Search Results (20)

Fibroblast growth factor receptor 2 (FGFR2) inhibitors such as pemigatinib are targeted therapies for cholangiocarcinoma with FGFR2 alterations. While generally well tolerated, they are associated with unique adverse events. Calciphylaxis, a potentially fatal vascular calcification disorder, is a rare complication. We present a 43-year-old woman with metastatic intrahepatic cholangiocarcinoma harboring an FGFR2 fusion who developed calciphylaxis after seven months of pemigatinib therapy. Despite drug discontinuation, antibiotics, and multidisciplinary supportive care, she deteriorated rapidly and died from sepsis and advanced disease. Histopathological analysis confirmed dermal and vascular calcifications consistent with calciphylaxis. This case highlights the importance of early recognition of cutaneous lesions in patients on FGFR inhibitors. Prompt cessation of therapy, management of metabolic derangements, and consideration of sodium thiosulfate may be lifesaving. Full article

Background and Clinical Significance: Calcinosis cutis is a rare condition that can develop through several mechanisms. These include dystrophic, calciphylaxis (classical, metastatic, and iatrogenic), and idiopathic mechanisms. Idiopathic calcinosis cutis is rare and always a diagnosis of exclusion. A particularly rare site for the development of idiopathic calcinosis cutis is the penis. Case Presentation: A previously healthy 18-year-old male presented to our institution with a three-month history of a painless, firm swelling on the outer layer of the prepucium in the area of the commissure. Histopathology of the excised specimen showed a varying caliber of calcium deposits within the dermis, ranging from small psammoma-like bodies to larger calcium deposits measuring up to 2.5 mm. The deposits were freely dispersed within the dermal collagen and did not exhibit vascular affinity, nor surrounding foci of inflammation. The epidermis was not involved, with only mild reactive hyperkeratosis. The results of detailed physical, imaging, and laboratory tests were normal, and hence the diagnosis of idiopathic calcinosis cutis of the penis was established. Conclusions: Penile calcinosis cutis is a rare condition that falls within the broader group of genital calcinosis cutis. The condition is typically present in young males and has an excellent prognosis after excision. Full article

Background: Calciphylaxis (calcific uremic arteriolopathy), is a rare disease characterized by subcutaneous vascular thrombosis and necrotic skin lesions, which mainly affects patients with kidney disease. This condition often has a poor prognosis, unclear pathophysiology, and lacks standardized treatment. Case Description: We present a case of calciphylaxis in a 53-year-old female patient who reported gradually worsening unbearable pain in her lower limbs and thighs, persisting for approximately 18 months. After appropriate examinations and biopsy of non-healing wounds, histopathology confirmed the diagnosis of calciphylaxis. The wounds were treated with dermo-epidermal (DE) grafts. Followingly, the patient underwent treatment in a hyperbaric chamber, after which the wounds decreased in size. Conclusions: Early diagnosis and a comprehensive approach to therapy are necessary to improve the management of calcification, a rare disease, and complications such as non-healing wounds. Full article

Background/Objectives: Calciphylaxis or calcific uremic arteriolopathy is a rare but highly lethal pathology that occurs most frequently in a uremic context, although it can also occur outside of this context. It is characterized by the appearance of necrotic skin lesions. Localization to the upper limbs is rare and has a similarly progressive evolution. Methods: We present a series of two cases—a male and a female—with calciphylaxis diagnoses (including biopsies) and with the patients undergoing dialysis for end-stage renal disease, both with infected and extensive necrotic lesions to the hands and fingers. Both cases required serial debridement treatments and amputations. A literature review was conducted using the precise search terms “calciphylaxis”, “upper limb”, “uremic calcific arteriolopathy”, and “end-stage renal disease” from January 2010 to May 2024. Results: One of the two reported cases ended with the patient’s death. The results of the literature review (comprising seven similar cases) confirmed the rarity of calciphylaxis lesion localization to the upper limbs and the high mortality rate among these patients despite administered treatments. No therapeutic protocol for these cases was confirmed. Conclusions: The treatment of calciphylaxis cases is multidisciplinary. Although surgical intervention is controversial, it is necessary in some cases, sometimes serially. Localization to the thoracic limbs has the same evolution and poor prognosis as other localizations. A standardized therapeutic protocol for these cases is still far from being established. Full article

Background/Objectives: Ectopic calcification is a pathological condition characterized by the mineralization of soft tissues due to the deposition of calcium phosphate crystals. Hexasodium fytate (CSL525, previously known as SNF472) is a crystallization inhibitor being developed for the treatment of ectopic calcification-related disorders. Our aim was to investigate CSL525 for the treatment of soft-tissue calcification disorders in animal models of pseudoxanthoma elasticum and calcinosis cutis. Methods: In a first study, abcc6^-/- zebrafish larvae were exposed to 1 mM CSL525 for 7 days or kept under the same conditions without CSL525, and spinal mineralization was quantified. In a second study, abcc6^-/- mice were administered subcutaneously with CSL525 at 15 mg/kg thrice weekly for eight weeks. Vehicle-treated WT (C57BL/6J) and abcc6^-/- mice served as controls, and muzzle skin calcification was quantified. In a third study, calcinosis cutis was induced in rats through subcutaneous administration of 0.15 mg FeCl₃ at two sites in the thorax. Rats were administered either subcutaneous CSL525 (60 mg/kg) or vehicle (0.9% NaCl), and calcium content was measured in the skin. Results: CSL525 significantly reduced the calcified area (~40%) in abcc6a^-/- zebrafish larvae. The abcc6^-/- mice receiving CSL525 showed a 57% inhibition of muzzle calcification compared to vehicle-treated abcc6^-/- mice. CSL525 inhibited skin calcification development by 60% in the calcinosis cutis rat model. Conclusions: CSL525 may prove beneficial not only in preventing the progression of cardiovascular calcification but also in treating other ectopic calcification conditions, including skin calcification associated with genetic disorders such as PXE. Full article

Calcific uremic arteriolopathy, also known as calciphylaxis, is a rare and often fatal condition most commonly occurring in patients with end-stage renal disease (ESRD). It is marked by extensive vascular calcification, resulting in tissue ischemia and the development of distinctive skin lesions. We report the case of a 38-year-old male with ESRD due to polycystic kidney disease, who developed calciphylaxis lesions following total parathyroidectomy (PTx). We also performed an electronic search of PubMed and Google Scholar from inception until December 2024, using the following keywords: ‘chronic kidney disease’, ‘dialysis’, ‘calciphylaxis’, ‘calcific uremic arteriolopathy’, ‘secondary hyperparathyroidism’, and ‘parathyroidectomy’. A literature review of calciphylaxis cases following PTx in chronic kidney disease (CKD) patients identified 14 cases reported up to the manuscript’s writing. Although PTx can be a treatment option for calciphylaxis related to severe secondary hyperparathyroidism (SHPT), leading to clinical improvement in some patients, there are atypical calciphylaxis cases occurring after PTx. While the mechanism is not fully understood, the sudden reduction in parathormone (PTH) levels leading to hypocalcemia and decreased bone turnover, together with an increased calcium loading in a patient at risk for abnormal mineralization, may promote vascular and soft tissue calcification. However, the long-term impact of severe SHPT with a delayed post-PTx manifestation cannot be ruled out. Clinicians should consider calciphylaxis in CKD patients with new painful skin lesions. Skin biopsy remains controversial, but a thorough clinical examination, and, in some cases, imaging are essential for a correct diagnosis. A multidisciplinary, personalized approach is crucial, with careful management of post-PTx hypocalcemia and calcium supplementation. Further research is needed to enhance understanding and treatment strategies. Full article

Introduction: Calciphylaxis, also known as calcific uremic arteriolopathy (CUA), is a rare and potentially fatal condition primarily affecting patients with end-stage renal disease (ESRD) on hemodialysis (HD). It is characterized by calcification in small blood vessels, leading to painful skin ulcers and high mortality rates. Case Description: This is a case of a 42-year-old female with ESRD on HD who developed calciphylaxis, presenting with non-healing ulcers on her thighs. Discussion: Despite initial treatments, including wound care and pain management, her condition did not improve. A skin biopsy was inconclusive, highlighting the diagnostic challenges associated with calciphylaxis. Based on clinical judgment, warfarin and calcium-based therapies were discontinued, and the patient’s HD regimen was adjusted. Due to the persistence of symptoms, sodium thiosulfate (STS) therapy was initiated, leading to significant improvement in her ulcers after six months of treatment. Conclusions: This case highlights the importance of clinical judgment in the diagnosis and management of calciphylaxis, particularly when histopathological diagnostic methods yield inconclusive results. Clinical criteria, alongside a thorough assessment of the patient’s history and presentation, are vital for achieving a timely diagnosis in such challenging cases. The successful use of sodium thiosulfate in this patient adds to the growing body of evidence supporting its use as a potential treatment for calciphylaxis, especially in cases that do not respond to conventional therapy. Full article

Late-onset Alzheimer’s disease (LOAD) is a chronic, multifactorial, and progressive neurodegenerative disease that associates with aging and is highly prevalent in our older population (≥65 years of age). This hypothesis generating this narrative review will examine the important role for the use of sodium thiosulfate (STS) as a possible multi-targeting treatment option for LOAD. Sulfur is widely available in our environment and is responsible for forming organosulfur compounds that are known to be associated with a wide range of biological activities in the brain. STS is known to have (i) antioxidant and (ii) anti-inflammatory properties; (iii) chelation properties for calcium and the pro-oxidative cation metals such as iron and copper; (iv) donor properties for hydrogen sulfide production; (v) possible restorative properties for brain endothelial-cell-derived bioavailable nitric oxide. Thus, it becomes apparent that STS has the potential for neuroprotection and neuromodulation and may allow for an attenuation of the progressive nature of neurodegeneration and impaired cognition in LOAD. STS has been successfully used to prevent cisplatin oxidative-stress-induced ototoxicity in the treatment of head and neck and solid cancers, cyanide and arsenic poisoning, and fungal skin diseases. Most recently, intravenous STS has become part of the treatment plan for calciphylaxis globally due to vascular calcification and ischemia-induced skin necrosis and ulceration. Side effects have been minimal with reports of metabolic acidosis and increased anion gap; as with any drug treatment, there is also the possibility of allergic reactions, possible long-term osteoporosis from animal studies to date, and minor side-effects of nausea, headache, and rhinorrhea if infused too rapidly. While STS poorly penetrates the intact blood–brain barrier(s) (BBBs), it could readily penetrate BBBs that are dysfunctional and disrupted to deliver its neuroprotective and neuromodulating effects in addition to its ability to penetrate the blood–cerebrospinal fluid barrier of the choroid plexus. Novel strategies such as the future use of nano-technology may be helpful in allowing an increased entry of STS into the brain. Full article

Dietary phytic acid/phytate/myo-inositol hexaphosphate (IP6), a phosphate reservoir in plants, was viewed as antinutrient, caused by an influence on the bioavailability of minerals through its chelating activity. However, there is a growing body of evidence indicating that IP6 has beneficial (e.g., antiinflammatory, antibacterial, and anticancer) effects on multiple biological processes. Also, IP6 and its metabolites are known to exist in mammalian cells, including human cells, and the role of IP6 as a functional molecule is attracting attention. IP6 can bind to the growth sites of hydroxy-apatite (HA) and calcium oxalate crystals to prevent their growth and hence inhibit pathological calcification. SNF472, hexasodium IP6, is currently being evaluated in clinical studies as a treatment for vascular calcification and calciphylaxis. However, since HA crystal growth within bone matrix is an essential process in bone formation, it is possible that IP6 intake may inhibit physiological mineralization and bone formation, although currently more published studies suggest that IP6 may contribute to bone health rather than inhibit bone formation. Given that IP6 and its metabolites are thought to have diverse activities and many health benefits, it remains important to consider the range of effects of IP6 on bone. Full article

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. Full article

Limited data are available on the utilization of sodium thiosulfate (STS) treatment for calciphylaxis in peritoneal dialysis (PD) patients, while it is well-studied in hemodialysis (HD) patients. A systematic literature search was conducted using Ovid MEDLINE, EBM Reviews—Cochrane Central Register of Controlled Trials, and EBM Reviews—Cochrane Database of Systematic Reviews to identify reported cases of PD patients with calciphylaxis who received STS. The search covered the inception of the databases through August 2022. Across 19 articles, this review identified 30 PD patients with calciphylaxis who received STS. These included 15 case reports, 2 case series, and 2 cohort studies. The administration routes and doses varied depending on the study. For intravenous (IV) administration (n = 18), STS doses ranged from 3.2 g twice daily to 25 g three times weekly for 5 weeks to 8 months. Outcomes included 44% of patients experiencing successful wound healing, 6% discontinuing STS due to adverse effects, 67% transitioning to HD, and 50% dying from calciphylaxis complications. For intraperitoneal (IP) administration (n = 5), STS doses ranged from 12.5 to 25 g three to four times weekly for 12 h to 3 months. Results showed 80% of patients achieving successful wound healing, 80% discontinuing STS due to adverse effects, 40% transitioning to HD, and 20% dying from IP STS-related chemical peritonitis. In cases where patients switched from IV to IP STS (n = 3), doses ranged from 12.5 to 25 g two to three times weekly for 2.5 to 5 months. Among them, 67% experienced successful wound healing, while 33% died from sepsis. Two cases utilized oral STS at a dose of 1500 mg twice daily for 6 and 11 months, resulting in successful wound healing without adverse effects or need for HD. However, one patient (50%) died due to small bowel obstruction. This systematic review provides an overview of STS treatment for PD patients with calciphylaxis. Although successful treatment cases exist, adverse effects were significant. Further research, including larger clinical studies and pharmacokinetic data, is necessary to establish the optimal route, dose, and efficacy of STS in PD patients. Full article

Calcinosis represents a severe complication of several autoimmune disorders. Soft-tissue calcifications have been classified into five major types: dystrophic, metastatic, idiopathic, iatrogenic, and calciphylaxis. Autoimmune diseases are usually associated with dystrophic calcifications, including calcinosis cutis, occurring in damaged or devitalized tissues in the presence of normal serum levels of calcium and phosphate. In particular, calcinosis cutis has been described in dermatomyositis, polymyositis, juvenile dermatomyositis, systemic sclerosis, systemic lupus erythematosus, primary Sjögren’s syndrome, overlap syndrome, mixed connective tissue disease, and rheumatoid arthritis. Calciphylaxis, a severe and life-threatening syndrome presenting with vascular calcifications and thrombosis, has also been associated with some autoimmune conditions. Due to the potentially disabling character of calcinosis cutis and calciphylaxis, physicians’ awareness about the clinical presentation and management of these diseases should be increased to select the most appropriate treatment option and avoid long-term complications. In this review, we aim to analyze the clinical features of calcinosis cutis and calciphylaxis associated with autoimmune diseases, and the main treatment strategies evaluated up to now for treating this potentially disabling disease. Full article

Amniotic membrane (AM) is an avascular structure composed of three different layers, which contain collagen, extracellular matrix, and biologically active cells (stem cells). Collagen, a naturally occurring matrix polymer, provides the structural matrix/strength of the amniotic membrane. Tissue remodeling is regulated by growth factors, cytokines, chemokines, and other regulatory molecules produced by endogenous cells within AM. Therefore, AM is considered an attractive skin-regenerating agent. This review discusses the application of AM in skin regeneration, including its preparation for application to the skin and its mechanisms of therapeutic healing in the skin. This review involved collecting research articles that have been published in several databases, including Google Scholar, PubMed, Science Direct, and Scopus. The search was conducted by using the keywords ‘amniotic membrane skin’, ‘amniotic membrane wound healing’, ‘amniotic membrane burn’, ‘amniotic membrane urethral defects’, ‘amniotic membrane junctional epidermolysis bullosa’, and ‘amniotic membrane calciphylaxis’. Ultimately, 87 articles are discussed in this review. Overall, AM has various activities that help in the regeneration and repair of damaged skin. Full article

Background: Rheopheresis is a double-filtration plasmapheresis that removes a defined spectrum of high-molecular-weight proteins to lower plasma viscosity and improves microcirculation disorders. This technique can be performed in hemodialysis (HD) patients with severe microischemia. Interestingly, some studies showed that rheopheresis sessions improve endothelial function. Methods: Our study evaluated the inflammatory and endothelial biomarker evolution in 23 HD patients treated or not with rheopheresis. A p value ≤ 0.001 was considered statistically significant. Results: Thirteen HD patients treated by rheopheresis either for a severe peripheral arterial disease (N = 8) or calciphylaxis (N = 5) were analyzed. Ten control HD patients were also included in order to avoid any misinterpretation of the rheopheresis effects in regard to the HD circuit. In the HD group without rheopheresis, the circulating endothelial adhesion molecules, cytokines, angiogenic factor concentrations, and circulating levels were not modified. In the HD group with rheopheresis, the circulating endothelial adhesion molecules (sVCAM-1, sP-selectin, and sE-selectin) experienced a significant reduction, except sICAM-1. Among the pro-inflammatory cytokines, TNF-α was significantly reduced by 32.6% [(−42.2)–(−22.5)] (p < 0.0001), while the anti-inflammatory cytokine IL-10 increased by 674% (306–1299) (p < 0.0001). Among the angiogenic factors, only sEndoglin experienced a significant reduction. The CEC level trended to increase from 13 (3–33) cells/mL to 43 (8–140) cells/mL (p = 0.002). We did not observe any difference on the pre-session values of the molecules of interest between the first rheopheresis session and the last rheopheresis session. Conclusion: Rheopheresis immediately modified the inflammation balance and the endothelial injury biomarkers. Further studies are needed to understand the mechanisms underlying these biological observations. Full article

Calcific uraemic arteriolopathy (CUA), also known as calciphylaxis, is a rare and often fatal condition, frequently diagnosed in end-stage renal disease (ESRD) patients. Although exact pathogenesis remains unclear, iron supplementation is suggested as a potential risk factor. Iron and erythropoietin are the main stay of treatment for anaemia in ESRD patients. Few observational studies support the role of iron in the pathogenesis of calciphylaxis although data from the pivotal trial was not strongly supportive of this argument, i.e., no difference in incidence of calciphylaxis between the low-dose and high-dose iron treatment arms. Elevated levels of vascular cell adhesion molecules in association with iron excess were postulated to the pathogenesis of CUA by causing inflammation and calcification within the microvasculature. In-addition, oxidative stress generated because of iron deposition in cases of systemic inflammation, such as those seen in ESRD, may play a role in vascular calcification. Despite these arguments, a direct correlation between cumulative iron exposure with CUA incidence is not clearly demonstrated in the literature. Consequently, we do not have evidence to recommend iron reduction or cessation in ESRD patients that develop CUA. Full article