Both clinical and histologic features are helpful in the diagnosis of ichthyoses (Table 4-1). Onset of symptoms, anatomic location of skin changes, birth history, and the condition of the infant’s skin at birth are helpful clues. In some instances, a skin biopsy can be diagnostic.

Ichthyosis vulgaris (Fig. 4-1A,B) usually develops around school age, and is characterized by generalized xerosis and scale, with characteristic sparing of the flexural skin. Additional findings include follicular accentuation (keratosis pilaris), hyperlinearity of palms and soles, and a personal or family history of atopy. Rare patients may have an associated palmar-plantar keratoderma. Skin biopsy demonstrates a decreased granular cell layer associated with moderate hyperkeratosis.

X-linked ichthyosis, in contrast, is usually present by one year of age, affects the posterior neck with “dirty”- appearing scales, and spares the palms and soles (Fig. 4-1C). The skin changes—gradually worsening with age— with the neck, face, and trunk ultimately developing thick, brown scales. The disease is caused by a defect in steroid sulfatase, an enzyme important in cholesterol synthesis and vital for normal development and function of the stratum corneum. Accumulation of cholesterol sulfate and a lack of tissue cholesterol ensue, leading to a disturbance in steroid hormone metabolism. Skin biopsy of X-linked ichthyosis is rarely diagnostic, and demonstrates a normal granular layer with hyperkeratosis.




 

Table 4-1. Clinical Features of the Major Inherited Ichthyoses

DISORDER

ONSET

TYPE OF SCALE

SITES

HISTOLOGY

OTHER FINDINGS

DEFECT

Ichthyosis vulgaris

Childhood

Fine

Palms, soles, extensors

Diminished granular layer

Atopy, keratosis pilaris

Filaggrin

X-linked ichthyosis

Birth or infancy

Coarse, brown

Neck, face, trunk, flexors

Normal granular layer

Corneal opacities

Steroid sulfatase

Epidermolytic hyperkeratosis

Birth

Erosions/bullae, coarse, verrucous

Generalized, especially flexors

Epidermolytic hyperkeratosis

Foul odor, pyogenic infections

Keratin

Congenital ichthyosiform erythroderma (CIE)

Birth

Fine, white, with erythroderma

Generalized with flexors, palms, soles

Increased granular layer, focal parakeratosis

Ectropion, nail dystrophy, poor growth, alopecia

ALOXE3/ ALOX12B

Lamellar ichthyosis

Birth

Platelike, dark, erythroderma

Generalized with flexors, palms, soles

Increased granular layer, hyperkeratosis

Same as CIE

Transglutaminase

Harlequin fetus

Birth

Massive thick plates

Generalized

Massive compact hyperkeratosis

Ectropion, eclabium, ear and limb deformities

ACBA12