Caffey disease or infantile cortical hyperostosis is a largely self-limiting disorder which affects infants. It causes bone changes, soft-tissue swelling, and irritability.
A rare variant known as prenatal onset cortical hyperostosis is severe and fatal, though it is probably a separate entity altogether 1. It is distinct from physiological periostitis which can be seen involving the diaphyses of the tibiae, humeri, and femora at the same age.
Children usually present within the first five months of life with tender and painful soft tissue swelling, erythema, fever, and irritability.
Caffey disease is a type I collagenopathy. Both familial and sporadic forms exist. There is evidence to suggest that the familial form is inherited in an autosomal dominant fashion with incomplete penetrance and variable expression 2,3.
The flat bones are most commonly affected:
- mandible: in 75-80% of cases
- scapula: 10% of cases
- ribs: lateral aspect; ipsilateral pleural effusion may appear
The ulnae are the long bones most commonly affected.
Lytic skull lesions have been reported.
The carpus, tarsus, phalanges and vertebral bodies are rarely involved.
Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and alkaline phosphatase (ALP) levels are often elevated. The combination of clinical picture, lab findings, and imaging findings is sufficient for a diagnosis.
Early, subacute, and late pathologic phases have been described, each with its accompanying radiologic features:
- characterized by periostitis
- the inflammatory process may extend to adjacent soft tissues
- cortical resorption may occur
- inflammation subsides
- periosteal thickening, with subsequent ossifying periostitis
- immature lamellar bone is deposited in layers under the periosteum, sometimes exuberantly
- osseous deposition may occur in adjacent soft tissues
- removal of peripheral bone, from inner to outer surface
- may produce a thin-walled bone with a large medullary cavity in long-standing cases
- cortical remodelling may also occur
- mandibular asymmetry and/or undergrowth
- persistent synostosis of the ribs: could cause scoliosis
- persistent synostosis of bones of the forearms and legs
- bowing of long bones
- leg length discrepancy
- disease recurrence in childhood
May show all or some of the following 4:
- periosteal reaction, either single-layered or lamellated
- subperiosteal cortical hyperostosis
- dense laminated subperiosteal new bone formation
- marked increase in cortical width and density
- in the involved long bones, only the diaphysis is affected, sparing the metaphysis and epiphysis; consequently, the bone becomes spindle-shaped
- soft tissue swelling over the involved bones
- the mandible, clavicle, and ribs are most often affected, particularly in sporadic cases
Radiographic evidence of the disease may persist for years after resolution of clinical symptoms.
Can identify soft tissue edema and early periosteal new bone formation. High-frequency transducers should be used.
Can show periostitis and soft tissue edema. It should be stressed that MRI usually does not offer much added-value in advancing the diagnosis 5, unless infection or neoplasia are high on the differential list; indeed, at times, MRI appearance may confound the radiologist. Hence, radiography should be the primary modality of investigation and follow-up.
During the active phase of the disease, there is markedly increased radiotracer uptake in the involved bones, both on bone and gallium (Ga-67) scans. The "bearded infant" appearance refers to intense radiotracer uptake in the mandible 6.
Nuclear scans can also be useful for showing the extent of skeletal involvement.
Treatment and prognosis
As noted above, Caffey disease is self-limiting and resolves spontaneously. Palliative treatment consists of NSAIDs, e.g. indomethacin.
History and etymology
Pediatric radiologist John Caffey (1895-1978) 7 first described infantile cortical hyperostosis with colleague WA Silverman in 1945.
- osteomyelitis: there are reports of association with Caffey disease
- non-accidental injury
- physiologic periostitis: isolated to the tibiae, femora, and humeri
- skeletal dysplasias with osteosclerosis
- hypervitaminosis A
- hypovitaminosis C (scurvy)
- prostaglandin E1 and E2 therapy (for intentionally maintaining ductus arteriosus patency)
- infection (e.g. syphilis, tuberculosis)
- Ewing sarcoma
- metastatic neuroblastoma
Other conditions can usually be excluded based on the narrow age range for the presentation of infantile cortical hyperostosis; the triad of irritability, swelling, and bone lesions; and the presence of mandibular involvement.
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