11 Vesiculopustular, Bullous and Erosive Diseases of The Neonate

134
CHA PTER 1 1
Vesiculopustular, Bullous and Erosive Diseases

of the Neonate
SECTION 2: SKIN DISORDERS
OF NEONATES AND INFANTS
Caroline Mahon1 & Anna E. Martinez2

1
Department of Dermatology, Bristol Royal Infirmary, University Hospitals Bristol NHS Foundation Trust, Bristol, UK
2
Paediatric Dermatology Department, Great Ormond St Hospital for Children NHS Trust, London, UK
Introduction, 134 Autoimmune causes of vesicular and Other causes of neonatal blistering, 149
Benign and/or physiological neonatal bullous lesions in the neonate, 146 Erosive lesions in the newborn infant, 150
vesiculopustular and bullous skin Genodermatoses associated with neonatal
lesions, 134 blistering, 147
Abstract becomes accustomed to a low‐humidity environment, is colonized

with commensal organisms and matures as an environmental barrier.
The skin of the neonate must make a rapid adaptation to extrau- Distinguishing between cutaneous eruptions that represent benign
terine life. A number of benign physiological vesiculopustular and or transient physiological cutaneous phenomena, infections, inflam-
bullous skin lesions present in the newborn period and these matory dermatoses and genodermatoses is essential to guide clinical
probably represent adaptive events as the skin of the neonate management.
Key points • Most transient and benign vesiculopustular eruptions require

no intervention when typical clinical features present in a well
• Self‐limiting physiological and benign vesiculopustular skin newborn infant, however there should be a low threshold for
eruptions are very common in the neonatal period. further investigation if lesions progress.
• Blistering and erosions are most commonly due to infectious
causes, however genodermatoses and autoimmune skin disorders
should be considered in the differential diagnosis.
Introduction Benign and/or physiological

The skin of the neonate must make a prompt adaptation neonatal vesiculopustular
to extrauterine life. A number of benign and physiological and bullous skin lesions
vesiculopustular and bullous skin lesions may present Milia (see also Chapter 6)
in the newborn period. These eruptions probably rep- Milia are 1‐ to 2‐mm firm, pearly‐white papular lesions
resent adaptive physiological events while the skin with a pseudopustular appearance.
of the neonate becomes accustomed to a low‐humidity
environment, is colonized with commensal organisms
and matures to establish itself as an environmental barrier. Epidemiology and pathogenesis. In prospective
Distinguishing between skin eruptions that represent observational studies documenting cutaneous lesions
benign and/or transient physiological phenomena, in otherwise well full‐term neonates the incidence of
infections, inflammatory dermatoses and genodermatoses primary or congenital milia ranged between 7.5%
is essential to avoid the unnecessary investigation and and 50% [1–4]. One study found that milia were
treatment of newborn infants with benign skin lesions, significantly more common in male than female infants
to appropriately investigate those with likely signifi- at less than 48 hours of age [4]. Milia are subepidermal
cant pathology and to counsel parents appropriately keratin‐containing cysts that represent an accumula-
(Tables 11.1 and 11.2). For further differential diagnoses tion of keratin within vellus hair‐associated sebaceous
please refer to Chapter 73. glands.
Harper’s Textbook of Pediatric Dermatology, Fourth Edition. Edited by Peter Hoeger, Veronica Kinsler and Albert Yan.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
Chapter 11 Vesiculopustular, Bullous and Erosive Diseases of the Neonate 135
Table 11.1 Differential diagnosis of vesiculopustular and bullous eruptions in the neonate
Pathophysiology Typical age of onset Clinical features Typical distribution Diagnostic investigations and
pathological features
Benign, self‐limiting and/or physiological vesiculopustular and bullous disorders

Milia At birth Pinpoint 1‐ to 2‐mm milky Cheeks, nasal bridge and Clinical diagnosis

papules alae, forehead Histopathology shows inclusion
cysts containing keratinized
stratum corneum
Miliaria crystallina At birth, or days to Confluent sheets or clusters of Forehead and trunk are most Clinical diagnosis
weeks of age 1‐ to 2‐mm fragile watery commonly involved Histopathology shows sub‐or intra‐
vesicles without inflammatory corneal eccrine duct obstruction
component
Erythema toxicum Typical onset at 1–2 days Small pinhead‐sized pustules Trunk and limbs excluding Clinical diagnosis
neonatorum (ETN) of age. May be seen as and vesicles associated with acral skin and mucous Pustule smear microscopy reveals
late as 2 weeks of age diffuse erythematous flares membranes predominant eosinophils
Miliaria rubra First days to weeks of Localized crops of erythematous Forehead, posterior neck, Clinical diagnosis
age papules and pustules trunk and proximal limbs Histopathology as for miliaria crystallina
Benign (or transient) Usually after the first Scattered superficial fragile Trunk, limbs, hands and feet Clinical diagnosis
neonatal pustular week of life and up pustules which erode leaving Mucous membranes are not Wright‐stained pustule smear
melanosis to 6 weeks of age a characteristic collarette of involved microscopy reveals predominant
fine scale and macular May infrequently occur on neutrophils (in contrast to ETN)
hyperpigmentation acral surfaces
Benign cephalic Onset within 1–2 Crops of fragile pustules and Face and scalp predominate. Clinical diagnosis
pustulosis weeks of age, up to vesicles associated with May occur over the neck
6 weeks of age erythema and often fine scale and upper chest
Neonatal eosinophilic At birth or weeks to Recurrent, intensely pruritic Scalp and acral sites Clinical diagnosis
pustulosis/pustular months of age pustulovesicular eruption Giemsa‐ or Wright‐stained smear
folliculitis microscopy of pustule contents
reveals abundant eosinophils
Acropustulosis of Typical onset within the Crops of inflammatory pustules Palmoplantar surfaces Clinical diagnosis
infancy first 8 weeks of age predominate Smears of pustule contents reveal
Occasionally present Dorsa of the hands and feet either neutrophil‐ or eosinophil‐
from birth may be involved predominant infiltrate
Infantile acne Onset usually from weeks Crops of comedonal and small Cheeks, chin and forehead Clinical diagnosis
to months of age cystic lesions.
Scarring may occur
Infective causes of vesiculopustular and bullous lesions in the neonate
Staphylococci At birth, or days to Superficial flaccid or fragile May occur at any site. Skin swab bacterial culture
(bullous impetigo and weeks of age blisters associated with The umbilical stump is a
staphylococcal desquamation and crusting common focus of bacterial
scalded skin May present as an exfoliative infection/colonization
syndrome) erythroderma with flexural
accentuation (staphylococcal
scalded skin syndrome)
Streptococcus At birth, or days to Superficial bullae and erosions May occur at any site Skin swab bacterial culture
pyogenes weeks of age associated with yellow crusts
Congenital or neonatal At birth, or days to Pustules and/or erosive skin Pustular lesions are generalized Skin swab microscopy and culture
candidiasis weeks of age lesions Congenital candidiasis may Microscopic examination of the
May be complicated by present as an erosive placenta and umbilical cord
pneumonia erythroderma The presence of microabscesses is
Skinfolds and the napkin highly suggestive of Candida
area are common sites of placentitis
involvement
Herpes simplex virus At birth, or days to Presents with either congenital Vesicles, bullae and erosions Viral swab HSV DNA PCR
(HSV) (types 1 and 2) weeks of age erythroderma and extensive may occur anywhere on Tzanck smear of blister base: balloon‐
skin loss or, in cases of the body and be localized like multinucleated giant cells and
postnatal infection, multiple or generalized eosinophilic inclusion bodies
clusters of monomorphic Mucosal lesions are common Direct immunofluorescence assay
vesicles and necrotic erosions (DFA) smear of vesicle contents or
on a background erythema mucocutaneous lesions
Histopathology shows acantholysis,
Infants may present with solitary keratinocytes within an
disseminated HSV infection intradermal blister cavity and viral
without skin lesions nuclear inclusion bodies
Clinical diagnosis
(Continued )
136 Section 2 Skin Disorders of the Neonate and Young Infant
Table 11.1 Continued
Neonatal varicella At birth or within days Polymorphous fragile May occur at any site Viral swab VZV DNA PCR from skin
zoster virus (VZV) to 2 weeks of age (if haemorrhagic vesicles and Neonatal VZV infection is lesions or CSF
mother develops superficial erosions on an generally associated with Tzanck smear of blister base reveals
primary varicella erythematous base disseminated disease and multinucleate giant cells in the
infection 1 week may be severe and epidermis with marginated
before or after life‐threatening chromatin
delivery) DFA testing of smear of vesicle
contents
Histopathology reveals intraepidermal
vesiculation, multinucleated giant
cells and nuclear inclusions
Congenital Listeria At birth Haemorrhagic and purpuric skin Generalized skin lesions Bacterial skin swabs and blood
monocytogenes lesions with associated associated with sepsis is cultures
pustular and necrotic lesions typical
Congenital syphilis At birth Generalized and nonspecific Palmoplantar pustules and T. pallidum observed in skin
annular, erythematous or desquamation are classical scrapings or skin biopsy by
purpuric lesions when present dark‐field microscopy, Giemsa or
Localized pustules, blisters and silver staining
erosions (‘pemphigus Serological testing has variable
syphiliticus’) sensitivity and specificity
Rhinitis, periostitis metaphyseal Serum VDRL is nonspecific and may
erosions, hepatosplenomegaly be falsely positive
and lymphadenopathy Placental histology may be helpful
Scabies Days to weeks of age Urticated papules and plaques, Scalp typically involved in Clinical diagnosis
pustules and vesicles infants as well as trunk, Microscopy of skin scraping reveals
Absence of excoriation in limbs, palms and soles scabies mites and/or ova
neonates is characteristic Examination of close Dermoscopy reveals linear scabetic
May present with nodules and contacts is mandatory burrows
may mimic urticaria Skin biopsy reveals intraepidermal
pigmentosa and subcorneal pustules
associated with eosinophils
Coxsackie‐type Typically after the first Crops of acral perioral and genital Oral mucosa, perioral skin, Clinical diagnosis
enterovirus week to 1 month papules and grey‐blue vesicles palms and soles as well as Viral swab enterovirus DNA PCR
of age on an erythematous base dorsal hands and feet
May be koebnerized to flexural Not infrequent in the genital
skin, especially in infants with skin, buttocks and
eczema inguinal folds
Autoimmune causes of vesiculopustular and bullous lesions in the neonate
Maternally‐transmitted autoimmune blistering diseases
Pemphigus vulgaris Onset at birth or during Flaccid bullae and erosions Typically generalized Histopathology reveals
(PV) and pemphigus the first 2 weeks of associated with crusting affecting the skin and the intraepidermal blister
foliaceus (PF) age affecting the skin and mucous mucous membranes Direct IF: intercellular deposits of
membranes in both PV and PF (neonates in contrast to IgG and/or C3 in the epidermis
adults have diffusely Indirect IF: may be performed on
distributed desmoglein‐3 serum
in both the skin and
mucous membranes)
Bullous pemphigoid Onset within days or Urticated plaques and tense Widespread tense vesicles Histopathology shows eosinophilic
(BP) weeks of age serous fluid‐filled or and bullae spongiosis with subepidermal
haemorrhagic bullae on an Mucous membranes are not blistering/clefting
inflammatory base affected Direct IF: linear deposition of IgG and/or
C3 along the basement membrane
Indirect IF: may be performed on
serum or blister fluid
NaCl salt‐split skin reveals IgG
deposition on the epidermal side
(blister roof)
Pemphigoid gestationis Within the first week of Annular crops of vesicles and Blistering may occur Direct IF: linear deposition of IgG and
(PG) age bullae on a background of anywhere C3 along the basement membrane
Neonates affected in polycyclic or urticarial Mucous membranes are not NaCl salt‐split skin reveals IgG
3–5% of pregnancies erythema affected deposition on the epidermal side
complicated by PG (blister roof)
(Continued )
Linear immunoglobulin Onset of blistering Crops of tense vesicles and Generalized blistering Skin biopsy reveals subepidermal
A bullous dermatosis reported as early as bullae Mucosal involvement is blistering with linear IgA
1–10 days of life common in neonates and deposition along the epidermal
may lead to life‐threatening basement membrane

aerodigestive complications
Paraneoplastic causes of vesiculopustular and bullous lesions in the neonate
Pustular dermatosis of First weeks to the first Crops of superficial Facial rash is commonly Histopathology reveals infiltrate of
myelodysplasia in month of life pustulovesicular lesions on a described but may occur immature myeloid cells within
Down syndrome background urticated anywhere epidermal spongiotic
erythema vesiculopustular cavities
Other causes of vesiculopustular and bullous lesions in the neonate
Langerhans cell At birth, or within the Multiple haemorrhagic Lesions usually are Histopathology reveals dense dermal
histiocytosis (LCH) first days of life papulovesicles generalized with infiltrate of Langerhans cells
May mimic miliary predominance of lesions Staining for CD1a, S100 and
haemangiomatosis in the scalp, inguinal folds Langerin are classically positive
Solitary congenital LCH tumours and genital areas Histopathology as above
or ulcers have been described May occur anywhere on the
and are frequently self‐resolving body
Bullous mastocytosis At birth, or within days Sparse or generalized bullae Lesions may occur anywhere Histopathology reveals dense
to weeks of life associated with widespread on the body dermal mast‐cell infiltrate with
red‐brown plaques and plane of blister cleavage through
macules the lamina lucida
CD117 positive
Bullous neonatal lupus At birth or at days to Bullae on an inflammatory base May occur anywhere on the Histopathology reveals subepidermal
erythematosus (NLE) weeks of age healing with milia body blistering and vacuolar
Sun‐exposed sites are degeneration of the basal layer
thought to be more prone Maternal anti‐Ro/SSA and/or
to NLE lesions anti‐La/SSB antibody positive
Hyperimmunoglobulin At birth, days, weeks or Generalized sterile papulopustular Face and scalp involvement Histopathology reveals eosinophil‐
E syndrome (HIES) months of age eruption occurring within 2 initially, progressing in rich infiltrate similar to that
months of life in 67% of cephalo‐ caudal direction seen in EPF
infants with HIES Markedly elevated serum IgE levels
Mucocutaneous candidiasis and Three known gene mutations
fungal paronychia are common (TYK2, STAT3, DOCK8)
Deficiency of At birth or days to Sheet‐like micropustular eruption Usually generalized pustular Due to deficiency of interleukin‐1
interleukin‐1 weeks of age on background erythema lesions scattered anywhere receptor antagonist (DIRA)
receptor antagonist resembling pustular psoriasis on the body Skin biopsy shows neutrophilic
(DIRA) Fever, arthritis and/or subcorneal pustules
osteomyelitis may be Molecular genetic testing for
associated mutations in ILRN1
Neonatal bullous At 1–2 months of age Multiple indurated annular May be localized or Histopathology reveals a dense
neutrophilic plaques associated with generalized dermal neutrophilic infiltrate
dermatosis vesicles and bullae or A florid peripheral neutrophilia is
(Sweet syndrome) pustulation on an common
erythematous base Often heralds an immunodeficiency
syndrome, leukaemia or
autoimmune/inflammatory disorder
Genodermatoses associated with neonatal blistering
Epidermolysis bullosa At birth, or within days Bullae, erosions and/or May occur anywhere, but IF of the skin biopsy may be
(EB) or weeks of age ulceration extremities and sites of diagnostic; confirm with genetic
May present with large areas trauma most common testing if available; rarely EM may
of congenital skin loss Aplasia cutis congenita may be required
(aplasia cutis) occur in all forms of EB
Congenital At days to weeks of Generalized severe Skin fragility, bullae and Histopathology reveals
erythropoietic age photosensitivity superficial erosions in subepidermal blistering with
porphyria Severe blistering may result from light‐exposed areas of skin cleavage within the lamina lucida
phototherapy treatment for May be associated with Markedly decreased erythrocyte
neonatal jaundice profound haemolytic uroporphyrinogen synthase
anaemia activity and/or markedly increased
Pink urine and urinary levels of urinary uroporphyrin I
fluorescence under and coproporphyrin I isomers
Wood’s lamp is Detection of biallelic pathogenic
characteristic variant in UROS, or rarely GATA1
(Continued )
Incontinentia pigmenti At birth or up to 6 Blaschkolinear crusted May occur anywhere on the Histopathology shows
weeks thereafter vesicopustules on an body, although the face is intraepidermal blistering with an
(skin lesions may first inflammatory base almost always spared eosinophilic infiltrate
present as late as 1 Cicatricial scalp alopecia is Molecular genetic testing: IKBKG
year of age) not infrequent reveals deletion of exons 4–10 in
80% of cases
Superficial At birth or within a few Bullae and erosions with Intermittent blistering and Skin biopsy reveals hyperkeratosis,
epidermolytic days of age minimal associated desquamation may occur vacuolated keratinocytes and
ichthyosis (previously background erythema anywhere on the body keratohyalin granules in the
ichthyosis bullosa of Superficial erosions and No mucosal involvement epidermal granular and spinous
Siemens) desquamation, so‐called layers
‘Mauserung phenomenon’ No associated acral Molecular genetic testing of KRT2
keratoderma
Epidermolytic At birth or within a few Congenital erythrodema and Generalized erythema and Clinical diagnosis
ichthyosis (previously days of age fragile superficial bullae blistering resulting in Skin swab bacterial culture
called epidermolytic appearing at or within days superficial erosions with Molecular genetic testing of
hyperkeratosis or of birth desquamation KRT1 and KRT10
bullous congenital Annular subtype described Secondary bacterial infection Skin biopsy shows variable
ichthyosiform May be confused with is common hyperkeratosis and acanthosis
erythroderma) staphylococcal scalded skin No mucosal involvement with vacuolar change and
syndrome and suprabasal Palmoplantar keratoderma thickening of the epidermal
forms of EB may be present from birth granular layer
(more commonly
associated in infants with
mutations in KRT1)
CSF, cerebrospinal fluid; DEJ, dermoepidermal junction; DFA, direct fluorescent antibody; IF, immunofluorescence; NaCl, sodium chloride; PCR, polymerase
chain reaction (in vitro nucleic acid amplification); VDRL Venereal Disease Research Laboratory (serological treponemal antibody test).
Table 11.2 Differential diagnosis of erosive or ulcerative skin lesions in the neonate
Pathophysiology Age at onset Clinical features Typical distribution Pathological features and
diagnostic investigations
Mechanical and/or iatrogenic causes of erosions in the neonate

Iatrogenic scalp At birth Localized erosions on the Anywhere on the scalp Clinical diagnosis
birth injuries vertex of the scalp due to Usually linear or crescenteric lesions
pH scalp electrode, ventouse
or forceps placement
May be confused with aplasia
cutis capitis
Sucking blisters At birth Isolated annular erosions, Typically present on the thumb, fingers or Clinical diagnosis
usually solitary medial aspect of the forearms
Infective causes of erosions in the neonate
Staphylococcal At birth or days to Erythroderma with widespread Generalized desquamation Skin swab bacterial culture
scalded skin weeks of age superficial desquamation Perioral, genital and flexural accentuation Skin biopsy shows subcorneal plane
syndrome (SSSS) classical of cleavage
The umbilical stump is a common focus of
infection
Congenital or At birth, days to Erythema associated with May be present with erythroderma, Clinical diagnosis
neonatal weeks of life generalized pustules and generalized micropustulation, scaling Skin swab bacterial culture
candidiasis genital erosions with or without ulceration (congenital
candidiasis) or be localized to the
napkin area, trunk and/or the skinfolds
Herpes simplex virus At birth or at a few Erythroderma with erosions May present with either localized Tzanck smear
(HSV) infection days of age and ulceration ulceration or extensive areas of DFA testing of skin smear
(types 1 and 2) denuded skin Viral swab HSV DNA PCR
from skin lesions or CSF
Skin biopsy
(Continued )
Fetal varicella At birth (if mother Stellate, well‐circumscribed May occur anywhere on the body Clinical diagnosis
(VZV) syndrome infected in the ulcerations (aplasia cutis) May be associated with limb hypoplasia, PCR swab for VZV DNA

first 20 weeks of often in a segmental or microcephaly, ocular abnormalities from skin lesions or CSF
pregnancy) dermatomal distribution (microphthalmia, chorioretinitis, Serum IgM (25% positive)
corneal alterations, cataracts) and
growth retardation
Primary varicella At birth, days or Eroded or ulcerated papules Usually generalized PCR swab for VZV DNA
zoster virus (VZV) weeks of life and vesicles
infection
Ecthyma Days and weeks Necrotic plaques and May be solitary or multiple and occur Bacterial skin swabs/blood cultures
gangrenosum after birth ulceration anywhere on the body for Pseudomonas aeruginosa
localized ulcerations
Congenital Listeria At birth Haemorrhagic areas, May occur anywhere on the skin Bacterial skin swabs/blood cultures
monocytogenes purpura, pustules and
infection bullae
Primary cutaneous Days to weeks after Erosions, ulcerations and Skin may be primarily inoculated Skin biopsy
aspergillosis birth pustulation superimposed through areas of macerated skin, or Fungal hyphae may be visible in
Particularly on background erythema infected at sites of adhesive skin fresh tissue stained with calcofluor
associated with taping or central or peripheral venous Haematoxylin and eosin staining
prematurity and catheter devices variably demonstrates Aspergillus
central venous hyphae
access Period acid–Schiff and Grocott silver
stains may add sensitivity
PCR detection of Aspergillus DNA in
fresh tissue
Autoimmune causes of erosive lesions in the neonate
Maternally‐transmitted autoimmune blistering disease
Pemphigus Onset at birth or In both PV and PF, infants Erosions may involve both the skin and Skin biopsy reveals epidermal
vulgaris during the first 2 present with localized or mucous membranes in neonates with acantholysis with intraepidermal
(PV), pemphigus weeks of life extensive flaccid fragile PF or PV plane of blister cleavage
foliaceus (PF) bullae and crusted erosions IF: intraepidermal IgG antibodies
Other causes of erosive lesions in the neonate
Congenital erosive At birth Mixed erosions, vesicles and Typically generalized skin involvement Clinical diagnosis
and vesicular bullae in early neonatal sparing mucous membranes Almost Skin biopsy findings depend on
dermatosis with period all cases involve >75% of skin surface disease stage
reticulated Reticulated atrophic but
supple scarring subtle scarring evolves over
weeks to months
Langerhans cell At birth, or within Multiple small haemorrhagic Seborrhoeic distribution is classical, but Skin biopsy shows dense dermal
histiocytosis days of life erosions and ulcerations may occur anywhere infiltrate of Langerhans cells
(LCH) CD1a, S100 and Langerin positive
staining
Congenital At birth Solitary eroded or ulcerated May occur at any site Solitary lesions are generally self‐
self‐healing papule and/or nodule healing and regress spontaneously
reticulo- over 3–6 months
histiocytosis
Bullous and At birth, or within Sparse or generalized erosions Lesions may be single or multiple and Skin biopsy reveals a dense dermal
diffuse days to weeks of and ulcers admixed with occur anywhere on the body mast‐cell infiltrate with plane of
cutaneous life bullae and vesicles blister cleavage through the
mastocytosis Skin may thicken markedly in lamina lucida
early postnatal life CD117 positive staining
Aplasia cutis At birth Well‐demarcated, often Localized or widespread ulcers or scars Skin biopsy reveals absence of
congenita stellate areas of absent or May occur anywhere, but most common epidermal and dermal structures
scarred skin on the vertex of the scalp and skin appendages
Lesions may be linear and
appear blaschkoid or
dermatomal in distribution
Methylmalonic At birth or within days Extensive erythema and Marked perioral accentuation Skin biopsy is nondiagnostic
acidaemia of birth superficial erosions Blood count often reveals neutropenia
and thrombocytopenia
Plasma amino acid profile is charac
teristic and confirms the diagnosis
(Continued )
Genodermatoses associated with erosions and ulceration

Epidermolysis At birth, days or Bullae, erosions and/or May present with large areas of Skin biopsy
bullosa (EB) weeks of ulceration, particularly denuded skin or skin loss IF and EM may confirm the
postnatal life extremities Nail changes may be present at birth diagnosis
May present with localized Genetic testing may be appropriate
area of aplasia cutis on one
or more limbs
Epidermolytic At birth Erythroderma with occasional Generalized superficial exfoliation and Clinical diagnosis
ichthyosis fragile bullae and erosions Skin biopsy shows variable
superficial exfoliation Congenital palmoplantar keratoderma hyperkeratosis and acanthosis
Desquamation is often may be evident with vacuolar change and
annular and may mimic thickening of the epidermal
SSSS and other bullous granular layer
disorders Mutational analysis of KRT1 and
KRT10 genes
Superficial At birth Occasional bullae and Intermittent blistering and Skin biopsy
epidermolytic minimal erythema desquamation may occur anywhere Mutational analysis of KRT2 gene
ichthyosis Superficial erosions and on the body
desquamation No mucosal involvement
Incontinentia At birth or up to Blaschkolinear erosions/ May occur anywhere on the body, Clinical diagnosis
pigmenti (IP) 6 weeks ulcerations although face is almost always spared Mutational analysis of IKBKG gene
thereafter
(may first occur as
late as 1 year
of age)
Focal dermal At birth Blaschkolinear aplastic streaks May occur anywhere on the body Clinical diagnosis
hypoplasia and/or dermal hypoplasia Sparse scalp hair and/or patchy Mutational analysis of
(Goltz syndrome) often associated with fat cicatricial alopecia are common PORCN gene
herniation and
telangiectasia
Limb malformations, ocular
abnormalities and
craniofacial dysmorphism
are common
Restrictive At birth Tight, shiny translucent Severe generalized skin restriction Clinical diagnosis
dermopathy skin associated with Erosions typically on extensor surfaces of Skin biopsy reveals hypergranulosis
localized erosions and the joints and absent sebaceous and
ulceration eccrine structures
Joint contractures, pinched Mutational analysis of ZMPSTE24
facial features and or LMNA
microstomia are
characteristic features
CSF, cerebrospinal fluid; DEJ, dermoepidermal junction; DFA, direct fluorescent antibody; EM, electron microscopy; IF, immunofluorescence; PCR,
polymerase chain reaction (in vitro nucleic acid amplification).
bridge. Bohn nodules may be mistaken for natal teeth.

Clinical features. Milia are typically present at birth and
Profuse congenital facial milia are a prominent feature of
their facial distribution is characteristic. Most commonly
Basan syndrome, a rare autosomal dominant dermatosis
they are found on the face, typically on the forehead and
also associated with transient acral bullae, lack of derma-
chin and in the nasolabial folds. Mucosal lesions, either
toglyphs, and palmoplantar hypohidrosis [5]. Other rare
on the palate (Epstein pearls) or alveolar surfaces (Bohn
disorders associated with persistent or widespread milia
nodules) are also common.
include oro‐facial‐digital syndrome, hereditary trichod-
ysplasia (Marie Unna hypotrichosis) (OMIM #146550),
Differential diagnosis. The appearance and distribution Loeys–Dietz syndrome (OMIM #609192) [6], follicular
of milia is usually typical and does not cause diagnostic atrophoderma–basal cell carcinoma (Bazex–Dupré–Christol)
confusion. Milia most closely resemble sebaceous hyper- syndrome (OMIM 301845) and Rombo syndrome (OMIM
plasia, also common in neonates, but in contrast, seba- 180730) characterized by vermiculate atrophoderma, milia,
ceous hyperplasia is almost always confined to the nasal hypotrichosis, trichoepitheliomas and basal cell carcinomas.
adhesive medical monitoring leads and tapes. Congenital

Laboratory/histology findings. The diagnosis is clinical.
lesions are uncommon, but have been reported [10].
The histological appearance of milia is classical. Typically a
In some cases, a history of intrapartum fever is suspected
globular cyst lined with several layers of stratified squa-
to have been the trigger [11].
mous epithelium containing keratinous material is associ-
Miliaria rubra is characterized by crops of nonfolli-
ated with the infundibular portion of a hair follicle or
cular vesicles on an inflammatory base. Most often the
eccrine sweat duct. There is no associated inflammation [7].

flexural skin and sites of friction such as the neck folds
are most prominently affected, but miliaria rubra also
Treatment and prevention. Primary milia in newborns commonly involves the trunk. Type 1 pseudoaldoster-
resolve spontaneously over weeks to months and require onism, a disorder of mineralocorticoid resistance, results
no treatment. in excess loss of salt through eccrine secretions and
appears to characteristically cause a recurrent pustular
Miliaria form of miliaria rubra [12].
Miliaria is a pustulovesicular eruption caused by eccrine
duct obstruction leading to subcutaneous sweat reten- Differential diagnosis. Vesicular lesions may evolve to
tion. Three forms are described: miliaria crystallina become pustular and mimic the infectious lesions of
(sudamina), miliaria rubra and miliaria profunda. These Staphylococcus aureus, Candida albicans and herpes simplex
forms are clinically and histopathologically distinct, the virus (HSV). Miliaria rubra may be mistaken for erythema
appearances depending on the level of eccrine duct toxicum neonatorum, however unlike erythema toxicum
obstruction. miliaria rubra has a predilection for flexural skin and
tends to recur.
Epidemiology and pathogenesis. In a retrospective study
of 5387 Japanese infants examined on a postnatal ward,
Laboratory/histology findings. Miliaria crystallina is
miliaria crystallina was diagnosed in 4.5% of newborns,
characterized by sterile subcorneal vesicles, miliaria rubra
with a peak incidence at 1 week of age [8]. Obstruction of
by intraepidermal vesicles and, in cases of miliaria pustu-
the epidermal component of the sweat ducts leads to
losa, vesicles and pustules are present at the level of the
accumulation of eccrine secretions within the epidermis
dermoepidermal junction. Miliaria can be distinguished
and subsequently superficial vesicle formation.
from infective lesions by the absence of inflammatory
cells, negative bacterial and viral swabs and the presence
Clinical features. Miliaria crystallina is the most super-
of giant keratinocytes on cytological examination of
ficial form of miliaria. Fragile sheets of superficial trans-
vesicle contents.
lucent noninflammatory vesicles measuring 1–3 mm in
diameter and containing watery fluid are most commonly
Treatment and prevention. Cooling measures are gener-
seen in the neck folds and axillae and on the back. Lesions
ally all that is required. Infants should be unwrapped if
on the face are not uncommon (Fig. 11.1). Onset is typically
tightly swaddled and removed from warm or excessively
in the first days of life, and lesions are exacerbated by
humid environments. If care in an incubator is required,
high‐humidity environments, phototherapy and occlusive
the humidity and temperature should be reduced and the
clothing and emollients [9]. Lesions may be found under
infant dressed in loose clothing.
Erythema toxicum neonatorum

(see also Chapter 6)
Erythema toxicum neonatorum (ETN) is characterized by
pinpoint vesicles and pustules appearing on a blotchy
background of ill‐defined macular erythema.
Epidemiology and pathogenesis. The incidence of ETN

in population studies of infants in neonatal units and
postnatal wards varies between 8% and 44% [3,4,11–13].
Incidence is higher in Caucasian infants [10,14] but ETN
is seen in all ethnic groups with incidence rates appearing
to depend on the timing of the neonatal skin examination.
Some authors have reported a preponderance of female
infants [15,16], but others have not [10,11]. The incidence
of ETN appears to increase with gestational age with most
studies [6,11,17–19] reporting a higher incidence in term
Fig. 11.1 Miliaria crystallina on the forehead of a neonate.
infants than in those born prematurely. Associations with
Source: © Crown copyright [2000‐2005] Auckland District Health Board. mode of delivery are unclear: some authors have observed
Image courtesy of Auckland District Health Board, Department of Newborn higher rates of ETN in infants born vaginally [10,11,13]
Services. New Zealand. and others in those born by caesarean section [4,12,20].
The cause of ETN is not known. Many have speculated

that ETN represents a type of cutaneous hypersensitivity
reaction and a normal physiological response to coloni-
zation of neonatal skin with commensal bacteria and
yeasts [21].
Clinical features. Lesions appear as early as day 2 of life

and as late as 10 days. Congenital lesions have rarely been
reported [22,23]. Typically an infant with ETN presents
with multiple macular areas of blotchy ill‐defined ery-
thema with a central 1‐ to 2‐mm papule or pustule, most
commonly on the trunk [10] but possibly involving any
Fig. 11.2 Transient pustular melanosis on the sole of the foot of a
area of the skin except acral sites. Occasionally infants newborn infant.Source: © Crown copyright [2000‐2005] Auckland District
present with florid ETN with marked erythema and urti- Health Board. Image courtesy of Auckland District Health Board,
carial papules or pustules. Infants are characteristically Department of Newborn Services. New Zealand.
asymptomatic. Lesions spontaneously resolve over 2–4 days
and tend not to recur.
Clinical features. Lesions are typically present at birth.
Differential diagnosis. Confusion between the skin Milky‐white to yellow, fragile pustular lesions without
lesions of ETN, miliaria rubra and neonatal cephalic pus- background erythema are most commonly seen on the
tulosis may arise, or they may occur concurrently. The forehead, bitemporal regions, cheeks, neck and back.
lesions of ETN can generally be clinically distinguished Involvement of the palms and soles is less frequent
from those of herpes simplex and varicella zoster virus or (Fig. 11.2). The fragile pustules rupture with minor trauma
Candida albicans. Eosinophilic pustular folliculitis may leaving pea‐sized pigmented macules with a peripheral
closely resemble ETN both clinically and histologically, collarette of fine scale. The hyperpigmentation may
although large pustules rather than papules are the pre- persist for weeks to months. In some cases neonates
dominant morphological finding in eosinophilic pustular present with annular hyperpigmented macules associ-
folliculitis. ated with a peripheral halo of fine scale soon after birth,
having presumably developed pustular lesions in utero.
Laboratory/histology findings. Microscopic evaluation
of a pustule smear stained with Giemsa or Wright stain Differential diagnosis. Infectious diseases, in particular
reveals an eosinophil‐dominant exudate. A peripheral staphylococcal and streptococcal pyoderma, candidiasis,
blood eosinophilia may be observed in 7–15% [24] of primary varicella zoster and herpes simplex virus and
affected neonates. Skin biopsy reveals dermal oedema syphilitic infections may all mimic TNPM. Other benign
with a primarily eosinophilic perivascular infiltrate. In neonatal eruptions confused with pustular melanosis
papular lesions an eosinophilic infiltrate centred in the include eosinophilic pustulosis, benign cephalic pustulosis
pilosebaceous unit may be observed. and ETN.
Treatment and prevention. Parents should be reassured Laboratory/histology findings. Microscopic examination
that the natural history is spontaneous resolution without of a Wright or Giemsa‐stained pustule smear reveals a
specific intervention. No treatment is required. predominance of neutrophils with only occasional eosin-
ophils. A skin biopsy is rarely required for diagnosis.
Transient neonatal pustular melanosis Histopathology reveals epidermal pustules with either
(see also Chapter 6) intra‐ or sub‐corneal collections of neutrophils with scat-
Transient neonatal pustular melanosis (TNPM), also tered eosinophils [22] and a basal and suprabasal increase
called benign pustular melanosis, is a self‐resolving in pigmentation, without pigmentary incontinence.
pustular eruption that typically presents in the first

month of life. Treatment and prevention. TNPM is a self‐limited
disease in newborns, and no treatment is required.
Epidemiology and pathogenesis. TNPM affects both
sexes equally with an overall incidence of approximately Neonatal and infantile eosinophilic
0.5–1% [4] and is more common in Afro‐Caribbean infants, pustulosis
in whom the incidence is 4.4% [25]. The aetiology is Neonatal eosinophilic pustulosis (NEP) is a rare eruption
unclear. It has been speculated that TNPM is a variant that appears to be associated with prematurity [27]. It is
form of ETN, and therefore a physiological response to probably a variant of eosinophilic pustular folliculitis
skin colonization with commensal microorganisms, (EPF), a relapsing and remitting eosinophil‐predominant
because multiple cases of infants with pustular melanosis pruritic pustular dermatosis of unknown aetiology first
followed by the subsequent appearance of classical described in Japanese adults by Ofuji et al. in 1970 [28]
lesions of ETN have been described [26]. (also referred to as Ofuji’s disease), but subsequently also
reported to occur in infancy and childhood [29]. An infan-

tile form of EPF was first described in 1981 [30], followed
by the publication of a case series of five children [31] in
1984. Infantile forms of EPF do not consistently present
with histological evidence of folliculitis. Although the
clinical history, lesion morphology and distribution are

similar in eosinophilic pustulosis of infancy (EPI) [32]
and NEP [33], rather than being distinct disorders, these
entities are likely to fall within the spectrum of EPF.
Additionally, a number of authors have commented on
the clinicopathological similarity between eosinophilic
pustulosis of infancy and acropustulosis of infancy [28,34]
and have suggested that this entity also falls within the
spectrum of EPF.
Epidemiology and pathogenesis. There are a handful

of case reports describing nonfollicular eosinophilic
pustulosis and eosinophilic folliculitis in neonates, all
of which were boys born at 26–28 weeks’ gestation with
onset at between 7 and 13 weeks of age [24,35,36]. Two
infants had a preceding history of Candida sepsis.
A large series of 15 infants with EPI accompanied by a
review of an additional 46 cases from the literature Fig. 11.3 Infantile eosinophilic pustulosis of the scalp in a child aged
found that EPI is more common in boys, with a 36 months.
male : female ratio of 4 : 1, with a mean age of onset
of 6 months with 95% of children presenting before In neonates, NEP is characterized by sterile pustules
14 months of age [37]. There appears to be no racial primarily or exclusively involving the scalp with less
predilection, although EPF appears to be more com- prominent involvement of the face, trunk and extremities.
monly reported and probably more readily recognized Although EPI is characterized by remissions and relapses,
in Japan than in other countries [38]. only one of the neonatal cases described developed
The pathogenesis is unknown. The clinicopathological recurrence.
similarities between hyperimmunoglobulin E syndrome,
EPI and NEP, and the fact that eosinophilic folliculitis is Differential diagnosis. Staphylococcal and streptococcal
well described in patients with human immunodeficiency impetigo should be excluded, as should neonatal herpes
virus (HIV) [39], haematological malignancies [40] and simplex and varicella zoster virus infection. Scabies mites
immunodeficiency syndromes [41] suggests that a dys- commonly infest the head and neck in young infants who
regulated or immature immune response to an as yet may present with a florid vesiculopustular eruption in
unknown trigger is responsible for the vigorous cutane- the scalp. Hyperimmunoglobulin E syndrome may pre-
ous eosinophilic response seen in these infants. In both sent in the neonatal period [42] and this diagnosis,
children and adults EPF should be considered a potential although rare, should also be considered, as there is
cutaneous marker of immunosuppression. considerable overlap in the clinical presentation and labo-
ratory and histopathological findings in both disorders.
Clinical features. Pustular lesions are typically clustered Other diagnoses that may mimic NEP or EPI include
in groups (in contrast to adult EPF in which lesions are Langerhans cell histiocytosis, neonatal pustular melanosis
classically annular) and favour the scalp and bitemporal and neonatal cephalic pustulosis.
areas (Fig. 11.3). In 65% of cases other body sites are
involved and may include the palms and soles. Pruritus Laboratory/histology findings. Eighty percent of EPI
is very common (84%) and many younger infants are cases and all the cases of affected neonates have an
noted to be unsettled and irritable [34]. Crops of pustules associated peripheral eosinophilia with leucocytosis
with an associated erythema mature and crust over a [34]. A Wright‐stained smear of pustular contents dem-
matter of days, then spontaneously heal without scarring onstrates abundant eosinophils. Histopathology reveals
over subsequent weeks. Recurrence is the rule (intervals perifollicular (54%) or interfollicular (32%) inflammatory
between flares ranging from 1 to 12 weeks) with multiple infiltrates in upper and mid dermis, comprising pre-
stereotyped episodes of pustulation occurring over dominantly eosinophils together with neutrophils and
months to years following which there is spontaneous mononuclear cells [33].
resolution in all cases. Eighty percent of infants experi-
ence spontaneous resolution by 3 years of age [34]. Treatment and prevention. Although spontaneous reso-
Affected infants are otherwise well and no systemic lution is the rule, and treatment not necessarily indicated,
involvement, beyond a florid blood eosinophilia with pruritus may be troublesome. Numerous treatments have
leucocytosis, has been reported. been utilized in EPI, including topical corticosteroids [43],
oral antihistamines [26], dapsone [29] and erythromycin

[26] with mixed results. In adult cases, indometacin [44] is
the treatment of choice with response rates of 80–90%,
however in young infants this agent has significant
adverse effects, particularly on renal perfusion. Oral
indometacin has been used successfully in childhood [45].
Topical tacrolimus [46] and indometacin [47] have both

been used successfully, and these may be appropriate
first‐line treatment options.
Infantile acropustulosis
Epidemiology and pathogenesis. Infantile acropustulo-

sis (IA) was first described in 1979 by Kahn et al. [48]
and Jarrat et al. [49] who proposed this term to describe Fig. 11.4 Infantile acropustulosis involving the foot of an 18‐month‐old infant.
a series of 15 infants with recurrent crops of pruritic pap-
ulopustules on acral skin and the distal extremities pre-
treated for scabies prior to presentation, only one infant
senting within the first 2 months of life and responding
having confirmed scabies by microscopic examination of
rapidly to treatment with dapsone. In some cases lesions
a skin scraping. Infants were followed up for 2–24 months,
were present at birth. It appeared initially that acropustulo-
the majority (18) improving significantly with topical
sis was almost exclusively seen in Afro‐Caribbean infants;
corticosteroid therapy alone. A further series of 25 cases
however, not long after, IA was reported in a number of
reported by Dromy et al. reported similar findings
countries in infants of various ethnic groups [50]. Male
although of note two children in this series with very late
infants have predominated in the cases reported in some
onset IA presented at 8 and 9.5 years with classical clinical
[45–47,51] but not all [52,53] of the series reported.
features [53].
A number of authors have highlighted similarities
between scabies infestation and AI because in most cases
Differential diagnosis. The primary differential diagnosis
the clinical findings are indistinguishable [54,55]. Indeed,
of AI is scabies infestation. Other diagnoses to consider
some authors feel that AI does not represent a separate
are pompholyx‐type dyshidrotic eczema, an id dermatitis
clinical entity, and have documented high rates of EPI in
associated with dermatophyte infection. A viral exan-
immigrant children and infants from developing countries
them, such as hand, foot and mouth disease (coxsackie
with high rates of endemic scabies [48,56]. It has been
virus), recurrent herpes simples virus infection or impe-
postulated that in fact most cases of IA are in fact a sequela
tigo should also be considered. In those with involvement
of scabies infestation in which a hypersensitivity reaction
beyond acral surfaces, (particularly if the face and scalp
to the scabies mite and its detritus perpetuates cyclic
are affected), the diagnosis of EPI should be entertained.
recurrent acral pustulation. Diagnostic difficulty is com-
Transient neonatal pustular melanosis and congenital
pounded by the fact that infants are often diagnosed and
cutaneous candidiasis should be considered if onset is
treated empirically for scabies, albeit appropriately, early
at birth.
in the course, and may present to their paediatrician or
dermatologist many months after detection of mites or
ova is possible through skin scrapings. At the same time, Laboratory/histology findings. Direct smears from
there also appears to be considerable clinicopathological pustule contents reveal either neutrophils or eosinophils
overlap between some cases of EPI and IA, leading to fur- although the infiltrate is often mixed. Biopsy of acral sites
ther diagnostic confusion, particularly in infants in whom is rarely performed but, where reported, histopathology
pustular lesions are widespread [26,28,31]. shows intraepidermal vesiculation with either most com-
monly neutrophilic [57] or mixed neutrophil and eosino-
Clinical features. Intensely pruritic palmoplantar papules phil [58] or eosinophil‐predominant infiltrate [50]. Biopsy
evolve into 3‐ to 4‐mm fragile superficial pustules over of a precursor acral lesion has revealed intraepidermal
1–2 days followed by desquamation leaving multiple necrolysis without a cellular infiltrate [59]. A peripheral
collarettes of peeling skin (Fig. 11.4). Typically cyclic recur- eosinophilia may accompany the acral eruption [50,56,60].
rences tend occur 3‐ to 4‐weekly and flares are reported to In general, although the histopathological features are
occur up to the age of 3 years [49]. The dorsal surfaces of distinctive, skin biopsy is not required to make the diag-
the hands and feet are also frequently involved. Some nosis of AI once characteristic lesions are seen and the
infants have generalized involvement including lesions typical clinical course is established.
in the scalp, strongly suggesting overlap with EPI [28,31].
Extreme pruritus is a universal finding and infants are Treatment and prevention. Potent (class I and II) topical
often very unsettled because of itch. In a case series of 21 corticosteroids are the first‐line treatment and effective in
infants diagnosed with AI reported by Mancini et al. [52] aborting an exacerbation if used early and aggressively
lesions were first noted at between 1 and 30 months of during flares [49,50]. Some authors have however
age (mean age 9.7 months). Fourteen infants (70%) were reported poor responses to topical corticosteroids and
questioned their usefulness, although many have not age, 29 of these were culture positive [62]. In a more recent
stated the potency of the corticosteroids used [45,46,54]. similar study of 104 neonates, positive lesional culture
Scabicides are generally not helpful once recurring pustu- was demonstrated in only 6 of 26 infants with cephalic
lation is established and are not indicated unless there is pustulosis [60]. Thus, while there appears to be a strong
documented infection of a first‐degree relative or close association between Malassezia colonization in newborns
contact, the eruption is localized and dermoscopic skin and the development of cephalic pustulosis, a causative

examination and/or scrapings are positive. Dapsone at relationship has not been conclusively demonstrated.
1–2 mg/kg/day has been used with rapid improvement
in pruritus and sustained remission without relapse Clinical features. Infants typically present with non-
[45,54,61] and may be appropriate in severe cases unre- follicular inflammatory papules, pustules and pseudove-
sponsive to topical treatment. A recent case reported com- sicular lesions on a background erythema distributed on
plete responses using a topical D3 analogue, Maxacalcitol the forehead, cheeks and chin. Lesions may less frequently
0.0025% ointment, twice daily in the acute phase, and 3–4 involve the neck and upper chest. The typical age of onset
days per week thereafter [55]. is 2–3 weeks, but infants may present as late as 6–8 weeks
Acropustulosis of infancy eventually remits spontane- of age. Lesions are characteristically asymptomatic, but
ously with less florid and frequent recurrences over time. parents are often very distressed about the appearance.
Parents need to be reassured that this often distressing The natural history is spontaneous resolution over
condition improves gradually with time and does eventu- 7–14 days in the majority of infants [60].
ally remit even without treatment.
Differential diagnosis. Lesions may mimic or indeed
Benign or neonatal cephalic pustulosis
coexist with those of miliaria rubra and seborrhoeic
Benign cephalic pustulosis is a very common self‐resolving
dermatitis. Benign cephalic pustulosis has been called
pustular eruption that favours the face and scalp. Lesions
‘neonatal acne’, causing confusion between this common
consist of inflammatory papules, pustules and pseu-
neonatal eruption and true infantile acne vulgaris, a rela-
dovesicles. The role of Malassezia furfur colonization in
tively rare condition in which children usually present at
causing or perpetuating this inflammatory eruption is
6–9 months of age with comedonal, papulopustular and
unclear. This entity differs both clinically and histopatho-
sometimes cystic lesions typically confined to the cheeks
logically from infantile acne, and the term ‘neonatal acne’
and thought to be primarily androgen‐driven.
should therefore be discouraged.
Epidemiology and pathogenesis. Neonatal cephalic Laboratory/histology findings. Skin scrapings of affected
pustulosis (NCP) is common, the prevalence varying areas or of pustule contents may be examined using
between 10% and 66% of healthy term newborns [62,63]. potassium hydroxide (KOH) or KOH–Calcofluor wet
Clinical overlap with, or concomitant miliaria rubra and mounts. Stains such as Giemsa or periodic acid–Schiff
seborrhoeic dermatitis may be frequently observed. (PAS), Grocott, and Gomori’s methenamine silver may
Infants of all ethnicities are affected and there is no be used to identify yeasts (and dermatophyte fungi, as
gender predilection. indicated). Culture of Malassezia spp. requires specific
Aractingi et al. first described this entity in 1991 [64] in media (Dixon agar) and a positive growth of Malassezia
a 4‐week‐old infant with a cephalic vesiculopustular generally correlates well with positive smear microscopy.
eruption from which M. furfur was isolated. Rapelanoro However the identification of Malassezia species neither
et al. proposed a set of diagnostic criteria in 1996, which confirms nor refutes the diagnosis of NCP, given that
included the isolation of M. furfur from microscopy of colonization is common, and diagnostic swabs or smears
pustular contents [65]. Other criteria were: age at onset, are generally not recommended unless there is a need to
the presence of lesions distributed on the head and neck investigate an alternative infectious diagnosis.
and clearance with topical 2% ketoconazole therapy.
However, in many cases of NCP Malassezia spp. cannot Treatment and prevention. As infants are typically symp-
be detected on microscopy of pustule smear or culture tom‐free and the eruption self‐limiting, no treatment is
leading to uncertainty about whether colonization or required. Parents should be counselled that the eruption is a
indeed infection with this organism is responsible for benign and transient phenomenon thought to be related to
NCP [59,60,66,67]. the colonization of newborn skin with nonpathogenic com-
Malassezia is a dimorphic lipophilic commensal yeast mensal organisms and that it will resolve without scarring.
and can be isolated from 90% of healthy adults [68], If deemed necessary, topical treatment with a combination
11–50% of term infants in the first days of life and 52–80% of an imidazole (such as 2% ketoconazole or clotrimazole)
after 1 week of age [59,69]. Two studies following term and 1% hydrocortisone cream can be applied twice daily for
infants from birth observing Malassezia colonization rates 3–5 days, which typically leads to rapid clearance.
over time and documenting whether the subsequent
development of cephalic pustulosis relates to positive Erosive pustular dermatosis of the scalp
identification of a Malassezia species have been published. Erosive pustular dermatosis of the scalp (EPDS) is a rare
In a study by Bernier et al. of 102 neonates, 56 were cause of scarring alopecia and is primarily reported in
diagnosed with cephalic pustulosis at 3 weeks postnatal elderly patients and associated with chronic sun‐damaged
skin. In most cases a traumatic or topically applied irritant quantities. IgG transfer to the fetus represents an impor-
trigger precedes the eruption [70]. tant adaptive mechanism conferring short‐lived passive
immunity to the neonate. At the same time, placental
Epidemiology and pathogenesis. Pye et al. first described immunoglobulin transfer from mothers with IgG‐mediated
EPDS in 1979 in a series of older women with sterile pus- autoimmune blistering diseases may result in clinical
tules, erosions and scarring alopecia that resolved with expression of these diseases in the infant at birth or
topical corticosteroid therapy [71]. Since then there have during the first days of life. Pemphigus vulgaris (PV),
been multiple case reports and series of adult patients, pemphigus foliaceus (PF), bullous pemphigoid (BP),
and a handful of case reports in neonates with associated pemphigoid gestationis (PG) as well as epidermolysis
scalp trauma sustained during instrumental or difficult bullosa acquisita (EBA) have all been reported in babies
vaginal delivery [72] and in one case of an infant with of affected mothers. In almost all cases blistering has
Klippel–Feil syndrome who at 3 months of age developed developed in babies whose mothers had active disease in
scarring alopecia with chronic scalp ulceration with no pregnancy, however occasionally neonatal disease has
antecedent history of injury to the head [73]. presented in cases in which the mother’s disease was well
controlled, or who had no disease manifestations prior
Clinical features. At birth infants were noted to have to delivery but subsequently developed autoimmune
either annular ulceration or, in one case, necrotic crescen- bullous disease [76].
teric scalp erosion secondary to vacuum extraction and,
in one case, ulceration in the scalp following prolonged Epidemiology and pathogenesis. The autoimmune‐mediated
labour. Days and weeks after the initial injury, a pro- blistering diseases are extremely rare in neonates but
longed chronic phase develops in which inflammation, should be considered in the differential diagnosis of gen-
crust, scaling and an associated alopecia persists for many eralized or localized blistering or erosive lesions present
months. In the case series reported by Siegel et al. [72], either at birth or soon after. Transplacental transfer of
inflammation, crusting and in some cases recurrent pus- maternal IgG results in disease expression in the new-
tulation persisted for between 4 months and 2 years. born infant. There are multiple case reports of neonatal
PV and BP presenting in the newborns of affected moth-
Differential diagnosis. A diagnosis of EPDS is primarily ers [77]. PG is thought to affect 5–10% of infants of affected
clinical as there are no specific histological features. mothers [78]. Reports of maternally transmitted EBA [79]
Dermatophyte infections closely mimic EPDS and these and pemphigus foliaceus (PF) [80] are extraordinarily
should be excluded, particularly in infants presenting rare and the incidence is unknown. Overall, only a minor-
beyond the immediate neonatal period. The differential ity of infants of mothers with an antenatal diagnosis of
diagnosis includes scalp aplasia cutis congenita. Other con- autoimmune blistering disease develop disease manifes-
ditions associated with congenital or early and persistent tations [81].
neonatal scalp ulceration include ankyloblepharon– Male and female infants are affected equally. The
ectodermal defects–cleft lip/palate (AEC) [74] and occurrence and severity of maternally transmitted PV
ectrodactyly–ectodermal dysplasia–cleft lip/palate (EEC). and BP appear to correlate with disease activity and
serum antibody titres during pregnancy, however there
Laboratory/histology findings. Skin biopsy is nonspe- are a number of reports of neonatal PV and BP presenting
cific. Most of the pathological features are consistent with in infants of mothers with well‐controlled or inactive
chronic inflammation and/or scar tissue [68]. disease [82]. Stillbirths and neonatal deaths have been
reported and thus far have occurred exclusively in cases
Treatment and prevention. Bacterial superinfection is of PV, all occurring in infants whose mothers had severe
common, but antibiotic therapy generally fails to result in or poorly controlled disease during pregnancy [83].
healing of the ulceration [68]. Potent topical corticos-
teroids are the mainstay of treatment in most cases Clinical features. Blistering or localized skin erosions are
once fungal and bacterial infection has been treated or usually present at birth or within the first few days of life,
excluded. In adults, topical tacrolimus 0.1%, dapsone 5% although they may first manifest as late as 2 weeks after
gel, calcipotriol, intralesional and oral corticosteroids and birth [84] (Fig. 11.5). The diagnosis is usually straightfor-
oral isotretinoin have all been reported to be helpful in ward once a history of a maternal autoimmune blistering
isolated case reports [75]. A degree of scarring alopecia is disease is established. Blisters are usually generalized and
the inevitable long‐term sequela in most cases. morphologically similar to adult manifestations of the
respective bullous diseases. However, important differ-
ences warrant mentioning. In contrast to adult patients,
Autoimmune causes of vesicular
neonates with PV present with generalized blistering and
and bullous lesions in the neonate
erosions as well as mucosal blistering because neonates
Bullae in the newborn due to maternal have more diffusely distributed desmoglein‐3, the pri-
autoimmune blistering disorders mary target antigen in PV in nonmucosal skin [85].
(see also Chapter 6)
Of the human immunoglobulins, only IgG and its sub- Differential diagnosis. Infections – bacterial, viral and
classes cross the placenta to the fetus in significant fungal – are the important differential diagnoses, followed
problems for the affected neonate [89]. Of the neonatal

cases reported, the age at presentation ranged from 1 to
10 days. Most had a clinical course complicated by signifi-
cant respiratory and/or feeding problems and required
systemic treatment. In one case, severe ocular scarring
resulted in blindness [90]. Although cases described in

the literature have generally been severe, the author has
personal experience of infants in whom blistering was
mild and self‐limiting, requiring only topical treatment.
However, close follow‐up of all infants is advised. In con-
trast to neonatal maternally‐transmitted autoimmune
blistering diseases which spontaneously improve over
weeks, infants with LABD tend to have a prolonged
course, suggesting that the origin of the IgA autoantibodies
Fig. 11.5 Bullous pemphigoid involving the sole of the foot in a 2‐month‐
is not maternal [83].
old infant
Differential diagnosis. Other diagnoses to consider

by toxin‐mediated eruptions such as staphylococcal scalded include staphylococcal and streptococcal pyoderma,
skin. Pemphigus lesions may closely mimic impetigo. bullous pemphigoid, neonatal lupus erythematosus and
bullous erythema multiforme.
Laboratory/histology findings. If autoimmune blistering
is suspected in a neonate, the diagnosis can be confirmed Laboratory/histology findings. LABD is characterized by
by indirect immunofluorescence testing of a cord blood subepidermal blistering with abundant neutrophilic and
sample or by obtaining lesional smear and/or biopsy for eosinophilic dermal infiltrates. The demonstration of lin-
histopathology as well as a biopsy of perilesional fresh ear deposition of IgA along the basement membrane
skin for direct immunofluorescence studies. through immunofluorescence studies is diagnostic.
Treatment and prevention. The prognosis is generally Treatment. Aggressive treatment with systemic corticos-
excellent. The natural history is generally spontaneous teroids is indicated if respiratory, ocular or oesophageal
resolution over 1–3 weeks as maternal IgG is cleared from involvement intercedes. Early ophthalmology assessment
the infant circulation [79]. Neonatal PG typically resolves is strongly recommended. Dapsone is generally consid-
more rapidly than PV, PF and BP; PG generally clears ered the mainstay of therapy for LABD in the longer term,
completely and spontaneously within days of delivery. and is considered an appropriate first‐line steroid‐sparing
Topical therapy with moderate‐potency corticosteroids is agent. Screening for glucose‐6‐phosphate deficiency
usually all that is required. Systemic corticosteroids are should always be performed before commencing therapy.
rarely indicated. In those with localized disease or blistering confined to
the skin, a mild to moderately potent topical corticoster-
Neonatal linear immunoglobulin A (IgA) oid could be safely employed.
bullous dermatosis
Epidemiology and pathogenesis. Linear immunoglobulin

Genodermatoses associated
IgA bullous dermatosis (LABD) is extremely rare in
with neonatal blistering
infancy. There are seven reported cases of LABD presenting Incontinentia pigmenti
in the neonatal period to date [86]. None of the affected
infants had mothers with linear IgA disease. The major Epidemiology and pathogenesis. Incontinentia pigmenti
target antigen of IgA autoantibodies is linear IgA disease (IP, OMIM #308300) is a rare X‐linked dominant genoder-
antigen‐1 (LAD‐1) a component of BP antigen 180 of the matosis resulting from mutations in the inhibitor of the
basement membrane zone [87]. Genetic susceptibility is kappa B kinase gamma (IKBKG) (previously known as
likely as HLA‐DR3, HLA‐B8 and HLA‐DQW2 subtypes NEMO or Nuclear factor kappa B Essential MOdulator)
are found more frequently in patients with LABD [88]. gene. Mutations in IKBKG lead to aberrant expression of
an essential modulator protein NF‐κB in ectodermal tis-
Clinical features. LABD presents at birth or within days sues, resulting in disturbed transcriptional regulation of
of birth as multiple crops of tense, serous, fluid‐filled genes involved in apoptotic pathways and inflammatory
vesicles and bullae. There may be background erythema, as well as immune responses [91].
but this is not seen in all cases. Lesions may be clustered The estimated population prevalence is 0.7 in 100 000
or appear ‘targetoid’, but the classical annular ‘string‐of‐ [92]. IP is seen almost exclusively in females and is usu-
pearl’ lesions associated with linear IgA disease of child- ally lethal in males. Males represent 6% of all reported
hood are usually seen in older children. Neonatal LABD cases (largely due to sex chromosome aneuploidies or
may result in severe and extensive mucosal and respira- somatic mosaicism) and infants of undetermined sex
tory tract involvement and therefore pose life‐threatening make up 2–3% of cases [93]. The phenotypic expression of
IKBKG mutations is highly variable even within families. Other differential diagnoses include the autoimmune
This is thought to be due to skewed X‐chromosome inac- blistering diseases. It is often helpful to properly undress
tivation combined with highly pleiotropic IKBKG expres- the infant with neonatal blistering as the characteristic
sion resulting in generally poor genotypic–phenotypic blaschkoid patterning of the vesicles in IP may not be
correlation [94]. Many cases of IP are sporadic, but 55% immediately obvious if only localized areas of affected
have an affected mother, who is often unaware of her skin are examined.
diagnosis [95].
Laboratory/histology findings. Peripheral blood eosino-
Clinical features. IP may be thought of as a unique form philia is a characteristic finding in the neonatal period.
of ectodermal dysplasia with a characteristic neonatal A skin biopsy may be diagnostic, but is often not neces-
phenotype. The skin is almost invariably involved in sary to make the diagnosis. The classical features are a
neonates with IP and is the defining clinical feature. spongiotic epidermis with intraepidermal eosinophilic
Classical linear vesiculopustular lesions are almost vesiculation, dyskeratotic keratinocytes and pigmentary
always present at birth, although they may first appear incontinence.
as late as the sixth week of life, and represent the first of
four classically‐described phases of cutaneous involve- Treatment and prevention. The natural history is spon-
ment. Blaschkolinear vesiculopustular lesions are most taneous evolution of blistering to warty hyperkeratotic
commonly seen on the arms, legs, trunk and scalp lesions and eventually macular, linear, whorled or retic-
(Fig. 11.6), almost always sparing the face [92]. ulate hyperpigmented streaks over months to years.
IP may be associated with neurological and/or ocular Most adult patients have very subtle skin findings [99].
sequelae. Neurological complications are the most com- No specific intervention is known to modify this course.
mon cause of death and are present in approximately Basic skin care measures may prevent superinfection and
30% of cases. Seizures due to cerebral ischaemia and/or bland emollients may be helpful for crusting and hyper-
structural parenchymal anomalies are the most common keratosis. Ophthalmological assessment in neonates
presentation in the neonatal period [96]. More than 90% with IP is mandatory as sight‐threatening ocular pathology
of neurological problems are evident by the age of 2 years may evolve rapidly after birth [100]. Routine imaging of
[97]. Ophthalmic disease is common, occurring in 36–77% the brain of all neonates with a diagnosis of IP has
of IP patients, and may evolve rapidly in early life. been advocated by some authors [101] but consensus is
Without early intervention almost 60% of these abnor- lacking. Genetic counselling and prenatal molecular
malities may result in irreversible visual loss [98]. genetic testing in subsequent pregnancies should be
offered to parents.
Differential diagnosis. The blistering skin lesions of IP
in newborns are most frequently confused with herpes
simplex infection, but also with congenital varicella. Focal dermal hypoplasia (Goltz syndrome)
Epidemiology and pathogenesis. Focal dermal hypo-

plasia (FDH; OMIM #305600) is a rare X‐linked dominant
multisystem disorder associated with cutaneous, skeletal,
ocular and vascular anomalies. FDH is due to mutations
in PORCN, a gene coding for the PORCN protein, impor-
tant in Wnt signalling pathways involved in the early
fetal development of both mesodermal and ectodermal
tissues [102].
Clinical features. Characteristic cutaneous lesions are

present at birth, and often blaschkolinear typically
atrophic or cicatricial streaks associated with telangiec-
tasia are found on the trunk and limbs (Fig. 11.7). The
streaks may be accompanied by vesicular lesions, fat
herniation through depressed linear areas of atrophic
skin (soft yellow nodules), erosions or areas of frank
aplasia cutis. Macular hypopigmented and/or hyper-
pigmented streaks may coexist, as may other ectodermal,
skeletal and eye abnormalities.
Differential diagnosis. Other X‐linked dominant syn-

dromes in which skin, ocular and distal limb anomalies
are a prominent feature include X‐linked dominant
Fig. 11.6 Incontinentia pigmenti. Blaschkolinear vesiculopustular and chondrodysplasia punctata type 2 (Conradi–Hünermann–
eroded streaks on the arm of a 2‐week‐old infant. Happle syndrome) and congenital hemidysplasia with
typically born prematurely with tight, rigid, shiny and

translucent skin. The facial gestalt is distinctive and char-
acterized by a pinched nose and a fixed open mouth.
Generalized arthrogryposis is common. Erosions and
ulceration of the skin are frequently described, particu-
larly over joint prominences. Pulmonary hypoplasia is

common. Infants are often stillborn or born prematurely,
and die early in the neonatal period, primarily because of
severe pulmonary insufficiency.
Differential diagnosis. The typical clinical features of RD

do not usually cause diagnostic confusion. However the
presence of widespread skin erosions or ulceration in a
low‐birthweight newborn may lead to the consideration
of congenital infection or lethal acantholytic forms of
epidermolysis bullosa in the differential diagnosis.
Laboratory/histology findings. Skin biopsy shows hyper-

granulosis with large keratohyalin granules, a paucity of
dermal elastic fibres and absence of pilosebaceous and
eccrine glands [106].
Treatment and prevention. RD caused by recessive

Fig. 11.7 Focal dermal hypoplasia. Blaschkolinear atrophic and cicatricial (typically null) mutations in ZMPSTE24 causes a severe
streaks associated with telangiectasia.
phenotype and is generally lethal either in utero or early
in the neonatal period [104–106]. Treatment is support-
ichthyosiform erythroderma and limb defects (CHILD ive. Genetic counselling and prenatal molecular genetic
syndrome). testing in subsequent pregnancies should be offered to
parents.
Laboratory/histology findings. FDH may be diagnosed
clinically based on the presence of characteristic major
findings in the skin and skeletal systems. Clinical diag-
Other causes of neonatal blistering
nostic criteria have been established [103]. Molecular Bullous and diffuse cutaneous mastocytosis
genetic testing may be helpful in cases in which the diag-
nosis is uncertain. Skin biopsy is nonspecific. Epidemiology and pathogenesis. Blistering caused by
localized mastocytosis or diffuse cutaneous mast cell
Treatment and prevention. No specific therapy alters the infiltration of the skin rarely manifests as widespread
natural history of FDH. Dressing of eroded areas may be blistering at birth. Classically three forms of cutaneous
required in the newborn period. mastocytosis in children are described: mastocytoma
(solitary or up to three isolated skin lesions), maculopap-
Restrictive dermopathy ular mastocytosis (urticaria pigmentosa), multiple discrete
skin lesions and diffuse cutaneous mastocytosis (DCM).
Epidemiology and pathogenesis. Restrictive dermop- Mastocytosis is caused by clonal mast cell proliferation
athy (RD, OMIM #275210) is a very rare autosomal associated with somatic activating mutations in c‐kit [107].
recessive disorder and typically lethal in the newborn
period. RD results from homozygous null mutations in Clinical features. All forms of cutaneous mastocytosis
ZMPSTE24 which codes for zinc metallopeptidase, a pro- may be associated with blistering in infancy, but DCM,
tease enzyme responsible for cleaving prelamin A to form the rarest subtype, presents with neonatal erythroderma
mature lamin A, and less commonly, heterozygous muta- and generalized bullae [108]. Approximately 25 cases
tions in LMNA coding for proteins lamin A and C. LMNA have been reported. The male : female ratio was 2.5 : 1.
gene mutations and missense ZMPSTE24 appear to con- Almost all infants presented with bullae at birth [109].
fer a milder phenotype [104]. Five infants died before the age of 6 months due to systemic
involvement. Transformation to mast cell leukaemia has
Clinical features. RD results in profound fetal hypokine- been described [110]. Initially the skin is erythematous
sia due to skin restriction in late gestation. There is often a and dermographism is a prominent feature. Gradual
history of polyhydramnios, growth restriction and poor generalized thickening of the skin then develops (pachy-
fetal movements evident after 22 weeks’ gestation. Early dermia). In contrast to urticaria pigmentosa and mastocy-
fetal ultrasound scanning is often unremarkable, and the toma, neonatal DCM is often associated with systemic
severe restrictive effect of the dermopathy not evident symptoms, notably recurrent flushing, dyspnoea, vomit-
until the late second or third trimester [105]. Infants are ing and diarrhoea [94]. Neonates with DCM may present
with prolonged bleeding or develop purpuric lesions, A number of hypotheses have been put forward in an
probably due to heparin release. The tendency to blister attempt to explain nonsyndromic forms of ACC including
usually improves over 3–4 years. incomplete fusion of midline mesodermal tissues [115],
local ischaemic or thrombotic events in utero and focal
Differential diagnosis. Bullous mastocytosis may mimic pressure necrosis. More recently the potential role of genes
all infectious and autoimmune causes of neonatal blister- regulating skin morphogenesis has been emphasized,
ing as well as epidermolysis bullosa. particularly given the very strong association between
ACC and multisystem and dysmorphic syndromes [116].
Laboratory/histology findings. Skin biopsy reveals a This subject is covered in detail in Chapter 9.
plane of blister cleavage within the lamina lucida and a
dense dermal mast cell infiltrate. Serum tryptase is ele- Congenital erosive and vesicular
vated in infants with extensive cutaneous disease as well dermatosis with reticulated supple
as those with systemic involvement and has no utility as scarring
a prognostic marker [111]. Consideration should be given
to investigating infants with extensive or symptomatic Epidemiology and pathogenesis. Congenital erosive and
disease for systemic involvement. vesicular dermatosis with reticulated supple scarring
(CEVD) is very rare. To date 29 cases have been reported.
Treatment and prevention. Antihistamines (both H1 and CEVD affects mostly preterm infants (79%) and neonates
H2 receptor blocking agents) and sodium cromoglicate whose mothers had chorioamnionitis [117]. The cause is
are the cornerstones of treatment. Tyrosine kinase inhibi- unknown.
tors targeting the c‐kit ligand are promising novel thera-
pies for infants with severe systemic manifestations [112]. Clinical features. CEVD often causes diagnostic confu-
Neonates with DCM are at increased risk of developing sion in the neonatal period. Infants present at birth with
anaphylaxis‐like episodes [113] and parents should be widespread vesicles, multiple erosions and/or extensive
informed and educated in managing these. Provision of areas of ulceration. Typically most of the body surface is
an adrenaline autoinjector pen should be considered. involved. Alopecia of the scalp (43%) and nail hypoplasia
Immunization reactions are common and have been (46%) is common. Acral skin involvement is infrequent
reported to trigger systemic symptoms as well as circula- (7%). Reported associated anomalies include seizures,
tory collapse. The administration of routine childhood microcephaly, ocular anomalies, hepatomegaly and
immunizations may require specialist supervision [114]. delayed development. A third of infants develop new
vesicular skin lesions after birth, although in all cases the
eroded and ulcerated areas gradually heal in the months
Erosive lesions in the newborn infant after birth leaving soft, reticulated, often hypopigmented
Aplasia cutis congenita scarring. Hypohidrosis commonly develops due to
Aplasia cutis congenita (ACC) describes any congenital eccrine gland loss secondary to scarring and heat intol-
absence of skin which may be isolated or associated with erance and compensatory hyperhidrosis in non‐scarred
a host of syndromic disorders. The most common presen- areas is well described. In the longer term some (18%)
tation is a localized congenital area of absent skin or scar infants develop recurrent herpes simplex skin infections
on the scalp in an otherwise healthy neonate (Fig. 11.8). to which these children may be vulnerable. There is
emerging evidence to suggest that in utero infection with
herpes simplex virus is the cause of CEVD, which explains
the high incidence of post-natal recurrence.
Differential diagnosis. The primary differential diagnosis

is congenital infection. Lesions may closely mimic those
of disseminated congenital herpes simplex and varicella
zoster virus as well as Candida albicans infection. Eroded
or ulcerated lesions may at birth resemble those seen
in forms of aplasia cutis congenita. Transient bullous
dermolysis of the newborn may present with similar
extensive erosions, but these lesions are superficial
and heal rapidly without scarring.
Laboratory/histology findings. Skin biopsy findings are

very nonspecific and depend on the age of the lesions.
Early histopathological features include dermal oedema
and a mixed infiltrate consisting mainly of neutrophils.
No features of vasculitis or thrombosis have been noted.
Fig. 11.8 Aplasia cutis congenita of the scalp associated with the ‘hair Direct immunofluorescence reveals nonspecific deposits
collar’ sign in a 3‐month‐old infant. of IgG, IgA, IgM, C3 and fibrin [118]. Biopsies of older
lesions show characteristic scarring with either decreased 26 Ferrándiz C, Coroleu W, Ribera M et al. Sterile transient neonatal
pustulosis is a precocious form of erythema toxicum neonatorum.
or absent follicular and eccrine structures [119].
Dermatology 1992;185:18–22.
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Derm Venereol 1970;50:195–203.
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30 Kasai Y, Uchida S, Sakuma M. Eosinophilic pustular folliculitis. Jpn J
tractures [120].
Dermatol 1981;91:1029–35.
31 Lucky AW, Esterly NB, Heskel N et al. Eosinophilic pustular folliculi-
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11 Vesiculopustular, Bullous and Erosive Diseases of The Neonate

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11 Vesiculopustular, Bullous and Erosive Diseases of The Neonate

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134

Vesiculopustular, Bullous and Erosive Diseases

Caroline Mahon1 & Anna E. Martinez2

Abstract becomes accustomed to a low‐humidity environment, is colonized

Key points • Most transient and benign vesiculopustular eruptions require

Introduction Benign and/or physiological

Benign, self‐limiting and/or physiological vesiculopustular and bullous disorders

SECTION 2: SKIN DISORDERS

Table 11.1 Continued

SECTION 2: SKIN DISORDERS

Table 11.1 Continued

Mechanical and/or iatrogenic causes of erosions in the neonate

Table 11.2 Continued

SECTION 2: SKIN DISORDERS

Table 11.2 Continued

Genodermatoses associated with erosions and ulceration

bridge. Bohn nodules may be mistaken for natal teeth.

adhesive medical monitoring leads and tapes. Congenital

SECTION 2: SKIN DISORDERS

Erythema toxicum neonatorum

Epidemiology and pathogenesis. The incidence of ETN

The cause of ETN is not known. Many have speculated

Clinical features. Lesions appear as early as day 2 of life

reported to occur in infancy and childhood [29]. An infan-

SECTION 2: SKIN DISORDERS

Epidemiology and pathogenesis. There are a handful

oral antihistamines [26], dapsone [29] and erythromycin

Topical tacrolimus [46] and indometacin [47] have both

Epidemiology and pathogenesis. Infantile acropustulo-

SECTION 2: SKIN DISORDERS

problems for the affected neonate [89]. Of the neonatal

SECTION 2: SKIN DISORDERS

Differential diagnosis. Other diagnoses to consider

Epidemiology and pathogenesis. Linear immunoglobulin

Epidemiology and pathogenesis. Focal dermal hypo-

Clinical features. Characteristic cutaneous lesions are

Differential diagnosis. Other X‐linked dominant syn-

typically born prematurely with tight, rigid, shiny and

SECTION 2: SKIN DISORDERS

Differential diagnosis. The typical clinical features of RD

Laboratory/histology findings. Skin biopsy shows hyper-

Treatment and prevention. RD caused by recessive

Differential diagnosis. The primary differential diagnosis

Laboratory/histology findings. Skin biopsy findings are

SECTION 2: SKIN DISORDERS

Dermatol 1986;122:1155–60. 91 Smahi A, Courtois G, Vabres P et al. Genomic rearrangement in

SECTION 2: SKIN DISORDERS

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