<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 Williams syndrome and can you explain it in depth? [/INST] Williams syndrome (WS) is a genetic disorder that affects many parts of the body. Facial features frequently include a broad forehead, underdeveloped chin, short nose, and full cheeks. Mild to moderate intellectual disability is observed in people with WS, with particular challenges with visual spatial tasks such as drawing. Verbal skills are relatively unaffected. Many people with WS have an outgoing personality, an openness to engaging with other people, and a happy disposition. Medical issues with teeth, heart problems (especially supravalvular aortic stenosis), and periods of high blood calcium are common.Williams syndrome is caused by a genetic abnormality, specifically a deletion of about 27 genes from the long arm of one of the two chromosome 7s. Typically, this occurs as a random event during the formation of the egg or sperm from which a person develops. In a small number of cases, it is inherited from an affected parent in an autosomal dominant manner. The different characteristic features have been linked to the loss of specific genes. The diagnosis is typically suspected based on symptoms and confirmed by genetic testing.Treatment of WS includes special education programs and various types of therapy. Surgery may be done to correct heart problems. Dietary changes or medications may be required for high blood calcium. The syndrome was first described in 1961 by New Zealander John C. P. Williams. Williams syndrome affects between one in 20,000 and one in 7,500 people at birth. Life expectancy is less than that of the general population, mostly due to the increased rates of heart disease.

Signs and symptoms
The most common symptoms of Williams syndrome are heart defects and unusual facial features. Other symptoms include failure to gain weight appropriately in infancy (failure to thrive) and low muscle tone. People with WS tend to have widely spaced teeth, a long philtrum, and a flattened nasal bridge.Most people with WS are highly verbal relative to their intelligence, and are often very sociable, having what has been described as a "cocktail party"-type personality.  People with Williams syndrome hyperfocus on the eyes of others in social engagements.

Physical
People with WS experience many cardiac problems, commonly heart murmurs and the narrowing of major blood vessels, as well as supravalvular aortic stenosis. Other symptoms may include gastrointestinal problems, such as severe or prolonged colic, abdominal pain and diverticulitis, nocturnal enuresis (bed wetting) and urinary difficulties, dental irregularities and defective tooth enamel, and hormone problems, the most common being hypercalcemia. Hypothyroidism has been reported to occur in children, although no proof has been found of it occurring in adults; adults with WS have a higher risk of developing type-2 diabetes, with some cases apparent as young as 21 years old.People with WS often have hyperacusia and phonophobia, which resembles noise-induced hearing loss, but this may be due to a malfunctioning auditory nerve.  People with WS can also tend to demonstrate a love of music, and they appear significantly more likely to possess absolute pitch. Also, higher prevalences of left-handedness and left-eye dominance seem to occur.Ophthalmologic issues are common in WS.  Up to 75% of subjects in some studies have strabismus (ocular misalignment), particularly esotropia, due to inherent subnormal binocular visual function
and cognitive deficits in visuospatial construction. People with WS have problems with visual processing, but this is related to difficulty in dealing with complex spatial relationships rather than depth perception per se.

Nervous system
Because of missing multiple genes, many effects on the brain are seen, including abnormalities in the cerebellum, right parietal lobe, and left frontal cortical regions.  This pattern is consistent with the visual-spatial disabilities and problems with behavioral timing often seen in WS.Frontal-cerebellar pathways, involved in behavioral timing, are often abnormally developed in people with WS, which may be related to their deficits in coordination and execution of fine motor tasks such as drawing and writing. In addition, people with WS often exhibit gross motor difficulties, including trouble walking downstairs,  overactive motor reflexes (hyperreflexia), and hyperactive, involuntary movement of the eyes (nystagmus).Williams syndrome is also noteworthy for exhibiting abnormalities in the parietal-dorsal areas of the neocortex, but not the ventral areas. The parietal-dorsal area handles visual processing that supports visual-spatial analysis of the environment, while the ventral is related to semantic recognition of visual stimuli, and the recognition of faces. Thus, people with WS are often able to visually identify and recognize whole objects, and refer to them by name, but struggle with visuospatial construction (seeing an object as being composed of many smaller parts, and recreating it) and orienting themselves in space.People with WS are often affable and hyperverbal, demonstrating the decreased inhibition ability that stems from dorsal-frontal deficits. Some studies suggest that the amygdala of a person with Williams syndrome has greater volume than the average persons (though it is smaller than average in childhood).
In general, neuroimaging studies demonstrate that people with WS have diminished amygdala reactivity in response to socially frightening stimuli (such as disapproving faces), but demonstrate hyperreactivity in the amygdala when presented with nonsocial fear stimuli (such as frightening animals). This may partially account for the apparent absence of social inhibition observed in people with the syndrome, as well as the prevalence of anxious symptoms (but see fear for details on the relationship between the amygdala and fear response). Also, some evidence indicates that people with WS exhibit  amygdalal hyperactivity when viewing happy facial expressions. They are talkative and eager to please, indicating a cocktail party personality.Increased volume and activation of the left auditory cortex has been observed in people with WS, which has been interpreted as a neural correlation of patients rhythm propensity and fondness of music. Similar sizes of the auditory cortex have been previously reported only in professional musicians.

Development
The earliest observable symptoms of WS include low birth weight, failure to thrive, trouble breastfeeding, nocturnal irritability, and gastroesophageal reflux. Facial dysmorphies thought to be characteristic of the syndrome are also present early in development, as are heart murmurs. Research on the development of the syndrome suggests that congenital heart disease is typically present at an early age, often at the infants first pediatric appointment. Heart problems in infancy often lead to the initial diagnosis of WS.Developmental delays are present in most cases of WS, and include delay of language abilities and delayed motor-skill development. People with WS develop language abilities quite late relative to other children, with the childs first word often occurring as late as 3 years of age. Language abilities are often observed to be deficient until adolescence, in terms of semantics, morphology, and phonology, though not in vocabulary.Williams syndrome is also marked by a delay in the development of motor skills. Infants with WS develop the ability to lift their heads and sit without support months later than typically developing children. These delays continue into childhood, where patients with WS are delayed in learning to walk. In young children, the observed motor delay is around 5–6 months, though some research suggests that children with WS have a delay in development that becomes more extreme with age. Children with motor delays as a result of WS are particularly behind in the development of coordination, fine motor skills such as writing and drawing, response time, and strength and dexterity of the arms. Impaired motor ability persists (and possibly worsens) as children with WS reach adolescence.Adults and adolescents with Williams syndrome typically achieve a below-average height and weight, compared with unaffected populations. As people with WS age, they frequently develop joint limitations and hypertonia, or abnormally increased muscle tone. Hypertension, gastrointestinal problems, and genitourinary symptoms often persist into adulthood, as well as cardiovascular problems. Adults  are typically limited in their ability to live independently or work in competitive employment settings, but this developmental impairment is attributed more to psychological symptoms than physiological problems.

Social and psychological
People with Williams syndrome report higher anxiety levels as well as phobia development, which may be associated with hyperacusis (high sensitivity to certain frequencies of sound). Compared with other children with delays, those with Williams syndrome display a significantly greater number of fears. 35% of these children met the DSM definition of having a phobia as compared with 1–4.3% for those with other types of developmental delays. Williams syndrome is also strongly associated with attention deficit hyperactivity disorder and related psychological symptoms such as poor concentration, hyperactivity, and social disinhibition.Furthermore, cognitive abilities (IQs) of people with WMS typically range from mild to moderate levels of intellectual disability. One study of 306 children with Williams syndrome found IQ scores ranging from 40 to 112 with a mean of 69.32 (the mean IQ score of the general population is 100). IQ scores above this range have been reported in people with smaller genetic deletions. In particular, people with Williams syndrome experience challenges in visual-motor skills and visuospatial construction. Most affected people are unable to spatially orient themselves and many experience difficulty when given a task that requires even the most basic visual problem-solving. Many adults with Williams syndrome cannot complete a simple six-piece puzzle designed for young children, for example. These visuospatial deficits may be related to damage to the dorsal cortical pathway for visual processing.Despite their physical and cognitive deficits, people with Williams syndrome exhibit impressive social and verbal abilities.  Williams patients can be highly verbal relative to their IQ. When children with Williams syndrome are asked to name an array of animals, they may well list a wild assortment of creatures such as a koala, saber-toothed cat, vulture, unicorn, sea lion, yak, ibex and Brontosaurus, a far greater verbal array than would be expected of children with IQs in the 60s.  Some other strengths that have been associated with Williams syndrome are auditory short-term memory and facial recognition skills. The language used by people with Williams syndrome differs notably from unaffected populations, including people matched for IQ. People with Williams syndrome tend to use speech that is rich in emotional descriptors, high in prosody (exaggerated rhythm and emotional intensity), and features unusual terms and strange idioms.Among the hallmark traits of people with Williams syndrome is an apparent lack of social inhibition. Dykens and Rosner (1999) found that 100% of those with Williams syndrome were kind-spirited, 90% sought the company of others, 87% empathize with others pain, 84% are caring, 83% are unselfish/forgiving, 75% never go unnoticed in a group, and 75% are happy when others do well.  Infants with Williams syndrome make normal and frequent eye contact, and young children with Williams will often approach and hug strangers. People affected by Williams syndrome typically have high empathy, showing relative strength in reading peoples eyes to gauge intentions, emotions, and mental states. The level of friendliness observed in people with Williams is often inappropriate for the social setting, however,  and teens and adults with Williams syndrome often experience social isolation, frustration, and loneliness despite their clear desire to connect to other people.While these children often came off as happy due to their sociable nature, often there are internal drawbacks to the way they act. 76–86% of these children were reported as believing that they either had few friends or problems with their friends. This is possibly due to the fact that although they are very friendly to strangers and love meeting new people, they may have trouble interacting on a deeper level. 73–93% were reported as unreserved with strangers, 67% highly sensitive to rejection, 65% susceptible to teasing, and the statistic for exploitation and abuse was unavailable. There are external problems as well. 91–96% demonstrate inattention, 75% impulsivity, 59–71% hyperactivity 46–74% tantrums, 32–60% disobedience, and 25–37% fighting and aggressive behavior.In one experiment, a group of children with Williams syndrome showed no signs of racial bias, unlike children without the syndrome. They did show gender bias, however, to a similar degree to children without the syndrome, suggesting separate mechanisms for these biases.

Cause
Williams syndrome is a microdeletion syndrome caused by the spontaneous deletion of genetic material from the chromosomal region 7q11.23. This is a hemizygous deletion, which results in haploinsufficient expression of the 25–27 genes in this region. CLIP2, ELN, GTF2I, GTF2IRD1, and LIMK1 are among the genes typically deleted. Hemizygosity for the ELN gene, which codes for the extracellular matrix protein elastin, is associated with connective-tissue abnormalities and cardiovascular disease (specifically supravalvular aortic stenosis and supravalvular pulmonary stenosis). Elastin insufficiency may also contribute to distinct faces, harsh or hoarse voice, hernias, and bladder diverticula often found in those with Williams syndrome. Hemizygosity in LIMK1, GTF2I, GTF2IRD1, and perhaps other genes may help explain the characteristic difficulties with visual–spatial tasks. Additionally, some evidence shows that the hemizygosity in several of these genes, including CLIP2, may contribute to the unique behavioral characteristics, learning disabilities, and other cognitive difficulties seen in WS.

Diagnosis
According to the Williams Syndrome Association, its diagnosis begins with the recognition of physical symptoms and markers, which is followed by a confirmatory genetic test. The physical signs that often indicate a suspected case of WS include puffiness around the eyes, a long philtrum, and a stellate pattern in the iris. Physiological symptoms that often contribute to a WS diagnosis are cardiovascular problems, particularly aortic or pulmonary stenosis, and feeding disturbance in infants. Developmental delays are often taken as an initial sign of the syndrome, as well.If a physician suspects a case of WS, the diagnosis is confirmed using one of two possible genetic tests: Micro-array analysis or the fluorescent in situ hybridization test, which examines chromosome 7 and probes for the existence of two copies of the elastin gene. Since 98-99% of individuals with WS lack half of the 7q11.23 region of chromosome 7, where the elastin gene is located, the presence of only one copy of the gene is a strong sign of WS.  This confirmatory genetic test has been validated in epidemiological studies  and has been demonstrated to be a more effective method of identifying WS than previous methods, which often relied on the presence of cardiovascular problems and facial features (which, while common, are not always present).Reliance on facial features to identify WS may cause a misdiagnosis of the condition. Among the more reliable features suggestive of WS are congenital heart disease, periorbital fullness ("puffy" eyes), and the presence of a long, smooth philtrum. Less reliable signs of the syndrome include anteverted nostrils, a wide mouth, and an elongated neck. Even with significant clinical experience,  reliably identifying Williams syndrome based on facial features alone is difficult.This is particularly the case in individuals of non-white backgrounds, where typical WS facial features (such as full lips) are more prevalent.

Treatment
No cure for Williams syndrome has been found. Suggested treatments include avoidance of extra calcium and vitamin D, and treating high levels of blood calcium. Blood-vessel narrowing can be a significant health problem and is treated on an individual basis.
Physical therapy is helpful to patients with joint stiffness and low muscle tone. Developmental and speech therapy can also help children and increase the success of their social interactions. Other treatments are based on a patients particular symptoms.The American Academy of Pediatrics recommends annual cardiology evaluations for individuals with WS. Other recommended assessments include ophthalmologic evaluations, an examination for inguinal hernia, objective hearing assessment, blood-pressure measurement, developmental and growth evaluation, orthopedic assessments on joints and muscle tone, and ongoing feeding and dietary assessments to manage constipation and urinary problems.Behavioral treatments have been shown to be effective. In regards to social skills, it may be effective to channel their nature by teaching basic skills. Some of these are the appropriate way to approach someone, how and when to socialize in settings such as school or the workplace, and warning of the signs and dangers of exploitation. For the fear that they demonstrate cognitive-behavioral approaches, such as therapy, they are the recommended treatments. One of the things to be careful of with this approach is to make sure that the patients charming nature does not mask any underlying feelings.Perhaps the most effective treatment for those with WS is music. Those affected have shown relative strength in regards to music, albeit only in pitch and rhythm tasks. Not only do they show strength in the field, but also a particular fondness for it. Music may help with the internal and external anxiety with which these people are more likely to be afflicted. Notably, the typical person processes music in the superior temporal and middle temporal gyri. Those with WS have reduced activation in these areas, but an increase in the right amygdala and cerebellum.People affected by WS are supported by multiple organizations, including the Canadian Association for Williams Syndrome and the Williams Syndrome Registry.

Epidemiology
Williams syndrome has historically been estimated to occur in roughly one in every 20,000 live births, but  more recent epidemiological studies have placed the occurrence rate at closer to one in every 7,500 live births, a significantly larger prevalence. As increasing evidence suggests WS is more common than originally noted (about 6% of all genetic cases of developmental disability), researchers have begun to theorize past underdiagnosis of the syndrome. One theorized reason for the increase in epidemiological estimates is that a substantial minority of individuals with the genetic markers of WS syndrome lack the characteristic facial features or the diminished intelligence  considered to be diagnostic of the syndrome, and often are not immediately recognized as having the syndrome.

History
Williams syndrome was first described by J. C. P. Williams and his colleagues, who wrote in 1961 of four patients with supravalvular aortic stenosis, mental disability, and facial features including a broad forehead, large chin, low-set, "drooping" cheeks, widely spaced eyes, and wide-set mouth. A year after this report, German physician A. J. Beuren described three new patients with the same presentation. This led to the syndromes full original name, Williams-Beuren syndrome, which is still used in some medical publications. From 1964 to 1975, small research reports broadened medical knowledge of this syndromes cardiovascular problems. Then in 1975, K. Jones and D. Smith conducted a large-scale report on numerous patients with WS, ranging in age from infancy to adulthood, and described the behavioral and observable physical symptoms in greater detail than previously recorded.

Society and culture
The adjective "elfin" may have originated to describe the facial features of people with WS; before its scientific cause was understood, people believed that individuals with the syndrome, who have exceptionally charming and kind personalities, had extraordinary, even magical, powers. This has been proposed to be the origin of the folklore of elves, fairies, and other forms of the good people or wee folk present in English folklore.In a review of the symptoms and features of the syndrome, Laskari, Smith, and Graham emphasized that many family members of individuals with WS reject use of terminology such as "elfin", as well as descriptions of social symptoms as "cocktail party syndrome". Physicians, family members of individuals with WS syndrome, and WS associations alike have called for the curtailment of such terms.One notable person with the syndrome is Gabrielle Marion-Rivard, a Canadian actress and singer who won the Canadian Screen Award for Best Actress in 2014 for her performance in the film Gabrielle. Another is Jeremy Vest, member of the Hows Your News? team, featured in the TV series and film of the same name.

Further reading
Articles
Fung, Lawrence K.; Quintin, Eve-Marie; Haas, Brian W.; Reiss, Allan L. (2012). "Conceptualizing neurodevelopmental disorders through a mechanistic understanding of fragile X syndrome and Williams syndrome". Current Opinion in Neurology (Review). 25 (2): 112–24. doi:10.1097/WCO.0b013e328351823c. PMC 3680360. PMID 22395002.
Karmiloff-Smith, A.; dSouza, D.; Dekker, T. M.; Van Herwegen, J.; Xu, F.; Rodic, M.; Ansari, D. (2012). "Genetic and environmental vulnerabilities in children with neurodevelopmental disorders". Proceedings of the National Academy of Sciences (Review). 109: 17261–5. Bibcode:2012PNAS..109S7261K. doi:10.1073/pnas.1121087109. JSTOR 41763522. PMC 3477396. PMID 23045661.
Kitagawa, Hirochika; Fujiki, Ryoji; Yoshimura, Kimihiro; Oya, Hiroyuki; Kato, Shigeaki (2011). "Williams syndrome is an epigenome-regulator disease". Endocrine Journal (Review). 58 (2): 77–85. doi:10.1507/endocrj.k10e-393 </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 Generalized pustular psoriasis and can you explain it in depth? [/INST] Generalized pustular psoriasis (GPP) is an extremely rare type of psoriasis that can present in a variety of forms. Unlike the most general and common forms of psoriasis, GPP usually covers the entire body and with pus-filled blisters rather than plaques. GPP can present at any age, but is rarer in young children. It can appear with or without previous psoriasis conditions or history, and can reoccur in periodic episodes.

Signs and symptoms
GPP presents as pustules and plaques over a wide area of the body. It differs from the localized form of pustular psoriasis in that patients are often febrile and systemically ill.However, the most prominent symptom, as described in the Archives of Dermatology, is "sheeted, pinhead-sized, sterile, sub-corneal pustules". The IPC roundtable adds that these pustules often occur either at the edges "of expanding, intensely inflammatory plaques" or "within erythrodermic skin".

Causes
Most cases of generalized pustular psoriasis present in patients with existing or prior psoriasis conditions. However, there are many cases of GPP that arise without a history of psoriasis.The Department of Dermatology of the University of São Paulo proposed a classification for these two conditions. Pso+ represents patients with a personal history of psoriasis and pso- represents patients with no history of psoriasis. They also identified a common factor among patients in each group: In the pso+ group, the most common precipitating factor is corticosteroid withdrawal. In the pso- group, the most common precipitating factor is infection.In a large portion of cases, the disease is brought on by some triggering factor. Through research and observation, many of these factors have been identified. The following table, from an article in Cutis, lists a few factors that have been observed as influential in the onset of GPP.

Source: "Table II", "Pustular Psoriasis" Farber and Nall, 1993

Genetic factors
Although there are likely to be multiple genetic factors and environmental triggers, mutations causing defects in the IL-36RN, CARD14 and AP1S3 genes have been shown to cause GPP.

Diagnosis
Classification
It is important to note that while there are different forms of GPP, they are not exclusive of each other. One can morph into another, or multiple forms can occur simultaneously.

von Zumbusch acute generalized pustular psoriasis
Von Zumbusch psoriasis is named after the German dermatologist Leo Ritter von Zumbusch (1874–1940), son of Kaspar von Zumbusch, who described the first documented case of generalized pustular psoriasis in the early 1900s. See Case Report #1.
Sometimes all or any of GPP is referred to as von Zumbusch psoriasis, but in the literature it is often distinguished as one specific form of GPP.Eugene M. Farber, MD and colleagues provide a description of von Zumbusch psoriasis in "Pustular Psoriasis", published in Cutis. They describe the pattern as having "waves of widespread or universally fiery redness". The affected areas are "painful and tender". Small sub-corneal pustules form, with sizes originally between 1 and 10 mm in diameter. These pustules may merge to form "yellow-green lakes of pus". The pustules dry out, and "Waves of scarlatiniform [resembling scarlet fever] peeling follow, removing the desiccating pustules". In regards to the onset, the von Zumbusch form may "supervene on any previous pattern of psoriasis". It also may or may not recur periodically.

Generalized pustular psoriasis of pregnancy (Impetigo herpetiformis)
This form of GPP tends to have symmetrical and grouped features. It usually onsets early in the third trimester of pregnancy, and generally persists until the child is born, but occasionally long after.
In 2009, Dr. Debeeka Hazarika, president of the North East States branch of the Indian Association of Dermatologists, Venereologists and Leprologists (IADVL), published an article titled "Generalized pustular psoriasis of pregnancy successfully treated with cyclosporine" in Indian J Dermatol Venereol Leprol. As reported by Hazarika, there have been up to nine instances where the disease was recurrent in subsequent pregnancies.
See Case Report 2
In 1979, Frank R. Murphy, MD and Lewis P. Stolman, MD reported on the case of a woman who developed generalized pustular psoriasis in response to doses of progestins, suggesting a link between progestogens and GPP. Most cases of GPP in pregnancy occur late in the third trimester, generally when production of progesterone increases.

Infantile and juvenile
GPP is a rare disease in general, but even more so in children. In 2010, an article was published in Pediatric Dermatology by the Department of Dermatology, University of São Paulo. The report acknowledged that psoriasis is a relatively common skin condition in children, but "the pustular variant is rare." Out of 1,262 cases of psoriasis in children, a "0.6% rate of pustular variants" was found. When GPP does occur in children, it usually appears during the first year of life.Khan et al. reported that in GPP patients ten or younger, less than 12% of cases are preceded by ordinary psoriasis. This differs greatly from GPP cases in adults, where 85% of GPP is preceded by typical psoriatic lesions.According to the article by the University of São Paulo, mentioned above, "The onset of childhood GPP is generally abrupt and accompanied by toxic features." The original acute episode usually lasts a few days, but "repeated waves of inflammation and pustulation may follow." It is important that the disease is managed immediately in order to prevent life-threatening complications, such as infection or [sepsis]. Other complications include "metabolical, hemo-dynamic, and thermoregulatory disturbances" which occur as a result of "alterations of the epidermal barrier."See Case Report 3

Circinate and annular
This type of psoriasis appears as round lesions. It begins as discrete areas that become raised and swollen. Pustules appear at the edges of the round lesions, creating rings. The pustules then dry out and leave a trail of scale as the lesion grows.See Case Report 4

Treatments
Treatments vary widely, and many different drugs have been documented as being successful. Some medications are successful in some patients, while unsuccessful in others. Below is a list of some medications used to treat GPP:
Etanercept
PUVA
Hydroxyurea
Dapsone
Systemic corticosteroids
Cyclosporin A
Adalimumab
Etretinate
Isotretinoin
Acitretin

Prognosis
GPP is a rare and severe type of psoriasis. It in rare cases it is said to be fatal and in some cases has driven patients to intensive burn units. An article published in Pediatric Dermatology said, "The GPP pattern is as an acute, episodic, and potentially life-threatening form of psoriasis." There is no cure-all treatment for GPP, and as such, the mortality rate is high. Ryan and Baker observed 155 patients with GPP, 106 of which were followed up with. 26 of those 106 died as a result of the psoriasis or the treatment. Their data gives a 25% mortality rate.

Case reports
Case report 1
Von Zumbusch observed a male patient, who had had classic psoriasis for several years, and who then went through recurrent episodes of bright [erythema] and [edema], which became studded with multiple pustules. Von Zumbusch observed this patient through nine hospital admissions over 10 years.

Case report 2
Hazarika gave a report of a 29-year-old woman with no family history of psoriasis, having had a normal first pregnancy, who presented with GPP in the twenty-eighth week of her second pregnancy </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 Plasma cell leukemia and can you explain it in depth? [/INST] Plasma cell leukemia (PCL) is a plasma cell dyscrasia, i.e. a disease involving the malignant degeneration of a subtype of white blood cells called plasma cells. It is the terminal stage and most aggressive form of these dyscrasias, constituting 2% to 4% of all cases of plasma cell malignancies. PCL may present as primary plasma cell leukemia, i.e. in patients without prior history of a plasma cell dyscrasia or as secondary plasma cell dyscrasia, i.e. in patients previously diagnosed with a history of its predecessor dyscrasia, multiple myeloma. The two forms of PCL appear to be at least partially distinct from each other. In all cases, however, PCL is an extremely serious, life-threatening, and therapeutically challenging disease.

Signs and symptoms
Primary PCL
The clinical presentation of primary PCL (pPCL) indicates a far more aggressive disease than that of a typical multiple myeloma case with its clinical features being a combination of those found in multiple myeloma and acute leukemia. Like multiple myeloma patients, pPCL patients exhibit pathologically high levels of monoclonal plasma cells in their bone marrow plus a malignant plasma cell-secreted circulating monoclonal myeloma protein, either IgG, IgA, a light chain, or none in 28-56%, 4-7%, 23-44%, or 0-12% of cases, respectively. Similar to B cell leukemias, but unlike multiple myeloma, pPCL patients exhibit relative high frequencies of splenomegaly, lymphadenopathy, hepatomegaly, kidney failure, bone marrow failure (i.e. thrombocytopenia, anemia, and/or, rarely, leukopenia), central nervous system defects, and peripheral neuropathies due to the invasion of these tissues by plasma cells and/or the deposition of their circulating monoclonal immunoglobulin in them. Compared to multiple myeloma patients, pPCL patients also: exhibit 1) high rates of developing a hypercalcemic crisis, i.e. a potentially life-threatening episode of high ionic calcium (Ca2+) levels in the blood due to excess bone re-absorption and/or renal failure; b)  higher levels of serum lactate dehydrogenase and Beta-2 microglobulin; and c) lower rates of bone but higher rates of soft tissue plasma cell tumors termed plasmacytomas.

Secondary PCL
Secondary PCL (sPCL) is diagnosed in 1-4% of patients known to have had multiple myeloma for a median time of ~21 months. It is the terminal phase of these patients myeloma disease. sPCL patients typically are highly symptomatic due to extensive disease with malignant plasma cell infiltrations in, and failures of, not only the bone marrow but also other organs. They have failed or broken through one or more treatment regimens and therefore may also show some of the toxic effects of these treatments.

Cause
PCL is caused by the development of an excessively high number of genetic abnormalities in plasma cells or, more particularly, their precursor B cells and plasmablasts (see plasma cells). This genetic instability is due to a myriad of acquired abnormalities including gene mutations; single nucleotide polymorphisms; depletions and duplications of parts of a gene, larger portion of a chromosome, or even an entire arm of a chromosome; translocations, deletions, and duplications of entire chromosomes; and increases and decreases in the expression of intact genes due to, e.g. the methylation of gene promotors and various less direct effects. These genetic abnormalities effect the Wnt signaling pathway, regulation of the cell cycle, RNA metabolism, protein folding, and cadherin-related cell adherence to extracellular matrix. These effects in turn control plasma cell proliferation, survival, apoptosis, adhesion to bone marrow, genome stability, and secretion of monoclonal immunoglobulins.Secondary plasma cell leukemia (sPCL) results from the comparatively slow development of plasma cell/plasma cell precursor genetic abnormalities which initially create a clone of cells that cause the premalignant condition of monoclonal gammopathy of undetermined significance. In a very small percentage of these cases, the progressive development of further genetic abnormalities serially create a clone(s) of plasma cells that cause the more serious but still premalignant disorder of smoldering multiple myeloma, overt myeloma cancer, and ultimately sPCL. In contrast to sPCL, pPCL presents de novo with a broad range of genetic abnormalities. For example, advanced methods for examining the genome viz., whole-exome sequencing and gene expression profiling, have identified 166 non-silent gene variants per pPCL patient sample at the time of diagnosis. These abnormalities are similar but not identical to those detected in sPCL while the abnormalities detected in sPCL more closely resemble those detected in multiple myeloma than do those of pPCL: the genetic data support the clinical data in suggesting that sPCL and pPCL are distinct diseases with sPCL among the two PCLs being more closely related to multiple myeloma. Examination of plasma cell immunophenotype by measuring certain of their cell surface antigens, particularly Cluster of differentiation. CD markers on plasma cells from patients with pPCL differ from those taken form multiple myeloma or sPCL patients. For example: pPCL plasma cells more often express CD20 antigen, which is considered important in anchoring plasma cells to the bone marrow stroma, than do those on plasma cells taken from myeloma patients (50% vs. 17%); pPCL plasma cells often lack CD56 antigen which is present on the majority of plasma cells taken form multiple myeloma patients; and pPCL plasma cells more frequently express CD28 than do sPCL plasma cells. Thus, immunophenotyping supports that notion that multiple myeloma, sPCL, and pPCL show critically important fundamental differences that may explain their different clinical presentations, courses, responses to therapy, and prognoses.

Diagnosis
The International Myeloma Working Group has defined the diagnostic criteria for plasma cell leukemia as the presence in blood of >2x109 plasma cells per liter or, alternatively, >20% of nucleated blood cells being plasma cells. More recently, the Group has suggested that values of 0.5x109 or 5%, respectively, may be more appropriate from a therapeutic viewpoint and therefore should be studied as a definitive criterion for the disease. A recent study supported this suggestion in finding that multiple myeloma patients with >5% circulating plasma cells had a prognosis much worse than that for multiple myeloma and similar to that for plasma cell leukemia. Flow cytometry immunophenotyping of blood cells to detect clonal phenotypes of plasma cells seen in multiple myeloma (e.g. the CD138+, CD38+, CD19−, CD45+/- phenotype) may be a more sensitive method to enumerate circulating clonal plasma cells and diagnose plasma cell leukemia.

Treatments
Prior to the use of newly developed drugs and treatment regimens, median survival rates from the time of diagnosis for pPCL and sPCL were 8–11 months and 2–8 months, respectively, even when treated very aggressively with the VAD regimen of vincristine, doxorubicin, and dexamethasone or the VCMP regimen of vincristine, carmustine, melphalan, and prednisone alternating with vincristine, carmustine, doxorubicin, and prednisone. The treatment of PCL patients, particularly pPCL patients, with newer methods appears to have made modest improvements in survival rates. However, the rarity of these two leukemias has limited individual studies to case reports on a small number of patients or retrospective analyses of patient records </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 Vernal keratoconjunctivitis and can you explain it in depth? [/INST] Vernal keratoconjunctivitis (VKC) is a recurrent, bilateral, and self-limiting inflammation of conjunctiva, having a periodic seasonal incidence.

Vernal keratopathy
Corneal involvement in VKC may be primary or secondary due to extension of limbal lesions. Vernal keratopathy includes 5 types of lesions.
Punctuate epithelial keratitis.
Ulcerative vernal keratitis (shield ulceration).
Vernal corneal plaques.
Subepithelial scarring.
Pseudogerontoxon.

Sign and symptoms
Symptoms- VKC is characterised by marked burning and itchy sensations which may be intolerable and accentuates when patient comes in a warm humid atmosphere. Associated symptoms include mild photophobia in case of corneal involvement, lacrimation, stringy discharge and heaviness of eyelids.
Signs of VKC can be described in three clinical forms (Cameron Classification):Palpebral form- Usually upper tarsal conjunctiva of both the eyes is involved. Typical lesion is characterized by the presence of hard, flat-topped papillae arranged in cobblestone or pavement stone fashion. In severe cases papillae undergo hypertrophy to produce cauliflower-like excrescences of giant papillae.
Bulbar form- It is characterised by dusky red triangular congestion of bulbar conjunctiva in palpebral area, gelatinous thickened accumulation of tissue around limbus and presence of discrete whitish raised dots along the limbus (Trantas spots).
Mixed form- Shows the features of both palpebral and bulbar types.

Cause
VKC is thought to be an allergic disorder in which IgE mediated mechanism play a role. Such patients often give family history of other atopic diseases such as hay fever, asthma or eczema, and their peripheral blood shows eosinophilia and increased serum IgE levels.

Risk factors
Age and sex – 4–20 years; more common in boys than girls.
Season – More common in summer. Hence, the name Spring catarrh is a misnomer. Recently it is being labelled as Warm weather conjunctivitis.
Climate – More prevalent in the tropics. VKC cases are mostly seen in hot months of summer, therefore, more suitable term for this condition is "summer catarrh" Ref.

Pathology
Conjunctival epithelium undergoes hyperplasia and sends downward projection into sub-epithelial tissue.
Adenoid layer shows marked cellular infiltration by eosinophils, lymphocytes, plasma cells and histiocytes.
Fibrous layer show proliferation which later undergoes hyaline changes.
Conjunctival vessels also show proliferation, increased permeability and vasodilation.

Diagnosis
Classification
Based on severity, authors have classified VKC into clinical grades:Grade 0 - Absence of symptoms
Grade 1 MILD - Symptoms but no corneal involvement
Grade 2 MODERATE - Symptoms with photophobia but no corneal involvement
Grade 3 SEVERE - Symptoms, photophobia, mild to moderate SPKs OR with Diffuse SPK or corneal ulcer

Treatment
Local therapy- Topical steroids are effective. Commonly used solutions are of fluorometholone, medrysone, betamethasone or dexamethasone. Mast cell stabilizers such as sodium cromoglycate (2%) drops 4–5 times a day are quite effective in controlling VKC, especially atopic ones. Azelastine eyedrops are also effective </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 Synchysis scintillans 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 Sickle cell retinopathy and can you explain it in depth? [/INST] Sickle cell retinopathy can be defined as retinal changes due to blood vessel damage in the eye of a person with a background of sickle cell disease. It can likely progress to loss of vision in late stages due to vitreous hemorrhage or retinal detachment. Sickle cell disease is a structural red blood cell disorder leading to consequences in multiple systems. It is characterized by chronic red blood cell destruction, vascular injury, and tissue ischemia causing damage to the brain, eyes, heart, lungs, kidneys, spleen, and musculoskeletal system.People affected by sickle cell disease are commonly of African or Asian descent. Emigration patterns towards the Western Hemisphere have led to increased numbers of persons affected by sickle cell disease in regions where it was previously uncommon. Knowledge and understanding of sickle cell disease and its management are now increasingly relevant in areas such as the European Union. At a young age, a great proportion of people living with sickle cell disease can develop retinal changes. Sickle cell disease consists of several subtypes; however, the Haemoglobin type C (HbSC) subtype carries the gravest prognosis for sickle cell retinopathy and vision changes.Regular retinal examinations can aid in early detection and treatment, thus reducing the impact of the condition and the risk of vision loss. Development and progression of sickle cell retinopathy can be favorably modified through management of the underling sickle cell disease. Treatment of the general disease can ameliorate its systemic effects.

Classification
Sickle cell retinopathy can be classified based on retinal changes into non-proliferative and proliferative subtypes.

Non-proliferative sickle cell retinopathy (NPSCR)
Non-proliferative sickle cell retinopathy (NPSCR) can feature the following retinal manifestations:

Venous tortuousity is commonly observed in patients with homozygous HbSS sickle cell disease. Numerous diseases that feature blood hyperviscosity similar to sickle cell disease can manifest as retinal venous tortuousity. Tortuosity is caused by arteriovenous shunting from the retinal periphery.
It can feature small bleeds of the retina known as intra-retinal hemorrhages, due to blockage of blood vessels by the sickled blood cells, thus triggering vessel wall necrosis. The resulting hemorrhages are initially bright red and oval shaped. As the hemorrhage ages over a period of days to weeks, the color then changes to a salmon hue known as a salmon patch. They are usually seen adjacent to the retinal arteriole.
Bleeding in the deeper layers of the retina leads to the appearance of dark lesions known as black sunburst spots. These oval or round shaped pigmented spots are formed due to RPE proliferation.
As the haemoglobin within the hemorrhage breaks down over time, yellow spots known as iridescent bodies are formed within the layers of the sensory retina.
Maculopathy occurs in a significant portion of patients affected by sickle cell retinopathy. It is more prevalent in homozygous HbSS type sickle cell disease. The fovea can be found within the macula and is known as the center of the visual field. Maculopathy in sickle cell retinopathy is due to long term changes of capillaries that interact at the fovea. Although ischemic changes may be apparent on the retina, maculopathy may be asymptomatic at first leaving visual acuity unchanged.
Central retinal artery occlusion is a known feature of non-proliferative sickle cell retinopathy that has a low incidence in patients with non proliferative sickle cell retinopathy.
Optic nerve sign is represented by dilated capillaries that can be visualized in the nerve using fluorescein angiography. Visual acuity often remains unchanged with this finding.
Angioid streaks: Angioid streaks may be seen in up to 6% of cases.

Proliferative sickle cell retinopathy (PSCR)
Proliferative sickle retinopathy is the most severe ocular complication of sickle cell disease. Even though PSCR begins in the first decade of life, the condition remains asymptomatic and unnoticed until visual symptoms occur due to vitreous hemorrhage or retinal detachment.

Goldberg classification
Goldberg classified PSR into following 5 different self-explanatory stages:

Stage of peripheral arterial occlusion and ischemia: It is the earliest abnormality that can be visualized by fundus examination. The occluded arterioles can be seen as dark red lines. They eventually turn into white silver-wire vessels.
Stage of peripheral arteriolar-venular anastomoses: Arteriolar-venular anastomoses develop as blood is diverted from blocked arteries to nearby venules.
Stage of neovascularization and fibrous proliferation: Neovascularization starts from the arteriolar-venular anastomoses, and grow into the ischemic retina. Characteristic fan-shaped appearance due to neovasularization is known as sea fan neovascularization.
Stage of vitreous hemorrhage. Peripheral neovascular tufts bleed and cause vitreous hemorrhage.
Stage of vitreoretinal traction bands and tractional retinal detachment: Traction on the sea fan and adjacent retina causes traction retinal detachment.

Signs and Symptoms
Comma sign: Comma shaped vessels in the bulbar conjunctiva is due to vascular occlusion of conjunctival vessels.
Vitreoretinal traction or retinal detachment cause flashes, floaters or dark shadows.
Sudden loss of vision may occur due to retinal artery occlusion, vitreous hemorrhage or retinal detachment.
Intravascular occlusions may be seen in optic disc vessels.

Cause
Normal adult hemoglobin A molecule comprises two α and two β globin chains associated with a heme ring. Mutation at the 6th position of the beta chain is the cause of sickle cell disease. Due to sickle cell disease, vascular occlusion may occur in the conjunctiva, iris, retina, or choroid. Retinal changes occur due to blockage of retinal blood vessels by abnormal RBCs.

Diagnosis
Diagnostic Techniques
Diagnosis is conducted in a multidisciplinary manner. The diagnosis of sickle cell disease can be confirmed by cation high performance liquid chromatography, haemoglobin electrophoresis in adolescents and adults and molecular genetic diagnosis in prenatal and neonatal populations. Anterior segment signs including the conjunctival sign and iris atrophy are ocular manifestations that are strongly indicative of sickle cell disease. Early stages of sickle cell retinopathy are asymptomatic. However, retinal changes that are diagnostic of sickle cell retinopathy can be visualized using fundoscopic examinations, retinography, fluorescein angiography and coherence tomography. Ultra Widefield Fluorescein Angiography is the gold standard for diagnosis of proliferative sickle cell retinopathy. It is an invasive method that assesses both anterior and posterior segment structures. Spectral Domain Optical Coherence Tomography and Coherence Tomography Angiography are non invasive methods of diagnosing proliferative retinopathy. Visual acuity and intraocular pressure assessments can also yield results that are diagnostic of sickle cell retinopathy.

Differential diagnosis
Sickle cell retinopathy should be differentiated from other retinal conditions that arise due to similar pathologies. The following differentials are classified by those pathologies.

Additional causes of macular ischemiaDiabetic retinopathy
Retinal embolization (talc retinopathy, internal carotid artery embolism)
Retinal vascular occlusion
Infectious retinopathyInflammatory diseases leading to ischemiaSarcoidosis
Retinal vasculitis
Intermediate uveitis
Acute retinal necrosisAlternative causes of ischemic vascular diseaseProliferative diabetic retinopathy
Central retinal vein occlusion
Branch retinal vein occlusion
Ocular ischemic syndromE
Radiation retinopathy
Retinopathy of prematurityUnclassified causesIncontinentia pigmenti
Autosomal dominant vitreoretinochoroidopathy
Chronic rhegmatogenous retinal detachment
Scleral buckle
Retinitis pigmentosa

Prevention
Screening
Screening is an important pillar of prevention of sickle cell retinopathy as it provides the benefit of early detection and treatment thus reducing complications. Screening also provides an opportunity for education of families predisposed to retinopathy as a result of a family history of sickle cell disease. Screening can take the form of DNA screening at birth and Ophthalmology-related examinations later in life.
DNA screening in newborns at risk of having sickle cell disease allows the early diagnosis of the disease. Families can then be educated on the possible effects of sickle cell disease at each stage of life.
Ophthalmology-related examinations - dilated fundoscopic examination is recommended from the age of 10 and biannually thereafter in patients with no abnormal retinal findings. Fluorescein angiography and angioscopy is recommended for patients with abnormal findings that may be indicative of proliferative sickle cell retinopathy. The frequency of follow up appointments is determined by the ophthalmologist based on the severity of the findings.

Care of systemic disease
Sickle cell disease is a systemic disease that affects several organs in the body. Management of the underlying disease can therefore prevent the development of retinopathy and slow its progression.
Fetal haemoglobin transfusion - Fetal haemoglobin (HbF) is a form of haemoglobin that is found in children up to 6 months after birth. This type of haemoglobin is beneficial in sickle cell patients as it resists modification to the sickled shape. As a result, transfusion of HbF in younger populations can prevent and slow the progression of sickle cell retinopathy.
Hydroxyurea administration - Hydroxyurea is a drug that can be used as an alternative method of increasing fetal haemoglobin levels in the blood of a patient with sickle cell disease. Hydroxyurea also provides the benefit of reducing inflammation.
Haematopoetic stem cell transplantation - This process is more commonly known as a bone marrow transplant. It is useful in the management of sickle cell disease. However, access to this method is limited due to cost and the need for a donor that is biologically compatible with the person requiring the transplant.
Anti-inflammatory and anti-adhesive drugs reduce the likelihood of occlusions in the small blood vessels of the retina therefore preventing the development of sickle cell retinopathy. There drugs include anti adhesive antibodies, anti-integrin antibodies, anti-Willebrand factor, sulfasalazine and statins.
Gene therapy has also been proven beneficial in the prevention of sickle cell retinopathy.

Treatment
Medical
Vascular endothelial growth factor (VEGF) is known to be associated with sea fan lesions which are types of neovascularization. Bevacizumab is an anti-VEGF drug used in intravitreal injection that is known to cause reversal of sea fan lesions and reduce the duration of vitreous hemorrhage. Intravitreal injection of anti-VEGF drugs can also be used prior to surgery to aid separation of tissues involved in the sea fan lesion and to reduce intraoperative and postoperative hemorrhage. It is useful in combination with photocoagulation.

Laser
Indications for laser photocoagulation include
Peripheral neovascularization of upwards of 60° circumference
Sickle cell retinopathy affecting both eyes
Large elevated sea fans
Rapid progression of neovascularizationThere are two methods of photocoagulation mainly used; feeder vessel coagulation and scatter laser coagulation </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 Hemifacial microsomia and can you explain it in depth? [/INST] Hemifacial microsomia (HFM) is a congenital disorder that affects the development of the lower half of the face, most commonly the ears, the mouth and the mandible. It usually occurs on one side of the face, but both sides are sometimes affected. If severe, it may result in difficulties in breathing due to obstruction of the trachea—sometimes even requiring a tracheotomy. With an incidence in the range of 1:3500 to 1:4500, it is the second most common birth defect of the face, after cleft lip and cleft palate.[1] HFM shares many similarities with Treacher Collins syndrome.

Presentation
The clinical presentation of HFM is quite variable. The severity may depend on the extent of the area with an insufficient blood supply in utero, and the gestational age of the fetus at which this occurs. In some people, the only physical manifestation may be a small and underdeveloped external ear. In more severe cases, multiple parts of the face may be affected. Some people with HFM may have sensorineural hearing loss and decreased visual acuity or even blindness.It can be thought of as a particularly severe form of HFM, in which extracranial anomalies are present to some extent. Some of the internal organs (especially the heart, kidneys, and lungs) may be underdeveloped, or in some cases even absent altogether. The affected organs are typically on the same side as the affected facial features, but bilateral involvement occurs in approximately 10% of cases. Deformities of the vertebral column such as scoliosis may also be observed.While there is no universally accepted grading scale, the OMENS scale (standing for Orbital, Mandible, Ear, Nerves and Soft tissue) was developed to help describe the heterogeneous phenotype that makes up this sequence or syndrome.Intellectual disability is not typically seen in people with HFM. Hemifacial microsomia sometimes results in temporomandibular joint disorders.

Cause
The condition develops in the fetus at approximately 4 weeks gestational age, when some form of vascular problem such as blood clotting leads to insufficient blood supply to the face. This can be caused by physical trauma, though there is some evidence of it being hereditary [2] </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 Gradenigos syndrome 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 Photic retinopathy and can you explain it in depth? [/INST] Photic retinopathy is damage to the eyes retina, particularly the macula, from prolonged exposure to solar radiation or other bright light, e.g., lasers or arc welders. The term includes solar, laser, and welders retinopathy and is synonymous with retinal phototoxicity. It usually occurs due to staring at the Sun, watching a solar eclipse, or viewing an ultraviolet, Illuminant D65, or other bright light.[1]

Signs and symptoms
Long-term reduced eyesight
Central or paracentral scotomaVision loss due to solar retinopathy is typically reversible, lasting for as short as one month to over one year. The fundus changes are variable and usually bilateral, mild cases often show no alteration and moderate to severe cases show a foveal yellow spot on the first days after exposure. After a few days it is replaced by a reddish dot often surrounded by pigment.
Permanent holes and lesions are possible; prognosis worsens with dilated pupils or prolonged exposure.

Pathophysiology
Although it is frequently claimed that the retina is burned by looking at the Sun, retinal damage appears to occur primarily due to photochemical injury rather than thermal injury. The temperature rise from looking at the Sun with a 3-mm pupil only causes a 4 °C increase in temperature, insufficient to photocoagulate </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 Alopecia totalis 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 Lupus vulgaris and can you explain it in depth? [/INST] Lupus vulgaris (also known as tuberculosis luposa) are painful cutaneous tuberculosis skin lesions with nodular appearance, most often on the face around the nose, eyelids, lips, cheeks, ears and neck </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 Meconium peritonitis 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 Occult macular dystrophy and can you explain it in depth? [/INST] Occult macular dystrophy (OMD) is a rare inherited degradation of the retina, characterized by progressive loss of function in the most sensitive part of the central retina (macula), the location of the highest concentration of light-sensitive cells (photoreceptors) but presenting no visible abnormality. "Occult" refers to the degradation in the fundus being difficult to discern. The disorder is called "dystrophy" instead of "degradation" to distinguish its genetic origin from other causes, such as age. OMD was first reported by Y. Miyake et al. in 1989.

Symptoms
Symptoms entail a loss of visual acuity in both eyes, including darkened vision, ring scotoma (ring of blindness close to the center of vision), color blindness, and difficulty with bright lights. The scotoma may cause text slightly away from the center of vision to disappear; the appearance would not be black (in early stages) but of the same color as the nearby background. Many lines of an Amsler grid would be faded or invisible to the patient. The area of invisibility on the Amsler grid spreads with time. Symptoms do not include headaches or eye pain. The loss of acuity tends to be symmetric between the eyes.

Etiology
OMD that is caused by mutations of the retinitis pigmentosa 1-like 1 (RP1L1) gene (OMIM 608581) is called Miyakes disease. While the mutation is dominant, OMD may manifest more strongly and earlier in children than in the parent (anticipation). However, cases have presented with no mutation to RP1L1. One study suggests that OMD arises because of two mutations arising simultaneously, one in RP1L1 and another in ABCA4.OMD is generally believed to be autosomal dominant, meaning that if you get the abnormal gene from only one parent, you can get the disease. However, this does not always seem to be the case.OMD differentiates from Stargardt macular dystrophy in which gene is mutated (RP1L1 instead of ABCA4), the process of OMD isnt a buildup of toxic lipofuscin, and Stargardt is regressive.

Physiology
The connection between these mutations and OMD is unclear, but cone density is significantly lower in patients with OMD compared to the general population. Use of adaptive optics to obtain high-resolution retinal images reveal abnormal changes in patients with OMD, including thinning of the foveal thickness and the outer nuclear layer and disruption of the IS/OS line and COST line.

Diagnosis
OMD returns negative results for a funduscopic inspection, fluorescein angiogram, and full-field electroretinogram (ERG), for both rod and cone components. The key to diagnosing this disorder is the multifocal ERG (mfERG), providing a single procedure for diagnosis. Onset is known to range from age 6 to 81, with about half of onsets occurring after age 65.

Differential diagnosis
A visual field test can differentiate between whether the reduced visual acuity is centered on the optic nerve or the fundus.
Once a neurological problem has, therefore, been ruled out, the disorders reduced visual acuity without visible fundus abnormalities may be misdiagnosed as optic neuritis, dominant optic atrophy, amblyopia, or nonorganic visual disorder.The combination of weak amplitudes in the mfERG with no visible fundus abnormalities then rules out other explanations.  For example, OMD presents negative for a full-field ERG while retinitis pigmentosa presents abnormal.

Prognosis
Since the abnormality is not in the eye lens, the disease is not correctable with eyeglasses. Vision becomes dimmer over the course of years as the macula loses function. Eventually the patient may become legally blind. The peripheral vision field is preserved. In other words, OMD does not cause total blindness, due to the concentration of the degradation at the cone-rich (color-sensitive) region of the retina </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 Cold injury 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 Chilblains and can you explain it in depth? [/INST] Chilblains, also known as pernio, is a medical condition in which damage occurs to capillary beds in the skin, most often in the hands or feet, when blood perfuses into the nearby tissue resulting in redness, itching, inflammation, and possibly blisters.  It occurs most frequently when predisposed individuals, predominantly women, are exposed to cold and humidity. Ulcerated chilblains are referred to as kibes. Temperature-related chilblains can be prevented by keeping the feet and hands warm in cold weather and avoiding exposing these areas to extreme temperature changes. Once  the  diagnosis  of  chilblains is made, first-line treatment includes avoiding cold, damp environments and wearing gloves and warm socks.Chilblains can be idiopathic (spontaneous and unrelated to another disease), but similar symptoms may also be a manifestation of another serious medical condition that must be investigated. Related medical conditions include Raynaud syndrome, erythromelalgia, frostbite, and trench foot, as well as connective tissue diseases such as lupus or vasculitis. In infants affected by Aicardi–Goutières syndrome (a rare inherited condition which affects the nervous system) chilblain-like symptoms occur together with severe neurologic disturbances and unexplained fevers.

Signs and symptoms
The areas most affected are the toes, fingers, earlobes, nose.
Blistering of affected area
Burning and itching sensation in extremities
Dermatitis in extremities
Ulceration (severe cases only)
Erythema (blanchable redness of the skin)
Pain in affected area
Skin discoloration, red to dark blueChilblains caused by exposure to low temperatures usually heal within 7–14 days.

Prevention
Exposure
Keep affected area warm, and avoid any extreme temperature changes (including very hot water).
Keep affected area dry.
Wear warm shoes, socks and gloves.
Wear a hat and a scarf to protect the ears and the nose.
Avoid tight fitting socks/shoes.

Other
Exercise at least four times a week to improve circulation.
Quit smoking, as it damages circulation.

Treatment
Nifedipine and amlodipine, which are vasodilators in the class of drugs known as calcium channel blockers, may help in some cases </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 Savant syndrome and can you explain it in depth? [/INST] Savant syndrome () is a rare condition in which someone with significant mental disabilities demonstrates certain abilities far in excess of average. The skills that savants excel at are generally related to memory. This may include rapid calculation, artistic ability, map making, or musical ability. Usually, only one exceptional skill is present.Those with the condition generally have a neurodevelopmental disorder such as autism spectrum disorder or have a brain injury. About half of cases are associated with autism, and these individuals may be known as "autistic savants". While the condition usually becomes apparent in childhood, some cases develop later in life. It is not recognized as a mental disorder within the DSM-5.Savant syndrome is estimated to affect around one in a million people. The condition affects more males than females, at a ratio of 6:1. The first medical account of the condition was in 1783. Among those with autism, 1 in 10 to 1 in 200 have savant syndrome to some degree. It is estimated that there are fewer than a hundred prodigious savants, with skills so extraordinary that they would be considered spectacular even for a non-impaired person, currently living.

Signs and symptoms
Savant skills are usually found in one or more of five major areas: art, memory, arithmetic, musical abilities, and spatial skills. The most common kinds of savants are calendrical savants, "human calendars" who can calculate the day of the week for any given date with speed and accuracy, or recall personal memories from any given date. Advanced memory is the key "superpower" in savant abilities.Approximately half of savants are autistic; the other half often have some form of central nervous system injury or disease. It is estimated that up to 10% of those with autism have some form of savant abilities.

Calendrical savants
A calendrical savant (or calendar savant) is someone who – despite having an intellectual disability – can name the day of the week of a date, or vice versa, on a limited range of decades or certain millennia. The rarity of human calendar calculators is possibly due to the lack of motivation to develop such skills among the general population, although mathematicians have developed formulas that allow them to obtain similar skills. Calendrical savants, on the other hand, may not be prone to invest in socially engaging skills.

Mechanism
Psychological
No widely accepted cognitive theory explains savants combination of talent and deficit. It has been suggested that individuals with autism are biased towards detail-focused processing and that this cognitive style predisposes individuals either with or without autism to savant talents. Another hypothesis is that savants hyper-systemize, thereby giving an impression of talent. Hyper-systemizing is an extreme state in the empathizing–systemizing theory that classifies people based on their skills in empathizing with others versus systemizing facts about the external world. Also, the attention to detail of savants is a consequence of enhanced perception or sensory hypersensitivity in these unique individuals. It has also been hypothesized that some savants operate by directly accessing deep, unfiltered information that exists in all human brains that is not normally available to conscious awareness.

Neurological
In some cases, savant syndrome can be induced following severe head trauma to the left anterior temporal lobe. Savant syndrome has been artificially replicated using low-frequency transcranial magnetic stimulation to temporarily disable this area of the brain.

Epidemiology
There are no objectively definitive statistics about how many people have savant skills </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 Pott disease and can you explain it in depth? [/INST] Pott disease is tuberculosis of the spine, usually due to haematogenous spread from other sites, often the lungs. The lower thoracic and upper lumbar vertebrae areas of the spine are most often affected.
It causes a kind of tuberculous arthritis of the intervertebral joints. The infection can spread from two adjacent vertebrae into the adjoining intervertebral disc space. If only one vertebra is affected, the disc is normal, but if two are involved, the disc, which is avascular, cannot receive nutrients, and collapses. In a process called caseous necrosis, the disc tissue dies, leading to vertebral narrowing and eventually to vertebral collapse and spinal damage. A dry soft-tissue mass often forms and superinfection is rare.
Spread of infection from the lumbar vertebrae to the psoas muscle, causing abscesses, is not uncommon.The disease is named after Percivall Pott, the British surgeon who first described it in the late 18th century.

Diagnosis
Blood tests– Complete blood count: leukocytosis
– Elevated erythrocyte sedimentation rate: >100 mm/hTuberculin skin test– Tuberculin skin test (purified protein derivative [PPD]) results are positive in 84–95% of patients with Pott disease who are not infected with HIV.
Radiographs of the spine– Radiographic changes associated with Pott disease present relatively late </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 Drug-induced lupus erythematosus and can you explain it in depth? [/INST] Drug-induced lupus erythematosus is an autoimmune disorder caused by chronic use of certain drugs. These drugs cause an autoimmune response (the body attacks its own cells) producing symptoms similar to those of systemic lupus erythematosus (SLE). There are 38 known medications to cause DIL but there are three that report the highest number of cases:  hydralazine, procainamide, and quinidine. While the criteria for diagnosing DIL has not been thoroughly established, symptoms of DIL typically present as muscle pain and joint pain. Generally, the symptoms recede after discontinuing use of the drugs.

Signs and symptoms
Signs and symptoms of drug-induced lupus erythematosus include the following:
Joint pain (arthralgia) and muscle pain (myalgia)
Fatigue
Serositis—inflammation of the tissues lining the heart and lungs.
Anti-histone antibodies in 95% of cases among those taking procainamide, hydralazine, chlorpromazine, and quinidine; however, these antibodies have been found in a smaller proportion of patients associated with other medications, including minocycline, propylthiouracil, and statins.These signs and symptoms are not side effects of the drugs taken which occur during short term use. DIL occurs over long-term and chronic use of the medications listed below. While these symptoms are similar to those of systemic lupus erythematosus, they are generally not as severe unless they are ignored which leads to more harsh symptoms, and in some reported cases, death.

Causes
The processes that lead to drug-induced lupus erythematosus are not entirely understood. The exact processes that occur are not known even after 50 years since its discovery, but many studies present theories on the mechanisms of DIL.A predisposing factor to developing DIL is N-acetylation speed, or the rate at which the body can metabolize the drug. This is greatly decreased in patients with a genetic deficiency of the enzyme N-acetyltransferase. A study showed that 29 of 30 patients with DIL were slow acetylators. In addition, these patients had more hydralazine metabolites in their urine than fast acetylators. These metabolites (byproducts of the interactions between the drug and constituents in the body) of hydralazine are said to have been created when white blood cells have been activated, meaning they are stimulated to produce a respiratory burst. Respiratory burst in white blood cells induces an increased production of free radicals and oxidants such as hydrogen peroxide. These oxidants have been found to react with hydralazine to produce a reactive species that is able to bond to protein. Monocytes, one type of white blood cell, detect the antigen and relay the recognition to T helper cells, creating antinuclear antibodies leading to an immune response. Further studies on the interactions between oxidants and hydralazine are necessary to understand the processes involved in DIL.Of the drugs that cause DIL, hydralazine has been found to cause a higher incidence </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 Anisomelia 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 Spigelian hernia and can you explain it in depth? [/INST] A Spigelian is the type of ventral hernia where aponeurotic fascia pushes through a hole in the junction of the linea semilunaris and the arcuate line creating a bulge. It appears in the abdomen lower quadrant between an area of dense fibrous tissue and abdominal wall muscles causing a (Spigelian aponeurosis).It is the protuberance, of omentum, adipose tissue, or bowel in that weak space between the abdominal wall muscles, that ultimately pushes the intestines or superficial fatty tissue through a hole causing a defect. As a result, it creates the movement of an organ or a loop of intestine in the weakened body space that it is not supposed to be in. It is at this separation (aponeurosis) in the ventral abdominal region, that herniation most commonly occurs.

Spigelian hernias are rare compared to other types of hernias because they do not develop under abdominal layers of fat but between fascia tissue that connects to muscle.  The Spigelian hernia is generally smaller in diameter, typically measuring 1–2 cm., and the risk of tissue becoming strangulated is high.

Signs and symptoms
Individuals typically present with either intermittent pain (coming and going), a lump, or mass all which are classic signs of a bowel obstruction. The patient may have a protuberance when standing in an upright position although discomfort can sometimes be confused by its anatomical region for a peptic ulceration. The bulge may be painful when the patient stretches but then goes away when they are lying down in a resting position. However, a number of patients present with no obvious symptoms but vague tenderness along the area in which the Spigelian fascia is located.

Diagnosis
Ultrasound Imaging or a CT Scan will provide better imaging for the detection of a hernia than an xray. The ultrasound probe should move from lateral to medially, a hypoechoic mass should appear anteriorly and medially to the inferior epigastric artery during Valsalva maneuver. The diagnosis of a Spigelian hernia is traditionally difficult if only given a history and physical examination. People who are good candidates for elective Spigelian hernia surgery, not only but also, after receiving an initial diagnostic consultation by a licensed medical professional, will be advised to see a physician to schedule surgery.

Treatment
The Spigelian hernia can be repaired by either an open procedure or laproscopic surgery because of the high risk of strangulation; surgery is straightforward, with only larger defects requiring a mesh prosthesis </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 Brachydactyly 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 Aquagenic urticaria and can you explain it in depth? [/INST] Aquagenic urticaria, also known as water allergy and water urticaria, is a rare form of physical urticaria in which hives develop on the skin after contact with water, regardless of its temperature. The condition typically results from contact with water of any type, temperature or additive.

Signs and symptoms
The main symptom of aquagenic urticaria is the development of physical hives, which may or may not itch. Itching after contact with water, without the development of physical hives, is known as aquagenic pruritus. Aquadynia is a condition in which pain occurs after contact with water.In severe cases, drinking water can result in swelling of the oral cavity , swelling of the throat  and in extreme cases, anaphylaxis.   The hives associated with aquagenic urticaria are typically small (approximately 1–3 mm), red- or skin-colored welts (called wheals) with clearly defined edges. It most commonly develops on the neck, upper trunk and arms, although it can occur anywhere on the body.  Once the water source is removed, the rash generally fades within 30 to 60 minutes.Water in all forms, such as tap or sea water, swimming pool water, sweat, tears, and saliva can induce the lesions.

Cause
The cause of aquagenic urticaria is not fully understood; however, several mechanisms have been proposed. Interaction between water and a component in or on the skin or sebum has been suggested. This theory suggests that a substance is formed by this interaction, the absorption of which causes perifollicular mast cell degranulation with release of histamine. Another proposed theory is of a water-soluble allergen in the epithelial tissues. Water dissolves the allergen, causing it to diffuse into the tissues, causing histamine release from sensitized mast cells.

Diagnosis
Diagnosis of aquagenic urticaria begins with a clinical history and water challenge test. The water challenge test consists of application of a 35°C water compress to the upper body for 30 minutes. Water of any temperature can provoke aquagenic urticaria; however, keeping the compress at a similar temperature to that of the human body (37 °C) avoids confusion with cold urticaria or cholinergic urticaria </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 uric acid nephropathy and can you explain it in depth? [/INST] Acute uric acid nephropathy (AUAN, also acute urate nephropathy) is a rapidly worsening (decreasing) kidney function (acute kidney injury) that is caused by high levels of uric acid in the urine (hyperuricosuria).

Causes
Acute uric acid nephropathy is usually seen as part of the acute tumour lysis syndrome in patients undergoing chemotherapy or radiation therapy for the treatment of malignancies with rapid cell turnover, such as leukemia and lymphoma. It may also occur in these patients before treatment is begun, due to spontaneous tumor cell lysis (high incidence in Burkitts lymphoma).
Acute uric acid nephropathy can also be caused by an acute attack of gout.

Pathophysiology
Acute uric acid nephropathy is caused by deposition of uric acid crystals within the kidney interstitium and tubules, leading to partial or complete obstruction of collecting ducts, renal pelvis, or ureter. This obstruction is usually bilateral, and patients follow the clinical course of acute kidney failure.

Diagnosis
The picture of acute kidney failure is observed: decreased urine production and rapidly rising serum creatinine levels. Acute uric acid nephropathy is differentiated from other forms of acute kidney failure by the finding of a urine uric acid/creatinine ratio > 1 in a random urine sample.

Prevention
Patients at risk for acute uric acid nephropathy can be given allopurinol or rasburicase (a recombinant urate oxidase) prior to treatment with cytotoxic drugs.

Treatment
Treatment is focused on preventing deposition of uric acid within the urinary system by increasing urine volume with potent diuretics such as furosemide. Raising the urinary pH to a level higher than 7 (alkalinization) is often difficult to attain, although sodium bicarbonate and/or acetazolamide are sometimes used in an attempt to increase uric acid solubility.
Dialysis (preferably hemodialysis) is started if the above measures fail.

References
Conger JD (1990). "Acute uric acid nephropathy". Med Clin North Am. 74 (4): 859–71. PMID 2195258.
Robinson RR, Yarger WE (1977) </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 Median nail dystrophy 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 Cyclothymia and can you explain it in depth? [/INST] Cyclothymia ( siy-kluh-THIY-mee-uh), also known as cyclothymic disorder, psychothemia/psychothymia, bipolar III, affective personality disorder and cyclothymic personality disorder, is a mental and behavioural disorder that involves numerous periods of symptoms of depression and periods of symptoms of elevated mood. These symptoms, however, are not sufficient to indicate a major depressive episode or a manic episode. Symptoms must last for more than one year in children and two years in adults.The cause of cyclothymia is unknown. Risk factors include a family history of bipolar disorder. Cyclothymia differs from bipolar in that major depression and mania are not found.Treatment is generally achieved with counseling and mood stabilizers such as lithium. It is estimated that 0.4-1% of people have cyclothymia at some point in their life. The disorders onset typically occurs in late childhood to early adulthood. Males and females are affected equally often.

Symptoms
People with cyclothymia experience both depressive phases and hypomanic phases (which are less severe than full manic episodes). The depressive and hypomanic symptoms in cyclothymia last for variable amounts of time due to the unstable and reactive nature of the disorder. The depressive phases are similar to major depressive disorder and are characterized by dulled thoughts and sensations and the lack of motivation for intellectual or social activities.  Most people with cyclothymia are generally fatigued and tend to sleep frequently and for long periods of time.  However, other people experience insomnia.Other symptoms of cyclothymic depression include indifference toward people or activities that used to be extremely important.  Cyclothymic depression also leads to difficulty making decisions.  In addition, people with this condition tend to be critical and complain easily.  Suicidal thoughts are common, even in mild forms of cyclothymia. In the depressive state, people with cyclothymia also experience physical complaints including frequent headaches, tightness in the head and chest, an empty sensation in the head, weakness, weight loss, and hair loss.The distinguishing factor between typical depression and cyclothymic depression is that in cyclothymic depression, there are instances of hypomania. People with cyclothymia can switch from the depressive state to the hypomanic state without warning to them or others. The duration and frequency of phases is unpredictable.In the hypomanic state, peoples thoughts become faster and they become more sociable and talkative. They may engage in spending sprees, spontaneous actions, have heightened self-esteem, and greater vanity. In contrast to a regular manic state that would be associated with bipolar I, symptoms in the hypomanic phase generally occur in a less severe form.Cyclothymia commonly occurs in conjunction with other disorders. Between 20 and 50 percent of people with depression, anxiety, and related disorders also have cyclothymia.  When people with cyclothymia seek mental health resources it tends to be for symptoms of their comorbid condition rather than for their symptoms of cyclothymia. In children and adolescents, the most common comorbidities with cyclothymia are anxiety disorders, impulse control issues, eating disorders, and ADHD. In adults, cyclothymia also tends to be comorbid with impulse control issues. Sensation-seeking behaviors occur in hypomanic states.  These often include gambling and compulsive sexuality in men, or compulsive buying and binge eating in women.In addition to sensation-related disorders, cyclothymia has also been associated with atypical depression. In one study, a connection was found between interpersonal sensitivity, mood reactivity (i.e., responding to actual or potential positive events with brighter mood), and cyclothymic mood swings, all of which are symptoms of atypical depression. Cyclothymia also tends to occur in conjunction with separation anxiety, where a person has anxiety as a result of separation from a caregiver, friend, or loved one. Other issues that tend to co-occur with cyclothymia include social anxiety, fear of rejection and a tendency toward hostility to those connected with past pain and rejection. People with cyclothymia tend to seek intense interpersonal relationships when in a hypomanic state and isolation when in a depressed state.  This generally leads to short, tumultuous relationships.

Causes
The cause is unknown. Risk factors include a family history of bipolar disorder.First-degree relatives of people with cyclothymia have major depressive disorder, bipolar I disorder, and bipolar II disorder more often than the general population. Substance-related disorders also may be at a higher risk within the family. First-degree relatives of a bipolar I individuals may have a higher risk of cyclothymic disorder than the general population.

Diagnosis
Cyclothymia is classified in DSM-5 as a subtype of bipolar disorder. The criteria are:
Periods of elevated mood and depressive symptoms for at least half the time during the last two years for adults and one year for children and teenagers.
Periods of stable moods last only two months at most.
Symptoms create significant problems in one or more areas of life.
Symptoms do not meet the criteria for bipolar disorder, major depression, or another mental disorder.
Symptoms are not caused by substance use or a medical condition.The DSM-5 criteria for cyclothymia are restrictive according to some researchers. This affects the diagnosis of cyclothymia because fewer people get diagnosed than potentially could. This means that a person who has some symptoms of the disorder might not be able to get treatment because they do not meet all of the necessary criteria described in DSM-5.  Furthermore, it also leads to more attention being placed on depression and other bipolar-spectrum disorders because if a person does not meet all the criteria for cyclothymia they are often given a depression or bipolar spectrum diagnosis. Improper diagnosis may lead some people with cyclothymia to be treated for a comorbid disorder rather than having their cyclothymic tendencies addressed.Cyclothymia is often not recognized by the affected individual or medical professionals due to its ostensibly mild symptoms. In addition, it is difficult to identify and classify. Due to disagreement and misconceptions among health and mental health professionals, cyclothymia is often diagnosed as "bipolar not otherwise specified". Cyclothymia is also often confused with borderline personality disorder due to their similar symptoms, especially in older adolescents and young adults.Most people with the disorder present in a depressive state, not realizing that their hypomanic states are abnormal. Mild manic episodes tend to be interpreted as part of the persons personality or simply a heightened mood. In addition, the disorder often manifests during childhood or adolescence, making it even more difficult for the person to distinguish between symptoms of the disorder and their personality. For example, people may think that they just have mood swings and not realize that these are a result of a psychiatric condition.

Management
Cognitive behavioral therapy (CBT) is considered potentially effective for people diagnosed with cyclothymia.Medication can be used in addition to behavioral approaches. However, mood stabilizers should be used before antidepressants, and if antidepressants are used they should be used with caution. Antidepressants are a concern due to the possibility of inducing hypomanic switches or rapid cycling.

History
In 1883, Karl Ludwig Kahlbaum identified a disorder characterized by recurring mood cycles. The disorder contained both melancholic and manic episodes that occurred in a milder form than in bipolar disorder.  This condition was coined "cyclothymia" by Kahlbaum and his student Ewald Hecker. Kahlbaum developed his theory of cyclothymia through his work with people presenting with these symptoms at the Kahlbaum Sanitarium in Goerlitz, Silesia (Germany). He was recognized as a leading hypnotherapist and psychotherapist of his day.  He was a progressive in the field of mental health, believing that mental illness should not carry a stigma and that people dealing with mental health issues should be treated humanely. Kalhbaum was the first to recognize that people with cyclothymia often do not seek help for the disorder due to its milder symptoms.Cyclothymia has been conceptualized in a variety of ways, including as a subtype of bipolar disorder, a temperament, a personality trait, and a personality disorder.  There is also an argument that cyclothymia should be considered a neurodevelopmental disorder. The two defining features of the disorder, according to DSM-5, are the presence of depressive and hypomanic symptoms, not meeting the threshold for a depressive or hypomanic episode. Cyclothymia is also classified as a subtype of bipolar disorder in DSM-5, but some researchers disagree with this classification and argue that it should be primarily defined as an exaggeration of mood and emotional instability. In the past, cyclothymia has been conceptualized to include other characteristics in addition to the flux between depression and hypomania, such as mood reactivity, impulsivity, and anxiety.

Epidemiology
Cyclothymia, known today as Cyclothymic Disorder, tends to be underdiagnosed due to its low intensity. The exact rates for Cyclothymia have not been widely studied. Some studies estimate that between 5 and 8% are affected at some point in their life whereas other studies suggest a rate ranging from 0.4 to 2.5%.Males appear to be affected equally often, though women are more likely to receive treatment. Cyclothymia is diagnosed in around fifty percent of people with depression who are evaluated in psychiatric outpatient settings.

Etymology
Cyclothymia is derived from the Greek word κυκλοθυμία (from κῦκλος, kyklos, "circle" and θυμός, thymos, "mood, emotion"). Therefore, it means "to cycle or circle between moods or emotions".

Research
Whether subtypes of bipolar disorder, such as cyclothymia, truly represent separate disorders or are part of a unique bipolar spectrum is debated in research.  Cyclothymia is typically not described in research studies or diagnosed in clinical settings, making it less recognizable and less understood by professionals </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 Hydrothorax and can you explain it in depth? [/INST] Hydrothorax is a type of pleural effusion in which transudate accumulates in the pleural cavity </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 Pseudostrabismus and can you explain it in depth? [/INST] Pseudostrabismus is the false appearance of crossed eyes </s>