Journal of Perinatology (2014) 34, 492–493 & 2014 Nature America, Inc. All rights reserved 0743-8346/14 www.nature.com/jp
PERINATAL/NEONATAL CASE PRESENTATION
Treatment with bisphosphonates in severe hypercalcemia due to subcutaneous fat necrosis in an infant with hypoxic-ischemic encephalopathy E Pe´rez Martı´nez1, M Camprubı´ Camprubı´2, M Ramos Cebria´n3, J Anto´n Lo´pez4, A Apodaca Saracho1, MG Lopez Ramos5 and A Garcı´a-Alix2 Subcutaneous fat necrosis (SCFN) is a rare entity that occurs generally in term or post-term newborns exposed to perinatal stressing factors. These cutaneous lesions appear during the first weeks of life and their potential complications, such as hypercalcemia, determine the prognosis. We present a full-term newborn with SCFN lesions that appeared at the age of 12 days and who, 1 week later, developed moderate hypercalcemia. In our patient, the standard treatment was not enough to normalize calcemia and, in order to prevent secondary effects, etidronate therapy was initiated and it successfully normalized calcium levels. When SCFN is diagnosed, it is important to detect early hypercalcemia and treat it aggressively. This case provides further evidence of etidronate as an alternative and effective treatment for moderate–severe hypercalcemia. Journal of Perinatology (2014) 34, 492–493; doi:10.1038/jp.2014.28 Keywords: bisphosphonates; etidronate; hypercalcemia; subcutaneous fat necrosis
INTRODUCTION Subcutaneous fat necrosis (SCFN) is a rare entity that appears mainly in term or post-term infants with predisposing risk factors such as perinatal asphyxia, hypothermia or obstetrical complications during labor or delivery.1 It is characterized by hard and painful nodules, purple or erythematous in color, typically located on the trunk, buttocks and root of members. These lesions usually appear during the first weeks of life and resolve in weeks or months. The importance of this condition lies in the associated complications, mainly abscess formation and hypercalcemia. Severe hypercalcemia is rare but it can have severe consequences and it is potentially lethal. CASE A full-term male was born via a cesarean section due to nonreassuring fetal status. The pregnancy had been uncomplicated. Apgar scores were 0, 4 and 7. The baby required resuscitation and he was transferred to our neonatal intensive care unit. On admission, he received moderate hypothermia due to hypoxic-ischemic encephalopathy (HIE), but the patient evolved to refractory septic shock that required extracorporeal membrane oxygenation for 6 days. By day 12 of life, while he was recovering, large patches of indurate, erythematic–purplish skin lesions appeared on his back and root of upper extremities (Figure 1). SCFN was suspected but, because of the great expanse of the lesion, a biopsy was performed to confirm the diagnosis. After 1 week, hypercalcemia (2.81 mmol l 1) with hypercalciuria (urinary calcium/creatinine ratio 0.69 mg mg 1) was detected. Treatment with hyperhydration and intravenous furosemide (1 mg kg 1 per
day) was started. Calcemia was normalized after 12 days and the patient was discharged. After 2 days, the patient was readmitted due to asymptomatic hypercalcemia (2 mmol l 1). He was treated with hyperhydration, intravenous furosemide, high doses of corticosteroids and a low-calcium diet as well as vitamin D. Despite the treatment, calcium levels did not normalize and he developed arterial hypertension requiring treatment. Owing to this, after 18 days of corticosteroid treatment (53 days old), bisphosphonate therapy with oral etidronate (10 mg /kg 1 per day in 2 doses) was started. The dose was increased progressively until a maximum of 16 mg kg 1 per day, and a complete normalization of calcium was achieved 12 days later. During the follow-up, calcium levels remained normal. Neither nephrocalcinosis nor other organ calcifications or renal function abnormalities were found. The etidronate dose was decreased slowly and the drug was stopped after 4 months of treatment. After this, the patient remained normocalcemic. No secondary effects of the drug were reported.
DISCUSSION SCFN has been classically associated with perinatal history of asphyxia and other neonatal stressing factors. The implementation of moderate hypothermia as the standard treatment of HIE has contributed to an increased incidence of SCFN.1 Hypercalcemia, the main complication of SCFN, can cause nephrocalcinosis, hypertension, vomit, growth failure, irritability and even seizures. In our patient, classic treatment (low-calcium diet and vitamin D, overhydration, diuretics and corticosteroids) was not enough to
1 Pediatric Department, Hospital Sant Joan de De´u, Barcelona, Spain; 2Neonatology Service, Hospital Sant Joan de De´u, Barcelona, Spain; 3Pediatric Nephrology Department, Hospital Sant Joan de De´u, Barcelona, Spain; 4Pediatric Rheumatology Department, Hospital Sant Joan de De´u, Barcelona, Spain and 5Pharmacy Department, Hospital Sant Joan de De´u, Barcelona, Spain. Correspondence: Dr MC Camprubı´, Neonatology Service, Hospital Sant Joan de De´u, Passeig Sant Joan de De´u, 2, 08950 Esplugues de Llobregat, Barcelona, Spain. E-mail:
[email protected] Received 20 November 2013; revised 21 January 2014; accepted 23 January 2014
Bisphosphonates in severe hypercalcemia due to SCFN E Pe´rez Martı´nez et al
493 obtain adequate calcium serum levels without secondary effects, and hence bisphosphonate therapy was started. Despite bisphosphonates having been used in pediatric population, the experience and the literature available for hypercalcemia treatment in SCFN is limited.2,3 Etidronate is a first-generation biphosphonate that acts like other bisphosphonates, inhibiting bone resorption. It should be used with caution in children as adverse effects are possible, mainly on bone growth, but some evidence exists that they could be safe for normalizing calcium levels in cases of hypercalcemia secondary to SCFN.2,3 Our case provides further support of the potential usefulness of bisphosphonates in the SCFN, particularly in patients with extensive lesions who may require prolonged treatment with corticosteroids, sparing them their side effects. Similarly, further studies about the use of biphosphonates in SCFN are needed in the future in order to determine which of them could be the best option. CONFLICT OF INTEREST The authors declare no conflict of interest.
ACKNOWLEDGEMENTS Research in the Neonatal Service is supported by BBDUE. No extra funding was secured for this study.
REFERENCES
Figure 1.
Clinical photograph of subcutaneous fat necrosis.
& 2014 Nature America, Inc.
1 Strohm B, Hobson A, Brocklehurst P, Edwards AD, Azzopardi D. Subcutaneous fat necrosis after moderate therapeutic hypothermia in neonates. Pediatrics 2011; 128: e450–e452. 2 Rice AM, Rivkees SA. Etidronate therapy for hypercalcemia in subcutaneous fat necrosis of the newborn. J Pediatr 1999; 134: 349–351. 3 Trullemans B, Bottu J, Van Nieuwenhuyse JP. Etidronate per os in subcutaneous fat necrosis with hypercalcemia and nephrocalcinosis. Arch Pediatr 2007; 14: 170–172.
Journal of Perinatology (2014), 492 – 493
