Use of Zoledronic Acid in a Neonate with Subcutaneous Fat Necrosis Complicated with Severe, Refractory Hypercalcemia

Abstract

Objective Subcutaneous fat necrosis (SCFN) is a rare condition that may occur in the neonatal period. SCFN is an inflammatory disorder of the adipose tissue, usually found in full-term healthy infants who have a history of intrauterine or perinatal distress. It is usually a self-limited condition; however, in some cases, it can get complicated, leading to severe hypercalcemia that may be life-threatening. Study Design We report and describe a classic presentation of SCFN that led to severe hypercalcemia refractory to standard treatment. The diagnosis of SCFN was made based on the finding of subcutaneous nodules and of hypercalcemia. The serum calcium level reached 16.6 mg/dL. Hypercalcemia was treated first with intravenous infusions of fluids and furosemide and then of methylprednisolone. This standard treatment was not effective; therefore, we administered a single low dose of zoledronic acid, which, in turn, was efficacious in ultimately managing the hypercalcemia. Conclusion Our case shows how a single low dose of zoledronic acid was safe and effective in managing severe hypercalcemia unresponsive to conventional treatment while minimizing the risk of hypocalcemic rebounds.

Subcutaneous fat necrosis of the newborn – An atypical case with typical complications

“…Diagnosis is essentially clinical, 9 although a skin biopsy may be useful in case of clinical doubt 4 . Differential diagnosis for SCFN may be difficult and includes sclerema neonatorum and cellulitis 1,2,4 …”

“…Subcutaneous fat necrosis of the newborn is usually a benign disease with an uncomplicated course 2 ; skin lesions tend to resolve in some weeks without sequelae or, less frequently, evolve into fibrotic scars and fat atrophy 1 . Nevertheless, complications may appear, like thrombocytopenia, hypoglycemia, hypertriglyceridemia, and most frequently, hypercalcemia 2…”

“…The hypothesized cause of hypercalcemia is that granulomatous inflammatory cells in SCFN express high levels of 1‐alpha‐hydroxylase, the enzyme that converts 25‐OH vitamin D3 to its active form (1,25‐dihydroxyvitamin D3), which can stimulate intestinal calcium uptake 2,7‐9,12 . Hypercalcemia can also be explained by an increased bone resorption in SCFN due to higher prostaglandin E levels, 1,13 and by an increased calcium mobilization from resolving areas of subcutaneous fat necrosis 4 …”

“…Diagnosis is essentially clinical 6 and prognosis is generally good, with a complete regression of skin lesions within few weeks 1,2 . Nevertheless, acute complications like hypercalcemia, hypertriglyceridemia, and thrombocytopenia may appear 1,5,6 . Hypercalcemia is the most frequent complication and can be potentially life‐threatening 7 …”

“…The pathogenesis of the disease remains unknown, although it has been associated in almost all cases with perinatal stress factors which cause hypoxia and adipocyte necrosis 1,3,6 . Predisposing factors include maternal diseases (gestational diabetes, preeclampsia) and neonatal conditions (hypothermia, infections, hypoxemia) 1,4‐6 …”