Clinical experience with intraperitoneal sodium thiosulphate for calciphylaxis in peritoneal dialysis: A case series.

Calciphylaxis is an uncommon but life-threatening syndrome in end-stage kidney disease, characterised by painful medial and intimal calcification of the arterioles in the deep dermis and subcutaneous tissues. Intravenous sodium thiosulfate serves as an off-label but effective treatment in haemodialysis patients. However, this approach confers considerable logistical challenges for affected peritoneal dialysis patients. In this case series, we demonstrate that intraperitoneal administration can be a safe, convenient and long-term alternative.

Profound metabolic acidosis in association with sodium thiosulfate therapy in a patient with calcific uremic arteriolopathy: a case report and literature review.

Calciphylaxis, also known as Calcific uremic arteriolopathy (CUA), is a serious disorder that presents with skin necrosis due to calcification of dermal and subcutaneous adipose tissue capillaries and arterioles. The condition occurs primarily in patients with end-stage renal disease (ESRD) on dialysis, and it carries high morbidity and mortality, primarily due to sepsis, with an estimated six-month survival of approximately 50%. Although there are no high-quality studies to guide the optimal treatment approach for patients with calciphylaxis, many retrospective studies and case series support treatment with sodium thiosulfate (STS). Despite the frequent use of STS as an off-label treatment, data regarding its safety and efficacy are limited. STS has generally been considered a safe drug with mild side effects. However, severe metabolic acidosis associated with STS is a rare and life-threatening complication of STS treatment and is often unpredictable. Herein, we report a 64-year-old female with ESRD on peritoneal dialysis (PD) who presented with a profound high anion gap metabolic acidosis and severe hyperkalemia while on STS treatment for CUA. No other etiology for her severe metabolic acidosis other than STS was identified. ESRD patients receiving STS should be monitored closely for this side effect. Dose reduction, increasing the duration of infusion, or even discontinuing STS treatment should be considered if severe metabolic acidosis develops.

A retrospective review of outcomes after hyperbaric oxygen therapy for the treatment of calciphylaxis.

BACKGROUND: Calciphylaxis is a thrombotic vasculopathy characterized by painful necrotic ulcerations. There are no Food and Drug Administration approved therapies despite high mortality. OBJECTIVE: To compare mortality and wound healing outcomes in patients treated with hyperbaric oxygen therapy (HBOT) in addition to intravenous sodium thiosulfate (IV STS) versus patients who received IV STS only. Findings were stratified by dialysis status and modality. METHODS: 93 patients were included, with 57 patients in the control group (IV STS) and 36 patients in the treatment group (HBOT + IV STS). Mortality data were analyzed with traditional survival analyses and Cox proportional hazard models. Longitudinal wound outcomes were analyzed with mixed effects modeling. RESULTS: Univariate survival analyses showed that full HBOT treatment was associated with significantly (P = .016) longer survival time. Increasing number of HBOT sessions was associated with improved mortality outcomes, with 1, 5, 10 and 20 sessions yielding decreasing hazard ratios. There was also a significant (P = .042) positive association between increasing number of HBOT sessions and increased wound score. LIMITATIONS: Data collection was retrospective. CONCLUSION: HBOT may have a role in the treatment of calciphylaxis with benefits demonstrated in both mortality and wound healing. Larger prospective studies are needed to identify which patients would most benefit from this intervention.

Intralesional Sodium Thiosulfate as Adjuvant Therapy in Severe Calciphylaxis.

Calciphylaxis is a rare disease characterized by calcification of the middle layer of small arteries and arterioles, causing secondary cuta-neous ischemia. The diagnosis is clinical but may be confirmed by histological examination. The optimal treatment is not exactly known, although there is consensus that a multifactorial approach is required. This report is regarding the case of a female patient with a kidney transplant requiring peritoneal dialysis, in the late postoperative period of partial parathyroidectomy due to severe hyperparathyroidism, with refractory hypocalcemia and severe calciphylaxis, subsequently treated with intralesional sodium thiosulfate due to initial intoler-ance to intravenous thiosulfate treatment. J Drugs Dermatol. 2023;22(12):e28-e30.     doi:10.36849/JDD.7362e.

Sodium Thiosulfate for Calciphylaxis Treatment in Patients on Peritoneal Dialysis: A Systematic 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 (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.

Skin lesions in a man with end-stage renal disease.

ABSTRACT: Calciphylaxis is an uncommon condition most often seen in patients with end-stage renal disease. It is easily mistaken for other more common conditions and requires a high level of suspicion to make a timely diagnosis. Although various treatments such as IV sodium thiosulfate and bisphosphonates have been used for management, calciphylaxis remains a condition with a high mortality that requires an interdisciplinary approach for optimal management.

Erythema nodosum with incidental calciphylaxis secondary to zoledronic acid and denosumab.

Erythema nodosum (EN) is the most common clinical presentation of panniculitis, an inflammatory process that affects subcutaneous cellular tissue, characterized by the acute appearance of painful erythematous nodules predominantly in the lower extremities. An unusual case of EN is presented below, secondary to the administration of zoledronic acid (ZA) and denosumab, in which incidental histopathological findings of calciphylaxis were also found.

Use of the optimized sodium thiosulfate regimen for the treatment of calciphylaxis in Chinese patients.

BACKGROUND: Sodium thiosulfate (STS) can be used to treat patients diagnosed with calciphylaxis, which is a rare life-threatening syndrome. However, our patients treated with the recommended STS regimen presented with serious adverse events, resulting in treatment withdrawal. Then an optimized STS regimen was used to increase the tolerance of patients to STS and improve treatment continuation. The curative effect of the new regimen is not yet definite. Therefore, this study aimed to evaluate the response to the use of the optimized STS regimen for the treatment of calciphylaxis in Chinese patients during the first three courses of treatment. METHODS: Demographic, clinical, and laboratory data were retrospectively collected on 31 calciphylaxis patients with chronic kidney disease (CKD) or end-stage kidney disease (ESKD) treated with the optimized STS regimen. The primary outcome was a clinical improvement. The secondary outcomes included survival rate and adverse events. RESULTS: Twenty-five patients (over 80%) achieved clinical improvement considering improvement or nonspecific changes of skin lesions (80.65%) and pain relief (100%). Furthermore, 54.84% of patients did not experience any adverse events and none died from complications. During a median follow-up of 9 months (interquartile range 4‒19), 27 patients (87.10%) survived; additionally, 13 patients (41.94%) survived after a one-year follow-up period. CONCLUSION: The optimized STS regimen is relatively safe, associated with satisfactory outcomes, and well tolerated by patients for short to medium treatment duration. Hence, it is a promising approach for the treatment of patients diagnosed with calciphylaxis.

Success of small-dose fractionated sodium thiosulfate in the treatment of calciphylaxis in a peritoneal dialysis patient.

BACKGROUND: Calciphylaxis, or calcific uremic arteriolopathy (CUA), is a rare, fatal disorder of microvascular calcification and thrombosis that typically affects patients with end-stage renal disease (ESRD) receiving long-term dialysis. Fewer reports describe calciphylaxis in peritoneal dialysis patients than hemodialysis patients as per a literature review. To date, there are no clear guidelines for CUA diagnosis and treatment. While sodium thiosulfate (STS) has been increasingly used for treatment in recent years, there have also been reports of severe side effects. There is no uniform standard for its usage and dosage, especially for peritoneal dialysis patients. CASE PRESENTATION: We present a case of a 40-year-old Chinese male patient with ESRD on peritoneal dialysis who developed calciphylaxis with severe painful cutaneous ulcers on the fingers and toes that were managed successfully for 6 months with comprehensive treatment composed mainly of small-dose fractionated sodium thiosulfate. CONCLUSIONS: Our experience suggests that the treatment of calciphylaxis requires timely and multi-angle intervention. Treatment with small-dose fractionated sodium thiosulfate has proven effective and tolerated in this patient.

Therapeutic success of sodium thiosulfate in treating cutaneous calciphylaxis in a patient with hyperphosphataemic familial tumoral calcinosis.

Calciphylaxis is a potencially disorder in patients with hyperphosphatemic familial tumoral calcinosis (HFTC). Patients commonly present livedo racemosa and retiform purpura, which may progress to necrosis and very painful ulcers. Treatment with sodium thiosulfate provides good results; however, intralesional and intravenous treatment can be limited by its adverse effects. Topical sodium thiosulfate has been successfully reported for cutaneous calcification associated with connective tissue diseases and calciphylaxis in patients with chronic kidney disease. We provide a case report of a patient with HFTC and calciphylaxis who was treated with topical sodium thiosulfate with a rapid and complete response with no side effects.

Vascular calcifications and calciphylaxis in a patient on concurrent haemodialysis and Coumadin therapy.

Calciphylaxis is a rare life-threatening condition, with calcification of small and medium-sized vessels leading to skin necrosis. It has a high morbidity and mortality, and most of the patients die from wound superinfection and sepsis. A 48-year-old man with a history of end-stage renal disease on haemodialysis and Coumadin therapy for venous thromboembolism presented with pulmonary oedema after missing two haemodialysis treatment. At examination, he had bilateral lower extremity dark brown, possibly necrotic, painful ulcers. He was diagnosed with calciphylaxis and treated with sevelamer hydrochloride, low calcium dialysate and sodium thiosulfate with haemodialysis. He received daily wound care with topical collagenase. After daily wound care treatment for 4 months, the patient's ulcers completely healed. The patient had been followed for 8 months, which included 29 additional readmissions, 3 admissions related to bacteraemia and 26 admissions with the diagnosis of pulmonary oedema and hyperkalaemia requiring haemodialysis.

Palliative Nerve Block for Penile Calciphylaxis: A Case Report on Ultrasound-Guided Phenol Neurolysis.

A 78-year-old man with uncontrolled diabetes, heart failure, and hemodialysis-dependent end-stage renal disease presented with intractable penile pain secondary to calciphylaxis and necrosis of his glans penis. Given pain refractory to pharmacologic management and refusal of surgery, treatment entailed an ultrasound-guided dorsal penile nerve block with 5 mL of aqueous 4% phenol bilaterally. The patient reported immediate relief and died pain-free 3 months later. While phenol nerve blocks are increasingly uncommon due to local tissue toxicity, the precision of ultrasound leverages phenol's denaturing and axonal demyelinating properties to facilitate long-term targeted neurolysis to palliate chronic nonmalignant pain.

The role of short-term, low dose intravenous ketamine infusion in Calciphylaxis.

Calciphylaxis is a small vessel vasculopathy causing subcutaneous ischemic necrosis. This condition is a recognized complication of end stage renal disease and is associated with severe pain. The mechanism of the pain generated by calciphylaxis is thought to be partly related to tissue ischemia, with a significant neuropathic component associated with neuronal hypoxic injury. The pain can be further exacerbated by the inflammatory process ensuing as a result of calciphylactic lesion infections which are commonly associated with this condition. Obtaining adequate pain relief is a challenging aspect of symptom control in calciphylaxis, and historically, patients suffering from calciphylaxis required high dose opioid medications to achieve satisfactory analgesia.This case report presents a multimodal pain management approach utilizing low dose ketamine infusion in an opioid-tolerant patient suffering from severe calciphylaxis-related pain. Ketamine is an anesthetic agent well established for its efficacy in the management of neuropathic pain in opioid-tolerant patients, and has been shown to prevent opioid-induced hyperalgesia and decrease opioid requirements. Prior published data studying pain control in calciphylaxis have mainly focused on subcutaneous ketamine administration which as noted in the literature, can be associated with infusion site complications. To the best of our knowledge, this report is first of its kind to describe successful use of ketamine infusion in treatment of acute calciphylaxis-related pain.Dose modification of ketamine is not required for patients with impaired renal function, and low dose intravenous ketamine infusion was associated with no reported adverse effects in our patient.

Potential effect of sodium thiosulfate in calciphylaxis: remission of intractable pain.

Calciphylaxis, a rare disease mainly seen in patients with chronic kidney disease, is characterised by ischaemic skin damages and excruciating pain. Calciphylaxis has poor prognosis which often results in amputation and high mortality. Although guidelines for the management of calciphylaxis are not available, sodium thiosulfate has shown efficacy in many clinical reports. We report the case of a 64-year-old advanced calciphylaxis male patient who had two amputations due to intolerable pain manifested as deteriorating ulcer. After he was treated with intravenous sodium thiosulfate (STS), his pain was significantly relieved with a healing trend of the big wound. One more amputation for the remission of intractable pain was avoided. The treatment experience indicates that sodium thiosulfate is of great value in quick pain relief and reducing suffering of calciphylaxis patients.