Vitamin D–Mediated Hypercalcemia in Slack Skin Disease: Evidence for Involvement of Extrarenal 25-Hydroxyvitamin D 1α-Hydroxylase

Abstract

Results: In uninvolved skin, expression of 1␣-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 1␣-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.

Hypercalcemia Induced by Rosai-Dorfman Disease in a Hemodialysis Patient: Histological Evidence of Extrarenal Calcitriol Overproduction

“…Taken together, the histological results confirmed the diagnosis of RDD, also called sinus histiocytosis with massive lymphadenopathy (6). An additional immunohistochemical analysis identified that the Rosai-Dorfman cells (recruited histiocytes) were positive for 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1, SC-67261, Santa Cruz Biotechnology, Inc., Dallas, USA), a rate-limiting enzyme that catalyzes the conversion of 25-hydroxyvtamin D into calcitriol (Fig.…”

“…Sarcoidosis, tuberculosis, leprosy, berylliosis and Crohn's disease are well-known granulomatous disorders associated with hypercalcemia (4,5). In these disorders, macrophage-lineage cells express 25-hydroxyvitamin D-1α-hydroxylase, leading to the overproduction of calcitriol in the extrarenal lesions; the negative feedback of calcitriol is disrupted in these cases (6,12,13). Glucocorticoid treatment is effective because it suppresses the 25-hydroxyvitamin D-1α-hydroxylase expression in macrophage-lineage cells by inhibiting interferon-gamma production, leading to the amelioration of hypercalcemia via a reduction in the level of serum calcitriol (12)(13)(14)(15) In the present case, the serum calcitriol level was relatively high compared to that observed in chronic dialysis patients; the mean serum calcitriol level in anuric hemodialysis patients has been shown to be 5.5±2.4 pg/mL (16).…”

“…In relatively rare situations, hypercalcemia accompanies granulomatous disease, including sarcoidosis, tuberculosis and Crohn's disease (3,4). In some cases, an elevated serum calcitriol level is noted and the extrarenal overproduction of calcitriol in granulomatous tissue is histologically confirmed (5,6).…”

Russian Association of Endocrinologists recommendations for diagnosis, treatment and prevention of vitamin D deficiency in adults

“…Также некоторые лекар-ственные препараты оказывают значимое влияние на метаболизм витамина D в организме и связаны с его повышенной деградацией в неактивные формы [43]. Напротив, при хронических гранулематозных заболеваниях и первичном гиперпаратиреозе на-блюдается повышенное превращение 25(ОН)D в 1,25(ОН) 2 D, что приводит к повышенному расходу запасов витамина [3,44,45].…”

Calcitriol-induced hypercalcemia in a patient with granulomatous mycosis fungoides and end-stage renal disease

“…There are various subtypes and variants in mycosis fungoides, and granulomatous mycosis fungoides and granulomatous slack skin disease are rare subtypes with granuloma formation [1,6] . To the best of our knowledge, only one case of hypercalcemia induced by elevated calcitriol has been reported in granulomatous slack skin disease [7] , but there have been no reports of hypercalcemia associated with granulomatous mycosis fungoides. A patient with calcitriol-induced hypercalcemia possibly in association with granulomatous mycosis fungoides and end-stage renal disease (ESRD) is reported.…”