Nonuremic Calciphylaxis: A Rare and Unexpected Diagnosis of Necrotic Ulcers.

Calciphylaxis is a rare and devastating condition found almost exclusively in patients with end-stage renal disease. Nonuremic calciphylaxis, an even more rare diagnosis, occurs in patients with preserved kidney function. We present a fatal case of nonuremic calciphylaxis with delayed and unexpected diagnosis despite early biopsy and testing. The patient presented with a 2-month history of painful ulceration to the left leg. Early biopsy was negative for calciphylaxis. Laboratory tests were negative for renal disease and autoimmune disorders. There was elevated parathyroid hormone (96 pg/mL) 3 months after initial presentation and documented cobalamin deficiency. The patient went on to develop wounds to both legs and her thighs. A second biopsy of a left thigh wound by means of the dermatology service revealed calciphylaxis. The purpose of this case report is to raise awareness of calciphylaxis as a differential diagnosis for chronic necrotic skin ulcers, especially in patients with preserved renal function and those on warfarin therapy.

Coexistence of nephrogenic systemic fibrosis and calciphylaxis in a gadolinium-naïve, chronic haemodialysis patient.

We present a case of a man in his 40s who was on haemodialysis for over 20 years presenting with rapidly progressive decline in mobility, associated with fixed flexion deformities of joints and peau d'orange appearance of skin together with areas of ulceration that was concerning for calciphylaxis. Skin biopsies were consistent with both nephrogenic systemic fibrosis and calciphylaxis. He has never had exposure to gadolinium-based contrast agent. His treatment included daily dialysis sessions, which were challenging due to vascular access issues and three times weekly sodium thiosulfate. He rapidly declined in hospital and died within 2 weeks of presentation while being treated for a hospital-acquired pneumonia.

Clinical characteristics and treatment modalities in uremic and non uremic calciphylaxis - a dermatological single-center experience.

Calciphylaxis (CP) is a serious, potentially life-threatening disease that presents with medial calcification of small-sized vessels and painful ischemic ulcerations. Although calciphylaxis is frequently seen in patients with end-stage kidney disease on dialysis (calcific uremic arteriolopathy, CUA), there are reported cases of nonuremic calciphylaxis (NUC), which often remain undiagnosed. We conducted a retrospective chart review at our dermatological hospital and evaluated data concerning the epidemiology, comorbidities, medication, laboratory abnormalities, and therapeutic approaches of 60 patients diagnosed with calciphylaxis between 01/2012 and 12/2022. We identified 21 patients diagnosed with NUC and 39 with kidney disease. The predilection sites of skin lesions were the lower legs in 88% (n = 53), followed by the thigh and gluteal regions in 7% (n = 4). Significant differences were identified in comorbidities, such as atrial fibrillation (p < 0.001) and hyperparathyroidism (p < 0.01) accounting for CUA patients. Medication with vitamin K antagonists (p < 0.001), phosphate binders (p < 0.001), and loop diuretics (p < 0.01) was found to be associated with the onset of calciphylaxis. Hyperphosphatemia (p < 0.001), increased parathyroid hormone (p < 0.01) and triglyceride levels (p < 0.01), hypoalbuminemia (p < 0.01) and decreased hemoglobin values (p < 0.001) in the CUA cohort were significantly different from those in the NUC group. All patients with CUA received systemic medication. In contrast, only 38% (n = 8) of patients with NUC received systemic treatment. Striking discrepancies in the treatment of both cohorts were detected. In particular, NUC remains a disease pattern that is still poorly understood and differs from CUA in several important parameters.

Calciphylaxis with atypical localisation in a woman 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.

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.

Repeat, Bilateral Femoral Nerve Blocks With Liposomal Bupivacaine for Analgesia in a Patient With Calciphylaxis: A Case Report.

A 39-year-old woman with juvenile idiopathic arthritis complicated by nonuremic calciphylaxis presented for pain management of bilateral lower extremity wounds requiring frequent dressing changes. Bilateral single-shot femoral nerve blocks using liposomal bupivacaine and 0.25% bupivacaine were performed. The patient reported decreased pain scores and had reduced opioid use for 72 hours postblock. Repeat, bilateral single-shot femoral nerve blocks with liposomal bupivacaine and 0.25% bupivacaine were performed approximately every 72 hours to maintain adequate analgesia. We conclude that off-label use of liposomal bupivacaine in femoral nerve blocks results in prolonged block duration without adverse effects or tachyphylaxis.

Calciphylaxis in a Patient With Lupus Nephritis and Acute Kidney Injury: A Rare Case Report and Literature Review.

Calciphylaxis is a rare and severe disease characterized by calcification, fibrosis, and thrombosis of small blood vessels. Although it primarily affects patients with end-stage renal disease (ESRD) on dialysis, limited cases have been reported of calciphylaxis in patients with acute kidney injury (AKI) and lupus. This case report describes the occurrence of calciphylaxis in a 35-year-old female recently diagnosed with lupus nephritis class IV and AKI requiring dialysis.

Surgical management of pain or infection secondary to calciphylaxis: a wound center's experience and algorithmic multidisciplinary approach.

BACKGROUND: The role of surgical management of calciphylaxis remains understudied. OBJECTIVE: This article reports a case series and algorithmic approach to the multidisciplinary management of calciphylaxis. METHODS: A single-center retrospective review of all adult patients with calciphylaxis treated surgically between January 2010 and November 2022 was performed. RESULTS: Eleven patients met inclusion criteria. The average age was 50.9 years ± 15.8 SD, and most patients were female (n = 7 [63.6%]). Surgery was indicated for infection (n = 6 [54.5%]) and/or intractable pain (n = 11 [100%]). Patients underwent an average of 2.9 excisional debridements during their hospital course. Following the final excision, wounds were left open in 5 cases (29.4%), closed primarily in 4 (23.5%), and local flaps were used in 3 (27.3%). Postoperatively, the mean time to healing was 57.4 days ± 12.6. Complications included dehiscence (n = 1 [9.1%]), progression to cellulitis (n = 2 [18.2%]), osteomyelitis (n = 1 [9.1%]), and lower extremity amputation (n = 2 [18.2%]). Of the 6 patients alive at the time of healing, 5 (83.3%) were no longer taking narcotic medications. At an average follow-up of 26.4 months ± 34.1, 7 patients (63.6%) were deceased, with an average time to mortality of 4.8 months ± 6.7. Of the 4 remaining patients, 3 (75.0%) were ambulatory by their most recent follow-up visit. CONCLUSION: While the morbidity and mortality associated with calciphylaxis are substantial, surgical excision is effective in reducing pain and improving quality of life in patients with this end-stage disease. Wound care centers are uniquely equipped with a variety of medical and surgical specialists with experience in treating chronic wounds and thus facilitate an efficient multidisciplinary model.

Black necrosis of the glans penis associated with calciphylaxis: A case report.

RATIONALE: Calciphylaxis, known as calcific uremic arteriolopathy, is a rare cause of dry gangrene. Despite an increase in the clinical recognition of demographic characteristics and risk factors associated with calciphylaxis, it remains a poorly understood disease with high mortality. PATIENT CONCERNS AND DIAGNOSES: We present a 45-year-old man, who was diagnosed with calciphylaxis disease, with a history of diabetes mellitus, end-stage renal disease and cirrhosis with a half-month evolution of painful dry gangrene on his glans penis and scrotum. The patient also presented with gangrene of fingers. INTERVENTIONS AND OUTCOMES: The patient and his family opted for palliative care. However, he died eventually. LESSONS: This case contributed to the current understanding of calciphylaxis. Since no standard treatment is available and the prognosis remained poor, early, and accurate diagnosis of calciphylaxis is important. We here report the current case and provide data for the diagnosis and treatment of this kind of disease.

Risk factors, treatment modalities, and clinical outcomes of penile calciphylaxis: systematic review.

PURPOSE: To perform a systematic review of case reports and case series to investigate risk factors, treatment modalities, and the outcome of penile calciphylaxis. METHOD: We performed a systematic search of the MEDLINE and Scopus databases to identify case reports or case series of penile calciphylaxis. The patient characteristics, laboratory investigations, diagnostic modalities, treatment modalities, and outcomes were extracted. We compared clinical characteristics and treatment between patients who survived or demised and between patients with clinical improvement and those without to identify the poor prognostic risk factors. RESULTS: Ninety-four articles were included from 86 case reports and 8 case series with 121 patients. Most of the patients were on hemodialysis (78.9%). The median time since starting dialysis was 48 months (24-96 months). Sodium thiosulfate was used to treat penile calciphylaxis in 23.6%. For surgical management, partial or total penectomy was performed in 45.5% of the patients. There was no association between sodium thiosulfate use, partial or total penectomy, and improvement in clinical outcomes. The mortality rate in patients with penile calciphylaxis was 47.8% and the median time to death was 3 months (0.75-9 months). The presence of extragenital involvement was significantly related to mortality (p = 0.03). CONCLUSION: A calcified penile artery results in penile calciphylaxis, a rare vascular phenomenon associated with high morbidity and mortality. Management of penile calciphylaxis includes the medical management of risk factors, surgical debridement, or penectomy. Therefore, early prevention and diagnosis as well as immediate appropriate treatment are needed.

Sailing between scylla and charybdis-anticoagulation dilemma in a patient with calciphylaxis and mechanical cardiac valve replacement: a case report and literature review.

Calciphylaxis is a rare and life-threatening condition in patients with end-stage kidney disease (ESKD). In this case report, we reported a 72-year-old female who had undergone aortic and mitral mechanical valve replacement 22 years ago due to rheumatic aortic and mitral stenosis. Following the valve replacement, she initiated warfarin treatment. Five years ago, she received a diagnosis of uremia and has since been undergoing regular hemodialysis. Ten months prior to her current admission, she experienced excruciating pain and was diagnosed with calciphylaxis. Additionally, an electrocardiogram revealed atrial fibrillation, while echocardiography indicated that the aortic and mitral mechanical valves were appropriately positioned, with normal perivalvular surroundings and good valve leaflet activity. No noticeable thrombosis was observed in the left atrium or left atrial appendage. Color Doppler imaging showed moderate stenosis in the lower extremity arteries, with no venous thromboembolism present. Extensive eggshell-like calcification within the arterial media was detected. The patient was managed with regular hemodialysis, symptomatic treatments (including anticoagulation and analgesia), and sodium thiosulfate. Unfortunately, symptomatic management provided limited relief, and during the one-month follow-up period, the patient passed away due to septic shock. Currently, there is insufficient conclusive evidence regarding alternative influential anticoagulants or appropriate prosthetic valve selection. For individuals with ESKD receiving maintenance hemodialysis, early identification, diagnosis, and treatment of calciphylaxis are of paramount importance.

Early diagnosis strategy of calciphylaxis in dialysis patients.

Calciphylaxis, a rapidly progressive and potentially life-threatening vascular calcification syndrome that clinically presents with persistently painful, ulcerative, or necrotizing skin lesions in multiple parts of the body, is predominantly observed in patients treated with dialysis. Early diagnosis of calciphylaxis is a key measure for reducing high disability and mortality. At present, there is no unified diagnostic standard for calciphylaxis, and there is a lack of effective early screening strategies. This paper summarized and discussed the diagnostic accuracy of calciphylaxis based on the latest research worldwide. We propose a modified strategy for the early diagnosis of calciphylaxis, which is suitable for dialysis patients to help clinicians better identify such disease and improve prognosis.

Clinical management of nonuremic calcific arteriolopathy: a report of three cases.

INTRODUCTION: Calcific arteriolopathy involves the deposition of insoluble calcium salts in the vasculature and soft tissues, leading to ischemia, thrombosis, and cutaneous necrosis. Calcific arteriolopathy is commonly associated with ESRD but can also occur outside of ESRD, known as NUC. OBJECTIVE: This article reviews the clinical management and outcomes of 3 cases of non-uremic calcific arteriolopathy. MATERIALS AND METHODS: This case series describes the clinical presentation and successful treatment of NUC in a community hospital-based outpatient wound center in southeastern Wisconsin. Factors presumed to be involved included chronic kidney disease-associated mineral bone disorder, dysregulation and deficiencies of the inhibitors of vascular calcifications, autoimmune dysfunction, and chronic inflammation. All 3 patients received multimodal treatment with wound hygiene, pain management, and infection control. In addition to these interventions, case 2 received NLFU. RESULTS: All 3 patients displayed increased tolerance of compression and debridement and successfully epithelialized with no discernible effect on long-term function or quality of life. Wound infection occurred in each case. The mean overall healing time was 20 weeks. CONCLUSION: The study findings suggest that successful management of NUC can be achieved using IV STS, early and aggressive infection treatment, pain control, and wound hygiene. In patients with NUC, NLFU may be an appropriate adjunct to expedite healing.

Multimodality approach to treat calciphylaxis in end-stage kidney disease patients.

A multimodality approach has been proposed as an effective treatment for calciphylaxis in patients with end-stage kidney disease. In this retrospective study, we report the cases of 12 end-stage kidney disease patients from l'Hôtel-Dieu de Québec hospital (Canada) who were diagnosed with calciphylaxis between 2004 and 2012 and treated with a multimodality clinical approach including sodium thiosulfate (STS). Statistical analyses were performed to evaluate the impacts of patients characteristics, the different interventions as well as therapy regimen on the therapeutic response. The majority of patients (n = 9) were hemodialyzed. The patients-associated comorbidities were consistent with previously reported risk factors for calciphylaxis: Diabetes (n = 11), calcium-based phosphate binders use (n = 10), warfarin use (n = 9), obesity (n = 7), female gender (n = 8) and intravenous iron use (n = 8). STS was given for a median duration of 81 days. 75% of the patients had a response (total or partial) including a complete response in 42% of patients. One-year mortality rate was low (25%). STS was used during a mean duration of 83.33 ± 41.52 days and with a total cumulating dose of 1129.00 ± 490.58 g. The recorded mean time before a complete response was 102.20 days (51-143). Pain improvement occurred after a mean time of 8.67 ± 10.06 days. None of the studied factors was statistically associated with a complete or a partial response to the multimodality approach. Although our data have a limited statistical power, they support treating calciphylaxis with a multimodality approach including STS as its effects are independent from important clinical variables.

Elastic fiber alterations and calcifications in calcific uremic arteriolopathy.

Calcific uremic arteriolopathy (CUA) is a severely morbid disease, affecting mostly dialyzed end-stage renal disease (ESRD) patients, associated with calcium deposits in the skin. Calcifications have been identified in ESRD patients without CUA, indicating that their presence is not specific to the disease. The objective of this retrospective multicenter study was to compare elastic fiber structure and skin calcifications in ESRD patients with CUA to those without CUA using innovative structural techniques. Fourteen ESRD patients with CUA were compared to 12 ESRD patients without CUA. Analyses of elastic fiber structure and skin calcifications using multiphoton microscopy followed by machine-learning analysis and field-emission scanning electron microscopy coupled with energy dispersive X-ray were performed. Elastic fibers specifically appeared fragmented in CUA. Quantitative analyses of multiphoton images showed that they were significantly straighter in ESRD patients with CUA than without CUA. Interstitial and vascular calcifications were observed in both groups of ESRD patients, but vascular calcifications specifically appeared massive and circumferential in CUA. Unlike interstitial calcifications, massive circumferential vascular calcifications and elastic fibers straightening appeared specific to CUA. The origins of such specific elastic fiber's alteration are still to be explored and may involve relationships with ischemic vascular or inflammatory processes.