Packing an unusual punch

Although dermatologists are very familiar with PXE, they're likely to see only a handful of cases during their careers, says Diane R. Baker, M.D., a Portland, Oregon-based dermatologist in private practice and clinical professor of dermatology at Oregon Health Sciences University, and newly-elected president of the American Academy of Dermatology.

However, she says that because its unusual skin symptoms occur early in life, "The dermatologist often is the one to make the diagnosis of PXE" in children.

"PXE is an inherited connective tissue disorder that involves calcification of elastic fibers in the skin, but also internally - especially in the eyes and the cardiovascular system," Dr. Baker explains.

Skin manifestations include yellowish papular lesions, while calcifications that occur within the internal elastic lamina of arteries throughout the body account for the morbidity of the disease, she adds.

Currently, Dr. Baker says, "The only treatment is to avoid other cardiovascular risk factors."

However, she says that oral phosphate binders used in treating chronic renal disease have shown promise in a small trial. In this trial, researchers treated six patients with aluminum hydroxide (1,200 mg three times daily) for a year and found that three patients showed clinical and biopsy improvement at both six and 12 months (Sherer D et al. J Am Acad Dermatol. 2005;53:610-615).

Because oral phosphate binders such as aluminum hydroxide decrease phosphate levels and draw calcium from tissues when used in patients with kidney disease, researchers theorized that these binders might draw calcium from the arteries and other tissues of patients with PXE, Dr. Baker says.

Though some patients improved, she tells Dermatology Times, "There was concern regarding elevated aluminum levels associated with these aluminum salts, which is also a concern in chronic renal failure patients treated with phosphate binders."

In these patients, Dr. Baker explains, high serum concentrations of aluminum can cause osteomalacia and central nervous system toxicities.

Searching for treatment alternatives

Therefore, she says researchers have begun looking into nonaluminum phosphate binders such as Renagel (sevelamer hydrochloride, Genzyme).

In a preliminary trial, patients treated with this drug achieved less improvement than those treated with aluminum hydroxide, Dr. Baker reports.

Despite this setback, she says that, due to the dearth of treatments for PXE, "It's encouraging that there's even something out there that might work in the future."

Scleredema specifics

Scleredema, on the other hand, represents a progressive hardening or thickening of the skin, usually of the upper back and arms, Dr. Baker says.

"Sometimes it's completely asymptomatic except for the difficulty and tightness in moving the skin. Other times, patients get an intense burning pain or itching with it," she says.

Scleredema results from increased deposition of glycoaminoglycans in the dermis, Dr. Baker says.

"Nobody really understands why that happens," although researchers have observed two forms of this illness - one in patients with diabetes, the other independent of diabetes, but perhaps following a respiratory or other infection, she adds.

"In the patients where it follows an infection," Dr. Baker says, "usually the condition eventually resolves spontaneously and doesn't present much of a problem."