Etty Bachar-Wikström, Jakob D. Wikström
DOI: 10.2340/00015555-3770

Darier disease is a severe, rare autosomal dominant inherited skin condition caused by mutations in the ATP2A2 gene encoding sarcoendoplasmic reticulum Ca2+-ATPase isoform 2 in the endoplasmic reticulum. Since sarcoendoplasmic reticulum Ca2+-ATPase isoform 2 is expressed in most tissues, and intracellular calcium homeostasis is of fundamental importance, it is conceivable that other organs besides the skin may be involved in Darier disease. This review focusses on the association of Darier disease with other organ dysfunctions and diseases, emphasizing their common molecular pathology. In conclusion, Darier disease should be considered a systemic condition that requires systemic and disease mechanism targeted treatments.

While research on the systemic aspects of Darier disease is still in its infancy, it is becoming clear that Darier disease is a multi-organ systemic condition. This not surprising, considering the overwhelming experimental evidence of the importance of sarcoendoplasmic reticulum Ca2+-ATPase isoform 2 in physiology and pathophysiology. While more data is needed, treating physicians should be aware of the risk of extracutaneous manifestations of Darier disease. Future research would benefit from more registry studies, as well as from systemic large-scale Darier disease cohort studies, in order to examine associations as well as to find direct experimental evidence of other organ dysfunctions and diseases.