Case report of self-improving collodion ichthyosis in the newborn

Abstract

Self-improving collodion ichthyosis (SICI) is a relatively rare subtype of autosomal recessive congenital ichthyosis (ARCI) that is often characterized by a collodion baby (CB) phenotype at birth. A newborn girl, just 1 hour old, presented with taut, shiny, thick yellow crusts, like parchment, and scales on her trunk and upper limbs. The tightening effect had caused both upper eyelids to appear everted, and her lips and auricles were deformed. Based on whole-exome sequencing and examination of the clinical phenotype, the patient was diagnosed with ARCI. After admission, the exposed mucosa was covered with a sterile Vaseline gauze dressing, and she was placed in an incubator set to a temperature of 32°C with a humidity level of 75%. One week later, the parchment-like scales had begun to flake off, and at the age of 3 weeks, all bodily skin appeared normal. SICI was diagnosed. After discharge, the patient was followed up to 3 months of age, at which time her growth and development were comparable to those of her peers. Clinicians should consider SICI as a possible diagnosis when analyzing the prognosis of patients with CB. Reducing water loss and maintaining the electrolyte balance are particularly important for SICI treatment.

Introduction

Collodion baby (CB) is a rare skin symptom associated with autosomal inherited disease, most of which occurs in premature infants. ¹ At birth, the skin of the entire body is covered with a thick, taut, shiny, glue-like crust formed by the proliferative stratum corneum, similar to collodion. The tension can lead to eyelid ectropion, lip deformation, and underdeveloped nasal and auricular cartilage. It can also affect the sucking and lung ventilation functions of the newborn, leading to dehydration, malnutrition, hypoxia, and lung infections.^1,2 Current thinking is that multiple types of autosomal recessive congenital ichthyosis (ARCI) can manifest as CB at birth, and ACRI has been found to be associated with mutations in ABCA12, ALOX12B, ALOXE3, CASP14, CERS3, CYP4F22, LIPN, NIPAL4/ICHTHYIN, PNPLA1, ALDH3A2, ERCC2/XPD, ABHD5, SDR9C7, SULT2B1, and TGM1 genes.^3,4

Self-improving collodion ichthyosis (SICI) is a rare type of ARCI. Owing to the rarity of this phenotype and the limited number of cases, its incidence and pathogenesis remain unclear. We report a case of SICI diagnosed and treated at Suqian Hospital which is affiliated with Xuzhou Medical University. The case provides valuable clinical data that can aid in further research on this disease.

Case description

A 1-hour-old girl was brought to the neonatal intensive care unit because of her abnormal skin appearance at birth. She was the first child of healthy, unrelated parents, and was born at full-term after an uncomplicated antenatal course. No asphyxia was observed during her birth, and her Apgar score was 9 at 1 minute and 10 at 5 minutes, with a birth weight of 2800 g, length of 49 cm, head circumference of 33.5 cm, and chest circumference of 32 cm. On physical examination, her entire body was covered with taut, shiny, thick yellow crusts, resembling parchment, and she had scales on her trunk and upper limbs. A tightening effect of the crusts had caused double upper eyelid ectropion, eclabium, and auricle deformation (Figure 1). Her pulse oxygen saturation was stable, and no abnormalities were found on physical examination of her heart, lungs, or nervous system.

Figure 1.

(a–b) The body is covered with taut, shiny, thick yellow crusts, like parchment, and multiple scales can be observed on the trunk and upper limbs. Notable facial features include double upper eyelid ectropion, eclabium, and auricle deformation.

After admission, peripheral blood was collected for testing, and no major abnormalities were found in blood culture, blood cell analysis, or levels of C-reactive protein or electrolytes. Chest radiography and color ultrasonography findings of her heart, brain, digestive system, and urinary system were also normal. Whole-exome sequencing showed that she had compound heterozygous mutations in the arachidonate 12-lipoxygenase, 12R type gene (ALOX12B), c.1798C > T (p.Arg600Trp) and c.1463G > A (p.Arg488His), originating from her mother and father, respectively (Figure 2). Therefore, she was diagnosed with ARCI.

Figure 2.

(a) The ALOX12B mutation c.1798C > T in the proband was inherited from her mother and (b) The ALOX12B mutation c.1463G > A in the proband was inherited from her father.

The initial temperature of the incubator was set to 32°C to provide an optimal environment for a newborn. To reduce the loss of moisture through the body surface, we used sterile Vaseline gauze dressings to cover the exposed mucosa, and maintained the air humidity in the incubator at 75%. Body weight, electrolyte levels, fluid intake, and output were monitored every 24 hours to maintain the newborn’s health. The child had good sucking ability and no symptoms of intolerance to breast milk; therefore, no special feeding methods were used during hospitalization. Antibiotics were not administered because indicators of infection were normal. After 1 week, the parchment-like membrane began to flake off. At the age of 3 weeks, the skin of the proband’s body had returned to normal, so she was diagnosed with SICI. The infant is currently 3 months old and has growth and development comparable to that of infants in the same age group with normal skin.

All treatments were administered after acquiring written consent from the child’s parents. The reporting of this study conforms to CARE guidelines. ⁵ Written informed consent was obtained from the child’s parents for the publication of these case report details.

Discussion

CB is not an independent disease but a rare clinical presentation of a heterogeneous group of skin disorders of cornification, often observed at birth in newborns with ARCI. ⁴ SICI is a rare subtype of ARCI that can be caused by mutations in various genes, including TGM1, ALOX12B, ALOXE3, and CYP4F22. In this case, a compound heterozygous mutation in ALOX12B was detected. Although the c.1798C > T variant has only been reported in one case study, c.1463G > A is a confirmed pathogenic variant that has been reported multiple times.^6–11 The above variants may be causative of CB in this case.

The initial symptom of SICI is CB, with the membrane covering the body detaching within a few weeks. The skin eventually becomes normal or is only mildly affected; hence, SICI is also known as self-healing CB. ¹² The clinical manifestations and genetic findings of our proband are consistent with SICI, and the diagnosis is clear. However, not all patients with SICIs exhibit typical clinical symptoms. Mazereeuw-Hautier and colleagues reported a case of SICI in a female newborn caused by a TGM1 mutation. ¹³ The baby was born with a typical collodion-like membrane, but it was limited to her distal limbs suggesting that the location of skin damage in SICI may be influenced by mutations in different pathogenic genes.

The ALOX12B gene contains 15 exons and encodes a 12R oxygenase containing 701 amino acids that is located in the epidermal granular layer. Mutations in ALOX12B lead to impaired synthesis of cell lipid membranes, mainly composed of ceramide, cholesterol, and free fatty acids, damaging the skin permeability barrier and accelerating water loss. ¹⁴ Therefore, the focus of SICI treatment during the neonatal period is to minimize trans-epidermal water loss (TEWL). The TEWL of newborns with SICI is seven times higher than that of healthy newborns, and increased TEWL can cause high sodium dehydration, heat loss, and body temperature instability. ¹⁵ According to European guidelines of the management of congenital ichthyoses, the most important step in the treatment of newborns with SICI is to place them in a humidified incubator. ¹⁶ During treatment, it is necessary to monitor their water and electrolyte balance, and energy consumption, and be alert to dehydration and hypernatremia. Therefore, the accurate calculation of fluid intake and output is crucial. The dynamic monitoring of weight changes is one of the best clinical indicators to measure whether nutrition and fluid intake are sufficient.^15,17 In this case, upon admission, the incubator was set at a temperature of 32°C and a humidity of 75%, and there was no electrolyte disturbance during hospitalization, indicating that these two initial parameters can be attempted in clinical practice.

In addition to SICI, mutations in ALOX12B can also lead to congenital ichthyosiform erythroderma and lamellar ichthyosis, which can also exhibit the collodion phenotype.^18,19 Thus, CB caused by ALOX12B mutations is not necessarily an SICI disease. At present, the diagnosis of SICI still depends on observing dynamic changes in the skin clinical phenotype and molecular genetics technology; therefore, the exact diagnosis is often completed a few weeks after birth. Thus, it is currently impossible to predict whether CB will develop into SICI or other severe ichthyosis phenotypes based on the ALOX12B mutation type at birth. The diagnosis of SICI in this case was made at 3 weeks of age when the skin had already returned to normal. However, recent studies have found that most patients gradually develop mild ichthyotic features, including dry skin, small local debris, low levels of sweating, heat intolerance, facial flushing, and palmoplantar keratosis.^20–23 Therefore, long-term follow-up is necessary.

This study suggests that clinicians should consider the possibility of SICI, a mild phenotype, when analyzing the prognosis of CB and providing genetic counseling. Owing to the rare reports of SICI and the inclusion of only one case in this study, the association between the SICI genotype and phenotype should be further studied by expanding the sample size.