How I Healed my Lupus
There is now considerable evidence from studies on patients with hereditary deficiencies of individual complement components that complement has specific roles in host defense, independent of other systems. Specific roles have most clearly been defined for deficiencies of C3 and C5-8 that are associated with diseases caused by bacterial agents. In these instances the component is directly involved in a physiologic mechanism that eliminates the disease agent (i.e., opsonization and bacterial lysis). A hypothesis, proposed more than 25 years ago, on specific roles for early complement components in host defense was that these components protect against lupus diseases. Evidence reviewed in this chapter has confirmed that the early complement proteins, C1 through C2 are directly involved in the host defense against lupus disease. It appears from the review of the prevalence of lupus disease with other complement components that these host defenses are related to biological activities of...
Systemic lupus erythematosus (SLE) is defined by its clinical features and the almost invariable presence of autoantibodies directed against certain components of cell nuclei. U The immunological features of SLE are the lupus erythematosus cell, antinuclear antibodies, immune complexes, complement activation, tissue deposition of immunoglobulins and complement, and other autoantibodies. A nonspecific B-cell polyclonal activation may be responsible for the initiation of the disease however, evidence of antigen-specific activation of antibody production also exists. Both of these mechanisms likely operate simultaneously to bring about manifestations of the disease. y Additionally, the linkage of certain antibodies with particular human leukocyte antigen (HLA) loci and a 30 to 50 percent coincidence of SLE in monozygotic twins suggest a genetic factor in the pathogenesis of the disease. y Tissue damage results from both immune complex mediated...
SLE associated with homozygous deficiency of the early components of complement was the first of the associations of early complement deficiency with lupus disease to be reported (13). A striking finding present in the first index case and subsequently confirmed was that some of the lupus disease in these patients, called atypical cutaneous lupus erythematosus for lack of a better term, differs from classic lupus in the following four ways 1) increased incidence of discoid skin lesions, 2) an absence of renal disease, 3) low or absent titers of ANA and antibodies to native DNA, and 4) infrequent findings of immunoglobulin and complement in the skin lesions (see section on C2 deficiency). These features were also found in some patients with complete deficiencies of C1q, C1r-C1s, and C4 that were reported later.
A number of patients with hereditary deficiencies of C1 esterase and lupus disease have been reported (44, 102-120). Of 25 affected patients 6 had SLE, 9 had discoid lupus erythematosus, and 10 had SLE-like disease. Three of the latter patients appeared to have atypical cutaneous LE there were insufficient data on the remainder for assessment. Three of the 5 lupus bands tested performed were negative as found in the atypical cutaneous LE lesions. The female to male ratio was 7 1. As with the hereditary C2 deficiency and the C4 deficiency, the lupus disease is characterized by a high incidence of skin rash, which often has been diagnosed as discoid lupus erythematosus some of these patients may have atypical cutaneous lupus erythematosus. most skin biopsies of the lesions showed no immunoglobulin or complement deposits. In 7 of 19 and 5 of 11 patients the ANA and 5 DNA antibody tests were negative respectively. Membranoproliferative glomerulonephritis was present in 4 of the 6 patients...
A 34-year-old Caucasian woman with partial lipodystrophy since age 5 years has been reported with classic SLE (100). The patient had pleuritis, polyarthritis, and a photosensitive rash on her arms. Lupus erythematosus cells, ANA, native DNA antibody, and rheumatoid factor tests were positive. C3 was markedly depressed, with normal levels of C1q, C2, and C4. C3Nef was demonstrated in the serum. A renal biopsy showed focal mesangial sclerosis without any electron-dense deposits on electron microscopy. This patient's lupus is classic SLE and bears little resemblance to the lupus-like syndrome seen in three of the homozygous CS-deficient cases, except that all had skin rashes and three had photosensitivity. The significance of any of these observations remains to be determined.
Lupus erythematosus (LE) is a clinical syndrome that has multiple, but largely unknown causes. It exhibits an extremely broad spectrum of symptoms, and it can range in severity from being potentially fatal within a few weeks to eliciting minor indolent symptoms which, prior to immunologic testing, are virtually undiagnosable. When limited to the skin, it is called discoid lupus erythematosus (DLE) when the viscera are symptomatically affected, it is termed systemic lupus erythematosus (SLE). The inciting causes activate immunologic mechanisms that mediate the pathological, predominantly inflammatory, tissue responses.
AT Antithrombin DVT deep vein thrombosis HIT heparin Induced thrombocytopenia RAI L plasminogen activator inhibitor PC
Tibodies, estrogen use, and pregnancy. The strong link between cancer and thrombosis has been recognized since the late 1800s.9 Tumor cells secrete a number of procoagulant substances that activate the clotting cascade. Furthermore, patients with cancer often have suppressed levels of protein C, protein S, and AT. Antiphospholipid antibodies, commonly found in patients with autoimmune disorders such as systemic lupus erythematosus and inflammatory bowel disease, can cause venous and arterial thrombosis.8 The antiphospholipid antibody syndrome is associated with repeated pregnancy loss. The precise mechanism by which these antibodies provoke thrombosis is unclear, but they activate the coagulation cascade and platelets, as well as inhibit the anticoagulant activity of proteins C and S. Estrogen-containing contraceptives, estrogen replacement therapy, and many of the selective estrogen receptor modulators (SERMs) increase the risk of venous thrombosis.2,10,11 While the mechanisms are...
Although the ANA is 95 sensitive for systemic lupus erythematosus (SLE), it is not specific and is seen in other diseases. Higher titers are more specific for SLE but may be seen in the other autoimmune diseases. About 20 of normal people have an ANA titer of 1 40 or higher, and 5 have a titer of 1 160 or higher. Less than 5 of patients with definite SLE have a negative ANA titer. Because of the high prevalence of positive ANAs in normal people, physicians need to reserve the diagnosis of SLE for patients who have clinical findings compatible with SLE. ANA titers correlate poorly with relapses, remission, and severity of disease and are not helpful in monitoring the course or response to therapy. ANA testing should be ordered when a connective tissue disease is considered, but it is not generally helpful in the evaluation of nonspecific complaints, such as fatigue or back pain (Solomon et al., 2002). Systemic lupus erythematosus Systemic sclerosis Drug-associated lupus Mixed...
Symptoms that bring patients to medical attention most often emanate from the lungs, skin, or the eyes (uveitis and lacrimal gland enlargement). Diagnosis of sarcoidosis may be delayed if symptoms are attributed to more common lung diseases such as asthma or chronic bronchitis (Judson et al., 2003). Pulmonary symptoms may result from bronchial obstruction, either external compression caused by adenopathy or granulomas within the airways. Progressive disease may cause damage to the lung parenchyma, with a restrictive pattern of pulmonary function and decreased diffusion capacity, consistent with progressive interstitial lung damage. Clinical features associated with a worse outcome include the presence of lupus pernio, chronic uveitis, hyper-calcemia or nephrocalcinosis, nasal mucosal involvement and bone cysts. Neurosarcoidosis and cardiac involvement can be especially challenging to diagnose.
Outside the United States, the most common cause of pleural disease is tuberculosis. In the United States, TB is still significant, but other disorders, such as pneumonia, HIV-related infections, connective tissue disease (especially lupus), and malignancies (mesothelioma, peripheral lung cancer) must also be considered. Pleural effusions can be caused by systemic sources of transudate (CHF, hepatic failure with ascites, autoimmune disease) or by local inflammatory processes (parapneumonic effusion, pancreatitis, neoplasia).
The anti-phospholipid syndrome (APS) is characterized by recurrent fetal loss, vascular thrombosis and thrombocytopenia occurring in the presence of anti-phospholipid (aPL) antibodies. Pregnancy loss is a defining criterion for APS and occurs with particularly high frequency in systemic lupus erythematosus (SLE) patients bearing this antibody.
Skin rash, predominantly with photosensitivity, occurred in 37 patients with negative lupus band tests in 3 of 9 cases reported. Glomerulonephritis was present in 16 patients with the membranoproliferative type present in 5 of the 8 cases characterized. Antinuclear antibodies were present in 24 of 35 patients tested but only 5 of 25 patients had antibodies to double stranded DNA. Although patients with complete C1q deficiency had some features of lupus disease, the diagnostic criteria for SLE were usually not met in most cases. The female to male ratio was 1.3 1 in the C1q deficient group compared to a ratio of 15 1 in classic SLE. Hereditary deficiencies of C1q can be subdivided into two major groups those with normal levels of C1q and those with depressed levels of C1q protein in the blood. Only individuals with homozygous deficiency are affected.
She also complains of increased facial hair growth and lower extremity muscle weakness. Physical exam reveals facial acne, facial hirsutism, truncal obesity, thin skin, and purple abdominal striae. Her past medical history is significant for hypertension, type 2 diabetes mellitus, hyperlipidemia, and lupus.
There have been 14 patients with C1r-C1s patients reported in the literature (24-28). C1r and C1s deficiencies usually occur together in affected individuals, perhaps because the C1r and C1s genes are located very close to each other on chromosome 12 where simultaneous deletions of both closely linked genes may occur. Some patients have been reported to have complete absence of both C1r and C1s whereas others have complete absence of one of the molecules and significantly decreased levels of the other. Eight of the 14 (57 ) had lupus disease all had skin rash, DLE was diagnosed in two and SLE in two. Five of eight had glomerulonephritis only one was characterized and had mesangioproliferative glomerulonephritis. The female to male ratio was 1.7 1. ANA was negative or weakly positive in 3 of 8, and DNA antibodies were negative in 3 of 5 patients studied. LE band tests were not reported.
This concept is supported also by other data in which blockage of complement activation ameliorates glomerulonephritis. New Zealand black x New Zealand white (NZB W) Fi mice spontaneously develop an autoimmune syndrome with notable similarities to human systemic lupus erythematosus. Female NZB W Fi mice treated with a monoclonal antibody specific for the C5 component of complement that blocks the cleavage of C5 and thus prevents the generation of the potent proinflammatory factors C5a and C5b-9 developed significantly less glomerulonephritis and in markedly increased survival (25). In mice Crry, another complement activation controlling cell surface protein expressed only in mice, has been shown to control the development of glomerulonephritis either when given in a form of treatment to mice prone to develop disease (26) or when genetically expressed as a soluble form (27).
There are no specific tests for lupus. The lupus erythematosus cell, formed when complexes of nuclei and antibodies are phagocytosed by PMNs, is highly specific but of low sensitivity. ANA, anti-double-stranded DNA, and antiphospholipid antibody are all markers for SLE, but antibody test results are misleading if not considered in the clinical context. From 2 to 5 of patients with SLE are ANA negative, whereas 5 of the normal population and up to 20 of healthy young women are ANA positive (Fritzler et al., 1985). Antibodies to an RNA-protein complex called Sm (anti-Smith antibody) and to double-stranded DNA (dsDNA) are almost unique for SLE, both being 95 specific. ESR is normally increased, whereas CRP is normal (Linares et al., 1986). In active SLE, serum complement (C3, C4, and often CH50) levels are depressed. ESR is often elevated during active disease but is not a precise indicator of disease activity. DNA autoantibodies also do not correlate well with periods of active disease....
A decrease in erythrocyte production can be multifactorial. Nutritional deficiencies (such as iron, vitamin B12, and folic acid) are common causes that are often easily treatable. In addition, patients with cancer and CKD are at risk for developing a hypo-productive anemia. Furthermore, patients with chronic immune-related diseases (such as rheumatoid arthritis and systemic lupus erythematosus) can develop anemia as a complication of their disease. Anemia related to chronic inflammatory conditions is typically termed anemia of chronic disease.
Autoimmune diseases are chronic disabling disorders in which immune dysregulation leads the body to attack its own organs and tissues. More than 80 autoimmune diseases have been identified. The most common of these diseases include systemic lupus erythematosus (SLE), multiple sclerosis, type 1 diabetes, autoimmune thyroid diseases, myasthenia gravis, and rheumatoid arthritis (RA). Collectively, autoimmune diseases are thought to affect approximately 14-22 million people in the U.S. and represent a significant physical, emotional, social, and fiscal burden to the country's health care system. For reasons that are not clear, the prevalence of autoimmune diseases appears to be rising. Further, the development of effective therapies has lagged behind the growing prominence of these diseases.
About 8 days before admission he developed a sore throat and fever. Two days before hospitalization he noted dark urine almost the color of reddish ale. He had been previously well and had been on university sports teams. He now worked as a journalist. He had had no serious past illnesses. He had many girlfriends and had been sexually active with a number of partners, some of whom he picked up in bars. He never had taken cocaine or other drugs and did not drink excessively. His mother had systemic lupus erythematosis. His father had hypertension, well controlled with medications.
Diseases of the musculoskeletal system are divided into two categories systemic and local. Patients with systemic disease, such as rheumatoid arthritis, systemic lupus erythematosus, or polymyositis, may appear chronically ill, with generalized weakness, pain, and episodic stiffness of the joints. Patients with local disease are basically healthy individuals who suffer restriction of motion and pain from a single area. Included in this group are patients suffering from back pain, tennis elbow, arthritis, or bursitis. Although these patients may have only local symptoms, their disability can greatly limit their work capacity, and the disease can have a severe impact on the quality of their life.
Myocarditis is an acquired cardiomyopathy that is due to an inflammation of the heart with either an infectious (e.g., viral, bacterial, fungal), parasitic (e.g., Chagas' disease, toxoplasmosis), or autoimmune (e.g., systemic lupus erythematosus, rheumatoid arthritis, acute rheumatic fever, Kawasaki syndrome) etiology (DeMaso 2004 Maron et al. 2006).
Lupus erythematosus) or drugs, or it is idiopathic. AHA is uncommon but can be dramatic on presentation. About 50 of patients have no associated disease. The Coombs antiglobulin test, performed directly and indirectly determines the presence of antibody coating the patient's RBCs or free antibody in the plasma capable of binding to RBCs in AHA diagnosis. The autoantibodies may fix complement or may target the red cell for phagocytosis by the RES.
Diseases such as lupus, transverse myelitis from viral and postinfectious causes, delayed radiation necrosis, and uncertain causes.42 Spinal cord swelling on MRI is most frequent in postinfectious and radiation-induced causes. Lesions wide in diameter tend to extend over more levels in a postinfectious transverse myelitis than in MS or trauma. The spinal fluid in MS is likely to reveal oligoclonal bands, whereas the fluid in patients with a postinfectious cause tends to reveal no bands but may contain more than 30 white cells. Gadolinium enhancement of lesions may occur MS and other causes. For spinal infarcts and systemic disease etiologies, the MRI lesions involve more than 2 vertebral levels and are centromedullary. The mean level of injury with spinal cord infarction is T-8 and the mean sensory level is T-12, associated with the cord's relative hypovascular zone from T-4 to T-8.43
Particularly with the complex symptom presentation and variable course of SLE, the adjustment of adolescents with SLE is of high concern (Beresford and Davidson 2006 Seawell and Danoff-Burg 2004). The array of medical and psychological manifestations of SLE clearly taxes the available coping resources of both the child and adolescent with lupus and the family (Bricou et al. 2006). In an investigation of 120 women with SLE, Dobkin et al. (2001) provided important data to indicate that as a group, women with this illness generally cope adequately with their disease over time. However, Finally, one area of interest that has emerged from the chronic illness literature has been health-related quality of life (McElhone et al. 2006). Ruperto et al. (2004) provided important data to indicate that patients with SLE have significant impairments in their health-related quality of life, particularly in the physical domain. These investigators observed that quality of life among individuals with...
To date, there have been no published intervention programs designed to enhance psychosocial adjustment and quality of life in children and adolescents with lupus. In one clinical trial that was sponsored by the National Institute of Arthritis and Muscu-loskeletal Disorders (Brown et al. 2008), participants included adolescent females with SLE with a mean age of 15 years. Participants were randomly assigned to one of three arms cognitive-behavioral intervention, educational intervention, or a delayed no contact control condition.
One female, age 15, was coping with lupus since age 8. She talked about the physical effects of this illness, and also the developmental ones of an adolescent. She expressed a desire to be less dependent upon her mother in many areas that she lacks control in because of the illness. A major concern was her inability to take part in normal activities and her mother's overprotectiveness of her, resulting in an inability to go new places and experience a fuller life. (p. 90)
Acute pericarditis may occur as a result of infection of viral origin, secondary to underlying collagen vascular disease, such as rheumatoid arthritis and lupus erythematosus, secondary to trauma, typically post-cardiac-surgery, following acute myocardial infarction, in uremia, and sometimes secondary to invasive tumors. In all these states the cardiac motion against the inflamed pericardium with its two surfaces the visceral and the parietal will give rise to generation of friction noise, which is termed the pericardial friction rub. Often the diagnosis of acute pericarditis can be confirmed if a typical pericardial friction rub is heard. The rub could be transient and may be missed and sometimes absent because of accumulation of fluid between the two surfaces of the pericardium, preventing friction. The pericardial effusion, as a result of the inflammation, may, however, be detected by echocardiography. The friction rub is also sometimes quite localized either over the lower sternal...
Circulating antibodies, like lupus anticoagulant (LA) and anticardiolipin antibodies, may be related to stroke. The LA is a phospholipid antibody that interferes with the formation of the prothrombin activator. In the laboratory, there is a prolonged activated partial thromboplastin time (PTT). Some patients with LA have SLE, but most do not. When antiphospholipids of the IgG, IgM, or IgA classes are found in the absence of a known systemic illness, and patients present with an increased incidence of spontaneous abortions, thrombophlebitis, pulmonary embolism, and large- and small-artery occlusions, the disorder is now referred to as primary antiphospholipid lupus anticoagulant (APLA) syndrome. The APLA-associated stroke syndrome is characterized by its younger age at onset, predominance in women, and high risk of recurrent thrombo-occlusive events. Some patients have mitral and aortic valve vegetations and ocular ischemia. In addition to the presence of LA or anticardiolipins, or...
CIDP is an acquired motor and sensory neuropathy of unknown cause. As with GBS, an immune-mediated patho-genesis is suspected. Unlike GBS, CIDP usually occurs in the absence of a preceding illness. Unusual exceptions include HIV infection, dysproteinemias, and lupus erythematosus. CIDP is predominantly a motor polyneuropathy affecting those of all ages, with a progressive or relapsing course. Weakness can be proximal or distal but usually develops in the legs over at least 2 months, distinguishing CIDP from GBS. Sensory changes include numbness or paresthesias but can be variable. DTRs are decreased or absent. Electrodiag-nostic and CSF findings are similar to those found in GBS. Treatment includes prednisone, along with plasmapheresis or IVIG. CIDP should be distinguished from other acquired and hereditary neuropathies.
Primary Raynaud's usually affects both hands and both feet and is not connected to another disorder. Secondary Raynaud's symptoms are part of other conditions or medications such as scleroderma, a thickening of the skin systemic lupus, chronic inflammation of the skin rheumatoid arthritis, chronic inflammation and swelling of tissue in the joints nerve problems or the side effects of heart, blood, or migraine medications.
Antiphospholipid antibodies (aPL) are a heterogenous family of antibodies of the IgG, IgM, or mixed classes with varying cross- reactivities. Antibodies within this family include anticardiolipin antibodies, antibodies responsible for the false- positive Venereal Disease Research Laboratory (VDRL) serology and the lupus anticoagulant. Antiphospholipid antibodies may be detected in a number of clinical settings. Normal elderly may have aPL of unclear significance. They may be seen in patients treated with phenothiazines, antiarrhythmics, and anticonvulsants, or in the context of infections or malignancy. Antiphospholipid antibodies are commonly seen in patients with systemic autoimmune disorders such as systemic lupus erythematosus. The primary antiphospholipid antibody syndrome comprises recurrent venous or arterial thrombosis, fetal loss, thrombocytopenia and positive results on serological tests for lupus anticoagulant or anticardiolipid antibodies....
Ethosuximide has been marketed in the United States since 1960 for the treatment of AS. It is the drug of choice in AE without TCS, against which it is ineffective. Ethosuximide blocks T-type Ca2+ channels that trigger and sustain rhythmical burst discharges in thalamic neurons. Trimethadione, which is no longer available in the United States, is the only other agent with a similar mechanism of action. Ethosuximide does not induce hepatic microsomal enzymes and is not protein-bound. Idiosyncratic reactions include headache, hiccups, blood dyscrasias, lupus-like syndromes, behavioral disturbances, and parkinsonism. Ethosuximide is available in 250 mg capsules and syrup (250 mg 5 ml). Carbamazepine, available in the United States since 1974, has a similar mechanism and spectrum of action as phenytoin. The carbamazepine-10, 11-epoxide metabolite also possesses anticonvulsant properties. Autoinduction occurs during the first several weeks of therapy, necessitating gradual titration....
In systemic lupus erythematosus (SLE), only two small uncontrolled studies (including together five men among 17 patients) using androgen therapy (nandrolone decanoate) have been reported (Hazelton et al. 1983 Lahita et al. 1992). This information is so limited that no conclusions can be drawn without larger and better-designed studies. Another double-blind study randomised 28 women with mild to moderate SLE to treatment with DHEA (200 mg daily) or placebo for three months. Treatment with this weak androgen precursor did not improve SLE disease activity index, number of flares, prednisone usage or physician overall assessment, although there was an improvement in the patients overall assessment of well-being (Van Vollenhoven etal. 1995).
Mediated diseases of the connective tissue (systemic lupus erythematosus SLE , scleroderma, polyarteritis nodosa, rheumatic fever, ankylosing spondylitis, and Reiter's syndrome) are discussed. Fig. 13. (Color Plate 9, following p. 270) Mixed connective tissue diseases (lupus, rheumatoid arthritis, scleroderma). (A) The patient had a mask facies with puckering of skin around lips and malar depigmentation. (B) The patient's hand showed ulnar deviation of the metacarpophalangeal (MP) joints as well as a taut shiny skin. Fig. 13. (Color Plate 9, following p. 270) Mixed connective tissue diseases (lupus, rheumatoid arthritis, scleroderma). (A) The patient had a mask facies with puckering of skin around lips and malar depigmentation. (B) The patient's hand showed ulnar deviation of the metacarpophalangeal (MP) joints as well as a taut shiny skin. Systemic Lupus Erythematosus SLE
The major serologic finding in the majority of patients is the presence of low-molecular-weight C1q precipitins, which have been demonstrated in most cases to be antibody to the C1q molecule (96). These antibodies can be demonstrated in this syndrome as well as in SLE, findings that are consistent with the original description of the low-molecular-weight C1q precipitin that was reported to be present not only in the first case of HUVS but in SLE patients as well (48). The majority of patients can be distinguished from those with SLE serologically because the majority of patients with the syndrome have negative ANA tests, negative assays for lupus erythematosus cells, and negative assays for dsDNA. A small number of patients identified were found to have low titered antibodies to Sm antigen. When patients with SLE were tested for anti-C1q antibodies by enzyme-linked immunosorbent assay (ELISA) 33.6 of 113 patients were positive (97). Plasma titers of anti-C1q antibodies were inversely...
Large chronic single ulcers may result from fungal infections such as aspergillosis or histoplasmosis. Infections by herpes simplex virus, cytomegalovirus, Mycobacterium organisms (which cause tuberculosis), and Treponema pallidum (which causes syphilis) are also well-known causes of this type of ulcer. Immunologic disorders such as pemphigus, systemic lupus erythe-matosus, bullous pemphigoid, and erosive lichen planus are often the cause of chronic multiple ulcers.
Although historically bilateral adrenal hemorrhage is associated with meningococcemia in children (Waterhouse-Friderichsen syndrome), bilateral adrenal insufficiency occurs most commonly in adults in association with anticoagulant therapy. Clinical conditions producing coagulopathies such as thrombocytopenia, anticardiolipin antibody, and lupus anticoagulant also result in bilateral adrenal hemorrhage. Trauma, either directly or through the destruction of the blood supply to the adrenal, may result in bilateral adrenal hemorrhage. Septicemia, although more commonly a cause of adrenal hemorrhage in children, may lead to adrenal hemorrhage in adults. Stress associated with illness, sepsis, or burns may lead to bilateral adrenal hemorrhage. Because of the rapidly fatal outcome of bilateral adrenal hemorrhage, the surgeon must suspect this clinical entity in these settings. Although Goolden in 185722 recognized the clinical entity of bilateral adrenal hemorrhage, not until the advent of...
Corticospinal tract produces an ipsilateral spastic weakness. Also, ipsilateral loss of proprioception below the level of the lesion results from interruption of the ascending fibers in the posterior columns. Loss of pain and temperature sensation occurs contralateral to the hemisection because the crossed spinothalamic tract is interrupted. The sensory level that is responsive to pain and temperature is usually located one or two segments below the level of the lesion. When the Brown-Sequard syndrome results from an extramedullary lesion, there may be segmental lower motor neuron and sensory signs at the level of the lesion due to damage to the roots and anterior horn cells, and these signs are the most reliable indication of the level of the lesion. This syndrome is most apparent in patients with traumatic hemisections of the spinal cord (e.g., due to a stab wound). Other causes are extramedullary tumors or abscesses and, less commonly, intrinsic lesions, especially vasculitis (as...
Homozygous C2 deficiency has an approximate prevalence of 1 20,000 in the western European Caucasian population. Over 100 patients with homozygous C2 deficiency have been reported (47). C2 deficiency was the first complement deficiency reported to be associated with SLE. This disease association has been confirmed as shown in a study of the first 52 kindred reported with homozygous C2 deficiency (48). Twenty-eight patients (34 ) had lupus disease with a female to male ratio of 8 1. Eighteen patients (22 ) were diagnosed as SLE but only 14 fulfilled ARA criteria for the diagnosis of SLE. The atypical aspects of the lupus disease present in the original index case (13) were also confirmed 10 patients, a third of the patients had atypical cutaneous LE. Idiopathic glomerulonephritis was present in 9 patients and recurrent infection in 8 patients 7 of the 9 patients with glomerulonephritis were males. The 8 patients with recurrent infections were all young children. Frequent infections...
Conditions to exclude include other mitochondrial diseases, primarily MERRF and MELAS any disease causing ophthalmoplegia when that is the sole presenting symptom, especially myasthenia gravis other diseases that cause multisystem involvement, such as collagen vascular diseases, particularly systemic lupus erythematosus and in the appropriate setting, Lyme disease (caused by infection with Borrelia burgdorferi) or Whipple's disease. The ultimate diagnosis is made by muscle biopsy and mtDNA analysis. There is no proven specific treatment, although coenzyme Q10 and carnitine have been used. Implanted cardiac pacemakers can be used for conduction defects. Associated endocrine abnormalities--growth hormone deficiency, diabetes mellitus, or hypoparathyroidism--can be treated medically. Although these conditions are considered chronic, complete heart block may result in sudden death.
Cerebral venous thrombosis (CVT) is an uncommon condition. Basic mechanisms of CVT include venous stasis, increased clotting tendency, and traumatic or infective changes in the venous walls. Various endocrine, hematological, immunological, vasculitic, infective, and neoplastic diseases may be associated with CVT. y In neonates and children, regional infections (otitis media and mastoiditis), neonatal asphyxia, severe dehydrations, and congenital heart diseases are common associated diseases. In young women, pregnancy, puerperium, oral contraceptive pills, and various connective tissue diseases like systemic lupus erythematosus are the major causes. Other causes include malignancies, antithrombin III protein C and protein S deficiencies, and Behcalet's disease. y , y
SS is seen in 0.5 to 2.0 percent of the population among the collagen vascular diseases, it is second in prevalence only to rheumatoid arthritis. 107 Ninety percent of patients are women. Onset usually occurs during middle age. 107 Genetic susceptibility is suggested by an association with HLA-B8, HLA-DR3, HLA-DR2, and HLA-DRw52. SS occurs in isolation in 50 percent of cases and in the context of rheumatoid arthritis, systemic lupus erythematosus, scleroderma, or another connective tissue disease in the remaining patients. 107
More typical SLE occurs among individuals with C5-C8 deficiencies. One case of homozygous C5 deficiency with SLE has been reported (57). There were no unusual features of SLE in this case. The lupus erythematosus, ANA, and dsDNA antibody tests were positive. The prominent skin lesions were typical of lupus. There were deposits of immunoglobulin and complement along the dermal-epidermal junction. There are three cases of homozygous C6 deficiency with SLE or SLE-like disease (58-60). One case had typical SLE, and one case had SLE-like disease with polyarthritis, pleurisy, and Raynaud's phenomenon. The lupus erythematosus and dsDNA tests were negative, the ANA was weakly positive, and an ssDNA test was positive. The third case had discoid lupus and Sjogren's syndrome with negative serologic test studies. Two cases of C7 deficiency have been reported with classical seropositive SLE (61). Two cases of C8 deficiencies have been reported one had classic seropositive SLE and the other had...
Differential diagnoses include other vasculopathies and autoimmune diseases such as systemic lupus erythematosus, scleroderma, polyarteritis nodosa, antiphospholipid antibody syndrome, GCA or TA. Other conditions such as pseudoxanthoma elasticum and Ehlers-Danlos may be considered as well. It is important to exclude proximal sources of emboli and atherosclerosis. y
There is no conclusive evidence that CIDP patients have a higher incidence of other medical conditions, including autoimmune disorders. However, associated disorders, including systemic lupus erythematosus, Hashimoto's thyroiditis, thyrotoxicosis, chronic active hepatitis, inflammatory bowel disease, urticaria, eczema, and psoriasis do occur in some CIDP patients.y A CIDP-like disorder may occur in the setting of monoclonal gammopathies of uncertain significance (MGUS), as well as with multiple myeloma, osteosclerotic myeloma and other lymphoproliferative disorders. These disorders are discussed as distinct entities in the following sections.
Non-infective endocarditis is termed nonbacterial thrombotic endocarditis (NBTE). It is characterized by the accumulation of sterile platelet and fibrin aggregates on the heart valves to form small vegetations. About 50 of NBTE cases occur in association with cancer, especially mucin-producing adenocarcinomas (particularly pancreatic carcinoma and non-small-cell lung cancer) and hematological malignancies (lymphoma and leukemia 24 ). Although only less than 2 of patients with cancer have NBTE, up to 50 of these patients with NBTE suffer from stroke 25 . A significant proportion of patients with NBTE have other disorders, including rheumatic heart disease, rheumatological diseases such as lupus (where it is referred to as Lipman-Sacks endocarditis), AIDS, gastrointestinal diseases such as cirrhosis, and severe systemic illness, such as burns or sepsis 26 . Small and large multi-territorial infarction is a radiographic sign in NBTE 27 . Thus, encephalopathy rather than focal deficits...
Antiphosholipid syndrome, systemic lupus erythematosus and other connective tissue diseases. In de Swiet, ed. Medical Disorders in Obstetric Practice, 4th edn. Oxford Blackwell Science, 2002 267-81 26. van Besien K, Hoffman R, Golichowski A. Pregnancy associated with lupus anticoagulant and heparin induced thrombocytopenia management with a low molecular weight heparinoid. Thromb Res 1991 62 23-9
In cystic fibrosis, 303, 304, 306, 308, 309 in sickle cell anemia disease, 1145t Lung transplantation. See also Solid-organ transplantation acute rejection, signs and symptoms of, 944t epidemiology and etiology of, 941 Lupus erythematosus, allergic drug reaction, 929t Luteinizing hormone at menopause, 870-871 in menstrual cycle, 843, 856, 856f Luteinizing hormone-releasing hormone, 1546 Luteinizing hormone-releasing hormone agonists in breast cancer, 1485, 1486t in cancer, 1468
Splinter hemorrhages are formed by extravasation of blood from longitudinal nail bed blood vessels into adjacent troughs. Splinter hemorrhages are very common. It has been estimated that up to 20 of all hospitalized patients have splinter hemorrhages. Their presence is most often related to local, light trauma, but these hemorrhages are commonly associated with systemic disease. Classically associated with subacute bacterial endocarditis, splinter hemorrhages may also be seen in leukemia, vasculitis, infection, rheumatoid arthritis, systemic lupus erythematosus, renal disease, liver disease, and diabetes mellitus, among other diseases. Splinter hemorrhages are depicted in Figure 8-10.
The two extremes of the disease may coexist. In these cases, the proximal third of the nail is atrophic and the distal two-thirds exhibits hypertrophic changes. The histopathological changes are non-specific, although they do enable the exclusion of a diagnosis of psoriasis, lupus erythematosus or other similar eruptions.
Patients on long-term high-dose amiodarone (600 mg d for 2 yr) may develop a blue-gray dermal melanosis ofthe face, especially ofthe areas exposed to the sun (131). It may take several months for the skin discoloration to resolve after stopping the drug because of its long half-life (132,133) (Fig. 17). A lupus-like syndrome has also been reported with amiodarone (134). Hyperthyroidism, hypothyroidism, liver dysfunction, and pulmonary fibrosis are other side effects of amiodarone (131). A lupus-like syndrome may occur with the use of procaine amide, but the butterfly rash is rarely seen (135). Pericarditis may also occasionally be seen (136). This drug may also produce a lupus-like syndrome and rarely a pericarditis (136). A malar butterfly rash is more often seen than in procaine-amide-induced lupus (136). This drug may produce a lupus-like syndrome but without the malar butterfly rash (135).
Episcleritis is a common, benign inflammatory condition of the episclera. It most often affects young adults. Most cases are idiopathic, though up to a third may be associated with systemic conditions, and some cases may also be caused by exogenous irritants or inflammatory stimuli. Associated systemic disorders include gout, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, and herpes zoster. The symptoms, which include foreign body sensation, mild pain, photophobia, and lacrimation, are generally self-limited. Visual acuity is normal.
In psoriasis (Figures 4.2-4.4) there is usually a yellow-red margin visible between the pink normal nail and the white separated area. In the 'oil spot' or 'salmon patch' variety, the separation between nail plate and nail bed may start in the middle of the nail this is sometimes surrounded by a yellow margin, inflammatory and eczematous diseases affecting the nail bed. Oil patches have been reported in systemic lupus erythematosus they may be extensive in lectitis purulenta et granulomatosa.
P., Osgood, S. A., Hayag, M. S., Barstad, P. A., Iverson, G. M., Coutts, S. M. (1994). Conjugates of double-stranded oligonucleotides with poly(ethy-lene glycol) and keyhole limpet hemocya-nin a model for treating systemic lupus erythematosus. Bioconjug Chem 5, 390-399.
A second disease for which convincing evidence survives is arthritis. According to Fernando Cabieses (1979), Peruvian museums have many vertebrae and bones that reveal typically rheumatic injuries. While examining these remains, A. Hrdlicka discovered a type of arthritis of the hip in adolescents, which modern experts identify as Calve-Perthes disease (Cabieses 1979). Another specific study on bone lesions in skeletons from Chancay, in coastal Peru, documents osteoarthritis in the skeletal remains (Berg 1972), and Jane Buikstra (in this volume, V.8) reports a convincing case of juvenile rheumatoid arthritis in an adolescent from the Tiwanaku period. A mummy of a young girl of the Huari culture exhibits one of the earliest known cases of collagen disease with many aspects compatible with SLE (systemic lupus erythematosus) (Allison et al. 1977).
Idiopathic thrombocytopenic purpura (ITP) Thrombotic thrombocytopenic purpura (TTP) Hemolytic uremic syndrome (HUS) Systemic lupus erythematosus Viral infection (HIV, CMV, EBV) Antiphospholipid antibodies Consumptive coagulopathy Drug-induced thrombocytopenia Type 2B von Willebrand disease Congenital The diagnosis of primary antiphospholipid syndrome requires the coexistence of clinical manifestations (either vascular thrombosis or pregnancy morbidity) with laboratory evidence of reproducible antiphospholipid antibodies (either lupus anticoagulant or anticardiolipin antibody)19. Primary antiphospholipid syndrome is associated with autoimmune thrombocytopenia in 20-40 of cases20. Thrombocytopenia is rarely severe and usually does not require treatment. If treatment is necessary, management options during pregnancy are similar to those for primary ITP. However, primary antiphospholipid syndrome is associated with recurrent spontaneous abortions before 10 weeks of gestation, and women...
To the overuse of glucose in the case of an insulinoma or to the underproduction of glucose. In many other instances, including alcoholism and hormone insufficiency syndromes, hypoglycemia can be due to antibodies that bind to insulin and release it inappropriately. This may be seen in multiple myeloma and systemic lupus erythematosus. A differentiation can often be made clinically by the amount of glucose that must be infused intravenously to prevent hypoglycemia and by testing for anti-insulin antibodies. Daily hepatic production of glucose ranges from 100 to 200 g. If more than 200 g of glucose is required to offset the hypoglycemia, the patient suffers from overuse of glucose, which would support the diagnosis of insulinoma.13
Phototoxicity should be suspected in any patient with severe or exaggerated sunburn. Photoallergy is easily misdiagnosed as allergic eczema or contact dermatitis, especially since onset is often delayed up to 2 days after exposure. Phytophotodermatitis may mimic severe sunburn or contact dermatitis, especially rhus dermatitis. Endogenous photosensitizers (endogenous photodermatoses) include solar urticaria, porphyria cutanea tarda, polymorphous light eruption, and systemic lupus erythrematosus. These may be provoked by visible light as well as by UV radiation.
Some cases of keratoconjunctivitis sicca are related to an autoimmune cause, particularly those patients with dry-ness of other mucous membranes. It also often occurs with rheumatoid arthritis, systemic lupus erythematosus, and Sjogren's syndrome. Initial treatment includes lubrication with artificial tears and ointments to supplement or replace the tear film deficit. In moderate or severe cases, an ophthalmologist may need to occlude the eyelid punctum surgically and perform a tarsorrhaphy to protect the corneal surface. Moisture chambers may also be prescribed. Topical antibiotics are required only if secondary infection occurs. Cyclosporine 0.05 (Restasis) is also useful in addressing inflammatory components of tear film insufficiency, when other treatments are insufficient.
Tobacco smoke on the intrapulmonary vessels has also been implicated, causing abnormal production of mediators that control vasoconstriction, vasodilatation, and vascular cell proliferation, leading to abnormal vascular remodeling and aberrant vascular physiology. These changes are similar to those seen in other forms of pulmonary hypertension. The vessels themselves may become distorted, occluded, and entrapped in replacement fibrosis, as may occur with various forms of interstitial pulmonary fibrosis. In addition, the vessels may be involved in a vasculitis. This may be an important mechanism in some disorders, such as collagen vascular disease (e.g., progressive systemic sclerosis, lupus erythematosus, and rheumatoid arthritis).
The number of involved joints and presence or absence of symmetry are criteria for further diagnosis of articular pain (Figs. 32-1 and 32-2). Monoarticular (one joint) or oligoarticular (several joints) arthritides can be caused by conditions such as osteoarthritis (OA), gout, pseudogout, or septic arthritis. Asymmetric polyarthritis occurs in ankylosing spondylitis, psoriatic arthritis, Reiter's disease, and spondyloarthropathies. Symmetric arthritis, meaning that the same joint is affected on the contralateral side but not necessarily to the same degree, is characteristic of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren's syndrome, polymyositis, and scleroderma. Fibromyalgia, reflex sympathetic dystrophy, and predominantly psychological Figure 32-1 Evaluation of monoarticular or pauciarticular symptoms. ANA, Antinuclear antibodies CBC, complete blood cell count ESR, erythrocyte sedimentation rate JRA, juvenile rheumatoid arthritis LFTs, liver function tests...
Prevalence rates of neuropsy-chiatric manifestations vary widely and range from 20 to 95 these variable rates may be due to lack of standard definitions in the literature and to the frequency of lupus-associated headaches (Benseler and Silverman 2007). Common neuropsychiatric sequelae include headaches, psychiatric manifestations (e.g., anxiety disorders, mood disorders, psychosis, cognitive dysfunction, and acute confusional state), cerebrovascular disease, seizures, and choreiform movements (Benseler and Silverman 2007). In the clinical setting, psychiatric consultations frequently are requested to assist in differentiating CNS lupus flares from corticosteroid-induced psychosis. Most of the guidance for this differential diagnosis in pediatric patients comes from case reports reported in the literature. Nonetheless, corti-costeroid-induced psychosis is believed to be rare and may be ruled out if occurring in the presence of common features of CNS lupus flares...
On examination can suggest very specific syndromes. Evidence of small vessel disease suggests systemic lupus erythematosus, a disorder associated with chorea flushed skin and vascular evidence of hyperviscosity suggests polycythemia, associated with chorea and ballism and vascular neck disease or evidence of cardiac embolic sources raises the possibility of multifocal strokes that can lead to parkinsonism or hyperkinesias.
It can be classified into scarring (absence of follicles) and nonscarring (presence of follicles) alopecia. Scarring alopecia is commonly caused by discoid lupus erythematosus (erythematous mottled pigmentation and atrophic scalp scarring) and folliculitis decalvans (multiple crops of pustules on the scalp). Occasionally, prolonged bacterial and inflammatory fungal infections (kerion) can induce scarring on the scalp. Nonscarring alopecia results from alopecia areata (annular areas of alopecia on the scalp or beard area), telogen effluvium (diffuse scalp shedding of hair 2 to 3 months after a stressful event, illness, or new medication), anagen effluvium (diffuse scalp shedding after chemotherapy), trichotillomania (constant pulling of the hair), traction alopecia (chronic tension of braided hair causing alopecia), and tinea capitis. Syphilis can cause a patchy, moth-eaten alopecia.
C4-deficient patients of two types have been characterized complete C4 deficiency, in which both the C4A and C4B protein products are absent, and partial C4 deficiencies, in which C4 levels are decreased and one or more of the genes for either C4A or C4B genes are missing. Complete C4 deficiency is rare among 25 reported patients 21 (84 ) had SLE or SLE-like disease (2937). Seventeen patients had skin rash, predominately with photosensitivity lupus band test were negative in four of the five cases studied. Nine patients had mainly mild glomerulonephritis the mesangial type was present in all seven cases characterized. ANA was negative or weakly positive in 10 of 20 patients tested. DNA antibody tests were negative in 9 of 11 patients tested. Anti SS-A(RO) was positive in 6 of 8 patients tested. The female to male ratio of affected patients was 2 1. There were two asymptomatic patients and single Partial deficiencies may exist in individuals who are missing one, two, or three of the C4...
The overwhelming evidence is that myasthenia gravis is due to an immune system dysfunction that produces an autodirected antibody against the acetylcholine receptor in the postsynaptic membrane of the neuromuscular junction. The evidence is clinical, laboratory, serologic, and therapeutic. The clinical evidence that myasthenia is an autoimmune disease is based on the association of myasthenia with vaccination, insect sting, infection, or trauma and its association with autoimmune diseases such as hypothyroidism, systemic lupus, and polymyositis. Many laboratory abnormalities point to the immune system dysfunction in myasthenia gravis. These include serologic abnormalities, increased incidence of a specific human leukocyte antigen (HLA-B8) in certain types of disease, histologic abnormalities of thymus and skeletal muscle, and abnormal responsiveness of lymphocytes to mitogens. Antinuclear antibodies are positive in uncomplicated myasthenia in about 18 percent of cases and in 54...
Basic coagulation studies in acquired hemophilia demonstrate a prolonged APPT with a normal PT and thrombin time (TT). If plasma from the patient is mixed with normal plasma, the APPT remains prolonged due to the inhibitor antibody neutralizing the FVIII in the normal plasma. FVIII inhibitors must be differentiated from a lupus inhibitor by specific tests because the clinical implications are profoundly different. Quantification of FVIII inhibitor is by the Bethesda assay, and checking this level may help in determining the choice of therapy and monitoring the progress of the patient.
Neutralizig monoclonal antibodies (mAb) to late C components appear to be more promising as therapeutic agents and so far mAbs to C5 have proved to be effective in vivo in preventing the onset and progression of collagen-induced arthritis (Wang, 1995), in ameliorating the glomerulonephritis in lupus prone mice (Wang, 1996), in reducing the size of infarct areas and the degree of apoptosis following myocardial ischemia and reperfusion (Vakeva, 1998), and in preventing hyperacute rejection of xenotranplanted organs (Wang, 1999). A humanized scFv anti-human C5 now available for clinical trials has been found to attenuate myocardial damage, cognitive deficits and blood loss in patents undergong ardiopulmonary bypass (Fitch, 1999) and is now being tested in chronic inflammatory diseases including rheumatoid arthritis, glomerulonephritis and other autoimmune diseases together with another variant form (Kaplan, 2002).
C activation products including TCC are usually found in plasma (Porcel, 1995), biological fluids (Sanders, 1988) and at tissue level, particularly kidney and skin (Biesecker, 1983 Biesecker, 1982) in patients with SLE. The levels of TCC, C3a and C4a increase significantly in these patients, as compared to those observed in patients with stable lupus and normal controls, and correlate with the score of disease activity representing therefore the most useful parameter to monitor the disease activity in terms of sensitivity and specificity (Porcel, 1995) even in the absence of clear changes in the levels of C3 and C4 (Gawryl, 1988 Falk, 1985). Increased levels of TCC are detected in the cerebrospinal fluid and serum in patients with Sjogren's syndrome presenting with clinical sign of involvement of the central nervous system (Sanders, 1988).
Several reports have presented evidence about the contribution of MBL deficiency in autoimmune diseases. In a number of studies involving patients with systemic lupus erythematosus (SLE), a higher incidence of MBL deficient subjects was documented than in the control groups (Davies et al., 1995 Lau et al., 1996 Sullivan et al., 1996 Davies et al., 1997). The adverse effects of MBL mutations on the propagation of rheumatoid arthritis (RA) have also been recognized (Garred et al., 2000 Graudal et al., 1998 Graudal et al., 2000 Ip et al., 2000). In a study on 128 type I diabetes Japanese patients MBL deficiency has been suggested to be a minor risk factor for possessing the disease (Tsutsumi et al., 2003). In contrast to the above observations a study on Japanese patients failed to detect any significant correlation between mutant MBL alleles and the occurrence of SLE or RA (Horiuchi et al., 2000). Moreover, Garred and coworkers found that RA patients with normal MBL alleles are more...
Deficiencies of C1r and C1s are rare but can cause severe disease conditions. The most common consequences of these deficiencies are systemic lupus erythematosus (SLE)-like syndromes and severe pyogenic infections. It has long been suggested that the SLE-like symptoms are the consequences of the inappropriate handling of immune complexes. Deficiency of C1r and C1s are almost exclusively coupled, probably due to the close physical proximity and the coordinated expression of the two genes (Morgan and Walport, 1991). However, recent studies revealed that selective and complete C1s deficiencies also exists (Inoue et al., 1998 Dragon et al., 2001). C1r and C1s have very restricted substrate specificities C1r can autoactivate and cleave C1s while C1s can cleave C2 and C4. Several lines
Systemic lupus Studies of systemic disorders, such as lupus erythematosus, Sjogren's syndrome, thyroid and adrenal disease, AIDS, and cancer, describe mood symptoms in subsets of patients. As with the more diffuse neurodegenerative diseases, such as Alzheimer's disease (Cummings and Victoroff, 1990), a classic lesion-deficit approach is generally difficult because consistent focal abnormalities are uncommon. Studies of plaque loci in patients with multiple sclerosis suggest an association of depression with lesions in the temporal lobes, although it is not yet clear whether this effect is lateralized (Honer et al., 1987).
In addition, low DHEAS levels may be a non-specific marker of poor health status and thereby associated with an increased risk of severe illness and death. Low DHEA(S) concentrations have been found in systemic lupus erythematosus, dementia, breast cancer and rheumatoid arthritis and there is an inverse relationship between serum DHEAS levels and severity of disease (Deighton etal. 1992). Chronic disease often leads to a shift of intra-adrenal biosynthesis away from DHEA(S) production favoring cortisol secretion (Parker etal. 1985). Thus, low DHEAS levels may indicate the presence of a not yet apparent disease, which determines a future risk of morbidity or even mortality.
Changes in large arteries supplying the brain, including the aorta, are mainly caused by atherosclerosis. Middle-sized and intracerebral arteries can also be affected by acute or chronic vascular diseases of inflammatory origin due to subacute to chronic infections, e.g. tuberculosis and lues, or due to collagen disorders, e.g. giant cell arteriitis, granulomatous angiitis of the CNS, panarteritis nodosa, and even more rarely systemic lupus erythematosus, Takayasu's arteriitis, Wegener granulomatosis, rheumatoid arterii-tis, Sjogren's syndrome, or Sneddon and Behcet's disease. In some diseases affecting the vessels of the brain the etiology and pathogenesis are still unclear, e.g. moyamoya disease and fibromuscular dysplasia, but these disorders are characterized by typical locations of the vascular changes. Some arteriopathies are hereditary, such as CADASIL (cerebral autosomal
Mutations in the MTHFR gene Prothrombin AG20210 mutation FV-Leiden mutation Factor VIII Acquired prothrombotic conditions Homocysteine Vitamin B12 Folic acid Inflammatory diseases Lupus anticoagulant Anticardiolipin IgG and IgM antibodies Anti-beta2-GP IgG and IgM antibodies Anti-prothrombin IgG and IgM antibodies
Particularly prothrombin gene and factor V Leiden mutations, and prothrombin mutation, as well as antithrombin, protein C and protein S deficiencies must be considered. Other conditions with risk for CVT are malignancies, inflammatory diseases and systemic lupus erythematodes. However, in 20-35 of CVT the etiology remains unknown.
In a number of studies DHEA supplementation has been used to modify immune functions and alter the course of immunopathies. Most studies have been performed in patients with systemic lupus erythematosus (SLE), a chronic autoimmune inflammatory disease of unknown etiology (Chang et al. 2002 Petri et al. 2002 Van Vollenhoven et al. 1995). The concept to use DHEA in the treatment of SLE was based on the observation that women are more often affected and that androgens and DHEA concentrations are low in patients with SLE (Lahita et al. 1987). Moreover, androgen treatment can modify the disease progression in an animal model of SLE (Melez et al. 1980). After preliminary evidence of a glucocorticoid-sparing effect of DHEA in patients with mild SLE (Van Vollenhoven et al. 1994) a randomized double-blind placebo-controlled trial was performed (200 mg DHEA orally for three months) (Van Vollenhoven et al. 1995). It demonstrated beneficial effects of DHEA on patient and physician overall...
The nomenclature for the disease differs somewhat, but in general it is called Raynaud disease, or primary Raynaud phenomenon, if these symptoms occur without evidence of any other associated disease process. In contrast, secondary Raynaud phenomenon occurs when the symptoms occur in association with a related disease process such as systemic lupus erythematosus or scleroderma.
Other disease-related factors that place people at greater risk of Achilles rupture include rheumatoid arthritis, lupus erythe-matosus, hypercholesterolemia, gout, dialysis, renal transplant, steroid therapy, endocrine dysfunction, infection, tumor, autoimmune disorders, diabetes mellitus, and the use of fluoroquinolones.
Autoimmune cerebritis including giant cell arterits, primary CNS artentis, and hypersensitivity arteritis and autoimmune induced dysautonomic states irom penpheral nervous system involvement including polyartentis and Wegener's granulomatosis. Systemic lupus erythematosus can affect either central or peripheral systems
Trigeminal sensory neuropathy may occur in association with connective tissue disorders such as mixed connective tissues disease, systemic sclerosis, Sjogren's syndrome, and systemic lupus erythematosus.1 , y Symptoms including facial dysesthesias, numbness, and loss of taste may be the presenting complaints. y In such cases, based on radiographical and electrophysiological testing, involvement of the gasserian ganglion is likely. Various infectious processes within the middle cranial fossa including syphilis, tuberculosis, and bacterial meningitis can affect the gasserian ganglion by inflammation, ischemia, or direct compression. Similarly, neoplasms in this region (meningiomas, schwannomas) can compress the ganglion within Meckel's cave.
Proptosis or periorbital fullness suggests an orbital process such as Graves' disease, orbital meningioma, or orbital pseudotumor. The patient's general appearance may suggest an underlying chromosomal, endocrinological, or metabolic disorder. For instance, the disfiguring frontal bossing and enlargement of the mandible and hands are characteristic of acromegaly associated with a growth hormone-secreting pituitary adenoma. The heart rate, blood pressure, and carotid and cardiac examinations are important in any patient with a possible ischemic event. Patients with pseudotumor cerebri tend to be young females with obesity or a history of recent weight gain. Skin lesions such as erythema migrans (Lyme disease) or malar rash (systemic lupus erythematosus), and abnormal discolorations, such as cafe(c)-au-lait spots and axillary freckling (neurofibromatosis), or hypopigmented ash-leaf spots (tuberous sclerosis) also may be helpful in guiding the evaluation of patients with visual...
Patients with sarcoidosis may have skin and cardiac involvement. The skin lesions that involve the face may take two forms red papules around the eyes, nose, and mouth, which are pruritic and do not ulcerate purple plaques that produce a bulbous nose, thickened cheeks, and thickened ears (lupus pernio) (101). There may also be erythema nodosum (red nodules on the legs) (101). Twenty percent of patients with sarcoidosis have cardiovascular findings at autopsy (102,103). Clinical manifestations include congestive heart failure, ventricular tachycardia, complete heart block, or cor pulmonale (102,103).
Laboratory studies may reveal evidence of vasculopathies like systemic lupus erythematosus or Sjoren's syndrome. White blood count elevations may suggest infections, and eosinophilia may indicate fungal disease. Altered glucose tolerance is seen with diabetes mellitus. Vitamin levels may indicate deficiencies of thiamine, folate, B12 , pyridoxine, or vitamin A.
Helper 2-type (Th2-type) immunity and successful pregnancy, whereas Th1-type immune reactivity is associated with pregnancy loss (12). Fetomaternal tolerance is partially dependent on the secretion of immunoregulatory cytokines, such as TGF-P and IL-10, by the decidua and placenta (13-16). These cytokines may promote the development of Th2-type cells and regulatory T cells that provide immunosuppressive mechanisms important in fetal survival. Conditions associated with recurrent spontaneous miscarriages and preterm labor are associated with an inflammatory reaction, the production of proinflammatory cytokines such as TNF-a IL-6, IL-1, and INF-7, and a conversion from a Th2 to a Th1 phenotype (14, 17). That autoimmune disorders, such as systemic lupus erythematosus (SLE) and the antiphospholipid syndrome are associated with poor pregnancy outcome underscores the critical role of the maternal immune response (18). Abnormalities in fetal regulation of the maternal immune response, even...
Unlike humans, in the mouse there are two Daf genes, Daf1 and Daf2. The Daf1 gene, like the human DAF gene, encodes GPI-anchored DAF that is ubiquitously expressed, while the Daf2 gene encodes transmembrane anchored DAF that is restricted in its distribution to the testes and spleen (Lin et al., 2001). Consequently for an animal model, the Daf1 gene was targeted. Daf1 knock-out mice (Lin et al., 2001 Miwa, 2001) provide a resource for studying several experimental animal models of disease including experimental autoimmune myasthenia gravis (EAMG), a murine model of systemic lupus erythrematosus (SLE) in MRL lpr mice, acute nephrotoxic serum (NTS)-induced nephritis, and dextran sodium sulfate (DSS)-induced colitis. In EAMG, the binding of anti-acetylcholine receptor (AChR) antibodies to the post-synaptic junction activates the classical pathway, ultimately leading to endplate damage (De Baets et al., 2003). Following anti-AChR mAb administration, as compared with Dafl* + littermates...
An association between maternal lupus erythematosus and congenital complete heart block was reported in 1966,40 and a decade later the association was confirmed.* Sinus node disease may occur in children with prenatal exposure to anti-Ro or anti-La antibodies.79 Complete heart block in utero or at birth is strongly associated with maternal antibodies to 48-kD SSB La, 52-kD SSA Ro, and 60-kD SSA Ro ribonucleoproteins and is strongly associated with the neonatal lupus syndrome.12 The fetal sinoatrial and atrioventricular nodes may calcify.2a Congenital heart block has emerged as an important model of passive
Scleroderma associated with Raynaud's phenomenon, disseminated lupus erythematosus, and causalgia of the median nerve. The condition may be idiopathic, congenital, and familial or acquired. A congenital, aberrant, painful hyponychium has been described associated with oblique, deep fractures of the nails. In one case an unusual acquired association of pterygium inversum unguis and lenticular atrophy of the palmar creases was recorded.
Geographic location Leishmaniasis (Spain), melioidosis (Southeast Asia, Australia), Kikuchi-Fujimoto disease (form of necrotizing lymphadenitis, Japan). Connective tissue diseases Juvenile rheumatoid arthritis (JRA, Still's disease), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), temporal arteritis, polymyalgia rheumatica (PMR). Neoplasms malignant neoplasm, lymphoma, leukemia. Other Familial Mediterranean fever in Ashkenazi Jews.
Sive medical workup to rule out serious medical illness, physicians should make an effort to avoid unnecessary and potentially harmful tests and procedures. Campo and Fritz (2001) noted that when somatization was presumed, the likelihood of subsequently discovering a previously undiagnosed physical disease was less than 10 . Nevertheless, certain physical illnesses are commonly overlooked and should be carefully considered as part of the diagnostic workup (see Table 8-5). Some medical conditions that may be confused with somatoform disorder include migraine syndromes, temporal lobe epilepsy, and central nervous system tumors (De-Maso and Beasley 1998). Multiple sclerosis, periodic paralysis, fibromyalgia, chronic systemic conditions, lupus, and endocrine disorders such as hypothyroid-ism may also be the source of symptom reporting (Spratt and DeMaso 2006). In addition, the presence of physical illness does not definitively exclude the possibility of pediatric somatization. Systemic...
Attack (often triggered by cold or stress), one or more digits turn white. Some minutes later, the color changes to bluish red. Normal color returns slowly. In severe cases, gangrene may ensue in fingers or toes. Once known as relapsing gangrene, Raynaud's syndrome may occur alone (Raynaud's disease) or with another condition such as scleroderma, lupus, or rheumatoid arthritis. It may be an occupational hazard for people who operate vibratory machinery such as jackhammers.
Fifteen individuals from seven families have been identified with homozygous factor H deficiency (124). The disease is inherited as an autosomal-recessive trait and results in the uncontrolled cleavage of C3. This C3 cleavage depletes the factor B and properdin components of the alternative pathway and depletes C5. Patients with factor H deficiency have been associated with recurrent bacterial infections including meningococcal meningitis, glomerulonephritis, SLE, and subacute cutaneous lupus erythematosus. In 21 relatives encompassing three generations for one reported patient, 10 had low factor H levels that indicated probable heterozygous deficiencies in these relatives. Decreased factor H serum levels, C3 serum levels, C3 functional activity, factor B levels, and properdin levels were all strongly associated for these heterozygous relatives.
Patients with a wide variety of autoimmune diseases including SLE, rheumatoid arthritis, hydralazine-induced lupus, discoid lupus erythematosus, primary phospholipid syndrome, essential mixed cryoglobulinemia, primary biliary cirrhosis, ulcerative colitis, and on cells in the MRL lpr mouse SLE model. The decrease in receptor numbers has been correlated with disease activity and can be reversed on the red cells by the production of new red cells stimulated by erythropoietin in some patients.
More than 90 of SLE patients eventually have a mucocu-taneous manifestation. The classic malar butterfly rash gave lupus its name, because it was thought to resemble the bite of the wolf. This rash is present in only one third of patients when it occurs, it is often after sunlight exposure. One third to two thirds of SLE patients are extremely photosensitive. Sun exposure not only can cause a maculopapular, ery-thematous rash but also can induce a flare of systemic symptoms. Other lesions can occur, such as bullae or generalized erythema. Subacute cutaneous lupus erythematosus (SCLE) occurs in sun-exposed areas of the skin, particularly on the upper torso, in two forms annular or papulosquamous lesions. The former variant might be confused with erythema annu-lare and the latter with psoriasis or lichen planus. About 70 of patients with photosensitivity have anti-Ro antibodies (Boumpas et al., 1995). SCLE lesions do not result in scarring. Discoid lupus lesions are raised plaques that...
The focus on cognitive sequelae in SLE is due to central nervous system (CNS) involvement inherent to the disease. SLE may affect many organs in the body including the brain. A slow decline in cognitive functions is frequently common among individuals with SLE, and it has been estimated that up to 60 of lupus patients experience gradual declines in cognitive functions (Takada 2008). Harrison and Ravdin (2002) observed that prevalence of cognitive impairments among individuals with SLE is quite variable given the diversity of demographics and disease presentation. Those cognitive functions that have been found to be impaired include short- and long-term memory, speed of information processing, ability to relate objects in space and time, and processing of emotions (for a review, see Takada 2008). Impairment may progress over the course of time and have significant impact on school or occupational functioning. Specific mechanisms underlying cognitive impairments in these individuals...
Another approach for targeted application is antigen-specific direction using antibody-conjugates. DAF was successfully targeted to the surface of Chinese hamster ovary cells by a conjugate of DAF and IgG anti-danasyl antibody (42). A similar antigen-targeted form of sCD59 has been produced (43). Recently conjugates were made between a CR2 fragment, which will recognize sites of C3 activation, and DAF and CD59 (44). These conjugates bound to C3 opsonized cells and were more than 20-fold more efficient than the untargeted molecules in inhibiting complement activation. In a mouse model of lupus nephritis CR2-DAF but not soluble DAF targeted the kidney.
Independent of C3 activation (139), but it is unclear whether this can occur in vivo. Monoclonal antibodies to mouse C5, like the mAb BB5.1 (140) were important tools to demonstrate the role of the terminal complement pathway in experimental diseases like collagen-induced arthritis (36) and lupus-like nephritis (141). Notably, such treatment of collagen-induced arthritis with anti-C5 antibody not only prevented disease onset, but also ameliorated established disease. An anti-rat C5 mAb was found to be protective in experimental myocardial infarction (142). The human anti-C5 antibody N19 8 described by Wurzner et al. (143) was a breakthrough in this field. It was used to demonstrate inhibition of terminal pathway activation in an artificial cardiopulmonary bypass model where leukocyte and platelet activation was also attenuated (144) and it prevented hyperacute graft rejection in a model of porcine-to-human heart transplantation (145). Later several anti-C5 antibodies have been...
Inflammation of the iris, iritis or iridocyclitis, is associated with severe pain, photophobia, lacrimation, decreased vision, and circumcorneal congestion. This congestion is caused by injection of the deep episcleral vessels (ciliary flush). The dilation of the iris vessels leads to transudation of protein into the aqueous humor and deposition of inflammatory cells on the corneal endothelium, known as keratic precipitates. As a result of this deposition, the iris becomes blurred and loses its distinctive radial appearance (a ''muddy iris''). There are many causes of iritis, including exogenous infection from perforating injuries secondary infection from the cornea, sclera, or retina endogenous infection such as tuberculosis, gonorrhea, syphilis, and viral and mycotic infections and systemic diseases such as rheumatoid arthritis, systemic lupus erythematosus, Reiter's disease, Behcet's syndrome, and relapsing polychondritis. Figure 10-63 shows the classic features of acute iritis.
Bowel disease, this condition is also seen in association with various blood dyscrasias (especially multiple myeloma), chronic active hepatitis, rheumatoid arthritis, systemic lupus erythematosus, and acute leukemias. Approximately 10 of all patients with ulcerative colitis, however, have cutaneous manifestations, especially pyoderma gangrenosum. The skin lesions of pyoderma gangrenosum are closely linked to the bowel disease exacerbations of bowel symptoms are associated with extension of existing lesions or development of new ones. Removal of the diseased bowel often leads to improvement in the cutaneous manifestations. Figure 8-88 shows the classic shin lesions of pyoderma gangrenosum in a patient with regional enteritis. See also Figure 17-6, which shows another patient with an exacerbation of ulcerative colitis and pyoderma gangrenosum of the shin.
Patients with Raynaud's phenomenon have reversible digital artery spasm precipitated by cold or emotional stress. The digits become pallid, then blue, and on rewarming or relief of the emotional stress become hyperemic. It is most commonly associated with collagen vascular disease (scleroderma or disseminated lupus erythematosus), but may also be associated with Buerger's disease, primary pulmonary hypertension, or thoracic outlet syndromes (81).
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