Osteomyelitis

Osteomyelitis represents an infection of bone. In children, it occurs most commonly in the metaphysis of long bones. About two-thirds of cases occur in the lower extremity, with the femur and tibia most often affected. Osteomyelitis is subdivided based on chronicity into acute osteomyelitis (symptom duration less than two weeks), subacute osteomyelitis (symptom duration from two to six weeks), and chronic osteomyelitis (symptom duration longer than six weeks).

Osteomyelitis in children most commonly occurs due to hematogenous seeding, that is, circulating bacteria in the bloodstream land in the bone. Osteomyelitis can also occur as a result of local spread of bacteria from an adjacent infection or from direct inoculation due to an open fracture or puncture wound.

In children, the metaphyseal capillaries make a sharp hairpin turn as they approach the physis. This turn decelerates the blood flow, which can allow bacterial seeding of bone to take place.

When bacterial seeding occurs, a local immune response leads to increased vascular permeability, edema, increased vascularity, and recruitment of polymorphonuclear leukocytes (PMNs). This purulence increases pressure within the medullary canal and can further obstruct blood flow. It can also cause extrusion of purulent fluid through the bone’s surface to the periosteum, resulting in a subperiosteal abscess. Increased pressure can cause venous stasis and thrombosis, leading to necrosis of bone. The necrotic and infected bone might become sequestered by new bone formation, making the eradication of bacteria difficult or impossible without surgical excision. (The new bone tissue is called an “involucrum” and the infected bone it surrounds is called the “sequestrum.”) At times, an involucrum may spontaneously break down and drain purulent fluid through a sinus tract to the skin.

In children under 18 months, the metaphyseal capillaries extend across the physis to the epiphysis. This allows infection to possibly damage the physis and seed the joint causing septic arthritis (see below).

Osteomyelitis in pediatric patients is most commonly caused by Staphylococcus aureus, followed by group A beta-hemolytic Streptococcus. Haemophilus influenzae infections were previously common, however the prevalence has decreased due to widespread immunization. Group B streptococcus and Enterobacter infections occur more commonly in infants and very young children. Salmonella infections may occur in children with Sickle Cell disease. Immunocompromised patients can develop infections from atypical pathogens.

The annual incidence of acute and subacute osteomyelitis in children is about 13 per 100,000, and there is no significant difference in occurrence rates between males and females. Children with immunodeficiency, diabetes, hemoglobinopathy, and systemic inflammatory conditions are at increased risk.

In acute osteomyelitis, patients typically present with fever and progressive pain. If the lower extremity, pelvis, or spine is involved, it is common for the patient to have a limp or refuse to walk. If the upper extremity is involved, it is common for the patient to refuse to use the extremity.

On physical exam, the patient usually does not look well. The affected region is typically swollen, warm to the touch, and tender to palpation. The patient may also have limited motion of the joint adjacent to the region of pain.

In subacute and chronic osteomyelitis, patients typically present with vague discomfort, but no fever or constitutional symptoms. Their primary complaint is typically well localized pain in the metaphysis of the long bone; however, this can also occur in the epiphysis or diaphysis. Patients typically report pain that is worse with activity and temporarily improved by rest. On physical exam, the patient typically does not look sick. The affected region is typically tender to palpation with mild swelling and possible limitations in range of motion of the joint adjacent to the region of pain. The patient may also have an antalgic gait.

Other diagnoses to consider include other musculoskeletal or soft tissue infections (e.g. septic arthritis, pyomyositis, cellulitis), inflammatory diseases (e.g. acute rheumatic fever), trauma, benign tumors (e.g. eosinophilic granuloma), and malignancies (e.g. leukemia, Ewing sarcoma, osteosarcoma).

If a patient presents with findings concerning for osteomyelitis, the following should be obtained as part of an initial work-up: a complete blood count (CBC) with differential, erythrocyte sedimentation rate (ESR or “sed rate”) and C-reactive protein (CRP), blood cultures, and x-rays of the affected region.

The CRP will typically become elevated within eight hours of onset of the infection. The ESR may not become elevated until 24 to 48 hours after infection onset. Although ESR and CRP are nonspecific, they are helpful in establishing a diagnosis. CRP is also useful for monitoring response to treatment. The white blood cell (WBC) count may also be elevated; however, a normal WBC does not exclude a diagnosis of osteomyelitis.

Blood cultures are helpful as they are able to identify the infecting organism in 40 to 50% of patients and allow targeted antibiotic therapy.

X-rays tend to be normal or only demonstrate soft tissue swelling in the acute phase, however periosteal reaction, osteolysis, joint space widening, and soft tissue changes may develop. X-rays are also useful to rule out other disorders.

MRI represents the best available imaging modality for diagnosing osteomyelitis. Typical findings include bone marrow edema manifested as increased marrow intensity of T2 sequences and decreased intensity on T1 sequences. MRI may also reveal intra-osseous or subperiosteal abscesses (Figure 1).

Features of chronic osteomyelitis such as cloaca, sinus tracts, or sequestra are also well demonstrated on MRI. MRI is particularly useful in that it has superior soft tissue contrast and can reveal other musculoskeletal pathology that may mimic osteomyelitis (e.g. cellulitis, pyomyositis, fracture etc.). Other modalities such as radionucleotide bone scan, CT, or ultrasound may be useful adjuvants, particularly with patients for whom MRI is contraindicated or not feasible.

If the diagnosis of acute osteomyelitis is suspected, the patient should undergo an MRI of the involved area. The presence of an intraosseous or subperiosteal abscess warrants surgical debridement.

Patients who do not require surgical debridement initially can be treated empirically with a trial of empiric intravenous antibiotics which are later tailored to the results of blood cultures. If patients fail to improve from a clinical and laboratory standpoint after 48-72 hours of empiric IV antibiotic therapy, repeat imaging and surgical debridement are indicated (Figure 2).

Antibiotics are typically continued for four to six weeks in total assuming clinical improvement and resolution of inflammatory markers. The timing of transition from IV to oral antibiotics is controversial, however it is often feasible to make this transition after several days, provided the patient is clinically improved.

If acute osteomyelitis is not treated, it can develop into chronic osteomyelitis and cause destruction of bone as well as extension of the infection to surrounding tissues.

With appropriate treatment, the patient's clinical exam should normalize over six to twelve weeks. Skeletally immature patients with a history of osteomyelitis near the ends of long bones should be monitored long term for signs of physeal arrest. Other potential complications of osteomyelitis include venous thromboembolic disease, pathologic fracture, and avascular necrosis.

Septic Arthritis

Septic arthritis is an infection of a joint. It occurs most commonly in the large joints of the lower extremities, such as the knees and hips, however it can occur in other locations as well.

Septic arthritis most commonly occurs due to hematogenous seeding of the synovium from an infection elsewhere in the body such as pneumonia, impetigo, or other skin infections. It can also occur as a result of local spread of bacteria from an adjacent osteomyelitis. This tends to happen in the setting of metaphyseal osteomyelitis when the metaphysis is intracapsular (hip, shoulder, elbow, ankle). Although much less common, penetrating wounds into the joint can also cause septic arthritis.

When spread hematogenously, bacteria travel via the bloodstream to the synovial capillaries, at which point they form microabscesses that rupture into the joint. When spread locally, bacteria in the epiphysis perforate the articular cartilage to enter the joint. When this occurs, the patient typically presents with an acute episode of septic arthritis and the osteomyelitis does not tend to become apparent for several days.

Once bacteria find their way into the joint, the acute synovial reaction results in the formation of a seropurulent exudate, ultimately leading to a painful joint effusion. During the inflammatory reaction, leukocytes release proteolytic enzymes, which can cause progressive and irreversible erosion of the articular cartilage, as well as the largely cartilaginous epiphysis. The increased intra-articular pressure can also reduce perfusion of the epiphysis, leading to avascular necrosis if left untreated. If the infection is not treated, loss of articular cartilage, joint fibrosis, bony alkalosis, bone destruction, and joint deformity can all occur.

The bacteria responsible for septic arthritis vary by the age of the patient.

In children under one month of age, the common causes are Staphylococcus aureus, Group B strep, Gram negative organisms, and Streptococcus pneumoniae.

In children between one month and three years of age, Staphylococcus aureus and Streptococcus pneumoniae are also common, but Streptococcus pyogenes, Kingella kingae, and Haemophilus influenza Type B are seen (the latter in unimmunized children in particular). These bacteria, with the exception of Kingella kingae, are seen in children older than three years of age as well.

In adolescents, the common causes are Staphylococcus aureus, Nisseria gonorrhoeae, Streptococcus pneumoniae, and Streptococcus pyogenes.

The annual incidence of septic arthritis in children in developed countries is about 4-5 per 100,000. It is more common in boys than girls, with a ratio of 2:1. Septic arthritis is not uncommon in healthy children, however children with immunodeficiency are at an increased risk.

In septic arthritis, patients typically present with acute onset guarding of a joint. Initially, pain is often poorly localized. A history of mild trauma is common (and might be coincidental); patients often have a history of a viral illness in the days to weeks prior to symptom onset.

If the lower extremity is involved, patients often have a limp or will completely refuse to bear weight on the extremity. If the upper extremity is involved, patient will often refuse to use the extremity. Patients typically also have systemic symptoms, such as malaise, fever, and poor appetite.

On physical exam, patients will often appear ill. They tend to hold the affected joint in a position to accommodate joint distention. Patients with septic arthritis of the hip tend to hold the hip in a flexed, abducted, and externally rotated position, whereas if the knee is involved, the joint is held in a slightly flexed position. Children are typically apprehensive, and resist attempts to examine the affected extremity. Any movement of the joint is typically painful. The joint is often tender to palpation. Joint effusions can be seen in subcutaneous joints such as the knee, elbow, and ankle. Effusions are often difficult to appreciate in less subcutaneous joints such as the hip, shoulder, and SI joint.

Other diagnoses to consider include transient synovitis, hemarthrosis, other infectious etiologies, inflammatory diseases, Legg-Calve-Perthes disease, and neoplastic processes. Hemarthrosis can occur secondary to hemophilia or trauma. Infectious etiologies to consider include osteomyelitis, pyomyositis, and Lyme disease. Inflammatory diseases to consider include juvenile idiopathic arthritis, reactive arthritis, and rheumatic fever. Neoplastic processes to consider include leukemia and pigmented villonodular synovitis (PVNS).

If a patient presents with findings concerning for septic arthritis, the following should be obtained as part of an initial work-up: CBC with differential, ESR, CRP, and x-rays of the affected region. The CRP will typically become elevated within six to eight hours of the onset of symptoms. The ESR may not be elevated until 24 to 48 hours after the onset of symptoms. Although ESR and CRP are nonspecific, they are helpful in establishing a diagnosis. CRP is also useful for monitoring response to treatment. WBC may be elevated; however, it is often not elevated early on. Initial x-rays are often normal; however, they may reveal joint space widening. X-rays are also useful to rule out other disorders. Ultrasound may be helpful to confirm the presence of a joint effusion (Figure 3). Blood cultures can also be helpful and are able to identify the infecting organism in 40 to 50% of patients.

The Kocher criteria can be used to assist with diagnosis of septic arthritis of the hip. The four criteria are as follows: a history of fever over 38.5 degrees Celsius, an inability to bear weight on the affected extremity, an ESR greater than 40 mm/hr, and WBC greater than 12,000 cells/microliter. If the patient has three or four of these predictors, their predicted probability of having septic arthritis is 93.1% and 99.6% respectively. A CRP > 2.0 mg/dL is also a strong independent predictor for septic arthritis.

If the diagnosis of septic arthritis is suspected, the patient should undergo urgent aspiration of the joint and analysis of the joint fluid consisting of at minimum a cell count, gram stain, and cultures. A cell count of over 50,000 WBC/mm^3, a positive gram stain, and positive cultures are all suggestive of septic arthritis, however the absence of those findings does not exclude this diagnosis.

Once the joint is aspirated (Figure 4) and the synovial fluid is sent for cultures, the patient should be started on empiric IV antibiotic therapy. Antibiotic coverage should then be narrowed based upon the culture results. The patient should then undergo urgent surgical debridement of the joint via either open arthrotomy or arthroscopic wash out. IV antibiotics are continued until the patient improves clinically, followed byoral antibiotics for another two to four weeks.

If septic arthritis is not treated, the release of enzymes into the joint by leukocytes to destroy the bacteria will also destroy the articular cartilage (hence the urgent need to remove the fluid, not only for diagnosis).

The increased intra-articular pressure during the inflammatory reaction can also decrease perfusion of the epiphysis, leading to avascular necrosis. Long-term, untreated septic arthritis can lead to joint fibrosis, bony alkalosis, bone destruction, and joint deformity.

With appropriate treatment, patients generally have good outcomes. Possible complications of septic arthritis include contracture, growth disturbance, and avascular necrosis. Patients who have recovered from septic arthritis should be monitored radiographically for sequelae of infection, particularly in cases of septic arthritis of the hip.

Transient Synovitis

Transient synovitis is self-limited inflammation of the synovium. It can occur in any large joint, however it most commonly occurs in the hip.

The pathophysiology of transient synovitis is poorly understood, however there is thought to be a link between transient synovitis and antecedent viral infections. Patients often have a history of a recent upper respiratory infection.

The annual incidence of transient synovitis in children ages one to thirteen is 0.2%. It is more common in boys than girls, with a ratio of 2:1. The average age at presentation is six. Transient synovitis is the most common cause of hip pain in children.

In transient synovitis, patients typically present with joint pain and a limp. If the lower extremity is involved, patients may refuse to bear weight on the extremity. On physical exam, patients are usually afebrile and generally do not appear ill. On examination of range of motion of the affected joint, pain tends to be most severe at the extremes of motion and minimal in the middle of the range of motion arc.

Transient synovitis is a diagnosis of exclusion. If the diagnosis of transient synovitis is suspected, it is important to ensure the patient does not have septic arthritis, in which case the patient would need IV antibiotics and an urgent debridement of the joint in the operating room to prevent rapid joint destruction.

The Kocher criteria are useful in helping to differentiate between transient synovitis and septic arthritis of the hip. If the patient meets one or two of the criteria, their predicted probability of having septic arthritis drops to 3% and 40% respectively, and transient synovitis rises on the differential.

Other differential diagnoses to consider include traumatic injury, Legg-Calvé-Perthes disease, juvenile inflammatory arthritis, Lyme arthritis, osteomyelitis, and slipped capital femoral epiphysis.

If the patient presents with findings concerning for transient synovitis, the following should be obtained as part of an initial work-up: CBC with differential, ESR, CRP, and x-rays of the affected region. In transient synovitis, WBC, ESR, and CRP are usually normal, however they may be slightly elevated. X-rays tend to be normal, however they are useful to rule out other disorders. If there is any suspicion for septic arthritis, the patient should undergo joint aspiration and the synovial fluid should be sent for testing. MRI may also be useful to evaluate for osteomyelitis.

Transient synovitis is usually self-limited and spontaneously resolves in one to two weeks. Patients may be treated symptomatically with rest and anti-inflammatories. Patients should be observed closely by a primary care physician or pediatric orthopedic surgeon. If symptoms persist beyond a few weeks, a diagnosis of transient synovitis is less likely and the patient should undergo work-up for other etiologies.

Symptoms of transient synovitis generally begin to improve within 24 to 48 hours; however, it may take a few weeks for joint irritation to completely resolve. The recurrence rate of transient synovitis is as high as 20%. There are no known long-term sequelae of transient synovitis.

Lyme Disease

Lyme disease is an illness that affects multiple body systems. It is caused by the spirochete Borrelia burgdorferi, which is transmitted by the Ixodes tick.

Ticks are generally located on low-lying vegetation. Once they become transmitted to the host, they attach themselves to the host's skin to feed on the blood. The ticks may attach to the skin on any part of the body; however, they often attach in areas that are difficult to see such as the groin, armpits, and scalp. They must generally be attached to the skin for 36 to 48 hours before bacteria can be transmitted.

Ixodes ticks have a two-year life cycle consisting of four distinct developmental stages: egg, larva, nymph, and adult. The lifecycle begins when an adult tick lays eggs in the spring. In the summer, the eggs emerge as larva, which feed on small invertebrates such as mice and squirrels. The larvae emerge as nymphs the following spring, and also feed on small invertebrates such as mice and squirrels. The nymphs then mold into adult ticks in the fall and feed on larger animals, such as deer. Ixodes ticks acquire the Borrelia burgdorferi spirochete by feeding on infested animals during the larva, nymph, and adult stages. Mice and deer are able to carry the spirochete, however they do not become infected. Only ticks in the nymph and adult stages are able to transmit Borrelia burgdorferi. Most humans become infected through nymph bites, as the nymphs are small (less than 2 mm) and often hard to see. Adult ticks tend to be seen and removed before they can transmit the bacteria.

During an Ixodes tick bite, the tick saliva disrupts the local immune system, which creates a protective environment for spirochete replication. Replication of the spirochetes within the dermis leads to a localized post inflammatory response, which causes a bull's-eye rash termed erythema chronicum migrans. Over a period of days, the spirochetes spread via the bloodstream to the joints, nervous system, and cardiac tissue. Once present in the joint, the spirochete leads to an inflammatory response, which ultimately resulted in synovial hypertrophy and accumulation of immune complexes in the synovial fluid.

The annual incidence of Lyme Disease is 7.9 per 100,000. The incidence is higher in the northeast (Maryland to northern Massachusetts), the upper Midwest (Minnesota and Wisconsin), and the west (northern California and Oregon). Lyme disease is most common in children aged five to nine, and infection most often occurs during the summer.

Lyme disease is characterized by three distinct phases: the early localized phase, the early disseminated phase, and the late phase.

The early localized phase tends to occur within one month of the tick bite. This phase consists of the erythema chronicum migrans skin lesion (Figure 5). The skin lesion expands over a period of days to weeks, reaching a diameter of up to 20 cm. At this point, patients may have systemic symptoms similar to those of a viral syndrome, including: fatigue, fever, anorexia, headache, neck stiffness, myalgias, and arthralgias.

The early disseminated phase tends to occur weeks to months after the tick bite. During this phase, pediatric patients often have multiple erythema migrans skin lesions. Conjunctivitis is also common and occurs in up to 10% of patients. Although rarer, patients may have cardiac or neurologic involvement. The most common neurologic manifestation is a Bell's palsy, or paralysis of the facial nerve. Other neurologic abnormalities that can occur include radiculopathy, cranial neuropathy, and meningitis. Cardiac manifestations that can occur include pericarditis and atrioventricular heart block.

The late phase tends to occur several months to years after the tick bite. During this phase, patients often have intermittent or persistent arthralgias of one or a few large joints, with the knee being most commonly affected. Radicular pain, distal paresthesias, and Lyme encephalopathy which leads to mild cognitive difficulties can also occur.

The differential diagnosis for Lyme disease includes acute rheumatic fever, idiopathic Bell's palsy, multiple sclerosis, peripheral neuritis, and reactive arthritis (formerly known as Reiter’s syndrome).

If a patient presents with the classic erythema chronicum migrans rash, no further diagnostic testing is needed and the patient can be assumed to have Lyme disease. If a patient does not have the classic rash at the time of evaluation, however, there is concern that a patient may be in the early localized phase of Lyme disease. The following labs should be obtained as part of an initial workup: CBC with differential, ESR, CRP, LFTs, and a Lyme enzyme immunoassay or immunofluorescence assay. WBC may be elevated; however, a normal WBC does not exclude a diagnosis of Lyme disease. ESR and CRP are often elevated, albeit to a lower level when compared to values reached in the setting of septic arthritis. LFTs may demonstrate liver function abnormalities. If initial serologic tests are equivocal or positive, a Western immunoblot test should be obtained to confirm the diagnosis.

If a patient is experiencing joint pain, x-rays of the affected region should be obtained. These will often be normal; however, they are useful to rule out other disorders. Distinguishing between septic arthritis and Lyme arthritis is quite difficult but Lyme arthritis tends to have less significant reduction in joint passive range of motion and the child will often be willing to bear weight or use the extremity. If septic arthritis is on the differential, the joint should be aspirated and the synovial fluid should be sent for cell count, gram stain, and cultures. In Lyme arthritis, the synovial fluid WBC is typically elevated, but to a less significant level than in other forms of septic arthritis. It is generally very difficult to culture Borrelia burgdorferi from the synovial fluid, and serologic tests are generally sufficient to support a diagnosis of Lyme arthritis. An ECG should be obtained if Lyme carditis is suspected. A lumbar puncture should be obtained if Lyme meningitis is suspected.

In the early stages of infection, Lyme disease is treated with oral antibiotics (typically doxycycline, amoxicillin, or cefuroxime) for two to four weeks. Children under eight should not receive doxycycline. If there is no resolution in symptoms after an initial course of antibiotics, a second course may be needed. If patients have neurologic or cardiac involvement, they may need IV antibiotics (typically ceftriaxone, cefotaxime, or penicillin G). Patients with chronic Lyme arthritis that does not respond to IV antibiotics may need to undergo surgical removal of the joint synovium.

If Lyme disease is not treated in the early stage, it can progress and the infection can spread to the joints, heart, and nervous system. If Lyme disease is treated in the early stages, patients tend to recover quickly and completely without long term sequelae. Even after treatment, patients can sometimes have Post-Treatment Lyme Disease Syndrome, which can include persistent joint pain, fatigue, and cognitive impairment.

Currently, there is no available vaccine against Borrelia burgdorferi, however there are steps that can be taken to decrease the risk of Ixodes tick bites. People in high risk areas can wear long sleeved shirts tucked into pants and pants tucked into socks to decrease exposed skin. Skin and clothing can be checked for ticks once inside. Insect repellant can also be used to decrease the risk of tick bites. If ticks are found on the skin, they should be removed using tweezers. The tweezers should be used to pull traction on the tick until it releases the skin. Alcohol should then be applied to the skin.