Journal of Perinatology (2008) 28, 453–460 r 2008 Nature Publishing Group All rights reserved. 0743-8346/08 $30 www.nature.com/jp STATE-OF-THE-ART Sclerema neonatorum: a review of nomenclature, clinical presentation, histological features, differential diagnoses and management

A Zeb and GL Darmstadt Department of International Health, International Center for Advancing Neonatal Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA

Introduction Objective: To review published literature on sclerema neonatorum (SN) in Sclerema neonatorum (SN) is classified under the Panniculitides, order to clarify its clinical presentation, histological features and a group of heterogeneous inflammatory diseases involving the management compared with two other diseases: subcutaneous fat necrosis subcutaneous adipose tissue.1,2 SN usually affects gravely ill, preterm of the newborn (SCFN) and scleredema. neonates in the first week of life.3–5 Itmanifestsasahardeningof Study Design: PubMed database was searched using the key words skin and subcutaneous adipose tissue to such an extent that it hinders Sclerema neonatorum. A total of 55 articles from peer-reviewed journals feeding and respiration, and usually culminates in death. were reviewed and summarized. Sclerema neonatorum was first described in the early nineteenth Result: SN, SCFN and scleredema are diseases of the subcutaneous century, and initially was confused by some authorities with adipose tissue. SN is characterized by hardening of the skin that gets scleredema. In the early twentieth century, when cases of bound down to the underlying muscle and bone, hindering respiration subcutaneous fat necrosis of the newborn (SCFN) were being and feeding and is associated with congenital anomalies, cyanosis, reported, they were initially classified erroneously as SN, thus 3,6–8 respiratory illnesses and sepsis. Histology of the skin biopsy shows adding to the existing confusion in nomenclature. 9 thickening of the trabeculae supporting the subcutaneous adipose tissue The last review on SN was published 20 years ago. In this paper, and a sparse inflammatory infiltrate of lymphocytes, histiocytes and we review the historical background of SN, its clinical presentation, multinucleate giant cells. SCFN has circumscribed hardening of skin on histological features and the differentiating features from SCFN and bony prominences with necrosis of adipocytes in subcutaneous tissue and scleredema. SN has a high case fatality rate, unlike the other two a dense granulomatous infiltrate on histology. Scleredema is conditions, which makes timely diagnosis and treatment important. characterized by hardening of the skin along with edema; histology shows inflammatory infiltrate and edema in skin and subcutaneous tissues. SN has a high case fatality rate whereas SCFN and scleredema are Methodology self-limiting and lesions resolve within a few weeks to months. A search of the PubMed database using the key words, sclerema Exchange transfusion may improve survival in SN. neonatorum, identified 180 articles. Those published in peer- reviewed journals and in English language were included in the Conclusion: The histological features of skin biopsy should be used to final review. Articles on SCFN and scleredema were also sought in establish diagnosis of SN, SCFN and scleredema as disease-specific the PubMed database using as search terms the names for treatment is imperative in SN due to high fatality. these conditions, and were reviewed to inform the discussion of Journal of Perinatology (2008) 28, 453–460; doi:10.1038/jp.2008.33; differential diagnoses. Snowballing technique was used to published online 27 March 2008 identify additional pertinent literature cited in the articles Keywords: neonatal; scleredema; subcutaneous fat necrosis of the reviewed. The total number of articles on SN that were reviewed in newborn; subcutaneous tissue detail and summarized was 55.

Correspondence: Professor GL Darmstadt, Department of International Health, International Center for Advancing Neonatal Health, Bloomberg School of Public Health, Johns Hopkins Results University, 615 North Wolfe Street, Baltimore, MD 21205, USA. History of nomenclature E-mail: [email protected] Received 19 October 2007; revised 23 January 2008; accepted 14 February 2008; published Sclerema neonatorum was first described as ‘acute sclerema’ in online 27 March 2008 1718 (Figure 1). Underwood presented a thorough description in Sclerema neonatorum A Zeb and GL Darmstadt 454

Scleredema Sclerema neonatorum (SN) Subcutaneous fat necrosis of the newborn (SCFN) Andry described “Endurcissement First described by Uzembezius as du tissue cellulaire” in 1785 (7,8) “Acute sclerema” in 1718 (3,6) Cases were reported as “Sclereme des adultes” in 1845 (7,8) Underwood presented a detailed description in 1784 as “Skin Fabyan described the histology of bound” (3,6,7,8) subcutaneous fat necrosis in 1907 (6)

Andry assumed Endurcissement du tissue cellulaire and Skin bound Bernheimer-Karrer called the condition “Benign were the same diseases in 1785 (7, 8) Sclerema” in 1922 (6)

Chaussier introduced “Sclereme” for Endurcissement du tissue Gray declared SN and SCFN as the same diseases in cellulaire in 1815 (6,7,8) 1926 (7, 8)

Parrot called Endurcissement du tissue cellulaire, “Oedema neonatorum” and skin bound, “Sclerema neonatorum”in 1877 (7,8) Since 1926, confusion between SN and SCFN has persisted. Some researchers contend that they may be In 1890, Ballantyne accepted the view of French and Italian variants of the same disease as cases have been reported researchers, based on epidemiological data, that both diseases were presenting with features of both diseases, whereas other the same and applied the term Sclerema neonatorum to both SN researchers hold the opinion that SN and SCFN are two and scleredema (7,8) different diseases (6, 10, 11)

Since 1890, there is confusion between SN and scleredema. There have been reports of cases of scleredema under the name of SN and cases with mixed features of SN and scleredema (12, 13)

Figure 1 History of nomenclature of sclerema neonatorum.

1784 and again in 1819 under another name, ‘skin bound’.3,6–8 were declared the same diseases.7,8 Thus, these three disorders of Meanwhile, in 1785, a French physician described a disease that he adipose tissues, SN, SCFN and scleredema have had multiple called ‘Endurcissement du tissue cellulaire,’ now known as names applied to them and have been confused and labeled at scleredema; however, at that time it was considered the times as a single disease with the interchangeable use of the term same as SN.7,8 The year 1815 saw the introduction of a new term, SN for all three conditions. Thus, the considerable confusion in the ‘sclereme’ for ‘Endurcissement du tissue cellulaire’. The French literature and the rarity of these conditions has hindered systematic regarded this condition as equivalent to skin bound, though descriptions of their features and pathogenesis and development of Underwood was convinced that they were two different entities.6–8 advances in management. In 1877, a new term, ‘oedema neonatorum’ was introduced for Since 1926, confusion has persisted in diagnosis of these ‘Endurcissement du tissue cellulaire’, and ‘sclerema neonatorum’ three clinical entities that have different clinical and histological was used to refer to skin bound.7,8 This nomenclature was used presentations. There has been confusion in these diseases as until 1895, when it was noticed that SN was more commonly seen cases having mixed features of SN and SCFN,6,10,11 and SN and in France and Italy as compared to Great Britain, Germany, scleredema have been reported.12,13 These cases have been Austria, Russia, Spain, Switzerland and the United States. Based on published under the term of SN, thus adding more to the the epidemiological data, Ballantyne, a British physician, argued confusion, and will be discussed in detail under the section erroneously that SN and ‘oedema neonatorum’ were the same of differential diagnoses. disease. Subsequently, the term sclerema neonatorum was applied to both conditions, skin bound and ‘oedema Clinical presentation neonatorum’.7,8 Sclerema neonatorum is seen in the first few days after birth but Cases of SCFN were being reported since 1845 under the term may develop immediately postpartum or as late as several weeks of ‘Sclereme des adultes’. Fabyan described the histological picture of life. The skin in affected neonates is smooth, cool, tense, mottled subcutaneous fat necrosis in 1907 whereas Bernheimer-Karrer purplish and hard. The skin cannot be pitted nor can it be picked called it ‘benign sclerema’ in 1922.6 In 1926, both SN and SCFN up and pinched into a fold as the skin is bound down to subjacent

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Table 1 Summary of published case series on sclerema neonatorum

Author (year) No. of Gestational M:F ratio Onset Maternal and labor Associated conditions in the Survival cases age complication affected neonate N(%)

Hughes and 19 Most term 9:55 (not Within first Four had complications, Six had cyanosis and eleven 4 (21) Hammond14 documented) 7 days of including preeclampsia, low body temperature or (1948) birth eclampsia, placenta previa difficulty with temperature and cord compression control at birth Comorbidities: sepsis, jaundice, intestinal obstruction, ileocolitis, ‘bloody snuffles’, bilateral otitis, pneumonia, diarrhea, gangrene of extremities Warwick et al.4 18 Most preterm 11:7 Within first Nine had complications, Comorbidities: sepsis, respiratory 7 (39) (1963) 7 days of including precipitous problems multiple congenital birth delivery, fetal distress, anomalies PPROM, maternal hyperpyrexia, abruptio placentae, gestational diabetes, twin gestation Khetarpal and 17 Most preterm 11:6 Within first 15 had no complications Comorbidities: septicemia, 3 (17.6) Subrahmanyam15 7 days of jaundice (1964) birth Villacorte and Frank3 9 Most preterm 6:3 Within first Six had complications, All infants had mild to moderate 2 (22) (1967) 7 days of including PPROM, cord respiratory distress at or shortly birth around neck, asthmatic after birth; 5 also developed bronchitis, abruption jaundice placentae, twin gestation Bwibo and 16 Most preterm 9:7 Within 15 had no complications Comorbidities: RDS and 2 (12.5) Anderson22 14 days Salmonella enteritis (1970) of birth

Abbreviations: F, female; M, male; PPROM, preterm premature rupture of membranes; RDS, respiratory distress syndrome; SN, Sclerema neonatorum.

subcutaneous tissue, including muscle and bone. The process Histological features typically begins in the buttocks, thighs or trunk but may spread to The histological findings of sclerematous skin lesions show involve any area of the body except the fat-free soles, palms and normal epidermis and dermis. The trabeculae forming the genitalia. The volume of the affected tissue does not change. framework of the subcutaneous tissue are broadened and Movement and respiration become hindered by the hardening. the fat spaces are diminished. There is a sparse inflammatory Temperature, pulse and respiratory rate decrease until death. infiltrate without fat necrosis. Needle-shaped crystals are Affected neonates have a variety of underlying conditions associated arranged radially in adipocytes.2,8,16,17 These crystals are with the process, including respiratory and gastrointestinal diseases, formed from triglycerides of stearic and palmitic acids, which sepsis and congenital malformations.3,4,14 Hughes and Hammond consist the neonatal subcutaneous fat.18 Proks has called are credited with compiling a case series on SN which is used as a these A crystals.18 He supports the idea that the excessive clinical definition. A summary of the clinical description, gender formation of A crystals, which are present in small amounts preponderance, associated maternal and delivery complications, in the neonatal subcutaneous fat, results in SN, whereas they comorbidities and survival of SN is shown in Table 1. Published recrystallize as large B crystals in SCFN.17 Horsfield and case series have shown this condition to occur primarily in preterm Yardley10 have carried out X-ray diffraction on skin biopsy neonates, more in boys than girls, most often within the first week of a neonate affected with features of both SN and SCFN, and of life and associated with congenital malformations and serious showed that the crystals in affected fat are larger than those illnesses. SN was not found to be associated with seasonal variation found in normal subcutaneous fat, whereas Paysk19 has or maternal parity.15 supported the idea that their presence is nondiagnostic of

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• Theory 1: Composition Subcutaneous fat of neonates has a high ratio of saturated fatty acids of neonatal fat which causes a slight decrease in unsaturated fatty acids. The saturated fat hardens due to a decrease in body temperature as a consequence of (Hughes et al 1948) circulatory collapse due to shock. • Elliott (1959) argues against this theory: Hardening of the subcutaneous fat does not occur until temperatures below freezing are reached and even then, the texture is quite unlike that of sclerema neonatorum.

Theory 2: Defective fat • Thickening of adipose tissue layer due to defect either in lipolytic metabolism enzymes or in lipid transport mechanism, which leads to decreased mobilization of fatty acids from this layer. Hughes et al (1948)

Kellum et al (1968)

Theory 3: Sign of • Associated with an underlying disease process, death is traceable to a severe toxicity specific disease and improvement is in response to treatment for a diagnosed disease process. Warwick et al (1963) • Kellum et al (1968) argues against this theory: Many infants sustain major systemic stresses, surgical procedures and major infections without Villacorte (1967) et al developing sclerema neonatorum.

Theory 4: Connective • Elliott: Special form of edema affecting the connective tissue that tissue of adipocytes supports the adipocytes, leading to thickening of the connective tissue. • Kellum et al: Inherent abnormality in adipocytes or connective tissue, Elliott (1959) causing thickening of the latter after birth. Kellum et al (1968)

Figure 2 Theories explaining the pathogenesis of sclerema neonatorum (SN).

SN as they are observed in fat cells of clinically normal mobilize fatty acids from subcutaneous adipose tissue due to either subcutaneous fat tissues of neonates who died of diseases a defect in adipose lipolytic enzymes or in one of the lipid transport other than SN. mechanisms.14,17 Normally, the level of free fatty acids in serum is low at birth and starts to rise within hours after birth due to rapid Pathogenesis mobilization of fatty acids from adipose tissues. These are Various theories on pathogenesis of SN have been proposed incorporated into triglycerides by the liver and supply metabolic (Figure 2). The basis for Theory 1 is the observation that the energy and thus contribute toward maintaining body temperature composition of neonatal fat differs from adult fat in the presence of of the neonate. Defective mobilization of these fatty acids from the high amounts of saturated fatty acids such as stearic and palmitic adipose tissues may result in their thickening.14,17,21 This also acids, which causes a slight decrease in the content of unsaturated explains why most of the neonates affected by SN have difficulty fatty acids such as oleic acid. Thus, neonatal fat has a relatively maintaining body temperature. high melting point and a low solidification point that gives it a Theory 3 pertains to SN being a sign of a grave underlying tendency to harden with falling body temperature. Hughes and disorder. Warwick et al.4 and Villacorte and Frank3 contend that SN Hammond support the idea that SN occurs under conditions represents a sign of severe toxicity necessitating specific treatment of low peripheral body temperature as a consequence of of the underlying disease process. They base their hypothesis on the circulatory collapse, for example, secondary to shock during an observation that death despite intensive care of infants with SN was underlying grave illness.14,20 Arguing against this theory, always traceable to a specific disease or combination of diseases, however, is the observation that hardening of subcutaneous fat whereas when their condition improved, it appeared in response to does not occur until temperatures below freezing point are reached treatment of a diagnosed disease process. Kellum et al.17 argue and even then the texture of the hardened skin is quite unlike against this hypothesis by stating that many more infants sustain that of SN.8 major systemic stresses like prematurity, dehydration, shock, Theory 2 advances that thickening of the subcutaneous layer in chilling, surgical procedures and major infections without the neonate with SN could be due to their decreased ability to developing SN.

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Theory 4 purports that SN is a special form of edema trauma as an etiology of SCFN are that it has occurred in deliveries affecting the connective tissue septa,8 and thus accounts for with no or minimal trauma.24 Silverman30 support the theory that the speed with which thickening of connective tissue septa an underlying biochemical defect in composition and metabolism sets in,17 an observation that Theory 2, which contends that of fat predisposes to this condition, whereas Elliott8 support the an inherent abnormality in adipocytes is responsible for the view that it is not true fat necrosis but adipose cell necrosis due to thickening, cannot explain. These theories have been summarized trauma and local anoxemia. The histopathological findings show in Figure 2. necrosis of subcutaneous adipocytes. There is an extensive inflammatory infiltrate consisting of lymphocytes, histiocytes, Management lipophages, multinucleate giant cells and eosinophils interspersed Local therapy or warming the body in an attempt to liquefy the among the adipocytes of the fat lobule. Needle-shaped crystals are saturated fatty acids has not proven to be beneficial.14 Steroids have not only seen mainly in multinucleate giant cells but also in been used but have not improved survival, though their use has lipocytes.2,8,16,17,24 These crystals are larger than those seen in SN shown to limit spread of skin lesions of SN.6,15,22,23 Marks24 has and are arranged in rosettes. They are not diagnostic of SCFN as proposed steroids to be beneficial as adjunctive therapy while they have been found as post-mortem breakdown products and in focusing on intensive therapy for sepsis and correction of fluid and lesions of BCG vaccination.18 electrolyte imbalance. Hughes and Hammond,14 Warwick et al.4 There have been reports of cases that have features of both, SN and Villacorte and Frank3 have emphasized the importance of and SCFN. One such case was reported by Brain,11 in which treating the underlying disease. thickening of skin extending from the back of the neck to the The outcome of SN with septicemia has been almost uniformly lowest ribs occurred in a full-term neonate born as a result of an fatal even with the use of antibiotics and supportive therapy. The uneventful delivery. The process began on the third to fourth day of additional use of exchange transfusion (ET), however, has shown birth. The skin was a brownish red color with an irregular nodular promising results in improving outcome of SN with culture-proven surface. There were two soft fluctuating cysts in the lower part on septicemia over the past three decades. One study of ET included each side of the midline. The skin of the affected area was normal only preterm infants25 whereas others26–29 included both in texture but firmly attached to the underlying subcutaneous preterm and term infants. It was concluded that there is tissue, which was indurated throughout the extent of the lesion. increased survival in neonates suffering from SN and sepsis when Histology of the affected skin showed the presence of a repeat ET is used early during the course of the disease. Sadana granulomatous infiltrate around the fat lobules.11 The presence et al.25 found greater improvement in survival after ET in the more of fluctuating cysts with a granulomatous infiltrate point premature group (28 to 32 week gestation) compared to those with toward the diagnosis of SCFN but the extent of the skin lesions, gestational age >32 weeks. This can be attributed to the induration of the skin and subcutaneous tissue are features of SN. immunological components, including enhanced humoral and This could be a case in which both conditions occur cellular immunity that are provided through ET to the simultaneously. immunologically immature neonates. ET also improves oxygen Joncas6 reported a similar case that presented features of both exchange by improving the peripheral and pulmonary circulation SN and SCFN. Horsfield and Yardley10 have published a case report and shifting the oxygen dissociation curve to the right, and of a full-term baby with thickened skin on the trunk, chest wall neutralizes endotoxins.26–29 and legs, and presence of hard discrete areas in the cheeks and buttocks. The baby had difficulty with sucking and swallowing and Differential diagnosis the condition resolved by the age of 5 months. The gestational age There are two other diseases of the subcutaneous fat that are at birth, presence of hard discrete areas on the cheeks and buttocks, important in the differential diagnosis of SN. One of them is SCFN, and the histological finding of granulomatous infiltrates which occurs in healthy infants, mostly post-term, within a few surrounding the fat lobules in a biopsy specimen from an area on days to weeks after birth. It is characterized by sharply the buttocks point toward the diagnosis of SCFN, but the thickening circumscribed areas of hardness that are attached to skin and move of the skin on the trunk, chest wall and legs is characteristic of SN. freely over muscle and bone. It develops over bony prominences on These cases could be variants in which both SN and SCFN occurred back, buttocks, thighs, shoulders, arms, neck and cheeks. Lesions simultaneously. Horsfield and Yardley10 support the idea that SN have a nonpitting, wooden-to-stony consistency and the overlying and SCFN are different manifestations of the same underlying skin may be discolored a reddish to a violescent hue. These lesions pathologic process whereas Marks24 believe them to be two different remain circumscribed, do not spread, disappear spontaneously over clinical entities. a period of months or turn cystic or calcify.22–24 Asphyxia, The other disease important for differential diagnosis of SN is mechanical and thermal trauma have been postulated in the scleredema, which occurs in premature infants and less frequently pathogenesis of SCFN. Arguments that go against the view of in term infants, usually in the first week of life. It is characterized

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Table 2 Summary of clinical features, histopathology and treatment of SN, SCFN and scleredema

Name of Onset of disease Preceding/associated Clinical description Histopathology Treatment Outcome disease illnesses

SN First week of Congenital malformations, Skin and subcutaneous Thickened connective Correction of fluid and Fatal life, mostly in respiratory, gastrointestinal tissue hardened and tissue with sparse electrolyte imbalance; premature diseases and sepsis bound to subjacent inflammatory infiltrate antibiotics for sepsis; neonates muscle and bone, may of lymphocytes, exchange transfusion involve the whole body histiocytes and except palms, soles and multinucleate giant cells genitalia SCFN First four weeks Usually appears in Circumscribed areas of Necrosis of lipocytes with Supportive therapy, Heal spontaneously of life, mostly in healthy neonates, may hardness attached to extensive inflammatory lesions not excised over months, lesions postmature occur with asphyxia, skin, move freely infiltrate may turn cystic or neonates mechanical and thermal over muscles calcify trauma and bone, do not spread Scleredema First week of Cold injury, diarrhea, Generalized firm, pitting Inflammatory Supportive therapy Heal spontaneously life, mostly in vomiting, infection edema with increase in infiltrate with edema premature neonate volume of affected part of skin and subcutaneous tissues

Abbreviations: SN, Sclerema neonatorum; SCFN, Subcutaneous fat necrosis of the newborn.

by generalized firm, pitting edema, which is more common in not clear whether the authors meant edema when stating lower extremities and manifests with an increase in the volume of swelling, as its presence along with the causative factor of exposure the affected part. It is often preceded by cold injury, vomiting, to cold would favor a diagnosis of scleredema. It is not the diarrhea or other acute infection. Body temperature is usually lowering of the core temperature but the peripheral temperature subnormal and the infant is apathetic.4,24,31,32 Histopathology that predisposes to development of SN.14 Ghosal and Nag shows lobular panniculitis without vasculitis with an inflammatory Chaudhuri12 reported a case series of 15 infants who developed infiltrate of lymphocytes and histiocytes in the fat lobules. sclerematous skin lesions while suffering from diarrhea. The There is marked edema in skin, subcutaneous tissue and onset of lesions was within 3 months, all had diarrhea, most sometimes underlying muscle.2,24,32 This condition differs from had vomiting and dehydration and two survived. The description scleredema adultorum, also known as scleredema adultorum of of skin lesions fits SN but the presence of edema in eight Buschke or acute sclerosis, which is a connective tissue disorder infants does not. There was no histology available on skin presenting in adults with brawny, hard, nonpitting skin that lesions. Some or all of these cases could be scleredema. Such cannot be moved freely over underlying tissue, but can be presentations have led to the speculation that scleredema is compressed between thumb and finger to produce superficial edema superimposed on SN.24 Milunsky and Levin34 have ridges. It occurs in three types and is characterized by deposition proposed that scleredema and SN are two different signs with a of mucopolysaccharides in and around the collagen fibers common pathogenesis. They argue that the major factor in the dermis.33 is the exposure to cold causing sluggish circulation and Some cases of scleredema have been published under the peripheral vasoconstriction, which contributes to the name of SN; consideration of these cases serves to illustrate development of tissue anoxia and increased vascular permeability. important principles in distinguishing among them. If hypothermia is severe enough or prolonged, fluid from Navarini-Meury et al.13 recently reported a case under the cellular and vascular spaces moves into the interstitial name of SN that was caused by inducing whole-body hypothermia, compartment, causing a sclerema-like feel of the skin and 3 h after birth for 72 h, as a neuroprotective mechanism to the subcutaneous tissues. prevent cerebral injury from birth asphyxia. The baby developed The above-stated cases demonstrate the confusion that exists in shell-like hardening of the skin of the back along with the differential diagnosis of SN with scleredema and SCFN. The swelling that resolved in 2 months. This occurred in skin differential diagnosis of SN with scleredema and SCFN along with that was in contact with the water-filled mattress used for the clinical presentation, histological findings, treatment and cooling. The shell-like hardening of skin points toward SN but it is outcome has been summarized in Table 2.

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CLINICAL PRESENTATION HISTOLOGICAL FEATURES DIAGNOSIS ON SKIN BIOPSY

Mostly preterm neonates with a Thickening of the supporting SN systemic disease or sepsis connective tissue of adipocytes, presenting with hardening of skin sparse inflammatory infiltrate of Alternate names: which is bound to underlying lymphocytes, histiocytes and Skin bound, preagonal subcutaneous tissue, muscle and multinucleate giant cells induration and sclerema bone; skin does not pit on pressure, adiposum lesions starts on trunk or lower limb and may become generalized

Term or post-term healthy neonate Adipose cell necrosis with SCFN presenting with circumscribed extensive inflammatory infiltrate areas of skin hardening over bony of lymphocytes, histiocytes, Alternate names: prominences, skin moves freely lipophages, multinucleate giant Adiponecrosis subcutanea, over underlying muscle and bone, cells and eosinophils ischemic fat necrosis and lesions remain localized and do not traumatic fat necrosis of the spread newborn

Mostly preterm neonates presenting Inflammatory infiltrate of Scleredema with skin hardening and lymphocytes and histiocytes with generalized firm pitting edema marked edema of skin and Alternate names: starting in lower extremities, subcutaneous tissues Edema neonatorum and preceded by cold injury, vomitting, sclerema edematosum diarrhea or infection

Thickened skin which extends on Presence of adipose cell necrosis Variant having mixed features the trunk, back or other parts of the and inflammatory infiltrate of of SN and SCFN body with circumscribed hardening lymphocytes, histiocytes, of skin on bony prominences or lipophages and multinucleate presence of fluctuating cysts giant cells

Thickened skin on trunk, back, Presence of inflammatory Variant having mixed features lower limbs or other parts of the infiltrate of lymphocytes and of sclerema neonatorum and body with edema and increase in multinucleate giant cells and scleredema volume of the affected part edema

Figure 3 Algorithm for diagnosis of sclerema neonatorum (SN), subcutaneous fat necrosis of the newborn (SCFN) and scleredema.

Conclusion steroids has been shown to limit spread of sclerematous lesions, we speculate that this provides some evidence that an immunological Sclerema neonatorum, scleredema and SCFN are skin conditions response is involved in the pathogenesis. All three conditions affecting the subcutaneous tissues of neonates in the first 1 to 2 require supportive therapy but SN requires more intensive care in weeks of life, with SN being generalized and the other two terms of correcting fluid and electrolyte imbalance and presenting with circumscribed lesions. Neonates suffering from SN administering antibiotics for sepsis. ET has shown promising have comorbidities like congenital malformations, respiratory and results in reversing SN in a setting of neonatal sepsis. gastrointestinal illnesses and sepsis. Though it is an inflammatory The overlapping use of names for these three clinical entities disease of the subcutaneous tissue, the presence of sparse has led to confusion in understanding their clinical presentation inflammatory infiltrates is attributed to poor immunological and histological features. There have been reports of cases that response of the gravely ill neonate with SN. Since the use of present with mixed features of SN and SCFN; and SN and

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