Download Chapter 37 - INFECTIOUS ARTHRITIS AND OSTEOMYELITIS

SECTION 5
Arthritis Related to Infection
Chapter 37
INFECTIOUS ARTHRITIS
AND OSTEOMYELITIS
Ronald M. Laxer and Carol B. Lindsley
The relation of infectious agents to arthritis is an area of
great interest to the rheumatologist. Important discoveries have led to an understanding of the origin, pathogenesis, treatment, and cure of at least one infection-related
arthritis—Lyme disease—and have given impetus to
investigations of other possible arthrogenic infectious
agents.
Arthritis related to infection can be regarded as septic,
reactive, or postinfectious.1 Septic arthritis occurs when
a viable infectious agent is present or has been present in
the synovial space. Although direct bacterial infection of
the joint constitutes the most widely recognized form of
septic arthritis, direct infection with viruses, spirochetes,
or fungi also occurs. Reactive arthritis is a response to an
infectious agent that is or has been present in some other
part of the body, usually the upper airway, gastrointestinal tract, or genitourinary tract. By definition, viable infectious agents are not recoverable from the synovial space
in patients with reactive arthritis, which may be regarded
as an autoimmune disorder resulting from immunological
crossreactivity between articular structures and infectious
antigens. The reactive arthritis group merges pathogenically with diseases such as the spondylarthritides. Postinfectious arthritis may be considered a special type of
reactive arthritis in which immune complexes containing
nonviable components of an initiating infectious agent
may be present in the inflamed joint. Lyme disease is discussed in Chapter 38, the reactive arthritides in Chapter
40, and poststreptococcal arthritis in Chapter 41.
The precise relation of infection to arthritis is complex
and by no means completely understood. As techniques
for the demonstration of infectious organisms improve,
the frequency with which they are detected in synovial
fluid or membrane is increasing, lending authority to the
suspicion that some or many of the chronic arthritides of
children are related to infectious diseases. Perhaps many
of the so-called reactive arthritides will be found to represent diseases in which living pathogens are present in the
joint and are, by definition, septic. In some of the viral
arthritides that fit the concept of reactive arthritis (i.e.,
joint disease follows the onset of the acute illness by days
or weeks), viral antigen or living virus can be isolated from
synovial fluid lymphocytes or membrane when appropriate techniques are used. The same has been true for Lyme
disease, in which early attempts to demonstrate Borrelia
were unsuccessful, although the organisms have since been
demonstrated by silver stain in several different laboratories. The lesson implicit in all of these observations is that
in chronic arthritides, which we currently consider aseptic, concerted investigations for infectious agents using
the most powerful techniques of molecular biology may
yet demonstrate the causative agent in the joint space.
Although study of infectious agents, such as viruses, as
possible initiators of some forms of arthritis in children has
attracted much attention, it is important to remember that
intraarticular and systemic bacterial infections remain the
most important curable causes of arthritis in childhood.
Septic Arthritis
Epidemiology
Septic arthritis of bacterial origin accounts for approximately 6.5% of all childhood arthritides.2 It has been suggested that its frequency might be increasing,3,4 although
the retrospective reviews from Dallas5 and Memphis6 did
not document an increase in incidence. In a 1997 report,
12.7% of 1158 patients with septic arthritis were children younger than 10 years old.7
559
560
SECTION 5 — ARTHRITIS RELATED TO INFECTION
Sex Ratio and Age at Onset
Septic arthritis is slightly less common in girls than in
boys, who account for 55% to 62% of patients in reported
series.8-10 Septic arthritis is found most often in the very
young11 and the very old; it may occur in the neonate, is
most common in children younger than 2-years-old, and
diminishes in frequency throughout childhood.5,12
Familial and Geographical Clustering
There does not appear to be a genetic predisposition to
septic arthritis. Typical cases of presumed septic arthritis
in which no pathogen is identified tend to occur in the
summer and fall,4 but geographical clustering has not been
reported. In spirochetal arthritis, such as Lyme disease,
there are marked geographic and seasonal outbreaks.
Etiology and Pathogenesis
A wide range of microorganisms can cause septic arthritis
in children; Staphylococcus aureus and nongroup A and
B streptococci are most common overall.7,12-14 However,
different organisms are more common at some ages and
in certain circumstances (Table 37–1). Haemophilus influenzae type B had been the most common infection identified in children younger than 2-years-old, but vaccination
of infants for H. influenzae has significantly decreased
the frequency of infection with this organism.13,15-18
Streptococcus pneumoniae is a frequent cause of infection in children younger than 2 years old and is common
in the older child.19,20 After a child reaches 2 years old,
S. aureus is the most frequently occurring organism.13
Group A streptococci and enterococci account for a small
proportion of all cases of septic arthritis in childhood
and are most prevalent in the 6- to 10-year age group.
Salmonella arthritis constitutes approximately 1% of all
cases of septic arthritis, and it is commonly associated
with sickle cell disease.21 Infection with Mycobacterium
Table 37–1
Common microorganisms involved in septic arthritis
and osteomyelitis
Age
Organisms
Neonate
Group B Streptococcus
Staphylococcus aureus
Gram-negative bacilli
Staphylococcus aureus
Streptococcus species
Haemophilus influenzae
Staphylococcus aureus
Streptococcus pneumoniae
Group A Streptococcus
Kingella kingae (some areas)
Staphylococcus aureus
Streptococcus pneumoniae
Group A Streptococcus
Neisseria gonorrhoeae
Infant
Child
Adolescent
tuberculosis is an unusual cause of septic monarthritis in
childhood. Other rare causes of infectious arthritis in children include Streptobacillus moniliformis (rat-bite fever),
Pseudomonas aeruginosa, Bacteroides species, Campylobacter fetus, Serratia species, Corynebacterium pyogenes,
Neisseria meningitis, Pasteurella multocida, and Propionibacterium acnes. Kingella kingae is emerging as an
important pathogen in children with septic arthritis22-24
and may account for a significant portion of culture negative cases.25 Most infections with this organism occur in
children younger than 5 years old, and 60% occur in children younger than 2 years old.26 In the neonate, S. aureus
(40% to 50%) or group B Streptococcus (20% to 25%)
are the most common causative organisms.5,9,27 Enterobacteriaceae, gonococcus, and Candida species are also
significant pathogens in the neonate.
Septic arthritis usually results from hematogenous
spread from a focus of infection elsewhere in the body.28
Direct extension of an infection from overlying soft tissues (e.g., cellulitis, abscess) or bone (e.g., osteomyelitis)29 or traumatic invasion of the joint accounts for only
15% to 20% of cases. In the hips, shoulders, ankles,
and elbows, the joint capsule overlies a portion of the
metaphysis. As a result, if a focus of underlying osteomyelitis breaks through the metaphysis, it may enter the
joint and result in septic arthritis. Joint damage results
from several mechanisms. Proliferation of bacteria in
the synovial membrane results in accumulation of polymorphonuclear (PMN) leukocytes and the inflammatory
effects outlined in Chapter 4. Synovial fluid contains
high levels of proinflammatory cytokines (tumor necrosis
factor-α, interleukin-1β)30 that mediate cartilage damage
by metalloproteinases.31 The ensuing damage to cartilaginous surfaces of the bone and the supporting structures
of the joint may be severe and permanent if treatment is
not urgently initiated.
Although trauma or extraarticular infection preceding onset of septic arthritis is common in case histories,
knowledge of the etiological significance of these factors
is incomplete.32 In one series, upper respiratory tract
infections preceded septic arthritis in approximately 50%
of patients, and approximately one-third had received
antibiotics within one week of onset.4 A history of a mild,
nonpenetrating injury to the affected extremity was elicited in approximately one-third of patients. Intravenous
(IV) drug users are at particular risk for septic arthritis of
the sacroiliac and sternoclavicular joints, usually caused
by gram-negative organisms.33 Other recognized risk factors include prosthetic joints, diabetes, alcoholism, recent
intraarticular steroids, and cutaneous ulcers.34 Chronic
inflammatory arthritis, such as juvenile idiopathic arthritis (JIA), may predispose to joint infection.35
Clinical Manifestations
Septic arthritis is usually accompanied by systemic
signs of illness (e.g., fever, vomiting, headache)36 and
may be a component of a more generalized infection
that might include meningitis, cellulitis, osteomyelitis,
or pharyngitis.37 Joint pain is usually severe, and the
infected joint and periarticular tissues are swollen, hot,
and sometimes erythematous. Passive and active motion
37 — INFECTIOUS ARTHRITIS AND OSTEOMYELITIS
561
of the joint is severely, often completely, restricted (i.e.,
­pseudoparalysis). Osteomyelitis frequently accompanies bacterial arthritis, and the presence of bone pain (as
opposed to joint pain) should alert the examiner to this
possibility. Other sites of hematogenous spread, although
less common, are nonetheless important (Table 37–2).4,8,9
Geographical variation exists with up to 24% multisite
involvement reported in some studies.39 Certain immune
deficiencies, such as chronic granulomatous disease or
acquired immunodeficiency syndrome (AIDS), may predispose to septic arthritis in multiple joints.
Affected Joints
Diagnosis
The joints of the lower extremity are most commonly
the sites of infection. 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 37–3).5,9,10 Pyogenic sacroiliac joint disease
can occur.38
A recent systematic review concluded that in the absence
of positive cultures in either the synovial fluid or the
blood, the overall clinical judgment of an experienced
clinician is superior to laboratory or radiological investigations for the diagnosis of septic arthritis.40 Guidelines
for the management of suspected septic arthritis have
been published for adults and may be applicable to the
older child as well.41 It is essential that every child with
acute unexplained monarthritis undergo aspiration of the
affected joint immediately, because septic arthritis continues to be associated with considerable morbidity and
mortality.18,42,43 Synovial fluid examination is outlined in
Table 37–4.
If an anaerobic organism or mycobacterium is suspected, enriched culture medium and special anaerobic
culture conditions are necessary. Children in whom septic
arthritis is considered should also have cultures of blood
and of any potential source of infection (e.g., cellulitis,
abscess, and cerebrospinal fluid) performed. Rapid antigen latex agglutination tests for H. influenzae, group B
and C streptococci, Neisseria meningitidis, and S. pneumoniae are available in most clinics. The polymerase
chain reaction (PCR) has proved useful in detecting evidence of infectious agents in synovial fluid,44-47 and realtime PCR may be even more beneficial in the investigation
of culture-negative septic arthritis.23,48
In a group of children with septic arthritis in whom the
bacterial agent was identified,5 Fink and Nelson reported
that synovial fluid was culture positive in 307 (79%) of
389 patients (Table 37–5).4,9,10 The remaining 21% had
positive cultures from sites other than the joint: blood
(10%), cerebrospinal fluid (3.8%), blood and cerebrospinal fluid (2.3%), and vagina (1.3%). One of five children
with culture-positive septic arthritis had a negative synovial fluid culture but a positive culture from elsewhere,
most often the blood. Initial inoculation of synovial fluid
Multiple Infected Joints
Although septic arthritis is most often a monarthritis,
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,5
septic arthritis was monarticular in 93.4% but affected
two joints in 4.4%, three in 1.7%, and four in 0.5% of
patients.
Table 37–2
Extraarticular sites of infection in children with septic
arthritis
Nelson and
Koontz8
Welkon
et al4
Speiser
et al9
Sites of Infection
n = 117 (%)
n = 95
(%)
n = 86 (%)
Osteomyelitis
Meningitis
Cellulitis, abscess
Respiratory tract
Middle ear
Urine
Genital tract
Pericardium
Pleura
12
4
19
4
-
12
4
20
-
26
11
9
9
3
1
1
1
1
Table 37–3
Frequency of infected joints in septic arthritis
Fink and Nelson5
Infected Joint
Knee
Hip
Ankle
Elbow
Shoulder
Wrist
PIP, MCP, MTP
Other
n = 591 (%)
40
23
13
14
4
4
1
1
Welkon et al4
Speiser et al9
Wilson and DiPaola10
Overall
n = 95 (%)
n = 86 (%)
n = 61 (%)
n = 833 (%)
46
25
15
5
4
5
30
29
17
11
2
1
10
-
29
40
21
3
3
1
1
39
25
14
12
4
3
2
1
MCP, metacarpophalangeal; MTP, metatarsophalangeal; PIP, proximal interphalangeal.
562
SECTION 5 — ARTHRITIS RELATED TO INFECTION
into blood culture bottles may increase the yield of some
organisms, especially Kingella kingae.24 Although an
organism can be identified in one-third to two-thirds or
more of patients by the culturing of all appropriate sites,
no causative organisms are ever identified in approximately one-third of children with pyogenic arthritis.49 In
these patients, the diagnosis of septic arthritis is based on
a typical history and the demonstration of frank pus by
arthrocentesis.
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 (see
Table 37–4). The synovial fluid white blood cell (WBC)
count is often markedly elevated, with 90% PMNs.
Speiser and colleagues9 reported that synovial WBC
counts in septic arthritis were less than 50,000/mm3 (50 ×
109/L) in 15% of children, 50,000 to 100,000/mm3
(50-100 × 109/L) in 34%, and more than 100,000/mm3
(100 × 109/L) in 51%. Fink and Nelson5 found a relatively low WBC count (less than 25,000/mm3 or 25 × 109)
in one-third of their patients.
The protein content is high (more than 2.5 g/dL), and
the glucose concentration compared with plasma glucose is usually low in septic arthritis, although it may be
normal. A Gram stain identifies the organism in one-half
of untreated patients but in only one-fifth of those who
Table 37–4
Synovial fluid examination in a child with suspected
septic arthritis
Synovial fluid aspiration must be done under strictly aseptic
conditions to minimize the risk of bacterial contamination.
Septic arthritis is strongly suggested if:
•Visual inspection finds cloudy, serosanguineous, or greenish
fluid.
•Cell count reveals elevated numbers of neutrophils (50,000
to 300,000/mm3) (50–300 ´ 109/L).
•Synovial fluid viscosity is low.
•Synovial fluid glucose is low (<30 mg/dL).
•Lactate dehydrogenase level is high (>500 IU).
•Gram stain is positive.
Culture is positive for about 70% of those tested.
have received antibiotics. A Gram stain provides rapid
c­ onfirmation 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.
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 than ESR. If the CRP
value is less than 1 mg/dL, the likelihood that the patient
does not have septic arthritis is 87%.50 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 (Fig. 37–1).51-55 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 develop as the disease progresses. These
changes are followed by marginal erosions and eventually
by ankylosis (Fig. 37–2).54 Computerized tomography
(CT) and especially magnetic resonance imaging (MRI)
are additional confirmatory techniques.
In the hip, accumulation of fluid within the joint displaces the gluteal fat lines laterally, or the obturator sign
(i.e., displacement of the margins of this muscle medially) may be present. Traction applied to the leg during
the radiographic procedure normally induces a radiolucent outline of the femoral head; this is referred to as the
Table 37–5
Laboratory confirmation of septic arthritis in children
Laboratory Confirmation
Confirmed diagnosis (culture positive)
Positive synovial fluid Gram stain
Positive synovial fluid culture
Positive blood culture
*Depends
†Depends
Fink and Nelson5
Welkon et al5
Speiser et al9
Wilson and DiPaola10
n = 591 (%)
n = 95 (%)
n = 86 (%)
n = 61 (%)
66
33
79
33
64
−
84
46
84
19 to 54*
36 to 70*
46
92
71 to 80†
41
on prior administration of antibiotics.
on procedure (aspiration = 80, arthrotomy = 71).
37 — INFECTIOUS ARTHRITIS AND OSTEOMYELITIS
­ vacuum” phenomenon. This lucency does not occur in
“
the presence of increased intraarticular fluid.54
Computerized tomography
As MRI is much better for the evaluation of soft tissues,
the role of CT is limited, except for the evaluation of
sacroiliac and sternoclavicular joints. It is also helpful to
guide aspirations and biopsies.
Plain
radiographs
Suspected
osteomyelitis
Yes
Osseous
abnormality
No
Reassess; evaluate
for osteomyelitis
Hip sonography
Joint
effusion
No
Yes
Aspiration,
therapy
MR imaging
for possible
osteomyelitis
and abscess
No
Response
in 48 hr
Ultrasonography
Detection of joint fluid by ultrasound helps guide fluid
aspiration. The ultrasonic detection of an effusion in the
hip of a child treated for osteomyelitis of the femur indicates the presence of septic arthritis of the joint.54 Color
Doppler may show increased capsular vascularity.
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.55 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.56 Radionuclide scans with gallium 67 or the patient’s indium
111-labeled granulocytes or monoclonal antibodies may
be helpful but are not routinely needed. 2-deoxy-2 [13F]
fluoro-D-glucose (FDG)-positron emission tomography
(PET)/CT may have an important role in the diagnosis
of difficult cases owing to the fact that PET is a relatively
fast, whole-body imaging modality and can be used to
find infectious foci outside of the bone or joint.56 It may
be particularly helpful for infections of the vertebrae.
Magnetic Resonance Imaging
Yes
Follow-up
radiographs
FIGURE 37–1 Flowchart of recommendations for evaluating septic arthritis in
children. (Adapted from Jaramillo D, Treves ST, Kasser JR et al: Osteomyelitis and
septic arthritis in children: appropriate use of imaging to guide treatment, AJR
Am J Roentgenol 165:399-403, 1995.)
A
563
Delineation of soft tissue structures by MRI is superior
to that provided by CT.53,54 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 spinecho images, and high signal intensity on fat-suppressed,
T2-weighted, fast spin-echo images).57 Articular cartilage and growth cartilage are depicted along with other
B
FIGURE 37–2 A, Questionable joint space widening of the right hip of a 10-year-old girl with fever and an irritable hip. B, Repeat x-ray film taken 20 days later
demonstrated epiphyseal demineralization and erosion (arrow).
564
SECTION 5 — ARTHRITIS RELATED TO INFECTION
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, 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.58
Treatment
The child with septic arthritis requires hospitalization and
consultation with an orthopaedic surgeon and specialist in
infectious diseases. Nonsteroidal antiinflammatory drugs
(NSAIDs) may be used to help minimize the effects of
inflammation, to control fever, and to contribute to pain
relief. IV dexamethasone was shown to reduce ­duration
of symptoms and minimize joint damage in a randomized, double-blind study, but is rarely, if ever used.59
A clinical practice guideline for the management of ­septic
arthritis in children has been proposed.60 It was demonstrated that this approach was effective in minimizing
bone scans, in minimizing the rate of joint drainage, in
accelerating the change to oral antibiotic administration,
and in shortening the duration of hospital stay. There
were no differences in outcomes such as readmission to
the hospital, recurrence of infection, or the development
of residual joint damage.
Antibiotics
In a child with septic arthritis, IV antibiotics should be
administered as promptly as possible. 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 outlined in Table
37–6 is suggested.38 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.42,61
It is prudent to monitor intravenous antibiotic efficacy with serum bactericidal titer determinations at frequent intervals initially and at follow-up for compliance,
especially if home therapy is instituted. After satisfactory control of the infectious process with IV antibiotic
a­ dministration is achieved (including resolution of fever,
significant decrease in pain, improvement in range of
motion, and falling laboratory measures of inflammation), treatment by the oral route in the hospital or on an
outpatient basis may be appropriate.62-64 Home IV antibiotic programs may also be effective in reducing the hospital stay. Such programs should be undertaken only after
careful consideration and consultation with an expert in
pediatric infectious disease.
If the cultures are negative, IV antibiotics should
be continued for a minimum of 21 days.1 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 are falling, the initial
antibiotics should be maintained. If the patient does not
appear to be responding, additional IV antibiotic coverage should be instituted. 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.
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. Similarly, open drainage is
worse than closed needle aspiration (except for specific
joints such as the hip and shoulder) and is attended by
significantly increased morbidity. Irrigation of the joint
at the time of aspiration has no demonstrated additional
benefit. Occasionally, arthroscopic examination is indicated. Intraarticular administration of antibiotic is unnecessary because therapeutic synovial fluid antibiotic levels
are readily achieved,65 and it may induce chemical synovitis in the infected joint.
Special Cases
Neonatal Septic Arthritis
Table 37–6
Recommended empirical antibiotic therapy by age
Age
Recommended Empirical Antibiotic Therapy
Neonate
Cloxacillin + gentamicin OR cloxacillin +
cefotaxime
Cefotaxime + cloxacillin OR cefuroxime
Cefazolin OR cloxacillin OR clindamycin
Ceftriaxone OR cefixime + azithromycin
Infant
Child
Adolescent
Alternatives appropriate to local epidemiology and patient ­comorbidities
(e.g., immunocompromise) may be needed. Vancomycin should be
­included in patients with high risk for MRSA.
In addition to S. aureus, group B Streptococcus and gramnegative bacteria can be the offending organisms in the
neonate.66 They are rare but potentially very serious
infections in this age group, may have a subtle presentation, and can occasionally be bilateral. They are much
more likely to occur in association with osteomyelitis
than in older children. Most affected newborns show
no fever, toxemia, or leukocytosis.67,68 Any infant who
has swelling in the region of the thigh or holds the leg
flexed, abducted, or externally rotated must be investigated promptly. Problems in early recognition of disease
undoubtedly contribute to the often disastrous outcome
of this involvement.69
37 — INFECTIOUS ARTHRITIS AND OSTEOMYELITIS
Septic Hip Joint
Septic arthritis of the hip is such an important problem
that it merits special attention.70,71 Because the risks of
missing this diagnosis are so high, there must a very low
threshold for hip aspiration to establish the diagnosis.72
The femoral head is intracapsular, and the arterial supply passes through the ligamentum teres through the
intracapsular space. Increased intracapsular pressure can
therefore interrupt the blood supply to the femoral head,
with disastrous consequences to its viability and to the
subsequent development of avascular necrosis.73 Meta­
physeal 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.74 The typical clinical picture is
that of an infant or young child who may have an unexplained fever; is irritable; and refuses to move an extremity, 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.
In very young or premature infants, a number of risk
factors predispose to septic hip joint arthritis.75 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
with septic arthritis between the ages of 1 month and 3
years, none was premature or had an umbilical catheter,
and only five 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 recorded76
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.77,78 Traction and immobilization for the first two to three days of
treatment provide pain relief, but should be followed by
passive and then active physiotherapy to prevent loss of
range of motion. 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.79
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.80 It is more
common in girls than in boys and is particularly likely
just after menstruation or with pregnancy.81 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
565
chills.82 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 chocolate agar will help in isolating
the organism. The possibility of sexual abuse should be
considered and appropriately investigated.
Tuberculous Arthritis
Tuberculous arthritis is seldom encountered in North
America or Europe, although its frequency may be
increasing because of immunosuppressive therapy, drugresistant strains of tuberculosis, and the human immunodeficiency virus (HIV) epidemic.83-85 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 monarthritis, often of the knee or
wrist, that eventually results in extreme destruction of the
joint and surrounding bones. Rarely, it manifests as acute
arthritis.86 Al Matar and colleagues87 have observed
two young children with tuberculous monarthritis that
mimicked oligoarticular JIA. They were unresponsive to
NSAIDs and intraarticular corticosteroids. One had a history of exposure, but the other child had no identifiable
contact with tuberculosis.
Joint infection occurs by hematogenous dissemination of the organism from adjoining osteomyelitis. Pott
disease is a consequence of vertebral osteomyelitis (Fig.
37–3). Tuberculous dactylitis may occur with cystic
expansion and destruction of bone (i.e., spina ventosa)
(Fig. 37–4).88 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 three-fourths of patients, synovial membrane biopsy and culture are preferred and confirm the diagnosis in almost all patients (Fig. 37–5). The
synovial WBC count is classically less than 50,000/mm3
(50 × 109/L), with a high proportion of mononuclear
cells. Genus-specific PCR is invaluable in the diagnosis.46
Rarely, a polyarthritis accompanies tuberculosis (i.e.,
Poncet disease); it probably represents a reactive arthritis
because culture of the inflamed joints fails to demonstrate
tubercle bacilli.89,90
Leprosy can result in articular changes and inflammatory disease, including polyarthritis and subcutaneous
nodules.91 Clinical differentiation from JIA may be difficult, especially if the possibility of leprosy is not considered in a nonendemic area.92 Mycobacterium leprae is not
always easily identified in synovial biopsies.93,94
Arthritis Associated with Brucellosis
Human Brucella infections are reported primarily from
European,95,96 Israeli,97 and South American98,99 clini­
cians with a substantial number of patients having
arthritis. Cases in North America are more likely to have
566
SECTION 5 — ARTHRITIS RELATED TO INFECTION
FIGURE 37–5 Synovial biopsy specimen of chronic inflammation in tuberculous joint disease in which a giant cell (arrow) is indicated.
FIGURE 37–3 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).
In 88 children from Israel,97 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,98 almost one-third
were children, and one third had arthritis. In the birth
to 15-year-old age group, peripheral arthritis of a hip
or knee was most common. Spondylitis and sacroiliac
arthritis became predominant after children reached 15
years old. Gomez-Reino and colleagues96 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 HLA-B27
has been demonstrated.95 Synovial fluid WBC counts
are only modestly elevated with a slight predominance
of mononuclear cells.98,102 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.96,99
Mycoplasma and Arthritis
Myalgia and arthralgia are common during pulmonary
infection with Mycoplasma pneumoniae. Objective oligoarticular, polyarticular, or migratory arthritis has also
been described.103 Sensitive screening tests may uncover
Mycoplasma as a cause of arthritis even in the absence of
pneumonia.104,105
Bartonella Infection and Arthritis
FIGURE 37–4 Advanced osseous destruction occurred in the foot of a child
with tuberculous dactylitis (i.e., spinal ventosa).
been acquired elsewhere.100 The species most frequently
implicated are Brucella melitensis96,98,99 and, less commonly, Brucella canis.101 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.
There have been rare reports of Bartonella henselae
infection causing arthritis in children (i.e., cat-scratch
disease).106-108 In two children, the disease mimicked
systemic JIA107,108; a third child had polyarthritis and
subcutaneous nodules.106 Arthropathy occurred in 3%
of patients in an Israeli registry. It was characterized by
large- and medium-sized mono-, oligo-, 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.109,110
37 — INFECTIOUS ARTHRITIS AND OSTEOMYELITIS
Arthritis in Immunocompromised Patients
Chronic inflammatory arthritis in patients with a primary
immunodeficiency is discussed in Chapter 42. Typical
septic arthritis has been reported infrequently in immunodeficient children.111 Mycoplasma is the most common cause of severe chronic erosive arthritis in patients
with congenital immunodeficiency syndromes112 and
has been recovered from joints of patients with AIDS.113
Ureaplasma urealyticum has been identified in patients
with agammaglobulinemia.114 Candida albicans is occasionally responsible for arthritis in immunosuppressed
patients.114,115
Course of the Disease and Prognosis
The outcome in septic arthritis is somewhat guarded
because, even with early and appropriate antibiotic treatment, permanent damage is common. The child usually
recovers from the acute illness, but with the passage of
time, reduction in range of motion, pain, and eventually
degeneration of the surfaces of the affected joint may
require surgical intervention. It is estimated that residual
dysfunction occurs in 10% to 25% of children, although
the changes (e.g., limited joint mobility, joint instability
of chronic subluxation) may not be apparent until years
later.4 Recently, a simplified radiographic classification
system has been developed to determine prognosis and
to guide surgical management of the sequelae of septic
arthritis of the hip.116
Osteomyelitis
Although osteomyelitis, like septic arthritis, is most often
encountered and treated by specialists in orthopaedics
and infectious diseases, its frequent association with septic arthritis and the diagnostic problems that it presents
require that it be included in this discussion.3,63,117-122
Definition and Classification
Osteomyelitis is an intraosseous infection with bacteria
or, rarely, fungi. It is classified as acute, subacute, or
chronic. Acute osteomyelitis is of recent onset and short
duration. It is most often hematogenous in origin but
may result from trauma such as a compound fracture or
puncture wound. It can be metaphyseal, epiphyseal, or
diaphyseal in location. Subacute osteomyelitis is of longer
duration and is usually caused by less virulent organisms.
Chronic osteomyelitis results from ineffective treatment
of acute osteomyelitis and is characterized by necrosis
and sequestration of bone.
Epidemiology
Acute osteomyelitis is somewhat less common than acute
septic arthritis. An incidence of 16.7 cases per year was
reported from an institution at which acute septic arthritis occurred at a rate of 28.4 cases per year.5 However, it
may be more common than septic arthritis in developing
countries of the world.123 Although its incidence may be
567
declining in many parts of the world, that is not necessarily the case everywhere.124 It occurs twice as often in boys
as in girls5,123 and is more common in younger children.
It can occur in the neonate.66
Etiology and Pathogenesis
S. aureus (50% to 80%) and the group A streptococci
(5% to 10%) are the predominant organisms at all
ages.5,125 Recently, CA-MRSA has emerged as an important pathogen.6,126,127 Up to 15% of children with CAMRSA that carry the genes encoding Panton-Valentin
leukocidin (pvl) have multiple sites of infection.128 These
organisms are also associated with chronic osteomyelitis.
Even before specific immunization, H. influenzae seldom
caused osteomyelitis (2% to 10%) and should now be even
less common.16,129 In certain circumstances, specific or
unusual organisms (15%) are found. For example, infection of the calcaneus or other bone in the foot associated
with a puncture wound through athletic footwear is likely
caused by P. aeruginosa.28,32,130,131 Osteomyelitis caused
by S. pneumoniae19,132 usually occurs in children with
associated diseases such as sickle cell anemia,133-135 asplenia,119,136 or hypogammaglobulinemia,120,137 although it
has been observed in young infants without underlying
disease.138 Salmonella osteomyelitis is a complication of
sickle cell anemia but also occurs in normal children.139
In the neonate, group B streptococci,140,141 gram-negative
organisms,142-144 and Candida in addition to S. aureus are
all potential causes of osteomyelitis. B. melitensis uncommonly results in osteomyelitis, but when it does, it has
a predilection for the vertebral bodies.101 Tuberculous
osteomyelitis may take various forms and may mimic
chronic pyogenic disease, Brodie abscess, tumor, or other
types of granuloma.145-147 B. henselae (the organism of
cat-scratch disease) has been identified as the causative
agent in a few patients with osteomyelitis.148-150
Clinical Manifestations
Fever, severe bone pain, and tenderness with or without local swelling should suggest the possibility of acute
osteomyelitis. Although a history of prior trauma is elicited in approximately one-third of young patients, its significance is uncertain. In the infant, fever may be minimal,
and localization of the pain may be difficult on physical
examination.151 Pseudoparalysis of a limb is often evident. The examiner may find clinical evidence of a preceding systemic infection. The site of the bone infection
is usually metaphyseal, and bony tenderness is elicited by
pressure near or over the infected area. There may also be
an area of overlying cellulitis, especially in the infant, in
whom the thin cortex allows pus to erode into the periosteal structures. The presence of a joint effusion adjacent
to the site of bone infection may reflect septic arthritis or
a sterile noninflammatory “sympathetic” effusion.152
Osteomyelitis in children has a predilection for the
metaphysis of rapidly growing bone. Many explanations
have been suggested for this tendency. The anatomical differences in vasculature in this area in children and its easily
compromised blood supply may in part explain the clinical observation (see Chapter 2). In one anatomical model,
568
SECTION 5 — ARTHRITIS RELATED TO INFECTION
Table 37–8
Table 37–7
Brodie abscess
Affected sites in septic osteomyelitis
Bone
Tibia
Clavicle
Fibula
Spine
Femur
Metatarsus, metacarpus, phalanx
Radius
Pelvis
Humerus
Ulna
Sternum
Mandible
Scapula
Rib
Talus
Calcaneus
Osteomyelitis*
(%)
25
<1
6
1
27
4
4
6
11
2
<1
<1
<1
<1
1
6
*Data
from Fink CW, Nelson JD: Septic arthritis and osteomyelitis in children, Clin Rheum Dis 12:423, 1986, and from Cole WG, Dalziel RE,
Leitl S: Treatment of acute osteomyelitis in childhood, J Bone Joint
Surg Br 64: 218, 1982.
bacteremia and, in some cases, preceding microtrauma
were sufficient to initiate disease.153 The bones of the lower
extremity are affected in two-thirds of patients; those of
the upper extremity account for approximately 25%,
but those of the skull, face, spine, and pelvis are the sites
of infection in fewer than 10% (Table 37–7).5,123,154-156
Less than 10% of children have two or more simultaneously infected bones; in some cases, five or more bones
are involved as part of a severe septicemic illness, usually
caused by staphylococci. This type of involvement must
be distinguished from chronic recurrent multifocal osteomyelitis (see Chapter 44).
Acute osteomyelitis can be associated with the development of deep-vein thromboses (DVT).157 In a series of
35 patients from Dallas who had osteomyelitis involving
the proximal humerus, femur, proximal tibia or fibula,
pelvis, or vertebrae, 10 had evidence of DVT based on
imaging studies, although it was only symptomatic in
one patient. In two patients, the DVT was related to
a central catheter placed for long-term antibiotic therapy, where as in the remaining eight, the DVT occurred
in veins adjacent to the site of infection. The authors
attributed the DVTs to the inflammatory response leading to localized endothelial damage and activation of
the coagulation cascade. Compounding factors include
the local edema, venous compression and immobility in
patients with lower extremity involvement. Organisms
with the pvl gene were more likely to be associated with
DVTs.158
Subacute Osteomyelitis
Compared with acute osteomyelitis, patients with subacute osteomyelitis usually have a longer duration of illness
(more than two weeks), experience less pain, often have
no fever, and have frequently taken a trial of ­antibiotics.
Characteristic
Findings or Procedures
Symptoms
Pain may be severe; child awakens
at night.
Evidence of a penetrating injury
of hematogenous spread
First week: soft tissue swelling
Second week: metaphyseal osteolytic
lesion with surrounding sclerosis
Sterile joint effusion; curettage samples and cultures may be negative.
Immobilization, nonsteroidal antiinflammatory drugs, antibiotics
Signs
Investigations
Treatment
Laboratory changes are less common, but radiographs
are usually abnormal and may be confused with Ewing
sarcoma or osteoid osteoma.124 Brodie abscess, a unique
form of subacute osteomyelitis, is usually of staphylococcal origin and may develop after a penetrating injury or by
hematogenous spread of an infection to the metaphysis.
It is characterized clinically by localized soft tissue swelling and tenderness with marked pain that may awaken
the child at night (Table 37–8). Radiographs demonstrate
only soft tissue swelling in the first week, but metaphyseal
osteolytic lesions are evident by the second week of the
illness. They are most common in the proximal or distal
ends of the tibia (Fig. 37–6).159,160 Culture of the abscess
may be negative. Treatment includes IV antibiotics, an
NSAID, and immobilization.
Chronic Osteomyelitis
Chronic osteomyelitis take places when symptoms occur
for longer than three months and 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) and represents inadequate treatment. This in
turn requires surgical excision. Complications of chronic
osteomyelitis include growth plate arrest or stimulation,
avascular necrosis, pathological fracture, septicemia,
and amyloidosis.124
Neonatal Osteomyelitis
Neonatal osteomyelitis merits special consideration.67
Up until a child reaches the age of approximately
18-months-old, 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.
37 — INFECTIOUS ARTHRITIS AND OSTEOMYELITIS
A
569
C
B
FIGURE 37–6 Brodie abscess is revealed in radiographs of the knee of a 16-month-old boy with acute hematogenous osteomyelitis inadequately treated one 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. (A to C, courtesy of Dr. B. Wood.)
Diagnosis
Treatment
As in septic arthritis, it is essential that every reasonable
attempt be made to identify the organism and determine its
antibiotic susceptibility.119 A high index of suspicion for
this diagnosis must be maintained in any child with unexplained pain, fever, or lack of use of an extremity. Aspiration of subperiosteal pus is the diagnostic procedure of
choice and, together with cultures of the blood, synovial
fluid, or an infected wound, should yield an organism in
approximately 70% to 80% of cases. Blood cultures alone
are positive in 30% to 50% of infants and children.161
A bone biopsy may be desirable or necessary if other sites
of culture prove negative. The elevated WBC count and
ESR are nonspecific and provide little help with diagnosis;
they are useful in assessing effectiveness of therapy.
Radiographic evaluation may delineate soft tissue
swelling very early, but osteoporosis is not evident until
days 10 to 14, and diagnostic findings may not be clear
until days 10 to 21 (Fig. 37–7).52 Radionuclide scanning
(i.e., technetium 99m polyphosphonate or diphosphonate) provides a sensitive if nonspecific method for the
early detection of increased blood flow and uptake in
the infected bone (see Fig. 37–7C).28,55,162 A bone scan is
particularly helpful in localizing osteomyelitis in the neonate or infection of the axial skeleton and in searching for
subclinical areas of infection in multifocal osteomyelitis.
A positive result is not necessarily diagnostic of osteomyelitis, but a negative scan is unlikely for a child with
bacterial osteomyelitis, except in the very early stages of
the illness.
MRI is superior to other modalities in identifying
changes in the marrow (see Fig. 37–7D).38,163-165 T1- or
T2-weighted MR images, fat suppression, and gadolinium enhancement can confirm a focal area of increased
inflammatory exudate (i.e., protons or water). A major
advantage of MRI in early disease over plain radiographs,
ultrasonography,166-168 or CT is the delineation of soft
tissue or subperiosteal pus (Fig. 37–8).169
In the absence of specific indications to the contrary,64 the initial antibiotic choices in the treatment of acute osteomyelitis
should be effective against MRSA (see Table 37–6). Screening of S. aureus for inducible clindamycin resistance with the
D-test helps determine whether the patient should be treated
with clindamycin or vancomycin.170 Linezolid may become
an important oral agent in the initial treatment and in the
treatment of clindamycin-resistant MRSA, although studies
to date are limited.171 IV antibiotics for four to six weeks have
been traditionally recommended with subsequent oral coverage if appropriate. Because of the complications that may
occur from central venous catheters required to maintain
IV access174 recent recommendations have included a shortened course of IV treatment.169,172,173 Surgical treatment,
which should be kept to a minimum,175 includes drainage
of subperiosteal and soft tissue abscesses and débridement of
associated lesions. Surgery is often needed for subacute and
chronic osteomyelitis. Immobilization of the extremity for
relief of pain is often necessary; otherwise, weight-bearing
may be permitted as tolerated by the patient.
Course of the Disease and Prognosis
The most dreaded complications of acute osteomyelitis
are chronic osteomyelitis and impaired bone growth.175
Chronic osteomyelitis should be suspected in a child
whose systemic symptoms have responded slowly or
incompletely to antibiotics or in whom there is a late
recurrence of pain at the affected site.
Differential Diagnosis and Related
Disorders
Both chronic recurrent multifocal osteomyelitis and synovitis, acne, pustulosis, hyperostosis, and osteomyelitis
syndrome are discussed extensively in Chapter 44.
570
SECTION 5 — ARTHRITIS RELATED TO INFECTION
A
C
B
D
FIGURE 37–7 A, Anteroposterior radiograph of the pelvis of a 14-year-old body with fever and an irritable left hip. This x-ray film (A) and close-up film of the left hip
(B) are normal. C, Bone scan documents increased uptake of technetium 99m in the area of the left proximal femur (arrow). D, Magnetic resonance imaging demonstrates an increased marrow signal in the same area of the left hip (arrow), which indicates acute osteomyelitis.
Arthritis Associated with Acne
Diskitis
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 (see
Chapter 24).176 It is possible that this syndrome is
another example of reactive arthritis, or it may even
be part of the autoinflammatory group of diseases.
Although arthritis lasts for only a few months in some
patients, recurrences over many years have been documented.177,178 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 phenomena179 and
isotretinoin causing an acute arthritis.180-183 Infliximab
for the treatment of arthritis has been reported to cause
acne.184
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.185 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
old (peak age, 1- to 3-years-old).186,187 The sex ratio is
approximately equal, although one review observed that
diskitis occurred more frequently in girls.188
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.189 The child, who usually has a low-grade
fever, often refuses to walk, stand, or bend over; and may
37 — INFECTIOUS ARTHRITIS AND OSTEOMYELITIS
complain of abdominal pain. Palpation of the spine produces well-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. 37–9). A technetium 99m bone scan is valuable diagnostically (Fig.
37–10). The L4-L5 interspace is most often affected
Suspected
osteomyelitis
Plain
radiographs
(44%), followed by L3-L4 (37%), L2-L3 (7%), and
L5-S1 (6%).186-191 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%.192
MRI may be valuable in differentiating infection from
other conditions, including idiopathic disk calcification
(Fig. 37–11).193-195 Aspiration of the disk space or disk
biopsy should not be routinely necessary. Immobilization
provides symptomatic relief. If bacterial infection is suspected, IV antibiotics should be instituted until results of
blood cultures are available.
Reassess
Whipple Disease
Negative
Osseous
abnormality
No
Whipple disease, first described in 1907,196 is rare in
childhood; approximately five afflicted children younger
than 15 years old have been reported.197 It 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.198-200 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 a 3 month old boy201 and a 7 ­year
old boy.202 There is also one report of central nervous
system disease in a young boy.197 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,203 although residual deformity does not.204
The joints most frequently affected are the ankles, knees,
shoulders, and wrists,203 and spondylitis has been reported
in 20%.204 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.205 A small
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 abdominal lymph nodes. Other diagnostic
tools include PCR and immunohistochemistry. Because
it takes several months to culture the organism, cultures
99mTc-MDP
bone scan
Yes
Positive
Contrastenhanced
MR imaging
Preoperative
evaluation of
spine (always)
pelvis
physis
Yes
No
Therapy
MR imaging for
possible abscess
No
Response
in 48 hr
Yes
Follow-up
radiograph
FIGURE 37–8 Flowchart of the recommendations for evaluating acute hematogenous osteomyelitis in children. (Adapted from Jaramillo D, Treves ST, Kasser
JR et al: Osteomyelitis and septic arthritis in children: appropriate use of imaging
to guide treatment, AJR Am J Roentgenol 165:399-403, 1995.)
A
571
B
FIGURE 37–9 A, Normal disk space is demonstrated on a lateral view of the lumbar spine. B, Diskitis has caused collapse of the disk space (arrow).
572
SECTION 5 — ARTHRITIS RELATED TO INFECTION
A
FIGURE 37–10 Technetium 99m bone scan of a 2.5-year-old girl with back
pain demonstrates increased uptake of the isotope in the inferior end plate of L2
and superior end plate of L3 (arrow), which is characteristic of diskitis. (courtesy
of Dr. H. Y. Nadel.)
are not recommended as a diagnostic tool, A genetic predisposition has been suggested based on the ubiquitous
nature of the organism, but causative genes have not
been identified. Antimicrobial therapy (e.g., ceftriaxone,
penicillin, doxycycline, cotrimoxazole, streptomycin) has
greatly improved the outcome in this disease.
Arthritis Caused by Viruses
A classification of viruses known to be associated with
arthritis in humans is shown in Table 37–9.206 The togaviruses account for most of the viral arthritides. In general,
viral arthritides occur much more often in adults than in
children.207 Arthralgia is more common than objective
arthritis, and both are usually migratory and of short
duration (one to two weeks), disappearing without residual joint disease. There are a number of potential mechanisms by which viruses may lead to arthritis, including
targeting the cells of innate immunity and adaptive immunity, inducing the production of autoantibodies and T cell
mediated autoimmunity, or directly infecting synovial
cells.208 As arthritis is seldom the main symptom of viral
disease, clues as to the etiology should be sought in the
history, including travel to areas where alphaviruses and
Human T-cell leukemia virus type-1 (HTLV-1) may be
common, a history of blood transfusions, IV drug abuse,
recent vaccinations, or ongoing epidemics or exposures.
Small joints are most often affected by rubella, hepatitis
B, and members of the alphavirus group (e.g., Ross River,
chikungunya), whereas one or two large joints (usually the
knees) are most often affected by mumps, varicella, and
other viruses. In some viral arthritides, virus (e.g., rubella,
varicella, herpes simplex, cytomegalovirus) can be isolated from the joint space; in others, only virus-­containing
immune complexes (e.g., hepatitis B, adenovirus 7)
are found; and in still others, neither virus nor viral
­antigen can be recovered from the joint.209 Whether this
represents limitations of recovery and culture techniques
B
C
FIGURE 37–11 A 10 year old male with back pain and diskitis. A, Axial T1
weighted fat-suppressed MR image postcontrast showing bone enhancement.
B, Sagittal T1-weighted fat-suppressed MR image following contrast administration with increased signal on the inferior aspect of the vertebral body surrounding an area of decreased enhancement. C, Sagittal T2 weighted MR image
showing increased signal intensity within the T7 vertebral body and narrowing
of the adjacent inferior disk (courtesy of Dr. P. Babyn).
or the fact that culture-negative viral arthritis is “reactive” rather than “septic” is unknown.
Rubella Virus
Rubella-associated arthropathy was recognized by Osler210
and was one of the most commonly identified virus-associated arthritides in North America. Musculoskeletal symptoms after natural rubella infection are relatively common
in young women. These symptoms are unusual in preadolescent children and in males, however, and are much less
frequent after rubella immunization than after natural
infection. Arthritis is more common after natural infection, and it is more severe and lasts longer.211
Arthralgia usually begins within seven days of the
appearance of the rash or 10 to 28 days after immunization. The joints of the fingers and, later, the knees are
most frequently affected. Joint pain may be accompanied
by warmth, erythema, and effusion, and tenosynovitis is
common. Carpal tunnel syndrome has also been reported.
These findings usually disappear within three to four
weeks but occasionally persist for months or even years.
In a study of natural rubella infection in 37 teenage students, 52% of girls and 8% of boys developed
objective arthritis,211 and an additional 13% and 48%,
respectively, experienced arthralgia. In a group of young
37 — INFECTIOUS ARTHRITIS AND OSTEOMYELITIS
Table 37–9
Viruses that cause arthritis in humans
Virus
Togaviruses
Rubivirus
Rubella
Alphaviruses
Ross River
Chikungunya
O’nyong-nyong
Mayaro
Sindbis
Ockelbo
Pogosta
Parvoviruses
Hepadnaviruses
Hepatitis B
Hepatitis C
Adenoviruses
Adenovirus 7
Herpesviruses
Epstein-Barr
Cytomegalovirus
Varicella-zoster
Herpes-simplex
Paramyxoviruses
Mumps
Enteroviruses
Echovirus
Coxsackievirus B
Orthopoxvirus
Variola virus (smallpox)
Vaccinia virus
Comment
Global; most reports from North
America and Europe
Australasia
Africa, Asia
Africa
South America
Africa, Asia, Australia
Sweden
Finland
B19 associated with fifth disease,
aplastic crises
Global
Global
Rare
Rare; suggested role in
­rheumatoid arthritis
Rare
Rare
Rare
Rare
Rare
Rare
Nonexistent today
Rare
Adapted from Petty RE, Tingle AJ: Arthritis and viral infection, J Pediatr
113:948, 1998.
women who received RA 27/3 rubella vaccine, 14%
developed an acute polyarthritis. Arthralgia and arthritis are most common in adults, although approximately
25% of prepubertal females develop arthralgia, and 10%
arthritis.212,213 Chronic arthritis in adult women has been
reported after vaccination in 5% to 11%.214,215 It has
been suggested that reinfection contributes to arthritis in
susceptible hosts.216,217 Rubella virus has been recovered
from the synovial fluid of patients with rubella arthritis
in many218,219 but not all instances.207,220 The virus was
isolated from synovial or peripheral blood mononuclear
cells in seven of 19 children with juvenile rheumatoid
arthritis but from no control subjects.221 Other investigations have shown no association.222
Parvovirus
Parvoviruses are the latest candidates in the list of viruses
putatively involved in the cause of rheumatoid arthritis in
adults.223,224 Parvovirus RA-1 has been isolated from the
573
synovial membrane of one patient with classic rheumatoid arthritis.225 A second parvovirus, B19, is the agent
responsible for erythema infectiosum (i.e., fifth disease or
slapped cheek syndrome).226,227 This illness is sometimes
accompanied by an arthritis not unlike that of rubella
infection.227-230
Arthralgia, symmetrical joint swelling, and morning
stiffness have been described in adults, especially women,
after parvovirus B19 infection.230 Carpal tunnel syndrome, hepatitis, and angioedema have been described.
This syndrome may be more widespread than previously
thought and may be considerably underdiagnosed. In
some patients, symptoms have persisted for years. An early
study of erythema infectiosum in 364 patients indicated
that joint pain, most often affecting knees and wrists, was
present during the first week in 77% of adults and 8%
of patients younger than 20-years-old.231 Subsequently,
it was determined that arthritis was most common in
patients who were HLA-DR4 positive.232 Whether or not
a chronic arthritis results from parvovirus B19 infection
is still controversial.209,233
Parvovirus infection is common and widespread.
Parvovirus B19 genome consists of a linear, 5.6-kD,
single-stranded deoxyribonucleic acid (DNA). There is
only one serotype of parvovirus B19. Human parvovirus
B19 has been implicated as the causative agent in erythema infectiosum, aplastic crises, some cases of hemophagocytic syndrome, and hydrops fetalis.234 Erythema
infectiosum, is a common exanthem of older children
that lasts for a few days to a week and presents with a
low-grade fever, an erythematous facial rash (“slapped
cheeks”), and a lacy, reticular rash on the extremities.
These manifestations often recur with malaise, irritability, and arthralgia.
Only a few cases of children with documented B19associated arthritis have been reported.228,235-237 Joint
symptoms tend to be mild and transient. In the children
reported by Reid and coworkers,238 there was symmetrical involvement of the small joints of the hands and feet.
In one child, the arthritis preceded development of the
rash. In another, arthritis persisted for three months.
Antinuclear antibodies and rheumatoid factors (RFs)
were absent in all of the patients in this series. Rivier and
colleagues236 described a 5-year-old boy with arthritis of
one knee that lasted for six weeks after typical erythema
infectiosum. Nocton and associates235 described acute
arthritis in 20 children with parvovirus B19 infections.
The arthritis was associated with constitutional symptoms in one-half of the children and was of brief duration
(less than four months) in 14. Six children had persistent
arthritis lasting up to 13 months; criteria for a diagnosis of JIA would have been met in this group. Laboratory results were generally normal, except for serological
evidence of the B19 infection. Usually, NSAID treatment
will suffice, but for patients with persistent symptoms,
intravenous immunoglobulin (IVIG) may be a treatment
option.239 A recent study on seroprevalence of parvovirus
B19 did not show an increase in patients with JIA compared with diseased or healthy controls.240
The precise relation of the viral infection to arthritis
has not been clarified. The virus has not been grown
from synovial fluid or blood from patients with joint
574
SECTION 5 — ARTHRITIS RELATED TO INFECTION
s­ ymptoms, although B19-specific DNA has been identified by hybridization in the synovial fluid of adults238
and by PCR amplification in synovial tissue.241 However, Soderlund and colleagues242 demonstrated
genomic B19 DNA in the synovium of joints that had
suffered trauma even more frequently than in those of
children with chronic arthritis. Inflammatory synovitis
may not be identifiable by arthroscopy. Although infection gives rise first to IgM antibodies243 and then to IgG
antibodies, there is no evidence that the arthropathy
represents an immune complex disease. Demonstration
of IgM antibodies, however, is essential to diagnosis.
The prevalence of IgG antibodies in the general population is too high to be diagnostically helpful, unless a
fourfold increase concurrent with the clinical symptoms
is demonstrated.244-246
Hepatitis B Arthritis–Dermatitis
Syndrome
and Asia.255 These viruses are transmitted by arthropods,
usually the mosquito, and incite an illness characterized
by arthritis and a rash that may be macular, papular,
vesicular, or purpuric. Although there are some virusspecific differences in these illnesses, they usually are mild
in children and occur with equal frequency in males and
in females.
In Ross River virus disease, the wrist is most commonly affected and is often accompanied by tenosynovitis and enthesitis at the insertion of the plantar fascia
into the calcaneus.255,256 The synovial fluid is said to be
highly characteristic, with a predominance of vacuolated
macrophages and very few PMNs. In chikungunya, the
knee is the most commonly involved joint, and back pain
and myalgia are prominent. The arthritis lasts one to two
weeks and is followed by complete recovery. Diagnosis
rests on the clinical presentation and an elevated level of
antibodies to the specific virus. Viral antigen has not been
recovered from synovial fluid.
Herpesviruses
In adults, up to 20% of infections with hepatitis B virus
are characterized by a period of rash and arthritis that
resembles serum sickness.247 The arthritis is often explosive in onset and often occurs in the preicteric phase
of hepatitis B infections. In a review of reported cases
of arthritis associated with hepatitis B infection,248 the
age of the patients ranged from 14 to 56 years, and
the male-to-female ratio was 1.5:1. The dermatitis is
characterized by a maculopapular rash, sometimes with
petechiae, or urticaria, and is most prominent on the
lower extremities. The arthritis usually begins abruptly
and symmetrically and affects the interphalangeal joints
in 82%, knees in 30%, and ankles in 24% of patients.
Although erythema and warmth are present, synovial
effusions are uncommon. Joint symptoms last for four
weeks on average, respond well to NSAIDs, and disappear without sequelae. The ESR is usually normal,
although serum and synovial fluid complement levels
are low in the early stages of the illness.249 Synovial
fluid has been reported to show a mononuclear cell
predominance.250 Electron microscopic evidence of
hepatitis antigen in the synovial membrane has been
reported.251
Four of the herpesviruses have been associated with
arthritis. Herpes simplex virus type 1 has been isolated
from the synovial fluid of one patient with arthritis and
disseminated herpes simplex infection.257 Epstein-Barr
virus has long been thought by some investigators to have
a primary role in the cause or pathogenesis of rheumatoid arthritis, although direct evidence is lacking.258-260
Arthritis is a rare complication of infectious mononucleosis.261-263 Cytomegalovirus is occasionally associated
with arthritis and has been isolated from synovial fluid in
one instance.257
Varicella-zoster infection is uncommonly complicated
by arthritis.264-271 However, there have been instances
of bacterial septic arthritis complicating chickenpox.269,272,273 In one instance, varicella-zoster virus was
grown from synovial fluid of an 8-year-old girl with acute,
painless monarthritis occurring three days after the onset
of chickenpox.264 The synovial fluid cells were predominantly lymphocytes.264,271,274 Occasionally, chickenpox
is associated with the emergence of psoriatic arthritis.275
Acute monarthritis has been reported in association with
herpes zoster in two adults.276,277
Hepatitis C
Mumps Virus
Hepatitis C virus is lymphotrophic and is associated with
rheumatic symptoms resulting from mixed cryoglobulinemia207 and producing an intermittent monoarticular or
oligoarticular nondestructive arthritis affecting large- and
medium-sized joints.252 A rheumatoid arthritis-like picture may also occur.253 As many of these patients may be
rheumatoid factor positive, the presence of anti-CCP has
been proposed as a useful tool in diagnosing true RA in
the hepatitis-C infected individual.254
The paramyxovirus (mumps) rarely causes arthritis.
In a 1984 review,278 only 32 cases were well documented. Since then, two additional patients have been
reported.279,280 The male-to-female ratio is 3.6:1, and
the peak age of occurrence is 21- to 30-years-old. Four
patients younger than 11 years old and seven between
the ages of 11 and 20 years have been described. Arthritis occasionally preceded parotitis but usually followed
by one to three weeks. In children, the arthritis was
mild, affected few joints, and lasted one to two weeks.
In postadolescent males, arthritis was often accompanied by orchitis and pancreatitis.278 It is reported that
the arthritis responds to ibuprofen or prednisone but
not to aspirin.278 The pathogenesis is unknown, and no
attempts at recovery of mumps virus from synovium
Alphaviruses
Epidemic polyarthritis caused by infection with one of the
alphaviruses is the most common virus-associated arthritis in Australia, the islands of the South Pacific, Africa,
37 — INFECTIOUS ARTHRITIS AND OSTEOMYELITIS
or synovial fluid have been reported. Arthritis has not
occurred after mumps ­immunization.
Human Immunodeficiency Virus
The spectrum of rheumatic diseases that can accompany
HIV infection is extremely large and has changed with
the introduction of highly active antiretroviral (HAART)
treatment. AIDS resulting from HIV infection may be
complicated by septic arthritis, although this is now
consi­dered rare.281 Virtually any organism can be responsible; S. aureus and Streptococcus species are the most
common. Although the precise nature of rheumatic syndromes associated with HIV infection remains controversial, a number of stereotypical presentations have been
documented in adults.282 These include reactive arthritis,
psoriasiform arthritis, and an undifferen­tiated spondyloarthropathy,283-287 often more severe than in patients without HIV infection. A similar picture has been observed in
children infected with HIV.287a Arthralgias occur initially
with viremia; lower extremity oligoarthritis or persistent
polyarthritis can supervene later. A study of 270 patients
concluded that the most frequent pattern of joint involvement was one of an acute onset, short duration, few if
any recurrences, and no erosive sequelae.288 The authors
have observed chronic oligoarthritis in two young children with HIV infection (one transplacental and one
related to blood products). Osteomyelitis may also occur;
tuberculosis infection is a relatively common cause.289 In
the post-HAART era, there has been a decline in reactive,
psoriatic, and infectious causes of musculoskeletal syndromes, but disorders such as osteoporosis, osteomalacia,
and osteonecrosis have become more prevalent.281
Other Viruses
There are reports of arthritis associated with adenovirus type 7 infections, although the virus was not isolated
from the synovial fluid, and diagnosis was confirmed
only on clinical and serological grounds.288,290,291 Echoviruses292-294 and coxsackie B viruses291,295 have been rarely
implicated as the cause of arthritis. Smallpox (variola
virus infection), now eradicated from the world, was often
accompanied by arthritis, especially in children younger
than 10 years old. Arthritis also followed cowpox vaccination.296 Human T cell leukemia virus type 1 HTLV-1
has been associated with a number of rheumatic disorders
in adults, including arthritis and Sjögren’s syndrome.297
A 1998 report298 outlined an outbreak of Sindbis virusinduced Pogosta disease (e.g., fever, rash, joint symptoms) in Finland.
Syndromes Presumably Related
to Viral Infection
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.299 Pain in the hip,
thigh, or knee may be of sudden or gradual onset and
lasts for an average of six days. Bilateral involvement
575
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.299,300 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.299 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,57 which is often the principal differential
­diagnosis.301
After a diagnostic ultrasound scan to confirm the presence of fluid, the hip joint should be aspirated to exclude
bacterial sepsis.302 The synovial fluid has a normal or
minimally increased cell count but may be under
high pressure.299 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 degrees of flexion to minimize intracapsular pressure.299 Long-term sequelae include Legg-Calvé-Perthes
disease in about 1.5% of cases,303,304 coxa magna, and
osteoarthritis. Recurrences are often accompanied by
low-grade fever.
Arthritis Associated with Other
Infections
Fungal Arthritis
Arthritis caused by fungal infection is rare305 and is almost
unknown in children beyond the neonatal period. Fungi
that have been reported as causing arthritis or osteomyelitis are C. albicans,306 Sporothrix schencii,307,308
Actinomyces israelii,309 Aspergillus fumigatus,310 Histoplasma capsulatum,311 Cryptococcus neoformans,311
Blastomyces dermatitidis,312 Coccidioides immitis,313
Paracoccidioides brasiliensis,314 Nocardia asteroides,315
and Pseudallescheria boydii.316 Candidal arthritis,306
often with accompanying osteomyelitis, is a recognized
entity in the newborn317,318 and occurs occasionally in
immunocompromised patients319,320 and in patients with
prosthetic joints.321
Sporotrichosis and Plant Thorn Synovitis
Infection with Sporothrix schenckii is a rare but significant
occupational hazard of gardeners, night-crawler farmers,
and field workers.307,308 Monarthritis or, less commonly,
polyarthritis resembling rheumatoid arthritis, has been
reported (Fig. 37–12). Synovial biopsy is often necessary
to make the diagnosis (Fig. 37–13). Other fungal infections are even less common causes of bone or joint infection in children. The interested reader is referred to the
review by Goldenberg and Cohen308 and to other select
references.310-316,318,321
Synovitis caused by the penetration of a plant thorn
into the joint space or surrounding structures is probably a reaction to the foreign material rather than an
576
SECTION 5 — ARTHRITIS RELATED TO INFECTION
Arthritis Caused by Spirochetes
Lyme Disease
The geographical and temporal clustering of cases of what
was thought to be juvenile rheumatoid arthritis in Old
Lyme, Connecticut, led to the discovery and ­description
of the cause, pathogenesis, and cure of Lyme disease.
This epidemiological work is one of the most important
developments of the past three decades in rheumatology
and provides a model for approaching the question of the
infectious cause of other chronic arthritides of childhood.
Unfortunately, work on the development of a safe and
effective vaccine has stalled.323 Chapter 38 provides a
complete discussion of classic Lyme disease.
Other Spirochetes and Arthritis
FIGURE 37–12 Destruction of the first metatarsophalangeal joint was caused
by sporotrichosis.
Arthritis rarely complicates leptospirosis (Leptospira
icterohemorrhagica)324 and syphilis (Treponema pallidum)325,326 Congenital syphilis causes juxtaepiphyseal
osteochondritis and periarthritis in infancy and syphilitic
dactylitis in early childhood (Fig. 37–14). Clutton joints—
relatively painless, recurrent, nonprogressive, symmetrical
synovitis of the knees—develop later.327
Parasites and Arthritis
There have been case reports of arthritis accompanying
a wide range of parasitic infestations,328 including Giardia intestinalis (lamblia),329 Endolimax nana,330 Toxocara canis,331 schistosomiasis,332 and others.333 In general,
the joint disease is presumably reactive or postinfectious
rather than septic and pursues a benign course with a good
prognosis.
Musculoskeletal Manifestations
of Systemic Bacterial Infections
FIGURE 37–13 Sporothrix schenckii is identified in a Gram-stained preparation of the synovial fluid aspirate.
­ utright infection, although the circumstances of the
o
injury may suggest the latter. The synovial effusion is
inflammatory, and culture occasionally yields a relatively
nonvirulent organism. In the case of rose thorn penetration, S. schenckii is the probable cause. More commonly,
the thorn of the palm tree or blackthorn is implicated.
There are signs of local inflammation, and radiographs
demonstrate periosteal new bone formation, a radiolucent defect in bone, or the presence of radiopaque foreign
material. CT is indicated if plain radiographic results are
negative. Because this disorder may develop months after
the initial injury, foreign-body synovitis may be ignored
as a diagnostic possibility. Treatment should be directed
at appropriate surgical exploration and removal of the
foreign material.322
Bacterial infection of ventricular shunts for the management of hydrocephalus may result in arthritis and
nephritis.334 RFs may be demonstrable in the sera of
these patients. Meningococcemia is complicated by
arthritis in up to 10% of cases.335 It is usually oligoarticular and occurs most often during the recovery phase,
when immune complexes can be demonstrated in the
synovium.336 It can also be complicated by acute septic
arthritis in the early stage of the disease. H. influenzae
type B meningitis may lead to a sterile arthritis.337
Infective endocarditis frequently causes arthralgia or
arthritis338,339 and signs suggesting vasculitis (e.g., Osler
nodes, Janeway lesions, Roth spots). The musculoskeletal signs and symptoms (e.g., arthralgia, arthritis, myalgia, low back pain) may precede other manifestations of
infective endocarditis by weeks.339 The arthritis is characteristically polyarticular and symmetrical, affecting both
large and small joints. An immune complex-mediated
pathogenesis is thought to be responsible, and the presence of hypocomplementemia,340 circulating immune
complexes,313 and sometimes RFs340 support this theory.
Specificity of the RFs is directed to the patient’s IgG in
combination with the infecting organism.
37 — INFECTIOUS ARTHRITIS AND OSTEOMYELITIS
A
577
B
FIGURE 37–14 Lesions of congenital syphilis were identified in a 6-month-old girl brought to the child abuse clinic because of multiple fractures that occurred
during the previous 10 days. Her rapid plasma reagin test result was 1:256. A, Bilateral, symmetrical, destructive metaphysitis lesions of the proximal ends of the
tibiae (Wimberger sign) (solid arrow) and periosteal new bone apposition (open arrow) can be seen. B, With penicillin therapy, the lesions have almost healed
two months later.
REFERENCES
3. P. Christiansen, B. Frederiksen, J. Glazowski, et al., Epidemiologic, bacteriologic, and long-term follow-up data of children with
acute hematogenous osteomyelitis and septic arthritis: a ten-year
review, J. Pediatr. Orthop. B 8 (1999) 302–305.
5. C.W. Fink, J.D. Nelson, Septic arthritis and osteomyelitis in children, Clin. Rheum. Dis. 12 (1986) 423–435.
16. A.W. Howard, D. Viskontas, C. Sabbagh, Reduction in osteomyelitis and septic arthritis related to Haemophilus influenzae type
B vaccination, J. Pediatr. Orthop. 19 (1999) 705–709.
23. S. Chometon, Y. Benito, M. Chaker, et al., Specific real-time polymerase chain reaction places Kingella kingae as the most common cause of osteoarticular infections in young children, Pediatr.
Infect. Dis. J. 26 (2007) 377–381.
24. P. Yagupsky, Kingella kingae: from medical rarity to an emerging
paediatric pathogen, Lancet Infect. Dis. 4 (2004) 358–367.
25. K.M. Kiang, F. Ogunmodede, B.A. Juni, et al., Outbreak of osteomyelitis/septic arthritis caused by Kingella kingae among child
care center attendees, Pediatrics 116 (2005) e206–e213.
34. C.J. Mathews, G. Coakley, Septic arthritis: current diagnostic and
therapeutic algorithm, Curr. Opin. Rheumatol. 20 (2008) 457–462.
39. T.R. Nunn, W.Y. Cheung, P.D. Rollinson, A prospective study of
pyogenic sepsis of the hip in childhood, J. Bone Joint Surg. Br. 89
(2007) 100–106.
40. C.J. Mathews, G. Kingsley, M. Field, et al., Management of septic
arthritis: a systematic review, Ann. Rheum. Dis. 66 (2007) 440–445.
46. I.M. van der Heijden, B. Wilbrink, L.M. Schouls, et al., Detection
of mycobacteria in joint samples from patients with arthritis using
a genus-specific polymerase chain reaction and sequence analysis,
Rheumatology (Oxford) 38 (1999) 547–553.
49. R.M. Lyon, J.D. Evanich, Culture-negative septic arthritis in children, J. Pediatr. Orthop. 19 (1999) 655–659.
51. R.F. Buchmann, D. Jaramillo, Imaging of articular disorders in
children, Radiol. Clin. North Am. 42 (2004) 151–168. vii.
52. D. Jaramillo, S.T. Treves, J.R. Kasser, et al., Osteomyelitis and
septic arthritis in children: appropriate use of imaging to guide
treatment, AJR 165 (1995) 399–403.
56. K.D. Stumpe, K. Strobel, Osteomyelitis and arthritis, Semin. Nucl.
Med. 39 (2009) 27–35.
58. M. Karchevsky, M.E. Schweitzer, W.B. Morrison, et al., MRI
findings of septic arthritis and associated osteomyelitis in adults,
AJR 182 (2004) 119–122.
60. M.S. Kocher, R. Mandiga, J.M. Murphy, et al., A clinical practice
guideline for treatment of septic arthritis in children: efficacy in
improving process of care and effect on outcome of septic arthritis
of the hip, J. Bone Joint Surg. Am. 85-A (2003) 994–999.
62. P.O. Newton, R.T. Ballock, J.S. Bradley, Oral antibiotic therapy of bacterial arthritis, Pediatr. Infect. Dis. J. 18 (1999)
1102–1103.
68. A.C. Offiah, Acute osteomyelitis, septic arthritis and discitis: differences between neonates and older children, Eur. J. Radiol. 60
(2006) 221–232.
69. R.R. Betz, D.R. Cooperman, J.M. Wopperer, et al., Late sequelae
of septic arthritis of the hip in infancy and childhood, J. Pediatr.
Orthop. 10 (1990) 365–372.
72. M.S. Kocher, How do you best diagnose septic arthritis of the
hip? in: J.G. Wright (Ed.), Evidence-based orthopedics, Saunders,
Philadelphia, 2009.
81. S.P. Brogadir, B.M. Schimmer, A.R. Myers, Spectrum of the gonococcal arthritis-dermatitis syndrome, Semin. Arthritis Rheum.
8 (1979) 177–183.
100. M.W. Shen, Diagnostic and therapeutic challenges of childhood brucellosis in a nonendemic country, Pediatrics 121 (2008)
e1178–e1183.
110. E. Maman, J. Bickels, M. Ephros, et al., Musculoskeletal manifestations of cat scratch disease, Clin. Infect. Dis. 45 (2007) 1535–1540.
113. M.S. Gilbert, L.M. Aledort, S. Seremetis, et al., Long term evaluation of septic arthritis in hemophilic patients, Clin. Orthop. Relat.
Res. (1996) 54–59.
578
SECTION 5 — ARTHRITIS RELATED TO INFECTION
114. B.I. Asmar, J. Andresen, W.J. Brown, Ureaplasma urealyticum
arthritis and bacteremia in agammaglobulinemia, Pediatr. Infect.
Dis. J. 17 (1998) 73–76.
116. E. Forlin, C. Milani, Sequelae of septic arthritis of the hip in
children: a new classification and a review of 41 hips, J. Pediatr.
Orthop. 28 (2008) 524–528.
121. R.J. Scott, M.R. Christofersen, W.W. Robertson Jr., et al., Acute
osteomyelitis in children: a review of 116 cases, J. Pediatr. Orthop.
10 (1990) 649–652.
126. R.J. Gorwitz, A review of community-associated methicillin-­
resistant Staphylococcus aureus skin and soft tissue infections,
Pediatr. Infect. Dis. J. 27 (2008) 1–7.
127. J. Saavedra-Lozano, A. Mejias, N. Ahmad, et al., Changing trends
in acute osteomyelitis in children: impact of methicillin-resistant
Staphylococcus aureus infections, J. Pediatr. Orthop. 28 (2008)
569–575.
143. L.T. Gutman, Acute, subacute, and chronic osteomyelitis and pyogenic arthritis in children, Curr. Probl. Pediatr. 15 (1985) 1–72.
147. M.N. Wang, W.M. Chen, K.S. Lee, et al., Tuberculous osteomyelitis in young children, J. Pediatr. Orthop. 19 (1999) 151–155.
152. M.H. Perlman, M.J. Patzakis, P.J. Kumar, et al., The incidence
of joint involvement with adjacent osteomyelitis in pediatric
patients,, J. Pediatr. Orthop. 20 (2000) 40–43.
156. P.N. Tyrrell, V.N. Cassar-Pullicino, S.M. Eisenstein, et al., Back
pain in childhood, Ann. Rheum. Dis. 55 (1996) 789–793.
160. N.E. Green, R.D. Beauchamp, P.P. Griffin, Primary subacute
epiphyseal osteomyelitis, J. Bone Joint Surg. Am. 63 (1981)
107–114.
161. J.J. McCarthy, J.P. Dormans, S.H. Kozin, et al., Musculoskeletal infections in children. Basic treatment principles and recent
advancements, J. Bone Joint Surg. Am. 86-A (2004) 850–863.
164. G.A. Mandell, Imaging in the diagnosis of musculoskeletal infections in children, Curr. Probl. Pediatr. 26 (1996) 218–237.
172. A. Karwowska, H.D. Davies, T. Jadavji, Epidemiology and outcome of osteomyelitis in the era of sequential intravenous-oral
therapy, Pediatr. Infect. Dis. J. 17 (1998) 1021–1026.
174. R. Ruebner, R. Keren, S. Coffin, et al., Complications of central
venous catheters used for the treatment of acute hematogenous
osteomyelitis, Pediatrics 117 (2006) 1210–1215.
185. F.L. Sapico, J.Z. Montgomerie, Pyogenic vertebral osteomyelitis:
report of nine cases and review of the literature, Rev. Infect. Dis.
1 (1979) 754–776.
193. M. Fernandez, C.L. Carrol, C.J. Baker, Discitis and vertebral
osteomyelitis in children: an 18-year review, Pediatrics 105 (2000)
1299–1304.
205. T. Schneider, V. Moos, C. Loddenkemper, et al., Whipple’s disease: new aspects of pathogenesis and treatment, Lancet Infect.
Dis. 8 (2008) 179–190.
206. R.E. Petty, A.J. Tingle, Arthritis and viral infection, J. Pediatr. 113
(1988) 948–949.
208. R. Franssila, K. Hedman, Infection and musculoskeletal conditions: Viral causes of arthritis, Best Pract. Res. Clin. Rheumatol.
20 (2006) 1139–1157.
235. J.J. Nocton, L.C. Miller, L.B. Tucker, et al., Human parvovirus
B19-associated arthritis in children, J. Pediatr. 122 (1993) 186–190.
248. R.D. Inman, Rheumatic manifestations of hepatitis B virus infection, Semin. Arthritis Rheum. 11 (1982) 406–420.
253. I. Rosner, M. Rozenbaum, E. Toubi, et al., The case for hepatitis
C arthritis, Semin. Arthritis Rheum. 33 (2004) 375–387.
269. P. Schreck, P. Schreck, J. Bradley, et al., Musculoskeletal complications of varicella, J. Bone Joint Surg. Am. 78 (1996) 1713–1719.
281. N. Patel, N. Patel, L.R. Espinoza, HIV infection and rheumatic
diseases: the changing spectrum of clinical enigma, Rheum. Dis. Clin.
North Am. 35 (2009) 139–161.
299. H. Wingstrand, Transient synovitis of the hip in the child, Acta.
Orthop. Scand. (Suppl.) 219 (1986) 1–61.
301. M.S. Kocher, D. Zurakowski, J.R. Kasser, Differentiating between
septic arthritis and transient synovitis of the hip in children: an
evidence-based clinical prediction algorithm, J. Bone Joint Surg.
Am. 81 (1999) 1662–1670.
Entire reference list is available online at www.expertconsult.com.