peau d’orange

Pseudoxanthoma Elasticum-Like Disease

Clinical Characteristics
Ocular Features: 

Retinitis pigmentosa has been diagnosed clinically and confirmed by ERG studies in some patients. The fundi in a few individuals have the typical angioid streaks and/or peau d’orange changes. The impact on visual acuity and its prognosis has not been systematically studied.

Systemic Features: 

The skin changes resulting from fragmentation and aberrant mineralization of connective tissue, particularly elastic fibers, resemble those seem in classic pseudoxanthoma elasticum. These include the presence of yellowish papules or leathery plaques with dot-like depressions (‘chicken skin’). However, the skin changes are more widespread and involve trunk as well as limbs and flexural areas. Ultrastructurally the elastic fibers are more severely fragmented than those in classic PXE.

Many patients in addition have deficiencies in vitamin K-dependent clotting factors such as II, VII, IX, and X. Epistaxis, spontaneous gingival bleeding and severe vaginal hemorrhages may occur. Cerebral aneurysms, vascular occlusions, and atherosclerotic plaques in the lower extremities have been reported in a few patients.

Genetics

Classic pseudoxanthoma elasticum is due to homozygous mutations in the ABCC6 (ATP-binding cassette subfamily C member 6) gene. However, in the PXE-like condition described here homozygous or compound heterozygous mutations in the GGCX (gamma-glutamyl carboxylase) gene (2p11.2) are responsible. Some heterozygous GGCX individuals in families with this genotype who are also heterozygous for ABCC6 mutations (doubly heterozygous) may have similar skin features. Thus the condition described here may also be a digenic disorder in some individuals.

Pseudoxanthoma elasticum-like disease is an autosomal recessive disorder.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

There is no treatment for the connective tissue defect but individual problems such as subretinal neovascularization, hemorrhages, and vascular occlusions may respond to appropriate therapy.

References
Article Title: 

Pseudoxanthoma Elasticum

Clinical Characteristics
Ocular Features: 

Breaks in Bruch membrane lead to the classic non-diagnostic ocular sign in this disease known as angioid streaks.  These are typically bilateral, reddish-brown curvilinear bands that vaguely resemble a vascular pattern seen most commonly in the posterior pole radiating from the peripapillary area.  They typically have their onset after the skin lesions appear.  The fundus may also have areas of yellow mottling temporal to the fovea suggestive of an orange peel surface.  These are sometimes labeled 'peau d'orange' and their appearance frequently precedes the appearance of angioid streaks.  Optic disc drusen are said to occur 20-50 times more frequently than in the general population and may be apparent before the appearance of angioid streaks.  A significant proportion of patients have atrophy of the RPE and outer retina, especially those with early onset and rapid progression of the disease.

The major threat to vision comes from the formation of subretinal neovascular nets which often bleed resulting in secondary scarring and fibrosis.  These frequently involve the central macula which is why central vision is primarily impacted and peripheral vision usually remains normal.  Macular involvement is evident at a mean age of 44 years and the majority of patients are visually handicapped by the age of 52 years.

Systemic Features: 

The skin has characteristic changes of several types due to defective elastin.  It is often lax and redundant with localized plaques of hyperkeratotic papules giving the typical 'plucked chicken' appearance.  The latter are typically seen in the skin of the neck, in inguinal folds and in the popliteal and antecubital spaces.  These may have their onset in childhood but sometimes later.  They are generally asymptomatic and primarily of cosmetic importance.  The oral, rectal, and vaginal mucosa may also be involved.  Focal deposits of calcium are often seen.

Vascular disease secondary to calcification of elastic media and intima are responsible for the major health problems in this disease but they usually are not evident until later in life.  Hemorrhage or occlusion often results.  At least 10% of individuals with this disease experience a gastrointestinal hemorrhage at some point in their lives and this can be life-threatening.  Intermittent claudication can be incapacitating.  Coronary artery disease is frequently a symptom.  Occlusive disease of the renal arteries can result in hypertension.  Malfunction of heart valves, especially the mitral valve, is common.

Genetics

This is an autosomal recessive disorder caused by mutations in the ABCC6 gene (16p13.1).  Females are affected nearly twice as often as males.  Some heterozygotes have minor manifestations of the disease but the full clinical picture is only seen in homozygotes.

Rare variant mutations in the ABCC6 gene may cause typical ocular changes without systemic manifestations.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Choroidal neovascularization should be treated.  Intravitreal injections of ranibizumab may be beneficial as a prophylactic measure for the preservation of central vision.  GI bleeds require prompt and vigorous treatment and cardiac valves sometimes require repair.  Redundant skin can be surgically removed.  Patients should avoid contact sports and activities requiring heavy lifting or straining.  Antibiotic prophylaxis should be considered for patients with heart valve disease before undergoing procedures.

References
Article Title: 
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