Dermatology

Aplasia Cutis Congenita (congenital skin anomaly)

Aplasia cutis congenita, 757.39 (congenital skin anomaly)

Are You Confident of the Diagnosis?

Aplasia cutis congenita (ACC) refers to any case in which there is congenital absence of skin at birth. The incidence is estimated to be between 0.5 and 1 in 10,000 newborns. It may be due to any number of causes, ranging from epidermolysis bullosa to incomplete closure of the neural tube. Ulcerations may show complete absence of all layers of the skin, even extending to the dura or bone. In utero healing can also occur, further contributing to the heterogenous appearance of ACC.

ACC was first described by Cordon in 1767 and then by Campbell in 1826. In 1986, Frieden created a classification of nine different groups of ACC based on the location and presence of other abnormalities (Table I). The scalp is involved in 86% of all solitary ACC cases and 15-20% of scalp defects may involve the underlying skull. Larger scalp defects are of more concern due to a higher risk of infection and hemorrhage. Smaller scalp lesions can heal in weeks, leaving behind an area of cicatricial alopecia (Figure 1). Most scalp lesions are single, but double and triple lesions can also occur.

Figure 1.

Healed area of ACC on the scalp. Hair does not grow due to presence of scar tissue and lack of hair follicles.

Table I.

Frieden's classification of aplasia cutis congenita
Group 1 Scalp ACC without other anomalies.
- membranous/bullous (may have underlying dysraphism and ectopic neural tissue)
- non membranous
Group 2 Scalp ACC with associated limb abnormalities (Adams-Oliver Syndrome)
Group 3 ACC with associated epidermal or organoid nevi
Group 4 ACC overlying an embryologic malformation such as a menigomyelocele, gastroschisis, or omphalocele.
Group 5 ACC with associated fetus papyraceus or placental infarct.
Group 6 ACC associated with epidermolysis bullosa.
Group 7 ACC localized to the extremities without blistering.
Group 8 ACC caused by specific teratogens.
Group 9 ACC with associated syndromes of malformation.

Characteristic features on physical examination

On the scalp, most presentations involve the vertex. Size of scalp defects may be as small as 0.5 cm or as large as 100 cm. Presentation at birth may be as varied as superficial erosion, deep ulceration, or healed scar. Some defects may have a membranous covering that can be filled with fluid, giving it a bullous appearance.

Bullous or membranous ACC of the scalp often has a hair collar (Figure 2) and has a well-rounded appearance, in contrast to nonmembranous ACC, which is usually more stellate or jagged. The hair collar has a peculiar appearance compared to the normal hair, often described as coarse or longer than the other hair (Figure 3). This suggests a dysraphism of the skull with the possible presence of ectopic neural tissue.

Figure 2.

Membranous ACC with hair collar Note also the presence of surrounding vascular stain, which raises the likelihood of ectopic neural tissue.

Figure 3.

Membranous ACC. Note the slightly darker, coarser hair surrounding the ACC.

Some authors have suggested that these cases represent a “forme fruste of a neural tube defect” as embryologic separation of both the neural and epithelial ectoderm from each other that occurs simultaneously during closure of the neural tube. This occurs during the third to fifth week of gestation. The hair collar sign, an established marker for ectopic neural tissue, has also been associated with encephaloceles, meningoceles, and heterotopic brain tissue.

Any child with nonmembranous ACC of the scalp (Figure 4) should be examined for limb defects, which occur in 84% of patients with Adams-Oliver syndrome (AOS). However, it is important to keep in mind that the limb defects can be subtle, including something as minor as an absent nail or broad fingertip.

Figure 4.

Nonmembranous ACC of the scalp. No limb defects were present.

More pronounced limb defects include brachydactyly, syndactyly, loss of terminal phalanges, or complete absence of a finger, toe, hand, foot, arm, or leg. Interdigital webs have also been reported in some cases of AOS. The limb defects are usually asymmetric with involvement of the lower limbs more commonly than the upper limbs.

Brachydactyly (shortening of the fingers or toes) is the most common limb defect in AOS. Other defects associated with AOS include cutis marmorata telangiectatica congenita [CMTC] (up to 25% of AOS patients), Central nervous system (CNS) and cardiovascular abnormalities (up to 20% of AOS patients), accessory nipples, and cleft lip.

In 1966 Bart et al described for the first time the association of ACC with epidermolysis bullosa (EB) (Figure 5) and dystrophic nails. Since that report, “Bart’s phenotype” of ACC has been seen in many different forms of EB. It is not known why ACC occurs in EB, although mechanical trauma from in utero kicking or pressure most likely leads to blistering with subsequent erosions.

Figure 5.

ACC associated with epidermolysis bullosa.

ACC has been described in association with certain medications, such as methimazole, valproic acid, and carbimazole. It has also been reported with herpes simplex virus and varicella zoster virus infection.

Isolated ACC of the extremities can also occur (Figure 6) without other anomalies.

Figure 6.

Isolated ACC of the forearm without any other anomalies.

Symmetric ACC can occur on the trunk (Figure 7).. This occurs in a twin pregnancy when there is fetal demise of one twin after the first trimester. It is hypothesized that a shift in blood flow occurs, leading to watershed areas to the skin in the living twin. The non-living twin becomes “mummified” within the placenta.

Figure 7.

ACC associated with fetus papyraceus (intrauterine fetal demise of other twin during early second trimester). This type of ACC is characterized by stellate erosions on both sides of the trunk.

Expected results of diagnostic studies

Histologic evaluation of bullous or membranous ACC reveals fibrovascular and/or edematous stroma, similar to the histopathologic appearance of encephaloceles or meningoceles. These findings further support the hypothesis that this type of ACC represents a forme fruste of a neural tube defect.

Histologic examination of nonbullous ACC of the scalp shows a layer of thin dermal collagen without overlaying epithelium or adnexal structures.

Magnetic resonance imaging (MRI) of the head is recommended in cases of bullous or membranous scalp ACC in order to evaluate for ectopic neural tissue. For larger nonmembranous scalp ACC, ultrasound can be used to check for underlying bony defects. When AOS is suspected, plain films of the extremities may be helpful to evaluate for subtle limb defects. Brain and cardiac imaging should also be performed as part of the work-up for AOS.

Diagnosis confirmation

Other things to consider in the differential of ACC include nevus sebaceous, herpes simplex virus infection, and trauma. Nevus sebaceous often has a slightly erythematous appearance at birth, mimicking a superficial erosion. Herpes infection is usually made up of grouped vesicles that can become eroded and look punched out. Birth trauma can produce erosions at the site of forceps or scalp electrodes but these should not occur over the vertex scalp, as typically occurs with ACC.

Who is at risk for Developing Aplasia Cutis Congenita?

ACC is typically sporadic but autosomal dominant and, rarely, autosomal recessive cases have been described. The incidence of ACC is estimated to be 3 in 10,000 births. When evaluating a patient with ACC it may be helpful to evaluate other family members for areas of healed ACC. On the scalp familial ACC is generally of the nonmembranous type whereas membranous ACC is usually sporadic.

ACC of the scalp has been reported in 35-50% of those affected with trisomy 13. ACC has also been reported in various ectodermal dysplasia syndromes.

In the past, ACC was thought to be due to intrauterine trauma, but there is only a history of trauma in a minority of cases. ACC has erroneously been assumed to be due to scalp electrodes or localized Staphylococcus infection.

Other factors have also been implicated in the pathogenesis of ACC including intrauterine trauma, vascular compromise, infection, and certain medications (eg, methimazole).

It is clear that ACC represents a phenotype that is due to various underlying causes or genotypes.

What is the Cause of Aplasia Cutis Congenita?

Etiology

Pathophysiology

The exact pathophysiology for ACC remains a mystery. However, various theories have been proposed, including intrauterine trauma, vascular compromise, teratogens such as infectious agents, and medications.

Some authors have suggested separating the cause of ACC into two categories: endogenous causes (developmental failure, syndromes) and exogenous causes (intrauterine trauma, infarction, and skin separation caused by rapid growth).

Membranous ACC of the scalp has been proposed to be due to incomplete closure of ectodermal fusion lines. There is often, but not always, a hair collar which suggests the presence of ectopic neural tissue.

Nonmembranous scalp ACC has been hypothesized to be due to tension-induced disruption of the skin where tensile forces are greatest during brain development. This explains why it occurs near the vertex. The defect may occur secondary to vascular disruption or biomechanical stretch.

Systemic Implications and Complications

Bullous or membranous scalp ACC should be evaluated by MRI for ectopic neural tissue.

When ACC occurs as part of AOS, evaluation for underlying central nervous system (CNS) and cardiac abnormalities should be performed.

When seen with epidermolysis bullosa, other abnormalities such as pyloric atresia or muscular dystrophy may be present.

Treatment Options

Treatment may consist of allowing the area to heal spontaneously, using conservative wound care such as twice daily petrolatum, silver sulfadiazine, or bacitracin application. Larger defects may require a bone or skin graft.

Some authors have suggested that skin grafting be done for defects greater than 3-4 cm. However, there have been reports of large skin defects with underlying absence of bone healing by secondary intention. It’s thought that in these cases, conservative treatment maintains dural induction of new bone formation and secondary closure of the cranial vault.

It is essential to assess for any associated abnormalities and refer to the appropriate specialist when indicated.

Optimal Therapeutic Approach for Aplasia Cutis Congenita

Scalp ACC

- Membranous -- MRI

- Nonmembranous -- consider ultrasound to assess for underlying skull defect, evaluate for any limb abnormalities that would support AOS; MRI is helpful in larger cases to evaluate for extent of involvement and risk of saggital sinus thrombosis

-Treatment with topical bacitracin or petrolatum 2-3 times a day until healed, consider skin and bone grafting for larger defects

AOS

-Brain and cardiac imaging

-Topical bacitracin or petrolatum 2-3 times a day until healed, consider skin and bone grafting for larger defects

Epidermolysis Bullosa

-Biopsy for electronmicroscopy or immunofluorescent mapping to determine type

-Non-stick dressings, topical antibiotics when indicated

Other cases of ACC

-Topical bacitracin or petrolatum 2-3 times a day until healed, consider skin graft in larger cases

-Consider physical therapy to prevent contractures when ACC is on the extremities

-Refer to genetics when part of a syndrome

Patient Management

After healing of the ACC, scar revision may be considered. This might be especially helpful on the scalp due to alopecia over the scar.

Unusual Clinical Scenarios to Consider in Patient Management

Some serious complications such as hemorrhage, infection, saggital sinus thrombosis, and hydrocephalus have been reported in some larger cases of scalp ACC. Skin flaps or grafts and tissue expanders may also be associated with perioperative complications, including poor regrowth of underlying bone.

Surgery may be considered in large defects due to a reported mortality risk of 20% due to meningitis or hemorrhage.

ACC has been described in certain syndromes. One of these is SCALP syndrome (Sebaceus nevus syndrome, CNS malformations, Aplasia cutis congenital, Limbal, dermoid, and Pigmented nevus). In this syndrome ACC tends to be directly adjacent or in close proximity to the nevus sebaceous.

Another condition to consider is Setleis syndrome. It is characterized by bitemporal scars resembling forceps marks, abnormalities of the eyelashes, and leonine facies.

What is the Evidence?

Starcevic, M, Sepec, MP, Zah, V. "A case of extensive aplasia cutis congenita: a conservative approach". Pediatr Dermato. 2010 Aug. pp. 1-2.

(This is a nice case report detailing a full thickness 8 × 12-cm defect of the scalp and skull that healed with closure of the skin and cranial vault using only sterile wound dressings and antibiotic ointment.)

Benjamin, LT, Trowers, AB, Schachner, LA. "Giant aplasia cutis congenita without associated anomalies". Pediatr Dermatol. vol. 21. 2004. pp. 150-3.

(This case report describes a large defect (10 × 9 cm) on the scalp with underlying absence of bone without any other anomalies.)

Martinez-Regueira, S, Vazquez-Lopez, ME, Somoza-Rubio, C, Morales-Redondo, R, Gonzalez-Gay, M. "Aplasia cutis in a defined population in from northwest Spain". Pediatr Dermatol. vol. 23. 2006. pp. 528-32.

(The authors review cases of ACC seen at their institution from 1994 to 2003. Specifically four cases of ACC were seen: three associated with epidermolysis bullosa and one case of isolated scalp ACC.)

Frieden, IJ. "Aplasia cutis congenita: a clinical review and proposal for classification". J Am Acad Dermatol. vol. 14. 1986. pp. 646-60.

(This is Ilona Frieden’s classic review in which she classifies ACC into nine different types.)

Baselga, E, Torrelo, A, Drolet, B, Zambrano, A, Alomar, A, Esterly, N. "Familial nonmembranous aplasia cutis of the scalp". Pediatr Dermatol. vol. 22. 2005. pp. 213-7.

(This is a nice review in which the authors discuss the differences between membranous and nonmembranous ACC of the scalp. They discuss six families with multiple members affected with nonmembranous ACC.)

Colon-Fontanez, F, Friedlander, SF, Newbury, R, Eichenfield, L. "Bullous aplasia cutis congenita". J Am Acad Dermatol. vol. 48. 2003. pp. S95-S98.

(The authors present a case of bullous ACC of the scalp and discuss that bullous or membranous ACC likely represent a forme fruste of a neural tube defect, based on similar histologic findings.)

Drolet, B, Prendiville, J, Golden, J, Enjolras, O, Esterly, N. "‘Membranous aplasia cutis’ with hair collars". Arch Dermatol. vol. 131. 1995. pp. 1427-31.

The authors go into great detail regarding why they believe membranous ACC to be a forme fruste of a neural tube defect.

Lam, J, Dohil, M, Eichenfield, L, Cunningham, B. "SCALP syndrome: sebaceous nevus syndrome, CNS malformations, aplasia cutis congenita, limbal dermoid, and pigmented nevus (giant congenital melanocytic nevus) with neurocutaneous melanosis: a distinct syndromic entity". J Am Acad Dermatol. vol. 58. 2008. pp. 884-888.

(The authors describe the presence of membranous ACC in SCALP syndrome.)

Drolet, BA, Clowry, L, McTigue, K, Esterly, N. "The hair collar sign: marker for cranial dysraphism". Pediatr.. vol. 96. 1995. pp. 309-13.

(The authors discuss the importance of the hair collar sign with ACC in alerting the clinician to the possibility of underlying ectopic neural tissue or CNS malformation.)The authors report four cases of ACC, three that healed with conservative treatment and one that was associated with other congenital anomalies and died 1-month after birth.

Loreti, A, Bracaglia, R, Selvaggi, G, Lahoud, P, Sturla, M, Farallo, E. "Aplasia cutis congenita: report of four cases and literature review". Eur J Plast Surg. vol. 27. 2004. pp. 114-19.

The authors report four cases of ACC, three that healed with conservative treatment and one that was associated with other congenital anomalies in which the patient died 1 month after birth.
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