<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 Interstitial cystitis and explain in detail? [/INST] Interstitial cystitis (IC), a type of bladder pain syndrome (BPS), is chronic pain in the bladder and pelvic floor of unknown cause. It is the urologic chronic pelvic pain syndrome of women. Symptoms include feeling the need to urinate right away, needing to urinate often, and pain with sex. IC/BPS is associated with depression and lower quality of life. Many of those affected also have irritable bowel syndrome and fibromyalgia.The cause of interstitial cystitis is unknown. While it can, it does not typically run in a family. The diagnosis is usually based on the symptoms after ruling out other conditions. Typically the urine culture is negative. Ulceration or inflammation may be seen on cystoscopy. Other conditions which can produce similar symptoms include overactive bladder, urinary tract infection (UTI), sexually transmitted infections, prostatitis, endometriosis in females, and bladder cancer.There is no cure for interstitial cystitis and management of this condition can be challenging. Treatments that may improve symptoms include lifestyle changes, medications, or procedures. Lifestyle changes may include stopping smoking and reducing stress. Medications may include ibuprofen, pentosan polysulfate, or amitriptyline. Procedures may include bladder distention, nerve stimulation, or surgery. Pelvic floor exercises and long term antibiotics are not recommended.In the United States and Europe, it is estimated that around 0.5% of people are affected. Women are affected about five times as often as men. Onset is typically in middle age. The term "interstitial cystitis" first came into use in 1887.

Signs and symptoms
The most common symptoms of IC/BPS are suprapubic pain, urinary frequency, painful sexual intercourse, and waking up from sleep to urinate.In general, symptoms may include painful urination described as a burning sensation in the urethra during urination, pelvic pain that is worsened with the consumption of certain foods or drinks, urinary urgency, and pressure in the bladder or pelvis. Other frequently described symptoms are urinary hesitancy (needing to wait for the urinary stream to begin, often caused by pelvic floor dysfunction and tension), and discomfort and difficulty driving, working, exercising, or traveling. Pelvic pain experienced by those with IC typically worsens with filling of the urinary bladder and may improve with urination.During cystoscopy, 5–10% of people with IC are found to have Hunners ulcers. A person with IC may have discomfort only in the urethra, while another might struggle with pain in the entire pelvis. Interstitial cystitis symptoms usually fall into one of two patterns: significant suprapubic pain with little frequency or a lesser amount of suprapubic pain but with increased urinary frequency.

Association with other conditions
Some people with IC/BPS have been diagnosed with other conditions such as irritable bowel syndrome (IBS), fibromyalgia, chronic fatigue syndrome, allergies, Sjögren syndrome, which raises the possibility that interstitial cystitis may be caused by mechanisms that cause these other conditions. There is also some evidence of an association between urologic pain syndromes, such as IC/BPS and CP/CPPS, with non-celiac gluten sensitivity in some people.In addition, men with IC/PBS are frequently diagnosed as having chronic nonbacterial prostatitis, and there is an extensive overlap of symptoms and treatment between the two conditions, leading researchers to posit that the conditions may share the same cause and pathology.

Causes
The cause of IC/BPS is not known. However, several explanations have been proposed and include the following: autoimmune theory, nerve theory, mast cell theory, leaky lining theory, infection theory, and a theory of production of a toxic substance in the urine. Other suggested etiological causes are neurologic, allergic, genetic, and stress-psychological. In addition, recent research shows that those with IC may have a substance in the urine that inhibits the growth of cells in the bladder epithelium. An infection may then predispose those people to develop IC. Evidence from clinical and laboratory studies confirms that mast cells play a central role in IC/BPS possibly due to their ability to release histamine and cause pain, swelling, scarring, and interfere with healing. Research has shown a proliferation of nerve fibers is present in the bladders of people with IC which is absent in the bladders of people who have not been diagnosed with IC.Regardless of the origin, most people with IC/BPS struggle with a damaged urothelium, or bladder lining. When the surface glycosaminoglycan (GAG) layer is damaged (via a urinary tract infection (UTI), excessive consumption of coffee or sodas, traumatic injury, etc.), urinary chemicals can "leak" into surrounding tissues, causing pain, inflammation, and urinary symptoms. Oral medications like pentosan polysulfate and medications placed directly into the bladder via a catheter sometimes work to repair and rebuild this damaged/wounded lining, allowing for a reduction in symptoms. Most literature supports the belief that ICs symptoms are associated with a defect in the bladder epithelium lining, allowing irritating substances in the urine to penetrate into the bladder—a breakdown of the bladder lining (also known as the adherence theory). Deficiency in this glycosaminoglycan layer on the surface of the bladder results in increased permeability of the underlying submucosal tissues.GP51 has been identified as a possible urinary biomarker for IC with significant variations in GP51 levels in those with IC when compared to individuals without interstitial cystitis.Numerous studies have noted the link between IC, anxiety, stress, hyper-responsiveness, and panic. Another proposed cause for interstitial cystitis is that the bodys immune system attacks the bladder. Biopsies on the bladder walls of people with IC usually contain mast cells.  Mast cells containing histamine packets gather when an allergic reaction is occurring. The body identifies the bladder wall as a foreign agent, and the histamine packets burst open and attack.  The body attacks itself, which is the basis of autoimmune disorders. Additionally, IC may be triggered by an unknown toxin or stimulus which causes nerves in the bladder wall to fire uncontrollably. When they fire, they release substances called neuropeptides that induce a cascade of reactions that cause pain in the bladder wall.

Genes
Some genetic subtypes, in some people, have been linked to the disorder.

An antiproliferative factor is secreted by the bladders of people with IC/BPS which inhibits bladder cell proliferation, thus possibly causing the missing bladder lining.
PAND, at gene map locus 13q22–q32, is associated with a constellation of disorders (a "pleiotropic syndrome") including IC/BPS and other bladder and kidney problems, thyroid diseases, serious headaches/migraines, panic disorder, and mitral valve prolapse.

Diagnosis
A diagnosis of IC/BPS is one of exclusion, as well as a review of clinical symptoms. The American Urological Association Guidelines recommend starting with a careful history of the person, physical examination and laboratory tests to assess and document symptoms of interstitial cytitis, as well as other potential disorders.
The KCl test, also known as the potassium sensitivity test, is no longer recommended. The test uses a mild potassium solution to evaluate the integrity of the bladder wall. Though the latter is not specific for IC/BPS, it has been determined to be helpful in predicting the use of compounds, such as pentosan polysulphate, which are designed to help repair the GAG layer.For complicated cases, the use of hydrodistention with cystoscopy may be helpful. Researchers, however, determined that this visual examination of the bladder wall after stretching the bladder was not specific for IC/BPS and that the test, itself, can contribute to the development of small glomerulations (petechial hemorrhages) often found in IC/BPS. Thus, a diagnosis of IC/BPS is one of exclusion, as well as a review of clinical symptoms.
In 2006, the ESSIC society proposed more rigorous and demanding diagnostic methods with specific classification criteria so that it cannot be confused with other, similar conditions. Specifically, they require that a person must have pain associated with the bladder, accompanied by one other urinary symptom. Thus, a person with just frequency or urgency would be excluded from a diagnosis. Secondly, they strongly encourage the exclusion of confusable diseases through an extensive and expensive series of tests including (A) a medical history and physical exam, (B) a dipstick urinalysis, various urine cultures, and a serum PSA in men over 40, (C) flowmetry and post-void residual urine volume by ultrasound scanning and (D) cystoscopy. A diagnosis of IC/BPS would be confirmed with a hydrodistention during cystoscopy with biopsy.They also propose a ranking system based upon the physical findings in the bladder. People would receive a numeric and letter based score based upon the severity of their disease as found during the hydrodistention. A score of 1–3 would relate to the severity of the disease and a rating of A–C represents biopsy findings. Thus, a person with 1A would have very mild symptoms and disease while a person with 3C would have the worst possible symptoms. Widely recognized scoring systems such as the OLeary Sant symptom and problem score have emerged to evaluate the severity of IC symptoms such as pain and urinary symptoms.

Differential diagnosis
The symptoms of IC/BPS are often misdiagnosed as a urinary tract infection. However, IC/BPS has not been shown to be caused by a bacterial infection and antibiotics are an ineffective treatment. IC/BPS is commonly misdiagnosed as chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in men, and endometriosis and uterine fibroids (in women).

Treatment
In 2011, the American Urological Association released consensus-based guideline for the diagnosis and treatment of interstitial cystitis.They include treatments ranging from conservative to more invasive:

First-line treatments — education, self care (diet modification), stress management
Second-line treatments — physical therapy, oral medications (amitriptyline, cimetidine or hydroxyzine, pentosan polysulfate), bladder instillations (DMSO, heparin, or lidocaine)
Third-line treatments — treatment of Hunners lesions (laser, fulguration or triamcinolone injection), hydrodistention (low pressure, short duration)
Fourth-line treatments — neuromodulation (sacral or pudendal nerve)
Fifth-line treatments — cyclosporine A, botulinum toxin (BTX-A)
Sixth-line treatments — surgical intervention (urinary diversion, augmentation, cystectomy)The American Urological Association guidelines also listed several discontinued treatments, including long-term oral antibiotics, intravesical bacillus Calmette Guerin, intravesical resiniferatoxin), high-pressure and long-duration hydrodistention, and systemic glucocorticoids.

Bladder distension
Bladder distension while under general anesthesia, also known as hydrodistention (a procedure which stretches the bladder capacity), has shown some success in reducing urinary frequency and giving short-term pain relief to those with IC. However, it is unknown exactly how this procedure causes pain relief. Recent studies show pressure on pelvic trigger points can relieve symptoms. The relief achieved by bladder distensions is only temporary (weeks or months), so is not viable as a long-term treatment for IC/BPS. The proportion of people with IC/BPS who experience relief from hydrodistention is currently unknown and evidence for this modality is limited by a lack of properly controlled studies. Bladder rupture and sepsis may be associated with prolonged, high-pressure hydrodistention.

Bladder instillations
Bladder instillation of medication is one of the main forms of treatment of interstitial cystitis, but evidence for its effectiveness is currently limited. Advantages of this treatment approach include direct contact of the medication with the bladder and low systemic side effects due to poor absorption of the medication. Single medications or a mixture of medications are commonly used in bladder instillation preparations. Dimethyl sulfoxide (DMSO) is the only approved bladder instillation for IC/BPS yet it is much less frequently used in urology clinics.A 50% solution of DMSO had the potential to create irreversible muscle contraction. However, a lesser solution of 25% was found to be reversible. Long-term use of DMSO is questionable, as its mechanism of action is not fully understood though DMSO is thought to inhibit mast cells and may have anti-inflammatory, muscle-relaxing, and analgesic effects. Other agents used for bladder instillations to treat interstitial cystitis include: heparin, lidocaine, chondroitin sulfate, hyaluronic acid, pentosan polysulfate, oxybutynin, and botulinum toxin A. Preliminary evidence suggests these agents are efficacious in reducing symptoms of interstitial cystitis, but further study with larger, randomized, controlled clinical trials is needed.

Diet
Diet modification is often recommended as a first-line method of self-treatment for interstitial cystitis, though rigorous controlled studies examining the impact diet has on interstitial cystitis signs and symptoms are currently lacking. An increase in fiber intake may alleviate symptoms. Individuals with interstitial cystitis often experience an increase in symptoms when they consume certain foods and beverages. Avoidance of these potential trigger foods and beverages such as caffeine-containing beverages including coffee, tea, and soda, alcoholic beverages, chocolate, citrus fruits, hot peppers, and artificial sweeteners may be helpful in alleviating symptoms. Diet triggers vary between individuals with IC; the best way for a person to discover his or her own triggers is to use an elimination diet. Sensitivity to trigger foods may be reduced if calcium glycerophosphate and/or sodium bicarbonate is consumed. The foundation of therapy is a modification of diet to help people avoid those foods which can further irritate the damaged bladder wall.The mechanism by which dietary modification benefits people with IC is unclear. Integration of neural signals from pelvic organs may mediate the effects of diet on symptoms of IC.

Medications
The antihistamine hydroxyzine failed to demonstrate superiority over placebo in treatment of people with IC in a randomized, controlled, clinical trial.Amitriptyline has been shown to be effective in reducing symptoms such as chronic pelvic pain and nocturia in many people with IC/BPS with a median dose of 75 mg daily. In one study, the antidepressant duloxetine was found to be ineffective as a treatment, although a patent exists for use of duloxetine in the context of IC, and is known to relieve neuropathic pain. The calcineurin inhibitor cyclosporine A has been studied as a treatment for interstitial cystitis due to its immunosuppressive properties. A prospective randomized study found cyclosporine A to be more effective at treating IC symptoms than pentosan polysulfate, but also had more adverse effects.Oral pentosan polysulfate is believed to repair the protective glycosaminoglycan coating of the bladder, but studies have encountered mixed results when attempting to determine if the effect is statistically significant compared to placebo.

Pelvic floor treatments
Urologic pelvic pain syndromes, such as IC/BPS and CP/CPPS, are characterized by pelvic muscle tenderness, and symptoms may be reduced with pelvic myofascial physical therapy.This may leave the pelvic area in a sensitized condition, resulting in a loop of muscle tension and heightened neurological feedback (neural wind-up), a form of myofascial pain syndrome. Current protocols, such as the Wise–Anderson Protocol, largely focus on stretches to release overtensed muscles in the pelvic or anal area (commonly referred to as trigger points), physical therapy to the area, and progressive relaxation therapy to reduce causative stress.Pelvic floor dysfunction is a fairly new area of specialty for physical therapists worldwide. The goal of therapy is to relax and lengthen the pelvic floor muscles, rather than to tighten and/or strengthen them as is the goal of therapy for people with urinary incontinence. Thus, traditional exercises such as Kegel exercises, which are used to strengthen pelvic muscles, can provoke pain and additional muscle tension. A specially trained physical therapist can provide direct, hands on evaluation of the muscles, both externally and internally.A therapeutic wand can also be used to perform pelvic floor muscle myofascial release to provide relief.

Surgery
Surgery is rarely used for IC/BPS. Surgical intervention is very unpredictable, and is considered a treatment of last resort for severe refractory cases of interstitial cystitis. Some people who opt for surgical intervention continue to experience pain after surgery. Typical surgical interventions for refractory cases of IC/BPS include: bladder augmentation, urinary diversion, transurethral fulguration and resection of ulcers, and bladder removal (cystectomy).Neuromodulation can be successful in treating IC/BPS symptoms, including pain. One electronic pain-killing option is TENS. Percutaneous tibial nerve stimulation stimulators have also been used, with varying degrees of success. Percutaneous sacral nerve root stimulation was able to produce statistically significant improvements in several parameters, including pain.

Alternative medicine
There is little evidence looking at the effects of alternative medicine though their use is common. There is tentative evidence that acupuncture may help pain associated with IC/BPS as part of other treatments. Despite a scarcity of controlled studies on alternative medicine and IC/BPS, "rather good results have been obtained" when acupuncture is combined with other treatments.Biofeedback, a relaxation technique aimed at helping people control functions of the autonomic nervous system, has shown some benefit in controlling pain associated with IC/BPS as part of a multimodal approach that may also include medication or hydrodistention of the bladder.

Prognosis
IC/BPS has a profound impact on quality of life. A 2007 Finnish epidemiologic study showed that two-thirds of women at moderate to high risk of having interstitial cystitis reported impairment in their quality of life and 35% of people with IC reported an impact on their sexual life. A 2012 survey showed that among a group of adult women with symptoms of interstitial cystitis, 11% reported suicidal thoughts in the past two weeks. Other research has shown that the impact of IC/BPS on quality of life is severe and may be comparable to the quality of life experienced in end-stage kidney disease or rheumatoid arthritis.International recognition of interstitial cystitis has grown and international urology conferences to address the heterogeneity in diagnostic criteria have recently been held. IC/PBS is now recognized with an official disability code in the United States of America.

Epidemiology
IC/BPS affects men and women of all cultures, socioeconomic backgrounds, and ages. Although the disease was previously believed to be a condition of menopausal women, growing numbers of men and women are being diagnosed in their twenties and younger. IC/BPS is not a rare condition. Early research suggested that the number of IC/BPS cases ranged from 1 in 100,000 to 5.1 in 1,000 of the general population. In recent years, the scientific community has achieved a much deeper understanding of the epidemiology of interstitial cystitis. Recent studies have revealed that between 2.7 and 6.53 million women in the USA have symptoms of IC and up to 12% of women may have early symptoms of IC/BPS. Further study has estimated that the condition is far more prevalent in men than previously thought ranging from 1.8 to 4.2 million men having symptoms of interstitial cystitis.The condition is officially recognized as a disability in the United States.

History
Philadelphia surgeon Joseph Parrish published the earliest record of interstitial cystitis in 1836 describing three cases of severe lower urinary tract symptoms without the presence of a bladder stone. The term "interstitial cystitis" was coined by Dr. Alexander Skene in 1887 to describe the disease. In 2002, the United States amended the Social Security Act to include interstitial cystitis as a disability. The first guideline for diagnosis and treatment of interstitial cystitis is released by a Japanese research team in 2009. The American Urological Association released the first American clinical practice guideline for diagnosing and treating IC/BPS in 2011.

Names
Originally called interstitial cystitis, this disorder was renamed to interstitial cystitis/bladder pain syndrome (IC/BPS) in the 2002–2010 timeframe. In 2007, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) began using the umbrella term urologic chronic pelvic pain syndrome (UCPPS) to refer to pelvic pain syndromes associated with the bladder (e.g., interstitial cystitis/bladder pain syndrome) and with the prostate gland or pelvis (e.g., chronic prostatitis/chronic pelvic pain syndrome).In 2008, terms currently in use in addition to IC/BPS include painful bladder syndrome, bladder pain syndrome and hypersensitive bladder syndrome, alone and in a variety of combinations. These different terms are being used in different parts of the world. The term "interstitial cystitis" is the primary term used in ICD-10 and MeSH. Grover et al. said, "The International Continence Society named the disease interstitial cystitis/painful bladder syndrome (IC/PBS) in 2002 [Abrams et al. 2002], while the Multinational Interstitial Cystitis Association have labeled it as painful bladder syndrome/interstitial cystitis (PBS/IC) [Hanno et al. 2005]. Recently, the European Society for the study of Interstitial Cystitis (ESSIC) proposed the moniker, bladder pain syndrome (BPS) [van de Merwe et al. 2008]."

See also
Chronic prostatitis/chronic pelvic pain syndrome—women have vestigial prostate glands that may cause IC/BPS-like symptoms. Men with IC/BPS may have prostatitis, and vice versa.
Overactive bladder
Trigger point—a key to myofascial pain syndrome.

References
External links

Interstitial cystitis at Curlie
Parsons, J. Kellogg; Parsons, C. Lowell (2004). "The Historical Origins of Interstitial Cystitis" </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 Iron poisoning and explain in detail? [/INST] Iron poisoning typically occurs from ingestion of excess iron that results in acute toxicity. Mild symptoms which occur within hours include vomiting, diarrhea, abdominal pain, and drowsiness. In more severe cases, symptoms can include tachypnea, low blood pressure, seizures, or coma. If left untreated, iron poisoning can lead to multi-organ failure resulting in permanent organ damage or death.Iron is available over the counter as a single entity supplement in an iron salt form or in combination with vitamin supplements and is commonly used in the treatment of anemias. Overdoses on iron can be categorized as unintentional ingestion which is predominantly associated with children or intentional ingestion involving suicide attempts in adults. Unintentional ingestion of iron containing drug products are a major cause of mortality in children under the age of 6 years old in the United States. As a response, in 1997 the US Food and Drug Administration (FDA) implemented a regulation requiring warning labels and unit dose packaging for products containing more than 30 mg of elemental iron per dose.The diagnosis of iron poisoning is based on clinical presentation including laboratory tests for serum iron concentrations and metabolic acidosis along with physical examination. Treatment for iron poisoning involves providing fluid replacement, gastrointestinal decontamination, administering deferoxamine intravenously, liver transplants, and monitoring the patients condition. The degree of intervention required depends on whether the patient is at risk for serious toxicity.

Signs and symptoms
Manifestation of iron poisoning may vary depending on the amount of iron ingested by the individual and is further classified by five stages based on timing of signs and symptoms. In mild to moderate cases, individuals may be asymptomatic or only experience mild gastrointestinal symptoms that resolve within six hours. In serious cases, individuals may present with systemic signs and symptoms and require treatment. Clinical presentation of iron poisoning in the absence of treatment progresses in five stages: the gastrointestinal phase, latent phase, metabolic acidosis and shock phase, hepatotoxicity phase, and bowel obstruction due to scarring.
The first indication of iron poisoning occurs within the first six hours post-ingestion and involves gastrointestinal symptoms including abdominal pain accompanied by nausea and vomiting with or without blood. Due to the disintegration of iron tablets, the stool may appear as black or dark green or gray. After the first stage, gastrointestinal symptoms appear to resolve in the latent phase and individuals may show signs of improvement. Following this stage, the iron begins to affect the cells of the bodys organs which manifests as numerous systemic signs and symptoms developing after 6 to 72 hours, in the metabolic acidosis phase. Individuals may present with signs of cardiogenic shock indicated by low blood pressure, rapid heart rate and severe shortness of breath. Hypovolemic shock occurs due to loss of blood from the gastrointestinal bleeding caused by the iron. During this phase, metabolic acidosis may also develop damaging internal organs such as the brain and liver. In the fourth stage taking place 12 to 96 hours after ingestion, liver toxicity and failure occurs as the cells begin to die. In the last stage of iron poisoning following 2 to 8 weeks after ingestion, scarring of the gastrointestinal mucosal lining resulting in bowel obstruction.

Cause
Pathophysiology
Iron is essential for the production of hemoglobin in red blood cells which is responsible for transporting oxygen throughout the body. In normal physiologic conditions, nonionic forms of iron (Fe°) are converted into ferrous iron (Fe2+) by gastric acid in the stomach. Ferrous iron is then absorbed in the small intestine where it is oxidized into its ferric iron (Fe3+) form before being released into the bloodstream. Free iron in the blood is toxic to the body as it disrupts normal cell function, damaging organs such as the liver, stomach, and cardiovascular system. The human body has protective mechanisms in place to prevent excess free ferric iron from circulating the body. When being transported throughout the body, iron is bound to an iron transporting protein called transferrin to prevent iron from being absorbed into different cells. Any excess iron is stored as ferritin in the liver. In the event of iron overdose, iron stores become oversaturated and the bodys protective mechanisms fail resulting in excess free circulating iron.

Toxic Dose
Iron poisoning can occur when doses of 20 to 60 mg/kg or more of elemental iron is ingested with most cases reporting primarily gastrointestinal symptoms. Systemic signs and symptoms shown in serious toxicity occur at higher doses exceeding 60 mg/kg. Ingesting above 120 mg/kg may be fatal. The therapeutic dose for iron deficiency anemia is 3–6 mg/kg/day. Individuals who have ingested less than 20 mg/kg of elemental iron typically do not exhibit symptoms. It is unlikely to get iron poisoning from diet alone with iron supplements being the cause of overdose. The amount of elemental iron in an iron supplement can be calculate based on the percentage it constitutes for per tablet. For example, a 300 mg tablet of ferrous fumarate will contain 100 mg of elemental iron or 33%.

Ferrous sulfate contains 20% elemental iron per mg of mineral salt
Ferrous gluconate contains 12% elemental iron per mg of mineral salt
Ferrous fumarate contains 33% elemental iron per mg of mineral salt

Diagnosis
Iron toxicity is primarily a clinical diagnosis that involves getting a detailed patient history and physical examination of the individuals signs and symptoms. Information such as how much iron was ingested and the timing should be gathered to assess the level of toxicity. Signs for severe iron poisoning should be evaluated such as any confusion or extreme lethargy, increased heart rates, low blood pressure for adults. In children, signs of shock can be noted with behavioral changes such as decreased responsiveness, crying, and inability to focus. Persistent vomiting is often associated with iron poisoning and also used to determine severity of iron poisoning. Laboratory tests such as measuring the peak serum iron level after 4 to 6 hours of ingestion can be useful in determining the severity of iron toxicity. In general, levels below 350mcg/dL are associated with more mild iron poisoning while upper levels above 500mcg/dL are associated with more severe iron poisoning. Measuring electrolyte levels, kidney function, serum glucose, liver function tests (enzymes and bilirubin), complete blood count, clotting time via prothrombin and partial thromboplastin time, anion gap for metabolic acidosis, should be conducted for clinical monitoring and confirmation of iron poisoning.The deferoxamine challenge test is a diagnostic test for confirming iron poisoning, however it is no longer recommended for diagnostic purposes due to concerns regarding the accuracy. Deferoxamine can be administered intramuscularly as a single dose where it then binds to free iron in the blood and is excreted into the urine turning it to a "brick orange" or pink/red/orange color. Radiographs are no longer used for diagnosis due to the lack of connection between severity of iron toxicity and the presence of radiopaque iron tablets in the stomach on X-rays. This method also requires that the ingested tablet to be radiopaque which most iron preparations are not.

Treatment
Management of acute iron poisoning involves providing a patient with respiratory support and intravenous deferoxamine. Patients exhibiting severe symptoms in the gastrointestinal phase should receive volume resuscitation to prevent hypovolemic shock from the loss of blood volume </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 Iron supplement and explain in detail? [/INST] Iron supplements, also known as iron salts and iron pills, are a number of iron formulations used to treat and prevent iron deficiency including iron deficiency anemia. For prevention they are only recommended in those with poor absorption, heavy menstrual periods, pregnancy, hemodialysis, or a diet low in iron. Prevention may also be used in low birth weight babies. They are taken by mouth, injection into a vein, or injection into a muscle. While benefits may be seen in days, up to two months may be required until iron levels return to normal.Common side effects include constipation, abdominal pain, dark stools, and diarrhea. Other side effects, which may occur with excessive use, include iron overload and iron toxicity. Ferrous salts used as supplements by mouth include ferrous fumarate, ferrous gluconate, ferrous succinate, and ferrous sulfate. Injectable forms include iron dextran and iron sucrose. They work by providing the iron needed for making red blood cells.Iron pills have been used medically since at least 1681, with an easy-to-use formulation being created in 1832. Ferrous salt is on the World Health Organizations List of Essential Medicines. Ferrous salts are available as a generic medication and over the counter. Slow release formulations, while available, are not recommended. In 2017, ferrous sulfate was the 92nd most commonly prescribed medication in the United States, with more than eight million prescriptions.

Medical uses
Iron supplements are used to treat iron deficiency and iron-deficiency anemia; parenteral irons can also be used to treat functional iron deficiency, where requirements for iron are greater than the bodys ability to supply iron such as in inflammatory states. The main criterion is that other causes of anemia have also been investigated, such as vitamin B12 or folate deficiency, drug induced or due to other poisons such as lead, as often the anemia has more than one underlying cause.
Iron deficiency anemia is classically a microcytic, hypochromic anemia. Generally, in the UK oral preparations are trialled before using parenteral delivery, unless there is the requirement for a rapid response, previous intolerance to oral iron or likely failure to respond. Intravenous iron may decrease the need for blood transfusions however it increases the risk of infections when compared to oral iron. A 2015 Cochrane Collaboration review found that daily oral supplementation of iron during pregnancy reduces the risk of maternal anemia and that effects on infant and on other maternal outcomes are not clear. Another review found tentative evidence that intermittent iron supplements by mouth for mothers and babies is similar to daily supplementation with fewer side effects. Supplements by mouth should be taken on an empty stomach, optionally with a small amount of food to reduce discomfort.

Athletes
Athletes may be at elevated risk of iron deficiency and so benefit from supplementation, but the circumstances vary between individuals and dosage should be based on tested ferritin levels, since in some cases supplementation may be harmful.

Frequent blood donors
Frequent blood donors may be advised to take iron supplements. Canadian Blood Services recommends discussing "taking iron supplements with your doctor or pharmacist" as "the amount of iron in most multivitamins may not meet your needs and iron supplements may be necessary". The American Red Cross recommends "taking a multivitamin with 18 mg of iron or an iron supplement with 18-38 mg of elemental iron for 60 days after each blood donation, for 120 days after each power red donation or after frequent platelet donations". A 2014 Cochrane Review found that blood donors were less likely to be deferred for low hemoglobin levels if they were taking oral iron supplements, although 29% of those who took them experienced side effects in contrast to the 17% that took a placebo. It is unknown what the long-term effects of iron supplementation for blood donors may be.

Side effects
Side effects of therapy with oral iron are most often diarrhea or constipation and epigastric abdominal discomfort. Taken after a meal, side effects decrease, but there is an increased risk of interaction with other substances. Side effects are dose-dependent, and the dose may be adjusted.
The patient may notice that their stools become black. This is completely harmless, but patients must be warned about this to avoid unnecessary concern. When iron supplements are given in a liquid form, teeth may reversibly discolor (this can be avoided through the use of a straw). Intramuscular injection can be painful, and brown discoloration may be noticed.
Treatments with iron(II) sulfate have higher incidence of adverse events than iron(III)-hydroxide polymaltose complex (IPC) or iron bis-glycinate chelate.Iron overdose has been one of the leading causes of death caused by toxicological agents in children younger than 6 years.Iron poisoning may result in mortality or short-term and long-term morbidity.

Infection risk
Because one of the functions of elevated ferritin (an acute phase reaction protein) in acute infections is thought to be to sequester iron from bacteria, it is generally thought that iron supplementation (which circumvents this mechanism) should be avoided in patients who have active bacterial infections. Replacement of iron stores is seldom such an emergency situation that it cannot wait for any such acute infection to be treated.
Some studies have found that iron supplementation can lead to an increase in infectious disease morbidity in areas where bacterial infections are common. For example, children receiving iron-enriched foods have demonstrated an increased rate in diarrhea overall and enteropathogen shedding. Iron deficiency protects against infection by creating an unfavorable environment for bacterial growth. Nevertheless, while iron deficiency might lessen infections by certain pathogenic diseases, it also leads to a reduction in resistance to other strains of viral or bacterial infections, such as Salmonella typhimurium or Entamoeba histolytica. Overall, it is sometimes difficult to decide whether iron supplementation will be beneficial or harmful to an individual in an environment that is prone to many infectious diseases; however this is a different question than the question of supplementation in individuals who are already ill with a bacterial infection.Children living in areas prone for malarial infections are also at risk of developing anemia. It was thought that iron supplementation given to such children could increase the risk of malarial infection in them. A Cochrane systematic review published in 2016 found high quality evidence that iron supplementation does not increase the risk of clinical malaria in children.

Contraindications
Contraindications often depend on the substance in question. Documented hypersensitivity to any ingredients and anemias without proper work-up (i.e., documentation of iron deficiency) is true of all preparations. Some can be used in iron deficiency, others require iron deficiency anaemia to be present. Some are also contraindicated in rheumatoid arthritis.

Hemochromatosis
Individuals may be genetically predisposed to excessive iron absorption, as is the case with those with HFE hereditary hemochromatosis. Within the general population, 1 out of 400 people has the homozygous form of this genetic trait, and 1 out of every 10 people has its heterozygous form. Neither individuals with the homozygous or heterozygous form should take iron supplements.

Interactions
Non-heme iron forms an insoluble complex with several other drugs, resulting in decreased absorption of both iron and the other drug. Examples include tetracycline, penicillamine, methyldopa, levodopa, bisphosphonates and quinolones. The same can occur with elements in food, such as calcium, which impacts both heme and non-heme iron absorption. Absorption of iron is better at a low pH (i.e. an acidic environment), and absorption is decreased if there is a simultaneous intake of antacids.
Many other substances decrease the rate of non-heme iron absorption. One example is tannins from foods such as tea and phytic acid. Because iron from plant sources is less easily absorbed than the heme-bound iron of animal sources, vegetarians and vegans should have a somewhat higher total daily iron intake than those who eat meat, fish or poultry.Taken after a meal, there are fewer side effects but there is also less absorption because of interaction and pH alteration. Generally, an interval of 2–3 hours between the iron intake and that of other drugs seems advisable, but is less convenient for patients and can impact on compliance.

History
The first pills were commonly known as Blauds pills, which were named after P. Blaud of Beaucaire, the French physician who introduced and started the use of these medications as a treatment for patients with anemia.

Administration
By mouth
Iron can be supplemented by mouth using various forms, such as iron(II) sulfate. This is the most common and well studied soluble iron salt sold under brand names such as Feratab, Fer-Iron, and Slow-FE. It is in complex with gluconate, dextran, carbonyl iron, and other salts. Ascorbic acid, vitamin C, increases the absorption of non-heme sources of iron.Heme iron polypeptide (HIP) (e.g. Proferrin ES and Proferrin Forte) can be used when regular iron supplements such as ferrous sulfate or ferrous fumarate are not tolerated or absorbed. A clinical study demonstrated that HIP increased serum iron levels 23 times greater than ferrous fumarate on a milligram-per-milligram basis.Another alternative is ferrous glycine sulfate or ferroglycine sulfate, has less gastrointestinal side-effects than standard preparations such as iron fumarate. It is unusual among oral preparations of iron supplements in that the iron in this preparation has very high oral bioavailability, especially in the liquid formulation. This option should be evaluated before resorting to parenteral therapy. It is especially useful in iron deficiency anemia associated with autoimmune gastritis and Helicobacter pylori gastritis, where it generally has satisfactory effect.Since iron stores in the body are generally depleted, and there is a limit to what the body can process (about 2–6 mg/kg of body mass per day; i.e. for a 100 kg/220 lb man this is equal to a maximum dose of 200–600 mg/per day) without iron poisoning, this is a chronic therapy which may take 3–6 months.Due to the frequent intolerance of oral iron and the slow improvement, parenteral iron is recommended in many indications.

By injection
Iron therapy (intravenously or intramuscular) is given when therapy by mouth has failed (not tolerated), oral absorption is seriously compromised (by illnesses, or when the person cannot swallow), benefit from oral therapy cannot be expected, or fast improvement is required (for example, prior to elective surgery). Parenteral therapy is more expensive than oral iron preparations and is not suitable during the first trimester of pregnancy.There are cases where parenteral iron is preferable over oral iron. These are cases where oral iron is not tolerated, where the haemoglobin needs to be increased quickly (e.g. post partum, post operatively, post transfusion), where there is an underlying inflammatory condition (e.g. inflammatory bowel disease) or renal patients, the benefits of parenteral iron far outweigh the risks. In many cases, use of intravenous iron such as ferric carboxymaltose has lower risks of adverse events than a blood transfusion and as long as the person is stable is a better alternative. Ultimately this always remains a clinical decision based on local guidelines, although National Guidelines are increasingly stipulating IV iron in certain groups of patients.Soluble iron salts have a significant risk of adverse effects and can cause toxicity due to damage to cellular macromolecules. Delivering iron parenterally has utilised various different molecules to limit this </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 Juvenile myoclonic epilepsy and explain in detail? [/INST] Juvenile myoclonic epilepsy (JME), also known as Janz syndrome, is a common form of genetic generalized epilepsy (previously known as idiopathic generalized epilepsy), representing 5-10% of all epilepsy cases. This disorder typically first presents between the ages of 12 and 18 with myoclonic seizure manifesting as sudden brief involuntary single or multiple episodes of muscle(s) contractions caused by an abnormal excessive or synchronous neuronal activity in the brain. These events typically occur after awakening from sleep, during the evening or upon sleep deprivation. JME is also characterized by generalized tonic-clonic seizures and a minority also have absence seizures. The genetics of JME are complex and rapidly evolving as over 20 chromosomal loci and multiple genes have been identified thus far. Given the genetic and clinical heterogeneity of JME some authors have suggested that it should be thought of as a spectrum disorder.

Epidemiology
The prevalence of JME is approximately 0.1-0.2 per 100,000 and constitutes approximately 5-10% of all epilepsies. Some studies suggest that JME is slightly more common in females than males. The onset of symptoms ranges between the ages of 8 and 36 years and has a peak between the ages of 12 and 18 years. Approximately 15% of children with childhood absence epilepsy and juvenile absence epilepsy subsequently develop JME. In most cases, myoclonic jerks precede the first generalized tonic-clonic seizure by a mean of 3.3 years. A long-term population-based study suggested that at 25 years from seizure onset all seizure types in JME resolved in 17% and in 13% only myoclonus remained despite discontinuing medication. Thus, disabling seizures resolve in around one-third of patients.

Signs and symptoms
There are three principle seizures types which may occur in JME: myoclonus, generalized tonic-clonic seizures and absence seizures.  Approximately one-third of patients have all three seizure types. The majority of patients (58.2%) have frequent myoclonic jerks and uncommon generalized tonic-clonic seizures. Absence seizures are believed to be the least common with studies estimating a prevalence of 10% to as high as 38%. Myoclonic status epilepticus may occur as a complication but it is uncommon.
Patient’s typically initially present to medical providers following their first generalized tonic-clonic seizure. It is often subsequently reported that the patient was having myoclonus for several years prior. The first generalized tonic-clonic seizure usually occurs in the context of a particular provoking factor such as sleep deprivation, stress or alcohol consumption. There are other potential provoking factors such as praxis induction which refers to the precipitation of seizures or epileptiform discharges in the context of a complex cognitive tasks. Patients with JME tend to perform worse on neuropsychological assessments in multiple cognitive domains and are also more likely to have psychiatric comorbidities such as depression and anxiety when compared to control populations. The majority of patients with JME report satisfaction with their health, work, friendships and social life.

Cause
JME is believed to be most often caused by a heterogeneous and complex interaction of multiple genes rather than an unidentified single genetic cause. Thus far seven genes and over 20 chromosomal loci have been implicated in the pathogenesis of JME. A minority of cases are caused by single genes and are inherited in an autosomal dominant fashion. The majority of the genes which have been associated with JME encode for ion channel subunits. More recently, variants in intestinal cell kinase which is encoded by a gene on chromosome 6p12 was found to be associated with JME. This gene is involved in mitosis, cell-cycle exit and radial neuroblast migration as well as apoptosis. Another gene that is associated with JME called EFHC1 has similar functions. These findings may explain subtle structural and functional brain abnormalities that are seen in patients with JME.JME is distinct from other forms of genetic generalized epilepsies due to the prominence of myoclonus. There is evidence that patients with JME have hyperexcitable motor cortexes that is most pronounced in the morning and after sleep deprivation. In addition, there is evidence that patients with JME have hyperexcitable and hyperconnected cortical networks that are involved in ictogenesis.

Genetics
CACNB4
CACNB4 is a gene that encodes the calcium channel β subunit protein. β subunits are important regulators of calcium channel current amplitude, voltage dependence, and also regulate channel trafficking. In mice, a naturally occurring null mutation leads to the "lethargic" phenotype. This is characterized by ataxia and lethargic behavior at early stages of development followed within days by the onset of both focal motor seizures as well as episodes of behavioral immobility which correlates with patterns of cortical spike and wave discharges at the EEG A premature-termination mutation R482X was identified in a patient with JME while an additional missense mutation C104F was identified in a German family with generalized epilepsy and praxis – induced seizures.The R482X mutation results in increased current amplitudes and an accelerated fast time constant of inactivation. Whether these modest functional differences may be in charge of JME remains to be established.  Calcium channel β4 subunit (CACNB4) is not strictly considered a putative JME gene because its mutation did not segregate in affected family members, and it was found in only one member of a JME family from Germany, and it has not been replicated.

GABRA1
GABRA1 is a gene that encodes for an α subunit of the GABA A receptor protein, which encodes one of the major inhibitory neurotransmitter receptors. There is one known mutation in this gene that is associated with JME, A322D, which is located in the third segment of the protein. This missense mutation results in channels with reduced peak GABA-evoked currents. Furthermore, the presence of such mutation alters the composition and reduces the expression of wild-type GABAA receptors.

GABRD
GABRD encodes the δ subunit of the GABA receptor, which is an important constituent of the GABAA receptor mediating tonic inhibition in neurons (extrasynaptic GABA receptors, i.e. receptors that are localized outside of the synapse). Among the mutations that have been reported in this in this gene, one (R220H) has been identified in a small family with JME.  This mutation affects GABAergic transmission by altering the surface expression of the receptor as well as reducing the channel – opening duration.

Myoclonin1/EFHC1
The final known associated gene is EFHC1. Myoclonin1/EFHC1 encodes for a protein that has been known to play a wide range of wild-type cell division, neuroblast migration and synapse/dendrite formation. EFHC1 is expressed in many tissues, including the brain, where it is localized to the soma and dendrites of neurons, particularly the hippocampal CA1 region, pyramidal neurons in the cerebral cortex, and Purkinje cells in the cerebellum.There are four JME-causing mutations discovered (D210N, R221H, F229L and D253Y). The mutations do not seem to alter the ability of the protein to colocalize with centrosomes and mitotic spindles but induce mitotic spindle defects. Moreover, the mutations impact radial and tangential migration during brain development. As such a theory has been put forward that JME may be the result of a brain developmental disorder.

Other loci
Three SNP alleles in BRD2, Cx-36 and ME2 and microdeletions in 15q13.3, 15q11.2 and 16p.13.11 also contribute risk to JME.

Diagnosis
Diagnosis is typically made based on patient history. The physical examination is usually normal. The primary diagnosis for JME is a good knowledge of patient history  and the neurologists familiarity with the myoclonic jerks, which are the hallmark of the syndrome. Additionally, an electroencephalogram (EEG), will indicate a characteristic pattern of waves and spikes associated with the syndrome such as generalized 4–6 Hz polyspike and slow wave discharges.  These discharges may be evoked by photic stimulation (blinking lights) and/or hyperventilation.
Both a magnetic resonance imaging scan (MRI) and computed tomography scan (CT scan) generally appear normal in JME patients </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 Kaposis sarcoma and explain in detail? [/INST] Kaposis sarcoma (KS) is a type of cancer that can form masses in the skin, in lymph nodes, in the mouth, or in other organs. The skin lesions are usually painless, purple and may be flat or raised. Lesions can occur singly, multiply in a limited area, or may be widespread. Depending on the sub-type of disease and level of immune suppression, KS may worsen either gradually or quickly. KS is caused by a combination of immune suppression (such as due to HIV/AIDS) and infection by Human herpesvirus 8 (HHV8 – also called KS-associated herpesvirus (KSHV)).Four sub-types are described: classic, endemic, immunosuppression therapy-related (also called iatrogenic), and epidemic (also called AIDS-related). Classic KS tends to affect older men in regions where KSHV is highly prevalent (Mediterranean, Eastern Europe, Middle East), is usually slow-growing, and most often affects only the legs. Endemic KS is most common in Sub-Saharan Africa and is more aggressive in children, while older adults present similarly to classic KS. Immunosuppression therapy-related KS generally occurs in people following organ transplantation and mostly affects the skin. Epidemic KS occurs in people with AIDS and many parts of the body can be affected. KS is diagnosed by tissue biopsy, while the extent of disease may be determined by medical imaging.Treatment is based on the sub-type, whether the condition is localized or widespread, and the persons immune function. Localized skin lesions may be treated by surgery, injections of chemotherapy into the lesion, or radiation therapy. Widespread disease may be treated with chemotherapy or biologic therapy. In those with HIV/AIDS, highly active antiretroviral therapy (HAART) prevents and often treats KS. In certain cases the addition of chemotherapy may be required. With widespread disease, death may occur.The condition is relatively common in people with HIV/AIDS and following organ transplant. Over 35% of people with AIDS may be affected. KS was first described by Moritz Kaposi in 1872. It became more widely known as one of the AIDS-defining illnesses in the 1980s. KSHV was discovered as a causative agent in 1994.

Signs and symptoms
KS lesions are nodules or blotches that may be red, purple, brown, or black, and are usually papular.They are typically found on the skin, but spread elsewhere is common, especially the mouth, gastrointestinal tract and respiratory tract. Growth can range from very slow to explosively fast, and is associated with significant mortality and morbidity.The lesions are painless, but become cosmetically disfiguring or interruptive to organs.

Skin
Commonly affected areas include the lower limbs, back, face, mouth, and genitalia. The lesions are usually as described above, but may occasionally be plaque-like (often on the soles of the feet) or even involved in skin breakdown with resulting fungating lesions.
Associated swelling may be from either local inflammation or lymphoedema (obstruction of local lymphatic vessels by the lesion). Skin lesions may be quite disfiguring for the patient, and a cause of much psychosocial pathology.

Mouth
The mouth is involved in about 30% of cases, and is the initial site in 15% of AIDS-related KS. In the mouth, the hard palate is most frequently affected, followed by the gums. Lesions in the mouth may be easily damaged by chewing and bleed or develop secondary infection, and even interfere with eating or speaking.

Gastrointestinal tract
Involvement can be common in those with transplant-related or AIDS-related KS, and it may occur in the absence of skin involvement. The gastrointestinal lesions may be silent or cause weight loss, pain, nausea/vomiting, diarrhea, bleeding (either vomiting blood or passing it with bowel movements), malabsorption, or intestinal obstruction.

Respiratory tract
Involvement of the airway can present with shortness of breath, fever, cough, coughing up blood or chest pain, or as an incidental finding on chest x-ray. The diagnosis is usually confirmed by bronchoscopy, when the lesions are directly seen and often biopsied. Kaposis sarcoma of the lung has a poor prognosis.

Cause
Kaposis sarcoma-associated herpesvirus (KSHV), also called HHV-8, is present in almost 100% of Kaposi sarcoma lesions, whether HIV-related, classic, endemic, or iatrogenic. KSHV encodes oncogenes, microRNAs and circular RNAs that promote cancer cell proliferation and escape from the immune system.

Transmission
In Europe and North America, KSHV is transmitted through saliva. Thus, kissing is a risk factor for transmission. Higher rates of transmission among gay and bisexual men have been attributed to "deep kissing" sexual partners with KSHV. Another alternative theory suggests that use of saliva as a sexual lubricant might be a major mode for transmission. Prudent advice is to use commercial lubricants when needed and avoid deep kissing with partners with KSHV infection or whose status is unknown.KSHV is also transmissible via organ transplantation and blood transfusion. Testing for the virus before these procedures is likely to effectively limit iatrogenic transmission.

Pathology
Despite its name, in general it is not considered a true sarcoma, which is a tumor arising from mesenchymal tissue. The histogenesis of KS remains controversial. KS may arise as a cancer of lymphatic endothelium and forms vascular channels that fill with blood cells, giving the tumor its characteristic bruise-like appearance.  KSHV proteins are uniformly detected in KS cancer cells.KS lesions contain tumor cells with a characteristic abnormal elongated shape, called spindle cells. The most typical feature of Kaposi sarcoma is the presence of spindle cells forming slits containing red blood cells. Mitotic activity is only moderate and pleomorphism is usually absent. The tumor is highly vascular, containing abnormally dense and irregular blood vessels, which leak red blood cells into the surrounding tissue and give the tumor its dark color. Inflammation around the tumor may produce swelling and pain. Variously sized PAS positive hyaline bodies are often seen in the cytoplasm or sometimes extracellularly.The spindle cells of Kaposi sarcoma differentiate toward endothelial cells, probably of lymph vessel rather than blood vessel origin. The consistent immunoreactivity for podoplanin supports the lymphatic nature of the lesion.

Diagnosis
Although KS may be suspected from the appearance of lesions and the patients risk factors, a definite diagnosis can be made only by biopsy and microscopic examination. Detection of the KSHV protein LANA in tumor cells confirms the diagnosis.In differential diagnosis, arteriovenous malformations, pyogenic granuloma and other vascular proliferations can be microscopically confused with KS.

Differential diagnosis of Kaposis sarcoma
Source:
Naevus
Histiocytoma
Cryptococcosis
Histoplasmosis
Leishmaniasis
Pneumocystis lesions
Dermatophytosis
Angioma
Bacillary angiomatosis
Pyogenic granuloma
Melanoma

Classification
HHV-8 is responsible for all varieties of KS. Since Moritz Kaposi first described the cancer, the disease has been reported in five separate clinical settings, with different presentations, epidemiology, and prognoses.: 599  All of the forms are infected with KSHV and are different manifestations of the same disease but have differences in clinical aggressiveness, prognosis, and treatment.

Classic Kaposi sarcoma most commonly appears early on the toes and soles as reddish, violaceous, or bluish-black macules and patches that spread and coalesce to form nodules or plaques.: 599  A small percentage of these patients may have visceral lesions. In most cases the treatment involves surgical removal of the lesion. The condition tends to be indolent and chronic, affecting elderly men from the Mediterranean region, Arab countries, or of Eastern European descent. Israeli Jews have a higher rate of KSHV/HHV-8 infection than European peoples.
Endemic KS, which has two types. Although this may be present worldwide, it has been originally described later in young African peoples, mainly those from sub-Saharan Africa. This variant is not related to HIV infection and is a more aggressive disease that infiltrates the skin extensively.African lymphadenopathic Kaposi sarcoma is aggressive, occurring in children under 10 years of age, presenting with lymph node involvement, with or without skin lesions.: 599
African cutaneous Kaposi sarcoma presents with nodular, infiltrative, vascular masses on the extremities, mostly in men between the ages of 20 and 50, and is endemic in tropical Africa.: 599
Immunosuppression-associated Kaposi sarcoma had been described, but only rarely until the advent of calcineurin inhibitors (such as ciclosporines, which are inhibitors of T-cell function) for transplant patients in the 1980s, when its incidence grew rapidly.  The tumor arises either when an HHV 8-infected organ is transplanted into someone who has not been exposed to the virus or when the transplant recipient already harbors pre-existing HHV 8 infection. Unlike classic Kaposi sarcoma, the site of presentation is more variable.: 600
AIDS-associated Kaposi sarcoma typically presents with cutaneous lesions that begin as one or several red to purple-red macules, rapidly progressing to papules, nodules, and plaques, with a predilection for the head, back, neck, trunk, and mucous membranes. In more advanced cases, lesions can be found in the stomach and intestines, the lymph nodes, and the lungs.: 599  Compared to other forms of KS, KS-AIDS stimulated more interest in KS research, as it was one of the first illnesses associated with AIDS and first described in 1981. This form of KS is over 300 times more common in AIDS patients than in renal transplant recipients. In this case, HHV 8 is sexually transmitted among people also at risk for sexually transmitted HIV infection.

Prevention
Blood tests to detect antibodies against KSHV have been developed and can be used to determine whether a person is at risk for transmitting the infection to their sexual partner, or whether an organ is infected before transplantation.  However, these tests are not available except as research tools, and, thus, there is little screening for persons at risk for becoming infected with KSHV, such as people following a transplant.

Treatment
Kaposi sarcoma is not curable, but it can often be treatable for many years. In KS associated with immunodeficiency or immunosuppression, treating the cause of the immune system dysfunction can slow or stop the progression of KS. In 40% or more of patients with AIDS-associated Kaposi sarcoma, the Kaposi lesions will shrink upon first starting highly active antiretroviral therapy (HAART). Therefore, HAART is considered the cornerstone of therapy in AIDS-associated Kaposi sarcoma. However, in a certain percentage of such people, Kaposi sarcoma may recur after many years on HAART, especially if HIV is not completely suppressed.
People with a few local lesions can often be treated with local measures such as radiation therapy or cryosurgery. Weak evidence suggests that antiretroviral therapy in combination with chemotherapy is more effective than either of those two therapies individually </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 Keloid and explain in detail? [/INST] Keloid, also known as keloid disorder and keloidal scar,
is the formation of a type of scar which, depending on its maturity, is composed mainly of either type III (early) or type I (late) collagen. It is a result of an overgrowth of granulation tissue (collagen type 3) at the site of a healed skin injury which is then slowly replaced by collagen type 1.  Keloids are firm, rubbery lesions or shiny, fibrous nodules, and can vary from pink to the color of the persons skin or red to dark brown in color. A keloid scar is benign and not contagious, but sometimes accompanied by severe itchiness, pain, and changes in texture. In severe cases, it can affect movement of skin. Worldwide, men and women of African, Asian, Hispanic and European descent can develop these raised scars. In the United States keloid scars are seen 15 times more frequently in people of sub-Saharan African descent than in people of European descent. There is a higher tendency to develop a keloid among those with a family history of keloids and people between the ages of 10 and 30 years.
Keloids should not be confused with hypertrophic scars, which are raised scars that do not grow beyond the boundaries of the original wound.

Signs and symptoms
Keloids expand in claw-like growths over normal skin. They have the capability to hurt with a needle-like pain or to itch, the degree of sensation varying from person to person.Keloids form within scar tissue. Collagen, used in wound repair, tends to overgrow in this area, sometimes producing a lump many times larger than that of the original scar. They can also range in color from pink to red. Although they usually occur at the site of an injury, keloids can also arise spontaneously.  They can occur at the site of a piercing and even from something as simple as a pimple or scratch. They can occur as a result of severe acne or chickenpox scarring, infection at a wound site, repeated trauma to an area, excessive skin tension during wound closure or a foreign body in a wound. Keloids can sometimes be sensitive to chlorine. If a keloid appears when someone is still growing, the keloid can continue to grow as well.

Location
Keloids can develop in any place where skin trauma has occurred. They can be the result of pimples, insect bites, scratching, burns, or other skin injury. Keloid scars can develop after surgery.
They are more common in some sites, such as the central chest (from a sternotomy), the back and shoulders (usually resulting from acne), and the ear lobes (from ear piercings). They can also occur on body piercings.The most common spots are earlobes, arms, pelvic region, and over the collar bone.

Cause
Most skin injury types can contribute to scarring. This includes burns, acne scars, chickenpox scars, ear piercing, scratches, surgical incisions, and vaccination sites.
According to the (US) National Center for Biotechnology Information, keloid scarring is common in young people between the ages of 10 and 20. Studies have shown that those with darker complexions are at a higher risk of keloid scarring as a result of skin trauma. They occur in 15–20% of individuals with sub-Saharan African, Asian or Latino ancestry, significantly less in those of a Caucasian background. Although it was previously believed that people with albinism did not get keloids, a recent report described the incidence of keloids in Africans with albinism. Keloids tend to have a genetic component, which means one is more likely to have keloids if one or both of their parents has them. However, no single gene has yet been identified which is a causing factor in keloid scarring but several susceptibility loci have been discovered, most notably in Chromosome 15.

Genetics
People who have ancestry from Sub-Saharan Africa, Asia, or Latin America are more likely to develop a keloid.  Among ethnic Chinese in Asia, the keloid is the most common skin condition. In the United States, keloids are more common in African Americans and Hispanic Americans than European Americans. Those who have a family history of keloids are also susceptible since about 1/3 of people who get keloids have a first-degree blood relative (mother, father, sister, brother, or child) who also gets keloids. This family trait is most common in people of African and/or Asian descent.
Development of keloids among twins also lends credibility to existence of a genetic susceptibility to develop keloids. Marneros et al. (1) reported four sets of identical twins with keloids; Ramakrishnan et al. also described a pair of twins who developed keloids at the same time after vaccination. Case series have reported clinically severe forms of keloids in individuals with a positive family history and black African ethnic origin.

Pathology
Histologically, keloids are fibrotic tumors characterized by a collection of atypical fibroblasts with excessive deposition of extracellular matrix components, especially collagen, fibronectin, elastin, and proteoglycans. Generally, they contain relatively acellular centers and thick, abundant collagen bundles that form nodules in the deep dermal portion of the lesion. Keloids present a therapeutic challenge that must be addressed, as these lesions can cause significant pain, pruritus (itching), and physical disfigurement. They may not improve in appearance over time and can limit mobility if located over a joint.Keloids affect both sexes equally, although the incidence in young female patients has been reported to be higher than in young males, probably reflecting the greater frequency of earlobe piercing among women.
The frequency of occurrence is 15 times higher in highly pigmented people. People of African descent have increased risk of keloid occurrences.

Treatments
Prevention of keloid scars in patients with a known predisposition to them includes preventing unnecessary trauma or surgery (such as ear piercing and elective mole removal) whenever possible. Any skin problems in predisposed individuals (e.g., acne, infections) should be treated as early as possible to minimize areas of inflammation.
Treatments (both preventive and therapeutic) available are pressure therapy, silicone gel sheeting, intra-lesional triamcinolone acetonide (TAC), cryosurgery (freezing), radiation, laser therapy (PDL), IFN, 5-FU and surgical excision as well as a multitude of extracts and topical agents. Appropriate treatment of a keloid scar is age-dependent: radiotherapy, anti-metabolites and corticosteroids would not be recommended to be used in children, in order to avoid harmful side effects, like growth abnormalities.In adults, corticosteroids combined with 5-FU and PDL in a triple therapy, enhance results and diminish side effects.Cryotherapy (or cryosurgery) refers to the application of extreme cold to treat keloids. This treatment method is easy to perform, effective and safe and has the least chance of recurrence.Surgical excision is currently still the most common treatment for a significant amount of keloid lesions. However, when used as the solitary form of treatment there is a large recurrence rate of between 70 and 100%. It has also been known to cause a larger lesion formation on recurrence. While not always successful alone, surgical excision when combined with other therapies dramatically decreases the recurrence rate. Examples of these therapies include but are not limited to radiation therapy, pressure therapy and laser ablation. Pressure therapy following surgical excision has shown promising results, especially in keloids of the ear and earlobe. The mechanism of how exactly pressure therapy works is unknown at present, but many patients with keloid scars and lesions have benefited from it.Intralesional injection with a corticosteroid such as Kenalog (triamcinolone acetonide) does appear to aid in the reduction of fibroblast activity, inflammation and pruritus.Tea tree oil, salt or other topical oil has no effect on keloid lesions.A 2022 systematic review included multiple studies on laser therapy for treating keloid scars. There was not enough evidence for the review authors to determine if laser therapy was more effective than other treatments. They were also unable to conclude if laser therapy leads to more harm than benefits compared with no treatment or different kinds of treatment.

Epidemiology
Persons of any age can develop a keloid. Children under 10 are less likely to develop keloids, even from ear piercing. Keloids may also develop from Pseudofolliculitis barbae; continued shaving when one has razor bumps will cause irritation to the bumps, infection, and over time keloids will form. Persons with razor bumps are advised to stop shaving in order for the skin to repair itself before undertaking any form of hair removal. The tendency to form keloids is speculated to be hereditary. Keloids can tend to appear to grow over time without even piercing the skin, almost acting out a slow tumorous growth; the reason for this tendency is unknown.
Extensive burns, either thermal or radiological, can lead to unusually large keloids; these are especially common in firebombing casualties, and were a signature effect of the atomic bombings of Hiroshima and Nagasaki.
True incidence and prevalence of keloid in United States is not known. Indeed, there has never been a population study to assess the epidemiology of this disorder.  In his 2001 publication, Marneros stated that “reported incidence of keloids in the general population ranges from a high of 16% among the adults in the Democratic Republic of the Congo to a low of 0.09% in England,” quoting from Blooms 1956 publication on heredity of keloids.  Clinical observations show that the disorder is more common among sub-Saharan Africans, African Americans and Asians, with unreliable and very wide estimated prevalence rates ranging from 4.5 to 16%.

History
Keloids were described by Egyptian surgeons around 1700 BC, recorded in the Smith papyrus, regarding surgical techniques. Baron Jean-Louis Alibert (1768–1837) identified the keloid as an entity in 1806. He called them cancroïde, later changing the name to chéloïde to avoid confusion with cancer. The word is derived from the Ancient Greek χηλή, chele, meaning "crab pincers", and the suffix -oid, meaning "like".
The famous American Civil War-era photograph "Whipped Peter" depicts an escaped former slave with extensive keloid scarring as a result of numerous brutal beatings from his former overseer.
Intralesional corticosteroid injections was introduced as a treatment in mid-1960s as a method to attenuate scaring.Pressure therapy has been use for prophylaxis and treatment of keloids since the 1970s.Topical silicone gel sheeting was introduced as a treatment in the early 1980s.

References
Further reading

Roßmann, Nico (2005). Beitrag zur Pathogenese des Keloids und seine Beeinflussbarkeit durch Steroidinjektionen [Contribution to the pathogenesis of the keloid and its influence by steroid injections] (PhD Thesis) (in German). OCLC 179740918.
Ogawa, Rei; Mitsuhashi, Kiyoshi; Hyakusoku, Hiko; Miyashita, Tuguhiro (2003). "Postoperative Electron-Beam Irradiation Therapy for Keloids and Hypertrophic Scars: Retrospective Study of 147 Cases Followed for More Than 18 Months" </s>