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Etiologic agents changing in skeletal infections
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Before the Haemophilus influenzae type b vaccine, this organism was the most common cause of septic arthritis in infants. Now, it is as rare as invasive disease caused by Haemophilus influenzae type b.
When recently presented with a child who had a swollen tender knee, the first diagnosis mentioned was Lyme or Borrelia.
Around this time of year, this is a reasonable diagnosis.
The knee joints are mainly involved, and it is well to remember that arthritis occurs weeks or even months following the rash. In one study, signs of early Lyme, erythema migrans or facial palsy were present in only 26% of those who had Lyme arthritis. When a rash occurred, arthritis was on the average of 4.3 months later, and in one case, 20 months post-rash. Thus, the absence of these early signs does not rule out the diagnosis.
The knee is most commonly involved (Pediatrics. 1998;102:905-908), and the joints are described as more swollen and hot than red and tender. Serologic tests may be helpful in confirming the diagnosis. The enzyme-linked immunosorbent assay (ELISA) should always be backed up by a Western blot. Therapy recommended in the Red Book includes “amoxicillin (50 mg/kg per day in three divided doses [maximum of 500 mg per dose]) (B-I), cefuroxime axetil (30 mg/kg per day in two divided doses [maximum of 500 mg per dose]) (B-III), or, if the patient is aged 8 years, doxycycline (4 mg/kg per day in two divided doses [maximum of 100 mg per dose]).” In spite of adequate therapy, some patients may have relapses or go on to have chronic disease. Joint involvement in another tickborne disease sometimes confused with Lyme, known as Southern tick-associated rash illness (STARI), is rare. This infection, which has been present in the Southeast, is creeping north and is seen as far north as Maine.
When I was in Los Angeles, every so often someone would appear, complaining of “Lyme disease.” Some patients had legitimate concerns, such as those who had been summering out on Long Island or in New England. Others had come to receive treatment for what they were told was chronic Lyme disease. As you are probably aware, the IDSA is currently the defendant in a lawsuit in which they have been accused of restraint of trade because their practice guidelines (Clin Infect Dis. 2006;43:1089-1134) do not recommend antimicrobial treatment. This statement is backed by published studies.
Post-Lyme syndrome is a diagnosis applied to some people who have chronic malaise, loss of memory, arthralgia and a host of other non-specific symptoms. There are many people out there with these symptoms who are undoubtedly ill. They have been variously diagnosed with chronic Epstein-Barr virus, fibromyalgia and chronic fatigue syndrome, among others. They are truly disabled by their illness, the cause of which is still not clear. In the chronic fatigue literature, a significant number of these patients were clinically depressed. Unfortunately, the specific diagnosis has been elusive. Serologic tests for Borrelia, Epstein-Barr virus and other agents usually will be unrewarding, and I would suggest that one not start down that road.
A relative newcomer has been Kingella, which is a gram-negative rod that previously was classified as a Moraxella and was the K in the group of organisms referred to as HACEK (Haemophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae). It now appears to be responsible for the largest number of joint infections in infants and has been the cause of a cluster of three cases that were reported in a day care center (MMWR. 2004;53:241-243). It is probably much more common than has been reported as the organism is quite fastidious. Joint fluid should be inoculated directly into aerobic broth cultures, which is something most orthopedists will not do unless specifically instructed to do so by the referring physician. Indeed, 35% of infectious disease specialists did not do this, and it was suggested that some skeletal infections in which no organism was identified may have resulted from improper specimen collection. Fortunately, the organism is responsive to many commonly used antimicrobial agents. It is possible that skeletal infections for which an etiologic agent has not been found may yield negative cultures because of pretreatment with Kingella-sensitive antimicrobials.
Staphylococcal joint or bone infections are still very much with us, but methicillin-resistant Staphylococcus aureus (MRSA) is now much more common than in prior years and is increasing in frequency. For these patients, oxacillin or nafcillin, which are the choices for methicillin-susceptible Staphylococcus aureus (MSSA), are useless. Clindamycin, which has been shown in clinical trials to successfully treat MSSA skeletal infections, are still a good choice for MRSA, but its use should be accompanied by sensitivity testing and a D-test. The latter will test for intrinsic and inducible resistance to clindamycin. At this point, one must turn to alternative drugs and probably to an infectious disease specialist.
In suspected cases of skeletal infections, magnetic resonance imaging has become the modality of choice for diagnosis. If it suggests infection, obtaining a specimen is important for confirming the diagnosis, as well as for identification of the organism and for obtaining sensitivities. Surgical intervention is also useful in draining pockets of pus and for relieving pressure on joints; if present, sequestra should be removed. In studies in which therapy was switched from parenteral to oral, patients generally had surgical removal of pus. The switch occurred as early as a few days after initiation of intravenous antimicrobial therapy if the patient was doing well clinically.
The question of how long one needs to treat has no clear answer. The duration seems to have increased in recent years in the absence of discernable evidence. This can probably be attributed to the belief that longer is better; the fear of lawsuits; and from the influence of our adult colleagues. It is important to appreciate that skeletal infections in children are generally hematogenous. Adult physicians frequently deal with patients who have wound infections resulting from trauma; patients with diabetes; or other patients who may have a compromised immune response post-surgery, often with indwelling foreign bodies. The duration of therapy has evolved in pediatric patients mainly from retrospective observations on the failure in cases, which have “not been treated long enough.” After a number of years, one cannot help but find exceptional cases in which failures occur, whatever the length of therapy. In the study still quoted in most of the pediatric infectious disease texts, it is stated that oral antibiotics are not continued following four weeks of parenteral therapy. It is interesting that they chose four weeks, because only one of 50 patients treated for staph osteomyelitis for more than 21 days, including none of the 28 patients treated from 22 days to 28 days, failed treatment (Am J Dis Child. 1975;129:1273).
It is important to remember that bone pain and fever have causes other than infection. In the past, rheumatic fever was, and in many other countries today, is still a common cause of fever and painful inflamed joints. It is estimated that about 500 cases occur annually in the United States (Pediatrics. 2007;20:503). Characteristically, there is migratory polyarthritis. However, multiple joint involvement in staphylococcal infections or sympathetic arthralgia due to this organism are not rare. Bone pain and fever in leukemia or bone malignancies must be considered. Frequently, these patients show up in a rheumatology clinic (Clin Ped. 2005;44:419). How about this one for a curve ball? This is an otherwise healthy newborn.
The diagnosis is cortical hyperostosis disease, or Caffey’s disease, seen with Kulkanya Chokephaibulkit, MD, in Bangkok, Thailand.