Indian Journal of Paediatric Dermatology

REVIEW ARTICLE
Year
: 2020  |  Volume : 21  |  Issue : 1  |  Page : 11--14

Neonatal subcutaneous fat necrosis as a close differential of neonatal sepsis: Case report and review of literature


Rahul Choudhary1, Garima Sachdeva2, Gaurav Katoch1,  
1 Department of Paediatrics, NDMC Medical College and Hindu Rao Hospital, Delhi, India
2 Department of Obstetrics and Gynaecology, NDMC Medical College and Hindu Rao Hospital, Delhi, India

Correspondence Address:
Dr Garima Sachdeva
House No-201, Top Floor, Dr Mukherjee Nagar, Delhi - 110 009
India

Abstract

Subcutaneous fat necrosis (SCFN) in a newborn is a rare self-limiting disorder associated with fatty tissue inflammation, mostly seen in term and postterm neonates. It is usually seen in the 1st week following a complicated delivery and is associated with lethargy, irritability, hypotonia, polyuria, polydipsia, vomiting, dehydration, and constipation. These neonates develop hypercalcemia, and C-reactive protein is persistently elevated. These features mimic neonatal sepsis. The characteristic lesions of SCFN are multiple erythematous nodules and these can guide to the final diagnosis. Here, we report a case of SCFN, which was initially misdiagnosed as neonatal sepsis and highlights the need for early diagnosis and treatment to prevent long-term complications. A literature search was done using PubMed, Medline, and Google Scholar databases using the mesh terms neonatal subcutaneous fat necrosis (SCFN) and subcutaneous fat necrosis (SFN).



How to cite this article:
Choudhary R, Sachdeva G, Katoch G. Neonatal subcutaneous fat necrosis as a close differential of neonatal sepsis: Case report and review of literature.Indian J Paediatr Dermatol 2020;21:11-14


How to cite this URL:
Choudhary R, Sachdeva G, Katoch G. Neonatal subcutaneous fat necrosis as a close differential of neonatal sepsis: Case report and review of literature. Indian J Paediatr Dermatol [serial online] 2020 [cited 2020 Jul 4 ];21:11-14
Available from: http://www.ijpd.in/text.asp?2020/21/1/11/273841


Full Text



 Introduction



Subcutaneous fat necrosis (SCFN) is a rare, self-limiting inflammation of adipose tissue, that usually affects term and postterm neonates within the first few weeks of life.[1] SCFN usually follows a complicated delivery. Various conditions that increase the risk of fat necrosis include perinatal asphyxia, cord prolapse, meconium aspiration, hypothermia, and neonatal sepsis.[2] Therapeutic hypothermia which is used for its neuroprotective action in neonates with birth asphyxia is also a risk factor for SCFN.[3] SCFN usually undergoes a spontaneous resolution. However, delay in diagnosis can lead to complications such as hypercalcemia, resulting in kidney injury, sudden cardiac arrest, and metastatic calcifications.[3]

Here, we report a case of subcutaneous fact necrosis which developed after a difficult delivery of a macrosomic baby, associated with shoulder dystocia and meconium-stained liquor, resulting in perinatal asphyxia, further complicated by hypoglycemia, hypercalcemia, and thrombocytopenia. The clinical presentation, diagnosis, and management options of subcutaneous fat necrosis are also discussed briefly.

 Case Report



We report the case of a male baby who was referred from the periphery to the neonatal nursery on day 6 of life due to suspected neonatal sepsis. There was a history of multiple episodes of fever spikes, recurrent vomiting, signs of dehydration such as depressed anterior fontanelle, and significant weight loss for 2 days. The baby was born to a diabetic mother at a 39-week 3-day period of gestation through a vaginal delivery. It was a difficult delivery, and the body weight of the baby was 4.02 kg.

Further, it was associated with shoulder dystocia managed with McRoberts maneuver and suprapubic pressure. Other significant perinatal history was the presence of meconium-stained liquor and birth asphyxia. Cord blood analysis at birth showed metabolic acidosis. There was a history of hypoglycemic episodes managed with 10% dextrose. The baby was in the nursery at the time of birth on continuous positive airway pressure ventilation, which was weaned on day 2 of life, and subsequently, the baby was shifted to the ward. On admission in the nursery (day 6), multiple erythematous firm nodules were noted on the back. Later, these nodules spread to the shoulders, anteromedial aspect of the thighs, and lateral part of the arms [Figure 1]. C-reactive protein (CRP) was elevated (480 mg/dl). Total leukocyte count was elevated (19,800), but platelet count was low (88,000). Hemoglobin, liver function tests, and renal function tests were within normal limits. The baby was started on intravenous antibiotics due to suspicion of neonatal sepsis while awaiting blood culture reports. Blood culture turned out to be sterile. Serum calcium was elevated (total serum calcium was 13.2 mg/dl and ionized calcium was 8 mg/dl). Skin biopsy was performed from a subcutaneous nodule with a provisional diagnosis of subcutaneous fat necrosis. The biopsy report revealed an inflammatory histiocytic reaction with extensive necrosis. There were intracytoplasmic deposits present within the adipocytes that formed radial eosinophilic crystals representing the triglyceride crystals which were dissolved during histological processing of the slide. Thus, the diagnosis of subcutaneous fat necrosis of the newborn was confirmed. Intravenous antibiotics were stopped. The baby was managed by maintaining adequate hydration, a diet deficient in calcium and Vitamin D, breastfeeding, and calcium-wasting diuretics. The neonate was observed for 2 weeks in the neonatal nursery. Eventually, some of the nodules regressed spontaneously [Figure 2]. Ionized calcium levels decreased (6.6 mg/dl) followed by the normalization of platelet count, but CRP was persistently elevated at low concentrations for a few weeks. The baby was discharged at 4 weeks of life. At discharge, ionized calcium levels further decreased to 5.98 mg/dl. The newborn was followed up in the outpatient department weekly with serum calcium and renal function tests. These lesions spontaneously resolved in 3 months with normalization of serum ionized calcium levels (5.2 mg/dl). After the resolution of the lesions, serum ionized calcium levels were followed once in 2 weeks up to the age of 6 months, which were within the normal limits (4.9–5.2 mg/dl).{Figure 1}{Figure 2}

 Discussion



A thorough literature search was done using words “subcutaneous fat necrosis,” “SFN,” and “SCFN” on PubMed, Medline, and Google Scholar databases.

Subcutaneous fat necrosis (SCFN) in the newborn results from inflammation of the subcutaneous fatty tissue. It typically presents with the erythematous nodules, isolated or clustered usually located on bony prominences, back, buttocks, arms, thighs, cheeks, and face.[3]

Hypercalcemia in these neonates leads to lethargy, irritability, hypotonia, polyuria, polydipsia, vomiting, dehydration, and constipation. These symptoms closely mimic neonatal sepsis. This patient was also mistaken for neonatal sepsis until these typical erythematous nodules developed on day 6 of life developed. The diagnosis was further confirmed by hypercalcemia and skin biopsy of a nodule. Thus, this differential of SCFN should be kept in mind while treating such patients to avoid unnecessary antibiotic exposure.

SCFN is associated with various maternal and fetal risk factors. Maternal risk factors include preeclampsia, gestational diabetes mellitus, iatrogenic (calcium channel blockers and cocaine), active or passive smoking, Rh isoimmunization, and traumatic delivery.[4] Fetal risk factors include cord prolapse, meconium aspiration, perinatal asphyxia, neonatal sepsis, and therapeutic hypothermia.[4],[5]

The pathophysiology of the disease is poorly understood. It results from impaired tissue perfusion resulting in tissue hypoxia due to cold- or stress-induced injury. It leads to subcutaneous fat crystallization in the neonate resulting in granulomatous reaction and tissue necrosis. Various hypotheses have been proposed for explaining hypercalcemia in these patients. The most widely accepted theory is the release of Vitamin D3 from these subcutaneous nodules which stimulate calcium uptake by the intestines.[6] Farooque et al. showed an increased expression of Vitamin D3-activating enzyme 1-alpha-hydroxylase in the skin biopsy sample of neonates with SCFN which explains increase Vitamin D levels and hypercalcemia in these neonates.[7]

Further, explanations given for hypercalcemia include the elevated levels of prostaglandin E and parathyroid hormone in these children, which stimulate bone resorption and hence hypercalcemia.[8] Increased prostaglandins also have a role to play initiating an inflammatory cascade resulting in thrombocytopenia, fever, and an increase in C-reactive protein levels.[8]

The diagnosis of SCFN is made by the presence of hypercalcemia and confirmed by skin biopsy. Histological findings include inflammatory histiocytic reaction with fat tissue necrosis. Extensive granulocytic infiltrate including macrophages, giant cells, eosinophils, and lymphocytes is present.[9] The frozen section reveals fat cells and giant cells containing radial crystals which stain with oil red O representing triglyceride deposition. Areas of calcification may be present.[9] Similar histopathological findings were noted in our patient. Imaging modalities including ultrasonography, computed tomography, and magnetic resonance imaging have a role in detecting soft-tissue calcification like nephrocalcinosis.[10]

Treatment in these patients is aimed at decreasing serum calcium levels. Maintaining adequate hydration and diet deficient in Vitamin D and calcium is helpful. Other drugs useful for the treatment of hypercalcemia include furosemide (calcium-wasting diuretic), prednisolone, and bisphosphonates (etidronate).[11],[12] Calcitonin is also an alternative treatment option for decreasing serum calcium levels in newborns with hypercalcemia.[13]

Calcium-wasting diuretics such as furosemide interfere with chloride-binding cotransport system and cause an increased excretion of water, sodium, calcium, magnesium, and chloride.[14]

Bisphosphonates such as etidronate have a valuable role in treating hypercalcemia in newborns with SCFN.[15],[16] They decrease bone resorption leading to a reduction in serum calcium levels.[17]

Corticosteroids such as prednisone are useful in SCFN because they decrease inflammation by inhibiting the release of inflammatory mediators, thereby decreasing capillary permeability.[2] Prednisone also inhibits the conversion of Vitamin D to its active form in the subcutaneous nodules of these newborns and therefore helps treat hypercalcemia.[14],[18]

Surgery is rarely needed in SCFN. Needle aspiration or surgical drainage of the fluctuant areas of fat necrosis is rarely done.[19]

The overall prognosis, if adequately treated, is excellent. It mostly results in self-resolution.[2] Hypertriglyceridemia may occur with the resolution of the lesions due to fatty acid mobilization from the necrotic adipose tissues.[3] Rarely, these areas of fat necrosis may result in scarring and ulceration. Some degree of subcutaneous atrophy is common.[2]

Delayed and inadequate treatment can lead to complications such as renal failure, sudden cardiac arrest, and metastatic calcifications (nephrocalcinosis; myocardial calcifications; calcification of the falx cerebri, liver, gastric mucosa, and inferior vena cava; and disseminated subcutaneous calcifications) owing to hypercalcemia.[3]

Periodic serum calcium monitoring in children with SCFN should be done in infants with a history of SCFN until the age of 6 months.[20] Serum calcium levels remain elevated for several months even after the resolution of subcutaneous fat necrosis.[6]

 Conclusion



SCFN usually has a favorable prognosis with spontaneous resolution within a few weeks to months. The symptoms of hypercalcemia in SCFN mimic neonatal sepsis and can lead to unnecessary exposure of the neonate to the antibiotics. These neonates should be periodically monitored for hypercalcemia, hypertriglyceridemia, hypoglycemia, and thrombocytopenia. Delayed diagnosis can lead to severe complications such as renal failure, sudden cardiac arrest, and metastatic calcifications. Periodic serum calcium monitoring should be done in infants with a history of SCFN until the age of 6 months.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Acknowledgment

We are extremely thankful to the parents of the newborn for their immense co-operation and for allowing us to publish the case and the photograph.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Wiadrowski TP, Marshman G. Subcutaneous fat necrosis of the newborn following hypothermia and complicated by pain and hypercalcaemia. Australas J Dermatol 2001;42:207-10.
2Shumer DE, Thaker V, Taylor GA, Wassner AJ. Severe hypercalcaemia due to subcutaneous fat necrosis: Presentation, management and complications. Arch Dis Child Fetal Neonatal Ed 2014;99:F419-21.
3Tran JT, Sheth AP. Complications of subcutaneous fat necrosis of the newborn: A case report and review of the literature. Pediatr Dermatol 2003;20:257-61.
4Rubin G, Spagnut G, Morandi F, Valerio E, Cutrone M. Subcutaneous fat necrosis of the newborn. Clin Case Rep 2015;3:1017-20.
5Verma S, Bailey SM, Mally PV, Wachtel EV. Subcutaneous fat necrosis and hypercalcemia after therapeutic hypothermia in patients with hypoxic-ischemic encephalopathy: A case series. Cureus 2018;10:e3074.
6Puzenat E, Aubin F, Zyka F, Fromentin C, Humbert P. Subcutaneous fat necrosis of the newborn with hypercalcemia. Ann Dermatol Venereol 2000;127:1087-9.
7Farooque A, Moss C, Zehnder D, Hewison M, Shaw NJ. Expression of 25-hydroxyvitamin D3-1alpha-hydroxylase in subcutaneous fat necrosis. Br J Dermatol 2009;160:423-5.
8Sharata H, Postellon DC, Hashimoto K. Subcutaneous fat necrosis, hypercalcemia, and prostaglandin E. Pediatr Dermatol 1995;12:43-7.
9Tajirian A, Ross R, Zeikus P, Robinson-Bostom L. Subcutaneous fat necrosis of the newborn with eosinophilic granules. J Cutan Pathol 2007;34:588-90.
10Vasireddy S, Long SD, Sacheti B, Mayforth RD. MRI and US findings of subcutaneous fat necrosis of the newborn. Pediatr Radiol 2009;39:73-6.
11Pérez Martínez E, Camprubí Camprubí M, Ramos Cebrián M, Antón López J, Apodaca Saracho A, Lopez Ramos MG, et al. Treatment with bisphosphonates in severe hypercalcemia due to subcutaneous fat necrosis in an infant with hypoxic-ischemic encephalopathy. J Perinatol 2014;34:492-3.
12Canpolat N, Özdil M, Kuruǧoǧlu S, Çalışkan S, Sever L. Nephrocalcinosis as a complication of subcutaneous fat necrosis of the newborn. Turk J Pediatr 2012;54:667-70.
13Alsofyani KA. Neonatal subcutaneous fat necrosis with hypercalcemia treatment using calcitonin. Saudi Med J 2018;39:622-6.
14Latos DL, Valentine AM. Treatment of hypercalcemia with furosemide and corticosteroids. W V Med J 1973;69:52-4.
15Di Bari JA, Nead JA, Schurman SJ. Zoledronic acid for neonatal subcutaneous fat necrosis. Clin Case Rep 2017;5:567-9.
16Bachrach LK, Lum CK. Etidronate in subcutaneous fat necrosis of the newborn. J Pediatr 1999;135:530-1.
17Rice AM, Rivkees SA. Etidronate therapy for hypercalcemia in subcutaneous fat necrosis of the newborn. J Pediatr 1999;134:349-51.
18Borgia F, De Pasquale L, Cacace C, Meo P, Guarneri C, Cannavo SP. Subcutaneous fat necrosis of the newborn: Be aware of hypercalcaemia. J Paediatr Child Health 2006;42:316-8.
19Beuzeboc Gérard M, Aillet S, Bertheuil N, Delliere V, Thienot S, Watier E. Surgical management of subcutaneous fat necrosis of the newborn required due to a lack of improvement: A very rare case. Br J Dermatol 2014;171:183-5.
20Akın MA, Akın L, Sarıcı D, Yılmaz I, Balkanlı S, Kurtoǧlu S. Follow-up during early infancy of newborns diagnosed with subcutaneous fat necrosis. J Clin Res Pediatr Endocrinol 2011;3:216-8.