Section B: Childhood Dermatology

PATIENT STORY

A 2-week-old infant is brought to the office for her first well-baby check. The parents noticed a rash on the face. You diagnose the white spots on the bridge of the nose as milia and benign cephalic pustulosis (BCP) on the cheeks. The parents are happy to hear that BCP and milia will go away without treatment (Figures 114-1 and 114-2).

INTRODUCTION

• Rashes are common in newborns. Physicians will be consulted frequently, as they are a common parental concern. Most newborn rashes are benign; however, a few are associated with more serious conditions. A newborn's skin shows a variety of changes during the first 2 months of life, and most are self-limited. Physicians must be prepared to identify common rashes and advise parents.¹

• Milia are inclusion cysts that appear as tiny white papules in the skin (see Figure 114-1) or on the roof of the mouth.

• BCP is an acneiform eruption appearing as noncomedonal papules or pustules with surrounding erythema on the skin of newborns (see Figure 114-2). BCP accounts for the vast majority of diagnosed neonatal acne. True neonatal acne, though, encompasses comedonal and papulopustular lesions.

• Congenital dermal melanocytosis (CDM) is a hereditary, congenital patch of bluish-black or bluish-gray pigment usually in the sacral area, back, and buttocks of infants (Figures 114-3 and 114-4).

• Erythema toxicum neonatorum (ETN) is a benign, self-limited skin eruption appearing as small yellow-white papules or vesicles with surrounding skin erythema (Figures 114-5 and 114-6).

SYNONYMS

• Milia are also called milk spots or oil seed.

• CDM is also known as Mongolian spots, Mongolian blue spots, slate grey patches, and dermal melanocytosis.

• ETN is also referred to as erythema toxicum, or toxic erythema of the newborn.

EPIDEMIOLOGY

• Approximately 40% to 50% of newborn infants in the United States develop milia.² This condition is mainly associated with newborns carried to full term or near term.

• BCP occurs in many newborns. It typically consists of erythematous papules and pustules but no comedones. BCP affects the forehead, chin, and cheeks. The eruption usually presents during the first 2 weeks of life.³

• The prevalence of CDM varies among different ethnic groups. It has been reported in approximately 96% of black infants, 90% of Native American infants, 81% to 90% of Asian infants, 46% to 70% of Hispanic infants, and 1% to 10% of white infants.^4,5

• ETN occurs in 30% to 70% of full-term infants and in 5% of premature infants. The incidence rises with increasing gestational age and birth weight.^6,7

ETIOLOGY AND PATHOPHYSIOLOGY

• Milia are inclusion cysts that contain trapped keratinized stratum corneum surrounded by a dense lymphocytic infiltrate. Milia are caused by retention of keratin within the dermis. They may rarely be associated with other abnormalities in syndromes such as epidermolysis bullosa and the orofacial digital syndrome (type 1).^2,8

• BCP has been associated with Malassezia species acquired from normal parental skin flora.³ Maternal androgenic hormones that stimulate sebaceous glands likely cause true neonatal acne.⁹

  • In true neonatal acne, histologic examination shows hyperplastic sebaceous glands with keratin-plugged orifices.

• CDM is a hereditary, congenital, developmental condition exclusively involving the skin. It results from entrapment of melanocytes in the dermis during their migration from the neural crest into the epidermis.

  • CDM is associated with cleft lip, spinal meningeal tumor, melanoma, and phakomatosis pigmentovascularis types 2 and 5.¹⁰

  • A few cases of extensive CDM have been reported with inborn errors of metabolism, the most common being Hurler syndrome, followed by gangliosidosis type 1, Niemann-Pick disease, Hunter syndrome, and mannosidosis.^3,4 In such cases, they are likely to persist rather than resolve.⁴

• The etiology of ETN is not known. ETN is thought to be an immune system reaction; the condition is associated with increased levels of immunologic and inflammatory mediators (e.g., interleukins, eotaxin).³

  • The eosinophilic infiltrate of ETN suggests an allergic-related or hypersensitivity-related etiology, but no allergens have been identified. Newborn skin appears to respond to any injury with an eosinophilic infiltrate.

  • Because ETN rarely is seen in premature infants, it is believed that mature newborn skin is required to produce this reaction pattern.

DIAGNOSIS

CLINICAL FEATURES

• Milia are characterized as tiny, pearly white papules (see Figure 114-1) that are actually small inclusion cysts ranging from 1 to 2 mm in diameter. No visible opening is present.²

  • Milia usually appear after 4 to 5 days of life in full-term newborns. Manifestations of milia may be delayed from days to weeks in infants born before term.^8,10

• BCP is a noncomedonal papulopustular eruption. True neonatal acne (Figure 114-2) includes comedones (i.e., whiteheads), papules, and pustules.³ Papules and pustules are the most frequent types of lesions (72.7%), followed by comedones only (22.7%).^2,9

• CDM (Figures 114-3 and 114-4) is a bluish-black macule or patch typically a few centimeters in diameter, although much larger lesions also can occur. Lesions may be solitary or numerous.

  • Generalized CDM involving large areas covering the entire posterior or anterior trunk and the extremities have been reported.

  • Several variants exist, including^4,5:

    • Persistent CDM—These are larger, have sharper margins, and persist for many years (Figure 114-4).

    • Aberrant CDM involve unusual sites such as the face or extremities.

    • Persistent aberrant CDM also are referred to as macular-type blue nevi.

• ETN commonly presents with a blotchy, evanescent, macular erythema (Figures 114-5 and 114-6).

  • The macules are irregular, blanchable, and vary in size.

  • In more severe cases (Figure 114-6), pale yellow or white wheals or papules on an erythematous base may follow. In approximately 10% of patients, 2- to 4-mm pustules develop.^1,7

  • ETN occurs within the first 4 days of life in full-term infants, with the peak onset within the first 48 hours following birth. Rare cases have been reported at birth.

  • Delayed onset can rarely occur in full-term and preterm infants up to 14 days of age.

  • Infants with ETN otherwise are healthy and lack systemic symptoms.

TYPICAL DISTRIBUTION

• Milia are found on the forehead, nose, upper lip, cheeks, and scalp. They can, however, occur anywhere and may be present at birth or appear subsequently. The milia on the child in Figure 114-1 were present at birth.

• BCP occurs on the face with a predilection for nose, cheeks, and chin (Figure 114-2).³

• CDM most commonly involve the lumbosacral area (Figure 114-3), but the buttocks, flanks, and shoulders (Figure 114-4) may be affected with extensive lesions.

• ETN sites of predilection include the forehead, face, trunk, and proximal extremities, typically sparing the genital and acral areas.³ Involvement of the mucous membranes rarely occurs (Figures 114-5 and 114-6).

LABS AND IMAGING

• No laboratory studies are required.

• Severe or persistent neonatal acne may warrant further work-up for congenital adrenal hyperplasia, a virilizing tumor, or other endocrinopathy.¹¹

• In extensive CDM involving the back, radiographic studies are needed to rule out a spinal meningeal tumor or anomaly.⁴

• ETN is often diagnosed clinically, based on history and physical examination, but a peripheral smear of intralesional contents can be done to confirm the diagnosis.⁷

  • A Tzanck smear or Gram stain shows inflammatory cells with greater than 90% eosinophils and variable numbers of neutrophils.

  • A complete blood count (CBC) may show eosinophilia in 7% to 18% of patients.¹² Eosinophilia may be more pronounced when the eruption shows a marked pustular component.

DIFFERENTIAL DIAGNOSIS

Other diagnoses that may be confused with milia, BCP, and ETN include:

• Miliaria—Heat rash (prickly heat) with tiny papules that can be red (miliaria rubra), clear (miliaria crystallina), or pustular (miliaria pustulosa) (Figure 114-7). Miliaria results from sweat retention caused by partial closure of eccrine structures. Both milia and miliaria result from immaturity of the skin structures, but they are clinically distinct entities.

• Neonatal pustular melanosis—This eruption, present at birth, consists of 2- to 4-mm nonerythematous vesicles filled with a milky fluid. This rash occurs in 5% of African-American newborns and in less than 1% of white newborns, and fades in the first 3 to 4 weeks of life (see Chapter 116, Pustular Diseases of Childhood).

• Sebaceous hyperplasia—Yellow papules present at birth, typically located on the nose, and resolve within two months (see Chapter 165, Sebaceous Hyperplasia). Attributed to fetal exposure to maternal androgen.¹¹

CDM may be confused with the following lesions also present at birth or shortly after:

• Congenital melanocytic nevi—These lesions are much less common (1% to 2% of newborns). They are of variable color from tan or brown to red or black, often within a single lesion and the pigment may fade off into surrounding skin. The borders are often irregular and the lesion can appear slightly raised over time (although a macular portion is usually found at the edges). Most congenital melanocytic nevi have a darker color and more discrete borders than CDM. A biopsy is only needed if melanoma is suspected (see Chapter 169, Congenital Melanocytic Nevi).

• There are reports of CDM being confused for the bruising that occurs in child abuse. A good history and a clear knowledge of the pattern of CDM should help to differentiate between these two entities.

ETN can be confused with the following:

• Folliculitis—Primary lesion is a papule or pustule pierced by a central hair, although the hair may not always be visualized. Deeper lesions present as erythematous, often fluctuant nodules. Folliculitis rarely occurs in the first few days of life when ETN is most commonly seen (see Chapter 123, Folliculitis).

• Chickenpox—The characteristic rash appears in crops of lesions beginning with red macules and passing through stages of papule, vesicle (on an erythematous base), pustule, and crust. Simultaneous presence of different stages of the rash is a hallmark. Infants are mostly born with adequate maternal antibodies to varicella, so that timing should differentiate between these two conditions (see Chapter 129, Chickenpox).

• Cutis marmorata (Figure 114-8) is reticulated mottled skin with symmetric involvement of the trunk and extremities produced by a vascular response to cold; the change resolves with heat. This entity can persist for weeks or months. No treatment is indicated.

• Harlequin color change affects 10% of full-term babies and occurs when the newborn lies on one side and erythema develops on one side of the body, while blanching is seen on the contralateral side. The color change fades after 30 seconds to 20 minutes and resolves with increased muscle activity or crying. It begins between the second to fifth days of life and lasts up to 3 weeks.¹³

• Neonatal lupus is a rare syndrome in which maternal autoantibodies are passively transferred to the baby, producing well-demarcated, erythematous, scaling patches that are often annular, predominately on the scalp, neck, or face (Figure 114-9). The condition is self-limited and resolves without scarring by 6 to 7 months of age. It is associated with congenital heart block. Treatment includes photoprotection; mild topical steroids may be helpful.

MANAGEMENT

FIRST LINE

• Milia, BCP, CDM, and ETN are benign conditions and parents should be reassured that they resolve with time. SORⒶ

• If treatment for BCP is pursued, topical azole creams will result in quick resolution of lesions.³ SORⒸ This includes OTC clotrimazole and miconazole.

SECOND LINE

• If treatment is chosen for severe neonatal acne, there is low-quality evidence for the following:

  • Comedones may be treated with azelaic acid cream 20% or tretinoin cream 0.025% to 0.05%.^14,15 SORⒸ

  • For inflammatory lesions, erythromycin solution 2% and benzoyl peroxide gel 2.5% may be used.^14,16 SORⒸ

  • Oral erythromycin is the preferred antibiotic if systemic therapy is pursued.¹⁴ SORⒸ

PROGNOSIS

• Milia usually disappear within a few weeks.

• BCP may persist for a few weeks to several months.

• CDM may persist for many years but usually disappear within 3 to 5 years and almost always by puberty.

• ETN usually lasts for several days but can change rapidly, with lesions appearing and disappearing in different areas over hours.

PARENT EDUCATION

• Milia is a benign self-limiting condition that disappears within a few weeks without leaving any scars. No drug therapy is required, and use of nonprescription rash medications is not recommended.

• BCP resolves on its own in weeks. Oils and lotions do not help and may actually aggravate the acne. An OTC azole cream may be used.

• CDM is likely to fade over time and may disappear by age 7 to 13 years.

• ETN will usually disappear within 2 weeks.

REFERENCES

PATIENT STORY

A baby girl is brought to the office because her mother is concerned over the growing strawberry hemangioma on her face. Her mother is reassured that most of these childhood hemangiomas regress over time and that there is no need for immediate treatment (Figure 115-1).

INTRODUCTION

Hemangiomas are the most common benign tumors of infancy, affecting approximately 5% to 10% of children with Caucasian ethnicity.¹

Up to 70% of hemangiomas are small and of cosmetic concern only and will resolve at the predictive rate of 10% per year, that is, 50% will have involuted by age 5; 90% by age 9.²

Segmental morphology, large size, and location on the face are predictive of poorer outcomes as measured by complication rates and suggest the need for further investigative study.³

SYNONYMS

Infantile hemangiomas, angiomas. Strawberry hemangiomas are also called superficial hemangiomas of infancy. Cavernous hemangiomas are also called deep hemangiomas of infancy.

EPIDEMIOLOGY

• Approximately 30% of hemangiomas are present at birth; the other 70% appear within the first few weeks of life.

• Although the most predictive condition involving infantile hemangioma is low birth weight, other factors to be considered are prematurity, fair-skinned infants, female sex (2.4:1), and even in some cases family history.^1,4

• In one study, the mothers of children with hemangiomas are of higher maternal age, have a higher incidence of preeclampsia and placenta previa, and are more likely to have had multiple-gestation pregnancies.⁵

ETIOLOGY AND PATHOPHYSIOLOGY

• Hemangiomas consist of an abnormally dense group of dilated blood vessels.

• Hemangiomas are characterized by an initial phase of rapid proliferation, followed by spontaneous and slow involution, often leading to complete regression.

• Vascular malformations do not exhibit rapid proliferation but rather grow in proportion to the child and are considered a separate and distinct diagnosis with differing treatment regimens.

• Most childhood hemangiomas are small and innocuous, but some grow to threaten a particular function or even life.

• Rapid growth during the first month of life is the historical hallmark of hemangiomas, when rapidly dividing endothelial cells are responsible for the enlargement of these lesions. The hemangiomas become elevated and may take on numerous morphologies (dome-shaped, lobulated, plaque-like, and/or tumoral). The proliferation phase occurs during the first year, with most growth taking place during the first 6 months of life. Proliferation then slows and the hemangioma begins to involute.

• The involutional phase may be rapid or prolonged. No specific feature has been identified in explaining the rate or completeness of involution. However, in one type of hemangioma, the rapidly involuting congenital hemangioma, the proliferation phase occurs entirely in utero such that the lesion is fully developed at birth, followed by complete involution during the second year of life.

• Of the lesions that have involuted by age 6 years, 38% will leave residual evidence of the hemangioma in the form of a scar, telangiectasia, or redundant, "bag-like" skin. The chance of a permanent scar increases the longer it takes to involute. For example, of the lesions that involute after age 6 years, 80% may exhibit a cosmetic deformity requiring surgical intervention. Surgical intervention should only be performed by trained specialists because of the propensity for excessive bleeding from these vascular lesions.⁶

DIAGNOSIS

CLINICAL FEATURES

Early lesions may be subtle, resembling a scratch or bruise, or alternatively may look like a small patch of telangiectasias or an area of hypopigmentation. A hemangioma can start off as a flat red mark, but as proliferation ensues, it grows to become a spongy mass protruding from the skin. The earliest sign of a hemangioma is blanching of the involved skin with a few fine telangiectasias followed by a red macule. Rarely, a shallow ulceration may be the first sign of an incipient hemangioma. Hemangiomas are typically diagnosed based on appearance, rarely warranting further diagnostic tests.⁷

Hemangiomas may be superficial, deep, or a combination of both. Superficial hemangiomas are well defined, are bright red, and appear as nodules or plaques located above clinically normal skin (see Figure 115-1). Deep hemangiomas are raised flesh-colored nodules, which often have a bluish hue and feel firm and rubbery (Figure 115-2).

Most are clinically insignificant unless they impinge on vital structures, ulcerate, bleed, incite a consumptive coagulopathy, or cause high-output cardiac failure or structural abnormalities. Blocking vision is a common reason needed for treatment (Figures 115-3 and 115-4).

TYPICAL DISTRIBUTION

Anywhere on the body, most often on the face, scalp, back, or chest.

IMAGING

Most hemangiomas of infancy do not need imaging. If the hemangioma is very large, deep, or undefined, MRI with and without IV gadolinium helps delineate the location and extent of hemangiomas while also differentiating them from high-flow vascular lesions, such as arteriovenous malformations.⁷ Ultrasound is a useful tool to differentiate hemangiomas from other subcutaneous structures such as cysts and lymph nodes as well as from other soft-tissue masses but is limited in determining the depth or extent of the hemangioma.⁸

Plain radiography may be useful for evaluating hemangiomas that impinge on an airway.⁷

BIOPSY

Biopsies are rarely needed and can be risky because vascular lesions may bleed profusely. If a biopsy is being considered, referral is recommended.

DIFFERENTIAL DIAGNOSIS

• Superficial capillary malformations that are frequently seen in infants include those above the eyelids and nape of the neck. These are called salmon patches and are not dangerous. The "angel's kisses" on the eyelids (Figure 115-5) usually disappear by age 2 years. The "stork bites" may last into adulthood but are rarely an issue because they are often covered by hair (Figure 115-6). These capillary malformations are a variant of nevus flammeus or port-wine stain. They are macular, sharply circumscribed, pink to purple, and varied in size (see Chapter 211, Hereditary and Congenital Vascular Skin Lesions).

• Blue rubber bleb nevus syndrome—Bluish cutaneous vascular malformations that empty with pressure; texture resembles rubbery nodules, similar to deep hemangiomas.⁹

• Maffucci syndrome—Rare congenital nonhereditary mesodermal dysplasia characterized by multiple enchondromata, cutaneous hemangiomas, and more recently spindle cell hemangiomas.¹⁰ It is important to identify Maffucci syndrome early because it is associated with an increased risk of malignancy. May appear as multiple vascular malformations of the skin with a "grape-like" appearance (see Chapter 211, Hereditary and Congenital Vascular Skin Lesions).

• Angiosarcoma—Rare, malignant endothelial tumor characterized as ill-defined red patches, plaques, or nodules (see Chapter 210, Acquired Vascular Skin Lesions).¹¹

• Arteriovenous malformation—Benign, single red papules on head or neck; may be cutaneous or mucosal.¹¹

• Infantile fibrosarcoma—A rare and highly malignant tumor of childhood that may take on the form of a highly vascularized mass, resembling a hemangioma, especially after a hemangioma has ulcerated as a result of rapid proliferation.¹²

MANAGEMENT

• The majority of hemangiomas will eventually involute without complications and require no treatment, but approximately 20% cause complications such as ulcerations or irreversible cutaneous expansion, or threaten vital structures such as the eyes, nose, or airways.¹³

• Hemangiomas in trauma-prone areas are the most likely to ulcerate. These include the diaper area (Figure 115-7) and the back of the head. Small ulcerations can be treated with topical mupirocin in morning and metronidazole gel in the evening. SORⒸ

• Any lower face or beard area hemangioma can be a marker for laryngeal hemangiomatosis (Figure 115-8). Snoring or frequent cough in such a child should prompt a referral to a head and neck surgeon.

• Any large segmental hemangioma on the face could be part of the PHACE syndrome:

  • P—Posterior fossa malformations

  • H—Hemangiomas, usually large, segmental, "plaque-like" lesions (Figure 115-9)

  • A—Arterial anomalies

  • C—Cardiac anomalies and coarctation of the aorta

  • E—Eye abnormalities, that is, microphthalmos, exophthalmos, colobomas, retinal vascular abnormalities, optic nerve atrophy, or iris hypertrophy or hypoplasia. A coloboma is a hole in one of the structures of the eye that can cause blindness (Figure 115-10).

Beta blockers are now the first-line therapy for cosmetically significant or function-impairing and rapidly proliferating infantile hemangiomas. Propranolol (FDA approved, 20 mg/5 mL) 1 mg/kg to 3 mg/kg dosages were used in the largest randomized controlled trial to date for treatment durations of 3 to 13 months, with the median length of treatment being 6 months (see Figure 115-10). The benefit of continuing treatment beyond 12 months is not clear.^14,15 SORⒷ

• Propranolol treatment can cause side effects such as diarrhea, sleep disturbance, electrolyte abnormalities, and/or cold extremities. Watch for the major side effects (which would warrant cessation of therapy), hypotension and hypoglycemia. Bronchial hyper-reactivity has also been reported. Monitoring the patient in the office after the first dose is advisable, although the treatment has been found to be safe in a number of studies.^14,15

• Combined treatment with propranolol and 940-nm diode laser for particularly severe hemangiomas was shown to be more effective for cosmesis in one study.¹⁶ Other studies have had differing results, with combined laser/propranolol treatment showing little to no advantage from the added laser therapy over propranolol alone.¹⁷

• For patients who cannot tolerate beta blocker therapy, prednisone 3 to 5 mg/kg per day had been shown to provide an effective and rapid way of treating hemangiomas, and in fact, was the treatment of choice prior to the discovery of beta blocker treatment for this condition.¹⁸ SORⒷ In a study, 68% of patients receiving systemic corticosteroid treatment with oral prednisone experienced rapid and virtually complete involution of hemangiomas.¹⁸ Another 25% experienced significant regression, and treatment demonstrated no effect in 7% of patients. The authors recommended treating with oral prednisone for 6 to 8 weeks, and in more severe cases, for 12 weeks.

• Side effects of oral steroid therapy include Cushingoid facies, mood changes/irritability, hypertension and increased susceptibility to infection, and short-term growth retardation, all of which seem to be transient and resolve after cessation of the therapy.¹⁸

• Ultrapotent topical corticosteroids have been found especially helpful in the treatment of small hemangiomas, especially periocular hemangiomas and those at sites prone to ulceration and disfigurement. Seventy-four percent of patients demonstrated good or at least partial response to treatment, with the majority experiencing cessation of growth before what would have been expected for their age. Thinner, more superficial hemangiomas demonstrated better improvement than thicker, deeper lesions.¹⁹ SORⒷ

• Intralesional corticosteroid injections, composed of a mixture containing triamcinolone acetonide (20 mg average dose) and betamethasone acetate (3 mg average dose) with varying number of injections, have been found to successfully treat head and neck childhood hemangiomas in properly selected infants. In a research study, 13% of the hemangiomas treated with intralesional injections almost completely involuted, 32% showed greater than 50% reduction in volume, 32% showed definite but less than 50% reduction in volume, and 23% showed little to no decrease in size.²⁰ SORⒷ Avoid intralesional steroids around the eye.

• Treatment with flashlamp-pumped pulsed-dye laser has been found to be an effective treatment method for superficial cutaneous hemangiomas at sites of potential functional impairment and on the face. In a study, 85% of patients were found to have excellent or good results with the flashlamp-pumped pulsed-dye laser. Hemangiomas with a deep component do not seem to benefit from flashlamp-pumped pulsed-dye laser therapy to the same degree as a truly superficial hemangioma, as the laser is limited by its depth of vascular injury.^21-23 SORⒷ The pulsed-dye laser seems especially promising with its ability to selectively damage blood vessels with minimal damage to surrounding tissues. This procedure is also associated with decreased pain and increased healing.²⁴ SORⒷ

• Facial hemangiomas causing severe functional disturbance and serious psychological distress are strong reasons to consider surgical excision before the child reaches the expected age of spontaneous regression. SORⒸ

• Large periocular hemangiomas demand prompt treatment to prevent debilitating consequences such as amblyopia (see Figure 115-2). Early treatment is also recommended for proliferative labial tumors because they not only have a tendency to bleed, but they also make eating difficult. Additionally, early treatment with a consideration for surgery is advised for hemangiomas located on the nasal tip, as they regress slowly and may ultimately result in distortion of the nasal framework.²³

• Surgical excision of involuted hemangiomas is not uncommon to remove residual tissue that may be causing cosmetic or functional impairment. Excision is performed in late involution to reduce the risk of hemorrhage.

• Depending on the location and how complex the hemangioma is, consultations with pediatric dermatologists, ophthalmologists, otolaryngologists, plastic surgeons, and pediatric neurosurgeons may be necessary to ensure proper care.

TOPICAL THERAPY

• Topical timolol ophthalmic gel or solution has been shown in a number of studies to effectively treat infantile hemangiomas (Figure 115-8).^25-27 SORⒷ One of the studies noted that predictors of better response were superficial type of hemangioma (p = 0.01), 0.5% timolol concentration (p = 0.01), and duration of use longer than 3 months (p = 0.04).¹⁶ SORⒷ Another study using 0.5% ophthalmic solution 3–4 times daily in patients with small superficial hemangiomas found that treatment was most effective in the early proliferative stage.²⁵ SORⒷ

FOLLOW-UP

Watchful waiting and serial observations during well-child examinations are recommended for uncomplicated hemangiomas of infancy. Hemangiomas with complicating factors need close follow-up on an individual basis.

PATIENT EDUCATION

Hemangiomas are benign and are not cancer. They are common, and up to 10% of lighter skinned infants will have one. Most hemangiomas will go away spontaneously and not need treatment. For those needing treatment, there are treatments that are safe and effective (oral propranolol and topical timolol). Feel free to show the great results of therapy of some of the largest and most worrisome hemangiomas in this chapter to the parents in your office (Figures 115-9, 115-10, 115-11).

Acknowledgment

We thank Mary Alice for the photographs of her daughter with PHACE syndrome. One can learn more about their family story at http://angelphace.com/. Also visit www.PHACEsyndromecommunity.org, the site for the organization that supports individuals with PHACE and their families.

REFERENCES

PATIENT STORY

A 1-year-old boy is brought for a second opinion about the recurrent pruritic vesicles and pustules on his hands and feet. This is the third episode, and in both previous episodes, the physicians thought the child had scabies. The child was treated with permethrin both times, and within 2 to 3 weeks the skin cleared. No other family members have had lesions or symptoms. Figures 116-1, 116-2, 116-3 demonstrate a typical case of infantile acropustulosis that is often misdiagnosed as scabies. Although the condition can be recurrent, it is ultimately self-limited and will resolve.

INTRODUCTION

Acropustulosis and transient neonatal pustular melanosis (TNPM) are pustular diseases that typically present in infancy. Acropustulosis is a pruritic vesiculopustular disease presenting between 2 and 10 months of age and remitting spontaneously by 36 months of age. TNPM is present at birth and characterized by 2- to 3-mm hyperpigmented macules and pustules. Acropustulosis may require symptomatic treatment of pruritus, but otherwise both illnesses are self-limiting.

EPIDEMIOLOGY

Acropustulosis:

• Rare, intensely pruritic, vesiculopustular disease of young children.¹

• Typically begins in the second or third months¹ of life and as late as 10 months of age.²

• Occur slightly more often in darker-skinned patients and males.¹

• Typically spontaneously remits by 6 to 36 months of life.²

Transient neonatal pustular melanosis:

• A disease of newborns.³

• Equal male-to-female ratio.³

• Seen in 4.4% of black infants and 0.6% of white infants.⁴

• Early, spontaneous remission.³

ETIOLOGY AND PATHOPHYSIOLOGY

Acropustulosis:

• The exact cause and mechanism have yet to be determined.⁵

• Some physicians speculate that it is a persistent reaction to scabies ("postscabies syndrome"). Suggestive of this infectious etiology, infantile acropustulosis will occasionally be concurrently present among siblings. Also, patients diagnosed with this disorder frequently have received prior treatment for scabies, which may either provide evidence of an infectious etiology or demonstrate the frequent misdiagnosis, as in the patient above. Odom et al. conclude that in some cases, this disease may represent a hypersensitivity reaction to Sarcoptes scabiei.⁴

Transient neonatal pustular melanosis:

• The etiology is uncertain⁶; however, it may result from an obstruction of the pilosebaceous orifice.³

DIAGNOSIS

• Acropustulosis—A work-up to rule out potentially serious infectious causes should be considered whenever confronted with a new pustular dermatosis early in a child's life. A work-up might include a scraping for scabies and KOH preparation as rapid diagnostic tests. If these studies are negative, the diagnosis may be made clinically as described below.

• TNPM—This diagnosis can be made clinically. However, if performed, a Wright stain of the exudate will reveal a predominance of neutrophils with an occasional eosinophil, and the Gram stain will be negative.³

CLINICAL FEATURES

Acropustulosis:

• These vesiculopustular lesions begin around the second or third months of life and are typically concentrated on the hands and feet (see Figures 116-1, 116-2, 116-3).¹

• They begin acutely as small pink papules and progress within 24 hours to pustules¹ of less than 5 mm in diameter.²

• Recurrent episodes of these intensely pruritic lesions typically last 10 days and may recur every 2 to 5 weeks,^1,2 decreasing in frequency and severity² until spontaneous remission around 3 years of age.¹ Because of the pruritic nature of these lesions, infants may be irritable and appear uncomfortable during eruptions.⁵

• There may be a residual scale and postinflammatory hyperpigmentation.²

Transient neonatal pustular melanosis:

• This condition is characterized by the presence at birth of 2- to 3-mm macules and pustules⁴ on a nonerythematous base (Figures 116-4 and 116-5).⁷

• The lesions probably evolve prenatally⁷ and subsequently rupture postnatally in 1 to 2 days.

• They heal with hyperpigmented macules that fade by 3 months of age,³ with lighter-skinned patients experiencing less hyperpigmentation.⁷

• Sometimes, the only evidence of the disease is the presence of small, brown macules with a rim of scale at birth.⁷

• Newborns with TNPM have no other systemic symptoms and are well appearing.⁶

TYPICAL DISTRIBUTION

• Acropustulosis—Although most commonly found on the palms and soles, the pustules may also be found on the dorsal surfaces of the hands and feet and occasionally the face, scalp, and trunk.⁵

• TNPM—They are most common on the face and chin; however, they may also be present on the neck, chest, sacrum, abdomen, and thighs.⁷

LABORATORY TESTING

• Acropustulosis—A blood count is not needed but might reveal a slight leukocytosis and frequently an eosinophilia. Stained smears of the lesions are also not needed but will demonstrate many neutrophils,¹ with some eosinophils possible early in the course.²

• TNPM—A Wright stain will reveal numerous neutrophils and some eosinophils, with a negative Gram stain.³ Blood counts should be normal, and no laboratory work-up is generally indicated.

DIFFERENTIAL DIAGNOSIS

• Scabies infestation—Characterized by pruritic, intraepidermal burrows and vesicles with scale and crust, most commonly found in the web spaces of the digits, wrists, elbow, genitals, and lower extremities. May be present in other family members and is not present at birth. Microscopic examination of the scrapings of the burrows may reveal mites, feces, eggs, or all of the above.³ Acropustulosis will be refractory to all scabies therapies, but scabies therapy may appear to work because each episode of acropustulosis is self-limited (see Chapter 149, Scabies).

• Erythema toxicum neonatorum—Appearing on the neonate 1 to 2 days after birth, this disease of unknown etiology causes 2- to 3-cm diffuse blotchy macules with 1- to 4-mm central vesicles. The lesions, which spare the palms and soles, contain a predominance of eosinophils and resolve spontaneously by 2 weeks of age (see Chapter 114, Normal Skin Changes).³

• Impetigo—A superficial infection of the skin with vesicles, bullae, and honey-colored crusts, caused by group A Streptococcus, or Staphylococcus aureus. Gram stain and culture should be positive (see Chapter 122, Impetigo).³

• Cutaneous candidiasis—Slightly pruritic areas of intensely erythematous papules, pustules, and plaques, possibly with white exudate, found around the genitals and folds of skin. Candida yeast forms present on KOH preparation or culture (see Chapter 142, Candidiasis).³

• Varicella—Characteristic "dewdrops on a rose petal" that develop in childhood. Uniformly distributed, pruritic, with known contacts likely. Now less common because of immunization (see Chapter 129, Chickenpox).

• Herpes—Grouped, painful vesicles on an erythematous base. May occur as gingivostomatitis in young children but rarely seen in the distribution of the pustular diseases of childhood. More likely to be vesicular rather than pustular (see Chapter 135, Herpes Simplex).

• Hand, foot, and mouth disease—This illness is caused by the coxsackievirus and produces papules and macules of the hands and feet that progress to flat vesicles before ulceration and eventual resolution. They typically affect the dorsum of the hands and feet and are also accompanied by painful oral lesions (see Chapter 134, Hand Foot Mouth Syndrome).³

• Psoriasis, pustular—This severe form of psoriasis is rare in children and is characterized by the acute appearance of diffuse, painful, pinpoint pustules with high fever, fatigue, and anorexia (see Chapter 158, Psoriasis).¹

MANAGEMENT

Acropustulosis:

• Oral corticosteroids generally are not effective¹ and not necessary in management.⁵ SORⒸ

• Topical corticosteroids have been shown to be effective in case series; no randomized controlled trials are available to verify efficacy. If corticosteroids are prescribed, use the lowest effective potency for the lowest amount of time to avoid side effects such as hypopigmentation and skin thinning.^8,9 SORⒸ

• Oral antihistamines may be helpful in controlling pruritus.¹ SORⒸ

• Pramoxine, lotion or cream, may be used topically for control of itching as it works by a different mechanism than antihistamines.⁵ SORⒸ

• Dapsone (1 to 2 mg/kg per day, maximum dose of 100 mg/day)⁵ has been used with good results. However, the risks of complications are generally considered to outweigh the benefits, unless the pruritus is debilitating.¹ SORⒸ

Transient neonatal pustular melanosis:

• No treatment is necessary. The parents should be reassured that the condition is benign and will resolve spontaneously with eventual normalization of any hyperpigmented macules.⁶ SORⒷ

PROGNOSIS

• Acropustulosis resolves spontaneously by 6 to 36 months of age.

• TNPM resolves spontaneously by 3 months of age.

FOLLOW-UP

Acropustulosis may require initial follow-up for control of symptoms and assurance of a stable disease course. With symptoms controlled, follow-up may be unnecessary as the child ages and the disease decreases in severity and frequency. If dapsone is prescribed, proper monitoring is indicated.

TNPM needs no specific follow-up other than normal well-child care.

PATIENT EDUCATION

Once other conditions have been ruled out, reassurance that these diseases are self-limited is the most important piece of information to communicate to the family.

REFERENCES

PATIENT STORY

A 2-month-old baby girl was brought to the office with a severe diaper rash that was not getting better with Desitin. Upon examination, the physician noted a white coating on the tongue and buccal mucosa. The diaper area was red with skin erosions and satellite lesions (Figure 117-1). History and physical are consistent with candidiasis of the mouth (thrush) and the diaper region. The child was treated with oral nystatin suspension and topical clotrimazole cream in the diaper area with good results.

INTRODUCTION

Diaper rash is a general term used to describe any type of red or inflammatory skin rash that is located in the diaper area.

SYNONYMS

Diaper dermatitis, napkin dermatitis.

EPIDEMIOLOGY

• Diaper dermatitis is the most common dermatitis of infancy.

• Variability in prevalence of 4% to 35% among children in their first 2 years of life in different studies.¹

• Diaper rash is thought to be present in 25% of children presenting for outpatient visits.²

• No differences in prevalence between genders or among ethnic groups.

• One study showed an incidence of 19.4% in children ages 3 to 6 months.¹

• Higher incidence among formula-fed compared with breastfed infants.¹

• Condition typically begins around age 3 weeks, peaks at age 9 to 12 months, and then decreases with age until it resolves completely with toilet training.³

• Individual episodes last from 1 day to 2 weeks.

• Aggravating factors include poor skin care, diarrhea, recent antibiotic use, and urinary tract abnormalities.

• Perianal streptococcal dermatitis occurs in children between 6 months and 10 years of age (Figures 117-2 and 117-3).

ETIOLOGY AND PATHOPHYSIOLOGY

• Primary diaper dermatitis—An acute skin inflammation in the diaper area with a multifactorial etiology.⁴ The main cause is irritation of thin skin as a result of prolonged contact with moisture including feces and urine. The multiple factors involved are:

  1. Occlusion/lack of exposure to air.

  2. Friction and mechanical trauma.

  3. Local irritants—Fecal proteases and lipases.

  4. Increased pH.

  5. Maceration of the stratum corneum with loss of the protective barrier function of skin.

• Irritant diaper dermatitis (IDD) is a combination of intertrigo (wet skin damaged from chafing) and miliaria (heat rash) when eccrine glands become obstructed from excessive hydration. It is a noninfectious, nonallergic, often asymptomatic contact dermatitis that typically lasts for less than 3 days after a change in diaper practices.

• Candidal diaper dermatitis—Within 3 days, 45% to 75% of diaper rashes are colonized with Candida albicans of fecal origin.

• Bacterial diaper dermatitis may be a secondary infection caused by Staphylococcus aureus or Streptococcus pyogenes.⁵ Other common bacterial isolates include Escherichia coli, Peptostreptococcus, and Bacteroides. Usually occurs during the warm summer months.

• Perianal streptococcal dermatitis is caused by group A b-hemolytic streptococci (see Figures 117-2 and 117-3).

RISK FACTORS

• Diarrhea.

• Formula-fed infants.

• Recent antibiotic use.

• Oral thrush.

• Poor skin care, including infrequent diaper changes and lack of barrier cream use.

DIAGNOSIS

CLINICAL FEATURES

• IDD begins with shiny erythema with or without scale and poorly demarcated margins on the convex skin surfaces in areas covered by diapers. Moderate cases can have papules, plaques, vesicles, and small superficial erosions that can progress to well-demarcated ulcerated nodules, typically with sparing of skin folds (Figure 117-4).

• Pustules or papules beyond the rash border (called "satellite lesions"), involvement of the skin folds, and white scaling all indicate a fungal infection with Candida (Figure 117-5).

• Secondary bacterial infections can have redness, honey-colored crusting, swelling, red streaking, and/or purulent discharge. With impetigo in the diaper area, bullae are not usually intact but instead present as superficial erosions.

• Perianal streptococcal dermatitis is a bright red, sharply demarcated rash sometimes associated with blood-streaked stools (see Figure 117-2).

TYPICAL DISTRIBUTION

Diaper dermatitis is primarily found on the buttocks, the genitalia, the mons pubis and lower abdomen, and the medial thighs. Be sure to evaluate for rashes outside of the diaper area as well. If Candida is suspected, the oropharynx should be inspected for signs of thrush, such as adherent white plaques on the mucosa.

LABORATORY STUDIES

Clinical diagnosis is based primarily on the physical examination. Rarely indicated tests that are occasionally used in more complicated cases include potassium hydroxide preparation for fungal elements, mineral oil preparation for scabies, complete blood count with differential, zinc level, or skin biopsy (Figure 117-6). A rapid strep test can be used to diagnose perianal streptococcal dermatitis (see Figures 117-2 and 117-3).

DIFFERENTIAL DIAGNOSIS

There are two distinctive severe variants of IDD. Jacquet's diaper dermatitis (dermatitis syphiloides posterosiva or erosive variant) is a term used to describe severe, slow-healing, noduloerosive lesions with heaped-up borders seen in children with persistent diarrhea.⁶ Granuloma gluteale infantum is a rare and poorly understood primary diaper dermatitis that presents with granulomatous nodules that can have large, raised, purple erosions with rolled margins. It resolves spontaneously over the course of a few months once the causative agent is discovered and removed, often with residual scarring and hyperpigmentation.⁷

Perianal pseudoverrucous papules are shiny, smooth, red, moist, flat-topped lesions that are commonly confused with the genital warts that occur in the context of Hirschsprung disease.

Secondary diaper dermatitis is an eruption in the diaper area with a defined etiology. Atopic dermatitis, seborrheic dermatitis, and psoriasis are examples of rashes that can appear anywhere on the body and can be exaggerated in the groin as a result of wearing diapers. Family history of atopy or psoriasis and rash in other locations besides the groin can be helpful.

Congenital syphilis, scabies, HIV, Langerhans cell histiocytosis, and acrodermatitis enteropathica are examples of rashes in the diaper area unrelated to the diaper. Allergic contact dermatitis as a result of an allergen in the diaper itself is possible but rare.

Suspect acrodermatitis enteropathica caused by zinc deficiency when the diaper dermatitis is severe and accompanied by perioral dermatitis (see Figure 117-6). The serum zinc level will be low and zinc supplementation will be needed.

MANAGEMENT

FIRST LINE

• Parental behavior change to keep the skin as exposed and dry as possible. SORⒷ Frequent diaper changes (as soon as they are wet or soiled and at least every 3 to 4 hours); use disposable diapers. SORⒷ Frequent gentle cleaning of the affected area with lukewarm tap water instead of commercial wipes containing alcohol and pat dry. A squeeze bottle with lukewarm water can be used to avoid rubbing the delicate skin.

• Superabsorbent diapers that pull moisture away from the skin are helpful.¹ SORⒷ

• Apply barrier preparations, including zinc oxide paste, petroleum jelly, vitamin A & D ointment, or Burow solution, to affected area after each diaper change.¹ SORⒷ A 2015 study demonstrated improvement with use of a 2% magnesium cream.⁸ Pastes are better than ointments, which, in turn, are better than creams or lotions. Avoid products with fragrances or preservatives to minimize allergic potential. Apply thickly like "icing on a cake." These barrier preparations should be used on top of other indicated therapies.

• For moderate to severe inflammation, consider a nonfluorinated, low-potency topical steroid such as 1% hydrocortisone ointment (up to 3 times daily) to the affected area until the dermatitis is gone. To avoid skin erosions, atrophy, and striae, it is best to not go beyond 2 weeks of therapy with any topical steroid on a baby's bottom.

• Avoid combination antifungal–steroid agents that contain steroids stronger than hydrocortisone (e.g., Lotrisone). Potent topical steroids can cause striae and skin erosions, hypothalamus–pituitary–adrenal axis suppression, and Cushing syndrome.¹

• For Candida, use topical nonprescription antifungal creams such as clotrimazole, miconazole after every diaper change until the rash resolves. SORⒷ For concomitant oral thrush, treat with oral nystatin swish and swallow 4 times daily.

• For mild bacterial infections, use topical antibiotic ointments such as bacitracin or mupirocin after every diaper change until the rash resolves. SORⒷ

• Recommend dye-free diapers for allergic contact dermatitis. SORⒷ

SECOND LINE

• Ciclopirox 0.77% topical suspension (Loprox), a broad-spectrum agent with antifungal, antibacterial, and anti-inflammatory properties, was used safely and effectively in 1 trial of 44 children to treat diaper dermatitis caused by Candida.¹ SORⒷ

• For more severe bacterial infections, consider a broad-spectrum oral antibiotic such as amoxicillin-clavulanate. Perianal bacterial dermatitis has been reported to be predominantly caused by S. aureus.⁶ Oral cephalexin is a good choice because it covers S. aureus and group A b-hemolytic streptococcus. If methicillin-resistant S. aureus (MRSA) is suspected, consider trimethoprim-sulfamethoxazole. SORⒷ

PREVENTION AND ROUTINE SKIN CARE

• Keep the diaper region as dry and clean as possible.

• Promote the use of barrier preparations daily to maintain skin integrity.

• There is no evidence to suggest that topical vitamin A prevents diaper dermatitis.⁹ SORⒷ

• Disposable diapers—Although many individual trials show benefits, a 2006 Cochrane review found that there is not enough evidence from good-quality randomized controlled trials to support or refute the use and type of disposable diapers for the prevention of diaper dermatitis in infants.¹⁰ SORⒷ

PROGNOSIS

Diaper dermatitis has an excellent prognosis when treated as above.

FOLLOW-UP

No follow-up needed unless the rash worsens or persists. The exception is severe bacterial infection where follow-up is recommended because recurrences are common.

PATIENT (PARENT) EDUCATION

Prevention and early treatment are the best strategies. Keep the child's diaper area as clean, cool, and dry as possible with frequent diaper changes. Do not use creams that contain boric acid, camphor, phenol, methyl salicylate, compound of benzoin, or talcum powder or cornstarch. Reassure parents that, although this common condition is sometimes distressing for parents and uncomfortable for children, it is rarely dangerous.

REFERENCES