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Congenital absence of skin
Clinical and laboratory studies Congenital absence of skin Donald L. Levin, M.D., Kenneth S. Nolan, M.D., and Nancy B. Esterly, M.D. Chicago and Elmhurst, IL A 5-day-old girl with congenital absence of skin, a single placental artery, and infarction of the placenta is described. These findings support a vascular etiology and provide additional evidence for a degenerative, rather than an aplastic or traumatic, origin of absent skin in the newborn. (J AM ACAD DERMATOL 2:203-206, 1980.)
Congenital absence of skin (CAS), or cutis aplasia congenita, was first reported by Cordon in 1767. 1 Since then, over 475 cases have been described. In his analysis of the world literature, Demmef found that most affected infants have a small, solitary lesion near the vertex of the scalp. Less often, other areas of the body may be involved.v" with or without associated defects. These rare lesions of trunk and limbs are often extensive and usually symrnetric.v" The etiology and pathogenesis of CAS have never been adequately explained. Recently, Mannino et aP reported two patients with CAS and fetus papyraceus and postulated that a vascular abnormality of the placenta could account for this unusual combination of events. Similarly, the female infant described in the following report had bilateral truncal CAS accompanied by scalp defects; gross and microscopic inspection of the placentademonstrated a large area of infarction. CASE REPORT A 5-day-old female infant was referred for consultation because of skin defects of the scalp and flanks (Figs. I and 2). She was the full-term product of a normal pregnancy. Labor was uncomplicated, and delivery was vaginal without forceps. No family members had similar lesions. From the Departments of Dermatology and Pediatrics, Northwestern University Medical School, Chicago, and Elmhurst Clinic, Elmhurst. Reprint requests to: Dr. Donald L. Levin, Department of Dermatology, Northwestern University Medical School, 303 E. Chicago Ave., Chicago, IL 60611.
0190-9622/801030203+04500.4010 © 1980 Am Acad Derrnatol
Physical examination revealed an active, alert female infant weighing 7 pounds, 15 ounces. Positive findings were limited to the skin, which showed a stellate scalp defect measuring 3x2.5 em just lateral to the midline at the vertex. The defect was covered with a yellowish crust, and the margins were raised and slightly erythematous. There were large linear defects with a thin membranous covering on the lateral chest walls. These extended from the axilla to below the rib cage. Pathologic examination of the placenta revealed a ax lO-cm infarct at one border. On microscopic examination, coagulation necrosis and thick-walled vessels with narrowed lumina were found. Sections of the urnbilical cord demonstrated only one artery and one vein. The lesions were initially managed conservatively by gentle cleansing and applications of Polysporin ointment with Telfa dressings. By the age of 5 months, the skin defects had healed completely by granulation from the margins. To improve her appearance, a plastic repair was then performed, with good cosmetic results. Pathologic examination of the excised tissue showed scar without evidence of epithelial appendages.
DISCUSSION
CAS is an unusual finding at birth. Clinically, it is characterized by solitary or multiple, sharply marginated, raw defects. These defects may be circular, elongate, stellate, or triangular, and of variable depth. -1 Rarely, they may extend through the subcutis to involve muscle and bone." Lesions may be ulcerated, bullous, cicatricial, or covered with a tough, translucent membrane. Most of the defects are found in the midline of the scalp near the vertex. When lesions are present on the trunk
203
Journal of the American Academy of Dermatology
204 Levin et al
Fig. 1. A. Linear defect on the right flank shortly after birth. B, Linear defect on the right flank at 5 months, showing complete healing with scar formation. C. Appearance of the right flank immediately after surgical repair.
CD Fig. 2. A. Linear defect on the left flank shortly after birth. B. Linear defect on the left flank at 5 months, showing complete healing with scar formation. C. Appearance of the left flank immediately after surgical repair.
and limbs, a bilateral symmetrical distribution is usua1. 2 Major complications of the scalp defects, particularly deep lesions involving dura and calvarium, include hernorrhage" and meningitis," which may result in death. Infection secondary to
skin loss" is the usual cause of death in CAS affecting other body sites. The overall mortality in CAS has been reported to be as high as 20%.2 With modem pediatric and neurosurgical? care, . however, survival has greatly improved. Most lesions heal uneventfully, with scarring within a few
Volume 2 Number 3 March, 1980
months." Large defects that fail to heal or produce unacceptable scars may be excised with primary closure or may be grafted, but smaller lesions usually do not require surgical intervention. Several congenital anomalies have been associated with CAS. These include trisomy 13,2.; congenital Heart disease," tracheoesophageal fistula," double cervix and uterus," congenital absence of one kidney, 10 cleft lip and cleft palate;" spastic paralysis with mental retardation;'! and cerebral malformation.F A few authors'"" have noted nail dystrophy in patients with CAS. Bart et al'" described a blistering eruption in several patients with CAS. The blisters were induced by trauma and arose on both skin and mucosal surfaces, thus resembling epidermolysis bullosa. The isolated scalp lesion of CAS may be confused with the iatrogenic defect caused by the use of a scalp electrode during labor.':' This distinction may have medical as well as legal ramifications. Several reports of CAS occurring in the same family are documented in the literature. In most kindreds, the defect appears to be transmitted in an autosomal-dominant fashion 10 , 15- 18 ; however, an autosomal-recessive mode of inheritance has been suggested by some authors.l'"?' Several theories have been proposed to explain the clinical findings in CAS. In early descriptions, mechanical trauma and pelvic exostosis" were suggested as causes of these defects, but, subsequently, the fading amniogenic theory became popular." This theory purported that adhesions formed between the amnion and the embryo as a result of inflammation of unknown origin. The adhesions were believed to cause traction on the developing skin of the fetus, resulting in a tom integument. Ingalls" attributed the defects of cutis aplasia to developmental factors. He believed that defective closure of the outermost portion of the neural tube could result in CAS, an explanation widely cited to explain the scalp defects but inadequate to account for symmetric lesions of the trunk and limbs. Alternatively, Pers'" postulated that a ring constriction formed in association with an amniotic band during the first 3 weeks of development of the embryo could account for cutis aplasia. More recently, Mannino et al" proposed a vas-
Congenital absence of skin
205
cular theory to explain the pathogenesis of CAS. They suggested that CAS of the body surfaces with or without scalp involvement might ,represent a different entity from small midline scalp defects. They reviewed 113 patients from the literature with CAS of the body and pointed out the rare familial incidence and the frequent occurrence of a monozygotic fetus papyraceus. They hypothesized that the death of one twin might cause vascular thrombosis in utero in the live twin by the passage of thromboplastic material via intertwin anastomotic placental vessels. In those infants with CAS and no fetus papyraceus, the passage of maternal thromboplastic material might cause chorionic thrombosis, resulting in infarcts in the placenta as well as in fetal organs, including skin. The combined findings of CAS, a single placental artery, and an extensive placental infarct, as noted in our patient, support the vascular theory proposed by Mannino et al'' and provide additional evidence for a degenerative, rather than an aplastic or traumatic, origin of CAS. We acknowledge the contribution of Ross Laboratories, Columbus, OH, in defraying the cost of color reproduction. REFERENCES I. Cordon M: Extrait d'une lettre au suject de trois enfants de la meme mere nes avec partie des extremites, denuee de peau. J Med Chir Pharm 26:556-557, 1767. 2. Demmel U: Clinical aspects of congenital skin defects. Eur J Pediatr 121:21-50, 1975. 3. Mannino FL, Jones KL, Benirschke K: Congenital skin defects and fetus papyraceus. J Pediatr 91:559-564, 1977. 4. Rudolph RI, Schwartz W, Leyden 11: Bitemporal aplasia cutis congenita. Arch Dermatol110:615·618, 1974. 5. Ingalls NW: Congenital defects of the scalp. Am J Obstet Gynecol 25:861-873, 1933. 6. Resnick SS, Koblenzer PJ, Pitts FW: Congenital absence of the scalp with associated vascular anomaly. Clin Pediatr 4:322-324, 1965. 7. Kosnik EJ, Sayers MP: Congenital scalp defects: Aplasia cutis congenita. J Neurosurg 42:32-36, 1975. 8. Deeken JH, Caplan RM: Aplasia cutis congenita. Arch Dermatol 102:386-389, 1970. 9. Cutlip BD, Cryan DM, Vineyard WR: Congenital scalp defects in mother and child. Am J Dis Child 113:597599, 1967. 10. Bart BJ, Gorlin RJ, Anderson VE, Lynch FW: Congenital localized absence of skin and associated abnormalities resembling epidermolysis bullosa. Arch Dcrmatol 93: 296-304, 1966. 11. Ruiz-Maldonado R, Tamayo L: Aplasia cutis congenita,
206 Levin et al
12. 13.
14.
15.
16.
spastic paralysis and mental retardation. Am J Dis Child 128:699-701, 1974. Fowler GW, Dumars KW: Cutis aplasia and cerebral malformation. Pediatrics 52:851-854, 1973. Harari Z, Pasmanik A, Dvoretzky I, Schewach-Millet M , Fisher BK: Apla sia cutis congenita with dystrophic nail changes. Dermatologica 153:363-368, 1976. Brown ZA, Jung AL, Stenchever MA: Aplasia cutis con genita and the fetal scalp electrode. Am J Obstet Gynecol 129:351-352, 1977. McMurray BR, Martin LW, Dignan PStJ , Fogelson MH: Hereditary aplasia cutis congenita and associated defects. Clin Pediatr 16:610-614, 1977 . Fisher M, Schneider R: Aplas ia cut is congenita in three successive generations. Arch Dermatol 108:252-253, 1973.
Journal of the American .Academyof Dermatology
17. Burton BK, Hauser L, Nadler HL: Congenital scalp defects with distal limb anomalies. J Mcd Genet 13:466468. 1976 . 18. Rauschkolb RR, Enriquez SI: Aplasi a cutis con genita. Arch Derrnatol 86:54-57, 1962. 19. Setlcis H, Kramer B, VaIcarcel M. Einhorn AH: Congen ital ectodermal dysplasia of the face . Pediatrics 32:540-548, 1963_ 20 . Kahn EA. Olmedo L: Congenital defects of the scalp. Plast Recon str Surg 6:435-439, 1950 . 21. Farmer AW, Maxrnen MD: Congenital absence of skin. Plast Reconstr Surg 25:291-297. 1960 . 22 . Pers M: Congenital absence of skin; Pathogenesis and relation to ring constriction . Acta Chir Scand 126:388396. 1963.
Congenital absence of skin (CAS), or cutis aplasia congenita, was first reported by Cordon in 1767. 1 Since then, over 475 cases have been described. In his analysis of the world literature, Demmef found that most affected infants have a small, solitary lesion near the vertex of the scalp. Less often, other areas of the body may be involved.v" with or without associated defects. These rare lesions of trunk and limbs are often extensive and usually symrnetric.v" The etiology and pathogenesis of CAS have never been adequately explained. Recently, Mannino et aP reported two patients with CAS and fetus papyraceus and postulated that a vascular abnormality of the placenta could account for this unusual combination of events. Similarly, the female infant described in the following report had bilateral truncal CAS accompanied by scalp defects; gross and microscopic inspection of the placentademonstrated a large area of infarction. CASE REPORT A 5-day-old female infant was referred for consultation because of skin defects of the scalp and flanks (Figs. I and 2). She was the full-term product of a normal pregnancy. Labor was uncomplicated, and delivery was vaginal without forceps. No family members had similar lesions. From the Departments of Dermatology and Pediatrics, Northwestern University Medical School, Chicago, and Elmhurst Clinic, Elmhurst. Reprint requests to: Dr. Donald L. Levin, Department of Dermatology, Northwestern University Medical School, 303 E. Chicago Ave., Chicago, IL 60611.
0190-9622/801030203+04500.4010 © 1980 Am Acad Derrnatol
Physical examination revealed an active, alert female infant weighing 7 pounds, 15 ounces. Positive findings were limited to the skin, which showed a stellate scalp defect measuring 3x2.5 em just lateral to the midline at the vertex. The defect was covered with a yellowish crust, and the margins were raised and slightly erythematous. There were large linear defects with a thin membranous covering on the lateral chest walls. These extended from the axilla to below the rib cage. Pathologic examination of the placenta revealed a ax lO-cm infarct at one border. On microscopic examination, coagulation necrosis and thick-walled vessels with narrowed lumina were found. Sections of the urnbilical cord demonstrated only one artery and one vein. The lesions were initially managed conservatively by gentle cleansing and applications of Polysporin ointment with Telfa dressings. By the age of 5 months, the skin defects had healed completely by granulation from the margins. To improve her appearance, a plastic repair was then performed, with good cosmetic results. Pathologic examination of the excised tissue showed scar without evidence of epithelial appendages.
DISCUSSION
CAS is an unusual finding at birth. Clinically, it is characterized by solitary or multiple, sharply marginated, raw defects. These defects may be circular, elongate, stellate, or triangular, and of variable depth. -1 Rarely, they may extend through the subcutis to involve muscle and bone." Lesions may be ulcerated, bullous, cicatricial, or covered with a tough, translucent membrane. Most of the defects are found in the midline of the scalp near the vertex. When lesions are present on the trunk
203
Journal of the American Academy of Dermatology
204 Levin et al
Fig. 1. A. Linear defect on the right flank shortly after birth. B, Linear defect on the right flank at 5 months, showing complete healing with scar formation. C. Appearance of the right flank immediately after surgical repair.
CD Fig. 2. A. Linear defect on the left flank shortly after birth. B. Linear defect on the left flank at 5 months, showing complete healing with scar formation. C. Appearance of the left flank immediately after surgical repair.
and limbs, a bilateral symmetrical distribution is usua1. 2 Major complications of the scalp defects, particularly deep lesions involving dura and calvarium, include hernorrhage" and meningitis," which may result in death. Infection secondary to
skin loss" is the usual cause of death in CAS affecting other body sites. The overall mortality in CAS has been reported to be as high as 20%.2 With modem pediatric and neurosurgical? care, . however, survival has greatly improved. Most lesions heal uneventfully, with scarring within a few
Volume 2 Number 3 March, 1980
months." Large defects that fail to heal or produce unacceptable scars may be excised with primary closure or may be grafted, but smaller lesions usually do not require surgical intervention. Several congenital anomalies have been associated with CAS. These include trisomy 13,2.; congenital Heart disease," tracheoesophageal fistula," double cervix and uterus," congenital absence of one kidney, 10 cleft lip and cleft palate;" spastic paralysis with mental retardation;'! and cerebral malformation.F A few authors'"" have noted nail dystrophy in patients with CAS. Bart et al'" described a blistering eruption in several patients with CAS. The blisters were induced by trauma and arose on both skin and mucosal surfaces, thus resembling epidermolysis bullosa. The isolated scalp lesion of CAS may be confused with the iatrogenic defect caused by the use of a scalp electrode during labor.':' This distinction may have medical as well as legal ramifications. Several reports of CAS occurring in the same family are documented in the literature. In most kindreds, the defect appears to be transmitted in an autosomal-dominant fashion 10 , 15- 18 ; however, an autosomal-recessive mode of inheritance has been suggested by some authors.l'"?' Several theories have been proposed to explain the clinical findings in CAS. In early descriptions, mechanical trauma and pelvic exostosis" were suggested as causes of these defects, but, subsequently, the fading amniogenic theory became popular." This theory purported that adhesions formed between the amnion and the embryo as a result of inflammation of unknown origin. The adhesions were believed to cause traction on the developing skin of the fetus, resulting in a tom integument. Ingalls" attributed the defects of cutis aplasia to developmental factors. He believed that defective closure of the outermost portion of the neural tube could result in CAS, an explanation widely cited to explain the scalp defects but inadequate to account for symmetric lesions of the trunk and limbs. Alternatively, Pers'" postulated that a ring constriction formed in association with an amniotic band during the first 3 weeks of development of the embryo could account for cutis aplasia. More recently, Mannino et al" proposed a vas-
Congenital absence of skin
205
cular theory to explain the pathogenesis of CAS. They suggested that CAS of the body surfaces with or without scalp involvement might ,represent a different entity from small midline scalp defects. They reviewed 113 patients from the literature with CAS of the body and pointed out the rare familial incidence and the frequent occurrence of a monozygotic fetus papyraceus. They hypothesized that the death of one twin might cause vascular thrombosis in utero in the live twin by the passage of thromboplastic material via intertwin anastomotic placental vessels. In those infants with CAS and no fetus papyraceus, the passage of maternal thromboplastic material might cause chorionic thrombosis, resulting in infarcts in the placenta as well as in fetal organs, including skin. The combined findings of CAS, a single placental artery, and an extensive placental infarct, as noted in our patient, support the vascular theory proposed by Mannino et al'' and provide additional evidence for a degenerative, rather than an aplastic or traumatic, origin of CAS. We acknowledge the contribution of Ross Laboratories, Columbus, OH, in defraying the cost of color reproduction. REFERENCES I. Cordon M: Extrait d'une lettre au suject de trois enfants de la meme mere nes avec partie des extremites, denuee de peau. J Med Chir Pharm 26:556-557, 1767. 2. Demmel U: Clinical aspects of congenital skin defects. Eur J Pediatr 121:21-50, 1975. 3. Mannino FL, Jones KL, Benirschke K: Congenital skin defects and fetus papyraceus. J Pediatr 91:559-564, 1977. 4. Rudolph RI, Schwartz W, Leyden 11: Bitemporal aplasia cutis congenita. Arch Dermatol110:615·618, 1974. 5. Ingalls NW: Congenital defects of the scalp. Am J Obstet Gynecol 25:861-873, 1933. 6. Resnick SS, Koblenzer PJ, Pitts FW: Congenital absence of the scalp with associated vascular anomaly. Clin Pediatr 4:322-324, 1965. 7. Kosnik EJ, Sayers MP: Congenital scalp defects: Aplasia cutis congenita. J Neurosurg 42:32-36, 1975. 8. Deeken JH, Caplan RM: Aplasia cutis congenita. Arch Dermatol 102:386-389, 1970. 9. Cutlip BD, Cryan DM, Vineyard WR: Congenital scalp defects in mother and child. Am J Dis Child 113:597599, 1967. 10. Bart BJ, Gorlin RJ, Anderson VE, Lynch FW: Congenital localized absence of skin and associated abnormalities resembling epidermolysis bullosa. Arch Dcrmatol 93: 296-304, 1966. 11. Ruiz-Maldonado R, Tamayo L: Aplasia cutis congenita,
206 Levin et al
12. 13.
14.
15.
16.
spastic paralysis and mental retardation. Am J Dis Child 128:699-701, 1974. Fowler GW, Dumars KW: Cutis aplasia and cerebral malformation. Pediatrics 52:851-854, 1973. Harari Z, Pasmanik A, Dvoretzky I, Schewach-Millet M , Fisher BK: Apla sia cutis congenita with dystrophic nail changes. Dermatologica 153:363-368, 1976. Brown ZA, Jung AL, Stenchever MA: Aplasia cutis con genita and the fetal scalp electrode. Am J Obstet Gynecol 129:351-352, 1977. McMurray BR, Martin LW, Dignan PStJ , Fogelson MH: Hereditary aplasia cutis congenita and associated defects. Clin Pediatr 16:610-614, 1977 . Fisher M, Schneider R: Aplas ia cut is congenita in three successive generations. Arch Dermatol 108:252-253, 1973.
Journal of the American .Academyof Dermatology
17. Burton BK, Hauser L, Nadler HL: Congenital scalp defects with distal limb anomalies. J Mcd Genet 13:466468. 1976 . 18. Rauschkolb RR, Enriquez SI: Aplasi a cutis con genita. Arch Derrnatol 86:54-57, 1962. 19. Setlcis H, Kramer B, VaIcarcel M. Einhorn AH: Congen ital ectodermal dysplasia of the face . Pediatrics 32:540-548, 1963_ 20 . Kahn EA. Olmedo L: Congenital defects of the scalp. Plast Recon str Surg 6:435-439, 1950 . 21. Farmer AW, Maxrnen MD: Congenital absence of skin. Plast Reconstr Surg 25:291-297. 1960 . 22 . Pers M: Congenital absence of skin; Pathogenesis and relation to ring constriction . Acta Chir Scand 126:388396. 1963.