11 Vesiculopustular, Bullous and Erosive Diseases of The Neonate
11 Vesiculopustular, Bullous and Erosive Diseases of The Neonate
11 Vesiculopustular, Bullous and Erosive Diseases of The Neonate
CHA PTER 1 1
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
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
(Continued )
136 Section 2 Skin Disorders of the Neonate and Young Infant
Pathophysiology Typical age of onset Clinical features Typical distribution Diagnostic investigations and
pathological features
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
SECTION 2: SKIN DISORDERS
OF NEONATES AND INFANTS
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 )
Table 11.1 Continued
Pathophysiology Typical age of onset Clinical features Typical distribution Diagnostic investigations and
pathological features
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
(Continued )
138 Section 2 Skin Disorders of the Neonate and Young Infant
Pathophysiology Typical age of onset Clinical features Typical distribution Diagnostic investigations and
pathological features
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
SECTION 2: SKIN DISORDERS
OF NEONATES AND INFANTS
(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
(Continued )
Chapter 11 Vesiculopustular, Bullous and Erosive Diseases of the Neonate 139
Pathophysiology Age at onset Clinical features Typical distribution Pathological features and
diagnostic investigations
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
(Continued )
140 Section 2 Skin Disorders of the Neonate and Young Infant
Pathophysiology Age at onset Clinical features Typical distribution Pathological features and
diagnostic investigations
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).
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
Chapter 11 Vesiculopustular, Bullous and Erosive Diseases of the Neonate 143
Infantile acropustulosis
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
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
146 Section 2 Skin Disorders of the Neonate and Young Infant
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
SECTION 2: SKIN DISORDERS
OF NEONATES AND INFANTS
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
Chapter 11 Vesiculopustular, Bullous and Erosive Diseases of the Neonate 147
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
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.
SECTION 2: SKIN DISORDERS
OF NEONATES AND INFANTS
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)
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,
SECTION 2: SKIN DISORDERS
OF NEONATES AND INFANTS
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.
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.
27 Finelt N, Kristal L. Patient characteristics of neonatal eosinophilic
Treatment and prevention. No specific treatment is pustulosis. Pediatr Dermatol 2013;30:e204–7.
known to be effective in improving the natural history of 28 Ofuji S, Ogino A, Horio T et al. Eosinophilic pustular folliculitis. Acta
Derm Venereol 1970;50:195–203.
the scarring and associated alopecia. One case report has 29 Giard F, Marcoux D, McCuaig C et al. Eosinophilic pustular folliculitis
58 Kimura M, Higuchi T, Yoshida M. Infantile acropustulosis treated 88 Sachs JA, Leonard J, Awad J et al. A comparative serological and
successfully with topical maxacalcitol. Acta Derm Venerol 2010;91: molecular study of linear IgA disease and dermatitis herpetiformis.
363–4. Br J Dermatol 1988;118:759–64.
59 Lucky AW, McGuire JS. Infantile acropustulosis with eosinophilic 89 Gluth MB, Witman PM, Thompson DM. Upper aerodigestive tract
pustules. J Pediatr 1982;100:428–9. complications in a neonate with linear IgA bullous dermatosis. Int J
60 Falanga V. Infantile acropustulosis with eosinophilia. J Am Acad Pediatr Otorhinolaryngol 2004;68:965–70.
Dermatol 1985;13:826–8. 90 Hurza LL, Mallory SB, Fitzgibbons J et al. Linear IgA bullous
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