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Dr. Gary's Natural Lupus Treatment ebook, will discuss lupus, its signs and symptoms, and remedies. The healing process of Natural Lupus Treatment is carried out through a simple step-by-step method that rehabilitates your immune system and boosts your supporting body systems to eliminate all lupus symptoms, the joint pains and swelling etc. 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. More here...

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Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE), also known simply as lupus, is a multisystem disease with protean clinical manifestations. When SLE affects the brain, causing what has been variously known as lupus cerebritis or neuropsychiatric lupus, a wide range of neurobehavioral features may follow. In many cases, multifocal white matter lesions are seen on brain MRI that likely represent ischemic lesions and infarcts related to the vasculopathy that is characteristic of SLE. Treatment often includes immunosuppressive

Lupus susceptibility loci

A new avenue of inquiry for broadly defining the genetic defects of lupus is that of genome-wide searches using dense chromosomal maps derived from polymorphic microsatellite markers. Micro-satellites or simple-sequence length polymorphisms (SSLP) are repeats of usually dinucleotides that exhibit a high degree of polymorphism in the number of repeats at a given chromosomal site. Lupus susceptibility genes and locia

Systemic Lupus Erythematosus Sle Human

It seems likely that the condition described by Hippocrates as herpes esthiomenos was a synonym for what is now known as systemic lupus erythematosus (SLE). In modern times this was first described by Cazenave and Clausit in 1852. In 1875 Hebra and Kaposi differentiated discoid lupus from the systemic form. By the beginning of the present century, Sir William Osier and others had comprehensively described many of the clinical features of the disease including involvement of the joints, kidney and central nervous system. The involvement of the heart in SLE was first recognized by Libman and Sachs in 1923 who described a classic form of endocarditis. In the mid-1930s Baehr, Klemperer and Schifrin stressed the structural changes in the glomeruli of lupus patients. In 1948 Hargreaves first identified the so-called LE cell but the modern era of antinuclear antibody detection was ushered in by Friou and colleagues when using immunofluorescence in 1957-1958. The first mouse model of human...

Chronic Cutaneous Lupus Erythematosus

Chronic cutaneous lupus erythematosus is referred to as discoid lupus erythematosus (DLE). It is an eruption that results in scarring and pigmentary changes in the skin. DLE is most commonly seen in African-Americans. Only 10 percent of patients with this type of lupus develop systemic disease. FIG. 238-3. Discoid lupus erythematosus. The external ear and preauricular cheek is a common site of involvement. Central depigmentation with surrounding erythema and hyperpigmentation is typical of discoid lupus erythematosus.

Discoid lupus erythematosus

Although discoid lupus erythematosus (DLE) is well recognised as a dermatological entity in dogs it is rarely reported in cats. There is no apparent age, sex or breed predisposition. Clinical signs consist of periocular crusts, erythema, vesicles and papules on the pinnae, and scaling and crusting of the footpads with focal depigmentation. There may be plaque-like erythematous excoriations involving the pinnae, neck, abdomen and groin, or generalised crusting and scaling. Skin biopsies have shown histological changes of

Acute Cutaneous Lupus Erythematosus

The classic eruption of acute cutaneous lupus is the malar or butterfly rash. In most cases, this eruption is associated with systemic disease. It usually occurs simultaneously with the onset or flare of SLE. This eruption is induced by ultraviolet radiation. The malar rash is more common in whites than in African-Americans. Diagnosis is based on clinical examination and the presence of other systemic symptoms suggestive of SLE. This eruption is by no means specific for lupus erythematosus. The differential diagnosis includes rosacea, erysipelas, dermatomyositis, seborrheic dermatitis, medication-induced photosensitivity, polymorphous light eruption, and allergic contact dermatitis. Skin biopsy may be helpful especially if the diagnosis is in question. Initial laboratory evaluation includes a complete blood count, chemistry profile to include BUN and creatinine, urinalysis with evaluation of urine sediment, antinuclear antibodies, double-stranded DNA, and complement.

Lupus Anticoagulant

The lupus anticoagulant is an antiphospholipid antibody that interferes in vitro with many of the coagulation reactions. Its name is a misnomer because the majority of affected patients do not have lupus and very few have a clinical bleeding disorder. The lupus anticoagulant is identified in 5 to 15 percent of patients with SLE. Associated conditions include other autoimmune disorders, drug reactions (procainamide and phenothiazines), malignancies, and patients with HIV-1 infection in the setting of acute opportunistic infections. Many affected patients have no underlying disease state. Clinically, many patients are asymptomatic, with the abnormality discovered on routine coagulation screening tests. Arterial or venous thromboses occur in 23 to 58 percent of patients. Recurrent fetal loss, thought to be due to thrombosis of placental vessels and placental infarction, is also common. Some patients have thrombocytopenia, but they also may have ITP. Bleeding abnormalities are uncommon in...

Introduction Clinical Setting

Immunoglobulin A (IgA) nephropathy was first described by the pathologist Jean Berger (1,2) and thus is sometimes called Berger's disease. Immunoglobulin A nephropathy is defined by the presence of IgA-dominant or co-dominant mesangial immunoglobulin deposits (Fig. 6.l) (3). Lupus glomerulonephritis, which may have IgA dominant or co-dominant deposits, is excluded from this diagnostic category. Immunoglobulin A nephropathy occurs as a primary (idiopathic) disease, as a component of Henoch-Sch nlein purpura small-vessel vasculitis, secondary to liver disease (especially alcoholic cirrhosis), and associated with a variety of inflammatory diseases including ankylosing spondylitis, psoriasis, Reiter's disease, uveitis, enteritis (e.g., Yersinia enterocolitica infection), inflammatory bowel disease, celiac disease, dermatitis herpetiformis, and HIV infection (4-6).

Understanding your immune systems role in endometriosis

The answer may lie in the immune system. The study of the immune system and its relation to endometriosis and other immune-related diseases (such as lupus, fibromyalgia, and chronic fatigue syndrome) has rapidly progressed in the last decade. The immune system does seem to play a role in endometriosis.

Apoptosis in immunity

The small minority of thymocytes that are positively selected exit the thymus and migrate to the peripheral lymphoid organs. Here they are faced with the possibility of reacting with previously unencountered self-antigens. Should this happen, the autoreactive mature T cell, all going to plan, should then undergo apoptosis, probably as a result of receiving an inappropriate activation signal (such as TCR engagement in the absence of CD28 costimulation). Should this peripheral deletion process fail for any reason, then autoimmunity can result. Unlike in the thymus, CD95-CD95L interactions do appear to be important for peripheral deletion, as both lpr and gld mice are impaired in peripheral deletion and develop a systemic lupus erythematosus (SLE)-like autoimmune disease as a result.

Considering environmental factors

Endometriosis is related to environmental contamination. Dioxin, one of the first pollutants scientists studied, is an example (see the sidebar Understanding dioxin exposure earlier in this chapter) of an environmental effect on endometriosis. Likewise, scientists can link pollutants to multiple sclerosis, lupus, thyroid disease, chronic fatigue syndrome, fibromyalgia, and even cancer.

Membranous Glomerulopathy

Membranous Glomerulopathy

Membranous glomerulopathy is a major cause of the nephrotic syndrome in adults (1,2). Only in the past decades has it been surpassed by focal and segmental glomerulosclerosis as the main cause of the nephrotic syndrome (3-5). Membranous glomerulopathy develops mostly idiopathically, but can also be seen in relation with and possibly secondary to, among others, hepatitis B, Sjogren's syndrome, transplantation, lupus erythematosus, diabetes mellitus, sarcoidosis, syphilis, exposure to certain drugs and heavy metals (penicillamine, bucillamine, gold, mercuric chloride), and malignancies (10 ), including carcinomas, carcinoids, sarcomas, lymphoma's, and leukemias (2,6-10). The possibility of a malignancy must be considered especially in older patients with membranous glomerulopathy. In these patients it is also imperative to perform urinary immunoelectropho-resis routinely to rule out myeloma and renal primary amyloidosis (AL) (2). Finally, idiopathic membranous glomerulopathy, of which...

Immunity can modulate behavior

The previous material has reviewed data indicating that behavioral triggers of the nervous system can regulate immunity. Several lines of evidence also indicate that components of an immune response can also signal the CNS. For example, many investigators have reported electrical changes in the hypothalamus following the administration of antigen. Others have reported that IL-1 stimulates release of corticotropin-releasing hormone from the hypothalamus into the hypophyseal portal circulation, where it can then activate the HPA axis. Moreover, the response to antigenic stimuli appears to be associated with the release of neurotransmitters and hormones produced by lymphocytes themselves. Finally, evidence suggests that these and or other signals from an activated immune system may be directly or indirectly signaling the CNS to actually modify the behavior of the organism. The most intriguing observations are those suggesting that the immunologic abnormalities of the lupus-prone strains...

Renal Anatomy and Basic Concepts and Methods in Renal Pathology

Most glomerulopathies are immunologically mediated and are the result of antibody-induced injury. This can occur as a consequence of antibody combining with an intrinsic antigen in the glomerulus or antibody combining either in situ or in the circulation with an extrinsic glomerular antigen, with immune complexes localizing or depositing in glomeruli. With circulating immune complexes, the antigens may be of endogenous or exogenous origin. Endogenous antigens occur in diseases such as systemic lupus ery-thematosus and include components of nuclei such as DNA, histones, etc. Exogenous antigens are usually of microorganism origin and include bacterial products, hepatitis B and C viral antigens, malarial antigen, etc. Circulating immune complexes are trapped or lodge in glomeruli in the mesangium and subendothelial aspects of capillary walls. Less commonly, they may be found in subepithelial locations. It is the electron microscope that precisely localizes the deposits. Certain diseases...

Etiology Pathogenesis

Investigations of human biopsies together with research using animal models and in vitro cell culture systems have generated some understanding of the underlying etiologic and pathogenetic mechanisms of lupus nephritis (23-27). The findings indicate that disturbed Fas-FasL-mediated apoptosis is a cause of autoimmunity in SLE (28-31). Subsequent breakdown in immunologic tolerance leads to the production of autoreactive B and T cells that, through either direct infiltration or their secretory products, initiate inflammation (32). Selective polyclonal B-cell expansion possibly related to disturbances in the idiotype network and genetic factors may be of primary importance in the initiation and development of autoim- munity as well (25,33-36). For example, the Fc gamma RIIIA-V F158 gene polymorphism has a significant impact on the development of lupus nephritis (37). Intriguingly, SLE and lupus nephritis have also been described in patients with autoimmune phenomena after infection with...

Clinicopathologic Correlations

Classification of lupus nephritis is considered useful to describe the patient's clinical status and for grouping patients with similar clinical profiles. Moreover, the classification is related to prognosis with respect to renal function and patient survival (40). It has been generally accepted that the use of the lupus nephritis classification facilitates the ease and reliability with which nephrologists and nephropathologists communicate information, and that it has greatly improved standardization and reproducibility of biopsy interpretation (45). In contrast, the prognostic value of the so-called activity and chronicity indices used by some in lupus nephritis is subject to discussion, and the utility of these indices is limited by concerns about their irreproducibility (15-17,72). Nevertheless, distinguishing active and sclerosing lesions (Table 8.3) may help determine prognosis and sensitivity to treatment in both lupus and other glomerulonephritides (73-76). In general, lesions...

Pathologic Findings Light Microscopy

A 70 of 77 patients tested for ANCA were positive (91 ) (44 P-ANCA and 26 C-ANCA). b 3 of 19 patients tested for ANCA were positive (16 ) (2 P-ANCA and 1 C-ANCA). c 4 patients had lupus and 1 post-streptococcal glomerulonephritis. d This patient also had a P-ANCA (MPO-ANCA). From Jennette and Falk (3). a 70 of 77 patients tested for ANCA were positive (91 ) (44 P-ANCA and 26 C-ANCA). b 3 of 19 patients tested for ANCA were positive (16 ) (2 P-ANCA and 1 C-ANCA). c 4 patients had lupus and 1 post-streptococcal glomerulonephritis. d This patient also had a P-ANCA (MPO-ANCA). From Jennette and Falk (3).

Skin Surface Analysis

Microanatomy The Epidermis

Skin surface analysis is often tailored to the goals of restorative surgery or nonsur-gical treatments. Patients undergoing scar revisions require analyses to include the resting skin tension lines. In the patient undergoing nasal reconstructive surgery after Mohs' resection, an analysis of the topographical units of the face is important. If cutaneous resurfacing is planned, an analysis of skin type and reaction to solar damage are also needed. Koebner's phenomenon is also an important consideration. This phenomenon describes the tendency for some skin diseases such as psoriasis, lichen planus, discoid lupus erythematosus, and herpes simplex to localize to areas of recent surgery or scars.

Prey Pursuit and Capture

For an American osprey (Pandion haliaetus) to intercept a fish in shallow water, it must perfectly time its descent and penetration of the water to match the location of its prey. Individual osprey have been observed catching many different kinds of fish, and this suggests that osprey learn to anticipate the position of their prey by observing something about individual fish (Bent, 1961). Numerous predators intercept moving prey (Curio, 1976), whether it is wolves (Canis lupus) taking down moose (Alces alces) in the Yukon or golden eagles (Aquila chrysaetos) catching rabbits (Lepus spp.) in the plains. The behavior seems to be a general one. But does it require an event timer

Pathological alterations of the classical pathway

The functioning of the classical pathway is disrupted in many circumstances. These include genetic deficiencies of single components complete deficiencies of Clq, Clr, Cls, C4, C2, C3, factors H and I have been reported. These are associated with susceptibility to infection and or inappropriate deposition of immune complexes. Low concentrations of MBL are associated with poor opsonization of yeast and some bacteria, and with recurrent infection in infants. Diminished synthesis of Cl-inh, or synthesis of inactive Cl-inh mutants is the cause of hereditary angioedema, and causes secondary consumption of C2 and C4. Autoantibodies to Cl-inh have been reported, which destabilize the Cl-inh-protease complex releasing free active protease these give rise to autoimmune angioedema. Autoantibodies to C3 con-vertases, termed nephritic factors, occur in mem-branoproliferative glomerulonephritis. These generally recognize C3bBb, but a few reports indicate reactivity against C4b2a. They stabilize...

Choice And Definition Of Problems To Be Studied

Using only a particular discipline's established methods may result in approaches that fail to reveal sufficient information about the problem being explored. This may be a difficulty for research surrounding medical problems particularly important to the elderly, women, men of color, and homosexual males. Pregnancy, childbirth, menstruation, menopause, lupus, sickle-cell disease, AIDS, and gerontology represent healthcare issues for which the methods of one discipline are clearly inadequate.

Chronic Renal Disease

Maternal risks associated with renal disease are linked to the degree of renal compromise. As renal function diminishes, fertility decreases. Pregnancy rarely occurs in women who have a preconception serum creatine of > 3 mg dL. Preterm delivery and superimposed preeclampsia frequently complicate pregnancies of patients with underlying renal disease. Patients with chronic pyelonephritis may have an increased number of recurrences due to bacteriuria, increased glucosuria, and mechanical compression of the ureter in the third trimester pregnancy. Those with a history of reflux nephropathy are at increased risk of sudden escalating hypertension and worsening renal function. Urolithiasis is associated with more frequent urinary tract infections. Patients with lupus nephropathy are at greatly increased risk for exacerbations of the disease and superimposed preeclampsia, particularly if their disease was not in remission for at least 6 months prior to conception.

Other Causes of Stroke

There are many other causes of stroke, most of which are rare. Inflammatory disorders can cause thickening of the vessel walls, with obstruction of blood flow, hemorrhage, and multifocal infarction. There are several forms of angiitis or vasculitis (Table II), including Moyamoya disease, Wegener's granulomatosis, and polyarteritis nodosa. Some forms of vascular disease are notoriously difficult to diagnose, and the vascular pathology is poorly understood (e.g., the vasculopathy of systemic lupus erythematosus). Traumatic causes of stroke include air, fat, and marrow embolism. Increased intracranial pressure resulting from trauma can lead to reduced cerebral perfusion pressure with watershed ischemia and infarction. Infections may cause stroke due to associated inflammatory changes in the vasculature (e.g., herpes zoster). Developmental vascular anomalies, such as cavernous, venous, or capillary malformations, may lead to stroke. Cardiac abnormalities such as atrial septal aneurysm can...

TABLE 1213 Diagnostic Studies in Seizure Patients

In any group of seizure patients, there is a subgroup in which the seizure is a symptom of an underlying disorder and is not due to idiopathic epilepsy. In such cases, correction of the primary problem makes seizure recurrence unlikely. Thus, the primary goal must be to uncover disorders that are readily identifiable and reversible. Symptomatic seizures of hypoglycemia, hypocalcemia, and electrolyte imbalance can be treated immediately. There is little risk of recurrence and no need for anticonvulsant use. Seizures occurring as a result of intracranial infections and craniocerebral trauma may require only immediate or short-term anticonvulsant use. Symptomatic seizures of systemic lupus erythematosus (SLE), sickle cell anemia, leukemia, arteriovenous malformations, and neoplasms may be the heralding

Immunogenetics and the cytokine system

The association with different HLA types and disease progression has been reported in most cohorts studied, although only a few of the associations stand up to multicenter analysis. One of the most striking associations is the association with HLA-B27 and nonprogressors and in Caucasian populations the association of HLA-A1, B8, DR3 with more rapid progression to disease. The latter haplotype is also associated with enhanced baseline immune activation that in turn is associated with other diseases of chronic activation such as systemic lupus erythematosus (SLE). It is of some interest that chimpanzees, which are 98 genetically similar to humans, do not have these haplotypes associated

Major immune activation

Immune activation, particularly with progressive renal failure, may be another cause for a patient failing to improve despite antibiotic treatment. In these patients blood cultures may have been negative (even if there has been no previous antibiotic treatment) and negative serology and microbiology will have excluded infection by cell dependent organisms. There may be doubt about the diagnosis but flamboyant vegetations are usually seen on echocardio-graphy and the patient may have had emboli. Changing the antibiotics fails to help. In these rare patients deterioration will continue until removal and replacement of the valve. No organisms may be grown from it or stain microscopically, but the rapid improvement that follows surgical intervention clearly shows that the bacterial antigen had persisted in the valve. There is a danger of such patients being falsely diagnosed as having Libmann-Sacks (in association with systemic lupus erythematosus) or marantic endocarditis but, unlike...

Wrong diagnosis or more than one diagnosis

It is possible that the patient being treated for infective endocarditis and not doing well may have been given a wrong or incomplete diagnosis. The patient may have been regarded as having culture negative infective endocarditis or the positive cultures may have been misleading or not have grown a typical organism. If vegetations are seen, they may not be caused by infective endocarditis and in reality may be sterile thrombotic vegetations in a patient with adenocarcinoma or systemic lupus. The fever and rise in acute phase reactants may be caused by lymphoma, tuberculosis, opportunistic infection in AIDS or active autoimmune disease or, rarely, the patient may have a fever producing portal of entry such as ulcerative colitis, or carcinoma or Hodgkin's disease in addition to infective endocarditis.

Central Nervous System

One of the most interesting side effects of NSAID use is aseptic meningitis. The literature reports cases in which patients repeatedly present with symptoms of headache, fever, neck stiffness, and fever within hours of taking NSAIDs. Cerebrospinal fluid analysis in these patients reveals elevated white blood cell, elevated protein, and normal or decreased glucose levels. Symptoms resolve after NSAID use is stopped and can be elicited with repeat NSAID challenges. This phenomenon is most often seen with patients who have underlying autoimmune diseases, such as systemic lupus erythematosus. The phenomenon is thought to be a hypersensitivity reaction. A complete workup to rule out infectious meningitis must be undertaken before the diagnosis of NSAID-induced aseptic meningitis is entertained.4

Hypersensitivity Reactions

Hypersensitivity reactions usually occur within 1 to 6 weeks of beginning phenytoin therapy and can include fever, systemic lupus erythematosus, erythema multiforme, toxic epidermal neurolysis, Stevens-Johnson syndrome, hepatitis, rhabdomyolysis, acute interstitial pneumonitis, lymphadenopathy, leukopenia, disseminated intravascular coagulation, and renal failure. One should always ask about a history of previous hypersensitivity reactions before deciding to restart phenytoin in the emergency department setting.

Human Neurological Diseases Studied by Microarray Technology

In addition, several investigators have turned to studying PBMCs in patients with MS, which are far more easily accessible than brain tissue. Expression studies of PBMCs have been revealing in other autoimmune disorders including lupus erythematosus and RA, as noted earlier. Sturzebecher et al. (2003) studied expression profiles of PBMCs in patients treated with interferon- (IFN- 3). This study included a design in which such PBMCs were exposed to IFN- 3 in vitro (called ex vivo experiments by the authors). Ten female patients in three classes were studied six responders to IFN- 3, two initial responders who developed neutralizing antibodies (Nab) and lost their responsiveness, and two who initially failed to respond (INR). The definition of significant differential expression was nonstandard either twofold in at least three of the six responders and not twofold decreased in four nonresponders (in so-called ex vivo experiments), or twofold in at

Recent advances in mechanisms underlying the Arthus reaction

As discussed above, recent data suggest that in the mouse the presence of an intact complement system is neither necessary nor sufficient to trigger or propagate an Arthus reaction. This is a surprising finding given that antibodies to C5a are effective at attenuating the reaction in rat and rabbits, and treatment with an anti-C5 mAb for 6 months prevents the spontaneous development of an autoimmune syndrome with features of systemic lupus erythematosus (SLE) in NZB W mice. In addition, a soluble form of the complement regulatory protein CD46 (membrane cofactor protein), which inhibits complement activation in vitro, reduces inflammatory cell influx and edema formation in the Arthus reaction. In the same model, soluble CD35 (CR1) and CD55 (decay-accelerating factor) were also effective as anti-inflammatory agents. See also Acute inflammatory reaction Adhesion molecules Anaphylatoxins Autoimmune diseases Mast cells Chemokines Cobra venom factor Complement, classical pathway Cytokines...

Neuroregenerative Mechanism Of Neuroimmunophilin Ligands

Corresponds to the mouse protein LN1, which could be involved in the progress of lupus nephritis.'' The results showed that ''PAHX has the physical capacity to interact with the FKBP12-like domain of FKBP52, but not with FKBP12 Also, '' the specific association of PAHX and FKBP52 is maintained in the presence of FK506. Although the function of PAHX FKBP52 complex is still unclear, this observation suggests that PAHX is a serous candidate for studying the cellular signaling pathway(s) involving FKBP52 in the presence of immunosuppressants.

TABLE 1153 Differential Diagnosis of Congestive Heart Failure Based on Age of Presentation

MYOCARDITIS AND CARDIOMYOPATHIES Myocarditis affects children of all ages and is the leading cause of end-stage cardiomyopathy requiring transplantation. Viral etiologies include enteroviruses (coxsackie, echovirus, and poliovirus), as well as mumps, influenza virus, and Varicella zoster. An emerging cause is HIV-associated myocarditis and chronic Epstein-Barr myocarditis. Many bacterial species have been associated with myopericarditis, but not myocarditis alone. Noninfectious causes include lupus erythematosus, toxins such as tricyclic antidepressants, and cocaine. Myocarditis is often preceded by a viral respiratory illness and needs to be differentiated from pneumonia. As with the latter diagnosis, presenting signs and symptoms are often respiratory distress, fever, tachypnea, and tachycardia. Clues that suggest myocarditis include generalized malaise, fever, and myalgias in age-appropriate children. 17,18 PERICARDITIS Usually, this presents as cardiomegaly that is discovered...

Class I Antidysrhythmic Agents

Common Emergency Department (ED) Indications Procainamide is a second-line agent generally used to treat and prevent recurrence of ventricular dysrhythmias, specifically stable ventricular tachycardia (VT) and premature ventricular contractions (PVCs) that are unresponsive to lidocaine. It is infrequently used in ventricular fibrillation (VF) or pulseless VT because it takes so long to achieve therapeutic concentrations. Procainamide may also be used for slowing or converting supraventricular tachycardias (SVT) including atrial flutter and fibrillation especially in Wolff-Parkinson-White (WPW) syndrome , paroxysmal supraventricular tachycardia (PSVT), paroxysmal atrial tachycardia (PAT), and paroxysmal atrioventricular (AV) junctional rhythm. Contraindications include complete AV heart block, second- or third-degree heart block (without an electrical pacemaker present), long QT intervals, and torsades de pointes. The drug should be used cautiously in patients with systemic lupus...

Circulating Anticoagulants

Acquired inhibitors of blood coagulation, also known as circulating anticoagulants, can have serious clinical consequences or only be laboratory phenomena that have little clinical impact. These inhibitors are antibodies directed against one or more of the coagulation factors. Although inhibitors have been described against most of the coagulation factors, the two most common are discussed here. Factor VIII inhibitors are a type of specific inhibitor, directed only against factor VIII. The lupus anticoagulant is a nonspecific inhibitor that is directed against several of the coagulation factors.

Idiopathic autoimmune thrombocytopenic purpura ITP

A relatively common disorder in adults, ITP often complicates diseases associated with defective immune regulation (e.g. systemic lupus erythematosus, HIV infection, lymphoproliferative disorders, Hodgkin's disease). The onset of thrombocytopenia and bleeding is usually less abrupt than in drug-induced immune thrombocytopenia caused by-drugs other than heparin. In adults, ITP is usually chronic and seldom remits spontaneously. IgG and or IgM autoantibodies react with GPIb, GPIIb-IIIa, or other antigens present on the ITP patient's platelets, on platelets from normal donors and, sometimes, on the patient's megakaryocytes. The IgG or IgM antibodies may fix and activate complement components on platelet surfaces however, complement fixation is often incomplete, and intravascular platelet lysis is much less common than in drug-induced immune thrombocytopenia (caused by drugs other than heparin). Macrophages have specific surface receptors for the Fc portion of IgGl and IgG3 molecules, as...

Other polyendocrine autoimmunity syndromes

Rarely, diabetes mellitus results from a decreased biological response to a normal amount of insulin. In type A insulin resistance, the problem lies in the insulin receptor, which is quantitatively or qualitatively abnormal, but in the type B syndrome autoantibodies to the insulin receptor produce diabetes mellitus. In vitro, using short-term culture experiments, these antibodies mimic the action of insulin, which may account for the occurrence of hypoglycemia in some patients. More typically, however, there is massive insulin resistance, so that even 15 000 units of insulin per day may not lower blood glucose, and prolonged in vitro experiments reveal the antagonistic properties of the antibodies. About one-third of these patients have other autoimmune diseases, including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, primary biliary cirrhosis, See also Adrenal autoimmunity Autoimmune diseases Candida, infection and immunity insulin-dependent diabetes mellitus, human...

Clinical Features

They do not clear centrally. Vesicles or bullae may be present. They may be unilateral or bilateral. When unilateral, erysipelas and cellulitis need to be distinguished from early herpes zoster infection. When bilateral, they may be mistaken for the malar eruption of systemic lupus erythematosus.

TABLE 2381 Medications Commonly Causing Photosensitivity Eruptions

The diagnosis is based on identifying the offending agent. If the diagnosis is unclear, other photosensitivity disorders, such as lupus erythematosus and polymorphous light eruption, should be excluded. Photopatch testing performed by a dermatologist or allergist may be helpful in identifying the photosensitizing agent.

Reassuring fetal heart rate patterns

The majority of fetal arrhythmias are benign and spontaneously convert to normal sinus rhythm by 24 hours after birth. Persistent tachyarrhythmias may cause fetal hydrops if present for many hours to days. Persistent bradyarrhythmias are often associated with fetal heart disease (eg, cardiomyopathy related to lupus), but seldom result in hypoxia or acidosis in fetal life.

Antepartum fetal surveillance techniques

Antepartum fetal surveillance should be initiated in pregnancies in which the risk of fetal demise is known to be increased. These problems can include maternal conditions such as antiphospholipid syndrome, chronic hypertension, renal disease, systemic lupus erythematosus, or type 1 diabetes mellitus. Monitoring should also be initiated in pregnancy-related conditions such as preeclampsia, intrauterine growth restriction (IUGR), multiple gestation, poor obstetrical history, or postterm pregnancy.

Background Definition

Systemic lupus erythematosus (SLE) is a multisystem inflammatory disease characterised by the presence of a wide variety of autoantibodies. Skin involvement is common, being present in 55-90 of cases.1 The characteristic skin lesions can be divided into acute, subacute and chronic subsets.2 The acute forms include the malar (butterfly) rash, papular lesions, urticaria, vasculitic lesions, hair loss and painless mouth ulcers. Subacute cutaneous lupus erythematosus (SCLE) is an uncommon form of cutaneous lupus, described as a clinical subset by Sontheimer in 1979.3 Chronic discoid lupus erythematosus (DLE) tends to be the most persistent of the skin lesions and may lead to unsightly scarring. It is most frequently seen as an isolated entity, but may also occur in people with the systemic form of lupus. Lupus panniculitis (also known as lupus profundus), neonatal lupus, lupus tumidus and bullous lupus are less commonly encountered forms of the disease.

Table 175 Drugs that can cause delirium

Levels, lupus erythematosus (LE) prep, antinuclear antibody (ANA), urinary porphyrins, ammonia, human immunodeficiency virus (HIV)), blood cultures, measurement of serum levels of medications, lumbar puncture, brain computerized tomography (CT), or magnetic resonance imaging (MRI), or electroencephalogram.

Other oral agents Benefits

We found no RCTs or controlled trials of other oral agents in cutaneous lupus. There are many case reports describing success in individuals or small numbers of patients. Favourable case reports describe cefuroxime,116 cyclophosphamide,117 ciclosporin A,118,119 cytarabine,120 interferon alfa (parenteral and intralesional),121,122 intravenous immunoglobulin,123,124 chimeric monoclonal antibodies,125 mycophenolate mofetil,126 and pulses of methylprednisolone.127 An open trial of sulfasalazine in 13 patients with cutaneous lupus demonstrated an excellent or good response in eight,128 and there is a favourable case report on the treatment of DLE with sulfasalazine.129

Cellular abnormalities

Transplantation experiments have documented that the genetic defects of lupus are associated with the lymphoid cell compartment. An increased number of activated memory phenotype T cells is observed in all lupus strains, B1 (Ly-1 ) cells are elevated in NZ mice, and there is a dramatic increase with age in BXSB of atypical monocytes. In Ipr and gld homozygous mice, there is a massive accumulation of a CD3+, CD48, B220+ T cell subset that appears to originate from the CD84 compartment. The T cells of all lupus mice manifest defective responses to in vitro activation signals, perhaps as a reflection of their previous activation in vivo. Several disturbances in cytokine production have been observed, particularly low production and response to interleukin 2 (IL-2), and increased production of interferon y (IFNy) and IL-10.

Major histocompatibility complex MHC genes

Although lupus susceptibility is not restricted to a single MHC haplotype (Table 1), the major contribution of certain MHC alleles to lupus susceptibility has been clearly demonstrated. In BXSB mice there is a dominant role for H-2 while for NZ mice, heterozygosity of the MHC (H-2d z) appears to confer higher susceptibility. Yet, H-2d z heterozygosity is not the only factor contributing to accelerated autoimmunity in the F1 hybrid, as crosses of NZB with SWR (H-2q) or BXSB (H-2b) also develop a disease similar to that of (NZB x W)F1 and crosses of NZB with congenic BALB c.H-2z are devoid of disease. Additional studies of H-2 congenic NZB mice revealed that the H-2bml2 haplotype predisposes to early onset lupus similar in severity to that in (NZB x W)F1, whereas the H-2h haplotype, which differs from the H-2l,ml21-A 3 gene only in three amino acids in the pcptidc-binding groove, predisposes to a mild autoimmune phenotype similar to that of the wild-type NZB (H-2d). This finding,...

The Ychromosome accelerator of autoimmunity

In contrast to the female predilection for lupus found in humans and most susceptible mouse strains, male BXSB mice develop a much more accelerated and severe disease than females. This striking sexual dimorphism is not hormonally-mediated, but results from a Y-chromosome autoimmune-accelerating (Yaa) gene that has not yet been cloned. The genetic contribution of Yaa to lupus susceptibility has been shown to be additive and dependent on other background genes. Non-autoimmune strains remain largely unaffected by the Yaa gene, whereas all lupus-susceptible strains develop an earlier and more severe disease that generally maintains the clinical characteristics of the background strain. For example, male NZW.Yaa congenies develop accelerated renal and cardiac disease and early death, while male NZB.Ytftf mice primarily show enhanced anti-red blood cell autoantibody production. Regarding the mechanisms responsible for the Yaa phenotype, double bone marrow chimera experiments using a...

Natural history of SLE

The prevalence of lupus varies according to ethnic group. Amongst black females it is approximately 1 in 250, amongst Chinese approximately 1 in 1000, amongst Caucasian about 1 in 4000. The female-to-male ratio in lupus is approximately 9 1 though some studies have indicated that there are families in which the disease occurs in mainly males and is transmitted through the fathers. Pregnancy for the lupus patient entails far more danger for the offspring than the mother. Generally speaking patients with very severe active lupus will not become pregnant and the risk of developing a major relapse during pregnancy seems to be mild to modest at worst. In contrast, the fetus is threatened by an increased predisposition to spontaneous abortion (which is associated with anticardiolipin antibodies) and prematurity which may be due to vasculitis affecting the placental blood supply. Approximately 1 in 20 of lupus mothers who have the anti-Ro or anti-La antibodies will give birth to children...

Thymic peptides as immunoregulators or biological response modifiers

Thymulin restores basal NK activity in spleen cell cultures obtained from old, but not young mice. It increases the release of interferon y (IFNy), IL-2 and IL-la by mitogen-stimulated cells of normal individuals, whereas it inhibits the release of these cytokines and also of IL-6 in systemic lupus erythematosus (SLE) patients. Inhibition of tumor necrosis factor a (TNFa) production was found in both groups. Thus, thymulin may function as an immunomodulator by exerting control over cytokine production.

Oral steroids Benefits

Sharma et a .25 published a summary of the management and clinical course of 41 patients with sarcoidosis treated at the University of Southern California's Sarcoidosis Clinic. Of the six patients with lupus pernio, five received oral corticosteroids, and only one had improvement of her lesions. Of the nine patients with skin plaques, seven received corticosteroids or chloroquine or both however, only one patient had improvement of his skin lesions. Corticosteroids were either not administered or their effects were not included for the remaining patients. Johns et al26 reported the results of an unpublished retrospective review by Hackett and Hambrick describing treatment of cutaneous sarcoidosis at Johns Hopkins Sarcoid Clinic. Systemic prednisone was used in 32 patients with cutaneous manifestations, and improvement of lesions was noted in 12 patients. Verdegem et al27 reported on four patients with ulcerative sarcoidosis. Case one had partial improvement of her lesions...

Plastic surgery Benefits

There are no systematic reviews or RCTs of the role of plastic surgery in the treatment of cutaneous sarcoidosis however, several case reports were found. In 1970, O'Brien described two patients successfully treated with plastic surgery for lupus pernio.75 In 1984, Shaw etal.76 described a man with a 6-year history of treatment-resistant lupus pernio successfully treated with surgical excision and split skin grafting the result remained good 2-5 years after surgery. Collison et al77 described a man with extensive ulcerative nodules of the lower extremities, which were resistant to topical intralesional steroids, oral steroids, hydroxychloroquine and methotrexate. He was treated with vigorous operative debridement and partial-thickness skin grafting. While the grafts were well accepted (80 ), the patient developed new ulcerating nodules in previously uninvolved skin 2 months after surgery. Stack etal.78 report on a black male with extensive facial lesions who was treated with CO2 laser...

Topical corticosteroids and intralesional injections

While topical corticosteroids and intralesional injections are often recommended as first-line treatment for the cutaneous manifestations of sarcoidosis,12,14,15,30 little evidence is presented regarding their efficacy for this indication. Khatri et al.80 describe a case of lupus pernio which improved with topical 0-05 halobetasol propionate twice daily for 10 weeks. Volden et al.81 describe three cases of cutaneous sarcoidosis that went into remission within 3-5 weeks of treatment with once-weekly clobetasol propionate covered with hydrocolloid dressing. The use of intralesional hydrocortisone and cortisone were reported in 1953 by Sullivan et al. 82 Eighteen skin lesions in five patients with cutaneous sarcoidosis were injected with 2-5 mg doses of hydrocortisone. All lesions developed evidence of regression by 14 days after the injection, with no evidence of recurrence 14 weeks later. Seven skin lesions in four patients were injected with 2-5 mg cortisone. All lesions improved but...

Aetiologyrisk factors

SJS-TEN is essentially drug induced (70-90 of cases). Graft versus host disease is another well-established aetiology, independent of drugs. A few cases are related to infection (Mycoplasma pneumoniae) other cases remain unexplained (idiopathic forms). The most extensive study of medication use and SJS-TEN pointed mainly to sulfonamides, anticonvulsant agents, non-steroidal anti-inflammatory drugs, allopurinol and chlormezanone.4 HIV infection dramatically increases the risk. A predisposing effect of autoimmune disorders, such as lupus, and an HLA-linked genetic susceptibility have been also suggested.

Differential Diagnosis

Careful history taking and physical examination should be used to rule out neurologic disease. A high index of suspicion should be maintained for physical disorders that have a vague onset, such as systemic lupus erythematosus, multiple sclerosis, polymyositis, Lyme disease, and drug toxicity or poisoning. Schizophrenia and depression may have associated conversion disorders. In somatization disorders, the symptoms are more chronic and involve multiple organ systems. With hypochondriasis, patients are usually without loss of function and display the conviction that some terrible undiscovered illness is present. Hypochondriacal patients will be overly concerned with symptoms. In cases of factitious symptoms, usually associated with malingering, patients will consciously complain about symptoms to

Geographical distribution and host range

The trypanosome is not host specific (Khan, 1977a Khan et al., 1980b), and experimentally infected fishes include the American eel (Anguilla rostrata), Atlantic cod (G. morhua), tomcod (Microgadus tom-cod), cunner (Tautogolabrus adspersus), striped wolffish (Anarhichas lupus), Vahl's eelpout (Lycodes vahlh), Arctic eelpout (Lycodes reticulatus), oceanpout (Macro-zoarces americanus), longhorn sculpin (Myoxocephalus octodecemspinosus),

Rheumatologie Disorders

Diagnosis Systemic Lupus Erythematosus . Condition then prednisone 50 mg PO qd. -Betamethasone dipropionate (Diprolene) 0.05 ointment applied bid. 1G. Extras CXR PA, LAT, ECG. Rheumatology consult. 11. Labs CBC, platelets, SMA 7& 12, INR PTT, ESR, complement CH-50, C3, C4, C-reactive protein, LE prep, Coombs test, VDRL, rheumatoid factor, ANA, DNA binding, lupus anticoagulant, anticardiolipin, antinuclear cytoplasmic antibody. UA.

Recurrent Renal Disease

The frequency and clinical significance of recurrence varies with the disease (14). The diseases that recur in > 25 are dense deposit disease (90 ), immunotactoid fibrillary glomerulonephritis (GN) (67 ), diabetes (> 50 ), IgA nephropathy (45 ), Henoch-Schonlein purpura (33 ), focal glomerular sclerosis (30 ), idiopathic hemolytic uremic syndrome (27 ), and type I membranoproliferative GN (27 ). Lupus nephritis and anti-GBM disease recur infrequently (< 5 ). The diagnosis of recurrence requires accurate classification of the original disease and lesions that differ from chronic allograft glomerulopathy.

Natural Plant Toxins In Foods

Despite their reputation as being the ultimate health food, alfalfa sprouts contain up to 15,000 ppm canavanine, an arginine analogue that can substitute for this amino acid in cellular proteins, thereby altering their function. Canavanine is also produced in other legumes such as the jack bean. Canavanine inhibits nitric oxide synthetase and induces heat-shock proteins in human cells in vitro (1). By virtue of its antimetabolic action, canavanine is under current consideration as an antitumor drug in combination with other antimetabolites such as 5-fluorouracil, but it has not yet been tested for carcinogenicity. Canavanine may cause autoimmune disorders such as lupus erythematosus in people (2). Primates fed alfalfa sprouts develop a severe toxic syndrome resembling human lupus.

Granulomatous Disease

Collagen vascular diseases are a group of disorders that includes systemic lupus erythematosus and systemic sclerosis or scleroderma. They are immunologically mediated. Nearly a quarter of systemic lupus patients develop oral lesion affecting the palate, buccal mucosa, or gingiva. These lesions may be lichenoid in

Native Valve Endocarditis Detection of Vegetation

Endocarditis Small Vegitation

(2-5 mm) on native heart valves that are commonly missed by TTE (Figure 7.2) 10,11 . Despite the superior image quality, TEE faces similar limitations in terms of false-positive and false-negative studies (Table 7.3). Libman-Sacks endocarditis refers to the case of vegetations that occur on the valves of patients with systemic lupus erythematosus (SLE) in the absence of infection 16 . Pathologically these vegetations

Membranoproliferative Glomerulonephritis

Membranoproliferative Glomerulonephritis

Merulonephritis has also been used for MPGN type I. Increased mononuclear cells and occasional neutrophils may be present. The proliferation is typically uniform and diffuse in idiopathic MPGN, contrasting the irregular involvement most commonly seen in proliferative lupus nephritis (Fig. 3.1). In secondary forms of MPGN, the injury may be more irregular. Crescents may occur in both idiopathic and secondary forms. Deposits do not involve extraglomerular sites. Lesions progress with less cellularity and more pronounced matrix accumulation and sclerosis over time (6). Tubular and vascular fibrosis and sclerosis proportional to glomerular scarring are seen late in the course.

Postinfectious Glomerulonephritis

Poststreptococcal nephritis is an immunologically mediated disease, in which both humoral and cellular immune mechanisms seem to play a role. In general, immune complexes deposited in the glomeruli could consist of either streptococcal antigen-antibody complexes or autologous antigen-antibody complexes. Over the years a large number of streptococcal anti-genic fractions have been proposed as the putative target antigen, but only a few of these are still under active study (1). These include a protein fraction antigenically similar to streptokinase, and a cationic proteinase (13). Increasing evidence now points to an in situ antigen-antibody reactivity in poststreptococcal glomerulonephritis, as in a number of other glomerulo-nephritides (6,14,15). The cationic proteinase, due to its charge, is well able to pass the glomerular basement membrane and therefore should be able to induce subepithelial immune complex formation. The immune complexes induce further damage with the...

Introgressive hybridization hybrid speciation and the evolution of human food sources

As reflected by the quotes from Vila et al. (2005), C. familiaris is a paradigm for demonstrating the role of introgressive hybridization between introduced, domesticated food sources and wild relatives. In particular, genetic evidence suggests that domestic dogs have repeatedly hybridized with their sister species, Canis lupus (i.e. the gray wolf Figure 9.4 Vila et al. 1997, 2003, 2005). Such hybridization is expected, given the occurrence of introgression between a variety of Canis species, including the close relatives of C. familiaris, the gray wolf, and the coyote. For example, introgressive hybridization between coyotes and wolves likely promoted by human-mediated habitat modification in North America has resulted in an extensive hybrid zone (Lehman et al. 1991). Indeed, this case is illustrative for understanding the genetic exchange between the domestic and wild forms in North America that contributed to the evolution of the food source for Native Americans. Like the...

Light Microscopy Immunofluorescence and Electron Microscopy

Lupus Nephritis Classes I and II Classes I and II lupus nephritis refer to pure mesangial glomerulopathy. These patients present clinically with mild hematuria, or proteinuria, or Figure 8.1. Lupus nephritis ISN RPS class II (mesangial) with granular mesangial immunoglobulin G (IgG) (immunofluorescence). Figure 8.1. Lupus nephritis ISN RPS class II (mesangial) with granular mesangial immunoglobulin G (IgG) (immunofluorescence). both. In general they have a good prognosis with respect to their renal function, and the histologic alterations remain stable in the majority of cases. However, functional deterioration and progression of glomerular lesions to more active or generalized proliferative forms occurs in about 20 of cases. In the past decades the availability of better supportive therapy and more selective use of immunosuppressive agents has led to improved survival of patients with mild forms of lupus glomerulonephritis, while new forms of immunosuppressive therapy are being...

Differential Diagnosis Of Seizures

Hyperkinetic movement disorders can be difficult to differentiate from complex partial seizures. Sydenham's chorea is infrequently seen today, and drug-induced chorea (ethosuximide, carbamazepine, or diphenhydramine hydrochloride) and lupus-induced chorea are likewise very uncommon. Tourette syndrome is more frequently seen, but rarely does the child appear acutely ill. Kinesogenic chorea is a movement disorder brought on by action and mimics simple motor partial seizures.

Magnetic Resonance Imaging

Adem Mri Findings

May have incidental lesions scattered in the deep white matter. Lesions seen with systemic lupus erythemato-sus are also located in the deep white matter but are not typically periventricular. Neurosarcoidosis may cause white matter abnormalities but frequently has associated meningeal enhancement due to leptomeningitis. ADEM may appear identical to MS. Lesions tend to resolve and do not recur. Gliomas may appear as solitary lesions, as may pseudotumor lesions of MS. Follow-up MRI may be definitive, although biopsy may be necessary to distinguish the two. Finally, inherited disorders of myelin, the leukodystrophies, demonstrate symmetric confluent rather than patchy, discrete lesions. A clinical history and examination are most helpful in providing alternate explanations for these abnormalities.

Physiologic and pathologic significance of the MAC

The MAC plays an important pathophysiologic role in several autoimmune and inflammatory diseases. In some cases this may be due to its cytotoxic effect, as in several immune hematologic diseases. In many instances, however, the pathophysiologic participation of the MAC is more likely related to its ability to elicit cell activation when present in sublytic amounts. The MAC has been implicated in renal diseases such as acute poststreptococcal glomerulonephritis, membranous and membranoproliferative type III nephropathy and lupus nephritis, in neurological diseases such as multiple sclerosis, Guillain-Barr syndrome and myasthenia gravis, in rheumatoid arthritis and immune-complex vasculitis, and in the extension of myocardial infarction lesions and

Interferon 7 Receptor

Ifn Myasthenia

Marsters SA, Pennica D, Bach E, Schreiber RD and Ash-kenazi A (1995) Interferon 7 signals via a high-affinitv multisubunit receptor complex that contains two types of polypeptide chain. Proceedings of the National Academy of Sciences of the USA 92 5401-5405 Meraz MA, White JM, Sheehan KCF et al (1996) Targeted disruption of the Statl gene in mice reveals unexpected physiologic specificity in the JAK-STAT signaling pathway. Cell 84 431-442. Ozmen I., Roman D, Fountoulakis M, Schmid G, Ryffcl B and Garotta G (1995) Experimental therapy of systemic lupus erythematosus the treatment of NZB W mice with mouse soluble infereron-gamma receptor inhibits the onset of glomerulonephritis. European Journal of Immunology 25 6-12. Pcrnis A, Gupta S, Gollob KJ et al (1995) Lack of interferon 7 receptor (3 chain and the prevention of interferon 7 signaling in TH 1 cells. Science 269 245-247. Schindler C and Darnell JE Jr (1995) Transcriptional responses to polypeptide ligands the JAK-STAT path way....

Acute Peripheral Neuropathies

Patients will have a modest CSF pleocytosis (up to 100 lymphocytes mm3), the presence of cells in the CSF should prompt consideration of other systemic diseases sometimes associated with GBS, such as HIV infection, lupus, and lymphoma. Lyme disease can present with a clinical picture similar to GBS and would be suggested by a CSF pleocytosis in combination with a history of tick bites or the presence of CSF Lyme antibodies. Carcinomatous meningitis also can present with similar symptoms but will be evident with malignant cells in the CSF or extremely high protein or low glucose levels. Tick paralysis mimics GBS, and all patients with suspected GBS should be examined thoroughly for ticks. Acute intermittent porphyria (discussed below) and spinal cord compression should be considered in the differential diagnosis the presence of upper motor neuron signs and bowel and bladder incontinence would suggest the latter.

Pavlovian conditioning and immunomodulation

That conditioned immunopharmacologic effects are of biological importance is apparent from Ader and Cohen's observations that the development of a systemic lupus erythematosus (SLE)-like autoimmune disease in (NZB x NZW)F, hybrid mice could be markedly delayed by treating animals under a partial schedule of pharmacologic reinforcement. That is, by substituting conditional stimuli that had been paired with CY for a proportion of the trials on which animals would normally have received active drug therapy, conditioned mice showed a significant delay in the onset of lupus using a cumulative dosage of CY that was, by itself, insufficient to alter the course of the autoimmune disease. Moreover, conditioned mice repeatedly re-exposed to the taste stimulus that had been paired with CY following the termination of active drug therapy survived significantly longer than conditioned animals that received no 'medication'.

Painless Visual Reduction Loss

Cardiac), thrombosis, giant-cell arteritis, vasculitis (lupus), sickle cell disease, and trauma. Often the patient will have atrial fibrillation. The retina will sustain irreversible damage within 90 min of total occlusion, so treatment should begin immediately. Unfortunately these patients rarely respond to therapy, but because the visual loss is usually so profound, every attempt should be made to reestablish circulation to the retina. Treatment in embolic cases (the majority) is aimed at trying to convert a CRAO into a branch retinal artery occlusion (BRAO). In the attempt to dislodge the embolus from the central artery and into one of its retinal branches, the other retinal branches may become reperfused, thereby reducing the size of the infarct. Maneuvers include digital massage, IOP-lowering drugs, and vasodilation techniques (breathing into a paper bag to increase Pa CO2). An ophthalmologist should be consulted immediately to evaluate the patient and decide whether performing...

Role of CD1 in the immune system

TCRa chain in conjunction with a restricted set of TCR VP families. During their differentiation in the thymus, these cells acquire several unique properties, i.e. they express natural killer cell receptors, and they display unusual cytokine secretion functions. In particular, the CD4+ subset secretes large amounts of interleukin 4 (IL-4) upon primary stimulation, within an hour of TCR engagement. Several studies indicated that NK1+ T cells could potentially influence the TH Th2 profile of the immune response, and thus could act as natural suppressors of graft-versus-host disease, mediate acute graft rejection, or regulate autoimmune symptoms in lupus and diabetes. As yet, however, there is no physiological phenomenon that these T cell subsets are associated with.

Differential Diagnosisdisease Variants

Other illnesses that present as a relapsing-remitting type of illness include Behcet's disease, characterized by oral or genital ulcerations, iridocyclitis, menin-goencephalitis, and thrombophlebitis. Lyme disease typically has radicular or peripheral nerve involvement but can be mistaken for MS because of its relapsing-remitting course and occasionally by its appearance on MRI. Sjogren's syndrome, in which individuals have vasculitis of the skin and peripheral nervous system associated with dry eyes and dry mouth, has also been confused with MS, in part because of MRI abnormalities that may mimic MS. Neurosarcoidosis may be a relapsing-remitting type of illness, but it generally has multiple cranial mononeuropathies. MRI shows lep-tomeningeal enhancement associated with intracranial disease. Cerebrovascular disease may be confused with MS, especially when interpreting MRI scans. Primary central nervous system vasculitis or systemic lupus erythematosus (SLE) may mimic the disease...

Molecules as antigens

Antigenic functions of nucleic acids were only recognized much later than those of proteins or polysaccharides. No immunogen has yet been prepared that would be capable of inducing in experimental animals antibodies to double-stranded DNA. Such antibodies are, nevertheless, available in humans suffering from systemic lupus erythematosus, as well as in mice and dogs with similar diseases. Their sera usually also contain antibodies to single-stranded, denatured DNA, as well as to RNA, double-stranded RNA, histone and nucleoprotein. It is possible to induce antibodies to single-stranded RNA or DNA, either by immunizing these, complexed with a macromolecule of opposite electrical charge, or by preparing conjugates of nucleosides, nucleotides or oligonucleotides, with proteins or synthetic polypeptide antigens, and using them as immunogens. Complex formation of methylated bovine serum albumin with synthetic polynucleotides, including some that were double-stranded and triple-stranded,...

Diversity of acute phase proteins

Finally, even within a species there is diversity in the acute phase response to different stimuli, to different disease processes and between different individuals. This has been most extensively studied in the case of CRP and SAA responses in humans, in whom there is a small number of serious inflammatory or tissue-damaging disorders characterized by absent or minimal acute phase production of these proteins. These exceptional disorders include systemic lupus erythematosus, dermatomyositis, Sjogren's disease, scleroderma, ulcerative colitis and leukemia, in all of which only a minority of patients have more than modest elevations of CRP or SAA concentration.

Cardiac valve disease associated with the antiphospholipid syndrome

The antiphospholipid (aPL) syndrome is an entity characterised by vascular thrombosis with frequent heart involvement, particularly valvar lesions.19 The syndrome is caused by the appearance of circulating aPL antibodies, which are spontaneously acquired circulating immunoglobulins directed against negatively charged phospholipids. aPL antibodies were initially found in sera of patients with systemic lupus erythematosus. They have since been found occasionally in other connective tissue diseases, as well as in drug induced, malignant, and infectious disorders. In addition, they have been found in subjects without any underlying disorder. Cardiac involvement is frequently seen under the broad umbrella of the aPL syndrome, and it can be present in many diverse ways.20 Initially, aPL antibodies were significantly associated with the finding of valve lesions in lupus patients. Nevertheless, systemic lupus is a complex disease in which multiple inflammatory, thrombotic, and degenerative...

Concluding remarks

It is the current view that autoantigens themselves drive the autoimmune response against them. In that view, nucleosomes are to be considered the relevant autoantigen for the genesis of antibodies to nucleosomes, histones and DNA. Indeed, it would not be expected that DNA occurs freely in the circulation or the organs of the immune system, since in the nucleus of the cell it is so tightly bound to the core histones. Evidence implicating the role of nucleosomes as the driving antigen has been obtained by several different groups. Datta and colleagues, studying the role of T cells in the induction of autoantibodies, found that in lupus mice 50 of the pathogenic T helper cells respond to nucleosomes. These nucleosome-specific T helper cells not only induced the production of nucleosome-specific autoantibodies by syngeneic B cells, but also the formation of See also Anti-inflammatory (nonsteroidal) drugs Autoantibodies, tests for Glucocorticoids Molecular mimicry Prostaglandins...

Drug Allergy

The clinical manifestations of drug allergy are widely varied and can involve all four types of hypersensitivity reactions. A generalized reaction similar to immune-complex or serum-sickness reactions is very common. Beginning usually in the first or second week after the administration of the drug, this reaction may take many weeks to subside after drug withdrawal. Generalized malaise, arthralgias, pruritus, urticarial eruptions, and fever are common. Drug fever may occur without other associated clinical findings and may also occur without an immunologic basis. Circulating immune complexes are probably responsible for the lupus-like reactions caused by some drugs. Cytotoxic reactions, such as penicillin-induced hemolytic anemia, can occur. Skin eruptions may include erythema, pruritus, urticaria, angioedema, erythema multiforme, and photosensitivity, and severe reactions, such as those seen in Stevens-Johnson syndrome and toxic epidermal necrolysis, may also occur. Pulmonary...

Autoantibodies

There is a spectrum of autoantibody reactivities ranging from organ-specific to non-organ-specific autoantibodies. Organ-specific autoantibodies react to antigens of only one tissue, such as to thyroid tissue. Non-organ-specific autoantibodies react with antigens common to all tissues, such as to different nuclear antigens, and are often associated with more generalized disorders, such as systemic lupus erythematosus. There is also a small group of intermediate autoantibodies with specificity to particular tissues but with a widespread distribution, such as smooth muscle. The description of the autoantibodies and their tests, presented below, will feature this range of reactivities, summarized in Table 1.

Skin antigens

Patients with autoimmune skin disease, such as pemphigus vulgaris or bullous pemphigoid (BP) develop autoantibodies that bind to epidermal antigens. These antibodies are identified by IIF, using tissue sections of skin (e.g. foreskin) or other squamous epithelium (e.g. monkey esophagus) as tissue substrate. Patients with pemphigus vulgaris show serum autoantibodies to the intracellular area of the epidermis in 80-90 of cases. These antibodies are IgG, most of them bind complement, and they are pathogenic, as demonstrated by serum transfer experiments. Low levels of pemphigus-like autoantibodies are sometimes found in other conditions, such as burns and systemic lupus erythematosus, as well as in normal individuals. These antibodies appear to correlate with disease activity and may be used to monitor therapy.

Function

B7-2 is the major costimulator for initiating both Tnl and TH2 immune responses because of its constitutive expression and more rapid upregulation. The need for two B7 proteins is unclear but many studies with murine models of autoimmunity show different effects of blocking B7-1 or B7-2. Whereas complete blockade with CTLA4-Ig or anti B7-1 plus anti-B7-2 mAbs prevents the development of disease in murine models of nonobese diabetes (NOD), systemic lupus erythematosus (SLE) and experimental autoimmune encephalitis (EAE), and alleviates symptoms in established disease, different effects are seen when either B7 is blocked. In NOD and SLE, anti-B7-2 mAb is sufficient to alleviate disease but in NOD, anti-B7-l mAb alone exacerbates disease. In contrast, anti-B7-l mAb alleviates EAE, whereas anti-B7-2 mAb exacerbates EAE. B7-1 is a more effective costimulator for weak peptide ligands and this may explain the importance of B7-1 in the progression of autoimmunity to subdominant epitopes.

Anthropocentrism

Many philosophers and social critics perceive anthropocentrism as a belief that, if it ever had a purpose, has now outlived its usefulness and become outmoded. Others maintain that anthropocentrism is in some sense inescapable. Just as spiders, if they could evaluate the world around them conceptually and articulate the result in language, would be arachnicentric (spiders are arachnids), so would wolves (genus Canis and species lupus) be lupucentric and cows (bovids) bovicentric. How, then, could humans be other than ho-mocentric But while we may, and perhaps must, accept that human values and experience determine the standpoint from which we project outward, it does not necessarily follow that overcoming our anthropocentrism is impossible. The human outlook is an essential reference point, but this does not mean that all values must be human centered. We cannot conclude that it is impossible to empathize (see EMPATHY FOR ANIMALS) and connect with nonhuman nature just because we...

Early descriptions

Autoimmune hepatitis (AH) is now the preferred name for the disease originally described as chronic active hepatitis (CAH) in the 1940s in reference to a protracted viral hepatitis among military personnel. However, CAH, as later understood, emerged from descriptions in the 1950s of a relapsing or progressive and usually fatal liver disease of young women of no ascertainable cause, but perhaps the result of subclinical viral hepatitis. Emphasis was given to endocrine abnormality, amenorrhea, striae and acne due to the diseased liver failing to metabolize steroid hormones, and to hyperglobulinemia with reversal of the albumin-globulin ratio in serum, a then popular liver functional index. Autoimmunity was later implicated because of findings of lupus erythematosus (LE) cells in the blood, and a positive serum complement fixation test with human tissue homogenates as antigen. Clinical and serological resemblances between CAH and systemic lupus erythematosus (SLE) led to the name lupoid...

Immunologic studies

In all of the above the antibody patterns were specific to patients with endocarditis and the level of IgM correlated with disease. The resolution of infection by appropriate antibiotic therapy saw a rapid reduction in IgM levels when samples were measured weekly. The description of these patterns has led to a further study in which they were used as a way of diagnosing culture-negative endocarditis. This is a syndrome in which the patient has proven endocarditis but consistently negative blood cultures. Negative serology was found in 28 patients where the diagnosis of endocarditis was rejected or, if proven, staphylococcal, yeast, gram-negative, systemic lupus erythematosus, due to Q fever or Chlamydia psittaci or nonbacterial thrombotic. Positive serology was found in 27 of the 34 patients where the response to antibiotics suggested streptococcal or enterococcal infections. In 22 of these there was objective evidence of endocarditis. Positive serology was also found in three out of...

Creactive Protein

Severe viral infections are usually associated with a significant acute phase response but localized viral infections are generally a much less potent stimulus for CRP production than bacterial infections. In addition there are some important disorders in which CRP levels are usually normal or only modestly increased, even in the presence of severe, active, tissue-damaging pathology. These include systemic lupus erythematosus (SLE), ulcerative colitis, derma-tomyositis, scleroderma, Sjogren's syndrome and leukemia. However, in all of them, intercurrent microbial, and especially bacterial, infection always stimulates a major acute phase response. The mechanisms underlying these phenomena are not known. Studies of SLE-like autoimmune disease in inbred mouse strains suggest that the acute phase response to this type of autologous tissue damage may be genetically determined, but the locus of gene action, whether at the level of mediators, receptors, acute phase protein synthesis or...

Laboratory Diagnosis

In clinical practice, e.g., for the planning of operations, diagnosis of congenital F XI deficiency is usually established by APTT-based assays, whereas molecular techniques are mostly restricted to scientific studies. However, there are conditions, such as consumption reactions or the presence of a high titer of lupus anticoagulant, where APTT-based tests may not be suitable and molecular methods are needed to identify a congenital deficiency state. For mutation analysis, genomic DNA is extracted and usually amplified by PCR with primers covering all 15 exons and the intron-exon boundaries. Frequently, primers are designed in such a way that a section of DNA encompassing a number of exons in close proximity to each other is amplified. 31,32 PCR may be directly followed by determination of nucleotide sequences of all PCR products, but frequently a mutation-screening technique such as single-stranded conformation polymorphism (SSCP) analysis is subsequently applied to avoid unnecessary...

Pancreatitis

Pancreatitis is not common in childhood. The most common cause is abdominal trauma. It can also occur as an idiopathic or postviral process (mumps, influenza, coxsackie, etc.) or be due to drugs or toxins. Systemic diseases such as cystic fibrosis, systemic lupus erythematous and a -,-antitrypsin deficiency can cause

Domestication

The first species to undergo the change from wild to domestic life was probably the wolf (Canis lupus), the ancestor of the dog.* The oldest known archaeological remains of a probable domesticated wolf come from a 14,000-year-old site in central Europe. Wild sheep (Ovis orientalis) and goats (Capra aegagrus) appear to have been domesticated more or less simultaneously in the Near East around 11,000 years ago, while remains of domesticated cattle (Bosprimigenius) and pigs* (Sus scrofa) first occur in the archaeological record around 8,000-9,000 years b.p. (before present) at various sites in Asia. Horses (Equus ferus), asses (Equus africanus), camels (Camelus spp.), water buffalo (Bubalus bubalis) and chickens* (Gallus gallus) all appear to have been domesticated in different parts of Asia and North Africa between 7,000 and 5,000 years ago, while the first domesticated cats* (Felis silvestris) appeared in ancient Egypt between 4,000 and 5,000 years ago. Meanwhile, in the New World,...

Disease association

Increased expression of hsp70s has been observed in autoimmune diseases such as scleroderma and systemic lupus erythematosus (SLE), but it is not clear whether this is a contributory factor or a consequence of disease. However, exposure of kera-tinocytes to ultraviolet light results in accumulation of HSP70 in the nucleoli and a concomitant increase in binding sites for autoantibodies to nuclear antigens which are a feature of erythematosus lesions. Some allelic variation has been found in the MHC-linked hsp70 genes, but numerous studies have failed to show a direct contribution of any of the variants to a particular autoimmune disease.

Chronic ITP

This is an autoimmune disorder which occurs most commonly in adults between the ages of 20 and 50 and is more common in women than in men (approximately 2 1). Unlike acute ITP, this disorder appears more insidiously, and extremely low platelet counts and severe mucosal bleeding are uncommon, although they may occur. Physical findings, as with acute ITP, reflect the degree of thrombocytopenia. An enlarged spleen or the presence of enlarged lymph nodes suggests another cause. A similar disorder, often associated with autoantibodies, is seen with a variety of illnesses, including collagen vascular disorders (e.g. systemic lupus erythematosus), lympho-proliferative disorders and certain infections, particularly human immunodeficiency virus (HIV). Blood counts are normal, except for the reduced platelet count, and bone marrow examination shows normal or increased numbers of megakaryocytes. Somewhat surprisingly platelet production studies show that, in the majority of chronic ITP patients,...

Hydralazine

Hydralazine, a smooth muscle vasodilator whose mechanism of action is poorly understood, is available both in tablet form and in parental form. Acute toxicity with hydralazine is uncommon, and no fatalities due to acute poisoning have been reported. Chronic use does lead to a hydralazine-induced systemic lupus erythematosus syndrome, but this generally occurs in individuals who have slow hepatic acetylation. Treatment is supportive the hypotension associated with hydralazine responds well to intravenous fluids. Vasopressors should be used with caution in order to avoid precipitating dysrhythmias. Dopamine should be used judiciously if a vasopressor is necessary. Symptomatic tachycardia can be cautiously treated with b blockers.

Immunoproteins

The human body is a nutrient rich environment and would be colonised rapidly by viruses, bacteria and other parasites if it were not protected by an immune system. This system not only recognises and destroys invading parasites (and even cancer cells), but does not attack the bodies own cells. Both properties are equally important for our survival. An attack of our immune system against our own cells is called autoimmune disease. Such diseases tend to be debilitating, protracted and eventually fatal. Examples are myasthenia gravis (antibody production against the muscle acetylcholine receptor), systemic lupus erythematosus (SLE) (reaction against nuclear antigens) or diabetes mel-litus type 1 (destruction of the -cells in the islets of Langerhans in the pancreas).

Clinical Diagnosis

The diagnosis of MS is clinically based, relying heavily on the neurologic history and physical examination. The diagnosis is suggested when a patient has either two or more prolonged (days to weeks) episodes with neurologic dysfunction that suggests distinct white matter pathology or spinal cord dysfunction that worsens over several months.11 Optic findings, lack of focal pathology, clinical remissions, cerebrospinal fluid (CSF) findings, and typical features such as dysautonomias all suggest the diagnosis of MS.12 Symptoms that mimic MS are seen with systemic lupus erythematosus (SLE), Lyme disease, neurosyphilis, and HIV disease. The clinical features of these other diseases, as well as the presence of consistent laboratory and neuroimaging findings in MS, can help to confirm the diagnosis of MS.

APS type II

Of the individual components do not differ from the isolated disorders in their severity or age of appearance. APS type II seems to be inherited as an autosomal dominant condition with incomplete penetrance. There is considerable variation, both within and between families, in the expression of the various components. Affected siblings usually share one or both HLA haplotypes. There is a strong association with HLA-A1, -B8, -DR3, which varies according to the disease components, but is generally greater than with the individual isolated diseases. In addition, HLA-DR4 is increased in frequency in these patients, due to its association with type 1 diabetes mellitus. However, not all patients have these HLA alleles (suggesting that other loci are involved in the predisposition to develop polyendocrinopathy) and some diseases known to be associated with HLA-DR3, such as systemic lupus erythematosus, do not appear to be unusually frequent in APS type II patients.

Miscellaneous

This is a self-limiting necrotizing lymphadenitis, possibly of autoimmune basis. Patient presents typically with nontender, persistent cervical lymphadenopathy. Excision biopsy of the enlarged lymph node is required for diagnosis. Some patients may have associated lupus erythematosis therefore, serology for anti-nuclear antibody and rheumatoid factor should be obtained.

Photosensitivity

The types of reactions to ultraviolet light are varied. In many disorders, ultraviolet light aggravates, but does not cause, the disease. Examples of this type of reaction include lupus erythematosus, porphyria cutanea tarda, dermatitis associated with niacin deficiency (pellagra), and recurrence of HSV. Other disorders are caused primarily by the sun. The most common is a sunburn reaction. Sunburn reaction, exogenously induced photosensitivity, and polymorphous light eruption are discussed here.

Perspectives

See also Autoimmune disease, pathogenesis Autoimmune disease, spontaneous experimental models Autoimmune diseases Autoimmunity Cytokine genes, regulation of Cytokines Insulin-dependent diabetes mellitus, animal models Neuroendocrine regulation of immunity Systemic lupus erythematosus, experimental models.

Immunoconglutinins

Nef was first described by Spitzer and colleagues in 1969 in patients with mesangiocapillary glomerulonephritis, but there is a stronger association with partial lipodystrophy. A few subjects with Nef have systemic-lupus erythematosus (SLE) and occasionally there is no associated disease.

Retinoids Benefits

We found one RCT involving 39 people with DLE and 19 with SCLE, in which hydroxychloroquine, 400-1200 mg day, was compared with acitretin, 50 mg day, over 8 weeks,10 described above in the section on hydroxychloroquine. We found three uncontrolled trials of oral retinoids (etretinate or acitretin) in chronic cutaneous lupus. A total of 64 people were treated, and 46 (72 ) cleared or experienced marked improvement.89-91

Dermatomyositis

Figure 45.1 This patient presented for the evaluation and treatment of her skin condition, which had been present for the past 6 months. A previous biopsy had revealed an interface dermatitis and her antinuclear antibody was positive. A working diagnosis of lupus erythematosus was made. Treatment with sunscreens and topical corticosteroids were ineffective. Hydroxychloroquine administration resulted in a severe cutaneous drug reaction that required hospitalisation

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