Scleroderma is a heterogeneous group of diseases that can be localized or systemic. Localized scleroderma is a fibrosis of the skin characterized by inflammation and thickening due to excessive ...collagen deposition, and systemic sclerosis (SSc) is characterized by vasculopathy, immune dysregulation and skin fibrosis. In general, the prognosis of scleroderma highly depends on the degree of visceral involvement and relates to the degree of skin fibrosis. Despite the numerous therapies used for patients with scleroderma, the disease-related morbidity and mortality are high. Studies have explored the effects of extracorporeal photopheresis (ECP) in scleroderma treatment. Originally used in the treatment of cutaneous T-cell lymphoma, ECP is an immunomodulatory procedure in which a patient's white blood cells are treated with 8-methoxypsoralen and exposed to UVA radiation to inhibit cell proliferation and induce immunosuppression.
Multiple lines of evidence suggest that ECP may be a safe and possibly effective therapy for patients with scleroderma, specifically demonstrating improvement in patients with cutaneous manifestations of the disease. However, future studies assessing its role in managing visceral involvement are needed. Our review aims to examine and consolidate the results of clinical studies and propose a possible role for ECP in the management of scleroderma.
ECP may be an effective and safe procedure for the treatment of SSc.
•Antibody levels verify the presence of B cell activation in connective tissue disease.•B cell activation markers are linked to global disease activity in rheumatic diseases.•Caution should be taken ...with these markers as patient comorbidities may affect their levels.
B cells play a central role in the pathogenesis of many autoimmune diseases, acting as antigen-presenting cells, producing inflammatory cytokines, and acting as a source of autoantibodies after differentiating into plasma cells. In this review, we aim to summarize and synthesize the literature for the utility of biomarkers of B cell activation (plasma immunoglobulins (Ig), free light chains (FLCs), and beta-2 microglobulin (β2M)) in monitoring inflammatory rheumatic connective tissue diseases, such as Sjogren’s syndrome (SS), systemic lupus erythematosus (SLE), dermatomyositis (DM), and systemic sclerosis (SSc). Clinically, it is quite difficult to gauge prognosis in these conditions as there, historically, have not been many quantitative markers of disease activity available. From our extensive literature review, Ig, FLC, and β2M may function as invaluable prognostic markers of ongoing disease activity, and potentially as biomarkers for response to therapy or disease relapse. They are inexpensive and unsophisticated tests that are vastly underused in the setting of autoimmune disease. However, clinicians still need to be aware of the potential of false positives in times of infection or plasma cell dyscrasia, as these disease states can artificially increase these biomarkers. Ultimately, the utility of serum Ig, FLCs, and β2M is clearly delineated in SS and SLE, and least investigated in DM, and additional prospective studies utilizing these biomarkers, and specific B cell targeted therapies are still needed.
Systemic sclerosis, also known as scleroderma, is an autoimmune disease characterized by cutaneous and visceral fibrosis, immune dysregulation, and vasculopathy. Generally, the degree of skin ...fibrosis is associated with an increased likelihood of visceral organ involvement. Its pathogenesis is poorly understood; however, it is clear that changes in both the innate and adaptive immune responses are associated with fibroblast dysfunction and vascular damage. Further, DNA damage has been postulated as one of the triggering factors in systemic sclerosis, although the association of DNA damage with the progression of this disease is more poorly established. Recently, abnormal DNA damage response repair pathways have also been identified in patients with systemic sclerosis, suggesting that cells from patients with this disease may be more susceptible to DNA damaging agents. Chemotherapeutic drugs and other DNA damaging agents have been associated with the development of systemic sclerosis, as these agents may provide additional "hits" that promote abnormal DNA damage responses and subsequent inflammatory changes. Herein, we present the case of a 39-year-old female who developed scleroderma after the treatment of her breast cancer with chemotherapeutic agents. Her scleroderma was subsequently successfully treated with autologous hematopoietic stem cell transplantation. We also completed a literature review for previously published cases of chemotherapy associated with systemic sclerosis and highlighted a role of DNA damage in promoting the disease. Our case is the first case of chemotherapy associated with systemic sclerosis treated with hematopoietic stem cell transplantation.
Little is known about the dosing and tolerability of sacubitril/valsartan (LCZ696; Entresto, Quebec, Canada) in a nonclinical trial population. This study was conducted to evaluate the use and ...tolerability of sacubitril/valsartan in patients followed at a multidisciplinary heart failure (HF) clinic. We performed a retrospective chart review of 126 patients with HF, initiated on sacubitril/valsartan, and seen at a specialty HF clinic between August 1, 2015, and August 1, 2017. We defined the target dose of sacubitril/valsartan as 200 mg twice a day. At baseline, median age was 67 years, 77% were men, median ejection fraction was 29%, and 86.5% of patients had symptoms of New York Heart Association class ≥II. Within 6 months of being transitioned onto sacubitril/valsartan therapy, 27.2% achieved the target dose of 200 mg twice a day, 40.8% achieved the target dose of 100 mg twice a day, and 32.0% achieved the target dose of 50 mg twice a day. The main reasons for not achieving target dose within 6 months included slower uptitration of therapy than in the trial (n = 41, 54.7%), a decrease in systolic blood pressure (n = 19, 25.3%), not completing blood work (n = 3, 4%), and patient noncompliance (n = 3, 4%). Overall, achievement of sacubitril/valsartan target doses was modest in a tertiary HF clinic, limited by various factors such as side effects and patientsʼ medication noncompliance. Implementation of patient and clinician support pathways may improve uptake, uptitration, and maintenance of evidence-based doses in clinical practice.
Aleukemic leukemia cutis is a rare condition in which malignant white cells invade the skin before they appear in the peripheral blood or bone marrow. It is often associated with a poor prognosis. ...The condition presents a diagnostic challenge as its manifestations are quite variable terms of lesion type. It can manifest as papules, nodules, and/or plaques, and in rare cases erythematous macules, blisters, and ulcers. The most commonly affected areas of the body are the lower extremities, followed by the upper extremities, back, trunk, and face. Due to the non-specific presentation of the disease, skin biopsy and comprehensive immunohistochemical testing can be extremely helpful in the diagnostic work-up. We describe a case of leukemia cutis presenting prior to acute myelogenous leukemia that was initially misdiagnosed as hyper-IgG4 disease.
Mohs micrographic surgery (MMS) is the gold standard treatment for high-risk facial non-melanoma skin cancer. However, patients' access to MMS is limited by cost. The muffin technique micrographic ...surgery (MTMS) is an alternative micrographic technique wherein the entire excised margin is evaluated post-operatively by a pathologist using paraffin-embedded material. Herein, we describe the implementation and the preliminary results of MTMS in an academic dermatology center.
To describe the MTMS and outline its efficacy and safety in a real-world clinical academic setting.
A retrospective chart review was conducted of all patients with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) who underwent MTMS at the University of Alberta Dermatology Center from June 2016 until July 2019.
A total of 69 patients were included (64 BCCs and 5 SCCs). 68.1% of surgeries had clear margins following the first incision, 100% after second round re-excisions. There were no observed cases of tumor recurrence after a median 40 months of follow-up. There were no major adverse events or complications.
MTMS is a superior alternative to simple excision of skin cancer by providing full margin control and residual tumor mapping.
Pragmatic trials test interventions using designs that produce results that may be more applicable to the population in which the intervention will be eventually applied.
To investigate how pragmatic ...or explanatory cardiovascular (CV) randomized clinical trials (RCT) are, and if this has changed over time.
Six major medical and CV journals, including New England Journal of Medicine, Lancet, JAMA, Circulation, European Heart Journal, and Journal of the American College of Cardiology.
All CV-related RCTs published during 2000, 2005, 2010, and 2015 were identified and included.
Included RCTs were assessed by 2 independent adjudicators with expertise in RCT and CV medicine.
The outcome measure was the level of pragmatism evaluated using the Pragmatic Explanatory Continuum Index Summary (PRECIS)-2 tool, which uses a 5-point ordinal scale (ranging from very pragmatic to very explanatory) across 9 domains of trial design, including eligibility, recruitment, setting, organization, intervention delivery, intervention adherence, follow-up, primary outcome, and analysis.
Of 616 RCTs, the mean (SD) PRECIS-2 score was 3.26 (0.70). The level of pragmatism increased over time from a mean (SD) score of 3.07 (0.74) in 2000 to 3.46 (0.67) in 2015 (P < .001 for trend; Cohen d relative effect size, 0.56). The increase occurred mainly in the domains of eligibility, setting, intervention delivery, and primary end point. PRECIS-2 score was higher for neutral trials than those with positive results (P < .001) and in phase III/IV trials compared with phase I/II trials (P < .001) but similar between different sources of funding (public, industry, or both; P = .38). More pragmatic trials had more sites, larger sample sizes, longer follow-ups, and mortality as the primary end point.
The level of pragmatism increased moderately over 2 decades of CV trials. Understanding the domains of current and future clinical trials will aid in the design and delivery of CV trials with broader application.
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