NeoQuest November 2022: Neonate with Large Congenital Skin Lesion on Trunk

A term male monochorionic, diamniotic twin born via an uncomplicated vaginal delivery has a stellate skin defect localized to the chest, axilla, and upper abdomen, which is noted at the time of birth (Figure 1). The pregnancy was complicated by fetal demise of the twin at 14 weeks’ gestation.        

Figure 1. The following skin lesions were present at the time of birth. A–B) Well-demarcated stellate skin lesions were noted on the left and right side of the infant's torso. C) No skin abnormalities were noted on the back. Images from: Lucena M, Zauk A. Large skin lesion and bilious emesis in a premature newborn. Neoreviews. 2022;23(11):e782–787¹

Which of the following clinical features is most likely associated with the diagnosis seen in this infant?

1. Delayed tooth eruption
2. Encephalitis
3. Intestinal atresia
4. Lack of lingual papillae
5. Telangiectasias

Answer: C. Intestinal atresia

Explanation:

Given the history of the intrauterine demise of the twin at 14 weeks’ gestational age, the symmetric stellate lesions on the chest, axilla, and upper abdomen are consistent with aplasia cutis congenita (ACC) with fetus papyraceus (FP). ACC is a rare congenital condition in which there is a partial or complete absence of skin, with or without involvement of deeper structures (eg, subcutaneous tissue, bone, and dura mater).^2,3 ACC with FP is a rare subtype of ACC typically seen in the surviving twin of multiple gestation pregnancies that are complicated by a fetal demise early in gestation.^2,3 It is characterized by a distinct area that lacks skin layers, manifesting as translucent ulcerated membranes distributed in a symmetric butterfly pattern on the trunk (Figure 1).^2,3

The exact pathogenesis for ACC with FP is unclear but is most likely secondary to an ischemic event related to the in-utero death of a twin.³ Ischemia can occur via two proposed mechanisms: exsanguination and/or activation of the coagulation cascade through shared vascular communications between the twins.³ Exsanguination in the surviving twin can occur after the dying fetus experiences severe hypotension, leading to a drastic shift in blood flow from the surviving twin to the dying twin.³ This acute episode of hypovolemia can result in a disruption in the vascular supply to the skin in the surviving twin, ultimately presenting as truncal ACC.³ The other theorized pathogenesis of ACC with FP is inappropriate activation of the coagulation cascade secondary to the transfer of thrombogenic material from the demised twin.³ This pathologic process can lead to placental infarction, inadequate perfusion to “watershed” regions (eg, skin over the trunk), and congenital absence of skin over these focal areas.³ Because monochorionic twin pregnancies are commonly complicated by placental anastomoses, they are highly susceptible to altered hemodynamics and/or thrombotic events associated with a single fetal demise.³ Consequently, approximately 90% of neonates born with ACC with FP are a product of monochorionic twin gestation as demonstrated in the clinical case described above.³ Not only does the vascular compromise seen in ACC with FP interfere with normal skin growth in utero, but it can also cause a disruption in other organ and tissue development, resulting in congenital abnormalities such as intestinal atresia (OPTION C).^4,5

It is crucial to differentiate ACC with FP from other congenital skin abnormalities that manifest with ulcerations or scars.³ The unique clinical history and presentation of ACC with FP help differentiate it from other ACC subtypes and congenital skin conditions.^2,3 In contrast to ACC with FP, incontinentia pigmenti, an X-linked dominant disorder that is typically lethal in males prior to birth, presents within the first few weeks after birth as erythematous blisters distributed along the lines of Blaschko (Figure 2).⁶ These lesions evolve into hyperkeratotic verrucous papules followed by hyperpigmented streaks or whorls during the neonatal and infant period.⁶ Along with skin lesions, infants with incontinentia pigmenti can have dental abnormalities (eg, delayed tooth eruption) (OPTION A), as well as hair, nail, neurologic, and ophthalmologic anomalies.⁶

Figure 2. Maculopapular lesions that follow a Blaschko linear distribution in a neonate with incontinentia pigmenti. Image from: Somalika P, Jain A, Chopra A, Singh A. Case 2: a newborn with a changing rash. Neoreviews. 2019;20(12):e740–e743

Although neonates with herpes simplex virus (HSV) infection acquired during delivery have classic vesiculopustular lesions, the cutaneous manifestations can vary and include ulcerations, bullae, and lesions resembling ACC.^7,8 In contrast to ACC with FP, herpetic lesions are rarely present at the time of delivery and do not have a symmetric stellate distribution localized to the trunk.^8,9 Neonates with congenital HSV infection can have multiorgan involvement and encephalitis (OPTION B).^7,8

Like ACC with FP, epidermolysis bullosa (EB), which is a group of inherited blistering disorders, can manifest as areas of fragile skin, blisters, and ulcerations.⁹ EB can be clinically distinguished from ACC with FP by the presence of multiple lesions spread diffusely over the body, generation of new lesions over time due to local trauma or friction, other ectodermal anomalies (eg, nail dystrophy), and identification of subepidermal blisters due to cleavage at a specific skin layer visualized on skin biopsy.⁹ The lack of lingual papillae at birth (Figure 3) (OPTION D) can be a subtle physical exam finding associated with dystrophic EB, a subtype of EB, which should trigger an urgent diagnostic evaluation.⁹

Figure 3. Absence of lingual papillae in a neonate with dystrophic EB. Image from: Lucky A, Whalen J, Rowe S, Marathe K, Gorell E. Diagnosis and care of the newborn with epidermolysis bullosa. Neoreviews. 2021;22(7):e438–e451

Similar to incontinentia pigmenti, focal dermal hypoplasia is an X-linked dominant multi-system disorder that includes specific skin abnormalities (eg, congenital patchy skin aplasia and skin hypo- or hyperpigmentation) that follow a Blaschko linear distribution.¹⁰ This distribution is not consistent with the pattern of the skin defect typically seen in individuals with ACC with FP (Figure 1). Although not present at birth, telangiectasias (OPTION E) can develop with age and are seen in approximately 80% of patients with focal dermal hypoplasia.¹⁰

Did you know?

• Antepartum diagnosis of fetus papyraceus, a flattened mummified fetus, can occur via ultrasound but is infrequent due to diagnostic imaging difficulties or lack of prenatal care.¹¹
• If a newborn demonstrates clinical features of ACC with FP at birth, routine placental examination and pathology are critical in identifying a retained mummified fetus or fetal parts located adjacent to the surviving infant’s placenta. This information immediately after birth can lead to timely clinical diagnosis and management of ACC with FP.¹¹

What syndromes or genetic disorders are associated with ACC?

To find the answer, please read the following article:

• Tollefson M. Aplasia cutis congenita. Neoreviews. 2012;13(5):e285–e292

NeoQuest November Authors
Neena Jube-Desai, MD, University of Maryland
Shanmukha Mukthapuram, MD, Cincinnati Children’s Hospital Medical Center

References:

1. Lucena M, Zauk A. Large skin lesion and bilious emesis in a premature newborn. Neoreviews. 2022;23(11):e782–787. 10.1542/neo.23-11-e782-e787
2. Tollefson M. Aplasia cutis congenita. Neoreviews. 2012;13(5):e285–e292
3. Humphrey SR, Hu X, Adamson K, Schaus A, Jensen JN, Drolet B. A practical approach to the evaluation and treatment of an infant with aplasia cutis congenita. J Perinatol. 2018;38(2):110–117
4. Schierz IAM, Giuffrè M, Del Vecchio A, Antona V, Corsello G, Piro E. Recognizable neonatal clinical features of aplasia cutis congenita. Ital J Pediatr. 2020;46(1):25
5. Sobczak A, Tomasik T, Zając A, Klasa B, Kruczek P, Kwinta P. New features of aplasia cutis congenita type 5 - Skin atrophy associated with respiratory insufficiency and multiple intestinal atresia caused by the early death of twin fetus. Pediatr Neonatol. 2019;60(4):473-474
6. Somalika P, Jain A, Chopra A, Singh A. Case 2: a newborn with a changing rash. Neoreviews. 2019;20(12):e740–e743
7. Wambach J, Morley S. Skin ulcerations in a preterm newborn. Neoreviews. 2009;10(11): e575–e578
8. Koch LH, Fisher RG, Chen C, Foster MM, Bass WT, Williams JV. Congenital herpes simplex virus infection: two unique cutaneous presentations associated with probable intrauterine transmission. J Am Acad Dermatol. 2009;60(2):312–315
9. Lucky A, Whalen J, Rowe S, Marathe K, Gorell E. Diagnosis and care of the newborn with epidermolysis bullosa. Neoreviews. 2021;22(7):e438–e451
10. Bostwick B, Van den Veyver IB, Sutton VR. Focal dermal hypoplasia. In: Adam MP, Everman DB, Mirzaa GM, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; May 15, 2008
11. Matovelo D, Ndaboine E. Fetus papyraceus causing dystocia in a rural setting: a case report. J Med Case Rep. 2015;9:178