<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 Cutis verticis gyrata and can you explain it in depth? [/INST] Cutis verticis gyrata is a medical condition usually associated with thickening of the scalp. The condition is identified by excessive thickening of the soft tissues of the scalp and characterized by ridges and furrows, which give the scalp a cerebriform appearance. Clinically, the ridges are hard and cannot be flattened on applying pressure. Patients show visible folds, ridges or creases on the surface of the top of the scalp. The number of folds can vary from two to roughly ten and are typically soft and spongy. The condition typically affects the central and rear regions of the scalp, but sometimes can involve the entire scalp.
Hair loss can occur over time where the scalp thickens, though hair within any furrows remains normal. Thus far, due to the (apparent) rarity of the condition, limited research exists and causes are as yet undetermined. What is known, is that the condition is not exclusively congenital.
The condition was first reported by Jean-Louis-Marc Alibert in 1837, who called it cutis sulcata. A clinical description of the condition was provided by Robert in 1843 and it was named by Paul Gerson Unna in 1907. It has also been called Robert-Unna syndrome, bulldog scalp, corrugated skin, cutis verticis plicata, and pachydermia verticis gyrata.

Cause
At this time, causes are unknown, but it is believed to not be congenital.

Diagnosis
There is no clinical diagnosis for CVG as cases are rarely seen and are often comorbid with other conditions.

Classifications
CVG is classified according to the presence, or lack of underlying cause. Studies suggest that CVG often occurs in individuals in a secondary form to other ailments. However, the condition can also be present on its own. CVG can be classified into two forms: ‘primary’ (essential and non-essential) and ‘secondary’.The classifications are:

Primary essential
Primary non-essential
SecondaryPrimary essential CVG is where the cause of the condition in unknown. It has no other associated abnormalities. This occurs mainly in men, with a male:female ratio of 5:1 or 6:1, and develops during or soon after puberty. Because of the slow progression of the condition, which usually occurs without symptom, it often passes unnoticed in the early stage.Primary non-essential CVG can be associated with neuropsychiatric disorders including cerebral palsy, epilepsy, seizures, and ophthalmologic abnormalities, most commonly cataracts.Secondary CVG occurs as a consequence of a number of diseases or drugs that produce changes in scalp structure. These include: acromegaly (excessive growth hormone levels due to pituitary gland tumours), and theoretically, the use of growth hormone itself or the use of drugs that mimic the effect of growth hormone (such as GHRP-6 and CJC-1295). It may also arise in association with melanocytic naevi (moles), birthmarks (including connective tissue naevi, fibromas and naevus lipomatosus), and inflammatory processes (e.g </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 Talaromycosis and can you explain it in depth? [/INST] Talaromycosis is a fungal infection that presents with painless skin lesions of face and neck, fever, anaemia, large lymph glands and liver.It is caused by the fungusTalaromyces marneffei, which is found in soil and decomposing organic matter.  The infection is thought to be acquired by breathing in the fungus from the environment, however, the environmental source of the organism is not known. It typically occurs in people who are already sick and unable to fight infection such as HIV/AIDS, cancer, organ transplant, long-term steroid use, old age, malnutrition or autoimmune disease. It generally does not affect healthy people and does not spread from person to person. Diagnosis is usually made by identification of the fungus from clinical specimens, either by microscopy or culture. Biopsies of skin lesions, lymph nodes, and bone marrow demonstrate the presence of organisms on histopathology. Medical imaging may reveal shadows in the lungs. The disease can look similar to tuberculosis and histoplasmosis.Talaromycosis may be prevented in people at high risk, using the antifungal medication itraconazole, and is treatable with amphotericin B followed by itraconazole or voriconazole. The disease is fatal in 75% of those not given treatment.Talaromycosis is endemic exclusively to southeast Asia (including southern China and eastern India), and particularly in young farmers. The exact number of people in the world affected is not known. Men are affected more than women. The first natural human case of talaromycosis was reported in 1973 in an American minister with Hodgkins disease who lived in Southeast Asia.

Signs and symptoms
There may be no symptoms, or talaromycosis may present with small painless skin lesions. The head and neck are most often affected. Other features include: fever, general discomfort, weight loss, cough, difficulty breathing, diarrhoea, abdominal pain, swelling of the spleen (splenomegaly), liver swelling (hepatomegaly), swollen lymph nodes (lymphadenopathy), and anemia. There may be no symptoms.In those without HIV infection, the lungs, liver, and mouth are usually affected, with systemic infection rarely occurring. The skin lesions are also often smooth. The disease tends to present differently in those with HIV infection; they are more likely to experience widespread infection. Their skin lesions however, are usually dented in the centre and can appear similar to molluscum contagiosum.

Cause
Talaromycosis is usually caused by T. marneffei, however, other species of the Talaromyces genus are also known to cause the disease in rare cases.

Risk factors
Talaromycosis rarely affects healthy people and generally occurs in people who are already sick and unable to fight infection such as HIV/AIDS, cancer, organ transplant, long-term steroid use, old age, malnutrition or autoimmune disease.

Mechanism
The infection is thought to be acquired through breathing in the organism from the environment. However, the exact source of infection is not known. The infection is not spread person-to-person. In Thailand, talaromycosis is more common during the rainy season; rain may promote the proliferation of the fungus in the environment.

Diagnosis
There is no accurate fast serological test. Diagnosis relies on identifying Talaromyces marneffei in cultures from clinical specimens such as sputum, blood, skin scrapings, lymph node, and bone marrow, by which time the disease is in the late-stage. Fungi in blood are found in half of case.Non-specific laboratory findings may show evidence of the fungus invading tissue, such as low platelets due to bone marrow infiltration, and elevated transaminases due to liver involvement.Biopsies of skin lesions, lymph nodes, and bone marrow demonstrate the presence of organisms on histopathology </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 hemolytic transfusion reaction and can you explain it in depth? [/INST] An acute hemolytic transfusion reaction (AHTR), also called immediate hemolytic transfusion reaction, is a life-threatening reaction to receiving a blood transfusion. AHTRs occur within 24 hours of the transfusion and can be triggered by a few milliliters of blood. The reaction is triggered by host antibodies destroying donor red blood cells. AHTR typically occurs when there is an ABO blood group incompatibility, and is most severe when type A donor blood is given to a type O recipient.

Signs and symptoms
Early acute hemolytic transfusion reactions are typically characterized by fever, which may be accompanied by rigors (chills). Mild cases are also typically characterized by abdominal, back, flank, or chest pain. More severe cases may be characterized by shortness of breath, low blood pressure, hemoglobinuria, and may progress to shock and disseminated intravascular coagulation. In anesthetized or unconscious patients, hematuria (blood in the urine) may be the first sign of AHTR. Other symptoms include nausea, vomiting, and wheezing.

Causes
The most common cause of acute hemolytic transfusion reaction is ABO incompatibility, which is typically due to human error that results in a recipient receiving the incorrect blood product. Rarely, other blood type incompatibilities can cause AHTR, the most common of which is Kidd antigen incompatibility. Rh, Kell, and Duffy antigen incompatibility have also been implicated in AHTR.

Mechanism
Antibodies against A and B blood groups (isohemagglutinins) present in the recipients blood destroy the donor red blood cells. They also activate the coagulation cascade (blood clotting system) via factor XII, which can lead to disseminated intravascular coagulation and kidney damage. Isohemagglutinins also activate the complement cascade via C3a and C5a, which then promote inflammatory cytokine release from white blood cells </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 Transfusion hemosiderosis and can you explain it in depth? [/INST] Transfusional hemosiderosis is the accumulation of iron in the body due to frequent blood transfusions. Iron accumulates in the liver and heart, but also endocrine organs. Frequent blood transfusions may be given to many patients, such as those with thalassemia, sickle cell disease, leukemia, aplastic anemia, or myelodysplastic syndrome, among others. It is diagnosed with a blood transferrin test and a liver biopsy. It is treated with venipuncture, erythrocytapheresis, and iron chelation therapy.

Signs and symptoms
Transfusional hemosiderosis can cause cardiac arrhythmia and cardiomyopathy.

Causes
Transfusional hemosiderosis is a potential side effect of frequent blood transfusions. These may be given for a number of conditions, including:

thalassemia.
sickle cell disease.
leukemia.
aplastic anemia.
myelodysplastic syndrome.

Mechanism
Hemoglobin, the oxygen-carrying molecule in a red blood cell, contains iron. The body has limited ways to store and remove iron.  When red blood cells (RBCs) die, they are consumed by macrophages. Transfused RBCs have shorter lifespans that native ones, so they die and are consumed more frequently by the macrophages, which causes the latter to die from excess iron which is then released into the blood. Therefore, with frequent blood transfusions, iron builds up in the body over time. This can enter the liver, heart, pancreas, and endocrine organs. Free iron increases the production of oxygen radicals (mostly hydroxyl radicals) that cause damage to cells (particularly their DNA).

Diagnosis
Transfusional hemosiderosis can be inferred with a blood transferrin test. Blood ferritin may be increased with a number of other conditions, so is less reliable for diagnosis. A liver biopsy may be used, which is the most accurate diagnostic technique. The level of siderosis seen in a liver biopsy can be graded by severity.

Treatment
Transfusional hemosiderosis is treated with a number of therapies. Venipuncture (phlebotomy) removes blood. Erythrocytapheresis filters red blood cells from the blood. Chelation therapy removes iron from the blood. This involves delivering iron chelating agents such as deferoxamine, deferiprone or deferasirox. If iron overload has caused damage to end-organs, this is generally irreversible and may require transplantation.

Prognosis
Transfusion hemosiderosis can cause permanent damage to tissues that may lead to death </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 Cortical desmoid 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 Pancreatitis and can you explain it in depth? [/INST] Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormones. There are two main types: acute pancreatitis, and chronic pancreatitis. Signs and symptoms of pancreatitis include pain in the upper abdomen, nausea and vomiting. The pain often goes into the back and is usually severe. In acute pancreatitis, a fever may occur, and symptoms typically resolve in a few days. In chronic pancreatitis weight loss, fatty stool, and diarrhea may occur. Complications may include infection, bleeding, diabetes mellitus, or problems with other organs.The two most common causes of acute pancreatitis are a gallstone blocking the common bile duct after the pancreatic duct has joined; and heavy alcohol use. Other causes include direct trauma, certain medications, infections such as mumps, and tumors. Chronic pancreatitis may develop as a result of acute pancreatitis. It is most commonly due to many years of heavy alcohol use. Other causes include high levels of blood fats, high blood calcium, some medications, and certain genetic disorders, such as cystic fibrosis, among others. Smoking increases the risk of both acute and chronic pancreatitis. Diagnosis of acute pancreatitis is based on a threefold increase in the blood of either amylase or lipase. In chronic pancreatitis, these tests may be normal. Medical imaging such as ultrasound and CT scan may also be useful.Acute pancreatitis is usually treated with intravenous fluids, pain medication, and sometimes antibiotics. Typically eating and drinking are disallowed, and a nasogastric tube is placed in the stomach. A procedure known as an endoscopic retrograde cholangiopancreatography (ERCP) may be done to examine the distal common bile duct and remove a gallstone if present. In those with gallstones the gallbladder is often also removed. In chronic pancreatitis, in addition to the above, temporary feeding through a nasogastric tube may be used to provide adequate nutrition. Long-term dietary changes and pancreatic enzyme replacement may be required. And occasionally surgery is done to remove parts of the pancreas.Globally, in 2015 about 8.9 million cases of pancreatitis occurred. This resulted in 132,700 deaths, up from 83,000 deaths in 1990. Acute pancreatitis occurs in about 30 per 100,000 people a year. New cases of chronic pancreatitis develop in about 8 per 100,000 people a year and currently affect about 50 per 100,000 people in the United States. It is more common in men than women. Often chronic pancreatitis starts between the ages of 30 and 40 while it is rare in children. Acute pancreatitis was first described on autopsy in 1882 while chronic pancreatitis was first described in 1946.

Signs and symptoms
The most common symptoms of pancreatitis are severe upper abdominal or left upper quadrant burning pain radiating to the back, nausea, and vomiting that is worse with eating. The physical examination will vary depending on severity and presence of internal bleeding. Blood pressure may be elevated by pain or decreased by dehydration or bleeding. Heart and respiratory rates are often elevated. The abdomen is usually tender but to a lesser degree than the pain itself. As is common in abdominal disease, bowel sounds may be reduced from reflex bowel paralysis. Fever or jaundice may be present. Chronic pancreatitis can lead to diabetes or pancreatic cancer. Unexplained weight loss may occur from a lack of pancreatic enzymes hindering digestion.

Complications
Early complications include shock, infection, systemic inflammatory response syndrome, low blood calcium, high blood glucose, and dehydration. Blood loss, dehydration, and fluid leaking into the abdominal cavity (ascites) can lead to kidney failure. Respiratory complications are often severe. Pleural effusion is usually present. Shallow breathing from pain can lead to lung collapse. Pancreatic enzymes may attack the lungs, causing inflammation. Severe inflammation can lead to intra-abdominal hypertension and abdominal compartment syndrome, further impairing renal and respiratory function and potentially requiring management with an open abdomen to relieve the pressure.Late complications include recurrent pancreatitis and the development of pancreatic pseudocysts—collections of pancreatic secretions that have been walled off by scar tissue. These may cause pain, become infected, rupture and bleed, block the bile duct and cause jaundice, or migrate around the abdomen. Acute necrotizing pancreatitis can lead to a pancreatic abscess, a collection of pus caused by necrosis, liquefaction, and infection. This happens in approximately 3% of cases or almost 60% of cases involving more than two pseudocysts and gas in the pancreas.

Causes
Eighty percent of cases of pancreatitis are caused by alcohol or gallstones. Gallstones are the single most common cause of acute pancreatitis. Alcohol is the single most common cause of chronic pancreatitis. Triglyceride levels greater than 1000 mg/dL (11.29 mmol/L) is another cause.

Medications
There are seven classes of medications associated with acute pancreatitis: statins, ACE inhibitors, oral contraceptives/hormone replacement therapy (HRT), diuretics, antiretroviral therapy, valproic acid, and oral hypoglycemic agents. Mechanisms of these drugs causing pancreatitis are not known exactly, but it is possible that statins have direct toxic effect on the pancreas or through the long-term accumulation of toxic metabolites. Meanwhile, ACE inhibitors cause angioedema of the pancreas through the accumulation of bradykinin. Birth control pills and HRT cause arterial thrombosis of the pancreas through the accumulation of fat (hypertriglyceridemia). Diuretics such as furosemide have a direct toxic effect on the pancreas. Meanwhile, thiazide diuretics cause hypertriglyceridemia and hypercalcemia, where the latter is the risk factor for pancreatic stones.HIV infection itself can cause a person to be more likely to get pancreatitis. Meanwhile, antiretroviral drugs may cause metabolic disturbances such as hyperglycemia and hypercholesterolemia, which predisposes to pancreatitis. Valproic acid may have direct toxic effect on the pancreas. There are various oral hypoglycemic agents that contributes to pancreatitis including metformin. But, glucagon-like peptide-1 (GLP-1) is more strongly associated with pancreatitis by promoting inflammation.Atypical antipsychotics such as clozapine, risperidone, and olanzapine can also cause pancreatitis.

Infection
A number of infectious agents have been recognized as causes of pancreatitis including:
Viruses
Coxsackie virus
Cytomegalovirus
Hepatitis B
Herpes simplex virus
Mumps
Varicella-zoster virus
Bacteria
Legionella
Leptospira
Mycoplasma
Salmonella
Fungi
Aspergillus
Parasites
Ascaris
Cryptosporidium
Toxoplasma

Other
Other common causes include trauma, autoimmune disease, high blood calcium, hypothermia, and endoscopic retrograde cholangiopancreatography (ERCP). Pancreas divisum is a common congenital malformation of the pancreas that may underlie some recurrent cases. Diabetes mellitus type 2 is associated with a 2.8-fold higher risk.Less common causes include pancreatic cancer, pancreatic duct stones, vasculitis (inflammation of the small blood vessels in the pancreas), and porphyria—particularly acute intermittent porphyria and erythropoietic protoporphyria.There is an inherited form that results in the activation of trypsinogen within the pancreas, leading to autodigestion. Involved genes may include trypsin 1, which codes for trypsinogen, SPINK1, which codes for a trypsin inhibitor, or cystic fibrosis transmembrane conductance regulator.The mnemonic GETSMASHED is often used to remember the common causes of pancreatitis: G—gallstones, E—ethanol, T—trauma, S—steroids, M—mumps, A—autoimmune pancreatitis, S—scorpion sting, H—hyperlipidemia, hypothermia, hyperparathyroidism, E—endoscopic retrograde cholangiopancreatography, D—drugs (commonly azathioprine, valproic acid, liraglutide).

Diagnosis
The differential diagnosis for pancreatitis includes but is not limited to cholecystitis, choledocholithiasis, perforated peptic ulcer, bowel infarction, small bowel obstruction, hepatitis, and mesenteric ischemia.Diagnosis requires 2 of the 3 following criteria:

Characteristic acute onset of epigastric or vague abdominal pain that may radiate to the back (see signs and symptoms above)
Serum amylase or lipase levels ≥ 3 times the upper limit of normal
An imaging study with characteristic changes. CT, MRI, abdominal ultrasound or endoscopic ultrasound can be used for diagnosis.Amylase and lipase are 2 enzymes produced by the pancreas. Elevations in lipase are generally considered a better indicator for pancreatitis as it has greater specificity and has a longer half life. However, both enzymes can be elevated in other disease states. In chronic pancreatitis, the fecal pancreatic elastase-1 (FPE-1) test is a marker of exocrine pancreatic function. Additional tests that may be useful in evaluating chronic pancreatitis include hemoglobin A1C, immunoglobulin G4, rheumatoid factor, and anti-nuclear antibody.For imaging, abdominal ultrasound is convenient, simple, non-invasive, and inexpensive. It is more sensitive and specific for pancreatitis from gallstones than other imaging modalities. However, in 25–35% of patients the view of the pancreas can be obstructed by bowel gas making it difficult to evaluate.A contrast-enhanced CT scan is usually performed more than 48 hours after the onset of pain to evaluate for pancreatic necrosis and extrapancreatic fluid as well as predict the severity of the disease. CT scanning earlier can be falsely reassuring.ERCP or an endoscopic ultrasound can also be used if a biliary cause for pancreatitis is suspected.

Treatment
The treatment of pancreatitis is supportive and depends on severity. Morphine generally is suitable for pain control. There are no clinical studies to suggest that morphine can aggravate or cause pancreatitis or cholecystitis.The treatment for acute pancreatitis will depend on whether the diagnosis is for the mild form of the condition, which causes no complications, or the severe form, which can cause serious complications.

Mild acute pancreatitis
The treatment of mild acute pancreatitis is successfully carried out by admission to a general hospital ward. Traditionally, people were not allowed to eat until the inflammation resolved but more recent evidence suggests early feeding is safe and improves outcomes, and may result in an ability to leave the hospital sooner.Due to inflammation occurring in pancreatitis, proinflammatory cytokines secreted into the bloodstream can cause inflammation throughout the body, including the lungs and can manifest as ARDS. Because pancreatitis can cause lung injury and affect normal lung function, supplemental oxygen is occasionally delivered through breathing tubes that are connected via the nose (e.g., nasal cannulae) or via a mask. The tubes can then be removed after a few days once it is clear that the condition is improving.
Dehydration may result during an episode of acute pancreatitis, so fluids will be provided intravenously.
Opioids may be used for the pain. When the pancreatitis is due to gallstones, early gallbladder removal also appears to improve outcomes.

Severe acute pancreatitis
Severe pancreatitis can cause organ failure, necrosis, infected necrosis, pseudocyst, and abscess. If diagnosed with severe acute pancreatitis, people will need to be admitted to a high-dependency unit or intensive care unit. It is likely that the levels of fluids inside the body will have dropped significantly as it diverts bodily fluids and nutrients in an attempt to repair the pancreas. The drop in fluid levels can lead to a reduction in the volume of blood within the body, which is known as hypovolemic shock. Hypovolemic shock can be life-threatening as it can very quickly starve the body of the oxygen-rich blood that it needs to survive. To avoid going into hypovolemic shock, fluids will be administered intravenously. Oxygen will be supplied through tubes attached to the nose and ventilation equipment may be used to assist with breathing. Feeding tubes may be used to provide nutrients, combined with appropriate analgesia.
As with mild acute pancreatitis, it will be necessary to treat the underlying cause—gallstones, discontinuing medications, cessation of alcohol, etc. If the cause is gallstones, it is likely that an ERCP procedure or removal of the gallbladder will be recommended. The gallbladder should be removed during the same hospital admission or within two weeks of pancreatitis onset so as to limit the risk of recurrent pancreatitis.
If the cause of pancreatitis is alcohol, cessation of alcohol consumption and treatment for alcohol dependency may improve pancreatitis. Even if the underlying cause is not related to alcohol consumption, doctors recommend avoiding it for at least six months as this can cause further damage to the pancreas during the recovery process.Oral intake, especially fats, is generally restricted initially but early enteral feeding within 48 hours has been shown to improve clinical outcomes. Fluids and electrolytes are replaced intravenously. Nutritional support is initiated via tube feeding to surpass the portion of the digestive tract most affected by secreted pancreatic enzymes if there is no improvement in the first 72–96 hours of treatment.

Prognosis
Severe acute pancreatitis has mortality rates around 2–9%, higher where necrosis of the pancreas has occurred.Several scoring systems are used to predict the severity of an attack of pancreatitis </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 Discrete papular lichen myxedematosus 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 Hajdu–Cheney syndrome and can you explain it in depth? [/INST] Hajdu–Cheney syndrome, also called acroosteolysis with osteoporosis and changes in skull and mandible, arthrodentoosteodysplasia and Cheney syndrome, is an extremely rare autosomal dominant congenital disorder of the connective tissue characterized by severe and excessive bone resorption leading to osteoporosis and a wide range of other possible symptoms. Mutations in the NOTCH2 gene, identified in 2011, cause HCS. HCS is so rare that only about 50 cases have been reported worldwide since the discovery of the syndrome in 1948

Signs and symptoms
Hajdu–Cheney syndrome causes many issues with an individuals connective tissues. Some general characteristics of an individual with Hajdu–Cheney syndrome include bone flexibility and deformities, short stature, delayed acquisition of speech and motor skills, dolichocephalic skull, Wormian bone, small maxilla, hypoplastic frontal sinuses, basilar impression, joint laxity, bulbous finger tips and severe osteoporosis. Wormian bone occurs when extra bones appear between cranial sutures. Fetuses with Hajdu–Cheney syndrome often will not be seen to unclench their hands on obstetrical ultrasound. They may also have low-set ears and their eyes may be farther apart than on a usual child, called hypertelorism. Childrens heads can have some deformities in their shape and size (plagiocephaly). Early tooth loss and bone deformities, such as serpentine tibiae and fibulae, are also common in those affected.

Genetics
Hajdu–Cheney syndrome is a monogenic disorder. The disorder is inherited and controlled by a single pair of genes. A single copy of the mutant gene on an autosome causes HCS. HCS is an autosomal dominant disorder, only one parent with the defective gene is needed to pass the disorder to the offspring.Mutations within the last coding exon of NOTCH2 that remove the PEST domain and escape the nonsense-mediated mRNA decay have been shown to be the main cause of Hajdu–Cheney syndrome. The NOTCH2 gene plays a very important role in skeletogenesis. Mutations of NOTCH2 that seem to cause HCS occur in the last coding exon of the gene (exon 34). These mutations remove PEST domains, which mediate proteosomal destruction of the protein. These PEST domains are removed due to the premature stop codon in the amino acid sequence. All HCS alleles are observed to have premature protein destruction before the PEST sequence is fully translated. The result is a mature NOTCH2 gene with a partially completed PEST sequence. In some cases, no PEST sequence at all is seen. This leads to the no proteosomal destruction of the protein.The NOTCH2 gene is ubiquitously expressed in all embryonic tissue. When researching HCS in mice, the homozygous deletion of NOTCH2 leads to death. This observation is important because it explains how the HCS phenotype is not isolated to only one system of the body. NOTCH2 is also shown to regulate RANK-L osteoclastogenesis, which is the production of functional osteoclasts. Osteoclasts are the component that breaks bone down. This is why bone loss is observed in HCS patients, due to the overactivation of RANK-L.

Pathogenesis
The mechanism thought to cause HCS is an abnormality in osteoblast and osteoid function. These are major components of bone development, and the low function of each leads to the weak bones that characterize HCS.

Diagnosis
One of the main methods of pinpointing a NOTCH2 mutation that leads to HCS is through whole genome sequencing. This is then followed by exome capture by means of in-solution hybridization. The exome part of the genome consists of exons. Parallel sequencing follows the hybridization, which results in about 3.5 Gb of sequence data. These sequence data are then analyzed. Through sequence analysis and symptom presentation in HCS patients, this proves to be the most definitive method of diagnosis.

Types
Laboratory testing reveals multiple mutations of HCS </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 VACTERL association and can you explain it in depth? [/INST] The VACTERL association (also VATER association, and less accurately VACTERL syndrome) refers to a recognized group of birth defects which tend to co-occur (see below). This pattern is a recognized association, as opposed to a syndrome, because there is no known pathogenetic cause to explain the grouped incidence.
Each child with this condition can be unique. At present this condition is treated after birth with issues being approached one at a time. Some infants are born with symptoms that cannot be treated and they do not survive. Also, VACTERL association can be linked to other similar conditions such as Klippel Feil and Goldenhar syndrome including crossovers of conditions.
No specific genetic or chromosome problem has been identified with VACTERL association. VACTERL can be seen with some chromosomal defects such as Trisomy 18 and is more frequently seen in babies of diabetic mothers. VACTERL association, however, is most likely caused by multiple factors.VACTERL association specifically refers to the abnormalities in structures derived from the embryonic mesoderm.

Signs and symptoms
The following features are observed with VACTERL association:
V - Vertebral anomalies
A - Anorectal malformations
C - Cardiovascular anomalies
T - Tracheoesophageal fistula
E - Esophageal atresia
R - Renal (Kidney) and/or radial anomalies
L - Limb defectsAlthough it was not conclusive whether VACTERL should be defined by at least two or three component defects, it is typically defined by the presence of at least three of the above congenital malformations.

Spine
Vertebral anomalies, or defects of the spinal column, usually consist of small (hypoplastic) vertebrae or hemivertebra where only one half of the bone is formed. About 80 percent of patients with VACTERL association will have vertebral anomalies. In early life these rarely cause any difficulties, although the presence of these defects on a chest x-ray may alert the physician to other defects associated with VACTERL. Later in life these spinal column abnormalities may put the child at risk for developing scoliosis, or curvature of the spine.

Anal defects
Anal atresia or imperforate anus is seen in about 55 to 90 percent of patients with VACTERL association. These anomalies are usually noted at birth. It often require surgery in the first days of life. Sometimes babies will require several surgeries to fully reconstruct the intestine and anal canal.

Cardiac defects
Up to 75 percent of patients with VACTERL association have been reported to have congenital heart disease. The most common heart defects seen with VACTERL association are ventricular septal defect (VSD), atrial septal defects and tetralogy of Fallot.
Less common defects are truncus arteriosus and transposition of the great arteries. It is subsequently thought that cardiac defects should be considered an extension of VACTERL.

Trachea and oesophagus
Oesophageal atresia with tracheoesophageal fistula (TO fistula or TOF) is seen in about 70 percent of patients with VACTERL association, although it can frequently occur as an isolated defect. 15 to 33 percent of patients with TO fistulas will also have congenital heart disease. However these babies usually have uncomplicated heart defects, like a ventricular septal defect, which may not require any surgery.

Kidneys
Kidney defects are seen in approximately 50 percent of patients with VACTERL association. In addition, up to 35 percent of patients with VACTERL association have a single umbilical artery (there are usually two arteries and one vein) which is often associated with additional kidney or urologic problems. Renal abnormalities in VACTERL association can be severe, with incomplete formation of one or both kidneys or urologic abnormalities such as obstruction of outflow of urine from the kidneys or severe reflux (backflow) of urine into the kidneys from the bladder. These problems can cause kidney failure early in life and may require kidney transplant. Many of these problems can be corrected surgically before any damage can occur.

Limbs
Limb defects occur in up to 70 percent of babies with VACTERL association and include a displaced or hypoplastic thumb, extra digits (polydactyly), fusion of digits (syndactyly) and forearm defects such as radial aplasia. Babies with limb defects on both sides tend to have kidney or urologic defects on both sides, while babies with limb defects on only one side of the body tend to have kidney problems on that same side.

Extension
Features secondary to VACTERL components are frequent enough to be considered an extension of VACTERL. These include: single umbilical artery, ambiguous genitalia, abdominal wall defects, diaphragmatic hernia, intestinal and respiratory anomalies, and oligohydramnios sequence defects.  Cardiac defects are thought to fit in this category.

Growth
Many babies with VACTERL are born small and have difficulty with gaining weight. Babies with VACTERL association, however, do tend to have normal development and normal intelligence.

Pathology
Patients with abnormal cardiac and kidney function may be more at risk for hemolytic uremic syndrome

Diagnosis
Differential diagnosis
Baller–Gerold syndrome
CHARGE syndrome
Currarino syndrome
DiGeorge syndrome
Fanconi anemia
Feingold syndrome
Fryns syndrome
MURCS association
Oculo-auriculo-vertebral syndrome
Opitz G/BBB syndrome
Holt–Oram syndrome
Pallister–Hall syndrome
Townes–Brocks syndrome
VACTERL with hydrocephalus

Management
Epidemiology
The incidence of VACTERL association is estimated to be approximately 1 in 10,000 to 1 in 40,000 live-born infants. It is seen more frequently in infants born to diabetic mothers. While most cases are sporadic, there are clearly families who present with multiple involved members.

History
The acronym VATER association was first described by Linda Quan, an emergency room physician, and David Smith, a man who was considered the father of dysmorphology in 1972, to define a non-random co-occurrence of the listed defects. Years later, research revealed that cardiac and renal abnormalities were common in the association, and the acronym was changed to VACTERL </s>


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<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 Myotonia congenita and can you explain it in depth? [/INST] Myotonia congenita is a congenital neuromuscular channelopathy that affects skeletal muscles (muscles used for movement). It is a genetic disorder. The hallmark of the disease is the failure of initiated contraction to terminate, often referred to as delayed relaxation of the muscles (myotonia) and rigidity. Symptoms include delayed relaxation of the muscles after voluntary contraction (myotonia), and may also include stiffness, hypertrophy (enlargement), transient weakness in some forms of the disorder (from certain genetic mutations), severe masseter spasm, and cramping. The condition is sometimes referred to as fainting goat syndrome, as it is responsible for the eponymous fainting seen in fainting goats when presented with a sudden stimulus. Of note, myotonia congenita has no association with malignant hyperthermia (MH).

Symptoms and signs
The prolonged muscle contractions, which occur most commonly in the leg muscles in recessive mutations, and more commonly in the hands, face, and eyelids in dominant mutations, are often enhanced by inactivity, and in some forms are relieved by repetitive movement known as "the warm-up effect". This effect often diminishes quickly with rest. Some individuals with myotonia congenita are prone to falling as a result of hasty movements or an inability to stabilize themselves after a loss of balance. During a fall, a person with myotonia congenita may experience partial or complete rigid paralysis that will quickly resolve once the event is over. However, a fall into cold water may render the person unable to move for the duration of submergence. As with myotonic goats, children are more prone to falling than adults, due to their impulsivity.The two major types of myotonia congenita are distinguished by the severity of their symptoms and their patterns of inheritance. Becker disease usually appears later in childhood than Thomsen disease, and causes more severe myotonia, muscle stiffness and transient weakness. Although myotonia in itself is not normally associated with pain, cramps or myalgia may develop. People with Becker disease often experience temporary attacks of muscle weakness, particularly in the arms and hands, brought on by movement after periods of rest. They may also develop mild, permanent muscle weakness over time. This muscle weakness is not observed in people with Thomsen disease. However, in recent times, as more of the individual mutations that cause myotonia congenita are identified, these limited disease classifications are becoming less widely used.Early symptoms in a child may include:
Difficulty swallowing
Gagging
Stiff movements that improve when they are repeated
Frequent falling
Difficulties opening eyelids after strenuous contraction or crying (von Graefes sign)Possible complications may include:
Aspiration pneumonia (caused by swallowing difficulties)
Frequent choking or gagging in infants (also caused by swallowing difficulties)
Abdominal muscle weakness
Chronic joint problems
Injury due to falls

Phenotypic variability
Both Thomsen and Becker myotonia have high phenotype variability. Severity of symptoms can vary greatly between individuals and throughout the lives of the individuals themselves. This may be partly because there are over 130 currently known different mutations that can cause the disorder, each with their own specifics, and also because myotonia congenita is an ion channel disorder, and ion channels are sensitive to internal and external environmental factors. It has been shown that pregnancy and the use of diuretics aggravate myotonia, and both these conditions are linked to the loss of divalent cations such as magnesium and calcium. It has further been shown that in chemically-induced myotonia in isolated rat muscle, myotonia could be dampened by increasing the magnesium and calcium content of the extracellular medium. This has also been shown for isolated human muscle.Adrenaline/epinephrine is well known to make myotonia worse in most individuals with the disorder, and a person with myotonia congenita may experience a sudden increase in difficulty with mobility in a particularly stressful situation during which adrenaline is released.Due to the invisible nature of the disorder, the fact that those with myotonia congenita often appear very fit and able bodied, the general lack of knowledge about the disorder by the general and medical community, and often by the individual themselves, and the potential for inconsistency with the symptoms, many people with myotonia congenita have experienced a degree of social persecution at one time or another because of the effects of their disorder.

The warm-up phenomenon
This phenomenon was described along with the disease by Thomsen in 1876 but its etiology remains unclear.Patients report that myotonia congenita may present itself in the following ways (this is from first hand experience). If the person is sedentary and then decides to walk up a set of stairs, by the third or fourth step their leg muscles begin to stiffen significantly, requiring them to slow down almost to a complete stop. But as the muscles loosen up, a few steps later, they can once again begin to climb the steps at a normal pace. If this person plays any kind of a sport, a good warm-up is mandatory. Otherwise if they need to quickly and intensively use their muscles, such as in a sprint race or a basketball game, their muscles will freeze up, causing them to slow down or almost come to a complete stop. But once the muscles are warmed up, they can once again function normally. This can happen in various muscles, even in muscles such as the tongue. For example, if a person has not spoken for awhile and then wants to speak, their tongue may be stiff at first causing the words to come out a little garbled, but after a few seconds of trying to speak, the tongue muscle will loosen up and then they can speak normally for the remainder of the time that they are conversing.Patients report that repeated contraction of muscle alleviates present myotonia with each contraction, such that myotonia is almost absent after a few contractions of the same muscle. The effect lasts about five minutes. There have been several proposed mechanisms for this phenomenon, but none have been demonstrated conclusively; one hypothesis is that the Na+/K+-ATPase is stimulated during the myotonic activity by increased intracellular Na+ in the cytosol of the muscle cell, increasing the activity of the Na+/K+-ATPase. However, in experiments with patients where the Na+/K+-ATPase had been blocked in the underarm by infusion of the Na+/K+-ATPase-blocker Ouabain, no effect on warm-up was observed. Another hypothesis states that the few remaining functional chloride channels in muscle may become more active with increased muscle activity.It has been proposed that inactivation of sodium channel protein type 4 subunit alpha, residing in skeletal muscle, could play an important role in the warm-up phenomenon. In particular, slow inactivation of the channel is believed to have a spatial and temporal extent that is correlated to warm-up and therefore may provide a plausible cause.

Causes
The disorder is caused by mutations in part of a gene (CLCN1) encoding the ClC-1 chloride channel, resulting in muscle fiber membranes having an unusually exaggerated response to stimulation (hyperexcitability).Three cases have been reported who were diagnosed with Thomsens myotonia and proved on genetic testing not to have mutations in the chloride gene but rather in the alpha-subunit of the voltage gated sodium channel (SCN4A). Like chloride channel mutations, patients with sodium channel mutations may have a very varied phenotype, making a diagnosis more difficult.

Mechanisms
Myotonia congenita is caused in humans by loss-of-function mutations in the gene CLCN1.  This is the gene encoding the protein CLCN1, that forms the ClC-1 chloride channel, critical for the normal function of skeletal muscle cells. This gene is also associated with the condition in horses, goats, and dogs. In short, in lack of sufficient functional chloride channels, the muscle fiber membrane becomes hyper-excitable and continues to be electrically active (firing action potentials) when stimulated, for longer periods of time, than a normal muscle fiber. This results in prolonged contraction/delayed relaxation of the muscle.The dysfunctional Cl− channels are located in the muscle fiber membrane and do not affect the motor nerve innervating the muscle. However, many studies have shown that denervation of muscle fibers alter the resting membrane conductance, but whether this affects myotonia in the muscle has been subject to heavy debate, and results from experiments are inconclusive.In skeletal muscle fibers, a large transverse tubule system with a high surface-area to volume ratio exists. The onset of skeletal muscle activity is associated with the initiation and propagation of action potentials again associated with an efflux of K+ to the extracellular fluid and transverse tubule system. When many action potentials are elicited subsequently more K+ is expelled from the cell into the transverse tubular system. As K+ accumulates in the transverse tubular system the equilibrium potential for K+ (EK+) normally around -80 mV, becomes more depolarized (depolarization), according to the Nernst equation. In skeletal muscle fibers the equilibrium potential for Cl− is around -80 mV, equal to that of K+ at rest. Cl− moves towards its equilibrium potential around -80 mV, while potassium moves towards its equilibrium potential more depolarized than -80 mV during activity. This results in a slightly more depolarized membrane potential of the fiber during repeated action potentials, see Goldman equation. The Na+ conductance is only elevated shortly compared to the K+ conductance during each action potential, which is why K+ largely determines the membrane potential (Cl− is passively distributed during rest).
In the case of myotonia congenita, the chloride channels that allow Cl− to move across the membrane towards its equilibrium potential are defective, thus K+ is the only ion determining the membrane potential, and as more and more K+ accumulates in the transverse tubular system with each subsequent action potential the fiber depolarizes until the membrane potential comes close enough to the action potential threshold for spontaneous activity to ensue
Spontaneous action potentials can arise for several seconds, leading to the delayed relaxation that is the hallmark of myotonia. Cessation of spontaneous activity is associated with sodium channel  inactivation (Nav1.4).

Diagnosis
Types
Two types of myotonia congenita exist, an autosomal dominant form and an autosomal recessive form. Autosomal dominant myotonia congenita (OMIM #160800) is also called Thomsen disease, after Danish/German physician Asmus Julius Thomas Thomsen (1815–1896), who himself had the disease and who wrote the first description of it in the medical literature (in 1876). Autosomal recessive myotonia congenita (OMIM #255700) is also called generalized myotonia, recessive generalized myotonia (RGM), Becker disease, and Becker myotonia, after the German professor Peter Emil Becker, who discovered its recessive nature.The term congenital in its sense of "clinically apparent from birth" applies only to Thomsen disease, as the clinical onset of Becker myotonia may be delayed up to the age of 4 to 6 years </s>


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<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 Murine typhus and can you explain it in depth? [/INST] Murine typhus, also known as endemic typhus or flea-borne typhus, is a form of typhus transmitted by fleas (Xenopsylla cheopis), usually on rats, in contrast to epidemic typhus which is usually transmitted by lice. Murine typhus is an under-recognized entity, as it is often confused with viral illnesses. Most people who are infected do not realize that they have been bitten by fleas. Historically the term "hunger-typhus" was used  in accounts by British POWs in Germany at the end of World War I when they described conditions in Germany.

Signs and symptoms
Symptoms of endemic typhus include headache, fever, muscle pain, joint pain, nausea and vomiting. 40–50% of patients will develop a discrete rash six days after the onset of signs. Up to 45% will develop neurological signs such as confusion, stupor, seizures or imbalance.
Symptoms may resemble those of measles, rubella, or possibly Rocky Mountain spotted fever. These symptoms are likely caused by a vasculitis caused by the rickettsia.

Causes
It is caused by the bacterium Rickettsia typhi, and is transmitted by the fleas that infest rats.  While rat fleas are the most common vectors, cat fleas and mouse fleas are less common modes of transmission. These fleas are not affected by the infection. Human infection occurs because of flea-fecal contamination of the bites on human skin. Rats, cats, and opossums maintain the rickettsia colonization by providing it with a host for its entire life cycle. Rats can develop the infection, and help spread the infection to other fleas that bite them, and help multiply the number of infected fleas that can then infect humans.
Less often, endemic typhus is caused by Rickettsia felis and transmitted by fleas carried by cats or opossums.
In the United States of America, murine typhus is found most commonly in southern California, Texas and Hawaii </s>


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<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 Psoriasis and can you explain it in depth? [/INST] Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, or purple on some people with darker skin, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complete body coverage. Injury to the skin can trigger psoriatic skin changes at that spot, which is known as the Koebner phenomenon.The five main types of psoriasis are plaque, guttate, inverse, pustular, and erythrodermic. Plaque psoriasis, also known as psoriasis vulgaris, makes up about 90% of cases. It typically presents as red patches with white scales on top. Areas of the body most commonly affected are the back of the forearms, shins, navel area, and scalp. Guttate psoriasis has drop-shaped lesions. Pustular psoriasis presents as small, noninfectious, pus-filled blisters. Inverse psoriasis forms red patches in skin folds. Erythrodermic psoriasis occurs when the rash becomes very widespread, and can develop from any of the other types. Fingernails and toenails are affected in most people with psoriasis at some point in time. This may include pits in the nails or changes in nail color.Psoriasis is generally thought to be a genetic disease that is triggered by environmental factors. If one twin has psoriasis, the other twin is three times more likely to be affected if the twins are identical than if they are nonidentical. This suggests that genetic factors predispose to psoriasis. Symptoms often worsen during winter and with certain medications, such as beta blockers or NSAIDs. Infections and psychological stress can also play a role.  The underlying mechanism involves the immune system reacting to skin cells. Diagnosis is typically based on the signs and symptoms.There is no known cure for psoriasis, but various treatments can help control the symptoms. These treatments include steroid creams, vitamin D3 cream, ultraviolet light, and immunosuppressive drugs, such as methotrexate. About 75% of skin involvement improves with creams alone. The disease affects 2–4% of  the population. Men and women are affected with equal frequency. The disease may begin at any age, but typically starts in adulthood. Psoriasis is associated with an increased risk of psoriatic arthritis, lymphomas, cardiovascular disease, Crohns disease, and depression. Psoriatic arthritis affects up to 30% of individuals with psoriasis.The word "psoriasis" is from Greek ψωρίασις, meaning "itching condition" or "being itchy" from psora, "itch", and -iasis, "action, condition".

Signs and symptoms
Plaque psoriasis
Psoriasis vulgaris (also known as chronic stationary psoriasis or plaque-like psoriasis) is the most common form and affects 85–90% of people with psoriasis. Plaque psoriasis typically appears as raised areas of inflamed skin covered with silvery-white, scaly skin. These areas are called plaques and are most commonly found on the elbows, knees, scalp, and back.

Other forms
Additional types of psoriasis comprise about 10% of cases. They include pustular, inverse, napkin, guttate, oral, and seborrheic-like forms.

Pustular psoriasis
Pustular psoriasis appears as raised bumps filled with noninfectious pus (pustules). The skin under and surrounding the pustules is red and tender. Pustular psoriasis can either be localized or more widespread throughout the body. Two types of localized pustular psoriasis include psoriasis pustulosa palmoplantaris and acrodermatitis continua of Hallopeau; both forms are localized to the hands and feet.

Inverse psoriasis
Inverse psoriasis (also known as flexural psoriasis) appears as smooth, inflamed patches of skin. The patches frequently affect skin folds, particularly around the genitals (between the thigh and groin), the armpits, in the skin folds of an overweight abdomen (known as panniculus), between the buttocks in the intergluteal cleft, and under the breasts in the inframammary fold. Heat, trauma, and infection are thought to play a role in the development of this atypical form of psoriasis.

Napkin psoriasis
Napkin psoriasis is a subtype of psoriasis common in infants characterized by red papules with silver scale in the diaper area that may extend to the torso or limbs. Napkin psoriasis is often misdiagnosed as napkin dermatitis (diaper rash).

Guttate psoriasis
Guttate psoriasis is characterized by numerous small, scaly, red or pink, droplet-like lesions (papules). These numerous spots of psoriasis appear over large areas of the body, primarily the trunk, but also the limbs and scalp. Guttate psoriasis is often triggered by a streptococcal infection, typically streptococcal pharyngitis.

Erythrodermic psoriasis
Psoriatic erythroderma (erythrodermic psoriasis) involves widespread inflammation and exfoliation of the skin over most of the body surface, often involving greater than 90% of the body surface area. It may be accompanied by severe dryness, itching, swelling, and pain. It can develop from any type of psoriasis. It is often the result of an exacerbation of unstable plaque psoriasis, particularly following the abrupt withdrawal of systemic glucocorticoids. This form of psoriasis can be fatal as the extreme inflammation and exfoliation disrupt the bodys ability to regulate temperature and perform barrier functions.

Mouth
Psoriasis in the mouth is very rare, in contrast to lichen planus, another common papulosquamous disorder that commonly involves both the skin and mouth. When psoriasis involves the oral mucosa (the lining of the mouth), it may be asymptomatic, but it may appear as white or grey-yellow plaques. Fissured tongue is the most common finding in those with oral psoriasis and has been reported to occur in 6.5–20% of people with psoriasis affecting the skin. The microscopic appearance of oral mucosa affected by geographic tongue (migratory stomatitis) is very similar to the appearance of psoriasis. However, modern studies have failed to demonstrate any link between the two conditions.

Seborrheic-like psoriasis
Seborrheic-like psoriasis is a common form of psoriasis with clinical aspects of psoriasis and seborrheic dermatitis, and it may be difficult to distinguish from the latter. This form of psoriasis typically manifests as red plaques with greasy scales in areas of higher sebum production such as the scalp, forehead, skin folds next to the nose, the skin surrounding the mouth, skin on the chest above the sternum, and in skin folds.

Psoriatic arthritis
Psoriatic arthritis is a form of chronic inflammatory arthritis that has a highly variable clinical presentation and frequently occurs in association with skin and nail psoriasis. It typically involves painful inflammation of the joints and surrounding connective tissue, and can occur in any joint, but most commonly affects the joints of the fingers and toes.  This can result in a sausage-shaped swelling of the fingers and toes known as dactylitis. Psoriatic arthritis can also affect the hips, knees, spine (spondylitis), and sacroiliac joint (sacroiliitis). About 30% of individuals with psoriasis will develop psoriatic arthritis. Skin manifestations of psoriasis tend to occur before arthritic manifestations in about 75% of cases.

Nail changes
Psoriasis can affect the nails and produces a variety of changes in the appearance of fingers and toenails. Nail psoriasis occurs in 40–45% of people with psoriasis affecting the skin, and has a lifetime incidence of 80–90% in those with psoriatic arthritis. These changes include pitting of the nails (pinhead-sized depressions in the nail is seen in 70% with nail psoriasis), whitening of the nail, small areas of bleeding from capillaries under the nail, yellow-reddish discoloration of the nails known as the oil drop or salmon spots, dryness, thickening of the skin under the nail (subungual hyperkeratosis), loosening and separation of the nail (onycholysis), and crumbling of the nail.

Medical signs
In addition to the appearance and distribution of the rash, specific medical signs may be used by medical practitioners to assist with diagnosis. These may include Auspitzs sign (pinpoint bleeding when scale is removed), Koebner phenomenon (psoriatic skin lesions induced by trauma to the skin), and itching and pain localized to papules and plaques.

Causes
The cause of psoriasis is not fully understood, but many theories exist.

Genetics
Around one-third of people with psoriasis report a family history of the disease, and researchers have identified genetic loci associated with the condition. Identical twin studies suggest a 70% chance of a twin developing psoriasis if the other twin has the disorder. The risk is around 20% for nonidentical twins. These findings suggest both a genetic susceptibility and an environmental response in developing psoriasis.Psoriasis has a strong hereditary component, and many genes are associated with it, but how those genes work together is unclear. Most of the identified genes relate to the immune system, particularly the major histocompatibility complex (MHC) and T cells. Genetic studies are valuable due to their ability to identify molecular mechanisms and pathways for further study and potential medication targets.Classic genome-wide linkage analysis has identified nine loci on different chromosomes associated with psoriasis. They are called psoriasis susceptibility 1 through 9 (PSORS1 through PSORS9). Within those loci are genes on pathways that lead to inflammation. Certain variations (mutations) of those genes are commonly found in psoriasis. Genome-wide association scans have identified other genes that are altered to characteristic variants in psoriasis. Some of these genes express inflammatory signal proteins, which affect cells in the immune system that are also involved in psoriasis. Some of these genes are also involved in other autoimmune diseases.The major determinant is PSORS1, which probably accounts for 35–50% of psoriasis heritability. It controls genes that affect the immune system or encode skin proteins that are overabundant with psoriasis. PSORS1 is located on chromosome 6 in the MHC, which controls important immune functions. Three genes in the PSORS1 locus have a strong association with psoriasis vulgaris: HLA-C variant HLA-Cw6, which encodes an MHC class I protein; CCHCR1, variant WWC, which encodes a coiled coil protein  overexpressed in psoriatic epidermis; and CDSN, variant allele 5, which encodes corneodesmosin, a protein expressed in the granular and cornified layers of the epidermis and upregulated in psoriasis.Two major immune system genes under investigation are interleukin-12 subunit beta (IL12B) on chromosome 5q, which expresses interleukin-12B; and IL23R on chromosome 1p, which expresses the interleukin-23 receptor, and is involved in T cell differentiation. Interleukin-23 receptor and IL12B have both been strongly linked with psoriasis. T cells are involved in the inflammatory process that leads to psoriasis.  These genes are on the pathway that upregulate tumor necrosis factor-α and nuclear factor κB, two genes involved in inflammation. The first gene directly linked to psoriasis was identified as the CARD14 gene located in the PSORS2 locus. A rare mutation in the gene encoding for the CARD14-regulated protein plus an environmental trigger was enough to cause plaque psoriasis (the most common form of psoriasis).

Lifestyle
Conditions reported as worsening the disease include chronic infections, stress, and changes in season and climate. Others factors that might worsen the condition include hot water, scratching psoriasis skin lesions, skin dryness, excessive alcohol consumption, cigarette smoking, and obesity. The effects of stopping cigarette smoking or alcohol misuse have yet to be studied as of 2019.

HIV
The rate of psoriasis in human immunodeficiency virus-positive (HIV) individuals is comparable to that of HIV-negative individuals, but psoriasis tends to be more severe in people infected with HIV. A much higher rate of psoriatic arthritis occurs in HIV-positive individuals with psoriasis than in those without the infection. The immune response in those infected with HIV is typically characterized by cellular signals from Th2 subset of CD4+ helper T cells, whereas the immune response in psoriasis vulgaris is characterized by a pattern of cellular signals typical of Th1 subset of CD4+ helper T cells and Th17 helper T cells. The diminished CD4+-T cell presence is thought to cause an overactivation of CD8+-T cells, which are responsible for the exacerbation of psoriasis in HIV-positive people. Psoriasis in those with HIV/AIDS is often severe and may be untreatable with conventional therapy. In those with long-term, well-controlled psoriasis, new HIV infection can trigger a severe flare-up of psoriasis and/or psoriatic arthritis.

Microbes
Psoriasis has been described as occurring after strep throat, and may be worsened by skin or gut colonization with Staphylococcus aureus, Malassezia spp., and Candida albicans. Guttate psoriasis often affects children and adolescents and can be triggered by a recent group A streptococcal infection (tonsillitis or pharyngitis).

Medications
Drug-induced psoriasis may occur with beta blockers, lithium, antimalarial medications, nonsteroidal anti-inflammatory drugs, terbinafine, calcium channel blockers, captopril, glyburide, granulocyte colony-stimulating factor, interleukins, interferons, lipid-lowering medications,: 197  and paradoxically TNF inhibitors such as infliximab or adalimumab. Withdrawal of corticosteroids (topical steroid cream) can aggravate psoriasis due to the rebound effect.

Pathophysiology
Psoriasis is characterized by an abnormally excessive and rapid growth of the epidermal layer of the skin. Abnormal production of skin cells (especially during wound repair) and an overabundance of skin cells result from the sequence of pathological events in psoriasis. The sequence of pathological events in psoriasis is thought to start with an initiation phase in which an event (skin trauma, infection, or drugs) leads to activation of the immune system and then the maintenance phase consisting of chronic progression of the disease. Skin cells are replaced every 3–5 days in psoriasis rather than the usual 28–30 days. These changes are believed to stem from the premature maturation of keratinocytes induced by an inflammatory cascade in the dermis involving dendritic cells, macrophages, and T cells (three subtypes of white blood cells). These immune cells move from the dermis to the epidermis and secrete inflammatory chemical signals (cytokines) such as interleukin-36γ, tumor necrosis factor-α, interleukin-1β, interleukin-6, and interleukin-22.  These secreted inflammatory signals are believed to stimulate keratinocytes to proliferate. One hypothesis is that psoriasis involves a defect in regulatory T cells, and in the regulatory cytokine interleukin-10. The inflammatory cytokines found in psoriatic nails and joints (in the case of psoriatic arthritis) are similar to those of psoriatic skin lesions, suggesting a common inflammatory mechanism.Gene mutations of proteins involved in the skins ability to function as a barrier have been identified as markers of susceptibility for the development of psoriasis.Deoxyribonucleic acid (DNA) released from dying cells acts as an inflammatory stimulus in psoriasis and stimulates the receptors on certain dendritic cells, which in turn produce the cytokine interferon-α.  In response to these chemical messages from dendritic cells and T cells, keratinocytes also secrete cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor-α, which signal downstream inflammatory cells to arrive and stimulate additional inflammation.Dendritic cells bridge the innate immune system and adaptive immune system. They are increased in psoriatic lesions and induce the proliferation of T cells and type 1 helper T cells (Th1). Targeted immunotherapy, as well as psoralen and ultraviolet A (PUVA) therapy, can reduce the number of dendritic cells and favors a Th2 cell cytokine secretion pattern over a Th1/Th17 cell cytokine profile. Psoriatic T cells move from the dermis into the epidermis and secrete interferon-γ and interleukin-17. Interleukin-23 is known to induce the production of interleukin-17 and interleukin-22. Interleukin-22 works in combination with interleukin-17 to induce keratinocytes to secrete neutrophil-attracting cytokines.

Diagnosis
A diagnosis of psoriasis is usually based on the appearance of the skin. Skin characteristics typical for psoriasis are scaly, erythematous plaques, papules, or patches of skin that may be painful and itch. No special blood tests or diagnostic procedures are usually required to make the diagnosis.The differential diagnosis of psoriasis includes dermatological conditions similar in appearance such as discoid eczema, seborrheic eczema, pityriasis rosea (may be confused with guttate psoriasis), nail fungus (may be confused with nail psoriasis) or cutaneous T cell lymphoma (50% of individuals with this cancer are initially misdiagnosed with psoriasis). Dermatologic manifestations of systemic illnesses such as the rash of secondary syphilis may also be confused with psoriasis.If the clinical diagnosis is uncertain, a skin biopsy or scraping may be performed to rule out other disorders and to confirm the diagnosis. Skin from a biopsy shows clubbed epidermal projections that interdigitate with dermis on microscopy. Epidermal thickening is another characteristic histologic finding of psoriasis lesions. The stratum granulosum layer of the epidermis is often missing or significantly decreased in psoriatic lesions; the skin cells from the most superficial layer of skin are also abnormal as they never fully mature. Unlike their mature counterparts, these superficial cells keep their nuclei. Inflammatory infiltrates can typically be seen on microscopy when examining skin tissue or joint tissue affected by psoriasis. Epidermal skin tissue affected by psoriatic inflammation often has many CD8+ T cells, while a predominance of CD4+ T cells makes up the inflammatory infiltrates of the dermal layer of skin and the joints.

Classification
Morphological
Psoriasis is classified as a papulosquamous disorder and is most commonly subdivided into different categories based on histological characteristics. Variants include plaque, pustular, guttate, and flexural psoriasis. Each form has a dedicated ICD-10 code. Psoriasis can also be classified into nonpustular and pustular types.

Pathogenetic
Another classification scheme considers genetic and demographic factors. Type 1 has a positive family history, starts before the age of 40, and is associated with the human leukocyte antigen, HLA-Cw6. Conversely, type 2 does not show a family history, presents after age 40, and is not associated with HLA-Cw6. Type 1 accounts for about 75% of persons with psoriasis.The classification of psoriasis as an autoimmune disease has sparked considerable debate. Researchers have proposed differing descriptions of psoriasis and psoriatic arthritis; some authors have classified them as autoimmune diseases while others have classified them as distinct from autoimmune diseases and referred to them as immune-mediated inflammatory diseases.

Severity
No consensus exists about how to classify the severity of psoriasis. Mild psoriasis has been defined as a percentage of body surface area (BSA)≤10, a Psoriasis Area and Severity Index (PASI) score ≤10, and a Dermatology Life Quality Index (DLQI)  score ≤10. Moderate to severe psoriasis was defined by the same group as BSA >10 or PASI score >10 and a DLQI score >10.The DLQI is a 10-question tool used to measure the impact of several dermatologic diseases on daily functioning. The DLQI score ranges from 0 (minimal impairment) to 30 (maximal impairment) and is calculated with each answer being assigned 0–3 points with higher scores indicating greater social or occupational impairment.The PASI is the most widely used measurement tool for psoriasis. It assesses the severity of lesions and the area affected and combines these two factors into a single score from 0 (no disease) to 72 (maximal disease). Nevertheless, the PASI can be too unwieldy to use outside of research settings, which has led to attempts to simplify the index for clinical use.

Management
While no cure is available for psoriasis, many treatment options exist. Topical agents are typically used for mild disease, phototherapy for moderate disease, and systemic agents for severe disease. There is no evidence to support the effectiveness of conventional topical and systemic drugs, biological therapy, or phototherapy for acute guttate psoriasis or an acute guttate flare of chronic psoriasis.

Topical agents
Topical corticosteroid preparations are the most effective agents when used continuously for eight weeks; retinoids and coal tar were found to be of limited benefit and may be no better than placebo. Greater benefit has been observed with very potent corticosteroids when compared to potent corticosteroids.
Vitamin D analogues such as paricalcitol are superior to placebo. Combination therapy with vitamin D and a corticosteroid are superior to either treatment alone and vitamin D is superior to coal tar for chronic plaque psoriasis.For psoriasis of the scalp, a 2016 review found dual therapy (vitamin D analogues and topical corticosteroids) or corticosteroid monotherapy to be more effective and safer than topical vitamin D analogues alone. Due to their similar safety profiles and minimal benefit of dual therapy over monotherapy, corticosteroid monotherapy appears to be an acceptable treatment for short-term treatment.Moisturizers and emollients such as mineral oil, petroleum jelly, calcipotriol, and decubal (an oil-in-water emollient) were found to increase the clearance of psoriatic plaques. Some emollients have been shown to be even more effective at clearing psoriatic plaques when combined with phototherapy. Certain emollients, though, have no impact on psoriasis plaque clearance or may even decrease the clearance achieved with phototherapy, e.g. the emollient salicylic acid is structurally similar to para-aminobenzoic acid, commonly found in sunscreen, and is known to interfere with phototherapy in psoriasis. Coconut oil, when used as an emollient in psoriasis, has been found to decrease plaque clearance with phototherapy.  Medicated creams and ointments applied directly to psoriatic plaques can help reduce inflammation, remove built-up scale, reduce skin turnover, and clear affected skin of plaques. Ointment and creams containing coal tar, dithranol, corticosteroids (i.e. desoximetasone), fluocinonide, vitamin D3 analogues (for example, calcipotriol), and retinoids are routinely used. (The use of the finger tip unit may be helpful in guiding how much topical treatment to use.)Vitamin D analogues may be useful with steroids; steroids alone have a higher rate of side effects. Vitamin D analogues may allow less steroids to be used.Another topical therapy used to treat psoriasis is a form of balneotherapy, which involves daily baths in the Dead Sea. This is usually done for four weeks with the benefit attributed to sun exposure and specifically UVB light. This is cost-effective and it has been propagated as an effective way to treat psoriasis without medication. Decreases of PASI scores greater than 75% and remission for several months have commonly been observed. Side effects may be mild such as itchiness, folliculitis, sunburn, poikiloderma, and a theoretical risk of nonmelanoma cancer or melanoma has been suggested. Some studies indicate no increased risk of melanoma in the long term. Data are inconclusive with respect to nonmelanoma skin cancer risk, but support the idea that the therapy is associated with an increased risk of benign forms of sun-induced skin damage such as, but not limited to, actinic elastosis or liver spots. Dead Sea balneotherapy is also effective for psoriatic arthritis. Tentative evidence indicates that balneophototherapy, a combination of salt bathes and exposure to ultraviolet B-light (UVB), in chronic plaque psoriasis is better than UVB alone.

UV phototherapy
Phototherapy in the form of sunlight has long been used for psoriasis. UVB wavelengths of 311–313 nanometers are most effective, and special lamps have been developed for this application. The exposure time should be controlled to avoid overexposure and burning of the skin. The UVB lamps should have a timer that turns off the lamp when the time ends. The amount of light used is determined by a persons skin type. Increased rates of cancer from treatment appear to be small. Narrowband UVB therapy has been demonstrated to have similar efficacy to psoralen and ultraviolet A phototherapy (PUVA). A 2013 meta-analysis found no difference in efficacy between NB-UVB and PUVA in the treatment of psoriasis, but NB-UVB is usually more convenient.One of the problems with clinical phototherapy is the difficulty many people have gaining access to a facility. Indoor tanning resources are almost ubiquitous today and could be considered as a means for people to get UV exposure when dermatologist-provided phototherapy is not available. Indoor tanning is already used by many people as a treatment for psoriasis; one indoor facility reported that 50% of its clients were using the center for psoriasis treatment; another reported 36% were doing the same thing. However, a concern with the use of commercial tanning is that tanning beds that primarily emit UVA might not effectively treat psoriasis. One study found that plaque psoriasis is responsive to erythemogenic doses of either UVA or UVB, as exposure to either can cause dissipation of psoriatic plaques. It does require more energy to reach erythemogenic dosing with UVA.UV light therapies all have risks; tanning beds are no exception, being listed by the World Health Organization as carcinogens. Exposure to UV light is known to increase the risks of melanoma and squamous cell and basal cell carcinomas; younger people with psoriasis, particularly those under age 35, are at increased risk from melanoma from UV light treatment. A review of studies recommends that people who are susceptible to skin cancers exercise caution when using UV light therapy as a treatment.A major mechanism of NB-UVB is the induction of DNA damage in the form of pyrimidine dimers. This type of phototherapy is useful in the treatment of psoriasis because the formation of these dimers interferes with the cell cycle and stops it. The interruption of the cell cycle induced by NB-UVB opposes the characteristic rapid division of skin cells seen in psoriasis. The activity of many types of immune cells found in the skin is also effectively suppressed by NB-UVB phototherapy treatments. The most common short-term side effect of this form of phototherapy is redness of the skin; less common side effects of NB-UVB phototherapy are itching and blistering of the treated skin, irritation of the eyes in the form of conjunctival inflammation or inflammation of the cornea, or cold sores due to reactivation of the herpes simplex virus in the skin surrounding the lips. Eye protection is usually given during phototherapy treatments.PUVA combines the oral or topical administration of psoralen with exposure to ultraviolet A (UVA) light. The mechanism of action of PUVA is unknown, but probably involves activation of psoralen by UVA light, which inhibits the abnormally rapid production of the cells in psoriatic skin.  There are multiple mechanisms of action associated with PUVA, including effects on the skins immune system. PUVA is associated with nausea, headache, fatigue, burning, and itching. Long-term treatment is associated with squamous cell carcinoma (but not with melanoma).  A combination therapy for moderate to severe psoriasis using PUVA plus acitretin resulted in benefit, but acitretin use has been associated with birth defects and liver damage.

Systemic agents
Psoriasis resistant to topical treatment and phototherapy may be treated with systemic therapies including medications by mouth or injectable treatments. People undergoing systemic treatment must have regular blood and liver function tests to check for medication toxicities. Pregnancy must be avoided for most of these treatments. The majority of people experience a recurrence of psoriasis after systemic treatment is discontinued.
Non-biologic systemic treatments frequently used for psoriasis include methotrexate, ciclosporin, hydroxycarbamide, fumarates such as dimethyl fumarate, and retinoids. Methotrexate and ciclosporin are medications that suppress the immune system; retinoids are synthetic forms of vitamin A. These agents are also regarded as first-line treatments for psoriatic erythroderma. Oral corticosteroids should not be used, for they can severely flare psoriasis upon their discontinuation.Biologics are manufactured proteins that interrupt the immune process involved in psoriasis. Unlike generalized immunosuppressive medical therapies such as methotrexate, biologics target specific aspects of the immune system contributing to psoriasis. These medications are generally well-tolerated, and limited long-term outcome data have demonstrated biologics to be safe for long-term use in moderate to severe plaque psoriasis. However, due to their immunosuppressive actions, biologics have been associated with a small increase in the risk for infection.Guidelines regard biologics as third-line treatment for plaque psoriasis following inadequate response to topical treatment, phototherapy, and non-biologic systemic treatments. The safety of biologics during pregnancy has not been assessed. European guidelines recommend avoiding biologics if a pregnancy is planned; anti-TNF therapies such as infliximab are not recommended for use in chronic carriers of the hepatitis B virus or individuals infected with HIV.Several monoclonal antibodies target cytokines, the molecules that cells use to send inflammatory signals to each other. TNF-α is one of the main executor inflammatory cytokines.  Four monoclonal antibodies (MAbs) (infliximab, adalimumab, golimumab, and certolizumab pegol) and one recombinant TNF-α decoy receptor, etanercept, have been developed to inhibit TNF-α signaling.  Additional monoclonal antibodies, such as ixekizumab, have been developed against pro-inflammatory cytokines and inhibit the inflammatory pathway at a different point than the anti-TNF-α antibodies.  IL-12 and IL-23 share a common domain, p40, which is the target of the FDA-approved ustekinumab. In 2017 the US FDA approved guselkumab for plaque psoriasis. There have been few studies of the efficacy of anti-TNF medications for psoriasis in children. One randomized control study suggested that 12 weeks of etanercept treatment reduced the extent of psoriasis in children with no lasting adverse effects.Two medications that target T cells are efalizumab and alefacept. Efalizumab is a monoclonal antibody that specifically targets the CD11a subunit of LFA-1. It also blocks the adhesion molecules on the endothelial cells that line blood vessels, which attract T cells. Efalizumab was voluntarily withdrawn from the European market in February 2009, and from the U.S. market in June 2009, by the manufacturer due to the medications association with cases of progressive multifocal leukoencephalopathy. Alefacept also blocks the molecules that dendritic cells use to communicate with T cells and even causes natural killer cells to kill T cells as a way of controlling inflammation. Apremilast may also be used.Individuals with psoriasis may develop neutralizing antibodies against monoclonal antibodies. Neutralization occurs when an antidrug antibody prevents a monoclonal antibody such as infliximab from binding antigen in a laboratory test. Specifically, neutralization occurs when the anti-drug antibody binds to infliximabs antigen binding site instead of TNF-α. When infliximab no longer binds tumor necrosis factor alpha, it no longer decreases inflammation, and psoriasis may worsen. Neutralizing antibodies have not been reported against etanercept, a biologic medication that is a fusion protein composed of two TNF-α receptors. The lack of neutralizing antibodies against etanercept is probably secondary to the innate presence of the TNF-α receptor, and the development of immune tolerance.A 2021 meta-analysis found that ixekizumab, secukinumab, brodalumab, guselkumab, certolizumab, and ustekinumab were the most effective biologics for treating psoriasis. In general, anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha biologics were found to be more effective than traditional systemic treatments. The immunologic pathways of psoriasis involve Th9, Th17, Th1 lymphocytes, and IL-22. The aforementioned biologic agents hinder different aspects of these pathways.Another treatment for moderate to severe psoriasis is fumaric acid esters (FAE) which may be similar in effectiveness to methotrexate.It has been theorized that antistreptococcal medications may improve guttate and chronic plaque psoriasis; however, the limited studies do not show that antibiotics are effective.

Surgery
Limited evidence suggests removal of the tonsils may benefit people with chronic plaque psoriasis, guttate psoriasis, and palmoplantar pustulosis.

Diet
Uncontrolled studies have suggested that individuals with psoriasis or psoriatic arthritis may benefit from a diet supplemented with fish oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A low-calorie diet appears to reduce the severity of psoriasis. Diet recommendations include consumption of cold water fish (preferably wild fish, not farmed) such as salmon, herring, and mackerel; extra virgin olive oil; legumes; vegetables; fruits; and whole grains; and avoid consumption of alcohol, red meat, and dairy products (due to their saturated fat). The effect of consumption of caffeine (including coffee, black tea, mate, and dark chocolate) remains to be determined.Many patients report improvements after consuming less tobacco, caffeine, sugar, nightshades (tomatoes, eggplant, peppers, paprika and white potatoes) and taking probiotics and oral Vitamin D.There is a higher rate of celiac disease among people with psoriasis. When adopting a gluten-free diet, disease severity generally decreases in people with celiac disease and those with anti-gliadin antibodies.

Prognosis
Most people with psoriasis experience nothing more than mild skin lesions that can be treated effectively with topical therapies.Psoriasis is known to hurt the quality of life of both the affected person and the individuals family members. Depending on the severity and location of outbreaks, individuals may experience significant physical discomfort and some disability. Itching and pain can interfere with basic functions, such as self-care and sleep. Participation in sporting activities, certain occupations, and caring for family members can become difficult activities for those with plaques located on their hands and feet. Plaques on the scalp can be particularly embarrassing, as flaky plaque in the hair can be mistaken for dandruff.Individuals with psoriasis may feel self-conscious about their appearance and have a poor self-image that stems from fear of public rejection and psychosexual concerns. Psoriasis has been associated with low self-esteem and depression is more common among those with the condition. People with psoriasis often feel prejudiced against due to the commonly held incorrect belief that psoriasis is contagious. Psychological distress can lead to significant depression and social isolation; a high rate of thoughts about suicide has been associated with psoriasis. Many tools exist to measure the quality of life of people with psoriasis and other dermatological disorders. Clinical research has indicated individuals often experience a diminished quality of life. Children with psoriasis may encounter bullying.Several conditions are associated with psoriasis. These occur more frequently in older people. Nearly half of individuals with psoriasis over the age of 65 have at least three comorbidities (concurrent conditions), and two-thirds have at least two comorbidities.

Cardiovascular disease
Psoriasis has been associated with obesity and several other cardiovascular and metabolic disturbances. The number of new cases per year of diabetes is 27% higher in people affected by psoriasis than in those without the condition. Severe psoriasis may be even more strongly associated with the development of diabetes than mild psoriasis. Younger people with psoriasis may also be at increased risk for developing diabetes. Individuals with psoriasis or psoriatic arthritis have a slightly higher risk of heart disease and heart attacks when compared to the general population. Cardiovascular disease risk appeared to be correlated with the severity of psoriasis and its duration. There is no strong evidence to suggest that psoriasis is associated with an increased risk of death from cardiovascular events. Methotrexate may provide a degree of protection for the heart.The odds of having hypertension are 1.58 times ( i.e. 58%) higher in people with psoriasis than those without the condition; these odds are even higher with severe cases of psoriasis. A similar association was noted in people who have psoriatic arthritis—the odds of having hypertension were found to be 2.07 times ( i.e. 107%) greater when compared to odds of the general population. The link between psoriasis and hypertension is not currently understood. Mechanisms hypothesized to be involved in this relationship include the following: dysregulation of the renin–angiotensin system, elevated levels of endothelin 1 in the blood, and increased oxidative stress. The number of new cases of the heart rhythm abnormality atrial fibrillation is 1.31 times ( i.e. 31%) higher in people with mild psoriasis and 1.63 times ( i.e. 63%) higher in people with severe psoriasis.  There may be a slightly increased risk of stroke associated with psoriasis, especially in severe cases. Treating high levels of cholesterol with statins has been associated with decreased psoriasis severity, as measured by PASI score, and has also been associated with improvements in other cardiovascular disease risk factors such as markers of inflammation. These cardioprotective effects are attributed to ability of statins to improve blood lipid profile and because of their anti-inflammatory effects. Statin use in those with psoriasis and hyperlipidemia was associated with decreased levels of high-sensitivity C-reactive protein and TNFα as well as decreased activity of the immune protein LFA-1. Compared to individuals without psoriasis, those affected by psoriasis are more likely to satisfy the criteria for metabolic syndrome.

Other diseases
The rates of Crohn disease and ulcerative colitis are increased when compared with the general population, by a factor of 3.8 and 7.5 respectively. People with psoriasis also have a higher risk of celiac disease. Few studies have evaluated the association of multiple sclerosis with psoriasis, and the relationship has been questioned. Psoriasis has been associated with a 16% increase in overall relative risk for non-skin cancer, thought to be attributed to systemic therapy, particularly methotrexate. People treated with long term systemic therapy for psoriasis have a 52% increased risk cancers of the lung and bronchus, a 205% increase in the risk of developing cancers of the upper gastrointestinal tract, a 31% increase in the risk of developing cancers of the urinary tract, a 90% increase in the risk of developing liver cancer, and a 46% increase in the risk of developing pancreatic cancer. The risk for development of non-melanoma skin cancers is also increased. Psoriasis increases the risk of developing squamous cell carcinoma of the skin by 431% and increases the risk of basal cell carcinoma by 100%. There is no increased risk of melanoma associated with psoriasis. People with psoriasis have a higher risk of developing cancer.

Epidemiology
Psoriasis is estimated to affect 2–4% of the population of the western world. The rate of psoriasis varies according to age, region and ethnicity; a combination of environmental and genetic factors is thought to be responsible for these differences. It can occur at any age, although it most commonly appears for the first time between the ages of 15 and 25 years. Approximately one third of people with psoriasis report being diagnosed before age 20. Psoriasis affects both sexes equally.Psoriasis affects about 6.7 million Americans and occurs more frequently in adults.Psoriasis is about five times more common in people of European descent than in people of Asian descent.People with inflammatory bowel disease such as Crohn disease or ulcerative colitis are at an increased risk of developing psoriasis. Psoriasis is more common in countries farther from the equator. Persons of white European ancestry are more likely to have psoriasis and the condition is relatively uncommon in African Americans and extremely uncommon in Native Americans.

History
Scholars believe psoriasis to have been included among the various skin conditions called tzaraath (translated as leprosy) in the Hebrew Bible, a condition imposed as a punishment for slander. The person was deemed "impure" (see tumah and taharah) during their affected phase and is ultimately treated by the kohen. However, it is more likely that this confusion arose from the use of the same Greek term for both conditions. The Greeks used the term lepra (λεπρα) for scaly skin conditions. They used the term psora to describe itchy skin conditions. It became known as Willans lepra in the late 18th century when English dermatologists Robert Willan and Thomas Bateman differentiated it from other skin diseases. Leprosy, they said, is distinguished by the regular, circular form of patches, while psoriasis is always irregular. Willan identified two categories: leprosa graecorum and psora leprosa.Psoriasis is thought to have first been described in Ancient Rome by Cornelius Celsus. The British dermatologist Thomas Bateman described a possible link between psoriasis and arthritic symptoms in 1813.The history of psoriasis is littered with treatments of dubious effectiveness and high toxicity. In the 18th and 19th centuries, Fowlers solution, which contains a poisonous and carcinogenic arsenic compound, was used by dermatologists as a treatment for psoriasis. Mercury was also used for psoriasis treatment during this time period. Sulfur, iodine, and phenol were also commonly used treatments for psoriasis during this era when it was incorrectly believed that psoriasis was an infectious disease. Coal tars were widely used with ultraviolet light irradiation as a topical treatment approach in the early 1900s. During the same time period, psoriatic arthritis cases were treated with intravenously administered gold preparations in the same manner as rheumatoid arthritis.

Society and culture
The International Federation of Psoriasis Associations (IFPA) is the global umbrella organization for national and regional psoriasis associations and also gathers the leading experts in psoriasis and psoriatic arthritis research for scientific conferences every three years. The Psoriasis International Network, a program of the Fondation René Touraine, gathers dermatologists, rheumatologists and other caregivers involved in the management of psoriasis. Non-profit organizations like the National Psoriasis Foundation in the United States, the Psoriasis Association in the United Kingdom, and Psoriasis Australia offer advocacy and education about psoriasis in their respective countries.

Cost
The annual cost for treating psoriasis in the United States is estimated as high as $32.5 billion, including $12.2 billion in direct costs. Pharmacy costs are the main source of direct expense, with biologic therapy the most prevalent. These costs increase significantly when co-morbid conditions such as heart disease, hypertension, diabetes, lung disease and psychiatric disorders are factored in </s>


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