Previously healthy 2-year-old presents with sore throat and limp

Issue: June 2013

A previously healthy 2-year-old female presents to the ED with the chief complaint of a sore throat and pain in the right lower extremity. The history of the chief complaint began 2 weeks earlier when she had symptoms of a mild upper respiratory tract infection. However, the pain in her right knee only began 2 days earlier. There was no history of injury.

Her medical history was unremarkable, with up-to-date immunizations. Her family/social history reveals no sick contacts or animal or insect exposure.

Richard H. Schwartz

Irina Remsburg

Examination at that time revealed a well-appearing, playful child with normal vital signs. The rest of her exam was equally normal, including her musculoskeletal system, with normal range of motion of the hips, knees and ankles. Believing that the right hip was the source of the limp, an ultrasound and routine hip radiographs were obtained and were interpreted as normal by a radiologist. The child subsequently was sent home with a presumptive diagnosis of transient (toxic) post-viral synovitis. Two days later, she was taken back to the office of her pediatrician because of recurrence of right lower extremity limp. Examination then confirmed the presence of a mild limp and right knee effusion without erythema or warmth (Figure 1).

Laboratory tests included a normal CBC and C-reactive protein (CRP). However, her erythrocyte sedimentation rate (ESR) was 58 mm/hour. Pending blood tests included a blood culture and Lyme disease titer. An ultrasound image of the right knee confirmed the presence of an effusion. A plain radiograph demonstrated some thickening of the synovial lining. After orthopedic consult, the diagnosis was again transient synovitis, with no further evaluation indicated. After overnight observation in the hospital, she showed improvement in weight bearing and gait and was discharged.

Examination confirmed the presence of a mild limp and right knee effusion without erythema or warmth (Figure 1). An MRI of the knee (Figure 2).

Image: Brien JH

Several days later, she was again seen by her pediatrician, at which time the knee effusion was still evident, although she was still able to walk without much discomfort and no fever was detected. A repeat CBC and CRP were again unremarkable. A repeat ESR was not ordered; however, a stat report from the laboratory, coincidentally at that time, reported that the blood taken at the initial visit was growing a Gram-variable coccobacillus. The patient was readmitted to the hospital with the diagnosis of septic arthritis and treated empirically with IV ceftriaxone (80 mg/kg), pending identification and sensitivity testing. An MRI of the knee is shown in Figure 2.

What’s Your Diagnosis?

A) Transient synovitis with contaminated culture

B) Reactive arthritis

C) Lyme arthritis

D) Septic arthritis due to Kingella kingae

The organism in the blood culture was soon identified as Kingella kingae. Arthrocentesis of the right knee revealed 10 mL of frank pus showing 22,750 leukocytes with 84% neutrophils. The Gram’s stain and culture were negative. The MRI revealed a large joint effusion along with thickened synovium, consistent with septic arthritis without osteomyelitis. An MRI showing osteomyelitis would reveal enhancement in the bone, as shown in Figure 3, osteomyelitis of the distal femur. As Kingella is known to be a cause of bacterial endocarditis, an echocardiogram was obtained, which was normal, as well as her cardiac exam.

The child received 6 days of IV ceftriaxone, and with significant clinical improvement and sensitivities showing penicillin-sensitive, she was discharged home to complete an additional 2 weeks of high-dose amoxicillin (90 mg/kg/day divided by three times daily), with a good outcome on follow-up.

Kingella septic arthritis

Kingella is an increasingly important emerging pathogen that causes bacteremic osteoarticular infections, particularly of the knee joint. In southern Israel and Paris, Kingella isolations from arthrocentesis or blood cultures taken from children aged younger than 5 years with osteoarthritis infections of the knee exceeded Staphylococcus aureus as the causative agent. The slow growth and/or the small number of Kingella organisms in synovial fluid frequently result in a failure of routine methods of detection. K. kingae may be the most frequent cause of septic arthritis in children aged younger than 4 years; however, PCR is often necessary for detection, without which 50% of the infections would be missed.

Pediatric patients with invasive K. kingae infections frequently present with minimal or no constitutional symptoms. Fever is frequently absent on admission, and most children appear only mildly or moderately ill. Symptoms and signs of Kingella joint infections are very similar to those of Lyme disease arthritis or transient (toxic) synovitis of the knee joint. Both of those conditions may produce visible swelling, mild warmth and erythema of the skin over the knee. However, pain is deceptively mild to moderate and affected children often can walk without a limp. Adding to the diagnostic difficulty, the total leukocyte count and inflammatory markers, such as the CRP and ESR, are usually minimally elevated. For 70% of young children with Kingella arthritis, the disease is usually diagnosed at least 1 week after onset of symptoms.

An MRI showing osteomyelitis would reveal enhancement in the bone, as shown in Figure 3.

K. kingae is a slow-growing, fastidious gram-variable or gram-negative, oxidase-positive, beta-hemolytic, short coccobacillus, and is a component of the normal oropharyngeal flora in children. Oropharyngeal carriage of Kingella is unusual prior to 6 months of age, after which it increases sharply from 12 to 24 months. It is difficult to identify on a Gram’s stain of blood or joint fluid, and may be initially misinterpreted on culture. Microbiology technicians often mistake Kingella as a contaminant. Additionally, growth is poor on sheep blood agar.

Detectable growth of blood or joint aspirate cultures takes a median of 4 days of incubation. Clinicians should suspect infection with K. kingae in young children with negative blood cultures and negative joint fluid cultures, especially in those with a sub-acute clinical presentation. Blood culture bottles should be kept under incubation for at least 7 days. If possible, pre-treatment joint fluid should be inoculated directly into several blood-culture bottles or tubes, as this technique increases the isolation of Kingella. PCR testing of the blood culture media and joint fluid improves the detection of Kingella species by 50% or more. Most K. kingae isolates are susceptible to amoxicillin or penicillin if beta-lactamase-negative. Ceftriaxone is also effective. The long-term prognosis is favorable in almost all cases that are treated with appropriate systemic antibiotics.

Transient (toxic) synovitis

Transient (toxic) synovitis is the most common self-limiting cause of none-traumatic acute unilateral hip or knee pain in young children. It is believed, but not proven, to be a post-viral synovial inflammatory condition. Presenting symptoms and signs of transient synovitis include hip or knee pain with weight-bearing in a child, often with low-grade fever and a recent history of a viral upper respiratory infection or gastrointestinal infection.

Physical examination of the affected joint reveals limitation of range of motion and resistance to weight-bearing. An affected hip is usually held in a position of flexion, external rotation and abduction, and resists range of motion testing. There may be minimal elevation of the leukocyte count and mild to moderate increase in the sedimentation rate. A small effusion may be seen on ultrasound examination of an affected joint. Management includes rest and nonsteroidal anti-inflammatory medications, such as ibuprofen. Symptoms usually last less than a week.

Lyme arthritis

In Lyme-disease-prevalent areas of the United States, episodic monoarticular arthritis, with a moderately swollen knee joint, is a frequent occurrence in the third (late) stage of Lyme disease. Signs and symptoms of Lyme arthritis closely resemble those of Kingella arthritis in that pain is mild to moderate, the swollen joint can bear weight, and inflammatory markers typically range from normal to moderately elevated. Unlike Kingella arthritis, there may be spontaneous but temporary resolution of the knee swelling, only to relapse after some interval. Although two-thirds of cases of Lyme arthritis involve only the knee joint, up to four joints may be affected in about one-third of cases. The course of the arthritis in an undiagnosed and untreated case of Lyme disease may become chronic.

Diagnosis is made clinically and by positive results on an enzyme immunoassay (EIA) or immunofluorescence assay (IFA), and if positive, verified by immunoblot assay (Western blot). Even after successful antibiotic therapy, antibodies may persist for months to years, and no further antibiotic treatment is necessary in the absence of attributable clinical manifestations. The treatment for uncomplicated Lyme arthritis is oral amoxicillin, cefuroxime or doxycycline (in children older than 7 years) for 28 days, per Red Book recommendations.

Reactive arthritis

Reactive arthritis is an inflammatory, sterile arthritis that occurs following certain viral infections such as parvovirus B19 or bacterial infections such as streptococcal pharyngitis, Yersinia enterocolitica, Shigella, Salmonella, Campylobacter, Meningococcus and Chlamydia. Up to 90% of reactive arthritides are associated with a positive HLA-B27. There are no specific laboratory criteria for this diagnosis. Reactive arthritis is occasionally preceded or accompanied by erythema multiforme.

Post-streptococcal reactive arthritis must be differentiated from acute rheumatic fever, both of which may be associated with elevation of anti-DNAase B and anti-streptolysin O (ASO) antibodies.

Columnist Comments

I would like to thank Dr. Richard Schwartz, Professor of Pediatrics at Virginia Commonwealth University School of Medicine, Inova Children’s Hospital campus and the University of Virginia School of Medicine, for putting this case together and drawing attention to this emerging infectious disease; along with Drs. Kamat and Remsburg, and for the guidance of my old friend and infectious disease colleague from our military days, Dr. David Ascher, Col. USAF (Retired).

Lastly, I would like to invite you to an excellent general pediatric meeting, co-sponsored by Texas Children’s Hospital/Baylor College of Medicine and McLane Children’s Hospital at Scott & White. It will be in the heart of Texas at the Hyatt Regency Lost Pines Resort July 11-13. Nestled in the Pines along the Colorado River near Bastrop, Texas, it’s also a great place for families, with lots of activities for children and only 20 minutes from Austin Bergstrom Airport. For more information, go to www.baylorcme.org/search/detail.cfm?cme=898, where you will find the brochure.

I hope to see you there.

References:

Yagupsky P. Pediatrics. 2011; 127(3):557-565.

For more information:

The columnists are all from the Department of Pediatrics, Inova Children’s Hospital, Falls Church, Va.: Richard H. Schwartz, MD, Staff Attending; Riva Kamat, MD, Hospitalist; Irina Remsburg, MD, Pediatric Resident; and David Ascher, MD, Chairman of the Department of Pediatrics. James H. Brien, DO, is a member of the Infectious Diseases in Children Editorial Board, and can be reached at jhbrien@aol.com.

Disclosure: The authors report no relevant financial disclosures.