Lupus Erythematosus Clinical Trials, Diagnosis, and Treatment

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Lupus Erythematosus

Systemic lupus erythematosus (SLE or lupus) is a chronic autoimmune disease that is potentially debilitating and sometimes fatal as the immune system attacks the body’s cells and tissue, resulting in inflammation and tissue damage. SLE can affect any part of the body, but most often harms the heart, joints, skin, lungs, blood vessels, liver, kidneys and nervous system. The course of the disease is unpredictable, with periods of illness (called flares) alternating with remission. Lupus can occur at any age, but is most common in women, particularly of non-European descent. Lupus is treatable symptomatically, mainly with corticosteroids and immunosuppressants, though there is currently no cure.

Current Research

For current research articles click - here

Classification

Lupus is a chronic autoimmune disease in which the body's own defense system attacks otherwise healthy tissue. Clinically, it can affect multiple organ systems including the heart, skin, joints, kidneys and nervous system. There are several types of lupus; generally when the word 'lupus' alone is used, it refers to the systemic lupus erythematosus or SLE as discussed in this article. Other types include:

Drug-induced lupus erythematosus, a drug-induced form of SLE; this type of lupus can occur equally for either gender.
Lupus nephritis, an inflammation of the kidneys caused by SLE.
Discoid lupus erythematosus, a skin disorder which causes a red, raised rash on the face, scalp or rest of the body, which can develop into SLE.
Subacute cutaneous lupus erythematosus, which causes non-scarring skin lesions on patches of skin exposed to sunlight.
Neonatal lupus, a rare disease affecting babies born to women with SLE, Sjögren's syndrome or sometimes no autoimmune disorder. It is theorized that maternal antibodies attack the fetus, causing skin rash, liver problems, low blood counts (which gradually fade) and rarely bradycardia.

Signs and Symptoms

SLE is one of several diseases known as the great imitator because its symptoms vary so widely it often mimics or is mistaken for other illnesses, and because the symptoms come and go unpredictably. Diagnosis can be elusive, with patients sometimes suffering unexplained symptoms and untreated SLE for years. Common initial and chronic complaints are fever, malaise, joint pains, myalgias and fatigue. Because they are so often seen with other diseases, these signs and symptoms are not part of the diagnostic criteria for SLE. When occurring in conjunction with other signs and symptoms (below), however, they are considered suggestive.

Dermatological Manifestations

As many as 30% of patients present with some dermatological symptoms (and 65% suffer such symptoms at some point), with 30% to 50% suffering from the classic malar rash (or butterfly rash) associated with the disease. Patients may present with discoid lupus (thick, red scaly patches on the skin). Alopecia, mouth, nasal, and vaginal ulcers, and lesions on the skin are also possible manifestations.

Musculoskeletal Manifestations

Patients most often seek medical attention for joint pain, with small joints of the hand and wrist usually affected, although any joint is at risk. Unlike rheumatoid arthritis, SLE arthropathy is not usually destructive of bone, however, deformities caused by the disease may become irreversible in as many as 20% of patients.

Hematological Manifestations

Anemia and iron deficiency may develop in as many as half of patients. Low platelet and white blood cell counts may be due to the disease or a side-effect of pharmacological treatment. Patients may have an association with antiphospholipid antibody syndrome (a thrombotic disorder) where autoantibodies to phospholipids are present in the patient's serum. Abnormalities associated with antiphospholipid antibody syndrome include a paradoxical prolonged PTT (which usually occurs in hemorrhagic disorders) and a positive test for antiphospholipid antibodies; the combination of such findings have earned the term "lupus anticoagulant positive". Another autoantibody finding in lupus is the anticardiolipin antibody which can cause a false positive test for syphilis.

Cardiac Manifestations

Patients may present with inflammation of various parts of the heart, such as pericarditis, myocarditis, and endocarditis. The endocarditis of SLE is characteristically non-infective (Libman-Sacks endocarditis) and involves either the mitral valve or the tricuspid valve. Atherosclerosis also tends to occur more often and advance more rapidly in SLE patients than in the general population.

Pulmonary Manifestations

Lung and pleura inflammation can cause pleuritis, pleural effusion, lupus pneumonitis, chronic diffuse interstitial lung disease, pulmonary hypertension, pulmonary emboli, pulmonary hemorrhage.

Hepatic Involvement

See autoimmune hepatitis

Renal Involvement

Painless hematuria or proteinuria may often be the only presenting renal symptom. Acute or chronic renal impairment may develop with lupus nephritis, leading to acute or end stage renal failure. Because of early recognition and management of SLE, end stage renal failure occurs in less than 5% of patients.

Histologically, a hallmark of SLE is membranous glomerulonephritis with "wire loop" abnormalities. This finding is due to immune complex deposition along the glomerular basement membrane leading to a typical granular appearance in immunofluorescence testing.

Neurological Manifestations

About 10% of patients may present with seizures or psychosis. A third may test positive for abnormalities in the cerebrospinal fluid.

T-Cell Abnormalities

Abnormalities in T cell signaling are associated with SLE, including deficiency in CD45 phosphatase and increased expression of CD40 ligand.

Other rarer manifestations

Lupus gastroenteritis, lupus pancreatitis, lupus cystitis, autoimmune inner ear disease, parasympathetic dysfunction, retinal vasculitis, and systemic vasculitis.

Other abnormalities include:

Increased expression of FcεRIγ, which replaces the sometimes deficient TCR ζ chain

Increased and sustained calcium levels in T cells

Moderate increase of inositol triphosphate

Reduction in PKC phosphorylation

Reduction in Ras-MAP kinase signaling

Deficiencies in protein kinase A I activity

Causes

Lupus research has dramatically increased in recent years but the exact cause of the disease is unknown and there is still no consensus on whether it is a single condition or a group of related diseases. SLE is a chronic inflammatory disease believed to be a type III hypersensitivity response with potential type II involvement, characterised by the body's production of antibodies against the nuclear components of its own cells. There are three mechanisms by which lupus is thought to develop: genetic predisposition, environmental triggers and drug reaction (drug-induced lupus).

Genetics

The first mechanism may arise genetically. Research indicates that SLE may have a genetic link. Lupus does run in families, but no single "lupus gene" has yet been identified. Instead, multiple genes appear to influence a person's chance of lupus developing when triggered by environmental factors. The most important genes are located on chromosome 6, where mutations may occur randomly (de novo) or be inherited. Additionally, people with SLE have an altered RUNX-1 binding site, which may be either cause or contributor (or both) to the condition. Altered binding sites for RUNX-1 have also been found in people with psoriasis and rheumatoid arthritis.

Environmental Triggers

The second mechanism may be due to environmental factors. These factors may not only exacerbate existing lupus conditions, but also trigger the initial onset. They include certain medications (such as some antidepressants and antibiotics), extreme stress, exposure to sunlight, hormones, and infections. Some researchers have sought to find a connection between certain infectious agents (viruses and bacteria), but no pathogen can be consistently linked to the disease. UV radiation has been shown to trigger the photosensitive lupus rash, but some evidence also suggests that UV light is capable of altering the structure of the DNA, leading to the creation of autoantibodies. Some researchers have found that women with silicone gel-filled breast implants have produced antibodies to their own collagen, but it is not known how often these antibodies occur in the general population and there is no data that show these antibodies cause connective tissue diseases such as lupus.

Drug Reactions

Drug-induced lupus erythematosus is a reversible condition that usually occurs in patients being treated for a long-term illness. Drug-induced lupus mimics systemic lupus. However, symptoms of drug-induced lupus generally disappear once a patient is taken off the medication which triggered the episode. There are about 400 medications currently in use that can cause this condition, though the most common drugs are procainamide, hydralazine and quinidine.

Non-SLE Forms of Lupus

Discoid (cutaneous) lupus is limited to skin symptoms and is diagnosed via biopsy of skin rash on the face, neck or scalp. Often an anti-nuclear antibody (ANA) test for discoid patients is negative or a low-titre positive. About 10% of discoid lupus patients eventually develop SLE.

Pathophysiology

Lupus is an example of pathophysiology, a disturbance of the normal functioning of the body. One manifestation of lupus is abnormalities in apoptosis, a type of programmed cell death in which aging or damaged cells are neatly disposed of as a part of normal growth or functioning.

Abnormalities in Apoptosis

Apoptosis is increased in monocytes and keratinocytes

Expression of Fas by B cells and T cells is increased

There are correlations between the apoptotic rates of lymphocytes and disease activity

Tangible body macrophages (TBMs) are large phagocytic cells in the germinal centers of secondary lymph nodes. They express CD68 protein. These cells normally engulf B cells which have undergone apoptosis after somatic hypermutation. In some patients with SLE, significantly fewer TBMs can be found, and these cells rarely contain material from apoptotic B cells. Also, uningested apoptotic nuclei can be found outside of TBMs. This material may present a threat to the tolerization of B cells and T cells. Dendritic cells in the germinal center may endocytose such antigenic material and present it to T cells, activating them. Also, apoptotic chromatin and nuclei may attach to the surfaces of follicular dendritic cells and make this material available for activating other B cells which may have randomly acquired self-specificity through somatic hypermutation.

Diagnosis

Some physicians make a diagnosis on the basis of the ACR classification criteria (see below). The criteria, however, were established mainly for use in scientific research (i.e. inclusion in randomized controlled trials), and patients may have lupus but never meet the full criteria.

Anti-nuclear antibody testing and anti-extractable nuclear antigen (anti-ENA) form the mainstay of serologic testing for lupus. Antiphospholipid antibodies occur more often in SLE, and can predispose for thrombosis. More specific are the anti-smith and anti-dsDNA antibodies. Other tests routinely performed in suspected SLE are complement system levels (low levels suggest consumption by the immune system), electrolytes and renal function (disturbed if the kidney is involved), liver enzymes and a complete blood count.

Formerly, the lupus erythematosus (LE) cell test was used for diagnosis, however those LE cells are only found in 50-75% of SLE patients, and are also found in some patients with rheumatoid arthritis, scleroderma, and drug sensitivities. Because of this, the LE cell test is now performed only rarely and is mostly of historical significance.

Diagnostic Criteria

The American College of Rheumatology (ACR) has established eleven criteria in 1982, which were revised in 1997 as a classificatory instrument to operationalise the definition of SLE in clinical trials. They were not intended to be used to diagnose individual patients and do not do well in that capacity. For inclusion in clinical trials, patients must meet the following three criteria to be classified as having SLE: (i) patient must present with four of the below eleven symptoms (ii) either simultaneously or serially (iii) during a given period of observation.

Malar rash (rash on cheeks)
Discoid lupus (red, scaly patches on skin which cause scarring)
Photosensitivity (exposure to ultraviolet light causes rash)
Oral ulcers: include oral or nasopharyngeal ulcers
Arthritis: nonerosive arthritis of two or more peripheral joints, with tenderness, swelling or effusion
Renal disorder: More than 0.5 g per day protein in urine, or cellular casts seen in urine under a microscope.
Neurologic disorder: Seizures or psychosis
Serositis: Pleuritis (inflammation of the membrane around the lungs) or pericarditis (inflammation of the membrane around the heart)
Hematologic disorder: Hemolytic anemia (low red blood cell count) or leukopenia (white blood cell count <4000/ul), lymphopenia (<1500/ul ) or thrombocytopenia (<100000/uL) in the absence of offending drug.
Anti-nuclear antibody test positive, very sensitive (98%) but non specific.
Immunologic disorder: Positive anti-Sm DNA, anti-ds DNA, anti-phospholipid antibody and/or false positive serological test for syphilis, presence of anti-ss DNA in 70% of patients (though also positive in patients with rheumatic disease and healthy persons

A useful mnemonic for these 11 criteria is SOAP BRAIN MD: Serositis (8), Oral ulcers (4), Arthritis (5), Photosensitivity (3), Blood Changes (9), Renal involvement (proteinuria or casts) (6), ANA (10), Immunological changes (11), Neurological signs (seizures, frank psychosis) (7), Malar Rash (1), Discoid Rash (2).

Alternatively, recursive partitioning has been used to identify more parsimonious criteria.

Some patients may have SLE without four criteria and SLE is associated with manifestations other than those listed in the criteria. Dr Graham R.V. Hughes, an authority on lupus in the UK, has published alternative criteria to diagnose SLE in 1982.

Common Misdiagnoses

Porphyria

Porphyrias are complex genetic disorders that share many symptoms with lupus, but impact the enzymes responsible for building heme, a component needed in heme proteins. Porphyrias are ecogenic disorders requiring both environmental and genetic backgrounds to manifest with a variety of symptoms and medical complications. They are noted for photosensitivity and have been associated with transient and permanent production of autoantibodies. The five major forms of dominantly inherited porphyrias (acute intermittent porphyria, porphyria cutanea tarda, hereditary coproporphyria, variegate porphyria and erythropoietic protoporphyria) have been detected in systemic lupus erythematosus and discoid lupus patients over the past 50 years. Physicians should have a high degree of suspicion of porphyrias in all lupus cases and act accordingly when patients are in a medical crisis that may be due to an underlying acute hepatic porphyria. Drug-induced lupus and photosensitivity warrant an investigation for an underlying porphyria since multiple drug reactions are a hallmark complication of porphyrias. Patients with both lupus and porphyrias should avoid porphyrinogenic drugs and hormone preparations.

Patients with acute hepatic porphyrias (acute intermittent porphyria, hereditary coproporphyria, variegate porphyria) have been detected in lupus patients with severe life-threatening "lupus" complications known as neurolupus. Symptoms are identical to acute hepatic porphyria attacks and include seizures, psychosis, peripheral neuropathy and syndrome of inappropriate antidiuretic hormone (SIADH) associated with dangerously low sodium levels (hyponatremia). Porphyria attacks require intervention with intravenous glucose, heme preparations and the discontinuation of dangerous porphyrinogenic drugs including antiseizure drugs. Several other lupus complications have been associated with porphyrias including pancreatitis and pericarditis. Porphyrin testing should be performed on urine, stool/bile and blood to detect all types of porphyrias, and repeat testing should be performed in suspicious cases. Appropriate enzyme tests or DNA testing should also be pursued to obtain a complete diagnosis which could include a dual porphyria.

Common dual diagnoses

SLE is sometimes diagnosed in conjunction with other conditions, including Rheumatoid Arthritis and Fibromyalgia.

Treatment

As lupus erythematosus is a chronic disease with no known cure, treatment is restricted to dealing with the symptoms; essentially this involves preventing flares and reducing their severity and duration when they occur. There are several means of preventing and dealing with flares, including drugs, alternative medicine and lifestyle changes.

Drug Therapy

Due to the variety of symptoms and organ system involvement with Lupus patients, the severity of the SLE in a particular patient must be assessed in order to successfully treat SLE. Mild or remittent disease can sometimes be safely left untreated. If required, non-steroidal anti-inflammatory drug and anti-malarials may be used.

In more severe cases, medications that modulate the immune system (primarily corticosteroids and immunosuppressants) are used to control the disease and prevent re-occurrence of symptoms (known as flares). Disease-modifying antirheumatic drugs (DMARDs) are used preventively to reduce incidence of flares, the process of the disease, and lower the need for steroid use; when flares occur, they are treated with corticosteroids. DMARDs commonly in use are anti-malarials and immunosupressants (e.g. methotrexate and azathioprine). Hydroxychloroquine (trade name Plaquenil) is an FDA approved anti-malarial used for constitutional, cutaneous, and articular manifestations, while Cyclophosphamide (trade names Cytoxan and Neosar) is used for severe glomerulonephritis or other organ-damaging complications, and in 2005, CellCept became accepted for treatment of lupus nephritis.

obesity, diabetes and osteoporosis. Depending on the dosage, corticosteroids can cause other side effects such as a puffy face, an unusually large appetite and difficulty sleeping. Those side effects can subside if and when the large initial dosage is reduced, but long term use of even low doses can cause high blood pressure and cataracts. Due to these side effects, steroids are avoided if possible.

Acupuncture

A 1985 study on lupus and acupuncture reported improvement of lupus sufferers over matched controls, though there was no placebo group for comparison. It is possible that acupuncture may be useful for the treatment some of the symptoms of lupus, but there needs to be more research done before a definitive statement can be made regarding acupuncture, and alternative medicine as a whole.

Lifestyle Changes

Other measures such as avoiding sunlight or covering up with sun protective clothing can also be effective in preventing problems due to photosensitivity. Weight loss is also recommended in overweight and obese patients to alleviate some of the effects of the disease, especially where joint involvement is significant.

Treatment Research

Other immunosuppressants and autologous stem cell transplants are under investigation as a possible cure. Recently, treatments that are more specific in modifying the particular subset of the immune cells (e.g. B- or T- cells) or cytokine proteins they secrete have been gaining attention. Research into new treatments has recently been accelerated by genetic discoveries, especially mapping of the human genome. According to a June 2006 market analysis report by Datamonitor, treatment for SLE could be on the verge of a breakthrough as there are numerous late-Phase trials currently being carried out.

Prevention

Lupus is not understood well enough to be prevented, but when the disease develops, quality of life can be improved through flare prevention. The warning signs of an impending flare include increased fatigue, pain, rash, fever, abdominal discomfort, headache and dizziness. Early recognition of warning signs and good communication with a doctor can help individuals with lupus remain active, experience less pain and reduce medical visits.

Prevention of Complications During Pregnancy

While most infants born to mothers with lupus are healthy, pregnant mothers with SLE should remain under a doctor's care until delivery. Neonatal lupus is rare, but identification of mothers at highest risk for complications allows for prompt treatment before or after birth. In addition, SLE can flare during pregnancy and proper treatment can maintain the health of the mother for longer. Women pregnant and known to have the antibodies for anti-Ro (SSA) or anti-La (SSB) should have echocardiograms during the 16th and 30th weeks of pregnancy to monitor the health of the heart and surrounding vasculature.

Prognosis

In the 1950s, most patients diagnosed with SLE lived fewer than five years. Advances in diagnosis and treatment have improved survival to the point where over 90% of patients now survive for more than ten years and many can live relatively asymptomatically. The most common cause of death is infection due to immunosuppression as a result of medications used to manage the disease. Prognosis is normally worse for men and children than for women. Fortunately, if symptoms present after age 60, the disease tends to run a more benign course. The ANA is the most sensitive screening test while Anti-Sm (Anti Smith) is the most specific. The DS-DNA antibody is also fairly specific and often fluctuates with disease activity. The DS-DNA titer is therefore sometimes useful to diagnose or monitor acute flares or response to treatment.

Epidemiology

Previously believed to be a rare disease, Lupus has seen an increase in awareness and education since the 1960s. This has helped many more patients get an accurate diagnosis making it possible to estimate the number of people with lupus. In the United States alone, it is estimated that between 270,000 and 1.5 million people have lupus, making it more common than cystic fibrosis or cerebral palsy. The disease affects both females and males, though young women are diagnosed nine times more often than men. SLE occurs with much greater severity among African-American women, who suffer more severe symptoms as well as a higher mortality rate. Worldwide, a conservative estimate states that over 5 million people have lupus.

Although SLE can occur in anyone at any age, it is most common in women of childbearing age. It affects 1 in 4000 people in the United States, with women becoming afflicted far more often than men. The disease appears to be more prevalent in women of African, Asian, Hispanic and Native American origin but this may be due to socioeconomic factors. People with relatives who suffer from SLE, rheumatoid arthritis or thrombotic thrombocytopenic purpura are at a slightly higher risk than the general population.

History

Medical historians have theorized people with porphyrias (a disease that shares many symptoms with Lupus) generated folklore stories of vampires and werewolves due to the photosensitivity, scarring, hair growth and porphyrin brownish-red stained teeth in severe recessive forms of porphyria or combinations of the disorders known as dual, homozygous or compound heterozygous porphyrias.

The history of lupus erythematosus can be divided into three periods: the classical, neoclassical, and modern. The classical period began when the disease was first recognized in the Middle Ages and saw the description of the dermatological manifestation of the disorder. The term lupus is attributed to the 12th century physician Rogerius, who used it to describe the classic malar rash. The neoclassical period was heralded by Móric Kaposi's recognition in 1872 of the systemic manifestations of the disease. The modern period began in 1948 with the discovery of the LE cell (the Lupus Erythematosus cell, a misnomer as it occurs with other diseases as well) and is characterised by advances in our knowledge of the pathophysiology and clinical-laboratory features of the disease, as well as advances in treatment.

Useful medication for the disease was first found in 1894, when quinine was first reported as an effective therapy. Four years later, the use of salicylates in conjunction with quinine was noted to be of still greater benefit. This was the best available treatment to patients until the middle of the twentieth century, when Hench discovered the efficacy of corticosteroids in the treatment of SLE.

Origins of 'Lupus Erythematosus'

There are several explanations ventured for the term lupus erythematosus. Lupus is Latin for wolf, and 'erythro' is derived from ερυθρός, Greek for "red." All explanations originate with the reddish, butterfly-shaped malar rash that the disease classically exhibits across the nose and cheeks.

In various accounts, some doctors thought the rash resembled the pattern of fur on a wolf's face.
In other accounts doctors thought that the rash, which was often more severe in earlier centuries, created lesions that resembled wolf bites or scratches.
Stranger still is the account that the term "Lupus" didn't come from Latin at all, but from the term for a French style of mask which women reportedly wore to conceal the rash on their faces.
Another common explanation for the term is that the disease's course involves repeated attacks like those of a voracious predator, leaving behind the red blotches

Famous Patients

Mika Murakami, a prodigal pianist and mathematician, died two weeks before her 12th birthday

Ray Walston, a well known character actor

Tim Raines, a former major league baseball player, primarily with the Montreal Expos

Ferdinand Marcos, former Philippine president, who died from complications of lupus in 1989

Flannery O'Connor, American fiction writer

Hugh Gaitskell, British politician

J Dilla (also known as Jay Dee, born James Dewitt Yancey), a hip-hop producer and beatmaker who died of the disease in 2006

Elaine Paige, British actress and singer

Michael Jackson, singer/songwriter, was diagnosed with discoid lupus and vitiligo in 1984.

Millie, the pet dog of former U.S. President George H. W. Bush and his wife Barbara Bush, was diagnosed with discoid lupus erythematosus

Charles Kuralt, former anchor of CBS Sunday Morning

Inday Ba (also known as N'Deaye Ba), a Swedish-born actress who died from complications of lupus at age 32

Caroline Dorough-Cochran, sister of Howie D. of the Backstreet Boys, who founded the Dorough Lupus Foundation in her memory

Mercedes Yvette, runner-up of Season Two of America's Next Top Model

Sophie Howard, a British glamour model

Leslie Hunt, an American singer and former American Idol semifinalist

Seal, an English singer

SLE in Popular Culture

Several episodes of American medical television drama House, M.D., have contained a false diagnosis of lupus. So many episodes have contained a reference to lupus, that a collaboration of scenes became one of the special features on the Second Season DVD. In the episode "Merry Little Christmas", House is revealed to store a secret stash of Vicodin in a lupus textbook. When asked why by Foreman, he replies "It's never lupus".

The FX cop series, The Shield, features a character that is battling lupus.

In Season 7 of ER, James Cromwell plays Bishop Stewart, a patient of Luka Kovac who is suffering from, and eventually passes away due to complications of, lupus.

(adapted from Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Lupus_erythematosus)

Findings From Current Research

Thrombotic Microangiopathic Hemolytic Anemia in a Patient with SLE: Diagnostic Difficulties

Authors: Shah AA, Higgins JP, Chakravarty EF.

AA Shah is a Postdoctoral Fellow in the Division of Rheumatology, Department of Medicine, at the Johns Hopkins University School of Medicine, Baltimore, MD.

Background A 19-year-old woman with newly diagnosed systemic lupus erythematosus (SLE) presented with hemolytic anemia, thrombocytopenia, hypertension, tonic-clonic seizures, blurry vision, nephrotic syndrome and renal insufficiency.Investigations At a general hospital, the investigations included brain MRI, echocardiography, laboratory tests including measurement of the amount of protein excreted daily, platelet count, levels of lactate dehydrogenase, creatinine and anticardiolipin antibodies, direct Coombs' test, peripheral blood smear, and measurement of blood pressure. At a tertiary institution the investigations included physical examination, electroencephalography, brain MRI, magnetic resonance angiography, repetition of laboratory tests plus measurement of von Willebrand factor-cleaving protease activity, measurement of levels of antibodies to double-stranded DNA and platelets, and renal biopsy.Diagnosis Thrombotic microangiopathic hemolytic anemia with a possible underlying diagnosis of malignant hypertension, antiphospholipid antibody syndrome, catastrophic antiphospholipid antibody syndrome, thrombotic thrombocytopenic purpura, or active SLE.Management At the general hospital, therapy included a single dose of intravenous cyclophosphamide 500 mg, eight daily plasma exchange treatments, three daily infusions of methylprednisolone 1 g followed by methylprednisolone 60 mg every 8 h, an infusion of rituximab 657 mg and ultrafiltration via hemodialysis. At the tertiary institution, therapy included an infusion of cyclophosphamide 650 mg, aspirin 81 mg daily, prednisone 40 mg daily, mycophenolate mofetil 750 mg twice daily, and aggressive management of hypertension.

Journal: Nat Clin Pract Rheumatol. 2007 Jun;3(6):357-62
Adapted from PubMed; click here to access full journal article.

Cutaneous Lupus Erythematosus Simulating Squamous Neoplasia: The Clinicopathologic Conundrum and Histopathologic Pitfalls

Authors: Zedek DC, Smith ET, Hitchcock MG, Feldman SR, Shelton BJ, White WL.

Department of Pathology, University of North Carolina Hospitals, Chapel Hill, North Carolina, USA.

BACKGROUND: The clinical distribution and character of cutaneous lupus erythematosus lesions can simulate squamous neoplasms, leading physicians to submit a shave biopsy specimen with a differential diagnosis of squamous neoplasm. OBJECTIVE: Our aim was to describe histologic features of interface dermatitis that cause difficulty in distinguishing between cutaneous lupus erythematosus and squamous neoplasia in shave biopsy specimens and to identify distinguishing criteria. METHODS: Twenty-six biopsy specimens from 10 patients initially diagnosed with squamous neoplasia that ultimately proved to be cutaneous lupus erythematosus were identified. Comparisons were made of these to 38 control biopsies of chronic cutaneous lupus erythematosus and 34 control biopsies of keratoses/carcinomas without lupus. All biopsies were scored (0 or 1: absent or present) with respect to 11 histologic criteria. RESULTS: The criteria of perifollicular inflammation, follicular plugging, vacuolar interface change, compact orthokeratosis, and acrosyringeal inflammation were significantly more common in the lupus cases than in the keratoses/carcinomas controls. The mean lupus case score was 6.88, lupus control score 6.55, and keratoses/carcinomas control score 5.08. LIMITATIONS: A limited number of patients were studied. Microscopic observations and assumptions with inherent subjectivity were used in establishing the histologic scores. CONCLUSION: Use of the criteria presented, although not absolute, should alert one to the possibility of lupus in an atypical squamous proliferation, especially in suspected squamous neoplasms that worsen or recur after therapy.

Journal: J Am Acad Dermatol. 2007 Jun;56(6):1013-20
Adapted from PubMed; click here to access full journal article.

Malar Rash Caused by Metal Allergy in a Patient with Systemic Lupus Erythematosus

Authors: Kosboth M, Chin-Loy A, Lyons R, Wesson SK, Reeves WH

Division of Rheumatology & Clinical Immunology and Center for Autoimmune Disease, University of Florida, Gainesville, FL 32610-0221, USA.

BACKGROUND: A 61-year-old woman with an 8-year history of systemic lupus erythematosus presented with a non-pruritic, erythematous, malar rash. Previously, she had tested positive for antinuclear antibody and autoantibodies to double-stranded DNA and Ro/SSA, and had an elevated erythrocyte sedimentation rate. She wore eyeglasses with metal frames and had recently gained weight, which caused the eyeglasses to have increased contact area with her face. INVESTIGATIONS: Physical examination, autoantibody testing, measurement of complement C3 and C4 levels, measurement of erythrocyte sedimentation rate, hypersensitivity patch testing, dimethylglyoxime test of the patient's eyeglass frames. DIAGNOSIS: Delayed-type hypersensitivity reaction to nickel and possibly to cobalt dichloride in the patient's eyeglass frames, which caused a malar rash that mimicked acute cutaneous lupus erythematosus. MANAGEMENT: The rash resolved completely with contact avoidance with the eyeglass frames.

Journal: Nat Clin Pract Rheumatol. 2007 Apr;3(4):240-5
Adapted from PubMed; click here to access full journal article.

Impact of Health Maintenance Organizations and Fee-for-Service on Health Care Utilization Among People with Systemic Lupus Erythematosus

Authors: Yelin E, Trupin L, Katz P, Criswell LA, Yazdany J, Gillis J, Panopalis P.

University of California, San Francisco, CA, USA. ed.yelin@ucsf.edu

OBJECTIVE: To compare health care utilization in people with systemic lupus erythematosus (SLE) in health maintenance organizations (HMOs) and fee-for-service (FFS). METHODS: A structured survey was administered to a cohort of 982 people with SLE who were assembled between 2002 and early 2005. A total of 2,656 person-years of observation were completed by the end of 2005. In each year, respondents reported their health care utilization and whether they had HMO or FFS coverage. We compared health care utilization of those in HMOs and FFS, with and without adjustment for socioeconomic, demographic, and health characteristics using repeated-measures regression techniques. RESULTS: Compared with people with SLE who were in FFS, those in HMOs were younger (3.3 years), received a diagnosis at an earlier age (3.6 years), had slightly less disease activity (0.4 on a 10-point scale), were more likely to be nonwhite (8.8%), were less likely to be below the poverty line (7.8%), and were less likely to have public insurance (29.7%). The 2 groups did not differ in other characteristics. On an unadjusted basis, subjects with SLE in HMOs had significantly fewer physician visits (3.1; 95% confidence interval [95% CI] 1.7, 4.5) and were less likely to report one or more outpatient surgical visits (6.3%; 95% CI 2.5, 10.0), and hospital admissions (5.5%; 95% CI 1.7, 9.3) than those in FFS. Adjustment reduced the differences in physician visits (2.3; 95% CI 1.1, 3.5), outpatient surgical rates (4.4%; 95% CI 0.6, 8.1), and hospital admission rates (4.0%, 95% CI 0.4, 7.7). CONCLUSION: Subjects with SLE in HMOs utilized substantially less ambulatory care and were less likely to have outpatient surgery and hospital admissions than those in FFS; the effects were not completely explained by socioeconomic, demographic, and health characteristics.

Journal: Arthritis Rheum. 2007 Apr 15;57(3):508-15
Adapted from PubMed; click here to access full journal article.

Reproductive and Menopausal Factors and Risk of Systemic Lupus Erythematosus in Women

Authors: Costenbader KH, Feskanich D, Stampfer MJ, Karlson EW.

Robert B. Brigham Arthritis and Musculoskeletal Diseases Clinical Research Center, Brigham and Women's Hospital, and Harvard School of Public Health, Boston, Massachusetts 02115, USA. KCostenbader@partners.org

OBJECTIVE: Systemic lupus erythematosus (SLE) occurs predominantly in women, and hormones may play a role in its etiology. This study was carried out to examine associations between female reproductive and menopausal factors and the development of SLE. METHODS: A cohort of 238,308 women was prospectively examined. Subjects were older women (ages 30-55 years at start) and younger women (ages 25-42 years at start) from the Nurses' Health Study (NHS) and NHSII cohorts. Incident SLE diagnosed between 1976 and 2003 was confirmed by medical record review. The relative risk (RR) of SLE was estimated separately in each cohort using Cox proportional hazards models, and then pooled using meta-analysis random effects models. RESULTS: Two hundred sixty-two incident cases of SLE were confirmed among the women. In multivariable models adjusted for reproductive and other risk factors, age<or=10 years at menarche (pooled RR 2.1, 95% confidence interval [95% CI] 1.4-3.2), oral contraceptive use (pooled RR 1.5, 95% CI 1.1-2.1), and use of postmenopausal hormones (RR 1.9, 95% CI 1.2-3.1) significantly increased the risk of SLE. An elevation of SLE risk was observed among postmenopausal women primarily after surgical menopause (RR 2.3, 95% CI 1.2-4.5), and also among women with earlier age at natural menopause (P for trend<0.05). Menstrual irregularity was associated with an increased risk of SLE among women in the younger (NHSII) cohort. Age at first birth, parity, and total duration of breastfeeding were not associated with SLE. CONCLUSION: Early age at menarche, oral contraceptive use, early age at menopause, surgical menopause, and postmenopausal use of hormones were each associated with an increased risk of SLE. These associations may point to the mechanisms underlying the pathogenesis of SLE.

Journal: Arthritis Rheum. 2007 Apr;56(4):1251-62
Adapted from PubMed; click here to access full journal article.

Concurrence of Systemic Lupus Erythematosus and Pemphigus: Coincidence or Correlation?

Authors: Malik M, Ahmed AR.

Department of Medicine, New England Baptist Hospital, Boston, MA 02120, USA

BACKGROUND: Pemphigus and systemic lupus erythematosus (SLE) have previously been reported to coexist in the same patient. However, the relationship between the 2 diseases has not been elucidated. OBJECTIVE: This review was conducted to examine the relationship between pemphigus and SLE when they occur together in the same patient. METHODS: We conducted a retrospective review of the literature to identify previously reported cases of pemphigus and SLE coexisting in the same patient. The temporal relationship, clinical course, response to therapy and effects of 1 disease on the other were examined. RESULTS: Eight patients with a dual diagnosis of pemphigus and SLE have been previously reported. Most were female and non-Caucasian, with a mean age of 41 years. In the 8 patients reviewed here clinical outcomes, organ system involvement and demographic profiles are more typical of SLE. Seven of these 8 patients had pemphigus vulgaris, and 1 had pemphigus erythematosus. The limited follow-up did not permit studying issues of disease interaction. An additional 17 patients with pemphigus have been reported who have features suggestive of SLE. Organ system involvement in these patients was less typical of SLE. CONCLUSION: It appears that a true dual diagnosis of pemphigus and SLE is less common than suggested by the literature. Comparing patients with only pemphigus or only SLE to those with both may provide insights into genetic predisposition and pathogenesis, and provide an opportunity to study the effects of drugs that influence their course. Copyright (c) 2007 S. Karger AG, Basel.

Journal: Dermatology. 2007;214(3):231-9
Adapted from PubMed; click here to access full journal article.

Diffusion Changes in Patients with Systemic Lupus Erythematosus

Authors: Zhang L, Harrison M, Heier LA, Zimmerman RD, Ravdin L, Lockshin M, Uluğ AM

Department of Radiology, Weill Medical College, Cornell University, New York, NY 10021, USA

BACKGROUND AND PURPOSE: Systemic lupus erythematosus (SLE) is an autoimmune disease in which almost all the organs are involved. Neuropsychiatric SLE is of one of the major concerns in the clinical evaluation of this disease. Routine magnetic resonance imaging (MRI) findings are often nonspecific or negative. In this study, we explored the use of diffusion tensor imaging in assisting with the diagnosis of SLE. METHODS: Data from 34 SLE patients (age range, 18-73 years) and 29 age-matched volunteers (age range, 29-64 years) were analyzed. MRI was performed on a 1.5-T clinical MR scanner with a quadrature head coil. The average diffusion constant (D(av)) and diffusion anisotropy maps [fractional anisotropy (FA)] were determined on a pixel-by-pixel basis. Regional diffusion measurements were made by region of interest in the genu and splenium of the corpus callosum (CC), anterior and posterior limb of the internal capsule (IC) and frontal lobe and thalamus. The diffusion distribution was fitted to a triple-Gaussian model. The mean of the brain tissue distribution was determined as a mean diffusion constant for the whole brain (BD(av)). Student's t test was used to determine the diffusion difference between SLE patients and control subjects. The SLE patients were separated into two groups according to their MRI results. A P value lower than .05 was considered to be statistically significant. RESULTS: Twenty of the 34 SLE patients with abnormal MRI results showed findings dominated by nonspecific white matter disease. The BD(av) and D(av) values of the frontal lobe, splenium CC and anterior IC were significantly higher in all SLE patients as compared with the control subjects. The SLE patients with normal MRI results also showed higher BD(av) and D(av) values in the frontal lobe, splenium and anterior and posterior limbs of the IC as compared with the control subjects. There was no significant difference in the D(av) values of the thalamus between the SLE patients and the control subjects. The BD(av) value in the SLE patient group was robustly correlated with the D(av) values of the frontal lobe, splenium and thalamus. These correlations were found to be similarly significant for the SLE patients with normal MRI findings. The diffusion anisotropy measurements showed that splenium CC had the highest FA value in both the control subjects and SLE patients. Overall, SLE patients had lower FA values in the genu and splenium CC as compared with the control subjects. In the group of patients with normal MRI findings, the FA values of the genu and splenium CC as well as the anterior IC were also lower than those in the control subjects. Pearson's correlation statistics revealed robust correlations between the measurements of D(av) and FA values in the SLE patient group. CONCLUSION: Quantitative diffusion imaging and diffusion anisotropy showed early changes in the brains of the SLE patients. Increased BD(av) and D(av) values of the frontal lobe as well as decreased anisotropy in the genu CC and anterior IC may represent preclinical signs of central nervous system involvement of SLE even when the routine MRI findings are negative or nonspecific. Quantitative diffusion analysis may prove to be useful in detecting the initial brain involvement of SLE and may enable monitoring of early disease progression and treatment efficacy.

Journal: Magn Reson Imaging. 2007 Apr;25(3):399-405. Epub 2006 Nov 29
Adapted from PubMed; click here to access full journal article.

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