🗂 總目錄｜ 📖 英文原文（本篇）｜ 📝 完整翻譯｜ ⭐ 精華筆記

Ichthyosis vulgaris

Clinical features This relatively common disorder (incidence of 1 : 250 to 1 : 1000 births) has an autosomal semidominant mode of inheritance.1,2 The disease is usually fairly mild and becomes apparent within the first few months or years of life. It affects the sexes equally and presents as dryness (xerosis) and slight to moderate fine scaling, particularly involving the extensor surfaces of arms and legs and may spare the flexures (Fig. 3.2A). The light-gray scales vary in quality from thick adherent shiny plates to simply dusty accumulations which, when scratched, leave a mark just as when one touches a dusty

54 Disorders of keratinization

Common ichthyoses Ichthyosis vulgaris semidominant

FLG

Nonsyndromic recessive X-linked ichthyosis (RXLI)

XR STS

Autosomal recessive congenital ichthyosis (ARCI) Lamellar ichthyosis (LI) AR TGM1 / NIPAL4 / ALOX12B / ABCA12 / PNPLA1 / CERS3 / LIPH

Congenital ichthyosiform erythroderma (CIE)

AR ALOXE3 / ALOX12B / ABCA12 / CYP4F22 / NIPAL4 / TGM1 / PNPLA1 / CERS3 / LIPH

Self-healing collodion baby (SICI) AR TGM1 / ALOXE3 / ALOX12B

Acral self-healing collodion baby AR TGM1

Bathing suit ichthyosis AR TGM1

Harlequin ichthyosis AR ABCA12

Keratinopathic ichthyosis (KPI) Epidermolytic ichthyosis (EI) AD KRT1 / KRT10

Superficial epidermolytic ichthyosis (SEI)

AD KRT2

Annular epidermolytic ichthyosis AD KRT1 / KRT10

Congenital reticular ichthyosiform erythroderma (CRIE)

AD KRT10 (KRT 1)

Ichthyosis Curth-Macklin AD KRT1

Autosomal recessive epidermolytic ichthyosis

AR KRT10

Other nonsyndromic forms Loricrin keratoderma AD LOR

Erythrokeratodermia variabilis AD (AR) GJB3 / GJB4

Inflammatory peeling skin disease (PSS type B)

AR CDSN

Exfoliative ichthyosis AR CSTA

Keratosis linearis-ichthyosis congenita-keratoderma (KLICK)

AR POMP

AD, Autosomal dominant; AR, autosomal recessive; SICI, self-improving congenital ichthyosis.

Pathogenesis Ichthyosis vulgaris is caused by loss-of-function mutations of the FLG gene that encodes for filaggrin, the major constituent of the keratohyalin granules.5,6 Patients may have one or two FLG mutations. The mutation status correlates with disease severity and ultrastructure, i.e., in line with the decreased amount of filaggrin, keratohyalin granules may be reduced, spongy or slightly crumbly.7 Filaggrin aggregates keratin intermediate filaments in the lower stratum corneum and is subsequently proteolyzed to form free amino acids, including urocanic and pyrrolidone carboxylic acids, which are critical as water-binding compounds in the stratum corneum. The clinical severity of ichthyosis vulgaris correlates with the reduction of keratohyalin granules. Reduced immunostaining for filaggrin correlates with the severity of the defect.8 Parents with one heterozygous filaggrin mutation may be asymptomatic, whereas affected offspring with two mutations often show classic ichthyosis vulgaris.5 FLG mutations are a major predisposing factor for atopic dermatitis (AD) and related allergies.9,10

surface. The truncal lesions tend to be thicker than those on the face and scalp. The rims of the ears are often scaly.3 There is a mild seasonal variation, with improvement of the condition in humid climates.2 The palms and soles show increased palmar and plantar markings (hyperlinearity), in contrast to pure X-linked ichthyosis (Fig. 3.2B).3 Affected patients often present keratosis pilaris (follicular hyperkeratosis) on the arms, buttocks and thighs and suffer from hypohidrosis. An association with keratosis punctata of the palms and soles has also been documented.4

Histologic features Ichthyosis vulgaris is characterized by mild to moderate orthohyperkeratosis associated with an acanthotic, atrophic or normal epidermis. The key

Mode of inheritance Gene

X-linked ichthyosis syndromes Recessive X-linked ichthyosis XR STS (and others)

Ichthyosis follicularis alopecia photophobia

XR MBTPS2

55 Ichthyosis

Conradi-Hünermann-Happle syndrome (CDPX2)

XD EBP

Autosomal ichthyosis syndromes with prominent hair abnormalities Netherton syndrome AR SPINK5

Severe dermatitis-multiple allergiesmetabolic wasting (SAM)

AR DSG1

Ichthyosis with hypotrichosis AR ST14

Neonatal ichthyosis-sclerosing cholangitis (NISCH)

AR CLDN1

Autosomal ichthyosis syndromes with prominent neurologic signs Refsum syndrome AR PHYH / PEX7

Multiple sulfatase deficiency AR SUMF1

Gaucher syndrome type 2 AR GBA

Sjögren-Larsson syndrome AR ALDH3A2

Dorfman-Chanarin syndrome AR ABHD5

Trichothiodystrophy AR C7ORF11 ERCC2 / XPD ERCC3 / XPB GTF2H5 / TTDA

Cerebral dysgenesis-neuropathyichthyosis-palmoplantar keratoderma (CEDNIK)

AR SNAP29

Arthrogryposis-renal dysfunction-cholestasis

AR VPS33B

Autosomal ichthyosis syndromes with deafness Keratitis ichthyosis deafness (KID) AD GJB2 (GJB6)

ELOVL4 deficiency AR ELOVL4

Mental retardation-enteropathy-deafnessneuropathy-ichthyosis-keratoderma (MEDNIK)

AR AP1S1

Autosomal ichthyosis syndromes with transient neonatal respiratory distress Ichthyosis prematurity syndrome AR SLC27A4

AD, Autosomal dominant; AR, autosomal recessive; CDPX2, chondrodysplasia punctata type 2.

feature is a thin or absent granular cell layer (Fig. 3.3).11,12,13 Regional variation in the thickness and/or presence of the granular cell layer may occur and therefore it is best to take the biopsy from a site of maximal scaling. The lesions of keratosis pilaris show dilated follicles containing large keratin plugs. In the upper dermis a mild perivascular lymphocytic infiltrate may be present. When ichthyosis vulgaris is associated with atopic dermatitis, parakeratosis and other signs of a spongiotic dermatitis can be found.

Differential diagnosis The histologic differential diagnosis includes other diseases characterized by orthohyperkeratosis and a reduced or absent stratum granulosum (Table 3.3).

Fig. 3.1 (A, B) Severe generalized ichthyosis: this was an incidental finding at autopsy. Ichthyosis can be very disfiguring and a considerable social disadvantage. (A,B) By Courtesey Ph. McKee.

Fig. 3.2 (A) Ichthyosis vulgaris: fine scaling, particularly involving the extremities and characteristically sparing the flexures. (B) Palms show typically increased skin markings.