Karakelides Helen, Geller Jordan L, Schroeter Arnold L, Chen Hong, Behn Philip S, Adams John S, Hewison Martin, Wermers Robert A
Department of Endocrinology, Metabolism and Nutrition, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
J Bone Miner Res. 2006 Sep;21(9):1496-9. doi: 10.1359/jbmr.060608.
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.
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.
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.
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.
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.
报告了一例肉芽肿性皮肤松弛症病例，我们研究了肾外1,25(OH)₂D在该患者高钙血症发病机制中的可能作用。皮肤中1α-OH的免疫定位显示上皮细胞和肉芽肿细胞同时出现失调。
诸如结节病等形成肉芽肿的疾病与活性1,25-二羟维生素D[1,25(OH)₂D]的肾外合成有关。在此，我们描述一例肉芽肿性皮肤松弛症病例，我们研究了肾外合成1,25(OH)₂D在该患者高钙血症发病机制中的可能作用。本研究的目的是阐明该患者高钙血症的病因。
这是一项针对一名19岁男性的病例研究，该患者患有T细胞淋巴增殖性疾病，诊断为肉芽肿性皮肤松弛症，伴有高钙血症且血清1,25(OH)₂D升高。通过对受累皮肤和未受累皮肤进行免疫组织化学分析，对催化1,25(OH)₂D合成的25-羟维生素D 1α-羟化酶（1α-羟化酶）的表达进行分析。梅奥基金会机构审查委员会和生物样本小组委员会批准了该研究。
在未受累皮肤中，1α-羟化酶的表达局限于表皮基底层，而松弛皮肤显示该酶在真皮肉芽肿和表皮基底层细胞中过度表达。
与肉芽肿性皮肤松弛综合征相关的高钙血症似乎是由表皮和真皮肉芽肿细胞中1α-羟化酶表达失调引起的。这与皮肤银屑病和结节病形成对比，在银屑病和结节病中，该酶的过度表达分别局限于角质形成细胞和肉芽肿。
