Ichthyoses and Erythrokeratodermas

• Ichthyoses and erythrokeratodermas represent a diverse group of disorders of cornification, which are characterized by a defective epidermal barrier due to abnormal differentiation and/or desquamation of keratinocytes.

• Ichthyoses feature diffuse scaling of the skin, often in a widespread distribution, whereas erythrokeratodermas present with circumscribed areas of hyperkeratosis without prominent scaling.

• These conditions usually have a genetic basis, with the occasional exception of acquired ichthyosis associated with disorders such as malnutrition, hypothyroidism, sarcoidosis, lymphoma, leprosy, or HIV infection.

• A thorough family history helps in recognizing the inheritance pattern; an affected parent suggests dominant inheritance, whereas inheritance in patients with unaffected parents may be autosomal recessive (especially with affected siblings or parental consanguinity), X-linked recessive (especially for a male patient with affected maternal male relatives), or dominant (e.g. due to a ‘new’ mutation or with incomplete penetrance).

• Clinical features that are useful in determining the type of ichthyosis include the time of presentation (e.g. at birth, ± a collodion membrane, vs. later in life), the quality and distribution of the scaling, other cutaneous manifestations (e.g. erythroderma, blistering, abnormal hair), and extracutaneous or laboratory findings (Table 46.1).

Table 46.1

Clues to the diagnosis of ichthyoses and erythrokeratodermas.

The disorders in this table are discussed in greater detail in the text or Table 46.2. Other rare ichthyoses and related disorders can also present with these findings.

^§ Keratitis has variable onset.

^* Hypernatremic dehydration occurs primarily in collodion babies and neonates with Netherton syndrome, EI, or Harlequin ichthyosis.

^** Elevated transaminases are common in NLSD.

^† Increased in Netherton and inflammatory peeling skin syndromes.

CIE, congenital ichthyosiform erythroderma; CHH, Conradi–Hünermann–Happle syndrome; EI, epidermolytic ichthyosis; CHILD, congenital hemidysplasia with ichthyosiform nevus and limb defects; IFAP, ichthyosis follicularis with atrichia and photophobia; KID, keratitis–ichthyosis–deafness syndrome; NLSD, neutral lipid storage disease; SLS, Sjögren–Larsson syndrome; TGM-1, transglutaminase-1; TTD, trichothiodystrophy.

• A few ichthyoses have characteristic histologic features (e.g. epidermolytic ichthyosis; see below).

• For conditions with a known molecular etiology, genetic testing can confirm the diagnosis in the patient and affected relatives as well as provide the basis for prenatal/preimplantation testing.

Ichthyosis Vulgaris (IV)

• The most common disorder of cornification, with a prevalence of at least 1 in 200.

• Autosomal semidominant inheritance – mild ichthyosis with a heterozygous filaggrin (FLG) mutation and more severe ichthyosis with mutations in both FLG alleles.

• Filaggrin deficiency results in impaired formation of cornified keratinocytes, increased transepidermal water loss, and a propensity for an inflammatory response upon exposure to irritants or allergens; this explains the pathogenic role of FLG mutations in atopic dermatitis as well as IV.

• Typically becomes apparent during infancy or early childhood and improves by adulthood; worsens in a cold, dry environment.

• Mild to moderate scaling favors the extensor extremities (Fig. 46.1), ranging from fine white scales to larger adherent scales (especially on the lower legs); the trunk, scalp, and forehead are occasionally affected, and flexural sites are characteristically spared.

Fig. 46.1 Ichthyosis vulgaris. Fine white scales on the lower extremities. Courtesy, Julie V. Schaffer, MD.

• Associated findings include hyperlinear palms (Fig. 46.2), keratosis pilaris, and atopic dermatitis (25–50% of patients, ± other atopic disorders such as asthma and allergic rhinitis).