Chapter XXII.7. Neonatal Rashes
Jessica M. Donigan, MD
Douglas W. Johnson, MD
July 2014

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A mother of a two day old female notes that her newborn has a rash on her face and chest. According to the patientís mother, the rash started as red spots, but now there are pus bumps too. She notes that the infant does not seem to be bothered by the rash.

On exam, the infant has normal vital signs and measurements. The skin exam reveals erythematous macules on the face and trunk, some of which have pustules in the center. She is otherwise well-appearing.

You make a clinical diagnosis of erythema toxicum neonatorum, and reassure the mother that this is a benign condition that is self-limited and will resolve within the next couple of weeks.


It is common for neonates to develop a cutaneous disorder. Many of these lesions are idiopathic while others may be due to maternal hormones, the immaturity of the newbornís epidermis, or infection. Neonatal skin differs from adult skin as it is 40% to 60% thinner, is less hairy, has a weaker attachment between the epidermis and dermis, and makes up a greater amount of the body surface area to weight ratio.

Erythema toxicum neonatorum (ETN) is an idiopathic condition that tends to occur during the first few days of life. The true incidence is unknown and has been reported as ranging from 5% to 75% of newborns. It is characterized by asymptomatic erythematous macules, papules, and pustules that may occur anywhere on the body, but sparing the palms and soles. The lesions tend to appear at 24 to 48 hours of age, beginning as 1 cm to 3 cm erythematous macules that may develop 1 mm to 4 mm vesicles or pustules within the center. Rarely, the lesions appear as late as 10 days after birth. Biopsy is rarely needed for the diagnosis as ETN is usually diagnosed clinically. However, histologically, the lesions contain folliculo-centric eosinophils. Wright or Giemsa staining will also show eosinophilia, and CBC may show peripheral eosinophilia. No treatment is necessary, as ETN spontaneously resolves without sequelae within 7 to 10 days. Rarely, the lesions persist for 2 to 3 weeks.

Sebaceous hyperplasia occurs in about 50% of neonates and is due to maternal androgen stimulation. This is characterized by multiple pinpoint, yellow to flesh-colored macules or papules on the nose, cheeks, and upper lips. These lesions tend to spontaneously resolve within the first few weeks of life, but may persist for up to 6 months.

Acne neonatorum is another condition that is due to maternal hormone stimulation. It occurs in 50% of newborns. Neonatal acne presents with erythematous papules and pustules on the face. Treatment other than gentle washing is usually unnecessary. However, in more severe cases, keratolytics or topical antibiotics can be used.

Neonatal cephalic pustulosis is an acneiform condition that has been associated with Malassezia fungal species. It is characterized by papules and pustules on the forehead, cheeks, and chin. These lesions respond to topical antifungal agents such as ketoconazole; however, treatment is usually unnecessary as the disease tends to be self-limited and resolve within several weeks.

Seborrheic dermatitis is discussed elsewhere in Section XXII of this book. However, it is worth mentioning again as it is a common condition. It is thought that seborrheic dermatitis is due to a hypersensitivity response to Malassezia which is a common fungus found on the skin. This condition occurs in areas where there is a high density of sebaceous glands, termed "seborrheic areas" which include the scalp, face, ears, trunk, and intertriginous areas. On the scalp, the condition is referred to as cradle cap. It is characterized by erythematous plaques with greasy yellow scales. The lesions are usually asymptomatic and diagnosis is clinical. Treatment of seborrheic dermatitis includes medicated shampoos such as selenium sulfide, zinc pyrithione, and tar. Low potency topical corticosteroids and topical antifungals can also be helpful.

Milia occur in 40% to 50% of infants and are caused by keratin retention within the dermis. Milia most commonly occur on the face, but may also be seen on the upper trunk, limbs, penis, or mucous membranes. When on the hard palate, these lesions are called Epsteinís pearls. Milia are characterized by multiple pinpoint to 2 mm pearly white or yellow papules. They tend to spontaneously resolve after three or four weeks of life, but may persist for a few months.

Miliaria is common in neonates and is caused by sweat retention due to the incomplete differentiation of the epidermis and its appendages (e.g., eccrine ducts). Eccrine ducts become plugged with keratin resulting in a collection of sweat beneath the obstruction which presents as vesicles. The two main types of miliaria seen in infants are miliaria crystallina and miliaria rubra. Miliaria crystallina presents as pinpoint vesicles while maliaria rubra is characterized by erythematous papules, vesicles, or both. Management of miliaria involves avoiding excess heat and humidity.

Diaper dermatitis is a non-specific diagnosis. The three most common types of diaper dermatitis are chafing dermatitis, irritant contact dermatitis, and candidiasis (candida diaper rash). As the name implies, chafing dermatitis is due to friction and occurs in areas where this is highest, including the medial aspects of the thighs, genitalia, buttocks, and abdomen. It presents as mild erythema and scaling. Treatment includes frequent diaper changes. Irritant contact dermatitis is due to contact with urine and feces, and chemicals in soaps, detergents, and topical preparations. Excessive heat and moisture also play a role. This disorder tends to involve the buttocks, vulva, perineum, lower abdomen, and proximal thighs, sparing the intertriginous creases. Treatment includes frequent diaper changes, non-irritating diaper wipes, and topical therapies such as petrolatum and zinc oxide. Diaper candidiasis may present as widespread, beefy red erythema on the buttocks, lower abdomen, and medial thighs. The diagnostic hallmark of diaper cadidiasis is pinpoint pustulovesicular satellite lesions. Other characteristic features are a raised edge and sharp marginization with white scales at the border. This condition can occur as a sequela of systemic antibiotic therapy or as a secondary infection of pre-existing diaper dermatitis. Diagnosis can be confirmed with potassium hydroxide (KOH) preparation of skin scrapings which reveals budding yeast, hyphae, or pseudohyphae. Skin scrapings can also be cultured on Sabouraudís agar; however, this usually takes 48 to 72 hours to confirm the diagnosis. Treatment includes topical anti-yeast agents such as nystatin, clotrimazole, and econazole.

Transient neonatal pustular melanosis is an idiopathic disorder that is less common than erythema toxicum neonatorum, and seen most commonly in neonates with darkly pigmented skin, occurring in 4% to 5% of African American newborns compared to 0.6% of Caucasian newborns. It presents at birth, or soon after, as pustules and vesicles that resolve within 48 hours and leave hyperpigmented macules that can take months to resolve. These lesions can occur anywhere (including the palms and soles), but are most commonly found on the forehead and mandible. Although unnecessary, histological evaluation demonstrates subcorneal pustules that are not folliculo-centric, with neutrophils being the primary inflammatory cell. Treatment is not necessary, as this is a benign, self-limited disorder.

Infantile acropustulosis is another idiopathic disorder that may present between birth and 2 years of age. While the exact cause of this condition is unknown, it has been proposed that it is a response to arthropod bites (e.g., scabies). This condition is characterized by recurrent, 1 mm to 2 mm pruritic vesiculopustules found on the palms and soles, and less commonly on the other aspects of the extremities. Although infantile acropustulosis tends to subside within 2 to 3 years, therapy is often required due to the intensely pruritic nature of the lesions. Antihistamines, topical corticosteroids, and dapsone are recommended for patients with severe pruritus.

Eosinophilic pustular folliculitis (EPF) is an idiopathic disorder that can be seen in adults as well as infants. It has been suggested that EPF and infantile acropustulosis are related disorders. Lesions most commonly occur on the scalp and extremities. As the name implies, the disease is characterized by follicular pustules. These lesions tend to be recurrent, like those seen in infantile acropustulosis. Histological evaluation demonstrates folliculo-centric pustules with an eosinophilic infiltrate. There may also be peripheral eosinophilia. Although EPF tends to be idiopathic, it is occasionally the presenting sign of hyperimmunoglobulinemia E syndrome. EPF is a self-limited condition that tends to resolve by 3 years of age. Treatment is symptomatic and includes topical corticosteroids and antihistamines.

Sucking blisters are seen in less than 0.5% of newborns and are a result of sucking in utero. They present as 0.5 cm to 2 cm bullae or erosions on the dorsal aspect of the fingers, thumbs, wrists, lips, or radial forearms. Lack of vesicles or erosions elsewhere helps to make this diagnosis. These lesions resolve quickly.

Epidermolysis bullosa (EB) refers to a group of uncommon, inherited mechanobullous disorders that result from genetic defects of structural proteins necessary for the attachment and integrity of the epidermis. Patients with EB develop vesicles and bullae as a result of very minor trauma. There are several types of EB with forms characterized by blisters localized to the hands and feet, to severe generalized forms that are lethal before two years of age. Definitive diagnosis of EB, particularly the specific subtype, cannot be readily achieved clinically. A technique known as immunomapping can be helpful in establishing the diagnosis. The skin is biopsied after being subjected to minor trauma, such as that caused by rubbing a pencil eraser over the area. The specimen is then exposed to antibodies directed against proteins located in different layers of the skin. Electron microscopy can also be useful in establishing the diagnosis. Treatment involves wound care and infection control.

Impetigo can present in newborns as early as 2 or 3 days after delivery. It presents as vesicles, pustules, or bullae on an erythematous base. Vesicles and bullous lesions are easily denuded leaving superficial erosions. Impetigo tends to occur in moist areas such as the groin, axillae, and neck folds.

Neonatal pustulosis, also known as S. aureus pustulosis, presents with small pustules on an erythematous base, most commonly in the diaper area. These lesions denude easily leaving superficial erosions.

Congenital toxoplasmosis is due to transplacental transmission of Toxoplasma gondii. The most common cutaneous manifestation is a maculopapular rash sparing the face, palms, and soles. Other skin findings include scarlatiniform eruptions, subcutaneous nodules, or blueberry muffin lesions. Blueberry muffin lesions are blue-red macules or papules that represent extramedullary erythropoeisis. Skin findings tend to develop in the first weeks of the illness, last for a week, and are followed by desquamation or hyperpigmentation.

Congenital varicella syndrome occurs as a result of maternal varicella infection during the first 20 weeks of gestation. The incidence of this syndrome is somewhat rare due to the fact that most women either acquire immunity from a childhood infection or the vaccine. Cutaneous manifestations include vesicles and/or scars.

Neonatal varicella occurs due to a maternal varicella infection during the last few weeks of pregnancy or the early postpartum period. Skin findings include disseminated erythematous papules, vesicles, and erosions. Neonates who were born to mothers who contracted varicella 5 days prior to or 2 days after delivery, should receive varicella-zoster immune globulin. These neonates should also receive intravenous acyclovir.

Congenital rubella syndrome (CRS) occurs as a result of maternal rubella infection during the first 16 to 20 weeks of gestation. This syndrome has become less common since the advent of the rubella vaccine. The classic cutaneous manifestation of CRS is the blueberry muffin lesion. These lesions are usually present at birth or developed within 24 hours. Other cutaneous findings in CRS include a generalized maculopapular rash, reticulated erythema of the face and extremities, hyperpigmentation, and recurrent urticaria. Treatment is supportive therapy with frequent ophthalmologic examinations.

Congenital cytomegalovirus (CMV) infection usually occurs as a result of primary maternal infection. Cutaneous manifestations of congenital CMV infection include petechiae, purpura, a generalized maculopapular rash, blueberry muffin lesions, and rarely, vesicular lesions.

Neonatal herpes simplex virus (HSV) infection is most commonly acquired during vaginal delivery, but can also result from an ascending infection in utero, or occur perinatally via contact with people who are infected. The majority of cases are caused by HSV type 2, and the risk of infection acquired during vaginally delivery is higher in mothers with primary genital herpes than in those with recurrent infection. The typical cutaneous manifestation of neonatal HSV is grouped vesicles on an erythematous base distributed on the presenting part of the neonate (most commonly the scalp and face). Pustules and erosions may also be present. Tzanck smear, direct fluorescent antibody assays, and/or viral cultures can be used to confirm neonatal HSV infection if skin lesions are present. PCR is helpful for rapid diagnosis. Treatment involves intravenous vidarabine or acyclovir.

Congenital syphilis has been increasing over the last 50 years. Caused by the spirochete Treponema pallidum, the risk of congenital syphilis is highest in mothers with untreated primary syphilis. Manifestations are divided into early congenital syphilis (prior to 2 years of age) and late congenital syphilis (after 2 years of age). Cutaneous manifestations of early congenital syphilis include maculopapular dermatitis on the palms and soles, condylomata lata, intractable diaper dermatitis, and mucous patches (fissures at mucocutaneous junctions). Skin findings of late congenital syphilis include gummas and rhagades (perioral fissuring). The treatment of congenital syphilis is parenteral penicillin G.


Questions

1. How do erythema toxicum neonatorum and transient neonatal pustular melanosis differ?

2. How do erythema toxicum neonatorum and eosinophilic pustular folliculitis differ?

3. What are the three most common types of diaper dermatitis?

4. Do erythema toxicum neonatorum, acne neonatorum, transient neonatal pustular melanosis, milia, or sebaceous hyperplasia require treatment?

5. What congenital infection is most commonly associated with a blueberry muffin baby?

6. What other congenital infections can present with blueberry muffin lesions?


References

1. Bolognia JL, Jorizzo JL, Schaffer JV. Dermatology, 3rd edition. 2012, Saunders.

2. Fitzpatrick JE, Morelli JG. Dermatology Secrets Plus, 4th edition. 2011, Elsevier.

3. Paller AS, Mancini AJ. Hurwitz Clinical Pediatric Dermatology, 4th edition. 2011, Saunders.

4. Wolff K, et. al. Fitzpatrickís Dermatology in General Medicine, 7th edition. 2008, McGraw-Hill. Chapter 106.


Answers to questions

1. Erythema toxicum neonatorum (ETN) does not have a racial predilection, as opposed to transient neonatal pustular melanosis (TNPM) which is more common in newborns with darkly pigmented skin. The pustules of TNPM are not surrounded by erythema, like in ETN, and in TNPM, there are hyperpigmented macules that appear after the resolution of the pustules. Additionally, histologic evaluation of ETN shows an folliculo-centric pustules with an abundance of eosinophils, whereas in TNPM the pustules are not centered around the follicles and neutrophils are the primary inflammatory cell.

2. Both erythema toxicum neonatorum (ETN) and eosinophilic pustular folliculitis (EPF) can present with follicular pustules that show an eosinophilic infiltrate histologically. ETN can occur anywhere on the body (sparing the palms and soles), whereas EPF tends to occur on the scalp and extremities. Unlike the lesions of ETN which resolve within a couple of weeks, the pustules seen in EPF are recurrent and can take up to three years to completely resolve.

3. Diaper dermatitis has many different causes with the three most common types being chafing dermatitis, irritant contact dermatitis, and diaper candidiasis.

4. No. Many of the most common lesions seen in newborns are transient and do not require treatment. These include erythema toxicum neonatorum, acne neonatorum, transient neonatal pustular melanosis, milia, and sebaceous hyperplasia.

5. Congenital rubella.

6. Toxoplasmosis, Cytomegalovirus, Enterovirus, Parvovirus B19.


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