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Medicina 2017Calciphylaxis is vasculopathy characterized by ischemia and painful skin necrosis due to calcification and intimal fibroplasia of thrombosis of the panicular arterioles....
Calciphylaxis is vasculopathy characterized by ischemia and painful skin necrosis due to calcification and intimal fibroplasia of thrombosis of the panicular arterioles. It most frequently compromises patients with terminal chronic renal failure and has a high mortality rate. Biopsy of skin lesions is used as a diagnostic method. No specific laboratory findings have been recorded. Skin lesions usually begin in the extremities like a painful purplish mottling similar to "livedo reticularis". The natural evolution is to ulcers and bedsores. The first line of treatment involves the care of skin lesions and antibiotic therapy. Sodium thiosulfate is used as treatment due to its antioxidant activity and as a chelating. Two clinical cases are here reported.
Topics: Adult; Calciphylaxis; Combined Modality Therapy; Debridement; Female; Humans; Kidney Failure, Chronic; Middle Aged
PubMed: 28825580
DOI: No ID Found -
Current Opinion in Rheumatology Nov 2022The aim of this study was to provide updated information on the prevalence, pathogenesis, diagnostics and therapeutics of calcinosis cutis associated with systemic... (Review)
Review
PURPOSE OF REVIEW
The aim of this study was to provide updated information on the prevalence, pathogenesis, diagnostics and therapeutics of calcinosis cutis associated with systemic sclerosis (SSc).
RECENT FINDINGS
Observational studies show ethnic and geographical differences in the prevalence of calcinosis. In addition to clinical and serological associations, biochemical studies and in-vivo models have attempted to explain theories behind its pathogenesis, including prolonged state of inflammation, mechanical stress, hypoxia and dysregulation in bone and phosphate metabolism. Long-term use of proton pump inhibitors may increase the risk for calcinosis in SSc. Few single-centre observational studies have shown mild benefit with minocycline and topical sodium thiosulfate.
SUMMARY
Calcinosis cutis is the deposition of insoluble calcium in the skin and subcutaneous tissues. It affects up to 40% of SSc patients and causes significant morbidity. Long disease duration, features of vascular dysfunction and osteoporosis have been associated with calcinosis. Altered levels of inorganic pyrophosphate and fibroblast growth factor-23 have been implicated in dysregulated phosphate metabolism that may lead to calcinosis in SSc. Plain radiography can help with diagnosis and quantifying the calcinosis burden. Surgical treatment remains the most effective therapy when feasible. At present, no medical therapies have proven efficacy in large randomized controlled trials.
Topics: Calcinosis; Calcium; Diphosphates; Humans; Minocycline; Proton Pump Inhibitors; Scleroderma, Systemic
PubMed: 35993867
DOI: 10.1097/BOR.0000000000000896 -
Actas Dermo-sifiliograficas Dec 2015Calcinosis cutis (CC) is defined as the deposition of calcium salts in the skin. The condition is divided into 5 types: calciphylaxis and dystrophic, metastatic,... (Review)
Review
Calcinosis cutis (CC) is defined as the deposition of calcium salts in the skin. The condition is divided into 5 types: calciphylaxis and dystrophic, metastatic, idiopathic, and iatrogenic CC. Dystrophic CC is the most common form and usually occurs in association with autoimmune diseases. CC can be treated surgically or with the use of drugs such as diltiazem, bisphosphonates, warfarin, ceftriaxone, probenecid, minocycline, or aluminum hydroxide. Calciphylaxis is defined as calcification of the media of small- and medium-sized blood vessels in the dermis and subcutaneous tissue. Clinically, calciphylaxis causes livedo racemosa, which progresses to retiform purpura and skin necrosis. First-line treatment is with sodium thiosulfate. We present a review of the calcifying disorders of the skin, focusing on their diagnosis and treatment.
Topics: Autoimmune Diseases; Calcinosis; Calciphylaxis; Calcium; Collagen Diseases; Diagnostic Imaging; Humans; Iatrogenic Disease; Phosphorus; Skin Diseases; Skin Diseases, Parasitic; Thiosulfates
PubMed: 26394755
DOI: 10.1016/j.ad.2015.09.001 -
Ugeskrift For Laeger Jan 2024Calciphylaxis is a rare condition characterised by painful necroses due to microvascular calcifications. It primarily affects individuals with end-stage renal disease...
Calciphylaxis is a rare condition characterised by painful necroses due to microvascular calcifications. It primarily affects individuals with end-stage renal disease and affected calcium-phosphate metabolism. This is a case report of a 55-year-old woman with end-stage renal disease who developed a necrotic ulcer at the breast due to calciphylaxis. Although treated with sodium thiosulfate and hyperbaric oxygen, the ulcer progressed and multiple necrotic calciphylaxis ulcers appeared. The treatment options and wound management are discussed while focusing on indications for surgical debridement.
Topics: Female; Humans; Middle Aged; Calciphylaxis; Calcium; Kidney Failure, Chronic; Ulcer
PubMed: 38235723
DOI: 10.61409/V08230540 -
JAMA Dermatology Mar 2017Classic calciphylaxis associated with renal failure is a life-threatening disease. Warfarin-associated calciphylaxis without renal injury has been described, but whether... (Review)
Review
IMPORTANCE
Classic calciphylaxis associated with renal failure is a life-threatening disease. Warfarin-associated calciphylaxis without renal injury has been described, but whether it is a subset of classic calciphylaxis or a different entity remains unknown. We describe 1 case of warfarin-associated calciphylaxis, present data from 2 others from our institution, and review all cases of warfarin-associated calciphylaxis available in the literature. Our review indicates that warfarin-associated calciphylaxis is clinically and pathophysiologically distinct from classic calciphylaxis.
OBJECTIVE
To review warfarin-associated calciphylaxis and determine its relationship to classic calciphylaxis.
DESIGN, SETTING, AND PARTICIPANTS
We searched MEDLINE and Ovid without language or date restrictions for case reports of calciphylaxis from the inpatient setting using the terms "calciphylaxis and warfarin," "non-uremic calciphylaxis," and "nonuremic calciphylaxis." We defined nonuremic calciphylaxis as a histopathologic diagnosis of calciphylaxis without severe kidney disease (serum creatinine level >3 mg/dL; glomerular filtration rate <15 mL/min; acute kidney injury requiring dialysis; and renal transplantation).
EXPOSURES
Each patient had been exposed to warfarin before the onset of calciphylaxis.
MAIN OUTCOMES AND MEASURES
Patient data were abstracted from published reports. Original patient medical records were requested and reviewed when possible.
RESULTS
We identified 18 patients with nonuremic calciphylaxis, 15 from the literature, and 3 from our institution. Patients were predominantly female (15 of 18 [83%]) with ages ranging from 19 to 86 years. Duration of warfarin therapy prior to calciphylaxis onset averaged 32 months. Lesions were usually located below the knees (in 12 of 18 [67%]). No cases reported elevated calcium-phosphate products (0 of 17 [0%]). Calcifications were most often noted in the tunica media (n = 8 [44%]) or in the vessel lumen and tunica intima (n = 7 [39%]). The most common treatments included substitution of heparin or low-molecular weight heparin for warfarin (n = 13 [72%]), intravenous sodium thiosulfate (n = 9 [50%]), and hyperbaric oxygen (n = 3 [17%]). The survival rate on hospital discharge was remarkably high, with 15 cases (83%) reporting full recovery and 3 cases ending in death.
CONCLUSIONS AND RELEVANCE
Warfarin-associated calciphylaxis is distinct from classic calciphylaxis in pathogenesis, course, and, particularly, outcome. This finding should influence clinical management of the disease and informs targeted treatment of the disease.
Topics: Anticoagulants; Calciphylaxis; Female; Humans; Leg Ulcer; Livedo Reticularis; Purpura; Warfarin
PubMed: 28099971
DOI: 10.1001/jamadermatol.2016.4821 -
Paediatrics & Child Health Jul 2023The past two decades have seen enormous advancements in medical knowledge around the role of genetic factors of variability, both in human disease and drug response.... (Review)
Review
The past two decades have seen enormous advancements in medical knowledge around the role of genetic factors of variability, both in human disease and drug response. This knowledge is increasingly being translated into guidelines that inform drug dosing, monitoring for efficacy and safety, and determining the suitability of specific agents to treat patients. Health Canada and the U.S. Food and Drug Administration have recommended using genetic information to guide dosing for more than 20 drugs. There are no current, comprehensive paediatric guidelines to assist health care professionals in the use of genetics to inform medication dosing, safety, and efficacy in children, and such guidance is urgently needed. This statement helps to guide clinician understanding of the role of pharmacogenetics and how to use this information when prescribing medications in paediatrics.
PubMed: 37287477
DOI: 10.1093/pch/pxad002 -
Cell Stress & Chaperones Sep 2020Near the end of 2019, SARS-CoV-2, a novel highly contagious coronavirus phylogenetically related to the SARS virus, entered the human population with lethal...
Near the end of 2019, SARS-CoV-2, a novel highly contagious coronavirus phylogenetically related to the SARS virus, entered the human population with lethal consequences. This special issue devoted to the resulting disease COVID-19 was not planned but instead the articles accumulated organically as researchers in the cell stress response field noticed similarities among the pathophysiology of COVID-19 infections and the responses that they studied in contexts unrelated to viral infection. We preface the issue with an introductory article which begins with a brief review of the structure and biology of SARS-CoV-2. As we collected and compared the COVID-19 articles, several shared themes emerged. In the second part of the introduction, each article is summarized briefly and the common themes that link each into a spontaneously arising chain of ideas and hypotheses are emphasized. These themes include growing evidence of molecular mimicry among the viral proteins and the proteins of patients. The realization that much of the consequences of such immune mimicry may play out on the plasma membrane of vascular endothelial cells raised the specter of autoimmune-induced vascular endothelial damage in multiple organs. Proposals of new therapeutic approaches have coalesced around the theme of inducing protection of the vascular endothelium. New chemical treatments that are proposed include stannous chloride, inducers of the gasotransmitter hydrogen sulfide such as sodium thiosulfate and inducers of the cytoprotective stress protein heme oxygenase. Oxygen delivered by ventilators is already in extensive use to provide life support for patients with severe COVID-19. Two articles propose to advance the use of oxygen to the level of a therapeutic treatment early in the detection of the virus in infected patients by delivering oxygen under elevated pressure in hyperbaric chambers. At elevated blood plasma concentrations, hyperbaric oxygen is capable of achieving results far beyond the capability of ventilators as it promotes the activation of transcription factors that control the establishment of inducible cellular defense systems.
Topics: COVID-19; Coronavirus; Coronavirus Infections; Endothelial Cells; Humans; Oxygen; Pandemics; Pneumonia, Viral; Viral Proteins
PubMed: 32889638
DOI: 10.1007/s12192-020-01155-4 -
Free Radical Biology & Medicine Aug 2023Ischemia-reperfusion injury is a critical liver condition during hepatic transplantation, trauma, or shock. An ischemic deprivation of antioxidants and energy...
Ischemia-reperfusion injury is a critical liver condition during hepatic transplantation, trauma, or shock. An ischemic deprivation of antioxidants and energy characterizes liver injury in such cases. In the face of increased reactive oxygen production, hepatocytes are vulnerable to the reperfusion driving ROS generation and multiple cell-death mechanisms. In this study, we investigate the importance of hydrogen sulfide as part of the liver's antioxidant pool and the therapeutic potency of the hydrogen sulfide donors sodium sulfide (NaS, fast releasing) and sodium thiosulfate (STS, NaSO, slow releasing). The mitoprotection and toxicity of STS and NaS were investigated on isolated mitochondria and a liver perfusion oxidative stress model by adding text-butyl hydroperoxide and hydrogen sulfide donors. The respiratory capacity of mitochondria, hepatocellular released LDH, glutathione, and lipid-peroxide levels were quantified. In addition, wild-type and cystathionine-γ-lyase knockout mice were subjected to warm selective ischemia-reperfusion injury by clamping the main inflow for 1 h followed by reperfusion of 1 or 24 h. A subset of animals was treated with STS shortly before reperfusion. Glutathione, plasma ALT, and lipid-peroxide levels were investigated alongside mitochondrial changes in structure (electron microscopy) and function (intravital microscopy). Liver tissue necrosis quantified 24 h after reperfusion indicates the net effects of the treatment on the organ. STS refuels and protects the endogenous antioxidant pool during liver ischemia-reperfusion injury. In addition, STS-mediated ROS scavenging significantly reduced lipid peroxidation and mitochondrial damage, resulting in better molecular and histopathological preservation of the liver tissue architecture. STS prevents tissue damage in liver ischemia-reperfusion injury by increasing the liver's antioxidant pool, thereby protecting mitochondrial integrity.
Topics: Mice; Animals; Antioxidants; Hydrogen Sulfide; Reactive Oxygen Species; Chemical and Drug Induced Liver Injury, Chronic; Liver; Reperfusion Injury; Ischemia; Glutathione; Peroxides; Reperfusion; Lipids
PubMed: 37105418
DOI: 10.1016/j.freeradbiomed.2023.04.012 -
International Journal of Molecular... Jun 2021Thiosulfate in the form of sodium thiosulfate (STS) is a major oxidation product of hydrogen sulfide (HS), an endogenous signaling molecule and the third member of the... (Review)
Review
Thiosulfate in the form of sodium thiosulfate (STS) is a major oxidation product of hydrogen sulfide (HS), an endogenous signaling molecule and the third member of the gasotransmitter family. STS is currently used in the clinical treatment of acute cyanide poisoning, cisplatin toxicities in cancer therapy, and calciphylaxis in dialysis patients. Burgeoning evidence show that STS has antioxidant and anti-inflammatory properties, making it a potential therapeutic candidate molecule that can target multiple molecular pathways in various diseases and drug-induced toxicities. This review discusses the biochemical and molecular pathways in the generation of STS from HS, its clinical usefulness, and potential clinical applications, as well as the molecular mechanisms underlying these clinical applications and a future perspective in kidney transplantation.
Topics: Animals; Gastrointestinal Hormones; Humans; Hydrogen Sulfide; Metabolic Networks and Pathways; Oxidation-Reduction; Reperfusion Injury; Thiosulfates
PubMed: 34208631
DOI: 10.3390/ijms22126452 -
BMJ Case Reports Aug 2015A 37-year-old African-American woman with end-stage renal disease presumed to be secondary to diabetes mellitus type 2, on daily peritoneal dialysis, was admitted for a...
A 37-year-old African-American woman with end-stage renal disease presumed to be secondary to diabetes mellitus type 2, on daily peritoneal dialysis, was admitted for a painful left lower extremity lesion. Examination revealed a large, dusky, tender region over the left lateral thigh. She was on warfarin for mechanical heart valves. Despite discontinuation of warfarin and placement on heparin, the lesion progressed to extend to the medial left thigh and medial and lateral right thigh. CT scan demonstrated arteriolar medial calcification and vascular calcification of the small subcutaneous vessels, without evidence of abscess or haematoma. The patient declined punch biopsy. Given the known risk factors of high calcium-phosphate and radiological findings, a diagnosis of calcific uraemic arteriolopathy was made. Phosphate-binder therapy was optimised. She was transitioned to daily haemodialysis, and sodium thiosulfate was initiated. Skin lesions demonstrated improvement at her 5 weeks posthospitalisation follow-up.
Topics: Adult; Arterioles; Calciphylaxis; Calcium; Chelating Agents; Female; Humans; Kidney Failure, Chronic; Phosphates; Renal Dialysis; Skin; Thigh; Thiosulfates; Uremia; Vascular Calcification
PubMed: 26315356
DOI: 10.1136/bcr-2014-207935