Neonatal Dermatoses

The following conditions are covered in this rotation guide:

• Erythema Toxicum Neonatorum

• Transient Neonatal Pustular Melanosis

• Candidiasis

• Neonatal Systemic Lupus Erythematosus

• Langerhans’-Cell Histiocytosis

• Seborrheic Dermatitis

Infantile acne and neonatal cephalic pustulosis are covered in the Neonatal Acne section in this rotation guide.

Erythema Toxicum Neonatorum

Erythema toxicum neonatorum is one of the most common neonatal skin eruptions. The estimated incidence is between 40% and 70%. It is more common in term infants and generally presents in the first week of life.

Presentation: This transient eruption presents with irregularly shaped erythematous macules with superimposed papules or pustules. The term “flea-bitten” has been used to describe the appearance. Individual lesions can last for up to one week and new lesions can develop over the course of several weeks.

Diagnosis: The diagnosis of erythema toxicum neonatorum is made clinically. However, microscopic examination of pustular contents will show eosinophils with Gram, Wright, or Giemsa stains. This is a self-limited condition that does not require treatment.

Transient Neonatal Pustular Melanosis

Presentation: Transient neonatal pustular melanosis is a benign rash that is more common in infants with skin of color. This eruption is distinguished by the presence of multiple superficial sterile pustules that rupture easily and leave behind a collarette of scale and hyperpigmented macules. The hyperpigmentation can last weeks to months. Areas of involvement include the face, neck, trunk, palms, and soles. When examined under the microscope, the pustular contents of these lesions show neutrophils.

Differential diagnosis of neonatal vesiculopustular eruptions includes the following:

• erythema toxicum neonatorum

• neonatal cephalic pustulosis

• transient neonatal pustular melanosis

• herpes simplex virus

• candida infection

• bullous impetigo

• syphilis

• eosinophilic pustular folliculitis

• miliaria

• acropustulosis of infancy

• scabies

Candidiasis

Two broad categories of candida infections occur in the neonatal period: congenital and neonatal candidiasis.

Congenital candidiasis: Congenital candidiasis is acquired in utero and presents at birth or immediately thereafter. Congenital cutaneous candidiasis presents as a diffuse eruption of macules, papules, and pustules. Involvement of the palms and soles is one diagnostic clue, as are nail changes (e.g., yellow discoloration). The diagnosis can be confirmed with skin scraping demonstrating spores and pseudohyphae or with fungal culture. In low birth weight or premature infants, congenital candidiasis presents with systemic infection with or without a desquamative rash. Risk factors for congenital candidiasis include uterine foreign bodies (e.g., intrauterine device) or cervical cerclage. Congenital candidiasis is a life-threatening infection that requires prompt treatment with systemic antifungals.

Thin erythematous finely scaly patches with satellite maculopapules, mainly on the exposed areas. (Source: Congenital Cutaneous Candidiasis. Case Reports 2016.)

Neonatal candidiasis is acquired during birth via passage through an infected birth canal. It has multiple clinical presentations that usually develop in the first weeks of life.

• Oral candidiasis (thrush):

  • Thrush is candida infection of the tongue, buccal mucosa, palate, and gingiva.

  • It presents with thick, white or grey plaques overlying an erythematous mucosal surface.

  • Unlike milk residue, these infectious plaques cannot be easily scraped off.

  • Nystatin suspension is the treatment of choice.
    

• Candidal intertrigo:

  • Candidal intertrigo presents as inflammation of the skin folds that can become superinfected with candida.

  • The presence of satellite papules or pustules, similar to candidal diaper dermatitis, is a clue to the diagnosis.

  • Culture can help determine etiologic an agent.

  • Treatment is with topical antifungal creams.

Neonatal Systemic Lupus Erythematosus

Neonatal lupus is caused by transplacental transfer of maternal anti-Ro (SSA) or anti-La (SSB) antibodies. One fourth of the mothers of affected infants are asymptomatic prior to delivery.

Clinical features:

• cutaneous lesions

  • photosensitivity

  • annular or polycyclic eruption

  • rash involving the head, scalp, trunk, or extremities

• internal involvement

  • elevated liver enzymes

  • cholestasis

  • hepatomegaly

• atrioventricular (mostly complete) heart block

• hematologic manifestations

  • anemia

  • neutropenia

  • thrombocytopenia
    

Clinical course: Cutaneous sequelae of neonatal lupus are generally managed expectantly. Sun protection is advised given the risk of photosensitivity. The skin findings generally remit within months when maternal antibodies disappear from the infant bloodstream. Fewer than 5% of infants with neonatal lupus will develop systemic lupus erythematosus later in life.

Treatment: If neonatal lupus is suspected, the patient, mother, or both should be checked for anti-Ro and anti-La antibodies. Electrocardiogram should be obtained to screen for heart block. Complete blood count (CBC) and hepatic function should also be checked.

A baby boy had a bright-red rash over his face within 2 hours after birth (Panel A). He also had clinical features consistent with trisomy 21, which was confirmed by karyotyping. The initial laboratory tests showed a hemoglobin level of 14 g per deciliter and a platelet count of 24,000 per cubic millimeter. At 4 weeks of age, the rash was reduced (Panel B). By the time the patient was 6 months old, the rash had resolved without specific therapy (Panel C). (Source: Neonatal Lupus. N Engl J Med 2014.)

Langerhans’-Cell Histiocytosis

Langerhans’-cell histiocytosis (LCH) refers to a group of disorders characterized by accumulation of dendritic-derived histiocytes in different organ systems, including the skin, bone, lungs, and pituitary gland. The clinical presentation is variable, ranging from isolated skin lesions to fulminant multisystem disease.

Classification: Historic categories used to classify LCH based on clinical phenotypes such as Hand-Schüller-Christian disease, Letterer-Siwe disease, and Hashimoto-Pritzker disease have been abandoned due to the recognition that not all cases fit into these categories. The current classification system uses LCH as an umbrella term and then describes the involvement of single or multiple organ systems, the degree of each organ’s involvement, and involvement of a “risk” organ. Risk organs include the liver, spleen, and bone marrow and are distinguished because involvement of these organ systems is suggestive of a poorer prognosis. ”Congenital self-healing Langerhans’-cell histiocytosis” (previously referred to as congenital self-healing reticulohistiocytosis) is a rare type characterized by cutaneous lesions present at birth or in the neonatal period, without systemic involvement.

There was debate as to whether LCH was an inflammatory or neoplastic process until genomic technology led to the discovery of somatic activating mutations in the MAPK pathway to support the neoplastic hypothesis.

The annual incidence of LCH is 4.6 cases per one million children younger than 15 years. Approximately 25% of patients have skin involvement.

Presentation: In infants, the presentation and clinical course of LCH is highly variable. The classic presentation is pink-to-brown papules and petechiae in a seborrheic distribution and inguinal creases. Some patients have skin-limited disease whereas others have progressive systemic disease. A retrospective review of 19 cases of LCH in the neonatal period described multiple cutaneous manifestations, including:

• vesicles, pustules

• seborrheic dermatitis-like eruption

• mucosal lesions (erosions, petechiae)

• erythematous papules

• nodular, ulcerative lesions

• petechiae
  

In this case series, the morphologic characteristics of cutaneous findings did not correlate with or predict the extent of systemic involvement. Some signs and symptoms of systemic involvement may include bone pain, polyuria and polydipsia, weight loss, and lymphadenopathy.

(Source: Langerhans Cell Histiocytosis Presenting as a Blueberry Muffin Rash. Lancet 2017.)

Various skin manifestations of LCH (Source: Langerhans-Cell Histiocytosis. N Engl J Med 2018.)

Differential diagnosis:

• seborrheic dermatitis

• psoriasis

• benign cephalic histiocytosis

• scabies

• atopic dermatitis

• diaper dermatitis
  

Recommended evaluation and workup:

• history and physical

• skin biopsy

• complete blood count (CBC)

• coagulation studies

• lactate dehydrogenase (LDH)

• comprehensive metabolic panel

• erythrocyte sedimentation rate (ESR)

• urine osmolality

• uric acid

• immunoglobulins

• chest radiograph

• skeletal survey

• abdominal ultrasound
  

Treatment: Patients with skin-limited disease have favorable outcomes and can be treated with topical glucocorticoids. The standard treatment for multifocal LCH remains conventional chemotherapy. Clinical trials are currently ongoing to determine the best regimen and treatment duration. The use of specific MAPK-inhibitors has not been well studied in children.

Patients need to be monitored, even after resolution of skin lesions, given the variable course for the development of disease sequelae or recurrence. All patients should undergo periodic history and physical exams and be considered for screening labs including CBC, ESR, liver enzymes, and albumin. More-specific monitoring guidelines for patients with systemic disease have been delineated by experts in this field.

Seborrheic Dermatitis

Seborrheic areas contain high concentrations of sebaceous glands and include the scalp, face, postauricular skin, and skin folds. Seborrheic dermatitis presents with scaly erythema in these areas. This condition is more common in both infants and adolescents and is thought to be related to overgrowth of and inflammatory reaction to the yeast Malassezia furfur. Many affected infants have isolated scalp disease, termed “cradle cap.” Seborrheic dermatitis should also be considered in the differential diagnosis of diaper dermatitis.

Greasy yellow scales on the scalp of a young infant. (Source: Baby With Cradle Cap. WikipediaCommons. Accessed September 2019.)

Generally, cradle cap is a self-limited condition that resolves by age 12 to 18 months. Seborrheic dermatitis in the form of dandruff is common in older children and adults.

Treatment: If treatment for infantile seborrheic dermatitis is desired, the scale from cradle cap can be removed with gentle shampooing with a soft brush. Massaged oil can also help with mechanical debridement. If persistent, shampoo containing ketoconazole or zine pyrithione can be used. Safety data regarding the use of selenium sulfide in infants is not robust, and salicylic acid products should be avoided because of concern for systemic absorption. In conjunction with topical antifungals, seborrheic dermatitis on the skin can additionally be treated with mild topical glucocorticoids, particularly in patients with erythema or pruritus.