<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Type 2 diabetes and can you explain it in depth? [/INST] Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, and unexplained weight loss. Symptoms may also include increased hunger, feeling tired, and sores that do not heal. Often symptoms come on slowly. Long-term complications from high blood sugar include heart disease, strokes, diabetic retinopathy which can result in blindness, kidney failure, and poor blood flow in the limbs which may lead to amputations. The sudden onset of hyperosmolar hyperglycemic state may occur; however, ketoacidosis is uncommon.Type 2 diabetes primarily occurs as a result of obesity and lack of exercise. Some people are genetically more at risk than others.Type 2 diabetes makes up about 90% of cases of diabetes, with the other 10% due primarily to type 1 diabetes and gestational diabetes. In type 1 diabetes there is a lower total level of insulin to control blood glucose, due to an autoimmune induced loss of insulin-producing beta cells in the pancreas. Diagnosis of diabetes is by blood tests such as fasting plasma glucose, oral glucose tolerance test, or glycated hemoglobin (A1C).Type 2 diabetes is largely preventable by staying a normal weight, exercising regularly, and eating a healthy diet (high in fruits and vegetables and low in sugar and saturated fats). Treatment involves exercise and dietary changes. If blood sugar levels are not adequately lowered, the medication metformin is typically recommended. Many people may eventually also require insulin injections. In those on insulin, routinely checking blood sugar levels is advised; however, this may not be needed in those taking pills. Bariatric surgery often improves diabetes in those who are obese.Rates of type 2 diabetes have increased markedly since 1960 in parallel with obesity. As of 2015 there were approximately 392 million people diagnosed with the disease compared to around 30 million in 1985. Typically it begins in middle or older age, although rates of type 2 diabetes are increasing in young people. Type 2 diabetes is associated with a ten-year-shorter life expectancy. Diabetes was one of the first diseases ever described, dating back to an Egyptian manuscript from c. 1500 BCE. The importance of insulin in the disease was determined in the 1920s.

Signs and symptoms
The classic symptoms of diabetes are frequent urination (polyuria), increased thirst (polydipsia), increased hunger (polyphagia), and weight loss. Other symptoms that are commonly present at diagnosis include a history of blurred vision, itchiness, peripheral neuropathy, recurrent vaginal infections, and fatigue. Other symptoms may include loss of taste.  Many people, however, have no symptoms during the first few years and are diagnosed on routine testing. A small number of people with type 2 diabetes can develop a hyperosmolar hyperglycemic state (a condition of very high blood sugar associated with a decreased level of consciousness and low blood pressure).

Complications
Type 2 diabetes is typically a chronic disease associated with a ten-year-shorter life expectancy. This is partly due to a number of complications with which it is associated, including: two to four times the risk of cardiovascular disease, including ischemic heart disease and stroke; a 20-fold increase in lower limb amputations, and increased rates of hospitalizations. In the developed world, and increasingly elsewhere, type 2 diabetes is the largest cause of nontraumatic blindness and kidney failure. It has also been associated with an increased risk of cognitive dysfunction and dementia through disease processes such as Alzheimers disease and vascular dementia. Other complications include hyperpigmentation of skin (acanthosis nigricans), sexual dysfunction, and frequent infections. There is also an association between type 2 diabetes and mild hearing loss.

Causes
The development of type 2 diabetes is caused by a combination of lifestyle and genetic factors. While some of these factors are under personal control, such as diet and obesity, other factors are not, such as increasing age, female sex, and genetics. Obesity is more common in women than men in many parts of Africa. The nutritional status of a mother during fetal development may also play a role, with one proposed mechanism being that of DNA methylation. The intestinal bacteria Prevotella copri and Bacteroides vulgatus have been connected with type 2 diabetes.

Lifestyle
Lifestyle factors are important to the development of type 2 diabetes, including obesity and being overweight (defined by a body mass index of greater than 25), lack of physical activity, poor diet, psychological stress, and urbanization. Excess body fat is associated with 30% of cases in those of Chinese and Japanese descent, 60–80% of cases in those of European and African descent, and 100% of cases in Pima Indians and Pacific Islanders. Among those who are not obese, a high waist–hip ratio is often present. Smoking appears to increase the risk of type 2 diabetes.  A lack of sleep has also been linked to type 2 diabetes. Laboratory studies have linked short-term sleep deprivations to changes in glucose metabolism, nervous system activity, or hormonal factors that may lead to diabetes.Dietary factors also influence the risk of developing type 2 diabetes. Consumption of sugar-sweetened drinks in excess is associated with an increased risk. The type of fats in the diet are important, with saturated fats and trans fatty acids increasing the risk, and polyunsaturated and monounsaturated fat decreasing the risk. Eating a lot of white rice appears to play a role in increasing risk. A lack of exercise is believed to cause 7% of cases. Persistent organic pollutants may also play a role.

Genetics
Most cases of diabetes involve many genes, with each being a small contributor to an increased probability of becoming a type 2 diabetic. The proportion of diabetes that is inherited is estimated at 72%. More than 36 genes and 80 single nucleotide polymorphisms (SNPs) had been found that contribute to the risk of type 2 diabetes. All of these genes together still only account for 10% of the total heritable component of the disease. The TCF7L2 allele, for example, increases the risk of developing diabetes by 1.5 times and is the greatest risk of the common genetic variants. Most of the genes linked to diabetes are involved in pancreatic beta cell functions.There are a number of rare cases of diabetes that arise due to an abnormality in a single gene (known as monogenic forms of diabetes or "other specific types of diabetes"). These include maturity onset diabetes of the young (MODY), Donohue syndrome, and Rabson–Mendenhall syndrome, among others. Maturity onset diabetes of the young constitute 1–5% of all cases of diabetes in young people.

Medical conditions
There are a number of medications and other health problems that can predispose to diabetes. Some of the medications include: glucocorticoids, thiazides, beta blockers, atypical antipsychotics, and statins. Those who have previously had gestational diabetes are at a higher risk of developing type 2 diabetes. Other health problems that are associated include: acromegaly, Cushings syndrome, hyperthyroidism, pheochromocytoma, and certain cancers such as glucagonomas. Individuals with cancer may be at a higher risk of mortality if they also have diabetes. Testosterone deficiency is also associated with type 2 diabetes. Eating disorders may also interact with type 2 diabetes, with bulimia nervosa increasing the risk and anorexia nervosa decreasing it.

Pathophysiology
Type 2 diabetes is due to insufficient insulin production from beta cells in the setting of insulin resistance. Insulin resistance, which is the inability of cells to respond adequately to normal levels of insulin, occurs primarily within the muscles, liver, and fat tissue. In the liver, insulin normally suppresses glucose release. However, in the setting of insulin resistance, the liver inappropriately releases glucose into the blood. The proportion of insulin resistance versus beta cell dysfunction differs among individuals, with some having primarily insulin resistance and only a minor defect in insulin secretion and others with slight insulin resistance and primarily a lack of insulin secretion.Other potentially important mechanisms associated with type 2 diabetes and insulin resistance include: increased breakdown of lipids within fat cells, resistance to and lack of incretin, high glucagon levels in the blood, increased retention of salt and water by the kidneys, and inappropriate regulation of metabolism by the central nervous system. However, not all people with insulin resistance develop diabetes since an impairment of insulin secretion by pancreatic beta cells is also required.In the early stages of insulin resistance, the mass of beta cells expands, increasing the output of insulin to compensate for the insulin insensitivity. But when type 2 diabetes has become manifest, a type 2 diabetic will have lost about half of their beta cells.Fatty acids in the beta cells activate FOXO1, resulting in apoptosis of the beta cells.The causes of the aging-related insulin resistance seen in obesity and in type 2 diabetes are uncertain. Effects of intracellular lipid metabolism and ATP production in liver and muscle cells may contribute to insulin resistance.  New evidence also points to a role of a brain region called the hypothalamus in the development of insulin resistance. For one thing, a gene called Dusp8 is linked with an increased risk for diabetes. This gene codes for a protein that regulates neuronal signaling in the hypothalamus. Also, infusions into the hypothalamus of a hormone called leptin normalize blood glucose and diminish insulin resistance in diabetic animals. Activation of hypothalamic cells by leptin has an important role in maintaining normal levels of blood glucose. Thus, both the endocrine cells of the pancreas AND cells in the hypothalamus may have a role in the etiology of type 2 diabetes.
Hypothalamic cells regulate blood glucose via projections to the autonomic nervous system. Autonomic innervation of liver and muscle cells stimulates an increased uptake of glucose. In diabetic humans, the control of blood glucose by the autonomic nervous system is abnormal. Leptin-sensitive, glucose regulating neurons become resistant to leptin during aging or during exposure to a high-fat diet. These leptin resistant neurons fail to restrain food intake, obesity, and blood glucose. The reasons for this lowered responsiveness to leptin are uncertain and are part of the puzzle of the causes of type 2 diabetes.Blood glucose levels can also be normalized in diabetic rodents by a single intrahypothalamic infusion of Fibroblast Growth Factor 1 (FGF1), an effect that persists for months even in severely diabetic animals. This remarkable cure of diabetes is accomplished by a stimulation of accessory brain cells called astrocytes.  Hypothalamic astrocytes that produce Fatty Acid Binding Protein 7 (FABP7) are targets of FGF1; these cells are also in close contact with leptin-sensitive neurons, influence their function, and regulate leptin sensitivity. An abnormal function of FABP7+ astrocytes thus may contribute to the resistance to leptin and insulin that appear during aging and during exposure to high-fat diets.
During aging, FABP7+ astrocytes develop cytoplasmic granules derived from degenerating mitochondria. This mitochondrial degeneration is partly due to the oxidative stress of the heightened amounts of fatty acids that are taken up by these cells and oxidized within mitochondria.  A pathological degeneration of mitochondria in these cells may compromise their normal functions and contribute to abnormalities in the control of blood glucose by the hypothalamus.

Diagnosis
The World Health Organization definition of diabetes (both type 1 and type 2) is for a single raised glucose reading with symptoms, otherwise raised values on two occasions, of either:
fasting plasma glucose ≥ 7.0 mmol/l (126 mg/dl)orwith a glucose tolerance test, two hours after the oral dose a plasma glucose ≥ 11.1 mmol/l (200 mg/dl)A random blood sugar of greater than 11.1 mmol/l (200 mg/dl) in association with typical symptoms or a glycated hemoglobin (HbA1c) of ≥ 48 mmol/mol (≥ 6.5 DCCT %) is another method of diagnosing diabetes. In 2009 an International Expert Committee that included representatives of the American Diabetes Association (ADA), the International Diabetes Federation (IDF), and the European Association for the Study of Diabetes (EASD) recommended that a threshold of ≥ 48 mmol/mol (≥ 6.5 DCCT %) should be used to diagnose diabetes. This recommendation was adopted by the American Diabetes Association in 2010. Positive tests should be repeated unless the person presents with typical symptoms and blood sugars >11.1 mmol/l (>200 mg/dl).
Threshold for diagnosis of diabetes is based on the relationship between results of glucose tolerance tests, fasting glucose or HbA1c and complications such as retinal problems. A fasting or random blood sugar is preferred over the glucose tolerance test, as they are more convenient for people. HbA1c has the advantages that fasting is not required and results are more stable but has the disadvantage that the test is more costly than measurement of blood glucose. It is estimated that 20% of people with diabetes in the United States do not realize that they have the disease.Type 2 diabetes is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. This is in contrast to type 1 diabetes in which there is an absolute insulin deficiency due to destruction of islet cells in the pancreas and gestational diabetes that is a new onset of high blood sugars associated with pregnancy. Type 1 and type 2 diabetes can typically be distinguished based on the presenting circumstances. If the diagnosis is in doubt antibody testing may be useful to confirm type 1 diabetes and C-peptide levels may be useful to confirm type 2 diabetes, with C-peptide levels normal or high in type 2 diabetes, but low in type 1 diabetes.

Screening
No major organization recommends universal screening for diabetes as there is no evidence that such a program improve outcomes. Screening is recommended by the United States Preventive Services Task Force (USPSTF) in adults without symptoms whose blood pressure is greater than 135/80 mmHg. For those whose blood pressure is less, the evidence is insufficient to recommend for or against screening. There is no evidence that it changes the risk of death in this group of people. They also recommend screening among those who are overweight and between the ages of 40 and 70.The World Health Organization recommends testing those groups at high risk and in 2014 the USPSTF is considering a similar recommendation. High-risk groups in the United States include: those over 45 years old; those with a first degree relative with diabetes; some ethnic groups, including Hispanics, African-Americans, and Native-Americans; a history of gestational diabetes; polycystic ovary syndrome; excess weight; and conditions associated with metabolic syndrome. The American Diabetes Association recommends screening those who have a BMI over 25 (in people of Asian descent screening is recommended for a BMI over 23).A Cochrane Systematic Review looking at the effects of screening on all-cause and diabetes-related mortality did not show any benefits in these outcomes for either screening or not-screening. This was based on only one included study, so no conclusions can be made on the benefits of screening, or lack thereof. This same review did not assess the effects on other outcomes such as adverse effects, incidence of type 2 diabetes, HbA1c or socioeconomic effects.In the UK, NICE guidelines suggest taking action to prevent diabetes for people with a body mass index (BMI) of 30. For people of Black African, African-Caribbean, South Asian and Chinese descent the recommendation to start prevention starts at the BMI of 27,5. A study based on a large sample of people in England suggest even lower BMIs for certain ethnic groups for the start of prevention, for example 24 in South Asian and 21 in Bangladeshi populations.

Prevention
Onset of type 2 diabetes can be delayed or prevented through proper nutrition and regular exercise. Intensive lifestyle measures may reduce the risk by over half. The benefit of exercise occurs regardless of the persons initial weight or subsequent weight loss. High levels of physical activity reduce the risk of diabetes by about 28%. Evidence for the benefit of dietary changes alone, however, is limited, with some evidence for a diet high in green leafy vegetables and some for limiting the intake of sugary drinks. There is an association between higher intake of sugar-sweetened fruit juice and diabetes, but no evidence of an association with 100% fruit juice. A 2019 review found evidence of benefit from dietary fiber.In those with impaired glucose tolerance, diet and exercise either alone or in combination with metformin or acarbose may decrease the risk of developing diabetes. Lifestyle interventions are more effective than metformin. A 2017 review found that, long term, lifestyle changes decreased the risk by 28%, while medication does not reduce risk after withdrawal. While low vitamin D levels are associated with an increased risk of diabetes, correcting the levels by supplementing vitamin D3 does not improve that risk.

Management
Management of type 2 diabetes focuses on lifestyle interventions, lowering other cardiovascular risk factors, and maintaining blood glucose levels in the normal range. Self-monitoring of blood glucose for people with newly diagnosed type 2 diabetes may be used in combination with education, although the benefit of self-monitoring in those not using multi-dose insulin is questionable. In those who do not want to measure blood levels, measuring urine levels may be done. Managing other cardiovascular risk factors, such as hypertension, high cholesterol, and microalbuminuria, improves a persons life expectancy. Decreasing the systolic blood pressure to less than 140 mmHg is associated with a lower risk of death and better outcomes. Intensive blood pressure management (less than 130/80 mmHg) as opposed to standard blood pressure management (less than 140-160 mmHg systolic to 85–100 mmHg diastolic) results in a slight decrease in stroke risk but no effect on overall risk of death.Intensive blood sugar lowering (HbA1c<6%) as opposed to standard blood sugar lowering (HbA1c of 7–7.9%) does not appear to change mortality. The goal of treatment is typically an HbA1c of 7 to 8% or a fasting glucose of less than 7.2 mmol/L (130 mg/dl); however these goals may be changed after professional clinical consultation, taking into account particular risks of hypoglycemia and life expectancy. Hypoglycemia is associated with adverse outcomes in older people with type 2 diabetes. Despite guidelines recommending that intensive blood sugar control be based on balancing immediate harms with long-term benefits, many people – for example people with a life expectancy of less than nine years who will not benefit, are over-treated.It is recommended that all people with type 2 diabetes get regular eye examinations. There is weak evidence suggesting that treating gum disease by scaling and root planing may result in a small short-term improvement in blood sugar levels for people with diabetes. There is no evidence to suggest that this improvement in blood sugar levels is maintained longer than four months. There is also not enough evidence to determine if medications to treat gum disease are effective at lowering blood sugar levels.

Lifestyle
Exercise
A proper diet and regular exercise are foundations of diabetic care, with one review indicating that a greater amount of exercise improved outcomes. Regular exercise may improve blood sugar control, decrease body fat content, and decrease blood lipid levels.

Diet
A diabetic diet which includes calorie restriction to promote weight loss is generally recommended. Other recommendations include emphasizing intake of fruits, vegetables, reduced saturated fat and low-fat dairy products, and with a macronutrient intake tailored to the individual, to distribute calories and carbohydrates throughout the day. Several diets may be effective such as the Dietary Approaches to Stop Hypertension (DASH), Mediterranean diet, low-fat diet, or monitored carbohydrate diets such as a low carbohydrate diet. Viscous fiber supplements may be useful in those with diabetes.Vegetarian diets in general have been related to lower diabetes risk, but do not offer advantages compared with diets which allow moderate amounts of animal products. There is not enough evidence to suggest that cinnamon improves blood sugar levels in people with type 2 diabetes. A 2021 review showed that consumption of tree nuts (walnuts, almonds, and hazelnuts) reduced fasting blood glucose in diabetic people.Culturally appropriate education may help people with type 2 diabetes control their blood sugar levels for up to 24 months. There is not enough evidence to determine if lifestyle interventions affect mortality in those who already have type 2 diabetes.As of 2015, there is insufficient data to recommend nonnutritive sweeteners, which may help reduce caloric intake.

Medications
Blood sugar control
There are several classes of anti-diabetic medications available. Metformin is generally recommended as a first line treatment as there is some evidence that it decreases mortality; however, this conclusion is questioned. Metformin should not be used in those with severe kidney or liver problems.A second oral agent of another class or insulin may be added if metformin is not sufficient after three months. Other classes of medications include: sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, SGLT2 inhibitors, and glucagon-like peptide-1 analogs. As of 2015 there was no significant difference between these agents. A 2018 review found that SGLT2 inhibitors and GLP-1 agonists, but not DPP-4 inhibitors, were associated with lower mortality than placebo or no treatment.Rosiglitazone, a thiazolidinedione, has not been found to improve long-term outcomes even though it improves blood sugar levels. Additionally it is associated with increased rates of heart disease and death.The effects of Plioglitazone have been compared in a Cochrane systematic review to that of other blood sugar lowering-medicine, including metformin, acarbose, and repaglinide, not showing any benefit in reducing the chance of developing type 2 diabetes in people at risk. It did, however, show reduction of risk of developing type 2 diabetes when compared to a placebo or to no treatment. These results should be interpreted considering that most of the data of the studies included in this review were of low or very-low certainty.
Injections of insulin may either be added to oral medication or used alone. Most people do not initially need insulin. When it is used, a long-acting formulation is typically added at night, with oral medications being continued. Doses are then increased to effect (blood sugar levels being well controlled). When nightly insulin is insufficient, twice daily insulin may achieve better control. The long acting insulins glargine and detemir are equally safe and effective, and do not appear much better than neutral protamine Hagedorn (NPH) insulin, but as they are significantly more expensive, they are not cost effective as of 2010. In those who are pregnant, insulin is generally the treatment of choice.

Blood pressure lowering
Many international guidelines recommend blood pressure treatment targets that are lower than 140/90 mmHg for people with diabetes. However, there is only limited evidence regarding what the lower targets should be. A 2016 systematic review found potential harm to treating to targets lower than 140 mmHg, and a subsequent review in 2019 found no evidence of additional benefit from blood pressure lowering to between 130–140mmHg, although there was an increased risk of adverse events.2015 American Diabetes Association recommendations are that people with diabetes and albuminuria should receive an inhibitor of the renin-angiotensin system to reduce the risks of progression to end-stage renal disease, cardiovascular events, and death. There is some evidence that angiotensin converting enzyme inhibitors (ACEIs) are superior to other inhibitors of the renin-angiotensin system such as angiotensin receptor blockers (ARBs), or aliskiren in preventing cardiovascular disease. Although a more recent review found similar effects of ACEIs and ARBs on major cardiovascular and renal outcomes. There is no evidence that combining ACEIs and ARBs provides additional benefits.

Other
The use of aspirin to prevent cardiovascular disease in diabetes is controversial. Aspirin is recommended in people at high risk of cardiovascular disease, however routine use of aspirin has not been found to improve outcomes in uncomplicated diabetes. 2015 American Diabetes Association recommendations for aspirin use (based on expert consensus or clinical experience) are that low-dose aspirin use is reasonable in adults with diabetes who are at intermediate risk of cardiovascular disease (10-year cardiovascular disease risk, 5–10%).Vitamin D supplementation to people with type 2 diabetes may improve markers of insulin resistance and HbA1c.Sharing their electronic health records with people who have type 2 diabetes helps them to reduce their blood sugar levels. It is a way of helping people understand their own health condition and involving them actively in its management.

Surgery
Weight loss surgery in those who are obese is an effective measure to treat diabetes. Many are able to maintain normal blood sugar levels with little or no medication following surgery and long-term mortality is decreased. There however is some short-term mortality risk of less than 1% from the surgery. The body mass index cutoffs for when surgery is appropriate are not yet clear. It is recommended that this option be considered in those who are unable to get both their weight and blood sugar under control.

Epidemiology
The International Diabetes Federation estimates nearly 537 million people lived with diabetes worldwide in 2021, 90–95% of whom have type 2 diabetes. Diabetes is common both in the developed and the developing world. It remains uncommon, however, in the least developed countries.Women seem to be at a greater risk as do certain ethnic groups, such as South Asians, Pacific Islanders, Latinos, and Native Americans. This may be due to enhanced sensitivity to a Western lifestyle in certain ethnic groups. Traditionally considered a disease of adults, type 2 diabetes is increasingly diagnosed in children in parallel with rising obesity rates. Type 2 diabetes is now diagnosed as frequently as type 1 diabetes in teenagers in the United States.Rates of diabetes in 1985 were estimated at 30 million, increasing to 135 million in 1995 and 217 million in 2005. This increase is believed to be primarily due to the global population aging, a decrease in exercise, and increasing rates of obesity. The five countries with the greatest number of people with diabetes as of 2000 are India having 31.7 million, China 20.8 million, the United States 17.7 million, Indonesia 8.4 million, and Japan 6.8 million. It is recognized as a global epidemic by the World Health Organization.

History
Diabetes is one of the first diseases described with an Egyptian manuscript from c. 1500 BCE mentioning "too great emptying of the urine." The first described cases are believed to be of type 1 diabetes. Indian physicians around the same time identified the disease and classified it as madhumeha or honey urine noting that the urine would attract ants. The term "diabetes" or "to pass through"  was first used in 230 BCE by the Greek Apollonius Memphites. The disease was rare during the time of the Roman empire with Galen commenting that he had only seen two cases during his career.Type 1 and type 2 diabetes were identified as separate conditions for the first time by the Indian physicians Sushruta and Charaka in 400–500 AD with type 1 associated with youth and type 2 with being overweight. Effective treatment was not developed until the early part of the 20th century when the Canadians Frederick Banting and Charles Best discovered insulin in 1921 and 1922. This was followed by the development of the long acting NPH insulin in the 1940s.In 1916, Elliot Joslin proposed that in people with diabetes, periods of fasting are helpful </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Gastroparesis and can you explain it in depth? [/INST] Gastroparesis (gastro- from Ancient Greek γαστήρ - gaster, "stomach"; and -paresis, πάρεσις - "partial paralysis"), also called delayed gastric emptying, is a medical disorder consisting of weak muscular contractions (peristalsis) of the stomach, resulting in food and liquid remaining in the stomach for a prolonged period of time. Stomach contents thus exit more slowly into the duodenum of the digestive tract.  This can result in irregular absorption of nutrients, inadequate nutrition, and poor glycemic control.Symptoms include nausea, vomiting, abdominal pain, feeling full soon after beginning to eat (early satiety), abdominal bloating, and heartburn. The most common known mechanism is autonomic neuropathy of the nerve which innervates the stomach: the vagus nerve. Uncontrolled diabetes mellitus is a major cause of this nerve damage; other causes include post-infectious and trauma to the vagus nerve.
Diagnosis is via one or more of the following: barium swallow X-ray, barium beefsteak meal, radioisotope gastric-emptying scan, gastric manometry, and esophagogastroduodenoscopy (EGD). Complications include malnutrition, fatigue, weight loss, vitamin deficiencies, intestinal obstruction due to bezoars, and  small intestine bacterial overgrowth.
Treatment includes dietary modifications, medications to stimulate gastric emptying, medications to reduce vomiting, and surgical approaches.

Signs and symptoms
The most common symptoms of gastroparesis are the following:
Chronic nausea
Vomiting (especially of undigested food)
Abdominal pain
A feeling of fullness after eating just a few bitesOther symptoms include the following:

Abdominal bloating
Body aches (myalgia)
Erratic blood glucose levels
Acid reflux (GERD)
Heartburn
Lack of appetite
Morning nausea
Muscle weakness
Night sweats
Palpitations
Spasms of the stomach wall
Constipation or infrequent bowel movements
Weight loss, malnutrition
Difficulty swallowingVomiting may not occur in all cases, as those affected may adjust their diets to include only small amounts of food.

Causes
Transient gastroparesis may arise in acute illness of any kind, as a consequence of certain cancer treatments or other drugs which affect digestive action, or due to abnormal eating patterns. The symptoms are almost identical to those of low stomach acid, therefore most doctors will usually recommend trying out supplemental hydrochloric acid before moving on to the invasive procedures required to confirm a damaged nerve. Patients with cancer may develop gastroparesis because of chemotherapy-induced neuropathy, immunosuppression followed by viral infections involving the GI tract, procedures such as celiac blocks, paraneoplastic neuropathy or myopathy, or after an allogeneic bone marrow transplant via graft-versus-host disease.Gastroparesis present similar symptoms to slow gastric emptying caused by certain opioid medications, antidepressants, and allergy medications, along with high blood pressure. For patients already with gastroparesis, these can make the condition worse. More than 50% of all gastroparesis cases are idiopathic in nature, with unknown causes. It is, however, frequently caused by autonomic neuropathy. This may occur in people with type 1 or type 2 diabetes, about 30–50% among long-standing diabetics. In fact, diabetes mellitus has been named as the most common cause of gastroparesis, as high levels of blood glucose may effect chemical changes in the nerves. The vagus nerve becomes damaged by years of high blood glucose or insufficient transport of glucose into cells resulting in gastroparesis. Adrenal and thyroid gland problems could also be a cause.Gastroparesis has also been associated with connective tissue diseases such as scleroderma and Ehlers–Danlos syndrome, and neurological conditions such as Parkinsons disease and multiple system atrophy. It may occur as part of a mitochondrial disease. Opioids and anticholinergic medications can cause medication-induced gastroparesis. Chronic gastroparesis can be caused by other types of damage to the vagus nerve, such as abdominal surgery. Heavy cigarette smoking is also a plausible cause since smoking causes damage to the stomach lining. Idiopathic gastroparesis (gastroparesis with no known cause) accounts for a third of all chronic cases; it is thought that many of these cases are due to an autoimmune response triggered by an acute viral infection. Gastroenteritis, mononucleosis, and other ailments have been anecdotally linked to the onset of the condition, but no systematic study has proven a link.People with gastroparesis are disproportionately female. One possible explanation for this finding is that women have an inherently slower stomach emptying time than men. A hormonal link has been suggested, as gastroparesis symptoms tend to worsen the week before menstruation when progesterone levels are highest. Neither theory has been proven definitively.

Mechanism
On the molecular level, it is thought that gastroparesis can be caused by the loss of neuronal nitric oxide expression since the cells in the GI tract secrete nitric oxide. This important signaling molecule has various responsibilities in the GI tract and in muscles throughout the body. When nitric oxide levels are low, the smooth muscle and other organs may not be able to function properly. Other important components of the stomach are the interstitial cells of Cajal (ICC) which act as a pacemaker since they transduce signals from motor neurons to produce an electrical rhythm in the smooth muscle cells. Lower nitric oxide levels also correlate with loss of ICC cells, which can ultimately lead to the loss of function in the smooth muscle in the stomach, as well as in other areas of the gastrointestinal tract.Pathogenesis of symptoms in diabetic gastroparesis include:

Loss of gastric neurons containing nitric oxide synthase (NOS) is responsible for defective accommodation reflex, which leads to early satiety and postprandial fullness.
Impaired electromechanical activity in the myenteric plexus is responsible for delayed gastric emptying, resulting in nausea and vomiting.
Sensory neuropathy in the gastric wall may be responsible for epigastric pain.
Abnormal pacemaker activity (tachybradyarrhythmia) may generate a noxious signal transmitted to the CNS to evoke nausea and vomiting.

Diagnosis
Gastroparesis can be diagnosed with tests such as barium swallow X-rays, manometry, and gastric emptying scans. For the X-ray, the patient drinks a liquid containing barium after fasting which will show up in the X-ray and the physician is able to see if there is still food in the stomach as well. This can be an easy way to identify whether the patient has delayed emptying of the stomach. The clinical definition for gastroparesis is based solely on the emptying time of the stomach (and not on other symptoms), and severity of symptoms does not necessarily correlate with the severity of gastroparesis. Therefore, some patients may have marked gastroparesis with few, if any, serious complications.In other cases or if the X-ray is inconclusive, the physician may have the patient eat a meal of toast, water, and eggs containing a radioactive isotope so they can watch as it is digested and see how slowly the digestive tract is moving. This can be helpful for diagnosing patients who are able to digest liquids but not solid foods.

Complications
Complications of gastroparesis include:

Fluctuations in blood glucose due to unpredictable digestion times due to changes in rate and amount of food passing into the small bowel. This makes diabetes worse, but does not cause diabetes. Lack of control of blood sugar levels will make the gastroparesis worsen.
General malnutrition due to the symptoms of the disease (which frequently include vomiting and reduced appetite) as well as the dietary changes necessary to manage it. This is especially true for vitamin deficiencies such as scurvy because of inability to tolerate fresh fruits.
Severe fatigue and weight loss due to calorie deficit
Intestinal obstruction due to the formation of bezoars (solid masses of undigested food). This can cause nausea and vomiting, which can in turn be life-threatening if they prevent food from passing the small intestine.
Small intestine bacterial overgrowth is commonly found in patients with gastroparesis.
Bacterial infection due to overgrowth in undigested food
A decrease in quality of life, since it can make keeping up with work and other responsibilities more difficult.

Treatment
Treatment includes dietary modifications, medications to stimulate gastric emptying, medications to reduce vomiting, and surgical approaches.Dietary treatment involves low fiber diets and, in some cases, restrictions on fat or solids. Eating smaller meals, spaced two to three hours apart has proved helpful. Avoiding foods like rice or beef that cause the individual problems such as pain in the abdomen or constipation will help avoid symptoms.Metoclopramide, a dopamine D2 receptor antagonist, increases contractility and resting tone within the GI tract to improve gastric emptying. In addition, dopamine antagonist action in the central nervous system prevents nausea and vomiting. Similarly, the dopamine receptor antagonist domperidone is used to treat gastroparesis. Erythromycin is known to improve emptying of the stomach but its effects are temporary due to tachyphylaxis and wane after a few weeks of consistent use. Sildenafil citrate, which increases blood flow to the genital area in men, is being used by some practitioners to stimulate the gastrointestinal tract in cases of diabetic gastroparesis. The antidepressant mirtazapine has proven effective in the treatment of gastroparesis unresponsive to conventional treatment. This is due to its antiemetic and appetite stimulant properties. Mirtazapine acts on the same serotonin receptor (5-HT3) as does the popular anti-emetic ondansetron. Camicinal is a motilin agonist for the treatment of gastroparesis.
In specific cases where treatment of chronic nausea and vomiting proves resistant to drugs, implantable gastric stimulation may be utilized. A medical device is implanted that applies neurostimulation to the muscles of the lower stomach to reduce the symptoms. This is only done in refractory cases that have failed all medical management (usually at least two years of treatment). Medically refractory gastroparesis may also be treated with a pyloromyotomy, which widens the gastric outlet by cutting the circular pylorus muscle. This can be done laparoscopically or endoscopically.  Vertical sleeve gastrectomy, a procedure in which a part or all of the affected portion of the stomach is removed, has been shown to have some success in the treatment of gastroparesis in obese patients, even curing it in some instances. Further studies have been recommended due to the limited sample size of previous studies.In cases of postinfectious gastroparesis, patients have symptoms and go undiagnosed for an average of 3 weeks to 6 months before their illness is identified correctly and treatment begins.

Prognosis
Post-infectious
Cases of post-infectious gastroparesis are self‐limiting, with recovery within 12 months of initial symptoms, although some cases last well over 2 years. In children, the duration tends to be shorter and the disease course milder than in adolescent and adults.

Diabetic gastropathy
Diabetic gastropathy is usually slowly progressive, and can become severe and lethal.

Prevalence
Post-infectious gastroparesis, which constitutes the majority of idiopathic gastroparesis cases, affects up to 4% of the American population. Women in their 20s and 30s seem to be susceptible. One study of 146 American gastroparesis patients found the mean age of patients was 34 years with 82% affected being women, while another study found the patients were young or middle aged and up to 90% were women.There has only been one true epidemiological study of idiopathic gastroparesis which was completed by the Rochester Epidemiology Project. They looked at patients from 1996 to 2006 who were seeking medical attention instead of a random population sample and found that the prevalence of delayed gastric emptying was fourfold higher in women. It is difficult for medical professionals and researchers to collect enough data and provide accurate numbers since studying gastroparesis requires specialized laboratories and equipment.

References
Further reading
Overview from NIDDK National Institute of Diabetes, Digestive, and Kidney Diseases at NIH
Camilleri M, Parkman HP, Shafi MA, Abell TL, Gerson L (January 2013). "Clinical guideline: management of gastroparesis" </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Irritant diaper dermatitis and can you explain it in depth? [/INST] Irritant diaper dermatitis (IDD, also called a diaper/nappy rash) is a generic term applied to skin rash in the diaper nappy area that are caused by various skin disorders and/or irritants.
Generic irritant diaper/nappy  dermatitis is characterized by joined patches of erythema and scaling mainly seen on the convex surfaces, with the skin folds spared.
Diaper/nappy dermatitis with secondary bacterial or fungal involvement tends to spread to concave surfaces (i.e. skin folds), as well as convex surfaces, and often exhibits a central red, beefy erythema with satellite pustules around the border.
It is usually considered a form of irritant contact dermatitis. The word "diaper" is in the name not because the diaper/nappy itself causes the rash but rather because the rash is associated with diaper use, being caused by the materials trapped by the diaper (usually feces). Allergic contact dermatitis has also been suggested, but there is little evidence for this cause. In adults with incontinence (fecal, urinary, or both), the rash is sometimes called incontinence-associated dermatitis (IAD).The term diaper candidiasis is used when a fungal origin is identified. The distinction is critical because the treatment (antifungals) is completely different.

Causes
Irritant diaper dermatitis develops when skin is exposed to prolonged wetness, increased skin pH caused by the combination, and subsequent reactions, of urine and feces, and resulting breakdown of the stratum corneum, or outermost layer of the skin.  This may be due to diarrhea, frequent stools, tight diapers, overexposure to ammonia, or allergic reactions.  In adults, the stratum corneum is composed of 25 to 30 layers of flattened dead keratinocytes, which are continuously shed and replaced from below. These dead cells are interlaid with lipids secreted by the stratum granulosum just underneath, which help to make this layer of the skin a waterproof barrier. The stratum corneums function is to reduce water loss, repel water, protect deeper layers of the skin from injury, and to repel microbial invasion of the skin. In infants, this layer of the skin is much thinner and more easily disrupted.

Urine
Although wetness alone has the effect of macerating the skin, softening the stratum corneum, and greatly increasing susceptibility to friction injury, urine has an additional impact on skin integrity because of its effect on skin pH. While studies show that ammonia alone is only a mild skin irritant, when urea breaks down in the presence of fecal urease it increases pH because ammonia is released, which in turn promotes the activity of fecal enzymes such as protease and lipase. These fecal enzymes increase the skins hydration and permeability to bile salts which also act as skin irritants.
There is no detectable difference in rates of diaper rash in conventional disposable diaper wearers and reusable cloth diaper wearers. "Babies wearing superabsorbent disposable diapers with a central gelling material have fewer episodes of diaper dermatitis compared with their counterparts wearing cloth diapers. However, keep in mind that superabsorbent diapers contain dyes that were suspected to cause allergic contact dermatitis (ACD)." Whether wearing cloth or disposable diapers they should be changed frequently to prevent diaper rash, even if they dont feel wet. To reduce the incidence of diaper rash, disposable diapers have been engineered to pull moisture away from the babys skin using synthetic non-biodegradable gel.  Today, cloth diapers use newly available superabsorbent microfiber cloth placed in a pocket with a layer of light permeable material that contacts the skin.  This design serves to pull moisture away from the skin in to the microfiber cloth.  This technology is used in most major pocket cloth diapers brands today.

Diet
The interaction between fecal enzyme activity and IDD explains the observation that infant diet and diaper rash are linked because fecal enzymes are in turn affected by diet. Breast-fed babies, for example, have a lower incidence of diaper rash, possibly because their stools have higher pH and lower enzymatic activity. Diaper rash is also most likely to be diagnosed in infants 8–12 months old, perhaps in response to an increase in eating solid foods and dietary changes around that age that affect fecal composition. Any time an infants diet undergoes a significant change (i.e. from breast milk to formula or from milk to solids) there appears to be an increased likelihood of diaper rash.The link between feces and IDD is also apparent in the observation that infants are more susceptible to developing diaper rash after treating with antibiotics, which affect the intestinal microflora. Also, there is an increased incidence of diaper rash in infants who have had diarrhea in the previous 48 hours, which may be because fecal enzymes such as lipase and protease are more active in feces which have passed rapidly through the gastrointestinal tract.

Secondary infections
The significance of secondary infection in IDD remains controversial. There seems to be no link between presence or absence of IDD and microbial counts. Although apparently healthy infants sometimes culture positive for Candida and other organisms without exhibiting any symptoms, there does seem to be a positive correlation between the severity of the diaper rash noted and the likelihood of secondary involvement. A wide variety of infections has been reported, including Staphylococcus aureus, Streptococcus pyogenes, Proteus mirabilis, enterococci and Pseudomonas aeruginosa, but it appears that Candida is the most common opportunistic invader in diaper areas.

Diagnosis
The diagnosis of IDD is made clinically, by observing the limitation of an erythematous eruption to the convex surfaces of the genital area and buttocks. If the diaper dermatitis occurs for greater than 3 days it may be colonized with Candida albicans, giving it the beefy red, sharply marginated, appearance of diaper candidiasis.

Differential diagnosis
Other rashes that  occur in the diaper area include seborrhoeic dermatitis and atopic dermatitis. Both Seborrheic and Atopic dermatitis require individualized treatment; they are not the subject of this article.

Seborrheic dermatitis, typified by oily, thick yellowish scales, is most commonly seen on the scalp (cradle cap) but can also appear in the inguinal folds.
Atopic dermatitis, or eczema, is associated with allergic reaction, often hereditary. This class of rashes may appear anywhere on the body and is characterized by intense itchiness.

Treatments
Possible treatments include minimizing diaper use, barrier creams, mild topical cortisones, and antifungal agents. A variety of other inflammatory and infectious processes can occur in the diaper area and an awareness of these secondary types of diaper dermatitis aids in the accurate diagnosis and treatment of patients.Overall, there is sparse evidence of sufficient quality to be certain of the effectiveness of the various treatments. Washcloths with cleansing, moisturising and protective properties may be better than soap and water, and skin cleansers may also be better than soap and water, but the certainty of evidence with regard other treatments is very low.

Diaper changing
The most effective treatment, although not the most practical one, is to discontinue use of diapers, allowing the affected skin to air out </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Digoxin toxicity and can you explain it in depth? [/INST] Digoxin toxicity, also known as digoxin poisoning, is a type of poisoning that occurs in people who take too much of the medication digoxin or eat plants such as foxglove that contain a similar substance. Symptoms are typically vague. They may include vomiting, loss of appetite, confusion, blurred vision, changes in color perception, and decreased energy. Potential complications include an irregular heartbeat, which can be either too fast or too slow.Toxicity may occur over a short period of time following an overdose or gradually during long-term treatment. Risk factors include low potassium, low magnesium, and high calcium. Digoxin is a medication used for heart failure or atrial fibrillation. An electrocardiogram is a routine part of diagnosis. Blood levels are only useful more than six hours following the last dose.Activated charcoal may be used if it can be given within two hours of the person taking the medication. Atropine may be used if the heart rate is slow while magnesium sulfate may be used in those with premature ventricular contractions. Treatment of severe toxicity is with digoxin-specific antibody fragments. Its use is recommended in those who have a serious dysrhythmia, are in cardiac arrest, or have a potassium of greater than 5 mmol/L. Low blood potassium or magnesium should also be corrected. Toxicity may reoccur within a few days after treatment.In Australia in 2012 there were about 140 documented cases. This is a decrease by half since 1994 as a result of decreased usage of digoxin. In the United States 2500 cases were reported in 2011 which resulted in 27 deaths. The condition was first described in 1785 by William Withering.

Signs and symptoms
Digoxin toxicity is often divided into acute or chronic toxicity. In both of these toxicity, cardiac effects are of the greatest concern. With an acute ingestion, symptoms such as nausea, vertigo, and vomiting are prominent. On the other hand, nonspecific symptoms are predominant in chronic toxicity. These symptoms include fatigue, malaise, and visual disturbances.The classic features of digoxin toxicity are nausea, vomiting, abdominal pain, headache, dizziness, confusion, delirium, vision disturbance (blurred or yellow vision). It is also associated with cardiac disturbances including irregular heartbeat, ventricular tachycardia, ventricular fibrillation, sinoatrial block and AV block.

Diagnosis
In individuals with suspected digoxin toxicity, a serum digoxin concentration, serum potassium concentration, creatinine, BUN, and serial electrocardiograms is obtained.

ECG
In digoxin toxicity, the finding of frequent premature ventricular beats (PVCs) is the most common and the earliest dysrhythmia. Sinus bradycardia is also very common. In addition, depressed conduction is a predominant feature of digoxin toxicity. Other ECG changes that suggest digoxin toxicity include bigeminal and trigeminal rhythms, ventricular bigeminy, and bidirectional ventricular tachycardia.

Blood test
The level of digoxin for treatment is typically 0.5-2 ng/mL </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Discoid lupus erythematosus and can you explain it in depth? [/INST] Discoid lupus erythematosus is the most common type of chronic cutaneous lupus (CCLE), an autoimmune skin condition on the lupus erythematosus spectrum of illnesses. It presents with red, painful, inflamed and coin-shaped patches of skin with a scaly and crusty appearance, most often on the scalp, cheeks, and ears. Hair loss may occur if the lesions are on the scalp. The lesions can then develop severe scarring, and the centre areas may appear lighter in color with a rim darker than the normal skin. These lesions can last for years without treatment.Patients with systemic lupus erythematous develop discoid lupus lesions with some frequency. However, patients who present initially with discoid lupus infrequently develop systemic lupus. Discoid lupus can be divided into localized, generalized, and childhood discoid lupus.The lesions are diagnosed by biopsy. Patients are first treated with sunscreen and topical steroids. If this does not work, an oral medication—most likely hydroxychloroquine or a related medication—can be tried.

Signs and symptoms
Morphology of lesions
Discoid lupus erythematosus (DLE) skin lesions first present as dull or purplish red, disc-shaped flat or raised and firm areas of skin. These lesions then develop increasing amounts of white, adherent scale. Finally, the lesions develop extensive scarring and/or atrophy, as well as pigment changes. They may also have overlying dried fluid, known as crust. On darker skin, the lesions often lose skin pigmentation in the center and develop increased, dark skin pigmentation around the rim. On lighter skin, the lesions often develop a gray color or have very little color change. More rarely, the lesions may be bright red and look like hives.

Location of lesions
The skin lesions are most often in sun-exposed areas localized above the neck, with favored sites being the scalp, bridge of the nose, upper cheeks, lower lip, and ear and hands  24% of patients also have lesions in the mouth (most often the palate), nose, eye, or vulva, which are all mucosal parts of the body.More rarely, patients may have lesions on the head and neck as well as the arms and trunk.

Special characteristics of some lesions
Scalp lesions
When discoid lupus is on the scalp, it starts as a red flat or raised area of skin that then loses hair and develops extensive scarring. The lesions often lose skin pigment and become white with areas of increased skin pigment, with or without areas of redness, and have a sunken appearance. They can have a smooth surface or have visible, dilated hair follicles on the surface.

Lip lesions
When discoid lupus is on the lip, it often has a grey or red colour with a thickened top layer of skin (known as hyperkeratosis), areas where the top layer has worn away (known as erosion), and a surrounding rim of redness.

Other symptoms
Patients may state that their lesions are itchy, tender, or asymptomatic. In addition to their skin lesions, they may also have swelling and redness around their eyes, as well as blepharitis.

Complications
Darker-skinned patients are often left with severe scarring and skin color changes even after the lesions get better. In addition, these patients have an increased, though still small, risk for aggressive skin squamous cell carcinoma.

Causes
Sun exposure triggers lesions in people with discoid lupus erythematous (DLE). Evidence does not clearly demonstrate a genetic component to DLE; however, genetics may predispose certain people to disease.

Mechanism
Most experts consider DLE an autoimmune disease since pathologists see antibodies when they biopsy the lesions and look at the tissue under the microscope. However, scientists do not understand the connection between these antibodies and the lesions seen in discoid lupus.Possibly, UV light damages skin cells, which then release material from their nuclei. This material diffuses to the dermoepidermal junction, where it binds to circulating antibodies, thereby leading to a series of inflammatory reactions by the immune system.Alternatively, dysfunctional T cells may lead to the disease.

Diagnosis
When a patient initially presents with discoid lupus, the doctor should ensure that the patient does not have systemic lupus erythematosus. The doctor will order tests to check for anti-nuclear antibodies in the patients serum, low white blood cell levels, and protein and/or blood in the urine.In order to help with diagnosis, the doctor may peel off the top layer of scale from a patients lesions in order to look at its underside. If the patients do indeed have discoid lupus, the doctor may see tiny spines of keratin that look like carpet tacks and are called langue au chat.Diagnosis is confirmed through biopsy. Typical biopsy findings include deposits of IgG and IgM antibodies at the dermoepidermal junction on direct immunofluorescence. This finding is 90% sensitive; however, false positives can occur with biopsies of facial lesions. In addition, pathologists often see groups of white blood cells, particularly T helper cells, around the follicles and blood vessels in the dermis. The epidermis appears thin and has effaced rete ridges as well as excess amounts of keratin clogging the openings of the follicles. The basal layer of the epidermis sometimes appears to have holes in it since some of the cells in this layer have broken apart. The remains of skin cells that have died through a process called apoptosis are visible in the upper layer of the dermis and the basal layer of the epidermis.The differential diagnosis includes actinic keratoses, sebborheic dermatitis, lupus vulgaris, sarcoidosis, drug rash, Bowens disease, lichen planus, tertiary syphilis, polymorphous light eruption, lymphocytic infiltration, psoriasis, and systemic lupus erythematosus.

Classification
Discoid lupus can be broadly classified into localized discoid lupus and generalized discoid lupus based on the location of the lesions. Patients who develop discoid lupus in childhood also have their own sub-type of disease.Hypertrophic lupus and lupus profundus are two special types of discoid lupus distinguished by their characteristic morphological findings.Finally, many patients with systemic lupus also develop discoid lupus lesions.

Localized
Most people with discoid lupus only have lesions above the neck and therefore have localized discoid lupus erythematosus.

Generalized
Rarely, patients may have lesions above and below the neck; these patients have generalized discoid lupus erythematosus. In addition to lesions in the typical above-the-neck locations, patients with generalized discoid lupus often have lesions on the thorax and the arms. These patients are often bald, with abnormal skin pigment on their scalp, and have severe scarring of the face and arms. Patients with generalized discoid lupus often have abnormal lab tests, such as an elevated ESR or a low white blood cell count. They also often have auto-antibodies, such as ANA or anti-ssDNA antibody.

Childhood
When patients develop discoid lupus in childhood, it differs from typical discoid lupus in several ways. Boys and girls are equally affected, and these patients later develop SLE more often. These patients also typically do not have any abnormal sensitivity to the sun.

Special types of discoid lupus lesions
Hypertrophic lupus
Some experts consider hypertrophic lupus erythematosus—which consists of lesions covered by a very thick, keratin-filled scale—an unusual subset of discoid lupus. Others consider it a distinct entity.

Lupus profundus
If a patient has discoid lupus lesions on top of lupus panniculitis, they have lupus profundus. These patients have firm, nontender nodules with defined borders underneath their discoid lupus lesions.

Systemic lupus erythematosus with discoid lupus lesions
In general, patients with discoid lupus who have only skin disease and no systemic symptoms have a genetically distinct disease from patients with SLE </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Dry eye syndrome and can you explain it in depth? [/INST] Dry eye syndrome (DES), also known as keratoconjunctivitis sicca (KCS), is the condition of having dry eyes. Other associated symptoms include irritation, redness, discharge, and easily fatigued eyes. Blurred vision may also occur. Symptoms range from mild and occasional to severe and continuous. Scarring of the cornea may occur in untreated cases.Dry eye occurs when either the eye does not produce enough tears or when the tears evaporate too quickly. This can result from contact lens use, meibomian gland dysfunction, pregnancy, Sjögren syndrome, vitamin A deficiency, omega-3 fatty acid deficiency, LASIK surgery, and certain medications such as antihistamines, some blood pressure medication, hormone replacement therapy, and antidepressants. Chronic conjunctivitis such as from tobacco smoke exposure or infection may also lead to the condition. Diagnosis is mostly based on the symptoms, though a number of other tests may be used.Treatment depends on the underlying cause. Artificial tears are usually the first line of treatment. Wrap-around glasses that fit close to the face may decrease tear evaporation. Stopping or changing certain medications may help. The medication ciclosporin or steroid eye drops may be used in some cases. Another option is lacrimal plugs that prevent tears from draining from the surface of the eye. Dry eye syndrome occasionally makes wearing contact lenses impossible.Dry eye syndrome is a common eye disease. It affects 5–34% of people to some degree depending on the population looked at. Among older people it affects up to 70%. In China it affects about 17% of people. The phrase "keratoconjunctivitis sicca" means "dryness of the cornea and conjunctiva" in Latin

Signs and symptoms
Typical symptoms of dry eye syndrome are dryness, burning and a sandy-gritty eye irritation that gets worse as the day goes on. Symptoms may also be described as itchy, stinging or tired eyes. Other symptoms are pain, redness, a pulling sensation, and pressure behind the eye. There may be a feeling that something, such as a speck of dirt, is in the eye. The resultant damage to the eyes surface increases discomfort and sensitivity to bright light. Both eyes usually are affected.There may also be a stringy discharge from the eyes. Although it may seem contradictory, dry eye can cause the eyes to water due to irritation. One may experience excessive tearing such as if something got into the eye. These reflex tears will not necessarily make the eyes feel better since they are the watery tears that are produced in response to injury, irritation, or emotion which lack the lubricating qualities necessary to prevent dry eye.Because blinking coats the eye with tears, symptoms are worsened by activities in which the rate of blinking is reduced due to prolonged use of the eyes. These activities include prolonged reading, computer usage (computer vision syndrome), driving, or watching television. Symptoms increase in windy, dusty or smoky (including cigarette smoke) areas, in dry environments high altitudes including airplanes, on days with low humidity, and in areas where an air conditioner (especially in a car), fan, heater, or even a hair dryer is being used. Symptoms reduce during cool, rainy, or foggy weather and in humid places, such as in the shower.Most people who have dry eyes experience mild irritation with no long-term effects. However, if the condition is left untreated or becomes severe, it can produce complications that can cause eye damage, resulting in impaired vision or (rarely) in the loss of vision.Symptom assessment is a key component of dry eye diagnosis – to the extent that many believe dry eye syndrome to be a symptom-based disease. Several questionnaires have been developed to determine a score that would allow for a diagnosis. The McMonnies & Ho dry eye questionnaire is often used in clinical studies of dry eyes.

Causes
Any abnormality of any one of the three layers of tears produces an unstable tear film, resulting in symptoms of dry eyes.

Increased evaporation
The most common cause of dry eye is increased evaporation of the tear film, typically as a result of Meibomian gland dysfunction. The meibomian glands are two sets of oil glands that line the upper and lower eyelids and secrete the oily outer layer of the tear film—the lipid layer. These glands often become clogged due to inflammation caused by blepharitis and/or rosacea, preventing an even distribution of oil. The result is an unstable lipid layer that leads to increased evaporation of the tear film.In severe cases of MGD, the meibomiam glands can atrophy and cease producing oil entirely.

Low humidity
Low humidity may cause dry eye syndrome.

Decreased tear production
Keratoconjunctivitis sicca can be caused by inadequate tear production from lacrimal hyposecretion. The aqueous tear layer is affected, resulting in aqueous tear deficiency (ATD). The lacrimal gland does not produce sufficient tears to keep the entire conjunctiva and cornea covered by a complete layer. This usually occurs in people who are otherwise healthy. Increased age is associated with decreased tearing. This is the most common type found in postmenopausal women.In many cases, aqueous deficient dry eye may have no apparent cause (idiopathic). Other causes include congenital alacrima, xerophthalmia, lacrimal gland ablation, and sensory denervation. In rare cases, it may be a symptom of collagen vascular diseases, including relapsing polychondritis, rheumatoid arthritis, granulomatosis with polyangiitis, and systemic lupus erythematosus. Sjögren syndrome and other autoimmune diseases are associated with aqueous tear deficiency. Drugs such as isotretinoin, sedatives, diuretics, tricyclic antidepressants, antihypertensives, oral contraceptives, antihistamines, nasal decongestants, beta-blockers, phenothiazines, atropine, and pain relieving opiates such as morphine can cause or worsen this condition. Infiltration of the lacrimal glands by sarcoidosis or tumors, or postradiation fibrosis of the lacrimal glands can also cause this condition. Recent attention has been paid to the composition of tears in normal or dry eye individuals. Only a small fraction of the estimated 1543 proteins in tears are differentially deficient or upregulated in dry eye, one of which is lacritin. Topical lacritin promotes tearing in rabbit preclinical studies. Also, topical treatment of eyes of dry eye mice (Aire knockout mouse model of dry eye) restored tearing, and suppressed both corneal staining and the size of inflammatory foci in lacrimal glands.

Additional causes
Aging is one of the most common causes of dry eyes because tear production decreases with age. Several classes of medications (both prescription and OTC) have been hypothesized as a major cause of dry eye, especially in the elderly. Particularly, anticholinergic medications that also cause dry mouth are believed to promote dry eye. Dry eye may also be caused by thermal or chemical burns, or (in epidemic cases) by adenoviruses.   A number of studies have found that diabetics are at increased risk for the disease.About half of all people who wear contact lenses complain of dry eyes. There are two potential connections between contact usage and dry eye. Traditionally, it was believed that soft contact lenses, which float on the tear film that covers the cornea, absorb the tears in the eyes. The connection between a loss in nerve sensitivity and tear production is also the subject of current research.Dry eye also occurs or becomes worse after LASIK and other refractive surgeries, in which the corneal nerves which stimulate tear secretion are cut during the creation of a corneal flap. Dry eye caused by these procedures usually resolves after several months, but it can be permanent. Persons who are thinking about refractive surgery should consider this.An eye injury or other problem with the eyes or eyelids, such as bulging eyes or a drooping eyelid can cause keratoconjunctivitis sicca. Disorders of the eyelid can impair the complex blinking motion required to spread tears.Abnormalities of the mucin tear layer caused by vitamin A deficiency, trachoma, diphtheric keratoconjunctivitis, mucocutaneous disorders and certain topical medications are also causes of keratoconjunctivitis sicca.Persons with keratoconjunctivitis sicca have elevated levels of tear nerve growth factor (NGF). It is possible that this eyes surface NGF plays an important role in ocular surface inflammation associated with dry eyes.

Pathophysiology
Having dry eyes for a while can lead to tiny abrasions on the surface of the eyes. In advanced cases, the epithelium undergoes pathologic changes, namely squamous metaplasia and loss of goblet cells. Some severe cases result in thickening of the corneal surface, corneal erosion, punctate keratopathy, epithelial defects, corneal ulceration (sterile and infected), corneal neovascularization, corneal scarring, corneal thinning, and even corneal perforation.Another contributing factor may be lacritin monomer deficiency. Lacritin monomer, active form of lacritin, is selectively decreased in aqueous deficient dry eye, Sjögren syndrome dry eye, contact lens-related dry eye and in blepharitis.

Diagnosis
Some tests allow patients to be classified into one of two categories, “aqueous-deficient” or “hyperevaporative.” Diagnostic guidelines were published in 2007 by the Dry Eye Workshop. A slit lamp examination can be performed to diagnose dry eyes and to document any damage to the eye. When realizing this test, the practitioner is testing the eyelid margin.A Schirmers test can measure the amount of moisture bathing the eye. This test is useful for determining the severity of the condition. A five-minute Schirmers test with and without anesthesia using a Whatman #41 filter paper 5 mm wide by 35 mm long is performed. For this test, wetting under 5 mm with or without anesthesia is considered diagnostic for dry eyes.If the results for the Schirmers test are abnormal, a Schirmer II test can be performed to measure reflex secretion. In this test, the nasal mucosa is irritated with a cotton-tipped applicator, after which tear production is measured with a Whatman #41 filter paper. For this test, wetting under 15 mm after five minutes is considered abnormal.A tear breakup time (TBUT) test measures the time it takes for tears to break up in the eye. The tear breakup time can be determined after placing a drop of fluorescein in the cul-de-sac.A tear protein analysis test measures the lysozyme contained within tears. In tears, lysozyme accounts for approximately 20 to 40 percent of total protein content.A lactoferrin analysis test provides good correlation with other tests.The presence of the recently described molecule Ap4A, naturally occurring in tears, is abnormally high in different states of ocular dryness. This molecule can be quantified biochemically simply by taking a tear sample with a plain Schirmer test. Utilizing this technique it is possible to determine the concentrations of Ap4A in the tears of patients and in such way diagnose objectively if the samples are indicative of dry eye.The tear osmolarity test has been proposed as a test for dry eye disease. Tear osmolarity may be a more sensitive method of diagnosing and grading the severity of dry eye compared to corneal and conjunctival staining, tear break-up time, Schirmer test, and meibomian gland grading. Others have recently questioned the utility of tear osmolarity in monitoring dry eye treatment.

Prevention
Avoiding refractive surgery (LASIK & PRK), limiting contact lens use, limiting computer screen use, avoiding environmental conditions can decrease symptoms. Complications can be prevented by use of wetting and lubricating drops and ointments.

Treatment
A variety of approaches can be taken to treatment. These can be summarised as: avoidance of exacerbating factors, tear stimulation and supplementation, increasing tear retention, and eyelid cleansing and treatment of eye inflammation.Dry eyes can be exacerbated by smoky environments, dust and air conditioning and by our natural tendency to reduce our blink rate when concentrating. Purposefully blinking, especially during computer use and resting tired eyes are basic steps that can be taken to minimise discomfort. Rubbing ones eyes can irritate them further, so should be avoided. Conditions such as blepharitis can often co-exist and paying particular attention to cleaning the eyelids morning and night with mild soaps and warm compresses can improve both conditions.

Environmental control
Dry, drafty environments and those with smoke and dust should be avoided. This includes avoiding hair dryers, heaters, air conditioners or fans, especially when these devices are directed toward the eyes. Wearing glasses or directing gaze downward, for example, by lowering computer screens can be helpful to protect the eyes when aggravating environmental factors cannot be avoided. Using a humidifier, especially in the winter, can help by adding moisture to the dry indoor air.

Rehydration
For mild and moderate cases, supplemental lubrication is the most important part of treatment.Application of artificial tears every few hours can provide temporary relief. Additional research is necessary to determine whether certain artificial tear formulations are superior to others in treating dry eye.

Autologous serum eye drops
A 2017 Cochrane review found mixed results when comparing autologous serum eye drops to artificial tears or saline. Evidence from the examined trials showed that autologous serum eye drops may have a small short-term benefit when compared to artificial tears, but there is no evidence of improvement after 2 weeks.

Additional options
Lubricating tear ointments can be used during the day, but they generally are used at bedtime due to poor vision after application. They contain white petrolatum, mineral oil, and similar lubricants. They serve as a lubricant and an emollient. Application requires pulling down the lower eyelid and applying a small amount (0.25 in) inside. Depending on the severity of the condition, it may be applied from every hour to just at bedtime. It should never be used with contact lenses. Specially designed glasses that form a moisture chamber around the eye may be used to create additional humidity.

Medication
Inflammation occurring in response to tears film hypertonicity can be suppressed by mild topical steroids or with topical immunosuppressants such as ciclosporin (Restasis). Elevated levels of tear NGF can be decreased with 0.1% prednisolone.Diquafosol, an agonist of the P2Y2 purinergic receptor, is approved in Japan for managing dry eye disease by promoting secretion of fluid and mucin from cells in the conjunctiva, rather than by directly stimulating the lacrimal glands.Lifitegrast was approved by the US FDA for the treatment of the condition in 2016.Varenicline (Tyrvaya by Oyster Point Pharma) was approved by the US FDA for the treatment of dry eye disease in October 2021.

Ciclosporin
Topical ciclosporin (topical ciclosporin A, tCSA) 0.05% ophthalmic emulsion is an immunosuppressant. The drug decreases surface inflammation. In a trial involving 1200 people, Restasis increased tear production in 15% of people, compared to 5% with placebo.It should not be used while wearing contact lenses, during eye infections or in people with a history of herpes virus infections. Side effects include burning sensation (common), redness, discharge, watery eyes, eye pain, foreign body sensation, itching, stinging, and blurred vision. Long term use of ciclosporin at high doses is associated with an increased risk of cancer.Cheaper generic alternatives are available in some countries.

Conserving tears
There are methods that allow both natural and artificial tears to stay longer.In each eye, there are two puncta – little openings that drain tears into the tear ducts. There are methods to partially or completely close the tear ducts. This blocks the flow of tears into the nose, and thus more tears are available to the eyes. Drainage into either one or both puncta in each eye can be blocked.
Punctal plugs are inserted into the puncta to block tear drainage. It is not clear if punctal plugs are effective at reducing dry eye syndrome symptoms. Punctal plugs are thought to be "relatively safe", however, their use may result in epiphora (watery eyes), and more rarely, serious infection and swelling of the tear sac where the tears drain. They are reserved for people with moderate or severe dry eye when other medical treatment has not been adequate.If punctal plugs are effective, thermal or electric cauterization of puncti can be performed. In thermal cauterization, a local anesthetic is used, and then a hot wire is applied. This shrinks the drainage area tissues and causes scarring, which closes the tear duct.

Other
Heating systems that try to unblock the oil glands in the eye has some preliminary evidence of benefit. Fish oil (omega-3) supplements are not effective in relieving symptoms.

Surgery
In severe cases of dry eyes, tarsorrhaphy may be performed where the eyelids are partially sewn together. This reduces the palpebral fissure (eyelid separation), ideally leading to a reduction in tear evaporation.

Prognosis
Keratoconjunctivitis sicca usually is a chronic problem. Its prognosis shows considerable variance, depending upon the severity of the condition. Most people have mild-to-moderate cases, and can be treated symptomatically with lubricants. This provides an adequate relief of symptoms.When dry eyes symptoms are severe, they can interfere with quality of life. People sometimes feel their vision blurs with use, or severe irritation to the point that they have trouble keeping their eyes open or they may not be able to work or drive.

Epidemiology
Keratoconjunctivitis sicca is relatively common within the United States, especially so in older patients. Specifically, the persons most likely to be affected by dry eyes are those aged 40 or older. 10–20% of adults experience Keratoconjunctivitis sicca. Approximately 1 to 4 million adults (age 65–84) in the USA are affected.While persons with autoimmune diseases have a high likelihood of having dry eyes, most persons with dry eyes do not have an autoimmune disease. Instances of Sjögren syndrome and keratoconjunctivitis sicca associated with it are present much more commonly in women, with a ratio of 9:1. In addition, milder forms of keratoconjunctivitis sicca also are more common in women. This is partly because hormonal changes, such as those that occur in pregnancy, menstruation, and menopause, can decrease tear production.In areas of the world where malnutrition is common, vitamin A deficiency is a common cause. This is rare in the United States.Racial predilections do not exist for this disease.

Synonyms
Other names for dry eye include dry eye syndrome, keratoconjunctivitis sicca (KCS), dysfunctional tear syndrome, lacrimal keratoconjunctivitis, evaporative tear deficiency, aqueous tear deficiency, and LASIK-induced neurotrophic epitheliopathy (LNE).

Other animals
Among other animals, dry eye can occur in dogs, cats, and horses.

Dogs
Keratoconjunctivitis sicca is common in dogs. Most cases are caused by a genetic predisposition, but chronic conjunctivitis, canine distemper, and drugs such as sulfasalazine and trimethoprim-sulfonamide also cause the disease. Symptoms include eye redness, a yellow or greenish discharge, corneal ulceration, pigmented cornea, and blood vessels on the cornea. Diagnosis is made by measuring tear production with a Schirmer tear test </s>