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Activation and anti-microbial effects of vitamin D in macrophages. 1) Circulating 25-hydroxyvitamin-D (25-(OH)D) binds to plasma vitamin D-binding protein and enters macrophage. 2) 25-(OH)D is converted into 1,25-dihydroxyvitamin-D (1,25-(OH) 2 D) by mitochondrial CYP27B1. 3) 1,25-(OH) 2 D binds to vitamin D receptor and enters the nucleus. 4) The vitamin D receptor-1,25-(OH) 2 D complex acts as a transcriptional factor, resulting in the expression of cathelicidins. 5) Cathelicidins are incorporated into phagosomes containing internalized pathogens to function as a bactericidal agent.
Source publication
After the initial description of extrarenal synthesis of 1,25-dihydroxyvitamin D (1,25-(OH)2D) three decades ago, extensive progress has been made in unraveling the immunomodulatory roles of vitamin D in the pathogenesis of granulomatous disorders, including sarcoidosis. It has been shown that 1,25-(OH)2D has dual effects on the immune system, incl...
Contexts in source publication
Context 1
... was shown that intracrine induction of CYP27B1 and VDR by monocytes follows PAMP sensing by TLRs 65 . This interaction results in the production of cathelicidins, a class of host defense peptides that facilitate microbial killing 61,66,67 ( Figure 2). Granuloma formation may result from defects in innate immunity that impair the elimination of inciting antigens 68 . ...
Context 2
... action has been demonstrated through downregulation of TLR2 and TLR4 expression in monocytes 71 and attenuation of T-helper type 1 (Th1) lymphocytes known to increase autoimmune response 64 . The beneficial effects of 1,25-(OH) 2 D are exerted by balancing the proinflammatory cytokines by Th1 cells that produce pro-inflammatory cytokines (including IL-2, IFN-γ, and TNF-α) and Th2 cells that produce anti-inflammatory cytokines (including IL-3, Il-4, IL-5, and IL-10) 61,72-75 ( Figure 2). ...
Citations
... While 25(OH)D levels offer a snapshot of vitamin D status, 1,25(OH) 2 D levels may provide more accurate information about the actual biological activity of vitamin D [42]. Measuring 1,25(OH) 2 D is crucial for diagnosing specific conditions like unexplained PTH-independent hypercalcemia associated with malignancies and granulomatous diseases, where there is an increased conversion to 1,25(OH) 2 D [44], sarcoidosis and pseudo vitamin D deficiency rickets [45,46]. Variations in 1,25(OH) 2 D levels may also indicate genetic mutations causing rare bone diseases like hereditary vitamin D-resistant rickets, vitamin D-dependent rickets, or idiopathic infantile hypercalcemia [46,47]. ...
... Direct effects of sarcoidosis on the calcium metabolism are welldescribed, particularly hypercalcaemia, which is usually due to the increased activity of macrophages, with altered high levels of calcitriol and low levels of 25-hydroxyvitamin D (Gianella et al., 2020). ...
Introduction: Sarcoidosis is a multisystemic granulomatous disease of unknown origin and unpredictable cause, characterized by a dysregulated immune response. If histopathological hallmark is represented by the presence of non-caseating granulomas, clinical manifestations are variable and symptoms are not specific, and they depend on organs affected. Although thoracic involvement (lung and mediastinum) is the most common clinical manifestation, any organ can be virtually affected.
Methods: This paper is structured as a narrative review. A literature search was performed in four electronic databases (Pubmed, Cochrane, Scopus, and Ovid Medline) and Google from inception until February 2023 for relevant studies, meta-analyses, and reviews on corticosteroids’ adverse events in sarcoidosis. English language only papers were included.
Discussion: Although antimetabolites (such as Methotrexate) and immunosuppressant agents can be used as alternative therapy in refractory cases, traditionally systemic glucocorticoids represent the first choice for sarcoidosis treatment. However, their use is still debated, due to potential adverse effects, leading to a wide spectrum of complications particularly in patients who required long-term therapy. Hence, this article aims to provide a comprehensive updated review on the safety profile of glucocorticoid treatment in patients with sarcoidosis and their systemic effects.
Conclusion: corticosteroids remain the first choice in Sarcoidosis, however, due to numerous side effects, dose and duration of treatment should be carefully adjusted and monitored by clinicians.
... Sama kamica nerkowa nie jest przeciwwskazaniem do korekcji niedoboru witaminy D na drodze standardowej suplementacji [37,46]. Rów nież dawne obawy o bezpieczeństwo suplementacji witaminy D u chorych z sarkoidozą nie znajdują potwierdzenia w najnowszych pracach [47]. ...
This review summarises the most recent data on the clinical significance of vitamin D in adult orthopaedics and traumatology. It covers practical aspects of vitamin D supplementation, along with their pathophysiological and epidemiological rationale. Special attention is given to the association between low vitamin D status and worse postoperative outcomes.
... (22) Overproduction of 1,25(OH) 2 D in sarcoidosis and other granulomatous diseases can cause increased osteoclastic bone resorption and hypercalcemia. (55) Increasing 24,25 (OH) 2 D (thereby lowering the 1,25(OH) 2 D:24,25(OH) 2 D ratio) may protect against these effects and therefore warrants investigation. Rather than being a catabolic waste product, 24,25(OH) 2 D may be important for normal bone development and integrity. ...
The relationship between vitamin D metabolites and lower body (pelvis and lower limb) overuse injury is unclear. In a prospective cohort study, we investigated the association between vitamin D metabolites and incidence of lower body overuse musculoskeletal and bone stress injury in young adults undergoing initial military training during all seasons. In 1637 men and 530 women (age, 22.6 ± 7.5 years; BMI, 24.0 ± 2.6 kg∙m-2 ; 94.3% white ethnicity), we measured serum 25-hydroxyvitamin D (25(OH)D) and 24,25-dihydroxyvitamin D (24,25(OH)2 D) by high-performance liquid chromatography tandem mass spectrometry, and 1,25-dihydroxyvitamin D (1,25(OH)2 D) by immunoassay during week 1 of training. We examined whether the relationship between 25(OH)D and 1,25(OH)2 D:24,25(OH)2 D ratio was associated with overuse injury. During 12 weeks training, 21.0% sustained ≥1 overuse musculoskeletal injury, and 5.6% sustained ≥1 bone stress injury. After controlling for sex, BMI, 2.4 km run time, smoking, bone injury history, and Army training course (Officer, standard, or Infantry), lower body overuse musculoskeletal injury incidence was higher for participants within the second lowest versus highest quartile of 24,25(OH)2 D (OR: 1.62 [95%CI 1.13-2.32; P = 0.009]) and lowest versus highest cluster of 25(OH)D and 1,25(OH)2 D:24,25(OH)2 D (OR: 6.30 [95%CI 1.89-21.2; P = 0.003]). Lower body bone stress injury incidence was higher for participants within the lowest versus highest quartile of 24,25(OH)2 D (OR: 4.02 [95%CI 1.82-8.87; P < 0.001]) and lowest versus highest cluster of 25(OH)D and 1,25(OH)2 D:24,25(OH)2 D (OR: 22.08 [95%CI 3.26-149.4; P = 0.001]), after controlling for the same covariates. Greater conversion of 25(OH)D to 24,25(OH)2 D, relative to 1,25(OH)2 D (i.e., low 1,25(OH)2 D:24,25(OH)2 D), and higher serum 24,25(OH)2 D were associated with a lower incidence of lower body overuse musculoskeletal and bone stress injury. Serum 24,25(OH)2 D may have a role in preventing overuse injury in young adults undertaking arduous physical training. This article is protected by copyright. All rights reserved.
... 14 15 Vitamin D attenuates inflammatory immune responses through its downregulation of Th1 lymphocytes. 16 Accordingly, it is inadvisable to forego vitamin D and calcium supplementation when it is indicated. Indeed, our patient's ACE level was noted to come down with vitamin D supplementation. ...
Vitamin D deficiency is relatively common, and its management in patients with sarcoidosis is challenging due to the risk of hypercalcaemia. Our patient had an autologous stem cell transplant for multiple sclerosis and was given high-dose vitamin D concurrently with immunosuppressive therapy. The patient subsequently presented with symptomatic hypercalcaemia and an acute kidney injury. A clinical and biochemical recovery was reached by withdrawing vitamin D and administering intravenous fluids. Interestingly, new evidence suggests that activated vitamin D can actually dampen the inflammatory process in sarcoidosis, and this was reflected in a reduction of our patient's serological markers of sarcoidosis activity. One large study found no significant risk of hypercalcaemia when low doses of vitamin D were used in sarcoidosis. Where indicated, and until clear guidelines are established, we suggest using low doses of vitamin D with cautious monitoring of calcium and renal function.
... Hypersensitivity to vitamin D can develop in people with sarcoidosis and some other lymphatic disorders, causing hypercalcaemia and its complications from exposure to sunshine alone or following supplementation. See the discussion regarding vitamin D and sarcoidosis in this recent review [110]. ...
Vitamin D3 has many important health benefits. Unfortunately, these benefits are not widely known among health care personnel and the general public. As a result, most of the world's population has serum 25-hydroxyvitamin D (25(OH)D) concentrations far below optimal values. This narrative review examines the evidence for the major causes of death including cardiovascular disease, hypertension, cancer, type 2 diabetes mellitus, and COVID-19 with regard to sub-optimal 25(OH)D concentrations. Evidence for the beneficial effects comes from a variety of approaches including ecological and observational studies, studies of mechanisms, and Mendelian randomization studies. Although randomized controlled trials (RCTs) are generally considered the strongest form of evidence for pharmaceutical drugs, the study designs and the conduct of RCTs performed for vitamin D have mostly been flawed for the following reasons: they have been based on vitamin D dose rather than on baseline and achieved 25(OH)D concentrations; they have involved participants with 25(OH)D concentrations above the population mean; they have given low vitamin D doses; and they have permitted other sources of vitamin D. Thus, the strongest evidence generally comes from the other types of studies. The general finding is that optimal 25(OH)D concentrations to support health and wellbeing are above 30 ng/mL (75 nmol/L) for cardiovascular disease and all-cause mortality rate, whereas the thresholds for several other outcomes appear to range up to 40 or 50 ng/mL. The most efficient way to achieve these concentrations is through vitamin D supplementation. Although additional studies are warranted, raising serum 25(OH)D concentrations to optimal concentrations will result in a significant reduction in preventable illness and death.
D Vitamini Kimyasal Yapısı ve Metabolizması Hülya Cenk D Vitamini Ve Genetik Aydın Rüstemoğlu D Vitamininin Normal Serum Düzeyleri, D Vitamin Düzeylerini Etkileyen Faktörler Ve D Vitamini Yetmezliği Sabiye Akbulut Serum D Vitamininin Ölçümü Andaç Uzdoğan, Çiğdem Yücel D Vitamini Biyoyararlanımı ve Doğal Beslenme Kaynakları Atilla Çifci, Halil İbrahim Yakut Sistemik D Vitamini Tedavi Ajanları, Biyoyararlanımı ve Tedavi Yönetimi Işıl Deniz Oğuz Topikal D Vitamini Tedavisi, Tedavi Yönetimi ve Kullanıldığı Hastalıklar Dursun Türkmen Deride D Vitamini Sentezi Mekanizmaları Abdullah Demirbaş, Ömer Faruk Elmas Güneşten Koruyucu Kullanımı ve D Vitamini Nursel Dilek, Yunus Saral D Vitamininin Deri Yapısı ve Fizyolojisine Etkisi Pelin Hızlı Deri Yaşlanması ve D Vitamini Ülker Gül Psoriasis ve D Vitamini Ülker Gül Psöriatik Artrit ve D Vitamini Mehmet Uçar Atopik Dermatit ve D Vitamini Ayşegül Ertuğrul, İlknur Bostancı Mast Hücresi ve Kutanöz Mastositozda D Vitamini Selçuk Doğan, Tülin Çataklı, İlknur Bostancı Ürtiker ve D Vitamini Kemal Özyurt Kaşıntı ve D Vitamini Kübra Yüce Atamulu Likenoid Dermatozlar ve D Vitamini Nihal Altunışık Vitiligo ve D Vitamini Ayşe Akbaş Melasma ve D Vitamini İbrahim Etem Arıca Rozase ve D Vitamini Nalan Saraç Akne ve D Vitamini Selma Korkmaz Hidradenitis Süpürativa ve D Vitamini Yılmaz Ulaş Seboreik Dermatit ve D Vitamini Dilek Başaran Otoimmün Büllöz Hastalıklar ve D Vitamini Sezgi Sarıkaya Solak Bağ Doku Hastalıkları ve D Vitamini Kevser Gök Behçet Hastalığı ve D Vitamini Şule Ketenci Ertaş, Ragıp Ertaş İdiyopatik Fotodermatozlar ve D Vitamini Bülent Nuri Kalaycı İktiyozis ve D Vitamini Tubanur Çetinarslan Epidermolizis Bülloza ve Vitamin D Eda Haşal Kseroderma Pigmentozum, Epidermodisplasia Verrusiformis ve D Vitamini Derya Yayla Nevüsler ve D Vitamini Serpil Şener, Suat Sezer Aktinik Keratoz ve Seboreik Keratozda D Vitamini Mahmut Sami Metin Deri Maliniteleri ve D Vitamini Sevda Önder Vaskülitler ve Vitamin D Havva Hilal Ayvaz Venöz Trombozis ve D Vitamini Cahit Yavuz Yara İyileşmesi ve D Vitamini Bülent Nuri Kalaycı Diyabetik Ayak Ülseri ve D Vitamini Gözde Ulutaş Demirbaş, Abdullah Demirbaş Granülomatöz Hastalıklar ve D Vitamini Selma Bakar Dertlioğlu Deri Enfeksiyonları ve Vitamin D Atıl Avcı Oral Mukoza Hastalıkları ve D Vitamini Ali İhsan Güleç Tırnak Sağlığı ve Hastalıklarında D Vitamini Hülya Cenk Alopesiler ve D Vitamini Munise Daye Hirsutizm ve D Vitamini Efşan Gürbüz Yontar Sistemik Kortikosteroid Kullanımında D Vitamini Desteği Selma Korkmaz Fototerapi ve D Vitamini Tuğba Özkök Akbulut Covıd-19 Ve Vitamin D Sibel Altunışık Toplu D Vitamini Tedavisinin Yan Etkileri ve D Vitamini Tedavisi Sürecinde Dikkat Edilecek Hususlar Dursun Türkmen, Nihal Altunışık D Vitamini Ve İlaç İlaç Etkileşimleri Şule Gökşin D Vitamini İntoksikasyonu Bedriye Müge SÖNMEZ
Acute calcium, phosphorus, or magnesium metabolic disturbances are rare. However, without accurate knowledge, clinicians cannot provide appropriate treatment. I aimed to perform a review to summarize the differences in symptoms depending on the severity of electrolyte imbalances, the causes, timing of clinically necessary interventions even in asymptomatic patients, and precautions to be observed when administering injectable drugs. Due to the increase in therapeutic drugs for various diseases and the elucidation of novel associated pathologies, the chances of encountering electrolyte disorders are increasing. Thus, knowledge of the electrolyte imbalances, appropriate collection of urine and blood samples for accurate diagnosis, and treatment are important for all clinicians.
Sarcoidosis is a chronic granulomatous disease that affects multiple organs systems in the body with unknown cause. Most of the patients are free of clinical symptom, sarcoidosis should be considered in differential diagnosis if non-caseous granuloma is noted in biopsies. Here we present a case of sarcoidosis related hypercalcemia due to increased level of 1,25-dihydroxyvitamin D level that increases the absorption of calcium from intestine.
Sarcoidosis is a multisystem disorder of unknown etiology characterized by accumulation of granulomas in affected tissue. Cutaneous manifestations are among the most common extrapulmonary manifestations in sarcoidosis and can lead to disfiguring disease requiring chronic therapy. In many patients, skin disease may be the first recognized manifestation of sarcoidosis, necessitating a thorough evaluation for systemic involvement. Although the precise etiology of sarcoidosis and the pathogenic mechanisms leading to granuloma formation, persistence, or resolution remain unclear, recent research has led to significant advances in our understanding of this disease. This article reviews recent advances in epidemiology, sarcoidosis clinical assessment with a focus on the dermatologist's role, disease pathogenesis, and new therapies in use and under investigation for cutaneous and systemic sarcoidosis.
