Infantile Cortical Hyperostosis (Caffey Disease)


Article Author:
Kristen Kirby


Article Editor:
John Wright


Editors In Chief:
Shivajee Nallamothu
Matthew Varacallo
Joshua Tuck


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes


Updated:
12/13/2018 1:59:44 PM

Introduction

Infantile cortical hyperostosis (ICH), also known as Caffey disease, was first reported by Roske in 1930 and described by Caffey and Silverman in 1945. ICH is a disorder affecting the skeletal system of children around 9 weeks of age.[1] ICH most commonly affects the mandible (70% to 90% of cases) and has the appearance of periosteal reaction. Most frequent locations affected are the ascending ramus and angle of the mandible. Also known to affect the clavicle, rib, ulna, scapula and rarely the ilia, parietal bones, and metatarsals. Usually unilateral when involving the scapula. ICH can affect all bones except cuboidal bones, vertebral bodies, and phalanges. Primary bone lesions are commonly asymmetric and localized to the diaphysis with sparing of the metaphysis and epiphysis resulting in spindle-shaped bones. The disease usually spontaneously resolves within 2 years.[2]

Etiology

Gensure et al. performed a genome-wide scan followed by fine mapping of individuals known to have the autosomal dominant form of ICH. Subsequently, genes were sequenced, and PCR amplification was performed. Gel electrophoresis confirmed that the affected individuals had a missense mutation in COL1A1.[3]

Epidemiology

ICH rarely occurs after 5 months of age.[4] Radiographic findings include cortical thickening (hyperostosis) and subperiosteal new bone formation. There is a prenatal form of the disease, called lethal prenatal cortical hyperostosis, that shows an autosomal recessive mode of inheritance and occurs before 35 weeks gestation. Polyhydramnios, angular deformities of the long bones, deformities of the ribs, prematurity, and lung disease are associated with this form. The infantile (classical) form that appears after 35 weeks is less severe and more common.[2] Ultrasound in utero can show changes such as bone curvature and cortex deformities consistent with ICH.[4]

Pathophysiology

The familial form of ICH is autosomal dominant with variable penetrance and classically is associated with a COL1A1 point gene mutation (3040C to T) on chromosome 17q21.[5] This missense mutation results in an arginine to cysteine substitution (R836C) in the triple helix of the alpha-1 chain of type 1 collagen. Type 1 collagen is important for bone mineralization and makes up about 9% of the bone matrix. Formation of these fibers require gathering of one a2 and two a1 procollagen chains followed by cleavage of the N and C termini by proteinases. Collagens provide strength and interact with proteins to form the extracellular matrix necessary for normal cell function.[6]

The relation between this missense mutation and the skeletal findings of ICH are unknown, but proposed mechanisms include an inability of chromosome interactions with proteins (IL-2), defective cross-linking between the bone and abnormal collagen, and decreased thermal stability of collagen.[6] The average age of presentation of the familial form of ICH is between 6 to 8 weeks, and it commonly involves the tibias. Twenty-four percent of infants present at birth with the familial form. The sporadic form of ICH usually involves the mandible with an average age of onset between 9 and 11 weeks. Some sporadic cases result from prolonged administration of prostaglandins E1 and E2 in infants with cyanotic heart disease.[4]

COL1A1 and COL1A2 gene mutations causes subtypes of Ehlers-Danlos syndrome and osteogenesis imperfecta. Gly substitutions in the triple helix lead to defective type I collagen resulting in fractures and findings consistent with osteogenesis imperfecta types II-IV. Some individuals with ICH have features seen in Ehlers-Danlos such as hyperextensible skin, joint hyper laxity, and inguinal hernias.[6]

Histopathology

Histologic findings in the early stages of disease are limited to the periosteum. Gradually the periosteum’s fibrous layer breaks down and becomes associated with muscles, tendons, and fascia. Osteoid trabeculae enter the muscles, soft tissue, and connective tissue, forming new bone and resulting in increased diameter. Eventually, the periosteum reforms a fibrous layer over the new bone, and the extra bone is removed.[4]

History and Physical

ICH commonly presents with sudden soft tissue swelling of the jaw and face, fever, and irritability. Some cases first present with swelling of the extremities followed by swelling of the face days later. These swellings become hard and fix to the bone and can also be red and painful.[1] Other clinical findings can include conjunctivitis, decreased movement of extremities, failure to thrive due to difficulty eating, and pallor.[1]

Evaluation

Laboratory findings can include increased erythrocyte sedimentation rate, C-reactive protein, alkaline phosphatase, or immunoglobulin levels and leukocytosis or thrombocytosis. There are cases of ICH where laboratory findings are all within normal limits.[5]

Genetic testing, if available, can confirm the presence of the missense mutation but the clinical course and radiographic findings should establish a clinical diagnosis. X-rays show gradual cortical thickening, periosteal bone formation around the diaphysis, and soft tissue swelling. Magnetic resonance imaging (MRI) is consistent with periosteal thickening, low-signal intensity in soft tissues on T1 sequences, and high-signal intensity on T2 sequences. Changes take 15 to 20 days to appear on x-rays, making it difficult to diagnose ICH in the early stages. Abnormal MRI findings may sometimes present before abnormal x-ray films.[2][4]

Treatment / Management

Treatment includes observation and counseling. Corticosteroids and non-steroidal anti-inflammatory medications such as naproxen, ibuprofen, and indomethacin have been reported to help with symptoms. Corticosteroids are not proven to prevent recurrences.[5]

Differential Diagnosis

Differential diagnoses include child abuse, malignancy, hypervitaminosis A, hypoparathyroidism, parotitis, osteomyelitis, prostaglandin administration, scurvy, or other collagen synthesis defect.[7][2][8]

Prognosis

Time of resolution can vary between weeks to years. Throughout the disease, swelling can improve in one area and reappear in the same or a different location. ICH usually spontaneously resolves within 2 years of age. On average, resolution occurs within 6 to 9 months. Both clinical symptoms and labs usually normalize during this time. There have been rare cases of reoccurrence in adolescence and adulthood.[4]

Complications

Complications include pleuritis, thoracic scoliosis, and exophthalmos. Rarely, bone deformities may require surgical correction at a later age.[4]

Enhancing Healthcare Team Outcomes

Soft tissue swelling and irritability in a child can raise concern for non-accidental trauma. Evaluation of other traumatic injuries or sentinel injuries is important. Requesting workup by a child abuse pediatrician can help prevent misdiagnosis. ICH can mimic child abuse but can be differentiated by the age of onset, site of involvement, lack of fracture, and limitation to the diaphysis. In ICH, the areas of new bone formation are usually thick and rounded versus tapering of the bone seen in child abuse. Periosteal reaction extending into the epiphysis is more indicative of physical abuse. It is very important for clinicians to be informed about diseases that can mimic child abuse, such as ICH, to come to a correct diagnosis.[9]


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Infantile Cortical Hyperostosis (Caffey Disease) - Questions

Take a quiz of the questions on this article.

Take Quiz
What is the most common location of bone lesions in sporadic cases of infantile cortical hyperostosis (ICH)?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What is a part of the clinical triad in infantile cortical hyperostosis (ICH)?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What type of mutation is associated with the familial form of infantile cortical hyperostosis?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which laboratory finding is commonly increased in infantile cortical hyperostosis (ICH)?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
In distinguishing between infantile cortical hyperostosis (ICH) and child abuse, which is more likely to be associated with ICH?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Infantile Cortical Hyperostosis (Caffey Disease) - References

References

CAFFEY J, Infantile cortical hyperostosis; a review of the clinical and radiographic features. Proceedings of the Royal Society of Medicine. 1957 May     [PubMed]
Navarre P,Pehlivanov I,Morin B, Recurrence of infantile cortical hyperostosis: a case report and review of the literature. Journal of pediatric orthopedics. 2013 Mar     [PubMed]
Khanduri S,Katyal G,Goyal A,Jain S,Sabharwal T,Chaudhary M, Caffey's Disease Sans Mandibular and Clavicular Involvement: A Rare Case Report. Cureus. 2017 Apr 16     [PubMed]
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? Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons. 2013 Jul     [PubMed]
Lo HP,Lau HY,Li CH,So KT, Infantile cortical hyperostosis (Caffey disease): a possible misdiagnosis as physical abuse. Hong Kong medical journal = Xianggang yi xue za zhi. 2010 Oct     [PubMed]
Fernández MA,Gebara E, [Neonatal cortical hyperostosis. A side effect of prolonged prostaglandin E1 infusion]. Archivos argentinos de pediatria. 2011 Apr     [PubMed]
Kamoun-Goldrat A,le Merrer M, Infantile cortical hyperostosis (Caffey disease): a review. Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons. 2008 Oct     [PubMed]
Nistala H,Mäkitie O,Jüppner H, Caffey disease: new perspectives on old questions. Bone. 2014 Mar     [PubMed]
Gensure RC,Mäkitie O,Barclay C,Chan C,Depalma SR,Bastepe M,Abuzahra H,Couper R,Mundlos S,Sillence D,Ala Kokko L,Seidman JG,Cole WG,Jüppner H, A novel COL1A1 mutation in infantile cortical hyperostosis (Caffey disease) expands the spectrum of collagen-related disorders. The Journal of clinical investigation. 2005 May     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Surgery-Orthopaedic. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Surgery-Orthopaedic, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Surgery-Orthopaedic, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Surgery-Orthopaedic. When it is time for the Surgery-Orthopaedic board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Surgery-Orthopaedic.