Vesicular, pustular, and bullous lesions in the

newborn and infant

Authors:
Erin Mathes, MD
Renee M Howard, MD
Section Editors:
Moise L Levy, MD
Leonard E Weisman, MD
Morven S Edwards, MD
Deputy Editor:
Rosamaria Corona, MD, DSc
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jan 2019. | This topic last updated: Dec 03, 2018.

INTRODUCTION Vesicles, bullae, and pustules in the newborn may be

caused by infections, congenital disorders, or other diseases. Benign and self-limited

disorders, including erythema toxicum neonatorum (picture 1A), transient neonatal
pustular melanosis (picture 2A-B), and neonatal acne (picture 3), do not require specific
therapy. However, certain infections and genetic disorders must be differentiated from
these self-limited conditions because treatment may be needed (table 1).

Benign pustular eruptions, vesiculopustular eruptions caused by infections,

and congenital/inherited bullous diseases presenting in the newborn are reviewed here.
Other benign neonatal skin and scalp lesions are discussed separately. (See "Skin
lesions in the newborn and infant".)

BENIGN VESICULOPUSTULAR ERUPTIONS Although most

vesiculopustular eruptions in newborns are benign and self-limiting, the differential

diagnosis includes conditions that require prompt recognition and treatment (table 1).

Erythema toxicum neonatorum — Erythema toxicum neonatorum (ETN) is a common

pustular disorder occurring in approximately 20 percent of neonates in the first 72 hours
of life [1-4]. It occurs more frequently in neonates with higher birthweight and greater
gestational age. The etiology is unknown. One hypothesis is that ETN represents an
acute, innate immune response to the penetration of skin-colonizing flora into the hair
follicle [5].

ETN presents with multiple erythematous macules and papules (1 to 3 mm in diameter)

that rapidly progress to pustules on an erythematous base (picture 1A-B) [6]. The
lesions are distributed over the trunk and proximal extremities, sparing the palms and
soles. They may be present at birth but typically appear within 24 to 48 hours. The rash

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usually resolves in five to seven days, although it may wax and wane before complete
resolution [7].

The diagnosis of ETN is usually made based on the clinical appearance. It can be
confirmed by microscopic examination of a Wright-stained smear of the contents of a
pustule that demonstrates numerous eosinophils and occasional neutrophils. However,
this usually is not necessary. A minority of patients (7 to 18 percent) may also have
peripheral eosinophilia [8]. If the presentation is atypical, cultures of the pustule
contents for bacteria, fungi, and viruses should be obtained (table 1); these are all
negative in ETN.

ETN resolves spontaneously. No treatment is necessary.

Transient neonatal pustular melanosis — Transient neonatal pustular melanosis

(TNPM) is less common than ETN. It mostly affects full-term black infants, although it is
described in all ethnic groups [4,9].

TNPM consists of three types of lesions [10]:

●Small pustules on a nonerythematous base; these usually are present at birth.

●Erythematous to hyperpigmented macules with a surrounding collarette of scale
(picture 2B); these develop as the pustules rupture and may persist for weeks to
months.
●Hyperpigmented macules that gradually fade over several weeks to months
(picture 2A).

Lesions in different stages may be present at the same time, even at birth [10].

The diagnosis of TNPM is usually based upon the clinical appearance. Microscopic
examination of a Wright-stained smear of the contents of a pustule demonstrates
numerous neutrophils and, in contrast with ETN, rare eosinophils. However, this is
usually not necessary. Culture, if performed, yields no organism.

No treatment is necessary.

Eosinophilic pustular folliculitis of infancy — Eosinophilic pustular folliculitis of

infancy (EPFI) is an uncommon dermatosis of unknown etiology occurring in newborns
and infants. Its relationship with the adult eosinophilic pustular folliculitis (Ofuji disease)
is uncertain. EPFI presents with recurrent crops of pruritic, follicular pustules, most
commonly on the scalp (picture 4) but also on the extremities (picture 5). In a
retrospective study of 61 cases of EPFI, the median age of onset was five months, with
a male to female ratio of 4:1 [11]. Tissue eosinophilia is a universal finding and can be
demonstrated by smear or biopsy. Some infants also have blood eosinophilia.
Recurrence is the rule, with outbreaks occurring at intervals of 1 to 12 weeks and
resolving in one to four weeks. Complete resolution occurs by age three in most
children [11].

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The diagnosis is based upon clinical features, course, and the demonstration of
eosinophils in pustule content or in skin biopsy. The differential diagnosis includes ETN,
TNPM, infantile acropustulosis (IA), herpes simplex infection, and impetigo.

Treatment is symptomatic. Topical corticosteroids appear to be effective in hastening

the lesions' resolution and controlling pruritus [11].

Neonatal cephalic pustulosis — Neonatal cephalic pustulosis is a common eruption

that occurs in approximately 20 percent of infants and does not appear to run in
families. Since this eruption is not caused by stimulation of sebaceous glands by
maternal and endogenous androgens, the eruption is no longer referred to as "neonatal
acne" in order to distinguish it from true infantile acne [12] (see 'Infantile acne' below).
An inflammatory reaction to skin colonization with Malassezia species has been
proposed as a pathogenetic mechanism, especially in severe cases, although one
series found no correlation between disease severity and lesional Malassezia culture
positivity or nonlesional skin colonization [13-15].

The mean age at onset is three weeks [16]. The presence of inflammatory papules and
pustules, the absence of comedones, and the characteristic distribution limited to the
face (especially the cheeks) and sometimes the scalp, are diagnostic in most cases
(picture 6). Neonatal cephalic pustulosis may appear very similar to miliaria rubra
(picture 7A-B). (See "Miliaria".)

In the majority of cases, neonatal cephalic pustulosis is mild and can be treated with
daily cleansing with soap and water and avoidance of exogenous oils and lotions [17].
The eruption usually resolves spontaneously within four months without scarring [17].
Application of 2% ketoconazole cream twice daily or 1% hydrocortisone cream once
daily may expedite clearance of lesions [18]. Affected newborns do not appear to have
a greater risk of acne in adolescence.

Infantile acne — Infantile acne is an uncommon and distinct entity from neonatal
cephalic pustulosis. It typically presents at three to four months of age but may rarely
occur in the first few weeks of life [19]. It results from hyperplasia of sebaceous glands
secondary to androgenic stimulation and is more common in boys [20,21]. The clinical
presentation is more severe than that of cephalic pustulosis and consists of typical
acneiform lesions, including comedones, inflammatory papules, pustules, and,
sometimes, nodules on the face (picture 8A-B) [12]. It usually clears spontaneously by
late in the first year of life but may persist until three years of age.

Treatment may be required because infantile acne can persist and occasionally cause
scarring, unlike neonatal cephalic pustulosis. When inflammation is mild or moderate,
mild keratolytic agents, such as benzoyl peroxide (2.5%), topical antibiotics
(eg, clindamycin or erythromycin), or topical retinoids may be used [22]. In more severe
cases, systemic therapy with oral erythromycin, trimethoprim-sulfamethoxazole, or
oral isotretinoin may be indicated [22-24].

Because skin irritation and dryness is a common side effect of commonly used topical
therapies, parents should be instructed to test for local reaction to topical therapies by

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applying a small amount to the antecubital fossa before widespread use or application
to the face [25]. Topical therapies should initially be applied every other night and
increased to every night as tolerated, unless otherwise indicated.

Severe, unremitting infantile acne may warrant evaluation for underlying androgen
excess due to congenital adrenal hyperplasia, a gonadal or adrenal tumor, or
precocious puberty [12,26]. Some patients have recurrence of severe acne at puberty.

Miliaria — Miliaria is a common finding in newborns, especially in warm climates. It is

caused by accumulation of sweat beneath eccrine sweat ducts that are obstructed by
keratin at the level of the stratum corneum. (See "Miliaria".)

Several types of lesions may result [20,25,27]:

●Miliaria crystallina is characterized by small, thin-walled vesicles resembling

dewdrops without inflammation (picture 9).
●Miliaria rubra ("heat rash," "prickly heat") occurs when the obstructed sweat leaks
into the dermis and causes a localized inflammatory response, resulting in small
groups of erythematous papules and pustules (picture 10).
●Miliaria pustulosa also results from localized inflammation; it consists of pustules
with an erythematous base similar to miliaria rubra.
●Miliaria profunda is papular or papulopustular and skin colored.

Miliaria rarely is present at birth. It usually develops during the first week of life,
especially in association with warming of the infant by an incubator, occlusive dressings
or clothing, or fever. It is characteristically distributed on the face, scalp, and
intertriginous areas.

The diagnosis of miliaria is based upon the clinical features. Microscopic examination of
a Wright-stained smear of the contents of a vesicular lesion demonstrates sparse
squamous cells and lymphocytes. However, this is usually not necessary.

No specific treatment is needed. Lesions usually resolve rapidly when the infant is
placed in a cooler environment with associated measures to reduce sweating, such as
light, loose clothing, and cool baths.

Infantile acropustulosis — Infantile acropustulosis (IA) is a benign vesiculopustular

condition with an often more chronic course than other benign neonatal lesions. The
etiology is unknown. A nonspecific hypersensitivity reaction to scabies has been
postulated because many patients have been treated for scabies before being
diagnosed with IA [28,29]. However, the diagnosis of scabies in these patients was
rarely verified microscopically [29]. One survey suggested that IA is common in
internationally adopted children, many of whom had been diagnosed with scabies after
living in crowded living conditions early in life [30]. Atopic dermatitis coexisted with IA in
half of these patients [30].

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Some suggest that black male infants are more commonly affected [31], but others
found no gender or racial predisposition [32]. A family history may be informative
because siblings are sometimes affected [32].

IA is characterized by recurrent crops of intensely pruritic vesiculopustules, mainly on

the palms and soles (picture 11A-B) but sometimes involving the dorsal aspect of the
hands and feet and the limbs (picture 12A-B). It may be present at birth or have onset
any time during the first year of life. Recurrences generally occur every two to four
weeks and may last 5 to 10 days. Infants are often fussy during these flares.

The differential diagnosis of IA includes dyshidrotic eczema, pustular psoriasis, ETN,

TNPM, EPFI, scabies, and impetigo (table 1) [6]. (See "Acute palmoplantar eczema
(dyshidrotic eczema)" and "Pustular psoriasis: Pathogenesis, clinical manifestations,
and diagnosis" and 'Erythema toxicum neonatorum' above and 'Transient neonatal
pustular melanosis' above.)

The diagnosis of IA is based upon clinical features. Because of the association with
scabies, skin scrapings should be examined [29,33]. Skin biopsy usually is not
necessary but, if performed, demonstrates a subcorneal pustule filled with neutrophils
and eosinophils [34].

IA typically resolves within two years. Therapy for IA has not been studied in
randomized trials, and the optimal treatment is controversial. Treatment with topical
corticosteroids, oral antihistamines, oral erythromycin, and oral dapsone have been
beneficial in case reports or case series, although the findings are inconsistent except
for dapsone [29,32,34-37]. Although dapsone is reliably effective, it has potentially
serious adverse effects [29].

In the largest series of IA patients, 20 of 21 were treated with high- to mid-potency

topical corticosteroids (group 1 to 4 (table 2)) once or twice per day [29]. The 18 who
returned for follow-up had improvement (decrease in the number of lesions, frequency
of recurrence, and pruritus) or marked improvement (complete resolution with no
recurrence). Improvement was noted between three days and two weeks after initiation
of therapy. No cutaneous or systemic complications were recorded.

We suggest mid- to high-potency topical corticosteroids (group 1 to 4 (table 2)) as the

first-line treatment for flares of IA [29,32]. Systemic absorption of topical corticosteroids
in IA is limited by the localized distribution of the lesions, the thickness of skin in the
affected (acral) areas, and the periodicity of the flares [6,29]. (See "General principles of
dermatologic therapy and topical corticosteroid use", section on 'Use in children'.)

Erythromycin (40 mg/kg per day by mouth) or oral antihistamines are alternatives to
topical corticosteroids. Erythromycin appears to have an anti-inflammatory effect.
Antihistamines are effective in relieving pruritus but only in high doses, suggesting that
sedation is necessary for efficacy [29,36].

We suggest that dapsone (1 to 2 mg/kg per day by mouth) be reserved for severe,
recalcitrant cases [29]. Adverse effects of dapsone may include peripheral neuropathy,

5
aplastic anemia, hepatitis, hemolytic anemia, and methemoglobinemia [29]. A glucose-
6-phosphate dehydrogenase (G6PD) screen should be done before starting dapsone.
(See "Diagnosis and management of glucose-6-phosphate dehydrogenase (G6PD)
deficiency".)

Vesiculopustular eruption and transient myeloproliferative disorder in Down

syndrome — Approximately 20 percent of newborns with Down syndrome present with
a transient myeloproliferative disorder (TMD, also called transient leukemia) [38-40]. In
rare instances, TMD is accompanied by a vesiculopustular eruption predominantly
located on the face that begins during the first few days of life. The examination of a
skin biopsy shows intraepidermal, spongiotic vesiculopustules and a perivascular
infiltrate containing immature myeloid cells, which are usually also present in the
peripheral blood. The skin lesions resolve spontaneously in one to three months, as the
TMD regresses. (See "Down syndrome: Clinical features and diagnosis", section on
'Transient myeloproliferative disorder'.)

INFECTIOUS VESICULOPUSTULAR ERUPTIONS Infection always

should be considered as a cause of vesiculobullous or pustular lesions in the newborn

[41]. Infectious disorders may be life threatening and require urgent therapeutic
intervention. The clinical features of the most common infectious vesiculopustular
eruptions in newborns are summarized in the table (table 1).

Viral infection — A number of viruses can cause vesiculopustular or bullous lesions in

the newborn. In most cases, lesions do not appear at birth but rather days to weeks
later. Herpes simplex virus (HSV) and varicella-zoster virus (VZV) are the two most
common etiologic agents, but cytomegalovirus (CMV) and coxsackievirus occasionally
can also be causative. (See "Overview of cytomegalovirus infections in
children" and "Enterovirus and parechovirus infections: Clinical features, laboratory
diagnosis, treatment, and prevention".)

Primary herpes simplex infection — Neonatal HSV infection is rare. It occurs before
42 days of age and primarily results from intrapartum exposure to maternal cervical or
vaginal lesions or by an ascending infection, sometimes through apparently intact
membranes [42]. Postnatal inoculation also may occur but is less common [43].

Symptoms can develop within days to four weeks after birth. HSV infection in newborns
usually develops in one of three patterns:

●Localized to the skin, eyes, and mouth

●Localized central nervous system (CNS) disease
●Fulminant, disseminated disease involving multiple organs

Although HSV infection can present with nonspecific symptoms, such as fever, poor
feeding, and decreased activity [43], skin lesions occur in the majority of patients and
may be present in all three patterns. The skin lesions typically consist of 1 to 3 mm
vesicles and erythematous papules that may develop into pustules, crusts, and erosions

6
(picture 13). They usually occur on the scalp (picture 14), sometimes associated with
placement of a fetal monitor electrode, or face (picture 15) [20]. Lesions also may occur
on the trunk (picture 16) or buttocks (especially with a breech presentation).

Lesions are not usually present at birth and develop at 6 to 13 days of age [20]. Infants
with lesions at birth (congenital HSV infection) have intrauterine, rather than perinatal,
infection and usually also are premature. They also can be microcephalic. Lesions
should be distinguished from other vesiculopustular disorders (table 1), such as
congenital candidiasis, transient pustular melanosis of the newborn (picture 2A-B), or
incontinentia pigmenti (picture 17). When lesions are present at birth, they usually
appear as superficial erosions.

Although most lesions in older children are self-limited, neonatal infections are more
likely to disseminate. Newborns with disseminated disease often appear septic, with
vascular instability, hepatic dysfunction, disseminated intravascular
coagulation, and/or respiratory failure. CNS disease presents with fever, lethargy, and
focal seizures.

The clinical manifestations, diagnosis, treatment, and prognosis of neonatal HSV

infection are discussed in detail separately. (See "Neonatal herpes simplex virus
infection: Clinical features and diagnosis", section on 'Clinical
manifestations' and "Neonatal herpes simplex virus infection: Management and
prevention".)

Varicella-zoster — Perinatally acquired varicella is a rare and serious illness

associated with a mortality rate up to 20 percent [44]. Newborns born to mothers who
are exposed to VZV or have clinical disease manifestations within three weeks of
delivery are at the greatest risk for infection. If the mother develops the rash between
four days before and two days after delivery, the newborn is likely to develop a
generalized and potentially fatal infection (picture 18). Varicella-zoster infection in the
newborn is discussed in detail separately. (See "Varicella-zoster infection in the
newborn".)

Bacterial infection — Bacterial infection in neonates may present with vesiculobullous

or pustular lesions. The most common organism to cause pustules accompanying
neonatal sepsis is Staphylococcus aureus. Because up to 60 percent of infants become
colonized in the first few weeks of life, this organism is also an important cause of
superficial skin infections [45]. Sepsis caused by Listeria monocytogenes, streptococcal
species, or Pseudomonas aeruginosa can have associated skin lesions, as
can Treponema pallidum infection (table 1).

Staphylococcal pustulosis — In newborns, cutaneous staphylococcal infection

usually presents with localized, superficial vesicular, pustular, or bullous lesions on an
erythematous base. Vesicles and bullae are easily ruptured, resulting in superficial
erosions and honey-colored crusts. Lesions usually are found in areas of trauma, such
as the diaper area (picture 19), circumcision wound, axillae, and periumbilical skin,

7
although they may appear anywhere on the body. Hospital outbreaks have been
reported [46].

The diagnosis is confirmed with demonstration of gram-positive cocci in clusters,

neutrophils on a Gram stain of the pustular fluid, and isolation of S. aureus on culture. If
lesions are extensive or the infant appears ill, a blood culture should be obtained prior to
starting treatment.

The evaluation and treatment (algorithm 1) of S. aureus skin infection in the newborn
infant are discussed separately. (See "Suspected Staphylococcus aureus and
streptococcal skin and soft tissue infections in neonates: Evaluation and management",
section on 'Antimicrobial therapy'.)

Staphylococcal scalded skin syndrome — Newborns are especially susceptible to

dissemination of S. aureus exfoliative toxins, producing the staphylococcal scalded skin
syndrome (SSSS or Ritter disease) [47]. The toxins act at the zona granulosa of the
epidermis, causing cleavage of desmoglein 1 complex, an important protein in
desmosomes (the organelles that help anchor keratinocytes to each other) [48]. This
results in the formation of fragile, flaccid bullae that often are no longer intact by the
time of presentation [49].

Presentation usually occurs at three to seven days of age and is rarely seen at birth
[20]. Affected infants are febrile and irritable, with diffuse, blanching erythema often
beginning around the mouth. Flaccid blisters appear one to two days later, especially in
areas of mechanical stress, including flexural areas, buttocks, hands, and feet (picture
20A-B). Gentle pressure applied to the skin results in separation of the upper epidermis
and wrinkling of the skin (Nikolsky's sign). In some cases, the entire upper epidermis
may be shed [20]. Affected infants often have conjunctivitis; mucous membranes are
not involved but may appear hyperemic.

Superficial desquamation occurs as the lesions heal [20]. Because the cleavage plane
of the blisters is intraepidermal, scars do not occur.

If SSSS is suspected, cultures should be obtained from blood, urine, nasopharynx,

umbilicus, abnormal skin, or any suspected focus of infection. The intact bullae are
sterile. Diagnosis is usually clinical, although it may be confirmed with skin biopsy that
shows a cleavage plane in the lower stratum granulosum with minimal necrosis [50].
However, biopsy is rarely required. The microscopic examination may be performed on
a frozen section to expedite treatment.

The biopsy will differentiate SSSS from toxic epidermal necrolysis (TEN), which is more
commonly seen in older children as a reaction to drugs or infections [51]. Pathology
specimens of TEN reveal a subepidermal cleavage plane and epidermal necrosis.
Additionally, unlike SSSS, involvement of mucous membranes is a frequent clinical
feature of TEN. (See "Stevens-Johnson syndrome and toxic epidermal necrolysis:
Pathogenesis, clinical manifestations, and diagnosis".)

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Treatment consists of prompt administration of intravenous penicillinase-resistant
penicillin, such as nafcillin or oxacillin; treatment with vancomycin should be considered
in areas with a high prevalence of community-acquired methicillin-resistant S.
aureus (CA-MRSA) or for patients who fail to respond to initial therapy, as SSSS
secondary to MRSA infection has been reported (table 3) [52,53]. (See "Staphylococcus
aureus in children: Overview of treatment of invasive infections", section on 'Treatment
of neonates'.)

Supportive skin care should be provided with the use of emollients, such as creams or
ointments, to improve barrier function. Fluid and electrolyte status should be monitored
with losses replaced as needed.

Streptococcal infection — Streptococcal skin infections may mimic those caused by

staphylococci, although they are less common. Epidemics of group
A Streptococcus (GAS) infections have been reported [54,55]. Affected newborns may
present with pustules and honey-colored crusts, often in association with a moist
umbilical cord stump or omphalitis.

Group B streptococci (GBS) most commonly cause neonatal sepsis. However, skin
lesions, such as bullae, erosions, and honey-colored crusts, occur rarely. Unlike other
bacterial skin lesions, those resulting from GBS may be present at birth or develop later
[56]. (See "Group B streptococcal infection in neonates and young infants", section on
'Clinical manifestations'.)

If streptococcal disease is suspected, Gram stain and culture of a skin lesion should be
obtained. Gram-positive cocci in chains will distinguish these from staphylococcal
infections, although culture is necessary to distinguish GAS from GBS. Cultures of
blood, urine, and cerebrospinal fluid are obtained to rule out evidence of disseminated
disease.

Pending the culture results, empiric therapy with

intravenous ampicillin and gentamicin should be administered. Once GBS is identified
as the sole causative organism, the therapy can be changed to penicillin G alone (table
4). (See "Group B streptococcal infection in neonates and young infants", section on
'Antimicrobial therapy'.)

Listeriosis — Infections resulting from L. monocytogenes can present in newborns

[57]. Clinical manifestations can occur early, before seven days, or late (after seven
days). Both forms can present with meningitis and signs of septicemia. Infants with the
early form often have multiple pustules on the skin and mucous membranes.
(See "Clinical manifestations and diagnosis of Listeria monocytogenes infection".)

Congenital syphilis — Congenital syphilis occurs when the spirochete T. pallidum is

transmitted from a pregnant woman to her fetus. It should always be included in the
differential diagnosis of a newborn with blisters or erosions, especially when present at
birth. The incidence has risen markedly in the past several years [58]. (See "Congenital
syphilis: Clinical features and diagnosis", section on 'Early congenital syphilis'.)

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Early manifestations can be quite variable. Infants may be normal at birth and become
symptomatic during the first five weeks of life. Hemorrhagic bullae and petechiae that
start on the palms and soles and spread to the trunk and extremities are nearly
pathognomonic of congenital syphilis (picture 21A-B). If ulcerative in nature, they are
highly contagious. A more common presentation is a papulosquamous eruption similar
to the exanthem of secondary syphilis in adults (picture 22) or a desquamative
dermatitis also involving the palms and soles. Other early manifestations include rhinitis
(snuffles), anemia, thrombocytopenia, lymphadenopathy, hepatomegaly, fever, and
poor feeding [59].

The diagnosis and treatment of congenital syphilis are discussed separately.

(See "Congenital syphilis: Clinical features and diagnosis" and "Congenital syphilis:
Evaluation, management, and prevention", section on 'Evaluation and management of
infants <1 month of age'.)

Fungal infection — Candida albicans infections are common in the neonatal period
and are usually benign. Case reports have been published of Aspergillus species
causing vesicular lesions in very low birth weight newborns [60,61].

Neonatal candidiasis — Neonatal candidiasis usually develops after the first week of
life. It is most likely to affect moist, warm regions and skin folds, such as in the diaper
area, or mucous membranes in the mouth, where it is known as thrush. Candidal diaper
dermatitis characteristically appears as an erythematous eruption in the inguinal region.
The rash classically has areas of confluent erythema with multiple tiny pustules or
discrete, erythematous papules and plaques with superficial scales (picture 23).
Satellite lesions are typically noted (picture 24A-B). Topical treatment is adequate in
most cases, as dissemination is rare. (See "Diaper dermatitis".)

Oropharyngeal candidiasis or thrush can manifest in several ways. The

pseudomembranous form is the most common and appears as white plaques on the
buccal mucosa, palate, tongue, or the oropharynx. Infants with thrush may be totally
asymptomatic or may refuse to eat because of discomfort from the infection. Topical
therapy (eg, nystatin) is usually effective. In breastfeeding infants, the mother also may
require treatment. (See "Candida infections in children", section on 'Oropharyngeal
candidiasis'.)

Congenital candidiasis — Congenital cutaneous candidiasis is a rare disorder that

results from a Candida spp. infection acquired in utero or during delivery. It presents at
birth or in the first few days of life with small, diffuse, erythematous macules and
pustules, often involving the palms and soles (picture 25A-B). The clinical
manifestations and treatment of congenital candidiasis are discussed separately.
(See "Clinical manifestations and diagnosis of Candida infection in neonates", section
on 'Congenital candidiasis' and "Treatment of Candida infection in neonates".)

Infestations

Scabies — Scabies is an uncommon cause of eruptions in the developed world but is

common worldwide [62]. The disorder is caused by infestation with the Sarcoptes

10
scabiei mite. The skin eruption is because of a hypersensitivity reaction to the proteins
of the female parasite, which burrows into the upper layers of the epidermis [63].
Transmission of scabies is usually from person to person by direct contact.
(See "Scabies: Epidemiology, clinical features, and diagnosis".)

Scabies may present as early as three to four weeks of age, the earliest time infants
can develop hypersensitivity to the mites, and is never present at birth. The
characteristic appearance is of erythematous papules that are intensely pruritic. Infants
are more likely than older children to develop vesicles, pustules, nodules, and crusting
[64]. The involvement can be localized initially, but then it becomes widespread and
often affects the hands, feet, and wrists, which usually are spared in older children and
adults (picture 26) [65]. The face may be involved because of contact with infested
maternal skin while breastfeeding. Infants may manifest poor feeding, fussiness, and
failure to thrive, presumably because of the intense pruritus, or be asymptomatic [66].

The diagnosis should be considered in an infant with a vesiculopustular eruption that

involves the palms and, especially, the soles (picture 27). It is often confused with
infantile acropustulosis, insect bites, impetigo, atopic dermatitis, or urticaria pigmentosa.
The combination of a pruritic eruption, characteristic distribution, and family involvement
is usually enough to establish a diagnosis. Mites or eggs can be demonstrated in
scrapings from burrows or papules [65].

The infant and all the household and close contacts should be treated simultaneously,
and environmental decontamination should also be performed. Treatment consists of
one application of permethrin 5% cream at bedtime to all skin surfaces in infants and
from the neck down in older family members; it should be washed off after 8 to 14 hours
[62]. Repeated applications may be needed, as the failure rate is significant. Ten to 20
percent of patients require retreatment in 7 to 10 days because of persistent symptoms
[67]. An alternative therapy for newborns is the application of 5 to 10% precipitated
sulfur in petrolatum.

CONGENITAL/INHERITED BULLOUS DISORDERS Several

uncommon congenital or inherited conditions may present with bullous lesions in the
newborn.

Sucking blisters — Congenital sucking blisters, a diagnosis of exclusion, are

noninflammatory, oval, thick-walled vesicles or bullae that contain sterile fluid [68]. The
lesions may be unilateral or bilateral and typically are located on the dorsal or radial
aspect of the wrists, hands, or fingers of neonates who are noted to suck excessively at
the involved regions (picture 28).

The differential diagnosis of sucking blisters includes herpes simplex virus infection,
bullous impetigo, congenital syphilis or candidiasis, neonatal lupus erythematosus, and
hereditary bullous diseases [68]. These disorders are usually, but not always,
accompanied by additional clinical signs or suggestive maternal history.

11
Observation of the neonate's sucking on the involved areas is the most helpful clue to
the correct diagnosis of congenital sucking blisters. Other suggestive features include
the absence of lesions in other areas, well appearance of the infant, and rapid
resolution of the lesions.

Epidermolysis bullosa — Epidermolysis bullosa (EB) is a group of inherited diseases

characterized by skin fragility and blister formation caused by minor skin trauma (picture
29). EB is broadly classified into four groups, based upon the level at which the blisters
form. These are EB simplex, junctional EB, dystrophic EB (DEB), and Kindler
syndrome. The pathogenesis, clinical manifestations, diagnosis, and management of
EB and Kindler syndrome are discussed in detail separately.
●(See "Epidemiology, pathogenesis, classification, and clinical features of
epidermolysis bullosa".)
●(See "Diagnosis of epidermolysis bullosa".)
●(See "Overview of the management of epidermolysis bullosa".)
●(See "Kindler syndrome".)

Bullous dermolysis of the newborn — Bullous dermolysis of the newborn (BDN),

previously called transient bullous dermolysis of the newborn, is a subtype of DEB
characterized by skin fragility and blister formation at birth that typically improves or
resolves within the first year of life (picture 30) [69,70]. Milia, atrophic scarring, and nail
dystrophy can persist [71]. Ultrastructurally, BDN shares the characteristic findings of
DEB, namely a split below the level of the lamina densa, disruption of anchoring fibrils,
and presence of electron-dense stellate or rod-like bodies within the dilated, rough,
endoplasmic reticulum of basal keratinocytes.

On immunofluorescence microscopy, intracytoplasmic, epidermal inclusions of C7

appear to be a unique characteristic of BDN [69].

Epidermolytic ichthyosis — Epidermolytic ichthyosis, also called epidermolytic

hyperkeratosis (EHK) or bullous congenital ichthyosiform erythroderma, is an autosomal
dominant disorder that typically presents in the neonatal period. Raw erosions and
ruptured bullae are present at birth and may be misdiagnosed as EB (picture 31) or
staphylococcal scalded skin syndrome. Frozen section of the roof of the ruptured bullae
using the "jelly roll" technique can be helpful in distinguishing these entities [72]. Bullae,
although not intact at birth, may continue to form throughout early childhood.
(See "Keratinopathic ichthyoses".)

Aplasia cutis congenita — Aplasia cutis congenita (ACC) is a rare, heterogeneous

group of congenital disorders characterized by focal or widespread absence of the skin
[73]. ACC can occur anywhere on the body, but the vast majority of cases occur on the
scalp midline as a solitary membranous or bullous lesion (picture 32). A conspicuous
collar of hair around a lesion on the scalp may indicate the presence of a structural
defect in underlying bone or central nervous system (picture 33). Associated vascular
stain, nodule and vertex, or midline location also increase this risk [74]. Clinical
subtypes are characterized by their location and pattern of lesions, associated
malformations, and mode of inheritance [75].

12
The classification, diagnosis, and management of ACC are discussed in detail
elsewhere. (See "Aplasia cutis congenita".)

Incontinentia pigmenti — Incontinentia pigmenti (IP) is an X-linked dominant

multisystem disease that is usually lethal in males in utero [76]. IP is caused by
mutations in the IKBKG/NEMO (inhibitor of kappa polypeptide gene enhancer in B-cells,
kinase gamma/nuclear factor-kappa B essential modulator) gene, encoding a regulatory
protein involved in the activation of genes involved in cell survival, inflammation, and
immunity. In females, it classically presents with a staged cutaneous eruption (table 5);
variable developmental abnormalities involving the teeth, hair, and nails; and ocular and
neurologic abnormalities.
●In stage 1, or the vesicular stage, erythematous papules and vesicles appear in
crops in linear streaks along the lines of Blaschko, usually beginning at birth or
within the first few weeks of life, with each crop lasting one to two weeks (picture
34).
●Stage 2, or the verrucous stage, consists of hyperkeratotic, warty papules or
plaques in linear or swirling patterns (picture 35).
●Stage 3, or the pigmented stage, presents as streaks of hyperpigmentation in a
"marble cake pattern" (picture 36).
●Stage 4, or the final stage, where the hyperpigmented streaks may evolve into
hypopigmented and atrophic patches or streaks.

All stages may be present simultaneously and may occur in utero. The clinical features,
diagnosis, and management of incontinentia pigmenti are discussed in detail elsewhere.
(See "Incontinentia pigmenti".)

Cutaneous mastocytosis — Cutaneous mastocytosis is an infiltrative skin disorder

that can present with vesicles and blisters in the newborn (picture 37A-B). The two main
forms are cutaneous mastocytomas, presenting with solitary or multiple erythematous
nodules, and maculopapular cutaneous mastocytosis (previously called urticaria
pigmentosa), which presents with multiple monomorphic, reddish-brown macules and
papules anywhere on the body, except the palms and soles (picture 37B). Both forms of
cutaneous mastocytosis may present with bullous lesions in infants. (See "Mastocytosis
(cutaneous and systemic): Epidemiology, pathogenesis, and clinical manifestations".)

SUMMARY AND RECOMMENDATIONS

●A variety of diseases can cause vesicular or pustular eruptions on the skin of

young infants. Benign and self-limited disorders, such as erythema toxicum
neonatorum (picture 1A), transient neonatal pustular melanosis (picture 2A-B), and
neonatal acne (picture 3), do not require specific therapy. However, certain
infections and genetic disorders must be differentiated from these self-limited
conditions because treatment may be needed (table 1). (See 'Introduction' above
and 'Benign vesiculopustular eruptions' above.)

13
 ●A thorough clinical history and physical exam provides important clues for
diagnosis. The possibility of a viral, bacterial, or fungal infection should always be
considered. (See 'Infectious vesiculopustular eruptions' above.)
●In addition to impetigo and localized pustulosis, Staphylococcus aureus infection
may cause staphylococcal scalded skin syndrome (SSSS). In SSSS, toxins
produced by the organism induce cutaneous erythema, bullae, and desquamation.
Microscopic examination of a frozen section of lesional skin is a quick method to
distinguish this disorder from toxic epidermal necrolysis. (See 'Staphylococcal
scalded skin syndrome' above.)
●Erythematous patches, papules, and pustules in intertriginous areas may occur in
neonatal candidiasis (picture 24A-B). Satellite lesions are a frequent finding.
(See 'Neonatal candidiasis' above.)
●Scabies in infants can present with inflammatory vesicles and/or pustules (picture
26). Lesions may be widespread and often involve the hands, wrists, and feet
(picture 27). (See 'Scabies' above and "Scabies: Epidemiology, clinical features,
and diagnosis".)
●Vesicular lesions following the lines of Blaschko on a newborn infant suggest the
possibility of incontinentia pigmenti, a rare, X-linked dominant disorder (picture 34).
Later stages of incontinentia pigmenti are characterized by verrucous papules and
pigmentary alteration. (See 'Incontinentia pigmenti' above.)
●An erosive patch or blister-like lesion on the scalp or another area of the body at
birth may occur due to a local absence of skin called aplasia cutis congenita
(picture 32). Aplasia cutis congenita is occasionally associated with other physical
defects or genetic disorders. A conspicuous collar of hair around a lesion on the
scalp may indicate the presence of an underlying structural defect (picture 33).
(See 'Aplasia cutis congenita' above.)

ACKNOWLEDGMENT The editorial staff at UpToDate would like to

acknowledge Josie A Pielop, MD, who contributed to an earlier version of this topic
review.
Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES
1. Reginatto FP, Muller FM, Peruzzo J, Cestari TF. Epidemiology and Predisposing
Factors for Erythema Toxicum Neonatorum and Transient Neonatal Pustular: A
Multicenter Study. Pediatr Dermatol 2017; 34:422.
2. Haveri FT, Inamadar AC. A cross-sectional prospective study of cutaneous lesions in
newborn. ISRN Dermatol 2014; 2014:360590.
3. Monteagudo B, Labandeira J, Cabanillas M, et al. Prospective study of erythema
toxicum neonatorum: epidemiology and predisposing factors. Pediatr Dermatol 2012;
29:166.

14
4. Reginatto FP, DeVilla D, Muller FM, et al. Prevalence and characterization of neonatal
skin disorders in the first 72h of life. J Pediatr (Rio J) 2017; 93:238.
5. Marchini G, Nelson A, Edner J, et al. Erythema toxicum neonatorum is an innate
immune response to commensal microbes penetrated into the skin of the newborn
infant. Pediatr Res 2005; 58:613.
6. Paller AS, Mancini AJ. Cutaneous disorders of the newborn. In: Hurwitz Clinical Pediatri
c Dermatology, 5th ed, Elsevier Saunders, Philadelphia 2016. p.16.
7. Carr JA, Hodgman JE, Freedman RI, Levan NE. Relationship between toxic erythema
and infant maturity. Am J Dis Child 1966; 112:129.
8. Berg FJ, Solomon LM. Erythema neonatorum toxicum. Arch Dis Child 1987; 62:327.
9. Ramamurthy RS, Reveri M, Esterly NB, et al. Transient neonatal pustular melanosis. J
Pediatr 1976; 88:831.
10. Barr RJ, Globerman LM, Werber FA. Transient neonatal pustular melanosis. Int J
Dermatol 1979; 18:636.
11. Hernández-Martín Á, Nuño-González A, Colmenero I, Torrelo A. Eosinophilic pustular
folliculitis of infancy: a series of 15 cases and review of the literature. J Am Acad
Dermatol 2013; 68:150.
12. Transient benign cutaneous lesions in the newborn. In: Neonatal Dermatology, 2nd ed,
Eichenfield LF, Frieden IJ, Esterly NB (Eds), Saunders, Philadelphia 2008. p.90.
13. Niamba P, Weill FX, Sarlangue J, et al. Is common neonatal cephalic pustulosis
(neonatal acne) triggered by Malassezia sympodialis? Arch Dermatol 1998; 134:995.
14. Bernier V, Weill FX, Hirigoyen V, et al. Skin colonization by Malassezia species in
neonates: a prospective study and relationship with neonatal cephalic pustulosis. Arch
Dermatol 2002; 138:215.
15. Ayhan M, Sancak B, Karaduman A, et al. Colonization of neonate skin by Malassezia
species: relationship with neonatal cephalic pustulosis. J Am Acad Dermatol 2007;
57:1012.
16. Katsambas AD, Katoulis AC, Stavropoulos P. Acne neonatorum: a study of 22 cases.
Int J Dermatol 1999; 38:128.
17. Paller AS, Mancini AJ. Disorders of the sebaceous and sweat glands. In: Hurwitz Clinica
l Pediatric Dermatology, 5th ed, Elsevier Saunders, Philadelphia 2015.
18. Rapelanoro R, Mortureux P, Couprie B, et al. Neonatal Malassezia furfur pustulosis.
Arch Dermatol 1996; 132:190.
19. Bree AF, Siegfried EC. Acne vulgaris in preadolescent children: recommendations for
evaluation. Pediatr Dermatol 2014; 31:27.
20. Hoath SB, Narendran V. The skin. In: Neonatal-Perinatal Medicine, 9th ed, Fanaroff AA,
Martin RJ, Walsh MC (Eds), Elsevier Mosby, St. Louis 2011. p.1705.
21. Serna-Tamayo C, Janniger CK, Micali G, Schwartz RA. Neonatal and infantile acne
vulgaris: an update. Cutis 2014; 94:13.
22. Cunliffe WJ, Baron SE, Coulson IH. A clinical and therapeutic study of 29 patients with
infantile acne. Br J Dermatol 2001; 145:463.
23. Barnes CJ, Eichenfield LF, Lee J, Cunningham BB. A practical approach for the use of
oral isotretinoin for infantile acne. Pediatr Dermatol 2005; 22:166.
24. Miller IM, Echeverría B, Torrelo A, Jemec GB. Infantile acne treated with oral
isotretinoin. Pediatr Dermatol 2013; 30:513.

15
25. O'Connor NR, McLaughlin MR, Ham P. Newborn skin: Part I. Common rashes. Am Fam
Physician 2008; 77:47.
26. Eichenfield LF, Krakowski AC, Piggott C, et al. Evidence-based recommendations for
the diagnosis and treatment of pediatric acne. Pediatrics 2013; 131 Suppl 3:S163.
27. Feng E, Janniger CK. Miliaria. Cutis 1995; 55:213.
28. Humeau S, Bureau B, Litoux P, Stalder JF. Infantile acropustulosis in six immigrant
children. Pediatr Dermatol 1995; 12:211.
29. Mancini AJ, Frieden IJ, Paller AS. Infantile acropustulosis revisited: history of scabies
and response to topical corticosteroids. Pediatr Dermatol 1998; 15:337.
30. Good LM, Good TJ, High WA. Infantile acropustulosis in internationally adopted
children. J Am Acad Dermatol 2011; 65:763.
31. Jennings JL, Burrows WM. Infantile acropustulosis. J Am Acad Dermatol 1983; 9:733.
32. Dromy R, Raz A, Metzker A. Infantile acropustulosis. Pediatr Dermatol 1991; 8:284.
33. Van Praag MC, Van Rooij RW, Folkers E, et al. Diagnosis and treatment of pustular
disorders in the neonate. Pediatr Dermatol 1997; 14:131.
34. Vignon-Pennamen MD, Wallach D. Infantile acropustulosis. A clinicopathologic study of
six cases. Arch Dermatol 1986; 122:1155.
35. Bundino S, Zina AM, Ubertalli S. Infantile acropustulosis. Dermatologica 1982; 165:615.
36. Kahn G, Rywlin AM. Acropustulosis of infancy. Arch Dermatol 1979; 115:831.
37. Findlay RF, Odom RB. Infantile acropustulosis. Am J Dis Child 1983; 137:455.
38. Narvaez-Rosales V, de-Ocariz MS, Carrasco-Daza D, et al. Neonatal vesiculopustular
eruption associated with transient myeloproliferative disorder: report of four cases. Int J
Dermatol 2013; 52:1202.
39. Piersigilli F, Diociaiuti A, Boldrini R, et al. Vesiculopustular eruption in a neonate with
trisomy 21 syndrome as a clue of transient myeloproliferative disorders. Cutis 2010;
85:286.
40. Uhara H, Shiohara M, Baba A, et al. Transient myeloproliferative disorder with
vesiculopustular eruption: Early smear is useful for quick diagnosis. J Am Acad
Dermatol 2009; 60:869.
41. Manice CS, Planet PJ, Chase HS, Lauren CT. Management of afebrile neonates with
pustules and vesicles in a pediatric emergency department. Pediatr Dermatol 2018;
35:660.
42. James SH, Kimberlin DW. Neonatal Herpes Simplex Virus Infection. Infect Dis Clin
North Am 2015; 29:391.
43. Curfman AL, Glissmeyer EW, Ahmad FA, et al. Initial Presentation of Neonatal Herpes
Simplex Virus Infection. J Pediatr 2016; 172:121.
44. Sauerbrei A, Wutzler P. Neonatal varicella. J Perinatol 2001; 21:545.
45. Speck WT, Driscoll JM, Polin RA, et al. Staphylococcal and streptococcal colonization
of the newborn infant: effect of antiseptic cord care. Am J Dis Child 1977; 131:1005.
46. Pimentel de Araujo F, Tinelli M, Battisti A, et al. An outbreak of skin infections in
neonates due to a Staphylococcus aureus strain producing the exfoliative toxin A.
Infection 2018; 46:49.
47. Mishra AK, Yadav P, Mishra A. A Systemic Review on Staphylococcal Scalded Skin
Syndrome (SSSS): A Rare and Critical Disease of Neonates. Open Microbiol J 2016;
10:150.

16
48. Patel GK, Finlay AY. Staphylococcal scalded skin syndrome: diagnosis and
management. Am J Clin Dermatol 2003; 4:165.
49. Ladhani S, Joannou CL, Lochrie DP, et al. Clinical, microbial, and biochemical aspects
of the exfoliative toxins causing staphylococcal scalded-skin syndrome. Clin Microbiol
Rev 1999; 12:224.
50. Elias PM, Fritsch P, Epstein EH. Staphylococcal scalded skin syndrome. Clinical
features, pathogenesis, and recent microbiological and biochemical developments. Arch
Dermatol 1977; 113:207.
51. Honig PJ, Gaisin A, Buck BE. Frozen section differentiation of drug-induced and
staphylococcal-induced toxic epidermal necrolysis. J Pediatr 1978; 92:504.
52. Ito Y, Funabashi Yoh M, Toda K, et al. Staphylococcal scalded-skin syndrome in an
adult due to methicillin-resistant Staphylococcus aureus. J Infect Chemother 2002;
8:256.
53. Chi CY, Wang SM, Lin HC, Liu CC. A clinical and microbiological comparison of
Staphylococcus aureus toxic shock and scalded skin syndromes in children. Clin Infect
Dis 2006; 42:181.
54. Isenberg HD, Tucci V, Lipsitz P, FAcklam RR. Clinical laboratory and epidemiological
investigations of a Streptococcus pyogenes cluster epidemic in a newborn nursery. J
Clin Microbiol 1984; 19:366.
55. Campbell JR, Arango CA, Garcia-Prats JA, Baker CJ. An outbreak of M serotype 1
group A Streptococcus in a neonatal intensive care unit. J Pediatr 1996; 129:396.
56. Kline A, O'Donnell E. Group B streptococcus as a cause of neonatal bullous skin
lesions. Pediatr Infect Dis J 1993; 12:165.
57. Barber M, Okubadejo OA. Maternal and neonatal listerosis: report of case and brief
review of literature of listeriosis in man. Br Med J 1965; 2:735.
58. Katz KA. Congenital Syphilis-Still a Shadow on the Land. JAMA Dermatol 2018;
154:1389.
59. Dorfman DH, Glaser JH. Congenital syphilis presenting in infants after the newborn
period. N Engl J Med 1990; 323:1299.
60. Rowen JL, Atkins JT, Levy ML, et al. Invasive fungal dermatitis in the < or = 1000-gram
neonate. Pediatrics 1995; 95:682.
61. Perzigian RW, Faix RG. Primary cutaneous aspergillosis in a preterm infant. Am J
Perinatol 1993; 10:269.
62. Nanda S, Reddy BS, Ramji S, Pandhi D. Analytical study of pustular eruptions in
neonates. Pediatr Dermatol 2002; 19:210.
63. American Academy of Pediatrics. Scabies. In: Red Book: 2015 Report of the Committee
on Infectious Diseases, 30th ed, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds),
American Academy of Pediatrics, Elk Grove Village, IL 2015.
64. Quarterman MJ, Lesher JL Jr. Neonatal scabies treated with permethrin 5% cream.
Pediatr Dermatol 1994; 11:264.
65. Hill TA, Cohen B. Scabies in babies. Pediatr Dermatol 2017; 34:690.
66. Hurwitz S. Scabies in babies. Am J Dis Child 1973; 126:226.
67. Meinking T, Taplin D, Vicaria M. Infestations. In: Pediatric Dermatology, 4th ed, Schach
ner LA, Hansen RC (Eds), Churchill Livingstone, New York 2010. p.1584.
68. Adam R, Schroten H. Picture of the month. Congenital sucking blisters. Arch Pediatr
Adolesc Med 2007; 161:607.

17
69. Heinecke G, Marinkovich MP, Rieger KE. Intraepidermal Type VII Collagen by
Immunofluorescence Mapping: A Specific Finding for Bullous Dermolysis of the
Newborn. Pediatr Dermatol 2017; 34:308.
70. Radkevich-Brown O, Shwayder T. Bullous dermolysis of the newborn: four new cases
and clinical review. Pediatr Dermatol 2013; 30:736.
71. Diociaiuti A, Castiglia D, Giancristoforo S, et al. Frequent Occurrence of Aplasia Cutis
Congenita in Bullous Dermolysis of the Newborn. Acta Derm Venereol 2016; 96:784.
72. Galler B, Bowen C, Arnold J, et al. Use of the frozen section 'jelly-roll' technique to aid in
the diagnosis of bullous congenital ichthyosiform erythroderma (epidermolytic
hyperkeratosis). J Cutan Pathol 2016; 43:434.
73. Bharti G, Groves L, David LR, et al. Aplasia cutis congenita: clinical management of a
rare congenital anomaly. J Craniofac Surg 2011; 22:159.
74. Patel DP, Castelo-Soccio L, Yan AC. Aplasia cutis congenita: Evaluation of signs
suggesting extracutaneous involvement. Pediatr Dermatol 2018; 35:e59.
75. Frieden IJ. Aplasia cutis congenita: a clinical review and proposal for classification. J
Am Acad Dermatol 1986; 14:646.
76. Swinney CC, Han DP, Karth PA. Incontinentia Pigmenti: A Comprehensive Review and
Update. Ophthalmic Surg Lasers Imaging Retina 2015; 46:650.

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