INTRODUCTION — Sclerema neonatorum is an uncommon severe panniculitis that manifests as a diffuse skin hardening in critically ill, premature, and low-birthweight infants [1]. The hardened skin and subcutaneous fat become bound down and adherent to underlying muscle and bone, such that the basic functions of breathing, feeding, and movement are restricted. Affected infants suffer from comorbid illnesses, including sepsis, dehydration, severe respiratory or gastrointestinal disease, and congenital malformations. Mortality is high; however, with current neonatal intensive care resources, sclerema neonatorum is thought to be exceptionally uncommon. Regardless, rare cases of sclerema neonatorum occurring in neonatal intensive care settings continue to be reported [2], and it is important that clinicians are able to diagnose and treat this entity.
This topic discusses the pathogenesis, clinical manifestations, diagnosis, and management of sclerema neonatorum. Subcutaneous fat necrosis of the newborn is discussed separately. (See "Subcutaneous fat necrosis of the newborn".)
EPIDEMIOLOGY — Sclerema neonatorum characteristically affects newborn infants and typically develops within the first week of life, although a few cases have been reported to occur beyond the neonatal period. Aggregation of case reports suggests that males may be affected slightly more often than females (male to female ratio, 1.6:1) [1]. Maternal parity does not appear to be a risk factor [3].
The incidence of sclerema neonatorum is not known. The largest case series have been published between 1940 and 1970, while fewer cases have been reported in last few decades [4]. It has been postulated that improved perinatal intensive care has substantially reduced the number of affected infants, rendering sclerema neonatorum a rare diagnosis in the setting of modern neonatal intensive care [5]. Limited data suggest that the incidence of sclerema neonatorum may be higher in areas with less access to high acuity neonatal care. A study evaluating premature newborns at a tertiary pediatric hospital in Bangladesh from 1998 to 2003 reported a 10 percent incidence of sclerema neonatorum [6].
PATHOGENESIS — The pathogenesis of sclerema neonatorum remains unknown. Subcutaneous adipose tissue in neonates is enriched in saturated fats as compared with the subcutaneous fat composition of older individuals. This special biochemical property of neonatal fat makes it more likely to harden in a cold environment. It has been suggested that decreased body temperatures encountered in clinical shock trigger subcutaneous adipose hardening in sclerema neonatorum [7]. However, fat hardening should not occur until skin temperature is below the freezing point, which argues against this explanation. Alternative theories propose that sclerema neonatorum is a consequence of abnormal fat metabolism, results from dysfunction of the connective tissue surrounding the adipocytes, or is a downstream effect triggered by systemic toxicity [8-10].
CLINICAL MANIFESTATIONS — The affected skin in sclerema neonatorum is waxy-appearing, tight, and adherent to underlying tissues. In some infants, the skin may be purple or mottled. The skin cannot be lifted, pinched, or depressed. Sclerema neonatorum classically develops symmetrically on the trunk, thighs, or buttocks, but the skin hardening quickly spreads to involve the subcutaneous fat of the entire body except for the fat-free areas of the genitalia, palms, and soles. The hardening of the facial skin may manifest as a mask-like, fixed facies.
The diffuse skin tightening limits the chest wall expansion and thus respiration, and it may also restrict feeding and other movement. Joint contractures are frequently noted. A case of severe extremity ischemia from a compartment syndrome-like effect in sclerema neonatorum has been described [11]. (See "Acute compartment syndrome of the extremities".)
Clinical course — As sclerema neonatorum develops in seriously ill newborns and further restricts respiration and other vital functions, it is associated with a high mortality rate. Case series estimated that approximately 13 to 39 percent of affected neonates survive [1]. Among survivors, typically there are no long-term skin complications [12].
DIAGNOSIS — The diagnosis of sclerema neonatorum is usually made clinically, based upon the observation of diffuse skin hardening in a gravely ill newborn. The affected skin is fixed to underlying tissue and cannot be folded, pinched, or pitted. If the diagnosis is in question, a skin biopsy may be valuable for histopathologic confirmation. (See 'Pathology' below.)
Pathology — Histopathologic findings that support a diagnosis of sclerema neonatorum include [5,13]:
●Necrosis of subcutaneous fat without significant inflammatory infiltrate and with no prominent granulomatous changes
●Formation of needle-shaped clefts in adipocytes, sometimes in a radial arrangement
●Fibrous thickening of tissue surrounding fat lobules
DIFFERENTIAL DIAGNOSIS — Conditions that may mimic sclerema neonatorum include:
●Subcutaneous fat necrosis of the newborn – Subcutaneous fat necrosis of the newborn typically presents around one to four weeks of life as circumscribed hardened areas of red-brown-tan skin in healthy-term or post-term neonates (picture 1). As opposed to sclerema neonatorum, lesions tend to remain localized, develop later in life, and, although firm, the skin freely moves over the underlying tissue (table 1). Risk factors for subcutaneous fat necrosis of the newborn include hypoxia, perinatal distress, and therapeutic hypothermia [14,15]. On histopathology, subcutaneous fat necrosis of the newborn demonstrates fat necrosis as well as numerous histiocytes, eosinophils, and multinucleated giant cells. Crystal cleft spaces similar to those in sclerema neonatorum may be observed within adipocytes, and calcification may be present [5,13]. In general, the clinical findings and the extensive inflammatory infiltrate on histopathology encountered in subcutaneous fat necrosis of the newborn help to distinguish it from sclerema neonatorum. (See "Subcutaneous fat necrosis of the newborn".)
●Cold panniculitis – Cold panniculitis is characterized by erythematous, firm, well-demarcated plaques that develop at sites where the skin has been subjected to cold temperatures (picture 2) [14]. It appears within hours to a few days after cold exposure and resolves spontaneously. Cases of cold panniculitis in infants have been reported after application of ice to the face to treat supraventricular tachycardia and also after use of cooling blankets during cardiac surgery [16]. Whereas the clinical findings may be very similar, the histopathology of cold panniculitis lacks the characteristic needle-shaped clefts observed in subcutaneous fat necrosis of the newborn, and cystic spaces are often apparent where fat cells have presumably ruptured [13].
●Scleredema – Scleredema has been rarely described in neonates, particularly among infants exposed to cold temperatures or those with severe diarrhea or infection during the first week of life [17,18]. Affected skin is visibly thickened and wax-like. The legs are involved more frequently than other body sites. In contrast to sclerema neonatorum, the skin is edematous and exhibits easy pitting [1]. The dermis and subcutaneous fat appear edematous on histopathology with lymphohistiocytic inflammation noted in the fat lobules.
Scleredema in adults (scleredema adultorum of Buschke) differs from that described in infants. Scleredema adultorum is associated with increased mucin disposition and thickened collagen. (See "Scleredema".)
●Restrictive dermopathy – Restrictive dermopathy is a lethal genetic disease characterized by abnormally tight skin from birth. Affected newborns are usually premature and present with diffusely hard skin that may shear or tear at areas of skin folding, such as the neck, inguinal folds, and lower abdomen (picture 3A-B). Additional clinical findings include joint contractures, ectropion, chest wall narrowing, hypoplastic clavicles, and a fixed O-shaped mouth. This condition is associated with polyhydramnios and pulmonary hypoplasia and is generally fatal in the newborn period. Histopathology shows flattened rete ridges, a thin dermis with horizontally oriented collagen, and incompletely developed skin appendages [19]. Recessive mutations in ZMPSTE24, which encodes a zinc metalloproteinase that processes the important nuclear envelope protein lamin A (encoded by LMNA), are responsible for most cases; however, dominant LMNA mutations have been found in restrictive dermopathy as well [20,21].
●Hutchinson-Gilford progeria syndrome – Sclerodermatous skin tightening has been uncommonly reported in infants with Hutchinson-Gilford progeria, with the youngest reported affected child being approximately two weeks of age [22]. Findings of prominent skin veins, alopecia, frontal bossing, bird-like nose, and micrognathia support the diagnosis. Skin biopsy typically demonstrates thickened dermal collagen but is nonspecific. Most cases are due to an autosomal dominant LMNA mutation [23]. (See "Hutchinson-Gilford progeria syndrome".)
MANAGEMENT — Diagnosis and treatment of concurrent illnesses is paramount for infants affected by sclerema neonatorum. Infections, metabolic disturbance, cardiac disease, and other congenital malformations must be treated promptly. Body temperature, fluid status, and electrolyte levels should be monitored and actively maintained within normal ranges.
In the 1960s and 1970s, the use of systemic corticosteroids for sclerema neonatorum did not appear to improve survival, although in some cases systemic corticosteroids may have limited the extension of existing lesions [3,24-26]. A case report describes successful treatment of a 1550 g preterm infant with progressive sclerema neonatorum in the context of hypoglycemia and sepsis with parenteral hydrocortisone, antibiotics, and supportive intensive care management [27]. However, additional study is needed to determine the efficacy of systemic corticosteroids for treatment of sclerema neonatorum in the context of neonatal intensive care practices.
Exchange transfusion has also been employed in the treatment of sclerema neonatorum [28-30]. One randomized clinical study reported 50 percent mortality in infants treated with exchange transfusion versus 95 percent in untreated infants. In a single case report, intravenous immunoglobulin infusion in a full-term infant with biopsy-proven sclerema neonatorum induced a transitory, mild clinical improvement of the skin, although the child died of respiratory failure secondary to chest wall skin tightening at six weeks of age [31].
SUMMARY AND RECOMMENDATIONS
●Sclerema neonatorum is an uncommon severe panniculitis that develops in critically ill neonates. Premature and low-birthweight infants are the most susceptible. Affected infants suffer from comorbid disease, including sepsis, congenital malformations, and severe respiratory or gastrointestinal illness. (See 'Introduction' above and 'Epidemiology' above.)
●The affected skin in sclerema neonatorum is waxy, tight, and adherent to underlying tissues. The skin-hardening develops symmetrically on the trunk, thighs, and buttocks but quickly spreads to involve the subcutaneous fat of the entire body symmetrically, sparing the areas that lack subcutaneous fat, such as palms, soles, and genitalia. (See 'Clinical manifestations' above.)
●The diagnosis of sclerema neonatorum is usually made clinically. If the diagnosis is uncertain, a skin biopsy may be helpful for confirmation. On histopathology, sclerema neonatorum shows needle-shaped clefts in adipocytes and fibrotic change around fat lobules without significant inflammation or granulomatous infiltrate. (See 'Diagnosis' above and 'Pathology' above.)
●Sclerema neonatorum is associated with a high mortality rate. As the condition develops within the context of serious illness in premature and low-birthweight neonates, prompt diagnosis and treatment of associated disease is critical. Limited available data suggest that exchange transfusion may help reduce mortality in affected infants. (See 'Management' above.)
