<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 Gingival enlargement and can you explain it in depth? [/INST] Gingival enlargement is an increase in the size of the gingiva (gums). It is a common feature of gingival disease. Gingival enlargement can be caused by a number of factors, including inflammatory conditions and the side effects of certain medications. The treatment is based on the cause. A closely related term is epulis, denoting a localized tumor (i.e. lump) on the gingiva.

Classification
The terms gingival hyperplasia and gingival hypertrophy have been used to describe this topic in the past.  These are not precise descriptions of gingival enlargement because these terms are strictly histologic diagnoses, and such diagnoses require microscopic analysis of a tissue sample. Hyperplasia refers to an increased number of cells, and hypertrophy refers to an increase in the size of individual cells. As these identifications cannot be performed with a clinical examination and evaluation of the tissue, the term gingival enlargement is more properly applied. Gingival enlargement has been classified according to cause into 5 general groups:
Inflammatory enlargement
Drug induced enlargement
Enlargement associated with systemic diseases or conditions
Neoplastic enlargement
False enlargement.

Causes
Inflammatory enlargement
Gingival enlargement has a multitude of causes.  The most common is chronic inflammatory gingival enlargement, when the gingivae are soft and discolored.  This is caused by tissue edema and infective cellular infiltration caused by prolonged exposure to bacterial plaque, and is treated with conventional periodontal treatment, such as scaling and root planing.Gingivitis and gingival enlargement are often seen in mouth breathers, as a result of irritation brought on by surface dehydration, but the manner in which it is caused has not been demonstrated.The accumulation and retention of plaque is the chief cause of inflammatory gingival enlargement.  Risk factors include poor oral hygiene, as well as physical irritation of the gingiva by improper restorative and orthodontic appliances.

Drug-induced enlargement
This type of gingival enlargement is sometimes termed "drug induced gingival enlargement" or "drug influenced gingival overgrowth", abbreviated to "DIGO". Gingival enlargement may also be associated with the administration of three different classes of drugs, all producing a similar response: Gingival overgrowth is a common side effect of phenytoin, termed "Phenytoin-induced gingival overgrowth" (PIGO).
anticonvulsants (such as phenytoin, phenobarbital, lamotrigine, vigabatrin, ethosuximide, topiramate and primidone NOT common for valproate)
calcium channel blockers (antihypertensives such as nifedipine, amlodipine, and verapamil). The dihydropyridine derivative isradipidine can replace nifedipine and does not induce gingival overgrowth.
cyclosporine, an immunosuppressant.Of all cases of DIGO, about 50% are attributed to phenytoin, 30% to cyclosporins and the remaining 10-20% to calcium channel blockers.
Drug-induced enlargement has been associated with a patients genetic predisposition, and its association with inflammation is debated.  Some investigators assert that underlying inflammation is necessary for the development of drug-induced enlargement, while others purport that the existing enlargement induced by the drug effect compounds plaque retention, thus furthering the tissue response. Careful attention to oral hygiene may reduce the severity of gingival hyperplasia. In most cases, discontinuing the culprit drug resolves the hyperplasia.

Enlargement associated with systemic factors
Many systemic diseases can develop oral manifestations that may include gingival enlargement, some that are related to conditions and others that are related to disease:
Conditioned enlargement
pregnancy
puberty
vitamin C deficiency
nonspecific, such as a pyogenic granuloma
Systemic disease causing enlargement
leukemia
granulolomatous diseases, such as granulomatosis with polyangiitis, sarcoidosis, or orofacial granulomatosis.
neoplasm
benign neoplasms, such as fibromas, papillomas and giant cell granulomas
malignant neoplasms, such as a carcinoma or malignant melanoma
false gingival enlargements, such as when there is an underlying bony or dental tissue lesion

Mechanism
Drug Induced gingival overgrowth:

Fibrotic type:
Elevated CTGF (a.k.a. CCN2) which is a matricellular protein known to be reliable for fibrosis.TGF-β increases drives CTGF/CCN2 (current molecular mechanisms unknown), but supports TGF-β as a therapeutic target.
CTGF is not down regulated in presence of inflammatory mediators (such as PGE2), unlike other tissues fibroblasts (such as kidney) which have their CTGF levels down regulated by the same PGE2.
Inflammatory Type

Management
The first line management of gingival overgrowth is improved oral hygiene, ensuring that the irritative plaque is removed from around the necks of the teeth and gums. Situations in which the chronic inflammatory gingival enlargement include significant fibrotic components that do not respond to and undergo shrinkage when exposed to scaling and root planing are treated with surgical removal of the excess tissue, most often with a procedure known as gingivectomy.In DIGO, improved oral hygiene and plaque control is still important to help reduce any inflammatory component that may be contributing to the overgrowth </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 Nasal glial heterotopia and can you explain it in depth? [/INST] Nasal glial heterotopia refers to congenital malformations of displaced normal, mature glial tissue, which are no longer in continuity with an intracranial component. This is distinctly different from an encephalocele, which is a herniation of brain tissue and/or leptomeninges, that develops through a defect in the skull, where there is a continuity with the cranial cavity.

Signs and symptoms
Patients come to clinical attention early in life (usually at birth or within the first few months), with a firm subcutaneous nodule at bridge of nose, or as a polypoid mass within the nasal cavity, or somewhere along the upper border of the nasal bow. If the patient presents with an intranasal mass, there may be obstruction, chronic rhinosinusitis, or nasal drainage. If there is a concurrent cerebrospinal fluid (CSF) leak, then an encephalocele is much more likely.This lesion is separated into two types based on the anatomic site of presentation:

Extranasal (60%):  Subcutaneous bridge of nose
Intranasal (30%):  Superior nasal cavity
Mixed (10%): Subcutaneous tissues and nasal cavity (larger lesions)

Pathology
The cut surface shows a smooth, homogeneous glistening to slippery cut surface, showing an appearance similar to brain. Sometimes, it is quite firm, especially when there is a large amount of associated fibrosis. The lesions are usually <2 cm in greatest dimension.
 The overlying skin or squamous mucosa is intact and uninvolved by the process. There is normal glial tissue set within a fibrous connective tissue stroma. There is such blending, that the underlying process may be difficult to detect without special studies. In a few cases, large gemistocytes, neurons, choroid plexus, ependyma, and retinal pigmented cells may be seen.

Histochemistry
A trichrome stain will highlight the dual components well, with the glial tissue staining red, while the background fibrosis stains a bright blue.

Immunohistochemistry
The glial tissue is highlighted with S100 protein and with glial fibrillary acidic protein, although the latter is much more sensitive for glial tissue.

Diagnosis
Differential diagnoses
The most common missed lesion is within the nasal cavity, where a fibrosed nasal polyp may be considered. However, it does not have glial tissue. Further, a polyp usually has mucoserous glands. The lesion is frequently misinterpreted as scar in the subcutaneous tissues, but scar in a < 2-year-old child would be uncommon. Special stains are frequently required to highlight the diagnosis.

Imaging findings
Imaging studies are performed before surgery or biopsy to preclude an intracranial connection. Images usually show a sharply circumscribed but expansile mass. It may be difficult to exclude the intracranial connection if the defect is small whether employing computed tomography or magnetic resonance.

Classification
While nasal glial heterotopia (NGH) is the preferred term, synonyms have included nasal glioma. However, this term is to be discouraged, as it implies a neoplasm or tumor, which it is not. By definition, nasal glial heterotopia is a specific type of choristoma. It is not a teratoma, however, which is a neoplasm comprising all three germ cell layers (ectoderm, endoderm, mesoderm). As a congenital malformation or ectopia, it is distinctly different from the trauma or iatrogenic development of an encephalocele.

Management
Although surgery is the treatment of choice, it must be preceded by imaging studies to exclude an intracranial connection. Potential complications include meningitis and a cerebrospinal fluid leak. Recurrences or more correctly persistence may be seen in up to 30% of patients if not completely excised.

Epidemiology
Nasal glial heterotopia is rare, while an encephalocele is uncommon </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 Webbed penis and can you explain it in depth? [/INST] Webbed penis also known as buried or concealed penis is an acquired or congenital condition in which the scrotal skin extends onto the ventral penile shaft. The penile shaft is buried in the scrotum or tethered to the scrotal midline by a fold or web of skin. The urethra and erectile bodies are usually normal. Webbed penis is usually asymptomatic, but the cosmetic appearance is often unacceptable. This condition may be corrected by surgical techniques.In the congenital form, the deformity represents an abnormality of the attachment between the penis and the scrotum; the penis, the urethra, and the remainder of the scrotum typically are normal.
Webbed penis may also be acquired (iatrogenic) after circumcision or other penile surgery, resulting from excessive removal of ventral penile skin; the penis can retract into the scrotum, resulting in secondary phimosis (trapped penis).

Signs and symptoms
Since the penis does not protrude when a man has this disorder, his ability to pass urine when he is standing or to participate in sexual intercourse will be impaired.
Visible signs may include but are not limited to:

Excessive skin and fat around the penis.
Tight, scarred preputial orifice.
Straining to urinate.

Cause
Webbed penis can be caused by various things such as:
Morbid obesity: which is known as excess fat around the genital area and abdomen, which makes the penis appear as though it is hidden.
Abnormalities that are there during birth – ligaments that attach the penis to underlying structures may be weaker than it is supposed to be.
Lymphedema: this is when swelling occurs around the scrotum area due to collection of lymph fluid, which may cause the penis to be buried inside tissue.
Acquired (iatrogenic) after circumcision or other penile surgery – resulting from excessive removal of ventral penile skin.

Mechanism and pathophysiology
Concealed penis is due to a lack of skin or an inelasticity of the penile skin and a weak penile skin fixation or excessive suprapubic fat, the penile webbed is characterized by a ventral fold of skin that connects the distal shaft and a penoscrotum, and a penis which is tucked away with the scar tissue that exists.
Concealed penis is an unusual circumcision complication. The excision of excess preputial skin occurs, although inadequate internal preputial epithelium is cut out. The new preputial orifice is thus distal to the gland and pushes the penile shaft into the supra-pubic fat at the level of mons pubis. In these cases, the released shaft includes a skin graft or local flaps. The other probability of this mechanism is that, since the penis continues to shrink into the mons pubis, the healed scarred pre-utile opening gradually becomes subcutaneously stuck. In such cases, the released shaft needs no skin graft or local flaps. For both mechanisms, the preputial skin is inadequately excised, causing the preputial holes to be distal from the pulse, trapping the pulp when the procedure is complete.In relation to lymphedema – When the lymph system operates normally, the lymph circulates through a series of vessels and ducts throughout the body. It then returns to the bloodstream with lymph. A blocking or failure in the genital area of this system may lead to a lymphatic leak into the soft tissues surrounding the system.
In relation to obesity – Obesity is a general cause of adult acquired buried penis. There are some parallels with buried penis seen in infants, frequently associated with poor skin suspension, abnormal excess fat accumulation in the pubic region, penis webbing, or penis trapping due to scarring post-circumcision. Similarly, adult buried penis is often associated with a laxity of connective tissue between the dart fascia and the penis, allowing the penis to tunnel more closely through the pre-pubic skin due to "hypermobility." This is exacerbated by obesity and weight gain as the phallus is covered by the suprapubic fat pad.

Diagnosis
Typically a physical examination may be used to diagnose a person with a buried penis. A doctor should be able to differentiate between buried penis and a tiny penis, known as micropenis.

Treatment
Adults with a buried penis either deal with or are subject to weight loss services. Weight loss programs are however sluggish and frequently do not "unbury" the penis; in addition, bad urine hygiene can lead to soft tissue infection.While the condition can resolve without intervention in young children, if infection is present, patients may ultimately need a definite reconstruction and urgent procedure </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 Sarcoidosis and can you explain it in depth? [/INST] Sarcoidosis (also known as Besnier-Boeck-Schaumann disease) is a disease involving abnormal collections of inflammatory cells that form lumps known as granulomata. The disease usually begins in the lungs, skin, or lymph nodes. Less commonly affected are the eyes, liver, heart, and brain. Any organ, however, can be affected. The signs and symptoms depend on the organ involved. Often, no, or only mild, symptoms are seen. When it affects the lungs, wheezing, coughing, shortness of breath, or chest pain may occur. Some may have Löfgren syndrome with fever, large lymph nodes, arthritis, and a rash known as erythema nodosum.The cause of sarcoidosis is unknown. Some believe it may be due to an immune reaction to a trigger such as an infection or chemicals in those who are genetically predisposed. Those with affected family members are at greater risk. Diagnosis is partly based on signs and symptoms, which may be supported by biopsy. Findings that make it likely include large lymph nodes at the root of the lung on both sides, high blood calcium with a normal parathyroid hormone level, or elevated levels of angiotensin-converting enzyme in the blood. The diagnosis should only be made after excluding other possible causes of similar symptoms such as tuberculosis.Sarcoidosis may resolve without any treatment within a few years. However, some people may have long-term or severe disease. Some symptoms may be improved with the use of anti-inflammatory drugs such as ibuprofen. In cases where the condition causes significant health problems, steroids such as prednisone are indicated. Medications such as methotrexate, chloroquine, or azathioprine may occasionally be used in an effort to decrease the side effects of steroids. The risk of death is  1–7%. The chance of the disease returning in someone who has had it previously is less than 5%.In 2015, pulmonary sarcoidosis and interstitial lung disease affected 1.9 million people globally and they resulted in 122,000 deaths. It is most common in Scandinavians, but occurs in all parts of the world. In the United States, risk is greater among black  people as opposed to white people. It usually begins between the ages of 20 and 50. It occurs more often in women than men. Sarcoidosis was first described in 1877 by the English doctor Jonathan Hutchinson as a non-painful skin disease.

Signs and symptoms
Sarcoidosis is a systemic inflammatory disease that can affect any organ, although it can be asymptomatic and is discovered by accident in about 5% of cases. Common symptoms, which tend to be vague, include fatigue (unrelieved by sleep; occurs in up to 85% of cases ), lack of energy, weight loss, joint aches and pains (which occur in about 70% of cases), arthritis (14–38% of cases), dry eyes, swelling of the knees, blurry vision, shortness of breath, a dry, hacking cough, or skin lesions. Less commonly, people may cough up blood. Sarcoidosis is also accompanied by psychological distress and symptoms of anxiety and depression, which are also associated with fatigue. The cutaneous symptoms vary, and range from rashes and noduli (small bumps) to erythema nodosum, granuloma annulare, or lupus pernio. Sarcoidosis and cancer may mimic one another, making the distinction difficult.The combination of erythema nodosum, bilateral hilar lymphadenopathy, and joint pain is called Löfgren syndrome, which has a relatively good prognosis. This form of the disease occurs significantly more often in Scandinavian patients than in those of non-Scandinavian origin.

Respiratory tract
Localization to the lungs is by far the most common manifestation of sarcoidosis. At least 90% of those affected experience lung involvement. Overall, about 50% develop permanent pulmonary abnormalities, and 5 to 15% have progressive fibrosis of the lung parenchyma. Sarcoidosis of the lung is primarily an interstitial lung disease in which the inflammatory process involves the alveoli, small bronchi, and small blood vessels. In acute and subacute cases,  physical examination usually reveals dry crackles. At least 5% of cases include pulmonary arterial hypertension. The upper respiratory tract (including the larynx, pharynx, and sinuses) may be affected, which occurs in between 5 and 10% of cases.The four stages of pulmonary involvement are based on radiological stage of the disease, which is helpful in prognosis:
Stage I: bilateral hilar lymphadenopathy (BHL) alone
Stage II: BHL with pulmonary infiltrates
Stage III: pulmonary infiltrates without BHL
Stage IV: fibrosisUse of the Scadding scale only provides general information regarding the prognosis of the pulmonary disease over time. Caution is recommended, as it only shows a general relation with physiological markers of the disease and the variation is such that it has limited applicability in individual assessments, including treatment decisions.

Skin
Sarcoidosis involves the skin in between 9 and 37% of cases and is more common in African Americans than in European Americans. The skin is the second-most commonly affected organ after the lungs. The most common lesions are erythema nodosum, plaques, maculopapular eruptions, subcutaneous nodules, and lupus pernio. Treatment is not required, since the lesions usually resolve spontaneously in 2–4 weeks. Although it may be disfiguring, cutaneous sarcoidosis rarely causes major problems. Sarcoidosis of the scalp presents with diffuse or patchy hair loss.

Heart
Histologically, sarcoidosis of the heart is an active granulomatous inflammation surrounded by reactive oedema. The distribution of affected areas is patchy with localised enlargement of heart muscles. This causes scarring and remodelling of the heart, which leads to dilatation of heart cavities and thinning of heart muscles. As the situation progresses, it leads to aneurysm of heart chambers. When the distribution is diffuse, there would be dilatation of both ventricles of the heart, causing heart failure and arrhythmia. When the conduction system in the intraventricular septum is affected, it would lead to heart block, ventricular tachycardia and ventricular arrhythmia, causing sudden death. Nevertheless, the involvement of pericardium and heart valves are uncommon.The frequency of cardiac involvement varies and is significantly influenced by race; in Japan, more than 25% of those with sarcoidosis have symptomatic cardiac involvement, whereas in the US and Europe, only about 5% of cases present with cardiac involvement. Autopsy studies in the US have revealed a frequency of cardiac involvement of about 20–30%, whereas autopsy studies in Japan have shown a frequency of 60%. The presentation of cardiac sarcoidosis can range from asymptomatic conduction abnormalities to fatal ventricular arrhythmia.Conduction abnormalities are the most common cardiac manifestations of sarcoidosis in humans and can include complete heart block. Second to conduction abnormalities, in frequency, are ventricular arrhythmias, which occurs in about 23% of cases with cardiac involvement. Sudden cardiac death, either due to ventricular arrhythmias or complete heart block is a rare complication of cardiac sarcoidosis. Cardiac sarcoidosis can cause fibrosis, granuloma formation, or the accumulation of fluid in the interstitium of the heart, or a combination of the former two. Cardiac sarcoidosis may also cause congestive heart failure when granulomas cause myocardial fibrosis and scarring. Congestive heart failure affects 25-75% of those with cardiac sarcoidosis. Diabetes mellitus and sarcoidosis-related arrhythmias are believed to be strong risk factors of heart failure in sarcoidosis. A small (20-40%) increased risk of acute myocardial infarction has also been described. Pulmonary arterial hypertension occurs by two mechanisms in cardiac sarcoidosis: reduced left heart function due to granulomas weakening the heart muscle or from impaired blood flow.

Eye
Eye involvement occurs in about 10–90% of cases. Manifestations in the eye include uveitis, uveoparotitis, and retinal inflammation, which may result in loss of visual acuity or blindness. The most common ophthalmologic manifestation of sarcoidosis is uveitis. The combination of anterior uveitis, parotitis, VII cranial nerve paralysis and fever is called uveoparotid fever or Heerfordt syndrome (D86.8). Development of scleral nodule associated with sarcoidosis has been observed.

Nervous system
Any of the components of the nervous system can be involved. Sarcoidosis affecting the nervous system is known as neurosarcoidosis. Cranial nerves are most commonly affected, accounting for about 5–30% of neurosarcoidosis cases, and peripheral facial nerve palsy, often bilateral, is the most common neurological manifestation of sarcoidosis. It occurs suddenly and is usually transient. The central nervous system involvement is present in 10–25% of sarcoidosis cases. Other common manifestations of neurosarcoidosis include optic nerve dysfunction, papilledema, palate dysfunction, neuroendocrine changes, hearing abnormalities, hypothalamic and pituitary abnormalities, chronic meningitis, and peripheral neuropathy. Myelopathy, that is spinal cord involvement, occurs in about 16–43% of neurosarcoidosis cases and is often associated with the poorest prognosis of the neurosarcoidosis subtypes. Whereas facial nerve palsies and acute meningitis due to sarcoidosis tend to have the most favourable prognosis, another common finding in sarcoidosis with neurological involvement is autonomic or sensory small-fiber neuropathy. Neuroendocrine sarcoidosis accounts for about 5–10% of neurosarcoidosis cases and can lead to diabetes insipidus, changes in menstrual cycle and hypothalamic dysfunction. The latter can lead to changes in body temperature, mood, and prolactin (see the endocrine and exocrine section for details).

Endocrine and exocrine
Prolactin is frequently increased in sarcoidosis, between 3 and 32% of cases have hyperprolactinemia this frequently leads to amenorrhea, galactorrhea, or nonpuerperal mastitis in women. It also frequently causes an increase in 1,25-dihydroxy vitamin D, the active metabolite of vitamin D, which is usually hydroxylated within the kidney, but in sarcoidosis patients, hydroxylation of vitamin D can occur outside the kidneys, namely inside the immune cells found in the granulomas the condition produces. 1,25-dihydroxy vitamin D is the main cause for hypercalcemia in sarcoidosis and is overproduced by sarcoid granulomata. Gamma-interferon produced by activated lymphocytes and macrophages plays a major role in the synthesis of 1 alpha, 25(OH)2D3. Hypercalciuria (excessive secretion of calcium in ones urine) and hypercalcemia (an excessively high amount of calcium in the blood) are seen in <10% of individuals and likely results from the increased 1,25-dihydroxy vitamin D production.Thyroid dysfunction is seen in 4.2–4.6% of cases.Parotid enlargement occurs in about 5–10% of cases. Bilateral involvement is the rule. The gland is usually not tender, but firm and smooth. Dry mouth can occur; other exocrine glands are affected only rarely. The eyes, their glands, or the parotid glands are affected in 20–50% of cases.

Gastrointestinal and genitourinary
Symptomatic gastrointestinal (GI)  involvement occurs in less than 1% of cases (if one excludes the liver), and most commonly the stomach is affected, although the small or large intestine may also be affected in a small portion of cases. Studies at autopsy have revealed GI involvement in less than 10% of people. These cases would likely mimic Crohns disease, which is a more commonly intestine-affecting granulomatous disease. About 1–3% of people have evidence of pancreatic involvement at autopsy. Symptomatic kidney involvement occurs in just 0.7% of cases, although evidence of kidney involvement at autopsy has been reported in up to 22% of people and occurs exclusively in cases of chronic disease. Symptomatic kidney involvement is usually nephrocalcinosis, although granulomatous interstitial nephritis that presents with reduced creatinine clearance and little proteinuria is a close second. Less commonly, the epididymis, testicles, prostate, ovaries, fallopian tubes, uterus, or the vulva may be affected, the latter may cause vulva itchiness. Testicular involvement has been reported in about 5% of people at autopsy. In males, sarcoidosis may lead to infertility.Around 70% of people have granulomas in their livers, although only in about 20–30% of cases, liver function test anomalies reflecting this fact are seen. About 5–15% of patients exhibit hepatomegaly. Only 5–30% of cases of liver involvement are symptomatic. Usually, these changes reflect a cholestatic pattern and include raised levels of alkaline phosphatase (which is the most common liver function test anomaly seen in those with sarcoidosis), while bilirubin and aminotransferases are only mildly elevated. Jaundice is rare.

Blood
Abnormal blood tests are frequent, accounting for over 50% of cases, but are not diagnostic. Lymphopenia is the most common blood anomaly in sarcoidosis. Anemia occurs in about 20% of people with sarcoidosis. Leukopenia is less common and occurs in even fewer cases but is rarely severe. Thrombocytopenia and hemolytic anemia are fairly rare. In the absence of splenomegaly, leukopenia may reflect bone marrow involvement, but the most common mechanism is a redistribution of blood T cells to sites of disease. Other nonspecific findings include monocytosis, occurring in the majority of sarcoidosis cases, increased hepatic enzymes or alkaline phosphatase. People with sarcoidosis often have immunologic anomalies like allergies to test antigens such as Candida or purified protein derivative. Polyclonal hypergammaglobulinemia is also a fairly common immunologic anomaly seen in sarcoidosis.Lymphadenopathy (swollen glands) is common in sarcoidosis and occurs in 15% of cases. Intrathoracic nodes are enlarged in 75 to 90% of all people; usually this involves the hilar nodes, but the paratracheal nodes are commonly involved. Peripheral lymphadenopathy is very common, particularly involving the cervical (the most common head and neck manifestation of the disease), axillary, epitrochlear, and inguinal nodes. Approximately 75% of cases show microscopic involvement of the spleen, although only in about 5–10% of cases does splenomegaly appear.

Bone, joints, and muscles
Sarcoidosis can be involved with the joints, bones, and muscles. This causes a wide variety of musculoskeletal complaints that act through different mechanisms.
About 5–15% of cases affect the bones, joints, or muscles.Arthritic syndromes can be categorized as acute or chronic.
Sarcoidosis patients with acute arthritis often also have bilateral hilar lymphadenopathy and erythema nodosum. These three associated syndromes often occur together in Löfgren syndrome. The arthritis symptoms of Löfgren syndrome occur most frequently in the ankles, followed by the knees, wrists, elbows, and metacarpophalangeal joints. Usually, true arthritis is not present, but instead, periarthritis appears as a swelling in the soft tissue around the joints that can be seen by ultrasonographic methods.
These joint symptoms tend to precede or occur at the same time as erythema nodosum develops. Even when erythema nodosum is absent, it is believed that the combination of hilar lymphadenopathy and ankle periarthritis can be considered as a variant of Löfgren syndrome.Enthesitis also occurs in about one-third of patients with acute sarcoid arthritis, mainly affecting the Achilles tendon and heels. Soft-tissue swelling of the ankles can be prominent, and biopsy of this soft tissue reveals no granulomas, but does show panniculitis similar to erythema nodosum.Chronic sarcoid arthritis usually occurs in the setting of more diffuse organ involvement. The ankles, knees, wrists, elbows, and hands may all be affected in the chronic form and often this presents itself in a polyarticular pattern. Dactylitis similar to that seen in psoriatic arthritis, that is associated with pain, swelling, overlying skin erythema, and underlying bony changes may also occur. Development of Jaccoud arthropathy (a nonerosive deformity) is very rarely seen.Bone involvement in sarcoidosis has been reported in 1–13% of cases. The most frequent sites of involvement are the hands and feet, whereas the spine is less commonly affected. Half of the patients with bony lesions experience pain and stiffness, whereas the other half remain asymptomatic.Periostitis is rarely seen in sarcoidosis and has been found to present itself at the femoral bone.

Cause
The exact cause of sarcoidosis is not known. The current working hypothesis is, in genetically susceptible individuals, sarcoidosis is caused through alteration to the immune response after exposure to an environmental, occupational, or infectious agent. Some cases may be caused by treatment with tumor necrosis factor (TNF) inhibitors like etanercept.

Genetics
The heritability of sarcoidosis varies according to ethnicity. About 20% of African Americans with sarcoidosis have a family member with the condition, whereas the same figure for European Americans is about 5%. Additionally, in African Americans, who seem to experience more severe and chronic disease, siblings and parents of sarcoidosis cases have about a 2.5-fold increased risk for developing the disease. In Swedish individuals heritability was found to be 39%. In this group, if a first-degree family member was affected, a person has a four-fold greater risk of being affected.Investigations of genetic susceptibility yielded many candidate genes, but only few were confirmed by further investigations and no reliable genetic markers are known.  Currently, the most interesting candidate gene is BTNL2; several HLA-DR risk alleles are also being investigated. In persistent sarcoidosis, the HLA haplotype HLA-B7-DR15 is either cooperating in disease or another gene between these two loci is associated. In nonpersistent disease,  a strong genetic association exists with HLA DR3-DQ2.  Cardiac sarcoid has been connected to tumor necrosis factor alpha (TNFA) variants.

Infectious agents
Several infectious agents appear to be significantly associated with sarcoidosis, but none of the known associations is specific enough to suggest a direct causative role. The major implicated infectious agents include: mycobacteria, fungi, borrelia, and rickettsia. A meta-analysis investigating the role of mycobacteria in sarcoidosis found it was present in 26.4% of cases, but they also detected a possible publication bias, so the results need further confirmation. Mycobacterium tuberculosis catalase-peroxidase has been identified as a possible antigen catalyst of sarcoidosis. The disease has also been reported by transmission via organ transplants. A large epidemiological study found little evidence that infectious diseases spanning years before sarcoidosis diagnosis could confer measurable risks for sarcoidosis diagnosis in the future.

Autoimmune
Association of autoimmune disorders has been frequently observed. The exact mechanism of this relation is not known, but some evidence supports the hypothesis that this is a consequence of Th1 lymphokine prevalence. Tests of delayed cutaneous hypersensitivity have been used to measure progression.

Pathophysiology
Granulomatous inflammation is characterized primarily by the accumulation of macrophages and activated T-lymphocytes, with increased production of key inflammatory mediators, tumor necrosis factor alpha (TNF), interferon gamma, interleukin 2 (IL-2), IL-8, IL-10, IL-12, IL-18, IL-23 and transforming growth factor beta (TGF-β), indicative of a T helper cell-mediated immune response.
Sarcoidosis has paradoxical effects on inflammatory processes; it is characterized by increased macrophage and CD4 helper T-cell activation, resulting in accelerated inflammation, but immune response to antigen challenges such as tuberculin is suppressed. This paradoxic state of simultaneous hyper- and hypoactivity is suggestive of a state of anergy. The anergy may also be responsible for the increased risk of infections and cancer. The regulatory T-lymphocytes in the periphery of sarcoid granulomas appear to suppress IL-2 secretion, which is hypothesized to cause the state of anergy by preventing antigen-specific memory responses.While TNF is widely believed to play an important role in the formation of granulomas (this is further supported by the finding that in animal models of mycobacterial granuloma formation inhibition of either TNF or IFN-γ production inhibits granuloma formation), sarcoidosis can and does still develop in those being treated with TNF antagonists like etanercept.
B cells also likely play a role in the pathophysiology of sarcoidosis. Serum levels of soluble human leukocyte antigen (HLA) class I antigens and angiotensin converting enzyme (ACE) are higher in people with sarcoidosis. Likewise the ratio of CD4/CD8 T cells in bronchoalveolar lavage is usually higher in people with pulmonary sarcoidosis (usually >3.5), although it can be normal or even abnormally low in some cases. Serum ACE levels have been found to usually correlate with total granuloma load.Cases of sarcoidosis have also been reported as part of the immune reconstitution syndrome of HIV, that is, when people receive treatment for HIV, their immune system rebounds and the result is that it starts to attack the antigens of opportunistic infections caught prior to said rebound and the resulting immune response starts to damage healthy tissue.

Histopathology
Sarcoidosis is characterized by the formation of non-necrotizing ("non-caseating") granulomas in various organs and tissues. Giant cells, specifically Langhans giant cells, are often seen in sarcoidosis. Schaumann bodies seen in sarcoidosis are calcium and protein inclusions inside of giant cells as part of a granuloma. Asteroid bodies can be seen in sarcoidosis. Hamazaki–Wesenberg bodies can be seen in lymph nodes and more rarely in lung biopsies with sarcoidosis and are inclusion bodies of lysosomes with protein, glycoprotein and iron.

Diagnosis
Diagnosis of sarcoidosis is a matter of exclusion, as there is no specific test for the condition. To exclude sarcoidosis in a case presenting with pulmonary symptoms might involve a chest radiograph, CT scan of chest, PET scan, CT-guided biopsy, mediastinoscopy, open lung biopsy, bronchoscopy with biopsy, endobronchial ultrasound, and endoscopic ultrasound with fine-needle aspiration of mediastinal lymph nodes (EBUS FNA). Tissue from biopsy of lymph nodes is subjected to both flow cytometry to rule out cancer and special stains (acid fast bacilli stain and Gömöri methenamine silver stain) to rule out microorganisms and fungi.Serum markers of sarcoidosis, include: serum amyloid A, soluble interleukin-2 receptor, lysozyme, angiotensin converting enzyme, and the glycoprotein KL-6. Angiotensin-converting enzyme blood levels are used in the monitoring of sarcoidosis. A bronchoalveolar lavage can show an elevated (of at least 3.5) CD4/CD8 T cell ratio, which is indicative (but not proof) of pulmonary sarcoidosis. In at least one study the induced sputum ratio of CD4/CD8 and level of TNF was correlated to those in the lavage fluid. A sarcoidosis-like lung disease called granulomatous–lymphocytic interstitial lung disease can be seen in patients with common variable immunodeficiency (CVID) and therefore serum antibody levels should be measured to exclude CVID.Differential diagnosis includes metastatic disease, lymphoma, septic emboli, rheumatoid nodules, granulomatosis with polyangiitis, varicella infection, tuberculosis, and atypical infections, such as Mycobacterium avium complex, cytomegalovirus, and cryptococcus. Sarcoidosis is confused most commonly with neoplastic diseases, such as lymphoma, or with disorders characterized also by a mononuclear cell granulomatous inflammatory process, such as the mycobacterial and fungal disorders.Chest radiograph changes are divided into four stages:
bihilar lymphadenopathy
bihilar lymphadenopathy and reticulonodular infiltrates
bilateral pulmonary infiltrates
fibrocystic sarcoidosis typically with upward hilar retraction, cystic and bullous changesAlthough people with stage 1 radiographs tend to have the acute or subacute, reversible form of the disease, those with stages 2 and 3 often have the chronic, progressive disease; these patterns do not represent consecutive "stages" of sarcoidosis. Thus, except for epidemiologic purposes, this categorization is mostly of historic interest.In sarcoidosis presenting in the Caucasian population, hilar adenopathy and erythema nodosum are the most common initial symptoms. In this population, a biopsy of the gastrocnemius muscle is a useful tool in correctly diagnosing the person. The presence of a noncaseating epithelioid granuloma in a gastrocnemius specimen is definitive evidence of sarcoidosis, as other tuberculoid and fungal diseases extremely rarely present histologically in this muscle.Cardiac magnetic resonance imaging (CMR) is one modality for diagnosing cardiac sarcoidosis. It has 78% specificity in diagnosing cardiac sarcoidosis. Its T2-weighted imaging can detect acute inflammation. Meanwhile, late gadolinium contrast (LGE) can detect fibrosis or scar. Lesions at the subpericardium and midwall enhancement of basal septum or inferolateral wall is strongly suggestive of sarcoidosis. MRI can also follow up on the treatment efficacy of corticosteroids and prognosis of cardiac sarcoidosis.PET scan is able to quantify disease activity which cannot be performed by CMR.

Classification
Sarcoidosis may be divided into the following types:

Treatment
Treatments for sarcoidosis vary greatly depending on the patient. At least half of patients require no systemic therapy. Most people (>75%) only require symptomatic treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen or aspirin. For those presenting with lung symptoms, unless the respiratory impairment is devastating, active pulmonary sarcoidosis is observed usually without therapy for two to three months; if the inflammation does not subside spontaneously, therapy is instituted.Major categories of drug interventions include glucocorticoids, antimetabolites, biologic agents especially monoclonal anti-tumor necrosis factor antibodies. Investigational treatments include specific antibiotic combinations and mesenchymal stem cells. If drug intervention is indicated, a step-wise approach is often used to explore alternatives in order of increasing side effects and to monitor potentially toxic effects.Corticosteroids, most commonly prednisone or prednisolone, have been the standard treatment for many years. In some people, this treatment can slow or reverse the course of the disease, but other people do not respond to steroid therapy. The use of corticosteroids in mild disease is controversial because in many cases the disease remits spontaneously.

Antimetabolites
Antimetabolites, also categorized as steroid-sparing agents, such as azathioprine, methotrexate, mycophenolic acid, and leflunomide are often used as alternatives to corticosteroids. Of these, methotrexate is most widely used and studied. Methotrexate is considered a first-line treatment in neurosarcoidosis, often in conjunction with corticosteroids. Long-term treatment with methotrexate is associated with liver damage in about 10% of people and hence may be a significant concern in people with liver involvement and requires regular liver function test monitoring. Methotrexate can also lead to pulmonary toxicity (lung damage), although this is fairly uncommon and more commonly it can confound the leukopenia caused by sarcoidosis. Due to these safety concerns it is often recommended that methotrexate is combined with folic acid in order to prevent toxicity. Azathioprine treatment can also lead to liver damage. However, the risk of infection appears to be about 40% lower in those treated with methotrexate instead of azathioprine. Leflunomide is being used as a replacement for methotrexate, possibly due to its purportedly lower rate of pulmonary toxicity. Mycophenolic acid has been used successfully in uveal sarcoidosis, neurosarcoidosis (especially CNS sarcoidosis; minimally effective in sarcoidosis myopathy), and pulmonary sarcoidosis.

Immunosuppressants
As the granulomas are caused by collections of immune system cells, particularly T cells, there has been some success using immunosuppressants (like cyclophosphamide, cladribine, chlorambucil, and cyclosporine), immunomodulatory (pentoxifylline and thalidomide), and anti-tumor necrosis factor treatment (such as infliximab, etanercept, golimumab, and adalimumab).In a clinical trial cyclosporine added to prednisone treatment failed to demonstrate any significant benefit over prednisone alone in people with pulmonary sarcoidosis, although there was evidence of increased toxicity from the addition of cyclosporine to the steroid treatment including infections, malignancies (cancers), hypertension, and kidney dysfunction. Likewise chlorambucil and cyclophosphamide are seldom used in the treatment of sarcoidosis due to their high degree of toxicity, especially their potential for causing malignancies. Infliximab has been used successfully to treat pulmonary sarcoidosis in clinical trials in a number of cases. Etanercept, on the other hand, has failed to demonstrate any significant efficacy in people with uveal sarcoidosis in a couple of clinical trials. Likewise golimumab has failed to show any benefit in those with pulmonary sarcoidosis. One clinical trial of adalimumab found treatment response in about half of subjects, which is similar to that seen with infliximab, but as adalimumab has better tolerability profile it may be preferred over infliximab.

Specific organ treatments
Ursodeoxycholic acid has been used successfully as a treatment for cases with liver involvement. Thalidomide has also been tried successfully as a treatment for treatment-resistant lupus pernio in a clinical trial, which may stem from its anti-TNF activity, although it failed to exhibit any efficacy in a pulmonary sarcoidosis clinical trial. Cutaneous disease may be successfully managed with antimalarials (such as chloroquine and hydroxychloroquine) and the tetracycline antibiotic, minocycline. Antimalarials have also demonstrated efficacy in treating sarcoidosis-induced hypercalcemia and neurosarcoidosis. Long-term use of antimalarials is limited, however, by their potential to cause irreversible blindness and hence the need for regular ophthalmologic screening. This toxicity is usually less of a problem with hydroxychloroquine than with chloroquine, although hydroxychloroquine can disturb the glucose homeostasis.Recently selective phosphodiesterase 4 (PDE4) inhibitors like apremilast (a thalidomide derivative), roflumilast, and the less subtype-selective PDE4 inhibitor, pentoxifylline, have been tried as a treatment for sarcoidosis, with successful results being obtained with apremilast in cutaneous sarcoidosis in a small open-label study. Pentoxifylline has been used successfully to treat acute disease although its use is greatly limited by its gastrointestinal toxicity (mostly nausea, vomiting, and diarrhea). Case reports have supported the efficacy of rituximab, an anti-CD20 monoclonal antibody and a clinical trial investigating atorvastatin as a treatment for sarcoidosis is under-way. ACE inhibitors have been reported to cause remission in cutaneous sarcoidosis and improvement in pulmonary sarcoidosis, including improvement in pulmonary function, remodeling of lung parenchyma and prevention of pulmonary fibrosis in separate case series. Nicotine patches have been found to possess anti-inflammatory effects in sarcoidosis patients, although whether they had disease-modifying effects requires further investigation. Antimycobacterial treatment (drugs that kill off mycobacteria, the causative agents behind tuberculosis and leprosy) has also proven itself effective in treating chronic cutaneous (that is, it affects the skin) sarcoidosis in one clinical trial. Quercetin has also been tried as a treatment for pulmonary sarcoidosis with some early success in one small trial.Because of its uncommon nature, the treatment of male reproductive tract sarcoidosis is controversial. Since the differential diagnosis includes testicular cancer, some recommend orchiectomy, even if evidence of sarcoidosis in other organs is present. In the newer approach, testicular, epididymal biopsy and resection of the largest lesion has been proposed.

Symptoms
People with sarcoidosis may have a range of symptoms that do not correspond with objective physical evidence of disease but that still decrease quality of life.Physical therapy, rehabilitation, and counseling can help avoid deconditioning,: 733  and improve social participation, psychological well-being, and activity levels. Key aspects are avoiding exercise intolerance and muscle weakness.: 734 Low or moderate-intensity physical training has been shown to improve fatigue, psychological health, and physical functioning in people sarcoidosis without adverse effects. Inspiratory muscle training has also decreased severe fatigue perception in subjects with early stages of sarcoidosis, as well as improving functional and maximal exercise capacity and respiratory muscle strength. The duration, frequency, and physical intensity of exercise needs to accommodate impairments such as joint pain, muscle pain, and fatigue.: 734 Neurostimulants such as methylphenidate and modafinil have shown some effectiveness as an adjunct for treatment of sarcoidosis fatigue.: 733 Treatments for symptomatic neuropathic pain in sarcoidosis patients is similar to that for other causes, and include antidepressants, anticonvulsants and prolonged-release opioids, however, only 30 to 60% of patients experience limited pain relief.: 733

Prognosis
The disease can remit spontaneously or become chronic, with exacerbations and remissions. In some cases, it can progress to pulmonary fibrosis and death. In benign cases, remission can occur in 24 to 36 months without treatment but regular follow ups are required. Some cases, however, may persist several decades. Two-thirds of people with the condition achieve a remission within 10 years of the diagnosis. When the heart is involved, the prognosis is generally less favourable, though corticosteroids appear effective in improving AV conduction. The prognosis tends to be less favourable in African Americans than in white Americans. In a Swedish population-based analysis, the majority of cases who did not have severe disease at diagnosis had comparable mortality to the general population. The risk for premature death was markedly (2.3-fold) increased compared to the general population for a smaller group of cases with severe disease at diagnosis. Serious infections, sometimes multiple during the course of disease, and heart failure might contribute to the higher risk of early death in some patients with sarcoidosis.Some 1990s studies indicated that people with sarcoidosis appear to be at significantly increased risk for cancer, in particular lung cancer, lymphomas, and cancer in other organs known to be affected in sarcoidosis. In sarcoidosis-lymphoma syndrome, sarcoidosis is followed by the development of a lymphoproliferative disorder such as non-Hodgkin lymphoma.  This may be attributed to the underlying immunological abnormalities that occur during the sarcoidosis disease process. Sarcoidosis can also follow cancer or occur concurrently with cancer. There have been reports of hairy cell leukemia, acute myeloid leukemia, and acute myeloblastic leukemia associated with sarcoidosis. Sometimes, sarcoidosis, even untreated, can be complicated by opportunistic infections although these are rare.

Epidemiology
Sarcoidosis most commonly affects young adults of both sexes, although studies have reported more cases in females. Incidence is highest for individuals younger than 40 and peaks in the age-group from 20 to 29 years; a second peak is observed for women over 50.Sarcoidosis occurs throughout the world in all races with an average incidence of 16.5 per 100,000 in men and 19 per 100,000 in women. The disease is most common in Northern European countries and the highest annual incidence of 60 per 100,000 is found in Sweden and Iceland. In the United Kingdom the prevalence is 16 in 100,000. In the United States, sarcoidosis is more common in people of African descent than Caucasians, with annual incidence reported as 35.5 and 10.9 per 100,000, respectively. Sarcoidosis is less commonly reported in South America, Spain, India, Canada, and the Philippines. There may be a higher susceptibility to sarcoidosis in those with celiac disease. An association between the two disorders has been suggested.There also has been a seasonal clustering observed in sarcoidosis-affected individuals. In Greece about 70% of diagnoses occur between March and May every year, in Spain about 50% of diagnoses occur between April and June, and in Japan it is mostly diagnosed during June and July.The differing incidence across the world may be at least partially attributable to the lack of screening programs in certain regions of the world, and the overshadowing presence of other granulomatous diseases, such as tuberculosis, that may interfere with the diagnosis of sarcoidosis where they are prevalent. There may also be differences in the severity of the disease between people of different ethnicities. Several studies suggest the presentation in people of African origin may be more severe and disseminated than for Caucasians, who are more likely to have asymptomatic disease. Manifestation appears to be slightly different according to race and sex. Erythema nodosum is far more common in men than in women and in Caucasians than in other races. In Japanese people, ophthalmologic and cardiac involvement are more common than in other races.It is more common in certain occupations, namely firefighters, educators, military personnel, those who work in industries where pesticides are used, law enforcement, and healthcare personnel. In the year after the September 11 attacks, the rate of sarcoidosis incidence went up four-fold (to 86 cases per 100,000).

History
It was first described in 1877 by Dr. Jonathan Hutchinson, a dermatologist as a condition causing red, raised rashes on the face, arms, and hands. In 1889 the term lupus pernio was coined by Dr. Ernest Besnier, another dermatologist. Later in 1892 lupus pernios histology was defined. In 1902 bone involvement was first described by a group of three doctors. Between 1909 and 1910 uveitis in sarcoidosis was first described, and later in 1915 it was emphasised, by Dr. Jörgen Nielsen Schaumann, that it was a systemic condition. This same year lung involvement was also described. In 1937 uveoparotid fever was first described and likewise in 1941 Löfgren syndrome was first described. In 1958 the first international conference on sarcoidosis was called in London, likewise the first USA sarcoidosis conference occurred in Washington, D.C., in the year 1961. It has also been called Besnier–Boeck disease or Besnier–Boeck–Schaumann disease.

Etymology
The word "sarcoidosis" comes from Greek [σάρκο-] sarco- meaning "flesh", the suffix -(e)ido (from the Greek εἶδος -eidos [usually omitting the initial e in English as the diphthong epsilon-iota in Classic Greek stands for a long "i" = English ee]) meaning "type", " resembles" or "like", and -sis, a common suffix in Greek meaning "condition". Thus the whole word means "a condition that resembles crude flesh".  The first cases of sarcoïdosis, which were recognised as a new pathological entity, in Scandinavia, at the end of the 19th century exhibited skin nodules resembling cutaneous sarcomas, hence the name initially given.

Society and culture
The World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) is an organisation of physicians involved in the diagnosis and treatment of sarcoidosis and related conditions. WASOG publishes the journal Sarcoidosis, Vasculitis and Diffuse Lung Diseases. Additionally, the Foundation for Sarcoidosis Research (FSR) is devoted to supporting research into sarcoidosis and its possible treatments.There have been concerns that World Trade Center rescue workers are at a heightened risk for sarcoidosis.Comedian and actor Bernie Mac had sarcoidosis. In 2005, he mentioned that the disease was in remission. His death on 9 August 2008 was caused by complications from pneumonia, though Macs agent states the sarcoidosis was not related to his fatal pneumonia.Karen "Duff" Duffy, MTV personality and actress, was diagnosed with neurosarcoidosis in 1995.American football player Reggie White died in 2004, with pulmonary and cardiac sarcoidosis being contributing factors to his fatal heart arrhythmia.Singer Sean Levert died in 2008 of sarcoidosis complications.Joseph Rago, Pulitzer Prize-winning writer known for his work at The Wall Street Journal, died of sarcoidosis complications in 2017.Several historical figures are suspected of having sarcoidosis. In a 2014 letter to the British medical journal The Lancet, it was suggested that the French Revolution leader Maximilien Robespierre may have had sarcoidosis, causing him impairment during his time as head of the Reign of Terror. The symptoms associated with Ludwig van Beethovens 1827 death have been described as possibly consistent with sarcoidosis. Author Robert Louis Stevenson (1850–1894) had a history of chronic coughs and chest complaints, and sarcoidosis has been suggested as a diagnosis.

Pregnancy
Sarcoidosis generally does not prevent successful pregnancy and delivery; the increase in estrogen levels during pregnancy may even have a slightly beneficial immunomodulatory effect </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 Glossitis and can you explain it in depth? [/INST] Glossitis can mean soreness of the tongue, or more usually inflammation with depapillation of the dorsal surface of the tongue (loss of the lingual papillae), leaving a smooth and erythematous (reddened) surface, (sometimes specifically termed atrophic glossitis). In a wider sense, glossitis can mean inflammation of the tongue generally. Glossitis is often caused by nutritional deficiencies and may be painless or cause discomfort. Glossitis usually responds well to treatment if the cause is identified and corrected. Tongue soreness caused by glossitis is differentiated from burning mouth syndrome, where there is no identifiable change in the appearance of the tongue, and there are no identifiable causes.

Symptoms
Depending upon what exact meaning of the word glossitis is implied, signs and symptoms might include:

Smooth, shiny appearance of the tongue, caused by loss of lingual papillae.
Tongue color changes, usually to a darker red color than the normal white-pink color of a healthy tongue.
Tongue swelling.
Difficulty with chewing, swallowing, or speaking (either because of tongue soreness or tongue swelling).
Burning sensation. Some use the term secondary burning mouth syndrome in cases where a detectable cause, such as glossitis, for an oral burning sensation.Depending upon the underlying cause, there may be additional signs and symptoms such as pallor, oral ulceration and angular cheilitis.

Causes
Anemias
Iron-deficiency anemia is mainly caused by blood loss, such as may occur during menses or gastrointestinal hemorrhage. This often results in a depapilled, atrophic glossitis, giving the tongue a bald and shiny appearance, along with pallor (paleness) of the lips and other mucous membranes a tendency towards recurrent oral ulceration, and cheilosis (swelling of the lips). The appearance of the tongue in iron deficiency anemia has been described as diffuse or patchy atrophy with tenderness or burning. One cause of iron deficiency anemia is sideropenic dysphagia (Plummer–Vinson or Paterson–Brown–Kelly syndrome) which is also characterized by esophageal webbing and dysphagia.Pernicious anemia is usually caused by autoimmune destruction of gastric parietal cells. Parietal cells secrete intrinsic factor which is required for the absorption of vitamin B12. Vitamin B12 deficiency results in megaloblastic anemia and may present as glossitis. The appearance of the tongue in vitamin B12 deficiency is described as "beefy"
or "fiery red and sore". There may be linear or patchy red lesions.

Vitamin B deficiencies
Vitamin B1 deficiency (thiamine deficiency) can cause glossitis. Vitamin B2 deficiency (ariboflavinosis) can cause glossitis, along with angular cheilitis, cheilosis, peripheral neuropathy and other signs and symptoms. The glossitis in vitamin B2 deficiency is described as magenta.  Vitamin B3 deficiency (pellagra) can cause glossitis. Vitamin B6 deficiency (pyridoxine deficiency) can cause glossitis, along with  angular cheilitis, cheilosis, peripheral neuropathy and seborrheic dermatitis. Folate deficiency (vitamin B9 deficiency) can cause glossitis, along with macrocytic anemia, thrombocytopenia, leukopenia, diarrhea, fatigue and possibly neurological signs. Apart from pernicious anemia discussed above, any other cause of vitamin B12 deficiency can cause glossitis, which tends to be painful, smooth and shiny.

Infections
Bacterial, viral or fungal infections can cause glossitis. Chronic Candida infections of the tongue can cause an atrophic glossitis known as median rhomboid glossitis.Syphilis is now relatively rare, but the tertiary stage can cause diffuse glossitis and atrophy of lingual papillae, termed "syphilitic glossitis", "luetic glossitis" or "atrophic glossitis of tertiary syphilis". It is caused by Treponema pallidum and is a sexually transmitted infection.

Other causes
Many conditions can cause glossitis via malnutrition or malabsorption, which creates the nutritional deficiencies described above, although other mechanisms may be involved in some of those conditions listed.

Alcoholism
Sprue (celiac disease, or tropical sprue), secondary to nutritional deficiencies
Crohn’s disease
Whipple disease
Glucagonoma syndrome
Cowden disease
Acquired immunodeficiency syndrome (AIDS)
Carcinoid syndrome
Kwashiorkor amyloidosis
Veganism and other specialized diets, without B12 supplementation.
Poor hydration and low saliva in the mouth, which allows bacteria to grow more readily
Mechanical irritation or injury from burns, rough edges of teeth or dental appliances, or other trauma
Tongue piercing Glossitis can be caused by the constant irritation by the ornament and by colonization of Candida albicans in site and on the ornament
Exposure to irritants such as tobacco, alcohol, hot foods, or spices
Allergic reaction to toothpaste, mouthwash, breath fresheners, dyes in confectionery, plastic in dentures or retainers, or certain blood-pressure medications (ACE inhibitors)
Administration of ganglion blockers (e.g., Tubocurarine, Mecamylamine).
Oral lichen planus, erythema multiforme, aphthous ulcer, pemphigus vulgaris
Heredity
Albuterol (bronchodilator medicine)A painful tongue may be an indication of an underlying serious medical condition and nearly always merits assessment by a physician or dental surgeon.

Diagnosis
Classification
Glossitis could be classified as a group of tongue diseases or gastrointestinal diseases. It may be primary, where there is no underlying cause, or secondary where it is a sign or symptom of another condition. It can be acute or chronic. Generally speaking, there are several clinical patterns of glossitis, some more common than others.

Atrophic glossitis
Atrophic glossitis, also known as bald tongue, smooth tongue, Hunter glossitis, Moeller glossitis, or Möller-Hunter glossitis, is a condition characterized by a smooth glossy tongue that is often tender/painful, caused by complete atrophy of the lingual papillae (depapillation). The dorsal tongue surface may be affected totally, or in patches, and may be associated with a burning sensation, pain and/or erythema. Atrophic glossitis is a non-specific finding, and has a great many causes, usually related to iron-deficiency anemia, pernicious anemia, B vitamin complex deficiencies, unrecognized and untreated celiac disease (which often presents without gastrointestinal symptoms), or other factors such as xerostomia (dry mouth). Although the terms Möller and Hunter glossitis were originally used to refer to specifically the glossitis that occurs in vitamin B12 deficiency secondary to pernicious anemia, they are now used as synonyms for atrophic glossitis generally. In this article, the term glossitis, unless otherwise specified, refers to atrophic glossitis.
Candidiasis may be a concurrent finding or an alternative cause of erythema, burning, and atrophy.

Median rhomboid glossitis
This condition is characterized by a persistent erythematous, rhomboidal depapillated lesion in the central area of the dorsum of the tongue, just in front of the circumvallate papillae. Median rhomboid glossitis is a type of oral candidiasis, and rarely causes any symptoms. It is treated with antifungal medication. Predisposing factors include use of corticosteroid sprays or inhalers or immunosuppression.

Benign migratory glossitis
Geographic tongue, also termed benign migratory glossitis, is a common condition which usually affects the dorsal surface of the tongue. It is characterized by patches of depapillation and erythema bordered by a whitish peripheral zone. These patches give the tongue the appearance of a map, hence the name. Unlike glossitis due to nutritional deficiencies and anemia, the lesions of geographic tongue move around the tongue over time. This is because in geographic tongue, new areas of the tongue become involved with the condition whilst previously affected areas heal, giving the appearance of a moving lesion. The cause is unknown, and there is no curative treatment. Rarely are there any symptoms associated with the lesions, but occasionally a burning sensation may be present, which is exacerbated by eating hot, spicy or acidic foodstuffs. Some consider geographic tongue to be an early stage of fissured tongue, since the two conditions often occur in combination.

Geometric glossitis
Geometric glossitis, also termed herpetic geometric glossitis, is a term used by some to refer to a chronic lesion associated with herpes simplex virus (HSV) type I infection, in which there is a deep fissure in the midline of the tongue, which gives off multiple branches. The lesion is usually very painful, and there may be erosions present in the depths of the fissures. Similar fissured lesions which are not associated with HSV, as may occur in fissured tongue, do not tend to be painful. The name comes from the geometric pattern of the fissures which are longitudinal, crossed or branched.  It is described as occurring in immunocompromized persons, e.g. who have leukemia. However, the association between herpes simplex and geometric glossitis is disputed by some due to a lack of gold standard techniques for diagnosis of intraoral herpetic lesions, and the high prevalence of asymptomatic viral shedding in immunocompromized individuals. Treatment is with systemic aciclovir.

Strawberry tongue
Strawberry tongue, or raspberry tongue, is glossitis which manifests with hyperplastic (enlarged) fungiform papillae, giving the appearance of a strawberry. White strawberry tongue is where there is a white coating on the tongue through which the hyperplastic fungiform papillae protrude. Red strawberry tongue is where the white coating is lost and a dark red, erythematous surface is revealed, interspaced with the hyperplastic fungiform papillae. White strawberry tongue is seen in early scarlet fever (a systemic infection of group A β- hemolytic streptococci), and red strawberry tongue occurs later, after 4–5 days </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 Placental site trophoblastic tumor and can you explain it in depth? [/INST]  </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 Ureterovaginal fistula and can you explain it in depth? [/INST] A ureterovaginal fistula is an abnormal passageway existing between the ureter and the vagina. It presents as urinary incontinence. Its impact on  women is to reduce the "quality of life dramatically."

Cause
A ureterovaginal fistula is a result of trauma, infection, pelvic surgery, radiation treatment and therapy, malignancy, or inflammatory bowel disease.  Symptoms can be troubling for women especially since some  clinicians delay treatment until inflammation is reduced and stronger tissue has formed.  The fistula may develop as a maternal birth injury from a long and protracted labor, long dilation time and expulsion period. Difficult deliveries can create pressure necrosis in the tissue that is being pushed between the head of the infant and the softer tissues of the vagina, ureters, and bladder.Radiographic imaging can assist clinicians in identifying the abnormality. A Ureterovaginal fistula is always indicative of an obstructed kidney necessitating emergency intervention followed later by an elective surgical repair of the fistula.

Treatment
Many women delay treatment for decades. Surgeons often will correct the fistula through major gynecological surgery </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 Tardive dyskinesia and can you explain it in depth? [/INST] Tardive dyskinesia (TD) is a disorder that results in involuntary, repetitive body movements, which may include grimacing, sticking out the tongue, or smacking the lips. Additionally, there may be rapid jerking movements or slow writhing movements. In about 20% of people with TD, the disorder interferes with daily functioning.Tardive dyskinesia occurs in some people as a result of long-term use of dopamine-receptor-blocking medications such as antipsychotics and metoclopramide. These medications are usually used for mental illness but may also be given for gastrointestinal or neurological problems. The condition typically develops only after months to years of use. The diagnosis is based on the symptoms after ruling out other potential causes.Efforts to prevent the condition include either using the lowest possible dose or discontinuing use of neuroleptics. Treatment includes stopping the neuroleptic medication if possible or switching to clozapine. Other medications such as valbenazine, tetrabenazine, or botulinum toxin may be used to lessen the symptoms. With treatment, some see a resolution of symptoms, while others do not.Rates in those on atypical antipsychotics are about 20%, while those on typical antipsychotics have rates of about 30%. The risk of acquiring the condition is greater in older people, for women, as well as patients with mood disorders and/or medical diagnoses receiving antipsychotic medications. The term "tardive dyskinesia" first came into use in 1964.

Signs and symptoms
Tardive dyskinesia is characterized by repetitive, involuntary movements. Some examples of these types of involuntary movements include:
Grimacing
Tongue movements
Lip smacking
Lip puckering
Pursing of the lips
Excessive eye blinking
Rapid, involuntary movements of the limbs, torso, and fingers may also occur.In some cases, an individuals legs can be so affected that walking becomes difficult or impossible. These symptoms are the opposite of people who are diagnosed with Parkinsons disease. People with Parkinsons have difficulty moving, whereas people with tardive dyskinesia have difficulty not moving.Respiratory irregularity, such as grunting and difficulty breathing, is another symptom associated with tardive dyskinesia, although studies have shown that the rate of people affected is relatively low.Tardive dyskinesia is often misdiagnosed as a mental illness rather than a neurological disorder, and as a result, people are prescribed neuroleptic drugs, which increase the probability that the person will develop a severe and disabling case, and shortening the typical survival period.Other closely related neurological disorders have been recognized as variants of tardive dyskinesia. Tardive dystonia is similar to standard dystonia but permanent. Tardive akathisia involves painful feelings of inner tension and anxiety and a compulsive drive to move the body. In some extreme cases, afflicted individuals experience so much internal tension that they lose their ability to sit still. Tardive tourettism is a tic disorder featuring the same symptoms as Tourette syndrome. The two disorders are extremely close in nature and often can only be differentiated by the details of their respective onsets. Tardive myoclonus, a rare disorder, presents as brief jerks of muscles in the face, neck, trunk, and extremities."AIMS Examination": This test is used when psychotropic medications have been prescribed because people sometimes develop tardive dyskinesia due to prolonged use of antipsychotic medications. The Abnormal Involuntary Movement Scale (AIMS) examination is a test used to identify the symptoms of tardive dyskinesia (TD). The test is not meant to tell whether there is an absence or presence of tardive dyskinesia. It just scales to the level of symptoms indicated by the actions observed. The levels range from none to severe. The AIMS examination was constructed in the 1970s to measure involuntary facial, trunk, and limb movements. It is best to do this test before and after the administration of the psychotropic drugs. Taking the AIMS consistently can help to track severity of TD over time.

Causes
Tardive dyskinesia was first described in the 1950s shortly after the introduction of chlorpromazine and other antipsychotic drugs. However, the exact mechanism of the disorder remains largely uncertain. The most compelling line of evidence suggests that tardive dyskinesia may result primarily from neuroleptic-induced dopamine supersensitivity in the nigrostriatal pathway, with the D2 dopamine receptor being most affected. Neuroleptics act primarily on this dopamine system, and older neuroleptics, which have greater affinity for the D2 binding site, are associated with high risk for tardive dyskinesia. The D2 hypersensitivity hypothesis is also supported by evidence of a dose–response relationship, withdrawal effects, studies on D2 agonists and antagonists, animal studies, and genetic polymorphism research.Given similar doses of the same neuroleptic, differences among individuals still exist in the likelihood of developing tardive dyskinesia. Such individual differences may be due to genetic polymorphisms, which code for D2 receptor binding site affinity, or prior exposure to environmental toxins. Decreased functional reserve or cognitive dysfunction, associated with aging, intellectual disability, alcohol and drug use, or traumatic head injuries, has also been shown to increase risk of developing the disorder among those treated with neuroleptics. Antipsychotic drugs can sometimes camouflage the signs of tardive dyskinesia from occurring in the early stages; this can happen from the individual having an increased dose of an antipsychotic drug. Often the symptoms of tardive dyskinesia are not apparent until the individual comes off of the antipsychotic drugs; however, when tardive dyskinesia worsens, the signs become visible.Other dopamine antagonists and antiemetics can cause tardive dyskinesia, such as metoclopramide and promethazine, used to treat gastrointestinal disorders. Atypical antipsychotics are considered lower-risk for causing TD than their typical counterparts with their relative rates of TD of 13.1% and 32.4% respectively in short-term trials with haloperidol being the main typical antipsychotic utilised in said trials. Quetiapine and clozapine are considered the lowest risk agents for precipitating TD. From 2008, there have been reported cases of the anti-psychotic medication aripiprazole, a partial agonist at D2 receptors, leading to tardive dyskinesia.
As of 2013, reports of tardive dyskinesia in aripiprazole have grown in number.
The available research seems to suggest that the concurrent prophylactic use of a neuroleptic and an antiparkinsonian drug is useless to avoid early extrapyramidal side-effects and may render the person more sensitive to tardive dyskinesia. Since 1973 the use of these drugs has been found to be associated with the development of tardive dyskinesia.

Risk factors
An increased risk of tardive dyskinesia has been associated with smoking in some studies, although a negative study does exist. There seems to be a cigarette smoke-exposure-dependent risk for TD in people who are antipsychotic-treated . Elderly people are also at a heightened risk for developing TD, as are females and those with organic brain injuries or diabetes mellitus and those with the negative symptoms of schizophrenia. TD is also more common in those that experience acute neurological side effects from antipsychotic drug treatment. Racial discrepancies in TD rate also exist, with Africans and African Americans having higher rates of TD after exposure to antipsychotics. Certain genetic risk factors for TD have been identified including polymorphisms in the genes encoding the D3, 5-HT2A and 5-HT2C receptors.

Diagnosis
Prevention
Prevention of tardive dyskinesia is achieved by using the lowest effective dose of a neuroleptic for the shortest time. However, with diseases of chronic psychosis such as schizophrenia, this strategy must be balanced with the fact that increased dosages of neuroleptics are more beneficial in preventing recurrence of psychosis. If tardive dyskinesia is diagnosed, the causative drug should be discontinued. Tardive dyskinesia may persist after withdrawal of the drug for months, years or even permanently. Some studies suggest that practitioners should consider using atypical antipsychotics as a substitute to typical antipsychotics for people requiring medication. These agents are associated with fewer neuromotor side effects and a lower risk of developing tardive dyskinesia.Studies have tested the use of melatonin, high dosage vitamins, and different antioxidants in concurrence with antipsychotic drugs (often used to treat schizophrenia) as a way of preventing and treating tardive dyskinesia. Although further research is needed, studies reported a much lower percentage of individuals developing tardive dyskinesia than the current rate of people  for those taking antipsychotic drugs. Tentative evidence supports the use of vitamin E for prevention.

Treatment
Valbenazine was approved by the FDA for tardive dyskinesia in April 2017. Tetrabenazine, which is a dopamine depleting drug, is sometimes used to treat tardive dyskinesia and other movement disorders (e.g. Huntingtons chorea). Deutetrabenazine, an isotopic isomer of tetrabenazine, was approved by the FDA for tardive dyskinesia in August 2017. Vitamin B6 has been reported to be an effective treatment for TD in two randomised double-blind placebo-controlled trials, but the overall evidence for its effectiveness is considered "weak." Clonidine may also be useful in the treatment of TD, although dose-limiting hypotension and sedation may hinder its usage. Botox injections are used for minor focal dystonia, but not in more advanced tardive dyskinesia. As of 2018 evidence is insufficient to support the use of benzodiazepines, baclofen, progabide, sodium valproate, gaboxadol, or calcium channel blockers (e.g. diltiazem).

Epidemiology
Tardive dyskinesia most commonly occurs in people with psychiatric conditions who are treated with antipsychotic medications for many years. The average rate of people affected has been estimated to be around 30% for individuals taking antipsychotic medication, such as that used to treat schizophrenia. A study being conducted at the Yale University School of Medicine has estimated that "32% of people develop persistent tics after 5 years on major tranquilizers, 57% by 15 years, and 68% by 25 years." More drastic data was found during a longitudinal study conducted on individuals 45 years of age and older who were taking antipsychotic drugs. According to this research study, 26% of people developed tardive dyskinesia after just one year on the medication </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 Acute necrotizing ulcerative gingivitis and can you explain it in depth? [/INST] Acute necrotizing ulcerative gingivitis (ANUG) is a common, non-contagious infection of the gums with sudden onset. The main features are painful, bleeding gums, and ulceration of inter-dental papillae (the sections of gum between adjacent teeth). This disease, along with necrotizing (ulcerative) periodontitis (NP or NUP) is classified as a necrotizing periodontal disease, one of the seven general types of gum disease caused by inflammation of the gums (periodontitis).
The often severe gum pain that characterizes ANUG distinguishes it from the more common chronic periodontitis which is rarely painful. If ANUG is improperly treated or neglected, it may become chronic and/or recurrent. The causative organisms are mostly anaerobic bacteria, particularly Fusobacteriota and spirochete species.
Predisposing factors include poor oral hygiene, smoking, poor nutrition, psychological stress, and a weakened immune system. When the attachments of the teeth to the bone are involved, the term NUP is used. Treatment of ANUG is by removal of dead gum tissue and antibiotics (usually metronidazole) in the acute phase, and improving oral hygiene to prevent recurrence. Although the condition has a rapid onset and is debilitating, it usually resolves quickly and does no serious harm. The informal name trench mouth arose during World War I as many soldiers developed the disease, probably because of the poor conditions and extreme psychological stress.

Signs and symptoms
In the early stages some affected people may complain of a feeling of tightness around the teeth. Three signs/symptoms must be present to diagnose this condition:
Severe gum pain.
Profuse gum bleeding that requires little or no provocation.
Interdental papillae are ulcerated with dead tissue. The papillary necrosis of NUG has been described as "punched out".Other signs and symptoms may be present, but not always.
Foul breath.
Bad taste (metallic taste).Malaise, fever and/or cervical lymph node enlargement are rare (unlike the typical features of herpetic stomatitis). Pain is fairly well localized to the affected areas. Systemic reactions may be more pronounced in children. Cancrum oris (noma) is a very rare complication, usually in debilitated children. Similar features but with more intense pain may be seen in necrotizing periodontitis in HIV/AIDS.

Causes
Necrotizing periodontal disease is caused by a mixed bacterial infection that includes anaerobes such as P. intermedia and Fusobacterium as well as spirochetes, such as Treponema.ANUG may also be associated with diseases in which the immune system is compromised, including HIV/AIDS.
ANUG is an opportunistic infection that occurs on a background of impaired local or systemic host defenses. The predisposing factors for ANUG are smoking, psychological stress, malnutrition, and immunosuppression.
The following zones of infection have been described (superficial to deep): the bacterial zone, the neutrophil rich zone, the necrotic zone and the spirochetal zone.

Diagnosis
Diagnosis is usually clinical. Smear for fusospirochaetal bacteria and leukocytes; blood picture occasionally. The important differentiation is with acute leukemia or herpetic stomatitis.

Classification
Necrotizing gingivitis is part of a spectrum of disease termed necrotizing periodontal diseases. It is the most minor form of this spectrum, with more advanced stages being termed necrotizing periodontitis, necrotizing stomatitis, and the most extreme, cancrum oris. Acute necrotizing ulcerative gingivitis (ANUG) refers to the clinical onset of NUG. The word acute is used because usually the onset is sudden. Other forms of NUG may be chronic or recurrent.
Necrotizing ulcerative periodontitis (NUP) is where the infection leads to attachment loss, and involves only the gingiva, periodontal ligament and alveolar ligament. Progression of the disease into tissue beyond the mucogingival junction characterizes necrotizing stomatitis.

Treatment
Treatment includes irrigation and debridement of necrotic areas (areas of dead and/or dying gum tissue), oral hygiene instruction and the uses of mouth rinses and pain medication. If there is systemic involvement, then oral antibiotics may be given, such as metronidazole. As these diseases are often associated with systemic medical issues, proper management of the systemic disorders is appropriate.

Prognosis
Untreated, the infection may lead to rapid destruction of the periodontium and can spread, as necrotizing stomatitis or noma, into neighbouring tissues in the cheeks, lips or the bones of the jaw.  As stated, the condition can occur and be especially dangerous in people with weakened immune systems. This progression to noma is possible in malnourished susceptible individuals, with severe disfigurement possible.

Epidemiology
In developed countries, this disease occurs mostly in young adults. In developing countries, NUG may occur in children of low socioeconomic status, usually occurring with malnutrition (especially inadequate protein intake) and shortly after the onset of viral infections (e.g. measles).Predisposing factors include smoking, viral respiratory infections and immune defects, such as in HIV/AIDS </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 Posthitis and can you explain it in depth? [/INST] Posthitis (pronounced pos-THI-tis) is the inflammation of the foreskin (prepuce) of the penis </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 Epidural hematoma and can you explain it in depth? [/INST] Epidural hematoma is when bleeding occurs between the tough outer membrane covering the brain (dura mater) and the skull. Often there is loss of consciousness following a head injury, a brief regaining of consciousness, and then loss of consciousness again. Other symptoms may include headache, confusion, vomiting, and an inability to move parts of the body. Complications may include seizures.The cause is typically head injury that results in a break of the temporal bone and bleeding from the middle meningeal artery. Occasionally it can occur as a result of a bleeding disorder or blood vessel malformation. Diagnosis is typically by a CT scan or MRI. When this condition occurs in the spine it is known as a spinal epidural hematoma.Treatment is generally by urgent surgery in the form of a craniotomy or burr hole. Without treatment, death typically results. The condition occurs in one to four percent of head injuries. Typically it occurs in young adults. Males are more often affected than females.

Signs and symptoms
Many people with epidural hematomas experience a lucid period immediately following the injury, with a delay before symptoms become evident. Because of this initial period of lucidity, it has been called "Talk and Die" syndrome. As blood accumulates, it starts to compress intracranial structures, which may impinge on the third cranial nerve, causing a fixed and dilated pupil on the side of the injury. The eye will be positioned down and out due to unopposed innervation of the fourth and sixth cranial nerves.Other symptoms include severe headache; weakness of the extremities on the opposite side from the lesion due to compression of the crossed pyramid pathways; and vision loss, also on the opposite side, due to compression of the posterior cerebral artery. In rare cases, small hematomas may be asymptomatic.If not treated promptly, epidural hematomas can cause tonsillar herniation, resulting in respiratory arrest. The trigeminal nerve may be involved late in the process as the pons is compressed, but this is not an important presentation, because the person may already be dead by the time it occurs. In the case of epidural hematoma in the posterior cranial fossa, tonsillar herniation causes Cushings triad: hypertension, bradycardia, and irregular breathing.

Causes
The most common cause of intracranial epidural hematoma is head injury, although spontaneous hemorrhages have been known to occur. Epidural hematomas occur in about 10% of traumatic brain injuries, mostly due to car accidents, assaults, or falls. They are often caused by acceleration-deceleration trauma and transverse forces.Epidural hematoma commonly results from a blow to the side (temporal bone) of the head. The pterion region, which overlies the middle meningeal artery, is relatively weak and prone to injury. Only 20 to 30% of epidural hematomas occur outside the region of the temporal bone. The brain may be injured by prominences on the inside of the skull as it scrapes past them. Epidural hematoma is usually found on the same side of the brain which was impacted by the blow, but on very rare occasions it can be due to a contrecoup injury.A "heat hematoma" is an epidural hematoma caused by severe thermal burn, causing contraction and exfoliation of the dura mater and exfoliate from the skull, in turn causing exudation of blood from the venous sinuses. The hematoma can be seen on autopsy as brick red, or as radiolucent on CT scan, because of heat-induced coagulation of the hematoma.

Pathophysiology
The break of the temporal bone causes bleeding from the middle meningeal artery,  hence epidural bleeding is often rapid as arteries are high-pressure flow. In 10% of cases, however, it comes from veins and can progress more slowly. A venous hematoma may be acute (occurring within a day of the injury and appearing as a swirling mass of blood without a clot), subacute (occurring in 2–4 days and appearing solid), or chronic (occurring in 7–20 days and appearing mixed or lucent).In adults, the temporal region accounts for 75% of cases. In children, however, they occur with similar frequency in the occipital, frontal, and posterior fossa regions. Epidural bleeds from arteries can grow until they reach their peak size 6–8 hours post-injury, spilling 25–75 cubic centimeters of blood into the intracranial space. As the hematoma expands, it strips the dura from the inside of the skull, causing an intense headache. It also increases intracranial pressure, causing the brain to shift, lose blood supply, be crushed against the skull, or herniate. Larger hematomas cause more damage. Epidural bleeds can quickly compress the brainstem, causing unconsciousness, abnormal posturing, and abnormal pupil responses to light.

Diagnosis
Diagnosis is typically by CT scan or MRI. MRIs have greater sensitivity and should be used if there is a high suspicion of epidural hematoma and a negative CT scan. Differential diagnoses include a transient ischemic attack, intracranial mass, or brain abscess.Epidural hematomas usually appear convex in shape because their expansion stops at the skulls sutures, where the dura mater is tightly attached to the skull. Thus, they expand inward toward the brain rather than along the inside of the skull, as occurs in subdural hematomas. Most people also have a skull fracture.Epidural hematomas may occur in combination with subdural hematomas, or either may occur alone. CT scans reveal subdural or epidural hematomas in 20% of unconscious people. In the hallmark of epidural hematoma, people may regain consciousness and appear completely normal during what is called a lucid interval, only to descend suddenly and rapidly into unconsciousness later. This lucid interval, which depends on the extent of the injury, is a key to diagnosing an epidural hematoma.

Treatment
Epidural hematoma is a surgical emergency. Delayed surgery can result in permanent brain damage or death. Without surgery, death usually follows, due to enlargement of the hematoma, causing a brain herniation. As with other types of intracranial hematomas, the blood almost always must be removed surgically to reduce the pressure on the brain. The hematoma is evacuated through a burr hole or craniotomy. If transfer to a facility with neurosurgery is unavailable, prolonged trephination (drilling a hole into the skull) may be performed in the emergency department </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 Palmar erythema and can you explain it in depth? [/INST]  </s>