Caffey disease
Updates to Article Attributes
Caffey disease or infantile cortical hyperostosis is a largely self-limiting disorder which affects infants. It causes bone changes, soft-tissue swelling, and irritability.
It is distinct from physiological periostitis which can be seen involving the diaphyses of the tibiae, humeri, and femora at the same age.
A rare variant known as prenatalprenatal onset cortical hyperostosis is severe and fatal, though it is probably a separate entity altogether 1.
Clinical presentation
Children usually present within the first five5 months of life with tender and painful soft tissue swelling, erythema, fever, and irritability.
Pathology
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.
Phases
Early, subacute, and late pathologic phases have been described, each with its accompanying radiologic features:
Early (acute)
characterised by periostitis
the inflammatory process may extend to adjacent soft tissues
cortical resorption may occur
Subacute
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
Late
-
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
Long-term sequelae
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
Location
The flat bones are most commonly affected:
mandible:
in75-80% of casesclavicles
scapula: 10% of cases
ribs: lateral aspect; ipsilateral pleural effusion may appear
calvaria
ilia
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.
Markers
Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and alkaline phosphatase (ALP) levels are often elevated. The combination of the clinical picture, lab findings, and imaging findings is sufficient for a diagnosis.
Phases
Early, subacute, and late pathologic phases have been described, each with its accompanying radiologic features:
Early (acute)
characterised by periostitisthe inflammatory process may extend to adjacent soft tissuescortical resorption may occur
Subacute
inflammation subsidesperiosteal thickening, with subsequent ossifying periostitisimmature lamellar bone is deposited in layers under the periosteum, sometimes exuberantlyosseous deposition may occur in adjacent soft tissues
Late
-
removal of peripheral bone, from inner to outer surfacemay produce a thin-walled bone with a large medullary cavity in long-standing cases
cortical remodelling may also occur
Long-term sequelae
mandibular asymmetry and/or undergrowthpersistent synostosis of the ribs: could cause scoliosispersistent synostosis of bones of the forearms and legsbowing of long bonesleg length discrepancydisease recurrence in childhood
Radiographic features
Plain radiograph
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.
Ultrasound
Can identify soft tissue oedema and early periosteal new bone formation. High-frequency transducers should be used.
MRI
Can show periostitis and soft tissue oedema. 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.
Nuclear imaging
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. Symptomatic treatment consists of NSAIDs, e.g. indomethacinindometacin.
History and etymology
Paediatric radiologist John Caffey (1895-1978) 7 first described infantile cortical hyperostosis with colleague WAW A Silverman in 1945.
Differential diagnosis
osteomyelitis: there are reports of association with Caffey disease
trauma
physiologic periostitis: isolated to the tibiae, femora, and humeri
skeletal dysplasias with osteosclerosis
prostaglandin E1 and E2 therapy (for intentionally maintaining ductus arteriosus patency)
infection (e.g. syphilis, tuberculosis)
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.
-<p><strong>Caffey disease</strong> or <strong>infantile cortical hyperostosis</strong> is a largely self-limiting disorder which affects infants. It causes bone changes, soft-tissue swelling, and irritability.</p><p>It is distinct from <a href="/articles/physiologic-periostitis">physiological periostitis</a> which can be seen involving the diaphyses of the tibiae, humeri, and femora at the same age. </p><p>A rare variant known as <a href="/articles/prenatal-onset-infantile-cortical-hyperostosis">pre</a><a href="/articles/prenatal-onset-infantile-cortical-hyperostosis">natal onset cortical hyperostosis</a> is severe and fatal, though it is probably a separate entity altogether <sup>1</sup>.</p><h4>Clinical presentation</h4><p>Children usually present within the first five months of life with tender and painful soft tissue swelling, erythema, fever, and irritability.</p><h4>Pathology</h4><p>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 <sup>2,3.</sup></p><h5>Location</h5><p>The flat bones are most commonly affected:</p><ul>-<li>mandible: in 75-80% of cases</li>-<li>clavicles</li>-<li>scapula: 10% of cases</li>-<li>ribs: lateral aspect; ipsilateral pleural effusion may appear</li>-<li>calvaria</li>-<li>ilia</li>-</ul><p>The ulnae are the long bones most commonly affected.</p><p>Lytic skull lesions have been reported.</p><p>The carpus, tarsus, phalanges and vertebral bodies are rarely involved.</p><h5>Markers</h5><p><a href="/articles/erythrocyte-sedimentation-rate">Erythrocyte sedimentation rate (ESR)</a>, <a href="/articles/c-reactive-protein-1">C-reactive protein (CRP)</a>, and <a href="/articles/alkaline-phosphatase">alkaline phosphatase (ALP)</a> levels are often elevated. The combination of the clinical picture, lab findings, and imaging findings is sufficient for a diagnosis.</p><h5>Phases</h5><p>Early, subacute, and late pathologic phases have been described, each with its accompanying radiologic features:</p><h6>Early (acute)</h6><ul>-<li>characterised by periostitis</li>-<li>the inflammatory process may extend to adjacent soft tissues</li>-<li>cortical resorption may occur</li>- +<p><strong>Caffey disease</strong> or <strong>infantile cortical hyperostosis</strong> is a largely self-limiting disorder which affects infants. It causes bone changes, soft-tissue swelling, and irritability.</p><p>It is distinct from <a href="/articles/physiologic-periostitis">physiological periostitis</a> which can be seen involving the diaphyses of the tibiae, humeri, and femora at the same age. </p><p>A rare variant known as <a href="/articles/prenatal-onset-infantile-cortical-hyperostosis">prenatal onset cortical hyperostosis</a> is severe and fatal, though it is probably a separate entity altogether <sup>1</sup>.</p><h4>Clinical presentation</h4><p>Children usually present within the first 5 months of life with tender and painful soft tissue swelling, erythema, fever, and irritability.</p><h4>Pathology</h4><p>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 <sup>2,3.</sup></p><h5>Phases</h5><p>Early, subacute, and late pathologic phases have been described, each with its accompanying radiologic features:</p><h6>Early (acute)</h6><ul>
- +<li><p>characterised by periostitis</p></li>
- +<li><p>the inflammatory process may extend to adjacent soft tissues</p></li>
- +<li><p>cortical resorption may occur</p></li>
-<li>inflammation subsides</li>-<li>periosteal thickening, with subsequent ossifying periostitis</li>-<li>immature lamellar bone is deposited in layers under the periosteum, sometimes exuberantly</li>-<li>osseous deposition may occur in adjacent soft tissues</li>- +<li><p>inflammation subsides</p></li>
- +<li><p>periosteal thickening, with subsequent ossifying periostitis</p></li>
- +<li><p>immature lamellar bone is deposited in layers under the periosteum, sometimes exuberantly</p></li>
- +<li><p>osseous deposition may occur in adjacent soft tissues</p></li>
-<li>removal of peripheral bone, from inner to outer surface<ul><li>may produce a thin-walled bone with a large medullary cavity in long-standing cases</li></ul>-</li>-<li>cortical remodelling may also occur</li>-</ul><h6>Long-term sequelae</h6><ul>-<li>mandibular asymmetry and/or undergrowth</li>-<li>persistent synostosis of the ribs: could cause scoliosis</li>-<li>persistent synostosis of bones of the forearms and legs</li>-<li>bowing of long bones</li>-<li>leg length discrepancy</li>-<li>disease recurrence in childhood</li>-</ul><h4>Radiographic features</h4><h5>Plain radiograph</h5><p>May show all or some of the following <sup>4</sup>: </p><ul>-<li>-<a href="/articles/periosteal-reaction">periosteal reaction</a>, either single-layered or lamellated</li>-<li>subperiosteal cortical hyperostosis</li>-<li>dense laminated subperiosteal new bone formation</li>-<li>marked increase in cortical width and density</li>-<li>in the involved long bones, only the diaphysis is affected, sparing the metaphysis and epiphysis; consequently, the bone becomes spindle-shaped</li>-<li>soft tissue swelling over the involved bones</li>-<li>the mandible, clavicle, and ribs are most often affected, particularly in sporadic cases</li>-</ul><p>Radiographic evidence of the disease may persist for years after resolution of clinical symptoms.</p><h5>Ultrasound </h5><p>Can identify soft tissue oedema and early periosteal new bone formation. High-frequency transducers should be used.</p><h5>MRI </h5><p>Can show periostitis and soft tissue oedema. It should be stressed that MRI usually does not offer much added-value in advancing the diagnosis <sup>5</sup> 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.</p><h5>Nuclear imaging</h5><p>During the active phase of the disease, there is markedly increased radiotracer uptake in the involved bones, both on <a href="/articles/bone-scan">bone</a> and <a href="/articles/gallium-67-scintigraphy-1">gallium (Ga-67) scans</a>. The <a href="/articles/bearded-infant-sign">"bearded infant" appearance</a> refers to intense radiotracer uptake in the mandible <sup>6</sup>. </p><p>Nuclear scans can also be useful for showing the extent of skeletal involvement.</p><h4>Treatment and prognosis</h4><p>As noted above, Caffey disease is self-limiting and resolves spontaneously. Symptomatic treatment consists of NSAIDs, e.g. indomethacin.</p><h4>History and etymology</h4><p>Paediatric radiologist <strong>John Caffey</strong> (1895-1978) <sup>7</sup> first described infantile cortical hyperostosis with colleague <strong>WA Silverman</strong> in 1945.</p><h4>Differential diagnosis</h4><ul>-<a href="/articles/osteomyelitis">osteomyelitis</a>: there are reports of association with Caffey disease</li>-<li><a href="/articles/suspected-physical-abuse-1">non-accidental injury</a></li>-<li>trauma</li>-<li>-<a href="/articles/physiologic-periostitis">physiologic periostitis</a>: isolated to the tibiae, femora, and humeri</li>-<li>-<a href="/articles/skeletal-dysplasia">skeletal dysplasias</a> with osteosclerosis</li>-<li><a href="/articles/vitamin-a-1">hypervitaminosis A</a></li>-<li><a href="/articles/hypovitaminosis-c-scurvy-1">hypovitaminosis C (scurvy)</a></li>-<li><a href="/articles/hyperphosphataemia">hyperphosphataemia</a></li>-<li>prostaglandin E1 and E2 therapy (for intentionally maintaining <a href="/articles/patent-ductus-arteriosus">ductus arteriosus patency</a>)</li>-<li>infection (e.g. <a href="/articles/syphilis">syphilis</a>, <a href="/articles/tuberculosis-musculoskeletal-manifestations-1">tuberculosis</a>)</li>-<li><a href="/articles/ewing-sarcoma">Ewing sarcoma</a></li>-<li>metastatic <a href="/articles/neuroblastoma">neuroblastoma</a>- +<p>removal of peripheral bone, from inner to outer surface</p>
- +<ul><li><p>may produce a thin-walled bone with a large medullary cavity in long-standing cases</p></li></ul>
- +<li><p>cortical remodelling may also occur</p></li>
- +</ul><h6>Long-term sequelae</h6><ul>
- +<li><p>mandibular asymmetry and/or undergrowth</p></li>
- +<li><p>persistent synostosis of the ribs: could cause scoliosis</p></li>
- +<li><p>persistent synostosis of bones of the forearms and legs</p></li>
- +<li><p>bowing of long bones</p></li>
- +<li><p>leg length discrepancy</p></li>
- +<li><p>disease recurrence in childhood</p></li>
- +</ul><h5>Location</h5><p>The flat bones are most commonly affected:</p><ul>
- +<li><p>mandible: 75-80% of cases</p></li>
- +<li><p>clavicles</p></li>
- +<li><p>scapula: 10% of cases</p></li>
- +<li><p>ribs: lateral aspect; ipsilateral pleural effusion may appear</p></li>
- +<li><p>calvaria</p></li>
- +<li><p>ilia</p></li>
- +</ul><p>The ulnae are the long bones most commonly affected.</p><p>Lytic skull lesions have been reported.</p><p>The carpus, tarsus, phalanges and vertebral bodies are rarely involved.</p><h5>Markers</h5><p><a href="/articles/erythrocyte-sedimentation-rate">Erythrocyte sedimentation rate (ESR)</a>, <a href="/articles/c-reactive-protein-1">C-reactive protein (CRP)</a>, and <a href="/articles/alkaline-phosphatase">alkaline phosphatase (ALP)</a> levels are often elevated. The combination of the clinical picture, lab findings, and imaging findings is sufficient for a diagnosis.</p><h4>Radiographic features</h4><h5>Plain radiograph</h5><p>May show all or some of the following <sup>4</sup>: </p><ul>
- +<li><p><a href="/articles/periosteal-reaction">periosteal reaction</a>, either single-layered or lamellated</p></li>
- +<li><p>subperiosteal cortical hyperostosis</p></li>
- +<li><p>dense laminated subperiosteal new bone formation</p></li>
- +<li><p>marked increase in cortical width and density</p></li>
- +<li><p>in the involved long bones, only the diaphysis is affected, sparing the metaphysis and epiphysis; consequently, the bone becomes spindle-shaped</p></li>
- +<li><p>soft tissue swelling over the involved bones</p></li>
- +<li><p>the mandible, clavicle, and ribs are most often affected, particularly in sporadic cases</p></li>
- +</ul><p>Radiographic evidence of the disease may persist for years after resolution of clinical symptoms.</p><h5>Ultrasound </h5><p>Can identify soft tissue oedema and early periosteal new bone formation. High-frequency transducers should be used.</p><h5>MRI </h5><p>Can show periostitis and soft tissue oedema. It should be stressed that MRI usually does not offer much added-value in advancing the diagnosis <sup>5</sup> 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.</p><h5>Nuclear imaging</h5><p>During the active phase of the disease, there is markedly increased radiotracer uptake in the involved bones, both on <a href="/articles/bone-scintigraphy-1">bone</a> and <a href="/articles/gallium-67-scintigraphy-1">gallium (Ga-67) scans</a>. The <a href="/articles/bearded-infant-sign">"bearded infant" appearance</a> refers to intense radiotracer uptake in the mandible <sup>6</sup>. </p><p>Nuclear scans can also be useful for showing the extent of skeletal involvement.</p><h4>Treatment and prognosis</h4><p>As noted above, Caffey disease is self-limiting and resolves spontaneously. Symptomatic treatment consists of NSAIDs, e.g. indometacin.</p><h4>History and etymology</h4><p>Paediatric radiologist <strong>John Caffey</strong> (1895-1978) <sup>7</sup> first described infantile cortical hyperostosis with colleague <strong>W A Silverman</strong> in 1945.</p><h4>Differential diagnosis</h4><ul>
- +<li><p><a href="/articles/osteomyelitis">osteomyelitis</a>: there are reports of association with Caffey disease</p></li>
- +<li><p><a href="/articles/suspected-physical-abuse-1">non-accidental injury</a></p></li>
- +<li><p>trauma</p></li>
- +<li><p><a href="/articles/physiologic-periostitis">physiologic periostitis</a>: isolated to the tibiae, femora, and humeri</p></li>
- +<li><p><a href="/articles/skeletal-dysplasia">skeletal dysplasias</a> with osteosclerosis</p></li>
- +<li><p><a href="/articles/vitamin-a-1">hypervitaminosis A</a></p></li>
- +<li><p><a href="/articles/hypovitaminosis-c-scurvy-1">hypovitaminosis C (scurvy)</a></p></li>
- +<li><p><a href="/articles/hyperphosphataemia">hyperphosphataemia</a></p></li>
- +<li><p>prostaglandin E1 and E2 therapy (for intentionally maintaining <a href="/articles/patent-ductus-arteriosus">ductus arteriosus patency</a>)</p></li>
- +<li><p>infection (e.g. <a href="/articles/syphilis">syphilis</a>, <a href="/articles/tuberculosis-musculoskeletal-manifestations-1">tuberculosis</a>)</p></li>
- +<li><p><a href="/articles/ewing-sarcoma">Ewing sarcoma</a></p></li>
- +<li><p>metastatic <a href="/articles/neuroblastoma">neuroblastoma</a></p></li>