PEMPix is the American Academy of Pediatrics Section on Emergency Medicine’s annual visual diagnosis competition. This year, in addition to the 10 finalists Maneesha Agarwal will be presenting at the National Conference and Exhibition we will be sharing four cases online in advance of the conference. This is the last of the four cases.

This case was submitted by
Dr. Inbar Plaut
PEM Fellow at UMASS Chan Medical School | UMASS Memorial Children’s Medical Center

IG handle(s): @inbar.y, @umasspem
Co-author: Zachary Binder

The Case

A 2-month-old male presents with 2-days of reluctance to move the right lower extremity. The mother describes the upper leg as feeling swollen and tense, and the patient cries when the area is touched. She denies any associated redness, warmth, or bruising to the area as well as any trauma or falls. He has otherwise been afebrile and acting at his baseline with normal oral intake and urine output. No recent illnesses or any other symptoms.

He does have a history of prematurity, born via vaginal delivery at 34 weeks due to maternal pre-eclampsia. He required external cephalic version for breech presentation. He spent 2 weeks in the NICU for respiratory distress but was discharged home after 2 weeks on room air and oral feeds. He has been doing well since discharge.

On exam, the child has normal vital signs and is generally well appearing. His right lower extremity is the only major abnormality. He is holding the hip in flexion with minimal movement of the right lower extremity. He has tenderness to palpation of the right thigh with minimal edema, but there is no overlying redness, warmth, or bruising. He has full passive range of motion of the right hip. The remainder of the right lower extremity is nontender to palpation and without abnormality. Additionally, he has full range of motion of the right knee and ankle.

Labs

  • Calcium 10.6  [Reference Range 8.7-10.7 mg/dL]
  • Phosphorus 6.7 [Reference Range 3.2-6.2 mg/dL]
  • Alk Phos 663 [Reference Range 150-350 U/L
  • AST: 34 [ Reference Range 30-80 U/L]
  • ALT: 29 [Reference Range 5-50 U/L]
  • Vitamin D, 25-Hydroxy: 24 [Reference Range: 30-100 ng/mL]​
  • PTH 26 [Reference Range 8-70 pg/mL]

Femur X-Rays are pictured below:

What’s the Diagnosis?

A. Congenital syphilis
B. Healing femur fracture
C. Osteomyelitis
D. Scurvy
E. Infantile cortical hyperostosis

E. Infantile Cortical Hyperostosis

The child protection team and orthopedics were consulted due to concern for possible healing femur fracture. A skeletal survey was completed and revealed smooth bridging calluses of the radii bilaterally. CT head showed focal right parietal bone thickening and sclerosis with widening of the diploic space. Given multiple areas of cortical hyperostosis in the absence of healing or acute fracture, a diagnosis of infantile cortical hyperostosis was made that was later confirmed with genetic testing. Orthopedics has continued to follow patient who has done well, including normal growth and no further episodes of pain.

Infantile cortical hyperostosis, also known as Caffey’s disease, is an autosomal dominant genetic condition linked to a mutation in the COL1A1 gene which encodes type I collagen. It causes changes in bones which typically begin in infancy and self-resolve by two years of age. Clinical presentation can include subperiosteal bone hyperplasia, swelling of the overlying soft tissue as well as associated fever and irritability. It most often affects the mandible and long bones. Patients typically present in infancy with pain with movement of limbs but are otherwise well-appearing with no associated symptoms. Elevations in white blood cell count, ESR, and alkaline phosphatase are common lab abnormalities[i]. These patients are often followed by orthopedics to ensure proper remodeling and growth of affected limbs, but the natural course is favorable with no intervention.

Congenital syphilis can present with “pseudo-paralysis” where infants do not move a limb due to pain. Bony changes often involve the metaphysis and diaphysis of the long bones. In addition, congenital syphilis will have other clinical manifestations including cutaneous lesions, jaundice, anemia, and snuffles. Infants whose mothers received regular prenatal care are unlikely to develop congenital syphilis as it is routinely screened for during pregnancy.

A healing femur fracture was a strong consideration in this case however there was no healing fracture line and the callus was longer than would be expected. Additionally, one would expect more acute pain immediately after the fracture and an improvement in pain as it heals, which does not align with this clinical presentation of concurrent new onset pain and callus formation on X-ray.

Infants with osteomyelitis could present similarly to our patient, although given it is an infection of the bone, one would expect the patient to have a fever, and other signs of infection such as erythema and warmth of the affected limb. Findings on XR are often seen later in the course and it would be unlikely for a patient to be well-appearing and afebrile at the time of evaluation for pain.

Ascorbic acid deficiency or scurvy can present with bone pain due to periosteal reaction. It is unlikely in an infant who is fed breastmilk or formula as Vitamin C is found in both. Scurvy will also have other clinical manifestations such as gingival hemorrhage, peri-follicular hemorrhage, and coiled, fragmented hair.

References

Glorieux FH. Caffey disease: an unlikely collagenopathy. J Clin Invest. 2005;115(5):1142-1144. doi:10.1172/JCI25148

CAFFEY J. (1957). Infantile cortical hyperostosis; a review of the clinical and radiographic features. Proceedings of the Royal Society of Medicine, 50(5), 347–354.

Gensure, R. C., Mäkitie, O., Barclay, C., Chan, C., Depalma, S. R., Bastepe, M., Abuzahra, H., Couper, R., Mundlos, S., Sillence, D., Ala Kokko, L., Seidman, J. G., Cole, W. G., & Jüppner, H. (2005). A novel COL1A1 mutation in infantile cortical hyperostosis (Caffey disease) expands the spectrum of collagen-related disorders. The Journal of clinical investigation, 115(5), 1250–1257. https://doi.org/10.1172/JCI22760

Stafford IA, Workowski KA, Bachmann LH. Syphilis Complicating Pregnancy and Congenital Syphilis. N Engl J Med. 2024;390(3):242-253. doi:10.1056/NEJMra2202762

Pan, T., Hennrikus, E. F., & Hennrikus, W. L. (2021). Modern Day Scurvy in Pediatric Orthopaedics: A Forgotten Illness. Journal of pediatric orthopedics, 41(3), e279–e284. https://doi.org/10.1097/BPO.0000000000001731