ifestations, suggesting that other modifying genes orenvironmental factors may affect ABCC6 expression.An interesting enigma is that despite the autosomallocation of ABCC6, virtually all published series anddata bases of individuals affected by PXE have analmost 2:1 preponderance of females, suggesting thepossibility of hormonal or other gender-related in-fluence on phenotype expression.

About 60 mutations of ABCC6 have so far beenpublished, and compound heterozygosity is com-mon. However, in many affected individuals, onlyone mutation can be found. These limitations mustbe considered in using genetic testing for presymp-tomatic or prenatal diagnosis or for genetic counsel-ing. One intriguing finding, awaiting confirmation, isthat the most common PXE mutation, R1141X, seenin 20% of cases, is associated with a four-fold increasein the prevalence of premature coronary arterydisease.

Research on PXE has been hampered by the lackof a suitable animal model. Recently, an ABCC6knockout mouse has been developed, and althoughit has not shown elastic tissue calcification, it may yetprove to be a good model for studying PXE at thebiochemical and cellular level.

Patients are ultimately most interested in effectivetreatments to ameliorate or prevent the com-plications of PXE, especially the visual ones, whichhave the greatest impact on the quality of life inaffected individuals. Dietary calcium restriction asa treatment approach remains controversial, un-proven, and potentially harmful. Currently, a rigor-ous randomized controlled trial of phosphatebinding gels in PXE is being conducted and it mayfinally establish whether measures to reduce elastictissue mineralization can alter the clinical man-ifestations of PXE. A prospective controlled trial ofphotodynamic therapy for choroidal neovasculari-zation in PXE, or at a minimum, a good retrospective

review of outcomes of this treatment, is needed. Thistreatment is becoming the standard of care withoutdata to substantiate its efficacy in PXE. Trials of anti-angiogenesis drugs in prevention of retinal bleedingare also needed. Although treatments for retinalcomplications of PXE are similar to those developedfor age related macular degeneration, it is clear thatthe strategies aimed at preventing and treating mac-ular degeneration have not been successful in PXE.Unless a major breakthrough in gene therapy occurs,the best hope for an effective treatment for PXE lies inbasic research aimed at the defective cellular trans-port mechanisms in this disorder.

There are two pseudoxanthoma elasticum supportgroups. For more information, visit the Web sites ofeither PXE, Inc., at www.pxe.org, or the NationalAssociation for Pseudoxanthoma Elasticum (NAPE)at www.napxe.org.

REFERENCES

1. Neldner KH. Pseudoxanthoma elasticum. Clin Dermatol 1988;

6:1-159.

2. Lebwohl M, Neldner K, Pope FM, De Paepe A, Christiano AM,

Boyd CD, et al. Classification of pseudoxanthoma elasticum:

Report of a consensus conference. J Am Acad Dermatol 1994;

30:103-7.

3. Uitto J, Pulkkinen L, Ringpfeil F. Molecular genetics of

pseudoxanthoma elasticum: A metabolic disorder at the

environment-genome interface? Trends Mol Med 2001;7:13-7.

4. Hu X, Plomp AS, van Soest S, Wijnholds J, de Jong PT, Bergen

AA. Pseudoxanthoma elasticum: A clinical, histopathological,

and molecular update. Surv Ophthalmol 2003;48:424-38.

5. Ilias A, Urban Z, Seidl TL, Le Saux O, Sinko E, Boyd CD, et al.

Loss of ATP-dependent transport activity in pseudoxanthoma

elasticum-associated mutants of human ABCC6 (MRP6). J Biol

Chem 2002;277:16860-7.

6. Hamlin N, Beck K, Bacchelli B, Cianciulli P, Pasquali-Ronchetti I,

Le Saux O. Acquired Pseudoxanthoma elasticum-like syn-

drome in beta-thalassaemia patients. Br J Haematol 2003;

122:852-4.

J AM ACAD DERMATOL

JULY 2004

S14 Bercovitch and Terry

PXE: The elephant in my room

Jessica Harper

Los Angeles, California

In 1960, when I was eleven years old, my mothernoticed an unusual rash on my neck and took meto a dermatologist, who told us I had a rare

0190-9622/$30.00

ª 2004 by the American Academy of Dermatology, Inc.

doi:10.1016/j.jaad.2004.01.014

condition called pseudoxanthoma elasticum. It wasa disease so rarely seen that the doctor wanted to putme (and my ‘‘chicken skin’’) on display for medicalstudents at nearby Northwestern University. (Mymother declined on my behalf.)

In those days, at least in the Chicago suburbs, littlewas known about the disease that we now call PXE.

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Harper S15

All I was told was that it involved the calcification ofthe elastic tissues, and that I should rub cortisonecream on my neck and wrap it in plastic wrap eachnight. One especially helpful doctor told me I’d growup to be like the rubber man in the freak show,whose skin stretched grotesquely. (My naughtybrother subsequently called me ‘‘rubber neck.’’)But, in all honesty, I didn’t take all of this veryseriously; I was a pre-adolescent with other things onmy mind.

As I got older, the rash on my neck spread, and itappeared at all my joints, where the skin is mostelastic. It started to make me self-conscious; oneclassmate accused me of not washing my neck;people would do double takes when they noticedit. I decided to wear my hair long and avoid wearingnecklaces. However, as I still thought that this diseasewas only aesthetically problematic, I wasn’t reallybothered by it too much.

When my career as an actress kicked into gear, Idid mostly theatre; the presence of a skin conditionwas irrelevant. But as I moved into films, I wasuneasy about concealing the rash; I requested specialmakeup and a high-collared wardrobe. In Penniesfrom Heaven, I had a beautiful Bob Mackie bathrobethat had to be re-designed at the neckline to accom-modate a long close-up. And, as time went on, it wastricky getting insured to act in a film, but becausemost film doctors know little about PXE, I managedto slip by.

Luckily, nobody told me (as some PXE-ers havebeen told) that having children was inadvisable, so Imarried and had two wonderful girls. At that point, Ichose to stay home more and act less, and startedwriting books and music for children (which ismostly what I do now.) The rash continued to spread;I started wearing a lot of scarves and turtlenecks, butwas still (as far as I knew) otherwise unaffected bythe disease.

Then, in the fall of 2001, I found the Web site of anorganization called PXE International, Inc., foundedby Sharon and Patrick Terry, the parents of twochildren with PXE. They sent me their newsletter,which changed my world: I looked at the Amsler gridprovided within and immediately noticed seriousdistortion in my vision. I went to the Jules Stein EyeInstitute at the University of California—Los Angelesand learned that I had a retinal bleed in my left eyethat could be the beginning of the loss of my centralvision. Ironically, I had played a blind woman ina play in New York some years before, and had spenttime with several visually impaired people, getting toknow them and observing how they coped. But ithad never occurred to me that the loss of my ownsight would ever be more than an acting exercise; nophysician had ever told me that vision loss is a verycommon occurrence in PXE patients. I was not onlyshocked, I was devastated.

I’ve received excellent care at the Jules SteinInstitute, and I’m grateful for it. I’m in a clinical trialthere now, testing a new drug which may halt andpossibly reverse macular degeneration. So far, thetreatment has stabilized my vision. But I can’t say Ilove having injections in my eye every six weeks, northat I look forward to facing what happens when thetrial ends, the drug is still unapproved, and I run outof treatment options.

I’m now on the board of PXE International, Inc.,and well-informed about the effects of PXE (includ-ing the potential for cardiovascular and gastrointes-tinal difficulties.) I have a very full and wonderful life;the sun shines all time in California, and I’m writingbooks and music and I adore my family. But I’manxious all the time. PXE, if you will, is like anelephant in my room; it’s there, big and threatening,and there’s no telling what it will do next.

For more information, visit the PXE International,Inc. Web site at www.pxe.org.