5,050 research outputs found

    Autoimmune hyperphosphatemic tumoral calcinosis in a patient with FGF23 autoantibodies

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    Hyperphosphatemic familial tumoral calcinosis (HFTC)/hyperostosis-hyperphosphatemia syndrome (HHS) is an autosomal recessive disorder of ectopic calcification due to deficiency of or resistance to intact fibroblast growth factor 23 (iFGF23). Inactivating mutations in FGF23, N-acetylgalactosaminyltransferase 3 (GALNT3), or KLOTHO (KL) have been reported as causing HFTC/HHS. We present what we believe is the first identified case of autoimmune hyperphosphatemic tumoral calcinosis in an 8-year-old boy. In addition to the classical clinical and biochemical features of hyperphosphatemic tumoral calcinosis, the patient exhibited markedly elevated intact and C-terminal FGF23 levels, suggestive of FGF23 resistance. However, no mutations in FGF23, KL, or FGF receptor 1 (FGFR1) were identified. He subsequently developed type 1 diabetes mellitus, which raised the possibility of an autoimmune cause for hyperphosphatemic tumoral calcinosis. Luciferase immunoprecipitation systems revealed markedly elevated FGF23 autoantibodies without detectable FGFR1 or Klotho autoantibodies. Using an in vitro FGF23 functional assay, we found that the FGF23 autoantibodies in the patient's plasma blocked downstream signaling via the MAPK/ERK signaling pathway in a dose-dependent manner. Thus, this report describes the first case, to our knowledge, of autoimmune hyperphosphatemic tumoral calcinosis with pathogenic autoantibodies targeting FGF23. Identification of this pathophysiology extends the etiologic spectrum of hyperphosphatemic tumoral calcinosis and suggests that immunomodulatory therapy may be an effective treatment

    Clinical phenotypes and biologic treatment use in juvenile dermatomyositis-associated calcinosis

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    Abstract Background Few risk factors have been identified for the development of calcinosis among patients with Juvenile Dermatomyositis, and currently no clinical phenotype has been associated with its development. We analyzed a large database of patients to further elucidate any relationships among patients with and without calcinosis. Method The CARRA legacy registry recruited pediatric rheumatology patients from 55 centers across North America from 2010 through 2014, including over 650 subjects with Juvenile Dermatomyositis. We compared the demographic characteristics, clinical disease features and treatment histories of those with and without calcinosis using univariate and multivariate logistic regression. Results Of the 631 patients included in the analysis, 84 (13%) had a current or prior history of calcinosis. These patients were statistically more likely to have longer durations of disease prior to diagnosis and treatment, have lipodystrophy and joint contractures, and to have received intravenous immune globulin or rituximab as treatments. Conclusions Calcinosis is found more often in patients with prolonged active disease, severe disease, and certain clinical features such as lipodystrophy and joint contractures. When these factors are combined with other known associations and predictors, groups of at-risk patients can be more effectively identified, treated and studied to improve overall outcomes

    An Unusual Combination of Neurological Manifestations and Sudden Vision Loss in a Child with Familial Hyperphosphatemic Tumoral Calcinosis

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    Hyperphosphatemia in the absence of renal failure is an unusual occurrence, particularly in children, but is a common primary feature of familial hyperphosphatemic tumor calcinosis. We report a child with hyperphosphatemia who presented with multiple episodes of neurologic dysfunction involving lower motor neuron facial nerve palsy along with sequential visual loss. He also had an episode of stroke. There was an extensive metastatic calcification of soft tissue and vasculature. Hyperphosphatemia with normal serum alkaline phosphatase, calcium, parathyroid hormone, and renal function was noted. He was managed with hemodialysis and sevelamer (3 months) without much success in reducing serum phosphate level, requiring continuous ambulatory peritoneal dialysis (3 years). Intact fibroblast growth factor 23 (FGF23) was undetectable, with C-terminal FGF23 fragments significantly elevated (2575 RU/ml, normal A (p.N162K) mutation in FGF23 exon 3, confirming the diagnoses of primary FGF23 deficiency, the first case to be reported from India

    From variome to phenome : pathogenesis, diagnosis and management of ectopic mineralization disorders

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    Ectopic mineralization - inappropriate biomineralization in soft tissues - is a frequent finding in physiological aging processes and several common disorders, which can be associated with significant morbidity and mortality. Further, pathologic mineralization is seen in several rare genetic disorders, which often present life-threatening phenotypes. These disorders are classified based on the mechanisms through which the mineralization occurs: metastatic or dystrophic calcification or ectopic ossification. Underlying mechanisms have been extensively studied, which resulted in several hypotheses regarding the etiology of mineralization in the extracellular matrix of soft tissue. These hypotheses include intracellular and extracellular mechanisms, such as the formation of matrix vesicles, aberrant osteogenic and chondrogenic signaling, apoptosis and oxidative stress. Though coherence between the different findings is not always clear, current insights have led to improvement of the diagnosis and management of ectopic mineralization patients, thus translating pathogenetic knowledge (variome) to the phenotype (phenome). In this review, we will focus on the clinical presentation, pathogenesis and management of primary genetic soft tissue mineralization disorders. As examples of dystrophic calcification disorders Pseudoxanthoma elasticum, Generalized arterial calcification of infancy, Keutel syndrome, Idiopathic basal ganglia calcification and Arterial calcification due to CD73 (NT5E) deficiency will be discussed. Hyperphosphatemic familial tumoral calcinosis will be reviewed as an example of mineralization disorders caused by metastatic calcification

    Tongue and tail necrosis in an atypical case of acute steroid responsive meningitis-arteritis in a dog

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    Acute steroid responsive meningitis-arteritis (SRMA) is a common neurological disorder in young dogs. Typical clinical symptoms of the acute form of SRMA are neck pain, depression and fever. This case report describes a 1.5-year-old Pointer with uncommon neurological deficits (unilateral multiple cranial nerve deficits and Homer's syndrome) and an exceptional necrosis of the tongue. This was believed to be part of the systemic vasculitis accompanying SRMA. The patient also developed tail necrosis and iatrogenic calcinosis cutis, which complicated further treatment of the dog

    Calcinosis and Myocarditis in Systemic Lupus Erythematosus Patient

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    Systemic lupus erythematosus (SLE) patients have multi-organ involvement related to their chronic inflammatory, autoimmune disease. Calcinosis can be clinical manifestations of SLE. Tissue calcinosis is reported in approximately 17% patients and myocarditis in 20-55% patients. Thus, both manifestations are not unusual in SLE. Tachypnea, tachycardia, pericardial effusion, and wheezing are often present and can be misleading in SLE patient.1,2 Calcinosis is less common in SLE, sometimesit is found as an incidental radiological finding. Calcification in SLE maybe periarticular, within joints or muscles, or in the subcutis (calcinosis universalis).1 Calcinosis is classified into four subsets: dystrophic, metastatic, idiopathic, or calciphylaxis/iatrogenic. When calcinosis cutis is isolated to a small area in extremities and joints, it is called calcinosis circumscripta; whereas its diffuse form, refers to calcinosis universalis, affects subcutaneous and fibrous structures of muscles and tendons. The pathophysiology of this condition is unknown and no effective therapy is currently available.3,4,5 Systemic lupus erythematosus can involve the myocardium, pericardium, cardiac valves,and coronary arteries. Myocarditis in SLE is not likely to produce major regional wall motion abnormalities but may contribute to global left ventricular dysfunction.7,8We report a young woman with SLE who developed calcinosis and myocarditis

    Is Anti-NXP2 Autoantibody a Risk Factor for Calcinosis and Poor Outcome in Juvenile Dermatomyositis Patients? Case Series

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    open9siJuvenile dermatomyositis (JDM) has a wide spectrum of clinical presentations. In the last decade, several myositis-specific antibodies have been identified in patients with JDM and connected with specific organ involvement or specific clinical picture. It has been published that the presence of anti-NXP2 autoantibodies presents a risk for calcinosis in patients with JDM. We aimed to investigate the prevalence of calcinosis and response to the treatment in JDM patients with anti-NXP2. In a retrospective, multinational, multicenter study, data on 26 JDM (19 F, 7 M) patients with positive anti-NXP2 were collected. The mean age at disease presentation was 6.5 years (SD 3.7), the median diagnosis delay was 4 months (range 0.5–27 months). Patients were divided into two groups (A and B) based on the presence of calcinosis, which occurred in 42% of anti-NXP2 positive JDM patients (group A). Four patients already had calcinosis at presentation, one developed calcinosis after 4 months, and 6 developed calcinosis later in the disease course (median 2 years, range 0.8–7.8). The differences in laboratory results were not statistically significant between the groups. The mean age at disease presentation (5.2/7.5 years) trended toward being younger in group A. Children with calcinosis were treated with several combinations of drugs. In four cases, rituximab and, in one case, anti-TNF alpha agents were used successfully. Disease outcome (by evaluation of the treating physician) was excellent in four, good in two, stable in two, and poor in three patients. None of the patients from group B had a poor disease outcome. In conclusion, JDM patients with anti-NXP2 are prone to develop calcinosis, especially if they present with the disease early, before 5 years of age. The development of calcinosis is associated with worse disease outcomes. The combination of several immunomodulatory drugs and biologic drugs can stop calcinosis progression; however, there are no evidence-based therapies for treating calcinosis in JDM patients.openToplak N.; Pimpale Chavan P.; Rosina S.; Dallos T.; Rotem Semo O.; Aguiar C.L.; Khubchandani R.; Ravelli A.; Patwardhan A.Toplak, N.; Pimpale Chavan, P.; Rosina, S.; Dallos, T.; Rotem Semo, O.; Aguiar, C. L.; Khubchandani, R.; Ravelli, A.; Patwardhan, A
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