Dermatologic Therapy, Vol. 26, 2013, 439–444 Printed in the United States · All rights reserved
© 2013 Wiley Periodicals, Inc.
DERMATOLOGIC THERAPY ISSN 1396-0296
INVITED ARTICLE
Aplasia cutis congenita: approach to evaluation and management John C. Browning The University of Texas Health Science Center at San Antonio, San Antonio, Texas
ABSTRACT: Aplasia cutis congenita (ACC) refers to any condition in which there is absence of skin at birth. This can be isolated ACC occurring on the scalp, with or without underlying ectopic neural tissue, or ACC can be associated with other conditions such as Adams–Oliver syndrome or epidermolysis bullosa. We discuss the different types of ACC and associated anomalies along with an approach to diagnosis and management. KEYWORDS: Adams–Oliver syndrome, aplasia cutis congenita
Introduction
Pathophysiology and evaluation
Aplasia cutis congenita (ACC) literally means congenital absence of skin at birth. It occurs most commonly on the scalp but can also affect any part of the body. Incidence of ACC is estimated to be between 0.5 and 1 in 10,000 newborns. ACC can be due to any number of causes, ranging from familial cases, epidermolysis bullosa (EB), and incomplete closure of the neural tube. At birth, ulcerations can be shallow or deep with complete absence of all layers of the skin, in some cases, extending to the dura or bone. In other cases, a healed scar might be the only finding due to in utero healing. The heterogeneous appearance of ACC makes understanding of the pathophysiology crucial in the diagnosis and management of these patients.
ACC was first described in 1767 by Cordon and then by Campbell in 1826 (1). Frieden, in 1986, created a classification of nine different groups of ACC based on the location and presence of other abnormalities (Table 1) (2). Although over 20 years have passed since then, Frieden’s classification system remains the standard for understanding ACC. The exact pathophysiology for ACC remains a mystery. However, various theories have been proposed including intrauterine trauma, vascular compromise, 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 (3). 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
Address correspondence and reprint requests to: John C. Browning, MD, FAAD, FAAP, Chief, Pediatric Dermatology, Assistant Professor of Pediatrics and Dermatology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MSC 7808, San Antonio, TX 78229, or email: [email protected]
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Table 1. Subtypes of ACC Group 1 Scalp ACC with other anomalies 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 meningomyelocele, 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
FIG. 1. Healed nonmembranous aplasia cutis congenita of the scalp with residual scar. Note jagged edge on the right.
ACC, aplasia cutis congenital.
the skin where tensile forces are greatest during brain development. This explains why it occurs near the vertex. The defect may be secondary to vascular disruption or biomechanical stretch (3). 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 (3). Solitary ACC is the most common presentation and 86% of all solitary ACC cases involve the scalp (2); 15–20% of scalp defects can involve the underlying skull (4) (FIG. 1). Larger scalp defects are more concerning due to a higher risk of infection and hemorrhage, particularly because of proximity to the dura or meninges. Smaller scalp lesions can heal in weeks, leaving behind an area of cicatricial alopecia (4) (FIG. 2). Occasionally, double and triple scalp lesions can also occur. ACC of the scalp has been reported in 35–50% of those affected with trisomy 13 (2). ACC has also been reported in various ectodermal dysplasia syndromes. On the scalp, the vertex is the most common site for presentation of ACC. Scalp defects can be as small as 0.5 cm or as large as 100 cm (2). As discussed earlier, presentation of scalp ACC at birth can be as varied as superficial erosion, deep ulceration, or healed scar. Some defects can have a membranous covering that can be filled with fluid, giving it a bullous appearance. Sometimes, the
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FIG. 2. Healed nonmembranous aplasia cutis congenita of the scalp, hidden by surrounding hair.
bullous fluid can be bloody, giving it a red or black appearance. Bullous or membranous ACC of the scalp often has a hair collar 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 with the normal hair, often described as coarse as or longer than the normal hair. In some cases, the hair collar can be subtle. The presence of a hair collar suggests dysraphism of the skull with the possible presence of ectopic neural tissue. Some authors have suggested that these cases represent a “forme fruste of a neural tube defect” (5,6) as embryologic separation of both the neural and the epithelial ectoderm from each other occurs simultaneously during closure of the neural tube. This occurs during the third to fifth week of gestation. The hair collar sign,
Aplasia cutis
an established marker for ectopic neural tissue, has also been associated with encephaloceles, meningoceles, and heterotopic brain tissue (7). Magnetic resonance imaging of the head is recommended in cases of midline bullous or membranous scalp ACC in order to evaluate for ectopic neural tissue (7). For larger nonmembranous scalp ACC, ultrasound can be used to check for underlying bony defects. Any child with nonmembranous ACC of the scalp should be examined for limb defects, which occur in 84% of patients with Adams–Oliver syndrome (AOS). AOS is a rare congenital disorder characterized by nonmembranous ACC of the vertex scalp, limb defects, and often cutis marmorata telangiectatica congenita (CMTC). It was first described by Adams and Oliver in 1945 (8). It is important to keep in mind that the limb defects in AOS can be subtle, including something as minor as an absent nail or broad fingertip (9). 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 the 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 (9). Plain films of the extremities may be helpful if there is a question about limb involvement. Other defects associated with AOS include CMTC (up to 25% of AOS patients), central nervous system (CNS) and cardiovascular abnormalities, accessory nipples, and cleft lip. Other reported anomalies include growth retardation, ACC of the knee, short palpebral fissures, dilated scalp veins, skin tags, hemangioma, undescended testes, wooly hair, microphthalmia, and hypoplastic optic nerve (10,11). Not all patients with AOS have ACC of the scalp, but it is present approximately 75% of the time. As in other cases of ACC, scalp defects can be mild or severe, in some cases even having underlying skull thinning or complete absence of the calvarium. Ultrasound is helpful in evaluating the extent of skull involvement. In 64% of AOS patients with ACC, an underlying skull defect is found (9). Skull defects may also occur, less commonly, without overlying ACC, and physical examination and ultrasound would be helpful in diagnosing these cases. When both ACC and limb defects are present, a diagnosis of AOS can confidently be made. Evaluation of the cardiovascular, CNS, gastrointestinal,
and genitourinary systems should then be performed. Referral to an appropriate specialist is indicated so that the correct studies can be ordered. AOS is thought to have an autosomal dominant mode of inheritance with variable expression, but sporadic and autosomal recessive cases have been described as well (10). The sporadic cases may appear sporadic due to incomplete penetrance. No gene has been found. Referral to a genetics specialist can also be helpful in providing counseling for familial cases. When a family history is present, ultrasound detection of a limb defect around 16 weeks gestation has been proposed as a mechanism for prenatal diagnosis. The exact pathogenesis of AOS is unknown, but vascular impairment in utero has been proposed as a possible mechanism. Cranial vertex and limb abnormalities support the hypothesis of impaired circulation in watershed areas during development. Other support for in utero vascular thrombotic accidents includes reports of AOS with dilated scalp veins, constriction rings, pulmonary hypertension, periventricular leukomalacia, and retinal folds. Another proposed mechanism for AOS includes abnormal pericyte recruitment, supported by a mouse model in which ALK1-deficient mice show poor migration, recruitment, and proliferation of pericytes. The pericyte is essential for the development of small vessels, and altered pericytes could lead to impaired blood to the skin, underlying skull, heart, and distal extremities (12). Because of the wide spectrum of anomalies in AOS, another hypothesis is that a gene mutation leads to aberrant morphogenesis. This may be due to a defect in angiogenesis or another morphogenic process. One recent theory proposes that a mutation in a bone morphogenetic protein is the underlying cause for AOS (12). Other theories have included impairment of intrauterine vascular development, adherence to fetal membranes, intrauterine trauma or compression, intrauterine herpetic infection, or drug exposure. Multiple genes have been studied for underlying mutations in AOS but no causative gene has been found. When present, CNS involvement may include spasticity, diffuse slow electroencephalogram activity, cerebral calcification, polymicrogyria, microcephaly, epilepsy, mental retardation, arrhinencephaly, hydrocephaly, and Dandy Walker malformation (10,13). Congenital heart defects have been reported in approximately 20% of AOS patients. Findings may
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include membranous subaortic stenosis, aortic stenosis, parachute mitral valve, ventricular septal defect, atrial septal defect, tetralogy of Fallot, coarctation of the aorta, bicuspid aortic valve, pulmonic stenosis, double outlet right ventricle, and pulmonary hypertension (14–17). When limb abnormalities are mild, then often no treatment is needed. When more severe, consultation with an orthopedic surgeon may be helpful. Mild cases of ACC and limb defects do not require ongoing treatment. If present, CNS or cardiac anomalies may necessitate ongoing care. In 1966, Bart et al. described for the first time the association of ACC with EB and dystrophic nails. Since that report, “Bart’s phenotype” of ACC has been seen in many different forms of EB (2). 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. When seen with EB, other abnormalities such as pyloric atresia or muscular dystrophy may be present (FIG. 3). ACC has also been commonly seen with fetus papyraceus. This occurs in a twin pregnancy when fetal demise of one twin happens during the late first or early second trimester. Fetus papyraceus results from mummification of the dead fetus. Earlier fetal demise would result in complete resorption, whereas later demise would require removal of the fetus, usually by dilatation and curettage. Acute hypovolemia of the healthy twin occurs due to massive shifts in placental vascular pressure and resistance with loss of the other twin. This leads to ischemia of the skin in symmetric watershed areas (FIG. 4). Occasionally, bowel atresias and cerebral infarction occur (18).
FIG. 3. Aplasia
cutis congenita associated with epidermolysis bullosa. (Photo courtesy of Dr. Moise Levy.)
442
ACC has been described in association with certain medications such as methimazole, valproic acid, and carbimazole (19). It has also been reported with herpes simplex virus and varicella zoster virus infection (19). ACC has been described in certain syndromes. One of these is SCALP syndrome (sebaceous nevus syndrome, CNS malformations, ACC, limbal, dermoid, and pigmented nevus). In this syndrome, ACC tends to be directly adjacent or in close proximity to the nevus sebaceous (20). Another condition to consider is the Setleis syndrome. It is characterized by bitemporal scars resembling forceps marks, abnormalities of the eyelashes, and leonine facies. Table 2 provides a summary of the evaluation and management of ACC.
Histology Histologic evaluation of bullous or membranous ACC reveals fibrovascular and/or edematous stroma (19), 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 overlying epithelium or adnexal structures (8).
Differential diagnosis Other things to consider in the differential of ACC include nevus sebaceous, herpes simplex virus
FIG. 4. Aplasia cutis congenita of the trunk in a surviving twin, associated with fetus papyraceus.
Aplasia cutis
Table 2. Evaluation and management of ACC Scalp ACC • Membranous: MRI • Nonmembranous: consider ultrasound to assess for underlying skull defect, evaluate for any limb abnormalities that would support AOS • Treatment: topical bacitracin or petrolatum two to three times a day until healed, consider skin and bone grafting for larger defects AOS • Brain and cardiac imaging • Topical bacitracin or petrolatum two to three times a day until healed, consider skin and bone grafting for larger defects Epidermolysis bullosa • Biopsy for electron microscopy or immunofluorescent mapping to determine type • Nonstick dressings, topical antibiotics when indicated Other cases of ACC • Topical bacitracin or petrolatum two to three 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 ACC, aplasia cutis congenital; AOS, Adams–Oliver syndrome; MRI, magnetic resonance imaging.
infection, and trauma. Nevus sebaceous often has a slightly erythematous appearance at birth, mimicking 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. 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 staphylococcal infection.
Treatment ACC of the scalp should be allowed to heal by secondary intention, when possible (21). As the child’s hair grows, the ACC scar can be concealed. Treatment consists of allowing the area to heal spontaneously using conservative wound care such as twice daily petrolatum, silver sulfadiazine, or bacitracin application. It is this author’s opinion that petrolatum is the best choice because of the low risk of contact allergy or systemic absorption. Larger defects may require a bone or skin graft. Some authors have suggested that skin grafting
be performed 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 (1). It is thought that in these cases conservative treatment maintains dural induction of new bone formation and secondary closure of the cranial vault. As discussed earlier, it is crucial to look for any associated abnormalities and refer to the appropriate specialist when indicated.
Ongoing 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 (1). Some serious complications, such as hemorrhage, infection, sagittal sinus thrombosis, and hydrocephalus, have been reported in some larger cases of scalp ACC (1). Skin flaps or grafts and tissue expanders may also be associated with perioperative complications including poor regrowth of underlying bone (1). Surgery may be considered in large defects due to a reported mortality risk of 20% due to meningitis or hemorrhage (4).
Conclusion It is clear that ACC represents a phenotype that is due to various underlying causes or genotypes. It is important to be aware of the different causes and presentations of ACC so that appropriate evaluation and management can be performed.
References 1. Starcevic M, Sepec MP, Zah V. A case of extensive aplasia cutis congenita: a conservative approach. Pediatr Dermatol 2010: 27 (5): 540–542. 2. Frieden IJ. Aplasia cutis congenita: a clinical review and proposal for classification. J Am Acad Dermatol 1986: 14 (4): 646–660. 3. Baselga E, Torrelo A, Drolet B, Zambrano A, Alomar A, Esterly N. Familial nonmenbranous aplasia cutis of the scalp. Pediatr Dermatol 2005: 22 (3): 213–217. 4. Benjamin LT, Trowers AB, Schachner LA. Giant aplasia cutis congenita without associated anomalies. Pediatr Dermatol 2004: 21 (2): 150–153. 5. Colon-Fontanez F, Friedlander SF, Newbury R, Eichenfield L. Bullous aplasia cutis congenita. J Am Acad Dermatol 2003: 48 (5): S95–S98. 6. Drolet B, Prendiville J, Golden J, Enjolras O, Esterly N. “Membranous aplasia cutis” with hair collars. Arch Dermatol 1995: 131: 1427–1431.
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Browning 7. Drolet BA, Clowry L, McTigue K, Esterly N. The hair collar sign: marker for cranial dysraphism. Pediatrics 1995: 96 (2): 309–313. 8. Seo JK, Kang JH, Lee HJ, Lee D, Sung HS, Hwang SW. A case of Adams-Oliver syndrome. Ann Dermatol. 2010: 22 (1): 96–98. 9. Narang T, Kanwar AJ, Dogra S. Adams-Oliver syndrome: a sporadic occurrence with minimal disease expression. Pediatr Dermatol 2008: 25 (1): 115–116. 10. Anandan V, Parveen B, Prabhavathy D, Priyavarthini V. Adams Oliver syndrome – a variant. Int J Dermatol 2008: 47 (12): 1260–1262. 11. Rajabian MH, Aghaei S. Adams-Oliver syndrome and isolated aplasia cutis congenita in two siblings. Dermatol Online J 2006: 12 (6): 17. 12. Baskar S, Kulkarni ML, Kulkarni AM, Vittalrao S, Kulkarni PM. Adams-Oliver syndrome: additions to the clinical features and possible role of BMP pathway. Am J Med Genet A 2009: 149A (8): 1678–1684. 13. Romaní J, Puig L, Aznar G, Demestre X, Altirriba O, Alomar A. Adams-Oliver syndrome with unusual central nervous system alterations. Pediatr Dermatol 1998: 15 (1): 48–50. 14. Dadzie OE, Tyszczuk L, Holder SE, Teixeira F, Charakida A, Scarisbrick J, Chu A. Adams-Oliver syndrome with widespread CMTC and fatal pulmonary vascular disease. Pediatr Dermatol 2007: 24 (6): 651–653.
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15. Heras Mulero C, Bartralot Soler R, Rodríguez-Cano L, et al. Aplasia cutis associated with coarctation of the aorta: could this be an incomplete form of Adams-Oliver syndrome? Br J Dermatol 2007: 157 (4): 836–837. 16. Sankhyan N, Kaushal RK, Jaswal RS. Adams-Oliver syndrome: a case with complete expression. J Dermatol 2006: 33 (6): 435–436. 17. Lin AE, Westgate MN, van der Velde ME, Lacro RV, Holmes LB. Adams-Oliver syndrome associated with cardiovascular malformations. Clin Dysmorphol 1998: 7 (4): 235–241. 18. Klein RQ, Robinson DM, Lieber CD, Antaya RJ. Symmetruc aplasia cutis congénita associated with fetus papyraceus: report of two cases. Pediatr Dermatol 2011: 28 (4): 467–469. 19. 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 2006: 23 (6): 528–532. 20. 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 2008: 58 (5): 884–888. 21. 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 2004: 27: 114–119.
© 2013 Wiley Periodicals, Inc.
DERMATOLOGIC THERAPY ISSN 1396-0296
INVITED ARTICLE
Aplasia cutis congenita: approach to evaluation and management John C. Browning The University of Texas Health Science Center at San Antonio, San Antonio, Texas
ABSTRACT: Aplasia cutis congenita (ACC) refers to any condition in which there is absence of skin at birth. This can be isolated ACC occurring on the scalp, with or without underlying ectopic neural tissue, or ACC can be associated with other conditions such as Adams–Oliver syndrome or epidermolysis bullosa. We discuss the different types of ACC and associated anomalies along with an approach to diagnosis and management. KEYWORDS: Adams–Oliver syndrome, aplasia cutis congenita
Introduction
Pathophysiology and evaluation
Aplasia cutis congenita (ACC) literally means congenital absence of skin at birth. It occurs most commonly on the scalp but can also affect any part of the body. Incidence of ACC is estimated to be between 0.5 and 1 in 10,000 newborns. ACC can be due to any number of causes, ranging from familial cases, epidermolysis bullosa (EB), and incomplete closure of the neural tube. At birth, ulcerations can be shallow or deep with complete absence of all layers of the skin, in some cases, extending to the dura or bone. In other cases, a healed scar might be the only finding due to in utero healing. The heterogeneous appearance of ACC makes understanding of the pathophysiology crucial in the diagnosis and management of these patients.
ACC was first described in 1767 by Cordon and then by Campbell in 1826 (1). Frieden, in 1986, created a classification of nine different groups of ACC based on the location and presence of other abnormalities (Table 1) (2). Although over 20 years have passed since then, Frieden’s classification system remains the standard for understanding ACC. The exact pathophysiology for ACC remains a mystery. However, various theories have been proposed including intrauterine trauma, vascular compromise, 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 (3). 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
Address correspondence and reprint requests to: John C. Browning, MD, FAAD, FAAP, Chief, Pediatric Dermatology, Assistant Professor of Pediatrics and Dermatology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MSC 7808, San Antonio, TX 78229, or email: [email protected]
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Table 1. Subtypes of ACC Group 1 Scalp ACC with other anomalies 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 meningomyelocele, 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
FIG. 1. Healed nonmembranous aplasia cutis congenita of the scalp with residual scar. Note jagged edge on the right.
ACC, aplasia cutis congenital.
the skin where tensile forces are greatest during brain development. This explains why it occurs near the vertex. The defect may be secondary to vascular disruption or biomechanical stretch (3). 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 (3). Solitary ACC is the most common presentation and 86% of all solitary ACC cases involve the scalp (2); 15–20% of scalp defects can involve the underlying skull (4) (FIG. 1). Larger scalp defects are more concerning due to a higher risk of infection and hemorrhage, particularly because of proximity to the dura or meninges. Smaller scalp lesions can heal in weeks, leaving behind an area of cicatricial alopecia (4) (FIG. 2). Occasionally, double and triple scalp lesions can also occur. ACC of the scalp has been reported in 35–50% of those affected with trisomy 13 (2). ACC has also been reported in various ectodermal dysplasia syndromes. On the scalp, the vertex is the most common site for presentation of ACC. Scalp defects can be as small as 0.5 cm or as large as 100 cm (2). As discussed earlier, presentation of scalp ACC at birth can be as varied as superficial erosion, deep ulceration, or healed scar. Some defects can have a membranous covering that can be filled with fluid, giving it a bullous appearance. Sometimes, the
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FIG. 2. Healed nonmembranous aplasia cutis congenita of the scalp, hidden by surrounding hair.
bullous fluid can be bloody, giving it a red or black appearance. Bullous or membranous ACC of the scalp often has a hair collar 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 with the normal hair, often described as coarse as or longer than the normal hair. In some cases, the hair collar can be subtle. The presence of a hair collar suggests dysraphism of the skull with the possible presence of ectopic neural tissue. Some authors have suggested that these cases represent a “forme fruste of a neural tube defect” (5,6) as embryologic separation of both the neural and the epithelial ectoderm from each other occurs simultaneously during closure of the neural tube. This occurs during the third to fifth week of gestation. The hair collar sign,
Aplasia cutis
an established marker for ectopic neural tissue, has also been associated with encephaloceles, meningoceles, and heterotopic brain tissue (7). Magnetic resonance imaging of the head is recommended in cases of midline bullous or membranous scalp ACC in order to evaluate for ectopic neural tissue (7). For larger nonmembranous scalp ACC, ultrasound can be used to check for underlying bony defects. Any child with nonmembranous ACC of the scalp should be examined for limb defects, which occur in 84% of patients with Adams–Oliver syndrome (AOS). AOS is a rare congenital disorder characterized by nonmembranous ACC of the vertex scalp, limb defects, and often cutis marmorata telangiectatica congenita (CMTC). It was first described by Adams and Oliver in 1945 (8). It is important to keep in mind that the limb defects in AOS can be subtle, including something as minor as an absent nail or broad fingertip (9). 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 the 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 (9). Plain films of the extremities may be helpful if there is a question about limb involvement. Other defects associated with AOS include CMTC (up to 25% of AOS patients), central nervous system (CNS) and cardiovascular abnormalities, accessory nipples, and cleft lip. Other reported anomalies include growth retardation, ACC of the knee, short palpebral fissures, dilated scalp veins, skin tags, hemangioma, undescended testes, wooly hair, microphthalmia, and hypoplastic optic nerve (10,11). Not all patients with AOS have ACC of the scalp, but it is present approximately 75% of the time. As in other cases of ACC, scalp defects can be mild or severe, in some cases even having underlying skull thinning or complete absence of the calvarium. Ultrasound is helpful in evaluating the extent of skull involvement. In 64% of AOS patients with ACC, an underlying skull defect is found (9). Skull defects may also occur, less commonly, without overlying ACC, and physical examination and ultrasound would be helpful in diagnosing these cases. When both ACC and limb defects are present, a diagnosis of AOS can confidently be made. Evaluation of the cardiovascular, CNS, gastrointestinal,
and genitourinary systems should then be performed. Referral to an appropriate specialist is indicated so that the correct studies can be ordered. AOS is thought to have an autosomal dominant mode of inheritance with variable expression, but sporadic and autosomal recessive cases have been described as well (10). The sporadic cases may appear sporadic due to incomplete penetrance. No gene has been found. Referral to a genetics specialist can also be helpful in providing counseling for familial cases. When a family history is present, ultrasound detection of a limb defect around 16 weeks gestation has been proposed as a mechanism for prenatal diagnosis. The exact pathogenesis of AOS is unknown, but vascular impairment in utero has been proposed as a possible mechanism. Cranial vertex and limb abnormalities support the hypothesis of impaired circulation in watershed areas during development. Other support for in utero vascular thrombotic accidents includes reports of AOS with dilated scalp veins, constriction rings, pulmonary hypertension, periventricular leukomalacia, and retinal folds. Another proposed mechanism for AOS includes abnormal pericyte recruitment, supported by a mouse model in which ALK1-deficient mice show poor migration, recruitment, and proliferation of pericytes. The pericyte is essential for the development of small vessels, and altered pericytes could lead to impaired blood to the skin, underlying skull, heart, and distal extremities (12). Because of the wide spectrum of anomalies in AOS, another hypothesis is that a gene mutation leads to aberrant morphogenesis. This may be due to a defect in angiogenesis or another morphogenic process. One recent theory proposes that a mutation in a bone morphogenetic protein is the underlying cause for AOS (12). Other theories have included impairment of intrauterine vascular development, adherence to fetal membranes, intrauterine trauma or compression, intrauterine herpetic infection, or drug exposure. Multiple genes have been studied for underlying mutations in AOS but no causative gene has been found. When present, CNS involvement may include spasticity, diffuse slow electroencephalogram activity, cerebral calcification, polymicrogyria, microcephaly, epilepsy, mental retardation, arrhinencephaly, hydrocephaly, and Dandy Walker malformation (10,13). Congenital heart defects have been reported in approximately 20% of AOS patients. Findings may
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include membranous subaortic stenosis, aortic stenosis, parachute mitral valve, ventricular septal defect, atrial septal defect, tetralogy of Fallot, coarctation of the aorta, bicuspid aortic valve, pulmonic stenosis, double outlet right ventricle, and pulmonary hypertension (14–17). When limb abnormalities are mild, then often no treatment is needed. When more severe, consultation with an orthopedic surgeon may be helpful. Mild cases of ACC and limb defects do not require ongoing treatment. If present, CNS or cardiac anomalies may necessitate ongoing care. In 1966, Bart et al. described for the first time the association of ACC with EB and dystrophic nails. Since that report, “Bart’s phenotype” of ACC has been seen in many different forms of EB (2). 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. When seen with EB, other abnormalities such as pyloric atresia or muscular dystrophy may be present (FIG. 3). ACC has also been commonly seen with fetus papyraceus. This occurs in a twin pregnancy when fetal demise of one twin happens during the late first or early second trimester. Fetus papyraceus results from mummification of the dead fetus. Earlier fetal demise would result in complete resorption, whereas later demise would require removal of the fetus, usually by dilatation and curettage. Acute hypovolemia of the healthy twin occurs due to massive shifts in placental vascular pressure and resistance with loss of the other twin. This leads to ischemia of the skin in symmetric watershed areas (FIG. 4). Occasionally, bowel atresias and cerebral infarction occur (18).
FIG. 3. Aplasia
cutis congenita associated with epidermolysis bullosa. (Photo courtesy of Dr. Moise Levy.)
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ACC has been described in association with certain medications such as methimazole, valproic acid, and carbimazole (19). It has also been reported with herpes simplex virus and varicella zoster virus infection (19). ACC has been described in certain syndromes. One of these is SCALP syndrome (sebaceous nevus syndrome, CNS malformations, ACC, limbal, dermoid, and pigmented nevus). In this syndrome, ACC tends to be directly adjacent or in close proximity to the nevus sebaceous (20). Another condition to consider is the Setleis syndrome. It is characterized by bitemporal scars resembling forceps marks, abnormalities of the eyelashes, and leonine facies. Table 2 provides a summary of the evaluation and management of ACC.
Histology Histologic evaluation of bullous or membranous ACC reveals fibrovascular and/or edematous stroma (19), 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 overlying epithelium or adnexal structures (8).
Differential diagnosis Other things to consider in the differential of ACC include nevus sebaceous, herpes simplex virus
FIG. 4. Aplasia cutis congenita of the trunk in a surviving twin, associated with fetus papyraceus.
Aplasia cutis
Table 2. Evaluation and management of ACC Scalp ACC • Membranous: MRI • Nonmembranous: consider ultrasound to assess for underlying skull defect, evaluate for any limb abnormalities that would support AOS • Treatment: topical bacitracin or petrolatum two to three times a day until healed, consider skin and bone grafting for larger defects AOS • Brain and cardiac imaging • Topical bacitracin or petrolatum two to three times a day until healed, consider skin and bone grafting for larger defects Epidermolysis bullosa • Biopsy for electron microscopy or immunofluorescent mapping to determine type • Nonstick dressings, topical antibiotics when indicated Other cases of ACC • Topical bacitracin or petrolatum two to three 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 ACC, aplasia cutis congenital; AOS, Adams–Oliver syndrome; MRI, magnetic resonance imaging.
infection, and trauma. Nevus sebaceous often has a slightly erythematous appearance at birth, mimicking 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. 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 staphylococcal infection.
Treatment ACC of the scalp should be allowed to heal by secondary intention, when possible (21). As the child’s hair grows, the ACC scar can be concealed. Treatment consists of allowing the area to heal spontaneously using conservative wound care such as twice daily petrolatum, silver sulfadiazine, or bacitracin application. It is this author’s opinion that petrolatum is the best choice because of the low risk of contact allergy or systemic absorption. Larger defects may require a bone or skin graft. Some authors have suggested that skin grafting
be performed 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 (1). It is thought that in these cases conservative treatment maintains dural induction of new bone formation and secondary closure of the cranial vault. As discussed earlier, it is crucial to look for any associated abnormalities and refer to the appropriate specialist when indicated.
Ongoing 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 (1). Some serious complications, such as hemorrhage, infection, sagittal sinus thrombosis, and hydrocephalus, have been reported in some larger cases of scalp ACC (1). Skin flaps or grafts and tissue expanders may also be associated with perioperative complications including poor regrowth of underlying bone (1). Surgery may be considered in large defects due to a reported mortality risk of 20% due to meningitis or hemorrhage (4).
Conclusion It is clear that ACC represents a phenotype that is due to various underlying causes or genotypes. It is important to be aware of the different causes and presentations of ACC so that appropriate evaluation and management can be performed.
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