8.9 Infantile skin

The term “newborn” or “neonatal” refers to a baby from birth to ca. 2 months of age and the term “Infant” denotes children from birth to 1-year old. Children from 1 year to the age of 4 years old are called toddlers.

Infant skin occurs after the newborn child’s transition from the in-utero environment to the status of self-sufficiency. Healthy full-term newborn skin is well-developed with a thick epidermis and complete stratum corneum and can already function properly.

Skin maturation starts during embryogenesis. The epidermis begins to stratify at the end of the first trimester, and shows definitive layers towards the end of the second trimester. The structural maturation of the skin is complete at 34 weeks of gestational age but pre-term neonates have decreased epidermal and stratum corneum thickness. After birth, human skin undergoes a maturation process with adaptation of the skin to a relatively dry environment compared with the in-utero situation. In newborns, dehydration and hypothermia, as well as percutaneous absorption of toxic agents, can have serious consequences. Transepidermal water loss (TEWL) decreases along with gestational and postnatal age and TEWL is a good marker of gestational age at birth.

Defects of different origin (genetic, traumatic) or interruptions in the maturation process by nutrition deficiency or drugs or infections may partly explain propensities to different skin problems of neonates and infants. Neonates and infants have a characteristic spectrum of skin problems and associated skin diseases.

In the course of skin maturation cell-to-cell connections and the number of cells in the epidermis increase and hereby rete ridges and dermal papillae are formed. In preterm neonates the dermoepidermal junction is looser and the anchoring structures are decreased being more susceptible to traumatic or infectious blister formation. Thus, the skin of newborns is much more permeable than the skin of older children. The external genitalia have especially thin skin. Various excipients used in skin care products may have greater toxicity in newborns than adults. Characteristically, the ratio of body surface to body mass is more than two times greater in newborns compared to adults, and newborns also lack functionally mature metabolic systems. Particular attention should be paid to products that are not rinsed off due to the risk of accumulation of potentially harmful excipients.

In newborn the superficial blood vessels have developed a horizontal plexus with an immaturely organized capillary network. The development of a fully organized capillary bed is usually accomplished by the age of 3-4 months. Many transient skin changes in newborn are based on the immature superficial microvasculature.

Based on a strong androgenic stimulation (mostly maternal androgens) the amount of sebum production is relatively high in the first weeks of life. Seborrhea subsequently decreases during the first months of life. Infants have lower amounts of melanin in the epidermis compared to adults. The adaptive increase of melanin begins with the first UV exposures. Frequent sunburns and exposure to sunlight in childhood are related to melanoma development and effective UV protection is warranted.

In term babies, surface skin acidity (pH) is neutral at birth but decreases during the first one to four days, and continues to drop during the first months, so that an infant’s skin pH level is usually between 5 and 5.5, which is higher than in the adult skin. The acid mantle plays an important role in skin defense and the composition of the microbiome. The vernix caseosa, which develops during the last trimester of gestation and is a complex mixture of water, protein and sebaceous lipids (barrier lipids such as hydrocarbons, wax esters, cholesteryl esters, diol diesters and triacylglycerols, with a characteristic sex diversity), is a protective covering. In addition to the immature epidermal barrier, preterm neonates lack the protective coating of vernix caseosa, thus having an increased risk of skin infections and hypothermia. In addition to the natural moisturizing functions, vernix is antimicrobial while containing lysozyme and lactoferrin and antimicrobial agents. In addition, vernix increases wound healing and contains anti-inflammatory molecules such as linoleic acid. Due to the important function of the vernix, bathing of the newborn during the first six hours of life is no longer recommended by the World Health Organization.

Immediately postpartum, skin microbiota are homogeneously distributed across the human body regardless of delivery method or gestational age. The skin of vaginally delivered newborns is colonized by vaginal Prevotella and Lactobacillus species, while the skin of neonates born by Caesarean section show a diverse community of cutibacteria, corynebacteria and micrococcae. However, at sites such as the nares and oral cavity, neonates born vaginally have bacterial communities equally similar to both maternal skin and vaginal flora. The similarity between mother and infant microbiota decreases over the first year of life, and becomes replaced by strains from close contacts and the environment. The early skin microbiome does not show anatomically site-specific composition, which starts to develop between 1-3 months of life, but still differs significantly from the adult skin microbiome until late adolescence.

Data on the fungal components of the infantile cutaneous microbiome (the mycobiome) is sparse. It is known that Malassezia colonization and diversity increase with age, becoming adult‐like by the first month of life.

As a barrier surface, the skin plays an important role as the first defense line and site of pathogen exposure of the innate and adaptive immune system. The abundant skin-associated immune tissue orchestrates the defense against pathogens, responds to environmental changes, and has also functions in homeostasis. The newborn is working with an innate immune system that is supported by the adaptive immune system. In newborn skin the amount of antimicrobial proteins, lysozyme and lactoferrin are higher than in adults. However, newborn skin contains fewer immune cells than adult skin but typically anti-inflammatory regulatory T-cells (Tregs) occur at higher density than in adult skin. The cellular and chemical environment of the infantile skin is skewed toward keeping the immune cells in an immunosuppressed or immunologically inert state. However, the early life skin environment is important in fostering the development of adaptive lymphocytes and immune cell differentiation.

The neural network develops early in the fetus and organizes with increasing postnatal age and consist of both somatic sensory and autonomic sympathetic fibers. Neurocutaneous responses and sensitivity to touch are important for overall development and skin function but also skin-skin contact and bonding with caregivers.

The thin skin of a preterm infant is most vulnerable and skin injuries are common in preterm infants admitted to a neonatal intensive care unit (NICU). The first stage of managing skin injuries is prevention based on the skin physiology at the given age of life. During admission to NICU, skin assessment is an essential part of care to reduce the risk of acquired skin injuries. The main types of injuries are bruises, blistering, excoriation, erythema and pressure injuries. The most common cause to bruises at a hospital setting are equipment used for blood sampling.

Full-term newborns tolerate early bathing in terms of temperature regulation but the WHO does not recommend early bathing during the first six hours of life. Full-term newborns may receive tub baths while for preterm infants swaddle baths are recommended and daily cleansing of preterm infant skin is not recommended. For most topical agents used in neonatology, there are alternatives that have fewer excipients. Particular attention should be devoted to topical agents due to the risk of accumulation of potentially harmful excipients. Due to the increased permeability of neonatal and infant skin, several topical agents should be used with caution in infants e.g. alcohol, ammonium lactate, glycerin, urea, salicylic acid, neomycin, lidocaine, prilocaine, povidone, calcipotriol, tacrolimus, pimecrolimus and corticosteroids.

Most skin problems in the newborn period and infancy are benign and transient. Eczematous eruptions (e.g. atopic dermatitis (AD) and seborrheic dermatitis (SD)), reactive pustular rashes (e.g. erythema toxicum neonatorum) and acne (acne infantum) are among the most frequent in newborns and small infants. Erythema toxicum neonatorum is relative common but its etiology is unknown. Barrier dysfunction, inflammation, and microbes contribute to the pathogenesis of AD, while the exact etiology of infantile SD affecting the face, ears, neck, and diaper area is unknown, but a relationship with the lipophilic yeast Malassezia is implicated (pustulosis cephalica neonatorum). The eczematous eruptions during infancy are discussed more in detail in connection of the specific types of eczema in the respective chapters.

Nevertheless, skin infections (e.g. bullous impetigo, staphylococcal scaled skin syndrome) and rare systemic diseases (e.g. Langerhans cell histiocytosis, cutaneous mastocytosis, Hyper IgE-syndrome) can also cause skin rashes. Also neonatal lupus erythematosus caused by trans-placental maternal autoantibodies should be recognized to rule out permanent cardiac abnormalities.

Milia and miliaria in newborn and small infants are based on the immaturity of adnexal structures of the still developing skin. Milia are frequent on newborn skin and are characterized by 1-2 mm sized white to yellow papules commonly on the face. Miliaria are usually red 1-2 mm sized papules concentrated on the trunk and are aggravated by high ambient temperatures. Both skin changes do not need treatment. Sebaceous hyperplasia on the nose and upper lip, as well as neonatal cephalic pustulosis with a facial papulopustular eruption during the first weeks or up to 6-8 weeks are common and transient.

Reactive pustular rashes are relatively frequent in the neonatal period. The most common transient pustular rash is erythema toxicum neonatorum, which usually is clinically diagnosed during the first week and disappears within 1-2 weeks after birth. Differential diagnoses include neonatal bullous impetigo and severe neonatal candida and herpes infections (sepsis).

Cutis marmorata is the most common transient skin change in newborn. It consists of a symmetric reticular erythema resulting from a physiological response to cold exposure (vasoconstriction of superficial dermal vessels). The phenomenon usually disappears during infancy.

Neonatal jaundice (icterus) is common and physiological and typically peaks at 3-4 days of age or in preterm infants. It is caused by tissue deposition of bilirubin.

Most genodermatoses manifest neonatally or during infancy. Genetic mutations in proteins associated with the dermoepidermal junction and the dermal anchoring cause different genetic blistering diseases (Epidermolysis bullosa). Incontinentia pigmenti manifests neonatally with linear blistering following the lines of Blaschko, turning into linear plaques on the trunk and extremities. X-linked dominant inheritance of IKBKG- mutations renders females affected with multisystem involvement frequently also the eyes, central nervous system and teeth.

Epidermal differentation disorders (EDD), formerly called ichthyoses, are group of cornification disorders, where the skin thickens, scales and is inflamed at variable levels but may also pose a severe barrier defect. A collodion membrane may encase the newborn, who later develop different, mostly severe, forms of nonsyndromatic EDDs (nEDD) formerly called lamellar ichthyosis, congenital icthyosiform erythroderma or self improving ichthyosis caused by pathogenic variants in several genes namely TGM1, ABCA12, ALOX12B, ALOXE3 and NIPAL4. Milder forms such as as FLG-nEDD (formerly ichthyosis vulgaris) and STS-sEDD (syndromic epidermal differentiation disorder) formerly called X-linked ichthyosis manifest typically during infancy, but boys with sEDD are usually born post- term and after prolonged labor and have increased risk of attention deficit disorders and autism. Some other EDDs are also part of a syndrome with extracutaneous features. Acrodermatitis enteropathica is a very rare disorder of infancy associated with zinc deficiency (inherited zinc transporter defect). It presents with the classic triad of peri-acral and periorificial dermatitis often mimicking atopic or seborrheic dermatitis, diarrhea and alopecia. The therapy consists of life-long zinc substitution.

Café-au-lait macules indicative of neurofibromatosis 1 and hypopigmented macules associated with tuberous sclerosis become increasingly evident neonatally and throughout infancy. Some EDDs affecting predominantly palmoplantar areas (pEDD, formerly called palmoplantar keratodermas) manifest during infancy and early childhood.

Laboratory investigations are rarely needed in skin diseases of infancy. In severe seborrheic dermatitis with periorificial distribution, zinc deficiency has to be excluded (serum zinc concentration). Microbiologic swabs may be needed if a skin infection with bacterial resistance problems is suspected (e.g. bullous impetigo due to MRSA). In newborns with pustular eruptions and systemic illness the exclusion (skin and blood specimens) of candida and herpes simplex sepsis is necessary.

A skin biopsy is warranted if systemic diseases (e.g. Langerhans cell histiocytosis, mastocytosis) are contemplated. In erythrodermic and cases of severe nEDDs, sEDDs and epidermolysis bullosa blood tests for e.g. full blood count, IgE, CRP, electrolytes and albumin and possible other specific test based on diagnosis should be conducted. Genetic tests are usually carried out if a specific genodermatosis is suspected (e.g. epidermolysis bullosa or EDDs).

The diagnosis of skin problems in newborns and infants is usually based on the clinical findings and a thorough history and evaluations of symptoms. A detailed examination of the skin, hair, nails and the mucous membranes (status) is essential.

Investigations (laboratory, microbiology, histology) are needed in rare cases and are guided by clinical differential diagnoses. Genetic diseases are often suspected based on clinical findings but the definitive confirmation and classification is done with genetic profiling.