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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