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    <recommendedItem id="20100101_19_438"
                     title="Rituximab Shows Promise in Scleroderma (CME/CE)"
                     score="0.011"
                     href="http://www.medpagetoday.com/Rheumatology/GeneralRheumatology/tb/18352?impressionId=1265753880849"
                     
      &lt;p&gt;Rituximab (Rituxan) improved lung function in patients with scleroderma, a small proof-of-principle study found.&lt;/p&gt;
&lt;p&gt;At one year, patients randomized to receive rituximab had a median 10.25% increase in forced vital capacity (FVC) compared with baseline, while those who received standard treatment had a deterioration of 5.04% (&lt;em&gt;P&lt;/em&gt;=0.002), according to Dimitrios Daoussis, MD, and colleagues from the University of Patras in Greece.&lt;/p&gt;
&lt;p&gt;There also was a significant 19.46% increase in diffusing capacity of carbon monoxide (DL&lt;sub&gt;co&lt;/sub&gt;) in the rituximab-treated patients, while the controls showed deterioration of 7.5% (&lt;em&gt;P&lt;/em&gt;=0.023), the researchers reported in the February issue of &lt;em&gt;Rheumatology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Interstitial lung disease is a common manifestation of diffuse scleroderma and represents the disease component that dictates prognosis because it can be progressive and typically responds poorly to treatment. Animal and human studies have suggested a possible pathogenic role for B cells in the disease.&lt;/p&gt;
&lt;p&gt;There have been a few reports of clinical and histologic improvements in scleroderma and in graft-versus-host disease (which shares some features with scleroderma) after treatment with the B-cell depleting monoclonal antibody rituximab.&lt;/p&gt;
&lt;p&gt;These encouraging early findings led Daoussis and colleagues to undertake an open-label, controlled study that included 14 patients with diffuse disease.&lt;/p&gt;
&lt;p&gt;Median age was 55 and mean disease duration was seven years.&lt;/p&gt;
&lt;p&gt;All patients continued their standard medications, which included various agents such as prednisone, bosentan (Tracleer), mycophenolate mofetil (CellCept), and cyclophosphamide.&lt;/p&gt;
&lt;p&gt;Those randomized to rituximab treatment also underwent four weekly pulses of the drug (375 mg/m&lt;sup&gt;2&lt;/sup&gt;) at baseline and six months later.&lt;/p&gt;
&lt;p&gt;By one year, the mean FVC in the rituximab group had risen from 68.13% of normal predicted value based on age, sex, and height, to 75.63% (&lt;em&gt;P&lt;/em&gt;=0.0018), while FVC in the control group fell nonsignificantly from 86% of normal to 81.67%.&lt;/p&gt;
&lt;p&gt;In the rituximab group, DL&lt;sub&gt;co&lt;/sub&gt; increased from a mean of 52.25% of normal at baseline to 62% (&lt;em&gt;P&lt;/em&gt;=0.017) at one year, while the controls decreased nonsignificantly from 65.33% to 60.17%.&lt;/p&gt;
&lt;p&gt;None of the patients treated with rituximab experienced worsening of FVC or DL&lt;sub&gt;co&lt;/sub&gt;, whereas lung function deteriorated in five controls.&lt;/p&gt;
&lt;p&gt;&quot;We should note, however, that patients in the control group tended to have more early disease and better lung function parameters (although not statistically different from the [rituximab] group) making them more likely to deteriorate over the time of the study,&quot; the investigators commented.&lt;/p&gt;
&lt;p&gt;Skin manifestations of the disease also showed improvements in the rituximab group. Skin thickening, as measured by the Modified Rodnan Skin Score, improved by 39.25% in the rituximab group and by 20.80% in the control group, a difference that was not statistically significant.&lt;/p&gt;
&lt;p&gt;Skin fibrosis also improved by a median of 38.33%, while it worsened by 5.23% in controls.&lt;/p&gt;
&lt;p&gt;Histologic improvement was seen in four of the rituximab-treated patients, corresponding with clinical benefits. One patient in the active treatment group had a significant reduction of fibrosis in both the papillary and reticular dermis, accompanied by an almost complete resolution of skin lesions.&lt;/p&gt;
&lt;p&gt;Improvement in skin fibrosis was most common in patients who had evidence of B-cell depletion in the skin.&lt;/p&gt;
&lt;p&gt;Overall function, as evaluated by the Health Assessment Questionnaire, improved from a median baseline score of 0.687 to 0.312 at one year (&lt;em&gt;P&lt;/em&gt;=0.03), while no change was seen in controls.&lt;/p&gt;
&lt;p&gt;The pathogenesis of scleroderma is poorly understood, according to the authors, but this study adds support to a possible role for B cells.&lt;/p&gt;
&lt;p&gt;In addition, rituximab indirectly targets T cells, which also are thought to be implicated.&lt;/p&gt;
&lt;p&gt;The authors noted potential limitations, including the study&apos;s small size and the fact that most patients had longstanding disease, had been treated with multiple immunosuppressive agents in the past, and were receiving concurrent therapies during the study.&lt;/p&gt;
&lt;p&gt;&quot;This is a proof-of-principle study that was performed in order to obtain preliminary data regarding the effect of [rituximab] on a limited number of patients,&quot; the authors wrote.&lt;/p&gt;
&lt;p&gt;&quot;Our data could serve as a good starting point for the design of larger scale, multicenter studies with longer evaluation periods and especially in earlier stages of the disease,&quot; they concluded.&lt;/p&gt;
&lt;p&gt;In an accompanying editorial, Robert W. Simms, MD, and Robert Lafyatis, MD, of Boston University, echoed concerns about the small number of patients and the lack of blinding in the study.&lt;/p&gt;
&lt;p&gt;&quot;One cannot...on the basis of this study, recommend rituximab in the routine clinical care of patients with scleroderma,&quot; the editorialists wrote.&lt;/p&gt;
&lt;p&gt;The findings will need to be replicated in a multicenter randomized trial, but &quot;do provide some hope that B-cell depletion might enhance the currently restricted therapeutic armamentarium of this disease.&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was funded by the Hellenic Rheumatology Society.&lt;/p&gt;&lt;p&gt;Funding to pay Open Access publication charges was provided by Roche Hellas.&lt;/p&gt;&lt;p&gt;Authors and editorialists declared to conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_330"
                     title="Immune Cells Point to Skin Cancer Risk after Transplants (CME/CE)"
                     score="0.007"
                     href="http://www.medpagetoday.com/Nephrology/KidneyTransplantation/tb/18200?impressionId=1265753880849"
                     
      Monitoring two types of immune cells in kidney transplant recipients might identify patients with an increased risk of skin cancer, British investigators reported.&lt;br&gt;
&lt;br&gt;Increased levels of T-regulatory cells (Tregs) more than doubled the risk of squamous cell cancer of the skin. Decreased levels of natural killer (NK) cells were associated with more than a five-fold increased risk of skin cancer.&lt;br&gt;
&lt;br&gt;Both immune parameters had substantially greater predictive power than a history of squamous-cell skin cancer, according to an online report in the &lt;em&gt;Journal of the American Society of Nephrology&lt;/em&gt; by a team of Oxford University investigators.&lt;/p&gt;
&lt;p&gt;&quot;Squamous cell cancer of the skin affects about 30% of kidney transplant patients after 10 years of immunosuppression,&quot; Robert Carroll, MD, currently of Queen Elizabeth Hospital in Woodville, Australia, observed in a statement.&lt;/p&gt;
&lt;p&gt;&quot;A small number of patients develop multiple skin cancers per year, but there is no laboratory test to determine which transplant recipients will develop multiple skin cancers in the future.&quot;&lt;/p&gt;
&lt;p&gt;&quot;If a test can confirm high risk of skin cancer development, this may help clinicians to tailor immunosuppressive regimens for individual patients,&quot; he added.&lt;/p&gt;
&lt;p&gt;Long-term immunosuppression, such as that required for transplant recipients, confers an increased risk of squamous-cell skin cancer.&lt;/p&gt;
&lt;p&gt;Estimates of the magnitude have ranged as high as 200 times greater than the general population, the authors wrote. Additionally, 3% of organ transplant recipients require extensive plastic surgery each year as a result of skin cancer lesions.&lt;/p&gt;
&lt;p&gt;Age at transplantation and the immunosuppression dosage are the principal determinants of skin-cancer risk, and the dosage of immunosuppression also influences the risk of metastasis from squamous-cell cancer of the skin.&lt;/p&gt;
&lt;p&gt;In the general population, cancer has been associated with increased levels of Tregs, including CDR&lt;sup&gt;+&lt;/sup&gt;CD25&lt;sup&gt;high&lt;/sup&gt;FOXP3&lt;sup&gt;+&lt;/sup&gt; and CD8&lt;sup&gt;+&lt;/sup&gt;CD28&lt;sup&gt;-&lt;/sup&gt; cells. The same types of cells could play a role in the risk of skin cancer among organ transplant recipients, the authors wrote.&lt;/p&gt;
&lt;p&gt;Within the tumor microenvironment, Tregs may impair the antitumor activity of CD8&lt;sup&gt;+&lt;/sup&gt; and NK cell. However, in organ transplant recipients, Tregs help control or prevent rejections and may help improve long-term outcomes.&lt;/p&gt;
&lt;p&gt;Different immunosuppressive drugs affect Tregs differently, the authors continued. Sirolimus (Rapamune), for example, increases the number of FOXP3&lt;sup&gt;+&lt;/sup&gt; cells, whereas cyclosporine decreases Treg numbers.&lt;/p&gt;
&lt;p&gt;&quot;Tregs have not been assessed in relation to cancer after transplantation,&quot; the authors wrote. &quot;We therefore investigated the hypothesis that squamous-cell cancer in kidney transplant recipients would be associated with an increased number of Tregs.&quot;&lt;/p&gt;
&lt;p&gt;To examine the hypothesis, investigators phenotyped peripheral blood from 65 kidney transplant recipients with squamous skin cancer and 51 recipients without skin cancer, matched for age, sex, and duration of immunosuppression.&lt;/p&gt;
&lt;p&gt;They also quantified lymphocyte populations in skin cancer lesions from a subset of 25 patients and matched them with 25 other nontransplant patients with squamous cell cancer of the skin.&lt;/p&gt;
&lt;p&gt;The kidney transplant recipients had a median follow-up of 340 days. The investigators found that a concentration of &amp;gt;35 peripheral FOXP3&lt;sup&gt;+&lt;/sup&gt;CD4&lt;sup&gt;+&lt;/sup&gt;CD127&lt;sup&gt;low&lt;/sup&gt; regulatory T cells/&amp;#181;L was associated with a hazard ratio for squamous cell skin cancer of 2.48 (95% CI 1.04 to 5.98).&lt;/p&gt;
&lt;p&gt;An NK cell count &amp;lt;100 cells/&amp;#181;L was associated with a skin cancer hazard ratio of 5.6 (95% CI 1.31 to 24). A history of squamous cell cancer of the skin increased the risk of skin cancer recurrence by a third (HR 1.33, 95% CI 1.15 to 1.53).&lt;/p&gt;
&lt;p&gt;&quot;If similar immune phenotypes are predictive in other kidney transplant recipient populations, then immune phenotype method has the potential to inform immunosuppressive regimen manipulation in kidney transplant recipients at high risk for developing multiple squamous cell cancers,&quot; the authors concluded.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The authors had no relevant disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_261"
                     title="Scrubbing Away Germs Can Backfire on Backsides (CME/CE)"
                     score="0"
                     href="http://www.medpagetoday.com/Pediatrics/GeneralPediatrics/tb/18121?impressionId=1265753880849"
                     
      Rashes from toilet seats are once again afflicting American children, and the rare condition is often misdiagnosed, which may delay proper treatment.&lt;br&gt;
&lt;br&gt;That&apos;s the conclusion from a report based of five-cases of toilet-seat contact dermatitis investigated by researchers at Johns Hopkins University School of Medicine and reported in the Jan. 25 issue of &lt;em&gt;Pediatrics&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;While toilet-seat dermatitis is commonly thought to result from allergies to wooden seats, the report concludes that another source is plastic toilet seats cleaned with harsh detergents.&lt;/p&gt;
&lt;p&gt;&quot;This case series and previous reports have documented that toilet-seat dermatitis is much more common than previously recognized in the U.S. and around the world,&quot; Bernard A. Cohen, MD, and colleagues wrote.&lt;/p&gt;
&lt;p&gt;&quot;Furthermore, the incidence of this condition is rising in North America because of a resurgent popularity of exotic-wood toilet seats and frequent use of detergents that contain highly irritant/sensitizing compounds such as quaternary ammonium compounds, phenol, formaldehyde, etc. in public restrooms.&quot;&lt;/p&gt;
&lt;p&gt;Of the cases analyzed by the authors, two occurred in the U.S. and the other three occurred in India.&lt;/p&gt;
&lt;p&gt;Both U.S. cases were girls, a 6-year-old who had a rash for over two years before it was correctly diagnosed and a 10-year-old whose rash lasted for a year. In both cases, the rashes seemed to worsen during the school year when the girls were using school restrooms. The younger girl&apos;s dermatitis twice became infected with methicillin-resistant &lt;em&gt;Staphylococcus aureus &lt;/em&gt;and required treatment with antibiotics.&lt;/p&gt;
&lt;p&gt;After doctors determined the rashes were the result of contact with toilet seats and instructed the girls to use toilet-seat covers and apply moisturizers and topical steroids to the affected areas, the eruptions cleared up within a few weeks.&lt;/p&gt;
&lt;p&gt;The cases in India included a 14-month old boy and two girls, 12 and 10.&lt;/p&gt;
&lt;p&gt;The boy and the 12-year-old girl were both initially misdiagnosed with ringworm and unsuccessfully treated with clotrimazole cream. The other girl was unsuccessfully treated with ayurvedic and homeopathic topical medications before doctors diagnosed toilet-seat dermatitis. Two of the children were instructed to use soaps that only exacerbated the problem.&lt;/p&gt;
&lt;p&gt;In all three cases, the rashes cleared up with some combination of topical steroids, using toilet-seat covers, replacing the household toilet seat, and limiting time on the toilet.&lt;/p&gt;
&lt;p&gt;The authors distinguished between two types of toilet-seat dermatitis: allergic contact dermatitis, the better described form of the condition, in which a patient develops allergy to wooden toilet seats, and irritant contact dermatitis, in which the rashes result from contact with harsh detergents used on plastic toilet seats.&lt;/p&gt;
&lt;p&gt;They noted that detergents used in public restrooms and in hospitals are potentially more irritating to the skin than those used at home and that alkaline detergents are more likely to cause skin irritation than acidic detergents, because they perturb the body&apos;s natural acidic environment.&lt;/p&gt;
&lt;p&gt;Toilet-seat dermatitis was first identified as an external skin rash in 1927. Exposure to wooden toilet seats and associated varnish, lacquers, and paints led to sensitization and development of an allergic contact dermatitis.&lt;/p&gt;
&lt;p&gt;The condition nearly disappeared in the U.S. in 1980s and 1990s, after public facilities and homeowners in the U.S. changed from wooden to plastic toilet seats and sanitary seat covers became readily available.&lt;/p&gt;
&lt;p&gt;However, in recent years the number of cases has grown as a result of homeowners installing toilet seats made of exotic woods and the increased use of harsh toilet seat detergents.&lt;/p&gt;
&lt;p&gt;Most reports have focused on adults with rashes, but little previous attention has focused on the condition in children. &quot;In this case series we describe toilet-seat contact dermatitis in children and underscore a typical history and physical findings that we hope will aid clinicians in recognizing this disease,&quot; the authors wrote.&lt;/p&gt;
&lt;p&gt;&quot;It is important to underscore that regular use of toilet-seat covers is the key to success in treatment,&quot; the authors wrote. &quot;Such seat covers can be purchased at any major retailer such as Walmart or online.&lt;/p&gt;
&lt;p&gt;As an alternative, newspaper cutouts could be used to provide barrier protection. Although it is possible to develop an allergy to toilet-seat covers, none have been reported thus far in the literature.&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The authors reported no sources of funding or financial conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_8_423"
                     title="FDA Wants Cancer Warning and UVA Protection Rating on Sunscreen Labels"
                     score="-0.005"
                     href="