Version May 2024
INTRODUCTION — Vesicles, bullae, and pustules in the newborn may be caused by infections, congenital disorders, or other diseases. Benign and self-limited disorders, including erythema toxicum neonatorum (picture 1A), transient neonatal pustular melanosis (picture 2A-D), and neonatal acne (picture 3), do not require specific therapy. However, certain infections and genetic disorders must be differentiated from these self-limited conditions because treatment may be needed (table 1).
Benign pustular eruptions, vesiculopustular eruptions caused by infections, and congenital/inherited bullous diseases presenting in the newborn are reviewed here. Other benign neonatal skin and scalp lesions are discussed separately. (See "Skin lesions in the newborn and infant".)
APPROACH TO DIAGNOSIS — It is critical to differentiate transient, benign eruptions of infants and newborns from those that require prompt diagnostic work-up and intervention. The approach to this diagnostic category requires familiarity with the morphology, timing, and course of common presentations that affect newborns and infants so that one can distinguish them from rarer, more serious conditions. In addition, knowledge of risk factors, exposures, and family history can also help narrow the differential diagnosis.
●A thorough clinical history and physical examination in most cases provide important clues for diagnosis.
●The possibility of a viral, bacterial, or fungal infection should always be considered.
●Vesicular lesions following the lines of Blaschko on a newborn infant suggest the possibility of incontinentia pigmenti, a rare, X-linked dominant disorder (picture 4).
●An erosive patch or blister-like lesion on the scalp or another area of the body at birth may occur due to a local absence of skin called aplasia cutis congenita (picture 5).
Features that suggest a potentially severe or life-threatening disease include:
●Widespread erythema and blistering
●Vital sign abnormalities
●Associated anomalies
●Poor growth
In such cases, diagnostic testing should be pursued, and the infant should be closely monitored when there is uncertainty and when infectious, severe, or life-threatening etiologies are on the differential diagnosis in a young infant.
BENIGN VESICULOPUSTULAR ERUPTIONS — Although most vesiculopustular eruptions in newborns are benign and self-limiting, the differential diagnosis includes conditions that require prompt recognition and treatment (table 1).
Generalized
Erythema toxicum neonatorum — Erythema toxicum neonatorum is a common, pustular disorder occurring in approximately 20 percent of neonates in the first 72 hours of life [1-4]. It occurs more frequently in neonates with higher birth weight and greater gestational age. The etiology is unknown. One hypothesis is that erythema toxicum neonatorum represents an acute, innate immune response to the penetration of skin-colonizing flora into the hair follicle [5].
●Clinical presentation – Erythema toxicum neonatorum presents with multiple erythematous macules and papules (1 to 3 mm in diameter) that rapidly progress to pustules on an erythematous base (picture 1A-C) [6]. The lesions are distributed over the trunk and proximal extremities, sparing the palms and soles. They may be present at birth but typically appear within 24 to 48 hours. The rash usually resolves in five to seven days, although it may wax and wane before complete resolution [7].
●Diagnosis – The diagnosis of erythema toxicum neonatorum is usually made based on the clinical appearance. It can be confirmed by microscopic examination of a Wright-stained smear of the contents of a pustule that demonstrates numerous eosinophils and occasional neutrophils (see "Evaluation of the peripheral blood smear", section on 'Slide preparation'). However, this is usually not necessary. A minority of patients (7 to 18 percent) may also have peripheral eosinophilia [8]. If the presentation is atypical, cultures of the pustule contents for bacteria, fungi, and viruses should be obtained (table 1). These are all negative in erythema toxicum neonatorum.
●Management – Erythema toxicum neonatorum resolves spontaneously. No treatment is necessary.
Transient neonatal pustular melanosis — Transient neonatal pustular melanosis is less common than erythema toxicum neonatorum. It mostly affects full-term Black infants and infants with darkly pigmented skin, although it is described in all ethnic groups [4,9].
●Clinical presentation – Transient neonatal pustular melanosis consists of three types of lesions [10]:
•Small pustules on a nonerythematous base. These are usually present at birth.
•Pink-red to brown-black macules with a surrounding collarette of scale (picture 2A, 2D). These develop as the pustules rupture and may persist for weeks to months.
•Brown-black macules that gradually fade over several weeks to months (picture 2B-C).
Lesions in different stages may be present at the same time (even at birth) [10].
●Diagnosis – The diagnosis of transient neonatal pustular melanosis is usually based upon the clinical appearance. Microscopic examination of a Wright-stained smear of the contents of a pustule demonstrates numerous neutrophils and, in contrast with erythema toxicum neonatorum, rare eosinophils. However, this is not usually necessary. Culture, if performed, yields no organism.
●Management – No treatment is necessary.
Miliaria — Miliaria is a common, transient, vesiculopapular disorder of newborns, especially in warm climates, caused by accumulation of sweat in obstructed eccrine sweat ducts [11-13].
Depending on the level of sweat duct obstruction, miliaria presents clinically as miliaria crystallina (picture 6), miliaria rubra (also called "heat rash" or "prickly heat" (picture 7A-B)), and miliaria profunda.
The diagnosis is usually clinical. No specific treatment is needed. Lesions usually resolve rapidly when the infant is placed in a cooler environment with associated measures to reduce sweating, such as light, loose clothing, and cool baths.
Miliaria is discussed in greater detail separately. (See "Miliaria".)
Localized
Eosinophilic pustular folliculitis of infancy — Eosinophilic pustular folliculitis of infancy is an uncommon dermatosis of unknown etiology occurring in newborns and infants. Its relationship with the adult eosinophilic pustular folliculitis (Ofuji disease) is uncertain.
●Clinical presentation – Eosinophilic pustular folliculitis of infancy presents with recurrent crops of pruritic, follicular pustules, most commonly on the scalp (picture 8) but also on the extremities (picture 9). In a retrospective study of 61 cases of eosinophilic pustular folliculitis of infancy, the median age of onset was five months, with a male-to-female ratio of 4:1 [14]. Tissue eosinophilia is a universal finding and can be demonstrated by smear or biopsy. Some infants also have blood eosinophilia. Recurrence is the rule, with outbreaks occurring at intervals of 1 to 12 weeks and resolving in one to four weeks. Complete resolution occurs by age 3 in most children [14].
●Diagnosis – The diagnosis is based upon clinical features, course, and the demonstration of eosinophils in pustule content or in skin biopsy. The differential diagnosis includes erythema toxicum neonatorum, transient neonatal pustular melanosis, infantile acropustulosis, herpes simplex infection, and impetigo.
●Treatment – Treatment is symptomatic. Topical corticosteroids appear to be effective in hastening the lesions' resolution and controlling pruritus [14].
Neonatal cephalic pustulosis — Neonatal cephalic pustulosis (previously called "neonatal acne") is a common eruption that occurs in approximately 20 percent of infants. This eruption is believed to be an inflammatory reaction to skin colonization with Malassezia species [15,16], although one series found no difference in the prevalence of Malassezia colonization between neonates with cephalic pustulosis and neonates without it [17].
Neonatal cephalic pustulosis is a separate entity from true infantile acne [18]. (See "Acne in infants, young children, and preadolescents".)
●Clinical presentation – The mean age at onset is three weeks [19]. The presence of inflammatory papules and pustules, the absence of comedones, and the characteristic distribution limited to the face (especially the cheeks) and sometimes the scalp are diagnostic in most cases (picture 10). Neonatal cephalic pustulosis may appear very similar to miliaria rubra (picture 11A-B). (See "Miliaria".)
●Treatment – In the majority of cases, neonatal cephalic pustulosis is mild and can be treated with daily cleansing with soap and water and avoidance of exogenous oils and lotions [20]. The eruption usually resolves spontaneously within four months without scarring [20]. Application of 2% ketoconazole cream twice daily or 1% hydrocortisone cream once daily may expedite clearance of lesions [21].
Infantile acne — Infantile acne is an uncommon and distinct entity from neonatal cephalic pustulosis. It typically presents at the age of 6 to 16 months (picture 12A-B) [22]. Infantile acne is caused by a prolonged, physiologic, and transient increase in the levels of adrenal androgens, which usually normalize around the age of six months [13,23]. It presents with typical, acneiform lesions, including comedones, inflammatory papules, pustules, and sometimes nodules on the face (picture 12A-B) [18].
The pathogenesis, clinical presentation, and management of infantile acne are discussed in greater detail separately. (See "Acne in infants, young children, and preadolescents".)
Infantile acropustulosis — Infantile acropustulosis is an uncommon, vesiculopustular disorder that often has a more chronic course than other benign neonatal eruptions.
The etiology is unknown. A nonspecific hypersensitivity reaction to scabies has been postulated because many patients have been treated for scabies before being diagnosed with infantile acropustulosis, but this association remains unproven [24,25].
●Clinical presentation – Infantile acropustulosis is characterized by recurrent crops of intensely pruritic vesiculopustules, mainly on the palms and soles (picture 13A-B) but sometimes involving the dorsal aspect of the hands and feet and the limbs (picture 14A-B). It may be present at birth or, more commonly, have onset any time during the first year of life. Recurrences generally occur every two to four weeks and may last 5 to 10 days.
●Diagnosis – The diagnosis of infantile acropustulosis is based upon clinical features. Because of the association with scabies, skin scrapings should be examined [25,26]. Skin biopsy is not usually necessary but, if performed, demonstrates a subcorneal pustule filled with neutrophils and eosinophils [27].
The differential diagnosis of infantile acropustulosis includes dyshidrotic eczema, pustular psoriasis, erythema toxicum neonatorum, transient neonatal pustular melanosis, eosinophilic pustular folliculitis of infancy, scabies, and impetigo (table 1) [6]. (See "Acute palmoplantar eczema (dyshidrotic eczema)" and "Pustular psoriasis: Pathogenesis, clinical manifestations, and diagnosis" and 'Erythema toxicum neonatorum' above and 'Transient neonatal pustular melanosis' above.)
●Treatment – Infantile acropustulosis typically resolves spontaneously within two years. Mid- to high-potency topical corticosteroids (groups 1 to 4 (table 2)) are the first-line treatment for flares of infantile acropustulosis [25,28]. Systemic absorption of topical corticosteroids in infantile acropustulosis is limited by the localized distribution of the lesions, the thickness of skin in the affected (acral) areas, and the periodicity of the flares [6,25]. (See "Topical corticosteroids: Use and adverse effects", section on 'Use in children'.)
Other treatments that have been reported as effective for infantile acropustulosis include oral antihistamines, oral erythromycin, and oral dapsone for several months duration [25,27-32].
Although dapsone is reliably effective, its potentially serious adverse effects limit its use [25]. Oral dapsone (1 to 2 mg/kg per day) should thus be reserved for severe, recalcitrant cases. Adverse effects of dapsone may include peripheral neuropathy, aplastic anemia, hepatitis, hemolytic anemia, and methemoglobinemia [25]. A glucose-6-phosphate dehydrogenase (G6PD) screening should be done before starting dapsone. (See "Diagnosis and management of glucose-6-phosphate dehydrogenase (G6PD) deficiency".)
Oral erythromycin (10 mg/kg/dose every six hours) or oral antihistamines are alternatives to topical corticosteroids. Erythromycin appears to have an anti-inflammatory effect. Antihistamines are effective in relieving pruritus but only in high doses, suggesting that sedation is necessary for efficacy [25,30].
Vesiculopustular eruption and transient myeloproliferative disorder in Down syndrome — Approximately 20 percent of newborns with Down syndrome present with transient myeloproliferative disorder (also called transient leukemia) [33-35]. In rare instances, transient myeloproliferative disorder is accompanied by a vesiculopustular eruption predominantly located on the face that begins during the first few days of life. The examination of a skin biopsy shows intraepidermal, spongiotic vesiculopustules and a perivascular infiltrate containing immature myeloid cells, which are also usually present in the peripheral blood. The skin lesions resolve spontaneously in one to three months, as the transient myeloproliferative disorder regresses. (See "Down syndrome: Clinical features and diagnosis", section on 'Transient myeloproliferative disorder'.)
INFECTIOUS VESICULOPUSTULAR ERUPTIONS — Infection should always be considered as a cause of vesiculobullous or pustular lesions in the newborn [36]. Infectious disorders may be life threatening and require urgent therapeutic intervention. The clinical features of the most common infectious vesiculopustular eruptions in newborns are summarized in the table (table 1).
Viral infection — A number of viruses can cause vesiculopustular or bullous lesions in the newborn. In most cases, lesions do not appear at birth but rather days to weeks later. Herpes simplex virus (HSV) and varicella-zoster virus (VZV) are the two most common etiologic agents, but cytomegalovirus and coxsackievirus can also occasionally be causative. (See "Overview of cytomegalovirus infections in children" and "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention".)
Neonatal herpes simplex virus infection — Neonatal HSV infection is rare. It primarily results from intrapartum exposure to maternal cervical or vaginal lesions or by an ascending infection, sometimes through apparently intact membranes [37]. Postnatal inoculation may also occur but is less common [38].
●Clinical presentation – Symptoms can develop within days to four weeks after birth. HSV infection in newborns usually develops in one of three patterns:
•Localized to the skin, eyes, and mouth (SEM disease)
•Localized central nervous system disease
•Disseminated disease involving multiple organs
Skin lesions occur in the majority of patients and may be present in all three infection patterns [38]. They are not usually present at birth and develop at 6 to 13 days of age [13]. Infants with lesions at birth (congenital HSV infection) have intrauterine, rather than perinatal, infection and are also usually premature.
The skin lesions typically consist of clusters of 1 to 3 mm vesicles and erythematous papules that may develop into pustules, crusts, and erosions (picture 15). They usually occur on the scalp (picture 16), sometimes associated with placement of a fetal monitor electrode, or face (picture 17) [13]. Lesions also may occur on the trunk (picture 18) or buttocks (especially with a breech presentation). When lesions are present at birth, they usually appear as superficial erosions.
Newborns with disseminated disease often present in the first week of life with nonspecific signs and symptoms of sepsis (eg, temperature dysregulation, lethargy, respiratory distress, abdominal distension, hepatomegaly, ascites). Central nervous system disease presents with fever, lethargy, and focal seizures.
●Diagnosis – The diagnosis of neonatal HSV is confirmed through isolation of HSV from multiple specimens (eg, swabs/scrapings/aspirate of vesicle fluid; mucosal swabs of conjunctivae, mouth, nasopharynx, and rectum; cerebrospinal fluid; blood or plasma) by viral culture, polymerase chain reaction, direct immunofluorescence assays, or enzyme immunoassays. (See "Epidemiology, clinical manifestations, and diagnosis of herpes simplex virus type 1 infection", section on 'Tests to confirm the diagnosis'.)
●Differential diagnosis – Neonatal HSV infection should be distinguished from other vesiculopustular disorders (table 1), such as congenital cutaneous candidiasis (picture 26B), transient neonatal pustular melanosis (picture 2C-D), and incontinentia pigmenti (picture 4). (See "Erythroderma in children", section on 'Congenital cutaneous candidiasis' and 'Transient neonatal pustular melanosis' above and "Incontinentia pigmenti".)
●Treatment – Neonatal HSV infection is treated with intravenous acyclovir and supportive measures [39].
The clinical presentation, diagnosis, and management of neonatal HSV infection are discussed in detail separately. (See "Neonatal herpes simplex virus infection: Clinical features and diagnosis" and "Neonatal herpes simplex virus infection: Management and prevention".)
Neonatal varicella-zoster virus infection — Perinatally acquired varicella is a rare and serious illness associated with a mortality rate of up to 20 percent [40]. Newborns born to mothers who are exposed to VZV or have clinical disease manifestations within two weeks of delivery are at the greatest risk for infection. If the mother develops the rash between five days before and two days after delivery, the newborn is likely to develop a generalized and potentially fatal infection [41].
●Clinical presentation – Neonatal varicella presents with fever in the first week of life, followed by the development of a cutaneous, macular eruption that rapidly progresses to papules and then to characteristic, vesicular lesions before crusting. It usually first appears on the head and then generalizes (picture 19).
●Diagnosis – The diagnosis of neonatal varicella is often made clinically, based on the characteristic appearance of the cutaneous eruption in various stages of development in a newborn born to a mother exposed to VZV or with clinical symptoms of varicella close to the time of delivery. The diagnosis can be confirmed by detection of the virus using polymerase chain reaction. (See "Diagnosis of varicella-zoster virus infection".)
●Treatment – Newborns with VZV infection are treated with intravenous acyclovir [42].
The clinical presentation, diagnosis, and management of VZV infection in the newborn are discussed in detail separately. (See "Varicella-zoster infection in the newborn".)
Monkeypox virus infection — Monkeypox virus infection (mpox) in infants during the 2022 global outbreak is uncommon [43]. However, mpox should be considered in the differential diagnosis of an infant presenting with a febrile illness and a vesicular or pustular skin eruption. Based on the descriptions of a few reported cases [44,45], mpox in infants initially presents with erythematous, macular lesions evolving in a few days to papules, vesicles, and pustules that may involve the whole skin surface (including the face, palms, and soles). In one case report of a severely ill newborn with mpox and concurrent adenovirus infection, the infant improved after receiving oral tecovirimat and intravenous cidofovir [44]. In another case, the infant was treated with oral tecovirimat and vaccinia immune globulin intravenous [45]. However, the safety and benefit of vaccinia immune globulin intravenous in children have not been established. All cases were acquired from close household contacts. (See "Epidemiology, clinical manifestations, and diagnosis of mpox (monkeypox)" and "Treatment and prevention of mpox (monkeypox)".)
Bacterial infection — Bacterial infection in neonates may present with vesiculobullous or pustular lesions. The most common pathogen causing skin and soft tissue infections in neonates is Staphylococcus aureus. Sepsis caused by Listeria monocytogenes, Streptococcus species, or Pseudomonas aeruginosa can have associated skin lesions, as can Treponema pallidum infection (table 1).
Staphylococcal pustulosis — In newborns, cutaneous staphylococcal infection usually presents with localized, superficial, vesicular, pustular, or bullous lesions on an erythematous base (picture 20). Vesicles and bullae are easily ruptured, resulting in superficial erosions and honey-colored crusts. Lesions are usually found in areas of trauma, such as the diaper area, circumcision wound, axillae, and periumbilical skin, although they may appear anywhere on the body.
The diagnosis is confirmed with demonstration of gram-positive cocci in clusters and neutrophils on a Gram stain of the pustular fluid and isolation of S. aureus on culture. If the lesions are extensive or the infant appears ill, a blood culture should be obtained prior to starting treatment.
The evaluation and treatment (algorithm 1) of S. aureus and streptococcal skin and soft tissue infection in the newborn are discussed separately. (See "Skin and soft tissue infections in neonates: Evaluation and management", section on 'Antimicrobial therapy'.)
Staphylococcal scalded skin syndrome — Newborns are susceptible to hematogenous dissemination of S. aureus exfoliative toxins, resulting in staphylococcal scalded skin syndrome (SSSS; or Ritter disease) [46]. Hospital outbreaks have been reported [47].
The two pathogenic toxins produced in SSSS are exfoliative (or epidermolytic) toxin A and exfoliative toxin B. They act as serine protease enzymes in the stratum granulosum that cleave desmoglein 1, an important desmosomal protein responsible for keratinocyte-to-keratinocyte adhesion [48]. This results in the formation of fragile, flaccid bullae that easily rupture in areas of friction, resulting in superficial erosions.
●Clinical presentation – Presentation usually occurs at three to seven days of age and is rarely seen at birth [13]. Affected infants are febrile and irritable, with diffuse, blanching erythema often beginning around the mouth. Flaccid blisters appear one to two days later, especially in areas of mechanical stress, including flexural areas, buttocks, hands, and feet. Gentle pressure applied to the skin results in separation of the upper epidermis and wrinkling of the skin (Nikolsky's sign). In some cases, the entire upper epidermis may be shed (picture 21A and picture 21B) [13]. Affected infants often have conjunctivitis; mucous membranes are not involved but may appear hyperemic.
Superficial desquamation occurs as the lesions heal [13]. Because the cleavage plane of the blisters is intraepidermal, scars do not occur.
●Diagnosis – If SSSS is suspected, cultures should be obtained from blood, urine, nasopharynx, umbilicus, abnormal skin, or any suspected focus of infection. The intact bullae are sterile. Diagnosis is usually clinical, although it may be confirmed with skin biopsy that shows a cleavage plane in the lower stratum granulosum with minimal necrosis [49]. However, biopsy is rarely required. The microscopic examination may be performed on a frozen section to expedite treatment.
●Differential diagnosis – SSSS should be differentiated from toxic epidermal necrolysis (TEN), which is more commonly seen in older children as a reaction to drugs or infections [50]. On histopathologic examination, TEN reveals a subepidermal cleavage plane and full-thickness epidermal necrosis. Additionally, unlike SSSS, the involvement of mucous membranes is a frequent clinical feature of TEN. (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis".)
●Treatment – Newborns with SSSS are treated in an inpatient setting. Seriously ill children should be admitted to an intensive care unit or burn unit. Treatment with intravenous penicillinase-resistant penicillin, such as nafcillin or oxacillin, should be promptly initiated. Vancomycin should be considered in areas with a high prevalence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) or for patients who fail to respond to initial therapy (table 3) [51,52]. (See "Staphylococcus aureus in children: Overview of treatment of invasive infections", section on 'Treatment of neonates'.)
Supportive care involves replacement of fluid and electrolyte losses and gentle skin care with petroleum jelly and nonadherent dressings.
SSSS is discussed in greater detail separately. (See "Staphylococcal scalded skin syndrome".)
Streptococcal infection — Streptococcal skin infections from group A or, rarely, group B Streptococcus may mimic those caused by S. aureus, although they are less common. Affected newborns may present with pustules and honey-colored crusts, often in association with a moist umbilical cord stump or omphalitis [53].
The diagnosis is confirmed with demonstration of gram-positive cocci in chains on Gram stain of the pustular fluid and isolation of Streptococcus in culture.
Pending the culture results, empiric therapy with intravenous ampicillin and gentamicin, which provides broad coverage for group B and other streptococci, some gram-negative enteric organisms, and L. monocytogenes, should be administered. Once Streptococcus is identified as the sole causative organism, the therapy can be changed to penicillin G alone (table 4). (See "Group B streptococcal infection in neonates and young infants", section on 'Antimicrobial therapy'.)
Listeriosis — Infections from L. monocytogenes can occur in newborns [54]. Clinical manifestations can occur early (before seven days) or late (after seven days). Both forms can present with meningitis and signs of septicemia. Infants with the early form often have multiple pustules on the skin and mucous membranes [55,56]. (See "Clinical manifestations and diagnosis of Listeria monocytogenes infection".)
Congenital syphilis — Congenital syphilis occurs when T. pallidum is transmitted from a pregnant woman to her fetus. It should always be included in the differential diagnosis of a newborn with blisters or erosions, especially when present at birth. The incidence has risen markedly in the past several years [57]. (See "Congenital syphilis: Clinical manifestations, evaluation, and diagnosis", section on 'Early congenital syphilis'.)
Early manifestations can be quite variable. Infants may be normal at birth and become symptomatic during the first five weeks of life. Hemorrhagic vesicles or bullae and petechiae that start on the palms and soles and spread to the trunk and extremities are nearly pathognomonic of congenital syphilis (picture 22A-B). If ulcerative in nature, they are highly contagious. A more common presentation is a papulosquamous eruption similar to the exanthem of secondary syphilis in adults (picture 23) or a desquamative dermatitis also involving the palms and soles. Other early manifestations include rhinitis (snuffles), anemia, thrombocytopenia, lymphadenopathy, hepatomegaly, fever, and poor feeding [58].
The diagnosis and treatment of congenital syphilis are discussed separately. (See "Congenital syphilis: Clinical manifestations, evaluation, and diagnosis" and "Congenital syphilis: Management and outcome".)
Fungal infection — Candida albicans infections are common in the neonatal period and are usually benign. Case reports have been published of Aspergillus species causing vesicular lesions in very low birth weight newborns [59,60].
Mucocutaneous candidiasis — Candida infection in the neonate usually develops after the first week of life. It is most likely to affect moist, warm regions and skin folds (eg, in the diaper area) or mucous membranes in the mouth (where it is known as thrush). Candidal diaper dermatitis characteristically appears as an erythematous eruption in the inguinal region. The rash classically has areas of confluent erythema with multiple tiny pustules or discrete, erythematous papules and plaques with superficial scale (picture 24). Satellite lesions are typically noted (picture 25A-B). Topical treatment is adequate in most cases, as dissemination is rare. (See "Diaper dermatitis".)
Congenital cutaneous candidiasis — Congenital cutaneous candidiasis is a rare disorder that results from a Candida spp infection acquired in utero or during delivery. It presents at birth or in the first few days of life with small, diffuse, erythematous macules and pustules, often involving the palms and soles (picture 26A-B). The clinical manifestations and treatment of congenital candidiasis are discussed separately. (See "Clinical manifestations and diagnosis of Candida infection in neonates", section on 'Congenital candidiasis' and "Treatment of Candida infection in neonates".)
Infestations
Scabies — Scabies is a relatively uncommon cause of pustular eruption in the newborn in resource-abundant regions but may be more common in resource-limited regions [61]. Scabies is caused by infestation with the Sarcoptes scabiei mite. The skin eruption results from a hypersensitivity reaction to the proteins of the female parasite, which burrows into the upper layers of the epidermis [62]. Transmission of scabies is usually from person to person by direct contact. (See "Scabies: Epidemiology, clinical features, and diagnosis".)
●Clinical presentation – Scabies may present as early as three to four weeks of age, the earliest time infants can develop hypersensitivity to the mites, but is never present at birth. The characteristic appearance is of erythematous papules that are intensely pruritic. Infants are more likely than older children to develop vesicles, pustules, nodules, and crusting [63]. The involvement can be localized initially, but then it becomes widespread and often affects the hands, feet, and wrists, which usually are spared in older children and adults (picture 27A) [64]. The face may be involved because of contact with infested maternal skin while breastfeeding. Infants may manifest poor feeding, fussiness, and failure to thrive, presumably because of the intense pruritus, or be asymptomatic [65].
●Diagnosis – The diagnosis should be considered in an infant with a vesiculopustular eruption that involves the palms and, especially, the soles (picture 28). The combination of a pruritic eruption, characteristic distribution, and household involvement is usually enough to establish a diagnosis. Mites or eggs can be demonstrated in scrapings from burrows or papules [64]. (See "Scabies: Epidemiology, clinical features, and diagnosis", section on 'Scabies preparation'.)
●Differential diagnosis – Scabies is often confused with infantile acropustulosis, insect bites, impetigo, atopic dermatitis, or urticaria pigmentosa.
●Treatment – The infant, all the household, and close contacts should be treated simultaneously, and environmental decontamination should also be performed. Treatment consists of one application of permethrin 5% cream at bedtime to all skin surfaces in infants (not approved for infants younger than two months) [66] and from the neck down in older household contacts. It should be washed off after 8 to 14 hours [61]. Repeated applications may be needed, as the failure rate is significant [67]. An alternative therapy for newborns is the application of 5 to 10% precipitated sulfur in petrolatum. (See "Scabies: Management".)
CONGENITAL/INHERITED DISORDERS — Several uncommon congenital or inherited conditions may present with bullous lesions in the newborn.
Sucking blisters — Congenital sucking blisters, a diagnosis of exclusion, are noninflammatory, oval, thick-walled vesicles or bullae that contain sterile fluid [68]. The lesions may be unilateral or bilateral and are typically located on the dorsal or radial aspect of the wrists, hands, or fingers of neonates who are noted to suck excessively at the involved regions (picture 29).
The differential diagnosis of sucking blisters includes herpes simplex virus infection, bullous impetigo, congenital syphilis or candidiasis, neonatal lupus erythematosus, and hereditary bullous diseases [68]. These disorders are usually, but not always, accompanied by additional clinical signs or suggestive maternal history.
Observation of the neonate's sucking on the involved areas is the most helpful clue to the correct diagnosis of congenital sucking blisters. Other suggestive features include the absence of lesions in other areas, well appearance of the infant, and rapid resolution of the lesions.
Congenital erosive and vesicular dermatosis — Congenital erosive and vesicular dermatosis (CEVD) is a rare condition presenting in the neonate with erythema, vesicles, erosions, ulcerations, and crusting predominantly involving the trunk and limbs that heal in the first few months of life with reticulate supple scarring [69,70]. The affected newborns are often premature. The pathogenesis of CEVD is unknown. Some cases have been associated with intrauterine herpes virus or fungal infections [71,72]. However, the role of infection in the pathogenesis of CEVD remains unclear.
Epidermolysis bullosa — Epidermolysis bullosa is a group of inherited diseases characterized by skin fragility and blister formation caused by minor skin trauma (picture 30). Epidermolysis bullosa is broadly classified into four groups, based upon the level at which the blisters form. These are epidermolysis bullosa simplex, junctional epidermolysis bullosa, dystrophic epidermolysis bullosa, and Kindler epidermolysis bullosa. The pathogenesis, clinical manifestations, diagnosis, and management of epidermolysis bullosa and Kindler epidermolysis bullosa are discussed in detail separately.
●(See "Epidermolysis bullosa: Epidemiology, pathogenesis, classification, and clinical features".)
●(See "Diagnosis of epidermolysis bullosa".)
●(See "Overview of the management of epidermolysis bullosa".)
●(See "Kindler epidermolysis bullosa".)
Bullous dermolysis of the newborn — Bullous dermolysis of the newborn, previously called transient bullous dermolysis of the newborn, is a subtype of dystrophic epidermolysis bullosa characterized by skin fragility and blister formation at birth that typically improves or resolves within the first year of life (picture 31) [73,74]. Milia, atrophic scarring, and nail dystrophy can persist [75]. Ultrastructurally, bullous dermolysis of the newborn shares the characteristic findings of dystrophic epidermolysis bullosa, namely a split below the level of the lamina densa; disruption of anchoring fibrils; and presence of electron-dense stellate or rod-like bodies within the dilated, rough, endoplasmic reticulum of basal keratinocytes. On immunofluorescence microscopy, intracytoplasmic, epidermal inclusions of C7 appear to be a unique characteristic of bullous dermolysis of the newborn [73].
Autoimmune bullous diseases — Pemphigus and bullous pemphigoid are exceedingly rare in infants [76,77]. In most cases, they present at birth with vesicles, blisters, or erosions. The most frequently involved sites are (in decreasing order) the trunk, head and neck, and acral areas. Mucous membranes are affected in approximately 30 to 40 percent of cases [77].
Epidermolytic ichthyosis — Epidermolytic ichthyosis, also called epidermolytic hyperkeratosis or bullous congenital ichthyosiform erythroderma, is an autosomal dominant disorder that typically presents in the neonatal period. Raw erosions and ruptured bullae are present at birth and may be misdiagnosed as epidermolysis bullosa (picture 32) or staphylococcal scalded skin syndrome. A frozen section of the roof of the ruptured bullae using the "jelly roll" technique can be helpful in distinguishing these entities [78]. Bullae, although not intact at birth, may continue to form throughout early childhood. (See "Keratinopathic ichthyoses", section on 'Epidermolytic ichthyosis'.)
Aplasia cutis congenita — Aplasia cutis congenita is a rare, heterogeneous group of congenital disorders characterized by focal or widespread absence of the skin [79]. Aplasia cutis congenita can occur anywhere on the body, but the vast majority of cases occur on the scalp midline as a solitary, membranous or bullous lesion (picture 5). A conspicuous collar of hair around a lesion on the scalp may indicate the presence of a structural defect in the underlying bone or central nervous system (picture 33). Associated vascular stain, nodule and vertex, or midline location also increase this risk [80]. Clinical subtypes are characterized by their location and pattern of lesions, associated malformations, and mode of inheritance [81].
The classification, diagnosis, and management of aplasia cutis congenita are discussed in detail elsewhere. (See "Aplasia cutis congenita".)
Incontinentia pigmenti — Incontinentia pigmenti is an X-linked, dominant, multisystem disease that is usually lethal in males in utero [82]. Incontinentia pigmenti is caused by mutations in the IKBKG/NEMO gene, encoding a regulatory protein involved in the activation of genes involved in cell survival, inflammation, and immunity.
In females, it classically presents with a staged, cutaneous eruption (table 5); variable developmental abnormalities involving the teeth, hair, and nails; and ocular and neurologic abnormalities.
●In stage 1, or the vesicular stage, erythematous papules and vesicles appear in crops in linear streaks along the lines of Blaschko, usually beginning at birth or within the first few weeks of life, with each crop lasting one to two weeks (picture 27B).
●Stage 2, or the verrucous stage, consists of hyperkeratotic, warty papules or plaques in linear or swirling patterns (picture 34).
●Stage 3, or the pigmented stage, presents as streaks of hyperpigmentation in a "marble cake pattern" (picture 35).
●Stage 4, or the final stage, where the hyperpigmented streaks may evolve into hypopigmented and atrophic patches or streaks.
All stages may be present simultaneously and may occur in utero. The clinical features, diagnosis, and management of incontinentia pigmenti are discussed in greater detail elsewhere. (See "Incontinentia pigmenti".)
Cutaneous mastocytosis — Cutaneous mastocytosis is an infiltrative skin disorder that can present with vesicles and blisters in the newborn (picture 36A-B). The two main forms are cutaneous mastocytomas, which present with solitary or multiple erythematous nodules, and maculopapular cutaneous mastocytosis (previously called urticaria pigmentosa), which presents with multiple monomorphic, reddish-brown macules and papules anywhere on the body (except the palms and soles) (picture 36B). Both forms of cutaneous mastocytosis may present with bullous lesions in infants. (See "Mastocytosis (cutaneous and systemic) in children: Epidemiology, clinical manifestations, evaluation, and diagnosis".)
SUMMARY AND RECOMMENDATIONS
●Benign and self-limited disorders – Benign and self-limited vesiculopustular disorders in the newborn may present as generalized eruptions (eg, erythema toxicum neonatorum (picture 1A), transient neonatal pustular melanosis (picture 2C-D), miliaria (picture 7B)) or localized eruptions (eg, neonatal cephalic pustulosis, infantile acropustulosis, infantile acne). In most cases, these disorders resolve spontaneously and do not require specific therapy. (See 'Benign vesiculopustular eruptions' above.)
●Infections/infestations – Common infections causing vesiculopustular eruptions include neonatal herpes simplex virus infection, neonatal varicella-zoster virus infection (picture 19), staphylococcal pustulosis (picture 20), and staphylococcal scalded skin syndrome (picture 21A-B). Erythematous patches, papules, and pustules in intertriginous areas may occur in neonatal candidiasis (picture 25A-B). Scabies is a common cause of acral vesiculopustular eruption, especially in resource-limited regions (picture 27A-B). (See 'Infectious vesiculopustular eruptions' above.)
●Congenital/inherited disorders – Several rare, inherited conditions may present with bullous lesions in the newborn. These include epidermolysis bullosa, epidermolytic ichthyosis, aplasia cutis congenita, and incontinentia pigmenti. (See 'Congenital/inherited disorders' above.)
●Principles of diagnosis
•A thorough clinical history and physical examination in most cases provide important clues for diagnosis.
•The possibility of a viral, bacterial, or fungal infection should always be considered.
•Vesicular lesions following the lines of Blaschko on a newborn infant suggest the possibility of incontinentia pigmenti, a rare, X-linked dominant disorder (picture 27B).
•An erosive patch or blister-like lesion on the scalp or another area of the body at birth may occur due to a local absence of skin called aplasia cutis congenita (picture 5).
Features that suggest a potentially severe or life-threatening disease include:
•Widespread erythema and blistering
•Vital sign abnormalities
•Associated anomalies
•Poor growth
In such cases, diagnostic testing should be pursued, and the infant should be closely monitored when there is uncertainty and when infectious, severe, or life-threatening etiologies are on the differential diagnosis in a young infant. (See 'Approach to diagnosis' above.)
ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Josie A Pielop, MD, and Renee M Howard, MD, who contributed to earlier versions of this topic review.
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