<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 Multiple system atrophy and can you explain it in depth? [/INST] Multiple system atrophy (MSA) is a rare neurodegenerative disorder characterized by autonomic dysfunction, tremors, slow movement, muscle rigidity, and postural instability (collectively known as parkinsonism) and ataxia. This is caused by progressive degeneration of neurons in several parts of the brain including the basal ganglia, inferior olivary nucleus, and cerebellum.
Many people affected by MSA experience dysfunction of the autonomic nervous system, which commonly manifests as orthostatic hypotension, impotence, loss of sweating, dry mouth and urinary retention and incontinence. Palsy of the vocal cords is an important and sometimes initial clinical manifestation of the disorder.
A modified form of the alpha-synuclein protein within affected neurons may cause MSA. About 55% of MSA cases occur in men, with those affected first showing symptoms at the age of 50–60 years. MSA often presents with some of the same symptoms as Parkinsons disease. However, those with MSA generally show little response to the dopamine medications used to treat Parkinsons disease and only about 9% of MSA patients with tremor exhibit a true parkinsonian pill-rolling tremor.MSA is distinct from multisystem proteinopathy, a more common muscle-wasting syndrome. MSA is also different from multiple organ dysfunction syndrome, sometimes referred to as multiple organ failure, and from multiple organ system failures, an often-fatal complication of septic shock and other severe illnesses or injuries.

Signs and symptoms
MSA is characterized by the following, which can be present in any combination:
autonomic dysfunction
parkinsonism (muscle rigidity +/ tremor and slow movement)
cerebellar ataxia (Poor coordination/unsteady walking, double vision)A variant with combined features of MSA and dementia with Lewy bodies may also exist. There have also been occasional instances of frontotemporal lobar degeneration associated with MSA.

Initial presentation
The most common first sign of MSA is the appearance of an "akinetic-rigid syndrome" (i.e. slowness of initiation of movement resembling Parkinsons disease) found in 62% at first presentation. Other common signs at onset include problems with balance (cerebellar ataxia) found in 22% at first presentation, followed by genito-urinary symptoms (9%): both men and women often experience urgency, frequency, incomplete bladder emptying, or an inability to pass urine (retention). About 1 in 5 MSA patients experience a fall in their first year of disease.For men, the first sign can be erectile dysfunction. Women have also reported reduced genital sensitivity.

Progression
As the disease progresses one of three groups of symptoms predominates.
These are:
Parkinsonism - slow, stiff movement, writing becomes small and spidery
Cerebellar dysfunction - difficulty coordinating movement and balance
Autonomic nervous system dysfunction - impaired automatic body functions, including one, some, or all of the following:postural or orthostatic hypotension, resulting in dizziness or fainting upon standing up
urinary incontinence or urinary retention
impotence
constipation
vocal cord paralysis
dry mouth and skin
trouble regulating body temperature due to sweating deficiency in all parts of the body
loud snoring, abnormal breathing or inspiratory stridor during sleep
other sleep disorders including sleep apnea, REM behavior disorder
double vision
muscle twitches
Cognitive impairment

Genetics
One study found a correlation between the deletion of genes in a specific genetic region and the development of MSA in a group of Japanese patients. The region in question includes the SHC2 gene which, in mice and rats, appears to have some function in the nervous system.  The authors of this study hypothesized that there may be a link between the deletion of the SHC2 and the development of MSA.A follow-up study was unable to replicate this finding in American MSA patients. The authors of the U.S. study concluded that "Our results indicate that SHC2 gene deletions underlie few, if any, cases of well-characterized MSA in the US population. This is in contrast to the Japanese experience reported by Sasaki et al., likely reflecting heterogeneity of the disease in different genetic backgrounds."Another study investigated the frequency of RFC1 intronic repeat expansions, a phenomenon implicated in CANVAS; a disease with a diagnostic overlap with MSA. The study concluded that these repeats were absent in pathologically confirmed MSA, suggesting an alternative genetic cause.

Pathophysiology
Multiple system atrophy can be explained as cell loss and gliosis or a proliferation of astrocytes in damaged areas of the central nervous system. This damage forms a scar which is then termed a glial scar. The presence of inclusion bodies known as Papp–Lantos bodies, in the movement, balance, and autonomic-control centres of the brain are the defining histopathologic hallmark of MSA.The major filamentous component of Papp-Lantos bodies, glial and neuronal cytoplasmic inclusions, is alpha-synuclein. Mutations in this substance may play a role in the disease. The conformation of the alpha-synuclein is different from that of alpha-synuclein in Lewy bodies. The disease probably starts with an oligodendrogliopathy.Tau proteins have been found in some glial cytoplasmic inclusion bodies.

Diagnosis
Clinical
Clinical diagnostic criteria were defined in 1998  and updated in 2007. Certain signs and symptoms of MSA also occur with other disorders, such as Parkinsons disease, making the diagnosis more difficult.

Radiologic
Both MRI and CT scanning may show a decrease in the size of the cerebellum and pons in those with cerebellar features (MSA-C). The putamen is hypointense on T2-weighted MRI and may show an increased deposition of iron in the Parkinsonian (MSA-P) form. In MSA-C, a "hot cross bun" sign is sometimes found; it reflects atrophy of the pontocerebellar tracts that give T2 hyper intense signal intensity in the atrophic pons.MRI changes are not required to diagnose the disease as these features are often absent, especially early in the course of the disease. Additionally, the changes can be quite subtle and  are usually missed by examiners who are not experienced with MSA.

Pathologic
Pathological diagnosis can only be made at autopsy by finding abundant GCIs on histological specimens of the central nervous system.Contrary to most other synucleinopathies, which develop α-synuclein inclusions primarily in neuronal cell populations, MSA presents with extensive pathological α-synuclein inclusions in the cytosol of oligodendrocytes (glial cytoplasmic inclusions), with limited pathology in neurons. MSA also differs from other synucleinopathies in its regional pathological presentation, with α-synuclein positive inclusions detected predominantly in the striatum, midbrain, pons, medulla and cerebellum, rather than the brainstem, limbic and cortical regions typically effected in Lewy inclusion diseases. However, recent studies using novel, monoclonal antibodies specific for C-terminally truncated α-synuclein (αSynΔC) have now shown that neuronal α-synuclein pathology is more abundant than previously thought. One group revealed robust α-synuclein pathology in the pontine nuclei and medullary inferior olivary nucleus upon histological analysis of neurological tissue from MSA patients.
Histopathological investigation on six cases of pathologically confirmed MSA, using antibodies directed at a variety of α-synuclein epitopes, revealed substantial variation in α-synuclein protein deposition across both cases and brain regions within cases, providing evidence for strains of aggregated conformers that may differentially promote pathological prion-like spread.In 2020, researchers at The University of Texas Health Science Center at Houston concluded that protein misfolding cyclic amplification could be used to distinguish between two progressive neurodegenerative diseases, Parkinson’s disease and multiple system atrophy, being the first process to give an objective diagnosis of Multiple System Atrophy instead of just a differential diagnosis.

Classification
MSA is one of several neurodegenerative diseases known as synucleinopathies: they have in common an abnormal accumulation of alpha-synuclein protein in various parts of the brain. Other synucleinopathies include Parkinsons disease, the Lewy body dementias, and other more rare conditions.

Old terminology
Historically, many terms were used to refer to this disorder, based on the predominant systems presented. These terms were  discontinued by consensus in 1996 and replaced with MSA and its subtypes, but awareness of these older terms and their definitions is helpful to understanding the relevant literature prior to 1996. These include striatonigral degeneration (SND), olivopontocerebellar atrophy (OPCA), and Shy–Drager syndrome. A table describing the characteristics and modern names of these conditions follows:

Current terminology
The current terminology and diagnostic criteria for the disease were established at a 2007 conference of experts and set forth in a position paper. This Second Consensus Statement defines two categories of MSA, based on the predominant symptoms of the disease at the time of evaluation. These are:

MSA with predominant parkinsonism (MSA-P) - defined as MSA where extrapyramidal features predominate. It is sometimes termed striatonigral degeneration, a parkinsonian variant.
MSA with cerebellar features (MSA-C) -  defined as MSA in which cerebellar ataxia predominates.  It is sometimes termed sporadic olivopontocerebellar atrophy.

Management
Supervision
Ongoing care from a neurologist specializing in movement disorders is recommended, because the complex symptoms of MSA are often not familiar to less-specialized neurologists. Hospice/homecare services can be very useful as disability progresses.

Drug therapy
Levodopa (L-Dopa), a drug used in the treatment of Parkinsons disease, improves parkinsonian symptoms in a small percentage of MSA patients. A recent trial reported that only 1.5% of MSA patients experienced any improvement at all when taking levodopa, their improvement was less than 50%, and even that improvement was a transient effect lasting less than one year. Poor response to L-Dopa has been suggested as a possible element in the differential diagnosis of MSA from Parkinsons disease.The drug riluzole is ineffective in treating MSA or PSP.

Rehabilitation
Management by rehabilitation professionals including physiatrists, physiotherapists, occupational therapists, speech therapists, and others for difficulties with walking/movement, daily tasks, and speech problems is essential.Physiotherapists can help to maintain the patients mobility and will help to prevent contractures. Instructing patients in gait training will help to improve their mobility and decrease their risk of falls. A physiotherapist may also prescribe mobility aids such as a cane or a walker to increase the patients safety.Speech therapists may assist in assessing, treating and supporting speech (dysarthria) and swallowing difficulties (dysphagia).  Speech changes mean that alternative communication may be needed, for example, communication aids or word charts.Early intervention of swallowing difficulties is particularly useful to allow for discussion around tube feeding further in the disease progression.  At some point in the progression of the disease, fluid and food modification may be implemented.

Avoidance of postural hypotension
One particularly serious problem, the drop in blood pressure upon standing up (with risk of fainting and thus injury from falling), often responds to fludrocortisone, a synthetic mineralocorticoid. Another common drug treatment is the alpha-agonist midodrine.Non-drug treatments include "head-up tilt" (elevating the head of the whole bed by about 10 degrees), salt tablets or increasing salt in the diet, generous intake of fluids, and pressure (elastic) stockings. Avoidance of triggers of low blood pressure, such as hot weather, alcohol, and dehydration, are crucial. The patient can be taught to move and transfer from sitting to standing slowly to decrease risk of falls and limit the effect of postural hypotension. Instruction in ankle pumping helps to return blood in the legs to the systemic circulation. Other preventative measures are raising the head of the bed by 8 in (20.3 cm), and the use of compression stockings and abdominal binders.

Support
Social workers and occupational therapists can also help with coping with disability through the provision of equipment and home adaptations, services for caregivers and access to healthcare services, both for the person with MSA as well as family caregivers.

Prognosis
The average lifespan after the onset of symptoms in patients with MSA is 6–10 years. Approximately 60% of patients require a wheelchair within five years of onset of the motor symptoms, and few patients survive beyond 12 years </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 17q12 microdeletion syndrome and can you explain it in depth? [/INST] 17q12 microdeletion syndrome, also known as 17q12 deletion syndrome, is a rare chromosomal anomaly caused by the deletion of a small amount of material from a region in the long arm of chromosome 17. It is typified by deletion of the HNF1B gene, resulting in kidney abnormalities and renal cysts and diabetes syndrome. It also has neurocognitive effects, and has been implicated as a genetic factor for autism and schizophrenia.
17q12 microdeletion syndrome is not to be confused with 17q12 microduplication syndrome, caused by the addition of genetic material in the same region from which it is removed in the microdeletion, or 17q21.31 microdeletion syndrome, another name for Koolen–De Vries syndrome.

Presentation
17q12 microdeletions have a variable phenotype, ranging from few or no symptoms to severe disability. The condition is thought to be underdiagnosed, and cases with milder phenotypes may not reach clinical attention unless they have an affected child themselves. The most characteristic symptom is renal cysts and diabetes syndrome (RCAD), also known as "type 5 diabetes", which is caused by deletion of the associated HNF1B gene in the region. RCAD is associated with kidney abnormalities and a characteristic form of diabetes that causes atrophy of the pancreas. However, some people with 17q12 microdeletions have normal renal function. RCAD is diagnosed in approximately 40% of people with 17q12 microdeletions, usually prior to age 25, while kidney abnormalities more broadly occur in approximately 85-90%.People with 17q12 microdeletions have a characteristic facial phenotype, albeit a subtle one not usually obvious in daily life. Macrocephaly is common, along with high arched eyebrows, flattening of the malar region, and epicanthic folds. Pathological short stature is possible, and a characteristic "short and stocky" body shape occurs in many cases.17q12 microdeletions are associated with neurocognitive and developmental involvement of variable severity. Some have mild to moderate intellectual disability; however, such impairment is not universal. Average intelligence is in the average to low average range. Speech delay is common, regardless of intellectual functioning. The most striking association between 17q12 microdeletions and neurodevelopment is the raised prevalence of autism spectrum disorder, with significant increases in both diagnosis and subclinical autistic traits. 17q12 microdeletions have been implicated as one of the major genetic causes of high-functioning autistic spectrum disorders. Schizophrenia is also a significant psychiatric complication of 17q12 microdeletion syndrome. 17q12 microdeletions are estimated to occur in approximately 1 in 1,600 people with schizophrenia, compared to an estimation of below 1 in 50,000 in the general population. Epilepsy, usually mild, occurs in approximately one-third of cases.Reproductive system anomalies are associated with 17q12 microdeletions, particularly in females. 17q12 microdeletions have been linked to uterine malformations, most frequently Müllerian agenesis, where the uterus and part of the vaginal canal are absent.

Causes
17q12 microdeletion syndrome is an autosomal dominant disorder, where one copy of the relevant mutation is enough to cause the condition. Most cases are de novo, or spontaneous mutations that do not occur in the probands parents; approximately 75% are de novo, while 25% are inherited. People with 17q12 microdeletions who have normal fertility have a 50% chance of passing the deletion down to their offspring. Environmental factors have not been implicated in the syndrome.

Diagnosis
Like other chromosomal microdeletions, 17q12 microdeletion syndrome is diagnosed via fluorescence in situ hybridization. Traditional karyotyping, used to diagnose major chromosomal disorders such as aneuploidy, is rarely sensitive enough to detect microdeletions.

Treatment
As the underlying 17q12 microdeletion is an innate genetic disorder, it cannot by itself be treated. Rather, treatment is symptomatic and supportive. The high prevalence of kidney disease indicates routine monitoring of renal function, particularly in people taking potentially nephrotoxic medications such as lithium. The comorbities involved in 17q12 microdeletion syndrome require caution in medical treatment; for instance, the increased risk of diabetes requires strict monitoring for post-transplantation diabetes mellitus in kidney transplant patients, as does the risk of weight gain and diabetes from neuroleptic drugs in those with a mental health diagnosis.

Epidemiology
The prevalence of 17q12 microdeletion syndrome is unknown, and it is likely to be underdiagnosed. 17q12 microdeletions are estimated to occur in approximately 1 in 600 people on the autism spectrum and 1 in 1,600 with schizophrenia, but are far rarer in the general population </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 Traumatic neuroma 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 Brain fag syndrome and can you explain it in depth? [/INST] Brain fag syndrome (BFS) describes a set of symptoms; somatic, sleep-related and cognitive complaints, difficulty in concentrating and retaining information, head and or neck pains, and eye pain. Brain Fag is very common in adolescents and young adults. It is believed to be the most common in these age ranges due to the immense amount of pressure occurring in life during these years. The condition was arguably first described in Nigerian high school and university students in the 1960s. It is considered a culture-bound syndrome caused by excessive pressure to be successful among the young.

Etymology
The term brain fag presumably stems from the verb meaning of the word, "To cause (a person, animal, or part of the body) to become tired; to fatigue, wear out" chiefly found in British English.

Classification
BFS is classified in the fourth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as a culture-bound syndrome.  Individuals with symptoms of brain fag must be differentiated from those with the syndrome according to the Brain Fag Syndrome Scale (BFSS); Ola et al said it would not be "surpris[ing] if BFS was called an equivalent of either depression or anxiety".

Causes
Brain Fag is typically driven in people with high anxiety and people with high stress levels. Morakinyo found in 20 people with BFS an achievement drive that was anxiety-related that led to the use of psychostimulants and consequent sleep deprivation which contributed to cognitive disruption </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 Persistent cloaca and can you explain it in depth? [/INST] A persistent cloaca is a symptom of a complex anorectal congenital disorder, in which the rectum, vagina, and urinary tract meet and fuse, creating a cloaca, a single common channel.

Signs and symptoms
Cloacas appear in a wide spectrum of variation in females born with the malformation </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 Patella fracture and can you explain it in depth? [/INST] A patella fracture is a break of the kneecap. Symptoms include pain, swelling, and bruising to the front of the knee. A person may also be unable to walk. Complications may include injury to the tibia, femur, or knee ligaments.It typically results from a hard blow to the front of the knee or falling on the knee. Occasionally it may occur from a strong contraction of the thigh muscles. Diagnosis is based on symptoms and confirmed with X-rays. In children an MRI may be required.Treatment may be with or without surgery, depending on the type of fracture. Undisplaced fracture can usually be treated by casting. Even some displaced fractures can be treated with casting as long as a person can straighten their leg without help. Typically the leg is immobilized in a straight position for the first three weeks and then increasing degrees of bending are allowed. Other types of fractures generally require surgery.Patella fractures make up about 1% of all broken bones. Males are affected more often than females. Those of middle age are most often affected. Outcomes with treatment are generally good.

Signs and symptoms
Also known as a broken kneecap, a patella fracture usually follows a history of trauma and commonly presents with swelling, pain, bruising and inability to both bend and straighten the knee. The pain is worse when trying to stand and the person may be unable to walk. The pain can also be aggravated by prolonged periods of sitting. A painful defect may be felt in the knee and there may be blood in the joint.

Complications
Complications may include injury to the tibia, femur, or knee ligaments. In the longer term, the knee may not regain full movement, pain may persist and there is an increased likelihood of osteoarthritis of the knee. If there is an associated open wound as in an open fracture, complications also include risk of infection, inability of the broken bones to reunite and osteonecrosis.

Diagnosis
Diagnosis is based on symptoms and confirmed with X-rays. In children an MRI may be required.

Differential diagnosis
Some people have a normal bipartite patella or two-part patella which can appear as a fracture. The fragment is usually seen in the top outer corner of the patella and can be distinguished from a fracture by being present in both knees.

Types
The patella can break in various ways depending on the way it is injured, and into two or more pieces. Types include transverse, with one fracture line and is the most common type, marginal, osteochondral and the rare vertical type, or stellate, where a direct compression force gives rise to a comminuted pattern. Patella fractures can be further classified as displaced, where the broken ends of bone do not line up correctly and separate by more than 2mm, or undisplaced and stable where pieces of bone remain in contact with each other. If fragments of patella bone stick out from the skin it is known as an open patella fracture, and closed if the overlying skin is intact.

Treatment
Treatment may be with or without surgery, depending on the type of fracture and whether the overlying skin is intact or broken.

Conservative
Undisplaced fractures can usually be treated by casting. Even some displaced fractures can be treated with casting as long as the person can straighten their leg without help, thus confirming that the quadriceps mechanism of the leg is intact. In this case the leg is immobilized in a straight position for the first three weeks and then increasing degrees of bending are allowed as healing occurs.

Surgery
Most patella fractures are transverse or comminuted, hence the quadriceps mechanism is disrupted and they are treated by a combination of wires in a tension band construct.
This unites the fractured bones, reconstructing the straightening mechanism of the leg.If the patella is broken in several places, that is  comminuted, then traditionally a patellectomy (removal of the whole patella) is performed in order to reconstruct the extensor mechanism and prevent the onset of an extension lag at the knee joint, resulting in instability. Some surgeons however would rather opt for internal fixation. A partial patellectomy is removal of only a portion of the patella, and may be carried out if at least 60% of the patella can be maintained.Open fractures of the patella require emergency treatment with irrigation, debridement and fixation.

Rehabilitation
Irrespective of surgical or non-surgical resolution to the fracture, a physical therapist can advise on progressive weight-bearing exercises and help with strengthening muscles of the leg, improving range of motion of the knee and in reducing stiffness.

Prognosis
Outcomes with treatment are generally good, unless there is involvement of the articular surface or the quadriceps mechanism. There is an increased risk of developing osteoarthritis in people who have broken their patella.There is limited evidence supporting the different surgical interventions for treating fractures of the patella in adults. There is also no evidence of trials that could evaluate the effects of surgical treatment compared with the conservative treatment or other different types of conservative interventions.

Epidemiology
Patella fractures make up about 1% of all broken bones </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 Bowel-associated dermatosis–arthritis syndrome and can you explain it in depth? [/INST] Bowel-associated dermatosis–arthritis syndrome (BADAS), is a complication of jejunoileal bypass surgery consisting of flu-like symptoms (fever, malaise), multiple painful joints (polyarthralgia), muscle aches (myalgia) and skin changes. It has been reported to occur in up to 20% of patients who had jejunoileal bypass surgery, a form of obesity surgery that is rarely performed today.An excessive immune response to gut bacteria is thought to cause BADAS. Antibiotics have been used successfully to treat the condition (including tetracyclines, macrolides, metronidazole and fluoroquinolones). Corticosteroids are an alternative. Surgical repair of the normal bowel transit, where possible, can be effective.
BADAS has later been reported in patients with inflammatory bowel disease, diverticulitis and following resection of the stomach (gastrectomy).
BADAS has also been reported following biliopancreatic diversion (a form of bariatric surgery, also known as Scopinaro procedure), and in one case, BADAS occurred in a patient with acute appendicitis </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 Autoimmune thyroiditis and can you explain it in depth? [/INST] Autoimmune thyroiditis, is a chronic disease in which the body interprets the thyroid glands and its hormone products T3, T4 and TSH as threats, therefore producing special antibodies that target the thyroids cells, thereby destroying it. It may present with hypothyroidism or hyperthyroidism and with or without a goiter.

Signs and symptoms
The symptoms may vary depending on the thyroid function, i.e. hyperthyroidism or hypothyroidism. Hyperthyroidism can cause sweating, rapid heart rate, anxiety, tremors, fatigue, difficulty sleeping, sudden weight loss, and protruding eyes. Hypothyroidism can cause weight gain, fatigue, dry skin, hair loss, intolerance to cold, and constipation. The effects of this disease may be permanent but can sometimes be transient.  Symptoms may come and go depending on whether the person receives treatment, and whether the treatment takes effect.

Causes
Thyroid autoimmunity is familial. The disease is said to be inherited as a dominant trait since it has been reported that as many as fifty percent of the first degree relatives of patients with some type of autoimmune thyroiditis present with thyroid antibodies in serum.Few studies have even related it to chromosome 21 because of its high correlation with patients with Down syndrome and familial Alzheimer disease </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 Alternariosis 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 Irlen syndrome and can you explain it in depth? [/INST] Irlen syndrome, occasionally referred to as scotopic sensitivity syndrome (SSS) or Meares–Irlen syndrome, is a postulated disorder of vision or image-processing in the brain. Irlen syndrome is also sometimes referred to as asfedia or visual stress. Many mainstream professionals are skeptical of the concept. Research on Irlen syndrome has produced mixed results, finding a possible neurological basis for the condition but little or no evidence supporting the most commonly proposed treatment using tinted eyeglasses or overlays to aid reading.

History
In 1980, New Zealand teacher Olive Meares described the visual distortions some individuals reported when reading from white paper. In 1983, American psychologist Helen Irlen wrote a paper about the use of coloured overlays aiding the reading abilities of some people. Similar symptoms were separately described by Meares and Irlen, each unaware of the others work. Irlen, who was the first to systematically define the condition, named her findings "scotopic sensitivity", though in the discussions and debates over the following years, some referred to it as Meares-Irlen syndrome. The Irlen Institute, founded by Helen Irlen, describes scotopic sensitivity as "a perceptual processing disorder" related to brain interpretations of colours and light.It remains controversial whether non-Irlen-certified Meares-Irlen syndrome and the original Irlen syndrome are the same condition. Irlen syndrome, for example, seems to include a broader array of symptoms, including severe variants of the core condition. Basic testing for scotopic sensitivity was tried by optometrists, opticians and orthoptists in UK hospitals, and by optometrists and opticians in private practice employing a technique that used the Intuitive Colorimeter, developed under Medical Research Council licence. An alternative approach to correct Irlen syndrome was tried by Orthoscopics franchise in the UK, with wide colour coverage and tints manufactured by Hoyato match. Other commercial organisations have produced sets of therapeutic tints, although most have not received scientific evaluation.Studies investigating Irlens syndrome as a treatable condition have been criticised for having a biased and subjective approach to their research.Treatments offered by Irlens practitioners have not been found to be effective in improving reading ability.

Classifications
Irlen divides Irlen syndromes into six types: photophobia, distortion of the fundus, graphical distortions during reading, decreased visual field, difficulty in ocular fixation during reading and change in depth perception.

Research
The disorders have been studied in several institutions, including the Psychology Department at Essex University, the former Applied Psychology Unit, Cambridge University in England, and in the case of Meares-Irlen syndrome, Visual Unit at Glasgow Caledonian University in Scotland. As of 2012 the Visual Stress Unit offered non-commercial diagnostic and therapeutic services to individuals, and provided advice to the Scottish National Health Service.
In Australia, Irlen syndrome was researched by Paul Whiting at the University of Sydney. Whiting set up the first Irlen Dyslexia Centre in Australia, which operated in the Childrens Centre at Sydney University for more than 15 years. Irlen syndrome was also studied in Australia by Greg Robinson (1944–2008) at the University of Newcastle. He was director of the Special Education Centre at the School of Education.In the US, peer-reviewed literature on the topic suggests that much is unknown about the cause of these disorders, ranging from the 2011 study in a journal of the American Academy of Pediatrics, "Irlen Colored Overlays Do not Alleviate Reading Difficulties" and the 2012 study in the journal Brain Topography, "A Functional Neuroimaging Case Study of Meares–Irlen Syndrome". The first, purely in relation to Meares-Irlen syndrome, finds that there is no evidence for one of the fundamental claims of therapeutic benefit. The second, which focused primarily on Irlen syndrome, found compelling evidence of unique brain function linked to the syndrome.

Treatment
The College of Optometrists (UK) has specified guidelines for optometrists who use the colorimeter system. A society for coloured lens prescribers has been established to provide a list of eye-care practitioners with expertise in the provision of coloured lenses for the treatment of visual stress.

Irlen Method
The Irlen Method uses coloured overlays and tinted lenses in the form of glass or contact lenses. The method is intended to reduce or eliminate perceptual processing errors; it is claimed the resultant retiming of visual signals in the brain improves the reading difficulties associated with scotopic sensitivity syndrome.

Scientific repudiation
Skepticism relating to scotopic sensitivity syndromes exact pathology has evolved on several fronts:

Whether it exists as a distinct, predictably identifiable disease with a reasonable pathophysiological mechanism, or whether a range of symptoms from other conditions are being placed under this convenient heading;
Whether it is causally or incidentally related to dyslexia, autism, or other conditions; and
Whether existing methods of scotopic sensitivity syndrome treatment are appropriate and effective.A 2009 report by the American Academy of Pediatrics (AAP) does not find that there is conclusive scientific evidence for the use of coloured lenses (one treatment used to relieve symptoms of scotopic sensitivity syndrome) although it acknowledges anecdotal evidence in support of customized colored lenses. When discussing its scientific basis, the AAP mentions that "[t]he method used to select the lens or filter color has been highly variable, the color selection has also shown considerable variability, and the test-retest consistency has been poor" (p. 843).
The association of scotopic sensitivity syndrome and dyslexia has been challenged by many authors in the optometric and ophthalmologic communities. Furthermore, many special education departments at universities challenge the validity of coloured lenses as an effective treatment for the condition as outlined by the Macquarie University Special Education Centre.
In a joint statement, The American Academy of Ophthalmology, American Academy of Pediatrics, American Association for Pediatric Ophthalmology and Strabismus and American Association of Certified Orthoptists firmly repudiated the use of lenses, stating that there was no scientific evidence supporting their use. The expense of such treatment is unwarranted and may divert resources from evidence-based treatment.
Critics claim that the symptoms of those with Scotopic Sensitivity Syndrome are related to already known visual perceptual and neurological disorders. According to a statement released by the American Optometric Association in 2004:
There is evidence that the underlying symptoms associated with specifically Meares Irlen Syndrome, are related to identifiable vision anomalies, e.g., accommodative, binocular, and ocular motor dysfunctions, in many patients seeking help from coloured lenses. Furthermore, such conditions return to normal function when appropriately treated with lenses, prisms, or vision therapy. When patients exhibiting Meares Irlen Syndrome were treated with vision therapy, their symptoms were relieved. These patients were no longer classified as exhibiting this syndrome, and therefore did not demonstrate a need for the coloured overlays or tinted lenses.
As outlined by Hyatt, Stephenson and Carter (2009):
In 1990, the Journal of Learning Disabilities published a special issue that provided intensive coverage of Irlen lenses. In the preface to the issue, the editor in chief, Wiederholt, noted that each of the studies had serious theoretical, medical/physical, and methodological flaws, but were published along with articles critiquing the studies to provide readers with an overview of the Irlen procedures as well as guidance for conducting quality research studies. He, along with Hoyt (1990), Parker (1990), and Solan (1990), noted that these initial studies by Blaskey et al. (1990), OConnor, Sofo, Kendall, and Olsen (1990), and Robinson and Conway (1990) failed to support the treatment validity of colored overlays.

See also
References
Further reading
Hyatt, Keith J (February 2010) </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 Neurotoxic shellfish poisoning and can you explain it in depth? [/INST] Neurotoxic shellfish poisoning (NSP) is caused by the consumption of brevetoxins, which are marine toxins produced by the dinoflagellate Karenia brevis (among several others). These toxins can produce a series of gastrointestinal and neurological effects. Outbreaks of NSP commonly take place following harmful algal bloom (HAB) events, commonly referred to as "Florida red tide" (given that blooms are more commonplace along the coasts of Florida and Texas, especially during late summer and early fall). Algal blooms are a naturally-occurring phenomenon, however their frequency has been increasing in recent decades at least in-part due to human activities, climate changes, and the eutrophication (over-abundance of plant nutrients as a result of agricultural runoff, deforestation, river bed erosion, etc.) of marine waters. HABs have been occurring for all of documented history, evidenced by the Native Americans understanding of the dangers of shellfish consumption during periods of marine bioluminescence (a phenomenon observed during algal blooms). Blooms have been noted to occur as far north as North Carolina and are commonly seen alongside the widespread death of fish and sea birds. In addition to the effects on human health, the economic impact of HAB-associated shellfish toxin outbreaks can have significant economic implications as well due to not only the associated healthcare costs, but the adverse impact on the commercial shellfish industry.

Causes
Humans are typically exposed to these potent natural toxins via filter-feeding mollusks (i.e., shellfish), because shellfish accumulate biotoxins in their flesh due to the way that they feed. Human exposure seems to be most common via consumption of commonly harvested shellfish such as clams, oysters, and mussels, although it has been proposed that exposure to lower levels of brevetoxins can take place following the consumption of certain planktivorous fish. Toxins will typically be found in the flesh of shellfish for up to 2–8 weeks following a HAB event, however there have been reports of toxin retention for nearly one year post-bloom. Notably, brevetoxins are tasteless and odorless and cannot be eradicated by rinsing, cleaning, cooking, freezing, or application of acid. To date, there is no reasonable means of preventing the uptake of toxins by shellfish, nor of removing the toxins from shellfish after harvest.

Biochemistry/Toxicology
Brevetoxins are a group of greater than ten lipid-soluble cyclic polyethers that bind to a specific site on the voltage-gated sodium channel (VGSC), leading to an influx of sodium ions into the cell. This results in activation of nerves and spontaneous nerve cell membrane depolarization and firing. Due to their lipid-solubility, brevetoxins are able to pass through cell membranes and cross the blood-brain barrier. They are metabolized primarily by the liver and are excreted in the bile, although it is thought that urinary excretion plays a role in toxin clearance as well. Additionally, brevetoxins can bind a separate site on VGSCs, causing release of neurotransmitters (such as acetylcholine), resulting in tracheal smooth muscle contraction and widespread mast cell degranulation.

Presentation and Diagnosis
Diagnosis of NSP is made based on clinical presentation as well as history findings including recent consumption of shellfish. On average, symptoms begin 3-4 hours after consumption, but can begin anywhere from several minutes to 18 hours afterward. Symptoms typically include neurologic and gastrointestinal issues including:
nauseavomiting
diarrhea
numbness and tingling in the lips, mouth, face, and extremitiesThe latter has been described as “nerves being on fire” or “ants crawling and biting all over”.Other less common symptoms can include:
ataxia
loss of coordination
limb paralysis
reversal of hot and cold sensations
slurred speech
headache
pupil dilation
generalized fatiguePatients may be thought to be disoriented or intoxicated. Rarely, patients may experience respiratory distress requiring ventilatory support </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 Thyroid hormone resistance and can you explain it in depth? [/INST] Thyroid hormone resistance (also resistance to thyroid hormone (RTH), and sometimes Refetoff syndrome) describes a rare syndrome in which the thyroid hormone levels are elevated but the thyroid stimulating hormone (TSH) level is not suppressed, or not completely suppressed as would be expected. The first report of the condition appeared in 1967. Essentially this is decreased end organ responsiveness to thyroid hormones </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 Monoarthritis and can you explain it in depth? [/INST] Monoarthritis is inflammation (arthritis) of one joint at a time. It is usually caused by trauma, infection, or crystalline  arthritis.

Causes
Septic arthritis
Septic arthritis is due to a bacterial infection to the joint. It requires urgent joint washout in the operating room followed by intravenous antibiotic therapy for large joints. Small joints or children can be treated with repeated aspirations and intravenous antibiotics.

Gout
In gout, the acute inflammatory arthritis is caused by excess uric acid caused by either overproduction or under-excretion. Before the age of menopause, women have a lower incidence than males, but the rates are equal above this age. Gout can cause mono- or polyarthritis, but usually results in monoarthritis first.

Pseudogout
When monoarthritis is caused by pseudogout (calcium pyrophosphate deposition disease, CPPD), the inflammation usually lasts days to weeks, and involves the knees in half of all attacks. Like gout, attacks can occur spontaneously or with physical trauma or metabolic stress </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 Cryofibrinogenemia and can you explain it in depth? [/INST] Cryofibrinogenemia refers to a condition classified as a fibrinogen disorder in which a persons blood plasma is allowed to cool substantially (i.e. from its normal temperature of 37 °C to the near-freezing temperature of 4 °C), causing the (reversible) precipitation of a complex containing fibrinogen, fibrin, fibronectin, and, occasionally, small amounts of fibrin split products, albumin, immunoglobulins and other plasma proteins.
Return of plasma to more normal temperature resolubilizes the precipitate.
Cryofibrinogenemia may occur in individuals that have no obvious evidence of precipitate-induced tissue damage (asymptomatic cryofibrinogenemia), or in consequence of cryofibrinogen precipitation resulting in blood clots in small and medium size arteries and veins.
When occurring in association with another causual disease, cryofibrinogenemic disease is referred as secondary cryofibrinogenemia; in the absence of such an association, it is referred to as primary cryofibrinogenemia.

Cryofibrinogen precipitation
The reasons for the cold temperature-induced in vitro as well as the in vivo precipitation of the fibrinogen-containing complex is unknown. The fibrinogen involved in precipitate formation appears to have a normal structure. This separates cryofibrinogenemia from two pathological blood-clotting/bleeding diseases that can mimic cryofibrinogenemia but are due to structurally abnormal fibrinogen viz., dysfibrinogenemia and hypodysfibrinogenemia. Based on in vitro studies, three causes have been hypothesized for the precipitate formed in cryofibrinogenemia. 1) The blood and plasma of individuals with cryofibrinogenemia lack the fibrinolysis activity that normally degrades and thereby resolubilizes the precipitate. This hypothesis is based on the findings that some but not all individuals with the disorder have abnormally high levels of one or two of the agents, alpha-1 antitrypsin and alpha-2-Macroglobulin, which inhibit the naturally occurring fibrinolytic agent, plasmin. 2) The blood of individuals has an increased ability of the pro-coagulant thrombin to bind fibrinogen and thereby promote coagulation. 3) The blood of individuals, particularly those with cryofibriognemic disease associated with other severe disorders, has high levels of immunological elements such as immunoglobulins or immune complexes that interact with fibronectin to promote blood clotting. This hypothesis is base on findings that some patients with cyrofibrinogenemic disease improve when treated with immunosuppressive drugs. Further basic research into this area is required.

Asymptomatic cryofibrinogenemia
The occurrence of cryofibrinogenemia as defined by a 4 °C-induced formation of fibrinogen-based precipitation in plasma occurs in 2% to 9% of asymptomatic individuals and 8% to 13% of hospitalized patients without symptoms attributable to this precipitation. Most of these cases have relatively low levels of cold temperature-induced fibrinogen precipitate levels (<50 milligram/liter of fibrinogen) and do not have a disorder associated with the development of cryofibrinogenmia.

Associated disorders
Cryoglobulinemia may occur without evidence of an underlying associated disorders, i.e. primary cryoglobulinemia (also termed essential cryoglobulinemia) or, far more commonly, with evidence of an underlying disease, i.e. secondary cryoglobulinemia. Secondary cryofibrinogenemia can develop in individuals with infection (~12% of cases), malignant or premalignant disorders (21%), vasculitis (25%), and autoimmune diseases (42%). In these cases of the secondary disorder, cryofibrinogenemia may or may not cause tissue injury and/or other symptoms and the actual cause-effect relationship between these diseases and the development of cryofibrinogenemia is unclear. Cryofibrinogenemia can also occur in association with the intake of certain drugs.

Infection-associated cryofibrinogenemia
Acute bacterial and mycobacterium infections are sometimes associated with cryofibriongenemia. In these cases, cryofibrinogenemia is usually transient and rapidly resolves after appropriate anti-bacterial treatment. In HIV/AIDS virus, Epstein–Barr virus, cytomegalovirus, varicella zoster virus, herpes simplex virus, and hepatitis virus infections any rise in circulating cryofibrinogen is more sustained and potentially symptomatic. For example, one large study of the most thoroughly study example of viral infection-associated cryofibrinogenmia, Hepatitis C infection, found that cryofibrinogenemia occurred in 37% of cases, was associated with concurrent cryoglobulinemia in 89% of cases, and led to significantly increased vascular disruption. Antiviral therapy resulted in complete resolution of the cryofibrinogenemia in only ~50% of these cases.

Malignancy-associated cryofibrinogenemia
Lymphoproliferative disorders such as B-cell lymphomas, T-cell lymphomas, chronic lymphocytic leukemia, and various plasma cell dyscrasias (e.g. multiple myeloma, Waldenströms macroglobulinemia, and the premalignant precursors to these two diseases, MGUS, smoldering multiple myeloma, IgM MGUS, and smoldering Waldenströms macroglobulinemia as well as adenocarcinomas of the stomach, liver, lung, colon, and other solid tumor cancers have been reported to be associated with symptomatic or asymptomatic cryfibrinogenemia.

Vasculitis-associated cryofibrinogenemia
Cryofibrinogenemia is often associated with inflammatory disease of the arteries and/or veins. These vasculitis-associated diseases include ANCA-associated vasculitides, giant cell arteritis, Behcet disease, polyarteritis nodosa, and Henoch–Schonlein purpura. Cryofibrinogenemia is also often associated with the inflammatory vasculitis that accompanies mixed Cryoglobulinemia#Classification, i.e. cryoglobulinemic vasculitis, particularly but not exclusively in instances where hepatitis C virus is an underlining disease.

Autoimmune disease-associated cryofibrinogenemia
A broad range of autoimmune diseases have been reported to be associated with cryofibrinogenemia. These diseases include systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, mixed connective tissue disease, polymyositis, dermatomyositis, systemic sclerosis, antiphospholipid antibody syndrome, Hashimoto disease, Graves disease, sarcoidosis, pyoderma gangrenosum, spondyloarthropathy, Crohns disease, and ulcerative colitis.

Cryofibrinogenemic disease
Symptoms and signs
Cryofibrinogenemic disease commonly begins in adults aged 40–50 years old with symptoms of the diseases occurring in the almost always affected organ, skin. Cutaneous symptoms include one or more of the following: cold contact-induced urticarial (which may be the first sign of the disease); painful episodes of finger and/or toe arterial spasms termed Raynaud phenomena; cyanosis, a palpable purpura termed cryofibrinogenemic purpura), and a lace-like purplish discoloration termed livedo reticularis all of which occur primarily in the lower extremities but some of which may occur in the nose, ears, and buttocks; non-healing painful ulcerations and gangrene of the areas impacted by the cited symptoms. Patients also have a history of cold sensitivity (~25% of cases), arthralgia (14–58%), neuritis (7–19%), myalgia (0–14%); and overt thrombosis of arteries and veins (25–40%) which may on rare occasions involve major arteries such of those of the brain and kidney. Signs of renal involvement (proteinuria, hematuria, decreased glomerular filtration rate, and/or, rarely, renal failure) occur in 4 to 25% of cases. Compared to secondary cryofibrinogemia, primary crygofibrinogenemia has a higher incidence of cutaneous lesions, arthralgia, and cold sensitivity while having a far lower incidence of renal involvement. Patients with secondary cryofibrinogenemia also exhibit signs and symptoms specific to the infectious, malignant, premalignant vasculitis, and autoimmune disorders associated with their disease. While rare, individuals with cryofibrinogenemic disease may experience pathological bleeding due to the consumption of blood clotting factors consequential to the formation of cryofibrinogen precipitates.

Diagnosis
Suggested diagnostic criteria for cryoglobulinemic disease fall into the following obligatory and additional categories:
Obligatory criteria: 1) cold sensitivity; 2) cutaneous symptoms (i.e. urticaria, purpura, Raynaud phenomenon, ulceration/necrosis/gangrene, and/or livedo reticularis); 3) arterial and/or venous thrombotic events; fever; 4) arthralgia/myalgia; 5) neuritis in >1 site; and 6) renal disorder.
Additional criteria: 1) typical biopsy findings at site(s) of involvement and 2) angiogram evidence of occlusion in one or more small to medium-sized arteries.The diagnosis of secondary cryofibrinogenemia also requires evidence for the cited infectious, malignant, premalignant vasculitis, and autoimmune disorders while the diagnosis of primary cryofibriongenemia requires a lack of evidence for 1) the cited associated disorders, 2) other vascular occlusive diseases, and 3) cryoglobulinemia.

Treatment
Studies on the treatment of cryofibrinoginemic disease have involved relatively few patients, are limited primarily to case reports, and differ based on whether the disease is primary or secondary. In all cases of cryofibrinogenemic disease, however, patients should avoid the exposure of affected body parts to cold weather or other environmental triggers of symptoms and avoid using cigarettes or other tobacco products. In severe cases, these individuals also risk developing serious thrombotic events which lead to tissue necrosis that may result in secondary bacterial infections and require intensive antimicrobial therapy and/or amputations. Careful treatment of these developments is required.

Primary cryofibrinogenemic disease
Success in treating the primary disease has been reported using blood clot lysing agents such as anabolic steroids (e.g. danazol or stanozolol which is no longer available in the United States), streptokinase, and streptodornase; anticoagulants such as heparin and warfarin, and immunosuppressive drug regimens such as a corticosteroid (e.g. prednisone) combined with either azathioprine of chlorambucil. Very moderate cases may do well by simply avoiding cold exposure. Treatment with a corticosteroid plus low-dose aspirin followed by maintenance therapy with an anabolic steroid where necessary are recommended for moderately severe cases. Very severe cases generally require an immunosuppressive drug regimen and if extreme or life-threatening require resorting to plasmaphoresis or plasma exchange. Cryofiltration apheresis, a method to remove plasma agents by removing cold-induced precipitated material, may be an effective alternative to plasmaphoresis and plasma exchange but is still regarded as second-line therapy for cryofibirnogenemic disease treatment.During the several years following its initial diagnosis, some 27 to 47% of primary cryofibrinoginemic diseases are complicated by the development of a B-cell or T-cell lymphoma. That is, the cryofibrinoginemic disease may appear to precede by years the malignant disorder to which it is associated. Accordingly, patients require careful follow-up not only to treat their primary cryofibrinoginemic disease but also to monitor them for movement to the diagnosis of secondary cryofibrinoginemic disease caused by the development of one of these hematological malignancies.

Secondary cryofibrinogenemic disease
Treatment of secondary cryofibrinoginemic disease may use the same methods used for treating the primary disease wherever necessary but focus on treating the associated infectious, malignant, premalignant, vasculitis, or autoimmune disorder with the methods prescribed for the associated disorder. Case report studies suggest that: corticosteroids and immunosuppressive drug regimens, antimicrobial therapy, and anti-neoplastic regimens can be effective treatments for controlling the cryfibrinoginemic disease in cases associated respectively with autoimmune, infectious, and premalignant/malignant disorders.

Prognosis
While the prognosis of cryofibrinoginemic disease varies greatly depending on its severity as well as the severity of its associated disorders, satisfactory clinical outcomes are reported in 50 to 80% of patients with primary or secondary disease treated with corticosteroid and/or immunosuppressive regimens. However, relapses occur within the first 6 months after stopping or decreasing therapy in 40 to 76% of cases. Sepsis resulting from infection of necrotic tissue is the most common threat to life in primary disease whereas the associated disorder is a critical determinant of prognosis in secondary disease.

See also
Cryofibrinogenemic purpura
Cryoglobulinemia
Dysfibrinogenemia
Hypodysfibrinogenemia

References
Further reading
Amdo, TD; Welker, JA (Mar 1, 2004). "An approach to the diagnosis and treatment of cryofibrinogenemia" (PDF). The American Journal of Medicine. 116 (5): 332–7. doi:10.1016/j.amjmed.2003.09.033. PMID 14984819. Archived from the original (PDF) on February 2, 2014. Retrieved January 25, 2014.
Michaud, M; Pourrat, J (Apr 2013). "Cryofibrinogenemia". Journal of Clinical Rheumatology. 19 (3): 142–8. doi:10.1097/RHU.0b013e318289e06e. PMID 23519183.
Kalbfleisch, John M.; Bird, Robert M. (3 November 1960). "Cryofibrinogenemia". New England Journal of Medicine. 263 (18): 881–886. doi:10.1056/NEJM196011032631803. PMID 13750865.
Begin, Philippe; Leclerc, Georgette (22 August 2013). "Familial Primary Cryofibrinogenemia". New England Journal of Medicine. 369 (8): e10. doi:10.1056/NEJMicm1300987. PMID 23964955.
van Geest, AJ; van Dooren-Greebe, RJ; Andriessen, MP; Blomjous, CE; Go, IH (Jan 1999). "Familial primary cryofibrinogenemia". Journal of the European Academy of Dermatology and Venereology </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 Neonatal lupus erythematosus and can you explain it in depth? [/INST] Neonatal lupus erythematosus is an autoimmune disease in an infant born to a mother with anti-Ro/SSA and with or without anti-La/SSB antibodies. The disease most commonly presents with a rash resembling subacute cutaneous lupus erythematosus and can have systemic abnormalities such as complete heart block or hepatosplenomegaly. Neonatal lupus is usually benign and self-limited. Many of the clinical manifestations are transient, but certain heart problems can be permanent. Diagnosis is based on maternal antibodies and clinical manifestations. Treatment and management is mainly supportive and focused on preventing complete heart block if possible.

Pathogenesis
Ro/SSA and La/SSB are proteins found inside cells. Anti-Ro/SSA and anti-La/SSB are antibodies that form against these proteins. These antibodies can be seen in autoimmune diseases, the most common being Lupus and Sjögrens. Mothers can have these antibodies circulating in their blood without having any signs or symptoms of an autoimmune disease.
Babies born to mothers with these antibodies have a chance of developing neonatal lupus erythematosus. This occurs when maternal anti-Ro/SSA and anti-La/SSB antibodies enter fetal circulation and affect neonatal organs by crossing the placenta using FcRn receptors. The mechanism in which the antibodies affect organs is not yet completely understood. For the heart, it is thought that these antibodies bind to cells in the heart that go through physiologic cell death during embryogenesis. This leads to heart cell injury which causes secondary fibrosis in the conduction system, ultimately causing heart block. These antibodies can also affect calcium channels which are needed to initiate action potentials. Disruption to action potential propagation can affect the AV and SA nodes which are part of the conduction system of the heart.Fetal susceptibility and environmental factors could also play a role in pathogenesis since not all infants develop congenital heart block even when exposed to antibodies.

Clinical manifestations
Neonatal lupus can present with several signs and symptoms. The most common manifestations involve the heart and skin. Problems involving the liver, gallbladder, brain, and blood can be seen but are usually transient.

Heart
Cardiac manifestations present more commonly in utero, but can also present after birth. The most common complications are varying degrees of heart block and endocardial fibroelastosis. A large percentage of infants diagnosed with isolated congenital heart block are associated to neonatal lupus. Heart block occurs when there is dysfunction in the conduction system, preventing impulses from traveling from the atria to the ventricles. Heart block can initially present with bradycardia in the prenatal period, usually around the second trimester. Infants with lower grades of heart block can progress to higher grades, but they can also present with rapid onset of complete heart block. Endocardial fibroelastosis is considered a type of cardiomyopathy that occurs in response to heart cell injury and can be seen with or without conduction system dysfunction.Common complications

First degree heart block
Second degree heart block
Third degree heart block (Complete heart block)
Endocardial fibroelastosisOther complications seen with neonatal lupus

Patent ductus arteriosus
Patent foramen ovale
Pulmonic stenosis
Pulmonary valvular dysplasia
Fusion of chordae tendineae of the tricuspid valve
Ostium secundum type atrial septal defects

Skin
A rash can be seen upon delivery. It is commonly found on the head and face, but can also be found on other parts of the body. It is most commonly seen around the eyes. The rash can be described as raised, red, and ring-shaped. The rash is not always visible at birth and can become more prominent after UV light exposure. Antibodies coming from the mother have a certain life span. Because of this, the rash usually lasts 6–8 months, resolving after the maternal antibodies are no longer in circulation. Telangiectasia has also been seen and can occur with or without the ring-shaped rash.
Red, ring-shaped rash of face and head
Telangiectasia

Liver and gallbladder
Severity in which the liver is affected can range from mildly elevated liver enzymes to liver failure.
Elevated transaminases
Hyperbilirubinemia
Cholestasis
Hepatitis

Blood
The conditions listed below have been reported with no issues of bleeding or sepsis.
Anemia
Neutropenia
Thrombocytopenia
Aplastic anemia

Brain
Although the conditions below have been reported, it is still uncertain that these manifestations are related to anti-Ro/SSA and anti-La/SSB antibodies. Majority of the neurologic conditions were found incidentally with no neurological signs or symptoms present and did not lead to physical disability or need for surgery.
Hydrocephalus
Macrocephaly
Vasculopathy
Hypocalcemic seizures
Spastic diplegia

Diagnosis
An infant is diagnosed with neonatal lupus if maternal antibodies, anti-Ro/SSA, anti-La/SSB, or less commonly anti-ribonucleoprotein, are present and if any of the clinical manifestations are present without any other explanation.

Screening
Screening includes testing for maternal antibodies and evaluating for heart block in utero. Universal screening is not recommended. Screening is usually performed when there is a higher likelihood for neonatal lupus such as individuals who are more likely to have antibodies due to autoimmune diseases or individuals who have had prior pregnancies complicated with neonatal lupus. If a fetus develops heart block, screening for maternal antibodies can be considered. Monitoring for heart block can be done using a fetal echocardiogram.

Management
Infants with neonatal lupus are managed with supportive care. This means treating or monitoring the symptoms that can occur from this disease. For example, avoiding sunlight so that the infants rash wont worsen. Many of the manifestations are transient, but once complete heart block occurs, it is irreversible. Heart block can be managed in utero if diagnosed during pregnancy. Infants born to mothers with anti-Ro/SSA and anti-La/SSB should have an ECG performed to check for heart abnormalities if none were seen while in the uterus.

In utero
Fetal heart block treatment varies based on the degree </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 Palmoplantar hyperhidrosis 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 Enterocutaneous fistula 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 Granuloma multiforme and can you explain it in depth? [/INST]  </s>