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Treatment of calcinosis cutis in systemic sclerosis and dermatomyositis: A review of the literature.Journal of the American Academy of... Feb 2020We have limited data on the treatment of calcinosis cutis associated with systemic sclerosis and dermatomyositis. (Review)
Review
BACKGROUND
We have limited data on the treatment of calcinosis cutis associated with systemic sclerosis and dermatomyositis.
OBJECTIVE
To assess the efficacy and tolerance of available treatments for calcinosis cutis based on previously published studies.
METHODS
We performed a systematic review of studies published in Medline, Embase, and the Cochrane library during 1980-July 2018. The strength of clinical data was graded according to the modified Oxford Centre for Evidence-Based Medicine levels of evidence.
RESULTS
In all, 30 studies (288 patients) were included. Eleven therapeutic classes, surgery, and physical treatments were identified as potential treatment options for calcinosis cutis. On the basis of results of a small randomized controlled trial and 4 retrospective studies, low-dose warfarin should not be used for calcinosis cutis (level IB evidence). The results of several studies suggest diltiazem and bisphosphonates might be useful treatment options (level IV). Considering biologic therapies, rituximab has shown promising results in treating both dermatomyositis and systemic sclerosis, whereas tumor necrosis factor inhibitors might be useful for treating juvenile dermatomyositis (level IV). Intralesional sodium thiosulfate might be a promising alternative (level IV).
LIMITATIONS
Few included studies had a high level of evidence.
CONCLUSION
This study highlights the efficacy and tolerance profiles of available treatments for calcinosis cutis, with a focus on level of evidence.
Topics: Calcinosis; Dermatologic Surgical Procedures; Dermatomyositis; Diltiazem; Humans; Injections, Intralesional; Physical Therapy Modalities; Randomized Controlled Trials as Topic; Rituximab; Scleroderma, Systemic; Skin Diseases; Thiosulfates; Treatment Outcome
PubMed: 31302187
DOI: 10.1016/j.jaad.2019.07.006 -
JAMA Network Open Apr 2023Calciphylaxis is a rare disease with high mortality mainly involving patients with chronic kidney disease (CKD). Sodium thiosulphate (STS) has been used as an off-label... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Calciphylaxis is a rare disease with high mortality mainly involving patients with chronic kidney disease (CKD). Sodium thiosulphate (STS) has been used as an off-label therapeutic in calciphylaxis, but there is a lack of clinical trials and studies that demonstrate its effect compared with those without STS treatment.
OBJECTIVE
To perform a meta-analysis of the cohort studies that provided data comparing outcomes among patients with calciphylaxis treated with and without intravenous STS.
DATA SOURCES
PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched using relevant terms and synonyms including sodium thiosulphate and calci* without language restriction.
STUDY SELECTION
The initial search was for cohort studies published before August 31, 2021, that included adult patients diagnosed with CKD experiencing calciphylaxis and could provide a comparison between patients treated with and without intravenous STS. Studies were excluded if they reported outcomes only from nonintravenous administration of STS or if the outcomes for CKD patients were not provided.
DATA EXTRACTION AND SYNTHESIS
Random-effects models were performed. The Egger test was used to measure publication bias. Heterogeneity was assessed using the I2 test.
MAIN OUTCOMES AND MEASURES
Skin lesion improvement and survival, synthesized as ratio data by a random-effects empirical Bayes model.
RESULTS
Among the 5601 publications retrieved from the targeted databases, 19 retrospective cohort studies including 422 patients (mean age, 57 years; 37.3% male) met the eligibility criteria. No difference was observed in skin lesion improvement (12 studies with 110 patients; risk ratio, 1.23; 95% CI, 0.85-1.78) between the STS and the comparator groups. No difference was noted for the risk of death (15 studies with 158 patients; risk ratio, 0.88; 95% CI, 0.70-1.10) and overall survival using time-to-event data (3 studies with 269 participants; hazard ratio, 0.82; 95% CI, 0.57-1.18). In meta-regression, lesion improvement associated with STS negatively correlated with publication year, implying that recent studies are more likely to report a null association compared with past studies (coefficient = -0.14; P = .008).
CONCLUSIONS AND RELEVANCE
Intravenous STS was not associated with skin lesion improvement or survival benefit in patients with CKD experiencing calciphylaxis. Future investigations are warranted to examine the efficacy and safety of therapies for patients with calciphylaxis.
Topics: Adult; Humans; Male; Middle Aged; Female; Calciphylaxis; Retrospective Studies; Bayes Theorem; Renal Insufficiency, Chronic
PubMed: 37099293
DOI: 10.1001/jamanetworkopen.2023.10068 -
Journal of the American Society of... May 2022Vascular calcification is associated with cardiovascular morbidity and mortality in people with CKD. Evidence-based interventions that may attenuate its progression in...
BACKGROUND
Vascular calcification is associated with cardiovascular morbidity and mortality in people with CKD. Evidence-based interventions that may attenuate its progression in CKD remain uncertain.
METHODS
We conducted a systematic review of prospective clinical trials of interventions to attenuate vascular calcification in people with CKD, compared with placebo, another comparator, or standard of care. We included prospective clinical trials (randomized and nonrandomized) involving participants with stage 3-5D CKD or kidney transplant recipients; the outcome was vascular calcification measured using radiologic methods. Quality of evidence was determined by the Cochrane risk of bias assessment tool and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method.
RESULTS
There were 77 trials (63 randomized) involving 6898 participants eligible for inclusion (median sample size, 50; median duration, 12 months); 58 involved participants on dialysis, 15 involved individuals with nondialysis CKD, and 4 involved kidney transplant recipients. Risk of bias was moderate over all. Trials involving magnesium and sodium thiosulfate consistently showed attenuation of vascular calcification. Trials involving intestinal phosphate binders, alterations in dialysate calcium concentration, vitamin K therapy, calcimimetics, and antiresorptive agents had conflicting or inconclusive outcomes. Trials involving vitamin D therapy and HMG-CoA reductase inhibitors did not demonstrate attenuation of vascular calcification. Mixed results were reported for single studies of exercise, vitamin E-coated or high-flux hemodialysis membranes, interdialytic sodium bicarbonate, SNF472, spironolactone, sotatercept, nicotinamide, and oral activated charcoal.
CONCLUSIONS
Currently, there are insufficient or conflicting data regarding interventions evaluated in clinical trials for mitigation of vascular calcification in people with CKD. Therapy involving magnesium or sodium thiosulfate appears most promising, but evaluable studies were small and of short duration.
Topics: Female; Humans; Magnesium; Male; Prospective Studies; Renal Dialysis; Renal Insufficiency, Chronic; Vascular Calcification
PubMed: 35232774
DOI: 10.1681/ASN.2021101327 -
Medicina (Kaunas, Lithuania) Jul 2023Limited data are available on the utilization of sodium thiosulfate (STS) treatment for calciphylaxis in peritoneal dialysis (PD) patients, while it is well-studied in... (Review)
Review
Limited data are available on the utilization of sodium thiosulfate (STS) treatment for calciphylaxis in peritoneal dialysis (PD) patients, while it is well-studied in hemodialysis (HD) patients. A systematic literature search was conducted using Ovid MEDLINE, EBM Reviews-Cochrane Central Register of Controlled Trials, and EBM Reviews-Cochrane Database of Systematic Reviews to identify reported cases of PD patients with calciphylaxis who received STS. The search covered the inception of the databases through August 2022. Across 19 articles, this review identified 30 PD patients with calciphylaxis who received STS. These included 15 case reports, 2 case series, and 2 cohort studies. The administration routes and doses varied depending on the study. For intravenous (IV) administration ( = 18), STS doses ranged from 3.2 g twice daily to 25 g three times weekly for 5 weeks to 8 months. Outcomes included 44% of patients experiencing successful wound healing, 6% discontinuing STS due to adverse effects, 67% transitioning to HD, and 50% dying from calciphylaxis complications. For intraperitoneal (IP) administration ( = 5), STS doses ranged from 12.5 to 25 g three to four times weekly for 12 h to 3 months. Results showed 80% of patients achieving successful wound healing, 80% discontinuing STS due to adverse effects, 40% transitioning to HD, and 20% dying from IP STS-related chemical peritonitis. In cases where patients switched from IV to IP STS ( = 3), doses ranged from 12.5 to 25 g two to three times weekly for 2.5 to 5 months. Among them, 67% experienced successful wound healing, while 33% died from sepsis. Two cases utilized oral STS at a dose of 1500 mg twice daily for 6 and 11 months, resulting in successful wound healing without adverse effects or need for HD. However, one patient (50%) died due to small bowel obstruction. This systematic review provides an overview of STS treatment for PD patients with calciphylaxis. Although successful treatment cases exist, adverse effects were significant. Further research, including larger clinical studies and pharmacokinetic data, is necessary to establish the optimal route, dose, and efficacy of STS in PD patients.
Topics: Humans; Calciphylaxis; Peritoneal Dialysis; Renal Dialysis
PubMed: 37512116
DOI: 10.3390/medicina59071306 -
Clinical Toxicology (Philadelphia, Pa.) Aug 2021Sodium azide is a highly toxic chemical. Its production has increased dramatically over the last 30 years due to its widespread use in vehicular airbags, and it is...
CONTEXT
Sodium azide is a highly toxic chemical. Its production has increased dramatically over the last 30 years due to its widespread use in vehicular airbags, and it is available for purchase online. Thus, accidental exposure to azide or use as a homicidal or suicidal agent could be on the rise, and secondary exposure to medical personnel can occur. No antidote exists for azide poisoning. We conducted a systematic review of azide poisoning to assess recent poisoning reports, exposure scenarios, clinical presentations, and treatment strategies.
METHODS
We searched both medical and newspaper databases to review the literature between 01/01/2000 and 12/31/2020, pairing the controlled vocabulary and keyword terms "sodium azide" or "hydrazoic acid" with terms relating to exposures and outcomes, such as "ingestion," "inhalation," "exposure," "poisoning," and "death." We included all peer-reviewed papers and news articles describing human azide poisoning cases from English and non-English publications that could be identified using English keywords. Data abstracted included the number, age, and gender of cases, mode of exposure, exposure setting, azide dose and route of exposure, symptoms, outcome, and treatment modalities.
RESULTS
We identified 663 peer-reviewed papers and 303 newspaper articles. After removing duplicated and non-qualifying sources, 54 publications were reviewed describing 156 cases, yielding an average of 7.8 reported azide poisoning cases per year. This rate is three times higher than in a previous review covering the period of 1927 to 1999. Poisoning occurred most commonly in laboratory workers, during secondary exposure of medical personnel, or from a ripped airbag. Hypotension occurred commonly, in some cases requiring vasopressors and one patient received an intra-aortic ballon pump. Gastric lavage and/or activated charcoal were used for oral azide ingestion, and sodium nitrite, sodium thiosulfate, and/or hydroxocobalamin were used in severely poisoned patients.
CONCLUSIONS
Recent increases in azide poisoning reports may stem from greater commercial use and availability. Treatment of systemic poisoning may require aggressive hemodynamic support due to profound hypotension. Based on mechanistic considerations, hydroxocobalamin is a rational choice for treating azide poisoning.
Topics: Adult; Aged; Antidotes; Female; Humans; Hypotension; Male; Middle Aged; Occupational Exposure; Poisoning; Sodium Azide; Sodium Nitrite; Suicide, Attempted; Thiosulfates
PubMed: 34128439
DOI: 10.1080/15563650.2021.1906888 -
Archives of Dermatological Research Aug 2022Calcinosis cutis is a deposition of calcium in the skin and subcutaneous tissue, often accompanied by pain, reduced mobility, and chronic infections. Limited evidence is... (Review)
Review
Calcinosis cutis is a deposition of calcium in the skin and subcutaneous tissue, often accompanied by pain, reduced mobility, and chronic infections. Limited evidence is available about the feasibility and efficacy of therapies alternative to systemic treatment and surgical excision, both of which often lead to unsatisfactory results or complications. We conducted a systematic review to evaluate the efficacy and safety of topical and intralesional sodium thiosulfate, extracorporeal shock-wave lithotripsy (ESWL), and laser for calcinosis cutis. PubMed, Embase, and Web of Science were searched. Reports of calciphylaxis and treatment combined with systemic medications were excluded. A total of 40 studies including 136 patients were analysed. Partial or complete remission after monotherapy was observed in 64% to 81% of cases. Self-applied topical sodium thiosulfate required patient's adherence (mean treatment duration, 4.9 months; range 2-24). Laser therapy enabled complete remission of microcalcifications after a single procedure (57%; 12/21). ESWL and intralesional sodium thiosulfate injections decreased calcinosis-associated pain (median reduction in VAS score, 3; range 0-9 and 1; range 0-5, respectively). The most common adverse event was scarring and hyperkeratosis, observed after CO laser (56%; 10/18). Intralesional sodium thiosulfate injections caused transient pain in over 11% of patients. Recurrences within the follow-up were rare (2%; 3/136). This study provides an overview of minimally invasive and local therapies that in selected cases might transcend conventional treatment. The limitation of this study is the poor level of evidence, which emerges mainly from non-randomized studies at high risk of bias.
Topics: Administration, Cutaneous; Calcinosis; Humans; Immunotherapy; Pain; Remission Induction
PubMed: 34165603
DOI: 10.1007/s00403-021-02264-5 -
Cardiovascular Journal of Africa Jul 2023In dialysis patients, vascular calcification is a common complication and is closely related to the morbidity and mortality of cardiovascular disease. We performed a... (Review)
Review
BACKGROUND
In dialysis patients, vascular calcification is a common complication and is closely related to the morbidity and mortality of cardiovascular disease. We performed a systematic review to determine the efficacy and safety of sodium thiosulfate (STS) in the progression of vascular calcification in dialysis patients with end-stage renal disease.
METHODS
The PubMed, Web of Science, Embase, Cochrane Library, Wanfang, CNKI, China Biology Medicine disc and Weipu databases were searched up to 9 March 2022 for clinical trials to synthesise findings on the efficacy and safety of STS in the progression of vascular calcification in dialysis patients. The primary outcome was coronary artery calcification scores (CACS) or abdominal aortic calcification scores (AACS) or Kauppila index. The secondary outcome was pulse-wave velocity (PWV). Laboratory data were shown in safety data. A random-effect model was used to provide the summary measures of effect [standardised mean difference (SMD) and 95% confidence interval (CI)].
RESULTS
Seven randomised, controlled trials and one nonrandomised, controlled trial involving 370 patients were included. Six studies reported that the progression of CACS or AACS was slower in the intravenous STS group compared with the control group (SMD -3.24, 95% CI: -5.29, -1.18, = 0.002). Two studies showed the increase in PWV was less in the STS group compared with the control group (SMD -0.52, 95% CI: -0.92, -0.13, = 0.009). During the trial period, a lower high-sensitivity C-reactive protein level (SMD 1.61, 95% CI: 0.19, 3.04, = 0.03), a decrease in serum bicarbonate level (SMD 0.67, 95% CI: 0.22, 1.11, = 0.003) and an increase in serum phosphate level (SMD -0.32, 95% CI: -0.62, -0.03, = 0.03) were noted in the intravenous STS group compared with the control group. However, serum calcium and parathyroid hormone levels showed no difference between the two groups after the trials. The most common adverse events were temporary nausea and vomiting, which occurred in 12.5 to 75% of patients.
CONCLUSIONS
Intravenous STS may slow down the progression of vascular calcification and ameliorate arterial stiffness in dialysis patients. Reliably defining the efficacy and safety of intravenous STS in attenuating the progression of vascular calcification requires a high-quality trial with a large sample size.
PubMed: 37526956
DOI: 10.5830/CVJA-2023-020 -
JAMA Network Open Aug 2021Platinum-induced ototoxic effects are a significant issue because platinum-based chemotherapy is one of the most commonly used therapeutic medications. Sodium... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Platinum-induced ototoxic effects are a significant issue because platinum-based chemotherapy is one of the most commonly used therapeutic medications. Sodium thiosulfate (STS) is considered a potential otoprotectant for the prevention of platinum-induced ototoxic effects that functions by binding the platinum-based agent, but its administration raises concerns regarding the substantial attenuation of the antineoplastic outcome associated with platinum.
OBJECTIVE
To evaluate the association between concurrent STS and reduced risk of ototoxic effects among patients undergoing platinum-based chemotherapy and to evaluate outcomes, including event-free survival, overall survival, and adverse outcomes.
DATA SOURCES
From inception through November 7, 2020, databases, including the Cochrane Library, PubMed, Embase, Web of Science, and Scopus, were searched.
STUDY SELECTION
Studies enrolling patients with cancer who were undergoing platinum-based chemotherapy that compared ototoxic effects development between patients who received STS and patients who did not and provided adequate information for meta-analysis were regarded as eligible. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines.
DATA EXTRACTION AND SYNTHESIS
The data were extracted by 2 reviewers independently. A random-effects model was used to explore objectives.
MAIN OUTCOMES AND MEASURES
Relative risks (RRs) for ototoxic effects development and hemopoietic event development comparing the experimental group and the control group were estimated. Secondary outcomes were hazard ratios (HRs) for event-free survival and overall survival. Sensitivity analysis and trial sequential analysis were conducted to further consolidate pooled results.
RESULTS
Among 4 eligible studies that were included, there were 3 randomized clinical trials and 1 controlled study. A total of 278 patients were allocated to the experimental group (ie, platinum-based chemotherapy plus STS; 158 patients, including 13 patients using contralatral ears of the control group as samples) or the control group (ie, chemotherapy; 133 patients, including 13 patients using contralateral ears of the experimental group as samples). Overall, patients who received STS had a statistically significantly decreased risk of ototoxic effects during the course of platinum-based chemotherapy (RR, 0.61; 95% CI, 0.49-0.77; P < .001; I2 = 5.0%) without a statistically significant increase in the risk of poor event-free survival (HR, 1.13; 95% CI, 0.70-1.82; P = .61; I2 = 0%) or overall survival (HR, 1.90; 95% CI, 0.90-4.03; P = .09; I2 = 0%). In the trial sequential analysis of event-free survival (z = -0.52) and overall survival (z = -1.68), although the cumulative z curves did not surpass the traditional significance boundary (-1.96 to 1.96 for both) or sequential monitoring boundary (event-free survival: -8.0 to 8.0; overall survival boundary not renderable in the analysis because the information size was too small) of the adjusted CI, they did not reach the required information size.
CONCLUSIONS AND RELEVANCE
This meta-analysis found that concurrent STS delivery was associated with a decreased risk of platinum-induced ototoxic effects among patients treated with platinum-induced chemotherapy. These findings suggest that concurrent STS for protection against ototoxic effects should be considered for patients indicated for platinum-based chemotherapy.
Topics: Adolescent; Adult; Antineoplastic Agents; Child; Clinical Trials as Topic; Female; Humans; Male; Ototoxicity; Platinum Compounds; Protective Agents; Thiosulfates; Young Adult
PubMed: 34338793
DOI: 10.1001/jamanetworkopen.2021.18895 -
Nephrology, Dialysis, Transplantation :... Feb 2023Vascular calcification (VC) is a common comorbidity among patients with chronic kidney disease (CKD), indicating major cardiovascular events. This study aimed to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vascular calcification (VC) is a common comorbidity among patients with chronic kidney disease (CKD), indicating major cardiovascular events. This study aimed to evaluate the effects and safety of intravenous sodium thiosulphate (STS) for VC in CKD patients.
METHODS
Electronic databases were searched for clinical trials that provided data comparing outcomes among patients treated with and without STS. The PRISMA guidelines were followed. Efficacy was assessed using calcification scores and arterial stiffness. Safety was examined by analyzing adverse symptoms, electrolytes and bone mineral density (BMD). Random-effects models were performed. Meta-regression and sensitivity analysis were done. The risk of bias was assessed using the Cochrane tools.
RESULTS
Among the 5601 publications, 6 studies involving 305 participants (mean age: 56 years, male: 56.6%) with all participants on maintenance hemodialysis met eligibility criteria. For efficacy, the progression in Agatston scores in the coronary arteries [107 patients, mean difference (MD): -241.27, 95% confidence interval (95% CI): -421.50 to -61.03] and iliac arteries (55 patients, MD: -382.00, 95% CI: -751.07 to -12.93) was lower in the STS treated group compared with controls. The increase in pulse wave velocity was lower in the STS group (104 patients, MD: -1.29 m/s, 95% CI: -2.24 to -0.34 m/s). No association was found between the change in calcification scores and STS regimen. For safety, gastrointestinal symptoms (e.g. nausea) and increased anion gap acidosis were noted. No reduction in BMD by STS was observed.
CONCLUSIONS
Intravenous STS may attenuate the progression of VC and arterial stiffness in hemodialysis patients. Large and well-designed randomized controlled trials are warranted.
Topics: Humans; Male; Middle Aged; Pulse Wave Analysis; Vascular Calcification; Renal Dialysis; Vascular Stiffness; Renal Insufficiency, Chronic
PubMed: 35521751
DOI: 10.1093/ndt/gfac171 -
Toxins Oct 2021Uremic pruritus is a distressful complication of chronic kidney disease and results in impaired quality of life and higher mortality rates. Intravenous sodium... (Meta-Analysis)
Meta-Analysis
Uremic pruritus is a distressful complication of chronic kidney disease and results in impaired quality of life and higher mortality rates. Intravenous sodium thiosulfate has been reported to alleviate pruritus in hemodialysis patients. We performed a systematic review and meta-analysis to estimate the efficacy of intravenous sodium thiosulfate in patients with uremic pruritus. A systematic search of electronic databases up to June 2021 was conducted for randomized controlled trials that evaluated the clinical effects of sodium thiosulfate in the management of patients with uremic pruritus. Two reviewers selected eligible articles and evaluated the risk of bias; the results of pruritus assessment and uremic pruritus-related laboratory parameters in selected studies were analyzed. There are four trials published between 2018 and 2021, which include 222 participants. The sodium thiosulfate group displayed significant decrease in the pruritus score (standardized mean difference = -3.52, 95% confidence interval = -5.63 to -1.41, = 0.001), without a significant increase in the adverse effects (risk ratio = 2.44, 95% confidence interval = 0.37 to 15.99, = 0.35) compared to the control group. Administration of sodium thiosulfate is found to be a safe and efficacious complementary therapy in improving uremic pruritus in patients with chronic kidney disease.
Topics: Antioxidants; Humans; Pruritus; Randomized Controlled Trials as Topic; Thiosulfates; Uremia; Vasodilator Agents
PubMed: 34822553
DOI: 10.3390/toxins13110769