Colin Ligon

Biomarkers in Scleroderma: Progressing from Association to Clinical Utility

Scleroderma is a heterogenous disease characterized by autoimmunity, a characteristic vasculopathy, and often widely varying extents of deep organ fibrosis. Recent advances in the understanding of scleroderma’s evolution have improved the ability to identify subgroups of patients with similar prognosis in order to improve risk stratification, enrich clinical trials for patients likely to benefit from specific therapies, and identify promising therapeutic targets for intervention. High-throughput technologies have recently identified fibrotic and inflammatory effectors in scleroderma that exhibit strong prognostic ability and may be tied to disease evolution. Increasingly, the use of collections of assayed circulating proteins and patterns of gene expression in tissue has replaced single-marker investigations in understanding the evolution of scleroderma and in objectively characterizing disease extent. Lastly, identification of shared patterns of disease evolution has allowed classification of patients into latent disease subtypes, which may allow rapid clinical prognostication and targeted management in both clinical and research settings. The concept of biomarkers in scleroderma is expanding to include nontraditional measures of aggregate protein signatures and disease evolution. This review examines the recent advances in biomarkers with a focus on those approaches poised to guide prospective management or themselves serve as quantitative surrogate disease outcomes.

The effect of vitamin D supplementation on glucose metabolism in type 2 diabetes mellitus: A systematic review and meta-analysis of intervention studies

AIMS We aimed to assess whether vitamin D supplementation improves glucose metabolism in adults with type 2 diabetes. METHODS PubMed and Cochrane database were searched up to July 1st 2016 for randomized controlled trials that assessed the relationship between vitamin D supplementation and glucose metabolism (change in hemoglobin A1C (HbA1C) and fasting blood glucose (FBG)) among adults with type 2 diabetes. RESULTS Twenty nine trials (3324 participants) were included in the systematic review. Among 22 studies included in the meta-analysis, 19 reported HbA1C, 16 reported FBG outcomes and 15 were deemed poor quality. There was a modest reduction in HbA1C (-0.32% [-0.53 to -0.10], I2=91.9%) compared to placebo after vitamin D supplementation but no effect on FBG (-2.33mg/dl [-6.62 to 1.95], I2=59.2%). In studies achieving repletion of vitamin D deficiency (n=7), there were greater mean reductions in HbA1C (-0.45%, [-1.09 to 0.20]) and FBG (-7.64mg/dl [-16.25 to 0.97]) although not significant. CONCLUSIONS We found a modest reduction of HbA1C after vitamin D treatment in adults with type 2 diabetes albeit with substantial heterogeneity between studies and no difference in FBG. Larger studies are needed to further evaluate the glycemic effects of vitamin D treatment especially in patients with vitamin D deficiency.

Oxalate nephropathy in systemic sclerosis: Case series and review of the literature

OBJECTIVE To increase awareness of oxalate nephropathy as a cause of acute kidney injury (AKI) among systemic sclerosis patients with small intestinal dysmotility and malabsorption, and to prompt consideration of dietary modification and early treatment of predisposing causes of oxalate nephropathy in this population. METHODS Two cases of biopsy-proven oxalate nephropathy were identified among systemic sclerosis patients in the course of direct clinical care. Subsequently, a retrospective search of the Johns Hopkins Pathology databases identified a third patient with systemic sclerosis who developed oxalate nephropathy. RESULTS Among the three patients with qualifying biopsies, all three had systemic sclerosis with lower gastrointestinal involvement. All three presented with diarrhea, malabsorption, and AKI. In two of the three patients, diarrhea was present for at least 2 years before the development of AKI; in the third, incidental oxalate nephropathy was noted 3 years before she developed AKI and extensive oxalate nephropathy in the setting of a prolonged mycobacterium avium-intracellulare enteritis. In the first case, oxalate crystals were present by urinalysis months before diagnosis by biopsy; in the second, hyperoxaluria was diagnosed by urine collection immediately after; and in the third, oxalate crystals had been noted incidentally on post-transplant renal biopsy 3 years before the development of fulminant oxalate nephropathy. All three patients died within a year after diagnosis. CONCLUSIONS Patients with systemic sclerosis and bowel dysmotility associated with chronic diarrhea and malabsorption may be at risk for an associated oxalate nephropathy. Regular screening of systemic sclerosis patients with small bowel malabsorption syndromes through routine urinalysis or 24-h urine oxalate collection, should be considered. Further studies defining the prevalence of this complication in systemic sclerosis, the benefit of dietary modification on hyperoxaluria, the effect of treating small intestinal bowel overgrowth with antibiotics, and the effectiveness of probiotics, calcium supplements, or magnesium supplements to prevent hyperoxaluria-associated renal disease in these patients, are warranted.

Rates of Serious Infections in HIV-Infected Patients Receiving Tumor Necrosis Factor Inhibitor Therapy for Concomitant Autoimmune Diseases

To estimate the incidence of serious infections in patients with HIV infection and autoimmune disease who were treated with tumor necrosis factor (TNF) inhibitors, and to compare these rates by stratified viral load levels.

The Rates of Serious Infections in HIV‐infected Patients Who Received Tumor Necrosis Factor (TNF)‐α Inhibitor Therapy for Concomitant Autoimmune Diseases

To estimate the incidence of serious infections in patients with HIV infection and autoimmune disease who were treated with tumor necrosis factor (TNF) inhibitors, and to compare these rates by stratified viral load levels.

Editorial: Scleroderma: Bringing a Disease From Black-and-White Into Technicolor.

The name “scleroderma” encompasses subtypes of a systemic disease (systemic sclerosis) that are linked together by common clinical and pathological features: skin thickening, Raynaud’s phenomenon, major organ failure with evidence of autoimmunity, tissue fibrosis, and a unique non-inflammatory multisystem vasculopathy. A challenge in managing scleroderma is defining as early as possible an individual patient’s disease course, to both predict clinical outcomes and to determine appropriate intervention. Recognizing that subtypes exist has led to various efforts to classify scleroderma into unique subgroups that might follow a similar and predictable clinical course. The modern classification of scleroderma represents 150 years of accumulated investigation into patients with varying degrees of characteristic skin thickening and a panoply of major organ dysfunction (1). This effort has resulted in an over-simplified classification of two subsets based on the extent of skin involvement alone.

Editorial: Scleroderma: Bringing a Disease From Black-and-White Into Technicolor: EDITORIAL

The name “scleroderma” encompasses subtypes of a systemic disease (systemic sclerosis) that are linked together by common clinical and pathological features: skin thickening, Raynaud’s phenomenon, major organ failure with evidence of autoimmunity, tissue fibrosis, and a unique non-inflammatory multisystem vasculopathy. A challenge in managing scleroderma is defining as early as possible an individual patient’s disease course, to both predict clinical outcomes and to determine appropriate intervention. Recognizing that subtypes exist has led to various efforts to classify scleroderma into unique subgroups that might follow a similar and predictable clinical course. The modern classification of scleroderma represents 150 years of accumulated investigation into patients with varying degrees of characteristic skin thickening and a panoply of major organ dysfunction (1). This effort has resulted in an over-simplified classification of two subsets based on the extent of skin involvement alone.

Scleroderma: Bringing a Disease from Black‐and‐White into Technicolor™

The name “scleroderma” encompasses subtypes of a systemic disease (systemic sclerosis) that are linked together by common clinical and pathological features: skin thickening, Raynaud’s phenomenon, major organ failure with evidence of autoimmunity, tissue fibrosis, and a unique non-inflammatory multisystem vasculopathy. A challenge in managing scleroderma is defining as early as possible an individual patient’s disease course, to both predict clinical outcomes and to determine appropriate intervention. Recognizing that subtypes exist has led to various efforts to classify scleroderma into unique subgroups that might follow a similar and predictable clinical course. The modern classification of scleroderma represents 150 years of accumulated investigation into patients with varying degrees of characteristic skin thickening and a panoply of major organ dysfunction (1). This effort has resulted in an over-simplified classification of two subsets based on the extent of skin involvement alone.

Elbow Loose Bodies

A 52-year-old right-handed woman, with occupational exposure to heavy cleaning equipment and newspaper delivery, presented to the Johns Hopkins Hospital emergency department in great distress. She had just exited the subway. While riding the train and holding a pole for stability, she abruptly developed excruciating pain and complete inability to flex or extend her left elbow. Rheumatology consultation identified unilateral fullness of the left elbow, with …