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.

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.

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.

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.

Cutaneous vascular calcifications in patients with chronic kidney disease and calcific uremic arteriolopathy: a cross-sectional study.

INTRODUCTION: Calcific uremic arteriolopathy is a life-threatening cutaneous condition in patients with chronic kidney disease. Often, clinical diagnosis is accompanied by histopathologic evaluations demonstrating vascular calcium deposits. We aimed to investigate the presence of cutaneous calcifications in non-lesional tissue in patients with chronic kidney disease, and the relation to systemic vascular calcification. METHODS: We investigated the presence of cutaneous vascular calcifications in non-lesional skin biopsies from patients with current or previous calcific uremic arteriolopathy and patients with different stages of chronic kidney disease without calcific uremic arteriolopathy, and explored their association with vascular calcification in other vascular beds. Systemic vascular calcification was examined by mammography and lumbar X-ray. RESULTS: Thirty-nine adults were enrolled (current or previous calcific uremic arteriolopathy, n = 9; end-stage chronic kidney disease, n = 12; chronic kidney disease stage 3b-4, n = 12; healthy controls, n = 6). All calcific uremic arteriolopathy patients had end-stage kidney disease. Cutaneous vascular calcifications were not present in any of the non-lesional skin punch biopsies. Breast arterial calcification was demonstrated in patients with calcific uremic arteriolopathy (75%) and chronic kidney disease (end-stage 67% and stage 3b-4 25%, respectively), but in none of the controls. All chronic kidney disease patients had systemic calcification on lumbar X-ray (median score 21, 22, and 15 in patients with calcific uremic arteriolopathy, end-stage kidney disease and chronic kidney disease stage 3b-4). The serum calcification propensity was significantly different between groups. DISCUSSION: Despite a high burden of systemic vascular calcification, cutaneous calcium deposits in non-lesional tissue could not be demonstrated histopathologically in patients with chronic kidney disease (with or without current or previous calcific uremic arteriolopathy). Further studies to determine whether these findings are representative or attributed to other factors are warranted.

[A Case of Penile Calciphylaxis in a Hemodialysis Patient].

In the present case of a 56-year-old male, hemodialysis was introduced from December 20XX-2 due to chronic renal failure caused by diabetic nephropathy. In February 20XX, a glans penis ulcer was observed. It gradually expanded. Angiography conducted in April revealed complete occlusion of the left internal pudendal artery and poor visualization of the bilateral penile arteries. Given the high risk of obstruction, endovascular treatment was not conducted. The glans penis ulcer continued to expand, and maintenance dialysis became difficult due to intractable pain. Opioids were introduced, but the pain could not be controlled. In May 20XX, the patient was referred to our department for surgical treatment, and partial penile resection was performed. The patient was diagnosed with penile calciphylaxis based on clinical findings and pathological diagnosis. After the surgery, the pain subsided considerably, and the patient is being followed on an out-patient basis.

Successful treatment of severe calciphylaxis in a renal transplant patient with previous total parathyroidectomy.

Calciphylaxis is a rare dermatological condition strongly associated with chronic kidney disease. The pathophysiology and optimum treatment remain uncertain. Calciphylaxis is known mostly to affect dialysis patients but is less frequently reported in renal transplant recipients. We report the case of a renal transplant recipient who had undergone previous total parathyroidectomy.

Intravenous Sodium Thiosulphate for Calciphylaxis of Chronic Kidney Disease: A Systematic Review and 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.

Characterizing the burden of calciphylaxis: a qualitative analysis.

Calciphylaxis is a debilitating disease associated with high mortality and morbidity secondary to pain, nonhealing wounds and frequent hospital admissions. We qualitatively assessed the burden of calciphylaxis on patient quality of life through semi-structured interviews with nine adult participants. Participants identified an inability to complete activities of daily living because of mobility impairment and decreased strength, although most denied complete dependence on others. All participants described pain as the worst aspect of disease, citing a variable course, unpredictability in severity and poor control despite medical therapy. Calciphylaxis also caused feelings of sadness and anger, having a negative impact on self-confidence. Supportive care needs to address the pervasive and severe nature of pain, mobility impairment and psychiatric comorbidities; such interventions may decrease the overall burden for patients with calciphylaxis.

Calciphylaxis and its co-occurrence with connective tissue diseases.

Calciphylaxis, also known as calcific uremic arteriopathy, is a rare calcification syndrome that presents as ischemic skin necrosis and severe pain. It has a high mortality rate and is characterised by calcification of the small and medium arteries and micro-thrombosis. Calciphylaxis mainly occurs in patients with end-stage renal disease. In recent years, there have been an increasing number of cases of calciphylaxis associated with connective tissue diseases. Given the absence of clear diagnostic criteria for calciphylaxis thus far, an early diagnosis is crucial for designing an effective multidisciplinary treatment plan. In this article, we review the research progress on calciphylaxis and describe its characteristics in the context of connective tissue diseases.

An Intensive Multidisciplinary Approach in Management of Extensive Nonuremic Calciphylaxis of the Bilateral Lower Extremities with Angioinvasive Fungus and Mold.

Management of infected wounds related to calciphylaxis poses a significant clinical challenge with high morbidity and mortality. Given no definitive management guidelines exist specific to nonuremic calciphylaxis, multiple modalities including sodium thiosulfate, antibiotics, hyperbaric oxygen therapy, and surgical debridement with wound care must be considered. When occurring over a large surface area, standard daily dressing changes are especially labor intensive, inefficient, and ineffective. Negative pressure wound therapy with instillation and dwell time offers broad wound coverage with ongoing therapeutic benefit. We present the case of a previously healthy 19-year-old woman who was transferred for tertiary level care of extensive nonuremic calciphylaxis wounds of the bilateral lower extremities complicated by angioinvasive coinfection with fungus and mold that was managed with a multidisciplinary approach of intensive medical management, aggressive surgical debridement, and negative pressure wound therapy with instillation of hypochlorous acid solution. Ultimately, she achieved full granulation and wound coverage with skin grafting. Large area, infected wounds related to nonuremic calciphylaxis can be successfully managed with multidisciplinary medical management, aggressive surgical debridement, and negative pressure wound therapy that can instill and dwell hypochlorous acid solution.

Understanding the zebras of wound care: an overview of atypical wounds.

Atypical wounds account for approximately 5% to 20% of chronic ulcerations. Typically, clinical suspicion of an uncommon etiology is warranted for wounds that do not show signs of healing with conventional care, that are associated with pain out of proportion to the clinical presentation, or that are atypical in appearance. This review provides a general overview of various atypical wound etiologies, clinical presentations and appearance, and current treatment protocols. The clinical presentation, pathophysiologic etiology, and current literature on each etiology are presented. The etiologies discussed are pyoderma gangrenosum, calciphylaxis, lichen planus, necrobiosis lipoidica, infectious ulcers, hidradenitis suppurativa, artefactual ulcers, hydroxyurea-induced ulcers, vasculopathies, and neoplastic ulcers. Patients with atypical wounds experience a poorer prognosis and slower healing rate compared with patients with typical wound etiologies (eg, vascular and diabetic wounds). Biopsy is often vital in wound care to identify and differentiate wound etiologies. It is important to note that multiple characteristics or histologic features can overlap in a biopsy with atypical wounds. Therefore, a biopsy will still require an understanding of the presentation of these different wounds and should only be used when appropriate. The proper diagnosis for an atypical wound can greatly hasten wound closure, decrease the cost for the patient and the health care system, and improve the patient's quality of life. Because of the limited availability of patient populations with atypical wound etiologies, literature concerning specific pathologies is limited. More research on each pathology is needed, as is a universally accepted treatment protocol for atypical wounds.

Chronic inflammation and calciphylaxis.

Calciphylaxis also known as calcific uraemic arteriolopathy is a rare condition mostly seen in patients with end-stage kidney disease. We report a case of a simultaneous-kidney-pancreas transplant patient with functioning grafts developing biopsy-proven calciphylaxis in the setting of chronic inflammation. Despite several modalities of management, the patient developed progression of her disease leading to multiple amputations. This case illustrates chronic inflammation driven by persistent infection as a probable contributing factor to the development and progression of calciphylaxis in a simultaneous kidney-pancreas recipient. Calciphylaxis should be considered in the differential for a painful, non-healing ulcer even in the absence of common risk factors.

Concurrent development of encapsulating peritoneal sclerosis and calciphylaxis in a patient with peritoneal dialysis for end-stage renal disease.

Both encapsulating peritoneal sclerosis (EPS) and calciphylaxis are rare but severe complications involving patients with end-stage renal disease. In this report, we discuss a unique case of a 73-year-old female patient who had undergone 8 years of peritoneal dialysis for IgA nephropathy and concurrently developed these two synchronous complications within 3 months of each other. Diagnosis and management of both conditions were discussed in detail as well as the possible association between the two. With surgical treatment for EPS and measures to minimise bone mineral disorder abnormalities, both complications have been successfully managed to date.