Autosomal recessive congenital ichthyosis (ARCI) is a term encompassing a group of rare disorders who share the same pathophysiological basis of the disease - impaired keratinization of the skin due to various hereditary mutations [1] [2] [3] [4]. Specifically, the keratinocytes are unable to create crucial lipid molecules in the stratum corneum that are involved in protection from the external environment [4]. Depending on the severity of the disorder, a few distinct phenotypes exist - lamellar ichthyosis (LI), congenital ichthyosiform erythroderma (CIE), and harlequin ichthyosis regarded as the most dangerous and life-threatening form of ARCI [1] [5] [6]. Congenital ichthyosiform erythroderma is mainly regarded as a severe form of ARCI, with first manifestations presenting as early as at birth - palmoplantar keratoderma, generalized redness of the skin, and diffuse white scaling [1] [2] [5]. Due to the loss of skin integrity, fissures and digital contractures, particularly in severe cases, are quite common [1] [2] [3]. In addition to these findings, many patients develop various other manifestations such as ectropion and loss of eyebrows. An abnormal lip formation (eclabium) have also been described [1] [2].

• Collapse

  These defects in the keratin protein network result in subsequent skin cell collapse and skin fragility. This clinically manifests as blistering, hyperkeratosis, and hyper proliferation. Onset of BCIE typically occurs in newborns. [austinpublishinggroup.com]

• Genu Valgum

  We present two cases of ichthyosiform erythroderma associated with severe bilateral genu valgum. Other musculoskeletal features associated with this condition are described. [ncbi.nlm.nih.gov]

• Short Arm

  X-linked ichthyosis (steroid sulphatase deficiency) and X-linked ocular albinism have been mapped to the Xp22.3 region and cases have been reported with both conditions due to a partial short-arm deletion of the X chromosome. [ncbi.nlm.nih.gov]

• Cutaneous Manifestation

  The diagnosis of congenital ichthyosiform erythroderma and other forms of ARCI rests on the ability of the physician to recognize the main cutaneous manifestations in the neonatal period. [symptoma.com]

• Neonate-Onset

  CIE is considered to be a severe subtype, distinguished by a neonatal onset of palmoplantar keratoderma, painful fissures, contractures of the digits, an eyebrow loss, and ectropion. [symptoma.com]

The diagnosis of congenital ichthyosiform erythroderma and other forms of ARCI rests on the ability of the physician to recognize the main cutaneous manifestations in the neonatal period. For this reason, the physical examination is the pivotal step in confirming any type of ARCI. Because CIE develops through an autosomal recessive pattern of inheritance, a detailed family history, which could potentially reveal similar findings in close relatives, is equally important.

Although clinical findings are considered to be sufficient to make the diagnosis of congenital ichthyosiform erythroderma, additional studies that may solidify suspicion are a histological examination of the skin and genetic studies. Main findings on skin biopsy samples include hyperkeratosis, increased mitotic activity, an abundance of blood vessels in the dermis, and a lymphocytic infiltrate [2]. The presence of mutations in any of the 12 genes that have been identified in many patients (most frequent genes involved are ABCA12, TGM1, ALOX12B, NIPAL4) may serve as a confirmation [1]. However, up to 15% of families in whom this condition is present do not possess any of the genetic mutations previously described in the literature [1]. Hence, clinical criteria remain the cornerstone in recognizing CIE.

• Trichophyton Rubrum

  Infection with Trichophyton rubrum was confirmed by culture. The patient responded to oral terbinafine antifungal treatment. [ncbi.nlm.nih.gov]

1. Richard G. Autosomal Recessive Congenital Ichthyosis. 2001 Jan 10 [Updated 2017 May 18]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
2. Fischer J, Faure A, Bouadjar B, et al. Two new loci for autosomal recessive ichthyosis on chromosomes 3p21 and 19p12-q12 and evidence for further genetic heterogeneity. Am J Hum Genet. 2000;66:904–913.
3. Wang T, Xu C, Zhou X, et al. Homozygous ALOXE3 Nonsense Variant Identified in a Patient with Non-Bullous Congenital Ichthyosiform Erythroderma Complicated by Superimposed Bullous Majocchi’s Granuloma: The Consequences of Skin Barrier Dysfunction. Slominski A, ed.Int J Mol Sci. 2015;16(9):21791-21801.
4. Elias PM, Williams ML, Holleran WM, Jiang YJ, Schmuth M. Pathogenesis of permeability barrier abnormalities in the ichthyoses: Inherited disorders of lipid metabolism. J. Lipid Res. 2008;49:697–714.
5. Pigg MH1, Bygum A, Gånemo A, et al. Spectrum of Autosomal Recessive Congenital Ichthyosis in Scandinavia: Clinical Characteristics and Novel and Recurrent Mutations in 132 Patients. Acta Derm Venereol. 2016;96(7):932-937.
6. Rodríguez-Pazos L, Ginarte M, Vega A, Toribio J. Autosomal recessive congenital ichthyosis. Actas Dermosifiliogr. 2013;104(4):270-284.