Misplaced Pages

#826173

98-461: The serology for the most common DR1 alleles is excellent. The serology for alleles *01:04 , *01:06 , *01:09 , *01:10 , *0112 , *0115 , and *0116 is unknown. DR1 is associated with seronegative- rheumatoid arthritis , penicillamine -induced myasthenia , and schizophrenia . DR1 is increased in patients with systemic sclerosis and arthritis and in ulcerative colitis with patients that have articular manifestations. DRB1*01:01

196-575: A biomarker of these events. Importantly inflammatory events are not limited to synovium but it appear to be systemic, evidence suggest that alterations in T helper profile favoring inflammation such as inflammatory IL-17A producing T helper cells and pathogenic Th17 cells are come from both memory and effector compartment in RA patients peripheral blood. Cytokines and chemokines attract and accumulate immune cells, i.e. activated T- and B cells, monocytes and macrophages from activated fibroblast-like synoviocytes, in

294-406: A low red blood cell count , inflammation around the lungs , and inflammation around the heart . Fever and low energy may also be present. Often, symptoms come on gradually over weeks to months. While the cause of rheumatoid arthritis is not clear, it is believed to involve a combination of genetic and environmental factors. The underlying mechanism involves the body's immune system attacking

392-470: A buildup of apoptotic debris can be observed in GC because of an ineffective clearance of apoptotic cells. Close to TBM, follicular dendritic cells (FDC) are localised in GC, which attach antigen material to their surface and, in contrast to bone marrow -derived DC, neither take it up nor present it via MHC molecules. Autoreactive B cells can accidentally emerge during somatic hypermutation and migrate into

490-546: A cSLE-like disorders. )(Note that mutations in the UNC93B1 gene may cause either cSLE or the chilblain lupus erythematosus form of cSLE. ) Mutations in a wide range of other genes do not by themselves cause SLE but two or more of them may act together, act in concert with environmental factors, or act in some but not other populations (e.g., cause SLE in Chinese but not Europeans) to cause SLE or an SLE-like syndrome but do so in only

588-408: A central area of fibrinoid necrosis that may be fissured and which corresponds to the fibrin -rich necrotic material found in and around an affected synovial space. Surrounding the necrosis is a layer of palisading macrophages and fibroblasts , corresponding to the intimal layer in synovium and a cuff of connective tissue containing clusters of lymphocytes and plasma cells , corresponding to

686-457: A definitive diagnosis is reached. Common initial and chronic complaints include fever , malaise , joint pains , muscle pains , and fatigue . Because these symptoms are so often seen in association with other diseases, these signs and symptoms are not part of the diagnostic criteria for SLE. When occurring in conjunction with other signs and symptoms, however, they are considered suggestive. While SLE can occur in both males and females, it

784-465: A key role in these pathogenic processes. Three phases of progression of RA are an initiation phase (due to non-specific inflammation), an amplification phase (due to T cell activation), and chronic inflammatory phase, with tissue injury resulting from the cytokines , IL–1 , TNF-alpha , and IL–6 . Factors allowing an abnormal immune response, once initiated, become permanent and chronic. These factors are genetic disorders which change regulation of

882-473: A low serum level of vitamin D ) often occurs in patients with SLE and that its level is particularly low in patients with more active SLE. Furthermore, 5 studies reported that SLE patients treated with vitamin D had significant reductions in the activity of their disease. However, other studies have found that the levels of vitamin D in SLE are not low, that vitamin D does not reduce their SLE's activity, and/or that

980-436: A mimic of RA, or be a sign of Still's disease , a seronegative, usually juvenile, variant of rheumatoid Arthritis. In 2010, the 2010 ACR / EULAR Rheumatoid Arthritis Classification Criteria were introduced. Systemic lupus erythematosus Lupus , formally called systemic lupus erythematosus ( SLE ), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of

1078-432: A more severe form of SLE termed childhood-onset systemic lupus erythematosus . The cause of SLE is not clear. It is thought to involve a combination of genetics and environmental factors . Among identical twins , if one is affected there is a 24% chance the other one will also develop the disease. Female sex hormones , sunlight, smoking, vitamin D deficiency , and certain infections are also believed to increase

SECTION 10

#1732854521827

1176-431: A person's overall functioning. This may be helped by balancing rest and exercise, the use of splints and braces , or the use of assistive devices. Pain medications , steroids , and NSAIDs are frequently used to help with symptoms. Disease-modifying antirheumatic drugs (DMARDs), such as hydroxychloroquine and methotrexate , may be used to try to slow the progression of disease. Biological DMARDs may be used when

1274-463: A person's risk. The mechanism involves an immune response by autoantibodies against a person's own tissues. These are most commonly anti-nuclear antibodies and they result in inflammation . Diagnosis can be difficult and is based on a combination of symptoms and laboratory tests. There are a number of other kinds of lupus erythematosus including discoid lupus erythematosus , neonatal lupus , and subacute cutaneous lupus erythematosus . There

1372-607: A population shift towards immature B cells. Memory B cells with increased CD27 +/ IgD —are less susceptible to immunosuppression. CD27-/IgD- memory B cells are associated with increased disease activity and renal lupus. T cells, which regulate B-cell responses and infiltrate target tissues, have defects in signaling, adhesion, co-stimulation, gene transcription, and alternative splicing. The cytokines B-lymphocyte stimulator (BLyS), also known as B-cell activating factor (BAFF), interleukin 6, interleukin 17, interleukin 18, type I interferons, and tumor necrosis factor α (TNFα) are involved in

1470-437: A positive test for antiphospholipid antibodies; the combination of such findings have earned the term " lupus anticoagulant -positive". Another autoantibody finding in SLE is the anti-cardiolipin antibody , which can cause a false positive test for syphilis . SLE may cause pericarditis (inflammation of the outer lining surrounding the heart), myocarditis (inflammation of the heart muscle), or endocarditis (inflammation of

1568-411: A pro-inflammatory form of cell death, is increased in T lymphocytes, due to mitochondrial dysfunction, oxidative stress, and depletion of ATP. Impaired clearance of dying cells is a potential pathway for the development of this systemic autoimmune disease . This includes deficient phagocytic activity, impaired lysosomal degradation, and scant serum components in addition to increased apoptosis . SLE

1666-653: A result have impaired degradation of internalized apoptotic debris, which results in chronic activation of Toll-like receptors and permeabilization of the phagolysosomal membrane, allowing activation of cytosolic sensors. In addition, intact apoptotic debris recycles back to the cell membrane and accumulate on the surface of the cell. Recent research has found an association between certain people with lupus (especially those with lupus nephritis ) and an impairment in degrading neutrophil extracellular traps (NETs). These were due to DNAse1 inhibiting factors, or NET protecting factors in people's serum, rather than abnormalities in

1764-761: A result of treating the disease. It can rarely present with intracranial hypertension syndrome , characterized by an elevated intracranial pressure , papilledema , and headache with occasional abducens nerve paresis , absence of a space-occupying lesion or ventricular enlargement, and normal cerebrospinal fluid chemical and hematological constituents. More rare manifestations are acute confusional state , Guillain–Barré syndrome , aseptic meningitis , autonomic disorder , demyelinating syndrome , mononeuropathy (which might manifest as mononeuritis multiplex ), movement disorder (more specifically, chorea ), myasthenia gravis , myelopathy , cranial neuropathy and plexopathy . Neurological disorders contribute to

1862-704: A significant percentage of morbidity and mortality in people with lupus. As a result, the neural side of lupus is being studied in hopes of reducing morbidity and mortality rates. One aspect of this disease is severe damage to the epithelial cells of the blood–brain barrier . In certain regions, depression affects up to 60% of women with SLE. Up to one-third of patients report that their eyes are affected. The most common diseases are dry eye syndrome and secondary Sjögren's syndrome , but episcleritis , scleritis , retinopathy (more often affecting both eyes than one), ischemic optic neuropathy , retinal detachment , and secondary angle-closure glaucoma may occur. In addition,

1960-447: A small percentage of cases. The development of a genetically-regulated trait or disorder that is dependent on the inheritance of two or more genes is termed oligogenic inheritance or polygenic inheritance . SLE is regarded as a prototype disease due to the significant overlap in its symptoms with other autoimmune diseases. Patients with SLE have higher levels of DNA damage than normal subjects, and several proteins involved in

2058-425: A specificity of around 95%. As with RF, ACPAs are many times present before symptoms have started. The by far most common clinical test for ACPAs is the anti- cyclic citrullinated peptide (anti CCP) ELISA. In 2008 a serological point-of-care test for the early detection of RA combined the detection of RF and anti-MCV with a sensitivity of 72% and specificity of 99.7%. To improve the diagnostic capture rate in

SECTION 20

#1732854521827

2156-435: A threat to the tolerization of B cells and T cells. Dendritic cells in the germinal center may endocytose such antigenic material and present it to T cells, activating them. Also, apoptotic chromatin and nuclei may attach to the surfaces of follicular dendritic cells and make this material available for activating other B cells that may have randomly acquired self-protein specificity through somatic hypermutation. Necrosis,

2254-424: Is a long-term autoimmune disorder that primarily affects joints . It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involved, with the same joints typically involved on both sides of the body. The disease may also affect other parts of the body, including skin, eyes, lungs, heart, nerves, and blood. This may result in

2352-533: Is also seen more often in those with relatives who have AA. Lung fibrosis is a recognized complication of rheumatoid arthritis. It is also a rare but well-recognized consequence of therapy (for example with methotrexate and leflunomide ). Caplan's syndrome describes lung nodules in individuals with RA and additional exposure to coal dust. Exudative pleural effusions are also associated with RA. People with RA are more prone to atherosclerosis , and risk of myocardial infarction (heart attack) and stroke

2450-604: Is an established risk factor for RA in Caucasian populations, increasing the risk three times compared to non-smokers, particularly in men, heavy smokers, and those who are rheumatoid factor positive. Modest alcohol consumption may be protective. Silica exposure has been linked to RA. No infectious agent has been consistently linked with RA and there is no evidence of disease clustering to indicate its infectious cause, but periodontal disease has been consistently associated with RA. The many negative findings suggest that either

2548-460: Is associated with colonic Crohn's disease and ulcerative colitis . DRB1*01:01/*0404 and *01:01/*0401 increases risk of mortality in rheumatoid arthritis, with ischemic heart disease and smoking. these same genotypes are associated with rheumatoid vasculitis. DRB1*01:02:DQB1*05:01 is associated with psoriasis vulgaris and tubulointerstitial nephritis & uveitis syndrome, but is relatively protective against juvenile diabetes. DR1-DQ5

2646-470: Is associated with defects in apoptotic clearance, and the damaging effects caused by apoptotic debris. Early apoptotic cells express "eat-me" signals, of cell-surface proteins such as phosphatidylserine, that prompt immune cells to engulf them. Apoptotic cells also express find-me signals to attract macrophages and dendritic cells. When apoptotic material is not removed correctly by phagocytes, they are captured instead by antigen-presenting cells, which leads to

2744-498: Is associated with rheumatoid arthritis, in anti-Jk(a) mediated hemolytic transfusion reactions, foliaceous pemphigus , HTLV-1-associated myelopathy/tropical spastic paraparesis, and lichen planus . In lyme disease arthritis, *01:01 appears to play a role in presentation of triggering microbial antigens. DRB1*01:02 is associated with rheumatoid arthritis, in anti-Jk(a) mediated hemolytic transfusion reactions, psoriasis vulgaris , and recurrent respiratory papillomatosis DRB1*01:03

2842-479: Is associated with tubulointerstitial nephritis & uveitis syndrome. DR1 are associated with rheumatoid arthritis, and while not the strongest association with the highest risk for early onset arthritis is within the DR4-bearing Native American population. There frequency of DR4-DQ8 haplotypes reach extreme nodal levels. Arthritis has been identified in a pre-Columbian remains from Italy,

2940-513: Is by far the most common abnormality of the blood cells which can be caused by a variety of mechanisms. The chronic inflammation caused by RA leads to raised hepcidin levels, leading to anemia of chronic disease where iron is poorly absorbed and also sequestered into macrophages . The red cells are of normal size and color (normocytic and Normochromic). A low white blood cell count usually only occurs in people with Felty's syndrome with an enlarged liver and spleen. The mechanism of neutropenia

3038-436: Is clinically suspected, a physician may test for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs measured as anti-CCP antibodies). The test is positive approximately two-thirds of the time, but a negative RF or CCP antibody does not rule out RA; rather, the arthritis is called seronegative , which occurs in approximately a third of people with RA. During the first year of illness, rheumatoid factor

HLA-DR1 - Misplaced Pages Continue

3136-564: Is complex. An increased platelet count occurs when inflammation is uncontrolled. The role of the circadian clock in rheumatoid arthritis suggests a correlation between an early morning rise in circulating levels of pro-inflammatory cytokines, such as interleukin-6 and painful morning joint stiffness. Renal amyloidosis can occur as a consequence of untreated chronic inflammation. Treatment with penicillamine or gold salts such as sodium aurothiomalate are recognized causes of membranous nephropathy . The eye can be directly affected in

3234-449: Is for joint pain , with the small joints of the hand and wrist usually affected, although all joints are at risk. More than 90 percent of those affected will experience joint or muscle pain at some time during the course of their illness. Unlike rheumatoid arthritis , lupus arthritis is less disabling and usually does not cause severe destruction of the joints. Fewer than ten percent of people with lupus arthritis will develop deformities of

3332-669: Is found far more often in women, and the symptoms associated with each sex are different. Females tend to have a greater number of relapses , a low white blood cell count , more arthritis , Raynaud syndrome , and psychiatric symptoms . Males tend to have more seizures , kidney disease , serositis (inflammation of tissues lining the lungs and heart), skin problems , and peripheral neuropathy . As many as 70% of people with lupus have some skin symptoms. The three main categories of lesions are chronic cutaneous (discoid) lupus, subacute cutaneous lupus, and acute cutaneous lupus. People with discoid lupus may exhibit thick, red scaly patches on

3430-444: Is important. Liver problems in people with rheumatoid arthritis may be due to the underlying disease process or as a result of the medications used to treat the disease. A coexisting autoimmune liver disease, such as primary biliary cirrhosis or autoimmune hepatitis may also cause problems. Peripheral neuropathy and mononeuritis multiplex may occur. The most common problem is carpal tunnel syndrome caused by compression of

3528-503: Is increased in people with RA compared to the general population, an association possibly due to the use of immunosuppression agents for treating RA. Periodontitis and tooth loss are common in people with rheumatoid arthritis. RA is a systemic (whole body) autoimmune disease. Some genetic and environmental factors affect the risk for RA. Worldwide, RA affects approximately 1% of the adult population and occurs one in 1,000 children. Studies show RA primarily affects individuals between

3626-766: Is induced at the site of inflammation and classified as nociceptive as opposed to neuropathic . The joints are often affected in a fairly symmetrical fashion, although this is not specific, and the initial presentation may be asymmetrical. As the pathology progresses the inflammatory activity leads to tendon tethering and erosion and destruction of the joint surface, which impairs range of movement and leads to deformity . The fingers may develop almost any deformity depending on which joints are most involved. Specific deformities , which also occur in osteoarthritis , include ulnar deviation , boutonniere deformity (also "buttonhole deformity", flexion of proximal interphalangeal joint and extension of distal interphalangeal joint of

3724-429: Is markedly increased. Other possible complications that may arise include: pericarditis , endocarditis , left ventricular failure, valvulitis and fibrosis . Many people with RA do not experience the same chest pain that others feel when they have angina or myocardial infarction. To reduce cardiovascular risk, it is crucial to maintain optimal control of the inflammation caused by RA (which may be involved in causing

3822-505: Is more likely to be negative with some individuals becoming seropositive over time. RF is a non-specific antibody and seen in about 10% of healthy people, in many other chronic infections like hepatitis C , and chronic autoimmune diseases such as Sjögren's syndrome and systemic lupus erythematosus . Therefore, the test is not specific for RA. Hence, new serological tests check for anti-citrullinated protein antibodies ACPAs. These tests are again positive in 61–75% of all RA cases, but with

3920-403: Is no cure for SLE, but there are experimental and symptomatic treatments. Treatments may include NSAIDs , corticosteroids , immunosuppressants , hydroxychloroquine , and methotrexate . Although corticosteroids are rapidly effective, long-term use results in side effects. Alternative medicine has not been shown to affect the disease. Men have higher mortality. SLE significantly increases

4018-683: Is one of the most difficult challenges in medicine, because it can involve so many different patterns of symptoms, some of which may be mistaken for signs of infectious disease or stroke. A common neurological disorder people with SLE have is headache , although the existence of a specific lupus headache and the optimal approach to headache in SLE cases remains controversial. Other common neuropsychiatric manifestations of SLE include cognitive disorder , mood disorder , cerebrovascular disease , seizures , polyneuropathy , anxiety disorder , psychosis , depression , and in some extreme cases, personality disorders. Steroid psychosis can also occur as

HLA-DR1 - Misplaced Pages Continue

4116-407: Is postulated to be partially caused by inflammatory cytokines . More general osteoporosis is probably contributed to by immobility, systemic cytokine effects, local cytokine release in bone marrow and corticosteroid therapy. The incidence of lymphoma is increased, although it is uncommon and associated with the chronic inflammation, not the treatment of RA. The risk of non-melanoma skin cancer

4214-527: Is the occurrence of SLE symptoms in an infant born from a mother with SLE, most commonly presenting with a rash resembling discoid lupus erythematosus , and sometimes with systemic abnormalities such as heart block or enlargement of the liver and spleen . Neonatal lupus is usually benign and self-limited. Medications for treatment of SLE can carry severe risks for female and male reproduction. Cyclophosphamide (also known as Cytoxan), can lead to infertility by causing premature ovarian insufficiency (POI),

4312-666: The adaptive immune response . Genetic factors interact with environmental risk factors for RA, with cigarette smoking as the most clearly defined risk factor. Other environmental and hormonal factors may explain higher risks for women, including onset after childbirth and hormonal medications. A possibility for increased susceptibility is that negative feedback mechanisms – which normally maintain tolerance – are overtaken by positive feedback mechanisms for certain antigens, such as IgG Fc bound by rheumatoid factor and citrullinated fibrinogen bound by antibodies to citrullinated peptides (ACPA – Anti–citrullinated protein antibody). A debate on

4410-720: The macrophage activation syndrome . Mutations in about 40 genes have been reported to cause cSLE and/or a cSLE-like disease. These genes include 5 which as of February, 2024 were classified as inborn errors of immunity genes, i.e., DNASE1L3 , TREX1 , IFIH1 , Tartrate-resistant acid phosphatase and PRKCD and 28 other genes, i.e., NEIL3 , TMEM173 , ADAR1 , NRAS , SAMHD1 , SOS1 , FASLG , FAS receptor gene , RAG1 , RAG2 , DNASE1 , SHOC2 , KRAS , PTPN11 , PTEN , BLK , RNASEH2A , RNASEH2B , RNASEH2C , Complement component 1qA , Complement component 1qB , Complement component 1r , Complement component 1s , Complement component 2 , Complement component 3 , UNC93B1 , and

4508-510: The mantle zone , autoreactive B cells require further survival signals from autoreactive helper T cells, which promote the maturation of autoantibody-producing plasma cells and B memory cells. In the presence of autoreactive T cells , a chronic autoimmune disease may be the consequence. Anti-nRNP autoantibodies to nRNP A and nRNP C initially targeted restricted, proline -rich motifs . Antibody binding subsequently spread to other epitopes . The similarity and cross-reactivity between

4606-705: The pleurae known as pleurisy , which can rarely give rise to shrinking lung syndrome involving a reduced lung volume. Other associated lung conditions include pneumonitis , chronic diffuse interstitial lung disease , pulmonary hypertension , pulmonary emboli , and pulmonary hemorrhage . Painless passage of blood or protein in the urine may often be the only presenting sign of kidney involvement. Acute or chronic renal impairment may develop with lupus nephritis , leading to acute or end-stage kidney failure . Because of early recognition and management of SLE with immunosuppressive drugs or corticosteroids, end-stage renal failure occurs in less than 5% of cases; except in

4704-401: The synovial membrane . Joints become swollen, tender and warm, and stiffness limits their movement. With time, multiple joints are affected ( polyarthritis ). Most commonly involved are the small joints of the hands , feet and cervical spine , but larger joints like the shoulder and knee can also be involved. Synovitis can lead to tethering of tissue with loss of movement and erosion of

4802-668: The DNAse1 itself. DNAse1 mutations in lupus have so far only been found in some Japanese cohorts. The clearance of early apoptotic cells is an important function in multicellular organisms. It leads to a progression of the apoptosis process and finally to secondary necrosis of the cells if this ability is disturbed. Necrotic cells release nuclear fragments as potential autoantigens , as well as internal danger signals, inducing maturation of dendritic cells (DCs) since they have lost their membranes' integrity. Increased appearance of apoptotic cells also stimulates inefficient clearance. That leads to

4900-548: The Fc receptors is mediated through the antibody's N-glycans, which are altered to promote inflammation in people with RA. This contributes to local inflammation in a joint, specifically the synovium with edema , vasodilation and entry of activated T-cells, mainly CD4 in microscopically nodular aggregates and CD8 in microscopically diffuse infiltrates. Synovial macrophages and dendritic cells function as antigen-presenting cells by expressing MHC class II molecules, which establishes

4998-487: The affected individual bearing the DRB1*01:01 allele. DRB1*01:01 and most DR4 have in common a 'shared epitope'. In this hypothesis a common region of the beta chain, positions 67 to 74, are common and may be integral to presenting auto-immunological peptides. HLA-DR1 is not genetically linked to DR51, DR52 or DR53, but is linked to HLA-DQ1 and DQ5 serotypes. Rheumatoid arthritis Rheumatoid arthritis ( RA )

SECTION 50

#1732854521827

5096-399: The ages of 40–60 years and is seen more commonly in females. A family history of RA increases the risk around three to five times; as of 2016, it was estimated that genetics may account for 40–65% of cases of seropositive RA, but only around 20% for seronegative RA. RA is strongly associated with genes of the inherited tissue type major histocompatibility complex (MHC) antigen. HLA-DR4 is

5194-629: The black population, where the risk is many times higher. The histological hallmark of SLE is membranous glomerulonephritis with "wire loop" abnormalities. This finding is due to immune complex deposition along the glomerular basement membrane , leading to a typical granular appearance in immunofluorescence testing. Neuropsychiatric syndromes can result when SLE affects the central or peripheral nervous system . The American College of Rheumatology defines 19 neuropsychiatric syndromes in systemic lupus erythematosus. The diagnosis of neuropsychiatric syndromes concurrent with SLE (now termed as NPSLE),

5292-705: The body. Several forms of vasculitis occur in RA, but are mostly seen with long-standing and untreated disease. The most common presentation is due to involvement of small- and medium-sized vessels. Rheumatoid vasculitis can thus commonly present with skin ulceration and vasculitic nerve infarction known as mononeuritis multiplex . Other, rather rare, skin associated symptoms include pyoderma gangrenosum , Sweet's syndrome , drug reactions, erythema nodosum , lobe panniculitis , atrophy of finger skin, palmar erythema , and skin fragility (often worsened by corticosteroid use). Diffuse alopecia areata (Diffuse AA) occurs more commonly in people with rheumatoid arthritis. RA

5390-419: The body. Symptoms vary among people and may be mild to severe. Common symptoms include painful and swollen joints , fever , chest pain , hair loss , mouth ulcers , swollen lymph nodes , feeling tired , and a red rash which is most commonly on the face. Often there are periods of illness, called flares , and periods of remission during which there are few symptoms. Children up to 18 years old develop

5488-415: The cardiovascular risk), and to use exercise and medications appropriately to reduce other cardiovascular risk factors such as blood lipids and blood pressure. Doctors who treat people with RA should be sensitive to cardiovascular risk when prescribing anti-inflammatory medications, and may want to consider prescribing routine use of low doses of aspirin if the gastrointestinal effects are tolerable. Anemia

5586-455: The cell nucleus . These antibody attacks are the immediate cause of SLE. SLE is a chronic inflammatory disease believed to be a type III hypersensitivity response with potential type II involvement. Reticulate and stellate acral pigmentation should be considered a possible manifestation of SLE and high titers of anti-cardiolipin antibodies , or a consequence of therapy. People with SLE have intense polyclonal B-cell activation, with

5684-505: The developing world are unclear. Lupus is Latin for 'wolf': the disease was so-named in the 13th century as the rash was thought to appear like a wolf's bite. SLE is one of several diseases known as " the great imitator " because it often mimics or is mistaken for other illnesses. SLE is a classical item in differential diagnosis , because SLE symptoms vary widely and come and go unpredictably. Diagnosis can thus be elusive, with some people having unexplained symptoms of SLE for years before

5782-706: The development of antinuclear antibodies. Monocytes isolated from whole blood of people with SLE show reduced expression of CD44 surface molecules involved in the uptake of apoptotic cells. Most of the monocytes and tingible body macrophages (TBMs), which are found in the germinal centres of lymph nodes , even show a definitely different morphology; they are smaller or scarce and die earlier. Serum components like complement factors, CRP , and some glycoproteins are, furthermore, decisively important for an efficiently operating phagocytosis. With SLE, these components are often missing, diminished, or inefficient. Macrophages during SLE fail to mature their lysosomes and as

5880-581: The disease does not respond to other treatments. However, they may have a greater rate of adverse effects. Surgery to repair, replace , or fuse joints may help in certain situations. RA affects about 24.5 million people as of 2015. This is 0.5–1% of adults in the developed world with between 5 and 50 per 100,000 people newly developing the condition each year. Onset is most frequent during middle age and women are affected 2.5 times as frequently as men. It resulted in 38,000 deaths in 2013, up from 28,000 deaths in 1990. The first recognized description of RA

5978-413: The disease or a side effect of pharmacological treatment. People with SLE may have an association with antiphospholipid antibody syndrome (a thrombotic disorder), wherein autoantibodies to phospholipids are present in their serum. Abnormalities associated with antiphospholipid antibody syndrome include a paradoxical prolonged partial thromboplastin time (which usually occurs in hemorrhagic disorders) and

SECTION 60

#1732854521827

6076-503: The drug. The VigiBase drug safety data repositor diagnosed 12,166 cases of drug-induced SLE recorded between 1968 and 2017. Among the 118 agents causing SLE, five main classes were most often associated with drug-induced SLE. These drugs were antiarrhythmic agents such as procainamide or quinidine ; antihypertensive agents such as hydralazine , captopril , or acebutolol ; antimicrobial agents such as minocycline , isoniazid , carbamazepine , or phenytoin ; and agents that inhibit

6174-429: The early detection of patients with RA and to risk stratify these individuals, the rheumatology field continues to seek complementary markers to both RF and anti-CCP. 14-3-3η ( YWHAH ) is one such marker that complements RF and anti-CCP, along with other serological measures like C-reactive protein . In a systematic review, 14-3-3η has been described as a welcome addition to the rheumatology field. The authors indicate that

6272-495: The form of episcleritis or scleritis , which when severe can very rarely progress to perforating scleromalacia. Rather more common is the indirect effect of keratoconjunctivitis sicca , which is a dryness of eyes and mouth caused by lymphocyte infiltration of lacrimal and salivary glands . When severe, dryness of the cornea can lead to keratitis and loss of vision as well as being painful. Preventive treatment of severe dryness with measures such as nasolacrimal duct blockage

6370-452: The generalized abnormal immune response has become established – which may take several years before any symptoms occur – plasma cells derived from B lymphocytes produce rheumatoid factors and ACPA of the IgG and IgM classes in large quantities. These activate macrophages through Fc receptor and complement binding, which is part of the intense inflammation in RA. Binding of an autoreactive antibody to

6468-419: The germinal center light zone. Autoreactive B cells, maturated coincidentally, normally do not receive survival signals by antigen planted on follicular dendritic cells and perish by apoptosis. In the case of clearance deficiency, apoptotic nuclear debris accumulates in the light zone of GC and gets attached to FDC. This serves as a germinal centre survival signal for autoreactive B-cells. After migration into

6566-447: The hand), swan neck deformity (hyperextension at proximal interphalangeal joint and flexion at distal interphalangeal joint) and "Z-thumb." "Z-thumb" or "Z-deformity" consists of hyperextension of the interphalangeal joint, fixed flexion and subluxation of the metacarpophalangeal joint and gives a "Z" appearance to the thumb. The hammer toe deformity may be seen. In the worst case, joints are known as arthritis mutilans due to

6664-540: The hands and feet are generally performed when many joints affected. In RA, there may be no changes in the early stages of the disease or the x-ray may show osteopenia near the joint, soft tissue swelling, and a smaller than normal joint space. As the disease advances, there may be bony erosions and subluxation. Other medical imaging techniques such as magnetic resonance imaging (MRI) and ultrasound are also used in RA. Technical advances in ultrasonography like high-frequency transducers (10 MHz or higher) have improved

6762-467: The hands and feet. People with SLE are at particular risk of developing osteoarticular tuberculosis . A possible association between rheumatoid arthritis and SLE has been suggested, and SLE may be associated with an increased risk of bone fractures in relatively young women. Anemia is common in children with SLE and develops in about 50% of cases. Low platelet count ( thrombocytopenia ) and low white blood cell count ( leukopenia ) may be due to

6860-429: The immune reaction in the tissue. The disease progresses by forming granulation tissue at the edges of the synovial lining, pannus with extensive angiogenesis and enzymes causing tissue damage. The fibroblast-like synoviocytes have a prominent role in these pathogenic processes. The synovium thickens, cartilage and underlying bone disintegrate, and the joint deteriorates, with raised calprotectin levels serving as

6958-430: The inflammation-inducing actions of interferon or tumor necrosis factor . Discoid (cutaneous) lupus is limited to skin symptoms and is diagnosed by biopsy of rash on the face, neck, scalp or arms. Approximately 5% of people with DLE progress to SLE. SLE is triggered by environmental factors that are unknown. In SLE, the body's immune system produces antibodies against self-protein , particularly against proteins in

7056-604: The inflammatory process and are potential therapeutic targets. SLE is associated with low C3 levels in the complement system . Tingible body macrophages (TBMs) – large phagocytic cells in the germinal centers of secondary lymph nodes  – express CD68 protein. These cells normally engulf B cells that have undergone apoptosis after somatic hypermutation . In some people with SLE, significantly fewer TBMs can be found, and these cells rarely contain material from apoptotic B cells. Also, uningested apoptotic nuclei can be found outside of TBMs. This material may present

7154-523: The inner lining of the heart). The endocarditis of SLE is non-infectious, and is also called Libman–Sacks endocarditis . It involves either the mitral valve or the tricuspid valve . Atherosclerosis also occurs more often and advances more rapidly than in the general population. Steroids are sometimes prescribed as an anti-inflammatory treatment for lupus; however, they can increase one's risk for heart disease, high cholesterol, and atherosclerosis. SLE can cause pleuritic pain as well as inflammation of

7252-423: The joint space. By signalling through RANKL and RANK , they eventually trigger osteoclast production, which degrades bone tissue. The fibroblast-like synoviocytes that are present in the synovium during rheumatoid arthritis display altered phenotype compared to the cells present in normal tissues. The aggressive phenotype of fibroblast-like synoviocytes in rheumatoid arthritis and the effect these cells have on

7350-403: The joint surface causing deformity and loss of function. The fibroblast-like synoviocytes (FLS), highly specialized mesenchymal cells found in the synovial membrane , have an active and prominent role in these pathogenic processes of the rheumatic joints. RA typically manifests with signs of inflammation, with the affected joints being swollen, warm, painful and stiff, particularly early in

7448-539: The joints. This results in inflammation and thickening of the joint capsule . It also affects the underlying bone and cartilage . The diagnosis is made mostly on the basis of a person's signs and symptoms. X-rays and laboratory testing may support a diagnosis or exclude other diseases with similar symptoms. Other diseases that may present similarly include systemic lupus erythematosus , psoriatic arthritis , and fibromyalgia among others. The goals of treatment are to reduce pain, decrease inflammation, and improve

7546-612: The loss of normal function of one's ovaries prior to age forty. Methotrexate can cause termination or deformity in fetuses and is a common abortifacient , and for men taking a high dose and planning to father, a discontinuation period of 6 months is recommended before insemination. Fatigue in SLE is probably multifactorial and has been related to not only disease activity or complications such as anemia or hypothyroidism , but also to pain , depression , poor sleep quality, poor physical fitness and lack of social support . Some studies have found that vitamin D deficiency (i.e.,

7644-812: The major genetic factor implicated – the relative importance varies across ethnic groups. Genome-wide association studies examining single-nucleotide polymorphisms have found around one hundred alleles associated with RA risk. Risk alleles within the HLA (particularly HLA-DRB1 ) genes harbor more risk than other loci. The HLA encodes proteins that control recognition of self- versus non-self molecules. Other risk loci include genes affecting co-stimulatory immune pathways—for example CD28 and CD40 , cytokine signaling, lymphocyte receptor activation threshold (e.g., PTPN22 ), and innate immune activation—appear to have less influence than HLA mutations. There are established epigenetic and environmental risk factors for RA. Smoking

7742-441: The maturation of DCs and also to the presentation of intracellular antigens of late apoptotic or secondary necrotic cells, via MHC molecules. Autoimmunity possibly results from the extended exposure to nuclear and intracellular autoantigens derived from late apoptotic and secondary necrotic cells. B and T cell tolerance for apoptotic cells is abrogated, and the lymphocytes get activated by these autoantigens; inflammation and

7840-765: The median nerve by swelling around the wrist. Rheumatoid disease of the spine can lead to myelopathy . Atlanto-axial subluxation can occur, owing to erosion of the odontoid process and/or transverse ligaments in the cervical spine 's connection to the skull. Such an erosion (>3mm) can give rise to vertebrae slipping over one another and compressing the spinal cord. Clumsiness is initially experienced, but without due care, this can progress to quadriplegia or even death. Constitutional symptoms including fatigue , low grade fever , malaise , morning stiffness , loss of appetite and loss of weight are common systemic manifestations seen in people with active RA. Local osteoporosis occurs in RA around inflamed joints. It

7938-430: The medication that triggered the episode is stopped. While there are no established criteria for diagnosing drug-induced SLE, most authors have agreed on the following definition: the afflicted patient had a sufficient and continuing exposure to the drug, at least one symptom compatible with SLE, no history suggestive of SLE before starting the drug, and resolution of symptoms within weeks or months after stopping intake of

8036-653: The medications used to treat SLE can cause eye disease: long-term glucocorticoid use can cause cataracts and secondary open-angle glaucoma, and long-term hydroxychloroquine treatment can cause vortex keratopathy and maculopathy . While most pregnancies have positive outcomes, there is a greater risk of adverse events occurring during pregnancy. SLE causes an increased rate of fetal death in utero and spontaneous abortion (miscarriage). The overall live-birth rate in people with SLE has been estimated to be 72%. Pregnancy outcome appears to be worse in people with SLE whose disease flares up during pregnancy. Neonatal lupus

8134-775: The microenvironment of the joint can be summarized into hallmarks that distinguish them from healthy fibroblast-like synoviocytes. These hallmark features of fibroblast-like synoviocytes in rheumatoid arthritis are divided into seven cell-intrinsic hallmarks and four cell-extrinsic hallmarks. The cell-intrinsic hallmarks are: reduced apoptosis, impaired contact inhibition, increased migratory invasive potential, changed epigenetic landscape, temporal and spatial heterogeneity, genomic instability and mutations, and reprogrammed cellular metabolism. The cell-extrinsic hallmarks of FLS in RA are: promotes osteoclastogenesis and bone erosion, contributes to cartilage degradation, induces synovial angiogenesis, and recruits and stimulates immune cells. X-rays of

8232-506: The morning on waking or following prolonged inactivity. Increased stiffness early in the morning is often a prominent feature of the disease and typically lasts for more than an hour. Gentle movements may relieve symptoms in early stages of the disease. These signs help distinguish rheumatoid from non-inflammatory problems of the joints, such as osteoarthritis . In arthritis of non-inflammatory causes, signs of inflammation and early morning stiffness are less prominent. The pain associated with RA

8330-452: The mutilating nature of the deformities. The rheumatoid nodule , which is sometimes in the skin, is the most common non-joint feature and occurs in 30% of people who have RA. It is a type of inflammatory reaction known to pathologists as a " necrotizing granuloma ". The initial pathologic process in nodule formation is unknown but may be essentially the same as the synovitis, since similar structural features occur in both. The nodule has

8428-432: The preservation of genomic stability show polymorphisms , some of which increase the risk for SLE development. Defective DNA repair is a likely mechanism underlying lupus development. Drug-induced lupus erythematosus is a (generally) reversible condition that usually occurs in people being treated for a long-term illness. Drug-induced lupus mimics SLE. However, symptoms of drug-induced lupus generally disappear once

8526-453: The production of autoantibodies by plasma cells is initiated. A clearance deficiency in the skin for apoptotic cells has also been observed in people with cutaneous lupus erythematosus (CLE). In healthy conditions, apoptotic lymphocytes are removed in germinal centers (GC) by specialized phagocytes, the tingible body macrophages (TBM), which is why no free apoptotic and potential autoantigenic material can be seen. In some people with SLE,

8624-457: The relative roles of B-cell produced immune complexes and T cell products in inflammation in RA has continued for 30 years, but neither cell is necessary at the site of inflammation, only autoantibodies to IgGFc, known as rheumatoid factors and ACPA, with ACPA having an 80% specificity for diagnosing RA. As with other autoimmune diseases, people with RA have abnormally glycosylated antibodies, which are believed to promote joint inflammation. Once

8722-537: The risk of cardiovascular disease , with this being the most common cause of death. While women with lupus have higher risk pregnancies, most are successful. Rate of SLE varies between countries from 20 to 70 per 100,000. Women of childbearing age are affected about nine times more often than men. While it most commonly begins between the ages of 15 and 45, a wide range of ages can be affected. Those of African , Caribbean , and Chinese descent are at higher risk than those of European descent . Rates of disease in

8820-517: The same fertilized egg ) and genome-wide association studies have identified numerous genes that by themselves promote the development of SLE, particularly childhood-onset SLE, i.e., cSLE, in rare cases of SLE/cSLE. The single-gene (also termed monogenic) causes of cSLE (or a cSLE-like disorder) develop in individuals before they reach 18 years of age. cSLE typically is more severe and potentially lethal than adult-onset SLE because it often involves SLE-induced neurologic disease, renal failure, and/or

8918-550: The serum based 14-3-η marker is additive to the armamentarium of existing tools available to clinicians, and that there is adequate clinical evidence to support its clinical benefits. Other blood tests are usually done to differentiate from other causes of arthritis, like the erythrocyte sedimentation rate (ESR), C-reactive protein, full blood count , kidney function , liver enzymes and other immunological tests (e.g., antinuclear antibody /ANA) are all performed at this stage. Elevated ferritin levels can reveal hemochromatosis ,

9016-453: The skin. Similarly, subacute cutaneous lupus manifests as red, scaly patches of skin but with distinct edges. Acute cutaneous lupus manifests as a rash. Some have the classic malar rash (commonly known as the butterfly rash ) associated with the disease. This rash occurs in 30–60% of people with SLE. Hair loss , mouth and nasal ulcers, and lesions on the skin are other possible manifestations. The most commonly sought medical attention

9114-436: The spatial resolution of ultrasound images depicting 20% more erosions than conventional radiography. Color Doppler and power Doppler ultrasound are useful in assessing the degree of synovial inflammation as they can show vascular signals of active synovitis. This is important, since in the early stages of RA, the synovium is primarily affected, and synovitis seems to be the best predictive marker of future joint damage. When RA

9212-445: The subintimal zone in synovitis. The typical rheumatoid nodule may be a few millimetres to a few centimetres in diameter and is usually found over bony prominences, such as the elbow , the heel , the knuckles , or other areas that sustain repeated mechanical stress. Nodules are associated with a positive RF ( rheumatoid factor ) titer , ACPA, and severe erosive arthritis. Rarely, these can occur in internal organs or at diverse sites on

9310-419: The trigger varies, or that it might, in fact, be a chance event inherent with the immune response. RA primarily starts as a state of persistent cellular activation leading to autoimmunity and immune complexes in joints and other organs where it manifests. The clinical manifestations of disease are primarily inflammation of the synovial membrane and joint damage, and the fibroblast-like synoviocytes play

9408-586: The two complement component 4 genes , C4A and C4B . (The C4A and C4B genes code respectively for complement component A and complement component B proteins. These two proteins combine to form the complement component 4 protein which plays various roles in regulating immune function. Individuals normally have multiple copies of the C4A and C4B gene but if they have reduced levels of one and/or both of these genes make low levels of complement component 4 protein and thereby are at risk for developing cSLE or

9506-1086: The vitamin D levels and responses to vitamin D treatment varied in different patient populations (i.e., varied based on whether the study was conducted on individuals living in Africa or Europe). Because of these conflicting findings, the following middle ground has been proposed for using vitamin D to treat SLE: a) patients with SLE that have 25-hydroxyvitamin D 2 plus 25-hydroxyvitamin D 3 serum levels less than 30 ng/ml should be treated with vitamin D to keep these levels at or above 30 ng/ml or, in patients having major SLE-related organ involvement, at 36 to 40 ng/ml and b) patients with 25-hydroxyvitamin D 2 plus 25-hydroxyvitamin D 3 levels at or above 30 ng/ml should not be treated with vitamin D unless they have major SLE-related organ involvement in which case they should be treated with 25-hydroxyvitamin D 2 plus 25-hydroxyvitamin D 3 to maintain their serum vitamin D levels between 36 and 40 ng/ml. Studies of identical twins (i.e., twins that develop from

9604-616: Was made in 1800 by Dr. Augustin Jacob Landré-Beauvais (1772–1840) of Paris. The term rheumatoid arthritis is based on the Greek for watery and inflamed joints. RA primarily affects joints , but it also affects other organs in more than 15–25% of cases. Associated problems include cardiovascular disease, osteoporosis , interstitial lung disease , infection, cancer , feeling tired, depression, mental difficulties, and trouble working. Arthritis of joints involves inflammation of

#826173