SHORT COMMUNICATION
397
ActaDV ActaDV
Advances in dermatology and venereology Acta Dermato-Venereologica
A Japanese Case of Ichthyosiform Erythroderma with a Novel Mutation in NIPAL4 / Ichthyin
Minori KUSAKABE 1, Makoto NAGAI 1, Eiji NAKANO 2, 3, Orie JITSUKAWA 1, Chikako NISHIGORI 2 and Kiyofumi YAMANISHI 1 *
1
Department of Dermatology, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, 2 Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, and 3 Department of Dermatology, Hyogo Prefectural Kaibara Hospital, Tanba, Hyogo, Japan. E-mail: kyamanis @ hyo-med. ac. jp Accepted Oct 12, 2016; Epub ahead of print Oct 14, 2016
Autosomal recessive congenital ichthyosis( ARCI) is an entity of rare genetic skin disorders with abnormal keratinization( 1). Harlequin ichthyosis is the most severe type of ARCI, usually caused by truncation mutations in ABCA12. In subtypes of ARCI, such as lamellar ichthy osis( LI) and, congenital ichthyosiform erythroderma( CIE) mutations in TGM1, ABCA12, NIPAL4, ALOXE3, ALOX12B, CERS3, CYP4F22 and PNPLA1 have been reported( 2 – 4). Mutations in NIPAL4, the gene encoding the NIPA-like domain containing 4 protein( NIPAL4 / ichthyin)( 5), have been identified in approximately 16 % of patients with ARCI( 2). We report here a case of ARCI with variable CIE symptoms. This is the first reported case with a mutation in NIPAL4 in East Asia.
CASE REPORT
A 41-year-old Japanese woman had had generalized dry skin and desquamation since birth. Her younger sister also had a similar skin condition with atopic dermatitis( AD), but the complication of AD was absent in the present case. No collodion baby phenotype was reported at birth in either sister. No other members of the patient’ s family had a history or symptoms of ichthyosis. On examination, the patient had erythroderma with generalized fine scales and occasional itching( Fig. 1a, b). She showed mild ectropion. Elabium was absent. The nails of both her first toes showed onychogryphosis( Fig. 1c), and her fingernails were mildly thickened with transverse ridges. Palmar hyperkeratosis was mild, but her soles were diffusely covered with thick scales( Fig. 1d). She reported anhidrosis and heat exhaustion in the summer months. Interestingly, a mild geographic lesion was distributed from her right shoulder to the centre of the upper back at her first visit( Fig. 1e). The lesions were surrounded by infiltrated diffuse ery themas with coarse scales and several small erosions, possibly due to scratching, were noted. However, 6 months later, the erythroderma had improved and milder ichthyosiform lesions were diffusely distributed over her entire body surface( Fig. 1f). Such variations in her erythroderma and scales were repeated and were not necessarily dependent on the season or sweating. Histology of a biopsy from her left
upper arm showed epidermal acanthosis and a homogeneously thickened stratum corneum( Fig. S1a 1). Loss or hypoplasia of granular layers and granular degeneration were absent. Several perivascular inflammatory infiltrates were noted. As differential diagnoses, ichthyosis vulgaris and epidermolytic ichthyosis were
Fig. 1. Clinical, ultrastructural and immunoflourescence findings. Mild ichthyosiform erythroderma with fine scales distributed on:( a) the abdomen; and( b) the legs.( c) Thickened and deformed nails of both first toes.( d) Diffusely hyperkeratotic soles with coarse scales.( e) Milder lesions surrounded by infiltrated diffuse erythemas with coarse scales.( f) Six months later, the skin condition was milder.( g) Ultrastructure of the epidermis. Lipid droplets( asterisk) and several small membranous structures( yellow arrow-heads) are visible in the stratum corneum. Bar = 0.5 μm.( h, i) Immunofluorescence for GluCer in:( h) healthy control skin, and( i) the patient’ s skin. A rabbit anti-GluCer antibody( 1:50 dilution)( Glycobiotech, Borstel, Germany) and reagents shown in the Fig. S1 1 legend were used. Images are merged views of GluCer( red), DAPI( blue) and differential interference contrast( DIC) images( white). Bar = 20 µ m.
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2017 Acta Dermato-Venereologica. doi: 10.2340 / 00015555-2550 Acta Derm Venereol 2017; 97: 397 – 398