CLINICAL HISTORY:

Signs and symptoms:  Diffuse scaling over trunk, neck and extremities

Previous Treatment:  Over the counter emollients (Eucerin®)

Other information:  Patient has a nephew with similar skin findings. His birth history was unremarkable with no prolonged labor or failure to progress and he had no history of undescended testes. Urology and ophthalmology exams were both within normal limits.

PHYSICAL EXAM:

On physical exam you can appreciate diffuse, adherent, plate-like brown scales on the trunk and extensor extremities with involvement of the neck as well as sparing of the palms and soles.

LABORATORY TESTS:

Serum lipoprotein electrophoresis- normal pattern
Peripheral blood fluorescent in situ hybridization (FISH) study- steroid sulfatase deficiency

DERMATOHISTOPATHOLOGY:

Microscopic description: Thickened and compact hyperkeratosis and hypergranulosis

DIFFERENTIAL DIAGNOSIS:

1.   Ichthyosis vulgaris
2.   X-linked ichthyosis
3.   Lamellar ichthyosis
4.   Xerosis
5.   None of the Above

SCROLL DOWN FOR ANSWER AND DISCUSSION.

CORRECT DIAGNOSIS:

X-linked ichthyosis

DISCUSSION:

X-linked ichthyosis is the second most common type of ichthyosis with ichthyosis vulgaris being most common. It affects between 1 in 2,000 to 6,000 males and has no geographic or racial predilections. It typically develops at birth or early infancy usually between 2 and 6 weeks of age with light-colored scaling with progression to large, dark scales giving the skin a dirty appearance. The scales are prominent on the extensor surfaces, pre-auricular, neck and upper trunk with or without flexural involvement. The palms and soles are typically spared and hair and nails are normal.

Extracutaneous manifestations are possible including comma shaped corneal opacities in affected males and female carriers. These are asymptomatic and do not affect visual acuity. Affected patients have an increased risk of cryptorchidism and testicular cancer even without a history of undescended testes. Placental steroid sulfatase deficiency is associated with prolonged labor and failure to progress during the birth of the affected patient. Since steroid sulfatase normally hydrolyzes cholesterol sulfate and sulfated steroid hormones, a deficiency leads to low estrogen levels resulting in difficulty initiating labor and a higher number of women requiring Cesarean sections.

X-linked ichthyosis is due to a genetic disorder of keratinization leading to a retention ichthyosis. It is caused by a deficiency of steroid sulfatase enzyme resulting from abnormalities in its coding gene. The gene is mapped to the distal part of the short arm of the X22 chromosome. This deficiency leads to accumulation of cholesterol sulfate and decreased cholesterol in the stratum corneum which causes persistent keratinocyte adhesion and abnormal desquamation.

The dermatohistopathology is nonspecific but generally shows mild to moderate compact orthokeratosis, a normal to thickened granular layer and mild to moderate acanthosis.

The differential diagnosis includes other common ichthyoses. The distinction is made clinically and with the aid of histopathology. Ichthyosis vulgaris is the most common type of ichthyosis and shows fine, white scales over the extensors with flexural sparing, keratosis pilaris and palmoplantar involvement. A decreased or absent granular layer is seen. Lamellar ichthyosis and congenital ichthyosiform erythroderma both present as colloidion babies at birth. Later, lamellar ichthyosis shows large quadrilateral plate-like scales and palmoplantar involvement with a normal granular layer seen on histopathology. Congenital ichthyosiform erythroderma shows finer white scales over the body, erythroderma and alopecia as well as a normal to decreased granular layer on histopathology. Bullous ichthyosiform erythroderma shows erythroderma, scaling and bullae early on which progress to intertriginous dark scales over time. On histopathology an increased granular layer with vacuolization of the granular and spinous layers is seen.

Diagnosis is made by demonstrating gene deletion, lack of enzyme activity, or an increase in one of the substrates of steroid sulfatase. A fluorescence in situ hybridization (FISH) study is performed on metaphase chromosomes from peripheral blood cells using a steroid sulfatase probe. The absence of a hybridization signal indicates a microdeletion of the steroid sulfatase gene. A steroid sulfatase assay will show reduced or absent enzyme activity in leukocytes, skin fibroblasts and keratinocytes. This is used to detect carriers and affected patients. Elevated cholesterol sulfate levels in the serum detected by chromatography or spectrophotometry may be used as well as PCR and lipoprotein electrophoresis since increased cholesterol sulfate increases electrophoretic mobility of low density lipoproteins. Maternal urine can be used to detect high levels of sulfated estrogen precursors or low levels of estriol and amniotic fluid analysis may be used prenatally to measure placental sulfatase activity and elevated DHEAS.

TREATMENT:

Actual treatment for this patient: Lac hydrin 12% cream BID

Other Treatment options:
Topical keratolytics such as ammonium lactate which contains lactic acid, an alpha hydroxy acid with keratolytic action via disadhesion of corneocytes is the most commonly used and successful treatment although emollients, hydrating agents and topical retinoids may be tried. Oral retinoids are reserved for rare or more significantly affected patients.

REFERENCES:

1. Ellison P et al. Chronic dark-brown scales. Arch Dermatol 1996;23:594-597.

2. Hernandez-Martin A et al. X-linked ichthyosis: an update. Br J Dermatol 1999;141:617-27.

3. Hirato et al. Steroid sulfatase activities in human leukocytes: biochemical and clinical aspects. Endocrinol Japan 1991;38(6):597-602.

4. Nomura K et al. A study of the steroid sulfatase gene in families. Acta Derm Venereol 1995;75(5):340-342.

5. Paller AS. Laboratory tests for ichthyosis. Dermatol Clin 1994;12(1):99-107.

Additional Comment:

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