Report

Aplasia cutis congenita: report of 22 cases Hela Mesrati, MD, Meriem Amouri, MD, Hend Chaaben, MD, Abdelrahmen Masmoudi, PH, Sonia Boudaya, PH, and Hamida Turki, PH

Department of Dermatology, Hedi Chaker Hospital, Sfax, Tunisia Correspondence Hela Mesrati, MD El Ain route km 1 Sfax 3029 Tunisia E-mail: [email protected] Conflicts of interest: None.

Abstract Background Aplasia cutis congenita (ACC) is a rare malformation characterized by absent or scarred areas of skin at birth. Although most commonly found on the scalp, ACC can also involve other locations. Its etiology and pathogenesis remain unclear. Objective To describe the epidemiologic, clinical, therapeutic, and evolutionary aspects of ACC through a hospital series. Methods We conducted a retrospective study from 1995 to 2012 and reported all cases of ACC. Results We enrolled 22 cases (14 girls and eight boys) of ACC during 18 years. The mean age at diagnosis was 5.7 years. Sixteen ACC involved the scalp, five the trunk, and one the left buttock. ACC was oval-shaped in 20 cases, triangular in one case, and linear in one case. The mean size was 4 cm. ACC was associated with bone defects in two cases, various malformations in eight (37.1%), and with syndromic malformation in three (Adams–Olivier syndrome: two cases; Goltz syndrome: one case). Conservative treatment consisting of wound dressing with vaseline was indicated in six cases. Bone reconstruction was performed in two cases. Regular follow-up and no treatment was recommended in 14 cases. Conclusion Our study emphasizes the frequent association of ACC with malformations (37.1%) and bone defects (9%).

Introduction

Results

Aplasia cutis congenita (ACC) is a rare congenital malformation of the skin characterized by a localized absence of skin. It may involve the epidermis, dermis, and/or subcutaneous fat.1 Only a few series are reported1,2 but none from a dermatology department. The scalp is commonly affected, but other sites can be involved. Despite many pathogenesis theories, the etiology of ACC is still incompletely known.2 Treatment is usually controversial. It may be conservative for small lesions or surgical for larger defects of skin and/or underlying bone.1

We enrolled 22 patients with ACC among 17,356 new consultants during 18 years (Table 1). This gives 0.01% incidence of ACC. There were 14 girls and eight boys (male to female ratio: 0.5). The age of our patients varied between one day and 35 years (mean 5.7 years). There were seven newborns (32%; aged between 1 and 20 d), nine infants (41%; between 1 month and 2 years), four children (18%; between 4 and 16 years), and two adults (9%; between 19 and 35 years old). There was neither family history of similar abnormalities nor maternal drug abuse or toxic substance ingestion during pregnancy. None of our newborns descended from a twin pregnancy. Respectively, at birth and on the moment of diagnosis, ACC presented as a scarred area (68 and 77%), fibrinous area (14 and 9%), or skin defect (14 and 14%). The clinical aspect was unspecified at birth in 4% of all cases. Aplasia cutis congenita involved the scalp in 16 cases (73%) (Fig. 1), the trunk in five cases, and the left buttock in one case (Fig. 2). It was oval-shaped in 20 cases,

Material and methods We collected all cases of ACC during a period of 18 years (1995–2012) by conducting a retrospective study in the Department of Dermatology, Hedi Chaker Hospital (Sfax, Tunisia). We studied the epidemiologic, clinical, therapeutic, 1370

and evolutionary aspects in these cases. Paraclinical investigations, if performed, were studied. International Journal of Dermatology 2015, 54, 1370–1375

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Table 1 Clinical characteristics of our patients with aplasia cutis congenita

Case 1 2 3 4 5 6 7 8 9 10

Age 5d 1y 1 mo 1 3 2 4 7 13 35

mo mo y y d y y

Sex

Clinical aspect 1 At birth 2 At the moment of diagnostic

Size (cm)

M F F

1 & 2 fibrinous area 1 & 2 cicatricial area 1 & 2 cicatricial area

9/5 2/1 7/2

F F M F F M F

5/4 1/0.5 3/2 10 6/4 2/1 8/4

11

1d

F

1 & 2 skin defect 1 & 2 cicatricial area 1 cicatricial area 1 & 2 cicatricial area 1 & 2 fibrinous area 1 & 2 cicatricial area 1 fibrinous area 2 cicatricial area 1 & 2 skin defect

12 13

12 d 3 mo

F F

1 & 2 cicatricial area 1 & 2 scarred area

2/1 2/1

14

20 d

F

1 & 2 cicatricial area

2/1

15

1y

M

1 & 2 cicatricial area

2/1

16 17

19 y 10 y

M M

3/2 1.5/1

18 19 20

5d 16 y 45 d

F M F

1 & 2 scarred area 1 unspecified 2 cicatricial area 1 & 2 skin defect 1 & 2 cicatricial area 1 & 2 cicatricial area

10/8 2/1 4/1

21

3d

F

1 & 2 cicatricial area

2.5

22

2y

M

1 & 2 cicatricial area

3/2

4/1

Location

Shape

Treatment

Outcome

Vertex Vertex Frontal region Vertex Vertex Vertex Vertex Vertex Vertex Vertex

Oval Oval Oval

Wound dressing None None

Unspecified Cicatricial alopecia Unspecified

Oval Oval Oval Oval Oval Oval Oval

Wound dressing None None None Wound dressing None Wound dressing

Cicatricial Cicatricial Cicatricial Cicatricial Cicatricial Cicatricial Cicatricial

Left buttock Sternum Sternum

Linear

Good healing with persistent cutaneous fistula Atrophic plaque Atrophic plaque

Lumbar region Lumbar region Vertex Gluteal region Vertex Vertex Frontal region Parietal region Vertex

Oval

Wound dressing. At 2 y, ilium reconstruction None Bone reconstruction of the sternum None

Triangular

None

Atrophic plaque

Oval Oval

None None

Scarred area Atrophic plaque

Oval Oval Oval

Wound dressing None None

Alopecia Alopecia Alopecia

Oval

None

Alopecia

Oval

None

Alopecia

Oval Oval

alopecia alopecia alopecia alopecia alopecia alopecia alopecia

Atrophic plaque

d, day(s); F, female; M, male; mo, month(s); y, year(s).

and triangular or linear each in one case. The mean size was 4 cm (1–10 cm). Aplasia cutis congenita was associated with bone defects in two cases (9%). It concerned the sternum or ilium, with each area in one case (Fig. 3). Various malformations were notified in eight cases (37.1%) (Table 2). Aplasia cutis congenita was included in Adams–Olivier syndrome in two cases and Goltz syndrome in one case. Radiological investigations were performed in 14 patients (63.7%). Standard radiography showed underlying bone defects of the sternum (case 11) and ilium (case 13) or agenesis of the phalanges in two cases (cases 8 and 18). A transfontanellar ultrasound performed in four patients was normal (cases 1, 2, 13, 18). Cardiac and abdominopelvic ultrasonographies performed in case 12 were also normal. Brain or spinal magnetic resonance imaging (MRI) was performed in seven patients (31%). Brain MRI was normal in four cases (cases 7, 10, 14, ª 2015 The International Society of Dermatology

18). Spinal MRI (three patients) showed a low spinal cord in two cases (cases 14 and 17) and was normal in case 11. We dressed ACC with Vaseline in six cases of small ACC. Bone reconstruction was performed in two cases. For the remaining cases, we recommended no treatment and regular follow-up. No complications such as hemorrhage or infection were reported. ACC of the scalp, healed with a scarring alopecia, occurred in 14 cases (Fig. 4). In two cases of low spinal cord, we referred our patients to a neurosurgeon. Clinical characteristics of our 22 patients are summarized in Table 1. Discussion The first cases of ACC were reported by Cordon in 1767 on the lower limb and Campbell in 1826 on the scalp (discussed by Maillet-Declerck et al.1). Since then, more International Journal of Dermatology 2015, 54, 1370–1375

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Figure 3 Patient 12: aplasia cutis congenita near to sternum (at age of 12 d)

Figure 1 Patient 18: aplasia cutis congenita of the scalp (at

5 d)

Figure 4 Patient 9: Cicatricial alopecia of the scalp (at 13

years)

Figure 2 Patient 11: skin defects on left buttock (at birth)

than 500 cases of varying severity but very few series have been reported.1,2 As expected, ACC is rare (0.01% in our study). To the best of our knowledge, there is no other series from our dermatology department. Over a period of more than 35 years, Maillet-Declerck et al.1 treated 29 cases of ACC of the scalp in their surgical department. This gives a much lower incidence than in our study. ACC affects girls more commonly than boys (two times more in our series).3 Most cases of ACC are located on the scalp (73–80% in our study). Only few cases of ACC are reported elsewhere.4 Lesions can be multiple, but ACC usually presents as a solitary lesion (100% in our study).5 International Journal of Dermatology 2015, 54, 1370–1375

Clinically, it may be an area of ulceration, membranous lesion, or atrophic scar.3,4,6 Extension through dermis, galea, and bone occur in 35% of cases (9% of our patients).6,7 The majority of ACC are diagnosed and addressed in the newborn period. This rule did not fit our series nor in that of Maillet-Declerck et al.1 Aplasia cutis congenita is typically sporadic. However, autosomal dominance and rarely autosomal recessive inheritance have been suggested.8 Thus all family members should be carefully examined for variable penetrance of the condition and its associations. In such cases, genetic counseling should be pursued. In our study, family history was negative for similar abnormalities. Many theories have been postulated to explain the occurrence of ACC; however, neither the pathogenesis ª 2015 The International Society of Dermatology

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Table 2 Malformations congenita

associated

with

Abnormality

Number of cases (%)

Hemangioma

4 (18.1)

Terminal phalanges hypoplasia Spinal dysraphism Deviation of the gluteal furrow Cutaneous fistula Mental retardation Mongolian spot Asymmetrical face, Cleft lip, Syndactyly Lobster-claw deformity of the left foot

2 (9) 2 (9) 3 (13.6) 1 1 1 1

aplasia

cutis

Patient nos 11: lumbar region, 13:upper lip 14:lumbar region 21: vulvar region 8, 18 14, 17 11, 14, 17 11 9 11 21

nor the etiology has been clarified yet.2 ACC has been attributed to many abnormalities such as focal pressure necrosis,2,7 neural tube defects,9 paucity or impaired vascular development in the cranial vertex,9 incomplete healing and fusion of the mesoderm,9 ischemic or thrombotic episodes,2,9,10 teratogen drugs (methimazole and carbimazole),11 and congenital infections (herpes simplex virus and varicella-zona virus).2 None of these factors has been reported in our patients. In 1986, Frieden conducted a clinical review and proposed a classification of ACC (Table 3), which divided it into nine groups according to the location and pattern of skin absence, causes, associated anomalies, and the type of inheritance.12 In our study, most cases of ACC (14 Table 3 Classification of ACC according to Frieden Type I Type II Type III Type IV Type V Type VI Type VII Type VIII Type IX

Report

patients) were defined as group I of this classification (ACC of the scalp without multiple abnormalities). Aplasia cutis congenita of the trunk has been seen in association with fetus papyraceus, presumably due to vascular occlusion by clots caused by the death of a twin in utero. This type V ACC has a distinctive and reproducible distribution pattern of bilateral symmetrical truncal, buttock, or thigh lesions.12 In our study, ACC of the trunk (sternum and buttock) does not fit this group. In these cases, ACC were asymmetrical with underlying bone defect (two cases) and with no history of fetus papyraceus. Aplasia cutis congenita may also be associated with the Adams–Oliver syndrome, Bart syndrome, trisomy 13 (Pataus syndrome), Wolf–Hirschhorn syndrome, Goltz syndrome, and Johanson–Blizzard syndrome. In their series of 29 cases, Maillet-Declerck et al.1 reported two ACC with Adams–Oliver syndrome and one with lethal trisomy 13. Adams–Oliver syndrome, diagnosed in two of our patients (group II of Frieden’s classification), is a rare congenital abnormality characterized by ACC and variable degrees of terminal transverse limb defects.13 Unlike our study, lower limbs were more affected than upper ones. Involvement included brachydactyly, syndactyly, agenesis of fingernails or toenails, loss of the terminal phalanges (100% of our cases of Adams–Oliver syndrome), or even more severe defects such as the complete absence of a finger, toe, hand, foot, or the entire limb.13 Other associated anomalies include cutis marmorata, dilated scalp veins, brain abnormalities, and cardiovascular malformations. In Goltz syndrome (one patient in our study), abnormalities involved the three tissue layers: ectoderm (skin, eyes), mesoderm (bones, teeth), and endoderm (various mucosas).14 Cutaneous manifestations included ACC, sparse hair, linear atrophy, papillomas, and palmoplantar hyperkeratoses. Skeletal anomalies include lobster-claw

12

ACC of the scalp without multiple abnormalities and with an autosomal dominant or sporadic inheritance ACC of the scalp with associated limb reduction abnormalities and an autosomal dominant inheritance ACC of the scalp with associated epidermal and organoid nevi, associated with corneal opacities and psychomotor retardation. The inheritance is sporadic ACC overlying embryologic malformations such as meningomyeloceles, spinal dysraphia, or leptomeningeal angiomatosis. This ACC affects any site, mostly the scalp and abdomen ACC associated with fetus papyraceus or placental infarcts. Affects any site, mostly symmetrical and linear ACC associated with epidermolysis bullosa, usually on the extremities. The inheritance depends on the type of epidermolysis bullosa ACC localized to the extremities without blistering and without associated abnormalities. This group affects mostly pretibial areas and the dorsal aspects of the hands and feet. The inheritance is autosomal dominant or recessive ACC caused by specific teratogens such as varicella or herpes simplex infections or in association with methimazole. This ACC appears mostly in the scalp region ACC associated with malformation syndromes such as trisomy 13 or ectodermal dysplasia

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deformity, hypoplasia, syndactyly, and facial asymmetry.14 They were all noticed in our patient (case 21) who would be classified as group IX of Friedens classification.12 A large number of isolated abnormalities have been described in patients with ACC, including ear malformations, colobomas, glaucoma, cleft lip and palate, absence of the nasal septum, choanal atresia, laryngomalacia, congenital heart diseases, umbilical hernia, renal anomalies, cryptorchidism, ambiguous genitalia, and distal limb anomalies.15,16 Aplasia cutis congenita may overlie overt or occult embryologic malformations such us myelomeningocele, porencephaly, spinal dysraphism, gastroschisis, and omphalocele.16 In our study, we present two cases of spinal dysraphism who presented with ACC on their backs (lumbar region). They were neurologically intact and did not undergo surgery. These two patients had group IV ACC according to the Frieden classification.12 Aplasia cutis congenita can be detected in prenatal ultrasonography examination. After birth, diagnosis of ACC is mainly clinical.17 Standard radiographs, cerebral and abdominal ultrasonography, echocardiography, and chromosome analysis must be performed to look for associated anomalies.18 Differential diagnosis includes atretic cephalocele, sinus pericranii, and heterotopic scalp tissues.9 Fetal MRI might be helpful in clarifying the diagnosis in these cases. No prenatal or MRI diagnosis was performed in our study. The treatment for ACC is controversial. Small areas of ACC usually heal, leaving atrophic plaques (six cases) or cicatricial alopecia in ACC of vertex (14 cases).19 Treatment is based on either conservative methods or surgery. Local wound care (six of our patients) is recommended for small lesions of