Subcutaneous fat necrosis of the newborn (SFNN) is an uncommon disorder characterized by firm, mobile, erythematous nodules and plaques over the trunk, arms, buttocks, thighs, and cheeks of full-term newborns.[1, 2] The nodules and plaques appear in the first several weeks of life. Subcutaneous fat necrosis of the newborn usually runs a self-limited course, but it may be complicated by hypercalcemia and other metabolic abnormalities.[1, 2]
The exact pathogenesis of subcutaneous fat necrosis of the newborn (SFNN) is not known. It is postulated that cold or stress-induced injury to immature fat cells results in the development of solidification and necrosis. A granulomatous infiltrate forms, which, through various pathways, may lead to life-threatening hypercalcemia. Staining of biopsy specimens demonstrates increased levels of 1alpha-hydroxylase within the granulomatous infiltrate, as is seen in other granulomatous conditions such as sarcoidosis.[3] Alpha-hydroxylase promotes the conversion of 25 OH D3 to its active form 1,25 OH 2D3; the latter increases intestinal absorption of calcium and calcium mobilization from bones, potentially leading to hypercalcemia.[1, 4, 5] Elevated levels of prostaglandin (PG) E2 have been reported in subcutaneous fat necrosis of the newborn.[6] and may contribute to hypercalcemia through a different pathway.
Alternative explanations for hypercalcemia include the release of calcium from necrotic fat cells or elevated parathyroid hormone (PTH) levels that indirectly increase serum calcium by promoting osteoclast activity.[7] A child with cyanotic heart disease treated with prostaglandins (intravenous PGE1) to maintain patent ductus arteriosus developed subcutaneous fat necrosis of the newborn; when the PGE1 was discontinued, the subcutaneous fat necrosis of the newborn resolved.[6] Elevated prostaglandins contribute to the inflammatory cascade that follows, marked by thrombocytopenia, high acute-phase reactants such as C-reactive protein, and fever.[8, 9] The latter has been attributed to increased levels of PGE2 and granuloma production of interleukin 1.
The cause of subcutaneous fat necrosis of the newborn (SFNN) is not known. Hypothermia is a common antecedent. The brown fat of neonates has a greater ratio of saturated palmitic acid to unsaturated oleic acid. Palmitic acid has a higher melting point than oleic acid, making it more susceptible to solidification and crystallization in response to lowered temperature. Many cases of subcutaneous fat necrosis of the newborn have been reported in newborns who sustained perinatal hypoxic-ischemic injury and were treated by hypothermia to prevent encephalopathy and serious brain injury.[10, 11, 12, 13] Cases of subcutaneous fat necrosis of the newborn have been reported after both whole-body cooling[14, 15, 16] and selective head-cooling.[17] One infant developed subcutaneous fat necrosis of the newborn after ice-bag placement for the treatment of supraventricular tachycardia[18] and another after hypothermic cardiac surgery.[1, 19]
Other neonatal stresses that have been associated with subcutaneous fat necrosis of the newborn include cesarean delivery,[1, 4, 20, 21] Rh factor incompatibility, meconium aspiration,[21] placenta previa, umbilical cord prolapse, anoxia, seizures,[21] preeclampsia, maternal cocaine abuse,[22] gestational diabetes,[23] maternal use of calcium antagonists during pregnancy,[24] familial dyslipidemia, and a family history of thrombophilia.[23] Some evidence implicates a maternal hypercoagulable state such as protein C deficiency and antiphospholipid syndrome.[23] Local pressure trauma during delivery from forceps, from prolonged labor, and from being large for gestational age (macrosomia) may play a role.[20, 21]
Frequency is unknown; subcutaneous fat necrosis of the newborn (SFNN) is rare.
Race
Race does not play a role.
Sex
Sex does not play a role.
Age
Subcutaneous fat necrosis of the newborn (SFNN) occurs in the first several weeks of life.[1, 2, 4] Hypercalcemia, if it occurs, begins in children aged 1-2 months.
Overall, the prognosis for subcutaneous fat necrosis of the newborn (SFNN) is excellent. Self-resolution without sequelae is the norm. It is a harmless, self-limited condition. As the lesions regress, hypertriglyceridemia may result from the mobilization of fatty acids from the affected adipose tissue. There may be atrophic scars.
The areas of fat necrosis may rarely progress to scarring or ulceration. Some degree of subcutaneous atrophy is common.[23] Soft tissue calcification may last for years. Nephrocalcinosis without evidence of adverse renal outcomes has been reported to persist up to 4 years after follow-up.[25] Rarely, significant morbidity (seizures, blindness, failure to thrive) and even mortality (from infection and cardiac arrest) can result from the associated hypercalcemia.[1, 26]
Newborns who develop subcutaneous fat necrosis of the newborn (SFNN) are usually healthy and full-term at delivery, although reports have described children with subcutaneous fat necrosis of the newborn who were born with macrosomia or postterm with normal size.[23] Most have had some antecedent obstetric trauma, meconium aspiration, asphyxia, hypothermia, or peripheral hypoxemia. Congenital ulceration has been reported.
Infants with subcutaneous fat necrosis of the newborn (SFNN) usually appear well. The condition begins as an area of edema and progresses to variably circumscribed nodules and plaques that have a deep, indurated feel, implying a panniculitis. The overlying skin may be flesh-colored, red, or purple and may look taut and shiny. The lesions are not warm and are commonly seen on the trunk, arms, buttocks, thighs, or cheeks. Pain may occur, with a frequency as high as 25% in one series.[23] As the lesions progress, they may become fluctuant and spontaneously drain necrotic fat.
See the images below.
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Ill-defined erythema overlying an indurated plaque of a newborn.
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Bruiselike indurated plaque of subcutaneous fat necrosis of the newborn on the lower back of a newborn.
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Ill-defined erythema and induration of subcutaneous fat necrosis of the newborn on the posterior calf of a newborn.
If mild hypercalcemia is present, findings might be absent or the child may display weight loss, irritability, lethargy, anorexia, apathy, constipation, or hypotonia. With severe hypercalcemia, examination may reveal failure to thrive, growth and mental retardation, vomiting, hypertension, seizures, shortening of the QT interval with cardiac arrhythmias, or renal failure. Tissue calcifications, including nephrocalcinosis (calcium deposition in the renal parenchyma), have been reported.[23] One case of hepatic and atrial myocardial calcification has been reported.[27]
Thrombocytopenia, anemia, hypoglycemia, and hyperlipidemia have also been reported in subcutaneous fat necrosis of the newborn (SFNN) and require close laboratory monitoring. Thrombocytopenia can be a clinical marker of asphyxia and is thought to result from elevated prostaglandin levels in areas of necrosis or increased platelet aggregation in the subcutaneous tissue of affected areas.[7] When inflammation resolves, so does the thrombocytopenia; bleeding problems are rare.[28]
Because perinatal stress associated with gestational diabetes increases infant susceptibility to subcutaneous fat necrosis of the newborn, it is unclear whether hypoglycemia in some subcutaneous fat necrosis of the newborn patients is a complication of subcutaneous fat necrosis of the newborn itself or due to elevated levels of insulin that result from gestational diabetes.[28] Hypertriglyceridemia is postulated to be a result of very low-density lipoprotein cholesterol release from necrotic fat; the triglycerides can be visualized as crystals in the cytoplasm of necrotic adipocytes.[28]
Screening for hypercalcemia is important since morbidity is far more likely to result from severe hypercalcemia than from the skin lesions of subcutaneous fat necrosis of the newborn (SFNN). A study by Shumer et al in 2014 found that 43% of infants with subcutaneous fat necrosis of the newborn and severe hypercalcemia (≥3 mmol/L before age 6 wk) were asymptomatic.[25] Calcium levels should be monitored at least biweekly[29] for several months. Shumer et al also reported that 6 of 7 infants with subcutaneous fat necrosis of the newborn and severe hypercalcemia had eosinophilia.[25]
Imaging studies such as ultrasonography, computed tomography, and magnetic resonance imaging have been used to aid in the diagnosis but are not necessary to diagnose subcutaneous fat necrosis of the newborn (SFNN).[1, 30, 31, 32]
In the setting of hypercalcemia, imaging studies may be useful to document the extent of tissue calcification (eg, in nephrocalcinosis).
Skin biopsy that includes subcutaneous fat is the traditional way to make a diagnosis. Punch biopsy can be adequate as long as it harvests subcutaneous fat. It has also been suggested that fine-needle aspiration biopsy, which is minimally invasive and far quicker, can be just as accurate.[33]
Key histological findings in subcutaneous fat necrosis of the newborn (SFNN) include fat lobule necrosis, crystallization of fat, and lipocytes present in a radial arrangement.[34] Patchy areas of fat necrosis are surrounded by a granulomatous infiltrate of lymphocytes, macrophages, and giant cells. Many of the fat cells and giant cells contain needle-shaped clefts that often lie in a radial arrangement. Frozen sections reveal doubly refractive crystals that stain with oil red O.[1, 35] Small foci of calcium are scattered throughout the necrotic fat, and, sometimes, extensive areas of calcification may be present. Biopsy specimens of older lesions may demonstrate fibrosis. Reports have described multinucleated giant cells containing eosinophilic granules, perhaps released from surrounding degranulating eosinophils.[1, 36]
Fine-needle aspiration findings depend on the stage of evolution. Early stages show minimal inflammation and minimal necrosis. Fat cells have a crystalline shape. Later stages show more advanced necrosis, inflammation with phagocytosis of cellular debris, and crystallization.[33]
See the image below.
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Histological slides of early and later stages of subcutaneous fat necrosis of the newborn after fine-needle aspiration biopsy. Courtesy of Elsevier (E....
Subcutaneous fat necrosis of the newborn (SFNN) is usually a self-limited process that does not require treatment. Interventions have focused on the prevention of subcutaneous fat necrosis of the newborn in the setting of hypothermia, the treatment of hypercalcemia, and pain management.
To reduce the likelihood of developing subcutaneous fat necrosis of the newborn in infants with hypoxic ischemic encephalopathy who were treated with moderate whole-body hypothermia, the following steps have been suggested[23] :
Periodic mobilization of infants
Use of a gentler cooling blanket that induces hypothermia gradually without abrupt temperature changes
Such an approach was associated with a lower incidence of subcutaneous fat necrosis of the newborn, lower C-reactive protein levels, lower serum calcium, and a higher number of platelets.[23]
Hypercalcemia should be treated aggressively with fluid loading and calcium-wasting diuretics such as furosemide. Infants should be on a low-calcium, low-vitamin D diet. Prednisone may be used if these measures fail; it interferes with the conversion of vitamin D to its active form in the subcutaneous fat necrosis of the newborn granulomas.[1, 35] Bisphosphonates, which reduce bone resorption, have also been used to treat hypercalcemia.[1, 37, 38, 39, 40] Administration of pamidronate for 3 consecutive days (0.25-, 0.25-, and 0.50-mg/kg/dose, respectively) has successfully restored normocalcemia.[41] Shumer reported that the combination of intravenous hydration, furosemide, glucocorticoids, and low-calcium diets restored normocalcemia in 9 days.[25]
For pain management in infants with subcutaneous fat necrosis of the newborn, dexmedetomidine is a good choice because of its minimal adverse effects on respiratory and gastrointestinal function.[42] Alternatively, morphine (1-2 mg 4 times per day) and prednisone (1 mg/kg per day) may act synergistically to manage pain.
Consultations include a dermatologist or pediatric dermatologist. A plastic surgeon or pediatric surgeon may be needed if aggressive debridement is warranted.
Because serum calcium may be elevated for several months after the resolution of subcutaneous fat necrosis of the newborn (SFNN), calcium levels should be checked periodically for at least 4 months.[1]
Clinical Context:
Furosemide increases excretion of calcium through diuresis. Furosemide increases the excretion of water by interfering with the chloride-binding co-transport system, which, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle and distal renal tubule. It causes increased excretion of water, sodium, chloride, magnesium, and calcium.
Clinical Context:
Prednisone may decrease inflammation by suppressing polymorphonuclear cell (PMN) activity, decreasing mediators of inflammation such as interleukins, and reversing increased capillary permeability.
Prednisone interferes with the conversion of vitamin D to its active form in the subcutaneous fat necrosis of the newborn granulomas and, thus, may be used to treat hypercalcemia.
Dirk M Elston, MD, Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine
Disclosure: Nothing to disclose.
Specialty Editors
David F Butler, MD, Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic
Disclosure: Nothing to disclose.
Edward F Chan, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania School of Medicine
Disclosure: Nothing to disclose.
Chief Editor
William D James, MD, Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine
Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD.
Additional Contributors
Daniel Mark Siegel, MD, MS, Clinical Professor of Dermatology, Department of Dermatology, State University of New York Downstate Medical Center
Disclosure: Nothing to disclose.
Acknowledgements
Howard Pride, MD Associate Physician, Departments of Pediatrics and Dermatology, Geisinger Medical Center
Howard Pride is a member of the following medical societies: American Academy of Dermatology and Society for Pediatric Dermatology
Hoath SB, Fanaroff AA, Walsh MC, eds. The Skin. Fanaroff and Martin’s Neonatal-Perinatal Medicine: Diseases of the Fetus and Infant. 9th ed. St. Louis, Mo: Elselvier Mosby; 2011. 1705.
Ill-defined erythema overlying an indurated plaque of a newborn.
Bruiselike indurated plaque of subcutaneous fat necrosis of the newborn on the lower back of a newborn.
Ill-defined erythema and induration of subcutaneous fat necrosis of the newborn on the posterior calf of a newborn.
Histological slides of early and later stages of subcutaneous fat necrosis of the newborn after fine-needle aspiration biopsy. Courtesy of Elsevier (Elston DM, Ferrringer T, Ko CJ, et al. Panniculitis. In: Dermatopathology. 2nd ed. Elsevier Limited; 2014:249-56).
Ill-defined erythema overlying an indurated plaque of a newborn.
Bruiselike indurated plaque of subcutaneous fat necrosis of the newborn on the lower back of a newborn.
Ill-defined erythema and induration of subcutaneous fat necrosis of the newborn on the posterior calf of a newborn.
Histological slides of early and later stages of subcutaneous fat necrosis of the newborn after fine-needle aspiration biopsy. Courtesy of Elsevier (Elston DM, Ferrringer T, Ko CJ, et al. Panniculitis. In: Dermatopathology. 2nd ed. Elsevier Limited; 2014:249-56).
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