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Technetium-99 bone scan demonstrating prominent vessels in bilateral lower extremities and areas of increased activity in the soft tissues of the inferior buttock bilaterally, both findings consistent with calcific uremic arteriolopathy
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Calcific uremic arteriolopathy (CUA) is a rare, life-threatening disease, typically affecting patients with end-stage renal disease. It is characterized by widespread vascular calcification, endothelial fibrosis and end-organ ischemia. The mortality rate is high with infection and sepsis being the most common causes of death. Common therapies inclu...
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... both feet. A skin biopsy was not performed; however, the diagnosis of calciphylaxis was strongly supported by a technetium-99 bone scan, which demonstrated prominent vessel calcifications within the upper and lower extremities bilaterally, as well as areas of intensely increased activity in the soft tissues of the inferior buttock bilaterally ( Fig. 1). At the time of the scan, the patient manifested evidence of ischemia only in both feet, with sparing of the upper extremities and ...
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Background
Calcific uremic arteriolopathy (CUA), also known as calciphylaxis, is a rare but life-threatening condition predominately occurring in patients with end-stage renal disease on dialysis. In the absence of randomized clinical trials to guide management, clinicians must rely on observational data. We have previously reported the outcomes of...
Calciphylaxis or calcific uremic arteriolopathy is an infrequent complication of end stage kidney disease. It is characterized by arteriolar medial calcification, thrombotic cutaneous ischemia, tissue necrosis often leading to ulceration, secondary infection and increased mortality rates. Current, multimodality treatment involves local wound care,...
Citations
... Headache, hypotension, thrombophlebitis (when STS is given through a peripheral IV cannula), and hypersensitivity to smells with anorexia have been reported 19,54,59,67 . One patient developed five beats of broad complex tachycardia during STS infusion, which did not recur 64 . ...
Calciphylaxis is a rare but important cause of severe morbidity, which predominantly affects patients with advanced chronic kidney disease. It is associated with mortality in excess of 50% at one year, and this has changed little over the last 20 years despite advances in our understanding of its underlying pathophysiology, and evolving treatment strategies. Sodium thiosulphate has played a prominent role in the treatment of calciphylaxis since its first use in 2004, with reports of success both in improving the severe pain associated with the condition and in the healing of calciphylaxis lesions. The literature documenting the use of sodium thiosulphate in the treatment of calciphylaxis is reviewed here, along with a detailed summary of case reports and case series. While there is reason to be optimistic with regard to the efficacy of sodium thiosulphate within a multifaceted and multidisciplinary approach to treatment, there is clearly much yet to be learned.
... Several of these agents were tried in our patient, with progression in calcinosis despite their use. Sodium thiosulfate is a potent antioxidant and vasodilator that also chelates and dissolves calcium deposits (8)(9)(10)(11). In addition to decreasing the pain associated with ulcerative skin disease and calciphylaxis, it has been shown to decrease dystrophic calcification in calcific uremic arteriolopathy (calciphylaxis), iatrogenic calcinosis cutis, and tumoral calcinosis (8)(9)(10). Although it is primarily administered intravenously, topical use has been described for ulcerations associated with lupus calcinosis and uremic calciphylaxis (10). ...
We report the successful use of abatacept and sodium thiosulfate in a patient with severe recalcitrant juvenile dermatomyositis complicated by ulcerative skin disease and progressive calcinosis. This combination therapy resulted in significant reductions in muscle and skin inflammation, decreased corticosteroid dependence, and halted the progression of calcinosis.
... [15] Since then sodium thiosulfate has been used to treat tumoral soft tissue calcification [16] and in several cases of calciphylaxis, including pediatric patients. [17,18] The mode of action of sodium thiosulfate is currently unknown. Two hypotheses have been proposed as follows: sodium thiosulfate may enhance calcium solubility in tissues and thus inhibit its precipitation, [19] or it may produce a salt of thiosulfate of calcium (S 2 O 3 Ca), which is extremely soluble and easily removed by dialysis. ...
Cutaneous calciphylaxis is a potentially fatal condition characterized by calcium deposition in dermal arterioles and the subsequent development of livedo reticularis, plaques, and extremely painful ulcers. This condition may be present in up to 4% of end-stage renal disease patients. Several treatments, which mainly attempt to control calcium phosphate metabolism, are available for this condition.
We describe two patients treated with sodium thiosulfate with good results. Moreover, we also performed a PubMed literature search of sodium thiosulfate treatment for calciphylaxis. We found 41 cases of which most (>90%) presented a rapid and sustained resolution, indicating this drug is a very good candidate for the treatment of this condition.
... The distribution of the lesions predominantly involves the lower limbs and the abdomen. Upper extremity [13,14], breast [13], penis, vulva [16], and cardiac and pulmonary [17] involvement have also been documented. Some authors suggest a distal distribution, in comparison with more proximal, portends a better prognosis [16]. ...
... Upper extremity [13,14], breast [13], penis, vulva [16], and cardiac and pulmonary [17] involvement have also been documented. Some authors suggest a distal distribution, in comparison with more proximal, portends a better prognosis [16]. However, this has not been proven. ...
... There may be associated intimal hyperplasia with partial obliteration of the vessel lumen. Acute or chronic panniculitis with a relative absence of inflammatory cells is a frequent feature [16]. Fibrin thrombi are often noted and are in close proximity to epidermal and dermal necrosis. ...
Calciphylaxis or calcific uremic arteriolopathy is an infrequent complication of end stage kidney disease. It is characterized by arteriolar medial calcification, thrombotic cutaneous ischemia, tissue necrosis often leading to ulceration, secondary infection and increased mortality rates. Current, multimodality treatment involves local wound care, well-controlled calcium, phosphate and parathyroid hormone levels and combination therapy with sodium thiosulfate and hyperbaric oxygen therapy. This combination therapy may be changing the historically poor prognosis of calcific uremic arteriolopathy reported in the literature. Peritoneal dialysis is considered a risk factor based on limited publications, however this remains to be proven. Clinical presentation, diagnosis, pathogenesis and treatment of calcific uremic arteriolopathy in these patients are no different from other patients manifesting with this condition.
... Les premiers symptômes sont le plus souvent l'existence de zones douloureuses cutané es ou graisseuses, avec parfois des nodosité s abdominales (Fig. 3, cas n Les atteintes distales des membres infé rieurs sont les plus fré quentes pouvant rarement conduire à des amputations des jambes [22] et même plus exceptionnellement des doigts [23]. Les atteintes thoraco-abdominales apparaissent les plus graves [24] notamment mammaires [25] pouvant mimer un cancer inflammatoire [26]. ...
Calciphylaxis (CPX) or calcific uraemic arteriolopathy is a rare life-threatening complication, affecting mainly dialysis patients. The condition is characterized by calcifications and thrombosis of the small cutaneous vessels and small vessels in the fat tissue, resulting in the development of necrotizing and non-healing ulcers. The development of these lesions leads to poor outcomes owing to infectious complications and some frequently associated unfavourable medical conditions: obesity, diabetes, and peripheral vascular disease. We report the case of six patients with different clinical forms of CPX in the past 10years with favourable outcomes observed in five of the six patients. The diagnosis was based on clinical presentation: bilateral and hyperalgesic necrotic lesions along with a history of mineral metabolism disorder or warfarin use. The therapeutic strategy included the following: daily dialysis, hyperbaric oxygen therapy, treatment of limb artery stenosis, maintenance of the optimal haemodynamic stability, delivery of cutaneous care, administration of analgesics and antibiotics, warfarin and calcium cessation, and additional therapy with cinacalcet or parathyroidectomy and therapy with bisphosphonates or sodium thiosulphate. Healing was observed in five out of six CPX patients by using this strategy that should be rapidly employed in order to decrease the necrotizing areas that result in poor outcomes. Prevention includes identification of at-risk patients in order to optimize the treatment of the identified risk factors for CPX.
... 64 is unknown with only 10 case reports identified to date (census date 25 January 2010). 54,[67][68][69][70] Previous reviewers have noted the following pertinent findings regarding the pediatric population: Increased risk in males (90% of the cases reported to date) with ESRD and secondary hyperparathyroidism, frequent distal extremity and visceral organ involvement, worse prognosis with acral-distal involvement, and increased resistance to medical treatment compared to the affected adult population. 69 However, clinicians should keep in mind that with the continuing increase in childhood obesity there may be a changing trend in the future involving more proximal adipose tissue related skin ulceration. ...
... There are now four successful outcomes regarding mortality with intravenous STS. 54,67 Recently, it has been suggested that CUA/calciphylaxis requires early and aggressive intervention with the use of multi-faceted therapeutic approaches as previously described with the recommendation of including conversion from peritoneal dialysis to hemodialysis, intravenous STS infusions, and hyperbaric oxygen therapy. 67 Appropriate dose adjustments should be made for the pediatric population 71 and intravenous STS at a dose of 25 g/1.7 m 2 diluted in 100 cc of number of ulcerations. ...
... 54,67 Recently, it has been suggested that CUA/calciphylaxis requires early and aggressive intervention with the use of multi-faceted therapeutic approaches as previously described with the recommendation of including conversion from peritoneal dialysis to hemodialysis, intravenous STS infusions, and hyperbaric oxygen therapy. 67 Appropriate dose adjustments should be made for the pediatric population 71 and intravenous STS at a dose of 25 g/1.7 m 2 diluted in 100 cc of number of ulcerations. In summary, one could say that the STS story has evolved from Selye to Sulfates. ...
Calcific uremic arteriolopathy (CUA)/calciphylaxis is an important cause of morbidity and mortality in patients with chronic kidney disease requiring renal replacement. Once thought to be rare, it is being increasingly recognized and reported on a global scale. The uremic milieu predisposes to multiple metabolic toxicities including increased levels of reactive oxygen species and inflammation. Increased oxidative stress and inflammation promote this arteriolopathy by adversely affecting endothelial function resulting in a prothrombotic milieu and significant remodeling effects on vascular smooth muscle cells. These arteriolar pathological effects include intimal hyperplasia, inflammation, endovascular fibrosis and vascular smooth muscle cell apoptosis and differentiation into bone forming osteoblast-like cells resulting in medial calcification. Systemic factors promoting this vascular condition include elevated calcium, parathyroid hormone, and hyperphosphatemia with consequent increases in the calcium x phosphate product. The uremic milieu contributes to a marked increased in upstream reactive oxygen species - oxidative stress and subsequent downstream increased inflammation, in part, via activation of the nuclear transcription factor NFkappaB and associated downstream cytokine pathways. Consitutive anti-calcification proteins such as Fetuin-A and matrix GLA proteins and their signaling pathways may be decreased, which further contributes to medial vascular calcification. The resulting clinical entity is painful, debilitating and contributes to the excess morbidity and mortality associated with chronic kidney disease and end stage renal disease. These same histopathologic conditions also occur in patients without uremia and therefore, the term calcific obliterative arteriolopathy could be utilized in these conditions.
... 64 is unknown with only 10 case reports identified to date (census date 25 January 2010). 54,[67][68][69][70] Previous reviewers have noted the following pertinent findings regarding the pediatric population: Increased risk in males (90% of the cases reported to date) with ESRD and secondary hyperparathyroidism, frequent distal extremity and visceral organ involvement, worse prognosis with acral-distal involvement, and increased resistance to medical treatment compared to the affected adult population. 69 However, clinicians should keep in mind that with the continuing increase in childhood obesity there may be a changing trend in the future involving more proximal adipose tissue related skin ulceration. ...
... There are now four successful outcomes regarding mortality with intravenous STS. 54,67 Recently, it has been suggested that CUA/calciphylaxis requires early and aggressive intervention with the use of multi-faceted therapeutic approaches as previously described with the recommendation of including conversion from peritoneal dialysis to hemodialysis, intravenous STS infusions, and hyperbaric oxygen therapy. 67 Appropriate dose adjustments should be made for the pediatric population 71 and intravenous STS at a dose of 25 g/1.7 m 2 diluted in 100 cc of number of ulcerations. ...
... 54,67 Recently, it has been suggested that CUA/calciphylaxis requires early and aggressive intervention with the use of multi-faceted therapeutic approaches as previously described with the recommendation of including conversion from peritoneal dialysis to hemodialysis, intravenous STS infusions, and hyperbaric oxygen therapy. 67 Appropriate dose adjustments should be made for the pediatric population 71 and intravenous STS at a dose of 25 g/1.7 m 2 diluted in 100 cc of number of ulcerations. In summary, one could say that the STS story has evolved from Selye to Sulfates. ...
Calcific uremic arteriolopathy (CUA)/calciphylaxis is an important cause of morbidity and mortality in patients with chronic kidney disease requiring renal replacement. Once thought to be rare, it is being increasingly recognized and reported on a global scale. The uremic milieu predisposes to multiple metabolic toxicities including increased levels of reactive oxygen species and inflammation. Increased oxidative stress and inflammation promote this arteriolopathy by adversely affecting endothelial function resulting in a prothrombotic milieu and significant remodeling effects on vascular smooth muscle cells. These arteriolar pathological effects include intimal hyperplasia, inflammation, endovascular fibrosis and vascular smooth muscle cell apoptosis and differentiation into bone forming osteoblast-like cells resulting in medial calcification. Systemic factors promoting this vascular condition include elevated calcium, parathyroid hormone and hyperphosphatemia with consequent increases in the calcium × phosphate product. The uremic milieu contributes to a marked increased in upstream reactive oxygen species—oxidative stress and subsequent downstream increased inflammation, in part, via activation of the nuclear transcription factor NFκB and associated downstream cytokine pathways. Consitutive anti-calcification proteins such as Fetuin-A and matrix GLA proteins and their signaling pathways may be decreased, which further contributes to medial vascular calcification. The resulting clinical entity is painful, debilitating and contributes to the excess morbidity and mortality associated with chronic kidney disease and end stage renal disease. These same histopathologic conditions also occur in patients without uremia and therefore, the term calcific obliterative arteriolopathy could be utilized in these conditions.
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 (n = 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 (n = 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 (n = 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.
Rationale:
Though to be rare, calcific uremic arteriolophathy (CUA) is an ectopic calcification entity causing pain and disabilities in patients with chronic renal insufficiency, thus increasing the morbidity and mortality.
Patient concern:
We report a case of four years old boy admitted with acute respiratory failure. Physical examination revealed: irritability, purple subcutaneous hard nodules, tachypnea, dry spasmodic cough, respiratory rate 45/min, heart rate 110/min, blood pressure 100/60 mmHg, with normal heart sounds, no murmurs, hepatomegaly with hepato-jugular reflux. He was diagnosed at 2 years old with stage 5 chronic kidney disease due to untreated posterior urethral valve, and subsequently started peritoneal dialysis. He developed severe renal osteodystrophy, refractory to standard phosphate binders.
Diagnoses:
Pathology examination revealed the presence of diffuse calcifications involving the skin, brain, heart, lung, kidney, stomach and pancreas, consistent with the underlying diagnosis of CUA.
Intervention:
Apart from standard treatment for end stage renal disease and associated co-morbidities, intensive care procedures have been initiated: oxygen therapy, continuous positive airway pressure, inotropic medication (Dopamine, Dobutamine), anticonvulsants (Diazepam), and antiedematous therapy (Dexamethasone).
Outcome:
His pulmonary function rapidly deteriorated up to the severe hypoxemia, seizures and cardio-respiratory arrest, despite the initiation of intensive care measures.
Lessons:
A careful follow up of small children might detect in time an abnormal urinary pattern. The diagnosis of growth failure should also trigger urgent further investigation.
