is a better predictor of septic arthritis than the ESR. If the CRP value is less than 1 mg/dL, the likelihood that the patient does not have septic arthritis was 87% in one study. Concentrations of other acute phase reactants are usually increased, but provide no additional useful information.

Radiological Examination

A number of imaging techniques may be helpful in evaluating a child with septic arthritis Plain radiographs are not diagnostic but might be helpful in excluding other disorders. They may show an underlying osteomyelitis as the etiology of the septic arthritis and may demonstrate only increased soft tissue and capsular swelling. Juxtaarticular osteoporosis reflects inflammatory hyperemia and is evident within several days after onset of infection. Cartilage loss and narrowing of the joint space and subluxation are late findings that develop as the disease progresses. These changes are followed by marginal erosions and eventually by ankylosis ( Fig. 41-1, A, E ). Computed tomography (CT) and especially magnetic resonance imaging (MRI) are additional confirmatory techniques.

A, Lateral view of the right knee in a 6-year-old boy with pain and fever demonstrates a large joint effusion. MRI obtained a few days later confirms a large joint effusion with diffuse synovial thickening on the sagittal STIR image (B) . The sagittal T1 fat-saturated image post-gadolinium (C) shows avid enhancement of the thickened synovium with nonenhancing pockets of fluid. There is also abnormal enhancement of the distal femoral epiphysis in keeping with osteomyelitis with bone abscess ( arrow ). AP (D) and lateral (E) radiographs of the right knee following treatment shows resolution of the joint effusion with patchy sclerosis in the distal femoral epiphysis indicating ongoing healing from osteomyelitis.

(Courtesy Dr. Jennifer Stimec.)

Computed Tomography

The role of CT is generally limited, as other imaging techniques are usually sufficient in children. It may be especially helpful for the evaluation of sacroiliac and sternoclavicular joints. It is also helpful, in combination with ultrasound, to guide aspirations and biopsies.

Ultrasonography

Detection of joint fluid by ultrasound can help guide fluid aspiration. The sonographic detection of an effusion in the hip of a child treated for osteomyelitis of the femur often indicates the presence of septic arthritis of the joint. Color Doppler may show increased capsular vascularity. In children, ultrasound is the imaging modality of choice for guidance during aspiration or biopsy whenever possible. It may be used in isolation or combination with other imaging modalities.

Radionuclide Scans

During the first few days of disease, when plain radiographs show only soft tissue changes, 99mTc-MDP scans reflect hyperemia of the infected area on blood flow studies and increased uptake of the isotope on both sides of the joint. Occasionally, decreased uptake may occur if significant accumulation of intraarticular fluid impedes local blood flow. This technique is useful in the early detection of joint or bone inflammation or infection, but it does not differentiate the two with certainty and cannot differentiate septic arthritis from synovitis from other causes (e.g., JIA). It is helpful in differentiating septic arthritis from osteomyelitis and soft tissue infection, and in the detection of multifocal joint infections. Radionuclide scans with gallium-67 or the patient’s indium-111-labeled granulocytes or monoclonal antibodies may be helpful but are not routinely needed. It is possible that 2-deoxy-2-[ ¹⁸ F] fluoro-D-glucose positron emission tomography (FDG-PET)/CT may have an important role in the diagnosis of difficult cases because PET is a relatively fast, whole-body imaging modality and can be used to find infectious foci outside of the bone or joint. It may be particularly helpful for infections of the vertebrae. In general, however, this modality has been replaced by MRI, which provides more detailed information without radiation exposure. PET positivity may help indicate which focus to approach for potential biopsy or aspiration.

Magnetic Resonance Imaging

Delineation of soft tissue structures by MRI is superior to that provided by CT. Changes may be seen as soon as 24 hours following infection. Synovial enhancement is detected in virtually all patients. Signal-intensity alterations in the bone marrow are characteristic, but not diagnostic of, septic arthritis (i.e., low intensity on fat-suppressed, gadolinium-enhanced, T1-weighted, spin-echo images, and high signal intensity on fat-suppressed, T2-weighted, fast spin-echo images) ( Fig. 41-1, B, C ). Articular cartilage and growth cartilage are depicted along with other fibrous structures, muscle, blood vessels, and synovial fluid. An abnormal collection of fluid or debris, often displacing the joint capsule, eroding into other tissues, or, in children, even leading to subluxation, supports the possibility of septic arthritis. Fat-suppressed, gadolinium-enhanced MRI is 100% sensitive and 79% specific for the diagnosis of septic arthritis in adults. MRI may be most helpful in children who do not respond to therapy in the predicted fashion to look for unresolved or other sites of infection in adjacent sites. As technology improves, MRI-guided biopsies or aspirations or other image fusion techniques are becoming useful diagnostic methods when the abnormality is only visible on MRI.

Antibiotics

In a child with septic arthritis, health care professionals should obtain cultures of blood, joint fluid and any other potential site of infection. IV antibiotics should then be administered as promptly as possible. The main issue that may influence the first dose is the timing of joint aspiration. In general, aspiration is preferred to identify organisms, but if any delay is anticipated, antibiotic treatment should be started as soon as blood cultures are obtained. The choice of antibiotic depends on the presence of predisposing factors; the age of the child; and the organisms suspected because of the Gram stain or rapid antigen detection tests (although it is hazardous to narrow initial treatment based solely on these results because either can be wrong). If the Gram stain and results of rapid antigen detection are negative or not available, an approach based on age (as outlined in Table 41-5 ) is suggested. For uncomplicated osteoarticular infection in infants and children, clindamycin was as effective as cephalosporin. The demonstration of an organism or antigen may support or contradict the generalizations outlined in this table and should influence the physician in selection of the initial antibiotic treatment.

Although monitoring intravenous antibiotic efficacy with serum bactericidal titer can be performed, it is seldom used unless response to therapy has been unsatisfactory. After satisfactory control—based on a combination of clinical signs such as absence of fever and improved movement of the affected joint plus laboratory parameters such as reduction of the WBC, ESR, and CRP—of the infectious process with IV antibiotic administration is achieved, treatment by the oral route in the hospital or on an outpatient basis may be appropriate. Trials have suggested that the duration of treatment can be shortened to 10 days in total. Home IV antibiotic programs may also be effective in reducing the hospital stay, but they may be associated with complications in up to 30% of children. Such programs should be undertaken only after careful consideration and consultation with an expert in pediatric infectious disease. The criteria for conversion from IV to oral therapy are uncertain. Although many criteria have been suggested, such as resolution of fever, significant decrease in pain, improvement in range of motion, and falling laboratory measures of inflammation, the most useful assessment is when the child starts to move the limb voluntarily with a reducing or absent fever.

If the cultures are negative, IV antibiotics should be continued for a minimum of 21 days. If the child’s clinical state is improving (i.e., temperature returning to normal, pain diminishing, range of motion improving) and the WBC count and ESR/CRP are falling, the initial antibiotics chosen should be maintained. If the patient does not appear to be responding, clinicians need to consider that the drug, dose, route, and compliance are appropriate, and the possibility of the reaccumulation of joint fluid or another site of infection. Because of various patterns of antibiotic susceptibility and resistance, guidelines regarding antibiotic choice and duration of treatment are constantly changing, and the physician is urged to review the most current recommendations. This is especially important with the rise in the incidence of community-acquired Methicillin-resistant Staphylococcus aureus (CA-MRSA), which requires specific antibiotic management. As noted previously, the total duration of therapy is controversial but in uncomplicated septic arthritis in a child who responds rapidly, 10 days is probably sufficient.

Aspiration and Drainage

The usefulness of repeated aspiration and drainage of an infected joint has been hotly debated. There is no dispute that an initial diagnostic arthrocentesis must be performed. Any joint that appears to be under pressure from an effusion can probably benefit from aspiration, if only for pain relief. Studies of the importance of repeated aspirations under other circumstances, however, have failed to show a consistent benefit. Open drainage is no better than closed needle aspiration (except for specific joints such as the hip and shoulder) and is attended by significantly increased morbidity. It is not known whether irrigation of the joint at the time of aspiration provides additional benefit with improved outcome. Occasionally, arthroscopic examination is indicated. Intraarticular administration of antibiotic is unnecessary because therapeutic synovial fluid antibiotic levels are readily achieved, and it may induce chemical synovitis in the infected joint.

Neonatal Septic Arthritis

In addition to S. aureus, group B Streptococcus and Gram-negative bacteria can be the offending organisms in the neonate. Infections with these organisms are rare but potentially extremely serious in this age group. They may have a subtle presentation and can occasionally be bilateral, and they are much more likely to occur in association with osteomyelitis than in older children. Most affected newborns show no fever, toxemia, or leukocytosis. Any infant who has swelling in the region of the thigh or holds the leg flexed, abducted, or externally rotated, or refuses to use the upper limb must be investigated promptly. Problems in early recognition of disease undoubtedly contribute to the often disastrous outcome of this involvement.

Septic Hip Joint

Septic arthritis of the hip is such an important problem that it merits special attention. Because the risks of missing this diagnosis are so high, there must a very low threshold for hip aspiration to establish the diagnosis. The femoral head is intracapsular, and the arterial supply passes through the ligamentum teres into the intracapsular space. Increased intracapsular pressure can therefore interrupt the blood supply to the femoral head, with disastrous consequences to its viability, leading to the subsequent development of avascular necrosis. Metaphyseal osteomyelitis readily leads to septic arthritis of the hip joint in the infant because nutrient blood vessels pass from the metaphysis through the epiphyseal growth plate and terminate in the distal ossification center.

Septic arthritis of the hip joint is most common in infants and very young children; 70% of patients are 4 years old or younger. The typical clinical picture is that of an infant or young child who may have an unexplained fever, is irritable, and refuses to move a leg, bear weight, or walk. Any movement of the hip is extremely painful, and the affected leg is held in a position of partial flexion, abduction, and external rotation at the hip. Occasionally, the child has lower abdominal pain or tenderness, sometimes with paralytic ileus.

The most common differential diagnosis for septic arthritis of the hip in the younger child is transient synovitis or irritable hip syndrome. Transient or toxic synovitis of the hip is an idiopathic disorder often preceded by a nonspecific upper respiratory tract infection. It occurs most commonly in boys (70%) between 3 and 10 years old. Pain in the hip, thigh, or knee may be of sudden or gradual onset and lasts for an average of 6 days. Bilateral involvement occurs in approximately 4% of cases. There is loss of internal rotation of the hip, and the hip may be held in the flexed, abducted position. The ESR and WBC count are usually normal. Radiographs often appear normal or may document widening of the joint space with lateral displacement of the femoral head because of effusion. These findings can be confirmed by CT or ultrasound studies. Radionuclide scanning may demonstrate a transient decrease in uptake of technetium 99m phosphate. Signal intensity is normal with MRI and differentiates toxic synovitis of the hip from a septic process, which is usually the principal differential diagnosis. After a diagnostic ultrasound scan to confirm the presence of fluid, the hip joint should be aspirated to exclude bacterial sepsis if the diagnosis is uncertain. The ability to weight bear and move the hip voluntarily, and the absence of elevated inflammatory markers, all suggest transient synovitis of the hip. The synovial fluid has a normal or minimally increased cell count but may be under high pressure. After aspiration, the pain and range of motion are dramatically improved, at least temporarily. Treatment includes the use of analgesics or NSAIDs, bed rest, and skin traction with the hip in 45° flexion to minimize intracapsular pressure. Long-term sequelae include Legg–Calvé–Perthes disease, which appears in about 1.5% of cases at some point in the future. The only other long-term sequela is the development of coxa magna, which fortunately is of no clinical significance. Recurrences are often accompanied by low-grade fever. Although prediction rules tend not to function well in the general population, possible criteria used to differentiate septic arthritis from irritable hip syndrome include refusal to bear weight; a fever of 38.5°C; ESR greater than 40 mm/hour; and WBC greater than 12 × 10 ⁹ /L. Another study suggested refusal to bear weight and CRP greater than 20 mg/L were highly predictive of septic arthritis.

In very young or premature infants, a number of risk factors predispose to septic arthritis of the hip. In a study of septic arthritis of the hip of 16 infants younger than 4 weeks old, 11 were premature, 7 had an umbilical catheter, and 12 had septicemia. In contrast, of 13 children between the ages of 1 month and 3 years with septic arthritis, none was premature or had an umbilical catheter, and only 5 were septicemic. A high frequency of preceding or accompanying osteomyelitis of the femur or pelvis has been observed. The association of septic arthritis of the hip and femoral venipuncture has been recorded and may account in part for the high frequency of arthritis of this site in the premature neonate.

Management of septic arthritis of the hip requires open drainage to minimize intraarticular pressure. Children are seldom immobilized, instead allowing early passive and active physiotherapy to prevent loss of range of motion. In the unusual circumstance of septic arthritis with subluxation or dislocation, older children require immobilization and neonates require a Pavlik harness for the hip. Prognosis is guarded even with the best treatment, especially in the neonate. The anatomy of the shoulder joint is not unlike that of the hip with respect to vascular supply. Septic arthritis of this joint, although rare, should be treated similarly.

Gonococcal Arthritis

In reported series of septic arthritis in children and adolescents, disease caused by N. gonorrhoeae appears to be uncommon. When it occurs, it is most common in the adolescent, although it occasionally occurs in the neonate in association with disseminated infection. It is more common in girls than in boys and is particularly likely just after menstruation or with pregnancy. Gonococcal arthritis usually develops in patients with primary asymptomatic genitourinary gonorrhea or with a gonococcal infection of the throat or rectum. The patient presents with a systemic illness characterized by fever and chills. A vesiculopustular rash, sparsely distributed on the extremities, commonly yields organisms on culture or Gram stain of the smear. Gonococcal arthritis may have an initial migratory phase and may be accompanied by tenosynovitis. In contrast to most patients with septic arthritis, those with gonococcal arthritis may present with a purulent arthritis of several joints. For a patient with suspected gonococcal arthritis, it is important to culture samples from the genital tract, throat, rectum, and any vesicles in addition to the affected joint. Special culture media with Thayer-Martin agar will help in isolating the organism. The possibility of sexual abuse should be considered and appropriately investigated.

Mycobacterial Arthritis

Tuberculous arthritis is seldom encountered in North America or Europe, although its frequency may be increasing because of immunosuppressive therapy, drug-resistant strains of tuberculosis, the human immunodeficiency virus (HIV) epidemic, and international travel. Tuberculous arthritis is by no means rare in other parts of the world. Typically, arthritis arises on a background of pulmonary tuberculosis as indolent, chronic monoarthritis, often of the knee or wrist, which eventually results in extreme destruction of the joint and surrounding bones. It manifests as acute arthritis in rare instances. Occasionally it may present as otherwise typical oligoarticular JIA in the absence of pulmonary disease. If a patient suspected of having oligoarticular JIA fails to respond to intraarticular corticosteroid treatment, the suspicion of tuberculous monoarthritis should be raised, especially if there may be a relevant travel history or contact with people from endemic areas.

Joint infection occurs by hematogenous dissemination of the organism or from adjoining osteomyelitis. For example, hip arthritis can result from spinal infection where organisms track down to the iliopsoas muscle that communicates with the joint. Chronic draining fistulae may develop. Pott disease is a consequence of vertebral osteomyelitis ( Fig. 41-2 ). Tuberculous dactylitis may occur with cystic expansion and destruction of bone (i.e., spina ventosa) ( Fig. 41-3 ). A family or environmental history of pulmonary tuberculosis and a positive purified protein derivative (Mantoux) skin test result suggest the possibility of tuberculous arthritis. Although synovial fluid cultures are positive in approximately 75% of patients, synovial membrane biopsy and culture are preferred and confirm the diagnosis in almost all patients ( Fig. 41-4 ). The synovial WBC count is classically less than 50,000/mm ³ (50 × 10 ⁹ /L), with a high proportion of mononuclear cells. Genus-specific PCR is invaluable in the diagnosis. Rarely, a polyarthritis accompanies tuberculosis (i.e., Poncet’s disease); it probably represents a reactive arthritis because culture of the inflamed joints fails to demonstrate tubercle bacilli.

Pott disease of the vertebral column in an adolescent boy with pulmonary tuberculosis produced destruction of the disk space and vertebral end-plate erosion ( arrow ).

Advanced osseous destruction occurred in the foot of a child with tuberculous dactylitis (i.e., spinal ventosa).

Synovial biopsy specimen of chronic inflammation in tuberculous joint disease in which a giant cell ( arrow ) is indicated.

Another mycobacterial disease that can result in arthritis is leprosy, caused by Mycobacterium leprae. Although the most common clinical manifestations are rash and peripheral neuropathy, arthritis occurs in approximately 75% of cases. Different types of arthritis in leprosy include Charcot joints, septic arthritis, acute polyarthritis, chronic arthritis, and tenosynovitis. Clinical differentiation from JIA may be difficult, especially if the possibility of leprosy is not considered in a nonendemic area; a high degree of clinical suspicion is required to make this diagnosis. Mycobacterium leprae is not always easily identified in synovial biopsies. Serologic testing may be helpful in confirming the diagnosis. Additional cases of leprosy have been reported following the institution of anti-TNF therapy in patients with rheumatoid arthritis.

Arthritis Associated With Brucellosis

Human Brucella infections are reported primarily from Europe, Israel, and South America, with a substantial number of patients having arthritis. Cases that develop in North America are more likely to have been acquired elsewhere. The species most frequently implicated are Brucella melitensis and, less commonly, Brucella canis. Unpasteurized milk is a source of infection.

The systemic illness is often mild in children but is usually characterized by undulant fever, gastrointestinal complaints, lymphadenopathy, and sometimes dermatitis. In 88 children from Israel, the classic triad of fever (91%), arthralgia or arthritis (83%), and hepatosplenomegaly (63%) was characteristic of most patients. In a large series of cases from Peru, almost one third were children, and one third had arthritis. In the neonate to 15-years-old age group, peripheral arthritis of a hip or knee was most common. In patients whose onset was after 15 years of age, sacroiliitis was the most common articular syndrome. Spondylitis and sacroiliac arthritis became predominant after children reached 15 years of age. Gomez-Reino and colleagues found that periarthritis without effusion was most common and that small joints and the spine were not affected. Whether this reflects differences in the infecting organism or in ascertainment is not known. No association with human leukocyte antigen (HLA)-B27 has been demonstrated. Synovial fluid WBC counts are only modestly elevated, with a slight predominance of mononuclear cells. Joint fluid culture is positive for the organism in some patients. Tetracyclines, aminoglycosides, rifampin, and trimethoprim-sulfamethoxazole, often in combination, provide effective treatment of the acute infection, although permanent sequelae may result.

Mycoplasma and Arthritis

Myalgia and arthralgia are common during pulmonary infection with Mycoplasma pneumoniae. Objective oligoarticular, polyarticular, or migratory arthritis has also been described. Sensitive screening tests may uncover Mycoplasma as a cause of arthritis even in the absence of pneumonia.

Bartonella Infection and Arthritis

There have been rare reports of Bartonella henselae infection causing arthritis in children (e.g., cat scratch disease). In two children, the disease mimicked systemic JIA ; a third child had polyarthritis and subcutaneous nodules. Arthropathy occurred in 3% of patients in an Israeli registry. It was characterized by large- and medium-sized monoarthritis, oligoarthritis, or polyarthritis (most commonly symmetric oligoarthritis), which was debilitating. Despite cat scratch disease being a disease of children and adolescents, in this series no patient under 20 years old had joint involvement. The arthrop­athy usually occurred concurrent with the lymphadenopathy. Erythema nodosum was more common in those with than without arthropathy.

Arthritis in Immunocompromised Patients

Chronic inflammatory arthritis in patients with a primary immunodeficiency is discussed in Chapter 46 . Typical septic arthritis has been reported infrequently in immunodeficient children. Mycoplasma is the most common cause of severe chronic erosive arthritis in patients with congenital immunodeficiency syndromes and has been recovered from joints of patients with AIDS. Ureaplasma urealyticum has been identified in patients with agammaglobulinemia. Candida albicans is occasionally responsible for arthritis in immunosuppressed patients. Patients with HIV have increased incidence of Streptococcus pneumoniae infection that requires broad-spectrum antibiotics.

Arthritis Associated With Acne

The association between arthritis and acne has been noted for decades. Most patients are male and have onset of musculoskeletal complications during adolescence. The syndrome includes severe truncal acne followed in several months by fever and arthralgia or arthritis, most often involving hips, knees, and shoulders. Myopathy may also accompany the disorder. It is possible that this syndrome is another example of reactive arthritis. Although arthritis lasts for only a few months in some patients, recurrences over many years have been documented. Treatment with NSAIDs and with antibiotics for control of the acne is indicated. Treatments for acne may also be associated with arthritis, such as minocycline-induced autoimmune phenomena and isotretinoin causing an acute arthritis. Infliximab for the treatment of arthritis has been reported to cause acne. Some cases fall under the category of the pyogenic arthritis pyoderma gangrenosum acne (PAPA) syndrome, reviewed in Chapter 47 . Recurrent attacks of acute episodes of monoarthritis and fever, resembling septic arthritis, may also be seen in patients with familial Mediterranean fever, also reviewed in Chapter 47 .

Whipple Disease

Whipple disease, first described in 1907, is rare in childhood, although primary infection with the causative organism may cause diarrhea and transitory fever in young children. The disease is caused by the bacterium Tropheryma whipplei, a ubiquitous organism present in the environment, and is characterized by abdominal pain, weight loss, diarrhea, and, in 65% to 90% of patients, arthralgias or arthritis that in most cases precedes other clinical signs by several years. Whipple disease occurs 10 times more frequently in males than in females and is most common in middle age, although it has been identified in young children. Migratory, peripheral joint pain and inflammation lasting hours to months occur over a period of many years, often in association with fatigue, weight loss, and anemia. Joint swelling with increased synovial fluid and restriction of range of motion may occur, although residual deformity does not. The joints most frequently affected are the ankles, knees, elbows, and wrists, and spondylitis has been reported in 20% of cases. Occasionally, arthritis or spondylodiscitis may be present in the absence of gastrointestinal symptoms, and Whipple disease should be considered in patients who are resistant to antirheumatic treatment. A significant percentage of the population, especially those who work with soil or in sewage plants, may be asymptomatic carriers. Periodic acid–Schiff–positive material and bacteria are detectable in macrophages infiltrating the upper small intestine and lymph nodes. Other diagnostic tools include PCR, immunohistochemistry, and electron microscopy. These tests may also be diagnostic on synovial tissue. Because it takes several months to culture the organism, cultures are not recommended as a diagnostic tool. Furthermore, patients with arthritis may not have gastrointestinal (GI) symptoms, and duodenojejunal biopsies will be negative. In such cases PCR is especially important. A genetic predisposition has been suggested based on the ubiquitous nature of the organism, but causative genes have not been identified. Antimicrobial therapy has greatly improved the outcome in this disease. In the absence of neurological involvement, the combination of doxycycline and hydroxychloroquine is the recommended first-line treatment. If there is neurological involvement, sulfadiazine should be added to this regimen. The immune reconstitution syndrome has been reported in several patients following successful treatment.

Subacute Osteomyelitis

Compared with acute osteomyelitis, patients with subacute osteomyelitis, defined as disease duration between 2 weeks to 3 months, experience less pain, often have no fever, and have frequently received a course of antibiotics. Laboratory changes are less common, but radiographs are usually abnormal and may be confused with Ewing sarcoma or osteoid osteoma. Brodie abscess, a unique form of subacute osteomyelitis, is usually of staphylococcal origin and may develop after a penetrating injury or more likely by hematogenous spread of an infection to the metaphysis. It is characterized clinically by tenderness with pain that may awaken the child at night. Radiographs demonstrate only soft tissue swelling early, but eventually metaphyseal osteolytic lesions are evident. They are most common in the proximal or distal ends of the tibia ( Fig. 41-5 ). Culture of the abscess may be negative. Treatment includes IV antibiotics, an NSAID, and immobilization.

Brodie abscess is revealed in radiographs of the knee of a 16-month-old boy with acute hematogenous osteomyelitis inadequately treated 1 month earlier. A, Central sequestration with a surrounding, ill-defined lytic margin. The patient was appropriately treated with antibiotics at this stage. B, One month later, the sequestrum has been removed by osteoclasts. C, One month later, the radiograph shows a well-defined lesion with sclerotic borders.

(Courtesy Dr. B. Wood.)

Chronic Osteomyelitis

Chronic osteomyelitis develops when acute osteomyelitis has been inadequately treated, or it develops in states of impaired host or antibiotic resistance. Reduced blood flow leads to the formation of a sequestrum, which may be surrounded by a sleeve of periosteal new bone (involucrum). Complications of chronic osteomyelitis include growth plate arrest or stimulation, avascular necrosis, pathological fracture, septicemia, and if it becomes chronic, amyloidosis.

Neonatal Osteomyelitis

Neonatal osteomyelitis merits special consideration. Until a child reaches the age of approximately 18 months, metaphyseal blood vessels can cross over the open physis into the epiphysis, permitting infection to move across the growth plate. The thin cortical bone of newborns allows infection to spread rapidly into the subperiosteal region, and the relative immune deficient state of the newborn allows for rapid spread. The lack of a systemic inflammatory response often leads to a delay in diagnosis, and involvement of more than one site is common. Although S. aureus remains the most common organism responsible for neonatal osteomyelitis, especially in newborns with central lines, group B streptococci, Gram-negative bacteria, and Candida albicans may also be responsible.

Diskitis

There is considerable dispute about whether diskitis is an infectious process. Infection of an intervertebral disk space from osteomyelitis of an adjoining vertebral body is rare. However, acute diskitis unassociated with vertebral osteomyelitis is a self-limited inflammation of an intervertebral disk that may be caused by pathogens of low virulence, although bacteria or viruses are seldom recovered by aspiration. S. aureus and Enterobacteriaceae or Kingella organisms are responsible in some patients. Diskitis occurs throughout childhood, but one half of the cases manifest before the patient reaches 4 years of age (peak age, 1 to 3 years old). The sex ratio is approximately equal, although one review observed that diskitis occurred more frequently in girls.

Clinical signs may be subtle. Diskitis is characterized by vague back pain and stiffness, often resulting in a characteristic tripod position during sitting or other unusual posturing. The child, who usually has a low-grade fever, often refuses to walk, stand, or bend over, and may complain of abdominal pain. Palpation of the spine may produce localized tenderness, usually in the lower lumbar region. The ESR is usually moderately elevated.

Plain radiographs of the affected area often appear normal until late in the disease ( Fig. 41-7 ). A technetium 99m bone scan or MRI is valuable diagnostically. The L4-L5 interspace is most often affected (44%), followed by L3-L4 (37%), L2-L3 (7%), and L5-S1 (6%). The cervical spine may also be involved. In one study, disk space narrowing occurred in 82% of children, and a bone scan was positive in 72%. MRI may be valuable in differentiating infection from other conditions, including idiopathic disk calcification ( Fig. 41-8 ). Aspiration of the disk space or disk biopsy should not be routinely necessary. Immobilization provides symptomatic relief. With signs of systemic infection, IV antibiotics should be instituted until results of blood cultures are available.

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