Assessment of diagnostic delay, morbidity, and mortality outcomes in 302 calciphylaxis patients over a 17-year period: A retrospective cohort study.

BACKGROUND: Calciphylaxis patients historically have experienced diagnostic challenges and high morbidity; however limited data is available examining these characteristics over time. OBJECTIVE: The primary goals were to a) investigate factors associated with diagnostic delay of calciphylaxis and b) assess morbidity outcomes. The secondary goal was to provide updated mortality rates. METHODS: A retrospective review of 302 adult patients diagnosed with calciphylaxis between January 1, 2006 and December 31, 2022 was conducted. Univariate and multivariate statistical analyses were performed. RESULTS: Nonnephrogenic calciphylaxis (P = .0004) and involvement of the fingers (P = .0001) were significantly associated with an increased diagnostic delay, whereas involvement of the arms (P = .01) and genitalia (P = .022) resulted in fewer days to diagnosis. Almost all patients with genitalia, finger, or toe involvement had nephrogenic disease. The number of complications per patient decreased with time, especially for wound infections (P = .028), increase in lesion number (P = .012), and recurrent hospitalizations (P = .020). Updated 1-year mortality rates were 36.70% and 30.77% for nephrogenic and nonnephrogenic calciphylaxis, respectively. LIMITATIONS: Limitations include the retrospective nature and data from a single institution. CONCLUSION: Diagnostic delay, particularly in nonnephrogenic calciphylaxis, and complications per patient decreased with time, highlighting the importance of continued awareness to expedite diagnosis. Mortality rates have continued to improve in recent years.

[Calciphylaxis, risk factors, treatment and outcomes. Retrospective study of 39 patients]. / Calcifilaxis, factores de riesgo, tratamiento y evolución. Estudio retrospectivo de 39 pacientes.

INTRODUCTION: Calciphylaxis is a serious vascular disorder characterized by calcification of tunica media, intimal hyperplasia, thrombosis, and skin necrosis. It was described in patients with renal failure (UC), although it can occur in its absence (NUC). Its risk factors are under study and its diagnosis can be complex. Over a decade ago, its mortality was estimated at 60-80%. Recent studies indicate that it has decreased (40%). METHODS: A retrospective study was carried out in the period between January 1, 2011 and December 31, 2019. The past medical record, clinical characteristics, laboratory and histopathological findings, and evolution of all patients with calciphylaxis evaluated at the Hospital Italiano de Buenos Aires were reviewed. RESULTS: Thirty-nine patients were included. Sixtyone percent were men and 39% were NUC cases. Eightytwo percent had arterial hypertension, 66% obesity and 46% diabetes. Of those, 49% received coumarin anticoagulants. All patients with NUC and 75% with UC presented ulcers with necrosis, located more frequently on the legs. In 72% of the cases the histological diagnosis was made with one biopsy. In all the treatment was multimodal and mortality at one year was 42%. CONCLUSION: We observed a high proportion of patients with NUC, in relation to what is reported in the literature, and that half received vitamin K antagonists. The histological diagnosis was made with one biopsy in most of the cases, as the surgical technique for taking the sample, the Von Kossa staining and the evaluation by an expert pathologist were the key of it.

Introducción: La calcifilaxis es un trastorno vascular grave caracterizado por depósito de calcio en túnica media arteriolar, trombosis y necrosis cutánea. Se describió en pacientes con insuficiencia renal (CU), aunque puede producirse en su ausencia (CNU). Sus factores de riesgo están en estudio y su diagnóstico puede ser complejo. Su mortalidad se estimaba en 60-80%, aunque trabajos recientes indican que ha disminuido (40%). Métodos: Estudio retrospectivo entre el 1/1/2011 y el 31/12/2019. Se revisaron los antecedentes, las características clínicas, los hallazgos de laboratorio e histopatológicos, y la evolución de todos los pacientes con diagnóstico de calcifilaxis evaluados en el Hospital Italiano de Buenos Aires. Resultados: Se incluyeron 39 pacientes. El 61.5% (24) eran hombres y 38.5% (15) fueron casos de CNU. De éstos, 82% presentaba hipertensión arterial, 66% obesidad y 46% diabetes. El 49% recibía anticoagulantes dicumarínicos. Todos los pacientes con CNU y 75% con CU presentaron úlceras de fondo necrótico, localizadas con mayor frecuencia en las piernas. En 72% de los casos el diagnóstico histológico se efectuó con una toma de biopsia. En todos, el tratamiento fue multimodal y la mortalidad al año fue de 42%. Conclusión: Observamos una elevada proporción de pacientes con CNU, en relación con lo comunicado en la literatura, y la mitad recibía anticoagulantes dicumarínicos. El diagnóstico histológico se efectuó por biopsia en la mayor parte de los casos, para lo cual la toma quirúrgica de la muestra, la tinción con Von Kossa y la evaluación por un patólogo experto fueron claves.

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.

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 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.

Nephrogenic Calciphylaxis Arising after Bariatric Surgery: A Case Series.

Nephrogenic calciphylaxis is associated with multiple risk factors including long-term dialysis dependence, hyperphosphatemia, hypercalcemia, parathyroid hormone derangements, vitamin K deficiency, obesity, diabetes mellitus, warfarin use, and female sex. Bariatric surgery is known to cause altered absorption, leading to mineral and hormonal abnormalities in addition to nutritional deficiency. Prior case reports on calciphylaxis development following bariatric surgery have been published, though are limited in number. We report a case series of five bariatric patients from a single institution who developed nephrogenic calciphylaxis between 2012 and 2018. These patients had a history of bariatric surgery, and at the time of calciphylaxis diagnosis, demonstrated laboratory abnormalities associated with surgery including hypercalcemia (n = 3), hyperparathyroidism (n = 2), hypoalbuminemia (n = 5), and vitamin D deficiency (n = 5), in addition to other medication exposures such as vitamin D supplementation (n = 2), calcium supplementation (n = 4), warfarin (n = 2), and intravenous iron (n = 1). Despite the multifactorial etiology of calciphylaxis and the many risk factors present in the subjects of this case series, we submit that bariatric surgery represents an additional potential risk factor for calciphylaxis directly stemming from the adverse impact of malabsorption and overuse of therapeutic supplementation. We draw attention to this phenomenon to encourage early consideration of calciphylaxis in the differential for painful skin lesions arising after bariatric surgery as swift intervention is essential for these high-risk patients.

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.

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.

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.

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.

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.

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.

Common Histological Features Suggesting Enchondral Ossification Pathways in Calciphylaxis of Various Origins: A Study of Human Subcutaneous Tissue Biopsies.

Calciphylaxis is a rare, yet underdiagnosed condition causing high mortality in patients with severe renal and cardiovascular disease. Since knowledge of the pathophysiology of calciphylaxis is limited, a differential analysis of histological alterations in patient subgroups with various comorbidities might expose different disease phenotypes and allow deeper insights into the pathophysiology of the condition. Histological markers of osteogenesis and calcification were investigated in a group of 18 patients with clinically and histologically verified calciphylaxis, using immunohistochemical staining. Analysis of staining intensity and distribution of marker proteins in histological structures was performed to evaluate distinct patterns between subgroups with different clinical comorbidities in comparison with a control group. In all cases, immunohistochemical staining for bone matrix proteins, bone-morphogenic proteins and matrix-Gla proteins co-localized with subcutaneous vascular and interstitial calcifications. Significant expression of bone-morphogenic protein-7 and active matrix-Gla protein was observed. Mortality was associated with renal comorbidities and increased expression of bone-morphogenic protein-7. However, no distinct histological patterns were found between subgroups with renal disease, warfarin intake or coexisting micro- and macro-angiopathies. The upregulation of osteogenic markers (including bone-morphogenic protein-7) plays a major role in the development of calciphylaxis. Clinical outcome correlates with kidney function and phosphate handling, suggesting different pathophysiological mechanisms. However, biopsy  at late-stage disease shows a common histological phenotype, involving enchondral ossification.

The application of MDT model for calciphylaxis management in patients with end-stage renal disease.

This study focuses on the application of nurse-led multidisciplinary collaborative therapy (MDT) management model for calciphylaxis prevention of patients with terminal renal disease. Through the establishment of a multidisciplinary management team spanning nephrology department, blood purification center, dermatology department, burn and plastic surgery department, infection department, stem cell platform, nutrition department, pain department, cardiology department, hydrotherapy group, dermatology group, and outpatient treatment room, the distribution of duties among team members were clarified to bring out the best advantages of a multidisciplinary teamwork during treatment and nursing. For patients with calciphylaxis symptoms in terminal renal disease, a case-by-case management model was carried out with the focus on personalised problem. We emphasised on personalised wound care, precise medication care, active pain management, psychological intervention and palliative care, the amelioration of calcium and phosphorus metabolism disorder, nutritional supplementation, and the therapeutic intervention based on human amniotic mesenchymal stem cell regeneration. The MDT model effectively compensates for traditional nursing mode and could serve as a novel clinical management modality for calciphylaxis prevention in patients with terminal renal disease.

Penile calciphylaxis in a patient with concurrent haemodialysis and Coumadin treatment.

A man in his 30s, with a medical history of end-stage renal disease on haemodialysis three times a week after kidney transplant rejection, anaemia of inflammatory disease, hypertension, atrial fibrillation, hyperlipidaemia, subtotal parathyroidectomy and aortic valve replacement on Coumadin treatment, presented to our institution with glans penis pain. Examination of the penis revealed a painful black eschar with ulceration on the glans penis with surrounding erythema. CT scan of the abdomen and pelvis and penile Doppler ultrasound revealed calcifications of the abdominal, pelvic and penile blood vessels. He was diagnosed with penile calciphylaxis, a very rare manifestation of calciphylaxis characterised by penile blood vessel calcification leading to occlusion, ischaemia and necrosis. Treatment with low calcium dialysate and sodium thiosulfate was initiated with haemodialysis. Five days after the treatment started, the patient's symptoms improved.