Oral mucosal cysts of the newborn (palatal cysts or epstein’s pearls, and alveolar cysts or bohn’s nodules) (SEE ALSO Chapter 30)

Epstein’s pearls and Bohn’s nodules are actually both similar to milia,²⁵ being microkeratocysts^29–31 located in the mouth. They are 1–2 mm, smooth, yellow to gray-white papules found singly or in clusters, most commonly on the median palatal raphe (68–81%). They also occur on the alveolar ridges (22%), more on the maxillary than the mandibular ridge, but rarely on both. They occur in 64–89% of normal neonates and are more common in Caucasian infants. A recent study from Taiwan of 420 neonates up to 3 days old examined by one dentist, revealed a 94% incidence of oral cysts.³²

Although there is no consistent use of nomenclature in the literature, usually when on the palate, these lesions have been called Epstein’s pearls, and when on the vestibular or lingual surfaces of the alveolar ridges, Bohn’s nodules (Fig. 7.2), and on the crest of the alveolar ridges, dental lamina cysts. The latter are thought to be derived from the ectoderm of the tooth bud.³³ Although Bohn and others had presumed that these were mucous gland cysts, more recent studies have shown them to be keratin cysts derived from the dental lamina. Both of these epidermal cysts occur in keratinized mucous membranes and form in embryonic lines of fusion. Epstein’s pearls originate from epithelial remnants after fusion of palatal shelves. In a recent study of 1021 Swedish neonates,³¹ most of the palatal cysts had discharged spontaneously and resolved by age 5 months. Interestingly, 17 children developed new palatal cysts postnatally. However, most of the alveolar cysts regressed. A study of 60 premature compared with 60 term infants showed a lower prevalence in the prematures (9% vs 30%).³⁴ The diagnosis is clinical. Other congenital papules in the mouth include gingival (alveolar) cysts of the newborn, congenital epulis (granular cell tumor), lymphangiomas, mucoceles, and ranulas (see also Chapter 30).²⁹

Perineal median raphe cysts and foreskin cysts

Other common locations for epidermal inclusion cysts are in the foreskin and along the ventral surface of the penis and scrotum (Fig. 7.3; see Fig. 9.8).³⁵ These lesions tend to be larger than the milia that appear on the head and neck, and may represent a developmental abnormality of fusion with entrapment of epidermal or urethral cells. Histologically, they usually have a stratified squamous epithelial lining, but may have pseudo­stratified columnar epithelium or ciliated or mucus-secreting cells as well, depending on which part of the urethra they are derived from. They often will enlarge throughout infancy and/or seem to appear after the newborn period, often in young men.³⁶ Some may be pigmented due to the presence of melanocytes and melanophages in the cyst lining.³⁷ They are benign and asymptomatic, although they may require surgical removal because of their large size or if they become infected.

Miliaria

Miliaria is a general term for describing obstructions of the eccrine ducts.³⁸ It occurs in 1–15% of normal neonates (Table 7.1). Miliaria occurs in infants in warm climates, or those who are being kept warm or are febrile. It is thus more common in non-air-conditioned nurseries and in hot, rather than in temperate climates.^4,6 The clinical manifestations of miliaria vary, depending on the level of the obstruction.

In the immediate newborn period, the most common form of miliaria is the most superficial, miliaria crystallina (sudamina). In miliaria crystallina, ductal obstruction is subcorneal or intracorneal. Obstruction at this level leads to very superficial trapping of sweat under the stratum corneum, producing typical small, crystal-clear vesicles that resemble water droplets on the skin (Fig. 7.4). These vesicles are extremely fragile and may be wiped away on cleansing of the skin. Miliaria crystallina usually appears in the first few days of life, but there are reports of congenital lesions.^39–42 Occasionally, there will be many neutrophils within the lesions, giving them a more pustular than vesicular appearance. The causes of ductal blockage or leakage are not known. Some authors, however, favor the hypothesis that the ductal occlusion is caused by extracellular polysaccharide substance (EPS) from Staphylococcus epidermidis.⁴³ Miliaria crystallina is precipitated by environmental overheating or fever, with consequent superficial retention of sweat in the obstructed ducts and surrounding epidermis. The diagnosis is clinical, although a smear of the clear fluid contents of the vesicles shows an absence of cellular material or, at most, a few neutrophils. Reducing the ambient temperature or treating the fever will prevent and/or treat miliaria. Miliaria crystallina is benign, but could be mistaken for more serious vesicular or pustular disorders such as herpes simplex.

Miliaria rubra is also common in overheated or febrile infants. Other terms for this disorder include ‘heat rash’ and ‘prickly heat.’ Miliaria rubra presents as erythematous, 1–3 mm papules or papulopustules on the head, neck, face, scalp, and trunk (Figs 7.5, 7.6). It can occur anywhere, but has a predilection for the forehead, upper trunk, and flexural or covered surfaces. The lesions are not follicular. When there is inflammation with multiple neutrophils in the lesions, as may be found under occlusion beneath monitor leads or bandages, miliaria rubra may look pustular and mimic worrisome conditions such as neonatal infections. Some authors subclassify this pustular form as miliaria pustulosa. Histologically, there is dermal inflammation around occluded eccrine ducts. The sweat duct obstruction is lower than in miliaria crystallina, but still intraepidermal. The diagnosis is made clinically, but if there is any doubt, a biopsy will confirm eccrine duct occlusion. The erythematous papules of miliaria rubra may mimic a variety of neonatal conditions, such as neonatal acne, as well as candidal, staphylococcal, or herpes simplex infections. Correcting the overheating is usually sufficient to manage miliaria.

Miliaria profunda, the third and deepest level of sweat duct obstruction, has occlusion at or below the dermoepidermal junction. It is rare in the newborn period. In older children and adults, this deep obstruction causes white papules representing dermal edema and can prevent adequate sweating, leading to hyperthermia.

Sebaceous hyperplasia

Sebaceous hyperplasia is most prominent on the face, especially around the nose and upper lip, where the density of sebaceous glands is highest. It occurs in 21–48% of normal newborns (Table 7.1). Sebaceous hyperplasia appears as follicular, regularly spaced, smooth white-yellow papules grouped into plaques (Figs 7.7, 7.8). There is no surrounding erythema. Hormonal (androgen) stimulation in utero, which comes from either the mother or the infant, causes hypertrophy of sebaceous glands. Premature infants are less affected, but sebaceous hyperplasia occurs in nearly half of term newborns.^6,7 Sebaceous hyperplasia gradually involutes in the first few weeks of life. The papules differ from milia, which are epidermal inclusion cysts, and are usually discrete, solitary, and whiter in color.

Erythema toxicum neonatorum (toxic erythema of the newborn, ‘flea bite’ dermatitis)

Erythema toxicum is unquestionably the best-known benign eruption in the newborn period, occurring in approximately half of term newborns.^40,43–45 Estimates of the incidence in large series range from 7% to 41% (Table 7.1), but frequencies as high as 72% have been reported.⁴⁴ In a recent Spanish study of 1000 newborns, 16.7% were found to be affected in the first 72 h of life.⁴⁶ The discrepancies in estimates of incidence may be due to the length of time these infants were observed. The presence of erythema toxicum has been well correlated with birthweight and gestational age.⁴⁷ Other apparently associated environmental factors include first pregnancy, summer or autumn season, milk-powder feedings, vaginal delivery, and duration of labor.⁴⁸ It is virtually never seen in premature infants or those weighing <2500 g. There is no sexual or racial predilection.⁴⁹ Congenital lesions can occur,^50–52 but the majority of cases have their onset between 24 and 48 h of life. Lesions wax and wane, usually lasting a week or less, but cases lasting beyond 7 days have been reported. Occasionally very atypical presentations are seen (i.e. onset as late as 10 days of age) and pustules contain predominantly neutrophils,^49,53 but such cases require careful evaluation and skin biopsy to exclude other causes.

The classic eruption consists of barely elevated yellowish papules or pustules measuring 1–3 mm in diameter, with a surrounding irregular macular flare or wheal of erythema measuring 1–3 cm. The irregular shape of the flare has been likened to that of a flea bite (Figs 7.9A, 7.10). Although the characteristic lesions of erythema toxicum are usually discrete and scattered (Fig. 7.9B), extensive cases with either clusters of pustules, confluent papules, or pustules with surrounding erythema forming huge erythematous plaques can occur and be more difficult to diagnose (Fig. 7.9C). Lesions may appear first on the face and spread to the trunk and extremities, but may appear anywhere on the body except on the palms and soles.

Histologically, the lesions are eosinophilic pustules and characteristically intrafollicular, occurring subcorneally above the entry of the sebaceous duct.⁵⁴ This follicular location explains the absence of lesions on the palms and soles. Peripheral eosinophilia has also been associated in a minority (about 15%) of cases.

The etiology of erythema toxicum is unknown: a graft-versus-host reaction against maternal lymphocytes has been postulated as a possible mechanism,⁵⁵ but recent studies failed to show the presence of maternal cells in these lesions.⁵⁶ Another theory proposes an immune response to microbial colonization through the hair follicles as early as 1 day of age.⁵⁷ Immunohistochemical analysis of lesions from 1-day-old infants supports the accumulation and activation of immune cells in erythema toxicum lesions.⁵⁸

A variety of inflammatory mediators such as IL-1α, IL-1β, IL-8, eotaxin, aquaporins 1 and 3, psoriasin, nitric oxide synthetases 1, 2 and 3, and HMGB-1 have been associated with erythema toxicum immunohistochemically.^45,59 Tryptase-expressing mast cells (but not the cathelicidin antimicrobial peptide LL-37) have been located in erythema toxicum biopsy specimens.⁶⁰

The diagnosis of erythema toxicum can usually be made by clinical appearance alone, but simple scraping of the pustule, smearing the contents onto a glass slide, and staining with Wright or Giemsa stain will reveal sheets of eosinophils with a few scattered neutrophils. Skin biopsy is rarely needed.

The differential diagnosis of erythema toxicum includes other pustular disorders of the newborn: infantile acropus­tulosis has a more acral rather than truncal distribution; herpes simplex has a more vesicular character, with subsequent crusting; staphylococcal impetigo has more well-developed pustules; congenital candidiasis has a positive KOH and can be more scaly. Transient neonatal pustular melanosis (TNPM) (see below) has primarily neutrophils in the infiltrate and is present at birth, and the pustules quickly disappear, leaving pigmented macules, but erythema toxicum and TNPM may appear together in some infants. Miliaria rubra can also present with erythematous papulopustules, but these favor the head and neck and are smaller lesions without the erythematous flare. No therapy is needed for erythema toxicum except for parental reassurance.

Transient neonatal pustular melanosis

This disorder was first described in 1976,⁶¹ although it had undoubtedly occurred before that time. In fact, an abstract in 1961⁶² is likely to give the first description of TNPM, which was then called ‘lentigines neonatorum.’ It occurs primarily in full-term African-descent infants in both sexes. In the 1976 report, 4.4% of African-American and 0.6% of Caucasian infants were affected.⁶¹ Lesions were always present at birth.

TNPM has three phases and hence three types of lesion. First, very superficial vesicopustules, ranging in size from 2 mm to as large as 10 mm, may be present in utero and are virtually always evident at birth (Fig. 7.11A). Because they are intracorneal and subcorneal, and thus very fragile, the pustules may be easily wiped away during the initial cleaning of the infant to remove vernix caseosa, so that the pustular phase may not be evident (Fig. 7.11B). The second phase is represented by a fine collarette of scale around the resolving pustule (Fig. 7.11C). The third phase consists of hyperpigmented brown macules at the site of previous pustulation (Fig. 7.11D). Although these macules have been called ‘lentigines’ (because of their resemblance to lentils), they are not true lentigines but appear to represent transient postinflammatory hyperpigmentation. They may last for up to several months before they fade. Some infants are born with these macules, the pustular phase having presumably occurred in utero. The most common location for TNPM has been under the chin, on the forehead, at the nape, and on the lower back and shins, although the face, trunk, palms, and soles are also affected.

The etiology of TNPM is unknown. However, some authors^63,64 have postulated that TNPM is a precocious form of erythema toxicum neonatorum, with clinical and histologic overlap. They have proposed the term sterile transient neonatal pustulosis to describe this overlap entity.⁶⁵ It is more likely, however, that these two conditions, which are both common, may coexist. In most infants there is little confusion based either on clinical appearance or time of onset.

Smears of the contents of the pustules stained with Giemsa or Wright stain show predominantly neutrophils, although a few eosinophils have also been reported. A biopsy is rarely needed for diagnosis. Histologically, these lesions consist of subcorneal pustules filled with neutrophils, fibrin, and rare eosinophils.⁶³ The differential diagnoses of transient benign pustular disorders in the neonate are summarized in Table 7.2. These benign conditions should be distinguished from neonatal staphylococcal infection, which would have a positive Giemsa stain on smear for polys and Gram-positive cocci and a positive bacterial culture, and for neonatal candidiasis, which would have a positive KOH examination for branching pseudohyphae and spores, as well as positive fungal cultures.