Vesiculopustular and Erosive Disorders in Newborns and Infants

Erythema Toxicum Neonatorum

Erythema toxicum neonatorum (ETN) is a very common, benign condition. Originally described by Netlinger in 1472, it was known as “toxic erythema of the newborn” and was renamed erythema toxicum neonatorum by Leiner in 1912 . ETN occurs in approximately half of full-term neonates and only rarely in premature infants or those weighing less than 2500 g .

It has no gender predilection and is most commonly observed in Causcasian infants, although this may be related to the difficulty in perceiving erythema in infants with darker skin .

Rarely presenting at birth, ETN usually begins 24 to 48 hours after delivery, followed by a waxing and waning course over the next few days. Although the onset may be as late as 1–2 weeks of age, additional diagnoses need to be considered. Five distinct components may be present in various combinations: erythematous macules, wheals, and small pustules, vesicles and papules, usually measuring 1–2 mm. The characteristic central papule with a surrounding erythematous flare is reminiscent of a flea bite ( Fig. 34.2 ). Mechanical irritation may precipitate new lesions.

ETN most frequently affects the trunk but can also involve the face, buttocks, and proximal extremities; it almost always spares the palms and soles . Individual lesions rarely persist for more than a day, are asymptomatic, and require no therapy.

The diagnosis of ETN is usually made on clinical grounds. When necessary, the demonstration of numerous eosinophils via Wright stain of pustular contents can help to confirm the diagnosis. Peripheral eosinophilia is occasionally present. Histologically, pustules are intrafollicular, subcorneal, or intraepidermal and are composed of eosinophils and occasional neutrophils . An eosinophilic infiltrate may also be present in the upper dermis. The pathogenesis of ETN is unknown, although an inflammatory response to microbial colonization of the follicle in the first days of life has been postulated .

The differential diagnosis includes other pustular disorders of the newborn, some of which may have important medical sequelae (see Table 34.1 ). Transient neonatal pustular melanosis (TNPM) is primarily neutrophilic, present at birth, usually affects infants with darkly pigmented skin, and resolves as pigmented macules that last weeks to months. However, overlap between ETN and TNPM has been observed (see below). Infantile acropustulosis is an acral, rather than truncal, eruption that usually appears after the neonatal period. Eosinophilic pustular folliculitis of infancy favors the scalp and features lesions that often become crusted and recur in crops over a period of months to years. Herpes simplex viral (HSV) infection presents with discrete vesicular lesions with progression to hemorrhagic crusting. Staphylococcus aureus infections manifest as more well-developed superficial pustules ( Fig. 34.3A ) or bullae that rapidly rupture, resulting in an erythematous base with a surrounding collarette. Congenital candidiasis presents with multiple tiny pustules and desquamation, with skin scrapings showing budding yeast and pseudohyphae on potassium hydroxide (KOH) examination ( Fig. 34.3B ). Both staphylococcal and candidal infections result in more persistent lesions that do not undergo the rapid spontaneous resolution characteristic of ETN. Miliaria rubra (prickly heat) is usually concentrated on the forehead and upper torso, with somewhat longer-lived lesions that lack a prominent erythematous flare or eosinophilic infiltrate .

Transient Neonatal Pustular Melanosis

Originally described in 1961 as “lentigines neonatorum” , the full spectrum of TNPM was not recognized until 15 years later . It occurs most commonly in black infants and is infrequently seen in Caucasians. Lesions are virtually always present at birth and they have three different morphologies that can coexist or occur sequentially. At delivery, superficial, 2–10 mm vesiculopustules ( Fig. 34.4A ) are present at sites such as the chin, forehead, nape of the neck, lower back, buttocks and shins, and, less often, the remainder of the face, trunk, palms, and soles. These lesions may go undetected, as the fragile intra- and subcorneal pustules can be subtle or wiped away during the first bath. The second phase features slightly hyperpigmented macules with fine collarettes of scale at sites of ruptured and resolving pustules ( Fig. 34.4B ). Finally, residual brown macules may persist for several months. The name “lentigines” is a misnomer, as these lesions result from postinflammatory hyperpigmentation. Sometimes only the brown macules are noted at birth, suggesting that a previous pustular phase occurred in utero . Less commonly, infants with TNPM may present at a few weeks of age with extensive pigmented macules but no history of preceding pustules.

Histologic examination is rarely necessary to make the diagnosis, but when performed on early lesions, it demonstrates intra- or subcorneal pustules containing primarily neutrophils and occasionally some eosinophils . Pigmented macules show increased melanin within basal keratinocytes. The pathogenesis is unknown, and the differential diagnosis is similar to that discussed above for ETN. No treatment is necessary, and parents should be reassured of the benign and self-limited nature of the condition.

Sterile Transient Neonatal Pustulosis

It has been postulated that TNPM is simply a variant of ETN, based on their overlapping clinical and histologic features as well as reports of the two conditions coexisting in the same patient. The term sterile transient neonatal pustulosis has been proposed to encompass the ETN–TNPM spectrum . However, most authors consider TNPM and ETN to represent separate entities.

Miliaria

Miliaria is a common condition that affects up to 15% of newborns, and it is seen more frequently in warm climates. Two types of miliaria (see Ch. 39 ) are typically observed in the newborn period. Miliaria crystallina , sometimes present at birth, is due to obstruction of the eccrine sweat duct as it courses through the stratum corneum. Sweat collects beneath the stratum corneum, causing clear, small, flaccid vesicles that are often likened to “dew drops” ( Fig. 34.5A ). Miliaria rubra , usually seen after the first week of life, is also caused by a blockage of the sweat ducts, but deeper within the spinous layer. The obstructed flow leads to leakage of fluid into the lower epidermis and upper dermis, resulting in an inflammatory response that produces small erythematous papules, papulovesicles, and pustules ( Fig. 34.5B ). Miliaria profunda , a variant caused by even deeper obstruction of the eccrine duct, is very rare in infants.

Both miliaria crystallina and miliaria rubra may be seen in relation to excessive warming inside an incubator, over-swaddling, fever, occlusive dressings, or a lack of air conditioning in warm climates. Lesions occur most commonly on the forehead, neck, and upper trunk as well as in areas of skin that have been occluded.

In miliaria crystallina, the characteristic histologic features are subcorneal or intracorneal vesicles that are centered on the acrosyringium with relatively little surrounding inflammation. In miliaria rubra, intraepidermal spongiosis and vesicles are seen along with a chronic inflammatory infiltrate in the dermis . An extracellular polysaccharide produced by Staphylococcus epidermidis present within the sweat duct may play a role , but this does not explain all cases, particularly congenital forms.

Miliaria resolves without treatment. Prevention is accomplished by avoidance of overheating and excessive swaddling when feasible.

Neonatal Cephalic Pustulosis

Historically referred to as “neonatal acne”, neonatal cephalic pustulosis lacks the comedones and more prolonged course that characterize infantile acne vulgaris ( Table 34.3 ; see Ch. 36 ). Neonatal cephalic pustulosis develops within the first 2–3 weeks of life and resolves spontaneously by 3 months of age. Discrete papulopustules overlying variable background erythema are most commonly seen on the cheeks but may also develop on the forehead ( Fig. 34.6 ), chin, eyelids, neck, upper chest, and scalp.

The results of some studies have suggested that an inflammatory response to Malassezia (Pityrosporum) spp. such as M. furfur, M. sympodialis , and M. globosa may be involved in the pathogenesis of neonatal cephalic pustulosis . However, other studies have found no correlation between colonization of neonatal skin with Malassezia spp. and the presence or severity of neonatal cephalic pustulosis . While these yeasts have been cultured from lesional skin in affected patients, they are part of the normal skin flora in humans, and thus their exact role in the condition remains uncertain.

A Giemsa-stained smear of pustular contents may demonstrate yeast forms, neutrophils, and other inflammatory cells; culture of Malassezia spp. requires specialized media . The eruption can be treated with a topical imidazole or hydrocortisone, but this is not usually necessary .

Cutaneous Candidiasis

Neonatal candidiasis is common and acquired during delivery or postnatally, whereas congenital candidiasis is uncommon and acquired in utero . In addition, premature newborns with a very low birth weight (often <1000 g) who develop cutaneous candidiasis prenatally or during the first two weeks of life can develop an “ invasive fungal dermatitis ” with a high risk of systemic involvement.

Neonatal candidiasis presents after the first week of life and involves primarily the diaper area and oral mucosa . In some patients, other intertriginous areas and the face may be affected. Pink–red patches with satellite papules and pustules are the characteristic findings; pustules and scaling may also be present at the peripheral border.

In contrast, the relatively uncommon congenital candidiasis presents with a more widespread eruption, usually evident at birth but sometimes appearing as late as the 6 ^th day of life. Risk factors include a foreign body in the uterus or cervix (e.g. retained intrauterine device, cervical cerclage), premature delivery, and a maternal history of vaginal candidiasis . Skin lesions occur on the face, trunk, and extremities; the palms and soles are often involved, but the diaper area and oral mucosa are usually spared. Cutaneous findings vary and can include erythematous papules, vesiculopustules, diffuse erythema, and fine scaling . Typically, erythematous papules appear first, followed by pustules and desquamation (see Fig. 34.3B ). Nail dystrophy with yellowing and transverse ridging may be present and is occasionally the only manifestation.

“ Invasive fungal dermatitis ” in very-low-birth-weight newborns often presents as widespread “burn-like” erythema with desquamation and erosions ( Fig. 34.7 ). Maceration in intertriginous areas may also be present. Additional risk factors include vaginal delivery, systemic corticosteroid administration, and prolonged hyperglycemia. Although Candida albicans is the most frequent pathogen, infections with other Candida spp. and rarely Trichosporon or Aspergillus spp. can have similar clinical findings.

In neonates, the differential diagnosis includes other infections (e.g. staphylococcal, streptococcal, listerial, HSV) as well as miliaria, ETN, and TNPM (see Table 34.1 ). Budding yeast and pseudohyphae in a KOH preparation that includes scale and/or the pustule and its roof points to the diagnosis, which can then be confirmed by culture. In congenital candidiasis, characteristic yellow–white papules may be found on the umbilical cord.

For neonatal candidiasis, a topical anti-yeast medication (e.g. imidazole cream) is usually sufficient. Even if involvement is localized, premature neonates with very low birth weights (<1500 g) should be closely observed, with cultures of blood, urine, and CSF as indicated; treatment with parenteral antifungals should be considered, if there are signs of systemic infection .

Treatment of congenital candidiasis is dependent on the gestational age and weight of the infant. Premature infants (<27 weeks' gestational age and <1500 g) are at greater risk for the development of disseminated systemic candidiasis and therefore should be treated with parenteral antifungal agents after cultures have been obtained from the blood, urine, and CSF . Infants of a more advanced gestational age with no evidence of systemic infection can be treated with topical therapy as discussed for neonatal candidiasis. However, regardless of gestational age, systemic antifungal therapy should be considered for infants with congenital candidiasis who have respiratory distress, an elevated white blood cell count with a left shift, or other signs of systemic infection .