PSEUDOXANTHOMA ELASTICUM: DIAGNOSTIC FEATURES, CLASSIFICATION, AND TREATMENT OPTIONS.
BACKGROUND
Pseudoxanthoma elasticum (PXE), a multisystem orphan disease, clinically affects the skin, the eyes, and the cardiovascular system with considerable morbidity and mortality. The clinical manifestations reflect the underlying pathology consisting of ectopic mineralization of peripheral connective tissues.


METHODS
The diagnostic criteria of PXE include characteristic clinical findings, together with histopathology of accumulation of pleiomorphic elastic structures in the dermis with progressive mineralization, and the presence of mutations in theABCC6gene. PXE-like cutaneous changes can also be encountered in other ectopic mineralization disorders, including generalized arterial calcification of infancy (GACI) caused by mutations in theENPP1gene. In some cases, overlapping clinical features of PXE/GACI, associated with mutations either inABCC6orENPP1, have been noted. PXE demonstrates considerable inter- and intrafamilial heterogeneity, and consequently, accurate diagnosis is required for appropriate classification with prognostic implications. There is no effective and specific treatment for the systemic manifestations of PXE, but effective therapies to counteract the ocular complications are in current clinical use.


CONCLUSIONS
A number of observations in the murine model, theAbcc6-/-mouse, have indicated that the mineral composition of diet, particularly the magnesium content, can influence the severity of the mineralization phenotype. These observations suggest that appropriate dietary interventions, coupled with lifestyle modifications, including smoking cessation, might alleviate the symptoms and improve the quality of life of individuals affected with this, currently intractable, orphan disease.
Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Philadelphia, PA.
Jouni
J
Uitto
Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Philadelphia, PA.
Qiujie
Q
Jiang
Institute of Enzymology, RCNS, Hungarian Academy of Sciences.
András
A
Váradi
Department of Dermatology, Warren Alpert Medical School of Brown University, Providence, RI ; PXE International, Washington, DC.
Lionel G
LG
Bercovitch
PXE International, Washington, DC.
Sharon F
SF
Terry
Pseudoxanthoma elasticum; ectopic mineralization disorders; generalized arterial calcification of infancy; heritable orphan diseases