Subcutaneous Fat Necrosis of the Newborn

Etiology

The etiology of subcutaneous fat necrosis of the newborn is unknown, but precipitating factors, such as asphyxia, hypothermia, meconium aspiration, obstetric trauma, and some systemic maternal diseases such as preeclampsia and diabetes, may play a role in the development of SCFN.[3] The role of hypothermia as a potential eliciting factor has additionally been suggested in newborns undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy (HIE). In a retrospective study of Del Pozzo-Magana and Ho, authors found 11 from 12 patients (91.1%) exposed to therapeutic hypothermia for HIE developed SCFN.[4] Additionally, local trauma during delivery may play a role in SCFN, although this condition has been described in multiple infants born by Caesarean delivery.[5]

Epidemiology

In a 20-year retrospective study conducted by Del Pozzo-Magana and Ho, only 30 cases were collected, affecting both males and females; all newborns were born at more than 37 weeks gestational age, with an average birth weight of 3800 g. Ninety percent had a history of a complicated delivery.[4] In a more extensive systematic review of the literature done by Stefanko et al., 126 patients with NSFN were included, with an incidence similar in males and females. The majority of patients (90%) were born at more than 37 weeks gestational age, with an average birth weight of 3455 g. In 20% of the cases, therapeutic hypothermia or body cooling was reported. 86% of the patients experienced intrauterine/perinatal distress.[3]

Pathophysiology

The pathogenesis of subcutaneous fat necrosis of the newborn is not entirely known. The organization of neonatal fat with high saturated fatty acids and its higher melting point in comparison with adult fat leads to a tendency for solidification and crystallization.[3] In regards to the extracutaneous abnormalities observed in SCFN, hypercalcemia is considered to be secondary to the granulomatous essence of SCFN, with increased macrophage activity, with subsequent expression of 1-alpha-hydroxylase, improving the intestinal absorption of calcium and its mobilization from bones after converting 25-hydroxyvitamin D3 to the active 1,25-dihydroxyvitamin D3.[6] Thrombocytopenia appears concurrently with the development of subcutaneous nodules. It is deemed to be caused by peripheral platelet sequestration, and dyslipidemias are caused by the mobilization of fatty acids from adipose tissue.[2]

Histopathology

The histopathologic changes in subcutaneous fat necrosis of the newborn include predominantly lobular panniculitis with a chronic inflammatory infiltrate, needle-shaped crystals inside macrophages, and adipocytes. Multinuclear giant cells and focal areas of calcification may also be discerned distributed throughout the necrotic fat.[5]

History and Physical

The median age of onset of skin lesions is six to ten days; 92% develop lesions in the first 28 days of life (56% in the first week).[3] SCFN is characterized by circum­scribed, mobile, erythematous-violaceous, subcutaneous nodules, or plaques. The lesions range from single small nodules (<1 cm) to multiple large nodules up to 8 cm in diameter.[7] According to Del Pozzo-Magana and Ho described that the most frequent clinical manifestations are subcutaneous nodules (100%), erythema (73%), pain (23%), and edema (13%). Arms and shoulders are the most frequently involved areas (57%).[4] Although mostly firm, lesions can become fluctuant and rupture, with subsequent drainage of a necrotic, chalk-like fatty substance.[7]

Of 126 studied infants, 51% developed hypercalcemia, more commonly identified in the neonatal period (57%), with 30% detected in the second month of life. Approximately half of the patients with hypercalcemia exhibited symptoms, including irritability, poor feeding, polyuria, polydipsia, constipation, hypotonia, failure to thrive, persistent nephrocalcinosis, and seizures.[3]

Evaluation

Timely identification of this condition is critical as it can additionally display significant extracutaneous abnormalities, including thrombocytopenia, hypertriglyceridemia, and hypercalcemia. For the most definitive diagnosis, both clinical presentation and skin biopsy must be considered.[6] However, to avoid skin biopsy, ultrasonography examination, along with Doppler blood flow analysis, has been proven to be effective in detecting subcutaneous fat necrosis of the newborn, it typically indicates subcutaneous high echo signal with or without calcifications.[8]

Del Pozzo-Magaña and Ho suggested guidelines for monitoring patients with SCFN. Once SCFN is diagnosed, serum levels of triglycerides, renal function tests, platelets, and glucose should be determined. In patients with normal values, only clinical follow-up is required. It is imperative to measure serum levels of ionized calcium in normocalcemic patients, it should be repeated weekly during the first month of life and then monthly until six months of age or after the resolution of skin lesions. Also, it is crucial to perform a renal ultrasound, especially in patients with hypercalcemia. When the initial imaging is normal, it can be repeated at three months of age or after the resolution of skin lesions.[4]

Treatment / Management

Treatment is mainly supportive, as cutaneous lesions resolve spontaneously in the majority of cases. Hypercalcemia should be aggressively corrected with hyperhydration, intravenous loop diuretics, and low calcium and vitamin D formulas; in refractory cases, bisphosphonate and systemic corticosteroids are recommended.[9](B3)

Differential Diagnosis

The primary differential diagnosis of subcutaneous fat necrosis of the newborn is sclerema neonatorum, extensive and symmetric sclerosis of the skin and subcutaneous fat; it is mostly reported in ill premature newborns; sclerema neonatorum is associated with congenital malformations, while SCFN is a self-limited benign condition, sclerema neonatorum carries a high mortality rate. Another differential diagnosis is neonatal scleroderma, which presents with progressive edema of the lower extremities; even though it is considered benign, gastrointestinal or respiratory infections usually precede it.[10]

Prognosis

Subcutaneous fat necrosis of the newborn is frequently a transitory, self-resolving condition. It resolves spontaneously within months and is likely to be underdiagnosed. Notwithstanding, it may be complicated by several hazardous hematologic and metabolic alterations that are crucial to monitor, including thrombocytopenia, hypoglycemia, hypertriglyceridemia, and, most importantly, hypercalcemia. Management of patients with SCFN requires regular clinical follow-up for at least six months and laboratory monitoring of potential complications.[11]

In the study of Mahé et al., the meantime to recovery from SCFN was 86 days (range 25 to 180). After resolution, patients may develop residual lipoatrophy. Resolution of the thrombocytopenia occurs subsequently to the resolution of SCFN.[12]

Stefanko et al. noticed that in 88% of the patients with hypercalcemia, the condition resolved within the first 84 days of life; nevertheless, one patient still had hypercalcemia at one year of age.[3]

The associated hypercalcemia has the potential to induce significant kidney damage if left untreated, so it is essential to estimate kidney involvement with a renal sonogram. Nephrocalcinosis was present in 83% of patients evaluated by renal ultrasound.[13]

Complications

Subcutaneous fat necrosis of the newborn commonly follows an uncomplicated course with spontaneous resolution over many weeks. Still, there are rare but serious complications for which the infant must be periodically observed: the most common abnormalities are thrombocytopenia, hypoglycemia, hypertriglyceridemia, and, most importantly, hypercalcemia. The pathophysiology of those complications is not entirely understood.[2]