<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Chronic atrophic rhinitis and explain in detail? [/INST] Chronic atrophic rhinitis, or simply atrophic rhinitis, is a chronic inflammation of the nose characterised by atrophy of nasal mucosa, including the glands, turbinate bones and the nerve elements supplying the nose. Chronic atrophic rhinitis may be primary and secondary. Special forms of chronic atrophic rhinitis are rhinitis sicca anterior and ozaena. It can also be described as the empty nose syndrome.

Signs and symptoms
It is most commonly seen in females.
It is reported among patients from lower socioeconomic groups.
The nasal cavities become roomy and are filled with foul smelling crusts which are black or dark green and dry, making expiration painful and difficult.
Microorganisms are known to multiply and produce a foul smell from the nose, though the patients may not be aware of this, because the nerve endings (responsible for the perception of smell) have become atrophied. This is called merciful anosmia.
Patients usually complain of nasal obstruction despite the roomy nasal cavity, which can be caused either by the obstruction produced by the discharge in the nose, or as a result of sensory loss due to atrophy of nerves in the nose, so the patient is unaware of the air flow </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Motor neuron disease and explain in detail? [/INST] Motor neuron diseases or motor neurone diseases (MNDs) are a group of rare neurodegenerative disorders that selectively affect motor neurons, the cells which control voluntary muscles of the body. They include amyotrophic lateral sclerosis (ALS), progressive bulbar palsy (PBP), pseudobulbar palsy, progressive muscular atrophy (PMA), primary lateral sclerosis (PLS), spinal muscular atrophy (SMA) and monomelic amyotrophy (MMA), as well as some rarer variants resembling ALS.
Motor neuron diseases affect both children and adults. While each motor neuron disease affects patients differently, they all cause movement-related symptoms, mainly muscle weakness. Most of these diseases seem to occur randomly without known causes, but some forms are inherited. Studies into these inherited forms have led to discoveries of various genes (e.g. SOD1) that are thought to be important in understanding how the disease occurs.Symptoms of motor neuron diseases can be first seen at birth or can come on slowly later in life. Most of these diseases worsen over time; while some, such as ALS, shorten ones life expectancy, others do not. Currently, there are no approved treatments for the majority of motor neuron disorders, and care is mostly symptomatic.

Signs and symptoms
Signs and symptoms depend on the specific disease, but motor neuron diseases typically manifest as a group of movement-related symptoms. They come on slowly, and worsen over the course of more than three months. Various patterns of muscle weakness are seen, and muscle cramps and spasms may occur. One can have difficulty breathing with climbing stairs (exertion), difficulty breathing when lying down (orthopnea), or even respiratory failure if breathing muscles become involved. Bulbar symptoms, including difficulty speaking (dysarthria), difficulty swallowing (dysphagia), and excessive saliva production (sialorrhea), can also occur. Sensation, or the ability to feel, is typically not affected. Emotional disturbance (e.g. pseudobulbar affect) and cognitive and behavioural changes (e.g. problems in word fluency, decision-making, and memory) are also seen. There can be lower motor neuron findings (e.g. muscle wasting, muscle twitching), upper motor neuron findings (e.g. brisk reflexes, Babinski reflex, Hoffmans reflex, increased muscle tone), or both.Motor neuron diseases are seen both in children and adults. Those that affect children tend to be inherited or familial, and their symptoms are either present at birth or appear before learning to walk. Those that affect adults tend to appear after age 40. The clinical course depends on the specific disease, but most progress or worsen over the course of months. Some are fatal (e.g. ALS), while others are not (e.g. PLS).

Patterns of weakness
Various patterns of muscle weakness occur in different motor neuron diseases. Weakness can be symmetric or asymmetric, and it can occur in body parts that are distal, proximal, or both. According to Statland et al., there are three main weakness patterns that are seen in motor neuron diseases, which are:
Asymmetric distal weakness without sensory loss (e.g. ALS, PLS, PMA, MMA)
Symmetric weakness without sensory loss (e.g. PMA, PLS)
Symmetric focal midline proximal weakness (neck, trunk, bulbar involvement; e.g. ALS, PBP, PLS)

Lower and upper motor neuron findings
Motor neuron diseases are on a spectrum in terms of upper and lower motor neuron involvement. Some have just lower or upper motor neuron findings, while others have a mix of both. Lower motor neuron (LMN) findings include muscle atrophy and fasciculations, and upper motor neuron (UMN) findings include hyperreflexia, spasticity, muscle spasm, and abnormal reflexes.Pure upper motor neuron diseases, or those with just UMN findings, include PLS.Pure lower motor neuron diseases, or those with just LMN findings, include PMA.Motor neuron diseases with both UMN and LMN findings include both familial and sporadic ALS.

Causes
Most cases are sporadic and their causes are usually not known. It is thought that environmental, toxic, viral, or genetic factors may be involved.

DNA damage
TARDBP (TAR DNA-binding protein 43), also referred to as TDP-43, is a critical component of the non-homologous end joining (NHEJ) enzymatic pathway that repairs DNA double-strand breaks in pluripotent stem cell-derived motor neurons. TDP-43 is rapidly recruited to double-strand breaks where it acts as a scaffold for the recruitment of the XRCC4-DNA ligase protein complex that then acts to repair double-strand breaks. About 95% of ALS patients have abnormalities in the nucleus-cytoplasmic localization in spinal motor neurons of TDP43. In TDP-43 depleted human neural stem cell-derived motor neurons, as well as in sporadic ALS patients’ spinal cord specimens there is significant double-strand break accumulation and reduced levels of NHEJ.

Associated risk factors
In adults, men are more commonly affected than women.

Diagnosis
Differential diagnosis can be challenging due to the number of overlapping symptoms, shared between several motor neuron diseases. Frequently, the diagnosis is based on clinical findings (i.e. LMN vs. UMN signs and symptoms, patterns of weakness), family history of MND, and a variation of tests, many of which are used to rule out disease mimics, which can manifest with identical symptoms.

Classification
Motor neuron disease describes a collection of clinical disorders, characterized by progressive muscle weakness and the degeneration of the motor neuron on electrophysiological testing. The term "motor neuron disease" has varying meanings in different countries </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Psorosperm and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Tennis elbow and explain in detail? [/INST] Tennis elbow, also known as lateral epicondylitis or enthesopathy of the extensor carpi radialis origin, is a condition in which the outer part of the elbow becomes painful and tender. The pain may also extend into the back of the forearm. Onset of symptoms is generally gradual although they can seem sudden and be misinterpreted as an injury. Golfers elbow is a similar condition that affects the inside of the elbow.Enthesopathies are idiopathic, meaning science has not yet determined the cause. Enthesopathies are most common in middle age (ages 35 to 60).It is often stated that the condition is caused by excessive use of the muscles of the back of the forearm, but this is not supported by experimental evidence and is a common misinterpretation or unhelpful thought about symptoms. It may be associated with work or sports, classically racquet sports, but most people with the condition are not exposed to these activities. The diagnosis is based on the symptoms and examination. Medical imaging is not particularly useful. Signs consistent with the diagnosis include pain when a subject tries to bend back the wrist when the wrist is against resistance.Treatment involves decreasing activities that bring on the symptoms together with physical therapy or other treatment gradually increasing loads. Pain medications such as NSAIDS or acetaminophen (paracetamol) may be used. A brace over the upper forearm may also be helpful. The role of corticosteroid injections is debated.

Signs and symptoms
Pain on the outer part of the elbow (lateral epicondyle)
Point tenderness over the lateral epicondyle—a prominent part of the bone on the outside of the elbow
Pain with resisted wrist extension or passive wrist flexionSymptoms associated with tennis elbow include, but are not limited to, pain from the outside of the elbow to the forearm and wrist and pain during extension of wrist.

Terminology
The term "tennis elbow" is widely used (although informal), but the condition should be understood as not limited to tennis players.  Historically, the medical term "lateral epicondylitis" was most commonly used for the condition, but "itis" implies inflammation and the condition is not inflammatory.Since histological findings reveal noninflammatory tissue, the terms “lateral elbow tendinopathy" and "tendinosis” are suggested. In 2019, a group of international experts suggested that "lateral elbow tendinopathy" was the most appropriate terminology. But a disease of an attachment point (or enthesia) is most accurately referred to as an "enthesopathy."

Causes
Enthesopathy of the extensor carpi radialis brevis origin is idiopathic, meaning that it has no known cause.Tennis players generally believe tennis elbow is caused by the repetitive nature of hitting thousands of tennis balls, which leads to tiny tears in the forearm tendon attachment at the elbow. Traditionally, people have speculated that tennis elbow is a type of repetitive strain injury resulting from tendon overuse and failed healing of the tendon, but there is no evidence of injury or repair on histopathology, and misinterpretation of painful activities as a source of damage is common.

Early experiments suggested that tennis elbow was primarily caused by overexertion. However, studies show that trauma such as direct blows to the epicondyle, a sudden forceful pull, or forceful extension cause more than half of these injuries. Repeatedly mis-hitting a tennis ball in the early stages of learning the sport causes shock to the elbow joint and may contribute to contracting the condition.

Pathophysiology
Histological findings include granulation tissue, micro-rupture, degenerative changes, and there is no traditional inflammation. Therefore, the disorder is more appropriately referred to as tendinosis or tendinopathy—more accurately an enthesopathy—rather than tendinitis. There is no evidence of inflammation or repair.The extensor digiti minimi also has a small origin site medial to the elbow that this condition can affect. The muscle involves the extension of the little finger and some extension of the wrist allowing for adaption to "snap" or flick the wrist—usually associated with a racquet swing. Most often, the extensor muscles become painful due to tendon breakdown from over-extension.  Improper form or movement allows for power in a swing to rotate through and around the wrist—creating a moment on that joint instead of the elbow joint or rotator cuff. This moment causes pressure to build impact forces to act on the tendon causing irritation and inflammation.Other speculative risk factors for lateral epicondylitis include taking up tennis later in life, unaccustomed strenuous activity, decreased mental chronometry and speed and repetitive eccentric contraction of muscle (controlled lengthening of a muscle group).

Diagnosis
Physical examination
Diagnosis is based on symptoms and clinical signs that are discrete and characteristic. For example, extension of the elbow and flexion of the wrist cause outer elbow pain. There is point tenderness at the origin of the extensor carpi radialis brevis muscle from the lateral epicondyle (extensor carpi radialis brevis origin), 1 cm distal and slightly anterior to the lateral epicondyle.  There is also pain with resisted wrist extension (Cozens test).

Medical imaging
Medical imaging is not necessary or helpful.X-rays can confirm and distinguish possibilities of existing causes of pain that are unrelated to tennis elbow, such as fracture or arthritis. Rarely, calcification can be found where the extensor muscles attach to the lateral epicondyle. Medical ultrasonography and magnetic resonance imaging (MRI) are other valuable tools for diagnosis but are frequently avoided due to the high cost.Longitudinal sonogram of the lateral elbow displays thickening and heterogeneity of the common extensor tendon that is consistent with tendinosis, as the ultrasound reveals calcifications, intrasubstance tears, and marked irregularity of the lateral epicondyle. Although the term “epicondylitis” is frequently used to describe this disorder, most histopathologic findings of studies have displayed no evidence of an acute, or a chronic inflammatory process. Histologic studies have demonstrated that this condition is the result of tendon degeneration, which replaces normal tissue with a disorganized arrangement of collagen.

Treatment
In some cases, severity of tennis elbow symptoms mend without any treatment, within six to 24 months. Tennis elbow left untreated can lead to chronic pain that degrades quality of daily living.

Physical therapy
There are several recommendations regarding prevention, treatment, and avoidance of recurrence that are largely speculative including stretches and progressive strengthening exercises to prevent re-irritation of the tendon and other exercise measures.One way to help treat minor cases of tennis elbow is simply to relax the affected arm. The rest lets stress and tightness within the forearm slowly relax and eventually have the arm in working condition—in a day or two, depending on the case.Other approaches that are not experimentally tested include eccentric exercise using a rubber bar. The exercise involves grasping a rubber bar, twisting it, then slowly untwisting it. Although it can be considered an evidence-based practice, long-term results have not yet been determined.There are differences in opinions on whether it is okay if pain occurs during these exercises. Some suggest pain of less than 5/10 is okay.Moderate evidence exists demonstrating that joint manipulation directed at the elbow and wrist and spinal manipulation directed at the cervical and thoracic spinal regions results in clinical changes to pain and function. There is also moderate evidence for short-term and mid-term effectiveness of cervical and thoracic spine manipulation as an add-on therapy to concentric and eccentric stretching plus mobilisation of wrist and forearm. Although not yet conclusive, the short-term analgesic effect of manipulation techniques may allow more vigorous stretching and strengthening exercises, resulting in a better and faster recovery process of the affected tendon in lateral epicondylitis.Low level laser therapy, administered at specific doses and wavelengths directly to the lateral elbow tendon insertions, may result in short-term pain relief and less disability.Extracorporeal shockwave therapy, while safe, is of unclear benefit.

Orthotic devices
Orthosis is a device externally used on the limb to improve the function or reduce the pain. Orthotics may be useful in tennis elbow, however long-term effects are unknown. There are two main types of orthoses prescribed for this problem: counterforce elbow orthoses and wrist extension orthoses.  Counterforce orthosis has a circumferential structure surrounding the arm. This orthosis usually has a strap which applies a binding force over the origin of the wrist extensors. The applied force by orthosis reduces the elongation within the musculotendinous fibers. Wrist extensor orthosis maintains the wrist in the slight extension. This position reduces the overloading strain at the lesion area.

Medication
Although anti-inflammatories are a commonly prescribed treatment for tennis elbow, the evidence for their effect is usually anecdotal with only limited studies showing a benefit. A systematic review found that topical non-steroidal anti-inflammatory drugs (NSAIDs) may improve pain in the short term (up to 4 weeks) but was unable to draw firm conclusions due to methodological issues. Evidence for oral NSAIDs is mixed.Evidence is poor for long term improvement from injections of any type, whether corticosteroids, botulinum toxin, prolotherapy or other substances. Corticosteroid injection may be effective in the short term however are of little benefit after a year, compared to a wait-and-see approach. A randomized control trial comparing the effect of corticosteroid injection, physiotherapy, or a combination of corticosteroid injection and physiotherapy found that patients treated with corticosteroid injection versus placebo had lower complete recovery or improvement at 1 year (Relative risk 0.86). Patients that received corticosteroid injection also had a higher recurrence rate at 1 year versus placebo (54% versus 12%, relative risk 0.23).
Complications from repeated steroid injections include skin problems such as hypopigmentation and fat atrophy leading to indentation of the skin around the injection site. Steroid injections against appear to be more effective than shock wave therapy. Botulinum toxin type A to paralyze the forearm extensor muscles in those with chronic tennis elbow that has not improved with conservative measures may be viable.

Surgery
Surgery is an option. Surgical methods include:
Lengthening, release, debridement, or repair of the origin of the extrinsic extensor muscles of the hand at the lateral epicondyleSurgical techniques for lateral epicondylitis can be done by open surgery, percutaneous surgery or arthroscopic surgery, with no high-quality evidence that any particular type is better or worse than another. Side effects include infection, damage to nerves and inability to straighten the arm.  A review of the evidence related to surgery found that published studies were of low quality and did not show that surgery was any more effective than other treatments.  A subsequent research trial showed that surgery was no more effective than sham surgery, where patients only received a skin incision, although the trial was limited by a small number of patients.

Prognosis
Response to initial therapy is common, but so is relapse (25% to 50%) and/or prolonged, moderate discomfort (40%).Depending upon severity and quantity of multiple tendon injuries that have built up, the extensor carpi radialis brevis may not be fully healed by conservative treatment.  Nirschl defines four stages of lateral epicondylitis, showing the introduction of permanent damage beginning at Stage 2.

Inflammatory changes that are reversible
Nonreversible pathologic changes to origin of the extensor carpi radialis brevis muscle
Rupture of ECRB muscle origin
Secondary changes such as fibrosis or calcification.

Epidemiology
In tennis players, about 39.7% have reported current or previous problems with their elbow. Less than one quarter (24%) of these athletes under the age of 50 reported that the tennis elbow symptoms were "severe" and "disabling," while 42% over the age of 50 did. More women (36%) than men (24%) considered their symptoms severe and disabling.  Tennis elbow is more prevalent in individuals over 40, where there is about a four-fold increase among men and two-fold increase among women.  Tennis elbow equally affects both sexes and, although men have a marginally higher overall prevalence rate as compared to women, this is not consistent within each age group, nor is it a statistically significant difference.Playing time is a significant factor in tennis elbow occurrence, with increased incidence with increased playing time being greater for respondents under 40. Individuals over 40 who played over two hours doubled their chance of injury. Those under 40 increased it 3.5 fold compared to those who played less than two hours per day.

History
German physician F. Runge is usually credited for the first description of the condition, calling it "writers cramp" (Schreibekrampf) in 1873.  Later, it was called "washer womens elbow" </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Sleep-related hypermotor epilepsy and explain in detail? [/INST] Sleep-related hypermotor epilepsy (SHE), previously known as nocturnal frontal lobe epilepsy, is a form of focal epilepsy characterized by seizures which arise during sleep. The seizures are most typically characterized by complex motor behaviors. It is a relatively uncommon form of epilepsy that constitutes approximately 9-13% of cases. This disorder is associated with cognitive impairment in at least half of patients as well as excessive daytime sleepiness due to poor sleep quality. This disorder is sometimes misdiagnosed as a non-epileptic sleep disorder. There are many potential causes of SHE including genetic, acquired injuries and structural abnormalities.

History
In 1981, Lugaresi and Cirignotta described a group of 5 patients with paroxysmal attacks of violent movements of the extremities and dystonic-tonic posturing. It was initially uncertain whether these events constituted seizures or something else. However, the patients had a good clinical response to the anti-seizure medication carbamazepine. Ultimately, the epileptic nature of this condition was confirmed with EEG and suggested that they were coming from the frontal lobe. The term “nocturnal frontal lobe epilepsy” was suggested as a name for this condition. Later in 2014, a consensus conference recommended that the name be changed to sleep-related hypermotor epilepsy. There were three main justifications for this change: (1) not all seizures arise from the frontal lobe; (2) seizures do not necessarily occur during the night but rather from sleep; (3) hypermotor describes the most common visible clinical manifestation of the seizures.

Symptoms
Seizures in SHE are brief and usually have an abrupt onset and offset. The observable clinical manifestations may consist of rapid, hyperkinetic movements as well as tonic/dystonic posturing of the limbs. Other potential manifestations include brief arousals from sleep or wandering ambulatory behavior. Non-motor manifestations (such as sensory or emotional phenomenon) are common and retained awareness during seizures may occur. Seizures usually occur during non-REM sleep. The frequency of seizures can be very high and as many as dozens may occur every night which results in poor sleep quality. In addition, many patients with SHE suffer from cognitive impairment and have behavioral/psychological problems. There are many risks associated with nocturnal seizures including concussion, suffocation and sudden unexpected death (SUDEP).

Cause
Approximately 86% of SHE cases are sporadic, 14% of patients have a family history of epilepsy and 5% are inherited in an autosomal dominant manner (i.e. autosomal dominant sleep-related hypermotor epilepsy). Both genetic, structural and multifactorial etiologies can occur. In structural cases, the most common pathology is focal cortical dysplasia.The first described mutation in SHE was found in genes coding for the neuronal nicotinic acetylcholine receptor. Since then multiple other genes have been identified including KCNT1, DEPDC5, NPRL2, NPRL3, PRIMA1, CABP4, CRH and others. In some cases, structural and genetic etiologies can coexist such as with mutations in DEPDC5.

Diagnosis
The condition may be difficult to diagnose and misdiagnosis is common.  The subject may be unaware they have a seizure disorder. To others, the involuntary movements made during sleep may appear no different from those typical of normal sleep. People who have nocturnal seizures may notice unusual conditions upon awakening in the morning, such as a headache, having wet the bed, having bitten the tongue, a bone or joint injury, muscle strains or weakness, fatigue, or lightheadedness </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Factitious dermatitis and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Favus and explain in detail? [/INST] Favus (Latin for "honeycomb") or tinea favosa is the severe form of tinea capitis, a skin infectious disease caused by the dermatophyte fungus Trichophyton schoenleinii. Typically the species affects the scalp, but occasionally occurs as onychomycosis, tinea barbae, or tinea corporis.
The word favid is more used than French word favus, which is close to the Latin etymology.

Presentation
The uncomplicated appearance is that of a number of yellowish, circular, cup-shaped crusts (scutulum or shield) grouped in patches like a honeycomb, each crust about the size of a split pea, with a bundle of hair projecting in the center. These increase in size and become crusted over, so that the characteristic lesion can only be seen round the edge of the scab. A mousy odour is often present. Growth continues to take place for several months, when scab and scutulum go away, leaving a shining bare patch destitute of hair. The disease is essentially chronic, lasting from ten to twenty years. It is caused by the growth of a fungus, and pathologically is the reaction of the tissues to the growth.The fungus was named after a microscopic structure termed "achorion" (a term not used in modern science), seen in scrapings of infected skin, which consists of slender, mycelial threads matted together, bearing oval, nucleated fungal substrate-arthroconidia either free or jointed. This structure is currently called "scutula." The fungus itself is now called Trichophyton schoenleinii.
During initial infection, the fungal spores would appear to enter through the unbroken cutaneous surface, and to germinate mostly in and around the hair follicle and sometimes in the shaft of the hair.

Species
Favus is the first human fungal disease in which a fungus was definitely identified by J. L. Schönlein in 1839. The discovery was published in a brief note of twenty lines in Müllers Archiv for that year (p. 82). In 1841, the Hungary-born French physician David Gruby independently described the fungus associated favus. The fungus was subsequently named by Robert Remak as Achorion schoenleinii in honor of its discoverer.
In 1892, two additional "species" of the fungus were described by Paul Gerson Unna, the Favus griseus, giving rise to greyish-yellow scutula, and the Favus sulphureus celerior, causing sulfur-yellow scutula of a rapid growth. This was in the days before scientists learned to rigorously distinguish microorganism identities from disease identities, and these antique, ambiguous disease-based names no longer have status either in mycology or in dermatology today.
Similar looking infections, sometimes diagnosed as favid but more often as atypical inflammatory tinea, may be caused by more common dermatophyte infections, in particular Microsporum gypseum, the most common soil-borne dermatophyte, and Trichophyton quinckeanum. The latter was previously called Trichophyton mentagrophytes var. quinckeanum, the agent of mouse favus infection.

Treatment
Up until the advent of modern therapies, favus was widespread worldwide; prior to Schönleins recognition of it as a fungal disease, it was frequently confused with Hansens disease, better known as leprosy, and affected Europeans were sometimes committed to leprosaria. Today, due to this species high susceptibility to the antifungal drug griseofulvin, it has been eliminated from most parts of the world except rural central Asia and scattered rural areas of Africa. It is mainly a disease connected to demographic poverty and isolation, but is so readily treatable that it is among the diseases most likely to be eliminated by modern medicine.

References

This article incorporates text from a publication now in the public domain: Chisholm, Hugh, ed. (1911). "Favus". Encyclopædia Britannica. Vol. 10 (11th ed.). Cambridge University Press. p. 215.
Kane, J., R.C. Summerbell, L. Sigler, S. Krajden, G. Land </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Multiple carboxylase deficiency and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Macular corneal dystrophy and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Septal panniculitis and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Gauchers disease and explain in detail? [/INST] Gauchers disease or Gaucher disease () (GD) is a genetic disorder in which glucocerebroside (a sphingolipid, also known as glucosylceramide) accumulates in cells and certain organs. The disorder is characterized by bruising, fatigue, anemia, low blood platelet count and enlargement of the liver and spleen, and is caused by a hereditary deficiency of the enzyme glucocerebrosidase (also known as glucosylceramidase), which acts on glucocerebroside. When the enzyme is defective, glucocerebroside accumulates, particularly in white blood cells and especially in macrophages (mononuclear leukocytes). Glucocerebroside can collect in the spleen, liver, kidneys, lungs, brain, and bone marrow.
Manifestations may include enlarged spleen and liver, liver malfunction, skeletal disorders or bone lesions that may be painful, severe neurological complications, swelling of lymph nodes and (occasionally) adjacent joints, distended abdomen, a brownish tint to the skin, anemia, low blood platelet count, and yellow fatty deposits on the white of the eye (sclera). Persons seriously affected may also be more susceptible to infection. Some forms of Gauchers disease may be treated with enzyme replacement therapy.
The disease is caused by a recessive mutation in the GBA gene located on chromosome 1 and affects both males and females. About one in 100 people in the United States are carriers of the most common type of Gaucher disease. The carrier rate among Ashkenazi Jews is 8.9% while the birth incidence is one in 450.Gauchers  disease is the most common of the lysosomal storage diseases. It is a form of sphingolipidosis (a subgroup of lysosomal storage diseases), as it involves dysfunctional metabolism of sphingolipids.The disease is named after the French physician Philippe Gaucher, who originally described it in 1882.

Signs and symptoms
Painless hepatomegaly and splenomegaly: the size of the spleen can be 1500–3000 g, as opposed to the normal size of 50–200 g. Splenomegaly may decrease the affected individuals capacity for eating by exerting pressure on the stomach. While painless, enlargement of spleen increases the risk of splenic rupture.
Hypersplenism and pancytopenia, the rapid and premature destruction of blood cells, leads to anemia, neutropenia, leukopenia, and thrombocytopenia (with an increased risk of infection and bleeding).
Cirrhosis of the liver is rare.
Severe pain associated with joints and bones occurs, frequently presenting in hips and knees.
Neurological symptoms occur only in some types of Gauchers (see below):
Type I: impaired olfaction and cognition
Type II: serious convulsions, hypertonia, intellectual disability, and apnea
Type III: muscle twitches known as myoclonus, convulsions, dementia, and ocular muscle apraxia
Parkinsons disease is recognized as being more common in Gauchers disease patients and their heterozygous carrier relatives.
Osteoporosis: 75% of patients develop visible bony abnormalities due to the accumulated glucosylceramide. A deformity of the distal femur in the shape of an Erlenmeyer flask  is commonly described.
Yellowish-brown skin pigmentation

Genetics
The three types of Gauchers disease are autosomal recessive. Both parents must be carriers for a child to be affected. If both parents are carriers, the chance of the disease is one in four, or 25%, with each pregnancy for an affected child. Genetic counseling and genetic testing are recommended for families who may be carriers of mutations.Each type has been linked to particular mutations. In all, about 80 known GBA gene mutations are grouped into three main types:
Type I (N370S homozygote), the most common, also called the "non-neuropathic" type occurs mainly in Ashkenazi Jews, at 100 times the occurrence in the general populace. The median age at diagnosis is 28 years of age, and life expectancy is mildly decreased.
Type II (one or two alleles L444P) is characterized by neurological problems in small children. The enzyme is hardly released into the lysosomes. Prognosis is poor: most die before the age of three.
Type III (also one or two copies of L444P, possibly delayed by protective polymorphisms) occurs in Swedish patients from the Norrbotten region. This group develops the disease somewhat later, but most die before their 30th birthday.The Gaucher-causing mutations may have entered the Ashkenazi Jewish gene pool in the early Middle Ages (48–55 generations ago).

Pathophysiology
The disease is caused by a defect in the housekeeping gene for lysosomal glucocerebrosidase (also known as beta-glucosidase, EC 3.2.1.45, PDB: 1OGS) on the first chromosome (1q22). The enzyme is a 55.6-kilodalton, 497-amino acid-long protein that catalyses the breakdown of glucocerebroside, a cell membrane constituent of red and white blood cells. In Gaucher disease, the enzyme is unable to function correctly and glucocerebroside accumulates. The macrophages that clear these cells are unable to eliminate the waste product, which accumulates in fibrils, and turn into Gaucher cells, which appear on light microscopy to resemble crumpled-up paper.The exact mechanism of neurotoxicity is not understood, but it is thought to involve a reaction to glucosylsphingosine.Different mutations in the GBA (beta-glucosidase) gene determine the remaining activity of the enzyme. In type I, there is some residual activity of the enzyme, accounting for the lack of neuropathology in this type. Although there is some correlation between genotype and phenotype, neither the amount of stored lipids, nor the residual enzyme activity correlates well with disease symptoms. This circumstance has called for alternative explanations accounting for disease symptoms including

jamming of the endo/lysosomal system
ER stress
altered lipid composition of membranes throughout the cell, including the plasma membrane, and consequent changes in the dynamic and signaling properties of the cell membrane
inflammation caused by cytokine secretion as a result of sphingolipid accumulation, and neurodegeneration caused by the accumulation of glucosylsphingosine, a neurotoxinHeterozygotes for particular acid beta-glucosidase mutations carry about a five-fold risk of developing Parkinsons disease, making this the most common known genetic risk factor for Parkinsons.Cancer risk may be increased, particularly myeloma. This is thought to be due to accumulation of glucosylceramide and complex glycosphingolipids.The role of inflammatory processes in Gaucher disease is poorly elucidated. However, sphingolipids are known to participate in inflammation and apoptosis, and markers of macrophage activation are elevated in people with Gaucher disease. These markers include angiotensin-converting enzyme, cathepsin S, chitotriosidase, and CCL18 in the blood plasma; and tumor necrosis factor alpha in splenic Gaucher cells (engorged macrophages).

Diagnosis
Gaucher disease is suggested based on the overall clinical picture.  Initial laboratory testing may include enzyme testing. As a result, lower than 15% of mean normal activity is considered to be diagnostic. Decreased enzyme levels will often be confirmed by genetic testing.  Numerous different mutations occur; sequencing of the beta-glucosidase gene is sometimes necessary to confirm the diagnosis. Prenatal diagnosis is available and is useful when a known genetic risk factor is present.A diagnosis can also be implied by biochemical abnormalities such as high alkaline phosphatase, angiotensin-converting enzyme, and immunoglobulin levels, or by cell analysis showing "crinkled paper" cytoplasm and glycolipid-laden macrophages.Some lysosomal enzymes are elevated, including tartrate-resistant acid phosphatase, hexosaminidase, and a human chitinase, chitotriosidase. This latter enzyme has proved to be very useful for monitoring Gauchers disease activity in response to treatment, and may reflect the severity of the disease

Classification
Gauchers disease (GD) has three common clinical subtypes. These subtypes have come under some criticism for not taking account of the full spectrum of observable symptoms (the phenotypes). Also, compound heterozygous variations occur which considerably increase the complexity of predicting disease course.
GD type I (non-neuropathic) is the most common and least severe form of the disease. Symptoms may begin early in life or in adulthood and mainly affect the liver, spleen, and bone. Enlarged liver and grossly enlarged spleen (together hepatosplenomegaly) are common; the spleen can rupture and cause additional complications. Skeletal weakness and bone disease may be extensive. Spleen enlargement and bone marrow replacement cause anemia, thrombocytopenia, and leukopenia. The brain and nervous system are not affected pathologically, but lung and, rarely, kidney impairment may occur. Patients in this group usually bruise easily (due to low levels of platelets) and experience fatigue due to low numbers of red blood cells. Depending on disease onset and severity, type I patients may live well into adulthood. The range and severity of symptoms can vary dramatically between patients.GD type II (acute infantile neuropathic) typically begins within 6 months of birth and has an incidence rate around one 1 in 100,000 live births. Symptoms include an enlarged liver and spleen, extensive and progressive brain damage, eye movement disorders, spasticity, seizures, limb rigidity, and a poor ability to suck and swallow. Affected children usually die by age two.
GD type III (chronic neuropathic) can begin at any time in childhood or even in adulthood, and occurs in about one in 100,000 live births. It is characterized by slowly progressive, but milder neurologic symptoms compared to the acute or type II version. Major symptoms include an enlarged spleen and/or liver, seizures, poor coordination, skeletal irregularities, eye movement disorders, blood disorders including anemia, and respiratory problems. Patients often live into their early teen years and adulthood.

Treatment
For those with type-I and most type-III, enzyme replacement treatment with intravenous recombinant glucocerebrosidase can decrease liver and spleen size, reduce skeletal abnormalities, and reverse other manifestations. This treatment costs about US$200,000 annually for a single person and should be continued for life. The rarity of the disease means dose-finding studies have been difficult to conduct, so controversy remains over the optimal dose and dosing frequency. Due to the low incidence, this has become an orphan drug in many countries, meaning a government recognizes and accommodates the financial constraints that limit research into drugs that address a small population.The first drug for Gauchers was alglucerase (Ceredase), which was a version of glucocerebrosidase that was harvested from human placental tissue and then modified with enzymes </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Chorioangioma and explain in detail? [/INST] Chorioangioma, or chorangioma, is a benign tumor of placenta. It is a hamartoma-like growth in the placenta consisting of blood vessels, and is seen in approximately 0.5 to 1% pregnancies.  It is mostly diagnosed ultrasonically in the second trimester of pregnancy. Large chorioangiomas are known to cause complications in pregnancy, while the smaller ones are asymptomatic.

Presentation
Most chorangiomas are not clinically significant, i.e. they do not have an adverse effect on placental function.

Complications
Large (greater than 4 or 5 cm.) or multiple chorioangiomas may lead to complication. The complications are polyhydramnios, preterm labour, hemolytic anemia, fetal cardiomegaly, fetal thrombocytopenia, intrauterine growth retardation, preeclampsia, abruption of placenta and congenital anomalies.

Pathogenesis
The origin of chorioangioma is from primitive chorionic mesenchyme. It develops when the blood vessels and stroma undergo rapid proliferation independent of the surrounding tissue. Based on histological features, chorioangioma is classified by Marchetti into three types:
Cellular type : This type is immature and contains mostly cellular elements packed compactly.
Angiomatous (vascular) type : This is the most common type of choriocarcinoma. It is distinguished by the presence of numerous small blood vessels.
Degenerative type : This is the mature type with degenerative changes.Each type is believed to represent a phase of tumor development. Chorioangioma has no malignant potential.

Diagnosis
Most chorioangiomas are asymptomatic. They are generally picked up in second trimester scan. Chorioangioma is seen as a hypo- or hyperechoic circumscribed mass that is distinct from the placenta at gray-scale US examination. Large lesions may contain fibrous septa. It is seen protruding into the amniotic cavity near the insertion of the cord </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Factor I deficiency and explain in detail? [/INST] Factor I deficiency, also known as fibrinogen deficiency, is a rare inherited bleeding disorder related to fibrinogen function in the blood coagulation cascade. It is typically subclassified into four distinct fibrinogen disorders: afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia, and hypodysfibrinogenemia.
Afibrinogenemia is defined as a lack of fibrinogen in the blood, clinically <20 mg/deciliter of plasma. The frequency of this disorder is estimated at between 0.5 and 2 per million. Within the United States, afibrinogenemia accounts for 24% of all inherited abnormalities of fibrinogen, while hypofibrinogenemia and dysfibrinogenemia account for 38% each.
Congenital hypofibrinogenemia is defined as a partial deficiency of fibrinogen, clinically 20–80/deciliter of plasma. Estimated frequency varies from <0.5 to 3 per million.
Dysfibrinogenemia is defined as malfunctioning or non-functioning fibrinogen in the blood, albeit at normal concentrations: 200–400 mg/deciliter of plasma. Dysfibrinogenemia may be an inherited disease and therefore termed congenital dysfibrinogenemia or secondary to another disease and therefore termed acquired dysfibrinogenemia. The congenital disorder is estimated to a frequency varying between 1 and 3 per million.
Hypodysfibrinogenemia is a partial deficiency of fibrinogen that is also malfunctioning. Hypodysfibrinogenemia is an extremely rare inherited disease.Clinically, these disorders are generally associated with an increased diathesis, i.e. propensity, to develop spontaneous bleeding episodes and excessive bleeding after even minor tissue injuries and surgeries; however, individuals with any of these disorders may also exhibit a propensity to pathological thrombosis episodes.Treatment of these disorders generally involves specialized centers and the establishment of preventive measures designed based on each individuals personal and family histories of the frequency and severity of previous bleeding and thrombosis episodes, and, in a select few cases, the predicted propensity of the genetic mutations which underlie their disorders to cause bleeding and thrombosis.

Signs and symptoms
Afibrinogenemia is typically the most severe of the three disorders. Common symptoms include bleeding of the umbilical cord at birth, traumatic and surgical bleeding, GI tract, oral and mucosal bleeding, spontaneous splenic rupture, and rarely intracranial hemorrhage and articular bleeding.
Symptoms of hypofibrinogenemia varies from mild to severe, but can include bleeding of the GI tract, oral and mucosal bleeding, and very rarely intracranial bleeding. More commonly it presents during traumatic bleeding or surgical procedures. Most cases (60%) of dysfibrinogenemia are asymptomatic, but 28% exhibit hemorrhaging similar to that described above while 20% exhibit thrombosis (i.e. excessive clotting).

Causes
The disorders associated with Factor I deficiency are generally inherited, although certain liver diseases can also affect fibrinogen levels and function (e.g. cirrhosis) </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Uterine inversion and explain in detail? [/INST] Uterine inversion is when the uterus turns inside out, usually following childbirth. Symptoms include postpartum bleeding, abdominal pain, a mass in the vagina, and low blood pressure. Rarely inversion may occur not in association with pregnancy.Risk factors include pulling on the umbilical cord or pushing on the top of the uterus before the placenta has detached. Other risk factors include uterine atony, placenta previa, and connective tissue disorders. Diagnosis is by seeing the inside of the uterus either in or coming out of the vagina.Treatment involves standard resuscitation together with replacing the uterus as rapidly as possible. If efforts at manual replacement are not successful surgery is required. After the uterus is replaced oxytocin and antibiotics are typically recommended. The placenta can then be removed if it is still attached.Uterine inversion occurs in about 1 in 2,000 to 1 in 10,000 deliveries. Rates are higher in the developing world </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Juvenile myelomonocytic leukemia and explain in detail? [/INST] Juvenile myelomonocytic leukemia (JMML) is a serious chronic leukemia (cancer of the blood) that affects children mostly aged 4 and younger. The name JMML now encompasses all diagnoses formerly referred to as juvenile chronic myeloid leukemia (JCML), chronic myelomonocytic leukemia of infancy, and infantile monosomy 7 syndrome. The average age of patients at diagnosis is 2 years old.  The World Health Organization has included JMML in the category of myelodysplastic and myeloproliferative disorders.

Signs and symptoms
The following symptoms are typical ones which lead to testing for JMML, though children with JMML may exhibit any combination of them: pallor, fever, infection, bleeding, cough, poor weight gain, a maculopapular rash (discolored but not raised, or small and raised but not containing pus), lymphadenopathy (enlarged lymph nodes), moderate hepatomegaly (enlarged liver), marked splenomegaly (enlarged spleen), leukocytosis (high white blood cell count in blood), absolute monocytosis (high monocyte count in blood), anemia (low red blood cell count in blood), and thrombocytopenia (low platelet count in blood).  Most of these conditions are common, nonspecific signs and symptoms.
Children with JMML and neurofibromatosis 1 (NF1) (about 14% of children with JMML are also clinically diagnosed with NF1, though up to 30% carry the NF1 gene mutation) may also exhibit any of the following symptoms associated with NF1 (in general, only young children with NF1 are at an increased risk of developing JMML):
6 or more café-au-lait (flat, coffee-colored) spots on the skin
2 or more neurofibromas (pea-size bumps that are noncancerous tumors) on or under the skin
Plexiform neurofibromas (larger areas on skin that appear swollen)
Optic glioma (a tumor on the optic nerve that affects vision)
Freckles under the arms or in the groin
2 or more Lisch nodules (tiny tan or brown-colored spots on the iris of the eye)
Various bone deformations including bowing of the legs below the knee, scoliosis, or thinning of the shin boneNoonan syndrome (NS) may predispose to the development of JMML or a myeloproliferative disorder (MPD) associated with NS (MPD/NS) which resembles JMML in the first weeks of life. However, MPD/NS may resolve without treatment. Children with JMML and Noonans syndrome may also exhibit any of the following most-common symptoms associated with Noonans syndrome:
Congenital heart defects, in particular, pulmonic stenosis (a narrowing of the valve from the heart to the lungs)
Undescended testicles in males
Excess skin and low hair line on back of neck
Widely set eyes
Diamond-shaped eyebrows
Ears that are low-set, backward-rotated, thick outer rim
Deeply grooved philtrum (upper lip line)
Learning delays

Genetics
About 90% of JMML patients have some sort of genetic abnormality in their leukemia cells that can be identified with laboratory testing. This includes:
15-20% of patients with neurofibromatosis 1 (NF1)
25% of patients with mutations in one of the RAS family of oncogenes (only in their leukemia cells)
Another 35% of patients with a mutation in a gene called PTPN11 (again, only in their leukemia cells).

Diagnosis
The following criteria are required in order to diagnose JMML:All 4 of the following:

No Philadelphia chromosome or BCR/ABL fusion gene.
Peripheral blood monocytosis >1 x 109/L.
Less than 20% blasts (including promonocytes) in the blood and bone marrow (blast count is less than 2% on average)
SplenomegalyAt least one of:
Mutation in RAS or PTPN11
Diagnosis of neurofibromatosis 1
Chromosome 7 monosomyOr two or more of the following criteria:

Hemoglobin F increased for age.
Immature granulocytes and nucleated red cells in the peripheral blood.
White blood cell count >10 x 109/L.
Clonal chromosomal abnormality (e.g., monosomy 7).
Granulocyte-macrophage colony-stimulating factor (GM-CSF) hypersensitivity of myeloid progenitors in vitro.These criteria are identified through blood tests and bone marrow tests.
The differential diagnosis list includes infectious diseases like Epstein–Barr virus, cytomegalovirus, human herpesvirus 6, histoplasma, mycobacteria, and toxoplasma, which can produce similar symptoms.

Treatment
There are two internationally accepted treatment protocols, which are geographically based:
North America: the Childrens Oncology Group (COG) JMML study
Europe: the European Working Group for Myelodysplastic Syndromes (EWOG-MDS) JMML studyThe following procedures are used in one or both of the current clinical approaches listed above:

Splenectomy
The theory behind splenectomy in JMML is that the spleen may trap leukemic cells, leading to the spleens enlargement, by harboring dormant JMML cells that are not eradicated by radiation therapy or chemotherapy for the active leukemia cells, thus leading to later relapse if the spleen is not removed. However, the impact of splenectomy on post-transplant relapse, though, is unknown.  The COG JMML study includes splenectomy as a standard component of treatment for all clinically stable patients.  The EWOG-MDS JMML study allows each childs physician to determine whether or not a splenectomy should be done, and large spleens are commonly removed prior to bone marrow transplant. When a splenectomy is scheduled, JMML patients are advised to receive vaccines against Streptococcus pneumoniae and Haemophilus influenza at least 2 weeks prior to the procedure. Following splenectomy, penicillin may be administered daily in order to protect the patient against bacterial infections that the spleen would otherwise have protected against; this daily preventative regimen will often continue indefinitely.

Chemotherapy
The role of chemotherapy or other pharmacologic treatments against JMML before bone marrow transplant has not been studied completely and its importance is still unknown. Chemotherapy by itself has proven unable to bring about long-term survival in JMML.

Low-dose conventional chemotherapy:  Studies have shown no influence from low-dose conventional chemotherapy on JMML patients’ length of survival. Some combinations of 6-mercaptopurine with other chemotherapy drugs have produced results such as decrease in organ size and increase or normalization of platelet and leukocyte count.
Intensive chemotherapy:  Complete remission with ongoing durability from JMML has not been possible through use of intensive chemotherapy, but it is still used at times because it has improved the condition of a small but significant number of JMML patients who do not display an aggressive disease.  The COG JMML study administers 2 cycles of fludarabine and cytarabine for 5 consecutive days along with 13-cis retinoic acid during and afterwards. The EWOG-MDS JMML study, however, does not recommend intensive chemotherapy before bone marrow transplant.
13-cis retinoic acid (Isotretinoin):  In the lab, 13-cis-retinoic acid has inhibited the growth of JMML cells.  The COG JMML study therefore includes 13-cis-retinoic acid in its treatment protocol, though its therapeutic value for JMML remains controversial.

Radiation
Radiation to the spleen does not generally result in a decrease in spleen size or reduction of platelet transfusion requirement.

Stem cell transplantation
The only treatment that has resulted in cures for JMML is stem cell transplantation, also known as a bone marrow transplant, with about a 50% survival rate.  The risk of relapsing after transplant is high, and has been recorded as high as 50%.  Generally, JMML clinical researchers recommend that a patient have a bone marrow transplant scheduled as soon as possible after diagnosis. A younger age at bone marrow transplant appears to predict a better outcome.

Donor:  Transplants from a matched family donor (MFD), matched unrelated donor (MUD), and matched unrelated umbilical cord blood donors have all shown similar relapse rates, though transplant-related deaths are higher with MUDs and mostly due to infectious causes. Extra medicinal protection, therefore, is usually given to recipients of MUD transplants to protect the child from Graft Versus Host Disease (GVHD). JMML patients are justified for MUD transplants if no MFD is available due to the low rate of survival without a bone marrow transplant.
Conditioning regimen: The COG JMML study involves 8 rounds of total-body irradiation (TBI) and doses of cyclophosphamide to prepare the JMML childs body for bone marrow transplant. Use of TBI is controversial, though, because of the possibility of late side-effects such as slower growth, sterility, learning disabilities, and secondary cancers, and the fact that radiation can have devastating effects on very young children. It is used in this study, however, due to the concern that chemotherapy alone might not be enough to kill dormant JMML cells. The EWOG-MDS JMML Study includes busulfan in place of TBI due to its own research findings that appeared to show that busulfan was more effective against leukemia in JMML than TBI. The EWOG-MDS study also involves cyclophosphamide and melphalan in its conditioning regimen.
Post transplant management: patients can experience relapse, causing treatment failure. It can be prevented by starting the patient with withdrawal of immunosuppressants and/or begin donor lymphocyte infusion.
Graft versus leukemia: Graft versus leukemia has been shown many times to play an important role in curing JMML, and it is usually evidenced in a child after bone marrow transplant through some amount of acute or chronic Graft Versus Host Disease (GVHD). Evidence of either acute or chronic GVHD is linked to a lower relapse rate in JMML. Careful management of immunosuppressant drugs for control of GVHD is essential in JMML; importantly, children who receive less of this prophylaxis have a lower relapse rate.  After bone marrow transplant, reducing ongoing immunosuppressive therapy has worked successfully to reverse the course of a bone marrow with a dropping donor percentage and to prevent a relapse. Donor lymphocyte infusion (DLI), on the other hand, does not frequently work to bring children with JMML back into remission.

Prognosis
Prognosis refers to how well a patient is expected to respond to treatment based on their individual characteristics at time of diagnosis. In JMML, three characteristic areas have been identified as significant in the prognosis of patients:
Without treatment, the survival [5 years?] of children with JMML is approximately 5%.  Only Hematopoietic Stem Cell Transplantation (HSCT), commonly referred to as a bone marrow or (umbilical) cord blood transplant, has been shown to be successful in curing a child of JMML.  With HSCT, recent research studies have found the survival rate to be approximately 50% </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Slipped capital femoral epiphysis and explain in detail? [/INST] Slipped capital femoral epiphysis (SCFE or skiffy, slipped upper femoral epiphysis, SUFE or souffy, coxa vara adolescentium) is a medical term referring to a fracture through the growth plate (physis), which results in slippage of the overlying end of the femur (metaphysis).
Normally, the head of the femur, called the capital, should sit squarely on the femoral neck. Abnormal movement along the growth plate results in the slip. The term slipped capital femoral epiphysis is actually a misnomer, because the epiphysis (end part of a bone) remains in its normal anatomical position in the acetabulum (hip socket) due to the ligamentum teres femoris. It is actually the metaphysis (neck part of a bone) which slips in an anterior direction with external rotation.
SCFE is the most common hip disorder in adolescence. SCFEs usually cause groin pain on the affected side, but sometimes cause knee or thigh pain. One in five cases involves both hips, resulting in pain on both sides of the body. SCFEs occurs slightly more commonly in adolescent males, especially young black males, although it also affects females. Whilst it can occur in any child, the major risk factor is childhood obesity. Symptoms include the gradual, progressive onset of thigh or knee pain with a painful limp. Hip motion will be limited, particularly internal rotation. Running, and other strenuous activity on legs, will also cause the hips to abnormally move due to the condition and can potentially worsen the pain. Stretching is very limited.

Signs and symptoms
Usually, a SCFE causes groin pain, but it may cause pain in only the thigh or knee, because the pain may be referred along the distribution of the obturator nerve. The pain may occur on both sides of the body (bilaterally), as up to 40 percent of cases involve slippage on both sides. In cases of bilateral SCFEs, they typically occur within one year of each other.  About 20 percent of all cases include a SCFE on both sides at the time of presentation.Signs of a SCFE include a waddling gait, decreased range of motion. Often the range of motion in the hip is restricted in internal rotation, abduction, and flexion. A person with a SCFE may prefer to hold their hip in flexion and external rotation.

Complications
Failure to treat a SCFE may lead to: death of bone tissue in the femoral head (avascular necrosis), degenerative hip disease (hip osteoarthritis), gait abnormalities and chronic pain.  SCFE is associated with a greater risk of arthritis of the hip joint later in life. 17–47 percent of acute cases of SCFE lead to the death of bone tissue (osteonecrosis) effects.

Cause
In general, SCFE is caused by increased force applied across the epiphysis, or a decrease in the resistance within the physis to shearing. Obesity is the by far the most significant risk factor. A study in Scotland looked at the weight of 600,000 infants, and followed them up to see who got SCFE. This study identified that obese children had an almost twenty times greater risk than thin children, with a dose-response- so the greater the weight of the child, the greater the risk of SCFE. In 65 percent of cases of SCFE, the person is over the 95th percentile for weight. Endocrine diseases may also contribute (though are far less of a risk than obesity), such as hypothyroidism, hypopituitarism, and renal osteodystrophy.Sometimes no single cause accounts for SCFE, and several factors play a role in the development of a SCFE i.e. both mechanical and endocrine (hormone-related) factors. Skeletal changes may also make someone at risk of SCFE, including femoral or acetabular retroversion, those these may simply be chronic skeletal manifestations of childhood obesity.

Pathophysiology
SCFE is a Salter-Harris type 1 fracture through the proximal femoral physis. Stress around the hip causes a shear force to be applied at the growth plate.  While trauma has a role in the manifestation of the fracture, an intrinsic weakness in the physeal cartilage also is present.  The almost exclusive incidence of SCFE during the adolescent growth spurt indicates a hormonal role. Obesity is another key predisposing factor in the development of SCFE.The fracture occurs at the hypertrophic zone of the physeal cartilage.  Stress on the hip causes the epiphysis to move posteriorly and medially. By convention, position and alignment in SCFE is described by referring to the relationship of the proximal fragment (capital femoral epiphysis) to the normal distal fragment (femoral neck). Because the physis has yet to close, the blood supply to the epiphysis still should be derived from the femoral neck; however, this late in childhood, the supply is tenuous and frequently lost after the fracture occurs. Manipulation of the fracture frequently results in osteonecrosis and the acute loss of articular cartilage (chondrolysis) because of the tenuous nature of the blood supply.

Diagnosis
The diagnosis is a combination of clinical suspicion plus radiological investigation.  Children with a SCFE experience a decrease in their range of motion, and are often unable to complete hip flexion or fully rotate the hip inward.  20–50% of SCFE are missed or misdiagnosed on their first presentation to a medical facility.  SCFEs may be initially overlooked, because the first symptom is knee pain, referred from the hip.  The knee is investigated and found to be normal.

The diagnosis requires x-rays of the pelvis, with anteriorposterior (AP) and frog-leg lateral views.  The appearance of the head of the femur in relation to the shaft likens that of a "melting ice cream cone", visible with Kleins line.  The severity of the disease can be measured using the Southwick angle.

Classification
Atypical/Typical
Loder classification
Stable
Unstable, practically defined as when the patient is unable to ambulate even with crutches
Temporal
Acute
Chronic
Acute-on-chronic
Radiological
Grade I = 0–33% slippage
Grade II = 34–50% slippage
Grade III = >50% slippage

Treatment
The disease can be treated with external in-situ pinning or open reduction and pinning.  Consultation with an orthopaedic surgeon is necessary to repair this problem.  Pinning the unaffected side prophylactically is not recommended for most patients, but may be appropriate if a second SCFE is very likely.Once SCFE is suspected, the patient should be non-weight bearing and remain on strict bed rest. In severe cases, after enough rest the patient may require physical therapy to regain strength and movement back to the leg. A SCFE is an orthopaedic emergency, as further slippage may result in occlusion of the blood supply and avascular necrosis (risk of 25 percent).  Almost all cases require surgery, which usually involves the placement of one or two pins into the femoral head to prevent further slippage.  The recommended screw placement is in the center of the epiphysis and perpendicular to the physis. Chances of a slippage occurring in the other hip are 20 percent within 18 months of diagnosis of the first slippage and consequently the opposite unaffected femur may also require pinning.The risk of reducing this fracture includes the disruption of the blood supply to the bone.  It has been shown in the past that attempts to correct the slippage by moving the head back into its correct position can cause the bone to die </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Blastomycosis and explain in detail? [/INST] Blastomycosis or blasto is a fungal infection caused by inhaling spores of a Blastomyces fungus. Only about half of people with the disease have symptoms, which can include fever, cough, night sweats, muscle pains, weight loss, chest pain, and feeling tired. Symptoms usually develop between three weeks and three months after breathing in the spores. Most blastomycosis infections affect the lungs. In 25 to 40% of cases, the infection also spreads to other parts of the body, such as the skin, bones or central nervous system. Although blastomycosis is especially dangerous for those with weak immune systems, most people diagnosed with blastomycosis have healthy immune systems.Blastomyces dermatitidis is found in the soil and decaying organic matter like wood or leaves. Outdoor activities like hunting or camping in wooded areas increase the risk of developing blastomycosis. There is no vaccine, but the risk of the disease can be reduced by not disturbing the soil. Treatment is typically with an azole drug such as itraconazole for mild or moderate disease. In severe cases, patients are treated with amphotericin B before azole treatment. In either event, the azole treatment lasts for 6–12 months. Overall, 4-6% of people who develop blastomycosis die; however, if the central nervous system is involved, this rises to 18%. People with AIDS or on medications that suppress the immune system have the highest risk of death at 25-40%.Blastomycosis is endemic to the eastern United States and Canada, especially the Ohio and Mississippi River valleys, the Great Lakes, and the St. Lawrence River valley. In these areas, there are about 1 to 2 cases per 100,000 per year. Less frequently, blastomycosis also occurs in Africa, the Middle East, India, and western North America. Blastomycosis also affects a broad range of non-human mammals, and dogs in particular are an order of magnitude more likely to contract the disease than humans. The ecological niche of Blastomyces in the wild is poorly understood, and it is unknown if there are any significant host animals.Blastomycosis has existed for millions of years but was first described by Thomas Caspar Gilchrist in 1894. Because of this, it is sometimes called "Gilchrists disease".

Signs and symptoms
The symptoms of blastomycosis cover a wide range, overlapping with more common conditions; for this reason, blastomycosis has often been called "the great pretender". Many cases are asymptomatic or subclinical. Lung symptoms are common, because the lungs are infected in 79% of blastomycosis cases. However, in 25-40% of cases the disease also disseminates to other organs, including the skin.The extent and severity of symptoms depends in part on a persons immune status; less than 50% of healthy people with blastomycosis have symptoms, while immunocompromised patients are especially likely to have the disease spread beyond the lungs to other organs like the skin and bones.Blastomycosis manifests as a primary lung infection in about 79% of cases. The onset is relatively slow and symptoms are suggestive of bacterial pneumonia, often leading to initial treatment with antibacterials. Because the symptoms are variable and nonspecific, blastomycosis is often not even considered in differential diagnosis until antibacterial treatment has failed, unless there are known risk factors or skin lesions. The disease may be misdiagnosed as a carcinoma, leading in some cases to surgical removal of the affected tissue. Upper lung lobes are involved somewhat more frequently than lower lobes. If untreated, many cases progress over a period of months to years to become disseminated blastomycosis.
Blastomycosis in the lungs may present a variety of symptoms, or no symptoms at all. If symptoms are present they may range from mild pneumonia resembling a pneumococcal infection to acute respiratory distress syndrome (ARDS). Common symptoms include fever, chills, headache, coughing, difficulty breathing, chest pain, and malaise. Without treatment, cases may progress to chronic pneumonia or ARDS.ARDS is an uncommon but dangerous manifestation of blastomycosis. It was seen in 9 of 72 blastomycosis cases studied in northeast Tennessee. Such cases may follow massive exposure, such during brush clearing operations. In the Tennessee study, the fatality rate was 89% in the ARDS cases, but only 10% in the non-ARDS cases.In disseminated blastomycosis, the large Blastomyces yeast cells translocate from the lungs and are trapped in capillary beds elsewhere in the body, where they cause lesions. The skin is the most common organ affected, being the site of lesions in approximately 60% of cases. The signature image of blastomycosis in textbooks is the indolent, verrucous or ulcerated dermal lesion seen in disseminated disease. Osteomyelitis is also common (12–60% of cases). Other recurring sites of dissemination are the genitourinary tract (kidney, prostate, epididymis; collectively ca. 25% of cases) and the brain (3–10% of cases). 40% of immunocompromised individuals have CNS involvement and present as brain abscess, epidural abscess or meningitis.
Blastomycosis in non-lung organs such as the skin may present a very wide range of symptoms, including the following:

skin lesions, which may be verrucous (wart-like) or ulcerated with small pustules at the margins.
bone or joint pain due to bone lytic lesions.
pain when urinating due to prostatitis.
hoarseness due to laryngeal involvement.
headache, confusion or other neurological symptoms caused by central nervous system involvement.

Cause
Blastomycosis is caused by dimorphic fungi in the genus Blastomyces, in the phylum Ascomycota and family Ajellomycetaceae. In eastern North America, the most common cause of blastomycosis is Blastomyces dermatitidis, but Blastomyces gilchristii has been associated with some outbreaks. In western North America, many cases of blastomycosis are caused by Blastomyces helicus, which most commonly attacks immunodeficient people and domestic animals. The species Blastomyces percursus causes many cases of blastomycosis in Africa and the Middle East. In Africa, blastomycosis may also be caused by Blastomyces emzantsi, which is often associated with infections outside the lungs.In endemic areas, Blastomyces dermatitidis lives in soil and rotten wood near lakes and rivers. Although it has never been directly observed growing in nature, it is thought to grow there as a cottony white mold, similar to the growth seen in artificial culture at 25 °C. The moist, acidic soil in the surrounding woodland harbors the fungus.

Pathogenesis
Inhaled conidia of Blastomyces are phagocytosed by neutrophils and macrophages in alveoli. Some of these escape phagocytosis and transform into yeast phase rapidly. Having thick walls, these are resistant to phagocytosis. Once they have transitioned to the yeast phase, the Blastomyces cells express the protein BAD-1, which helps the yeast cells attach to host cells, and also impairs activation of immune cells while inhibiting release of tumor necrosis factor.
 In lung tissue, the cells multiply and may also disseminate through blood and lymphatics to other organs, including the skin, bone, genitourinary tract, and brain. The incubation period for pulmonary blastomycosis is 3 to 15 weeks, although 30–50% of infections are asymptomatic.

Diagnosis
Because the symptoms of blastomycosis resemble those of many other conditions, including tuberculosis and lung cancer, diagnosis is often delayed. In 40% of cases, the diagnosis takes more than a month. A rapid diagnosis can however be made based on microscopic examination of sputum samples or samples obtained from a tissue biopsy or bronchoalveolar lavage.Once suspected, the diagnosis of blastomycosis can usually be confirmed by demonstration of the characteristic broad based budding organisms in sputum or tissues by KOH prep, cytology, or histology. Tissue biopsy of skin or other organs may be required in order to diagnose extra-pulmonary disease. Blastomycosis is histologically associated with granulomatous nodules.
Commercially available urine antigen testing appears to be quite sensitive in suggesting the diagnosis in cases where the organism is not readily detected. However, commercial antigen tests have a high degree of cross-reactivity with other endemic fungal conditions such as histoplasmosis, and thus cannot distinguish blastomycosis from other similar conditions.  This cross-reactivity is caused by these related fungal organisms using similar galactomannans in the cell wall.While culture of the Blastomyces organism remains the definitive diagnostic standard, its slow growing nature can lead to a delay of up to four weeks. In addition, sometimes blood and sputum cultures may not detect blastomycosis. Cultures of the cerebrospinal fluid also have poor sensitivity compared to histopathological examination of the affected tissue.

Treatment
Under Infectious Disease Society of America guidelines, severe cases of blastomycosis and cases with central nervous system (CNS) involvement are treated initially with amphotericin B, followed by a lengthy course of an azole drug such as itraconazole. In most cases the amphotericin treatment lasts for 1–2 weeks, but in cases of CNS involvement it may last for up to 6 weeks. Cases that do not require amphotericin B treatment are treated with a lengthy course of an azole drug.Among azole drugs, itraconazole is generally the treatment of choice. Voriconazole is often recommended for CNS blastomycosis cases due to its ability to pass the blood-brain barrier. Other azole drugs that may be used include fluconazole. Ketoconazole was the azole drug first used for blastomycosis treatment, but has been largely replaced by itraconazole because ketoconazole is less effective and less tolerated by patients. The azole treatment generally lasts for a minimum of six months. Cure rates from itraconazole treatment are nearly 95%. Relapse is rare but does occur even after a full course of treatment.

Prognosis
Published estimates of the case fatality rate for blastomycosis have varied from 4% to 78%. A 2020 meta-analysis of published studies found an overall mortality rate of 6.6%. This rose to 37% for immunocompromised patients and 75% for patients with ARDS. A 2021 analysis of 20 years of disease surveillance data from the five US states where blastomycosis is reportable found an overall mortality rate of 8% and a hospitalization rate of 57%. These numbers may be affected by the under-reporting of mild cases.

Epidemiology
Incidence in most endemic areas is about 0.5 per 100,000 population, with occasional local areas attaining as high as 12 per 100,000. Most Canadian data fit this picture. In Ontario, Canada, considering both endemic and non-endemic areas, the overall incidence is around 0.3 cases per 100,000; northern Ontario, mostly endemic, has 2.44 per 100,000. Manitoba is calculated at 0.62 cases per 100,000. Remarkably higher incidence was shown for the Kenora, Ontario region: 117 per 100,000 overall, with aboriginal reserve communities experiencing 404.9 per 100,000. In the United States, the incidence of blastomycosis is similarly high in hyperendemic areas. For example, the city of Eagle River, Vilas County, Wisconsin, which has an incidence rate of 101.3 per 100,000; the county as a whole has been shown in two successive studies to have an incidence of about 40 cases per 100,000. An incidence of 277 per 100,000 was roughly calculated based on 9 cases seen in a Wisconsin aboriginal reservation during a time in which extensive excavation was done for new housing construction. The new case rates are greater in northern states such as Wisconsin, where from 1986 to 1995 there were 1.4 cases per 100,000 people.The study of outbreaks as well as trends in individual cases of blastomycosis has clarified a number of important matters. Some of these relate to the ongoing effort to understand the source of infectious inoculum of this species, while others relate to which groups of people are especially likely to become infected. Human blastomycosis is primarily associated with forested areas and open watersheds; It primarily affects otherwise healthy, vigorous people, mostly middle-aged, who acquire the disease while working or undertaking recreational activities in sites conventionally considered clean, healthy and in many cases beautiful. Repeatedly associated activities include hunting, especially raccoon hunting, where accompanying dogs also tend to be affected, as well as working with wood or plant material in forested or riparian areas, involvement in forestry in highly endemic areas, excavation, fishing and possibly gardening and trapping.

Urban infections
There is also a developing profile of urban and other domestic blastomycosis cases, beginning with an outbreak tentatively attributed to construction dust in Westmont, Illinois. The city of Rockford, Illinois, was also documented as a hyperendemic area based on incidence rates as high as 6.67 per 100,000 population for some areas of the city. Though proximity to open watersheds was linked to incidence in some areas, suggesting that outdoor activity within the city may be connected to many cases, there is also an increasing body of evidence that even the interiors of buildings may be risk areas. An early case concerned a prisoner who was confined to prison during the whole of his likely blastomycotic incubation period. An epidemiological survey found that although many patients who contracted blastomycosis had engaged in fishing, hunting, gardening, outdoor work and excavation, the most strongly linked association in patients was living or visiting near waterways. Based on a similar finding in a Louisiana study, it has been suggested that place of residence might be the most important single factor in blastomycosis epidemiology in north central Wisconsin. Follow-up epidemiological and case studies indicated that clusters of cases were often associated with particular domiciles, often spread out over a period of years, and that there were uncommon but regularly occurring cases in which pets kept mostly or entirely indoors, in particular cats, contracted blastomycosis. The occurrence of blastomycosis, then, is an issue strongly linked to housing and domestic circumstances.

Seasonal trends
Seasonality and weather also appear to be linked to contraction of blastomycosis. Many studies have suggested an association between blastomycosis contraction and cool to moderately warm, moist periods of the spring and autumn or, in relatively warm winter areas. However, the entire summer or a known summer exposure date is included in the association in some studies. Occasional studies fail to detect a seasonal link. In terms of weather, both unusually dry weather and unusually moist weather have been cited. The seemingly contradictory data can most likely be reconciled by proposing that B. dermatitidis prospers in its natural habitats in times of moisture and moderate warmth, but that inoculum formed during these periods remains alive for some time and can be released into the air by subsequent dust formation under dry conditions. Indeed, dust per se or construction potentially linked to dust has been associated with several outbreaks The data, then, tend to link blastomycosis to all weather, climate and atmospheric conditions except freezing weather, periods of snow cover, and extended periods of hot, dry summer weather in which soil is not agitated.

Gender bias
Sex is another factor inconstantly linked to contraction of blastomycosis: though many studies show more men than women affected, some show no sex-related bias. As mentioned above, most cases are in middle aged adults, but all age groups are affected, and cases in children are not uncommon.

Ethnic populations
Ethnic group or race is frequently investigated in epidemiological studies of blastomycosis, but is potentially confounded by differences in residence and in quality and accessibility of medical care, factors that have not been stringently controlled for to date. In the United States, some studies show a disproportionately high incidence and/or mortality rate for blastomycosis among Black people.In Canada, some studies, but not others, indicate that First Nations people have a disproportionately high incidence of blastomycosis. Incidence in First Nations children may be unusually high. The Canadian data in some areas may be confounded or explained by the tendency to establish indigenous communities in wooded, riparian, northern areas corresponding to the core habitat of B. dermatitidis, often with known B. dermatitidis habitats such as woodpiles and beaver constructions in the near vicinity.

Communicability
Blastomycosis is not considered contagious, either among humans or between animals and humans. However, there are a very small number of cases of human-to-human transmission of B. dermatitidis related to dermal contact or sexual transmission of disseminated blastomycosis of the genital tract among spouses.

History
The organisms causing blastomycosis have existed for millions of years. The pathogenic group of onygenalean fungi that give rise to conditions including blastomycosis and histoplasmosis emerged approximately 150 million years ago. The most closely related blastomycosis-causing fungi, Blastomyces dermatitidis and Blastomyces gilchristii, diverged during the Pleistocene, approximately 1.9 million years ago.At the Koster Site in Illinois, evidence pointing to possible blastomycosis infections among Late Woodland Native Americans has been identified. At that site, Dr. Jane Buikstra found evidence for what may have been an epidemic of a serious spinal disease in adolescents and young adults. Several of the skeletons showed lesions in the spinal vertebrae in the lower back. There are two modern diseases that produce lesions in the bone similar to the ones Dr. Buikstra found in these prehistoric specimens: spinal TB and blastomycosis. The bony lesions in these two diseases are practically identical. Blastomycosis seems more probable as these young people in Late Woodland and Mississippian times may have been affected because they were spending more time cultivating plants than their Middle Woodland predecessors had done. If true, it would be another severe penalty Late Woodland people had to pay as they shifted to agriculture as a way of life, and it would be a contributing factor to shortening their lifespans compared to those of the Middle Woodland people.Blastomycosis was first described by Thomas Caspar Gilchrist in 1894, as a skin disease. Because of this, blastomycosis is sometimes called "Gilchrists disease". Gilchrist initially identified the cause of the disease as a protozoan, but later correctly identified it as a fungus. In 1898 he and William Royal Stokes published the first description of Blastomyces dermatitidis. Gilchrist referred to the disease as "blastomycetic dermatitis".
The systemic spread of blastomycosis was first described in 1902, in a case that had been misdiagnosed as a combination of tuberculosis and a blastomycosis skin infection. In 1907, the dimorphic nature of the Blastomyces fungus was first identified. In 1912, the first case of canine blastomycosis was reported.Prior to the 1930s, blastomycosis was not clearly distinguished from similar fungal conditions. A paper by Rhoda Williams Benham in 1934 distinguished the causative agent of blastomycosis from cryptococcosis and coccidioidomycosis.In the early 1950s, blastomycosis was first determined to be a primarily respiratory disease, with most skin lesions caused by systemic spread from an initial lung infection. In 1952, the first documented case outside North or Central America, in Tunisia, was reported. The 1950s also saw the first introduction of antifungal drugs including amphotericin B. Before 1950, the fatality rate for disseminated blastomycosis was 92%, and treatment options were limited to iodide compounds, radiation therapy, and surgery. The first azole antifungal drug, ketoconazole, was developed in the 1970s and approved in the United States in 1981.Prior to 2013, the only species known to cause blastomycosis was B. dermatitidis. Since that time, genomic analysis has identified multiple other Blastomyces species causing blastomycosis, including B. gilchristii (2013), B. helicus (reassigned from the genus Emmonsia in 2017), B. percursus (2017), and B. emzantsi (2020).

Other animals
Blastomycosis affects a broad range of mammals. As with humans, most animals that become infected were formerly healthy and immunocompetent. Dogs are frequently affected; blastomycosis is eight to ten times more common in dogs than in humans. Sporting and hound breeds are at the greatest risk. Cats and horses can also be infected. Cats with feline immunodeficiency virus are particularly at risk. However, the overall risk of blastomycosis in cats is 28 to 100 times lower than in dogs. Cases of blastomycosis have also been reported in captive lions and tigers, in a wild North American black bear, and in marine mammals such as the Atlantic bottlenose dolphin.The nonspecific symptoms that make blastomycosis difficult to diagnose in humans also complicate veterinary diagnosis. Cats in particular are often only diagnosed after death.Dogs and humans frequently acquire blastomycosis from the same exposure event. In most such cases, the infection in the dog becomes apparent before the human infection. This may be due to a shortened incubation period, caused by the dog inhaling larger quantities of Blastomyces spores than the human.In veterinary care, blastomycosis is typically treated with itraconazole. 70% of treated dogs respond to medication and recover. In dogs as in humans, the prognosis for blastomycosis depends on the severity of the symptoms.

Additional images
See also
Histoplasmosis
Paracoccidioidomycosis

References
Further reading
Castillo CG, Kauffman CA, Miceli MH (2016). "Blastomycosis". Infectious Disease Clinics of North America. 30 (1): 247–264 </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Erythrokeratodermia variabilis and explain in detail? [/INST]  </s>