OFF-LABEL USE OF PAMIDRONATE IN HYPER-CALCEMIC NEWBORN AFFECTED BY SUBCUTANEOUS FAT NECROSIS AFTER THERAPEUTIC HYPOTERMIA

Background: Subcutaneous fat necrosis is a dermatological disorder with characteristic subcutaneous nodules or plaques. It has a benign nature and generally runs a self-limiting course, although can cause significant and dangerous complications, including hypercalcemia. Outbreak of hypercalcemia occurs even several months after hypothermic treatment in asymptomatic or symptomatic way. Irritability, lethargy, hypotonia, emesis, polyuria, polydipsia, constipation and failure to thrive are the most common symptoms of hypercalcemia while seizures, cardiac arrest and acute or chronic renal failure are the most serious manifestations. Chronic hypercalcemia is also associated with nephrocalcinosis and metastatic calcifications of skin, heart, lever and vessels. Low calcium and vitamine D formula preparation milk, diuretics, such as furosemide, and corticosteroids are first-line treatments. In some refractory case pamidronate is used. Pamidronate is a biphosphonate which can modulate bone turnover by leading hydroxyapatite crystals, and it can inhibit osteoclastic bone resorption. Observation: A male full-term infant weighing 2,300 grams was born after an emergency cesarean section due to fetal heart rate decelerations. His initial Apgar scores were 1 at 1 minute, 4 at 5 minutes and 8 at 15 minutes. Due to hypoxicischaemic encephalopathy (stage 1 of Sarnat classification, with abnormal voltage and paroxysmal activities at electroencephalogram),a whole-body therapeutic hypothermia was initiated before sixth hour of life. It was performed to a target rectal temperature of 33,5°C, for about 36 hours. In the third day of life, he developed characteristic subcutaneous fat necrosis skin lesions, such as firm, indurated plaques and red and violaceous nodules, on the upper back area and buttocks. One month after the hypotermic treatment the infant developed a rapid, asymptomatic increase of calcemia. First his milk was changed to a very low calcium and vitamin D formula preparation, without a clinical improvement. Hypercalcemia (total serum calcium 13,8 mg/dL [reference range 9-10.9 mg/dL] and ionized calcium 1,96 mmol/L [reference range 1,12-1,32 mmol/L]) was successfully treated with a 3-days therapy of intravenous pamidronate at dose of 0,5 mg/kg/die. No side effects were detected during the treatment and then serum calcium levels remained stable.