Sandbox:Mounika

# Chronic Spontaneous Urticaria
Chronic spontaneous urticaria by definition is the presence of urticaria/hives, angioedema, or sometimes both for a duration of six weeks or longer. It affects adults more than children, and women are affected more often than men.
- Diagnosis of CSU is often clinical, based on the episodic appearance of characteristic urticarial lesions, with or without angioedema, on most days of the week, for a period of six weeks or longer. In 80 to 90 percent of adults and children with CSU, no specific etiology can be identified.
- Skin biopsy is not needed for routine diagnosis of CSU, although it is indicated to exclude urticarial vasculitis if there are signs or symptoms consistent with a vasculitic process or in the rare patients with features of mastocytosis.
- Tests used in investigation of pathogenesis include the autologous serum and plasma skin tests (ASST/APST), assays for autoantibodies directed against immunoglobulin (Ig)E or Fc-epsilon-RI, and also in vitro assessments of basophil function. However, these tests lack specificity and prognostic value, are not standardized across laboratories, and are not recommended for routine clinical use.
- Several hypotheses about the pathogenesis of chronic idiopathic urticaria have been proposed, although the data for each are incomplete, and none appear to be helpful for determining treatment or prognosis. The most accepted hypothesis involves histamine-releasing factors and defects in basophil signaling and/or function.
- CSU is a self-limited disease in the vast majority of patients.Spontaneous remission occurs in 30 to 50 percent of patients by one year, and the average duration of disease is two to five years. Up to 20 percent of patients still have symptoms persisting beyond five years. Those with more severe symptoms tend to have longer-lasting disease.
- Patients with chronic spontaneous urticaria are often frustrated and anxious
- Although no external cause is identified in most patients, numerous factors can aggravate the condition.
- Understanding these triggers and learning to avoid those that are relevant to the individual patient are critical components of successful management. Education should begin as soon as the diagnosis is made.
- H1 antihistamines are recommended as initial therapy for all patients with chronic spontaneous Urticaria.
- Less-sedating, second-generation agents (eg, cetirizine, levocetirizine, fexofenadine, loratadine, desloratadine)are more recommended over older first-generation agents (eg, hydroxyzine, diphenhydramine, chlorpheniramine, or mizolastine)

## Treatment Response
- Around 50% of the patients may not achieve complete control of symptoms using standard doses of second-generation H1 antihistamines alone.
- a stepwise approach to increasing therapy is appropriate for this patient group(Non Responders).
- As we increase doses or as different agents are introduced, it is important to discontinue any that have not been beneficial, so that medications do not accumulate
One or more of the following interventions are recommended for those who have persistent symptoms:
- Increasing the dose of the second-generation H1 antihistamine to up to four times the standard dose (after which, international guidelines suggest adding Omalizumab)
- Adding a different second-generation antihistamine
- Adding an H2 antagonist
- Adding a leukotriene-receptor antagonist
- Adding a first-generation H1 antihistamine at bedtime
For patients whose symptoms persist, increasing the dose of first-generation H1 antihistamine gradually is suggested. These patients need to be informed about sedation and anticholinergic side effects.
Usage of Systemic glucocorticoids should be reserved for short-term control of refractory symptoms.
Symptoms that persist despite step 3 therapy or who are intolerant of dose advancement of first-generation H1 antihistamines are considered to have refractory disease.
Once symptoms are controlled, we continue the drug(s) required for control for a minimum of1 to 3 months before attempting to taper or discontinue medications. 
We recommend extending this maintenance period even longer in patients whose symptoms were particularly difficult to suppress.

# Overview
AndersenTawil syndrome, also called Andersen syndrome and Long QT syndrome 7, is a form of Long QT syndrome. It is a rare genetic disorder, and is inherited in an autosomal dominant pattern.

# Classification
There is no established system for the classification of .
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 may be classified according to  into  subtypes/groups: , , , and .
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 may be classified into  subtypes based on , , and .
 may be classified into several subtypes based on , , and .
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Based on the duration of symptoms,  may be classified as either acute or chronic.
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If the staging system involves specific and characteristic findings and features:
According to the , there are  stages of  based on the , , and . Each stage is assigned a  and a  that designate the  and .
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The staging of  is based on the .
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There is no established system for the staging of .

# Pathophysiology
- It is thought that Anderson Tawil disease is caused by mutation in KCNJ2 or KCNJ5 gene.
- KCNJ2 encodes the subunit of the potassium channel Kir2.1 .
- KCNJ5 encodes the G proteinactivated inwardly rectifying potassium channel 4 (Kir3.4).
It is characterized by the triad: ventricular arrhythmias, periodic paralysis or muscle weakness, and skeletal dysmorphism, most commonly micrognathia, clinodactyly.
However, the phenotype is various (Statland et al., 2004). 
Coexistence of ATS with other genetic disorder was described only in research concerning the influence of KCNH2 polymorphism NM_000238.2:c.2690A>C p.(Lys897Thr) on ATS manifestation (Jagodzinska et al., 2016).

# Differentiating ((Page name)) from other Diseases
 must be differentiated from other diseases that cause , , and , such as , , and .
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 must be differentiated from , , and .

# Epidemiology and Demographics
The incidence/prevalence of  is approximately  per 100,000 individuals worldwide.
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In , the incidence/prevalence of  was estimated to be  cases per 100,000 individuals worldwide.
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In , the incidence of  is approximately  per 100,000 individuals with a case-fatality rate of %.
Patients of all age groups may develop .
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The incidence of  increases with age; the median age at diagnosis is  years.
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 commonly affects individuals younger than/older than  years of age.
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 is usually first diagnosed among .
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 commonly affects .
There is no racial predilection to .
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 usually affects individuals of the  race.  individuals are less likely to develop .
 affects men and women equally.
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 are more commonly affected by  than . The  to  ratio is approximately  to 1.
The majority of  cases are reported in .
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 is a common/rare disease that tends to affect  and .

# Screening
Surveillance: Annual screening of asymptomatic individuals with a KCNJ2 pathogenic variant with a 12-lead ECG and 24-hour Holter monitoring.
There is insufficient evidence to recommend routine screening for .
According to the , screening for  is not recommended.
According to the , screening for  by  is recommended every  among patients with , , and .

# Natural History, Complications, and Prognosis
If left untreated, % of patients with  may progress to develop , , and .
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Common complications of  include , , and .
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Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with  is approximately %.

# Diagnosis

## Diagnostic Study of Choice
There are no established criteria for the diagnosis of ATS. Diagnosis is established in an individual with characteristic clinical and ECG findings and/or identification of a pathogenic variant in KCNJ2.

### Establishing the Diagnosis
The diagnosis of ATS is established in a proband with the presence of A or B in Suggestive Findings and/or by identification of a heterozygous pathogenic variant in KCNJ2 by molecular genetic testing (see Table 1).
Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing, multigene panel) and comprehensive genomic testing (exome sequencing, genome sequencing) depending on the phenotype.
Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of ATS is broad, individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those with a phenotype indistinguishable from many other inherited disorders with cardiac arrhythmias are more likely to be diagnosed using genomic testing (see Option 2).

### Suggestive Findings
Andersen-Tawil syndrome (ATS) should be suspected in individuals with either A or B:
A.
Presence of two of the following three criteria:
Periodic paralysis
Symptomatic cardiac arrhythmias or electrocardiographic evidence of enlarged U-waves, ventricular ectopy, or a prolonged QTc or QUc interval
Characteristic facies, dental anomalies, small hands and feet, AND at least two of the following:
Low-set ears
Widely spaced eyes
Small mandible
Fifth-digit clinodactyly
Syndactyly of toes 2 and 3
B.
One of the above three criteria AND at least one other family member who meets two of the three criteria 

### Supportive Findings
Individuals with either episodic weakness or cardiac symptoms require careful evaluation by a neurologist and/or cardiologist as well as measurement of serum potassium concentration (baseline and during attacks of flaccid paralysis), a 12-lead ECG, a 24-hour Holter monitor, and possibly the long exercise protocol.
Serum potassium concentration during episodes of weakness may be elevated, normal, or, most commonly, reduced (<3.5 mmol/U).
Routine nerve conduction electrophysiology is normal between episodes. A more sensitive electrophysiologic study, the long exercise protocol, may reveal an immediate post-exercise increment followed by an abnormal decrement in the compound motor action potential amplitude (>40%) or area (>50%) 20-40 minutes post exercise  . In a study of 11 individuals with ATS, 82% met long-exercise amplitude decrement criteria for abnormal testing .
Electrocardiogram may reveal characteristic abnormalities including prominent U waves, prolonged Q-U intervals, premature ventricular contractions, polymorphic ventricular tachycardia, and bidirectional ventricular tachycardia.
24-hour Holter monitoring is important to document the presence, frequency, and duration of ventricular tachycardia (VT) and the presence or absence of associated symptoms

## History and Symptoms
The majority of patients with  are asymptomatic.
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The hallmark of  is . A positive history of  and  is suggestive of . The most common symptoms of  include , , and . Common symptoms of  include , , and . Less common symptoms of  include , , and .

## Physical Examination
Patients with  usually appear . Physical examination of patients with  is usually remarkable for , , and .
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Common physical examination findings of  include , , and .
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The presence of  on physical examination is diagnostic of .
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The presence of  on physical examination is highly suggestive of .

## Laboratory Findings
An elevated/reduced concentration of serum/blood/urinary/CSF/other  is diagnostic of .
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Laboratory findings consistent with the diagnosis of  include , , and .
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 is usually normal among patients with .
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Some patients with  may have elevated/reduced concentration of , which is usually suggestive of .
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There are no diagnostic laboratory findings associated with .

## Electrocardiogram
There are no ECG findings associated with .
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An ECG may be helpful in the diagnosis of . Findings on an ECG suggestive of/diagnostic of  include , , and .

## X-ray
There are no x-ray findings associated with .
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An x-ray may be helpful in the diagnosis of . Findings on an x-ray suggestive of/diagnostic of  include , , and .
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There are no x-ray findings associated with . However, an x-ray may be helpful in the diagnosis of complications of , which include , , and .

## Echocardiography or Ultrasound
There are no echocardiography/ultrasound  findings associated with .
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Echocardiography/ultrasound  may be helpful in the diagnosis of . Findings on an echocardiography/ultrasound suggestive of/diagnostic of  include , , and .
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There are no echocardiography/ultrasound  findings associated with . However, an echocardiography/ultrasound  may be helpful in the diagnosis of complications of , which include , , and .

## CT scan
There are no CT scan findings associated with .
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 CT scan may be helpful in the diagnosis of . Findings on CT scan suggestive of/diagnostic of  include , , and .
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There are no CT scan findings associated with . However, a CT scan may be helpful in the diagnosis of complications of , which include , , and .

## MRI
There are no MRI findings associated with .
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 MRI may be helpful in the diagnosis of . Findings on MRI suggestive of/diagnostic of  include , , and .
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There are no MRI findings associated with . However, a MRI may be helpful in the diagnosis of complications of , which include , , and .

## Other Imaging Findings
There are no other imaging findings associated with .
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 may be helpful in the diagnosis of . Findings on an  suggestive of/diagnostic of  include , , and .

## Other Diagnostic Studies
There are no other diagnostic studies associated with .
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 may be helpful in the diagnosis of . Findings suggestive of/diagnostic of  include , , and .
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Other diagnostic studies for  include , which demonstrates , , and , and , which demonstrates , , and .

# Treatment

## Medical Therapy
Treatment of manifestations: For episodic weakness: if serum potassium concentration is low (<3.0 mmol/L), administration of oral potassium (20-30 mEq/L) every 15-30 minutes (not to exceed 200 mEq in a 12-hour period) until the serum concentration normalizes; if a relative drop in serum potassium within the normal range causes episodic paralysis, an individual potassium replacement regimen with a goal of maintaining serum potassium levels in the high range of normal can be considered; if serum potassium concentration is high, ingesting carbohydrates may lower serum potassium levels. Mild exercise may shorten or reduce the severity of the attack.
Management of individuals with ATS requires the coordinated input of a neurologist familiar with the treatment of periodic paralysis and a cardiologist familiar with the treatment of cardiac arrhythmias. To date, no randomized clinical therapeutic trials have been conducted on ATS.
Management of attacks of episodic weakness depends on the associated serum potassium concentration:
If the serum potassium concentration is low (<3.0 mmol/L), administer oral potassium (20-30 mEq/L) every 15-30 minutes (not to exceed 200 mEq in a 12-hour period) until the serum concentration normalizes often shortens the attack. As dysphagia is almost never a problem during attacks of paralysis, oral potassium replacement is the safest route. If intravenous potassium replacement is needed, a 5% mannitol solution instead of a saline or glucose solution (both of which may exacerbate weakness) is recommended. Close monitoring of serum potassium concentrations and ECG is necessary during potassium replacement therapy in an emergency setting to avoid secondary hyperkalemia.
Whether a relative drop in serum potassium within the normal range causes episodic paralysis is not clear. If such cases are suspected, affected individuals can work with their physician to devise an individual potassium replacement regimen, with a goal of maintaining serum potassium levels in the high range of normal.
Attacks of weakness when serum potassium concentration is high usually resolve within 60 minutes. Episodes may be shortened by ingesting carbohydrates or continuing mild exercise. Intravenous calcium gluconate is rarely necessary for management in an individual seen in an emergency setting.
Vasovagal syncope in individuals with ATS mandates a careful cardiology assessment.
Agents/circumstances to avoid: Medications known to prolong QT intervals; salbutamol inhalers (may exacerbate cardiac arrhythmias); thiazide and other potassium-wasting diuretics (may provoke drug-induced hypokalemia and could aggravate the QT interval prolongation).
Evaluation of relatives at risk: Molecular genetic testing if the pathogenic variant is known; if not, detailed neurologic and cardiologic evaluation, 12-lead ECG, and 24-hour Holter monitoring to reduce morbidity and mortality through early diagnosis and treatment of at-risk relatives.

## Primary Prevention
Prevention of primary manifestations: Reduction in frequency and severity of episodic attacks of weakness with lifestyle/dietary modification to avoid known triggers; use of carbonic anhydrase inhibitors; daily use of slow-release potassium supplements; implantable cardioverter-defibrillator for those with tachycardia-induced syncope. Empiric treatment with flecainide should be considered for significant, frequent ventricular arrhythmias in the setting of reduced left ventricular function.
Prophylactic treatment aimed at reduction of attack frequency and severity can be achieved, as in other forms of periodic paralysis, with the following:
Lifestyle and dietary modification to avoid known triggers
Use of carbonic anhydrase inhibitors (acetazolamide: adults 125-1,000 mg daily and children 5-10 mg/kg/day divided 1-2x/day or dichlorphenamide 50-200 mg/1-2x/day). Use of potassium-sparing diuretic should be individualized based on patient needs.
Daily use of slow-release potassium supplements, which may also be helpful in controlling attack rates in individuals prone to hypokalemia. Elevating the serum potassium concentration (>4 mEq/L) has the added benefit of narrowing the QT interval, thus reducing the risk of LQT-associated arrhythmias.
An implantable cardioverter-defibrillator in individuals with tachycardia-induced syncope 
Empiric treatment with flecainide  should be considered for significant, frequent ventricular arrhythmias in the setting of reduced left ventricular function . A prospective open label study in ten individuals with ATS and a confirmed KCNJ2 pathogenic variant tested the effect of flecainide, a type 1c antiarrhythmic, for the prevention of cardiac arrhythmias . Outcomes included a 24-hour Holter monitor before and after treatment and a treadmill exercise test. Flecainide was found to significantly reduce the number of ventricular arrhythmias seen on Holter monitor and to suppress exercise-induced ventricular arrhythmias. Individuals were then followed for a mean of 23 months and no syncope or cardiac arrest was documented. Other case studies have reported beneficial effects with flecainide . A recent study showed that fleicainide suppresses arrhythmogenicity through Na+/Ca2+ exchanger flux in induced pluripotent stem cells derived from patients with ATS . Thus, flecainide may reduce cardiac arrhythmias in ATS.

## Secondary Prevention
Prevention of secondary complications: Cautious use of antiarrhythmic drugs (particularly class I drugs) that may paradoxically exacerbate the neuromuscular symptoms.
There are no established measures for the secondary prevention of ATS.