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Journal of Perinatology (2008) 28, 453460

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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

Objective: To review published literature on sclerema neonatorum (SN) in


order to clarify its clinical presentation, histological features and
management compared with two other diseases: subcutaneous fat necrosis
of the newborn (SCFN) and scleredema.

Study Design: PubMed database was searched using the key words
Sclerema neonatorum. A total of 55 articles from peer-reviewed journals
were reviewed and summarized.
Result: SN, SCFN and scleredema are diseases of the subcutaneous
adipose tissue. SN is characterized by hardening of the skin that gets
bound down to the underlying muscle and bone, hindering respiration
and feeding and is associated with congenital anomalies, cyanosis,
respiratory illnesses and sepsis. Histology of the skin biopsy shows
thickening of the trabeculae supporting the subcutaneous adipose tissue
and a sparse inflammatory infiltrate of lymphocytes, histiocytes and
multinucleate giant cells. SCFN has circumscribed hardening of skin on
bony prominences with necrosis of adipocytes in subcutaneous tissue and
a dense granulomatous infiltrate on histology. Scleredema is
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
self-limiting and lesions resolve within a few weeks to months.
Exchange transfusion may improve survival in SN.
Conclusion: The histological features of skin biopsy should be used to
establish diagnosis of SN, SCFN and scleredema as disease-specific
treatment is imperative in SN due to high fatality.
Journal of Perinatology (2008) 28, 453460; doi:10.1038/jp.2008.33;
published online 27 March 2008
Keywords: neonatal; scleredema; subcutaneous fat necrosis of the
newborn; subcutaneous tissue
Correspondence: Professor GL Darmstadt, Department of International Health, International
Center for Advancing Neonatal Health, Bloomberg School of Public Health, Johns Hopkins
University, 615 North Wolfe Street, Baltimore, MD 21205, USA.
E-mail: gdarmsta@jhsph.edu
Received 19 October 2007; revised 23 January 2008; accepted 14 February 2008; published
online 27 March 2008

Introduction
Sclerema neonatorum (SN) is classified under the Panniculitides,
a group of heterogeneous inflammatory diseases involving the
subcutaneous adipose tissue.1,2 SN usually affects gravely ill, preterm
neonates in the first week of life.35 It manifests as a hardening of
skin and subcutaneous adipose tissue to such an extent that it hinders
feeding and respiration, and usually culminates in death.
Sclerema neonatorum was first described in the early nineteenth
century, and initially was confused by some authorities with
scleredema. In the early twentieth century, when cases of
subcutaneous fat necrosis of the newborn (SCFN) were being
reported, they were initially classified erroneously as SN, thus
adding to the existing confusion in nomenclature.3,68
The last review on SN was published 20 years ago.9 In this paper,
we review the historical background of SN, its clinical presentation,
histological features and the differentiating features from SCFN and
scleredema. SN has a high case fatality rate, unlike the other two
conditions, which makes timely diagnosis and treatment important.

Methodology
A search of the PubMed database using the key words, sclerema
neonatorum, identified 180 articles. Those published in peerreviewed journals and in English language were included in the
final review. Articles on SCFN and scleredema were also sought in
the PubMed database using as search terms the names for
these conditions, and were reviewed to inform the discussion of
differential diagnoses. Snowballing technique was used to
identify additional pertinent literature cited in the articles
reviewed. The total number of articles on SN that were reviewed in
detail and summarized was 55.

Results
History of nomenclature
Sclerema neonatorum was first described as acute sclerema in
1718 (Figure 1). Underwood presented a thorough description in

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Scleredema

Sclerema neonatorum (SN)

Andry described Endurcissement


du tissue cellulaire in 1785 (7,8)

First described by Uzembezius as


Acute sclerema in 1718 (3,6)
Underwood presented a detailed
description in 1784 as Skin
bound (3,6,7,8)

Andry assumed Endurcissement du tissue cellulaire and Skin bound


were the same diseases in 1785 (7, 8)
Chaussier introduced Sclereme for Endurcissement du tissue
cellulaire in 1815 (6,7,8)
Parrot called Endurcissement du tissue cellulaire, Oedema
neonatorum and skin bound, Sclerema neonatorumin 1877 (7,8)
In 1890, Ballantyne accepted the view of French and Italian
researchers, based on epidemiological data, that both diseases were
the same and applied the term Sclerema neonatorum to both SN
and scleredema (7,8)

Subcutaneous fat necrosis of the


newborn (SCFN)
Cases were reported as Sclereme des
adultes in 1845 (7,8)
Fabyan described the histology of
subcutaneous fat necrosis in 1907 (6)
Bernheimer-Karrer called the condition Benign
Sclerema in 1922 (6)

Gray declared SN and SCFN as the same diseases in


1926 (7, 8)

Since 1926, confusion between SN and SCFN has


persisted. Some researchers contend that they may be
variants of the same disease as cases have been reported
presenting with features of both diseases, whereas other
researchers hold the opinion that SN and SCFN are two
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.3,68


Meanwhile, in 1785, a French physician described a disease that he
called Endurcissement du tissue cellulaire, now known as
scleredema; however, at that time it was considered the
same as SN.7,8 The year 1815 saw the introduction of a new term,
sclereme for Endurcissement du tissue cellulaire. The French
regarded this condition as equivalent to skin bound, though
Underwood was convinced that they were two different entities.68
In 1877, a new term, oedema neonatorum was introduced for
Endurcissement du tissue cellulaire, and sclerema neonatorum
was used to refer to skin bound.7,8 This nomenclature was used
until 1895, when it was noticed that SN was more commonly seen
in France and Italy as compared to Great Britain, Germany,
Austria, Russia, Spain, Switzerland and the United States. Based on
the epidemiological data, Ballantyne, a British physician, argued
erroneously that SN and oedema neonatorum were the same
disease. Subsequently, the term sclerema neonatorum was
applied to both conditions, skin bound and oedema
neonatorum.7,8
Cases of SCFN were being reported since 1845 under the term
Sclereme des adultes. Fabyan described the histological picture of
subcutaneous fat necrosis in 1907 whereas Bernheimer-Karrer
called it benign sclerema in 1922.6 In 1926, both SN and SCFN
Journal of Perinatology

were declared the same diseases.7,8 Thus, these three disorders of


adipose tissues, SN, SCFN and scleredema have had multiple
names applied to them and have been confused and labeled at
times as a single disease with the interchangeable use of the term
SN for all three conditions. Thus, the considerable confusion in the
literature and the rarity of these conditions has hindered systematic
descriptions of their features and pathogenesis and development of
advances in management.
Since 1926, confusion has persisted in diagnosis of these
three clinical entities that have different clinical and histological
presentations. There has been confusion in these diseases as
cases having mixed features of SN and SCFN,6,10,11 and SN and
scleredema have been reported.12,13 These cases have been
published under the term of SN, thus adding more to the
confusion, and will be discussed in detail under the section
of differential diagnoses.
Clinical presentation
Sclerema neonatorum is seen in the first few days after birth but
may develop immediately postpartum or as late as several weeks of
life. The skin in affected neonates is smooth, cool, tense, mottled
purplish and hard. The skin cannot be pitted nor can it be picked
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
cases

Gestational
age

M:F ratio

Onset

Maternal and labor


complication

Associated conditions in the


affected neonate

Survival
N (%)

Hughes and
Hammond14
(1948)

19

Most term

9:55 (not
documented)

Within first
7 days of
birth

Four had complications,


including preeclampsia,
eclampsia, placenta previa
and cord compression

4 (21)

Most preterm

11:7

Within first
7 days of
birth

17

Most preterm

11:6

Most preterm

6:3

Within first
7 days of
birth
Within first
7 days of
birth

Nine had complications,


including precipitous
delivery, fetal distress,
PPROM, maternal
hyperpyrexia, abruptio
placentae, gestational
diabetes, twin gestation
15 had no complications

Six had cyanosis and eleven


low body temperature or
difficulty with temperature
control at birth
Comorbidities: sepsis, jaundice,
intestinal obstruction, ileocolitis,
bloody snuffles, bilateral otitis,
pneumonia, diarrhea, gangrene
of extremities
Comorbidities: sepsis, respiratory
problems multiple congenital
anomalies

Warwick et al.4
(1963)

18

Khetarpal and
Subrahmanyam15
(1964)
Villacorte and Frank3
(1967)

Bwibo and
Anderson22
(1970)

16

Most preterm

9:7

Within
14 days
of birth

Six had complications,


including PPROM, cord
around neck, asthmatic
bronchitis, abruption
placentae, twin gestation
15 had no complications

7 (39)

Comorbidities: septicemia,
jaundice

3 (17.6)

All infants had mild to moderate


respiratory distress at or shortly
after birth; 5 also developed
jaundice

2 (22)

Comorbidities: RDS and


Salmonella enteritis

2 (12.5)

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


typically begins in the buttocks, thighs or trunk but may spread to
involve any area of the body except the fat-free soles, palms and
genitalia. The volume of the affected tissue does not change.
Movement and respiration become hindered by the hardening.
Temperature, pulse and respiratory rate decrease until death.
Affected neonates have a variety of underlying conditions associated
with the process, including respiratory and gastrointestinal diseases,
sepsis and congenital malformations.3,4,14 Hughes and Hammond
are credited with compiling a case series on SN which is used as a
clinical definition. A summary of the clinical description, gender
preponderance, associated maternal and delivery complications,
comorbidities and survival of SN is shown in Table 1. Published
case series have shown this condition to occur primarily in preterm
neonates, more in boys than girls, most often within the first week
of life and associated with congenital malformations and serious
illnesses. SN was not found to be associated with seasonal variation
or maternal parity.15

Histological features
The histological findings of sclerematous skin lesions show
normal epidermis and dermis. The trabeculae forming the
framework of the subcutaneous tissue are broadened and
the fat spaces are diminished. There is a sparse inflammatory
infiltrate without fat necrosis. Needle-shaped crystals are
arranged radially in adipocytes.2,8,16,17 These crystals are
formed from triglycerides of stearic and palmitic acids, which
consist the neonatal subcutaneous fat.18 Proks has called
these A crystals.18 He supports the idea that the excessive
formation of A crystals, which are present in small amounts
in the neonatal subcutaneous fat, results in SN, whereas they
recrystallize as large B crystals in SCFN.17 Horsfield and
Yardley10 have carried out X-ray diffraction on skin biopsy
of a neonate affected with features of both SN and SCFN, and
showed that the crystals in affected fat are larger than those
found in normal subcutaneous fat, whereas Paysk19 has
supported the idea that their presence is nondiagnostic of
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Theory 1: Composition
of neonatal fat

(Hughes et al 1948)

Theory 2: Defective fat


metabolism

Subcutaneous fat of neonates has a high ratio of saturated fatty acids


which causes a slight decrease in unsaturated fatty acids. The saturated fat
hardens due to a decrease in body temperature as a consequence of
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.

Thickening of adipose tissue layer due to defect either in lipolytic


enzymes or in lipid transport mechanism, which leads to decreased
mobilization of fatty acids from this layer.

Theory 3: Sign of
severe toxicity

Warwick et al (1963)

Associated with an underlying disease process, death is traceable to a


specific disease and improvement is in response to treatment for a
diagnosed disease process.
Kellum et al (1968) argues against this theory: Many infants sustain major
systemic stresses, surgical procedures and major infections without
developing sclerema neonatorum.

Hughes et al (1948)
Kellum et al (1968)

Villacorte (1967) et al

Theory 4: Connective
tissue of adipocytes
Elliott (1959)

Elliott: Special form of edema affecting the connective tissue that


supports the adipocytes, leading to thickening of the connective tissue.

Kellum et al: Inherent abnormality in adipocytes or connective tissue,


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


subcutaneous fat tissues of neonates who died of diseases
other than SN.
Pathogenesis
Various theories on pathogenesis of SN have been proposed
(Figure 2). The basis for Theory 1 is the observation that the
composition of neonatal fat differs from adult fat in the presence of
high amounts of saturated fatty acids such as stearic and palmitic
acids, which causes a slight decrease in the content of unsaturated
fatty acids such as oleic acid. Thus, neonatal fat has a relatively
high melting point and a low solidification point that gives it a
tendency to harden with falling body temperature. Hughes and
Hammond support the idea that SN occurs under conditions
of low peripheral body temperature as a consequence of
circulatory collapse, for example, secondary to shock during an
underlying grave illness.14,20 Arguing against this theory,
however, is the observation that hardening of subcutaneous fat
does not occur until temperatures below freezing point are reached
and even then the texture of the hardened skin is quite unlike
that of SN.8
Theory 2 advances that thickening of the subcutaneous layer in
the neonate with SN could be due to their decreased ability to
Journal of Perinatology

mobilize fatty acids from subcutaneous adipose tissue due to either


a defect in adipose lipolytic enzymes or in one of the lipid transport
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
mobilization of fatty acids from adipose tissues. These are
incorporated into triglycerides by the liver and supply metabolic
energy and thus contribute toward maintaining body temperature
of the neonate. Defective mobilization of these fatty acids from the
adipose tissues may result in their thickening.14,17,21 This also
explains why most of the neonates affected by SN have difficulty
maintaining body temperature.
Theory 3 pertains to SN being a sign of a grave underlying
disorder. Warwick et al.4 and Villacorte and Frank3 contend that SN
represents a sign of severe toxicity necessitating specific treatment
of the underlying disease process. They base their hypothesis on the
observation that death despite intensive care of infants with SN was
always traceable to a specific disease or combination of diseases,
whereas when their condition improved, it appeared in response to
treatment of a diagnosed disease process. Kellum et al.17 argue
against this hypothesis by stating that many more infants sustain
major systemic stresses like prematurity, dehydration, shock,
chilling, surgical procedures and major infections without
developing SN.

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457

Theory 4 purports that SN is a special form of edema


affecting the connective tissue septa,8 and thus accounts for
the speed with which thickening of connective tissue septa
sets in,17 an observation that Theory 2, which contends that
an inherent abnormality in adipocytes is responsible for the
thickening, cannot explain. These theories have been summarized
in Figure 2.
Management
Local therapy or warming the body in an attempt to liquefy the
saturated fatty acids has not proven to be beneficial.14 Steroids have
been used but have not improved survival, though their use has
shown to limit spread of skin lesions of SN.6,15,22,23 Marks24 has
proposed steroids to be beneficial as adjunctive therapy while
focusing on intensive therapy for sepsis and correction of fluid and
electrolyte imbalance. Hughes and Hammond,14 Warwick et al.4
and Villacorte and Frank3 have emphasized the importance of
treating the underlying disease.
The outcome of SN with septicemia has been almost uniformly
fatal even with the use of antibiotics and supportive therapy. The
additional use of exchange transfusion (ET), however, has shown
promising results in improving outcome of SN with culture-proven
septicemia over the past three decades. One study of ET included
only preterm infants25 whereas others2629 included both
preterm and term infants. It was concluded that there is
increased survival in neonates suffering from SN and sepsis when
repeat ET is used early during the course of the disease. Sadana
et al.25 found greater improvement in survival after ET in the more
premature group (28 to 32 week gestation) compared to those with
gestational age >32 weeks. This can be attributed to the
immunological components, including enhanced humoral and
cellular immunity that are provided through ET to the
immunologically immature neonates. ET also improves oxygen
exchange by improving the peripheral and pulmonary circulation
and shifting the oxygen dissociation curve to the right, and
neutralizes endotoxins.2629
Differential diagnosis
There are two other diseases of the subcutaneous fat that are
important in the differential diagnosis of SN. One of them is SCFN,
which occurs in healthy infants, mostly post-term, within a few
days to weeks after birth. It is characterized by sharply
circumscribed areas of hardness that are attached to skin and move
freely over muscle and bone. It develops over bony prominences on
back, buttocks, thighs, shoulders, arms, neck and cheeks. Lesions
have a nonpitting, wooden-to-stony consistency and the overlying
skin may be discolored a reddish to a violescent hue. These lesions
remain circumscribed, do not spread, disappear spontaneously over
a period of months or turn cystic or calcify.2224 Asphyxia,
mechanical and thermal trauma have been postulated in the
pathogenesis of SCFN. Arguments that go against the view of

trauma as an etiology of SCFN are that it has occurred in deliveries


with no or minimal trauma.24 Silverman30 support the theory that
an underlying biochemical defect in composition and metabolism
of fat predisposes to this condition, whereas Elliott8 support the
view that it is not true fat necrosis but adipose cell necrosis due to
trauma and local anoxemia. The histopathological findings show
necrosis of subcutaneous adipocytes. There is an extensive
inflammatory infiltrate consisting of lymphocytes, histiocytes,
lipophages, multinucleate giant cells and eosinophils interspersed
among the adipocytes of the fat lobule. Needle-shaped crystals are
not only seen mainly in multinucleate giant cells but also in
lipocytes.2,8,16,17,24 These crystals are larger than those seen in SN
and are arranged in rosettes. They are not diagnostic of SCFN as
they have been found as post-mortem breakdown products and in
lesions of BCG vaccination.18
There have been reports of cases that have features of both, SN
and SCFN. One such case was reported by Brain,11 in which
thickening of skin extending from the back of the neck to the
lowest ribs occurred in a full-term neonate born as a result of an
uneventful delivery. The process began on the third to fourth day of
birth. The skin was a brownish red color with an irregular nodular
surface. There were two soft fluctuating cysts in the lower part on
each side of the midline. The skin of the affected area was normal
in texture but firmly attached to the underlying subcutaneous
tissue, which was indurated throughout the extent of the lesion.
Histology of the affected skin showed the presence of a
granulomatous infiltrate around the fat lobules.11 The presence
of fluctuating cysts with a granulomatous infiltrate point
toward the diagnosis of SCFN but the extent of the skin lesions,
induration of the skin and subcutaneous tissue are features of SN.
This could be a case in which both conditions occur
simultaneously.
Joncas6 reported a similar case that presented features of both
SN and SCFN. Horsfield and Yardley10 have published a case report
of a full-term baby with thickened skin on the trunk, chest wall
and legs, and presence of hard discrete areas in the cheeks and
buttocks. The baby had difficulty with sucking and swallowing and
the condition resolved by the age of 5 months. The gestational age
at birth, presence of hard discrete areas on the cheeks and buttocks,
and the histological finding of granulomatous infiltrates
surrounding the fat lobules in a biopsy specimen from an area on
the buttocks point toward the diagnosis of SCFN, but the thickening
of the skin on the trunk, chest wall and legs is characteristic of SN.
These cases could be variants in which both SN and SCFN occurred
simultaneously. Horsfield and Yardley10 support the idea that SN
and SCFN are different manifestations of the same underlying
pathologic process whereas Marks24 believe them to be two different
clinical entities.
The other disease important for differential diagnosis of SN is
scleredema, which occurs in premature infants and less frequently
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
disease

Onset of disease

Preceding/associated
illnesses

Clinical description

Histopathology

Treatment

Outcome

SN

First week of
life, mostly in
premature
neonates

Congenital malformations,
respiratory, gastrointestinal
diseases and sepsis

Thickened connective
tissue with sparse
inflammatory infiltrate
of lymphocytes,
histiocytes and
multinucleate giant cells

Correction of fluid and


electrolyte imbalance;
antibiotics for sepsis;
exchange transfusion

Fatal

SCFN

First four weeks


of life, mostly in
postmature
neonates

Necrosis of lipocytes with


extensive inflammatory
infiltrate

Supportive therapy,
lesions not excised

Heal spontaneously
over months, lesions
may turn cystic or
calcify

Scleredema

First week of
life, mostly in
premature neonate

Usually appears in
healthy neonates, may
occur with asphyxia,
mechanical and thermal
trauma
Cold injury, diarrhea,
vomiting, infection

Skin and subcutaneous


tissue hardened and
bound to subjacent
muscle and bone, may
involve the whole body
except palms, soles and
genitalia
Circumscribed areas of
hardness attached to
skin, move freely
over muscles
and bone, do not spread
Generalized firm, pitting
edema with increase in
volume of affected part

Inflammatory
infiltrate with edema
of skin and subcutaneous
tissues

Supportive therapy

Heal spontaneously

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

by generalized firm, pitting edema, which is more common in


lower extremities and manifests with an increase in the volume of
the affected part. It is often preceded by cold injury, vomiting,
diarrhea or other acute infection. Body temperature is usually
subnormal and the infant is apathetic.4,24,31,32 Histopathology
shows lobular panniculitis without vasculitis with an inflammatory
infiltrate of lymphocytes and histiocytes in the fat lobules.
There is marked edema in skin, subcutaneous tissue and
sometimes underlying muscle.2,24,32 This condition differs from
scleredema adultorum, also known as scleredema adultorum of
Buschke or acute sclerosis, which is a connective tissue disorder
presenting in adults with brawny, hard, nonpitting skin that
cannot be moved freely over underlying tissue, but can be
compressed between thumb and finger to produce superficial
ridges. It occurs in three types and is characterized by deposition
of mucopolysaccharides in and around the collagen fibers
in the dermis.33
Some cases of scleredema have been published under the
name of SN; consideration of these cases serves to illustrate
important principles in distinguishing among them.
Navarini-Meury et al.13 recently reported a case under the
name of SN that was caused by inducing whole-body hypothermia,
3 h after birth for 72 h, as a neuroprotective mechanism to
prevent cerebral injury from birth asphyxia. The baby developed
shell-like hardening of the skin of the back along with
swelling that resolved in 2 months. This occurred in skin
that was in contact with the water-filled mattress used for
cooling. The shell-like hardening of skin points toward SN but it is
Journal of Perinatology

not clear whether the authors meant edema when stating


swelling, as its presence along with the causative factor of exposure
to cold would favor a diagnosis of scleredema. It is not the
lowering of the core temperature but the peripheral temperature
that predisposes to development of SN.14 Ghosal and Nag
Chaudhuri12 reported a case series of 15 infants who developed
sclerematous skin lesions while suffering from diarrhea. The
onset of lesions was within 3 months, all had diarrhea, most
had vomiting and dehydration and two survived. The description
of skin lesions fits SN but the presence of edema in eight
infants does not. There was no histology available on skin
lesions. Some or all of these cases could be scleredema. Such
presentations have led to the speculation that scleredema is
edema superimposed on SN.24 Milunsky and Levin34 have
proposed that scleredema and SN are two different signs with a
common pathogenesis. They argue that the major factor
is the exposure to cold causing sluggish circulation and
peripheral vasoconstriction, which contributes to the
development of tissue anoxia and increased vascular permeability.
If hypothermia is severe enough or prolonged, fluid from
cellular and vascular spaces moves into the interstitial
compartment, causing a sclerema-like feel of the skin and
the subcutaneous tissues.
The above-stated cases demonstrate the confusion that exists in
the differential diagnosis of SN with scleredema and SCFN. The
differential diagnosis of SN with scleredema and SCFN along with
the clinical presentation, histological findings, treatment and
outcome has been summarized in Table 2.

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CLINICAL PRESENTATION

HISTOLOGICAL FEATURES
ON SKIN BIOPSY

DIAGNOSIS

Mostly preterm neonates with a


systemic disease or sepsis
presenting with hardening of skin
which is bound to underlying
subcutaneous tissue, muscle and
bone; skin does not pit on pressure,
lesions starts on trunk or lower
limb and may become generalized

Thickening of the supporting


connective tissue of adipocytes,
sparse inflammatory infiltrate of
lymphocytes, histiocytes and
multinucleate giant cells

SN

Term or post-term healthy neonate


presenting with circumscribed
areas of skin hardening over bony
prominences, skin moves freely
over underlying muscle and bone,
lesions remain localized and do not
spread

Adipose cell necrosis with


extensive inflammatory infiltrate
of lymphocytes, histiocytes,
lipophages, multinucleate giant
cells and eosinophils

Mostly preterm neonates presenting


with skin hardening and
generalized firm pitting edema
starting in lower extremities,
preceded by cold injury, vomitting,
diarrhea or infection

Inflammatory infiltrate of
lymphocytes and histiocytes with
marked edema of skin and
subcutaneous tissues

Thickened skin which extends on


the trunk, back or other parts of the
body with circumscribed hardening
of skin on bony prominences or
presence of fluctuating cysts

Presence of adipose cell necrosis


and inflammatory infiltrate of
lymphocytes, histiocytes,
lipophages and multinucleate
giant cells

Variant having mixed features


of SN and SCFN

Thickened skin on trunk, back,


lower limbs or other parts of the
body with edema and increase in
volume of the affected part

Presence of inflammatory
infiltrate of lymphocytes and
multinucleate giant cells and
edema

Variant having mixed features


of sclerema neonatorum and
scleredema

Alternate names:
Skin bound, preagonal
induration and sclerema
adiposum

SCFN
Alternate names:
Adiponecrosis subcutanea,
ischemic fat necrosis and
traumatic fat necrosis of the
newborn

Scleredema
Alternate names:
Edema neonatorum and
sclerema edematosum

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

Conclusion
Sclerema neonatorum, scleredema and SCFN are skin conditions
affecting the subcutaneous tissues of neonates in the first 1 to 2
weeks of life, with SN being generalized and the other two
presenting with circumscribed lesions. Neonates suffering from SN
have comorbidities like congenital malformations, respiratory and
gastrointestinal illnesses and sepsis. Though it is an inflammatory
disease of the subcutaneous tissue, the presence of sparse
inflammatory infiltrates is attributed to poor immunological
response of the gravely ill neonate with SN. Since the use of

steroids has been shown to limit spread of sclerematous lesions, we


speculate that this provides some evidence that an immunological
response is involved in the pathogenesis. All three conditions
require supportive therapy but SN requires more intensive care in
terms of correcting fluid and electrolyte imbalance and
administering antibiotics for sepsis. ET has shown promising
results in reversing SN in a setting of neonatal sepsis.
The overlapping use of names for these three clinical entities
has led to confusion in understanding their clinical presentation
and histological features. There have been reports of cases that
present with mixed features of SN and SCFN; and SN and
Journal of Perinatology

Sclerema neonatorum
A Zeb and GL Darmstadt

460

scleredema. In such cases, the histological features of the skin


biopsy should be used for diagnosis as disease-specific treatment is
imperative in SN due to high fatality. The presence of crystals in
histological findings should not be used for diagnosing SN and
SCFN; instead, the absence and presence of granulomatous
infiltrate should be used, and the presence of edema favors a
diagnosis of scleredema. An algorithm is presented in Figure 3,
which uses the clinical presentation and skin biopsy findings as
guidance to correct diagnosis of these three clinical conditions.
Conflict of interest
There is no financial or professional duality of interest for the
authors to disclose.
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