Vitamin D-mediated hypercalcemia in slack skin disease: evidence for involvement of extrarenal 25-hydroxyvitamin D 1alpha-hydroxylase.
A case of granulomatous slack skin disease is presented in which we studied the possible involvement of extrarenal 1,25(OH)2D in the pathogenesis of the patient's hypercalcemia. Immunolocalization of 1alpha-OH in skin showed simultaneous dysregulation in epithelial and granulomatous cells.


BACKGROUND
Granuloma-forming diseases such as sarcoidosis are associated with extrarenal synthesis of active 1,25-dihydroxyvitamin D [1,25(OH)2D]. Here we describe a case of granulomatous slack skin disease in which we have studied the possible involvement of extrarenal synthesis of 1,25(OH)2D in the pathogenesis of the patient's hypercalcemia. The aim of the study was to clarify the etiology of hypercalcemia in this patient.


METHODS
This was a case study of a 19-year-old man with a T-cell lymphoproliferative disorder diagnosed as granulomatous slack skin disease who presented with hypercalcemia and raised serum 1,25(OH)2D. Analysis of expression of the enzyme 25-hydroxyvitamin D 1alpha-hydroxylase (1alpha-hydroxylase), which catalyzes synthesis of 1,25(OH)2D, was carried out by immunohistochemical analysis of involved and uninvolved skin. Approval was granted by the Mayo Foundation Institutional Review Board and Biospecimens Subcommittee.


RESULTS
In uninvolved skin, expression of 1alpha-hydroxylase was confined to the basal layer of the epidermis, whereas slack skin showed overexpression of the enzyme in dermal granulomata and basal cells of the epidermis.


CONCLUSIONS
Hypercalcemia associated with granulomatous slack skin syndrome seems to be caused by dysregulation of 1alpha-hydroxylase expression in both epidermal and dermal granulomatous cells. This contrasts with psoriasis and sarcoidosis of the skin, in which overexpression of the enzyme is restricted to keratinocytes and granulomata, respectively.
Karakelides
Helen
H
Department of Endocrinology, Metabolism and Nutrition, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
Geller
Jordan L
JL
Schroeter
Arnold L
AL
Chen
Hong
H
Behn
Philip S
PS
Adams
John S
JS
Hewison
Martin
M
Wermers
Robert A
RA
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism / Q000502:physiology*; D000328:Adult; D006801:Humans; D006934:Hypercalcemia / Q000139:chemically induced* / Q000150:complications* / Q000378:metabolism; D007150:Immunohistochemistry; D016410:Lymphoma, T-Cell, Cutaneous / Q000097:blood* / Q000150:complications*; D008297:Male; D011565:Psoriasis / Q000378:metabolism; D012507:Sarcoidosis / Q000378:metabolism; D014807:Vitamin D / Q000009:adverse effects* / Q000378:metabolism
D014807:Vitamin D; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase