Download Subcutaneous fat necrosis of the newborn following hypothermia

Australasian Journal of Dermatology (2001) 42, 207–210
CAS E REPORT
Subcutaneous fat necrosis of the newborn
following hypothermia and complicated by pain
and hypercalcaemia
Todd P Wiadrowski and Gillian Marshman
Flinders Medical Centre, Bedford Park, South Australia, Australia
SUMMARY
A female infant was delivered at term with complications of severe meconium aspiration and birth
asphyxia. Surface cooling was performed in the first
24 hours as part of the management of her birth
asphyxia. Woody erythema was noted at 24 hours,
followed by the formation of red–purple nodules on the
6th day. Clinical findings in the first 24 hours were suggestive of cold panniculitis. However, clinical and histological findings progressed to be in keeping with the
diagnosis of subcutaneous fat necrosis of the newborn
(SCFN). Furthermore, the immediate postnatal period
was complicated by pain resistant to treatment with
opiates. Asymptomatic hypercalcaemia was noted on
periodic testing at 7 weeks and treated by rehydration,
diuretics, prednisolone, etidronate and a low-calcium
and -vitamin D diet. A review of the clinical and histological findings of the relevant panniculitides occurring
in the postnatal period is presented, as well as a review
of the treatment of hypercalcaemia in SCFN.
Key words: cold panniculitis, corticosteroids, etidronate, infants, opiates, panniculitis.
INTRODUCTION
Subcutaneous fat necrosis of the newborn (SCFN) is a transient panniculitis of neonates typically presenting within the
first 6 weeks of life. Most reported cases involve infants at full
term or post-dates and of normal size for dates, but often with
a history of birth asphyxia, meconium aspiration, cyanosis,
seizures and hypothermia. An association with maternal
diabetes and pre-eclampsia has been reported.1 The natural
Correspondence: Dr G Marshman, Dermatology Unit, Department
of Internal Medicine, Flinders Medical Centre, Flinders Drive, Bedford
Park, SA 5042, Australia.
Todd P Wiadrowski, BM, BS. Gillian Marshman, FACD.
Submitted 12 September 2000; accepted 6 February 2001.
history of the condition is for resolution without scarring. The
most common complication of SCFN is hypercalcaemia,
which has been associated with neonatal death.2 We describe
a child with an overlapping clinical presentation following
medically induced hypothermia to treat birth asphyxia. In this
case, the initial clinical features of cold panniculitis progressed
to those of SCFN, both clinically and histologically. This
patient’s case was further complicated by pain and hypercalcaemia.
CASE REPORT
A female infant was born at term weighing 4350 g. Standard
maternal prenatal screens revealed no significant abnormalities (haemoglobin, group and screen, glucose tolerance test,
rubella serology, syphilis serology, hepatitis B surface antigen, hepatitis C serology, HIV serology and midstream urine
specimen). The mother was noted to have mild hypertension
with associated oedema and albuminuria in the third
trimester. No medications were taken during the pregnancy.
Table 1 details the significant events after delivery and over
the ensuing months. During the first 24 hours, the child was
noted to be hypotensive with cardiogenic shock requiring
dopamine, had a pneumothorax, acute renal failure and a
mild disseminated intravascular coagulation. Within the first
hours of life, a decision was made for paralysis and sedation,
with her core temperature kept between 32 and 33°C to treat
her birth asphyxia. Hypothermia was achieved with the use
of ice packs applied to the skin and turning off the overhead
heating lamps. Her temperature was monitored via a rectal
probe. This temperature was held for 24 hours, then raised
to 35°C and then 37°C over a 3 day period.
Approximately 24 hours post-delivery, a pink woody oedematous change was noted on the infant’s thighs and back, as
well as petechiae on the right ankle. This progressively worsened over the ensuing 4 days and the buttocks were noted to
be exquisitely tender to touch with grimacing and shrill cry.
Plaques and nodules formed within these background
changes at 6 days of age. A clinical diagnosis of SCFN was
made (Fig. 1).
Histology revealed an acute panniculitis with frank fat
necrosis and needle-like clefts (Fig. 2), which confirmed the
clinical diagnosis of SCFN.
208
TP Wiadrowski and G Marshman
Figure 1 Purple nodules formed on erythematous and oedematous
buttock skin at seven days postnatally.
Figure 2 Skin biopsy from sacral nodule demonstrating radially
arranged needle shaped clefts at seven days postnatally (H&E).
Pain was poorly controlled by morphine. Due to continued
difficulties with analgesia and the formation of new plaques
and nodules, prednisolone was added at a dose of 1 mg/kg per
day on day 34. This led to a definite improvement in pain
control and subjective improvement in the intensity of the
erythema.
Weekly measurements of serum calcium detected hypercalcaemia at a corrected level of 3.74 mmol/L (normal
range 2.20–2.75 mmol/L) 49 days after delivery. The infant’s
weight at this time was 4910 g. Intravenous access was
particularly difficult to attain in this infant and, therefore,
initial treatment was with oral fluids, frusemide (8 mg, orally
b.d.) and spironolactone (5 mg, orally b.d.). Prednisolone was
being administered at a dose of 5 mg on alternate days when
hypercalcaemia was detected and this was then increased to
5 mg, daily.
After 4 days treatment, as described above, calcium levels
were stable, but without significant decline. Etidronate
was started at an oral dose of 25 mg, twice daily. Due to the
irritant nature of etidronate and the patient’s underlying
gastro-oesophageal reflux (GOR), the infant was nursed in
an upright position for 30 min following administration. It
was also suggested that etidronate should not be given
within 2 hours of milk feeds because calcium–drug binding
may occur and reduce absorption. Cisapride (1 mg, orally
t.d.s.) had already been commenced for the treatment of
the infant’s GOR and this was continued while etidronate
was being administered. Calcium, parathyroid hormone and
1,25(OH)2-vitamin D3 levels were 3.49 mmol/L, 0.4 pmol/L
(normal range 1.1–6.9 pmol/L) and 55 pmol/L (normal range
50–160 pmol/L), respectively. These levels were taken at the
same time as the etidronate was started and it should be noted
that the infant had been taking prednisolone for 19 days prior
to this. A low-calcium and -vitamin D formula (Locasol) was
commenced on day 54 and frusemide and spironolactone were
ceased. Etidronate was continued for a total of 8 days treatment. At this time, calcium levels had normalized.
Prednisolone was weaned over the ensuing 21 days because
the infant’s pain had settled.
Locasol was continued for 7 months and, when the
child was weaned onto solids, a diet low in calcium was
used initially. This diet consisted of fruit, vegetables, meat,
cereals, such as rolled oats and semolina, and avoidance of
dairy products. It was noted that some cereals, in particular
Table 1
Time-course of presented case
Delivery
2 min
5 min
10 min
First hour’s
24 h
Day 4
Day 5
Day 6
Day 7
Day 26
Day 34
Day 49
Day 53
Day 54
Day 61
Day 82
6 months
Mid-cavity forceps delivery at term, thin meconium, cord pH 6.97
Apgar score 2
Apgar score 4
Apgar score 5, first spontaneous gasp followed this
Endotracheal oxygen, adrenaline, hypothermia-induced paralysis and sedation
Woody pink oedematous change on thighs and back, petechiae of right ankle
Buttocks noted to be tender to touch
Morphine added
Nodules arise within previously erythematous and oedematous areas
Biopsy taken; histology shows needle-shaped clefts in lipocytes and fat necrosis
Cisapride started
Prednisolone added at 1 mg/kg per day with subsequent improvement in pain relief
Hypercalcaemia 3.74 mmol/L corrected, treatment commenced with oral rehydration, frusemide and spironolactone, prednisolone
dose increased back to 1 mg/kg per day
Hypercalcaemia 3.49 mmol/L corrected, etidronate 25 mg twice daily; normal vitamin D level
Locasol added, frusemide and spironolactone ceased
Etidronate ceased
Prednisolone ceased
Resolution of most nodules
Subcutaneous fat necrosis of the newborn
baby rice cereals, are fortified with calcium and should be
avoided. A diet free of restrictions was commenced after
7 months.
The infant continued to display nodules, predominantly on
the proximal extremities and back, with slow resolution of
most of these lesions by 6 months. At 9 months, the firm
nodules that were present at her previous visit had altered
little. Magnetic resonance imaging (MRI) was performed.
Calcification was not present. The MRI appearances were of
septate lesions composed of soft tissue and lipid. The nodules
are stable and asymptomatic and further biopsy has not been
performed.
DISCUSSION
Subcutaneous fat necrosis of the newborn is an uncommon
transient panniculitis seen in term to post-term neonates that
usually resolves without scarring. Lesions often develop on
skin that initially appears oedematous prior to the formation
of red–purple nodules and plaques.1,3 The nodular lesions of
SCFN may present during the first 6 weeks, with one study
reporting 45% of lesions arising in the first week of life.4 A differential diagnosis would include sclerema neonatorum (SN)
and cold panniculitis, as outlined in Table 2.
Our patient was noted to have pink woody oedematous skin
on the thighs and back 24 hours after delivery. The distribution
of these areas corresponded to the areas of application of the
ice packs used to lower the child’s core temperature.
Therefore, these features could be in keeping with cold panniculitis. However, at 6 days post-delivery, nodules were noted
that steadily increased in size. These nodules were biopsied
and demonstrated features in keeping with SCFN. Therefore,
while we have clinical and histological evidence of SCFN, the
lack of a biopsy specimen of the earliest lesion allows us only
to speculate that, on clinical grounds, the infant either had an
atypical presentation of SCFN or that this is a case of cold
panniculitis progressing to SCFN.
Painful lesions that proved to be difficult to control with
opiate analgesia complicated the course of our case. An infant
with painful SCFN requiring the use of morphine has been
reported following the maternal use of amlodipine.10 Painful
lesions in cases of SCFN without the maternal use of a calcium
Table 2
209
channel blocker have not been highlighted. In our case, the
infant’s lesions were noted to be painful as nodules began to
arise. Cold panniculitis has been described as having tender
nodules in adults6 and it is not unreasonable to expect these
lesions may be tender in infants. Morphine, at doses of 1–2 mg
four times a day, was administered without complete pain control. It was decided to add prednisolone at a dose of 1 mg/kg
per day. This had a synergistic effect with morphine, giving
complete pain control with doses of morphine that were previously insufficient. There was also some subjective improvement in the erythema overlying the nodules as well as a
decrease in nodule size. We believe that the use of prednisolone should be strongly considered over the short-term in
cases complicated by painful lesions. Evidence is lacking
as to whether this changes the overall disease course or
progression.
Hypercalcaemia complicating SCFN is well recognized, but
the pathogenesis is yet to be fully determined. Hypercalcaemia
occurs between 2 and 16 weeks, most commonly at 6–7
weeks.7 Clinically, the most common feature is failure to thrive
(90%), followed by fever, vomiting, feeding difficulties,
irritability and listlessness. Mortality from hypercalcaemia
complicating SCFN has been estimated at 15%.2 Because the
child may have been discharged by the time these features
arise, education of the parents to recognize these symptoms
and report this to the managing physician is essential. To the
best of our knowledge there are no specific guidelines for
routine monitoring of serum calcium levels in these cases. For
our patient, it was decided to perform weekly investigations
of serum calcium and albumin levels until 16 weeks of age.
Once a diagnosis of hypercalcaemia has been made, treatment options considered are outlined in Table 3.11 It is necessary to stress the importance of adequate hydration in the
treatment of hypercalcaemia. Rehydration with a resultant
increase in intravascular volume will increase glomerular
filtration rate and increase renal calcium clearance.12
Loop diuretics are used to achieve increased calcium
excretion by inhibiting calcium reabsorption and preventing
volume overload secondary to the rehydration. Thiazide
diuretics should not be used because they increase distal
tubular reabsorption of calcium and, therefore, may aggravate
the process.
Differential diagnosis of subcutaneous fat necrosis of the newborn1,3,5–9
Subcutaneous fat necrosis
Delivery
Full term/post-dates
Predisposing factors Maternal diabetes, hypertension
Birth asphyxia, meconium aspiration, cyanosis,
seizures, hypothermia
Onset
First 6 weeks
Signs
Red, blue nodules on trunk, buttock, arms, face,
eyes
Cold panniculitis
Sclerema neonatorum
Nil specific
No maternal factors
Cold stress
Preterm neonate
No maternal factors
Uneventful delivery
Within 72 hours of exposure
Red, blue induration plaques
Within the first week
Diffuse yellow–white nodules,
sparing the genitalia, palms
and soles
Needle-shaped clefts in
lipocytes, nil to mild
inflammatory infiltrate or fat
necrosis, septa widened by
oedema
Poor, 75% mortality
Histology
Fat necrosis, foreign body giant cells, lymphocytic
infiltrate, radially arranged needle-shaped clefts
in lipocytes
Lobular panniculitis, mixed
infiltrate, no needle-shaped
clefts
Prognosis
Generally very good; hypercalcaemia carries a 15% Excellent
mortality rate
210
Table 3
TP Wiadrowski and G Marshman
Management of an infant with subcutaneous fat necrosis of the newborn11–14
Panniculitis
Hypercalcaemia
Pain
Education of parents regarding disease and symptoms and signs of hypercalcaemia (failure to thrive, fever, vomiting,
feeding difficulties, irritability and listlessness); protect areas of panniculitis from trauma plus dressings for ulceration
Weekly serum calcium and albumin levels to 16 weeks of age; rehydration, dietary vitamin D and calcium restriction,
frusemide and prednisolone; consider etidronate if other measures fail
Opiates, prednisolone
Prednisolone is used in the treatment of hypercalcaemia,
particularly in cases associated with haematogenous malignancy or cases of 1,25(OH)2-vitamin D3 excess, such as
sarcoidosis. It has been suggested that the pathogenesis of
hypercalcaemia in SCFN may be similar to that of sarcoidosis
and, therefore, prednisolone would have a role in its treatment.
In our case, prednisolone was administered for 15 days prior
to the onset of hypercalcaemia. This may suggest that either
the dose was inadequate, that prednisolone alone is unable
to treat hypercalcaemia associated with SCFN or that
the pathogenesis is unrelated or only partially related to the
production of 1,25(OH)2-vitamin D3. We can only comment
that, in our case, hypercalcaemia occurred despite the use of
prednisolone and that vitamin D3 levels, when taken, were
normal.
Etidronate is a member of the bisphosphonate group of
drugs that are known to decrease bone resorption. Etidronate
has been reported to be successful in the management hypercalcaemia associated with SCFN13 and, due to the resistant
nature of the hypercalcaemia to first-line treatments described
above, this was embarked upon. The dose used was 5 mg/kg,
which was in keeping with the previous report. The use of
bisphosphonates, while effective in our case, should not be
embarked on lightly because their effect on bone production,
growth plates and mineralization is yet to be clarified.14
However, once etidronate was started, calcium levels fell to
normal, at which time etidronate was ceased.
A low-calcium and -vitamin D3 formula should also be
added at the earliest possible stage and would optimally
have been best used in association with the initial treatments
as described above if it had been readily available at our
institution.
In conclusion, we present a case with early clinical features
in keeping with cold panniculitis, but an overall clinical and
histological picture of SCFN. This case was unusual in that it
was complicated by significant pain in the infant only partially
controlled with opiate anaesthesia. Oral prednisolone
appeared to act synergistically with morphine to control this
infant’s pain and should be considered for use in similar cases.
In this case, etidronate was used with success over an 8 day
course to control hypercalcaemia when first-line treatment
failed. Normal serum calcium levels were subsequently maintained with dietary measures.
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