Subcutaneous Fat Necrosis
Hilary Rowe, BScPharm
VIHA Pharmacy Resident 2009-10
Neonatal ICU Rotation
June 9th, 2010
Outline
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Objectives
Patient Case
Background
Clinical Question
Review of Evidence
Recommendation
Monitoring
Objectives
• Review pathophysiology for subcutaneous fat
necrosis and hypercalcemia
• Be able to list:
– 3 therapies used to treat hypercalcemia
– The mg/kg dose of pamidronate used in
neonates
– The lab parameters to monitor & their
normal ranges
Miss. Baby Girl B
• ID: 5 week old girl wt 4,024 g
• CC: Palpable fat necrosis, ↑ ionized Ca 1.55
mmol/L (started May 14th)
• HPI: ↑ ionized calcium since 1 month of age
Subcutaneous
Fat Necrosis
Miss. Baby Girl B
• PMHx: Born at 365 by emergency cesarean
section for fetal distress (↓HR) and prenatal
diagnosis of gastroschisis
– Resuscitated x 5 min
– APGAR 1 at 1min, 1 at 5min, 3 at 10 min
– Treated with therapeutic hypothermia
(whole body) to reduce risk of brain injury
– Gastroschisis- Repaired surgically at birth
Miss. Baby Girl B
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Meds PTA: None
Allergies: NKA
SH: Mom 22 yo (G3P1A1) with 3 yo daughter
Discharge Plan: Unknown
Review of Systems
System Findings
CNS
•Activity-quiet & alert
•Normal cry & good suck
•Temp 371
•Previous seizures- started
April 12th (last 19th) after
hypothermia protocol ended
HEENT •Unremarkable
Resp
•RR 30 (normal 25-40)
•Respirations clear and easy
Medications
•Phenobarbital
25mg daily
•Level 85umol/L
(65-170umol/L)
Review of Systems
System Findings
Cardio
GI
•HR 146 (normal 120-160)
•No murmur
•Palpable brachial and
femoral pulses
•No edema
•Gastroschisis- Repaired
surgically at birth
•No stool today
•Passed gas and burped
Medications
Review of Systems
System
Findings
Liver
April 18th
•↑AST 40 (10-36)
•↑ALT 157 (10-55)
•↑Conj Bili 6 (0-4)
•SrCr 29
•Urea 6
•Output 5.6mL/kg/hr
•Ca:Cr ratio ↑ 5.06 (<2)
GU
Medications
Review of Systems
System
Heme
Findings
Medications
•↓ RBC 3.9, ↓Hgb 99, ↑ Plt •Lipid 1.7g/kg/day
554
•TG ↑2.52 (0.3-1.9 mmol/L)
Fluids & ↓ Na 133, K+ 4.4, ↓Cl 94
Lytes
•EBM 20mL/hr
•Dextrose
3.71g/kg/day
•Trophamine
1.1g/kg/day
•Total Fluid Intake
160ml/kg/day
Review of Systems
Review of Systems
Review of Systems
Review of Systems
System
Findings
Minerals •April 21st iCa2+1.33
•May 14th iCa2+↑1.55
(normal 1.1-1.3 mmol/L)
Skin
•Intact, pink, skin with
palpable fat necrosis
Musculo •Normal tone & reflexes
skeletal
Medications
•Limited Ca,
hyperhydration (May
15-19)
•Furosemide 4mg IV
Q12h (May 18-22)
Review of Systems
Medical Problems List
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Gastroschisis- Repaired surgically at birth
Hypoxic-Ischemic Encephalopathy (HIE)
Subcutaneous Fat Necrosis (SCFN)
Hypercalcemia
DRP’s
• BB is at risk of poor weight gain secondary to
a poorly-functioning GI tract and requires
daily assessment of her TPN
• BB is at risk of rickets secondary to an
interaction between Phenobarbital and
Vitamin D (hyper-metabolism) and would
benefit from reassessment of her vitamin D
supplementation
DRP’s
BB is at risk of renal dysfunction and mortality
secondary to high levels of serum ionized
calcium despite current therapies and
requires reassessment of her drug therapy
Subcutaneous Fat necrosis
• Seen in 1st week of life in full term babies
– Obstetric trauma, meconium aspiration,
hypoxemia or hypothermia
• Signs & Symptoms
– Painful, firm, indurated, red nodules on
buttocks, trunk, arms and cheeks
• ↑ saturated fatty acids in subcutaneous tissue
from defective neonatal fat metabolism,
worsened by neonatal stress & fat necrosis
from trauma during delivery
Subcutaneous Fat necrosis
• The fat of neonates is made of saturated fatty
acids with a relatively high melting point
• Neonatal stress resulting in hypothermia may
induce fat to undergo crystallization, causing
necrosis
• Hypercalcemia in SCFN may result in
significant morbidity
• Incidence of hypercalcemia complicating
SCFN is not known
Hypercalcemia
• Causes
– Osteoclast activation and ↑ production of 1,25
dihydroxyvitamin D3 by macrophages
increased bone turnover
• Hypercalcemia is usually noticed 4-6 weeks
after skin lesions
Hypercalcemia
Hypercalcemia can cause
• Metastatic calcifications in the heart,
inferior vena cava & liver
• Nephrocalcinosis and nephrolithiasis
secondary to hypercalciuria occurs within
4-6 months of onset
• Thrombocytopenia and hyperlipidemia
• Death
SCFN & Hypercalcemia
• SCFN is a self-limiting condition and needs
no treatment except when associated with
hypercalcemia
• Requires:
– Regular monitoring of serum calcium levels
– Therapy:
• ↓calcium and vitamin D in the diet
• Hyperhydration ~200mL/kg/day
• IV furosemide
NICU Discussion
Rounds
• Physician discussed that baby has ↑ calcium
and that he has seen pamidronate used at
other hospitals
• Physician wanted to know
– What dose to give
– How often to give it
– If there is evidence for this indication
– What the safety risks are?
Clinical Question
P
In a 5 week old baby with elevated ionized
calcium and subcutaneous fat necrosis
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Pamidronate
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Hyperhydration, IV Furosemide and limiting Vit D
& Calcium
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Reduce the ionized calcium
Reduce morbidity and mortality
Prevent complications in the heart, liver and
kidneys
Search Strategy
• PubMed, Embase, Google
• Search terms:
– Subcutaneous fat necrosis
– Hypercalcemia & gastroschisis
– Hypercalcemia in neonates
– Hypercalcemia treatment
– Hypercalcemia and pamidronate
• Found
– Case reports
Alos et al. Horm Res 2006
Design Retrospective chart review 2001-2004
P
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•4 newborns with SCFN and hypercalcemia
•Pamidronate 0.25-0.5mg/kg/dose infused over
4 hours
•IV fluids, low calcium diet & Furosemide
•Prevent nephrocalcinosis (renal ultrasound)
•Normalize hypercalcemia (iCa2+)
•Bone density of lumbar spine (DXA)
Alos et al. Horm Res 2006
• 4 full-term newborns with SCFN & hypercalcemia
• SCFN diagnosed on
– Skin nodules (red or purple, indurated)
– Serum ionized calcium (1.12-1.25 mmol/L)
– Serum 25- hydroxy vitamin D (25-85 nmol/L)
– 1, 25-dihydroxy vitamin D (41-145 pmol/L)
– PTH (1.3-7.6 pmol/L)
– Urinary Ca:Cr ratio (<2)
Alos et al. Horm Res 2006
Our Patient
35
1.55
5.06
Alos et al. Horm Res 2006
Case 1
• Born via cesarean for fetal distress
• 1st developed haematuria &
thrombocytopenia due to renal vein
thrombosis
• 2nd indurated SCFN lesion on back and
shoulders
• At 42 days-weight dropped from 90th to 10th
percentile and baby developed renal failure
Alos et al. Horm Res 2006
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SrCr 107 umol/L (23-93)
Hypercalcemia iCa2+ 2.19 mmol/L
Ca:Cr 3.24
Patient received hyperhydration, 6 doses of
IV furosemide 1mg/kg and low Ca and
Vitamin D in diet iCa2+ 2.3 mmol/L
• Day 45, 46, 47 pamidronate 0.25mg/kg per
dose
• Day 54 iCa2+ normalized
Alos et al. Horm Res 2006
• At 3 mo no skin lesions, normal iCa2+,
moderate nephrocalcinosis with normal renal
function
• At 18 mo growth in 75th percentile, bone age
was identical to actual age, BMD Z score was
0SD
• 3 years old growth curve was still 75th
percentile, nephrocalcinosis disappeared on
renal ultrasounds
Alos et al. Horm Res 2006
Case 2
• Born via cesarean for fetal distress
• During 1st few days of life developed SCFN
• Hypercalcemia discovered on day 6
• Vitamin D supplementation was stopped
• Day 30 iCa2+ 1.58 mmol/L
• Ca:Cr 6.5
• Hyperhydration and 4 doses of furosemide
1mg/kg
Alos et al. Horm Res 2006
• Pamidronate 0.25mg/kg on day 33 and 36
• Ca:Cr normalized day 38, iCa2+ normalized
day 39
• Day 54 3rd dose of pamidronate given as
iCa2+ ↑ to 1.45mmol/L & Ca:Cr 1.5
Alos et al. Horm Res 2006
• At 2 mo skin lesions almost gone, calcium
continued to be normal, mild nephrocalcinosis
on renal ultrasound
• At 6 mo nephrocalcinosis had disappeared
• At 2 years length 95th percentile, normal
development, BMD Z score +1SD
Alos et al. Horm Res 2006
Case 3
• Delivered at term with meconium aspiration
and transient thrombocytosis
• Day 1 had SCFN (on cheeks had feeding
difficulty)
• 11th day hypercalcemia noted iCa2+ 1.64
• Fluid hydration, IV furosemide 1mg/kg x 1
dose, low calcium and vitamin D diet
Alos et al. Horm Res 2006
• Day 18 & 24 pamidronate 0.25mg/kg
• Day 29 & 37 pamidronate 0.5mg/kg because
of ↑ iCa2+ but normal Ca:Cr
• At 3 mo all skin lesions gone
• At 2 & 7 mo no nephrocalcinosis on renal
ultrasound
Alos et al. Horm Res 2006
• Growth was at 50th percentile
• BMD Z score at 7 mo was 0SD
• At 7 & 13 mo motor development was normal
Alos et al. Horm Res 2006
Case 4
• Delivered at term with meconium aspiration
• Mother had diabetes
• 6th day SCFN-scalp and back
• Day 12 hypercalcemia
• Day 20 iCa2+ 1.49mmol/L
• Ca:Cr 3.58
Alos et al. Horm Res 2006
• IV Hydration with no Furosemide
• Day 26 pamidroante 0.25mg/kg + 2 doses
pamidroante 0.5mg/kg days on 27 & 28
• Day 29 Ca:Cr normalized
• Day 31 iCa2+ normalized
• At 3 mo SCFN gone, iCa2+ 1.37 mmol/L,
Ca: Cr 1.3 mmol/mol
Alos et al. Horm Res 2006
• At 3 & 9 mo no nephrocalcinosis
• BMD Z score at 3 mo was 0SD
• At 9 mo Length was on the 50th percentile
Alos et al. Horm Res 2006
• Furosemide & steroids can increase renal
calcium excretion and the risk of
nephrocalcinosis
• Pamidronate inhibits bone resorption which
results in ↓ serum calcium so it reduces the
renal calcium load
– it does not ↑ the risk of nephrocalcinosis
Alos et al. Horm Res 2006
Conclusion
• 3-4 doses of pamidronate 0.25-0.5mg/kg is
effective to reduce serum calcium
• ? if used as 1st line it could ↓ the risk of
nephrocalcinosis
– commentary disagrees but pt was on
steroid and furosemide 1st
Goals of Therapy
Patient’s Family Goals
• Discharge baby home with fewest
complications
Team Goals
• ↓ the risk of nephrocalcinosis
• Normalize serum iCa2+
• Resolve SCFN
• Decrease morbidity & mortality
• Minimize adverse drug events
Therapeutic Options
•Limit Vitamin D
•Limit Calcium intake
•Hyperhydration 180mL/kg
•IV Furosemide
•Pamidronate 0.25-0.5mg/kg
Recommendation
• Initiate pamidronate 1mg (0.25mg/kg) if
ionized calcium level >1.4mmol/L
• Monitor ionized calcium daily
-Expect drop in calcium in 48-72 hours
• Determine subsequent doses based on
response (up to 4 doses)
•Patients iCa2+ dropped to 1.38mmol/L so
pamidronate was not initiated
Monitoring
Adverse Events
Monitor
Who
Growth
RN &
(percentile)
Pharmacist
Nephrocalcinosis Physician
via renal
ultrasound
When
How Long
Daily
While in
hospital
Once
At 3 mo
Monitoring
Efficacy
Monitor
Who
When
How Long
iCa2+
Physician &
Pharmacist
Physician &
Pharmacist
Daily
X 7 days then
weekly
X 7 days then
weekly
Physician
At 3 mo
Ca:Cr ratio
BMD Z
score
Weekly
Once
Questions?
References
1. Alos N, Eugene D, Fillion M et al.
Pamidronate: Treatment for severe
hypercalcemia in neonatal subcutaneous fat
necrosis. Horm Res 2006; 65: 289-94.
2. Vijayakumar M, Prahlad N, Nammalwar BR
and Shanmughasundharam R.
Subcutaneous fat necrosis with
hypercalcemia. Indian Pediatrics April 17,
2006; 43: 360-63.