Search Results (13)

Background/Objectives: Calcinosis cutis universalis is a rare and severe manifestation of dystrophic calcification, most associated with connective tissue diseases such as dermatomyositis, systemic sclerosis, and systemic lupus erythematosus. It is characterized by widespread deposition of calcium salts throughout the soft tissues, leading to pain, recurrent infections, restricted mobility, and significant impairment in daily functioning and quality of life. Management remains challenging due to the absence of standardized treatment guidelines with risks including delayed wound healing and recurrence. Adjunctive therapies may support symptom control in refractory cases. Conclusions: Management of calcinosis cutis universalis requires an individualized, multimodal strategy. Based on available evidence and expert opinion, a stepwise therapeutic decision-making algorithm integrating medical, minimally invasive, and surgical approaches is proposed to guide clinical practice and the variable efficacy of available therapies. This review aims to summarize current therapeutic strategies and to propose a pragmatic approach to clinical decision-making. Methods: A narrative review of the literature was conducted using PubMed and Google Scholar. The review focused primarily on calcinosis cutis universalis and severe or extensive forms of calcinosis cutis, with particular emphasis on surgical management and its integration with medical and minimally invasive treatments. Results: Pharmacological treatments—including bisphosphonates, calcium-channel blockers, tetracyclines, phosphate binders, probenecid, immunomodulatory agents, biologics, colchicine, sodium thiosulfate and JAK inhibitors—show heterogeneous and often partial efficacy, with more favorable responses in early or localized disease. Surgical interventions such as excision, curettage, CO₂ laser ablation, and reconstructive procedures provide meaningful symptomatic relief in selected patients but are associated. Full article

Calcium deposition within soft tissues is a significant pathological process, bearing significant implications for animal and human health. It is classified into four categories, including dystrophic, metastatic, idiopathic, and iatrogenic. It involves multiple molecular mechanisms. Vascular calcification includes medial artery mineralization, siderocalcinosis in equine cerebral arteries, and vitamin D-induced arterial mineralization in multiple species. Renal and urinary mineralization occurs with kidney disease, uremic gastropathy, and ethylene glycol toxicity. Calcinosis cutis is associated with renal insufficiency and systemic fungal infections and is commonly observed in dogs with hyperadrenocorticism, while calcinosis circumscripta occurs at pressure points secondarily to trauma. Multiple pathogens are responsible for soft tissue calcification; they can be zoonotic and include Mycobacterium spp., Brucella spp., Toxoplasma gondii, and Echinococcus granulosus, underscoring the translational role of veterinary medicine surveillance from a public health standpoint. In addition, the placental chorioallantois is frequently affected by idiopathic or infection-induced calcification, highlighting the convergence of metabolic dysregulation and infectious mechanisms. Tissue calcifications provide valuable insights into disease mechanisms and diagnostic challenges, with comparative pathology serving as a powerful tool to enhance our understanding of these processes from a One Health standpoint. 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/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

Background/Objectives: Calcinosis cutis (CC) is a condition that may develop in the course of several autoimmune connective tissue diseases (ACTDs). Among these, the conditions most frequently associated with CC are systemic sclerosis (SSc) and dermatomyositis (DM). Despite both the prevalence and diversity of available treatment options, therapeutic recommendations remain not fully established due to a limited number of studies and lack of unambiguous evidence regarding their effectiveness. Case Presentation: We report two cases of patients with DM and concomitant massive cutaneous calcifications who were treated: in the case of a 71-year-old man with DM and past medical history of primary cutaneous T-cell lymphoma (CTCL) who received intralesional (IL) 25% sodium thiosulfate (STS) with platelet-rich plasma (PRP) injections, and, in the case of a second patient, 24-year-old woman with nephrolithiasis, who received intravenous immunoglobulin (IVIG) infusions at a dose of 2 g/kg in combination with prednisone at a dose of 5 mg/day. Conclusions: The applied treatment led to reduction in pain, size, and number of calcified lesions. Additionally, healing of fingertip ulcers after PRP injections was observed. While this report highlights only two isolated cases, the use of IVIG and STS with PRP injections appears to be an effective treatment method. Nevertheless, both standardization and additional research are required. Full article

Introduction: Calcinosis cutis (CC), the pathological deposition of calcium salts in the skin, is a frequent and challenging complication of systemic sclerosis (SSc). Despite its high prevalence, the underlying pathophysiology remains poorly understood, complicating treatment strategies. Material and Methods: This narrative review synthesizes the literature on CC in the context of SSc. The current understanding and treatment of CC in SSc is reviewed, focusing on the role of hypoxia in its pathogenesis and the therapeutic potential of sodium thiosulfate (STS). Results and Discussion: Research indicates a potential link between hypoxia and the development of CC in SSc, shedding light on novel pathogenic mechanisms. Additionally, promising results from treatments such as STS spurs interest in conducting larger, randomized controlled trials to validate these findings. Full article

Calcified tissue exposed in a leg ulcer can become infected and develop into a nidus of infection leading to sepsis. This case details a patient with a leg wound secondary to skin biopsy. This leg ulceration did not heal due to an underlying calcified mass and led to five hospital admissions for sepsis. She was diagnosed as having calcinosis cutis, which was suspected to be the source of her infections. The calcified mass was resected, and she healed uneventfully without further infections. Calcified soft-tissue masses should be considered in nonhealing leg ulcers and ulcers with multiple recurrent infections. Radiographs can be used to diagnose this condition, and surgical excision can be considered in cases of infection. Full article

Background/Objectives: Calcinosis cutis is the deposition of insoluble calcium salts, which may cause inflammation, ulceration, pain, and restricted joint mobility. It rarely develops in damaged tissues (dystrophic subtype), most frequently in autoimmune connective tissue diseases (CTDs), but there is very limited data on the prevalence. Also, therapy remains an unsolved issue. In this study, we aimed to collect data on the prevalence of calcinosis in CTD patients to highlight that it is a considerable problem. Methods: A retrospective study was conducted in our department to assess the epidemiology of dystrophic calcinosis in CTDs between January 2003 and January 2024. Results: A total of 839 CTD patients were identified, of whom 56 had calcinosis (6.67%). The mean age of the calcinosis patients at diagnosis of underlying CTD was 41.16 ± 19.47 years. The mean time interval from the onset of calcinosis was 5.96 ± 8.62 years. Systemic sclerosis was the most common CTD complicated by calcinosis (n = 22). Conclusions: Our results are comparable to those reported previously in the literature. Although calcinosis is rare in the overall population, it is a present and unsolved problem in CTD patients. Therefore, further studies are needed on the factors involved in the development and progression of calcinosis as well as its treatment. Full article

(1) Background: Calcinosis of the skin mainly appears in connective tissue disorders (dystrophic subtype). It may cause inflammation, ulceration, pain, and restricted joint mobility. Management is difficult; sodium thiosulfate is one potential therapeutic agent with promising data on intralesional and topical formulation for smaller calcified lesions. There are very limited data on systemic administration. (2) Methods: A retrospective study was conducted at our department to assess the efficacy of oral and intravenous sodium thiosulfate in dystrophic calcinosis between 2003 and 2023. (3) Results: Seven patients were identified, who received systemic sodium thiosulfate (intravenous or oral). The mean duration of calcinosis at the time of administration was 3.8 ± 4 years (range 0–11). Intravenous sodium thiosulfate was administered in doses of 12.5–25 g two or three times during one week of the month for 4.5 ± 3.9 months on average. Orally, 1–8 g was administered daily for 29.1 ± 40.9 months on average. Four of seven patients had a partial response (57.1%). Despite no complete response, pain, ulceration and inflammation frequency decreased, and sodium thiosulfate prevented further progression in responsive patients. (4) Conclusions: Based on our experience and literature data, systemic sodium thiosulfate may be a potential adjunct therapy in calcinosis, especially if inflamed or ulcerating. 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

Calcinosis cutis is the deposition of calcium salts in the skin and subcutaneous tissue, manifesting as variably shaped papules, nodules, and plaques that can substantially impair quality of life. The pathophysiology of calcinosis cutis involves dysregulation of proinflammatory cytokines, leukocytes, and other components of the innate immune system. In some conditions associated with calcinosis cutis, elevated serum calcium, phosphate, and vitamin D may also perturb innate immunity. The mechanisms by which these lead to cutaneous and subcutaneous calcification likely parallel those seen in vascular calcification. The role of aberrant innate immunity is further supported by the association between various autoantibodies with calcinosis cutis, such as anti-MDA5, anti-NXP2, anti-centromere, and anti-topoisomerase I. Treatments for calcinosis cutis remain limited and largely experimental, although mechanistically many therapies appear to focus on dampening innate immune responses. Further research is needed to better understand the innate immune pathophysiology and establish treatment options based on randomized-controlled trials. Full article

(1) Background: Calcinosis cutis is a frequent symptom of autoimmune connective tissue diseases leading to pain, transcutaneous expulsion of calcified material and bacterial superinfection. There is a high need for new therapeutic options as no standardized treatment algorithm is established. While case reports indicate beneficial effects of bisphosphonates, standardized evaluation of treatment effects is missing. (2) Methods: In this retrospective analysis we evaluate the effects of intravenous pamidronate, a second-generation bisphosphonate, in seven patients with calcinosis cutis using consecutive clinical pictures, radiological examinations and patient’s subjective evaluation. (3) Results: 5/6 patients reported a reduction of pain, improvement of general condition and cessation of calcinosis progression. Regression of skin lesions was detectable in clinical pictures of 2/6 patients, while 1/6 patients had stable disease. Radiological examination revealed improvement or stable disease in 3/5 patients. Fever was the most common side effect. One out of seven patients developed osteonecrosis of the jaw. (4) Conclusions: Bisphosphonates appear to have beneficial effects in a subgroup of calcinosis cutis patients. While patient’s subjective evaluation was mainly positive, objective assessments showed improvement in approximately half of the cases. With regard to potential severe side effects, a careful risk-benefit evaluation is necessary before treatment initiation. Full article

Systemic sclerosis (SSc) is an autoimmune disease with fibrosis of the skin and/or internal organs, causing a decrease in quality of life and survival. There is no causative therapy, and the pathophysiology of the SSc remains unclear. Studies showed that lipid metabolism was relevant for autoimmune diseases, but little is known about the role of lipids in SSc. In the present study, we sought to explore the phospholipid profile of SSc by using the lipidomics approach. We also aimed to analyze lipidomics results for different clinical manifestations of SSc. Experiments were performed using high-performance liquid chromatography coupled to mass spectrometry for the lipidomic profiling of plasma samples from patients with SSc. Our study showed, for the first time, significant changes in the level of phospholipids such as plasmalogens and sphingomyelins from the plasma of SSc patients as compared to controls. Phosphatidylcholine plasmalogens species and sphingomyelins were significantly increased in SSc patients as compared to controls. Our results also demonstrated a significant association of changes in the metabolism of phospholipids (phosphatidylcholine and phosphatidylethanolamine plasmalogens species and sphingomyelins) with different clinical manifestations of SSc. Further lipidomic studies might lead to the detection of lipids as new biomarkers or therapeutic targets of SSc. Full article