Genodermatoses

Tammie Ferringer

A summary table of the ‘Key histologic features of genodermatoses’ can be found in the on-line content for this book.

Pseudoxanthoma elasticum

Key features

• Curled and frayed, calcified elastic fibers in the reticular dermis (pink or blue squiggles)

• Elastic tissue (Verhoeff–Van Gieson) and calcium (Von Kossa) stains highlight the distorted elastic fibers

Fig 12-1 Pseudoxanthoma elasticum

Fig 12-2 ‘Bramble bush’ elastic fibers induced by penicillamine

Pseudoxanthoma elasticum is an autosomal-recessive and, less commonly, autosomal-dominant disorder due to a mutation in the ABCC6 transporter gene. It results in calcification of the elastic fibers of the skin, eyes, and artery walls. The skin changes become apparent around the second decade and simulate “plucked chicken skin” in the flexural areas. Biopsy of a scar may reveal the elastic tissue abnormalities in a patient with no cutaneous lesions. Eye changes include angioid streaks and retinal hemorrhage that may cause blindness. The vascular changes may lead to hypertension, stroke, myocardial infarction, mitral valve prolapse, and gastrointestinal hemorrhage.

Differential Diagnosis

Angioid streaks, due to rupture in Bruch’s membrane, are associated with other disorders. The mnemonic “PEPSI LiTe” is helpful in remembering the associated diseases:

• Penicillamine

• Ehlers–Danlos syndrome

• Pseudoxanthoma elasticum/Paget’s disease of bone

• Sickle cell anemia

• Increased phosphate

• Lead poisoning

• Thalassemia

Ichthyosis vulgaris

Key features

• Compact orthohyperkeratosis with paradoxically diminished or absent granular layer

Fig 12-3 Ichthyosis vulgaris

In most other conditions, hyperorthokeratosis is associated with a prominent granular layer and parakeratosis is associated with a diminished or absent granular layer. Ichthyosis vulgaris (in which there is little to no granular layer despite hyperkeratosis) and axillary granular parakeratosis (in which there is a granular layer despite the presence of parakeratosis) are exceptions to this rule.

Ichthyosis vulgaris is an autosomal-dominant disorder with retention of the stratum corneum (rather than hyperproliferation) resulting in hyperkeratosis. There is a deficiency in profilaggrin resulting in inadequate keratohyaline granule synthesis. There are fine brown to transparent scales that spare the flexures. Accentuation of the palmoplantar creases, keratosis pilaris, and coexisting atopic dermatitis may be present.

Acquired ichthyosis in association with malignancy, especially Hodgkin’s lymphoma, may clinically and histologically mimic ichthyosis vulgaris. Acquired ichthyosis may also occur with niacin therapy.