Case 1: A four-month-old boy with bilateral arm swelling

A previously well, four-month-old boy developed tender swelling of both forearms of one months’ duration associated with irritability and moderate fever. An x-ray of the left forearm, performed at a local hospital, revealed a periosteal reaction over the ulna but no fracture line. With a clinical suspicion of osteomyelitis, he was prescribed a course of intravenous antimicrobials. His fever subsided but the swelling and irritability persisted, which prompted the parents to seek a second opinion from our institute.

On admission, he was healthy and alert but persistently irritable and was experiencing tenderness over both forearms. A uniform, diffuse, nonfluctuant, immobile, bony thickening of the ulna was palpable at the diaphyses bilaterally (Figure 1A). The overlying skin, and the wrist and elbow joints were normal. No swelling or lymphadenopathy was palpable at any other sites. A repeat x-ray of the left forearm showed an increased periosteal reaction over the left ulna (Figure 1B). An x-ray of the right forearm revealed a similar periosteal reaction along the ulnar shaft and a minimal periosteal reaction along the midradial shaft but no fracture was observed (Figure 1C). Other laboratory investigations found a hemoglobin level of 9.9 g/L, a total leukocyte count of 16.7×10⁹/L (neutrophil 48%, lymphocytes 45%), an erythrocyte sedimentation rate of 40 mm/h, a serum calcium level of 2.18 mmol/L, a phosphorus level of 1.58 mmol/L and an alkaline phosphatase level of 258 IU/L (normal <470 IU/L). Blood and urine cultures were sterile. The Venereal Disease Research Laboratory test was negative in both the mother and child. A technetium-99m-labelled, methyl-diphosphonate bone scan revealed evidence of symmetrically increased osteoblastic activity in the maxilla, mandible, mastoid and bilateral forearm bones.

Figure 1).

A Clinical photograph of the right forearm showing a uniform, diffuse, nonfluctuant, immobile, bony thickening of the ulna palpable at the diaphyses. B X-ray of the left forearm showing an increased periosteal reaction over the left ulna. C Radiograph of the right forearm showing a periosteal reaction along the ulnar shaft and a minimal periosteal reaction along the midradial shaft. No fracture line is apparent

CASE 1 DIAGNOSIS: INFANTILE CORTICAL HYPERTOSIS

The characteristic triad of irritability, swelling and bone lesions, and the patient’s age at presentation and the mandibular involvement in the bone scan comfirmed the diagnosis of infantile cortical hyperostosis (ICH) or Caffey-Silverman/Caffey disease, which was recognized by Caffey and Silverman (1) in 1945. This self-limiting condition of infancy becomes clinically evident before five to seven months of age, with the average age of onset being nine weeks, and resolves before two years of age.

The most common site of bone involvement is the mandible (75% to 80%) followed by the clavicles, ulna, scapula, tibia and ribs. ICH has been reported to affect all of the tubular bones except the phalanges. The ulna, as shown in the present patient, appears to be considerably more vulnerable than the radius and may be markedly thickened when the radius appears to be normal. The metaphyses and epiphyses are usually spared, although epiphyseal involvement with resulting leg-length discrepancy has been reported.

Fever associated with ICH may be due to high prostaglandin levels or excessive metabolic activity in the bones (2). Histological analysis of cortical areas affected by ICH reveals an abnormal deposition of hyperplastic, immature lamellar bone that has replaced the original cortical bone, periosteal thickening, subperiosteal cellular proliferation and marrow fibrosis. Collectively, these findings are suggestive of a common inflammatory reaction, which can be corroborated by laboratory findings of anemia, leukocytosis, thrombocytosis, and an increased erythrocyte sedimentation rate and alkaline phosphatase level.

A bone scan is more sensitive but less specific than computed tomography or magnetic resonance imaging for diagnosing ICH. There are no published studies comparing these modalities directly (2). Although magnetic resonance imaging is an excellent tool for differentiating bony and soft tissue structures, and identifying subperiosteal hemorrhage and the extent of soft tissue involvement, it has no additional value in the management of the patient. Radiographical examination, in addition to clinical history and physical examination, is considered to be sufficient with regard to the differential diagnosis and follow-up of ICH.

ICH requires differentiation from other clinicoradiological mimics, such as scurvy, osteomyelitis, syphilitic osteochondritis, hypervitaminosis A, metastatic neuroblastoma, Ewing’s sarcoma and child abuse. Initially, the present patient was treated for osteomyelitis. However, the partial response to antibiotics was questionable, considering the natural course of ICH, in which symptoms are known to regress while new areas of swelling and hyperostosis appear. The distribution of abnormalities (mandible, scapulae) and the predominantly diaphyseal location of the lesions were important characteristics in the scintigraphical differential diagnosis. Additionally, in the present case, the striking pattern of involvement, sterile cultures and the absence of subperiosteal collection were suggestive of ICH.

The present patient’s treatment was supportive, using nonsteroidal anti-inflammatory drugs and corticosteroids, because one of the proposed mechanisms of ICH is a disturbance of endogenous prostaglandin regulation (2). The prognosis for ICH is good, with gradual regression of bony changes in six to nine months. Reported sequelae include fusion of adjacent bones, such as ribs, tibia and fibula, radius and ulna; anterior bowing of the tibia or femur; and limb-length inequality. The present patient was prescribed liquid ibuprofen (10 mg/kg/day) for two weeks for pain relief and irritability, but the response was poor. Furthermore, persistent irritability, the inability to bear weight, restriction of movements and a poor response to nonsteroidal anti-inflammatory drugs prompted the use of prednisolone (1.5 mg/kg/day for two weeks followed by tapering over the next four weeks). The patient responded dramatically and the swelling gradually reduced in size. At one year follow-up, the child had grown well, attained normal milestones and had not reported any recurrence of swelling or osteological complications, as is typical, due to the benign nature of the disease.

CLINICAL PEARLS

• ICH has characteristic diagnostic features, which in the majority of cases include the age of onset, the triad of irritability, swelling and peculiar bone lesions, and mandibular involvement.

• ICH’s protean manifestations may mimic osteomyelitis.

• Peculiar bone findings associated with ICH include cortical thickening due to periosteal new bone formation in the diaphysis of long tubular bones, the mandible and the clavicle, with associated perifocal, tender soft tissue thickening.