<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Alcoholism and explain in detail? [/INST] Alcoholism is, broadly, any drinking of alcohol that results in significant mental or physical health problems. Because there is disagreement on the definition of the word alcoholism, it is not a recognized diagnostic entity. Predominant diagnostic classifications are alcohol use disorder (DSM-5) or alcohol dependence (ICD-11); these are defined in their respective sources.Excessive alcohol use can damage all organ systems, but it particularly affects the brain, heart, liver, pancreas and immune system. Alcoholism can result in mental illness, delirium tremens, Wernicke–Korsakoff syndrome, irregular heartbeat, an impaired immune response, liver cirrhosis and increased cancer risk. Drinking during pregnancy can result in fetal alcohol spectrum disorders. Women are generally more sensitive than men to the harmful effects of alcohol, primarily due to their smaller body weight, lower capacity to metabolize alcohol, and higher proportion of body fat. In a small number of individuals, prolonged, severe alcohol misuse ultimately leads to cognitive impairment and frank dementia.
Environment and genetics are two factors in the risk of development of alcoholism, with about half the risk attributed to each. Stress and associated disorders, including anxiety, are key factors in the development of alcoholism as alcohol consumption can temporarily reduce dysphoria. Someone with a parent or sibling with an alcohol use disorder is three to four times more likely to develop an alcohol use disorder themselves, but only a minority of them do. Environmental factors include social, cultural and behavioral influences. High stress levels and anxiety, as well as alcohols inexpensive cost and easy accessibility, increase the risk. People may continue to drink partly to prevent or improve symptoms of withdrawal. After a person stops drinking alcohol, they may experience a low level of withdrawal lasting for months. Medically, alcoholism is considered both a physical and mental illness. Questionnaires are usually used to detect possible alcoholism. Further information is then collected to confirm the diagnosis.Prevention of alcoholism may be attempted by reducing the experience of stress and anxiety in individuals. It can be attempted by regulating and limiting the sale of alcohol (particularly to minors), taxing alcohol to increase its cost, and providing education and treatment.Treatment of alcoholism may take several forms. Due to medical problems that can occur during withdrawal, alcohol cessation should be controlled carefully. One common method involves the use of benzodiazepine medications, such as diazepam. These can be taken while admitted to a health care institution or individually. The medications acamprosate, disulfiram or naltrexone may also be used to help prevent further drinking. Mental illness or other addictions may complicate treatment. Various forms of individual or group therapy or support groups are used to attempt to keep a person from returning to alcoholism. One support group is Alcoholics Anonymous.The World Health Organization has estimated that as of 2016, there were 380 million people with alcoholism worldwide (5.1% of the population over 15 years of age). As of 2015 in the United States, about 17 million (7%) of adults and 0.7 million (2.8%) of those age 12 to 17 years of age are affected. Alcoholism is most common among males and young adults. Geographically, it is least common in Africa (1.1% of the population) and has the highest rates in Eastern Europe (11%). Alcoholism directly resulted in 139,000 deaths in 2013, up from 112,000 deaths in 1990. A total of 3.3 million deaths (5.9% of all deaths) are believed to be due to alcohol. Alcoholism reduces a persons life expectancy by approximately ten years. Many terms, some slurs and others informal, have been used to refer to people affected by alcoholism; the expressions include tippler, drunkard, dipsomaniac and souse. In 1979, the World Health Organization discouraged the use of alcoholism due to its inexact meaning, preferring alcohol dependence syndrome.

Signs and symptoms
The risk of alcohol dependence begins at low levels of drinking and increases directly with both the volume of alcohol consumed and a pattern of drinking larger amounts on an occasion, to the point of intoxication, which is sometimes called binge drinking.

Long-term misuse
Alcoholism is characterised by an increased tolerance to alcohol – which means that an individual can consume more alcohol – and physical dependence on alcohol, which makes it hard for an individual to control their consumption. The physical dependency caused by alcohol can lead to an affected individual having a very strong urge to drink alcohol. These characteristics play a role in decreasing the ability to stop drinking of an individual with an alcohol use disorder. Alcoholism can have adverse effects on mental health, contributing to psychiatric disorders and increasing the risk of suicide. A depressed mood is a common symptom of heavy alcohol drinkers.

Warning signs
Warning signs of alcoholism include the consumption of increasing amounts of alcohol and frequent intoxication, preoccupation with drinking to the exclusion of other activities, promises to quit drinking and failure to keep those promises, the inability to remember what was said or done while drinking (colloquially known as "blackouts"), personality changes associated with drinking, denial or the making of excuses for drinking, the refusal to admit excessive drinking, dysfunction or other problems at work or school, the loss of interest in personal appearance or hygiene, marital and economic problems, and the complaint of poor health, with loss of appetite, respiratory infections, or increased anxiety.

Physical
Short-term effects
Drinking enough to cause a blood alcohol concentration (BAC) of 0.03–0.12% typically causes an overall improvement in mood and possible euphoria (a "happy" feeling), increased self-confidence and sociability, decreased anxiety, a flushed, red appearance in the face and impaired judgment and fine muscle coordination. A BAC of 0.09% to 0.25% causes lethargy, sedation, balance problems and blurred vision. A BAC of 0.18% to 0.30% causes profound confusion, impaired speech (e.g. slurred speech), staggering, dizziness and vomiting. A BAC from 0.25% to 0.40% causes stupor, unconsciousness, anterograde amnesia, vomiting (death may occur due to inhalation of vomit while unconscious) and respiratory depression (potentially life-threatening). A BAC from 0.35% to 0.80% causes a coma (unconsciousness), life-threatening respiratory depression and possibly fatal alcohol poisoning. With all alcoholic beverages, drinking while driving, operating an aircraft or heavy machinery increases the risk of an accident; many countries have penalties for drunk driving.

Long-term effects
Having more than one drink a day for women or two drinks for men increases the risk of heart disease, high blood pressure, atrial fibrillation, and stroke. Risk is greater with binge drinking, which may also result in violence or accidents. About 3.3 million deaths (5.9% of all deaths) are believed to be due to alcohol each year. Alcoholism reduces a persons life expectancy by around ten years and alcohol use is the third leading cause of early death in the United States. Long-term alcohol misuse can cause a number of physical symptoms, including cirrhosis of the liver, pancreatitis, epilepsy, polyneuropathy, alcoholic dementia, heart disease, nutritional deficiencies, peptic ulcers and sexual dysfunction, and can eventually be fatal. Other physical effects include an increased risk of developing cardiovascular disease, malabsorption, alcoholic liver disease, and several cancers. Damage to the central nervous system and peripheral nervous system can occur from sustained alcohol consumption. A wide range of immunologic defects can result and there may be a generalized skeletal fragility, in addition to a recognized tendency to accidental injury, resulting in a propensity for bone fractures.Women develop long-term complications of alcohol dependence more rapidly than do men, women also have a higher mortality rate from alcoholism than men. Examples of long-term complications include brain, heart, and liver damage and an increased risk of breast cancer. Additionally, heavy drinking over time has been found to have a negative effect on reproductive functioning in women. This results in reproductive dysfunction such as anovulation, decreased ovarian mass, problems or irregularity of the menstrual cycle, and early menopause. Alcoholic ketoacidosis can occur in individuals who chronically misuse alcohol and have a recent history of binge drinking. The amount of alcohol that can be biologically processed and its effects differ between sexes. Equal dosages of alcohol consumed by men and women generally result in women having higher blood alcohol concentrations (BACs), since women generally have a lower weight and higher percentage of body fat and therefore a lower volume of distribution for alcohol than men.

Psychiatric
Long-term misuse of alcohol can cause a wide range of mental health problems. Severe cognitive problems are common; approximately 10% of all dementia cases are related to alcohol consumption, making it the second leading cause of dementia. Excessive alcohol use causes damage to brain function, and psychological health can be increasingly affected over time. Social skills are significantly impaired in people with alcoholism due to the neurotoxic effects of alcohol on the brain, especially the prefrontal cortex area of the brain. The social skills that are impaired by alcohol use disorder include impairments in perceiving facial emotions, prosody, perception problems, and theory of mind deficits; the ability to understand humor is also impaired in people who misuse alcohol. Psychiatric disorders are common in people with alcohol use disorders, with as many as 25% also having severe psychiatric disturbances. The most prevalent psychiatric symptoms are anxiety and depression disorders. Psychiatric symptoms usually initially worsen during alcohol withdrawal, but typically improve or disappear with continued abstinence. Psychosis, confusion, and organic brain syndrome may be caused by alcohol misuse, which can lead to a misdiagnosis such as schizophrenia. Panic disorder can develop or worsen as a direct result of long-term alcohol misuse.The co-occurrence of major depressive disorder and alcoholism is well documented. Among those with comorbid occurrences, a distinction is commonly made between depressive episodes that remit with alcohol abstinence ("substance-induced"), and depressive episodes that are primary and do not remit with abstinence ("independent" episodes). Additional use of other drugs may increase the risk of depression. Psychiatric disorders differ depending on gender. Women who have alcohol-use disorders often have a co-occurring psychiatric diagnosis such as major depression, anxiety, panic disorder, bulimia, post-traumatic stress disorder (PTSD), or borderline personality disorder. Men with alcohol-use disorders more often have a co-occurring diagnosis of narcissistic or antisocial personality disorder, bipolar disorder, schizophrenia, impulse disorders or attention deficit/hyperactivity disorder (ADHD). Women with alcohol use disorder are more likely to experience physical or sexual assault, abuse, and domestic violence than women in the general population, which can lead to higher instances of psychiatric disorders and greater dependence on alcohol.

Social effects
Serious social problems arise from alcohol use disorder; these dilemmas are caused by the pathological changes in the brain and the intoxicating effects of alcohol. Alcohol misuse is associated with an increased risk of committing criminal offences, including child abuse, domestic violence, rape, burglary and assault. Alcoholism is associated with loss of employment, which can lead to financial problems. Drinking at inappropriate times and behavior caused by reduced judgment can lead to legal consequences, such as criminal charges for drunk driving or public disorder, or civil penalties for tortious behavior. An alcoholics behavior and mental impairment while drunk can profoundly affect those surrounding him and lead to isolation from family and friends. This isolation can lead to marital conflict and divorce, or contribute to domestic violence. Alcoholism can also lead to child neglect, with subsequent lasting damage to the emotional development of children of people with alcohol use disorders. For this reason, children of people with alcohol use disorders can develop a number of emotional problems. For example, they can become afraid of their parents, because of their unstable mood behaviors. They may develop shame over their inadequacy to liberate their parents from alcoholism and, as a result of this, may develop self-image problems, which can lead to depression.

Alcohol withdrawal
As with similar substances with a sedative-hypnotic mechanism, such as barbiturates and benzodiazepines, withdrawal from alcohol dependence can be fatal if it is not properly managed. Alcohols primary effect is the increase in stimulation of the GABAA receptor, promoting central nervous system depression. With repeated heavy consumption of alcohol, these receptors are desensitized and reduced in number, resulting in tolerance and physical dependence. When alcohol consumption is stopped too abruptly, the persons nervous system experiences uncontrolled synapse firing. This can result in symptoms that include anxiety, life-threatening seizures, delirium tremens, hallucinations, shakes and possible heart failure. Other neurotransmitter systems are also involved, especially dopamine, NMDA and glutamate.Severe acute withdrawal symptoms such as delirium tremens and seizures rarely occur after 1-week post cessation of alcohol. The acute withdrawal phase can be defined as lasting between one and three weeks. In the period of 3–6 weeks following cessation, anxiety, depression, fatigue, and sleep disturbance are common. Similar post-acute withdrawal symptoms have also been observed in animal models of alcohol dependence and withdrawal.A kindling effect also occurs in people with alcohol use disorders whereby each subsequent withdrawal syndrome is more severe than the previous withdrawal episode; this is due to neuroadaptations which occur as a result of periods of abstinence followed by re-exposure to alcohol. Individuals who have had multiple withdrawal episodes are more likely to develop seizures and experience more severe anxiety during withdrawal from alcohol than alcohol-dependent individuals without a history of past alcohol withdrawal episodes. The kindling effect leads to persistent functional changes in brain neural circuits as well as to gene expression. Kindling also results in the intensification of psychological symptoms of alcohol withdrawal. There are decision tools and questionnaires that help guide physicians in evaluating alcohol withdrawal. For example, the CIWA-Ar objectifies alcohol withdrawal symptoms in order to guide therapy decisions which allows for an efficient interview while at the same time retaining clinical usefulness, validity, and reliability, ensuring proper care for withdrawal patients, who can be in danger of death.

Causes
A complex combination of genetic and environmental factors influences the risk of the development of alcoholism. Genes that influence the metabolism of alcohol also influence the risk of alcoholism, as can a family history of alcoholism. There is compelling evidence that alcohol use at an early age may influence the expression of genes which increase the risk of alcohol dependence. These genetic and epigenetic results are regarded as consistent with large longitudinal population studies finding that the younger the age of drinking onset, the greater the prevalence of lifetime alcohol dependence.Severe childhood trauma is also associated with a general increase in the risk of drug dependency. Lack of peer and family support is associated with an increased risk of alcoholism developing. Genetics and adolescence are associated with an increased sensitivity to the neurotoxic effects of chronic alcohol misuse. Cortical degeneration due to the neurotoxic effects increases impulsive behaviour, which may contribute to the development, persistence and severity of alcohol use disorders. There is evidence that with abstinence, there is a reversal of at least some of the alcohol induced central nervous system damage. The use of cannabis was associated with later problems with alcohol use. Alcohol use was associated with an increased probability of later use of tobacco and illegal drugs such as cannabis.

Availability
Alcohol is the most available, widely consumed, and widely misused recreational drug. Beer alone is the worlds most widely consumed alcoholic beverage; it is the third-most popular drink overall, after water and tea. It is thought by some to be the oldest fermented beverage.

Gender difference
Based on combined data in the US from SAMHSAs 2004–2005 National Surveys on Drug Use & Health, the rate of past-year alcohol dependence or misuse among persons aged 12 or older varied by level of alcohol use: 44.7% of past month heavy drinkers, 18.5% binge drinkers, 3.8% past month non-binge drinkers, and 1.3% of those who did not drink alcohol in the past month met the criteria for alcohol dependence or misuse in the past year. Males had higher rates than females for all measures of drinking in the past month: any alcohol use (57.5% vs. 45%), binge drinking (30.8% vs. 15.1%), and heavy alcohol use (10.5% vs. 3.3%), and males were twice as likely as females to have met the criteria for alcohol dependence or misuse in the past year (10.5% vs. 5.1%).

Genetic variation
There are genetic variations that affect the risk for alcoholism. Some of these variations are more common in individuals with ancestry from certain areas, for example Africa, East Asia, the Middle East and Europe. The variants with strongest effect are in genes that encode the main enzymes of alcohol metabolism, ADH1B and ALDH2. These genetic factors influence the rate at which alcohol and its initial metabolic product, acetaldehyde, are metabolized. They are found at different frequencies in people from different parts of the world. The alcohol dehydrogenase allele ADH1B*2 causes a more rapid metabolism of alcohol to acetaldehyde, and reduces risk for alcoholism; it is most common in individuals from East Asia and the Middle East. The alcohol dehydrogenase allele ADH1B*3 also causes a more rapid metabolism of alcohol. The allele ADH1B*3 is only found in some individuals of African descent and certain Native American tribes. African Americans and Native Americans with this allele have a reduced risk of developing alcoholism. Native Americans, however, have a significantly higher rate of alcoholism than average; risk factors such as cultural environmental effects (e.g. trauma) have been proposed to explain the higher rates. The aldehyde dehydrogenase allele ALDH2*2 greatly reduces the rate at which acetaldehyde, the initial product of alcohol metabolism, is removed by conversion to acetate; it greatly reduces the risk for alcoholism.A genome-wide association study (GWAS) of more than 100,000 human individuals identified variants of the gene KLB, which encodes the transmembrane protein β-Klotho, as highly associated with alcohol consumption. The protein β-Klotho is an essential element in cell surface receptors for hormones involved in modulation of appetites for simple sugars and alcohol. Several large GWAS have found differences in the genetics of alcohol consumption and alcohol dependence, although the two are to some degree related.

DNA damage
Alcohol-induced DNA damage, when not properly repaired, may have a key role in the neurotoxicity induced by alcohol. Metabolic conversion of ethanol to acetaldehyde can occur in the brain and the neurotoxic effects of ethanol appear to be associated with acetaldehyde induced DNA damages including DNA adducts and crosslinks. In addition to acetaldehyde, alcohol metabolism produces potentially genotoxic reactive oxygen species, which have been demonstrated to cause oxidative DNA damage.

Diagnosis
Definition
Misuse, problem use, abuse, and heavy use of alcohol refer to improper use of alcohol, which may cause physical, social, or moral harm to the drinker. The Dietary Guidelines for Americans defines "moderate use" as no more than two alcoholic beverages a day for men and no more than one alcoholic beverage a day for women. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) defines binge drinking as the amount of alcohol leading to a blood alcohol content (BAC) of 0.08, which, for most adults, would be reached by consuming five drinks for men or four for women over a two-hour period. According to the NIAAA, men may be at risk for alcohol-related problems if their alcohol consumption exceeds 14 standard drinks per week or 4 drinks per day, and women may be at risk if they have more than 7 standard drinks per week or 3 drinks per day. It defines a standard drink as one 12-ounce bottle of beer, one 5-ounce glass of wine, or 1.5 ounces of distilled spirits. Despite this risk, a 2014 report in the National Survey on Drug Use and Health found that only 10% of either "heavy drinkers" or "binge drinkers" defined according to the above criteria also met the criteria for alcohol dependence, while only 1.3% of non-binge drinkers met the criteria. An inference drawn from this study is that evidence-based policy strategies and clinical preventive services may effectively reduce binge drinking without requiring addiction treatment in most cases.

Alcoholism
The term alcoholism is commonly used amongst laypeople, but the word is poorly defined. Despite the imprecision inherent in the term, there have been attempts to define how the word alcoholism should be interpreted when encountered. In 1992, it was defined by the National Council on Alcoholism and Drug Dependence (NCADD) and ASAM as "a primary, chronic disease characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking." MeSH has had an entry for alcoholism since 1999, and references the 1992 definition.The WHO calls alcoholism "a term of long-standing use and variable meaning", and use of the term was disfavored by a 1979 WHO expert committee.
In professional and research contexts, the term alcoholism is not currently favored, but rather alcohol abuse, alcohol dependence, or alcohol use disorder are used. Talbot (1989) observes that alcoholism in the classical disease model follows a progressive course: if a person continues to drink, their condition will worsen. This will lead to harmful consequences in their life, physically, mentally, emotionally and socially. Johnson (1980) explores the emotional progression of the addicts response to alcohol. He looks at this in four phases. The first two are considered "normal" drinking and the last two are viewed as "typical" alcoholic drinking. Johnsons four phases consist of:

Learning the mood swing. A person is introduced to alcohol (in some cultures this can happen at a relatively young age), and the person enjoys the happy feeling it produces. At this stage, there is no emotional cost.
Seeking the mood swing. A person will drink to regain that feeling of euphoria experienced in phase 1; the drinking will increase as more intoxication is required to achieve the same effect. Again at this stage, there are no significant consequences.
At the third stage there are physical and social consequences, i.e., hangovers, family problems, work problems, etc. A person will continue to drink excessively, disregarding the problems.
The fourth stage can be detrimental, as Johnson cites it as a risk for premature death. As a person now drinks to feel normal, they block out the feelings of overwhelming guilt, remorse, anxiety, and shame they experience when sober.

DSM and ICD
In the United States, the Diagnostic and Statistical Manual of Mental Disorders (DSM) is the most common diagnostic guide for substance use disorders, whereas most countries use the International Classification of Diseases (ICD) for diagnostic (and other) purposes. The two manuals use similar but not identical nomenclature to classify alcohol problems.

Social barriers
Attitudes and social stereotypes can create barriers to the detection and treatment of alcohol use disorder. This is more of a barrier for women than men. Fear of stigmatization may lead women to deny that they have a medical condition, to hide their drinking, and to drink alone. This pattern, in turn, leads family, physicians, and others to be less likely to suspect that a woman they know has alcohol use disorder. In contrast, reduced fear of stigma may lead men to admit that they are having a medical condition, to display their drinking publicly, and to drink in groups. This pattern, in turn, leads family, physicians, and others to be more likely to suspect that a man they know is someone with an alcohol use disorder.

Screening
Screening is recommended among those over the age of 18. Several tools may be used to detect a loss of control of alcohol use. These tools are mostly self-reports in questionnaire form. Another common theme is a score or tally that sums up the general severity of alcohol use.The CAGE questionnaire, named for its four questions, is one such example that may be used to screen patients quickly in a doctors office.

Two "yes" responses indicate that the respondent should be investigated further.
The questionnaire asks the following questions:

Have you ever felt you needed to Cut down on your drinking?
Have people Annoyed you by criticizing your drinking?
Have you ever felt Guilty about drinking?
Have you ever felt you needed a drink first thing in the morning (Eye-opener) to steady your nerves or to get rid of a hangover?
The CAGE questionnaire has demonstrated a high effectiveness in detecting alcohol-related problems; however, it has limitations in people with less severe alcohol-related problems, white women and college students.Other tests are sometimes used for the detection of alcohol dependence, such as the Alcohol Dependence Data Questionnaire, which is a more sensitive diagnostic test than the CAGE questionnaire. It helps distinguish a diagnosis of alcohol dependence from one of heavy alcohol use. The Michigan Alcohol Screening Test (MAST) is a screening tool for alcoholism widely used by courts to determine the appropriate sentencing for people convicted of alcohol-related offenses, driving under the influence being the most common. The Alcohol Use Disorders Identification Test (AUDIT), a screening questionnaire developed by the World Health Organization, is unique in that it has been validated in six countries and is used internationally. Like the CAGE questionnaire, it uses a simple set of questions – a high score earning a deeper investigation. The Paddington Alcohol Test (PAT) was designed to screen for alcohol-related problems amongst those attending Accident and Emergency departments. It concords well with the AUDIT questionnaire but is administered in a fifth of the time.

Urine and blood tests
There are reliable tests for the actual use of alcohol, one common test being that of blood alcohol content (BAC). These tests do not differentiate people with alcohol use disorders from people without; however, long-term heavy drinking does have a few recognizable effects on the body, including:
Macrocytosis (enlarged MCV)
Elevated GGT
Moderate elevation of AST and ALT and an AST: ALT ratio of 2:1
High carbohydrate deficient transferrin (CDT)With regard to alcoholism, BAC is useful to judge alcohol tolerance, which in turn is a sign of alcoholism. Electrolyte and acid-base abnormalities including hypokalemia, hypomagnesemia, hyponatremia, hyperuricemia, metabolic acidosis, and respiratory alkalosis are common in people with alcohol use disorders.However, none of these blood tests for biological markers is as sensitive as screening questionnaires.

Prevention
The World Health Organization, the European Union and other regional bodies, national governments and parliaments have formed alcohol policies in order to reduce the harm of alcoholism. Increasing the age at which licit drugs that are susceptible to misuse, such as alcohol, can be purchased, and banning or restricting alcohol beverage advertising are common methods to reduce alcohol use among adolescents and young adults in particular. Credible, evidence-based educational campaigns in the mass media about the consequences of alcohol misuse have been recommended. Guidelines for parents to prevent alcohol misuse amongst adolescents, and for helping young people with mental health problems have also been suggested.

Management
Treatments are varied because there are multiple perspectives of alcoholism. Those who approach alcoholism as a medical condition or disease recommend differing treatments from, for instance, those who approach the condition as one of social choice. Most treatments focus on helping people discontinue their alcohol intake, followed up with life training and/or social support to help them resist a return to alcohol use. Since alcoholism involves multiple factors which encourage a person to continue drinking, they must all be addressed to successfully prevent a relapse. An example of this kind of treatment is detoxification followed by a combination of supportive therapy, attendance at self-help groups, and ongoing development of coping mechanisms. Much of the treatment community for alcoholism supports an abstinence-based zero tolerance approach popularized by the 12 step program of Alcoholics Anonymous; however, some prefer a harm-reduction approach.

Cessation of alcohol intake
Medical treatment for alcohol detoxification usually involves administration of a benzodiazepine, in order to ameliorate alcohol withdrawal syndromes adverse impact. The addition of phenobarbital improves outcomes if benzodiazepine administration lacks the usually efficacy, and phenobarbital alone might be an effective treatment. Propofol also might enhance treatment for individuals showing limited therapeutic response to a benzodiazepine. Individuals who are only at risk of mild to moderate withdrawal symptoms can be treated as outpatients. Individuals at risk of a severe withdrawal syndrome as well as those who have significant or acute comorbid conditions can be treated as inpatients. Direct treatment can be followed by a treatment program for alcohol dependence or alcohol use disorder to attempt to reduce the risk of relapse. Experiences following alcohol withdrawal, such as depressed mood and anxiety, can take weeks or months to abate while other symptoms persist longer due to persisting neuroadaptations.

Psychological
Various forms of group therapy or psychotherapy are often utilized to encourage and support abstinence from alcohol, or to reduce alcohol consumption to levels that are not associated with adverse outcomes. Mutual-aid group-counseling is an approach used to facilitate relapse prevention. Alcoholics Anonymous was one of the earliest organizations formed to provide mutual peer support and it is still the largest. Others include LifeRing Secular Recovery, SMART Recovery, Women for Sobriety, and Secular Organizations for Sobriety.Manualized Twelve Step Facilitation (TSF) interventions (i.e. therapy which encourages active, long-term Alcoholics Anonymous participation) for Alcohol Use Disorder lead to higher abstinence rates, compared to other clinical interventions and to wait-list control groups.

Moderate drinking
Rationing and moderation programs such as Moderation Management and DrinkWise do not mandate complete abstinence. While most people with alcohol use disorders are unable to limit their drinking in this way, some return to moderate drinking. A 2002 US study by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) showed that 17.7% of individuals diagnosed as alcohol dependent more than one year prior returned to low-risk drinking. This group, however, showed fewer initial symptoms of dependency.A follow-up study, using the same subjects that were judged to be in remission in 2001–2002, examined the rates of return to problem drinking in 2004–2005. The study found abstinence from alcohol was the most stable form of remission for recovering alcoholics. There was also a 1973 study showing chronic alcoholics drinking moderately again, but a 1982 follow-up showed that 95% of subjects were not able to maintain drinking in moderation over the long term. Another study was a long-term (60 year) follow-up of two groups of alcoholic men which concluded that "return to controlled drinking rarely persisted for much more than a decade without relapse or evolution into abstinence." Internet based measures appear to be useful at least in the short term.

Medications
In the United States there are four approved medications for alcoholism: acamprosate, two methods of using naltrexone and disulfiram.
Acamprosate may stabilise the brain chemistry that is altered due to alcohol dependence via antagonising the actions of glutamate, a neurotransmitter which is hyperactive in the post-withdrawal phase. By reducing excessive NMDA activity which occurs at the onset of alcohol withdrawal, acamprosate can reduce or prevent alcohol withdrawal related neurotoxicity. Acamprosate reduces the risk of relapse amongst alcohol-dependent persons.
Naltrexone is a competitive antagonist for opioid receptors, effectively blocking the effects of endorphins and opioids. Naltrexone is used to decrease cravings for alcohol and encourage abstinence. Alcohol causes the body to release endorphins, which in turn release dopamine and activate the reward pathways; hence in the body Naltrexone reduces the pleasurable effects from consuming alcohol. Evidence supports a reduced risk of relapse among alcohol-dependent persons and a decrease in excessive drinking. Nalmefene also appears effective and works in a similar manner.
Disulfiram prevents the elimination of acetaldehyde, a chemical the body produces when breaking down ethanol. Acetaldehyde itself is the cause of many hangover symptoms from alcohol use. The overall effect is discomfort when alcohol is ingested: an extremely fast-acting and long-lasting, uncomfortable hangover.Several other drugs are also used and many are under investigation.

Benzodiazepines, while useful in the management of acute alcohol withdrawal, if used long-term can cause a worse outcome in alcoholism. Alcoholics on chronic benzodiazepines have a lower rate of achieving abstinence from alcohol than those not taking benzodiazepines. This class of drugs is commonly prescribed to alcoholics for insomnia or anxiety management. Initiating prescriptions of benzodiazepines or sedative-hypnotics in individuals in recovery has a high rate of relapse with one author reporting more than a quarter of people relapsed after being prescribed sedative-hypnotics. Those who are long-term users of benzodiazepines should not be withdrawn rapidly, as severe anxiety and panic may develop, which are known risk factors for alcohol use disorder relapse. Taper regimes of 6–12 months have been found to be the most successful, with reduced intensity of withdrawal.
Calcium carbimide works in the same way as disulfiram; it has an advantage in that the occasional adverse effects of disulfiram, hepatotoxicity and drowsiness, do not occur with calcium carbimide.
Ondansetron and topiramate are supported by tentative evidence in people with certain genetic patterns. Evidence for ondansetron is stronger in people who have recently started to abuse alcohol. Topiramate is a derivative of the naturally occurring sugar monosaccharide D-fructose. Review articles characterize topiramate as showing "encouraging", "promising", "efficacious", and "insufficient" results in the treatment of alcohol use disorders.Evidence does not support the use of selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), antipsychotics, or gabapentin.

Research
Topiramate, a derivative of the naturally occurring sugar monosaccharide D-fructose, has been found effective in helping alcoholics quit or cut back on the amount they drink. Evidence suggests that topiramate antagonizes excitatory glutamate receptors, inhibits dopamine release, and enhances inhibitory gamma-aminobutyric acid function. A 2008 review of the effectiveness of topiramate concluded that the results of published trials are promising, however as of 2008, data was insufficient to support using topiramate in conjunction with brief weekly compliance counseling as a first-line agent for alcohol dependence. A 2010 review found that topiramate may be superior to existing alcohol pharmacotherapeutic options. Topiramate effectively reduces craving and alcohol withdrawal severity as well as improving quality-of-life-ratings.Baclofen, a GABAB receptor agonist, is under study for the treatment of alcoholism. According to a 2017 Cochrane Systematic Review, there is insufficient evidence to determine the effectiveness or safety for the use of baclofen for withdrawal symptoms in alcoholism. Psilocybin-assisted psychotherapy is under study for the treatment of patients with alcohol use disorder.

Dual addictions and dependencies
Alcoholics may also require treatment for other psychotropic drug addictions and drug dependencies. The most common dual dependence syndrome with alcohol dependence is benzodiazepine dependence, with studies showing 10–20% of alcohol-dependent individuals had problems of dependence and/or misuse problems of benzodiazepine drugs such as diazepam or clonazepam. These drugs are, like alcohol, depressants. Benzodiazepines may be used legally, if they are prescribed by doctors for anxiety problems or other mood disorders, or they may be purchased as illegal drugs. Benzodiazepine use increases cravings for alcohol and the volume of alcohol consumed by problem drinkers. Benzodiazepine dependency requires careful reduction in dosage to avoid benzodiazepine withdrawal syndrome and other health consequences. Dependence on other sedative-hypnotics such as zolpidem and zopiclone as well as opiates and illegal drugs is common in alcoholics. Alcohol itself is a sedative-hypnotic and is cross-tolerant with other sedative-hypnotics such as barbiturates, benzodiazepines and nonbenzodiazepines. Dependence upon and withdrawal from sedative-hypnotics can be medically severe and, as with alcohol withdrawal, there is a risk of psychosis or seizures if not properly managed.

Epidemiology
The World Health Organization estimates that as of 2016 there are 380 million people with alcoholism worldwide (5.1% of the population over 15 years of age). Substance use disorders are a major public health problem facing many countries. "The most common substance of abuse/dependence in patients presenting for treatment is alcohol." In the United Kingdom, the number of dependent drinkers was calculated as over 2.8 million in 2001. About 12% of American adults have had an alcohol dependence problem at some time in their life. In the United States and Western Europe, 10 to 20% of men and 5 to 10% of women at some point in their lives will meet criteria for alcoholism. Estonia had the highest death rate from alcohol in Europe in 2015 at 8.8 per 100,000 population. In the United States, 30% of people admitted to hospital have a problem related to alcohol.Within the medical and scientific communities, there is a broad consensus regarding alcoholism as a disease state. For example, the American Medical Association considers alcohol a drug and states that "drug addiction is a chronic, relapsing brain disease characterized by compulsive drug seeking and use despite often devastating consequences. It results from a complex interplay of biological vulnerability, environmental exposure, and developmental factors (e.g., stage of brain maturity)." Alcoholism has a higher prevalence among men, though, in recent decades, the proportion of female alcoholics has increased. Current evidence indicates that in both men and women, alcoholism is 50–60% genetically determined, leaving 40–50% for environmental influences. Most alcoholics develop alcoholism during adolescence or young adulthood.

Prognosis
Alcoholism often reduces a persons life expectancy by around ten years. The most common cause of death in alcoholics is from cardiovascular complications. There is a high rate of suicide in chronic alcoholics, which increases the longer a person drinks. Approximately 3–15% of alcoholics commit suicide, and research has found that over 50% of all suicides are associated with alcohol or drug dependence. This is believed to be due to alcohol causing physiological distortion of brain chemistry, as well as social isolation. Suicide is also very common in adolescent alcohol abusers, with 25% of suicides in adolescents being related to alcohol abuse. Among those with alcohol dependence after one year, some met the criteria for low-risk drinking, even though only 25.5% of the group received any treatment, with the breakdown as follows: 25% were found to be still dependent, 27.3% were in partial remission (some symptoms persist), 11.8% asymptomatic drinkers (consumption increases chances of relapse) and 35.9% were fully recovered – made up of 17.7% low-risk drinkers plus 18.2% abstainers. In contrast, however, the results of a long-term (60-year) follow-up of two groups of alcoholic men indicated that "return to controlled drinking rarely persisted for much more than a decade without relapse or evolution into abstinence." There was also "return-to-controlled drinking, as reported in short-term studies, is often a mirage."

History
Historically the name dipsomania was coined by German physician C. W. Hufeland in 1819 before it was superseded by alcoholism. That term now has a more specific meaning. The term alcoholism was first used in 1849 by the Swedish physician Magnus Huss to describe the systemic adverse effects of alcohol.Alcohol has a long history of use and misuse throughout recorded history. Biblical, Egyptian and Babylonian sources record the history of abuse and dependence on alcohol. In some ancient cultures alcohol was worshiped and in others, its misuse was condemned. Excessive alcohol misuse and drunkenness were recognized as causing social problems even thousands of years ago. However, the defining of habitual drunkenness as it was then known as and its adverse consequences were not well established medically until the 18th century. In 1647 a Greek monk named Agapios was the first to document that chronic alcohol misuse was associated with toxicity to the nervous system and body which resulted in a range of medical disorders such as seizures, paralysis, and internal bleeding. In the 1910s and 1920s, the effects of alcohol misuse and chronic drunkenness boosted membership of the temperance movement and led to the prohibition of alcohol in many Western countries, nationwide bans on the production, importation, transportation, and sale of alcoholic beverages that generally remained in place until the late 1920s or early 1930s; these policies resulted in the decline of death rates from cirrhosis and alcoholism. In 2005, alcohol dependence and misuse was estimated to cost the US economy approximately 220 billion dollars per year, more than cancer and obesity.

Society and culture
The various health problems associated with long-term alcohol consumption are generally perceived as detrimental to society, for example, money due to lost labor-hours, medical costs due to injuries due to drunkenness and organ damage from long-term use, and secondary treatment costs, such as the costs of rehabilitation facilities and detoxification centers. Alcohol use is a major contributing factor for head injuries, motor vehicle injuries (27%), interpersonal violence (18%), suicides (18%), and epilepsy (13%). Beyond the financial costs that alcohol consumption imposes, there are also significant social costs to both the alcoholic and their family and friends. For instance, alcohol consumption by a pregnant woman can lead to an incurable and damaging condition known as fetal alcohol syndrome, which often results in cognitive deficits, mental health problems, an inability to live independently and an increased risk of criminal behaviour, all of which can cause emotional stress for parents and caregivers. Estimates of the economic costs of alcohol misuse, collected by the World Health Organization, vary from one to six% of a countrys GDP. One Australian estimate pegged alcohols social costs at 24% of all drug misuse costs; a similar Canadian study concluded alcohols share was 41%. One study quantified the cost to the UK of all forms of alcohol misuse in 2001 as £18.5–20 billion. All economic costs in the United States in 2006 have been estimated at $223.5 billion.The idea of hitting rock bottom refers to an experience of stress that can be attributed to alcohol misuse. There is no single definition for this idea, and people may identify their own lowest points in terms of lost jobs, lost relationships, health problems, legal problems, or other consequences of alcohol misuse. The concept is promoted by 12-step recovery groups and researchers using the transtheoretical model of motivation for behavior change </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Chagas disease and explain in detail? [/INST] Chagas disease, also known as American trypanosomiasis, is a tropical parasitic disease caused by Trypanosoma cruzi. It is spread mostly by insects in the subfamily Triatominae, known as "kissing bugs". The symptoms change over the course of the infection. In the early stage, symptoms are typically either not present or mild, and may include fever, swollen lymph nodes, headaches, or swelling at the site of the bite. After four to eight weeks, untreated individuals enter the chronic phase of disease, which in most cases does not result in further symptoms. Up to 45% of people with chronic infections develop heart disease 10–30 years after the initial illness, which can lead to heart failure. Digestive complications, including an enlarged esophagus or an enlarged colon, may also occur in up to 21% of people, and up to 10% of people may experience nerve damage.T. cruzi is commonly spread to humans and other mammals by the bite of a kissing bug. The disease may also be spread through blood transfusion, organ transplantation, consuming food or drink contaminated with the parasites, and vertical transmission (from a mother to her baby). Diagnosis of early disease is by finding the parasite in the blood using a microscope or detecting its DNA by polymerase chain reaction. Chronic disease is diagnosed by finding antibodies for T. cruzi in the blood.Prevention focuses on eliminating kissing bugs and avoiding their bites. This may involve the use of insecticides or bed-nets. Other preventive efforts include screening blood used for transfusions. As of 2022, a vaccine has not been developed. Early infections are treatable with the medications benznidazole or nifurtimox, which usually cure the disease if given shortly after the person is infected, but become less effective the longer a person has had Chagas disease. When used in chronic disease, medication may delay or prevent the development of end-stage symptoms. Benznidazole and nifurtimox often cause side effects, including skin disorders, digestive system irritation, and neurological symptoms, which can result in treatment being discontinued. As of 2019, new drugs for Chagas disease are under development, and experimental vaccines have been studied in animal models.It is estimated that 6.5 million people, mostly in Mexico, Central America and South America, have Chagas disease as of 2019, resulting in approximately 9,490 annual deaths. Most people with the disease are poor, and most do not realize they are infected. Large-scale population migrations have carried Chagas disease to new regions, which include the United States and many European countries. The disease affects more than 150 types of animals.The disease was first described in 1909 by Brazilian physician Carlos Chagas, after whom it is named. Chagas disease is classified as a neglected tropical disease.

Signs and symptoms
Chagas disease occurs in two stages: an acute stage, which develops one to two weeks after the insect bite, and a chronic stage, which develops over many years. The acute stage is often symptom-free. When present, the symptoms are typically minor and not specific to any particular disease. Signs and symptoms include fever, malaise, headache, and enlargement of the liver, spleen, and lymph nodes. Sometimes, people develop a swollen nodule at the site of infection, which is called "Romañas sign" if it is on the eyelid, or a "chagoma" if it is elsewhere on the skin. In rare cases (less than 1–5%), infected individuals develop severe acute disease, which can involve inflammation of the heart muscle, fluid accumulation around the heart, and inflammation of the brain and surrounding tissues, and may be life-threatening. The acute phase typically lasts four to eight weeks and resolves without treatment.Unless treated with antiparasitic drugs, individuals remain infected with T. cruzi after recovering from the acute phase. Most chronic infections are asymptomatic, which is referred to as indeterminate chronic Chagas disease. However, over decades with the disease, approximately 30–40% of people develop organ dysfunction (determinate chronic Chagas disease), which most often affects the heart or digestive system.The most common long-term manifestation is heart disease, which occurs in 14–45% of people with chronic Chagas disease. People with Chagas heart disease often experience heart palpitations, and sometimes fainting, due to irregular heart function. By electrocardiogram, people with Chagas heart disease most frequently have arrhythmias. As the disease progresses, the hearts ventricles become enlarged (dilated cardiomyopathy), which reduces its ability to pump blood. In many cases the first sign of Chagas heart disease is heart failure, thromboembolism, or chest pain associated with abnormalities in the microvasculature.Also common in chronic Chagas disease is damage to the digestive system, which affects 10–21% of people. Enlargement of the esophagus or colon are the most common digestive issues. Those with enlarged esophagus often experience pain (odynophagia) or trouble swallowing (dysphagia), acid reflux, cough, and weight loss. Individuals with enlarged colon often experience constipation, and may develop severe blockage of the intestine or its blood supply. Up to 10% of chronically infected individuals develop nerve damage that can result in numbness and altered reflexes or movement. While chronic disease typically develops over decades, some individuals with Chagas disease (less than 10%) progress to heart damage directly after acute disease.Signs and symptoms differ for people infected with T. cruzi through less common routes. People infected through ingestion of parasites tend to develop severe disease within three weeks of consumption, with symptoms including fever, vomiting, shortness of breath, cough, and pain in the chest, abdomen, and muscles. Those infected congenitally typically have few to no symptoms, but can have mild non-specific symptoms, or severe symptoms such as jaundice, respiratory distress, and heart problems. People infected through organ transplant or blood transfusion tend to have symptoms similar to those of vector-borne disease, but the symptoms may not manifest for anywhere from a week to five months. Chronically infected individuals who become immunosuppressed due to HIV infection can have particularly severe and distinct disease, most commonly characterized by inflammation in the brain and surrounding tissue or brain abscesses. Symptoms vary widely based on the size and location of brain abscesses, but typically include fever, headaches, seizures, loss of sensation, or other neurological issues that indicate particular sites of nervous system damage. Occasionally, these individuals also experience acute heart inflammation, skin lesions, and disease of the stomach, intestine, or peritoneum.

Cause
Chagas disease is caused by infection with the protozoan parasite T. cruzi, which is typically introduced into humans through the bite of triatomine bugs, also called "kissing bugs". When the insect defecates at the bite site, motile T. cruzi forms called trypomastigotes enter the bloodstream and invade various host cells. Inside a host cell, the parasite transforms into a replicative form called an amastigote, which undergoes several rounds of replication. The replicated amastigotes transform back into trypomastigotes, which burst the host cell and are released into the bloodstream. Trypomastigotes then disseminate throughout the body to various tissues, where they invade cells and replicate. Over many years, cycles of parasite replication and immune response can severely damage these tissues, particularly the heart and digestive tract.

Transmission
T. cruzi can be transmitted by various triatomine bugs in the genera Triatoma, Panstrongylus, and Rhodnius. The primary vectors for human infection are the species of triatomine bugs that inhabit human dwellings, namely Triatoma infestans, Rhodnius prolixus, Triatoma dimidiata and Panstrongylus megistus. These insects are known by a number of local names, including vinchuca in Argentina, Bolivia, Chile and Paraguay, barbeiro (the barber) in Brazil, pito in Colombia, chinche in Central America, and chipo in Venezuela. The bugs tend to feed at night, preferring moist surfaces near the eyes or mouth. A triatomine bug can become infected with T. cruzi when it feeds on an infected host. T. cruzi replicates in the insects intestinal tract and is shed in the bugs feces. When an infected triatomine feeds, it pierces the skin and takes in a blood meal, defecating at the same time to make room for the new meal. The bite is typically painless, but causes itching. Scratching at the bite introduces the T. cruzi-laden feces into the bite wound, initiating infection.In addition to classical vector spread, Chagas disease can be transmitted through consumption of food or drink contaminated with triatomine insects or their feces. Since heating or drying kills the parasites, drinks and especially fruit juices are the most frequent source of infection. This oral route of transmission has been implicated in several outbreaks, where it led to unusually severe symptoms, likely due to infection with a higher parasite load than from the bite of a triatomine bug.T. cruzi can be transmitted independent of the triatomine bug during blood transfusion, following organ transplantation, or across the placenta during pregnancy. Transfusion with the blood of an infected donor infects the recipient 10–25% of the time. To prevent this, blood donations are screened for T. cruzi in many countries with endemic Chagas disease, as well as the United States. Similarly, transplantation of solid organs from an infected donor can transmit T. cruzi to the recipient. This is especially true for heart transplant, which transmits T. cruzi 75–100% of the time, and less so for transplantation of the liver (0–29%) or a kidney (0–19%). An infected mother can pass T. cruzi to her child through the placenta; this occurs in up to 15% of births by infected mothers. As of 2019, 22.5% of new infections occurred through congenital transmission.

Pathophysiology
In the acute phase of the disease, signs and symptoms are caused directly by the replication of T. cruzi and the immune systems response to it. During this phase, T. cruzi can be found in various tissues throughout the body and circulating in the blood. During the initial weeks of infection, parasite replication is brought under control by production of antibodies and activation of the hosts inflammatory response, particularly cells that target intracellular pathogens such as NK cells and macrophages, driven by inflammation-signaling molecules like TNF-α and IFN-γ.During chronic Chagas disease, long-term organ damage develops over years due to continued replication of the parasite and damage from the immune system. Early in the course of the disease, T. cruzi is found frequently in the striated muscle fibers of the heart. As disease progresses, the heart becomes generally enlarged, with substantial regions of cardiac muscle fiber replaced by scar tissue and fat. Areas of active inflammation are scattered throughout the heart, with each housing inflammatory immune cells, typically macrophages and T cells. Late in the disease, parasites are rarely detected in the heart, and may be present at only very low levels.In the heart, colon, and esophagus, chronic disease leads to a massive loss of nerve endings. In the heart, this may contribute to arrythmias and other cardiac dysfunction. In the colon and esophagus, loss of nervous system control is the major driver of organ dysfunction. Loss of nerves impairs the movement of food through the digestive tract, which can lead to blockage of the esophagus or colon and restriction of their blood supply.

Diagnosis
The presence of T. cruzi in the blood is diagnostic of Chagas disease. During the acute phase of infection, it can be detected by microscopic examination of fresh anticoagulated blood, or its buffy coat, for motile parasites; or by preparation of thin and thick blood smears stained with Giemsa, for direct visualization of parasites. Blood smear examination detects parasites in 34–85% of cases. The sensitivity increases if techniques such as microhematocrit centrifugation are used to concentrate the blood. On microscopic examination of stained blood smears, T. cruzi trypomastigotes appear as S or U-shaped organisms with a flagellum connected to the body by an undulating membrane. A nucleus and a smaller structure called a kinetoplast are visible inside the parasites body; the kinetoplast of T. cruzi is relatively large, which helps to distinguish it from other species of trypanosomes that infect humans.Alternatively, T. cruzi DNA can be detected by polymerase chain reaction (PCR). In acute and congenital Chagas disease, PCR is more sensitive than microscopy, and it is more reliable than antibody-based tests for the diagnosis of congenital disease because it is not affected by transfer of antibodies against T. cruzi from a mother to her baby (passive immunity). PCR is also used to monitor T. cruzi levels in organ transplant recipients and immunosuppressed people, which allows infection or reactivation to be detected at an early stage.In chronic Chagas disease, the concentration of parasites in the blood is too low to be reliably detected by microscopy or PCR, so the diagnosis is usually made using serological tests, which detect immunoglobulin G antibodies against T. cruzi in the blood. Two positive serology results, using different test methods, are required to confirm the diagnosis. If the test results are inconclusive, additional testing methods such as Western blot can be used.Various rapid diagnostic tests for Chagas disease are available. These tests are easily transported and can be performed by people without special training. They are useful for screening large numbers of people and testing people who cannot access healthcare facilities, but their sensitivity is relatively low, and it is recommended that a second method is used to confirm a positive result.T. cruzi parasites can be grown from blood samples by blood culture, xenodiagnosis, or by inoculating animals with the persons blood. In the blood culture method, the persons red blood cells are separated from the plasma and added to a specialized growth medium to encourage multiplication of the parasite. It can take up to six months to obtain the result. Xenodiagnosis involves feeding the blood to triatomine insects, then examining their feces for the parasite 30 to 60 days later. These methods are not routinely used, as they are slow and have low sensitivity.

Prevention
Efforts to prevent Chagas disease have largely focused on vector control to limit exposure to triatomine bugs. Insecticide-spraying programs have been the mainstay of vector control, consisting of spraying homes and the surrounding areas with residual insecticides. This was originally done with organochlorine, organophosphate, and carbamate insecticides, which were supplanted in the 1980s with pyrethroids. These programs have drastically reduced transmission in Brazil and Chile, and eliminated major vectors from certain regions: Triatoma infestans from Brazil, Chile, Uruguay, and parts of Peru and Paraguay, as well as Rhodnius prolixus from Central America. Vector control in some regions has been hindered by the development of insecticide resistance among triatomine bugs. In response, vector control programs have implemented alternative insecticides (e.g. fenitrothion and bendiocarb in Argentina and Bolivia), treatment of domesticated animals (which are also fed on by triatomine bugs) with pesticides, pesticide-impregnated paints, and other experimental approaches. In areas with triatomine bugs, transmission of T. cruzi can be prevented by sleeping under bed nets and by housing improvements that prevent triatomine bugs from colonizing houses.Blood transfusion was formerly the second-most common mode of transmission for Chagas disease. T. cruzi can survive in refrigerated stored blood, and can survive freezing and thawing, allowing it to persist in whole blood, packed red blood cells, granulocytes, cryoprecipitate, and platelets. The development and implementation of blood bank screening tests has dramatically reduced the risk of infection during blood transfusion. Nearly all blood donations in Latin American countries undergo Chagas screening. Widespread screening is also common in non-endemic nations with significant populations of immigrants from endemic areas, including the United Kingdom (implemented in 1999), Spain (2005), the United States (2007), France and Sweden (2009), Switzerland (2012), and Belgium (2013). Serological tests, typically ELISAs, are used to detect antibodies against T. cruzi proteins in donor blood.Other modes of transmission have been targeted by Chagas disease prevention programs. Treating T. cruzi-infected mothers during pregnancy reduces the risk of congenital transmission of the infection. To this end, many countries in Latin America have implemented routine screening of pregnant women and infants for T. cruzi infection, and the World Health Organization recommends screening all children born to infected mothers to prevent congenital infection from developing into chronic disease. Similarly to blood transfusions, many countries with endemic Chagas disease screen organs for transplantation with serological tests.There is no vaccine against Chagas disease. Several experimental vaccines have been tested in animals infected with T. cruzi and were able to reduce parasite numbers in the blood and heart, but no vaccine candidates had undergone clinical trials in humans as of 2016.

Management
Chagas disease is managed using antiparasitic drugs to eliminate T. cruzi from the body, and symptomatic treatment to address the effects of the infection. As of 2018, benznidazole and nifurtimox were the antiparasitic drugs of choice for treating Chagas disease, though benznidazole is the only drug available in most of Latin America. For either drug, treatment typically consists of two to three oral doses per day for 60 to 90 days. Antiparasitic treatment is most effective early in the course of infection: it eliminates T. cruzi from 50 to 80% of people in the acute phase, but only 20–60% of those in the chronic phase. Treatment of chronic disease is more effective in children than in adults, and the cure rate for congenital disease approaches 100% if treated in the first year of life. Antiparasitic treatment can also slow the progression of the disease and reduce the possibility of congenital transmission. Elimination of T. cruzi does not cure the cardiac and gastrointestinal damage caused by chronic Chagas disease, so these conditions must be treated separately. Antiparasitic treatment is not recommended for people who have already developed dilated cardiomyopathy.Benznidazole is usually considered the first-line treatment because it has milder adverse effects than nifurtimox, and its efficacy is better understood. Both benznidazole and nifurtimox have common side effects that can result in treatment being discontinued. The most common side effects of benznidazole are skin rash, digestive problems, decreased appetite, weakness, headache, and sleeping problems. These side effects can sometimes be treated with antihistamines or corticosteroids, and are generally reversed when treatment is stopped. However, benzidazole is discontinued in up to 29% of cases. Nifurtimox has more frequent side effects, affecting up to 97.5% of individuals taking the drug. The most common side effects are loss of appetite, weight loss, nausea and vomiting, and various neurological disorders including mood changes, insomnia, paresthesia and peripheral neuropathy. Treatment is discontinued in up to 75% of cases. Both drugs are contraindicated for use in pregnant women and people with liver or kidney failure. As of 2019, resistance to these drugs has been reported.

Complications
In the chronic stage, treatment involves managing the clinical manifestations of the disease. The treatment of Chagas cardiomyopathy is similar to that of other forms of heart disease. Beta blockers and ACE inhibitors may be prescribed, but some people with Chagas disease may not be able to take the standard dose of these drugs because they have low blood pressure or a low heart rate. To manage irregular heartbeats, people may be prescribed anti-arrhythmic drugs such as amiodarone, or have a pacemaker implanted. Blood thinners may be used to prevent thromboembolism and stroke. Chronic heart disease caused by Chagas is a common reason for heart transplantation surgery. Because transplant recipients take immunosuppressive drugs to prevent organ rejection, they are monitored using PCR to detect reactivation of the disease. People with Chagas disease who undergo heart transplantation have higher survival rates than the average heart transplant recipient.Mild gastrointestinal disease may be treated symptomatically, such as by using laxatives for constipation, or taking a prokinetic drug like metoclopramide before meals to relieve esophageal symptoms. Surgery to sever the muscles of the lower esophageal sphincter (cardiomyotomy) may be performed in more severe cases of esophageal disease, and surgical removal of the affected part of the organ may be required for advanced megacolon and megaesophagus.

Epidemiology
In 2019, an estimated 6.5 million people worldwide had Chagas disease, with approximately 173,000 new infections and 9,490 deaths each year. The disease resulted in a global annual economic burden estimated at US$7.2 billion in 2013, 86% of which is borne by endemic countries. Chagas disease results in the loss of over 800,000 disability-adjusted life years each year.The endemic area of Chagas disease stretches from the southern United States to northern Chile and Argentina, with Bolivia (6.1%), Argentina (3.6%), and Paraguay (2.1%) exhibiting the highest prevalence of the disease. Within continental Latin America, Chagas disease is endemic to 21 countries: Argentina, Belize, Bolivia, Brazil, Chile, Colombia, Costa Rica, Ecuador, El Salvador, French Guiana, Guatemala, Guyana, Honduras, Mexico, Nicaragua, Panama, Paraguay, Peru, Suriname, Uruguay, and Venezuela. In endemic areas, due largely to vector control efforts and screening of blood donations, annual infections and deaths have fallen by 67% and more than 73% respectively from their peaks in the 1980s to 2010. Transmission by insect vector and blood transfusion has been completely interrupted in Uruguay (1997), Chile (1999), and Brazil (2006), and in Argentina, vectorial transmission had been interrupted in 13 of the 19 endemic provinces as of 2001. During Venezuelas humanitarian crisis, vectorial transmission has begun occurring in areas where it had previously been interrupted, and Chagas disease seroprevalence rates have increased. Transmission rates have also risen in the Gran Chaco region due to insecticide resistance and in the Amazon basin due to oral transmission.While the rate of vector-transmitted Chagas disease has declined throughout most of Latin America, the rate of orally transmitted disease has risen, possibly due to increasing urbanization and deforestation bringing people into closer contact with triatomines and altering the distribution of triatomine species. Orally transmitted Chagas disease is of particular concern in Venezuela, where 16 outbreaks have been recorded between 2007 and 2018.Chagas exists in two different ecological zones: In the Southern Cone region, the main vector lives in and around human homes. In Central America and Mexico, the main vector species lives both inside dwellings and in uninhabited areas. In both zones, Chagas occurs almost exclusively in rural areas, where T. cruzi also circulates in wild and domestic animals. T. cruzi commonly infects more than 100 species of mammals across Latin America including opossums (Didelphis spp.), armadillos, marmosets, bats, various rodents and dogs all of which can be infected by the vectors or orally by eating triatomine bugs and other infected animals. For entomophagous animals this is a common mode. Didelphis spp. are unique in that they do not require the triatomine for transmission, completing the life cycle through their own urine and feces. Veterinary transmission also occurs through vertical transmission through the placenta, blood transfusion and organ transplants.

Non-endemic countries
Though Chagas is traditionally considered a disease of rural Latin America, international migration has dispersed those with the disease to numerous non-endemic countries, primarily in North America and Europe. As of 2020, approximately 300,000 infected people are living in the United States, and in 2018 it was estimated that 30,000 to 40,000 Americans had Chagas cardiomyopathy. The vast majority of cases in the United States occur in immigrants from Latin America, but local transmission is possible. Eleven triatomine species are native to the United States, and some southern states have persistent cycles of disease transmission between insect vectors and animal reservoirs, which include woodrats, possums, raccoons, armadillos and skunks. However, locally acquired infection is very rare: only 28 cases were documented from 1955 to 2015. As of 2013, the cost of treatment in the United States was estimated to be US$900 million annually (global cost $7 billion), which included hospitalization and medical devices such as pacemakers.Chagas disease affects approximately 68,000 to 123,000 people in Europe as of 2019. Spain, which has a high rate of immigration from Latin America, has the highest prevalence of the disease. It is estimated that 50,000 to 70,000 Spanish people are living with Chagas disease, accounting for the majority of European cases. The prevalence varies widely within European countries due to differing immigration patterns. Italy has the second highest prevalence, followed by the Netherlands, the United Kingdom, and Germany.

History
T. cruzi likely circulated in South American mammals long before the arrival of humans on the continent. T. cruzi has been detected in ancient human remains across South America, from a 9000-year-old Chinchorro mummy in the Atacama Desert, to remains of various ages in Minas Gerais, to an 1100-year-old mummy as far north as the Chihuahuan Desert near the Rio Grande. Many early written accounts describe symptoms consistent with Chagas disease, with early descriptions of the disease sometimes attributed to Miguel Diaz Pimenta (1707), Luís Gomes Ferreira (1735), and Theodoro J. H. Langgaard (1842).The formal description of Chagas disease was made by Carlos Chagas in 1909 after examining a two-year-old girl with fever, swollen lymph nodes, and an enlarged spleen and liver. Upon examination of her blood, Chagas saw trypanosomes identical to those he had recently identified from the hindgut of triatomine bugs and named Trypanosoma cruzi in honor of his mentor, Brazilian physician Oswaldo Cruz. He sent infected triatomine bugs to Cruz in Rio de Janeiro, who showed the bite of the infected triatomine could transmit T. cruzi to marmoset monkeys as well. In just two years, 1908 and 1909, Chagas published descriptions of the disease, the organism that caused it, and the insect vector required for infection. Almost immediately thereafter, at the suggestion of Miguel Couto, then professor of the Faculdade de Medicina do Rio de Janeiro, the disease was widely referred to as "Chagas disease". Chagas discovery brought him national and international renown, but in highlighting the inadequacies of the Brazilian governments response to the disease, Chagas attracted criticism to himself and to the disease that bore his name, stifling research on his discovery and likely frustrating his nomination for the Nobel Prize in 1921.In the 1930s, Salvador Mazza rekindled Chagas disease research, describing over a thousand cases in Argentinas Chaco Province. In Argentina, the disease is known as mal de Chagas-Mazza in his honor. Serological tests for Chagas disease were introduced in the 1940s, demonstrating that infection with T. cruzi was widespread across Latin America. This, combined with successes eliminating the malaria vector through insecticide use, spurred the creation of public health campaigns focused on treating houses with insecticides to eradicate triatomine bugs. The 1950s saw the discovery that treating blood with crystal violet could eradicate the parasite, leading to its widespread use in transfusion screening programs in Latin America. Large-scale control programs began to take form in the 1960s, first in São Paulo, then various locations in Argentina, then national-level programs across Latin America. These programs received a major boost in the 1980s with the introduction of pyrethroid insecticides, which did not leave stains or odors after application and were longer-lasting and more cost-effective. Regional bodies dedicated to controlling Chagas disease arose through support of the Pan American Health Organization, with the Initiative of the Southern Cone for the Elimination of Chagas Diseases launching in 1991, followed by the Initiative of the Andean countries (1997), Initiative of the Central American countries (1997), and the Initiative of the Amazon countries (2004).

Research
Treatments
Fexinidazole, an antiparasitic drug approved for treating African trypanosomiasis, has shown activity against Chagas disease in animal models. As of 2019, it is undergoing phase II clinical trials for chronic Chagas disease in Spain. Other drug candidates include GNF6702, a proteasome inhibitor that is effective against Chagas disease in mice and is undergoing preliminary toxicity studies, and AN4169, which has had promising results in animal models.A number of experimental vaccines have been tested in animals. In addition to subunit vaccines, some approaches have involved vaccination with attenuated T. cruzi parasites or organisms that express some of the same antigens as T. cruzi but do not cause human disease, such as Trypanosoma rangeli or Phytomonas serpens. DNA vaccination has also been explored </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Behçets disease and explain in detail? [/INST] Behçets disease (BD) is a type of inflammatory disorder which affects multiple parts of the body. The most common symptoms include painful sores on the mucous membranes of the mouth and other parts of the body, inflammation of parts of the eye, and arthritis. The sores can last from a few days, up to a week or more. Less commonly there may be inflammation of the brain or spinal cord, blood clots, aneurysms, or blindness. Often, the symptoms come and go.The cause is unknown. It is believed to be partly genetic. Behçets is not contagious. Diagnosis is based on at least three episodes of mouth sores in a year together with at least two of the following: genital sores, eye inflammation, skin sores, a positive skin prick test.There is no cure. Treatments may include immunosuppressive medication such as corticosteroids and lifestyle changes. Lidocaine mouthwash may help with the pain. Colchicine may decrease the frequency of attacks.While rare in the United States and Europe, it is more common in the Middle East and Asia. In Turkey, for example, about 2 per 1,000 are affected. Onset is usually in a persons 20s or 40s. The disease was initially described by Turkish dermatologist Hulusi Behçet in 1937.

Signs and symptoms
Skin and mucosa
Nearly all people with Behçets disease present with some form of painful ulcerations inside the mouth. They are a form of aphthous ulcers or non-scarring oral lesions. The oral lesions are similar to those found in inflammatory bowel disease and can be relapsing. Painful genital ulcerations usually develop around the anus, vulva, or scrotum and cause scarring in 75 percent of the patients. Additionally, patients may present with erythema nodosum, cutaneous pustular vasculitis, and lesions similar to pyoderma gangrenosum.

Eyes
Inflammatory eye disease can develop early in the disease course and lead to permanent vision loss in 20 percent of cases. Ocular involvement can be in the form of posterior uveitis, anterior uveitis, or retinal vasculitis. Anterior uveitis presents with painful eyes, conjuctival redness, hypopyon, and decreased visual acuity, while posterior uveitis presents with painless decreased visual acuity and visual field floaters. A rare form of ocular (eye) involvement in this syndrome is retinal vasculitis which presents with painless decrease of vision with the possibility of floaters or visual field defects.Optic nerve involvement in Behçets disease is rare, typically presenting as progressive optic atrophy and visual loss. However, cases of acute optic neuropathy (specifically anterior ischemic optic neuropathy) have also been reported to occur. Optic nerve atrophy has been identified as the most common cause of visual impairment. Behçets disease may result in primary or secondary optic nerve involvement. Papilledema as a result of dural sinus thrombosis and atrophy resulting from retinal disease, have been characterized as secondary causes of optic nerve atrophy in Behçets disease.Signs and symptoms of acute optic neuropathy include painless loss of vision which may affect either one or both eyes, reduced visual acuity, reduced color vision, relative afferent pupillary defect, central scotoma, swollen optic disc, macular edema, or retrobulbar pain. When these symptoms occur with concurrent mucocutaneous ulcerations, they raise suspicion of acute optic neuropathy in Behçets Disease. Progressive optic atrophy may result in decreased visual acuity or color vision. Intracranial hypertension with papilledema may be present.Episcleritis may occur, which causes eye redness and mild pain, without a significant impact on vision.

Bowels
Gastrointestinal (GI) manifestations include abdominal pain, nausea, and diarrhea with or without blood, and they often involve the ileocecal valve. Some patients with BD experience abdominal tenderness, bloating, and general abdominal discomfort. When mild this can resemble irritable bowel syndrome; more severe cases bear similarities to inflammatory bowel diseases such as ulcerative colitis or Crohns.

Lungs
Lung involvement is typically in the form of hemoptysis, pleuritis, cough, or fever, and in severe cases can be life-threatening if the outlet pulmonary artery develops an aneurysm which ruptures causing severe vascular collapse and death from bleeding in the lungs. Nodules, consolidations, cavities and ground glass lesions are common in patients with pulmonary involvement. Pulmonary artery thrombosis may occur.

Joints
Arthritis is seen in up to half of people, and is usually a non-erosive poly or oligoarthritis primarily of the large joints of the lower extremities.

Brain
Central nervous system (CNS) involvement most often occurs as a chronic meningoencephalitis. Lesions tend to occur in the brainstem, the basal ganglia and deep hemispheric white matter and may resemble those of multiple sclerosis (MS). Brainstem atrophy is seen in chronic cases.Neurological involvements range from aseptic meningitis to vascular thrombosis such as dural sinus thrombosis and organic brain syndrome manifesting with confusion, seizures, and memory loss. Sudden hearing loss (sensorineural) is often associated with it. They often appear late in the progression of the disease but are associated with a poor prognosis.

Heart
Pericarditis is a frequent cardiac manifestation. Chronic aortic regurgitation due to aortic root disease may also be seen. Although infrequent, myocardial infarction (heart attack) with angiographically identified acute coronary artery thrombosis has been reported, including one case with a pathologically demonstrable lesion due to arteritis found at autopsy.

Blood vessels
Blood vessel problems are observed in 7–29% of people with arterial lesions representing 15% of vascular lesions. Arterial lesions pose a greater risk. Most common arterial lesions are occlusions or stenosis and aneurysms or pseudoaneurysms.

Cause
The cause is not well-defined, but it is primarily characterized by auto-inflammation of the blood vessels. Although sometimes erroneously referred to as a diagnosis of exclusion, the diagnosis can sometimes be reached by pathologic examination of the affected areas.The primary mechanism of the damage is autoimmune, which by definition is an overactive immune system that targets the patients own body. The involvement of a subset of T cells (Th17) seems to be important. The primary cause is not well known. In fact, no one knows yet why the immune system starts to behave this way in Behçets disease. There does however seem to be a genetic component involved, as first degree relatives of the affected patients are often affected in more than the expected proportion for the general population.Research suggests that previous infections may provoke the autoimmune responses present in Behçets disease. Heat shock proteins (HSPs) are present in some bacteria and serve as a "danger signal" to the immune system. However, some HSPs share a similarity in bacteria and humans. The anti-HSP60 and anti-HSP65 antibodies that target HSPs produced by Streptococci (including S. sanguinis and S. pyogenes) and Mycobacterium tuberculosis can also target human HSPs, leading to immune responses linked to uveitis and various symptoms shown in parenchymal neuro-Behçets disease.An association with the GIMAP ("GTPase of the immunity-associated protein") family of genes on the long arm of chromosome 7 (7q36.1) has been reported. The genes implicated were GIMAP1, GIMAP2 and GIMAP4.

Pathophysiology
Behçets disease is considered more prevalent in the areas surrounding the old silk trading routes in the Middle East and in Central Asia. Thus, it is sometimes known as Silk Road disease. However, this disease is not restricted to people from these regions. A large number of serological studies show a linkage between the disease and HLA-B51. HLA-B51 is more frequently found from the Middle East to South Eastern Siberia, but the incidence of B51 in some studies was 3 fold higher than the normal population. However, B51 tends not to be found in disease when a certain SUMO4 gene variant is involved, and symptoms appear to be milder when HLA-B27 is present. At the current time, a similar infectious origin has not yet been confirmed that leads to Behçets disease, but certain strains of S. sanguinis has been found to have a homologous antigenicity.Vasculitis resulting in occlusion of the vessels supplying the optic nerve may be the cause of acute optic neuropathy and progressive optic atrophy in Behçets disease. Histological evaluation in a reported case of acute optic neuropathy demonstrated substitution of the axonal portion of the optic nerve with fibrous astrocytes without retinal changes. CNS involvement in Behçets disease may lead to intracranial hypertension most commonly due to dural venous sinus thrombosis and subsequent secondary optic atrophy.

Diagnosis
There is no specific pathological testing or technique available for the diagnosis of the disease, although the International Study Group criteria for the disease are highly sensitive and specific, involving clinical criteria and a pathergy test. Behçets disease has a high degree of resemblance to diseases that cause mucocutaneous lesions such as Herpes simplex labialis, and therefore clinical suspicion should be maintained until all the common causes of oral lesions are ruled out from the differential diagnosis.Visual acuity, or color vision loss with concurrent mucocutaneous lesions or systemic Behçets disease symptoms should raise suspicion of optic nerve involvement in Behçets disease and prompt a work-up for Behçets disease if not previously diagnosed in addition to an ocular work-up. Diagnosis of Behçets disease is based on clinical findings including oral and genital ulcers, skin lesions such as erythema nodosum, acne, or folliculitis, ocular inflammatory findings and a pathergy reaction. Inflammatory markers such ESR, and CRP may be elevated. A complete ophthalmic examination may include a slit lamp examination, optical coherence tomography to detect nerve loss, visual field examinations, fundoscopic examination to assess optic disc atrophy and retinal disease, fundoscopic angiography, and visual evoked potentials, which may demonstrate increased latency. Optic nerve enhancement may be identified on Magnetic Resonance Imaging (MRI) in some patients with acute optic neuropathy. However, a normal study does not rule out optic neuropathy. Cerebrospinal fluid (CSF) analysis may demonstrate elevated protein level with or without pleocytosis. Imaging including angiography may be indicated to identify dural venous sinus thrombosis as a cause of intracranial hypertension and optic atrophy.

Diagnostic guidelines
According to the International Study Group guidelines, for a patient to be diagnosed with Behçets disease, the patient must have oral (aphthous) ulcers (any shape, size, or number at least 3 times in any 12 months period) along with 2 out of the following 4 "hallmark" symptoms:
eye inflammation (iritis, uveitis, retinal vasculitis, cells in the vitreous)
genital ulcers (including anal ulcers and spots in the genital region and swollen testicles or epididymitis in men)
pathergy reaction (papule >2 mm dia. 24–48 hrs or more after needle-prick). The pathergy test has a specificity of 95 percent to 100 percent, but the results are often negative in American and European patients
skin lesions (papulo-pustules, folliculitis, erythema nodosum, acne in post-adolescents not on corticosteroids)Despite the inclusive criteria set forth by the International Study Group, there are cases where not all the criteria can be met and therefore a diagnosis cannot readily be made. There is however a set of clinical findings that a physician can rely upon in making a tentative diagnosis of the disease; essentially Behçets disease does not always follow the International Study Group guidelines and so a high degree of suspicion for a patient who presents having any number of the following findings is necessary:
arthritis/arthralgia
cardio-vascular problems of an inflammatory origin
changes of personality, psychoses
deep vein thrombosis
epididymitis
extreme exhaustion - chronic fatigue
inflammatory problems in chest and lungs
mouth ulcers
nervous system symptoms
problems with hearing or balance
stomach or bowel inflammation
superficial thrombophlebitis
any other members of the family with a diagnosis of Behçets disease.

Treatment
Current treatment is aimed at easing the symptoms, reducing inflammation, and controlling the immune system. The quality of the evidence for treating the oral ulcers associated with Behçets disease, however, is poor.High-dose corticosteroid therapy is often used for severe disease manifestations. Anti-TNF therapy such as infliximab has shown promise in treating the uveitis associated with the disease. Another Anti-TNF agent, etanercept, may be useful in people with mainly skin and mucosal symptoms. Apremilast may also be used to treat oral ulcers associated with Behçets disease.Interferon alpha-2a may also be an effective alternative treatment, particularly for the genital and oral ulcers as well as ocular lesions. Azathioprine, when used in combination with interferon alpha-2b also shows promise, and colchicine can be useful for treating some genital ulcers, erythema nodosum, and arthritis. Benzathine‐penicillin may also reduce new arthritic attacks.Thalidomide has also been used due to its immune-modifying effect. Dapsone and rebamipide have been shown, in small studies, to have beneficial results for mucocutaneous lesions.Given its rarity, the optimal treatment for acute optic neuropathy in Behçets disease has not been established. Early identification and treatment are essential. Response to ciclosporin, periocular triamcinolone, and IV methylprednisone followed by oral prednisone has been reported although relapses leading to irreversible visual loss may occur even with treatment. Immunosuppressants such as interferon-alpha and tumour necrosis factor antagonists may improve though not completely reverse symptoms of ocular Behçets disease, which may progress over time despite treatment. When symptoms are limited to the anterior chamber of the eye prognosis is improved. Posterior involvement, particularly optic nerve involvement, is a poor prognostic indicator. Secondary optic nerve atrophy is frequently irreversible. Lumbar puncture or surgical treatment may be required to prevent optic atrophy in cases of intracranial hypertension refractory to treatment with immunomodulators and steroids.IVIG could be a treatment for severe or complicated cases.

Surgery
Surgical treatment of arterial manifestations of BD bears many pitfalls since the obliterative endarteritis of vasa vasorum causes thickening of the medial layer and splitting of elastin fibers. Therefore, anastomotic pseudoaneurysms are likely to form, as well as pseudoaneurysms at the site of the puncture in case of angiography or endovascular treatment; furthermore, early graft occlusion may occur.For these reasons, invasive treatment should not be performed in the acute and active phases of the disease when inflammation is at its peak. The evaluation of diseases activity is usually based on relapsing symptoms, ESR (erythrocyte sedimentation rate), and serum levels of CRP (C‐reactive protein).Endovascular treatment can be an effective and safe alternative to open surgery, with less postoperative complications, faster recovery time, and reduced need for intensive care, while offering patency rates and procedural success rates comparable with those of surgery. This notwithstanding, long‐term results of endovascular treatment in BD are still to be determined.

Epidemiology
The syndrome is rare in the United States, Africa and South America, but is common in the Middle East and Asia, suggesting a possible cause endemic to those areas. A theory suggested that past exposure to lethal infectious agents might have fixed the genetic susceptibility factors to Behçets disease in those area. An estimated 15,000 to 20,000 Americans have been diagnosed with this disease. In the UK, it is estimated to have about 1 case for every 100,000 people. Globally, males are affected more frequently than females.In an epidemiologic study, 56 percent of patients with Behçets disease developed ocular involvement at a mean age of 30. Ocular involvement was the first manifestation of Behçets disease in 8.6 percent of patients. Ocular Behçets disease with involvement of the optic nerve is rarely reported. Among patients with ocular Behçets disease funduscopic findings of optic atrophy, and optic disc paleness have been identified with a frequency of 17.9 percent and 7.4 percent, respectively. Other fundoscopic findings include vascular sheathing (23.7%), retinal hemorrhage (9%), macular edema (11.3%), branch retinal vein occlusion (5.8%), and retinal edema (6.6%). However, optic atrophy was the most significant cause of visual impairment identified in 54 percent of patients with ocular Behçets disease and permanent visual impairment.The prevalence of this disease increases from North to South. It follows a more severe course in patients with an early age of onset particularly in patients with eye and gastrointestinal involvement.

Pregnancy
With Behçets disease as a pre-existing disease in pregnancy or acquired, the pregnancy does not have an adverse effect on the course of Behçets disease and may possibly ameliorate its course. Still, there is a substantial variability in clinical course between patients and even for different pregnancies in the same patient </s>