J-LSMS 2014 | Annual Archive

Journal of the Louisiana State Medical Society

giant cells, with or without calcifications. The background appearance may range from scanty inflammation with no significant necrosis of adipocytes to numerous inflammatory cells with dirty necrotic background, depending on the stage of the disease. 15 DIFFERENTIAL DIAGNOSIS The differential diagnosis of SCFN can be broad, and clinicopathologic correlation is essential to make the correct and timely diagnosis so that appropriate measures can be taken to prevent the potential serious complication hyper- calcemia. 14 When fluctuant nodules or skin rashes are present, especially in critically ill or immunocompromised patients, infectious etiology such as bacterial cellulitis, toxic shock syn- drome, abscess, and erysipelas should be ruled out first. Skin and subcutaneous infection generally manifests in warmth, swelling, and pain of the lesion, whereas SCFN remains normothermic to palpation. Histopathologically, infection of skin and subcutaneous tissue can show mostly neutrophilic lobular panniculitis or suppurative granulomas, which may require special stains (Gram, periodic acid-Schiff, acid-fast stain) to identify pathogenic microorganisms. Cultures of skin lesions may be necessary if special stains fail to detect pathogens and clinical suspicion for infection remains high. Needle-shaped clefts are generally absent in adipocytes. Skin lesions due to infection usually resolve with systemic antibiotic therapy. Cold panniculitis is inflammation of subcutaneous adipose tissue caused by direct exposure to cold. The clinical appear- ance of cold panniculitis may overlap with early stage SCFN. It usually has no maternal factors and tends to occur within 72 hours of cold exposure. Clinically, it usually presents as red-blue indurated plaques or nodules. Histopathologically, cold panniculitis is a lobular panniculitis with nonspecific inflammatory infiltrate of lymphocytes and histiocytes, most prominent at the dermosubcutaneous junction in the fat lobules and without needle-shaped clefts and adipocyte necrosis. Cold panniculitis generally resolves spontaneously after further cold exposure is avoided. Sclerema neonatorum is a very rare panniculitis affecting primarily ill preterm neonates in the first week of life. Unlike SCFN, which has aforementioned risk factors, sclerema neo- natorum usually has no maternal factors with an uneventful delivery and is often associated with congenital anomalies, serious respiratory illness, and sepsis. Sclerema neonatorum manifests as diffuse hardening of the skin - sparing soles, palms, and genitalia - which firmly attaches to the underneath muscle and bone, leading to impaired feeding and breath- ing; whereas SCFN presents as circumscribed hardening of the skin, which moves freely over the underneath muscle and bone. Histopathologically, sclerema neonatorum is characterized by thickening of the connective tissue septa of the subcutaneous fat; absent to sparse inflammatory in- filtrate of lymphocytes, histiocytes and multinucleate giant cells; radially arranged needle-shaped clefts in adipocytes;

and absence of adipocyte necrosis and calcification. Unlike SCFN, which is localized and self-limiting with an excellent prognosis, sclerema neonatorum rapidly generalizes and has a poor prognosis with amortality rate of 75%. The presence of needle-shaped clefts is rather a nonspecific feature for SCFN and sclerema neonatorum, and hence, clinical presentation and degree of inflammation aremore important for diagnosis. Scleredema is a rare and self-limiting skin condition affect- ing primarily preterm neonates in the first week of life. The risk factors of scleredema include cold injury, dehydration, diarrhea, vomiting, and infection. Clinically, scleredema manifests as generalized firmpitting edema more commonly seen in lower extremities. Histopathologically, scleredema is characterized by a lobular panniculitis with inflammation and marked edema of skin and subcutaneous tissue without needle-shaped clefts and adipocyte necrosis. The prognosis of scleredema is good, and skin lesions heal spontaneously with supportive care. Poststeroid panniculitis is a rare panniculitis occurring in neonates who had an abrupt taper or sudden withdrawal of high-dose systemic corticosteroids therapy. Clinically, post- steroid panniculitis presents as erythematous nodules on the cheek and chin within days to weeks after the withdrawal of corticosteroids. Histopathologically, poststeroid panniculitis can mimic SCFN by displaying a mixed inflammation of less intensity, as well as needle-shaped clefts in adipocytes and histiocytes. PATHOGENESIS The pathogenesis of SCFN and hypercalcemia is unclear. It has been suggested that perinatal events, such as birth as- phyxia or hypothermia, can shunt blood fromperipheral skin and subcutaneous tissue to central vital organs and result in subcutaneous stresses, e.g. hypoperfusion and hypoxemia, which in turn lead to injury and crystallization of adipocytes, inflammation, and granulomatous reaction. Normal adipose tissue contains triglycerides in a variable proportion of satu- rated and unsaturated fatty acids. The neonatal adipose tissue has a higher ratio of saturated to unsaturated fatty acids than the adult counterpart, which determines a higher melting point and a lower solidification point of the adipose tissue. These unique features predispose neonatal adipose tissue to an increased risk for crystallization on exposure to stress factors such as hypothermia. The most popular hypothesis of hypercalcemia in SCFN is the extrarenal production of 1, 25-(OH) 2 D 3 , leading to increased intestinal absorption of calcium. SCFN can ex- hibit a strong expression of 1 a -hydroxylase in inflammatory infiltrate, suggesting that 1, 25-(OH) 2 D 3 may be produced by macrophages in subcutaneous granulomas. 1 However, Burden et al. showed that elevated serum 1, 25-(OH) 2 D 3 was observed in only one out of four patients. 2 Therefore, other possible mechanisms such as activation of osteoclasts and enhanced bone calcium turnover resulting from elevated prostaglandin E2 may also play a role in the pathogenesis of hypercalcemia.

98 J La State Med Soc VOL 166 May/June 2014

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