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As in other organs, the diagnosis of endogenous cutaneous overload diseases is based on histopathological analysis of the lesions using special stainings, even if the clinical appearance is sometimes very suggestive. The lesions are sometimes very subtle and can be included in the group of "invisible" dermatoses, such as primary macular cutaneous amyloidosis or calciphylaxis. Superficial dermal melanosis or pigmentary incontinence generally reflects the post-inflammatory stage of a chronic or recurrent interface dermatitis. Section levels should be systematically performed to look for active lesions of diagnostic interest: Alcian blue staining to identify dermal mucinosis (connectivitis) and pan-T markers (fixed pigmented erythema, lichenoid mycosis fungoides, and vitiligo). Some pathologies have a prognostic impact, either because they reflect an underlying disease, monoclonal gammopathies, in particular myeloma, being one of the most common conditions in this context (AL amyloidosis, xanthoma and xanthogranuloma, scleromyxedema), or because they can be associated with visceral damage (AL amyloidosis, scleromyxedema). The clinical-pathological comparison is mandatory to rule out differential diagnoses, especially for life-threatening diseases: nodular amyloidosis and primary cutaneous amyloidosis versus systemic AL amyloidosis, papular mucinosis versus scleromyxedema and calcific panniculitis versus calciphylaxis., (Copyright © 2024 The Author. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Calciphylaxis is a rare and life-threatening condition characterized by cutaneous necrosis resulting from vessel calcification and thrombosis. Commonly associated with end-stage renal disease and hyperparathyroidism, calciphylaxis presents as retiform purpura evolving into necrotic eschars., Case Report: This report details an atypical case of non-nephrogenic unilateral bullous calciphylaxis in a 71-year-old female, emphasizing the importance of considering calciphylaxis in the differential diagnosis of bullous disorders. The patient's presentation included hemorrhagic bullae on the left leg, prompting a challenging differential diagnosis. Diagnosis was confirmed by skin biopsy, highlighting the role of confirmatory biopsy in atypical cases such as this, with a broad differential diagnosis. Treatment involved intravenous sodium thiosulfate infusions and wound care, resulting in significant improvement after 6 months., Conclusion: This case underscores the diagnostic complexity of bullous calciphylaxis, and clinicians are urged to consider this condition in patients with painful bullae and retiform purpura. Early recognition is crucial for initiating prompt intervention and improving outcomes in patients with this high-mortality disease.

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.

Introduction: Calciphylaxis is a lethal and rare disease characterized by ischemic and necrotic skin lesions caused by vascular calcification of adipose tissue. There have been many risk factors analyzed in the literature; however, the pathogenesis of calciphylaxis is still not well understood and treatment options are limited due to the lack of interventional studies. Our objectives were to describe risk factors, prevalence, incidence, and outcomes for calciphylaxis in hemodialysis patients within the Fraser Health Renal Program. Methods: This was a retrospective matched case-control study of hemodialysis patients within the Fraser Health Renal Program. Hemodialysis patients with calciphylaxis were matched to hemodialysis patients without calciphylaxis in a 1:2 ratio for age and sex from September 2, 2017 to July 3, 2020. Findings: There was a total of 40 calciphylaxis cases matched to 80 controls. In the univariate analysis, peritoneal dialysis, higher body mass index, lower serum iron, lower transferrin saturation, sevelamer, cinacalcet, warfarin, iron (PO), and insulin were associated with increased risk of calciphylaxis. In the multivariate analysis, only peritoneal dialysis, serum iron, sevelamer, and warfarin were identified as significant and strong risk factors associated with calciphylaxis. A low prevalence of 1.9% and high mortality rate of 57.5% at 12 months was found for calciphylaxis cases. Discussion: Significant risk factors associated with calciphylaxis were peritoneal dialysis, serum iron, sevelamer, and warfarin. Future studies should further investigate the impact of minimizing exposure to these risk factors to reduce calciphylaxis development., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Calcific uremic arteriolopathy (CUA) represents a rare but severe disease with high morbimortality. The authors present the case of a 58-year-old male patient with chronic kidney disease due to obstructive uropathy, on hemodialysis (HD). He started HD due to uremic syndrome with a severe renal dysfunction, dysregulation of calcium and phosphate metabolism, and he presented with distal penile ischemia, which was treated with surgical debridement and hyperbaric oxygen therapy. Four months later, painful distal digital necrosis of both hands was observed. Extensive arterial calcification was observed on X-ray. A skin biopsy confirmed the presence of CUA. Sodium thiosulfate was administered for 3 months, HD was intensified, and hyperphosphatemia control was achieved, with progressive improvement of the lesions. This case illustrates an uncommon presentation of CUA in a patient on HD for a few months, non-diabetic and not anticoagulated, but with a severe dysregulation of calcium and phosphate metabolism.

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.

Competing Interests: The authors declare no conflicts of interest.

Calciphylaxis is a rare disease that typically presents in patients with end-stage renal disease and can be a diagnostic challenge. Calcium deposition with fibrin thrombi and necrosis of the overlying epidermis may support the diagnosis; however, depending on the stage of the disease, skin biopsy can have low sensitivity and specificity, and may be contraindicated in some situations. We discuss the utility of imaging studies in supporting the diagnosis of calciphylaxis. ( SKINmed . 2022;20:450-451).

A 58-year-old woman with a history of morbid obesity, asthma, and prior warfarin use presented to the hospital with shortness of breath and a three-month history of painful, ulcerated ulcers with retiform purpura of her bilateral distal extremities. A punch biopsy specimen demonstrated focal necrosis and hyalinization of the adipose tissue with subtle arteriolar calcium deposition, findings consistent with calciphylaxis. We discuss the presentation of non-uremic calciphylaxis and review the risk factors, pathophysiology, and interdisciplinary management approach of this rare disease.

Calciphylaxis, also known as calcific uremic arteriolopathy (CUA), is typically characterized by subcutaneous tissue calcification and excruciatingly painful cutaneous lesions with high mortality. It is critical for dermatologists to make early diagnosis and appropriate management, yet currently only 56% of calciphylaxis cases are correctly diagnosed by conventional histological stain1. Specially, the identification of subtle calcium deposits of subcutaneous can be challenging but is believed crucial for early diagnosis of calciphylaxis2. More sensitive calcification staining is in high demand. In this study, Fluo-3 AM was found to be a rapid, sensitive and reliable fluorescent probe for the detection of calcium deposits and could be a promising diagnostic tool for calciphylaxis., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Attempts have been made to establish discriminative criteria between classic calciphylaxis (CPX) and those cases in which cutaneous vascular calcification (CVC) represents an incidental finding (epiphenomenon)., Methods: Retrospective, observational cohort study of patients with CVC to distinguish clinicopathological features between CVC as classic CPX (CVC in cutaneous lesions with erythematous-violaceous plaques with or without ulceration) or as an epiphenomenon (CVC in cutaneous lesions with known diagnosis). Different clinicopathological parameters and the presence of perieccrine calcification and pseudoxanthoma elasticum (PXE)-like changes were evaluated., Results: Sixty-six patients were studied. The CPX group showed a significantly higher percentage of renal failure, hypertension, altered laboratory parameters, painful lesions, and mortality rate. Histopathologically, the CPX group was associated with more than one vessel per field involved with subintimal concentric calcification and perieccrine calcification (observed exclusively in the CPX group), while PXE-like changes, although more frequent in the CPX group, were also observed in the epiphenomenon group., Conclusion: Perieccrine calcification and the presence of more than one vessel per field involved by concentric pattern calcification could be used as a diagnostic marker of CPX. Although PXE-like changes are not an exclusive marker, they could suggest CPX diagnosis., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Calciphylaxis is an uncommon but devastating disorder characterized by vascular calcification and subsequent cutaneous tissue necrosis. This results in exquisitely painful and slow healing wounds that portend exceptionally high morbidity and mortality. The diagnosis of this condition can be complicated because there are no conclusive serologic, radiographic or visual signs that this disease is manifesting. The differential of tissue necrosis is broad, and identifying calciphylaxis requires an adroit understanding of the risk factors and physical signs that should raise suspicion of this condition. Reviews on this subject are uncommon and lack directed commentary from disease experts on the best diagnostic approach for patients suffering from this disease. The goal of this article is to update practicing dermatologists on the current standard of care for calciphylaxis., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2022 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Calciphylaxis and the arteriolosclerotic ulcer of Martorell (ASUM) represent two entities of cutaneous calcific arteriolopathies. Their differential diagnosis can be challenging, given similarities in their clinical and histological presentation. Calcification patterns have been proposed as a possible discriminative histological criterion, however, a systematic microstructural comparative analysis is lacking., Objectives: The study aimed at a systematic comparative microstructural analysis of the calcification patterns in calciphylaxis versus ASUM., Materials & Methods: Skin biopsies of patients with leg ulcers due to calciphylaxis (20) and ASUM (69) diagnosed at three European wound care centres (Vienna, Bern, Zurich) were included. The extent of calcification, arteriolar calcification pattern and presence of extra-arteriolar calcification were assessed., Results: All calciphylaxis and most ASUM patients (77%) presented with arteriolar calcification. Although the mean number of calcified vessels and the proportion of calcified area were significantly higher in calciphylaxis specimens (p = 0.003 and p = 0.0171), there was no significant difference in the pattern of arteriolar calcification (p = 0.177). Interestingly, extra-arteriolar calcification was detected in the majority of both calciphylaxis (93.3%) and ASUM samples (85.2%, p = 0.639). Notably, Alizarin Red S staining was superior to H&E for the detection of calcifications of both entities (p = 0.014 and p < 0.0001), and to von Kossa staining for ASUM samples (p = 0.0001). However, no differences could be observed between cases with uraemic and non-uraemic calciphylaxis or ulcerations located on the upper and lower leg., Conclusion: Our results indicate that extra-arteriolar calcification is not only present in calciphylaxis, but can also be detected in ASUM suggesting a lack of specificity for this finding. However, more specific calcification stains, such as Alizarin Red S, should be used in suspected cases, as calcifications may be overlooked using conventional H&E staining.

Calciphylaxis is considered a critical inflammatory dermatosis with potentially devastating clinical consequences. Skin biopsies are expedited for evaluation and are often considered as a gold standard for diagnostic confirmation and exclusion of other conditions. The key histopathological features include a combination of vascular and extra-vascular calcifications, intravascular microthrombi, and changes related to resulting ischemia. The pathological diagnosis of calciphylaxis is not always a straightforward process as it can be influenced by a number of factors. The specificity of pathological diagnosis of calciphylaxis has been questioned and a systematic approach with multidisciplinary collaboration is required to avoid potential errors.

Report &#95;Case Presentation X Photo Vignette &#95;Letter Authors declare that the contents of this article are their own original unpublished findings. Title: Cutaneous calciphylaxis of the glans penis presenting as a gangrenous ulceration Authors: Marie Danset, Cécile Lesort, Denis Jullien, Jean Kanitakis Affiliations: Dermatology Department, Edouard Herriot Hospital, Hospices Civils de Lyon, Claude Bernard Lyon I University, Lyon, France Corresponding Author: Jean Kanitakis, Department of Dermatology, Edouard Herriot Hospital Group, 69437 Lyon Cedex 03, France, Tel: 33-472110301, Email: jean.kanitakis@univ-lyon1.fr Abstract: Calciphylaxis is a rare microvascular disorder causing necrotic skin ulcers. It is characterized by deposits of calcium within vascular walls but its precise pathogenesis remains poorly understood. A major risk factor is end-stage renal disease on dialysis. We report a 67-year-old man with calciphylaxis revealed by an unusual necrotic ulcer of the glans penis. The patient also presented with bilateral panniculitis of the thighs and a calf ulcer. All those lesions were painful, highlighting the value of pain as a diagnostic clue. Penile involvement of calciphylaxis is rare and biopsy is often avoided in this area. However, rapid diagnosis of calciphylaxis is important because early treatment has a better chance of being successful. Our patient's condition deteriorated rapidly with development of bilateral retinal artery occlusion and he died shortly thereafter. This case further highlights the fact that calciphylaxis is a systemic vascular disease with an ominous prognosis.

Vascular occlusion has multiple, diverse clinical manifestations, some of which can have grave consequences for patients. It also has a wide variety of causes, including thrombi, which we recently addressed in partI of this review. In this second part, we look at additional causes of vascular occlusion., (Copyright © 2020 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Unproven stem cell treatments may involve serious health, personal, and financial considerations. Due to worldwide spread, illegal stem cell therapies have become a major public health problem. We have already witnessed numerous reports in the mass media of severe and occasionally even fatal outcomes after such therapies. However, there are only few scientifically documented cases in which the causality between stem cell therapy and side effects cannot be refuted., Case Presentation: Here we present a case report of a 48-year-old patient with serious side effects, including disseminated skin ulcers, hepatitis, and cardiomyopathy, with eventual fatal outcome following unproven stem cell treatment., Conclusions: The case of the patient presented here draws attention to the worst possible outcome of stem cell tourism. To effectively combat this issue, professionals and patients should be empowered with the right knowledge on possible side effects.

Competing Interests: Competing interests: None declared.

While initial reports regarding coronavirus disease 2019 (COVID-19) focused on its pulmonary manifestations, more recent literature describes multisystem abnormalities related to its associated microvascular angiopathy. Calciphylaxis is a rare systemic condition characterized by tissue necrosis in the setting of systemic microvascular calcifications. Both COVID-19 and calciphylaxis are procoagulant diagnoses associated with vascular-mediated cutaneous findings. To our knowledge, this is the first report to document the coexistence of COVID-19 associated retiform thrombotic purpura and calciphylaxis in a single patient, to link the pathologic etiologies of the two entities, and to describe the concomitant diagnoses' associated radiologic findings.

Calciphylaxis is a highly morbid disease that is strongly associated with chronic kidney disease (CKD); however, the histologic criteria for diagnosis have not been well established nor have their specificity for calciphylaxis been determined. This retrospective study aimed to examine the prevalence of histologic features commonly associated with calciphylaxis in noncalciphylaxis patients. We also sought to evaluate whether these features may be more prevalent in patients with CKD. To assess this, healthy marginal skin tissue from above-the-knee amputation specimens was compared between patients with CKD (n = 23) and without CKD (n = 47). Intravascular calcification of capillaries or small-to-medium arterioles was detected on von Kossa stain in 40.0% of the entire cohort. Capillary calcification and intravascular thrombosis were more prevalent in patients with CKD. Finely stippled capillary calcification was present in 26.1% of patients with CKD versus 8.5% of patients without CKD (P = 0.0484), and intravascular thrombosis was present in 8.7% of patients with CKD and 0.0% of patients without CKD (P = 0.0403). None of the patients in this study had clinical evidence of calciphylaxis at presentation and in at least a 1-year follow-up period. This study confirms that the histologic features previously associated with calciphylaxis are nonspecific and are more prevalent in patients with CKD.

Calciphylaxis is a cutaneous vasculopathy with high morbidity and mortality characterized by vascular intimal fibrosis, calcification, stenosis, thrombosis, and eventual tissue death due to ischemia. Histopathologic diagnosis is often difficult, frequently necessitating multiple tissues samples due to lack of specific histopathologic features and subtle changes on biopsies of early lesions. In this study, we review the reported clinical and histopathologic features of calciphylaxis, correlating them with relevant imaging, ancillary studies, and pathophysiology. Although many histopathologic changes seen in calciphylaxis are also reported in other conditions (eg, Mönckeberg sclerosis, lupus panniculitis, pancreatic panniculitis, and peripheral artery disease), calcification of subcutaneous small vessels, thrombosis and/or ischemic changes, pseudoxanthoma elasticum-like changes in the subcutis, and perieccrine calcification may serve as helpful clues. von Kossa and Alizarin red stains can assist in the identification of subtle calcification. Netlike calcification of the affected blood vessels on imaging further supports the diagnosis. Studies into the pathophysiology of calciphylaxis are ongoing and will hopefully facilitate the development of additional diagnostic adjuncts to increase sensitivity and specificity for the diagnosis of this disease.

Calciphylaxis, otherwise known as calcific uremic arteriolopathy, is an aggressive disease characterized by painful, ischemic skin lesions with histologic findings of microvascular calcification involving the fat. It is most commonly seen in patients with end-stage renal disease who are on dialysis. Early diagnosis is pivotal for optimal management. However, calciphylaxis can be challenging to diagnose, as many diseases can bear a clinical resemblance to calciphylaxis. Skin biopsies are often necessitated for diagnosis, but unfortunately, one is commonly challenged with a suboptimal amount of subcutaneous fat that does not always show the classic findings of microvascular calcification. However, when calciphylaxis is clinically suspected, the microscopic detection of subcutaneous pseudoxanthoma elasticum (PXE)-like changes, although not unequivocally diagnostic of calciphylaxis, can be a helpful clue in the diagnosis. We report a case of a 49-year-old woman who was diagnosed with uremic calciphylaxis on the basis of the clinical scenario, laboratory testing, and microscopic presence of subcutaneous PXE-like changes that was highlighted with the elastic and von Kossa stains. This case demonstrates the importance of recognizing subcutaneous PXE-like changes on suboptimal skin biopsies that lack microvascular calcification, especially in those patients who are clinically suspect for calciphylaxis as to prevent delay in diagnosis and treatment.

Competing Interests: None

Calciphylaxis is a rare and severe disease that manifests with painful skin ulceration and necrosis. Herein, we report five patients of hemodialysis patients with skin biopsy-proven calciphylaxis at a single facility. One patient had undergone parathyroidectomy (PTx) due to severe secondary hyperparathyroidism, four had been treated with vitamin D receptor activators, and two were on warfarin therapy. All patients had hyperphosphatemia, and one had hypercalcemia. The intact parathyroid hormone level at diagnosis was 2 pg/ml in the patient after PTx, while three patients were within the target range. The average period after diagnosis of calciphylaxis was 2 months. Skin lesions were present on the thighs and lower legs in two patients, and on the dorsum of the foot in one patient. In skin biopsy, calcification was found in the arteriolar media in four patients, and calcium (Ca) was deposited in the dermal lesion in one patient. All patients received local cures, surgical debridement, antibiotics to control infectious diseases, and strict control of serum Ca and phosphate. Calcimimetics were used in all patients except one who had undergone PTx one month before, sodium thiosulfate was used in 4 patients, and low Ca dialysate was used in three patients. The average follow-up period was 7.4 months. Four patients were cured, and one died due to infection. We suggest that multidisciplinary management for infectious diseases, surgical debridement, strict control of mineral and bone markers from the early stage, and elimination of risk factors may improve the course of calciphylaxis, which is a life-threatening disease.

In this article we focus on updates in select etiologies of retiform purpura. These causes of retiform purpura, in addition to bacterial or fungal sepsis, disseminated intravascular coagulation, purpura fulminans, and catastrophic antiphospholipid syndrome, are important diagnoses with potential for morbidity and mortality. Important aspects in the pathophysiology, patient demographics and risk factors, updates in the diagnostic workup, histopathology, and treatment of these specific conditions are discussed., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Although diffuse dermal angiomatosis (DDA), a rare acquired reactive cutaneous vascular disorder, has been previously reported in association with calciphylaxis (CP), the clinical significance of this relationship has not yet been elucidated., Methods: A total of 24 cases of CP diagnosed from 2013 to 2018 were retrospectively reviewed for the presence of associated DDA. Pertinent clinical information for each patient was also collected, and statistical analysis was performed using multivariable logistic regression, Student t test and Fisher exact test., Results: African American race and comorbid congestive heart failure were the only variables that demonstrated independent, statistically significant association with the presence of DDA. End-stage renal failure, diabetes mellitus, immunosuppressive and hypercoagulable states, arrhythmia, body mass index, hypertension, coronary artery disease, patient age, duration of CP symptoms, gender, time interval from biopsy to death, anticoagulation therapy and sodium thiosulfate administration at the time of biopsy did not demonstrate a statistically significant association with DDA., Conclusion: DDA does not appear to be associated with disease severity or prognosis in cases of CP; however, in our population CP with concurrent DDA was more prevalent in African Americans and individuals with congestive heart failure., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Patients with chronic kidney disease (CKD) have a predisposition to develop vascular calcification due to dysregulated homeostatic mechanisms, which lead to an imbalance in the circulatory promoters and inhibitors of vascular calcification, leading to a net calcification stress. These factors promote ectopic calcification and induce vascular smooth muscle cells to undergo osteogenic differentiation and actively calcify the vascular media. The article summarizes clinically relevant pathogenic mechanisms of vascular calcification in patients with CKD and in dialysis patients and summarizes novel therapeutic interventions. In addition to the management of traditional cardiovascular risk factors, patients with CKD-mineral and bone disorder need close attention in the management of the mineral metabolism to prevent adverse effects on the bone and vascular compartments. This article reviews current evidence and therapeutic guidelines in the management of mineral metabolism in CKD and dialysis., (© 2019 Wiley Periodicals, Inc.)

Diagnosis of calciphylaxis is crucial, yet its distinction from other vascular diseases can be challenging. Although vascular calcification and thrombosis are hallmarks of calciphylaxis, the incidence and patterns of these features in other vascular diseases have not been well characterized. The specificity of fine calcium deposits in vessel walls (identifiable on von Kossa [VK] stain only) and other extravascular calcifications is not entirely clear. We retrospectively examined the clinicopathologic features in calciphylaxis (n=27), gangrene and viable skin at amputation margin (n=20 each), chronic stasis (n=22), and thrombotic vasculopathy (n=19) to identify useful discriminators. Calcification of subcutaneous small vessels appreciable on hematoxylin and eosin stain was relatively specific for calciphylaxis, although sensitivity was low (56%). VK detected fine calcium deposits in vessel walls not appreciable on hematoxylin and eosin, however, specificity was limited by frequent finding of similar deposits in peripheral artery disease. Combining calcium deposits detected by VK and thrombosis of subcutaneous small vessels resulted in optimal sensitivity (85%) and specificity (88%) for calciphylaxis. Similar observations applied to medium-sized vessel calcification. Calcification of eccrine gland basement membranes, elastic fibers, and perineurium did not effectively distinguish calciphylaxis from other groups. Diffuse dermal angiomatosis was exclusively found in calciphylaxis in this study. In conclusion, VK is useful in enhancing the detection of vascular calcification and avoiding the false-negative diagnosis, but this finding requires concomitant subcutaneous small vessel thrombosis to support a diagnosis of calciphylaxis. Diffuse dermal angiomatosis should increase suspicion for underlying calciphylaxis and prompt deeper sampling in the appropriate clinical setting.

Calciphylaxis is a rare and life-threatening disease that classically manifests with painful skin lesions. It occurs mainly in patients with end-stage renal disease (ESRD) treated with dialysis, has poor outcomes, and has no FDA-approved treatment. Our cohort study aims to examine the clinical and pathological features of calciphylaxis and investigates the correlation between cutaneous clinical manifestations and histopathological findings. Data from 70 calciphylaxis patients who were evaluated at the Massachusetts General Hospital between January 2014 and April 2018 were collected from the institutional electronic database. The median age was 58 years (interquartile range [IQR]: 49-69 years), 60% were women, and 73% were of white race. Most (74%) patients reported severe pain at the time of calciphylaxis diagnosis with a median pain intensity score of 8/10 (IQR: 6-10) on a 0-10 pain scale. The median time from symptom onset to clinical diagnosis was 9 weeks (IQR: 6-16 weeks). The majority (87%) of patients presented with open necrotic wounds (advanced stage lesion) at the time of diagnosis. Common cutaneous clinical features included ulceration (79%), induration (57%), and erythema (41%), while common pathological features included cutaneous microvascular calcification (86%) and necrosis (73%). The presence of fibrin thrombi in skin biopsies was associated with pain severity (p = 0.04). The stage of a skin lesion positively correlated with the presence of necrosis on histological analyses (p = 0.02). These findings have implications for improving understanding of calciphylaxis origins and for developing novel treatments., Competing Interests: The authors have declared that no competing interests exist.

General Purpose: To provide information on the pathogenesis, clinical features, diagnosis, and treatment of calciphylaxis., Target Audience: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care., Learning Objectives/outcomes: After participating in this educational activity, the participant should be better able to:1. Recognize the pathogenesis and clinical features of and risk factors for calciphylaxis.2. Explain the diagnosis and management of a patient with calciphylaxis., Abstract: Calciphylaxis is a cutaneous ischemic infarct caused by total occlusion of blood vessels initiated by vascular calcification. Until recently, treatments have been limited to controlling its risk factors and optimizing wound care. However, recent advances in clinical understanding of the mechanism of calciphylaxis have identified promising potential therapeutic targets. This article is a narrative review summarizing the clinical features, diagnosis, pathogenesis, and treatment of calciphylaxis.

Background: Calciphylaxis is a life threatening complication in renal patients. Of great importance is the identification of concomitant factors for calciphylaxis. Due to the variability of clinical presentation the evaluation of such factors may be obscured when calciphylaxis diagnosis is based just on clinical features. We aimed to characterize associated factors only in patients with calciphylaxis proven by histomorphological parameters in addition to clinical presentation., Methods: In a single center retrospective study we analyzed 15 patients in an 8 year period from 2008 to 2016. Only patients with clinical features and histomorphological proof of calciphylaxis were included. Criteria for histological diagnosis of calciphylaxis were intimal hyperplasia, micro thrombi or von Kossa stain positive media calcification., Results: The mean age of patients was 64.8 years. Nine patients (60%) were female; 12 (80%) were obese with a Body-Mass-Index (BMI) > 30 kg/m 2 ; 3 (20%) had no renal disease; 12 (80%) had CKD 4 or 5 and 10 (66.7%) had end-stage renal disease (ESRD). One-year mortality in the entire cohort was 73.3%. With respect to medication history, the majority of patients (n = 13 (86.7%)) received vitamin K antagonists (VKA); 10 (66.7%) were treated with vitamin D; 6 (40%) had oral calcium supplementation; 5 (33.3%) had been treated with corticosteroids; 12 (80%) were on proton pump inhibitors (PPI); 13 (86.7%) patients had a clinical proven hyperparathyroidism. Ten (66.7%) patients presented with hypoalbuminemia at diagnosis., Conclusions: The evaluation of biopsy proven calciphylaxis demonstrates that especially treatment with vitamin K antagonists and liver dysfunction are most important concomitant factors in development of calciphylaxis. As progression and development of calciphylaxis are chronic rather than acute processes, early use of DOACs instead of VKA might be beneficial and reduce the incidence of calciphylaxis.

A 72-year-old female patient presented with an end-stage renal disease on on-line hemodiafiltration and warfarin therapy with advanced ulcerated calciphylaxis on the lower extremities, complicated by two episodes of cellulitis. She was successfully treated for 8 months with intravenous sodium thiosulfate in combination with modification of medication and dialysis treatment, careful wound care, and other supportive measures. Calciphylaxis is an uncommon life-threatening systemic disease, mostly occurring in patients with chronic kidney disease and other risk factors. Vascular calcifications and inflammation lead to thrombotic occlusions of the cutaneous and subcutaneous arterioles, which provoke livedoid painful plaques with possible progression to necrotic ulcers. Conventional treatment is supportive. In recent decades, off-label treatment with sodium thiosulfate, a potent calcium chelator, antioxidant, and vasodilator, has been increasingly reported to be highly efficient in calciphylaxis, leading to significantly lower mortality rates. Knowledge of advancement in the treatment of calciphylaxis, which was previously a highly fatal disease, is important for physicians and other professionals from various medical fields.