ACC constitutes a heterogeneous group of congenital defects characterized by the localized absence of skin. The first case was described by Cordon in 1767 [4]. The most frequent form of presentation is sporadic. Hereditary forms have also been described, including autosomal dominant forms with low penetrance and autosomal recessive forms [5].
Extracranial involvement is rare but has been described in the literature, especially on the trunk and upper extremities [6]. The clinical presentation in such cases is highly varied, and its evolution is intimately linked to the aetiology of the defect and to point pregnancy when it occurs [7]. Different studies have observed clear differences in the mode of foetal healing when the wound occurs during the first two trimesters of pregnancy compared to the third trimester. Before 24 weeks of gestation, the foetus is able to perform regenerative healing without fibrous scar formation. In the last stage of pregnancy, the process is similar to that during extrauterine life and is generally associated with more adverse effects [8].
At present, the exact mechanism that causes the characteristic absence of skin in ACC is not yet known. Theories have been proposed regarding the clinical presentation of lesions and the obstetric history. Classically, 5 different theories have been proposed: foetus-foetus transfusion, vascularization and coagulation disorders, amniotic membrane adhesions, biomechanical alterations, and external teratogenic agents [9].
Abnormalities in placental vascularization, thrombosis/placental infarction, and changes in circulatory dynamics are postulated as the main theories in cases of ACC associated with a foetus papyraceous (type V of the Frieden classification). The clinical presentation tends to be bilateral and symmetrical, with predominant involvement of the trunk and a stellate appearance of the lesions [10, 11]. The history of a deceased foetus during the first trimester of pregnancy is present in case 1 and constitutes the main aetiological hypothesis in this case. The observed lesions are also consistent with this ACC subtype. Metformin and insulin, drugs that the patient’s mother took during pregnancy, have not been associated with significant teratogenesis, and their role as an aetiological factor is rejected.
In case 2, the position of the foetal head on the control ultrasound (a tendency towards extension) would justify the decubitus of the nose against the uterine walls, which would condition not only the loss of substance but the deviation of the associated columella. These biomechanical alterations would justify the appearance of the lesion in this specific area but cannot rule out the presence of adhesions to the amniotic membrane that would explain the disruption of the skin.
Cases 3 and 4 showed lesions of the extremities that are examples of ACC type VII according to the Frieden classification. However, both cases show deep skin involvement, with eschar-like lesions affecting deep tissues. In addition, the patients presented distal atrophy of the affected limbs and some movement restrictions, which led to a consideration of nerve involvement. This type of lesion has been described in the literature as CVICS, a syndrome characterized by muscle necrosis and nerve paralysis secondary to an increase in intracompartment pressure [12, 13].
The difference between CVICS and ACC is not clear, so much that some authors have proposed that ACC subtype VII includes lesions described as ischaemic contractures. In reality, the distinction is rather conceptual: ACC constitutes a clinical diagnosis, while CVICS describes the pathophysiological mechanism [12].
In most cases of CVICS described in the literature, the lesions tend to be located in the upper limbs [14, 15]; however, it can also affect the lower limbs. In the third patient in our series, premature membrane rupture with associated severe oligohydramnios, as well as an alteration in the normal position of the foetus, was a risk factor associated with an increase in intracompartment pressure [14, 16]. In addition, the location of the lesion at the level of the head of the fibula is a risk factor in itself, since it is an area with little soft tissue coverage and therefore increased vulnerability to pressure. Similarly, the scarcity of amniotic fluid conditions a state of foetal immobility that predisposes patients to lower bone mineralization, which favours stress fractures [17].
In this specific case, the antecedent of an invasive antenatal procedure was also considered a possible cause of the injury. However, this does not seem like a very plausible explanation, since, in addition to the fact that the procedure was performed without entering the amniotic cavity, the characteristics of the wound, including the complete absence of scarring at birth, suggest prolonged aggravation over time rather than development late in pregnancy.
Regarding the patient in case 2, lesions related to the CVICS have been described more frequently in the volar aspect of the upper limb, with variable extension. At birth, the ulcers did not present the characteristic yellowing of lesions caused by increased intracompartment pressure; however, hypotrophy of the arm was clear, as was nerve paralysis. A careful examination of the affected limb showed that the intrauterine lesion had been more extensive but that some of the skin had already healed. Although there was no clear evidence, the authors postulated that the lesion could have occurred early in pregnancy and that most of the skin regeneration had occurred in utero.
The differential diagnosis of the latter cases included entities such as neonatal gangrene, necrotizing fasciitis or congenital varicella. However, the Doppler study of the extremities did not show vascular involvement, and the maternal history did not suggest a congenital infection. The absence of blisters ruled out an association with epidermolysis bullosa. In case 4, an important differential diagnosis to take into account would be amniotic band syndrome; however, in this pathology, it is common to find other associated defects in the affected limb due to the effect of constrictive bands. In addition, expression of the lesions as ulcers is infrequent; instead, they usually manifest as deep circumferential depressions [12].
Regarding wound healing, it is important to take into account the regenerative capacity during the early neonatal period, during which there is less production of fibrous scar tissue than in later stages [18]. This fact makes conservative treatment the first choice, since in our experience, the generated scar will be well-formed and will not be associated with limitations in function. Similarly, when the extremities are, we believe that it is of utmost importance to initiate rehabilitation treatment early. The effects of increased intracompartment pressure are not limited to the skin but can include muscle hypotrophy, ligamentous contracture and nerve paralysis that would benefit from early musculoskeletal stimulation.
The limitations of the study lie in its retrospective nature and the fact that the case series was limited to a single centre. In addition, to complete the aetiological diagnosis, it would have been useful to have pathological studies showing the degree and type of skin involvement. However, few cases with these characteristics are presented in the literature, and therefore, it is important to contribute to the study of this condition by detailing the experience at each centre.