Rhinitis is defined as inflammation of the nasal membranes1 and is characterized by a symptom complex that consists of any combination of the following: sneezing, nasal congestion, nasal itching, and rhinorrhea. The eyes, ears, sinuses, and throat can also be involved. Allergic rhinitis is the most common cause of rhinitis. It is an extremely common condition, affecting approximately 20% of the population. While allergic rhinitis is not a life-threatening condition, complications can occur and the condition can significantly impair quality of life, which leads to a number of indirect costs. The total direct and indirect cost of allergic rhinitis was recently estimated to be $5.3 billion per year.
Pathophysiology
Allergic rhinitis involves inflammation of the mucous membranes of the nose, eyes, eustachian tubes, middle ear, sinuses, and pharynx. The nose invariably is involved, and the other organs are affected in certain individuals. Inflammation of the mucous membranes is characterized by a complex interaction of inflammatory mediators but ultimately is triggered by an immunoglobulin E (IgE)–mediated response to an extrinsic protein.
The tendency to develop allergic, or IgE-mediated, reactions to extrinsic allergens (proteins capable of causing an allergic reaction) has a genetic component. In susceptible individuals, exposure to certain foreign proteins leads to allergic sensitization, which is characterized by the production of specific IgE directed against these proteins. This specific IgE coats the surface of mast cells, which are present in the nasal mucosa. When the specific protein (eg, a specific pollen grain) is inhaled into the nose, it can bind to the IgE on the mast cells, leading to immediate and delayed release of a number of mediators.
The mediators that are immediately released include histamine, tryptase, chymase, kinins, and heparin. The mast cells quickly synthesize other mediators, including leukotrienes and prostaglandin D2. These mediators, via various interactions, ultimately lead to the symptoms of rhinorrhea (ie, nasal congestion, sneezing, itching, redness, tearing, swelling, ear pressure, postnasal drip). Mucous glands are stimulated, leading to increased secretions. Vascular permeability is increased, leading to plasma exudation. Vasodilation occurs, leading to congestion and pressure. Sensory nerves are stimulated, leading to sneezing and itching. All of these events can occur in minutes; hence, this reaction is called the early, or immediate, phase of the reaction.
Over 4-8 hours, these mediators, through a complex interplay of events, lead to the recruitment of other inflammatory cells to the mucosa, such as neutrophils, eosinophils, lymphocytes, and macrophages. This results in continued inflammation, termed the late-phase response. The symptoms of the late-phase response are similar to those of the early phase, but less sneezing and itching and more congestion and mucus production tend to occur. The late phase may persist for hours or days.
Systemic effects, including fatigue, sleepiness, and malaise, can occur from the inflammatory response. These symptoms often contribute to impaired quality of life.
Frequency
United States
Allergic rhinitis affects approximately 40 million people in the United States. Recent US figures suggest a 20% cumulative prevalence rate.
International
Scandinavian studies have demonstrated a cumulative prevalence rate of 15% in men and 14% in women. The prevalence of allergic rhinitis may vary within and among countries. This may be due to geographic differences in the types and potency of different allergens and the overall aeroallergen burden.
Mortality/Morbidity
While allergic rhinitis itself is not life-threatening (unless accompanied by severe asthma or anaphylaxis), morbidity from the condition can be significant. Allergic rhinitis often coexists with other disorders, such as asthma, and may be associated with asthma exacerbations. It is also associated with otitis media, eustachian tube dysfunction, sinusitis, nasal polyps, allergic conjunctivitis, and atopic dermatitis. Allergic rhinitis may also contribute to learning difficulties, sleep disorders, and fatigue.
A number of complications that can lead to increased morbidity or even mortality can occur secondary to allergic rhinitis. Possible complications include otitis media, eustachian tube dysfunction, acute sinusitis, and chronic sinusitis.
Allergic rhinitis can be associated with a number of comorbid conditions, including asthma, atopic dermatitis, and nasal polyps. Evidence now suggests that uncontrolled allergic rhinitis can actually worsen the inflammation associated with asthma or atopic dermatitis. This could lead to further morbidity and even mortality.
Allergic rhinitis can frequently lead to significant impairment of quality of life. Symptoms such as fatigue, drowsiness (due to the disease or to medications), and malaise can lead to impaired work and school performance, missed school or work days, and traffic accidents. The overall cost (direct and indirect) of allergic rhinitis was recently estimated to be $5.3 billion per year.
Race
Allergic rhinitis occurs in persons of all races. Prevalence of allergic rhinitis seems to vary among different populations and cultures, which may be due to genetic differences, geographic factors or environmental differences, or other population-based factors.
Sex
In childhood, allergic rhinitis is more common in boys than in girls, but in adulthood, the prevalence is approximately equal between men and women.
Age
Onset of allergic rhinitis is common in childhood, adolescence, and early adult years, with a mean age of onset 8-11 years, but allergic rhinitis may occur in persons of any age. In 80% of cases, allergic rhinitis develops by age 20 years. The prevalence of allergic rhinitis has been reported to be as high as 40% in children, subsequently decreasing with age. In the geriatric population, rhinitis is less commonly allergic in nature.
Read further HERE
Showing posts with label immunology. Show all posts
Showing posts with label immunology. Show all posts
Tuesday, 29 July 2008
Friday, 6 June 2008
Shock, Hypovolemic
Hypovolemic shock refers to a medical or surgical condition in which rapid fluid loss results in multiple organ failure due to inadequate circulating volume and subsequent inadequate perfusion. Most often, hypovolemic shock is secondary to rapid blood loss (hemorrhagic shock).
Acute external blood loss secondary to penetrating trauma and severe GI bleeding disorders are 2 common causes of hemorrhagic shock. Hemorrhagic shock can also result from significant acute internal blood loss into the thoracic and abdominal cavities.
Two common causes of rapid internal blood loss are solid organ injury and rupture of an abdominal aortic aneurysm. Hypovolemic shock can result from significant fluid (other than blood) loss. Two examples of hypovolemic shock secondary to fluid loss include refractory gastroenteritis and extensive burns. The remainder of this article concentrates mainly on hypovolemic shock secondary to blood loss and the controversies surrounding the treatment of this condition. The reader is referred to other articles for discussions of the pathophysiology and treatment for hypovolemic shock resulting from losses of fluid other than blood.
The many life-threatening injuries experienced during the wars of the 1900s have significantly affected the development of the principles of hemorrhagic shock resuscitation. During World War I, W.B. Cannon recommended delaying fluid resuscitation until the cause of the hemorrhagic shock was repaired surgically. Crystalloids and blood were used extensively during World War II for the treatment of patients in unstable conditions. Experience from the Korean and Vietnam wars revealed that volume resuscitation and early surgical intervention were paramount for surviving traumatic injuries resulting in hemorrhagic shock. These and other principles helped in the development of present guidelines for the treatment of traumatic hemorrhagic shock. However, recent investigators have questioned these guidelines, and today, controversies exist concerning the optimal treatment of hemorrhagic shock.For more information, see Medscape's Trauma Resource Center.
Pathophysiology
The human body responds to acute hemorrhage by activating the following major physiologic systems: the hematologic, cardiovascular, renal, and neuroendocrine systems.
The hematologic system responds to an acute severe blood loss by activating the coagulation cascade and contracting the bleeding vessels (by means of local thromboxane A2 release). In addition, platelets are activated (also by means of local thromboxane A2 release) and form an immature clot on the bleeding source. The damaged vessel exposes collagen, which subsequently causes fibrin deposition and stabilization of the clot. Approximately 24 hours are needed for complete clot fibrination and mature formation.
The cardiovascular system initially responds to hypovolemic shock by increasing the heart rate, increasing myocardial contractility, and constricting peripheral blood vessels. This response occurs secondary to an increased release of norepinephrine and decreased baseline vagal tone (regulated by the baroreceptors in the carotid arch, aortic arch, left atrium, and pulmonary vessels). The cardiovascular system also responds by redistributing blood to the brain, heart, and kidneys and away from skin, muscle, and GI tract.
The renal system responds to hemorrhagic shock by stimulating an increase in renin secretion from the juxtaglomerular apparatus. Renin converts angiotensinogen to angiotensin I, which subsequently is converted to angiotensin II by the lungs and liver. Angiotensin II has 2 main effects, both of which help to reverse hemorrhagic shock, vasoconstriction of arteriolar smooth muscle, and stimulation of aldosterone secretion by the adrenal cortex. Aldosterone is responsible for active sodium reabsorption and subsequent water conservation.
The neuroendocrine system responds to hemorrhagic shock by causing an increase in circulating antidiuretic hormone (ADH). ADH is released from the posterior pituitary gland in response to a decrease in BP (as detected by baroreceptors) and a decrease in the sodium concentration (as detected by osmoreceptors). ADH indirectly leads to an increased reabsorption of water and salt (NaCl) by the distal tubule, the collecting ducts, and the loop of Henle.
The pathophysiology of hypovolemic shock is much more involved than what was just listed. To explore the pathophysiology in more detail, references for further reading are provided in the bibliography. These intricate mechanisms list above are effective in maintaining vital organ perfusion in severe blood loss. Without fluid and blood resuscitation and/or correction of the underlying pathology causing the hemorrhage, cardiac perfusion eventually diminishes, and multiple organ failure soon follows.
Read more HERE
Acute external blood loss secondary to penetrating trauma and severe GI bleeding disorders are 2 common causes of hemorrhagic shock. Hemorrhagic shock can also result from significant acute internal blood loss into the thoracic and abdominal cavities.
Two common causes of rapid internal blood loss are solid organ injury and rupture of an abdominal aortic aneurysm. Hypovolemic shock can result from significant fluid (other than blood) loss. Two examples of hypovolemic shock secondary to fluid loss include refractory gastroenteritis and extensive burns. The remainder of this article concentrates mainly on hypovolemic shock secondary to blood loss and the controversies surrounding the treatment of this condition. The reader is referred to other articles for discussions of the pathophysiology and treatment for hypovolemic shock resulting from losses of fluid other than blood.
The many life-threatening injuries experienced during the wars of the 1900s have significantly affected the development of the principles of hemorrhagic shock resuscitation. During World War I, W.B. Cannon recommended delaying fluid resuscitation until the cause of the hemorrhagic shock was repaired surgically. Crystalloids and blood were used extensively during World War II for the treatment of patients in unstable conditions. Experience from the Korean and Vietnam wars revealed that volume resuscitation and early surgical intervention were paramount for surviving traumatic injuries resulting in hemorrhagic shock. These and other principles helped in the development of present guidelines for the treatment of traumatic hemorrhagic shock. However, recent investigators have questioned these guidelines, and today, controversies exist concerning the optimal treatment of hemorrhagic shock.For more information, see Medscape's Trauma Resource Center.
Pathophysiology
The human body responds to acute hemorrhage by activating the following major physiologic systems: the hematologic, cardiovascular, renal, and neuroendocrine systems.
The hematologic system responds to an acute severe blood loss by activating the coagulation cascade and contracting the bleeding vessels (by means of local thromboxane A2 release). In addition, platelets are activated (also by means of local thromboxane A2 release) and form an immature clot on the bleeding source. The damaged vessel exposes collagen, which subsequently causes fibrin deposition and stabilization of the clot. Approximately 24 hours are needed for complete clot fibrination and mature formation.
The cardiovascular system initially responds to hypovolemic shock by increasing the heart rate, increasing myocardial contractility, and constricting peripheral blood vessels. This response occurs secondary to an increased release of norepinephrine and decreased baseline vagal tone (regulated by the baroreceptors in the carotid arch, aortic arch, left atrium, and pulmonary vessels). The cardiovascular system also responds by redistributing blood to the brain, heart, and kidneys and away from skin, muscle, and GI tract.
The renal system responds to hemorrhagic shock by stimulating an increase in renin secretion from the juxtaglomerular apparatus. Renin converts angiotensinogen to angiotensin I, which subsequently is converted to angiotensin II by the lungs and liver. Angiotensin II has 2 main effects, both of which help to reverse hemorrhagic shock, vasoconstriction of arteriolar smooth muscle, and stimulation of aldosterone secretion by the adrenal cortex. Aldosterone is responsible for active sodium reabsorption and subsequent water conservation.
The neuroendocrine system responds to hemorrhagic shock by causing an increase in circulating antidiuretic hormone (ADH). ADH is released from the posterior pituitary gland in response to a decrease in BP (as detected by baroreceptors) and a decrease in the sodium concentration (as detected by osmoreceptors). ADH indirectly leads to an increased reabsorption of water and salt (NaCl) by the distal tubule, the collecting ducts, and the loop of Henle.
The pathophysiology of hypovolemic shock is much more involved than what was just listed. To explore the pathophysiology in more detail, references for further reading are provided in the bibliography. These intricate mechanisms list above are effective in maintaining vital organ perfusion in severe blood loss. Without fluid and blood resuscitation and/or correction of the underlying pathology causing the hemorrhage, cardiac perfusion eventually diminishes, and multiple organ failure soon follows.
Read more HERE
Thursday, 5 June 2008
Anaphylaxis
Anaphylaxis refers to a severe allergic reaction in which prominent dermal and systemic signs and symptoms manifest. The full-blown syndrome includes urticaria (hives) and/or angioedema with hypotension and bronchospasm. The classic form, described in 1902, involves prior sensitization to an allergen with later re-exposure, producing symptoms via an immunologic mechanism. An anaphylactoid reaction produces a very similar clinical syndrome but is not immune-mediated. Treatment for both conditions is similar, and this article uses the term anaphylaxis to refer to both conditions unless otherwise specified.
Pathophysiology
Rapid onset of increased secretion from mucous membranes, increased bronchial smooth muscle tone, decreased vascular smooth muscle tone, and increased capillary permeability occur after exposure to an inciting substance. These effects are produced by the release of mediators, which include histamine, leukotriene C4, prostaglandin D2, and tryptase.
In the classic form, mediator release occurs when the antigen (allergen) binds to antigen-specific immunoglobulin E (IgE) attached to previously sensitized basophils and mast cells. The mediators are released almost immediately when the antigen binds. In an anaphylactoid reaction, exposure to an inciting substance causes direct release of mediators, a process that is not mediated by IgE. Increased mucous secretion and increased bronchial smooth muscle tone, as well as airway edema, contribute to the respiratory symptoms observed in anaphylaxis. Cardiovascular effects result from decreased vascular tone and capillary leakage. Histamine release in skin causes urticarial skin lesions.
The most common inciting agents in anaphylaxis are parenteral antibiotics (especially penicillins), IV contrast materials, Hymenoptera stings, and certain foods (most notably, peanuts). Oral medications and many other types of exposures also have been implicated. Anaphylaxis also may be idiopathic.
Frequency
United States
The true incidence of anaphylaxis is unknown, partly because of the lack of a precise definition of the syndrome. Some clinicians reserve the term for the full-blown syndrome, while others use it to describe milder cases. Fatal anaphylaxis is relatively rare; milder forms occur much more frequently. Some authors consider up to 15% of the US population "at risk" for anaphylaxis. The frequency of anaphylaxis is increasing and this has been attributed to the increased number of potential allergens to which people are exposed. Up to 500-1,000 fatal cases of anaphylaxis per year are estimated to occur in the US.
International
Reactions to insects and other venomous plants and animals are more prevalent in tropical areas because of the greater biodiversity in these areas.
Mortality/Morbidity
Approximately 1 in 5000 exposures to a parenteral dose of a penicillin or cephalosporin antibiotic causes anaphylaxis. More than 100 deaths per year are reported in the United States. Fewer than 100 fatal reactions to Hymenoptera stings are reported each year in the United States but this is considered to be an underestimate. One to 2% of people receiving IV radiocontrast experience some sort of reaction. The majority of these reactions are minor, and fatalities are rare. Low molecular weight contrast causes fewer and less severe reactions.
Race
Well-described racial differences in the incidence or severity of anaphylaxis do not exist. Cultural and socioeconomic differences may influence exposure rates.
Sex
No major differences have been reported in the incidence and prevalence of anaphylactic reactions between men and women.
Age
Anaphylaxis occurs in all age groups. While prior exposure is essential for the development of true anaphylaxis, reactions occur even when no documented prior exposure exists. Thus, patients may react to a first exposure to an antibiotic or insect sting. Adults are exposed to more potential allergens than are pediatric patients. The elderly have the greatest risk of mortality from anaphylaxis due to the presence of preexisting disease.
Read more HERE
Pathophysiology
Rapid onset of increased secretion from mucous membranes, increased bronchial smooth muscle tone, decreased vascular smooth muscle tone, and increased capillary permeability occur after exposure to an inciting substance. These effects are produced by the release of mediators, which include histamine, leukotriene C4, prostaglandin D2, and tryptase.
In the classic form, mediator release occurs when the antigen (allergen) binds to antigen-specific immunoglobulin E (IgE) attached to previously sensitized basophils and mast cells. The mediators are released almost immediately when the antigen binds. In an anaphylactoid reaction, exposure to an inciting substance causes direct release of mediators, a process that is not mediated by IgE. Increased mucous secretion and increased bronchial smooth muscle tone, as well as airway edema, contribute to the respiratory symptoms observed in anaphylaxis. Cardiovascular effects result from decreased vascular tone and capillary leakage. Histamine release in skin causes urticarial skin lesions.
The most common inciting agents in anaphylaxis are parenteral antibiotics (especially penicillins), IV contrast materials, Hymenoptera stings, and certain foods (most notably, peanuts). Oral medications and many other types of exposures also have been implicated. Anaphylaxis also may be idiopathic.
Frequency
United States
The true incidence of anaphylaxis is unknown, partly because of the lack of a precise definition of the syndrome. Some clinicians reserve the term for the full-blown syndrome, while others use it to describe milder cases. Fatal anaphylaxis is relatively rare; milder forms occur much more frequently. Some authors consider up to 15% of the US population "at risk" for anaphylaxis. The frequency of anaphylaxis is increasing and this has been attributed to the increased number of potential allergens to which people are exposed. Up to 500-1,000 fatal cases of anaphylaxis per year are estimated to occur in the US.
International
Reactions to insects and other venomous plants and animals are more prevalent in tropical areas because of the greater biodiversity in these areas.
Mortality/Morbidity
Approximately 1 in 5000 exposures to a parenteral dose of a penicillin or cephalosporin antibiotic causes anaphylaxis. More than 100 deaths per year are reported in the United States. Fewer than 100 fatal reactions to Hymenoptera stings are reported each year in the United States but this is considered to be an underestimate. One to 2% of people receiving IV radiocontrast experience some sort of reaction. The majority of these reactions are minor, and fatalities are rare. Low molecular weight contrast causes fewer and less severe reactions.
Race
Well-described racial differences in the incidence or severity of anaphylaxis do not exist. Cultural and socioeconomic differences may influence exposure rates.
Sex
No major differences have been reported in the incidence and prevalence of anaphylactic reactions between men and women.
Age
Anaphylaxis occurs in all age groups. While prior exposure is essential for the development of true anaphylaxis, reactions occur even when no documented prior exposure exists. Thus, patients may react to a first exposure to an antibiotic or insect sting. Adults are exposed to more potential allergens than are pediatric patients. The elderly have the greatest risk of mortality from anaphylaxis due to the presence of preexisting disease.
Read more HERE
Wednesday, 4 June 2008
Stevens-Johnson Syndrome
Background
First described in 1922, Stevens-Johnson syndrome (SJS) is an immune-complex–mediated hypersensitivity complex that is a severe expression of erythema multiforme. It is known by some as erythema multiforme major, but disagreement exists in the literature. Most authors and experts consider SJS and toxic epidermal necrolysis (TEN) different manifestations of the same disease. For that reason, many refer to the entity as SJS/TEN. SJS typically involves the skin and the mucous membranes. While minor presentations may occur, significant involvement of oral, nasal, eye, vaginal, urethral, GI, and lower respiratory tract mucous membranes may develop in the course of the illness. GI and respiratory involvement may progress to necrosis. SJS is a serious systemic disorder with the potential for severe morbidity and even death. Missed diagnosis is common.
Although several classification schemes have been reported, the simplest breaks the disease down as follows:1
SJS - A "minor form of TEN," with less than 10% body surface area (BSA) detachment
Overlapping SJS/TEN - Detachment of 10-30% BSA
TEN - Detachment of more than 30% BSA
Pathophysiology
SJS is an immune-complex–mediated hypersensitivity disorder that may be caused by many drugs, viral infections, and malignancies. Cocaine recently has been added to the list of drugs capable of producing the syndrome. In up to half of cases, no specific etiology has been identified.
Pathologically, cell death results causing separation of the epidermis from the dermis. The death receptor, Fas, and its ligand, FasL, have been linked to the process. Some have also linked inflammatory cytokines to the pathogenesis.
Frequency
United States
Cases tend to have a propensity for the early spring and winter.
International
SJS occurs with a worldwide distribution similar in etiology and occurrence to that in the United States.
Mortality/Morbidity
Mortality is determined primarily by the extent of skin sloughing. When BSA sloughing is less than 10%, the mortality rate is approximately 1-5%. However, when more than 30% BSA sloughing is present, the mortality rate is between 25% and 35%.
See SCORTEN for a more complete discussion of severity of illness and mortality.
Lesions may continue to erupt in crops for as long as 2-3 weeks. Mucosal pseudomembrane formation may lead to mucosal scarring and loss of function of the involved organ system. Esophageal strictures may occur when extensive involvement of the esophagus exists. Mucosal shedding in the tracheobronchial tree may lead to respiratory failure.
Ocular sequelae may include corneal ulceration and anterior uveitis. Blindness may develop secondary to severe keratitis or panophthalmitis in 3-10% of patients. Vaginal stenosis and penile scarring have been reported. Renal complications are rare.
Race
A Caucasian predominance has been reported.
Sex
The male-to-female ratio is 2:1.
Age
Most patients are in the second to fourth decade of their lives; however, cases have been reported in children as young as 3 months.
Read more HERE
First described in 1922, Stevens-Johnson syndrome (SJS) is an immune-complex–mediated hypersensitivity complex that is a severe expression of erythema multiforme. It is known by some as erythema multiforme major, but disagreement exists in the literature. Most authors and experts consider SJS and toxic epidermal necrolysis (TEN) different manifestations of the same disease. For that reason, many refer to the entity as SJS/TEN. SJS typically involves the skin and the mucous membranes. While minor presentations may occur, significant involvement of oral, nasal, eye, vaginal, urethral, GI, and lower respiratory tract mucous membranes may develop in the course of the illness. GI and respiratory involvement may progress to necrosis. SJS is a serious systemic disorder with the potential for severe morbidity and even death. Missed diagnosis is common.
Although several classification schemes have been reported, the simplest breaks the disease down as follows:1
SJS - A "minor form of TEN," with less than 10% body surface area (BSA) detachment
Overlapping SJS/TEN - Detachment of 10-30% BSA
TEN - Detachment of more than 30% BSA
Pathophysiology
SJS is an immune-complex–mediated hypersensitivity disorder that may be caused by many drugs, viral infections, and malignancies. Cocaine recently has been added to the list of drugs capable of producing the syndrome. In up to half of cases, no specific etiology has been identified.
Pathologically, cell death results causing separation of the epidermis from the dermis. The death receptor, Fas, and its ligand, FasL, have been linked to the process. Some have also linked inflammatory cytokines to the pathogenesis.
Frequency
United States
Cases tend to have a propensity for the early spring and winter.
International
SJS occurs with a worldwide distribution similar in etiology and occurrence to that in the United States.
Mortality/Morbidity
Mortality is determined primarily by the extent of skin sloughing. When BSA sloughing is less than 10%, the mortality rate is approximately 1-5%. However, when more than 30% BSA sloughing is present, the mortality rate is between 25% and 35%.
See SCORTEN for a more complete discussion of severity of illness and mortality.
Lesions may continue to erupt in crops for as long as 2-3 weeks. Mucosal pseudomembrane formation may lead to mucosal scarring and loss of function of the involved organ system. Esophageal strictures may occur when extensive involvement of the esophagus exists. Mucosal shedding in the tracheobronchial tree may lead to respiratory failure.
Ocular sequelae may include corneal ulceration and anterior uveitis. Blindness may develop secondary to severe keratitis or panophthalmitis in 3-10% of patients. Vaginal stenosis and penile scarring have been reported. Renal complications are rare.
Race
A Caucasian predominance has been reported.
Sex
The male-to-female ratio is 2:1.
Age
Most patients are in the second to fourth decade of their lives; however, cases have been reported in children as young as 3 months.
Read more HERE
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