A white 2-year-old boy was evaluated for fever and a limp. He was well until 3 weeks prior to admission when he was diagnosed with otitis media and was treated with amoxicillin. He continued to have daily fevers for the next 12 days; during this period, he was seen twice by his primary physician and was told that he had a viral infection. As the fevers continued, he developed a persistent limp for which the parents didn't seek medical care for another 5 days. At that time, a complete blood count (CBC) by his primary physician was normal. A bone scan at an outside hospital reportedly showed increased uptake in the right proximal femur; he was transferred to Children's Memorial Hospital for treatment of presumed osteomyelitis.
The family history and past medical history are unremarkable.
On physical examination, he was a healthy-appearing boy. His vital signs were unremarkable save for a rectal temperature of 390C. His growth parameters were in the 50th percentile. The general physical examination was normal. He had an antalgic gait with avoidance of weight bearing on the right leg. He had full range of motion of all his joints. There was no point tenderness or swelling of any joint or extremity.
Laboratory evaluation on admission included hemoglobin 9.8 g/dL, white blood count 6,300/mm3 with 32% neutrophils, 7% immature neutrophils, 57% lymphocytes, and 4% monocytes; the platelet count was 286,000/mm.3 The erythrocyte sedimentation rate (ESR) was 96 mm/h and the C-reactive protein was 3.45 mg/dL .
Ben Katz, MD, derator: Should we be concerned that the parents didn't seek care sooner, since he was limping for 5 days?
Rebecca Reindel, MD, pediatric resident: To be fair, these parents were very appropriately concerned. They felt that they had been seen 3 times in the last 2 weeks and had been reassured that everything was OK; so they didn't rush in.
Robert Tanz, MD, general academic pediatrician: When we see patients, it's always worth emphasizing that they should come back or call if there's a change in the child's clinical status.
Doug Nordli, MD, pediatric neurologist: As a neurologist, I'm always trying to localize the pathology. A gait abnormality could be due to pain, weakness, or loss of balance. Loss of balance could be due to a sensory problem (loss of proper joint position sense), difficulty with the vestibular apparatus, or problems with coordination of muscle movement due to defects in the cerebellum and cerebellar outflow tracts. Since there's no localized tenderness or swelling on physical examination, we need to keep an open mind. Other potential sources of pain and abnormal gait could be in the spine (eg, discitis, epidural abscess, tumor) or abdomen (eg, psoas abscess).
Robert Listernick, MD, general academic pediatrician: Why were both a CRP and an ESR performed?
Dr. Katz: The literature suggests mat the CRP rises and falls faster than the ESR in inflammatory states. As such, some orthopedists tend to use it more often to follow children who are being tested for osteomyelitis. There's certainly no reason to get both.
Can we look at the radiographs that were performed?
Cynthia Rigsby, MD, pediatric radiologist: X-rays of the right lower extremity were entirely normal; there was no evidence of periosteal elevation. An ultrasound of the hip didn't show any effusion. A bone scan was performed at the outside hospital, with views limited to the pelvis and the proximal lower extremities. There is asymmetry in tracer uptake between the right and left hip; me physician has to make a clinical distinction as to which of these two areas is the abnormal one. In addition, there was a definite area of increased uptake in the right proximal femur.
Dr. Katz: He had been symptomatic for 3 weeks. Would the lack of periosteal elevation on the plain films this late in the clinical course of a child with osteomyelitis be unusual?
Dr. Rigsby: A good rule of thumb in adults is that one expects to see x-ray changes by 14 days after the onset of symptoms. However, we've seen many children, particularly infants, who have had significant x-ray findings early in their course.
Dr. Katz: Is magnetic resonance imaging (MRI) useful in the diagnosis of osteomyelitis?
Dr. Rigsby: Osteomyelitis causes inflammation of the bone marrow, which is readily identified by MRI. In most cases, MRI is unnecessary. However, MRI can be helpful if an abscess in the soft tissue or bone is suspected. Obviously, this should be performed only if the physician has a good idea which bone or part of the body is involved. Unlike a bone scan, which can investigate the entire skeleton, MRI's are performed on targeted areas.
Dr. Katz: What's the role of needle aspiration of the bone in the management of osteomyelitis?
John Grayhack, MD, pediatric orthopedist: We always like to recover an organism, if possible, so that we can tailor the antibiotic therapy. The proximal tibia and distal femur, two common areas of osteomyelitis, are easy to aspirate. The proximal femur is more difficult, requiring sedation and ultrasonographic or computed tomography guidance; certainly a hip effusion should be aspirated as well.
Dr. Katz: We made the decision the night of admission to treat him with antibiotics for presumed osteomyelitis. Admittedly, I was uncomfortable with this diagnosis because of the dual abnormalities on the bone scan and the lack of findings on the plain film. However, as it was the beginning of a weekend and other diagnostic modalities might not have been readily available, I thought it was the prudent thing to do.
Dr. Listernick: While diagnosis and treatment of a septic hip necessitates prompt action, this is not usually the case with osteomyelitis. Too often (not in this case), I've seen other physicians start antibiotics without at least considering the possibility of a bone aspiration in order to make a microbiologic diagnosis.
Dr. Grayhack: There's a risk of waiting too long in children who have infection involving the proximal femoral metaphysis, which can rupture into the hip joint space creating a septic arthritis.
Dr. Katz: Over the weekend, his pain decreased although he remained febrile. I was still concerned that this was something other than osteomyelitis, and I asked the rheumatologists to see him.
Marissa Klein-Gitelman, MD, pediatric rheumatologist: When I'm asked to see a child with suspected arthritis, I first consider certain epidemiologic factors. Rheumatologie causes of arthritis are more common in girls and in children over 3 years of age. Boys over the age of 10 are more likely to develop a spondyloarthropathy. This boy had fewer than 5 joints involved; if he had a rheumatologic cause of arthritis, this would place him into the categories of either oligoarticular juvenile idiopathic arthritis (JIA) or systemiconset JIA.
Next, I look at the entire clinical scenario. Although fever can be seen in JIA, he didn't have the classic fever pattern seen in the systemiconset form. These children often have one or two spikes of fever each day above 40° C; in between spikes, the body temperature usually plummets below 37° C. This child had constant fevers, according to the nurses' fever curve. In addition, in cases of systemic-onset JIA, there is often a history of an evanescent macular red rash that appears on different areas of the body.
Finally, the quality of his pain was unusual for children with JIA. His parents stated that during this illness he often awoke in the middle of the night screaming in pain. In the context of bone and joint pathology, this tends to occur, in my experience, in children who have osteoid osteoma, malignancy, or occasionally osteomyelitis. For all of these reasons, I felt that he didn't have a rheumatologic cause of his clinical syndrome.
Dr. Tanz: Just to add to the list of causes of screaming pain in the middle of the night, I would include both growing pains and night terrors. Obviously, neither applies in this case.
Dr. Katz: So, although he was initially treated for osteomyelitis, we were uncomfortable with that diagnosis and were looking for other potential etiologies. As Dr. Klein-Gitelman stated, we considered that this child could have a malignancy. Are serum chemistries such as uric acid or lactate dehydrogenase (LDH) reasonable screening tests for malignancies?
David Walterhouse, MD, pediatric oncologist: We can see elevated levels of LDH and uric acid in those malignancies in which there is a large tumor load with rapid tumor cell turnover. This most commonly occurs in Burkitt's lymphoma and T-cell leukemias. As a screening test for malignancy, measurement of these levels is not specific and only modestly sensitive at best.
Dr. Katz: For all the reasons mentioned, we felt uncomfortable with the diagnosis of osteomyelitis and ordered an MRI scan of the pelvic bones.
Dr. Rigsby: On the T2-weighted coronal images, there were circular areas of abnormal signal throughout both femoral shafts almost all the way to the metaphyses. The same abnormal signals were seen in all the pelvic bones. On the axial images, there were multiple holes in the pelvic bones, with increased signal in the surrounding soft tissue. In sum, there's a diffuse process involving the bones and bone marrow with little evidence of soft tissue involvement. Although I could provide a differential diagnosis, this is almost certainly the result of metastatic neuroblastoma. A subsequent computed tomography scan revealed a left suprarenal mass.
Phillip Fitchev, MD, pediatric pathologist: The mass consisted of small, round, blue cells with scant cytoplasm, dark irregular nuclei, with poorly defined cell borders. This is classic for neuroblastoma. A bone marrow biopsy had similar clusters of cells. In addition, the tumor was poorly differentiated without elements of ganglioneuroma or ganglioneuroblastoma, which suggests a poorer prognosis.
Dr. Rigsby: Before we move on, there's an important teaching point here. Limited pictures of the child's proximal lower extremities were performed on the bone scan done at the outside hospital. If views of the entire body were performed, as I believe should be done in every bone scan, undoubtedly multiple areas of abnormality would have been identified, allowing easier diagnosis. We see this phenomenon quite often in pediatric radiology where one area of the body has normal imaging but the pathology is elsewhere. A classic example is the child with a limp who has normal hip films but subsequently is diagnosed with a tibial greenstick fracture.
Dr. Katz: How should this child be treated?
Dr. Walterhouse: This child had an abdominal tumor with metastatic disease to the bone and bone marrow giving him Stage IV disease. Since he's over the age of 1 year, he is in a very poor prognostic group who have an approximately 20% chance of long-term survival. We are currently doing a study looking at the efficacy of high dose chemotherapy followed by three tandem stem cell rescues. The logic is that by intensifying the initial chemotherapy, we may be able to improve the outcome. A study in the New England Journal of Medicine in 1999 randomized 400 children with high risk neuroblastoma (Stage IV or Stage ?? with poor risk factors) to receive standard chemotherapy or high dose chemotherapy followed by a single bone marrow transplant. The latter group had a significantly better 3-year survival.
Dr. Katz: Let me play devil's advocate. This child's pain is minimal and he doesn't feel particularly ill. Given that he has a disease with a dismal prognosis, why not wait until he's sicker before making his life miserable from chemotherapy?
Dr. Walterhouse: The family actually proposed that. However, I didn't feel that this strategy was in his best interest. It's possible that by delaying therapy until he's sicker we'll have lost the window of opportunity to treat him effectively. He's more likely to tolerate the chemotherapy if he starts out in a healthier state.
Dr. Katz: This child has a 4year-old brother. How should he be prepared for the upheaval that's about to occur in this family's life?
Jean Schwab, MSW, pediatric social worker: The first thing the team must do is listen to the family and let them express their fears. In order to help the siblings of pediatric cancer patients, it's crucial to understand their developmental levels. A 4-year-old child thrives on routine and needs black and white answers to questions. He's not going to care about the name of the cancer or side effects of the chemotherapy. Rather, he's going to be asking questions such as, "Why are you going to the hospital again?" or, "Can I come to the hospital?" or, "He got a Winnie the Pooh. Can I have a Winnie the Pooh?" Most important, his parents need to stress to him repeatedly that he did nothing wrong and that they love him. Kids have a unique ability to take the blame for something that they have no power over.
Dr. Katz: This mother was pregnant. She asked me whether she should bank the baby's umbilical cord blood for possible future treatment.
Reggie Duerst, MD, pediatric oncologist: The role of allogeneic stem cell transplant in solid tumors is not well defined yet. However, in leukemia, allogeneic transplant is the treatment of choice. There is a bank for cord blood at Oakland Children's Hospital that is funded by the federal government. If a child is diagnosed with a disease that's treatable by allogenic transplant, they will process a sibling's cord blood for the family, cryopreserve it, and store it. Even if a child has acute lymphocytic leukemia in which there's a less than 10% chance of ever needing a transplant, they will process and store the cells.
Dr. Katz: Thank you everybody.