Consultations and additional studies
The Orthopedic Surgery and Oncology services were consulted due to a strong concern for malignancy. A skeletal survey was obtained (Figures 2A and 2B), and the patient was admitted to the Oncology Service for further management, with the tentative plan by Oncology to obtain an MRI of the left leg and a computed tomography (CT) scan of the chest the following morning.
Upon further review of the patient’s x-rays and skeletal survey, multiple specialists—including pediatric radiologists—agreed that the imaging showed marked cortical hyperostosis of the mandible, ribs, and left tibia and fibula—diagnostic of Caffey disease.
Caffey disease (also known as infantile cortical hyperostosis, Caffey-Silverman syndrome, or Smyth syndrome) is a rare, self-limiting condition that should be included in the differential diagnosis of soft tissue swelling in infants. It presents in approximately 3 per 1000 infants prior to 6 months of age, although this is thought to be an underestimation due to underdiagnosis. The condition affects males and females equally and has no ethnic predilection.5 The average age of onset is 9 weeks.6 It is usually characterized by irritability, soft tissue swelling, and cortical bone thickening; however, irritability was not seen in this patient.7,8
Delayed diagnosis may occur because the disorder can present with nonspecific symptoms such as fever, fussiness, and decreased appetite, and therefore can mimic other diagnoses, such as malignancy, trauma, and infection. Swelling usually occurs suddenly and may be red, firm, and/or tender.7 Laboratory tests may reveal leukocytosis, thrombocytosis, and/or elevated inflammatory markers, all of which were noted in this patient.
The etiology of Caffey disease is unclear, but it is thought to be a type I collagenopathy. Both sporadic and familial forms occur. The mandible is the most likely affected bone in sporadic cases, whereas the tibia is most likely affected in familial cases. Autosomal dominant and autosomal recessive patterns of inheritance have been reported by reviewing pedigrees of unrelated families.9
In families with autosomal dominant inheritance, a missense mutation has been found in COL1A1, which codes for the alpha 1 chain of type I collagen.6,10 Interestingly, other reported mutations that affect the synthesis of type I collagen include osteogenesis imperfecta (OI) and Ehlers-Danlos syndrome. It is unclear why a missense mutation would stimulate hyperostosis, and it is also unclear why this mutation would affect individuals at a specific age.
The autosomal recessive pattern is distinct from the classic presentation of Caffey disease in that it is associated with prenatal onset and has a much more severe course (eg, angulations and shortness of long bones, polyhydramnios, and fetal hydrops, in addition to marked hyperostosis) and a poorer prognosis.11
With good clinical suspicion and multidisciplinary input, early identification of Caffey disease can prevent unnecessary workup and invasive procedures. Diagnosis is made by physical exam and radiographic findings. Although imaging may be variable during the clinical course, the classic finding is cortical diaphyseal periosteal new bone formation. Usually x-ray suffices to clinch the diagnosis; however, MRI could add additional value in diagnosis if infection or malignancy is high on the differential or if there is a question of subperiosteal hemorrhage.12
Because Caffey disease doesn’t affect epiphyses or metaphyses, growth potential should not be affected. The pattern of bone involvement is usually multifocal and asymmetric.5 Involved bones typically include the mandible, clavicles, ribs, and long bones. The involvement of the mandible—the most frequently affected bone—is usually pathognomonic and affected in 70% to 90% of cases.8 With mandibular involvement, infants may refuse to eat, leading to failure to thrive.
Caffey disease usually resolves within 6 to 12 months. Treatment typically consists of nonsteroidal anti-inflammatory drugs (NSAIDs) as needed. The use of steroids has been proposed to accelerate bone remodeling and may be trialed if there is a poor response to NSAIDs. In rare cases, Caffey disease can cause enough long-term bony deformity (eg, excessive hyperostosis leading to fusion of adjacent bones) that surgical correction is needed. Other complications include exophthalmos, pleuritis, and recurrence of disease.7,8
For this patient, no additional imaging was obtained, and she did not require any medical or surgical intervention. She was discharged home with plans to follow up with Orthopedic Surgery. Serial x-rays obtained during outpatient clinic visits with Orthopedic Surgery demonstrated interval bone remodeling (Figures 3A, 3B, 3C), with marked improvement and minimal residual deformity noted 10 months after discharge.
1. Menashe SJ, Iyer RS, Parisi MT, Otto RK, Stanescu AL. Pediatric chest radiographs: common and less common errors. AJR Am J Roentgenol. 2016:1-9.
2. Velaphi S, Cilliers A, Beckh-Arnold E, Mokhachane M, Mphahlele R, Pettifor J. Cortical hyperostosis in an infant on prolonged prostaglandin infusion: case report and literature review. J Perinatol. 2004;24(4):263-265.
3. Woo K, Emery J, Peabody J. Cortical hyperostosis: a complication of prolonged prostaglandin infusion in infants awaiting cardiac transplantation. Pediatrics. 1994;93(3):417-420.
4. Christian CW, States LJ. Medical mimics of child abuse. AJR Am J Roentgenol. 2017;208(5):982-990.
5. Prior AR, Moldovan O, Azevedo A, Moniz C. Caffey disease in neonatal period: the importance of the family! BMJ Case Rep. 2012;2012:bcr2012006996.
6. Glorieux FH. Caffey disease: an unlikely collagenopathy. J Clin Invest. 2005;115(5):1142-1144.
7. Kamoun-Goldrat A, le Merrer M. Infantile cortical hyperostosis (Caffey disease): a review. J Oral Maxillofac Surg. 2008;66(10):2145-2150.
8. Shandilya R, Gadre KS, Sharma J, Joshi P. Infantile cortical hyperostosis (Caffey disease): a case report and review of the literature--where are we after 70 years? J Oral Maxillofac Surg. 2013;71(7):1195-1201.
9. Barba WP, Freriks DJ. The familial occurrence of infantile cortical hyperostosis in utero. J Pediatr. 1953;42(2):141-150.
10. Gensure RC, Makitie O, Barclay C, et al. A novel COL1A1 mutation in infantile cortical hyperostosis (Caffey disease) expands the spectrum of collagen-related disorders. J Clin Invest. 2005;115(5):1250-1257.
11. Schweiger S, Chaoui R, Tennstedt C, Lehmann K, Mundlos S, Tinschert S. Antenatal onset of cortical hyperostosis (Caffey disease): case report and review. Am J Med Genet A. 2003;120A(4):547-552.
12. Sanders DG, Weijers RE. MRI findings in Caffey's disease. Pediatr Radiol. 1994;24(5):325-327.