Disorders of keratinization

Chapter 4 Disorders of keratinization

H. Alan Arbuckle, MD, FAAP, FAAD , Lori D. Prok, MD

1. What are the ichthyosiform dermatoses?

The ichthyosiform dermatoses are a heterogeneous group of disorders presenting with excessive scaling of the skin. The inherited forms of the ichthyoses are most common, although the condition can occur secondary to other diseases.

2. What does “ichthyosis” mean?

The term ichthyosis is derived from the Greek root ichthy, meaning fish, indicative of the scales on the skin of affected individuals.

3. How common are the congenital ichthyoses? How are they inherited?

• Ichthyosis vulgaris: Incidence of 1:250; autosomal dominant

• X-linked ichthyosis: Incidence of 1:6000; X-linked recessive

• Epidermolytic hyperkeratosis: Incidence of 1:300,000; autosomal dominant

• Congenital ichthyosiform erythroderma (CIE): Incidence of 1:100,000; autosomal recessive

• Lamellar ichthyosis: Incidence of 1:300,000; autosomal recessive

• Harlequin fetus: Rare; autosomal recessive

Akiyama M: The clinical spectrum of nonbullous congenital ichthyosiform erythroderma and lamellar ichthyosis, Clin Exp Dermatol 28(3):235–240, 2003.

DiGiovanna J: Ichthyosis: etiology, diagnosis, and management, Am J Clin Dermatol 4(2):81–95, 2003.

Shwayder T: Disorders of keratinization: diagnosis and management, Am J Clin Dermatol 5(1):17–29, 2004.

4. What features help differentiate the most common inherited ichthyoses?

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.

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

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.

Figure 4-1. A, Grandfather and granddaughter with ichthyosis vulgaris. B, Palmar hyperkeratosis, a finding often associated with ichthyosis vulgaris. C, X-linked ichthyosis, showing characteristic coarse, brown scales. D, Young child with congenital ichthyosiform erythroderma demonstrating diffuse erythema and scale.

(A, B, and D, courtesy of James E. Fitzpatrick, MD.)

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.

5. What genetic defect is responsible for X-linked ichthyosis (XLI)?

Ninety percent of patients with XLI have deletions in the STS gene on chromosome Xp22.3, leading to steroid sulfatase deficiency and the classic phenotype of XLI. However, some patients have larger deletions at this site, encompassing neighboring genes. These patients present with more complicated forms of XLI representing contiguous gene deletion syndromes (OMIM [Online Mendelian Inheritance in Man] #308100).

6. What additional phenotypes may patients with XLI contiguous gene syndromes exhibit?

Hypogonadotropic hypogonadism and anosmia (Kallman’s syndrome), chondrodysplasia punctata, short stature, and/or ocular albinism may be present in these patients in addition to X-linked ichthyosis.

7. What important birth history may be obtained in patients with XLI?

Labor may be protracted or fail to progress when the fetus is affected with XLI. This is directly related to the defect in steroid sulfatase, which leads to abnormal steroid hormone metabolism. Female carriers may also exhibit asymptomatic corneal opacities.

8. Name the hereditary syndromes presenting with ichthyosis as a component.

See Table 4-2.

9. What is a collodion baby?

A collodion baby is a newborn infant whose skin looks like a “baked apple,” with a shiny, tough, membrane-like covering. This term describes a phenotype that occurs in several types of ichthyosis. Although congenital ichthyosiform erythroderma is the most common underlying condition (Fig. 4-1

Only gold members can continue reading. Log In or Register to continue