Abu Zubair meriwayatkan dari Jabir bin Abdullah bahwa Nabi Muhammad SAW bersabda:

"Setiap penyakit ada obatnya. Jika obat yang tepat diberikan dengan izin Allah, penyakit itu akan sembuh".

(HR. Muslim, Ahmad dan Hakim).

Minggu, 20 Desember 2009


Cellulitis involving the hand.

Cellulitis involving the lower extremity.

Cellulitis involving the abdominal wall.


Rhinitis Medicamentosa


Rhinitis medicamentosa (RM), also known as rebound rhinitis or chemical rhinitis, is a condition characterized by nasal congestion without rhinorrhea or sneezing that is triggered by the use of topical vasoconstrictive medications for more than 4-6 days.1,2,3 Underlying reasons for decongestant use can usually be identified, such as allergy, nonallergic rhinoplasty, chronic rhinosinusitis, nasal polyps, night-time use of continuous positive airway pressure (CPAP), or upper respiratory tract infection. In such cases, other clinical signs such as rhinorrhea, postnasal drainage, and headaches may also be seen.

The term rhinitis medicamentosa is also used in some literature to describe adverse nasal congestion due to medications other than topical decongestion, such as oral contraceptives, psychotropic medications, and antihypertensive medications, although different mechanisms are involved.4 In order to differentiate between these similar conditions, the latter is called drug-induced rhinitis. Management of rhinitis medicamentosa is focused on withdrawal of nasal decongestants and treatment of congestion and underlying condition with appropriate medications.

The nasal mucosa are rich in resistance blood vessels (small arterioles, arteries, and arteriovenous anastomoses) that drain into capacitance venous sinusoids. The sinusoids are innervated with sympathetic fibers; release of endogenous norepinephrine stimulates alpha-1 and alpha-2 adrenoreceptors, which leads to reduced blood flow, increased venous return into capacitance vessels, and, as a result, decreased nasal congestion. Parasympathetic nervous fibers release acetylcholine, which increases nasal secretions, and vasoactive intestinal peptide (VIP), which causes vasodilation. Upon stimulation, abundant sensory C-fibers release neurokinin A, calcitonin gene-related peptide, and substance P, through which various receptors downregulate sympathetic vasoconstriction, leading to congestion.

Upon stimulation of mast cells, eosinophils, and basophils, a complex milieu of local inflammatory mediators is released. These cells contribute to nasal congestion through the release of histamine, kinins, prostaglandins, and arachidonic acid metabolites. Goblet cells can also be activated by such mediators to increase production of mucin, which, in turn, promotes congestion.

Histologic changes consistent with rhinitis medicamentosa include nasociliary loss, squamous cell metaplasia, epithelial edema, epithelial cell denudation, goblet cell hyperplasia, increased expression of the epidermal growth factor receptor, and inflammatory cell infiltration.5,6

The pathophysiology of rhinitis medicamentosa is not well understood.1 Based on knowledge of the physiology of the nasal mucosa, various hypotheses exist; they mainly focus on dysregulation of sympathetic/parasympathetic tone by exogenous vasoconstricting molecules. Proposed mechanisms describe secondary decrease in production of endogenous norepinephrine through a negative feedback mechanism;7 sympathomimetic amines, which have activity at both alpha and beta sites, have a beta effect that outlasts the alpha effect and causes rebound swelling;8 increased parasympathetic activity, vascular permeability, and edema formation by altering vasomotor tone, thus creating the rebound congestion.9

Nasal decongestants

Two classes of nasal decongestants are described: sympathomimetics and imidazolines. Sympathomimetic amines (eg, pseudoephedrine, amphetamine, Benzedrine, mescaline, phenylephrine, ephedrine) activate sympathetic nerves through presynaptic release of endogenous norepinephrine, which subsequently binds to alpha-receptors and causes vasoconstriction. Rebound vasodilation may be induced through weak affinity toward beta-adrenoreceptors. Imidazolines (eg, xylometazoline, oxymetazoline, naphazoline, clonidine) cause vasoconstriction primarily through alpha2-adrenoreceptors, but may also decrease endogenous norepinephrine though a negative feedback mechanism.

Benzalkonium chloride
Benzalkonium chloride (BKC) is a preservative commonly used in aqueous nasal, ophthalmic, and optic products that are available both by prescription and over the counter. It has been in use since 1935, and the American College of Toxicology concludes that it can be safely used as an antimicrobial agent at concentrations ≤0.1%.10 Over the past several years, conflicting reports have described damage to human nasal epithelia or exacerbation of rhinitis medicamentosa associated with intranasal products that contain benzalkonium chloride (BKC).11,12,13,14,15 More recent review of the literature demonstrates that intranasal products with BKC seem to be safe and well tolerated for short-term and long-term use.10

Natural decongestants (alternative medicine)

Many patients use alternative preparations with decongestant properties. Most of them are oral; intranasal preparations include various menthol-based nasal sprays and onion vapor. The efficacy and safety for such decongestants are not known, and no data are available on rhinitis medicamentosa as a result of long-term use of natural decongestants.

United States

The incidence of rhinitis medicamentosa may be underreported because of over-the-counter availability of decongestants. In a survey of 119 allergists, 6.7% had rhinitis medicamentosa. In a study conducted over 10 years in an otolaryngology (ENT) office, the incidence of rhinitis medicamentosa was 1%.16 In another study, an ENT practitioner diagnosed rhinitis medicamentosa in 52 out of 100 consecutive noninfectious patients who presented with nasal obstruction.

Similar frequency ranges occur in Europe.

With continued usage, rhinitis medicamentosa can lead to chronic sinusitis, atrophic rhinitis, and permanent turbinate hyperplasia. Patients develop psychological dependence and an abstinence syndrome upon withdrawal of medication, which consists of headaches, sleep disturbances, restlessness, irritability and anxiety. Rhinitis medicamentosa may predispose patients to chronic sinusitis, otitis media, or atrophic rhinitis. Neonatal respiratory distress syndrome due to the use of topical phenylephrine has been described.17 No deaths are reported.

Rhinitis medicamentosa occurs at a similar rate in men and women.

Peak incidence occurs in young and middle-aged adults.
Symptoms are confined to the nose and consist of chronic nasal congestion without significant rhinorrhea or sneezing.
Symptoms do not change based on the season or whether the patient is spending time indoors or outdoors.
Information about use of decongestant may not be volunteered by patients, as temporary relief of symptoms is often thought to result from the use of nasal spray. The physician must ask about nose spray usage to diagnose rhinitis medicamentosa.18
The frequency and duration of nasal spray use is also important.
In an effort to control symptoms, patients often try to increase both the dose and the frequency of topical decongestants, which leads to dependency.
The most frequent clinical history is a patient with congestion from a cold or rhinitis who experiences congestion, uses an over-the-counter decongestant for relief, and then continues to use the decongestant for weeks, months, or years. Cessation of the decongestant is followed by rebound congestion within hours that is quite profound, leading to more use of the decongestant. The more the decongestant is used, the shorter the period of relief. This eventually leads to the patient seeking medical care.
Physical findings are confined to the nasal cavity.
The nasal mucous membranes may appear "beefy-red" with punctate bleeding, granular, or boggy, with areas of increased tissue friability and profuse stringy mucoid discharge. However, reports exist of the mucosa appearing pale and anemic.
The appearance of the nasal mucosa often suggests rhinitis medicamentosa because of the redness and irritation of the mucosa.
Patients with RM often snore, have sleep apnea, and mouth-breath resulting in sore throat and dry mouth complains.
Patients with rhinitis medicamentosa often snore, have sleep apnea, or breathe mostly through their mouths. This can result in sore throat and dry mouth.

Abuse of topical nasal vasoconstrictive medication use is the only known cause of rhinitis medicamentosa. Sympathomimetic amines include ephedrine and phenylephrine; imidazoline derivatives include oxymetazoline and xylometazoline.

Medications associated with drug-induced rhinitis include the following:
Antihypertensives, such as reserpine, hydralazine, guanethidine, methyldopa, prazosin, doxazosin, reserpine, and chlorothiazide
Beta-blockers, such as propranolol and nadolol
Phosphodiesterase type 5 inhibitors, such as sildenafil, tadalafil, and vardenafil
Hormones, such as exogenous estrogens and oral contraceptives
Antidepressants and antipsychotics, including thioridazine, chlordiazepoxide-amitriptyline, risperidone, and perphenazine
Nonsteroidal anti-inflammatory drugs (NSAIDs)

Associated factors that cause nasal stuffiness include the following:
Allergic rhinitis, nonallergic rhinopathy
Deviated nasal septum
Basal polyps, ASA triad (ie, nasal polyps, asthma, and aspiring intolerance)
Use of CPAP machine at night for sleep apnea
Upper respiratory infection
Other conditions with high levels of estrogen, such as puberty in boys and girls, menarche


Rhinitis, Allergic


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.2 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,3,4 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.5
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.6

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.6,7,8

The mediators that are immediately released include histamine, tryptase, chymase, kinins, and heparin.7,8 The mast cells quickly synthesize other mediators, including leukotrienes and prostaglandin D2.9,10,11 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.12 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.12 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.
United States

Allergic rhinitis affects approximately 40 million people in the United States.13 Recent US figures suggest a 20% cumulative prevalence rate.14,15

Scandinavian studies have demonstrated a cumulative prevalence rate of 15% in men and 14% in women.16 The prevalence of allergic rhinitis may vary within and among countries.17,18,19,20 This may be due to geographic differences in the types and potency of different allergens and the overall aeroallergen burden.

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.21,22,23

Allergic rhinitis is also associated with otitis media, eustachian tube dysfunction, sinusitis, nasal polyps, allergic conjunctivitis, and atopic dermatitis.1,2,24 It may also contribute to learning difficulties, sleep disorders, and fatigue.25,26,27

Numerous 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 asthma21,22,23 or atopic dermatitis.24 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.5


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.

In childhood, allergic rhinitis is more common in boys than in girls, but in adulthood, the prevalence is approximately equal between men and women.

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.28 The prevalence of allergic rhinitis has been reported to be as high as 40% in children, subsequently decreasing with age.14,15 In the geriatric population, rhinitis is less commonly allergic in nature.

Obtaining a detailed history is important in the evaluation of allergic rhinitis. Important elements include an evaluation of the nature, duration, and time course of symptoms; possible triggers for symptoms; response to medications; comorbid conditions; family history of allergic diseases; environmental exposures; occupational exposures; and effects on quality of life. A thorough history may help identify specific triggers, suggesting an allergic etiology for the rhinitis.

Symptoms that can be associated with allergic rhinitis include sneezing, itching (of nose, eyes, ears, palate), rhinorrhea, postnasal drip, congestion, anosmia, headache, earache, tearing, red eyes, eye swelling, fatigue, drowsiness, and malaise.2
Symptoms and chronicity
Determine the age of onset of symptoms and whether symptoms have been present continuously since onset. While the onset of allergic rhinitis can occur well into adulthood, most patients develop symptoms by age 20 years.28
Determine the time pattern of symptoms and whether symptoms occur at a consistent level throughout the year (ie, perennial rhinitis), only occur in specific seasons (ie, seasonal rhinitis), or a combination of the two. During periods of exacerbation, determine whether symptoms occur on a daily basis or only on an episodic basis. Determine whether the symptoms are present all day or only at specific times during the day. This information can help suggest the diagnosis and determine possible triggers.
Determine which organ systems are affected and the specific symptoms. Some patients have exclusive involvement of the nose, while others have involvement of multiple organs. Some patients primarily have sneezing, itching, tearing, and watery rhinorrhea (the classic hayfever presentation), while others may only complain of congestion. Significant complaints of congestion, particularly if unilateral, might suggest the possibility of structural obstruction, such as a polyp, foreign body, or deviated septum.
Trigger factors
Determine whether symptoms are related temporally to specific trigger factors. This might include exposure to pollens outdoors, mold spores while doing yard work, specific animals, or dust while cleaning the house.
Irritant triggers such as smoke, pollution, and strong smells can aggravate symptoms in a patient with allergic rhinitis. These are also common triggers of vasomotor rhinitis. Many patients have both allergic rhinitis and vasomotor rhinitis.
Other patients may describe year-round symptoms that do not appear to be associated with specific triggers. This could be consistent with nonallergic rhinitis, but perennial allergens, such as dust mite or animal exposure, should also be considered in this situation. With chronic exposure and chronic symptoms, the patient may not be able to associate symptoms with a particular trigger.
Response to treatment
Response to treatment with antihistamines supports the diagnosis of allergic rhinitis, although sneezing, itching, and rhinorrhea associated with nonallergic rhinitis can also improve with antihistamines.29
Response to intranasal corticosteroids supports the diagnosis of allergic rhinitis, although some cases of nonallergic rhinitis (particularly the nonallergic rhinitis with eosinophils syndrome [NARES]) also improve with nasal steroids.
Comorbid conditions
Patients with allergic rhinitis may have other atopic conditions such as asthma21,22 or atopic dermatitis.24 Of patients with allergic rhinitis, 20% also have symptoms of asthma. Uncontrolled allergic rhinitis may cause worsening of asthma23 or even atopic dermatitis.24 Explore this possibility when obtaining the patient history.
Look for conditions that can occur as complications of allergic rhinitis. Sinusitis occurs quite frequently. Other possible complications include otitis media, sleep disturbance or apnea, dental problems (overbite), and palatal abnormalities. The treatment plan might be different if one of these complications is present. Nasal polyps occur in association with allergic rhinitis, although whether allergic rhinitis actually causes polyps remains unclear. Polyps may not respond to medical treatment and might predispose a patient to sinusitis or sleep disturbance (due to congestion).
Investigate past medical history, including other current medical conditions. Diseases such as hypothyroidism or sarcoidosis can cause nonallergic rhinitis. Concomitant medical conditions might influence the choice of medication.
Family history
Because allergic rhinitis has a significant genetic component,30 a positive family history for atopy makes the diagnosis more likely.
In fact, a greater risk of allergic rhinitis exists if both parents are atopic than if one parent is atopic. However, the cause of allergic rhinitis appears to be multifactorial, and a person with no family history of allergic rhinitis can develop allergic rhinitis.
Environmental and occupational exposure
A thorough history of environmental exposures helps to identify specific allergic triggers. This should include investigation of risk factors for exposure to perennial allergens (eg, dust mites, mold, pets).31,32 Risk factors for dust mite exposure include carpeting, heat, humidity, and bedding that does not have dust mite–proof covers. Chronic dampness in the home is a risk factor for mold exposure. A history of hobbies and recreational activities helps determine risk and a time pattern of pollen exposure.
Ask about the environment of the workplace or school. This might include exposure to ordinary perennial allergens (eg, mites, mold, pet dander) or unique occupational allergens (eg, laboratory animals, animal products, grains and organic materials, wood dust, latex, enzymes).
Effects on quality of life
An accurate assessment of the morbidity of allergic rhinitis cannot be obtained without asking about the effects on the patient's quality of life. Specific validated questionnaires are available to help determine effects on quality of life.3,4
Determine the presence of symptoms such as fatigue, malaise, drowsiness (which may or may not be related to medication), and headache.
Investigate sleep quality and ability to function at work.


The physical examination should focus on the nose, but examination of facial features, eyes, ears, oropharynx, neck, lungs, and skin is also important. Look for physical findings that may be consistent with a systemic disease that is associated with rhinitis.

General facial features
"Allergic shiners" are dark circles around the eyes and are related to vasodilation or nasal congestion.2,33
"Nasal crease" is a horizontal crease across the lower half of the bridge of the nose that is caused by repeated upward rubbing of the tip of the nose by the palm of the hand (ie, the "allergic salute").2,33
The nasal examination is best accomplished with a nasal speculum or an otoscope with nasal adapter. In the specialist's office, a rigid or flexible rhinolaryngoscope may be used.
The mucosa of the nasal turbinates may be swollen (boggy) and have a pale, bluish-gray color. Some patients may have predominant erythema of the mucosa, which can also be observed with rhinitis medicamentosa, infection, or vasomotor rhinitis. While pale, boggy, blue-gray mucosa is typical for allergic rhinitis, mucosal examination findings cannot definitively distinguish between allergic and nonallergic causes of rhinitis.
Assess the character and quantity of nasal mucus. Thin and watery secretions are frequently associated with allergic rhinitis, while thick and purulent secretions are usually associated with sinusitis; however, thicker, purulent, colored mucus can also occur with allergic rhinitis.
Examine the nasal septum to look for any deviation or septal perforation, which may be present due to chronic rhinitis, granulomatous disease, cocaine abuse, prior surgery, topical decongestant abuse, or, rarely, topical steroid overuse.
Examine the nasal cavity for other masses such as polyps or tumors. Polyps are firm gray masses that are often attached by a stalk, which may not be visible. After spraying a topical decongestant, polyps do not shrink, while the surrounding nasal mucosa does shrink.
Ears, eyes, and oropharynx
Perform otoscopy to look for tympanic membrane retraction, air-fluid levels, or bubbles. Performing pneumatic otoscopy can be considered to look for abnormal tympanic membrane mobility. These findings can be associated with allergic rhinitis, particularly if eustachian tube dysfunction or secondary otitis media is present.
Ocular examination may reveal findings of injection and swelling of the palpebral conjunctivae, with excess tear production. Dennie-Morgan lines (prominent creases below the inferior eyelid) are associated with allergic rhinitis.34
The term "cobblestoning" is used to describe streaks of lymphoid tissue on the posterior pharynx, which is commonly observed with allergic rhinitis. Tonsillar hypertrophy can also be observed. Malocclusion (overbite) and a high-arched palate can be observed in patients who breathe from their mouths excessively.35
Neck: Look for evidence of lymphadenopathy or thyroid disease.
Lungs: Look for the characteristic findings of asthma.
Skin: Evaluate for possible atopic dermatitis.
Other: Look for any evidence of systemic diseases that may cause rhinitis (eg, sarcoidosis, hypothyroidism, immunodeficiency, ciliary dyskinesia syndrome, other connective tissue diseases).
The causes of allergic rhinitis may differ depending on whether the symptoms are seasonal, perennial, or sporadic/episodic. Some patients are sensitive to multiple allergens and can have perennial allergic rhinitis with seasonal exacerbations. While food allergy can cause rhinitis, particularly in children, it is rarely a cause of allergic rhinitis in the absence of gastrointestinal or skin symptoms.

Seasonal allergic rhinitis is commonly caused by allergy to seasonal pollens and outdoor molds.
Pollens (tree, grass, and weed)
Tree pollens, which vary by geographic location, are typically present in high counts during the spring, although some species produce their pollens in the fall. Common tree families associated with allergic rhinitis include birch, oak, maple, cedar, olive, and elm.
Grass pollens also vary by geographic location. Most of the common grass species are associated with allergic rhinitis, including Kentucky bluegrass, orchard, redtop, timothy, vernal, meadow fescue, Bermuda, and perennial rye. A number of these grasses are cross-reactive, meaning that they have similar antigenic structures (ie, proteins recognized by specific IgE in allergic sensitization). Consequently, a person who is allergic to one species is also likely to be sensitive to a number of other species. The grass pollens are most prominent from the late spring through the fall but can be present year-round in warmer climates.
Weed pollens also vary geographically. Many of the weeds, such as short ragweed, which is a common cause of allergic rhinitis in much of the United States, are most prominent in the late summer and fall. Other weed pollens are present year-round, particularly in warmer climates. Common weeds associated with allergic rhinitis include short ragweed, western ragweed, pigweed, sage, mugwort, yellow dock, sheep sorrel, English plantain, lamb's quarters, and Russian thistle.
Outdoor molds
Atmospheric conditions can affect the growth and dispersion of a number of molds; therefore, their airborne prevalence may vary depending on climate and season.
For example, Alternaria and Cladosporium are particularly prevalent in the dry and windy conditions of the Great Plains states, where they grow on grasses and grains. Their dispersion often peaks on sunny afternoons. They are virtually absent when snow is on the ground in winter, and they peak in the summer months and early fall.
Aspergillus and Penicillium can be found both outdoors and indoors (particularly in humid households), with variable growth depending on the season or climate. Their spores can also be dispersed in dry conditions.
Perennial allergic rhinitis is typically caused by allergens within the home but can also be caused by outdoor allergens that are present year-round.36 In warmer climates, grass pollens can be present throughout the year. In some climates, individuals may be symptomatic due to trees and grasses in the warmer months and molds and weeds in the winter.
House dust mites
In the United States, 2 major house dust mite species are associated with allergic rhinitis. These are Dermatophagoides farinae and Dermatophagoides pteronyssinus.31
These mites feed on organic material in households, particularly the skin that is shed from humans and pets. They can be found in carpets, upholstered furniture, pillows, mattresses, comforters, and stuffed toys.
While they thrive in warmer temperatures and high humidity, they can be found year-round in many households. On the other hand, dust mites are rare in arid climates.
Allergy to indoor pets is a common cause of perennial allergic rhinitis.31,32
Cat and dog allergies are encountered most commonly in allergy practice, although allergy has been reported to occur with most of the furry animals and birds that are kept as indoor pets.
Cockroaches: While cockroach allergy is most frequently considered a cause of asthma, particularly in the inner city, it can also cause perennial allergic rhinitis in infested households.37,38
Rodents: Rodent infestation may be associated with allergic sensitization.39,40,41
Sporadic allergic rhinitis, intermittent brief episodes of allergic rhinitis, is caused by intermittent exposure to an allergen. Often, this is due to pets or animals to which a person is not usually exposed. Sporadic allergic rhinitis can also be due to pollens, molds, or indoor allergens to which a person is not usually exposed. While allergy to specific foods can cause rhinitis, an individual affected by food allergy also usually has some combination of gastrointestinal, skin, and lung involvement. In this situation, the history findings usually suggest an association with a particular food. Watery rhinorrhea occurring shortly after eating may be vasomotor (and not allergic) in nature, mediated via the vagus nerve. This often is called gustatory rhinitis.
Occupational allergic rhinitis, which is caused by exposure to allergens in the workplace, can be sporadic, seasonal, or perennial. People who work near animals (eg, veterinarians, laboratory researchers, farm workers) might have episodic symptoms when exposed to certain animals, daily symptoms while at the workplace, or even continual symptoms (which can persist in the evenings and weekends with severe sensitivity due to persistent late-phase inflammation). Some workers who may have seasonal symptoms include farmers, agricultural workers (exposure to pollens, animals, mold spores, and grains), and other outdoor workers. Other significant occupational allergens that may cause allergic rhinitis include wood dust, latex (due to inhalation of powder from gloves), acid anhydrides, glues, and psyllium (eg, nursing home workers who administer it as medication).


Food Allergies


Adverse food reactions can be broadly classified into 2 categories.1 The first category consists of immunologically-mediated adverse reactions to foods that are termed food allergies. Food allergies can result in disorders with an acute onset of symptoms following ingestion of the triggering food allergen (eg, anaphylaxis) and in chronic disorders (eg, atopic dermatitis).

The second category is composed of adverse reactions that are not immune-mediated. An example is lactose intolerance caused by a deficiency of lactase. Adverse reactions to foods can also occur from toxic (eg, bacterial food poisoning) or pharmacologic (eg, caffeine) effects.


Food allergies are primarily the result of immune responses to food proteins.2 Normally, noninflammatory immune responses develop to ingested foods in a process called oral tolerance.3 For reasons that remain unclear, but likely include environmental and genetic factors, tolerance may be abrogated, leading to adverse immune responses. While sensitization (eg, development of an immunoglobulin E [IgE] immune response) to an allergen has been primarily assumed to occur from ingestion, this may not always be the case. For example, oral allergy syndrome (pollen-food related syndrome) describes an allergic response to specific raw fruits or vegetables that share homologous proteins with pollens; the initial route of sensitization is respiratory exposure to pollen proteins rather than oral exposure to food proteins. The skin may be another potential route of sensitization.4

IgE antibody – mediated responses are the most widely recognized form of food allergy and account for acute reactions. Patients with atopy produce IgE antibodies to specific epitopes (areas of the protein) of one or more food allergens. These antibodies bind to high-affinity IgE receptors on circulating basophils and tissue mast cells present throughout the body, including the skin, gastrointestinal tract, and respiratory tract.

Subsequent allergen exposure binds and cross links IgE antibodies on the cell surface, resulting in receptor activation and intracellular signaling that initiates the release of inflammatory mediators (eg, histamine) and synthesis of additional factors (eg, chemotactic factors, cytokines) that promote allergic inflammation. The effects of these mediators on surrounding tissues result in vasodilatation, smooth muscle contraction, and mucus secretion, which, in turn, are responsible for the spectrum of clinical symptoms observed during acute allergic reactions to food.

Cell-mediated responses to food allergens may also mediate allergic responses, particularly in disorders with delayed or chronic symptoms. For example, food protein – induced enterocolitis syndrome (FPIES), a gastrointestinal food allergy, appears to be mediated by T-cell elaboration of the cytokine tumor necrosis factor (TNF)-alpha.5 Persons with atopic dermatitis that flares with ingestion of milk have been noted to have T cells that, in vitro, express the homing receptor cutaneous lymphocyte antigen, which is thought to home the cell to the skin and mediate the response.6 Celiac disease is the result of an immune response to gluten proteins in grains; this disorder is reviewed in the eMedicine Pediatrics article Celiac Disease.

Food allergens are typically water-soluble glycoproteins resistant to heating and proteolysis with molecular weights of 10-70 kd. These characteristics facilitate the absorption of these allergens across mucosal surfaces. Numerous food allergens are purified and well-characterized, such as peanut Ara h1, Ara h2, and Ara h3; chicken egg white Gal d1, Gal d2, and Gal d3; soybean-Gly m1; fish-Gad c1; and shrimp-Pen a1. Closely related foods frequently contain allergens that crossreact immunologically (ie, lead to the generation of specific IgE antibodies detectable by skin prick or in vitro testing) but less frequently crossreact clinically.7 Recently, delayed allergic reactions to meat proteins have been attributed to reactions to carbohydrate moieties.8

General surveys report that as many as 25-30% of households consider at least 1 family member to have a food allergy.9,10 This high rate is not supported by controlled studies in which oral food challenges (a medically supervised, gradual test feeding) are used to confirm patient histories.11,12 The actual prevalence of food allergies is estimated to be 5-6% in infants and children and 3.7 % in adults.13

However, comprehensive studies that include oral food challenges are few in number. Considering allergy to milk, egg, peanut, and seafood in a meta-analysis of 6 international studies using oral food challenges, estimated rates of 1-10.8% were obtained.14 In a meta-analysis including allergy to fruits and vegetables (excluding peanut), only 6 international studies included oral food challenges, and estimates of allergy varied widely from 0.1-4.3% for fruits and tree nuts to 0.1-1.4% for vegetables to under 1% for wheat, soy, and sesame.15

Studies in the United States and the United Kingdom indicate a rise in peanut allergy among young children in the past decade.16,17 One study showed an increase of peanut allergy in children from 0.4% in 1997 to 0.8% in 2002.16 Recent studies from Canada and the United Kingdom indicate allergy rates to peanut of over 1% in children.18,19

Based upon available studies, estimations of the rate of food allergies in children have been summarized as follows for common food allergens: cow milk, 2.5%; eggs, 1.3%; peanuts, 0.8%; wheat, 0.4%; and soy, 0.4%.13 Allergic reactions to non-protein food additives are uncommon.20
Severe anaphylactic reactions, including death, can occur following the ingestion of food.21,22,23,24 Symptoms observed in a food-induced anaphylactic reaction may involve the skin, gastrointestinal tract, and respiratory tract. Frequently observed symptoms include oropharyngeal pruritus, angioedema (eg, laryngeal edema), stridor, dysphonia, cough, dyspnea, wheezing, nausea, vomiting, diarrhea, flushing, urticaria, and angioedema. Fatalities result from severe laryngeal edema, irreversible bronchospasm, refractory hypotension, or a combination thereof.
Peanuts, tree nuts, fish, and shellfish are the foods most often implicated in severe food-induced anaphylactic reactions, though anaphylactic reactions have been reported to a wide variety of foods. Fatalities caused by reactions to milk are increasingly noted.22
Risk factors or associations for fatal food-induced anaphylaxis include: (1) the presence of asthma, especially in patients with poorly controlled disease; (2) previous episodes of anaphylaxis with the incriminated food; (3) a failure to recognize early symptoms of anaphylaxis; and (4) a delay or lack of immediate use of epinephrine to treat the allergic reaction.21,22,23,24 Teenagers and young adults appear to be overrepresented in registries of food allergy fatalities and present a special risk group.
No predilection is known.
Among children, males appear to be more affected; among adults, females are more frequently affected.16
In infants and children younger than 3 years, the prevalence of food allergy is approximately 5-6%.13
The estimated prevalence in adults is approximately 3.7%.13
Necessary elements of a thorough medical history
Develop a complete list of all foods suspected to cause symptoms.
Discuss the manner of preparation of the food (cooked, raw, added spices or other ingredients).
Determine the minimum quantity of food exposure required to cause the symptoms.
Determine the reproducibility of symptoms upon exposure to the food.
Obtain a thorough description of each reaction, including the following:
The route of exposure (ingestion, skin contact, inhalation) and dose
The timing of the onset of symptoms in relation to food exposure
All observed symptoms and each one’s severity
The duration of the reaction
The treatment provided and the clinical response to treatment
The most recent reaction
Inquire about a personal or family history of other allergic disease.
Inquire about eliciting factors that can potentiate a food-allergic reaction (eg, exercise25 , nonsteroidal anti-inflammatory drugs [NSAIDs], alcohol)

Clinical manifestations and disorders26
Cutaneous reactions
These are the most common clinical manifestations of an allergic reaction to a food or food additive.
Symptoms range from acute urticaria (most common) to flushing to angioedema to exacerbations of atopic dermatitis.
Food allergy is rarely the cause of chronic urticaria or angioedema.
Atopic dermatitis27
Controversy surrounds the role of food allergy in the pathogenesis of atopic dermatitis. Studies show that of patients with moderate chronic atopic dermatitis, 35-40% have IgE-mediated food allergy.28,29
Both food-specific IgE-mediated and cellular mechanisms appear responsible for chronic eczematous inflammation.
Removal of a specific food allergen leads to reduction or resolution of clinical symptoms in affected patients; reintroduction of the food exacerbates the atopic dermatitis.30,31 Reintroduction of a suspected food allergen should be performed under medical supervision because, in some instances, initial reintroduction of the food after a period of dietary elimination has resulted in more significant symptoms than were observed when the food was regularly ingested.32
Prophylactic studies show that avoiding particular foods (eg, cow milk, eggs, peanuts) helps delay the onset of atopic dermatitis.33
Celiac disease: Celiac disease is the result of an immune response to gluten proteins in grain. This disorder is reviewed in the eMedicine Pediatrics article Celiac Disease.
Dermatitis herpetiformis
This is a form of non-IgE cell-mediated hypersensitivity related to celiac disease. It is a blistering skin disorder that manifests clinically with a chronic and intensely pruritic rash with a symmetrical distribution.
Elimination of gluten from the diet usually leads to resolution of skin symptoms.
IgE-mediated gastrointestinal food allergy
These food allergy reactions include immediate hypersensitivity reactions and the pollen-food allergy syndrome (oral allergy syndrome).
Specific gastrointestinal symptoms include nausea, vomiting, abdominal pain, and cramping. Diarrhea is found less frequently.
Pollen-food allergy syndrome (oral allergy syndrome)
Patients with this syndrome develop itching or tingling of the lips, tongue, palate, and throat following the ingestion of certain foods. In addition, edema of the lips, tongue, and uvula and a sensation of tightness in the throat may be observed. In fewer than 3% of cases, symptoms progress to more systemic reactions, such as laryngeal edema or hypotension.34
This syndrome is caused by cross-reactivity between certain pollen and food allergens. For example, individuals with ragweed allergy may experience oropharyngeal symptoms following the ingestion of bananas or melons, and patients with birch pollen allergy may experience these symptoms following the ingestion of raw carrots, celery, potato, apple, peach or hazelnut.
Mixed IgE/non-IgE gastrointestinal food allergy (eosinophilic esophagitis and gastroenteritis)35
Symptoms vary according to location of eosinophilia. Typical symptoms include postprandial nausea, abdominal pain, and a sensation of early satiety. Eosinophilic esophagitis may manifest as reflux symptoms and dysphagia; food impaction can occur as well.
Children may experience weight loss or failure to thrive.
CBC count and differential findings may show eosinophilia in approximately 50% of patients; however, this is not diagnostic. Typically, endoscopy and biopsy must be performed in order to establish the presence of eosinophils in the affected segment of the gut. While a dense eosinophil infiltrate may be seen anywhere from the lower esophagus through the large bowel, involvement is patchy and variable.
An elemental (no potential allergens) or oligoantigenic diet (a diet that removes common allergenic foods) and trials of food elimination may be required to determine the role of foods in a patient's condition. Eosinophilic esophagitis does not respond to acid blockade therapy.
In addition to diet therapy (or in place of diet therapy), treatment with anti-inflammatory medications (eg, corticosteroids) may be needed.
Non–IgE-mediated gastrointestinal food allergy
Food protein – induced enterocolitis syndrome typically manifests in the first few months of life with severe projectile vomiting, diarrhea, and failure to thrive.36
Cow milk and soy protein formulas are usually responsible for these reactions. However, solid foods may also trigger these reactions, especially rice and oats.37
When the allergen is removed from the diet, symptoms resolve. Re-exposure prior to resolution results in a delayed (2 h) onset of vomiting, lethargy, increase in the peripheral blood polymorphonuclear leukocyte count, and, later, diarrhea. Hypotension and methemoglobinemia may occur.
Infants who are chronically ingesting the allergen typically appear lethargic, wasted, and dehydrated. The presentation may mimic sepsis. An oral food challenge may establish the diagnosis but is not always needed if the history is clear. No other definitive diagnostic tests are available.
Breastfed infants may have mucus and blood in their stool, attributed to food allergens ingested by the mother, primarily cow milk. This allergic proctocolitis does not typically lead to anemia and is not associated with vomiting or poor growth. Maternal exclusion of the allergen resolves the bleeding. Eosinophilic inflammation of the rectum is noted if a biopsy is performed.38,2 Additional causes of bleeding (eg, infection, fissures) should be considered.
Upper and lower respiratory tract reactions
Upper respiratory reactions typically include nasal congestion, sneezing, nasal pruritus, or rhinorrhea. They are usually observed in conjunction with ocular, skin, or gastrointestinal symptoms.
IgE-mediated pulmonary symptoms may include laryngeal edema, cough, or bronchospasm.
The role of food allergy in the pathogenesis of asthma is a controversial area of investigation.
At the National Jewish Center for Immunology and Respiratory Medicine, 67 (24%) of the 279 children with a history of food-induced asthma were documented to have a positive result after a blinded food challenge, which included wheezing. Interestingly, only 5 (2%) of these patients had wheezing as their only objective adverse symptom.40
In a related report, 320 children with atopic dermatitis undergoing blinded food challenges at Johns Hopkins Hospital were monitored for respiratory reactions. Overall, 34 (17%) of 205 children with positive results from food challenges developed wheezing as part of their reaction. Therefore, a conservative estimate is that 5-10% of patients with asthma have food-induced allergy symptoms.41
In a pediatric case-controlled study comparing 19 children who required ventilation for an exacerbation of asthma and 38 control subjects matched by sex, age, and ethnicity, coincident food allergy was found to be independently associated with life-threatening asthma.42
Wheezing as the only manifestation of an allergic reaction to food is rare.
Food-induced pulmonary hemosiderosis (Heiner syndrome)
This is a rare disorder characterized by recurrent episodes of pneumonia associated with pulmonary infiltrates, hemosiderosis, gastrointestinal blood loss, iron deficiency anemia, and failure to thrive in infants.
While the precise immunologic mechanism is unknown, it is thought to be secondary to a non-IgE hypersensitivity process.
Food-induced anaphylaxis
Following the ingestion of food, severe anaphylactic reactions (ie, systemic allergic reactions), including death, can occur.
Symptoms may include the following:
Oropharyngeal pruritus
Angioedema (eg, laryngeal edema)
Ocular injection, ocular pruritus, conjunctival edema, periocular swelling
Nasal congestion, nasal pruritus, rhinorrhea, and sneezing
Wheezing, bronchospasm
Abdominal pain
A feeling of impending doom
Cardiovascular collapse
Anaphylaxis can occur without skin symptoms24
Food-associated, exercise-induced anaphylaxis describes a disorder in which exercise is tolerated and a food or foods are tolerated, but when exercise follows ingestion of a specific food or foods, anaphylaxis results.43
The physical examination findings are most useful for assessing overall nutritional status, growth parameters, and signs of other allergic disease, such as atopic dermatitis, allergic rhinitis, or asthma.
Findings from a comprehensive physical examination can help rule out other conditions that may mimic food allergy.
Any food protein can trigger an allergic response, and allergic reactions to a large number of foods have been documented; however, only a small group of foods account for most of these reactions.
Eggs, milk, peanuts, soy, fish, shellfish, tree nuts, and wheat are the foods most often implicated in allergic reactions that have been confirmed in well-controlled blinded food challenges. Sesame appears to be an emerging allergen.
Investigations of near-fatal or fatal anaphylactic reactions following food ingestion reveal that most are caused by peanuts, tree nuts, and shellfish, although milk has been increasingly reported.




Portier and Richet first coined the term anaphylaxis in 1902 when a second vaccinating dose of sea anemone toxin caused a dog's death. They named this response anaphylaxis, which is derived from the Greek words a - (against) and – phylaxis (immunity, protection).

Anaphylaxis is an acute multiorgan system reaction, potentially fatal, caused by the release of chemical mediators from mast cells and basophils.1,2 The most common organ systems involved include the cutaneous, respiratory, cardiovascular, and gastrointestinal systems.

Anaphylaxis has no universally accepted clinical definition. The traditional nomenclature for anaphylaxis reserves the term anaphylactic for IgE-dependent reactions and the term anaphylactoid for IgE-independent events, which are clinically indistinguishable. The World Allergy Organization, which is an international umbrella organization representing more than 70 national and regional professional societies dedicated to allergy and clinical immunology, has recommended replacing this terminology with immunologic (IgE-mediated and non-IgE-mediated [eg, IgG and immune complex complement-mediated]) and non-immunologic anaphylaxis.3

Clinically, anaphylaxis is considered likely to be present if any 1 of the 3 following criteria is satisfied within minutes to hours:
Acute symptoms involving skin, mucosal surface, or both, and at least one of the following: respiratory compromise, hypotension, or end-organ dysfunction
Two or more of the following occur rapidly after exposure to a likely allergen: hypotension, respiratory compromise, persistent gastrointestinal symptoms, or involvement of skin or mucosal surface
Hypotension develops after exposure to an allergen known to cause symptoms for that patient: age-specific low blood pressure or decline of systolic blood pressure of more than 30% compared to baseline

In clinical practice, however, delaying treatment until the development of symptoms affecting multiple organs is risky, since the ultimate severity of anaphylaxis is difficult to predict from its outset.

Click here to read the updated practice parameter on the diagnosis and management of anaphylaxis from the Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; and Joint Council of Allergy, Asthma and Immunology. Note that guidelines for the emergency medical treatment of anaphylaxis vary internationally.4


When mast cells and basophils degranulate, whether by IgE- or non–IgE-mediated mechanisms, preformed histamine and newly generated leukotrienes, prostaglandins, and platelet activating factor (PAF) are released. The physiologic responses to these mediators include smooth muscle spasm in the respiratory and gastrointestinal tract, vasodilation, increased vascular permeability, and stimulation of sensory nerve endings.

These physiologic events lead to some or all of the classic symptoms of anaphylaxis: flushing; urticaria/angioedema; pruritus; bronchospasm; laryngeal edema; abdominal cramping with nausea, vomiting, and diarrhea; and feeling of impending doom. Concomitant signs and symptoms can include rhinorrhea, dysphonia, metallic taste, uterine cramps, light-headedness, and headache. Hypotension, cardiac arrhythmias, syncope, and shock can result from intravascular volume loss, vasodilation, and myocardial dysfunction. Increased vascular permeability can produce a shift of 35% of vascular volume to the extravascular space within 10 minutes.

Additional mediators activate other pathways of inflammation: the neutral proteases, tryptase and chymase; proteoglycans such as heparin and chondroitin sulfate; and chemokines and cytokines. These mediators can activate the kallikrein-kinin contact system, the complement cascade, and coagulation pathways. The development and severity of anaphylaxis also depend on the responsiveness of cells targeted by these mediators. IL-4 and IL-13 are cytokines important in the initial generation of antibody and inflammatory cell responses to anaphylaxis. No comparable studies have been conducted in humans, but anaphylactic effects in mice depend on IL-4Rα-dependent IL-4/IL-13 activation of the transcription factor, STAT-6 (signal transducer and activator of transcription 6).5 Eosinophils may be inflammatory (release cytotoxic granule-associated proteins, for example) or anti-inflammatory (metabolize vasoactive mediators, for example).

Under rigid experimental conditions, histamine infusion alone is sufficient to produce most of the symptoms of anaphylaxis. Histamine mediates its effects through activation of histamine 1 (H1) and histamine 2 (H2) receptors. Vasodilation, hypotension, and flushing are mediated by both H1 receptors and H2 receptors. H1 receptors alone mediate coronary artery vasoconstriction, tachycardia, vascular permeability, pruritus, bronchospasm, and rhinorrhea. H2 receptors increase atrial and ventricular contractility, atrial chronotropy, and coronary artery vasodilation. H3 receptors in experimental models of canine anaphylaxis appear to influence cardiovascular responses to norepinephrine. The importance of H3 receptors in humans is unknown.
Effects on the Cardiovascular System

Anaphylaxis has been associated clinically with myocardial ischemia, atrial and ventricular arrhythmias, conduction defects, and T-wave abnormalities. Whether such changes are related to direct mediator effects on the myocardium, to exacerbation of preexisting myocardial insufficiency by the adverse hemodynamic effects of anaphylaxis, to epinephrine released endogenously by the adrenals in response to stress, or to therapeutically injected epinephrine is unclear.

Since mast cells accumulate at sites of coronary atherosclerotic plaques, and immunoglobulins bound to mast cells can trigger mast cell degranulation, some investigators have suggested that anaphylaxis may promote plaque rupture, thus risking myocardial ischemia. Stimulation of the H1 histamine receptor may also produce coronary artery vasospasm. PAF also delays atrioventricular conduction, decreases coronary artery blood flow, and has negative inotropic effects.

Calcitonin gene-related peptide (CGRP), a sensory neurotransmitter that is widely distributed in cardiovascular tissues, may help to counteract coronary artery vasoconstriction during anaphylaxis. CGRP relaxes vascular smooth muscle and has cardioprotective effects in animal models of anaphylaxis.

While tachycardia is the rule, bradycardia can occur during anaphylaxis. Thus, bradycardia may not be as useful to separate anaphylaxis from a vasodepressor reaction as previously thought. Relative bradycardia (initial tachycardia followed by decreased heart rate despite worsening hypotension) has been reported in the setting of experimentally induced insect sting anaphylaxis.

Two distinct physiologic responses occur in mammals experiencing hypovolemia.6 The initial response to hypovolemia is a baroreceptor-mediated increase in overall cardiac sympathetic drive and a concomitant withdrawal of resting vagal drive, which together produce peripheral vasoconstriction and tachycardia. When effective blood volume decreases by 20-30 percent, a second phase follows, which is characterized by withdrawal of vasoconstrictor drive, relative or absolute bradycardia, increased vasopressin, further catecholamine release as the adrenals become more active, and hypotension. Hypotension in this hypovolemic setting is independent of the bradycardia, since it persists when the bradycardia reverses with atropine administration.

The implications of relative or absolute bradycardia in human anaphylaxis and hypovolemic shock have not been studied. However, one retrospective review of approximately 11,000 trauma patients found that mortality was lower with the 29 percent of hypotensive patients who were bradycardic when they were compared to the group of hypotensive individuals who were tachycardic, after adjustment for other mortality factors.7 Thus, bradycardia may have a specific compensatory role in these settings.

Conduction defects and sympatholytic medications may also produce bradycardia. Excessive venous pooling with decreased venous return (also seen in vasodepressor reactions) may activate tension-sensitive sensory receptors in the inferoposterior portions of the left ventricle, thus resulting in a cardio-inhibitory (Bezold-Jarisch) reflex that stimulates the vagus nerve and causes bradycardia.
United States

The true incidence is unknown. Moneret-Vautrin et al reviewed the published literature and stated that severe anaphylaxis affects at least 1-3 persons per 10,000 population.8 Neugut et al estimated that 1-15% of the US population is at risk of experiencing an anaphylactic or anaphylactoid reaction.9 They estimated that the rate of actual anaphylaxis to food was 0.0004%, 0.7-10% for penicillin, 0.22-1% for radiocontrast media (RCM), and 0.5-5% after insect stings.

A population-based study from Olmsted County, Minnesota, found an average annual incidence of anaphylaxis of 21 cases per 100,000 person-years.10 Ingestion of a suspect food was the cause in 36% of cases; a medication, subcutaneous immunotherapy (SCIT), or a diagnostic agent was the cause in 17% of cases; and an insect sting was the cause in 15% of cases. Thirty-two percent of cases were considered idiopathic. Episodes of anaphylaxis occurred more frequently from July through September, which is attributable to insect stings.

In a study of patients referred to a university-affiliated allergy-immunology practice in Memphis, Tennessee, food was the cause of anaphylaxis in 34% of patients, medications in 20%, and exercise in 7% (anaphylaxis due to insect stings or SCIT were excluded from the study).11 The cause of anaphylaxis could not be determined in 59% of patients (ie, they were diagnosed with idiopathic anaphylaxis). A separate study estimated the number of cases of idiopathic anaphylaxis in the United States to be 20,000-47,000 cases per year (approximately 8-19 episodes per 100,000 person-years).


The incidence of anaphylaxis does not appear to vary significantly between countries. Two European studies detected a lower average annual incidence than found in the Olmsted County study (3.2 cases of anaphylactic shock per 100,000 person-years in Denmark; 9.8 cases of out-of-hospital anaphylaxis per 100,000 person-years in Munich, Germany12 ). Rates in Europe range from 1-3 cases per 10,000.13,12 Simons and colleagues examined the rate of epinephrine prescriptions for a population of 1.15 million patients in Manitoba, Canada, and found that 0.95% of this population was prescribed epinephrine, an indicator of perceived risk that future anaphylaxis may occur.14
Fatalities from anaphylaxis are infrequent but not rare. Estimates range from 0.65-2% of patients with anaphylaxis.15,16 The case-fatality rate from the Olmsted County study was 0.65%.10 Reactions to foods are thought to be the most common cause of anaphylaxis when it occurs outside of the hospital and are estimated to cause 150 deaths per year in the United States. Severe reactions to penicillin occur with a frequency of 1-5 cases per 10,000 patient courses, with fatalities in 1 case per 50,000-100,000 courses. Insect sting anaphylaxis causes approximately 25-50 deaths per year. Anaphylaxis to radiocontrast media (RCM) was estimated to have caused 500 deaths in 1982, although this number has likely decreased because of increased awareness and the use of pretreatment regimens and/or lower osmolar agents for patients with a history of RCM reaction.
In the United Kingdom, half of fatal anaphylaxis episodes have an iatrogenic cause (eg, anesthesia, antibiotics, RCM), while foods and insect stings each account for a quarter of the fatal episodes.
The most common causes of death are cardiovascular collapse and respiratory compromise. One report examined 214 anaphylactic fatalities for which the mode of death could be surmised in 196, 98 of which were due to asphyxia (49 lower airways [bronchospasm], 26 both upper and lower airways, and 23 upper airways [angioedema]). The fatalities from acute bronchospasm occurred almost exclusively in those with preexisting asthma. Another analysis of 23 unselected cases of fatal anaphylaxis determined that 16 of 20 “immediate” deaths (death occurring within one hour of symptom onset) and 16 of the 23 cases that underwent autopsy were due to upper airway edema.
Death can occur rapidly. An analysis of anaphylaxis fatalities occurring in the United Kingdom from 1992 to 2001 revealed the interval between initial onset of food anaphylaxis symptoms and fatal cardiopulmonary arrest averaged 25-35 minutes, which was longer than for drugs (mean, 10-20 minutes pre-hospital; 5 minutes in-hospital) or for insect stings (10-15 minutes).
Race has no known effect on the risk of anaphylaxis.
In the Olmsted County study, men and women were equally affected.10
The Memphis study showed a slight female predominance.11
Earlier studies have suggested that episodes of anaphylaxis to intravenous muscle relaxants, aspirin, and latex are more common in women, while insect sting anaphylaxis is more common in men. These sex discrepancies are likely a function of exposure frequency.
Anaphylaxis can occur at any age. In the Olmsted County study, the age range was 6 months to 89 years.10 The mean age was 29 ±19 years. The Memphis study had an age range of 1-79 years, with a mean of 37 years.11
Simons and colleagues noted the highest frequency of epinephrine prescriptions for boys aged 12-17 months (5.3%).14 The rate was 1.4% for those younger than 17 years, 0.9% for those aged 17-64 years, and 0.3% for those aged 65 years or older.
Severe food allergy is more common in children than in adults. However, the frequency in adults may be increasing, since severe food allergy often persists into adulthood.
Anaphylaxis to radiocontrast media (RCM), insect stings, and anesthetics has been reported to be more common in adults than in children. Whether this is a function of exposure frequency or increased sensitivity is unclear.

Other risk factors
Atopy is a risk factor. In the Olmsted County study, 53% of the patients with anaphylaxis had a history of atopic diseases (eg, allergic rhinitis, asthma, atopic dermatitis).10 The Memphis study detected atopy in 37% of the patients.11 Other studies have shown atopy to be a risk factor for anaphylaxis from foods, exercise-induced anaphylaxis, idiopathic anaphylaxis, radiocontrast reactions, and latex reactions. Underlying atopy does not appear to be a risk factor for reactions to penicillin or insect stings.
Route and timing of administration affect anaphylactic potential. The oral route of administration is less likely to cause a reaction, and such reactions are usually less severe, although fatal reactions occur following ingestions of foods by someone who is allergic. The longer the interval between exposures, the less likely an anaphylactic (IgE-mediated) reaction will recur. This is thought to be due to catabolism and decreased synthesis of allergen-specific IgE over time. This does not appear to be the case for IgE-independent reactions.
Geographic location previously was thought to be irrelevant, but a British report has challenged that assumption. Analysis of hospital discharge summaries after anaphylaxis suggests that individuals living in rural areas and in the southern and western parts of England have an increased incidence of anaphylaxis.
Asthma is a risk factor for fatal anaphylaxis.
Delayed administration of epinephrine is also a risk factor for fatal outcomes.17
Posture also influences anaphylaxis outcomes. In a retrospective review of pre-hospital anaphylactic fatalities in the UK, the postural history was known for ten individuals.18 Four of the ten fatalities were associated with the assumption of an upright or sitting posture during anaphylaxis. Postmortem findings were consistent with pulseless electrical activity and an "empty heart" attributed to reduced venous return from vasodilation and redistribution of intravascular volume from the central to the peripheral compartment.

In most studies, the frequency of signs and symptoms of anaphylaxis is grouped by organ system. For example, 100% of patients with anaphylaxis in the Olmsted County study had cutaneous manifestations, consistent with the study's definition of anaphylaxis, which required one symptom of generalized mediator release (mostly skin manifestations).10 Nevertheless, other studies have reported that 90% of patients have cutaneous involvement. The Olmsted study observed that 69% had respiratory manifestations, 41% had cardiovascular involvement, and 24% had oral or gastrointestinal manifestations.10 Other studies have reported similar findings.

Children, however, may be different. An Australian study evaluated 57 children under age 16 years who presented to a pediatric emergency department over a three-year period. Cutaneous features were noted in 82.5%, whereas 95% had respiratory symptoms.

Patients often initially describe a sense of impending doom, accompanied by pruritus and flushing. This can evolve rapidly into the following symptoms, broken down by organ system:
Cutaneous/ocular - Flushing, urticaria, angioedema, cutaneous and/or conjunctival pruritus, warmth, and swelling
Respiratory - Nasal congestion, rhinorrhea, throat tightness, wheezing, shortness of breath, cough, hoarseness
Cardiovascular - Dizziness, weakness, syncope, chest pain, palpitations
Gastrointestinal – Dysphagia, nausea, vomiting, diarrhea, bloating, cramps
Neurologic - Headache, dizziness, blurred vision, and seizure (very rare and often associated with hypotension)
Other – Metallic taste, feeling of impending doom
Symptoms usually begin within 5-30 minutes from the time the culprit antigen is injected but can occur within seconds. If the antigen is ingested, symptoms usually occur within minutes to 2 hours. In rare cases, symptoms can be delayed in onset for several hours. Anaphylaxis, however, occurs as part of a clinical continuum. It can begin with relatively minor cutaneous symptoms and rapidly progress to life-threatening respiratory or cardiovascular manifestations. In general, the more rapidly anaphylaxis develops after exposure to an offending stimulus, the more likely the reaction is to be severe.


The first priority should be to assess the patient's airway, breathing, circulation, and adequacy of mentation (eg, alertness, orientation, coherence of thought).

Severe angioedema of the tongue and lips may obstruct airflow.
Laryngeal edema may manifest as stridor or severe air hunger.
Loss of voice, hoarseness, and/or dysphonia may occur.
Bronchospasm, airway edema, and mucus hypersecretion may manifest as wheezing. In the surgical setting, increased pressure of ventilation can be the only manifestation of bronchospasm.
Hypoxia can cause altered mentation.
Tachycardia is present in one fourth of patients, usually as a compensatory response to reduced intravascular volume or to stress from compensatory catecholamine release.
Bradycardia is more suggestive of a vasodepressor (vasovagal) reaction, although it has been observed in anaphylaxis (see Pathophysiology).
Hypotension (and resultant loss of consciousness) may be observed secondary to capillary leak, vasodilation, and hypoxic myocardial depression.
Cardiovascular collapse and shock can occur immediately, without any other findings. This is an especially important consideration in the surgical setting.
Cutaneous findings may be delayed or absent in rapidly progressive anaphylaxis. Urticaria (hives) can occur anywhere on the body, often localizing to the superficial dermal layers of the palms, soles, and inner thighs. The lesions vary in size and are erythematous, raised, and highly pruritic.
Angioedema (soft tissue swelling) is also commonly observed. These lesions involve the deeper dermal layers of skin. It is usually nonpruritic and nonpitting. Common areas of involvement are the larynx, lips, eyelids, hands, feet, and genitalia.
Generalized (whole-body) erythema (or flushing) without urticaria or angioedema is also occasionally observed.
Gastrointestinal: Vomiting, diarrhea, and abdominal distention are frequently observed.


IgE-mediated anaphylaxis: This is the classic form of anaphylaxis, whereby a sensitizing antigen elicits an IgE antibody response in a susceptible individual. The antigen-specific IgE antibodies then bind to mast cells and basophils. Subsequent exposure to the sensitizing antigen causes cross-linking of cell-bound IgE, resulting in mast cell (and/or basophil) degranulation. Typical examples of IgE-mediated anaphylaxis include the reactions to many drugs, insect stings, and foods.
Certain drugs cause IgE-mediated anaphylaxis. Most cases of IgE-mediated drug anaphylaxis in the United States are due to penicillin and other beta-lactam antibiotics.
Penicillin is metabolized to a major determinant, benzylpenicilloyl, and multiple minor determinants. Penicillin and its metabolites are haptens, small molecules that only elicit an immune response when conjugated with carrier proteins.
Other beta-lactam antibiotics may cross-react with penicillins or may have unique structures that also act as haptens. The incidence rate of anaphylaxis to cephalosporins in penicillin-anaphylactic patients appears to be much less than the 10% frequently quoted. Pichichero reviewed this complicated literature and offers specific guidance for the use of cephalosporins in patients who have a history of IgE-mediated reactions to penicillin.19
Patients with less well-defined reactions to penicillin have a very low risk (1-2%) of developing anaphylaxis to cephalosporins. The rate of skin-test reactivity to imipenem in patients with a known penicillin allergy is almost 50%. In contrast, no known in vitro or clinical crossreactivity exists between penicillins and aztreonam.
Many other drugs have been implicated less frequently in IgE-mediated anaphylaxis.
In the surgical setting, anaphylactic reactions are most often due to muscle relaxants and latex but can also be due to hypnotics, antibiotics, opioids, colloids, and other agents. Volatile anesthetic agents can cause immune-mediated hepatic toxicity but have not been implicated in anaphylactic reactions.
Insect stings, that is, venoms from Hymenoptera insects (eg, bees, yellow jackets, hornets, wasps, fire ants), can elicit an allergen-specific IgE antibody response. From 0.5%-3% of the US population experiences a systemic reaction after being stung.20
Hypersensitivity to foods is a problem encountered throughout the industrialized world.17 In the United States, an estimated 4 million Americans have well-substantiated food allergies. In Montreal, 1.5% of early elementary school students were found to be sensitized to peanuts. Reactions to foods are thought to be the most common prehospital (outpatient) cause of anaphylaxis and are estimated to cause 125 deaths per year in the United States.
Certain foods are more likely than others to elicit an IgE antibody response and lead to anaphylaxis. Foods likely to elicit an IgE antibody response in all age groups include peanuts, tree nuts, fish, and shellfish. Foods likely to elicit an IgE antibody response in children also include eggs, soy, and milk.
An analysis of 32 fatalities thought to be due to food-induced anaphylaxis revealed that peanuts likely were the responsible food in 62% of the cases. In placebo-controlled food challenges, peanut-sensitive patients can react to as little as 100 µg of peanut protein.21 The Olmsted County study, in agreement with earlier studies, found that food ingestion was the leading cause of anaphylaxis, accounting for as many as one third of all cases.10 Scombroid fish poisoning can occasionally mimic food-induced anaphylaxis. Bacteria in spoiled fish produce enzymes capable of decarboxylating histidine to produce biogenic amines, including histamine and cis-urocanic acid, which is also capable of mast cell degranulation.
Latex hypersensitivity is a phenomenon that has been recognized in the last 20 years, corresponding with the increased use of latex gloves because of the HIV and hepatitis B and C epidemics and the institution of universal precautions. In 1995, an estimated 8-17% of healthcare professionals were at risk for latex reactions. The incidence rate is decreasing, at least in part, because of increased awareness, improved manufacturing practices, and a change to unpowdered latex and nonlatex gloves.
Allergen-specific subcutaneous immunotherapy (SCIT) can cause IgE-mediated anaphylaxis. Allergy injections are a common trigger for anaphylaxis. This is not unexpected because the treatment is based on injecting an allergen to which the patient is sensitive. However, life-threatening reactions are rare. Three studies suggest that fatalities from SCIT occur at a rate of approximately 1 per 2,500,000 injections.22,23,24 A total of 104 fatalities due to SCIT and skin testing were reported from 1945-2001.

Risk factors for severe anaphylaxis due to immunotherapy include poorly controlled asthma, concurrent use of beta-blockers, high allergen dose, errors in administration, and lack of a sufficient observation period following the injection. Near-fatal reactions (NFR) to subcutaneous immunotherapy also have been examined retrospectively. Of 646 allergist-immunologists who responded to a survey on reactions, 273 reported NFR. The investigators defined an NFR as respiratory compromise, hypotension, or both, requiring emergency epinephrine. Hypotension was reported in 80% and respiratory failure occurred in 10% of NFRs, exclusively in subjects with asthma. Epinephrine was delayed or not administered in 6% of these cases.

Aspirin and nonsteroidal anti-inflammatory drugs
Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) in the past have been classified as IgE-independent because reactions were thought to occur from aberrant metabolism of arachidonic acid. Isolated cutaneous reactions to aspirin/NSAIDs and bronchospasm in aspirin-sensitive asthmatics (often in association with nasal polyposis) are indeed mediated through IgE-independent mechanisms. Blockade of cyclooxygenase by these drugs causes the prostanoid pathway to shut down, resulting in an overproduction of leukotrienes via the 5-lipoxygenase pathway. These patients have marked cross-reactivity between aspirin and most NSAIDs.
Anaphylaxis after taking these drugs apparently occurs via a different mechanism that is more consistent with IgE-mediated anaphylaxis. With true anaphylaxis, the different cyclooxygenase inhibitors do not appear to cross-react. Anaphylaxis only occurs after 2 or more exposures to the implicated drug, suggesting a need for prior sensitization. Finally, patients with true anaphylaxis do not usually have underlying asthma, nasal polyposis, or urticaria. In one study of nearly 52,000 people taking NSAIDs, 35 developed anaphylactic shock.

Immunologic, IgE-independent reactions
Complement-mediated reactions
Anaphylaxis resulting from administration of blood products, including intravenous immunoglobulin, or animal antiserum is due, at least in part, to activation of complement. Immune complexes formed either in vivo or in vitro can activate the complement cascade.
Certain byproducts of the cascade, namely plasma-activated complement 3 (C3a), plasma-activated complement 4 (C4a), and plasma-activated complement 5 (C5a), are called anaphylatoxins and are capable of causing mast cell/basophil degranulation.
Exercise-induced anaphylaxis
This is a rare syndrome that can take one of two forms. The first form is ingestant dependent, requiring both exercise and the recent ingestion of particular foods (eg, wheat, celery) or medications (eg, NSAIDs) to cause an episode of anaphylaxis. In these patients, exercise alone does not produce an episode, and ingesting the culprit food or medication alone does not cause an episode.
The second form is characterized by intermittent episodes of anaphylaxis during exercise, independent of any food ingestion. Anaphylaxis does not necessarily occur during every episode of physical exertion.
Anaphylaxis associated with systemic mastocytosis
Anaphylaxis can be a manifestation of systemic mastocytosis, a disease characterized by excessive mast cell numbers in multiple organs.
Such patients appear to be at increased risk for food and venom reactions. Alcohol, vancomycin, opioids, radiocontrast media (RCM), and other biologic agents that can degranulate mast cells directly are discouraged.
Idiopathic anaphylaxis25
This is a syndrome of recurrent anaphylaxis for which no consistent triggers can be determined despite an exhaustive search. This recurrent syndrome should be distinguished from a single episode of anaphylaxis for which the etiology may be unclear.
Most patients treated with antihistamines and steroids have complete remission following tapering of steroids. Others require long-term prophylaxis with high doses of H1 antihistamines.
Idiopathic anaphylaxis can be categorized as infrequent (<6 episodes per year) or frequent (³6 episodes per year or 2 or more episodes within the last 2 months).25 One approach is expectant treatment with epinephrine, antihistamines, and prednisone for individuals who have infrequent episodes and a prolonged taper of prednisone for those with frequent episodes.
Most of these patients are female, and atopy appears to be an underlying risk factor.
Two thirds of patients have 5 or fewer episodes per year, while one third have more than 5 episodes per year.
A subpopulation of women develops anaphylaxis in relationship to their menstrual cycle; this phenomenon is known as catamenial anaphylaxis.26,27 In severe cases, these patients require manipulation of their hormonal levels by medical pituitary suppression and even oophorectomy. Most of these patients react to shifts in progesterone levels, and the diagnosis can be confirmed by provoking an anaphylactic event through administration of low doses of progesterone.
Nonimmunologic reactions
Certain agents (ie, direct mast cell activators) are thought to cause direct, nonimmunologic release of mediators from mast cells. These include opioids, RCM, dextrans, protamine, and vancomycin. Mechanisms underlying these reactions are poorly understood but may involve specific receptors (eg, opioids) or non–receptor-mediated mast cell activation (eg, hyperosmolarity). Evidence also exists that RCM, dextrans, and protamine can activate several inflammatory pathways, including complement, coagulation, and vasoactive (kallikrein-kinin) systems.


Immediate hypersensitivity reactions

Sensitization phase of an immunoglobulin E–mediated allergic reaction.


Ishihara Test for Color Blindness

What numbers do you see revealed in the patterns of dots below?

Normal Color Vision
Left Right
Top 25 29
Middle 45 56
Bottom 6 8

Red-Green Color Blind
Left Right
Top 25 Spots
Middle Spots 56
Bottom Spots Spots

Another interesting color blindness test is below
The test is simpler.

The individual with normal color vision will see a 5 revealed in the dot pattern.
An individual with Red/Green (the most common) color blindness will see a 2 revealed in the dots.


Jual Rumah Kontrakan 2 Pintu

Jual Rumah Kontrakan 2 Pintu
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