Natural Lupus Cure and Treatment

Natural Lupus Treatment System

Dr. Gary Levin is helping lupus patients with a step-by-step system that rehabilitates your immune system and boosts the bodys natural supporting systems to begin eliminating all lupus symptoms. With these materials, users will learn why alternative treatment methods work better than conventional ones, how to treat all types of lupus, a simple vitamin regimen and nutrition method that will heal their body, and much more. Actually there is no cure yet discovered for lupus, however, you will find methods to control and manage its signs and symptoms. The aim of the treatments of lupus generally would be to let the patient experience more comfort and lesser pain. Read more here...

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Discoid lupus erythematosus

Disease may be limited to the skin and assume the chronic discoid form, with scaling red plaques and follicular plugging. Healing of these lesions is associated with central scarring and atrophy. Although chronic discoid lupus erythematosus remains primarily cutaneous in the majority of patients, SLE will develop in a small percentage (about 5 ). Conversely, patients with SLE may have discoid lesions among the cutaneous manifestations of their disease. Certain types of skin lesions, such as those of subacute cutaneous lupus erythematosus, may reflect a specific immunogenetic predisposition. 2. Therapy follows the same principles as those outlined for skin disease in SLE avoidance of sun and ultraviolet exposure and use of topical steroids and hydroxychloroquine (see Chapter.11 for more information regarding discoid lupus erythematosus).

Systemic lupus erythematosus and scleroderma

There are no well-documented cases of occult malignancy presenting as SLE. Although antinuclear antibodies can be present in patients with solid neoplasms or leukemias who lack other evidence of a rheumatic syndrome, the significance of this is not understood. LE cells or antinuclear antibodies can be seen in patients with lymphoma or angioimmunoblastic lymphadenopathy with dysproteinemia (AILD). Diagnostic confusion may arise, as lymphadenopathy and splenomegaly are features also common in SLE. A lupuslike antibody syndrome, manifested by typical SLE serologic and laboratory abnormalities but lacking clinical criteria for SLE, has been associated with certain tumors and myelodysplastic disorders. For example, hypernephroma has been found in a peripartum woman, but this may have been an incidental finding because a similar lupuslike antibody syndrome can occur during pregnancy. Other tumors include gastric, cervical, and breast carcinomas,...

New Peptide Analogue for Treating Lupus Patients The Potential of Peptide P140

By testing a series of overlapping peptides, we identified an epitope present in residues 131-151 of the spliceosomal U1-70K small nuclear ribonucleoprotein (snRNP), recognized very early by IgG antibodies and CD4+ LN T cells from both H-2k MRL lpr and H-2d z BW lupus-prone mice (Monneaux et al. 2000, 2001). Fibroblasts transfected with MHC class II molecules were used to demonstrate that peptides 131-151 readily binds I-Ak, I-Ek, I-Ad and I-Ed murine MHC molecules (Monneaux et al. 2000, 2001). We further showed that an analogue of this sequence phosphory-lated on Ser140 (named peptide P140) was strongly recognized by LN and peripheral CD4+ T cells and by IgG antibodies from MRL lpr mice (Monneaux, 2003, 2004). This analogue and the cognate peptides 131-151 were used in therapeutic trials in lupus-prone mice to investigate their ability to restore tolerance. Young MRL lpr mice were given the peptides i.v. in saline (4 X 100 xg), and we found that P140 peptide, but not the...

Reduced Number and Function of CD4CD25highFoxP3 Regulatory T Cells in Patients with Systemic Lupus Erythematosus

CD4+CD25+ regulatory T cells (Tregs) play an important role in maintaining tolerance to self-antigens controlling occurrence of autoimmune diseases. Recently, it has been shown that the transcription factor forkhead box P3 (FoxP3) is specifically expressed on CD4+CD25+ T cells. FoxP3 has been described as the master control gene for the development and function of Tregs. We characterized CD4+CD25+CTLA-4+FoxP3+ T cells in 43 patients with systemic lupus erythematosus (SLE). Twenty of them comprised a group of newly admitted patients with the first manifestations of the disease, and the second group included patients that were treated with cytostatics and steroids. The results revealed a significant decrease in CD4+CD25+ and CD4+CD25high T cells numbers in patients from group I compared with control and group II patients. Coexpression of FoxP3 on CD4+CD25+ T cells was significantly reduced in both groups regardless the therapy. The ability of Tregs to suppress proliferation of...

Human endogenous retroviruses and systemic lupus erythematosus

A role of retroviruses in SLE pathogenesis is supported by an increasing body of evidence. A possible retroviral link with SLE was suspected initially because of the similarity of autoimmune manifestations and immune dysregulation between patients who have SLE and those infected with known human retroviruses, such as HIV-1. It has been shown that one third of patients who have SLE produce high-titer antibodies to various retroviral proteins, including Gag, Env, and Nef, and the p24 capsid antigen of HIV-1 and HTLV, in the absence of overt retroviral infection 16-18 . This phenomenon was attributed to molecular mimicry between retroviral antigens and host proteins. Actually, patients who have SLE also produce antibodies to HERV proteins and the striking amino acid similarities between certain Gag proteins and human autoantigens, such as a component of U1 sn-ribonucleoprotein (70K protein), topoisomerase I, and SS-B La, have suggested that the natural targets of some antibodies in SLE...

Aberrant Adaptive Immunity in Lupus

Vertebrates acquire adaptive immunity after birth, which is a response to specific antigens that involves B and T cells of the immune system and frequently leads to a state of immune memory (Iwasaki and Medzhitov 2004). The adaptive immune system produces antibodies and T cells that are highly specific for a particular pathogen (or antigen). The relative specificity of SLE sera to a selected subset of nuclear antigens (as opposed to reacting to the whole universe of antigens) suggests that lupus genes must be impacting adaptive immunity at some level. Our recent genetic dissection studies have indicated that Sle1z may be one such locus gene (Figure. 1). The Sle1z interval, located on distal chromosome 1, is perhaps one of the most extensively studied chromosomal intervals in murine lupus, since it confers disease susceptibility in multiple spontaneous lupus models including the BWF1, SNF1, BXSB, and NZM2410 mice (Morel and Wakeland 2000). The Sle1z interval is home to three Genetic...

Genetic Dissection of Murine Lupus

The NZM2410 mouse strain is a New Zealand Black(NZB) White(NZW)-derived inbred strain that spontaneously develops highly penetrant lupus with nephritis that is very similar to human SLE (Rudofsky et al. 1993). By performing a genetic analysis (i.e., linkage study) of SLE susceptibility, several different chromosomal intervals, in particular Sle1z on chromosome 1, Sle2z on chromosome 4, and Sle3z on chromosome 7, have been found to confer lupus susceptibility in this mouse model (Morel et al. 1994). By introgressing these different chromosomal intervals individually onto the relatively healthy C57BL 6 (B6) background, congenic strains bearing Slez, Sle2z, and Sle3z have been generated for further functional analysis (Morel et al. 1997). Hence, for the first time, researchers are able to study monogenic models of lupus as opposed to studying polygenic strains or patients. Thus, genetic simplification by congenic dissection has transformed the study of a polygenic disease into a series...

SLE 1 2 3Genetic Dissection of Lupus

Systemic lupus erythematosus (SLE) is a chronic and complex autoimmune disease of unknown etiology, characterized by the presence of widespread immunological abnormalities and multiorgan injury. An important advance over the past decade has been our understanding of how different genetic loci (or genes) may dictate specific immune abnormalities in lupus. Genetic dissection has unveiled some of the mystery enshrouding lupus pathogenesis. It appears that there are at least two distinct events leading to disease. The first involves a breach in the adaptive immune system and the second involves a dysregulation of innate immunity. Co-ordinate dysregulation of both checkpoints is necessary for full-blown lupus to ensue. The challenge ahead is to understand how these two checkpoints are regulated in human SLE, and to devise therapeutic strategies that target both checkpoints.

Potential of Peptide Therapeutics for Treating Lupus Patients

Relatively recently has emerged the idea of using peptides described as sequences able to modulate the autoimmune response, as these peptides will only target specific autoreactive B and T cells (Singh 2000). Several successful attempts of peptide-based therapy have been described in murine model of lupus (Monneaux and Muller 2004). Some peptides corresponding to antibody idiotypes for example the pCONS peptide, a consensus peptide derived from the variable heavy chain (VH) region of NZBxNZW (BW) IgG antibodies to DNA and predicted to possess T cell stimulatory activity (Hahn et al. 2001 Hahn et al. 2005), or peptides derived from the sequence of the complementary-determining regions 1 and 3 (pCDR1 and pCDR3) of a human anti-DNA monoclonal antibody that bears the so-called 16 6 Id (Zinger et al. 2003) have been used with remarkable efficacy in BW lupus mice. An impressive protective effect was also observed in MRL lpr mice with a peptide identified using combinatorial chemistry...

Lupus Pregnancy

Early (uncontrolled) studies suggested an increased risk for disease flare during pregnancy and the immediate postpartum period. Recent case-control studies, however, support little or no increased risk for flare during these periods. The definition of lupus flare at any time is not uniform however, this issue is more complicated in pregnancy because physiologic changes in normal or complicated pregnancy can mimic symptoms of SLE flare. Some standard measures of lupus activity are invalid in the pregnant patient. Normal pregnancy may be associated with palmar and facial erythema, chloasma gravidarum, anemia, mild thrombocytopenia, edema, and an increased erythrocyte sedimentation rate. Pregnancy-induced toxemia may present with hypertension, renal insufficiency, proteinuria, generalized edema, marked thrombocytopenia, disseminated intravascular coagulation, and seizures. Eclampsia may also be associated with decreased complement levels. Changes felt to...

Lupus erythematosus

The lupus band test (LBT) demonstrates deposits of immunoglobulin and complement at the dermal-epidermal junction by direct immunofluorescent staining of the skin. Biopsy of cutaneous lesions in DLE or systemic lupus erythematosus (SLE) yields a positive LBT in about 90 of patients. B. Discoid lupus erythematosus. The characteristic lesion of DLE is a scaly plaque that ranges in color from red to violaceous, with sharply-defined borders, central atrophy, telangiectasia, and areas of hypopigmentation or hyperpigmentation. Keratinous plugging of the hair follicles can sometimes be detected as tiny rough projections across the lesion. Lesions may be multiple and asymmetric and are most commonly found on the head and neck, particularly in the malar areas, ears, and scalp. When the scalp is involved, hair loss with scarring at the site of the lesion results. Lesions on the oral and nasal mucosae may ulcerate. Lesions of DLE produce scarring those that result in severe scarring may,...

Effects on B Cells and Immunoglobulin Production

Studies involving administration of IL-10 protein, IL-10 gene delivery, IL-10 transgenic animals or inhibition of IL-10 activity by neutralizing mAb or gene knock-out animals suggest that the in vivo role of IL-10 in B cell function is limited.5-7 For instance, plasma immunoglobulin levels are normal in IL-10 - - mice.8 An important exception is represented by a model of antibody-dependent autoimmunity such as systemic lupus erythematosus (SLE), in which IL-10 neutralization does affect disease onset.9

IL10 and B Cell Activation in Humans

Spontaneously produce auto-antibodies to nuclear antigens, and 60 develop terminal immune complex-mediated glomerulonephritis between 3 and 12 months of age. However, efforts to demonstrate a role for BCL-2 in SLE have met with mixed results.38'46'47'49'59-63 In a recent study, Miret et al found that serum level of IL-10 and amount of BCL-2 protein in PBMC lysates did not correlate in SLE patients.38 However, increased BCL-2 and increased IL-10 did individually correlate with higher SLEDAI disease index. Further study is necessary to understand the importance of a role for IL-10 mediated prevention of spontaneous B cell apoptosis in SLE. In a small, open-label clinical trial, anti-IL-10 treatment of lupus patients with cutaneous and joint manifestations resulted in improvement to clinically inactive disease

Antiphospholipid syndrome

Antiphospholipid syndrome is an autoimmune disease characterized by arterial or venous thrombosis and often by multiple fetal losses and throm-bocytopenia, in association with the presence of antiphospholipid antibodies (mainly aCL and lupus anticoagulant) antiphospholipid antibodies have also been detected in patients with acute and chronic infections and malignant diseases 99 . Initially, a high prevalence of antiphospholipid antibodies with a low frequency of associated thrombosis has also been noted among patients with HIV infection, but with HAART, more secondary antiphos-pholipid syndrome cases have been reported 100 . Hepatitis C virus-HIV

IL10 Polymorphisms and SLE

Systemic lupus erythematosus (SLE) is characterized by inflammatory damage in different organ systems and by the excessive production of autoantibodies, especially to a spectrum of nuclear antigens such as DNA and to other intracellular antigens involved in transcription and translation. 3,64 Genetic factors seem to play a crucial role in disease susceptibility as shown by linkage analyses in human families with SLE.65 Genes also seem to contribute to the extreme heterogeneity in disease progression among individuals.66 Different data has emphasized the role of the 1q21-q44 region of human chromosome 1, which contains the IL-10 gene (i.e., 1q31-q32), and which is syntenic with a segment of the murine genome containing several different susceptibility loci for lupus-like diseases.67 IL-10, which is active in B cell lineages, can promote the production of antibodies, and might play a direct pathogenic role in SLE.68 Abnormalities in cytokine production, and increased sera levels of...

Simone Mocellin

Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease characterized by B cell hyperactivity leading to excessive auto-antibody production.1,2 SLE patients have high levels of circulating auto-antibodies against a number of nuclear antigens including double stranded DNA (dsDNA) and ribonucleoproteins. Tissue damage is triggered by an inflammatory response to immune complex deposition and is widespread (Fig. 1). The primary cause of morbidity and mortality is glomerulonephritis which develops in about 60 of patients. Upon discovery that IL-10 both inhibits Th1 responses and is a potent cofactor for B cell survival, proliferation, differentiation, and immunoglobulin secretion, a potential role in the pathogenesis of SLE has been hypothesized.3-5 Overal lines of evidence support this hypothesis and prompt for the clinical implementation of the anti-IL-10 therapeutic approach for the treatment of patients affected with this disease.4

IL10 and Murine SLE

Furthermore, continuous administration of IL-10 to NZB W F1 mice from 4 weeks of age accelerated development of autoimmunity. The protection mediated by anti-IL-10 treatment was shown to correlate with increased TNFa production and could be abrogated by treatment with anti-TNFa antibodies. Thus, the efficacy of anti-IL-10 in this mouse model of lupus nephritis is likely due to the blockage of the effects of IL-10 on TNFa-producing cells such as macrophages and T lymphocytes. The role of IL-10 in mouse models of SLE may not reflect the full extent of IL-10 involvement in the pathogenesis of SLE in humans because mouse B cells do not respond to IL-10 as human B cells do. While IL-10 dramatically increases proliferation, differentiation, and antibody production by anti-CD40 stimulated human B cells in culture, no such activity is seen on mouse splenic B cells.

Acutephase reactants

Normal Westergren ESR values are 0 to 15 mm h for male subjects and 0 to 20 mm h for female subjects. A normal ESR value tends to exclude active inflammatory disorders such as acute rheumatic fever, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and temporal arteritis-polymyalgia rheumatica (TA-PMR). The ESR is of some use in following the course (including therapeutic responses) of chronic inflammatory disorders. III. Antinuclear antibodies (ANAs) A wide array of antibodies to nuclear and cytoplasmic cellular antigens is found in lupus and other rheumatic diseases by immunofluorescence, immunoassay, and immunodiffusion. Different profiles of ANAs in rheumatic diseases have been described and have been correlated with clinical features. The LE cell test is obsolete as a result of its poor sensitivity compared with ANA assay. (Some aspects of the clinical application of ANA data are discussed in ChapterJO.)

Genomic and Proteomic Analysis of Immune Tolerance

Likewise, microarray analysis continues to evolve as a broadly applicable and powerful method to identify candidate genes, expression levels of which are altered during diverse biological processes. Recent studies have aimed, through array analysis, to dissect the processes underlying allograft changes during surgery and transplant rejection or acceptance (112-114), as well as in organ-specific autoimmune responses (115). Furthermore, the central importance of DCs to tolerance regulation has lead to focused examination of their gene regulation following exposure to tolerogenic (e.g., IL-10, vitamin D3) (116,117) or inflammatory stimuli (e.g., TLR ligands) (118). Similarly, peripheral blood mononuclear cells possess global patterns of gene expression dictated by their exposure to immunomodulatory cytokines and other factors, and as such, the resultant molecular signature of these cells may disclose the condition of the body. Bennett et al. (119) demonstrated the power of microarray...

Series Editors Introduction

The critical role of the inflammatory response in the pathophysiology of certain nervous system disorders has been appreciated for quite some time. Currently, rapidly accelerating knowledge of new molecular mechanisms known to be involved in systemic inflammatory disorders has extended to the investigation of a number of peripheral and central neurological disorders. Many of those discussed in this volume have been the usual suspects for immunemediated, inflammatory neurological disorders such as, for example, multiple sclerosis, acute disseminated encephalomyelitis, optic neuritis, transverse myelitis, central nervous system (CNS) vasculitis, and neuropsychiatry systemic lupus erythematosis. Importantly, possible inflammatory mechanisms are now also undergoing scrutiny in chronic neurological diseases traditionally classified as neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases.

Noninflammatory conditions

Avascular necrosis of bone (also called osteonecrosis) is associated with monarticular pain and decreased range of motion in hips, knees, or shoulders resulting from ischemic necrosis of bone and the underlying bone marrow. While half of patients have no obvious cause, this condition is associated with steroid use, systemic lupus erythematosus (with or without a history of corticosteroid therapy), alcoholism, hemoglobinopathies, and Gaucher's disease.

Deficiency of Plasmacytoid DCs in AD

Plasmacytoid DCs are CD1a negative as well as CD11c negative but positive for the a-chain of the IL-3 receptor (CD123) and the blood-dendritic cell antigen (BDCA)-2. They are equipped with specific pattern recognition receptors of the innate immune system which enable them to sense microbial pathogens and thereby defend our organism against bacterial and viral infections (Soumelis and Liu 2006). Plasmacytoid DCs in the peripheral blood of AD patients have been shown to bear the FceRI receptor on their surface which is densely occupied with IgE molecules (Novak et al. 2004a). IgE receptor expression of pDC correlates with the IgE serum levels, indicating that IgE in the micromilieu might be necessary to stabilize this structure on the cell surface of pDC. Further on, activation of FceRI on pDC counter-regulates the toll-like receptor (TLR)-9 pathway involved in the regulation of the type I IFN production, which is required for the defence against virus infections (Schroeder et al....

Early Domesticates Dogs and Reindeer

Dogs (Canis familiaris) are generally recognized as the earliest known domesticated animals. They were widespread across the Northern Hemisphere before other animals were domesticated. They were derived from wolves (Canis lupus), with whom they are fully interfertile. The earliest known dog is in a burial site in Northern Iraq that dates from 12,000 to 10,000 b.c.e. Other sites, dating from 10,000 to 7000 b.c.e., have been documented in England, Palestine, Japan, and Idaho. While it may have first occurred in China (a Chinese wolf has some of the detailed physical features of dogs), domestication probably occurred at a number of separate sites. Dogs accompanied the American Indians when they occupied the Americas in several waves prior to the end of the last ice age. Dingoes were brought to Australia by

Selected sources of patient education materials and resources

Arthritis Foundation, Atlanta, GA (telephone 1-800-283-7800) and local chapters produce a range of printed information pamphlets and educational audiovisual programs for patients, publish a patient newsletter, and will provide information about mutual aid and self-help groups for people with arthritis. These include the SLESH (systemic lupus erythematosus self-help) course, PACE (people with arthritis can exercise) course, and ASH (arthritis self-help) course.


The gold compounds are contraindicated in patients with known hypersensitivity to any component of the drug. Parenteral administration is contraindicated in patients with uncontrolled diabetes, hepatic disease, uncontrolled hypertension, uncontrolled congestive heart failure, systemic lupus erythematosus, and blood dyscrasias and in those with recent radiotherapy. Oral administration is contraindicated in patients with necrotizing enterocolitis, pulmonary fibrosis, and hema-tologic disorders and during pregnancy (Category C) and lactation.

Death Receptors and the

FasL is a type II membrane protein belonging to the TNF family. FasL is expressed primarily on activated T cells, some tumor cells, and immune-privileged sites such as the eye and the testis 9 . FasL induces apoptosis in cells expressing the Fas receptor. Fas is a type I membrane protein of the TNF receptor family that was discovered due to the ability of specific antibodies to induce apoptosis in lymphoid tumor lines expressing the molecule. Two naturally occurring mutations in mice have emphasized the importance of Fas and FasL in the control of autoimmunity, the Ipr and gld mutations, respectively. These mice display increased autoimmunity, which is characterized by a generalized and progressive lymphoproliferation resembling systemic lupus erythematosus. They suffer from a large accumulation of CD4- CD8- T cells in the spleen and lymph nodes. Genetic analysis has determined that a retroviral insertion into the Fas gene causes premature interruption of transcription in Ipr mice. A...

Differential diagnosis

Systemic lupus erythematosus and other connective tissue disorders. The symmetric joint inflammation of RA and SLE may be indistinguishable. However, in SLE, erosions do not develop, and the joint disease is commonly accompanied by such manifestations of SLE as fever, serositis, nephritis, dermatitis, cytopenias, and antinuclear antibody (ANA) and anti-DNA seropositivity. Other connective tissue disorders, such as scleroderma and the vasculitides, may present with an RA-like polyarthritis, or this may develop later.

Diffeentiall diagnosis Treatment

Sjogren's syndrome (SS) is a chronic inflammatory disease associated with lymphocytic infiltration of exocrine glands. Certain clinical, serologic, and genetic differences are found among patients with SS alone, also called primary SS (patients with keratoconjunctivitis and xerostomia in the absence of any other definable connective tissue disease). These differences suggest varying etiologies for similar clinical manifestations of disease. The most commonly accepted definition of SS has been the presence of two of the following findings (a) keratoconjunctivitis sicca (dry eyes), (b) xerostomia (dry mouth), and (c) one of the connective tissue disease syndromes. Secondary SS is defined as keratoconjunctivitis and xerostomia as features of a connective tissue disease. Rheumatoid arthritis (RA) is the most common connective tissue disease seen in association with secondary SS, but others have been well-documented and include systemic lupus erythematosus (SLE), scleroderma, polymyositis,...

Immunopathology of autoimmune diseases

Type III hypersensitivity reactions are seen in autoimmune diseases where the autoantibody binds to self-antigens free in tissue fluids or in the general circulation. The resulting complexes are free to circulate throughout the body. However, they may become quite large (depending on the relative concentrations of antibody and antigen) and therefore, insoluble. This results in their precipitation in the tissues and blood vessels. Particularly vulnerable are tissues with large filtering membranes such as the kidneys, joints and choroid plexus, where the presence of immune complexes results in the activation of the complement cascade and inflammatory sequelae (Figure 5.4). As a direct consequence, localised cell death occurs and the function of the organ or tissues involved may be lost due to blockage of blood vessels by clot formation (e.g. vasculitis in systemic lupus erythematosus).

Musculoskeletal system

Myocardial disease, evidenced by signs ranging from persistent tachycardia to frank myocardial infarction, may also occur. The basis is often unknown but may include primary muscle involvement. Atherosclerosis is the most common cause of coronary artery disease in SLE, but coronary vasculitis may occur. Determination of anti-cardiolipin antibodies may be useful in lupus patients with myocardial infarction.

Routine laboratory examination may reveal abnormalities 1 Hematology

Prolongation of the partial thromboplastin time. Antibodies to both individual components of the clotting cascade (VIII, IX, XII) and to the prothrombin-converting complex have been described. The lupus anticoagulant is not corrected by addition of normal plasma to the patient's plasma. In the presence of normal platelets, the lupus anticoagulant does not appear to cause clinically significant bleeding, but it does lead to an increased propensity to venous and arterial thrombosis. e. False-positive reaction to serologic test for syphilis. A small percentage of biologic false-positive reactions show a positive fluorescent treponemal antibody, which can be distinguished from a true positive by its beaded appearance. Circulating lupus anticoagulants and anti-cardiolipin antibodies are associated with a false-positive reaction to the serologic test for syphilis. VI. Differential diagnosis. The diagnostic strategy for SLE involves recognition of a multisystem disease, the presence of...

Mononuclear Phagocytes In Specific Immunity

Changes in the cell surface expression of the MHC Class II gene product HLA-DR have been recorded in both non-organ and organ-specific autoimmune diseases. For example, epithelial cells in the thyroid of many patients with Graves' disease show high levels of HLA-DR an antigen not usually found on normal thyroid epithelium. In addition, abnormal presentation of foreign antigens (resulting from an unusual association between an antigen such as a drug or microorganism and HLA-DR) has been implicated as a cause of systemic lupus erythematosus. Such an association would appear as an altered self-antigen, thus providing a new epitope that may be recognised, and reacted to, by Th cells. As a consequence, the latter produce lymphokines that stimulate the differentiation and proliferation of activated, self-reactive, B cells.

Prosthetic joint infection

Because prosthetic joint infection is a catastrophic event for the patient, prevention is of considerable importance. The hematogenous route is responsible for 20 to 40 of these infections. The use of prophylactic antibiotics in patients with prosthetic joints for events or procedures associated with anticipated bacteremia is controversial at the present time, and the adequacy and cost effectiveness of such measures have not been determined. The American Dental Association and the American Academy of Orthopedic Surgeons have jointly advised that prophylactic antibiotics be given to selected patients undergoing dental procedures associated with significant bleeding (including periodontal scaling). The selected patient populations include persons with inflammatory arthropathies (including rheumatoid arthritis and systemic lupus erythematosis), immunosuppression, diabetes mellitus, malnutrition, hemophilia, previous prosthetic joint infection, and all those who have undergone...

Summario In Interlinoua

Un numero de si-appellate tests pathognomonic esseva etiam examinate con respecto a lor specificitate diagnostic. Istos include (1) tests biochimic pro cancere e pregnantia, (2) le test a acido p-tolueno-sulfonic pro lupus erythematose, (3) amino-peptidase de leucina pro carcinoma del pancreas, (4) amylase pro pancreatitis acute, (5) phosphatase acidic pro carcinoma del glandula prostatic, (6) porphobilinogeno pro porphyria acute, (7) absorption de rubee Congo pro amyloidosis, e (8) proteina Bence Jones pro myeloma multiple,

Thiazides and Related Diuretics

The thiazide diuretics are used cautiously in patients with liver or kidney disease, lupus erythe-matosus (may exacerbate or activate the disease), or diabetes. Additive hypotensive effects occur when the thiazides are given with alcohol, other antihypertensive drugs, or nitrates.

Prevention of Venous Thromboembolism

Urologic patients are at increased risk for the development of postoperative deep vein thrombosis (DVT) and pulmonary emboli. Benizri et al. found that 10 of patients not given prophylactic medication had DVT after TURP (12). Generic risk factors for postoperative phleboth-rombosis and pulmonary embolism include hypercoagulability (anti-thrombin III deficiency, circulating lupus anticoagulant estrogen use, malignancy) stasis cause by obstructed venous outflow, congestive heart failure, or immobility and vascular endothelial injury as a result of previous surgery or trauma. A particularly high-risk group includes those patients with a history of previous thromboembolism resulting from atrial fibrillation. In those patients with standard risk factors, we prefer conservative measures such as the use of anti-embolic stockings, pneumatic sequential compression boots, adequate hydration, and early ambulation. Consultation should be obtained for patients perceived to be at intermediate or...

Arrival Of Pml Cases And An Electron Microscope

Multifocal Microscopy

In the fall of 1962, a particularly stimulating consultation case was presented to me by the pathologist of a downtown Madison hospital. The patient, a 33-year-old woman with lupus erythematosus, had died after several weeks of progressive cerebellar disease. The slides showed a multifocal demyelinating disease with a most striking combination of giant tumor-like astrocytes and large numbers of oligodendrocytes with greatly enlarged nuclei deeply stained with hematoxylin. There were no distinct inclusion bodies as one sees with herpes viruses. I was fascinated and knew I had never seen this disease before. I showed the slides to a visiting neuropathologist and he, too, was at a loss. At that time I was in the midst of a very time-consuming experiment with a group of sophomore students. It involved the induction of brain tumors in chicken with Rous sarcoma virus. There was no time for a library search. However, I did show the slides to Dr. Chou, and to my utter surprise, and delight,...

Neutropenia Associated with Common Variable Immunodeficiency

CVID usually becomes manifest in patients between 20 and 30 years of age and only occasionally in childhood. Most patients manifest recurrent infections of the sinopul-monary tract. They are also prone to develop noncaseating granulomas of the skin, gut, and other organs. These patients are predisposed to develop autoimmune disorders such as immune thrombocytopenic purpura (ITP), systemic lupus erythe-matosus (SLE), and thyroiditis.

Carnivore Social Organization

Most carnivores are not particularly social, but some do have elaborate social organizations. Many of these are based on the efficiency of group hunting in the pursuit of large prey or on the ability of a group to defend a large food supply from scavengers. The gray wolf (Canis lupus) and African hunting dog (Lycaon pictus) are examples. In both cases, the social group, or pack, consists of a male and female pair and their offspring of several years. There are exceptions, solitary carnivores and carnivores that form temporary family units during the breeding season, such as the red fox (Vulpes vulpes), which hunt prey smaller than themselves. The coyote (Canis latrans) can switch social systems to use the food available most efficiently. It forms packs similar to those of the gray wolf when its main prey is large or when it can

Complement Deficiencies

Genetic deficiencies have been described for each of the complement components. Homozygous deficiencies in any of the early components of the classical pathway (C1q, C1r, C1s, C4, and C2) exhibit similar symptoms, notably a marked increase in immune-complex diseases such as systemic lupus erythematosus, glomerulonephritis, and vasculitis. These deficiencies highlight the importance of the early complement reactions in generating C3b, and the critical role of C3b in solubilization and clearance of immune complexes. In addition to immune-

Clinical Aspects Immunity

A disease that results from an immune response to one's own tissues is classified as an autoimmune disorder. The cause may be a failure in the immune system or a reaction to body cells that have been slightly altered by mutation or disease. The list of diseases that are believed to be caused, at least in part, by autoim-munity is long. Some, such as systemic lupus erythematosus (SLE), systemic sclerosis (scleroderma), and Sj gren syndrome, affect tissues in multiple systems. Others target more specific organs or systems. Examples are pernicious anemia, rheumatoid arthritis, Graves disease (of the thyroid), myasthenia gravis (a muscle disease), fibromyalgia syndrome (a musculoskeletal disorder), rheumatic heart disease, and glomerulonephritis (a kidney disease). These diseases are discussed in more detail in other chapters. systemic lupus er_ythematosu_s_ Systemic lupus erythematosus

Regulation of Type I Ifn Gene Expression

Type Ifn Dependent Genes

RIG-I pathway, this pathway does not seem to lead to the activation of IRF-5 (P.M. Pitha, unpublished results). Thus additional studies of differences in the MyD88-dependent and -independent signaling pathways leading to the activation of IRF-5 are clearly warranted. Lastly, a connection between IRF-5 and IFNa induction has been suggested by the observation that one of the genetic risk factors of systemic lupus erythematosus (SLE), which is associated with a constitutive IFNa production, was identified as a mutated IRF-5 haplotype, which drives an increased expression of IRF-5 (Graham et al. 2006) (see the chapter by Crow, this volume).

Dog Wolf and Coyote Facts

Wolves Natural Habitat

Genus and species Ten genera and thirty-five species, including Canis familiaris (domestic dog), C. lupus (gray wolf), C. rufus (red wolf), C. latrans (coyote) Geographical location Dogs live on every continent except Antarctica wolves are not found in Africa, South America, and Australia coyotes live only in North and Central America Habitat Mostly prairies, forests, and mountains Gestational period Approximately two months Life span Ranges from an average of eight to twelve years, longer in captivity or domestication

Popliteal Lymph Node Assay

Studies in mice showed that an enlarged popliteal lymph node (PLN), characteristic of a GVH reaction, can be induced in Fi hybrids by injecting parental cells into the footpad. The lymph node weights and cellularity index in the treated footpad differ from those of control footpads in the same animal (Gleichmann et al., 1984). In addition, there marked similarities between the immunological and histological features of the PLN response and GVH (Krystyniak etal., 1992). Recent studies have demonstrated that footpad inoculation of drugs known to cause autoimmune or GVH reactions in humans gave positive reactions in the PLN assay (PLNA). Generally, positive PLNA responses were associated with drugs causing generalized lymphadenopathy, serum sickness, lupus, or scleroderma-like responses (Descotes and Verdier, 1995).

Other serologic tests

Lupus antibodies that inhibit the activation of thrombin can be identified by a prolonged partial thromboplastin time and a normal or slightly prolonged thromboplastin time in the absence of anticoagulant therapy. Antibodies in SLE sera that inactivate factors VII, XI, and XII have also been identified. Clinically significant bleeding is rare, whereas an association with vascular thrombosis is well documented. False-positive serologic tests for syphilis and cardiolipin antibodies. False-positive serologic tests for syphilis are present in as many as 25 of SLE patients. The test is frequently positive in patients with the lupus anticoagulant antibodies against phospholipid antigens are most likely responsible for both phenomena. Antibodies against cardiolipin are determined by immunoassays. High titers of IgG anticardiolipin antibodies in SLE are associated with thrombosis. Hepatitis B (HB) and hepatitis C serologic tests (see Chapter.3.2.). Syndromes associated...

The dosage is 100 mg twice daily Mycophenolate Mofetil Cell Cept

Pruritus and skin rash represent the most common side effects and can occur at any time. They can be treated by either lowering the dosage or administering antihistamines. If necessary, the therapy may be interrupted until the rash resolves. Stomatitis also occurs. Alteration of taste is frequent, independent of dosage, and self-limited, with resolution in 2 to 3 months despite continued drug administration. Bone marrow depression may occur precipitously at any time. If the platelet count falls below 80,000 to 100,000, therapy must be discontinued. The most common late toxic effect is immune complex nephropathy. Proteinuria may be seen in 20 of patients. If proteinuria exceeds 1 g d, the dosage should be reduced. Nephrotic syndrome, hypoalbuminemia, or hematuria requires discontinuation of the drug. Less common side effects include autoimmune syndromes (lupus syndromes, Goodpasture's syndrome, myasthenia gravis, pemphigus, stenosing alveolitis, polymyositis), which necessitate prompt...

Vasospastic claudication

As with claudication caused by atherosclerosis, Raynaud's phenomenon is a clinical diagnosis. No practical laboratory test exists to diagnose peripheral vasospasm. The physician should elicit the symptoms by taking a detailed history. Color charts can also be used. The patient is asked to identify the color of the skin during a typical episode by choosing colors from actual photographs of Raynaud's attacks. Patients with peripheral vasospasm are classified as having primary or secondary Raynaud's phenomenon. In primary Raynaud's phenomenon, the patient has symmetrical attacks in the absence of digital pitting, ulceration, or gangrene. The nailfold capillaries are normal and screening tests for connective tissue disease, like erythrocyte sedimentation rate, antinuclear antibodies, immunoglobulin electrophoresis, etc. are normal. The prognosis of primary vasospasm is usually benign, provided the appropriate protective measures from direct exposure to cold are taken. The situation is...

Autoimmunity Can Develop Spontaneously in Animals

Hashimotos Lymph Nodes

New Zealand Black (NZB) mice and F1 hybrids of NZB and New Zealand White (NZW) mice spontaneously develop autoimmune diseases that closely resemble systemic lupus ery-thematosus. NZB mice spontaneously develop autoimmune hemolytic anemia between 2 and 4 months of age, at which time various auto-antibodies can be detected, including antibodies to erythrocytes, nuclear proteins, DNA, and T lymphocytes. F1 hybrid animals develop glomerulonephritis from immune-complex deposits in the kidney and die prematurely by 18 months. As in human SLE, the incidence of autoimmunity in the (NZB X NZW)F1 hybrids is greater in females. An accelerated and severe form of systemic autoimmune disease resembling systemic lupus erythematosus develops in

Animal Models of Autoimmunity

Three different models of spontaneous and two experimental SLE models have been described. The cross between New Zealand Black (NZB) and New Zealand White (NZW) yields hybrids that spontaneously develop a disease similar to human SLE. Hybrid BxSB mice also develop a lupuslike disease that occurs primarily in males. Mice carrying the Ipr gene on an MRL strain background also spontaneously develop SLE (Dixon, 1982).

Clinical Aspects of the Urinary System Infections

Foley Cath Removal Female

Although the name simply means inflammation of the kidney and glomeruli, glomerulonephritis is a specific disorder that occurs after an immunologic reaction. It is usually a response to infection in another system, commonly a streptococcal infection of the respiratory tract or a skin infection. It may also accompany autoimmune diseases such as lupus erythematosus. The symptoms are hypertension, edema, and oliguria, the passage of small amounts of urine. This urine is highly concentrated. Because of damage to kidney tissue, blood and proteins escape into the nephrons, causing hematuria, blood in the urine, and proteinuria, protein in the urine. Blood cells may also form into small molds of the kidney tubule, called casts, which can be found in the urine.

Mitral Valve Endocarditis

Marantic Endocarditis Tee

Infective endocarditis remains an all too common illness, with a significant risk of morbidity and mortality (see also Chap. 78). Traditionally, the diagnosis has been based on either the cumulative results of blood cultures, physical examination, and laboratory findings or on pathologic proof of infected valvular vegetations at surgery or autopsy. Echocardiography may play an important role in infective endocarditis in regard to diagnosis, detection of associated cardiac abnormalities and hemodynamic dysfunction, prognosis, and the need for surgery. Vegetations can now be visualized noninvasively in many (but not all) cases of endocarditis and have become the echocardiographic hallmark of this disorder.396-398 Thus, even though TTE cannot exclude endocarditis, abnormal findings may strongly suggest the disorder, even in the presence of negative blood cultures. Since no single abnormality has 100 percent diagnostic accuracy for infective endocarditis, strategies for diagnosis have...

The Complement System Clears Immune Complexes from Circulation

The importance of the complement system in clearing immune complexes is seen in patients with the autoimmune disease systemic lupus erythematosus (SLE). These individuals produce large quantities of immune complexes and suffer tissue damage as a result of complement-mediated lysis and the induction of type II or type III hypersensitivity (see Chapter 16). Although complement plays a significant role in the development of tissue damage in SLE, the paradoxical finding is that deficiencies in C1, C2, C4, and CR1 predispose an individual to SLE indeed, 90 of individuals who completely lack C4 develop SLE. The complement deficiencies are thought to interfere with effective solubilization and clearance of immune complexes as a result, these complexes persist, leading to tissue damage by the very system whose deficiency was to blame.

N Miscellaneous musculoskeletal problems in patients with neoplasia

Discoid lupus erythematosus lesions may develop into epidermoid carcinoma. Patients with eosinophilic fasciitis are at increased risk for associated aplastic anemia and lymphoproliferative disease. Patients with systemic lupus erythematosus do not appear to be at increased risk for malignancy, except for neoplasia complicating cytotoxic therapy ( Table

Case 20 Cardiac Tamponade From Massive Pericardial Effusion

Cardiac Tamponade

Beck described a triad of hypotension, muffled heart sounds, and elevated jugular venous pressure due to cardiac tamponade from pericardial effusion. Immediate pericardiocentesis is life-saving. The common causes of pericardial effusion include malignancy, congestive heart failure, tuberculosis, systemic lupus erythe-matosus, Dressler's syndrome, and uremia. This CXR shows a globular enlargement of the heart, typical of a large pericardial effusion. In addition, there is a mass in the right lung in keeping with the primary lung cancer.

Type III hypersensitivity

Glomeruli Filtering Membrane

Type III hypersensitivity reactions are also the result of immune complex formation. Soluble antigen binds to specific antibody and may form large antigen antibody lattices, which can activate complement (Figure 5.4). These complexes can also be deposited in organs, particularly those with filtering membranes such as the kidneys and the joints. This type of hypersensitivity is responsible for the damage caused by inflammation in the glomeruli of the kidneys (glomerulonephritis) in a disease called systemic lupus erythematosus caused by DNA anti-DNA immune complexes. The distinction between Type II and Type III hypersensitivity is that the immune complexes that initiate the inflammation in the former contain cell-associated antigens.

Multiple System Disorders Involving Muscles Polymyositis

Polymyositis is inflammation of skeletal muscle leading to weakness, frequently associated with dysphagia (difficulty in swallowing) or cardiac problems. The cause is unknown and may be related to viral infection or autoimmunity. Often the disorder is associated with some other systemic disease such as rheumatoid arthritis or lupus erythematosus.

Roles of Mast Cells in Autoimmune Inflammation

You Can Grow Your Intelligence

Observed in rheumatoid arthritis, MS, and systemic lupus erythematosus (SLE) or by complement or cytokines that are present locally. In MS, this can contribute to the activation of CNS antigen-presenting cells and direct destruction of the myelin sheath. Likewise, mast cell products may be directly involved in joint destruction in RA. Mast cell chemokines, particularly IL-8, that recruit neutrophils appear to be important in bullous pemphigus (84). As proposed for mast cells in allergic responses, these cells also may have influence during the inductive phase of disease. The influence of mast cells on dendritic cells at the site of antigen entry may regulate dendritic cell function or T-cell development directly (Fig. 2).

Monoclonal Antibodies May Be Used to Treat Autoimmunity

Monoclonal antibodies have been used successfully to treat autoimmune disease in several animal models. For example, a high percentage of (NZB X NZW) F1 mice given weekly injections of high doses of monoclonal antibody specific for the CD4 membrane molecule recovered from their autoimmune lupus-like symptoms (Figure 20-11). Similar positive results were observed in NOD mice, in which treatment with an anti-CD4 monoclonal antibody led to disappearance of the lymphocytic infiltration and diabetic symptoms. Weekly injections of anti-CD4 monoclonal antibody into (NZB X NZW) Ft mice exhibiting autoimmune lupus-like symptoms significantly increased their survival rate. Adapted from D. Wofsy, 1988, Prog. Allergy 45 106.

Evolution Animal Life

In a population owing to chance interbreeding the mating of closely related individuals, which tends to increase the appearance of recessive genes migration the movement of individuals, resulting in gene flow, changing the proportions of genotypes in a population mutation alteration in the physical structure of the DNA, resulting in a genetic change that can be inherited natural selection the process of differential reproduction in which some phe-notypes are better suited to life in the existing environment and thus are more likely to survive speciation the formation of new species as a result of geographic, physiological, anatomical, or behavioral factors species the basic category of biological classification representing a group of potentially or actually interbreeding natural populations which are reproduc-tively isolated from other such groups taxon (pl. taxa) group of related organisms at one of several levels such as the family Canidae, the genus Canis, or the species Canis...

Lymphoproliferative disorders

Angioimmunoblastic lymphadenopathy can be associated with rash, polyarthritis, polyclonal hypergammaglobulinemia, and Coombs'-positive hemolytic anemia. This condition may mimic systemic lupus erythematosus (SLE). 5. Myelodysplastic disorders have also been associated with a variety of musculoskeletal symptoms and signs, including polyarthritis, lupuslike conditions, polychondritis, vasculitis, and erythromelalgia.

What can the transcriptome tell us about the immunome

Alternative splicing, as seen in 42 of human transcripts of which 74 affect protein coding sequences (Modrek et al 2001), has relevance for non-Mendelian disease aetiology (Stamm 2002). Among immune-related transcripts, Tcr and Ig are prone to premature termination codons caused by frameshift and nonsense mutations due to rearrangement. Two groups have independently shown that aberrant Tcrfi transcripts with nonsense codons are down-regulated by nonsense-mediated decay factor UPF2 and internal ribosome entry sites (Wang et al 2002a, Mendell et al 2002). On the other hand, Tcrfi transcript mutations that generate premature termination or nonsense codons are compensated for by an increase in the number of alternatively spliced transcripts that skip the nonsense codon (Wang et al 2002b), thereby retaining some protein function. It will be interesting to see whether the interdependency of RNA scanning and alternative splicing affects TCR repertoire and is associated...

Classification of autoimmune disease

The classical example of a non-organ-specific autoimmune disease is systemic lupus erythematosus (SLE) in which the autoimmune response is directed to a number of different tissue antigens. Such non-organ-specific diseases may develop as a result of an abnormal immune response to a single antigen, which is expressed in many tissues.

Special management considerations

Medications associated with drug-induced lupus (see Ta.b e,.3.0.-2) have been used extensively and effectively in patients with idiopathic SLE. Although the risk for exacerbating the underlying disease is often discussed, such risk has not been established and does not contraindicate the use of an otherwise indicated medication. 7. Transplantation. SLE patients may undergo renal transplantation without any apparent increase in morbidity in comparison with other transplantation populations. Recurrences of lupus in transplanted allografts are rare. A. Drug-induced lupus. Many drugs (see Table.3.0,-2) have been implicated in the induction of a lupuslike syndrome, with manifestations ranging from an isolated positive ANA test result to a clinical lupus syndrome. Procainamide and hydralazine are the drugs most frequently reported to produce a lupuslike syndrome. 2. Laboratory studies. The laboratory profile of a patient with drug-induced lupus may help distinguish the...

Reduction In Neutrophil Count

Neutrophils have a short life span, and their precursors must divide rapidly in the bone marrow to maintain levels of these cells in the circulation. For this reason, agents such as radiation and certain drugs (e.g., chemotherapeutic drugs) that specifically damage rapidly dividing cells are likely to cause neutropenia. Occasionally, neutropenia develops in such autoimmune diseases as Sjogren's syndrome or systemic lupus erythematosus in these conditions, autoantibodies destroy the neutrophils. Transient neutropenia often develops after certain bacterial or viral infections, but neutrophil counts return to normal as the infection is cleared.

Affected Organs And Cell Types In Polyomavirusassociated Disease And Persistent Virus Infection

In patients with autoimmune diseases in Taiwan, about 40 were found by PCR to be excreters of polyomaviruses. Interestingly, in 15 , double infections were detected, but none was positive for BKV viruria alone (Chang et al., 1996a). Further extension of the study confirmed the lack of BKV viruria in Taiwan (Tsai et al., 1997). In contrast, patients from Scandinavia with systemic lupus erythematosus had higher levels of BK viruria than healthy control subjects, whereas JCV shedding was in the range of the normal sex-matched control group. In a follow-up study, the authors found a high prevalence of intermittent or even continuous shedding of BKV at 1 year. Immunosuppressive drugs such as corticosteroids, azathioprine, cyclophosphamide, and or metho- Pregnancy is the most common condition of altered immunocompetence that has been linked to polyomavirus activation (Coleman et al., 1980 Lecatsas et al., 1981). The onset of virus excretion is related to time of gestation, most often...


Diseases to be considered in the differential diagnosis of EN are erythema induratum, Weber-Christian disease, subcutaneous nodular fat necrosis in association with pancreatic disease, recurrent thrombophlebitis, cutaneous arteritis, and lupus profundus.

Final Remarks

Peptides encompassing T cell epitopes represent promising tools for manipulating immune regulation in autoimmune diseases, such as lupus. Examples in other experimental models of autoimmunity (e.g. in experimental autoimmune encephalomyelitis, experimental myasthenia gravis or diabetic NOD mice) also show spectacular protective effects. It is possible that for long-term therapeutic applications it will be necessary to combine several independent strategies, which can be introduced simultaneously or sequentially. These strategies could target T cells but also B cells, CD8+ suppressor cells and regulatory T and B cells. The results obtained in different laboratories are quite encouraging and a number of T cell-specific agents with clinical potential have recently emerged (Isenberg and Rahman 2006 Kaul et al. 2006 Liu et al. 2007). The P140 peptide which interferes with intra and intermolecular epitope spreading in MRL lpr mice and consequently interrupts, at least transiently, the...


Regulate antitumor and antiviral responses of NK cells. At least one human disease, XLP, is causally related to defective signaling via members of the CD2 family of molecules. In addition, polymorphisms in CD2 family members may also contribute to autoimmunity in lupus-prone mice. A feature that seems characteristic of this family of molecules is stimulatory homotypic interactions between NK cells 2B4, CD48, CS1, and NTB-A are all involved in such interactions. Furthermore, analysis of ITSM and SAP signaling has yielded the description of a novel signaling pathway that impacts not only NK cells but also numerous other cell types that express ITSM-bearing receptors. Gene-deficient mouse models have been particularly informative for the CD2 family and have sometimes given surprising results, possibly due to the complexity and multitude of functions these receptors have (Killeen et al. 1992 Gonzalez-Cabrero et al. 1999 Lee et al. 2004b Wang et al. 2004 Howie et al. 2005). Generation of...


Nearly 70 of patients will present with joint complaints. The arthropathy is usually an RA-like polyarthritis that is nonerosive. The diagnosis of SLE is based on the multisystem clinical presentation and is supported by the finding of serum antinuclear antibodies.

Childhood myositis

With Raynaud's phenomenon, sclerodactyly, arthralgia, and myalgia (about 50 ). Proximal muscle weakness is seen in 40 at presentation, and the characteristic rash of DM in 20 . The presenting features reflect the underlying connective tissue disease systemic sclerosis, systemic lupus erythematosus, and rheumatoid arthritis are the diseases most commonly associated with PM features. Sicca syndrome and necrotizing vasculitis are also associated with PM-DM.


RFs are anti-globulin antibodies that bind to the Fc portions of IgG. The mechanisms initiating RF secretion and its exact role in disease pathogenesis have not been established. RF is found in the serum of 75 to 80 of RA patients, is locally produced in rheumatoid synovial tissue, and may be present in the serum of patients with other disease characterized by B-cell or immune hyperreactivity, such as systemic lupus erythematosus (SLE) and bacterial endocarditis. The presence of high RF titers is associated with severe, erosive disease, a worse functional outcome, rheumatoid nodules, other extraarticular disease manifestations, and HLA-DR4 positivity.


First symptoms usually occur between the second and fourth decades of life but may be seen in any age group. The presentation of SLE in the elderly (as much as 10 of the total lupus population in some series) may differ from that in younger patients. C. Ethnic distribution. Although lupus occurs in all races, its prevalence is not equally distributed among all groups. SLE occurs more commonly in the United States than in England and more often in blacks than in whites. Hispanic and black patients have been noted to have more severe disease. The average annual incidence in the United States is approximately 27.5 per million population for female whites and 75.4 per million for female blacks. The reported prevalence figures for women vary widely from 1 in 1,000 to 1 in 10,000. A. Clinical disease. Family members of SLE patients are more likely to have lupus or another connective tissue disease. The risk for development of SLE in a sibling of persons affected by SLE is...


Various auto-antibodies may contribute to tissue injury. Attempts to correlate specific clinical patterns of disease with specific types of auto-antibodies have been partially successful. For example, anti-DNA antibodies have been found in renal glomerular lesions. Sicca syndrome with SLE has been associated with La (SS-B) antibodies. Ro (SS-A) antibodies have been associated with neonatal lupus, congenital complete heart block, and subacute cutaneous lupus. The lupus anticoagulant and anti-cardiolipin antibodies are associated with thrombosis, thrombocytopenia, and increased fetal wastage. Although the titer of ANAs does not necessarily correlate with disease activity, the levels of anti-DNA antibodies may vary with clinical disease. Because results vary, this test cannot be used as the sole guide to therapy. 4. Drugs. Many drugs have been associated with the development of ANAs and, in some cases, a clinical lupuslike syndrome ( T.ab e.30-2) procainamide and hydralazine are the...

Pulmonary system

Pneumonitis as evidenced by rales on physical examination and patchy infiltrates or platelike atelectasis on chest radiography is a diagnostic problem. Because SLE patients are often compromised hosts, infection by either common or uncommon agents must be considered. Lupus pneumonitis does occur, but this diagnosis requires exclusion of other processes. Progressive lupus pneumonitis ending in acute pulmonary insufficiency is uncommon. Lung biopsy may be required to establish a diagnosis, especially in the setting of persistent or progressive findings despite therapy. Abnormal findings on pulmonary function tests such as moderate restrictive and obstructive deficits are common, but patients usually have mild or no associated symptoms. F. Gastrointestinal systems. Abdominal pain is a common complaint and may reflect gastrointestinal disorders associated with medications or intrinsic SLE-related pathology. Sterile peritonitis (serositis) and mesenteric vasculitis may be difficult to...


Syndromes associated with vasculitis such as Henoch-Schonlein purpura and systemic lupus erythematosus, can give rise to both abdominal pain (caused by involvement of mesenteric arteries) and arthritis. Diagnostic and treatment efforts are directed at the primary disease.

TLR7 and TLR8

Because GU-rich sequences are found in viral as well as endogenous RNA, TLR7 and 8, as has been described for TLR3, may also detect self-RNA acting in this way as sensors of endogenous danger signals (Heil et al. 2004). Accordingly, small nuclear ribonucleoproteins (snRNPs), which are a major component of the immune complexes associated with the pathogenesis of the autoimmune disease systemic lupus erythematosus (SLE) activate human pDCs to produce IFN-a, proinflammatory cytokines and to upregulate co-stimulatory molecules when the UlsnRNA is intact (Savarese et al. 2006). The recognition of UlsnRNA is dependent on TLR7. Therefore in certain circumstances, detection of self-RNA by these TLRs can contribute to autoimmune disease.


This antimalarial drug initially was used by rheumatologists to treat lupus. Subsequent placebo-controlled trials showed it to be effective in RA, especially in patients with a short duration of disease. It is usually given at a dose of 400 mg per day. However, hydroxychloroquine is not as effective as other DMARDs such as methotrexate, sulphasalazine or injectable gold in improving clinical measures (eg, joint counts and ESR) and has little effect on disease progression measured on X-ray. Hydroxychloroquine is therefore used mainly in early or mild RA because of its favourable tolera-bility and toxicity profiles more recently it has become an important component of combination regimes.

Clinical Trials

Thalidomide has subsequently been studied in several diseases in which immuno-logically mediated mechanisms cause pathology. Thalidomide is effective for recurrent oral, esophageal, and rectal apthous ulcers in patients with AIDS (128). It is also beneficial in chronic graft-versus-host disease after bone marrow transplantation, discoid lupus erythematosus, Behcet's disease, and pyoderma gangrenosum and other inflammatory skin diseases. Thalidomide also has modest activity in HIV wasting syndrome, severe ulcerative colitis, microsporidial diarrhea, wasting in HIV-infected patients with TB, and refractory M. avium complex infection in HIV-noninfected persons. Adjunc-tive immunotherapy with thalidomide was studied in a double-blind placebo-controlled trial of 39 HIV-infected adults with and without active TB (129). Patients with active TB treated with thalidomide had decreased plasma TNF-a and HIV-1 viral levels and greater weight gain than patients in the placebo group.


Binomial nomenclature the two-word system used for naming every individual species the wolf, for example, is Canis lupus eukaryote an organism whose cells have internal structures, such as a nucleus and a mitochondrion, separated from one another and from the rest of the cytoplasm by membranes kingdom the broadest category of organisms the system currently used recognizes five kingdoms Monera, Protista, Fungi, Animalia, and Plantae nomenclature the part of systematics that deals with establishing a valid name for a species, according to specific guidelines


The glucocorticoids are used as replacement therapy for adrenocortical insufficiency, to treat allergic reactions, collagen diseases (eg, systemic lupus erythematosus), dermatologic conditions, rheumatic disorders, shock, and other conditions (see Display 50-1). The anti-inflammatory activity of these hormones make them valuable as anti-inflammatories and as immuno-suppressants to suppress inflammation and modify the immune response.

Scalp hair

Totalis Areata

Certain follicles of the scalp regress with age to produce tine vellus instead of coarse terminal hairs. This patterned baldness often starts as temporal recession, progressing to thinning of hair over the crown. It is common in males and is androgen dependent, prevented by prepubertal castration but not reversed by castration in maturity. Temporal recession is less common in women and may suggest virilisation. Loss or thinning of hair over the frontal region is an almost constant finding in the rare condition myotonic dystrophy, and is also seen in systemic lupus erythematosus.


Douglas Pouch

Because 50 of the implanting embryo's genome is derived from the father, it is a foreign body that potentially should be rejected by the maternal system. Recent evidence suggests that a combination of factors protects the conceptus, including production of immunosuppressive cytokines and proteins and the expression of an unusual major histocompatibility complex class IB molecule (HLA-G) that blocks recognition of the conceptus as foreign tissue. If the mother has autoimmune disease, for example systemic lupus erythe-matosus, antibodies generated by the disease may attack the conceptus and reject it.

Major signs

Sydenham's chorea is a late manifestation of ARF and may follow other manifestations of ARF or may appear alone. It is characterized by involuntary, purposeless, abrupt, and nonrepetitive movements, muscular weakness, and emotional lability. The abnormal movements subside during sleep. When subtle, chorea is demonstrated when (a) squeezing the examiner's hand reveals an erratic milkmaid's grip, (b) raising the hand straight ahead causes pronation of one or both arms, (c) extending the hands straight ahead causes spooning of the hand with wrist flexion and extension of fingers, and (d) protruding the tongue produces snakelike darting movements. Because the latent period from streptococcal infection to chorea is 1 to 6 months, anti-streptolysin O (ASO) titers and levels of acute-phase reactants may be normal. Investigation of other streptococcal antigens usually will reveal one or more with rising titers in all but those patients with isolated chorea. The duration of chorea ranges...


Revised (1982) criteria for the classification of systemic lupus erythematosus7 The proposed classification is based on 11 criteria. For the purpose of identifying patients in clinical studies, a person is said to have SLE if any four or more of the 11 criteria are present, serially or simultaneously, during any interval of observation.

Autoimmune Disorders

Dle Blisters

Lupus erythematosus (LE) is a chronic inflammatory autoimmune disease of connective tissue. The more widespread form of the disease, systemic lupus erythematosus (SLE), involves the skin and other organs. The discoid form (DLE) involves only the skin. It is seen as rough, raised, violet-tinted papules, usually limited to the face and scalp. There may also be a butterfly-shaped rash across the nose and cheeks that is typical of this disease. The skin lesions of lupus are worsened by exposure to the ultraviolet radiation in sunlight. SLE is more prevalent in women than in men and has a higher incidence among Asians and blacks than in other populations.

Neurologic disease

Systemic lupus erythematosus-related psychosis. The occurrence of SLE-related psychosis does not necessarily require an increase in steroid therapy. If adequate behavioral control is achieved with major tranquilizers and no organic signs are present on either physical examination or cerebrospinal fluid analysis, corticosteroids are not initiated or increased.

Blood vessels

Un the pulps, most commonly in systemic lupus erythematosus (Fig. 2.27B). Raynaud's phenomenon is described on page 110, Venous abnormalities are seldom seen, but the linear marks caused by the intravenous injection of drugs of addicts ('mainliners') arc characteristic (Fig. 2.30).


Until recently, death had not been a complication associated with PV. Now, however, in two multilevel procedures patients have died. Though the exact details are not known, there was pulmonary compromise, which is suspected to have been due to fat (from the vertebral marrow) or cement emboli. A safe number of vertebrae to treat at one time has yet to be definitely established. Mathis et al. reported treating seven vertebrae in a 35-year-old patient with multiple fractures associated with steroid use for lupus.46 This patient's therapy occurred in three treatment sessions. Because the introduction of cement is a hydraulic event with as much marrow pushed out of the intertra-becular space as cement injected, there is concern about fat emboli in large-volume cement injections. For reasons described earlier, I recommend treating no more than three vertebrae in any one session. Additionally, there are no data that support the prophylactic use of PV to treat vertebra that are believed to be...

Sicca syndrome

The plethora of autoimmune laboratory findings coupled with an array of cutaneous, articular, central nervous system, and visceral inflammatory disease has, at times, produced some diagnostic uncertainty. Often, particularly when HIV infects young women, the clinical and laboratory manifestations may be virtually indistinguishable from those of systemic lupus erythematosus. Fortunately, in the majority of HIV-infected persons who are positive for antinuclear antibodies, they are present in very low titers, and rarely, if ever, is anti-ds-DNA antibody demonstrated. Patients with collagen vascular disease often have cross-reacting antibodies against constituents of the HIV or cells infected with HIV, which leads to false-positive results of assays for HIV antibodies. Typically, however, they demonstrate antibodies to only one or two proteins of HIV on Western blot, not to products of all three major retroviral genes (gag, pol, and env) simultaneously. Therefore,...


Some studies conclude that male patients are more dissatisfied and experience greater sexual dysfunction than do female patients, but in others, women reported greater sexual dissatisfaction. In a study of female patients with systemic lupus erythematosus, poor sexual adjustment was best predicted by severe disease, older age, poor premorbid sexual relationships, and poor quality of the current relationship.


Monoclonal Antibodies And Immunogenicity

Adverse events observed in patients treated with infliximab include infusion reactions such as delayed hypersensitivity, formation of anti-chimeric antibodies and anti-dsDNA autoantibodies and, in rare cases, onset of drug-induced lupus. Approximately 3 of patients in the ACCENT I trial developed delayed hypersensitivity reactions manifested by serum-sickness-like symptoms. This may be due to the fact that a proportion of the molecule is still of murine origin and therefore potentially immuno-genic. Attempts are therefore being made to produce less immunogenic biologic agents, thereby increasing their human proportion (Fig. 4).

Related syndromes

Patients with rheumatic diseases can often demonstrate overlapping features. Mixed connective tissue disease is an antibody-defined overlap connective tissue disease demonstrating features of lupus, systemic sclerosis, and myositis. Patients often present with puffy hands and arthralgias, and joint symptoms can be a prominent part of the clinical course. Raynaud's phenomena, esophageal dysmotility, and interstitial lung disease in addition to inflammatory myopathy can be seen. These patients have antinuclear antibodies that stain in a speckled pattern of immunofluorescence and detectable and often high titers of antibodies to ribonucleoproteins (anti-RNP). Patients with various features of rheumatoid arthritis, systemic sclerosis, lupus, polymyositis, and other rheumatic signs and symptoms but with nonspecific serologies are classified as having undifferentiated connective tissue disease. With observation, a classic disease may emerge. Therapy tends...

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