Lyme Disease Support Group

By Charles Bankhead, Staff Writer, MedPage Today

Published: May 15, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Action Points

Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Explain that that 15% of patients with cutaneous lupus erythematosus (CLE) progressed to systemic lupus erythematosus (SLE) if they had only CLE at the initial visit.

Note that patients who had CLE and progressed to SLE had more moderate and severe symptoms compared with patients who had SLE at their initial visit.

RALEIGH, N.C. -- A small number of cutaneous lupus erythematosus (CLE) patients progressed to systemic lupus erythematosus (SLE), and those that did had more moderate and severe symptoms, data from a longitudinal cohort study showed.

More than a third of patients who progressed to SLE by American College of Rheumatology criteria (ACR) had moderate or severe systemic symptoms. However, few patients progressed to SLE if they had only CLE at the initial visit.

In contrast, almost 90% of patients who had both CLE and SLE at initial visit had no or only mild systemic symptoms, as reported here at the Society for Investigative Dermatology meeting.

"I think we can comfort patients with this information," Isabela Wieczorek, of the University of Pennsylvania in Philadelphia, told MedPage Today. "If patients have cutaneous lupus, we can tell them that the likelihood of developing SLE is not too high and if they do, hopefully the symptoms won't be too severe -- not neurological disease and renal disease."

"But we still have to monitor them. We still have to do blood tests and urine tests to make sure they are not developing systemic symptoms [and] ask them about arthritis," she added.

Several studies have documented conversion or progression from CLE to SLE, as well as the proportion of patients who have both conditions. However, little information exists regarding patient and clinical characteristics of individuals who have both types of lupus, particularly those who progress.

A cohort of almost 200 patients with CLE provided an opportunity to examine symptoms in patients who have or who develop CLE and SLE. The patients were initially seen from 2007 to 2011. The cohort consisted of 111 patients who had CLE only and 85 who had CLE and SLE at the initial visit.

Patients who had CLE and SLE were younger (42 versus 50 for those with CLE only, P<0.001), more likely to be women (89% versus 69%, P=0.0014), less likely to be white (50% versus 70.6%, P<0.001), and had longer disease duration (10.2 versus 7.3 years, P=0.024).

Additionally, patients with CLE and SLE at initial visit had significantly more muscle involvement (54% versus 3%, P<0.001), renal involvement (28% versus 2%, P<0.001), hematologic involvement (11.8% versus 2.7%, P=0.0095), and neurologic involvement (9.4% versus 0, P=0.001).

With regard to disease severity, 98.2% of patients with CLE only had no or mild symptoms versus 76.5% of those with CLE and SLE (P<0.001).

During a median follow-up of 8 years, 13 of 85 (15%) patients with CLE only subsequently developed SLE.

The most common ACR criteria leading to a diagnosis of SLE were cutaneous in nature: photosensitivity, malar, discoid rash, and oral ulcers.

Patients who progressed also were more likely to test positive for antinuclear antibodies than were patients who did not progress to SLE.

Five of 13 (38.5%) patients who progressed from CLE only to CLE and SLE had moderate or severe symptoms compared with the patients who had SLE at the initial visit (13.4%).

"Whether patients progressed to SLE or initially had CLE and SLE, in most cases they had no or only mild symptoms," Wieczorek said.

Wieczorek and co-investigators had no relevant disclosures.

Primary source: Society for Investigative Dermatology

Source reference:

Wieczorek IT, et al "Progression from cutaneous to systemic lupus erythematosus by ACR criteria usually occurs with mild disease and few systemic symptoms" SID 2012; Abstract 264.

http://www.medpagetoday.com/MeetingCoverage/SID/32708? utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 Everyday Health, Inc. All rights reserved.

May 2012

As earlier diagnosis and improved therapies have greatly increased the life expectancy associated with systemic lupus erythematosus (lupus), people with lupus now must face a longer-term problem: an increased risk of cardiovascular disease.

Studies suggest that for a premenopausal woman with lupus, the risk of a heart attack or stroke is increased, says Laura Schanberg, M.D., a researcher supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).

That risk, she says, is due to the premature development of atherosclerosis, or hardening of the arteries, which can occur as a result of the disease or its treatment.

Dr. Schanberg, professor of pediatrics at Duke University School of Medicine, and Dr. Christy Sandborg, M.D., of Standford University have questioned whether treating preemptively with statin drugs, which have been proven to reduce heart attacks and strokes in people with, or at risk for, atherosclerosis, might help protect children and adolescents with lupus years down the road.

New findings of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) study provide important insights.

The 36-month study, which was also supported by the Childhood Arthritis and Rheumatology Research Alliance (CARRA), enrolled 221 pediatric lupus patients at 21 sites across the United States, and compared outcomes of children given the statin drug atorvastatin to those given placebo.

Because children usually don’t have myocardial infarctions or strokes – the ultimate indicator of whether the drugs were effective — the researchers instead measured carotid intima-media thickness (CIMT) to assess outcomes.

CIMT — a test that uses ultrasound to determine the thickness of the intimal and medial layers of the carotid artery walls – can help doctors predict the risk of heart attack and stroke. Thicker walls mean an increased risk of cardiovascular events.

For every unit that they thicken, the risk of a cardiovascular event goes up.

In children, the rate of progression ideally should be zero, says Dr. Schanberg.

For children with lupus, however, the scientists found that the rate of progression was not zero.

Children with lupus have a significantly increased rate of progression even in childhood, and treatment with statins made no statistically significant change in that progression, the study showed.

The researchers suggest that further analyses may identify subgroups of children who may benefit from targeted statin therapy.

While the study failed to show a significant benefit of statins overall, that’s not necessarily bad news, because it lets doctors know they don’t need to prescribe statins for every child with lupus from the time they are diagnosed, says Dr. Schanberg.

This finding will spare children the cost and potential side effects of a drug that’s not proven beneficial.

At the same time, it suggests that for certain children the drugs may, in fact, be helpful.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the U.S. Department of Health and Human Services’ National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases.

For more information about the NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS website at http://www.niams.nih.gov.

Schanberg LE, et al. Use of atorvastatin in systemic lupus erythematosus in children and adolescents. Arthritis Rheum. 2012 Jan;64(1):285-96. doi: 10.1002/art.30645. [PubMed - indexed for MEDLINE] PMID: 22031171

NIH…Turning Discovery Into Health ... no copyright shown

http://www.niams.nih.gov/News_and_Events/ Spotlight_on_Research/2012/ statins_atherosclerosis_lupus.asp

By John Gever, Senior Editor, MedPage Today

Published: June 11, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

1 comment(s)

Take Posttest

Action Points

This case series was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Patients with treatment-resistant lupus showed dramatic improvement when they received the myeloma drug bortezomib (Velcade).

[b]Note that this use of bortezomib is not currently approved, although it could be an option in patients who fail to improve with standard immunosuppressant-based treatment if confirmed by future studies.

BERLIN -- Patients with treatment-resistant lupus showed dramatic improvement when they received the myeloma drug bortezomib (Velcade), a [/b]researcher said here.

One to four courses of bortezomib treatment of 13 patients with refractory systemic lupus erythematosus (SLE) led to marked reductions in symptom scores and anti-dsDNA antibodies, according to Reinhard Voll, MD, of University Medical Center Freiburg in Freiburg, Germany.

Although this use of bortezomib is not currently approved, Voll said it could be an option in patients who fail to improve with standard immunosuppressant-based treatment.

He presented the case series at the European League Against Rheumatism's annual meeting.

The rationale for bortezomib in SLE is that the drug's target, the proteasome complex within cells, is critical to the survival of long-lived, antibody-producing plasma cells that are at the root of SLE.

A 2008 study in mice led by Voll showed that bortezomib depleted these cells and alleviated a murine form of lupus nephritis.

That success prompted Voll and colleagues to attempt bortezomib treatment in patients with SLE that was unresponsive to standard therapies.

In all of the 13 patients included in the case series, multiple conventional drugs had been tried:

mycophenolate mofetil (MMF), azathioprine, cyclophosphamide, and other immunosuppressants, as well as anti-malarial drugs that are the mainstays of SLE therapy.

Initially, Voll told MedPage Today, he administered bortezomib in a series of three injections per 8-day course, at 1.3 mg/m2 per injection. Later, when two other centers in Germany began treating some patients, they gave a fourth injection on day 11, which is the standard bortezomib regimen for hematologic malignancies.

Up to four courses were given, with rest periods of 10 to 14 days in between. Treatment was stopped when disease activity was substantially reduced or severe side effects developed.

Most patients also received 20 mg of dexamethasone, and MMF and anti-malarials were also continued during bortezomib treatment.

After bortezomib treatment was finished, patients received maintenance therapy with standard drugs, mostly MMF and hydroxychloroquine.

Bortezomib treatment had to be stopped in three patients because of adverse events -- two for polyneuropathy (a well-known side effect of bortezomib) and one for fever.

All three, however, showed major reductions in SLE Disease Activity Index (SLEDAI) scores and anti-dsDNA antibody levels.

Two patients were lost to follow-up, but the other eight also had marked improvements.

For example, three patients with SLEDAI scores of 20 or higher before starting bortezomib had declines of more than 10 points with treatment.

Only one patient did not have a reduction of at least four SLEDAI points during bortezomib treatment, and that patient later saw a four-point decline while on maintenance therapy for 6 months.

Among all other patients with 6 months of follow-up, the bortezomib-induced improvement persisted, Voll reported.

In addition to the two cases of polyneuropathy, which disappeared after bortezomib was stopped, other adverse events included herpes zoster infection, urinary tract infection, headache, nausea, rhinitis, and allergic skin reaction.

Each occurred in one or two patients.

Voll and colleagues also examined another issue involved with bortezomib, which is that it can compromise vaccine effectiveness. They measured hepatitis B and tetanus toxoid antibody titres in patients.

These were depressed somewhat with treatment. Means for tetanus toxoid antibodies were reduced by about 20% and by more than 80% for hepatitis B, but they remained within the protective range, Voll said.

The drug's cost (about $1,300 per injection, Voll said) was covered by patients' insurers or the treating hospitals.

Bortezomib's manufacturer, the Millennium Pharmaceuticals unit of Takeda, did not provide the drug or otherwise assist on the treatment.

Voll said the next step should be a formal clinical trial, which he hopes Millennium will sponsor.

Voll said the company had expressed interest, but may want to use another unidentified proteasome inhibitor in development that may be safer than bortezomib.

The study had no commercial funding. Individual hospitals and patients' insurers paid for bortezomib.

Voll reported a pending patent application on the use of bortezomib for depletion of long-lived plasma cells, which has been licensed by Millennium/Takeda.

Primary source: European League Against Rheumatism

Source reference:

Voll R, et al "Successful treatment of refractory SLE patients with the proteasome inhibitor bortezomib – a case series" EULAR 2012; Abstract SAT0203.

http://www.medpagetoday.com/MeetingCoverage/EULAR/33200? utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 Everyday Health, Inc. All rights reserved.

Take steps to limit stress

By Diana Kohnle

Monday, June 25, 2012

Related MedlinePlus Page

Lupus

(HealthDay News) -- The U.S. Department of Health and Human Services Office on Women's Health suggests how to help control lupus:

•Learn to recognize when a flare-up is imminent.

•Get plenty of rest and try not to push yourself too hard.

•Try to control stress.

•Limit exposure to sunlight and halogen or fluorescent lights.

•Be careful to avoid injury or infection.

•Don't stop taking lupus medications unless your doctor says so.

•Exercise moderately, but get your doctor's approval first.

•Talk to your doctor about any other medications you are taking to see if any could trigger a lupus flare-up.

http://www.nlm.nih.gov/medlineplus/news/ fullstory_126603.html

Copyright (c) 2012 HealthDay. All rights reserved.

By Nancy Walsh, Staff Writer, MedPage Today

Published: July 02, 2012

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Take Posttest

Action Points

Note that, in this study of patients in the UK with juvenile onset SLE, patients were predominantly female and there was a greater risk of the disease in non-Caucasians.

Also note that severe organ involvement and significant disease activity were primary characteristics in children with juvenile SLE in this UK cohort.

Major organ involvement can occur rapidly in juvenile-onset systemic lupus erythematosus (SLE) even with near universal corticosteroid use, data from a U.K. national cohort showed.

After only 4.5 years of follow-up,

91% of young lupus patients already had hematologic manifestations of the disease,

82% had musculoskeletal involvement,

80% had developed kidney problems, and

26% had neurologic abnormalities,

according to Michael W. Beresford, MBChB, PhD, of the University of Liverpool, and colleagues.

A total of 93% had received oral prednisone, despite the potential for serious long-term adverse effects with this treatment.

"Alternative therapies to relieve the burden of corticosteroids in this population are urgently needed," the researchers wrote in the July issue of Arthritis & Rheumatism.

The overall prognosis in juvenile SLE has improved in recent decades, with 10-year survival now reaching 90%, but much less is known about the disease manifestations and its treatment compared with adult-onset lupus.

To more fully characterize these concerns, Beresford and colleagues analyzed data from a collaborative network that has enrolled children with the disease from across the U.K. since 2006.

Of the 198 children included in the study, 85% were female, with a median age at disease onset of 12.6 years.

Among the slightly more than half who were white, the standardized incidence rate was 0.1 per 100,000, while incidence rates were 2 and 2.5 per 100,000 for blacks and Asians.

A notable 38% of the children had a family history of autoimmune disease, including 16% with rheumatoid arthritis, 15% with lupus, and 13% with thyroid disease, suggesting a strong genetic influence, according to the researchers.

Among the hematologic manifestations were lymphopenia in 73% of patients, leukopenia in 32%, hemolytic anemia in 27%, and thrombocytopenia in 20%.

A total of 69% also had anti-double-stranded DNA antibodies and 36% had antiphospholipid antibodies.

To assess disease activity, the researchers used the pediatric version of the British Isles Lupus Assessment Group index as modified in 2004 (pBILAG-2004), which they found to be more sensitive than the American College of Rheumatology criteria.

For instance, the ACR criteria identified neurologic involvement in only 10% of the cohort, compared with 26% identified by pBILAG-2004.

Disease activity did respond to treatment, with mean scores falling from 8.5 to 2 (P<0.01), but within less than 5 years disease damage had already begun to accrue.

Of particular concern was the neurologic damage, which was already present in 8% of children, and included psychosis, seizures, and cerebrovascular accidents.

Renal damage had developed in 4%, including one case of end-stage renal failure, vascular damage in 3%, and musculoskeletal changes in 6%.

The severe scarring alopecia afflicting 10% of the patients also posed particular problems, "and may have devastating effects on patients who are already adapting to taking medications, attending hospital, trying to gain peer acceptance, and trying to attain educational qualifications," the researchers wrote.

An important difference they found in this young cohort compared with adults was that the damage was primarily caused by the disease itself, whereas in patients with later-onset disease, the damage tends to be associated with steroid use.

Approximately half of the patients were diagnosed as teenagers, "a critical time for adolescent growth, puberty, education, and emotional maturation," Beresford and colleagues observed.

"This emphasizes the importance of access to specialist, multidisciplinary pediatric and adolescent holistic care for patients with juvenile SLE," they stated.

They also stressed the need for rapid diagnosis, which can be challenging because of the typical gradual and nonspecific onset of lupus in children, and for safer, more effective treatments.

The use of rituximab (Rituxan), while not formally evaluated in this population, may be a key steroid-sparing agent, they noted.

The research group is continuing to enroll patients with both definite and probable juvenile SLE, with the goal of further defining the disease characteristics and ultimately improving overall care for these vulnerable patients.

The study was supported by the Newcastle-upon-Tyne Alder Hey Kidney Fund and Lupus UK.

The authors reported no financial conflicts of interest.

Primary source: Arthritis & Rheumatism

Source reference:

Watson L, et al "Disease activity, severity, and damage in the UK juvenile-onset systemic lupus erythematosus cohort" Arthritis Rheum 2012; DOI: 10.1002/art.34410.

http://www.medpagetoday.com/Rheumatology/Lupus/33575? utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 Everyday Health, Inc. All rights reserved.

By Nancy Walsh, Staff Writer, MedPage Today

Published: July 06, 2012

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Take Posttest

Action Points

A study found that belimumab combined with conventional treatment improved biomarkers and clinical disease activity in patients with systemic lupus erythematosus.

Note that although the drug, which is a B-cell inhibitor, decreased some B-cell subsets associated with disease activity, antigen-specific antibody responses to previous vaccines -- a marker of memory B-cell activity -- appeared unchanged.

Patients with systemic lupus erythematosus (SLE) treated with belimumab (Benlysta) showed significant changes in immunologic biomarkers along with their clinical responses, a post-hoc analysis of two clinical trials showed.

During the course of a year, immunoglobulin G (IgG) levels fell by 15.3% in patients receiving belimumab along with standard therapies, compared with a decrease of 2.5% for those receiving placebo along with their conventional treatments (P<0.001), according to William Stohl, MD, PhD, of the University of Southern California in Los Angeles, and colleagues.

Meanwhile, patients whose IgG fell to normal levels by month four had response rates of 65% on an index of clinical disease activity at 1 year, compared with rates of 50% for patients with persistently high levels (P<0.001), the researchers reported in the July Arthritis & Rheumatism.

Studies have suggested that following the abnormal immune biomarkers that are the hallmark of SLE could help predict clinical response and the development of flares, the authors noted in their introduction.

Belimumab is a monoclonal antibody that neutralizes B lymphocyte stimulator (BLyS), and has been shown effective in patients with SLE who are positive for anti-nuclear antibody or anti-double stranded (ds) DNA.

To see if biomarkers correlated with clinical response to the drug, Stohl and colleagues analyzed data from two phase III trials that evaluated belimumab in monthly doses of 1 mg/kg or 10 mg/kg.

In both studies, which included 1,684 patients, participants receiving the 10-mg dose plus standard SLE treatment with agents including anti-malarials, immunosuppressives, and steroids had significant improvements in the SLE responder index at one year.

During the course of the year, levels of anti-dsDNA had fallen by 40.8% among patients receiving the 10-mg dose, compared with a reduction of 10.2% in the placebo group.

Other autoantibodies also decreased significantly more with treatment than with placebo:

Anti-Sm, 51.2% versus 28.8% (P<0.001)

IgG anticardiolipin antibody, 32.1% versus 22.7% (P<0.05)

Anti-ribosomal P, 54% versus 8.2% (P<0.001)

Improvements in complement also were observed, rising to normal levels in more patients receiving belimumab and falling to abnormal levels in patients receiving placebo (P=0.002).

The increases in complement tracked with clinical response, as patients whose C4 levels had normalized after 1 month and 4 months had response rates of 52% and 54%, respectively, while patients whose C4 levels remained low had response rates of 41% (P=0.02) and 42% (P<0.01).

Similarly, only 19% of patients whose C3 levels had risen to normal levels by 1 month had a severe flare during the year-long study, compared with 27% of those with persistently low levels (P=0.04).

Among the effects of treatment on lymphocytes were significant decreases in B-cell subtypes associated with disease activity, such as CD19+ and CD20+ cells (P<0.001), without effects on memory B cells or T cells that are needed for proper immune system functioning.

For instance, in patients who had received pneumococcal or tetanus immunizations within the previous 5 years, no changes in vaccine antigen-specific antibody levels were seen, which was "consistent with the preservation of memory B cells and T cells," the researchers noted.

Unlike other B cells, such as plasma cell subsets, memory B cells do not appear to need BLyS for survival, they explained.

In the two randomized studies, serious infections were not seen more commonly among patients receiving belimumab.

"Taken together, these results suggest that belimumab treatment does not compromise the immune response to infection," they wrote.

The study was supported by Human Genome Sciences and the National Institutes of Health.

Several of the authors have received fees and honoraria from Human Genome Sciences and GlaxoSmithKline, and some also hold stock in Human Genome Sciences.

Primary source: Arthritis & Rheumatism

Source reference:

Stohl W, et al "Belimumab reduces autoantibodies, normalizes low complement levels, and reduces select B cell populations in patients with systemic lupus erythematosus" Arthritis Rheum 2012; 64: 2328-2337.

http://www.medpagetoday.com/Rheumatology/Lupus/33637? utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 Everyday Health, Inc. All rights reserved.

Lupus is a chronic autoimmune disease, which causes inflammation of various parts of the body, especially the skin, joints and kidneys. It may also affect the blood.

The immune system normally protects the body against viruses, bacteria and other foreign invaders.

In an autoimmune disease like lupus, the immune system loses its ability to tell the difference between foreign substances and its own cells and tissues. The immune system then makes antibodies directed against the body itself.

When lupus first sets in, symptoms such as fatigue and pain are often non-specific. They can be signs of so many other health problems, which can make diagnosis hard.

The most common complaint people have is fatigue that is so severe it stops them from being able to function normally. This fatigue is often related to fibromyalgia. Fever, muscle and joint pain are also quite common.

Select a symptom to learn more about how the body is affected by lupus and how commonly each symptom can occur during the course of lupus.

Muscle & Joint Pain

95% of people with lupus experience muscle and joint pain.

. Fever Greater Than 100° F

90% of people with lupus get a fever of more than 100 degrees Fahrenheit (38 degrees Celsius).

. Prolonged or Extreme Fatigue

81% of people with lupus suffer from prolonged or extreme fatigue.

. Anemia

71% of people with lupus simultaneously suffer from anemia.

. Kidney Problems

50% of people with lupus find that their kidneys are affected. Symptoms include weight gain, swollen ankles, high blood pressure, and decreased kidney function.

. Pain in the Chest

45% of people with lupus experience a pain in their chest upon breathing deeply. This condition is called pleurisy.

. Rashes

80% of people with lupus observe rashes on their skin. A butterfly-shaped rash across the cheeks and nose is especially common (42%).

. Light Sensitivity

30% of people with lupus become sensitive to light, a condition called photosensitivity.

. Hair Loss

27% of people with lupus experience hair loss resulting in patchy or bald spots.

. Abnormal Blood Clotting

20% of people with lupus report abnormal blood clotting problems.

. Eye Disease

20% of people with lupus concurrently suffer from eye complications such as dry eyes, eye inflammation, and eyelid rashes.

. Seizures

15% of people with lupus experience seizures.

. Mouth or Nose Ulcers

12% of people with lupus report ulcers on their nose or mouth.

.If you have several of these symptoms, please consult your doctor. To determine whether you have lupus, it is necessary to receive a professional medical evaluation.

..

http://www.couldihavelupus.gov/symptoms.cfm?

By Nancy Walsh, Staff Writer, MedPage Today

Published: August 02, 2012

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania

Action Points

Histologic features seen on kidney biopsy are currently used as the standard for the diagnosis of lupus nephritis and are typically used to guide treatment.

Note that this study suggests that specific urinary biomarkers are associated with specific tissue changes observed in conjunction with lupus nephritis activity and chronicity, and may be helpful in the noninvasive measurement of activity, chronicity, and the presence of membranous disease.

Combinations of urinary biomarkers reflect the renal tissue changes occurring in lupus nephritis and ultimately may be useful for noninvasive disease assessment, researchers suggested.

Four markers together accurately predicted a renal biopsy activity score of 7 or higher with a sensitivity of 72%, a specificity of 66%, and an area under the receiver operating characteristic curve (AUC) of 0.85 (95% CI 0.69 to 1), according to Hermine Brunner, MD, of Cincinnati Children's Hospital, and colleagues.

In addition, three of the markers predicted a biopsy chronicity index score of 4 or higher, with a sensitivity of 73%, a specificity of 67%, and an AUC of 0.83 (95% CI 0.67 to 0.93), the researchers reported in the August Arthritis & Rheumatism.

Those scores are considered cutoffs for poor outcomes, they noted.

Current practice requires kidney biopsy for the diagnosis of lupus nephritis and for following the effects of treatment.

This is because conventional measures of kidney function such as proteinuria and glomerular filtration rate are "too inaccurate to reliably discriminate between the acute inflammatory changes that are amenable to immunosuppressive therapy and the chronic degenerative changes that will not improve despite control of [systemic lupus erythematosus] activity," they explained.

Brunner and colleagues previously identified a group of biomarkers that correlated well with clinical measures of renal disease, such as the Systemic Lupus Disease Activity Index–renal domain, but whether these markers, with or without the traditional measures of kidney function, also reflected the histologic processes involved has not yet been determined.

So they explored the possible correlations among these factors in 76 patients whose median age was 23 and who had active inflammation and degeneration on renal biopsy as evidenced by features such as mesangial and capillary proliferation, cellular crescents, and glomerular sclerosis.

Most of the patients were female, and the majority were receiving glucocorticoids and other immunosuppressives.

The urinary biomarkers measured included alpha1-acid glycoprotein (AAG), transferrin (TF), ceruloplasmin (CP), neutrophil gelatinase-associated lipocalin (NGAL), and monocyte chemotactic protein 1 (MCP-1).

Traditional measures of kidney function included glomerular filtration rate (GFR), protein-to-creatinine (P:C) ratio, and levels of C3, C4, and serum creatinine.

On univariate analysis, the researchers evaluated the accuracy, as shown by the AUC, for each of the biomarkers in identifying biopsy activity index scores, biopsy chronicity index scores, and the presence of class V membranous lupus nephritis.

They found good to excellent accuracy (AUC 0.71 or higher) for predicting high biopsy activity scores for AAG, TF, CP, MCP-1, and P:C ratio, and excellent accuracy (AUC 0.81 or higher) for glomerular filtration rate and serum creatinine in predicting high biopsy chronicity scores.

On multivariate analysis, the combination of markers that predicted the high biopsy activity score was MCP-1, CP, AAG, and P:C ratio, while the combination that predicted the high chronicity score was NGAL, MCP-1, and glomerular filtration rate.

For class V membranous nephritis, the predictors were MCP-1, AAG, TF, C4, and glomerular filtration rate, with a sensitivity of 75%, a specificity of 48%, and an AUC of 0.75 (95% CI 0.62 to 0.86).

In discussing the individual biomarkers, the researcher noted that:

MCP-1 is a recognized predictor of lupus nephritis flare and has been shown in animal studies to influence proteinuria and survival.

The AAG marker is most often linked with histologic findings such as crescents and mesangial proliferation and is elevated in other inflammatory diseases of the kidney, functioning as a regulator of the glomerular capillary wall.

Capillary and mesangial proliferation have been associated with increases in TF and also in CP, a protein involved in tissue remodeling after injury to the renal tubules.

Together, these markers "yielded excellent diagnostic abilities" in lupus nephritis, suggesting that "accurate longitudinal noninvasive assessment of [lupus nephritis] activity and chronicity is feasible," Brunner and colleagues observed.

However, "the presented analyses also suggest that additional markers are needed to provide the highly accurate (AUC>0.9) diagnostic tests that are urgently needed by clinicians to help guide [lupus nephritis] therapy," they wrote.

The authors have been supported by the Alliance for Lupus Research, the Cincinnati Children's Hospital, the National Institutes of Health, the Hopkins Lupus Cohort, the National Center for Research Resources, and the Department of Defense.

Two of the authors are co-inventors on patents for lupus nephritis biomarker panels, and one has received fees from Abbott and Alere.

Primary source: Arthritis & Rheumatism

Source reference:

Brunner H, et al "Association of noninvasively measured renal protein biomarkers with histologic features of lupus nephritis" Arthritis Rheum 2012; 64: 2687-2697.

http://www.medpagetoday.com/Rheumatology/Lupus/34009? utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 Everyday Health, Inc. All rights reserved.

By Nancy Walsh, Staff Writer, MedPage Today

Published: September 01, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Action Points

Cardiovascular disease may play a major role in the premature cognitive decline that afflicts many patients with systemic lupus erythematosus.

Note that the risk of cognitive dysfunction was increased in patients who had antiphospholipid antibodies, which are associated with thrombotic events, stroke, and myocardial infarction in lupus.

Cardiovascular disease may play a major role in the premature cognitive decline that afflicts many patients with systemic lupus erythematosus, a longitudinal study revealed.

The likelihood of cognitive impairment was doubled in patients with hypertension (OR 2.06, 95% CI 1.19 to 3.56) or a history of stroke (OR 2.27, 95% CI 1.16 to 4.43), according to Sara Murray, MD, and colleagues from the University of California San Francisco.

Risk was also increased in patients who had antiphospholipid antibodies, which are associated with thrombotic events, stroke, and myocardial infarction in lupus (OR 2.10, 95% CI 1.3 to 3.41), the researchers reported in the September Arthritis Care & Research.

Estimates for the prevalence of cognitive dysfunction among patients with systemic lupus erythematosus range from 20% to 80%, but the causes of this impairment have been unclear.

Patients with lupus also have high rates of early cardiovascular disease, and because other studies have clearly shown cognitive worsening in association with heart disease in the general population, the researchers sought to explore this in a large cohort of patients with systemic lupus erythematosus.

Cognitive function was assessed in annual telephone interviews on tests of memory impairment and verbal fluency.

Impairment was defined as a score of −1 standard deviation or worse compared with normal values for age.

Among 694 patients enrolled in the Lupus Outcomes Study, 15% were found to have cognitive impairment after 7 years of follow-up.

Patient characteristics associated with cognitive dysfunction included smoking, greater disease activity, lower educational achievement, and living in poverty.

Depression also was more common, as were diabetes, hypertension, stroke, and antiphospholipid antibodies.

In an unadjusted analysis, cognitive decline was associated with hypertension, diabetes, smoking, stroke, high disease activity, and antiphospholipid antibodies.

In a model adjusting only for lupus-related features, significant associations were seen for disease activity (OR 1.04, 95% CI 1.01 to 1.07) and antiphospholipid antibodies (OR 2.14, 95% CI 1.34 to 3.41, P<0.05 for both).

And in a model that also included cardiovascular risk factors, cognitive decline was associated with antiphospholipid antibodies (OR 2.24, 95% CI 1.39 to 3.61) and hypertension (OR 2.08, 95% CI 1.21 to 3.58, P<0.05 for both).

But in the final model, which also included cardiovascular events such as myocardial infarction and stroke, the significant associations were with hypertension, stroke, and antiphospholipid antibodies (P<0.05 for all).

In a further analysis, a history of stroke was more common among patients with the most severe cognitive impairment compared with mild impairment (32.3% versus 14.5%, P=0.036).

"The association with severe impairment identified in our study suggests that stroke may represent an endpoint on a spectrum of disease pathology that leads to cognitive dysfunction, at which point outcomes are more severe," Murray and colleagues observed.

The researchers noted that, while the mechanisms by which hypertension might contribute to cognitive decline are not fully understood, atrophic changes in the brain of hypertensive individuals have been shown on imaging studies, particularly in the prefrontal cortex.

The specific reasons by which antiphospholipid antibodies might have a negative influence on cognition also are unclear, but could be through thrombotic mechanisms or by direct neural effects of the antibodies.

The researchers noted that their study did have limitations, including the self-report of cardiovascular events and risk factors.

In addition, no information was available as to the severity or timing of events.

"Therefore, we do not know the temporal relationship between cognitive dysfunction and stroke, which could be critical to understanding the pathogenesis," they pointed out.

A more thorough understanding of the link between cardiovascular disease and cognitive decline could provide an opportunity to identify those patients most likely to be affected.

Some of the risk factors for cognitive decline, including hypertension, are modifiable, they stressed.

"Future longitudinal studies are necessary to clarify the causality of these relationships. A better understanding of specific targets for prevention and intervention can serve to minimize the burden of one of the most common neuropsychiatric syndromes occurring in [systemic lupus erythematosus]," they concluded.

The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Arthritis Foundation, a Kirkland Scholar Award, the Rosalind Russell Medical Research Center for Arthritis, and the U.S. Public Health Service.

The authors reported no conflicts of interest.

Primary source: Arthritis Care & Research

Source reference:

Murray S, et al "Cardiovascular disease and cognitive dysfunction in systemic lupus erythematosus" Arthritis Care Res 2012; 64: 1328-1333.

http://www.medpagetoday.com/Rheumatology/Lupus/34521? utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 Everyday Health, Inc. All rights reserved.

This autoimmune disease appears to raise risk for preeclampsia

By Robert Preidt

Friday, November 2, 2012

FRIDAY, Nov. 2 (HealthDay News) --

A new study suggests that pregnant women with the autoimmune disease lupus may have a twofold increased risk of preeclampsia, a dangerous condition characterized by high blood pressure and protein in the urine.

Preeclampsia can lead to serious health problems such as seizure, stroke and organ failure and cause the death of the mother and/or baby.

The researchers also found that the use of disease-modifying antirheumatic drugs (DMARDs) during pregnancy was associated with a statistically insignificant increased risk of preeclampsia.

These medications are used to treat lupus and other autoimmune diseases such as rheumatoid arthritis, although their use during pregnancy is rare.

The slightly higher risk associated with antirheumatic drugs could be explained by the severity of autoimmune disease among users, according to the study, which was published in the November issue of the journal Arthritis Care & Research.

This class of medications includes methotrexate (brand names Rheumatrex and Trexall), hydroxychloroquine (Plaquenil, Quineprox), etanercept (Enbrel) and adalimumab (Humira).

Understanding how their use affects women with autoimmune disease is important, especially during pregnancy, lead author Kristin Palmsten, of the Harvard School of Public Health, said in a journal news release.

Palmsten and her colleagues looked at data on nearly 307,000 pregnancies among almost 225,000 women in the province of British Columbia, Canada.

"Our findings uphold previous evidence, showing that women with [lupus] had twice the risk of developing preeclampsia," she said.

"The statistically non-significant increase in preeclampsia risk found for DMARDs was reduced when we more fully accounted for the potential effect of the autoimmune diseases, suggesting that the underlying disease or severity of the disease was likely contributing to the increased risk of preeclampsia among DMARD users."

Further research is needed to confirm the findings, and studies should focus on use of DMARDs and preeclampsia in women with specific autoimmune diseases, the researchers concluded.

The new study found a link between lupus and preeclampsia. It did not prove a cause-and-effect relationship.

SOURCE: Arthritis Care & Research, news release, Oct. 31, 2012

http://www.nlm.nih.gov/medlineplus/news/ fullstory_130948.html

Copyright (c) 2012 HealthDay. All rights reserved.