X-Linked Ichthyosis

A 4-year-old boy was referred for evaluation of refractory eczema that first appeared at 1 month of age. His mother thought that his skin always seemed “dirty” and she was unable to remove the scales completely. He was born via cesarean section because of failure of labor to progress; the delivery was otherwise uncomplicated. Development was normal. He had no history of asthma or allergies or family history of rashes.

On examination, the boy appeared healthy. He had fine, adherent, white to tan scales on his body, with relative sparing of the central face and axillae. No erythema or crusting was present. Hair and nails were normal. No eye abnormalities were noted. Testes were descended bilaterally. The clinical history and physical findings suggested a diagnosis of X-linked ichthyosis.

This X-linked recessive disease is characterized by a deficiency in the steroid sulfatase (STS) enzyme and affects 1 in 6000 male infants. The deficiency causes failure of keratinocytes to shed normally, resulting in hyperkeratosis and prominent, large, polygonal dirty brown scales on the neck, extremities, trunk, and buttocks. The condition generally appears as small, diffuse white scales that become larger and darker as the child ages. In contrast to atopic dermatitis, which typically begins at age 3 to 6 months, X-linked ichthyosis occurs at 2 to 6 weeks of age. It is constant, unlike the rash of atopic dermatitis, which often has flares and remissions. The scaling classically spares the flexural areas and face, which are often involved in children with atopic dermatitis.^1,2 Ichthyosis vulgaris is also in the differential diagnosis of this condition and may be difficult to differentiate clinically. This condition is often described as thin, white to translucent scales that also spare the flexural areas. Ichthyosis vulgaris is not associated with the other findings discussed below. Ichthyoses are usually less pruritic than classic eczema. All of these conditions may improve with age.^1,2 The diagnosis of X-linked ichthyosis may be suggested by biopsy and confirmed definitively with an enzyme assay that shows decreased STS activity.¹

X-linked ichthyosis is associated with comma-shaped corneal opacities in up to 50% of patients.² These opacities do not affect visual acuity but may cause corneal erosions. Cryptorchidism occurs in 20% of infants and is associated with an increased risk of testicular cancer.² These patients require a thorough genital examination and referral to a pediatric urologist if one or both testes are undescended. A deficiency of the STS enzyme in the placenta of a mother carrying an affected fetus can cause failure of labor to begin or progress. X-linked ichthyosis has also been associated with attention-deficit/hyperactivity disorder, because a deficiency in the STS gene affects the production of neurosteroids.³

Treatment focuses on diminishing abnormal keratinization by facilitating the elimination of scales and preventing their proliferation. First-line therapy includes topical emollients and keratolytics, although the latter must be used with caution in young infants, because of potential for systemic toxicity. Other treatment options include petrolatum, 40% to 60% propylene glycol in water, alpha hydroxy acids, and lactic acid. Topical retinoids may also help.² Oral retinoids are reserved for patients with severe disease.¹

In patients with a family history of the disease, prenatal diagnosis can be made via amniocentesis and chorionic villus sampling with an STS assay that detects the enzyme deficiency. Case reports have also described an association between STS deficiency and an undetectable unconjugated estriol in second-trimester maternal serum screening.^4,5

References:

REFERENCES:

1. Hernández-Martin A, González-Sarmiento R, De Unamuno P. X-linked ichthyosis: an update. Br J Dermatol. 1999;141:617-627.

2. Fernandes NF, Janniger CK, Schwartz RA. X-linked ichthyosis: an oculocutaneous genodermatosis. J Am Acad Dermatol. 2010;62:480-485.

3. Brookes KJ, Hawi Z, Kirley A, et al. Association of the steroid sulfatase (STS) gene with attention deficit hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet. 2008;147B:1531-1535.

4. Watanabe T, Fujimori K, Kato K, et al. Prenatal diagnosis for placental steroid salfatase deficiency with fluorescence in situ hybridization: a case of X-linked ichthyosis. J Obstet Gynaecol Res. 2003;29:427-430.

5. Langlois S, Armstrong L, Gall K, et al. Steroid sulfatase deficiency and contiguous gene deletion syndrome amongst pregnant patients with low serum unconjugated estriols. Prenat Diagn. 2009;29:966-974.