A rare variant of Caffey's disease – X-rays, bone scan and FDG PET findings

INTRODUCTION

Caffey's disease, also called as infantile cortical hyperostosis (ICH), is a genetic disorder characterized by an infantile episode of massive subperiosteal new bone formation that typically involves the diaphysis of the long bones, mandible and clavicles.[1] A clinical triad of fever, soft-tissue swelling and hyperirritability characterizes it.

CASE REPORT

An 18-month-old boy was referred for a bone scan. He had a history of fever of 4 months duration with swelling of the limbs. The child was irritable. His blood investigations showed thrombocytopenia (<35,000) and his alkaline phosphatase levels were elevated (1417.4 KA units; normal 4–11 KA units). His hemoglobin was very low at 6.9 gm %. His serum calcium and phosphorus levels were normal. There were multiple swellings over his upper and lower limbs, with bowing of the lower limbs. His radiological skeletal survey revealed marked periosteal new bone formation surrounding the diaphysis of long bones [Figure 1a–e], but the mandible and clavicles were spared. A bone scan done with 99m Tc-MDP (methyl diphosphonate) showed diffusely increased tracer uptake in all the long bones [Figure 2]. The bones of the axial skeleton and of hands and the feet showed normal tracer distribution. A fluorodeoxyglucose positron emission tomography (FDG PET) scan done to assess the metabolic activity showed patchy FDG uptake in the long bones, ankle joint and anterior ends of few ribs [Figure 3]. His clinical and imaging findings led to the diagnosis of Caffey's disease. Though the mandibular involvement is a diagnostic criterion, it may not always be involved. The mandible is involved in about 75–80% of the cases. Caffey's disease is known to occur in early part of life (less then 5 months of age), but late presentations have been reported.[2–5] It has been reported by Ventura et al. that the late onset disease (after the first year of life) is characterized by a longer duration of the disease with more frequency of relapses, absence of mandibular involvement and presence of eosinophilia.[6]

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Figure 1 (a) X-ray of the pelvis with both femurs – It shows extensive periosteal reaction in both the femurs; (b) Radiographs of the distal femurs, tibia and fibula. All these bones show extensive new bone formation; (c) Shows radius, ulna and distal aspects of the humerus and also shows extensive new bone formation in all the Long bones. The visualized metacarpal bones are normal; (d and e) Radiographs of skull and chest showing normal mandible, clavicles and ribs

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Figure 2 The bone scan images (anterior and posterior views) show diffusely increased tracer concentration in all the long bones. The bones of the axial skeleton are spared

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Figure 3 Whole body FDG PET scan image (MIP) showing patchy FDG uptake in the long bones, ankle joint and anterior ends of few ribs

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DISCUSSION

ICH is an uncommon disease, usually commencing in infancy, which affects predominantly the skeleton and adjacent facial, muscular and connective tissue. It was first reported as a distinct entity in 1945 by Caffey and Silverman.[7]

Laboratory analysis usually shows an elevated erythrocyte sedimentation rate (ESR) and an elevated serum alkaline phosphate, moderate leukocytosis and anemia.

There may be involvement of a single bone or multiple bones. Sequential involvement is common, with one area being affected initially followed by other sites. The most commonly involved bones are mandible, clavicles and ribs.[8] The radiographic abnormalities are virtually diagnostic of Caffey's disease, but bone scans can be used to further document the extent of skeletal involvement.[9–11] The distribution of abnormalities and the degree of extension of the lesions are important characteristics in the scintigraphic differential diagnosis, but radiographs are best used in making the diagnosis.[11]

The cause of ICH remains unclear. Many clinical and pathological features suggest that an infectious agent is responsible for the disease. The presence of severe and protracted fever, an elevated ESR, occasional pleural exudates in association with thoracic cage lesions and clustering of cases in time and location are the clinical findings consistent with an infection.[12] Features suggesting an inflammatory etiology include acute inflammatory changes in the periosteum during the initial stage and clinical improvement after the administration of steroids.

It exists in two forms – familial and sporadic. The tibia is the predominant bone to be affected in the familial form, while the mandible is mostly affected in the sporadic form.[13]

The typical radiological feature is a marked new bone formation surrounding the diaphysis of long bones, i.e., periostitis and hyperostosis. Although these findings in an infant can also be observed in rickets and scurvy, the absence of epiphyseal or metaphyseal alterations and the resolution of clinical and radiographic features over a period of time in patients with ICH allow its differentiation from these disorders. In cases of child abuse, in addition to calcifying subperiosteal hematomas, micro fractures and metaphyseal irregularities are seen. In hypervitaminosis A, there is a metaphyseal predilection, mandibular involvement is rare and serum vitamin A levels are elevated.

Long-term administration of prostaglandin E in infants with ductus-dependent cyanotic congenital heart disease is associated with periostitis and cortical hyperostosis; findings that are very similar to those of ICH.[1415]

To our knowledge, a PET scan in ICH has never been reported earlier.