calcitriol and Sarcoidosis

The synthesis of vitamin D is altered by the granulomatous inflammation of sarcoidosis leading to increased production of 1, 25-dihydroxyvitamin D. Mounting evidence suggests that vitamin D is an immunomodulating hormone that inhibits both antigen presentation by cells of the innate immune system, and the cytokine release and proliferation of Th1 cells. These and other extraskeletal health benefits have led to an increase in vitamin D assessment and pharmacological supplementation in the general population. This review highlights the altered synthesis and general immunomodulating properties of vitamin D with a special emphasis on known interactions with sarcoidosis. In addition, the assessment of vitamin D nutritional status, its pharmacological supplementation, and the management of bone health in patients with sarcoidosis are reviewed.

Topics: Animals; Bone and Bones; Calcium; Cell Proliferation; Cytokines; Humans; Nutritional Status; Sarcoidosis; Th1 Cells; Vitamin D

Hypercalcemia is a highly prevalent complication of sarcoidosis. A medical history of a patient with sarcoidosis is shown as case report. Depending on the population studied about 2-63% of sarcoidosis patients show hypercalcemia. The major difference in the prevalence of hypercalcemia may be in part due to the undulating course of subacute sarcoidosis, so hypercalcemia may be missed when serum calcium is not frequently measured. Hypercalciuria appears to be twice as prevalent then hypercalcemia and should be looked for in every sarcoidosis patient. Hypercalcemia in sarcoidosis is due to the uncontrolled synthesis of 1,25-dihydroxyvitamin D3 by macrophages. 1,25-dihydroxyvitamin D3 leads to an increased absorption of calcium in the intestine and to an increased resorption of calcium in the bone. Immunoregulatory properties have been ascribed to 1,25-dihydroxyvitamin D3. It is an important inhibitor of interleukin-2 and of interferon-gamma-synthesis, two cytokines that are important in granuloma formation in sarcoidosis. It is thought that 1,25-dihydroxyvitamin D3 counterregulates uncontrolled granuloma formation. Treatment of hypercalcemia depends on the serum level of hypercalcemia and its persistence. Generally sarcoidotic patients should be advised to avoid sun exposition to reduce vitamin D3 synthesis in the skin, to omit fish oils that are rich of vitamin D and to produce more than two liters urine a day by adapting fluid intake. Although severe hypercalcemia seems to be rare, glucocorticosteroid treatment should be started if corrected total calcium level rises beyond 3 mmol/l. If hypercalcemia is symptomatic, treatment should be started even at lower levels. Glucocorticosteroids act by inhibition of the overly 1alpha-hydroxylase activity of macrophages. Alternatively, treatment with chloroquine or ketoconazole can be established. If isolated hypercalciuria without hypercalcemia is present with evidence for recurrent nephrolithiasis, patients can be treated with a thiazide diuretic.

Topics: Aged; Calcitriol; Calcium; Cross-Sectional Studies; Dose-Response Relationship, Drug; Female; Fluid Therapy; Humans; Hypercalcemia; Hypercalciuria; Kidney Failure, Chronic; Macrophages; Nephrocalcinosis; Parathyroid Hormone; Prednisone; Risk Factors; Sarcoidosis; Vitamin D

From time to time there have been reports of autoimmune disease succumbing to tetracycline antibiotics, but many have assumed this was due to coincidence, or to some ill-defined 'anti-inflammatory property' of the tetracyclines. But now the inflammation of sarcoidosis has succumbed to antibiotics in two independent studies. This review examines the cell wall deficient (antibiotic resistant) bacteria which have been found in tissue from patients with sarcoidosis. It examines how such bacteria can infect the phagocytes of the immune system, and how they may therefore be responsible for not only sarcoid inflammation, but also for other autoimmune disease. Proof positive of a bacterial pathogenesis for Sarcoidosis includes not only the demonstrated ability of these studies to put the disease into remission, but also the severity of Jarisch-Herxheimer shock resulting from endotoxin release as the microbes are killed. Studies delineating the hormone responsible for phagocyte differentiation in the Th1 immune response, 1,25-dihydroxyvitamin D, are discussed, and its utility as a marker of Th1 immune inflammation is reviewed. Finally, data showing that the behavior of this hormone is also aberrant in rheumatoid arthritis, systemic lupus erythematosus, and Parkinson's, raise the possibility that these diseases may also have a CWD bacterial pathogenesis.

Topics: Animals; Anti-Bacterial Agents; Arthritis, Rheumatoid; Autoimmune Diseases; Bacteria; Doxycycline; Forecasting; Humans; Lupus Erythematosus, Systemic; Minocycline; Parkinson Disease; Phagocytes; Sarcoidosis; Secondary Prevention; Tetracyclines; Vitamin D

While several case reports suggest an association between sarcoidosis and multiple myeloma (MM), few cases involve smoldering MM. We report a case of sarcoidosis and smoldering MM discovered simultaneously in a patient admitted for hypercalcemia. Initial tests raised suspicion for sarcoidosis and MM, prompting invasive testing. Surgical lung biopsy revealed necrotizing granulomas, which could represent sarcoidosis in the appropriate setting. Thus, sarcoidosis was diagnosed following a negative infectious workup. Bone marrow biopsy revealed 13% plasma cells leading to subsequent diagnosis of smoldering MM. This case demonstrates the challenge of determining disease activity when other causes of CRAB symptoms are present.

Topics: Humans; Hypercalcemia; Male; Middle Aged; Sarcoidosis; Smoldering Multiple Myeloma; Vitamin D

Americans are increasingly receiving vitamin D supplementation, often based on low-measured 25-hydroxy-vitamin D (25-OH-vit D). In sarcoidosis, there is often increased metabolism of 25-OH-vit D to 1,25-dihydroxy-vitamin D (1,25-OH-vit D), so 25-OH-vit D may remain low, despite high levels of 1,25-OH-vit D. In such cases, vitamin D supplementation may lead to hypercalcemia.. We randomly selected 196 patients with sarcoidosis who received at least 1 prescription of vitamin D between 2005 and 2011 and 196 control patients. Primary outcome was the incidence of hypercalcemia during the 2 years following the vitamin D prescription. A secondary outcome was the proportion of patients who had received vitamin D prescriptions and who had adequate blood work performed before the prescription.. The 25-OH-vit D and 1,25-OH-vit D levels were measured in only 70% and 23%, respectively, of those receiving supplementation. Hypercalcemia was noted more frequently in the group that received vitamin D (42.3%) as compared with the nonsupplemented group (18.3%), P < 0.0001. Patients who received a vitamin D prescription developed moderate and severe hypercalcemia more frequently (12.8%) as compared to the group that did not receive vitamin D (3.6%), P = 0.001. In multivariate analysis, having a prescription for vitamin D increased the risk of developing hypercalcemia to approximately 2-fold. The risk of developing hypercalcemia (odds ratio = 4.1) was increased with renal failure.. Our study demonstrates that a substantial proportion of patients with sarcoidosis who receive vitamin D are not getting appropriate pretesting. This increases their risk for developing hypercalcemia.

Topics: Calcium; Dietary Supplements; Dose-Response Relationship, Drug; Female; Humans; Hypercalcemia; Male; Middle Aged; Retrospective Studies; Sarcoidosis; Vitamin D

A bone biopsy specimen in a long-term hemodialysis patient with sarcoidosis coexisting with severe hypoparathyroidism has demonstrated that a persistent near physiological level of 1,25-dihydroxyvitamin D3 contributes to the preservation of bone remodeling and has the potential to retard the development of vascular calcification and atherosclerosis. Sarcoidosis-related hypercalcemia and hypoparathyroidism, which is characterized by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) overproduction, is rarely seen in hemodialysis patients. Herein, we describe a 60-year-old Japanese woman on hemodialysis for 35 years who presented with malaise and hypercalcemia. Severe hypoparathyroidism without parathyroidectomy and a preserved 1,25(OH)2D3 level were detected. Computed tomography showed bilateral axillary lymphadenopathy and minimal aortic and soft tissue calcification. The axillary node biopsy led to a definite diagnosis of sarcoidosis. A bone biopsy specimen obtained from the right iliac crest showed remodeling of normal lamellar bone with scalloped cement lines and clear double labeling by tetracycline on fluorescence microscopy. Histomorphometric analysis revealed that the bone formation rate was preserved (30.0 %/year), together with a decrease of osteoid volume (5.75 %) and fibrous volume (0 %), indicating that the patient did not have adynamic bone disease and only showed mild disease. This is the first documented case of sarcoidosis-related hypercalcemia associated with severe hypoparathyroidism in a long-term hemodialysis patient who underwent bone histomorphometry. Our findings suggest that, in hemodialysis patients with sarcoidosis coexisting with severe hypoparathyroidism, a persistent near physiological level of 1,25(OH)2D3 contributes to the preservation of bone remodeling and has the potential to retard the development of vascular calcification and atherosclerosis.

Topics: Bone and Bones; Bone Remodeling; Female; Humans; Hypercalcemia; Hypoparathyroidism; Middle Aged; Renal Dialysis; Sarcoidosis; Vitamin D

Sarcoidosis is a multi-system disorder characterized by non-caseating epithelioid granulomas in multiple organs. Renal involvement may usually occur as granulomatous interstitial nephritis, but renal failure is uncommon. We report a case of renal-limited sarcoidosis diagnosed by renal biopsy, associated with abnormal calcium metabolism.. A 30-year-old Caucasian male presented with unexplained renal function impairment and hypercalcemia. The patient did not have any history of kidney disease, cough, skin rash, dysuria, hematuria or any other symptoms. Physical examination was unremarkable. Serum creatinine was 2.2 mg/dl and serum calcium was 11.5 mg/dl. Serum intact parathyroid hormone level (12 pg/mL) was decreased. Serum angiotensin-converting enzyme (ACE), 1,25-dihydroxyvitamin D (1,alpha-25 vit D) and pre-proparathyroid hormone (PTHrP) levels and urinary calcium excretion were all in normal range. The renal biopsy showed severe interstitial nephritis with non-caseating granuloma. The patient was treated with prednisone with starting dose of 1 mg/kg. After 2 months of prednisone therapy, serum creatinine decreased. However, because of continued of hypercalcemia unresponsive to low calcium diet and prednisone, chloroquine was prescribed. Six months after the onset, the patient's serum creatinine is stable at 1.30 mg/dl, serum calcium is 10.8 mg/dl, and serum ACE and 1,alpha-25 vit D levels are in normal range. He does not have any signs of extra-renal relapse.. The mechanisms of abnormal calcium metabolism in this patient with renal-limited sarcoidosis are unclear.

Topics: Adult; Biopsy; Humans; Hypercalcemia; Kidney; Kidney Diseases; Male; Sarcoidosis; Vitamin D

Profound hypercalcemia is usually due to underlying malignancy.. We describe a case of granulomatous myositis presenting with extreme hypercalcemia of 20.1 mg/dl and generalized weakness that did not resolve despite rapid correction of serum calcium. The disease process was unmasked by cholecalciferol supplementation. Initial search for a malignant process yielded no diagnosis, but an elevated 1,25-dihydroxyvitamin D level, in the setting of a suppressed PTH and undetectable PTHrP, pointed to the presence of excessive 1α-hydroxylase activity.. Biopsy of the vastus lateralis muscle showed extensive granulomatous myositis. Immunohistochemical staining for 1α-hydroxylase was localized to the multinucleated giant cells and histiocytes. Musculoskeletal magnetic resonance imaging showed involvement of proximal muscle groups of both thighs and upper limbs.. Measurement of vitamin D metabolites is pivotal in diagnosing 1,25-dihydroxyvitamin D-mediated hypercalcemia. Granulomatous disease can occasionally cause profound hypercalcemia and needs to be considered in the differential diagnosis. 1,25-Dihydroxyvitamin D-mediated hypercalcemia is responsive to glucocorticoid therapy.

Topics: Aged; Female; Granuloma; Humans; Hypercalcemia; Myositis; Sarcoidosis; Vitamin D

Topics: Calcifediol; Clinical Laboratory Techniques; Diagnosis, Differential; Dietary Supplements; Ergocalciferols; Humans; Malabsorption Syndromes; Osteoporosis; Polymorphism, Genetic; Receptors, Calcitriol; Reference Values; Renal Insufficiency; Sarcoidosis; Sunscreening Agents; Vitamin D; Vitamin D Deficiency

PTH is excessively secreted to develop hypercalcemia and accelerate bone turnover in patients with primary hyperparathyroidism. PTH stimulates the production of 1,25-dihydroxyvitamin D [1,25(OH)2D] that in turn suppresses the synthesis of PTH in parathyroid cells.. The objective of the study was to clarify whether 1,25(OH)2D indeed inhibits circulating levels of PTH and influences bone turnover, even in a patient with primary hyperparathyroidism.. We evaluated PTH levels in a patient with primary hyperparathyroidism and coexistent sarcoidosis whose serum 1,25(OH)2D levels were independent of PTH.. The present case was treated with prednisolone before and after surgical resection of parathyroid adenoma, and Ca-regulating hormones and bone markers were measured.. Serum Ca and PTH levels significantly decreased after parathyroid surgery, whereas serum 1,25(OH)2D levels remained high. Prednisolone administration promptly decreased serum 1,25(OH)2D levels and reciprocally increased PTH levels despite consistent serum Ca levels either before or after surgery. PTH levels were negatively correlated with serum 1,25(OH)2D levels before and after surgery. Urine N-telopeptides, serum osteocalcin, and bone-type alkaline phosphatase all decreased to physiological ranges after parathyroid surgery.. These results suggest that 1,25(OH)2D indeed inhibits the production of PTH not to exacerbate hypercalcemia in a patient with primary hyperparathyroidism. Furthermore, PTH but not 1,25(OH)2D may primarily be involved in the stimulation of bone turnover.

Topics: Aged; Biomarkers; Bone and Bones; Calcium; Female; Hormones; Humans; Hyperparathyroidism, Primary; Osmolar Concentration; Parathyroid Hormone; Sarcoidosis; Vitamin D

Measurement of serum 1,25-dihydroxyvitamin D levels is important for diagnosis of various calcium metabolism disorders. Conventional assays for 1,25-dihydroxyvitamin D employed specific 1,25-dihydroxyvitamin D receptor as binding site for the ligand and thus, biologically active 1,25-dihydroxyvitamin D ligand, which is labeled with 3H, was required. Usage of 3H made assays cumbersome works. A new assay which uses specific antibody as the binding site and the radioligand labeled with 125I is now available as a commercial kit. Using these kits, we first studied basically the reproducibility, recovery, cross-reactivity and comparison with conventional assays. All of those results were satisfactory. Secondly, we measured clinically in 111 healthy adults and in patients with various disorders such as renal failure, primary hyperparathyroidism, hypoparathyroidism and sarcoidosis. This newly available kit for measurement of circulating 1,25-dihydroxyvitamin D is proved to be useful in clinical evaluation of calcium metabolic disorders.

Topics: Acute Kidney Injury; Adult; Aged; Binding Sites; Calcium; Female; Humans; Hyperparathyroidism; Hypoparathyroidism; Male; Middle Aged; Radioimmunoassay; Radioligand Assay; Sarcoidosis; Vitamin D

We report a case of a female patient with sarcoidosis who presented with a generalized lymphadenopathy and a strong IgG serological test of toxoplasmosis. Progressive lymphadenopathy with a rising plasma calcium (up to 15 mg dL-1) with a normal plasma 1,25-dihydroxy vitamin D concentration occurred later. Corticosteroid therapy resulted in prompt clinical and biochemical responses with normalization of plasma calcium and a significant reduction in 1,25-dihydroxy vitamin D concentration. This is an exceptional presentation of sarcoidosis with severe hypercalcaemia and normal vitamin D metabolites.

Topics: Adult; Diagnosis, Differential; Female; Humans; Hypercalcemia; Lymphatic Diseases; Sarcoidosis; Toxoplasmosis; Vitamin D