P3C017: A Case of Severe Neonatal Hypercalcemia Secondary to Subcutaneous Fat Necrosis Treated with Pamidronate

Introduction: Subcutaneous fat necrosis of the newborn (SCFN) is a rare, self-limiting condition; however, it may be associated with hypercalcemia, which may sometimes reach life-threatening levels that can result in significant morbidity and mortality. Approaches used for the management of this potentially life-threatening condition, include hyperhydration, calciuric diuretics, corticosteroids, and in more resistant cases pamidronate, a bisphosphonate. We report our experience with early use of a short course of pamidronate in a neonate with severe hypercalcemia secondary to SCFN.

Case Description: A 20-day-old infant came to the emergency department for evaluation of erythematous, firm subcutaneous nodules on both shoulders, proximal extremities, and buttocks. The baby was born by vaginal delivery at term via a home water birth.

Apgar scores were 3, 8, and 10 at 1, 5, and 10 minutes. Skin findings were consistent with SCFN (Figure 1). That prompted further laboratory studies that showed hypercalcemia on admission (15.8 mg/dl) [Table 1]. Despite hyperhydration, calcitonin, and furosemide treatment for 24 hours, Ca+2 only decreased to 13.6 mg/dl.

On day 2, an initial dose of 0.5 mg/kg of pamidronate was administered. On day 3, due to persistently elevated Ca+2 levels, a 2nd dose of pamidronate was administered. On Day 4, the Ca+2 level dropped to 6.8 mg/dl, leading to the discontinuation of all medications.
The baby was observed for two days following treatment. A renal ultrasound before discharge showed no evidence of nephrocalcinosis. He was discharged on a low-calcium formula with close follow-up.

Discussion: SCFN is usually benign, with a self-limiting course. Risk factors include perinatal asphyxia, trauma, prolonged hypothermia (including medically-induced hypothermia that is increasingly being used to treat neonatal encephalopathy). Certain complications can occur including thrombocytopenia and hypercalcemia that could lead, in rare cases, to metastatic calcification.

Several theories are suggested to explain the mechanism of hypercalcemia, including increased prostaglandin activity leading to osteoclast activation, calcium release from necrotic fat cells, and increased production of 1,25-dihydroxy vitamin D by macrophages.

Treatment of hypercalcemia starts with adequate hydration and, if appropriate, loop diuretics. Also, a milk formula with low calcium and vitamin D content should be considered. A second line of therapy includes glucocorticoids or the use of a short course of bisphosphonates, as we did in our case. Bisphosphonates have mild side effects compared to other treatment options.

Conclusion: Given pamidronate’s decreased risk of nephrocalcinosis, reduced renal calcium load, and mild side effects compared to furosemide and steroids, it should be considered the first-line treatment for SCFN in combination with calcitonin and aggressive hydration.