Infantile cortical hyperostosis (ICH), also called
Caffey disease, occasionally presents as pyrexia of unknown origin (PUO).
We report one of a pair of twins, who presented as PUO, was diagnosed to
have ICH on a radionuclide bone scintigram and did not improve on
treatment with ibuprofen.
Case Report
A 2-month-old boy, one of a pair of dizygotic twins,
presented with fever for 2 weeks. He was irritable, but his activity and
weight gain were satisfactory. Clinical examination did not reveal any
localizing features. His serum C-reactive protein (CRP) was elevated
(>10 mg/L) through the illness. There was anemia and persistent severe
thrombocytosis (platelet count 1,100 × 109/L). An extensive laboratory
work-up for cause of fever was unrewarding. The bones appeared normal on
the initial whole body skiagram. There was no response to empirical
antibiotic and anti- malarial therapy.
An abdominal X-ray done on day 84 of life, for
abdominal distension, incidentally showed mild widening of 2 lower ribs
on the right side. Ultrasonography did not show sub-periosteal
collections. Bone scintigraphy, performed with methylene di-phosphonic
acid (MDP), demonstrated blood pool and delayed phase images suggestive
of inflammation in all the ribs on the right side, the lowest rib on the
left and the mandible, but the vertebrae were spared (Fig. 1). On
the basis of scintigraphy, ICH was suspected. The disease progressed and
an X-ray done a week later showed classical findings of thick
irregular bone cortex in a distribution similar to the radio nuclide
scintigram (Fig. 2). Serum alkaline phosphatase was normal.
 |
 |
| Fig. 1.
Radio nuclide bone scan (posterior view) on day 85 showing
involvement of all ribs on the right side, lowest rib on the left
and the mandible. |
Fig. 2
Plain X-ray of the chest (antero-posterior view) showing cortical
hyperostosis of the ribs.
|
He was started on Ibuprofen at a dose of 10
mg/kg/dose 8 hourly and fever subsided within a week. However the child
remained irritable, continued to have elevated CRP levels and developed
chest wall tenderness after 4 weeks of Ibuprofen therapy. At this time,
since the platelet counts had dropped to 800-900 × 109/L, Ibuprofen was
replaced by oral prednisolone (1mg/kg/day). Within 10 days, the child’s
irritability and pain subsided, platelet counts deceased to 630 × 109/L
and CRP turned negative. He became completely asymptomatic by 1 month,
following which the prednisolone was tapered off.
A radionuclide bone scan done at 6 months of life
showed near complete resolution, with a solitary residual hot spot in
the right hemi-thorax. There has been no recurrence of the disease till
1 year of age. His linear growth has been normal till 1 year.
The fraternal twin was investigated for ICH but bone
scintigraphy and skeletal X-rays were normal. He has also been
followed up till 1 year and his linear growth is within normal limits.
Discussion
Infantile cortical hyperostosis is characterized by
hyperirritability, soft tissue swelling and cortical hyperostosis. The
median age of presentation is around 9 weeks of age. Our patient
presented as a PUO from 6 weeks, and the disease was suspected on an
X-ray done in the course of investigations. Fever in ICH may be due
to high prostag-landin levels or due to excessive metabolic activity in
the bones.
The commonest site of bone involvement described in
literature is the mandible followed by the clavicles, ulna, scapula,
tibia and ribs(1,2). Vertebrae and phalanges have never been reported to
be involved. Radionuclide bone scintigraphy is generally considered to
be non-specific for ICH, because multi-focal osteomyelitis can present
with a similar picture. However, in our case, the striking pattern of
involvement, sterile cultures and absence of sub-periosteal collection
left us with no other differential diagnosis.
Several hypotheses have been proposed for the
etiology of ICH. Since similar lesions have been described in infants
who receive exogenous prostaglandins, one of the proposed mechanisms is
a disturbance of endogenous prostaglandin regulation. Some authors have
tried prostaglandin inhibitors, such as naproxen and indomethacin, and
intravenous gamma-globulin with some success(3,4). Naproxen has been
reported to produce immediate and complete resolution of signs in a
young girl who was having frequent relapses. Indomethacin, at a dose of
3 mg/kg per day starting at the age of 9 months, was used to treat a
pair of twins who were otherwise dependent on prednisolone. Indomethacin
therapy allowed the cessation of prednisolone and disease flares were
thereafter infrequent and responsive to indomethacin.
We used Ibuprofen for treatment. While selecting this
drug, our considerations were that we have a convenient pediatric liquid
formulation available, and being a platelet inhibitor, it would be
preferred to steroids in a situation where there is thrombocytosis. The
initial response to Ibuprofen in our patient was encouraging, but apart
from defervescence, there appeared to be no change in the disease
process. Hence, we started corticosteroids after an adequate trial of
Ibuprofen.
The course of the illness is generally benign and
recovers completely in many cases without treatment by 1 year (5).
Relapses have been sporadically reported. The normal height at 1 year
and lack of osteological complications in the index patient
corroborates the benign nature of the disease. Bone scan is more
sensitive, but less specific than CT scan or MRI for diagnosing ICH.
There are no studies directly comparing these modalities. Most cases are
sporadic, but autosomal dominant and autosomal recessive patterns have
also been described(6). The fraternal twin of our patient has remained
normal on follow up till 1 year of age.
Contributors: SD made the diagnosis and managed
the patient, NJ wrote the manuscript, AN performed and interpreted the
scans, KM was involved in the management of the patient.
Funding: None.
Competing interests: None declared.
