An arm and a leg: A case of rheumatoid vasculitis and antiphospholipid antibody syndrome.

Rheumatoid vasculitis is a rare extra-articular complication of rheumatoid arthritis. The most common manifestation is cutaneous; however, it can manifest in various organ systems and is associated with a high degree of morbidity and mortality. Diagnosis is challenging, and there are no validated diagnostic or classification criteria. Most cases should be confirmed with tissue biopsy when possible given the severity of disease and the extent of immunosuppression required to treat this condition. We report the case of a 54-year-old white woman with long-standing, uncontrolled, and seropositive rheumatoid arthritis with a history of elevated anticardiolipin IgG and IgM antibodies who presented with acute stenosis of her left femoral artery which ultimately required a left above-the-knee amputation. Histopathology revealed findings consistent with vasculitis and thrombosis, and subsequent imaging revealed multifocal arterial and venous thromboses. She was diagnosed with rheumatoid vasculitis and antiphospholipid antibody syndrome, and was treated with high-dose glucocorticoids, cyclophosphamide, and warfarin. Rheumatoid vasculitis is a rare but devastating complication of rheumatoid arthritis, and vigilance for this condition must be maintained, especially in patients with long-standing, seropositive disease.

Tacrolimus induced pseudogout following allogeneic hematopoietic cell transplant.

INTRODUCTION: Crystalline arthritis (CA), characterized by acute joint pain and erythema secondary to calcium pyrophosphate deposition (CPPD, or pseudogout) or monosodium urate crystals (gout), is a potentially underreported complication following allogeneic hematopoietic cell transplant (alloHCT). Graft-versus-host disease prophylaxis with calcineurin inhibitors (CNIs) causes hypomagnesemia and hyperuricemia, resulting in CA. CA related to tacrolimus has yet to be characterized following alloHCT. CASE REPORT: We retrospectively reviewed records of 450 consecutive patients undergoing alloHCT and identified 15 (3.3% incidence) who developed CA on tacrolimus. Large joints were involved in 10 (66.7%) patients, all patients had recent hypomagnesemia, and no patient had hyperuricemia, suggesting CPPD was the most likely etiology.Management and outcome: Eleven (73.3%) patients received systemic corticosteroids; 6 as initial therapy and 5 added to or substituted for colchicine in the setting of slow or inadequate response. The median duration of corticosteroid therapy was 6 days, however 2 patients (13.3%) required prolonged maintenance due to recurrence. Eleven (73.3%) patients received colchicine; 9 as initial therapy and 2 added to or substituted for corticosteroids in the setting of slow or inadequate response. The median duration of colchicine therapy was 18 days. The median time to symptom resolution was 21 days. DISCUSSION: Patients on tacrolimus following alloHCT presenting with acute joint pain and erythema should be evaluated for CPPD. Hypomagnesemia secondary to CNIs is likely the precipitating factor for CPPD in this population. Patients can effectively be managed with systemic corticosteroids and/or colchicine, however prolonged duration of treatment and even maintenance may be necessary. Based on the Naranjo Algorithm, CPPD secondary to tacrolimus induced hypomagnesemia is a possible adverse drug event, with a score of 3-4.

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.

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

OBJECTIVE: 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. METHODS: Using a unified search strategy, 4 centers identified HIV-infected patients exposed to TNF inhibitors. Patient characteristics and infection data were assessed via chart review in all patients who were ≥18 years old and who received TNF inhibitor therapy after HIV diagnosis, between January 1999 and March 2015. RESULTS: We studied 23 patients with 26 uses of TNF inhibitor therapy (86.7 person-years of followup). Two (8.7%) experienced at least 1 serious infection episode, for an overall incidence rate of 2.55 per 100 patient-years (95% confidence interval [95% CI] 0.28-9.23). The incidence rate per 100 patient-years was 3.28 (95% CI 0.04-18.26) among patients with a viral load >500 copies/ml at therapy initiation and 2.09 (0.03-11.65) among patients with a viral load ≤500 copies/ml. CONCLUSION: This study suggests that the rate of serious infections in patients with HIV infection under active care who have received treatment with TNF inhibitors may be comparable to the rates observed in registry databases.

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.

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.

Are children still at risk for lead poisoning?

BACKGROUND: The prevalence of elevated blood lead levels (EBLLs) has decreased nationally, creating challenges in identifying children at risk. METHODS: In a community known to have lead hazards, we screened children with a field-administered capillary blood lead test and asked parents to complete a questionnaire about lead risk factors. RESULTS: Of the 77 child-parent pairs screened with a blood lead test and a parental questionnaire, 4 had finger stick blood lead levels of ≥10 µg/dL. Of these, one child had a confirmatory venous blood lead level >10 µg/dL (1.3%; 95% CI = 0.0%-4.7%), which is near the US prevalence but less than the historic prevalence for this region. A median of 2 risk factors for each of the environmental, behavioral, and knowledge/awareness domains were noted. CONCLUSIONS: Despite a low prevalence of children with EBLL, parental report suggested that approximately 29% of children had lead-based paint in their home environment.

Effectiveness of home-based, multi-trigger, multicomponent interventions with an environmental focus for reducing asthma morbidity: a community guide systematic review.

CONTEXT: Asthma exacerbations are commonly triggered by exposure to allergens and irritants within the home. The purpose of this review was to evaluate evidence that interventions that target reducing these triggers through home visits may be beneficial in improving asthma outcomes. The interventions involve home visits by trained personnel to conduct two or more components that address asthma triggers in the home. Intervention components focus on reducing exposures to a range of asthma triggers (allergens and irritants) through environmental assessment, education, and remediation. EVIDENCE ACQUISITION: Using methods previously developed for the Guide to Community Preventive Services, a systematic review was conducted to evaluate the evidence on effectiveness of home-based, multi-trigger, multicomponent interventions with an environmental focus to improve asthma-related morbidity outcomes. The literature search identified over 10,800 citations. Of these, 23 studies met intervention and quality criteria for inclusion in the final analysis. EVIDENCE SYNTHESIS: In the 20 studies targeting children and adolescents, the number of days with asthma symptoms (symptom-days) was reduced by 0.8 days per 2 weeks, which is equivalent to 21.0 symptom-days per year (range of values: reduction of 0.6 to 2.3 days per year); school days missed were reduced by 12.3 days per year (range of values: reduction of 3.4 to 31.2 days per year); and the number of asthma acute care visits were reduced by 0.57 visits per year (interquartile interval: reduction of 0.33 to 1.71 visits per year). Only three studies reported outcomes among adults with asthma, finding inconsistent results. CONCLUSIONS: Home-based, multi-trigger, multicomponent interventions with an environmental focus are effective in improving overall quality of life and productivity in children and adolescents with asthma. The effectiveness of these interventions in adults is inconclusive due to the small number of studies and inconsistent results. Additional studies are needed to (1) evaluate the effectiveness of these interventions in adults and (2) determine the individual contributions of the various intervention components.

Impact of systemic corticosteroids on healthcare utilization in patients with sarcoidosis.

INTRODUCTION: Practical complications of chronic systemic corticosteroid (SC) use in patients with sarcoidosis are poorly characterized. The objective of this study was to determine the impact of SC use in patients with sarcoidosis on unscheduled sarcoidosis-attributed and nonsarcoidosis-attributed healthcare utilization (SHCU and NSHCU, respectively). METHODS: Retrospective analysis of patient-reported HCU between clinic visits at a university hospital sarcoidosis outpatient clinic. RESULTS: A total of 441 included patients had a mean (standard deviation) of 2.4 (1.2) organs involved, were followed up for a mean of 2.9 (2.4) years and received a median cumulative dose of 2680 mg of prednisone. Patients in the higher 50th percentile of cumulated SC reported a higher unadjusted mean annual SHCU (0.33 versus 0.22, P < 0.0001 by Wilcoxon rank-sum test) but a similar mean annual NSHCU (0.83 versus 1.00, P = .88). After adjustment for age, race and sex, persons in the higher 50th percentile of corticosteroid exposure had a similar odds of overall NSHCU (adjusted odds ratio = 1.03, 95% CI = 0.74­1.44) but a 2.2 (95% CI = 1.5­3.3) odds of greater nonsarcoidosis attributable emergency department visits. In separate analysis of the reasons for NSHCU, persons with greater SC use had a 1.74 (95% CI = 1.16­2.62) odds of more infectious disease-related complaints and a trend toward more visits for cardiovascular problems (OR = 1.49, 95% CI = 0.96­2.32). CONCLUSIONS: Greater SC use is associated with small but significant increase in HCU related to infection and increased unscheduled emergency department visits for complaints not directly attributable to sarcoidosis.