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Objectives: The objective of this study is to better characterize the features and outcomes of a large population of patients with mixed connective tissue disease (MCTD). Methods: We performed an observational retrospective multicenter cohort study in France. Patients who fulfilled at least one diagnostic criterion set for MCTD and none of the criteria for other differentiated CTD (dCTD) were included. Results: Three hundred and thirty patients (88% females, median [interquartile range] age of 35 years [26–45]) were included. The diagnostic criteria of Sharp or Kasukawa were met by 97.3% and 93.3% of patients, respectively. None met other classification criteria without fulfilling Sharp or Kasukawa criteria. After a median follow‐up of 8 (3–14) years, 149 (45.2%) patients achieved remission, 92 (27.9%) had interstitial lung disease, 25 (7.6%) had pulmonary hypertension, and 18 (5.6%) died. Eighty‐five (25.8%) patients progressed to a dCTD, mainly systemic sclerosis (15.8%) or systemic lupus erythematosus (10.6%). Median duration between diagnosis and progression to a dCTD was 5 (2–11) years. The presence at MCTD diagnosis of an abnormal pattern on nailfold capillaroscopy (odds ratio [OR] = 2.44, 95% confidence interval [95%CI] [1.11–5.58]) and parotid swelling (OR = 3.86, 95%CI [1.31–11.4]) were statistically associated with progression to a dCTD. Patients who did not progress to a dCTD were more likely to achieve remission at the last follow‐up (51.8% vs. 25.9%). Conclusions: This study shows that MCTD is a distinct entity that can be classified using either Kasukawa or Sharp criteria, and that only 25.8% of patients progress to a dCTD during follow‐up. [ABSTRACT FROM AUTHOR]

Wilson's disease (WD) is a rare inherited disease due to the mutation of the ATP7B gene, resulting in impaired hepatic copper excretion and its pathological accumulation in various organs such as the liver, the nervous system, or the kidneys. Whereas liver failure and neuropsychiatric disorders are the most common features, less is known about the renal complications. We conducted a review of the literature to define the characteristics and pathophysiology of kidney involvement during WD. This review shed light on strong evidence for direct copper toxicity to renal tubular cells. Excessive tubular copper accumulation might present with various degrees of tubular dysfunction, ranging from mild hydroelectrolytic and acid–base disorders to complete Fanconi syndrome. Proximal and distal renal tubular acidosis also favors development of nephrolithiasis, nephrocalcinosis, and bone metabolism abnormalities. Indirect complications might involve renal hypoperfusion as occurs in hepatorenal or cardiorenal syndrome, but also tubular casts' formation during acute hemolysis, rhabdomyolysis, or bile cast nephropathy. Acute kidney failure is not uncommon in severe WD patients, and independently increases mortality. Finally, specific and long-term therapy by D-penicillamin, one of the most efficient drugs in WD, can cause glomerular injuries, such as membranous nephropathy, minimal-change disease, and, rarely, severe glomerulonephritis. Altogether, our study supports the need for interdisciplinary evaluation of WD patients involving nephrologists, with regular monitoring of tubular and glomerular functions, to provide adequate prevention of renal and bone involvement. [ABSTRACT FROM AUTHOR]

Background: Wilson's disease (WD) is a rare genetic condition characterized by a copper overload in organs secondary to mutation in ATP7B gene. Lifelong decoppering treatments are the keystone of the treatment but must be regularly adapted to obtain a correct copper balance and could lead to copper deficiency (CD). Objectives: Study the characteristics of CD in WD patients. Methods: CD cases from our cohort of 338 WD patients have been investigated. CD was defined by the association of serum copper, exchangeable copper and urinary copper excretion assays less than two standard deviations from the mean with cytopenia and/or neurological damage of spinal cord origin. A systematic review of literature about cases of CD in WD patient was performed in PubMed database according to PRISMA guidelines. Results: Three WD patients were diagnosed with CD in our cohort. Review of the literature found 17 other patients. Most of the patients had anemia and neutropenia associated with neurological symptoms (especially progressive posterior cord syndrome). All the patients were treated with Zinc salts and the symptoms occurred more than a decade after the initiation of treatment. The adaptation of the treatment allowed a correction of the cytopenia but only a partial improvement of the neurological symptoms. Conclusions: WD patients can develop CD after many years of zinc therapy. Anemia and neutropenia are red flags that should evoke CD. [ABSTRACT FROM AUTHOR]

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disorder characterized by an uncontrolled, persistent, hyperimmune response. It can be triggered by an infectious, neoplastic, or autoimmune event. The involvement of cytomegalovirus (CMV) in the onset of HLH is subject to debate, and the epidemiology of CMV-associated HLH (HLH-CMV) remains poorly characterized. We identified 5 cases of HLH-CMV in our hospital, systematically searched the PubMed database for publications on HLH-CMV, and reviewed 57 publications with a total of 67 cases of HLH-CMV. Only 48 patients (71.6%) were immunodeficient, suggesting that HLH-CMV can occur in immunocompetent patients. The major cause of underlying immunodepression (51%) was inflammatory bowel disease (mainly treated with azathioprine). CMV infection was nearly always symptomatic, and lung involvement was frequent (31 cases). Fifty-five patients recovered. Nineteen patients were treated for CMV infection only and had a good outcome, suggesting that antiviral drugs might be the cornerstone of HLH-CMV treatment. [ABSTRACT FROM AUTHOR]