In internal medicine , relapse or recidivism is a recurrence of a past (typically medical) condition. For example, multiple sclerosis and malaria often exhibit peaks of activity and sometimes very long periods of dormancy, followed by relapse or recrudescence .
118-410: 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 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
236-676: A genetic predisposition , other cases have been associated with infectious triggers or exposure to environmental factors, implying a complex interplay between genes and environment in their etiology. Some of the most common diseases that are generally categorized as autoimmune include coeliac disease , type 1 diabetes , Graves' disease , inflammatory bowel diseases (such as Crohn's disease and ulcerative colitis ), multiple sclerosis , alopecia areata , Addison's disease , pernicious anemia , psoriasis , rheumatoid arthritis , and systemic lupus erythematosus . Diagnosing autoimmune diseases can be challenging due to their diverse presentations and
354-409: A social hierarchy as well as a difference in the function of cocaine to reinforce self-administration in these animal groups. Socially dominant animals exhibit higher availability of D2 receptors and fail to maintain self-administration. Drug taking and relapse are heavily influenced by a number of factors including the pharmacokinetics , dose , and neurochemistry of the drug itself as well as
472-469: 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
590-543: 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
708-457: A crucial step in triggering autoimmune diseases. The exact mechanisms by which they contribute to disease onset remain to be fully understood. For instance, certain autoimmune conditions like Guillain-Barre syndrome and rheumatic fever are thought to be triggered by infections. Furthermore, analysis of large-scale data has revealed a significant link between SARS-CoV-2 infection (the causative agent of COVID-19 ) and an increased risk of developing
826-403: A function that is compromised in autoimmune diseases. In healthy individuals, immune tolerance prevents the immune system from attacking the body's own cells. When this process fails, the immune system may produce antibodies against its own tissues, leading to an autoimmune response. The elimination of self-reactive T cells occurs primarily through a mechanism known as "negative selection" within
944-473: A genetic component. Some conditions, like lupus and multiple sclerosis, often occur in several members of the same family, indicating a potential hereditary link. Additionally, certain genes have been identified that increase the risk of developing specific autoimmune diseases. Evidence suggests a strong genetic component in the development of autoimmune diseases. For instance, conditions such as lupus and multiple sclerosis frequently appear in multiple members of
1062-515: A higher concordance rate among identical twins compared with fraternal twins. For instance, the rate in multiple sclerosis is 35% in identical twins compared to 6% in fraternal twins. There is increasing evidence that certain genes selected during evolution offer a balance between susceptibility to infection and the capacity to avoid autoimmune diseases. For example, variants in the ERAP2 gene provide some resistance to infection even though they increase
1180-415: A lesser role in craving in humans than in the laboratory models. The validity of the model can be examined in three ways: formal equivalence , correlational models, and functional equivalence. There is moderate formal equivalence, or face validity , meaning that the model somewhat resembles relapse as it occurs outside of the laboratory setting; however, there is little face validity for the procedures as
1298-470: 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
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#17328593806611416-419: A model of craving. The predictive validity , which is assessed by correlational models, has yet to be determined for the procedures. There is sound functional equivalence for the model, which suggests that relapse in the laboratory is reasonably similar to that in nature. Further research into other manipulations or reinforcements that could limit drug-taking in non-human primates would be extremely beneficial to
1534-416: A paradoxical prolonged partial thromboplastin time (which usually occurs in hemorrhagic disorders) and a positive test for antiphospholipid antibodies; the combination of such findings have earned the term " lupus anticoagulant -positive". Another autoantibody finding in SLE is the anti-cardiolipin antibody , which can cause a false positive test for syphilis . SLE may cause pericarditis (inflammation of
1652-484: A pivotal role in the diagnosis of autoimmune diseases. These tests can identify the presence of certain autoantibodies or other immune markers that indicate a self-directed immune response. In some cases, imaging studies may be used to assess the extent of organ involvement and damage. For example, chest x-rays or CT scans can identify lung involvement in diseases like rheumatoid arthritis or systemic lupus erythematosus, while an MRI can reveal inflammation or damage in
1770-607: 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
1888-442: A potential causative factor in the development of autoimmune diseases, such as dermatomyositis. Furthermore, exposure to pesticides has been linked with an increased risk of developing rheumatoid arthritis. Vitamin D, on the other hand, appears to play a protective role, particularly in older populations, by preventing immune dysfunctions. Infectious agents are also being increasingly recognized for their role as T cell activators —
2006-410: A primate chair equipped with a response lever. The animal is seated in a ventilated chamber and trained on a schedule of drug self-administration. In many studies the self-administration task begins with presentation of a stimulus light (located near the response panel) that may change colors or turn off upon completion of the operant task. The change in visual stimulus is accompanied by an injection of
2124-409: 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
2242-516: 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 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
2360-651: 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
2478-758: 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
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#17328593806612596-701: 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,
2714-442: 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
2832-421: A strong desire or intention to use the drug, a feeling termed craving by Abraham Wikler in 1948. The propensity for craving is heavily influenced by all three triggers to relapse and is now an accepted hallmark of substance dependence . Stress is one of the most powerful stimuli for reinstating drug use because stress cues stimulate craving and drug-seeking behavior during abstinence . Stress-induced craving
2950-440: A thorough evaluation of the patient's medical history and a comprehensive physical examination. Clinicians often pay close attention to the patient's symptoms, family history of autoimmune diseases, and any exposure to environmental factors that might trigger an autoimmune response. The physical examination can reveal signs of inflammation or organ damage, which are common features of autoimmune disorders. Laboratory testing plays
3068-434: 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,
3186-427: A wide range of new-onset autoimmune diseases. Women typically make up some 80% of autoimmune disease patients. Whilst many proposals have been made for the cause of this high weighting, no clear explanation is available. A possible role for hormonal factors has been suggested. For example, some autoimmune diseases tend to flare during pregnancy (possibly as an evolutionary mechanism to increase health protection for
3304-448: Is a marked increase in progesterone levels and a decrease in estradiol levels during the luteal phase . Anxiety , irritability, and depression , three symptoms of both withdrawal and the human menstrual cycle, are most severe in the luteal phase. Symptoms of withdrawal not associated with the cycle, such as hunger, are also enhanced during the luteal phase, which suggests the role of estradiol and progesterone in enhancing symptoms above
3422-421: Is a systemic autoimmune disease that affects multiple organs, including the skin, joints, kidneys, and the nervous system. It is characterized by a widespread loss of immune tolerance. The disease is characterized by periods of flares and remissions, and symptoms range from mild to severe. Women, especially those of childbearing age, are disproportionately affected. Type 1 diabetes is a condition resulting from
3540-426: 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 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
3658-447: Is also predictive of time to relapse. Comparably, addicted individuals show an increased susceptibility to stressors than do non-addicted controls. Examples of stressors that may induce reinstatement include emotions of fear , sadness , or anger , a physical stressor such as a footshock or elevated sound level, or a social event. Drug-priming is exposing the abstinent user to the addictive substances, which will induce reinstatement of
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3776-427: Is associated with an increased risk of central nervous system cancer, primarily in the brain. Rheumatoid arthritis (RA) primarily targets the joints, causing persistent inflammation that results in joint damage and pain. It is often symmetrical, meaning that if one hand or knee has it, the other one does too. RA can also affect the heart, lungs, and eyes. Additionally, the chronic inflammation and over-activation of
3894-470: 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
4012-561: 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 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
4130-473: 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 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
4248-492: Is correlated with lymphoproliferative disorders . Graves' disease is a condition characterized by development of autoantibodies to thyroid-stimulating hormone receptors. The binding of the autoantibodies to the receptors results in unregulated production and release of thyroid hormone , which can lead to stimulatory effects such as rapid heart rate, weight loss, nervousness, and irritability. Other symptoms more specific to Graves' disease include bulging eyes and swelling of
4366-406: Is cue exposure, during which the abstinent user is repeatedly exposed to the most salient triggers without exposure to the substance in hopes that the substance will gradually lose the ability to induce drug-seeking behavior. This approach is likely to reduce the severity of a relapse than to prevent one from occurring altogether. Another method teaches addicts basic coping mechanisms to avoid using
4484-529: Is equipped with several mechanisms to maintain a delicate balance between defending against foreign invaders and protecting its own cells. To achieve this, it generates both T cells and B cells , which are capable of reacting with self-proteins. However, in a healthy immune response, self-reactive cells are generally either eliminated before they become active, rendered inert via a process called anergy, or their activities are suppressed by regulatory cells. A familial tendency to develop autoimmune diseases suggests
4602-442: Is estimated that over 80 recognized types of autoimmune diseases exist, this section provides an overview of some of the most common and well-studied forms. Coeliac disease is an immune reaction to eating gluten , a protein found in wheat , barley , and rye . For those with the disease, eating gluten triggers an immune response in the small intestine , leading to damage on the villi , small fingerlike projections that line
4720-429: Is estimated that there are more than 80 recognized autoimmune diseases, with recent scientific evidence suggesting the existence of potentially more than 100 distinct conditions. Nearly any body part can be involved. Autoimmune diseases are a separate class from autoinflammatory diseases . Both are characterized by an immune system malfunction which may cause similar symptoms, such as rash, swelling, or fatigue, but
4838-518: 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 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
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4956-411: 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 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
5074-677: 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
5192-525: 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),
5310-474: Is the recurrence of pathological drug use, self harm or other symptoms after a period of recovery. Relapse is often observed in individuals who have developed a drug addiction or a form of drug dependence , as well as those who have a mental disorder . The availability of the dopamine receptor D2 plays a role in self-administration and the reinforcing effects of cocaine and other stimulants . The D2 receptor availability has an inverse relationship to
5428-503: Is widely used in human subjects because it has much higher resolution and eliminates exposure to radiation . Although the reinstatement protocols are used frequently in laboratory settings there are some limitations to the validity of the procedures as a model of craving and relapse in humans. The primary limiting factor is that in humans, relapse rarely follows the strict extinction of drug-seeking behavior. Additionally, human self-reports show that drug-associated stimuli play
5546-485: The dopamine receptor D2 , and changes in the medial prefrontal cortex are prominent targets for pharmacotherapy to prevent relapse because they are heavily linked to drug-induced, stress-induced, and cue-induced relapse. Receptor recovery can be upregulated by administration of receptor antagonists , while pharmacotherapeutic treatments for neruoadaptations in the medial prefrontal cortex are still relatively ineffective due to lacking knowledge of these adaptations on
5664-897: The illicit drug . It is important to address any deficits in coping skills, to identify the needs that likely induce drug-seeking , and to develop another way to meet them. Relapse prevention attempts to group the factors that contribute to relapse into two broad categories: immediate determinants and covert antecedents. Immediate determinants are the environmental and emotional situations that are associated with relapse, including high-risk situations that threaten an individual’s sense of control, coping strategies , and outcome expectancies . Covert antecedents, which are less obvious factors influencing relapse, include lifestyle factors such as stress level and balance, and urges and cravings . The relapse prevention model teaches addicts to anticipate relapse by recognizing and coping with various immediate determinants and covert antecedents. The RP model shows
5782-715: 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
5900-508: 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
6018-471: The molecular and cellular level. The various behavioral approaches to treating relapse focus on the precursors and consequences of drug-taking and reinstatement. Cognitive-behavioral techniques (CBT) incorporate Pavlovian conditioning and operant conditioning , characterized by positive reinforcement and negative reinforcement , in order to alter the cognitions , thoughts , and emotions associated with drug-taking behavior. A main approach of CBT
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#17328593806616136-698: 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
6254-666: 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
6372-442: The ability of the animal to reinstate self-administration , and to learn complex behaviors in order to obtain the drug. Animal studies have shown that a reduction in negative withdrawal symptoms is not necessary to maintain drug taking in laboratory animals; the key to these studies is operant conditioning and reinforcement. To self-administer the drug of interest the animal is implanted with an intravenous catheter and seated in
6490-440: 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 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
6608-470: The bacterium that causes strep throat , Streptococcus pyogenes , might trigger rheumatic fever , an autoimmune response affecting the heart. Similarly, some studies propose a link between the Epstein–Barr virus , responsible for mononucleosis, and the subsequent development of multiple sclerosis or lupus. Another area of interest is the immune system's ability to distinguish between self and non-self,
6726-627: 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),
6844-492: The body's immune system mistakenly attacking its own cells and tissues, causing inflammation and damage. However, due to the broad range of autoimmune diseases, the specific presentation of symptoms can significantly vary based on the type of disease, the organ systems affected, and individual factors such as age, sex, hormonal status, and environmental influences. An individual may simultaneously have more than one autoimmune disease (known as polyautoimmunity), further complicating
6962-497: The body's self-molecules. This phenomenon, known as molecular mimicry , can lead to cross-reactivity, where the immune response to such infections inadvertently results in the production of antibodies that also react with self-antigens. An example of this is Guillain–Barré syndrome , in which antibodies generated in response to a C. jejuni infection also react with the gangliosides in the myelin sheath of peripheral nerve axons. Diagnosing autoimmune disorders can be complex due to
7080-528: The brain and spinal cord in multiple sclerosis. Given the variety and nonspecific nature of symptoms that can be associated with autoimmune diseases, differential diagnosis—determining which of several diseases with similar symptoms is causing a patient's illness—is an important part of the diagnostic process. This often involves ruling out other potential causes of symptoms, such as infections, malignancies, or genetic disorders. Relapse In psychiatry , relapse or reinstatement of drug-seeking behavior ,
7198-923: The cardinal cause or mechanism of the diseases are different. A key difference is a malfunction of the innate immune system in autoinflammatory diseases, whereas in autoimmune diseases there is a malfunction of the adaptive immune system . Symptoms of autoimmune diseases can significantly vary, primarily based on the specific type of the disease and the body part that it affects. Symptoms are often diverse and can be fleeting, fluctuating from mild to severe, and typically comprise low-grade fever , fatigue , and general malaise . However, some autoimmune diseases may present with more specific symptoms such as joint pain , skin rashes (e.g., urticaria ), or neurological symptoms. The exact causes of autoimmune diseases remain unclear and are likely multifactorial, involving both genetic and environmental influences. While some diseases like lupus exhibit familial aggregation, suggesting
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#17328593806617316-450: 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
7434-422: The child), when hormone levels are high, and improve after menopause, when hormone levels decrease. Women may also naturally have autoimmune disease trigger events in puberty and pregnancy. Under-reporting by men may also be a factor, as men may interact less with the health system than women. Certain viral and bacterial infections have been linked to autoimmune diseases. For instance, research suggests that
7552-442: The complexity and multifaceted nature of these conditions. Various environmental triggers are identified, some of which include: Chemicals, which are either a part of the immediate environment or found in drugs, are key players in this context. Examples of such chemicals include hydrazines , hair dyes , trichloroethylene , tartrazines , hazardous wastes, and industrial emissions. Ultraviolet radiation has been implicated as
7670-478: The consequences of drug use as opposed to its precursors. Addict behavior is reinforced , by reward or punishment , based on ability to remain abstinent . A common example of contingency management is a token or voucher system , in which abstinence is rewarded with tokens or vouchers that individuals can redeem for various retail items. There are vast ethical limitations in drug addiction research because humans cannot be allowed to self-administer drugs for
7788-530: 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 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
7906-447: The development and progression of various autoimmune diseases, either directly or as catalysts. Current research suggests that up to seventy percent of autoimmune diseases could be attributed to environmental influences, which encompass an array of elements such as chemicals, infectious agents, dietary habits, and gut dysbiosis. However, a unifying theory that definitively explains the onset of autoimmune diseases remains elusive, emphasizing
8024-704: 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
8142-424: The diagnosis of an autoimmune condition, often in conjunction with tests for specific biological markers, but also help monitor disease progression and response to treatment. Ultimately, due to the diverse nature of autoimmune diseases, a multidimensional approach is often needed for the management of these conditions, taking into consideration the variety of symptoms and their impacts on individuals' lives. While it
8260-430: The diagnostic criteria established for any one connective tissue disease. Some 30–40% transition to a specific connective tissue disease over time. The exact causes of autoimmune diseases remain largely unknown; however, research has suggested that a combination of genetic, environmental, and hormonal factors, as well as certain infections, may contribute to the development of these disorders. The human immune system
8378-526: 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 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
8496-408: The disease. Men have higher mortality. SLE significantly increases 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
8614-417: The drug in question it will likely begin working on the operant task for which it was previously reinforced. The stimulus may be the drug itself, the visual stimulus that was initially paired with the drug intake, or a stressor such as an acoustic startle or foot shock. However, the stimulus used to trigger reinstatement can influence the psychological processes involved. Neuroimaging has contributed to
8732-423: The drug taker’s environment and drug-related history. Reinstatement of drug use after a period of non-use or abstinence is typically initiated by one or a combination of the three main triggers: stress , re-exposure to the drug or drug-priming, and environmental cues. These factors may induce a neurochemical response in the drug taker that mimics the drug and thus triggers reinstatement. These cues may lead to
8850-435: The drug-seeking behavior and drug self-administration. Stimuli that have a pre-existing association with a given drug or with use of that drug can trigger both craving and reinstatement. These cues include any items, places, or people associated with the drug. Relapse treatment is somewhat of a misnomer because relapse itself is a treatment failure; however there exist three main approaches that are currently used to reduce
8968-429: The drug. The visual stimulus associated with the drug and completion of the task is also removed. The extinction sessions are continued until the animal ceases the drug-seeking behavior by pressing the lever. After the animal’s drug-seeking behavior is extinguished, a stimulus is presented to promote the reinstatement of that same drug-seeking behavior (i.e., relapse). For example, if the animal receives an injection of
9086-503: 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
9204-402: The early 1900s, and since then, advancements in understanding and management of these conditions have been substantial, though much more is needed to fully unravel their complex etiology and pathophysiology . Autoimmune diseases represent a vast and diverse category of disorders that, despite their differences, share some common symptomatic threads. These shared symptoms occur as a result of
9322-406: The field. There exists a higher rate of relapse, shorter periods of abstinence , and higher responsiveness to drug-related cues in women as compared to men. One study suggests that the ovarian hormones , estradiol and progesterone , that exist in females at fluctuating levels throughout the menstrual cycle (or estrous cycle in rodents), play a significant role in drug-primed relapse. There
9440-450: The gastrointestinal tract and some lymphoproliferative cancers. Multiple sclerosis (MS) is a neurodegenerative disease in which the immune system attacks myelin , a protective covering of nerve fibers in the central nervous system, causing communication problems between the brain and the rest of the body. Symptoms can include fatigue, difficulty walking, numbness or tingling, muscle weakness, and problems with coordination and balance. MS
9558-418: 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
9676-418: The given drug through the implanted catheter. This schedule is maintained until the animals learn the task. Extinction in non-human primates is analogous, with some limitations, to abstinence in humans. In order to extinguish drug-seeking behavior the drug is substituted with a saline solution. When the animal performs the task it has been trained to perform it is no longer reinforced with an injection of
9794-415: The greatest success with treatment of alcoholism but it has not been proven superior to other treatment options. Relapse may also be more likely to occur during certain times, such as the holiday season when stress levels are typically higher. So, emphasizing relapse prevention strategies during these times is ideal. In contrast to the behavioral approaches above, contingency management concentrates on
9912-471: The identification of the neural components involved in drug reinstatement as well as drug-taking determinants such as the pharmokinetics , neurochemistry , and dose of the drug. The neuroimaging techniques used in non-human primates include positron emission tomography (PET), which uses radiolabeled ligand tracers to measure neurochemistry in vivo and single-photon emission computed tomography (SPECT). Functional magnetic resonance imaging (fMRI)
10030-452: The immune system attacking insulin-producing beta cells in the pancreas , leading to high blood sugar levels. Symptoms include increased thirst , frequent urination , and unexplained weight loss . It is most commonly diagnosed in children and young adults. Undifferentiated connective tissue disease occurs when people have features of connective tissue disease, such as blood test results and external characteristics, but do not fulfill
10148-406: The immune system creates an environment that favors further malignant transformation of other cells, perhaps explaining the associations with cancer of the lungs and skin as well as the increased risk of other hematologic cancers, none of which are directly affected by the inflammation of joints. Psoriasis is a skin condition characterized by the rapid buildup of skin cells, leading to scaling on
10266-428: 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
10384-600: 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
10502-428: The initial drug use, and prevent reinstatement of the drug. Medications can normalize the long-term changes that occur in the brain and nervous system as a result of prolonged drug use. This method of therapy is complex and multi-faceted because the brain target for the desire to use the drug may be different from the target induced by the drug itself. The availability of various neurotransmitter receptors , such as
10620-413: The initial targets of nRNP and Sm autoantibodies identifies a likely commonality in cause and a focal point for intermolecular epitope spreading. Autoimmune disease An autoimmune disease is a condition that results from an anomalous response of the adaptive immune system , wherein it mistakenly targets and attacks healthy, functioning parts of the body as if they were foreign organisms. It
10738-451: The level existing prior to drug exposure during long periods of abstinence , a fact which may have implications in relapse treatment . Social interactions , such as the formation of linear dominance hierarchies , also play a role in vulnerability to substance use. Animal studies suggest that there exists a difference in D2 receptor availability between dominant and subordinate animals within
10856-421: The likelihood of drug relapse. These include pharmacotherapy , cognitive behavioral techniques , and contingency management . The main goals of treating substance dependence and preventing relapse are to identify the needs that were previously met by use of the drug and to develop the skills needed to meet those needs in an alternative way. Various medications are used to stabilize an addicted user, reduce
10974-624: The location and type of autoimmune response. For instance, in rheumatoid arthritis, an autoimmune disease primarily affecting the joints, symptoms typically include joint pain, swelling, and stiffness. On the other hand, type 1 diabetes, which results from an autoimmune attack on the insulin-producing cells of the pancreas, primarily presents with symptoms related to high blood sugar, such as increased thirst, frequent urination, and unexplained weight loss. Commonly affected areas in autoimmune diseases include blood vessels, connective tissues, joints, muscles, red blood cells, skin, and endocrine glands such as
11092-608: 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.,
11210-420: The lower legs . Inflammatory bowel disease encompasses conditions characterized by chronic inflammation of the digestive tract, including Crohn's disease and ulcerative colitis . In both cases, individuals lose immune tolerance for normal bacteria present in the gut microbiome . Symptoms include severe diarrhea, abdominal pain, fatigue, and weight loss. Inflammatory bowel disease is associated with cancers of
11328-473: 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 the skin. Similarly, subacute cutaneous lupus manifests as red, scaly patches of skin but with distinct edges. Acute cutaneous lupus manifests as
11446-440: 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
11564-428: 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
11682-649: 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
11800-402: The naturally occurring level of the menstrual cycle. The symptoms of craving also increase during the luteal phase in humans (it is important to note that the opposite result occurs in female subjects with cocaine addiction suggesting that cyclic changes may be specific for different addictive substances). Further, the drug-primed response is decreased during the luteal phase suggesting a time in
11918-646: The outer lining surrounding the heart), myocarditis (inflammation of the heart muscle), or endocarditis (inflammation of 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
12036-579: The overactive immune response. In certain cases, intravenous immunoglobulin may be administered to regulate the immune system. Despite these treatments often leading to symptom improvement, they usually do not offer a cure and long-term management is often required. In terms of prevalence, a UK study found that 10% of the population were affected by an autoimmune disease. Women are more commonly affected than men. Autoimmune diseases predominantly begin in adulthood, although they can start at any age. The initial recognition of autoimmune diseases dates back to
12154-430: 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
12272-452: 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,
12390-426: The purpose of being studied. However, much can be learned about drugs and the neurobiology of drug taking by the examination of laboratory animals. Most studies are performed on rodents or non-human primates with the latter being most comparable to humans in pharmacokinetics , anatomy of the prefrontal cortex , social behavior , and life span . Other advantages to studying relapse in non-human primates include
12508-671: The risk of autoimmunity (positive selection). In contrast, variants in the TYK2 gene protect against autoimmune diseases but increase the risk of infection (negative selection). This suggests the benefits of infection resistance may outweigh the risks of autoimmune diseases, particularly given the historically high risk of infection. Several experimental methods such as the genome-wide association studies have been used to identify genetic risk variants that may be responsible for diseases such as type 1 diabetes and rheumatoid arthritis. A significant number of environmental factors have been implicated in
12626-538: The same family, signifying a potential hereditary link. Furthermore, certain genes have been identified that augment the risk of developing specific autoimmune diseases. Experimental methods like genome-wide association studies have proven instrumental in pinpointing genetic risk variants potentially responsible for autoimmune diseases. For example, these studies have been used to identify risk variants for diseases such as type 1 diabetes and rheumatoid arthritis. In twin studies, autoimmune diseases consistently demonstrate
12744-514: 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
12862-484: The skin's surface. Inflammation and redness around the scales is common. Some individuals with psoriasis also develop psoriatic arthritis , which causes joint pain, stiffness, and swelling. Sjögren syndrome is a long-term autoimmune disease that affects the body's moisture-producing glands (lacrimal and salivary), and often seriously affects other organ systems, such as the lungs, kidneys, and nervous system. Systemic lupus erythematosus , referred to simply as lupus,
12980-457: The small intestine and promote nutrient absorption. This explains the increased risk of gastrointestinal cancers , as the gastrointestinal tract includes the esophagus, stomach, small intestine, large intestine, rectum, and anus, all areas that the ingested gluten would traverse in digestion. The incidence of gastrointestinal cancer can be partially reduced or eliminated if a patient removes gluten from their diet. Additionally, coeliac disease
13098-631: The symptomatology. Symptoms that are commonly associated with autoimmune diseases include: Specific autoimmune diseases have a wide range of other symptoms, with examples including dry mouth, dry eyes, tingling and numbness in parts of the body, unexpected weight loss or gain, and diarrhoea. These symptoms often reflect the body's systemic inflammatory response. However, their occurrence and intensity can fluctuate over time, leading to periods of heightened disease activity, referred to as flare-ups, and periods of relative inactivity, known as remissions. The specific presentation of symptoms largely depends on
13216-414: The thymus, an organ responsible for the maturation of T cells. This process serves as a key line of defense against autoimmunity. If these protective mechanisms fail, a pool of self-reactive cells can become functional within the immune system, contributing to the development of autoimmune diseases. Some infectious agents, like Campylobacter jejuni , bear antigens that resemble, but are not identical to,
13334-400: The thyroid gland (in diseases like Hashimoto's thyroiditis and Graves' disease) and the pancreas (in type 1 diabetes). The impacts of these diseases can range from localized damage to certain tissues, alteration in organ growth and function, to more systemic effects when multiple tissues throughout the body are affected. The appearance of these signs and symptoms can not only provide clues for
13452-405: The transient nature of many symptoms. Treatment modalities for autoimmune diseases vary based on the type of disease and its severity. Therapeutic approaches primarily aim to manage symptoms, reduce immune system activity, and maintain the body's ability to fight diseases. Nonsteroidal anti-inflammatory drugs (NSAIDs) and immunosuppressants are commonly used to reduce inflammation and control
13570-582: 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
13688-1085: 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
13806-455: The vulnerability of reinforcing effects of the drug . With the D2 receptors becoming limited, the user becomes more susceptible to the reinforcing effects of cocaine. It is currently unknown if a predisposition to low D2 receptor availability is possible; however, most studies support the idea that changes in D2 receptor availability are a result , rather than a precursor , of cocaine use. It has also been noted that D2 receptors may return to
13924-414: The wide range of diseases within this category and their often overlapping symptoms. Accurate diagnosis is crucial for determining appropriate treatment strategies. Generally, the diagnostic process involves a combination of medical history evaluation, physical examination , laboratory tests , and, in some cases, imaging or biopsies . The first step in diagnosing autoimmune disorders typically involves
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