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Pathophysiology Of Urticaria And Angioedema

Flow Chart Pathology Urticaria

Mast cells and basophils have high-affinity receptors for IgE on their surfaces. If an individual develops a specific IgE response to an antigen, re-exposure to that antigen has the potential of crosslinking IgE on the mast cell or basophil, causing cellular degranulation. Degranulation of mast cells and basophils results in histamine release as well as prostaglandin D2 and leukotriene C4 from mast cells, plus other mediators of inflammation. If the mast cells are located in the skin, the patient will develop urticaria. However, if there is more generalized degranulation of mast cells and basophils, the patient can develop bronchospasm and cardiovascular collapse. Thus, the crosslinking of IgE by an allergen, such as penicillin, or a food allergen, such as peanut, results in the degranulation of mast cells or basophils and causes acute urticaria. In patients with chronic urticaria, there is no specific allergen that can be identified that crosslinks specific IgE on the surface of mast...

Treatment Of Urticaria And Angioedema

In the primary care setting, the common encounter is with that patient who develops acute urticaria following the ingestion of a food or medicine to which he or she is allergic. The patient with an acute allergic reaction often develops urticaria with or without an-gioedema. If the allergic response extends beyond the skin, bronchospasm, laryngeal edema, or hypotension from cardiovascular collapse might occur. However, in the case of urticaria and angioedema, the patient is treated first by avoidance of that agent. If the patient is hemodynamically stable, the acute urticaria will resolve over the next 12-24 h if there is no further allergen exposure. Treatment of Acute Urticaria and Angioedema sedation and mucosal drying. Recently developed second-generation antihistamines (e.g., cetirizine Zyrtec fexofenadine Allegra loratadine Claritin desloratadine Clarinex ) are less soporific and have been demonstrated to be safe and effective in the treatment of urticaria. If the acute...

Selection of Individuals

All individuals who have severe symptoms of anaphylaxis and have positive venom skin tests should receive VIT (Table 1). Children who have had very mild reactions with dermal symptoms only do not require therapy. Their families should be advised to keep epinephrine and antihistamines available. Adults who have had similar mild anaphylaxis can probably be treated in a similar fashion, but there is less evidence to support this practice in adults than in children. Currently VIT is still recommended for these adults. Those individuals who have had reactions of moderate intensity such as mild asthma, nausea, and urticaria, without serious life-threatening reactions, might also be treated without immunotherapy and with the availability of emergency medication. They are likely to have similar moderate reactions to subsequent stings. This decision is influenced by other factors such as risk of exposure, other disease processes, such as cardiac disease, and medication use.

What are the typical side effects of opioids

Opioid side effects include respiratory depression, nausea and vomiting, pruritus, cough suppression, urinary retention, and biliary tract spasm. Some opioids may induce histamine release and cause hives, bronchospasm, and hypotension. Intravenous opioids may cause abdominal and chest wall rigidity. Most opioids, with the notable exception of meperidine, produce a dose-dependent bradycardia.

Drugs targeting the RAS

Two prominent classes of antihypertensive drugs, the ACE inhibitors, e.g. benazepril, and the ARBs, e.g. valsartan, function by blocking the RAS. Despite the demonstrated efficacy of these drugs in controlling hypertension and reducing endorgan damage, both mechanisms of action have some disadvantages 10 . Complete inhibition of ACE does not prevent the conversion of Ang I to Ang II by other peptidases, including chymase. Indeed, in cardiac tissue, most Ang II is produced by enzymes other than ACE. In contrast, inhibition of bradykinin cleavage by ACE causes the side effects of coughing and angioedema in a substantial number of patients. Although the ARBs prevent binding of Ang II to AT1, high levels of Ang II and its cleavage products remain in circulation and are available to activate AT2, AT3 and AT4. Renin is anticipated to be a superior target for antihypertensives 31,32 .

Classification And Etiological Considerations

Urticaria and angioedema are classified by several characteristics. The most common classification scheme is based on duration. Urticaria that lasts less than 6 wk is deemed acute, and episodes that persist beyond 6 wk are classified as chronic. Designation of acute or chronic urticaria by duration is important, as it portends underlying pathophysiology and should guide both the prognosis and the therapeutic interventions. Acute urticaria is very common in both children and adults. The acute type is a self-limited process that occurs when mast cells in the skin degranulate. This process is an isolated event and often occurs following exposure to an allergen. It is mediated by immunoglobulin (Ig)E, which is affixed to the surface of mast cells in the skin. When the allergen advances via the bloodstream to the mast cells in the skin, IgE is crosslinked, and the mast cells degranulate. This degranulation results in the release of a host of mediators of inflammation, including histamine,...

Suggested Reading

Chemokines in allergic inflammation. J Allergy Clin Immunol 1997 99 273-277. Dayan CM, Daniels GH. Chronic autoimmune thyroiditis. N Engl J Med 1996 335 99-107. Finn A, Kaplan AP, Fretwell R, Qu R, Long J. A double-blind, placebo-controlled trial of fexofenadine HCl in the treatment of chronic idiopathic urticaria (CIU). J Allergy Clin Immunol 1999 103 1071-1078. Greaves MW. Chronic urticaria. N Engl J Med 1995 332(26) 1767-1772. of histamine release in chronic urticaria. N Engl J Med 1993 328 1599-1604. Kaplan AP. Urticaria and angioedema. In Allergy. Philadelphia WB Saunders, 1997 573-592. Monroe EW, Finn AF, Patel P, et al. Efficacy and safety of desloratadine 5 mg once daily in the treatment of chronic idiopathic urticaria a double-blind randomized placebo controlled trial. J Am Acad Dermatol 2003 535-541. urticaria. J Am Acad Dermatol 1998 19 138-139. Nimi N, Francis DM, Kerman F, et al. Dermal mast cell activators by auto-anitbodies against the high affinity IgE receptor...

Hand Eruptions In Health Care Workers

Health care workers with hand eruptions may have irritant dermatitis, atopic hand eczema, dyshidrotic eczema, psoriasis, allergic contact dermatitis, contact urticaria (usually to natural rubber latex), contact urticaria or protein contact dermatitis to glove powder, or many other conditions. Glove reactions have become so common, however, and the consequences so serious on occasion, that protocols for health care workers are appearing in many hospitals. When health care workers develop hand eczema, the reactions may or may not be related to gloves. Similar to any other hand eczema, management requires avoidance of irritants, and it requires a search for possible allergy to rubber chemicals in latex gloves (especially thiuram and carbamates), contact urticaria to latex proteins, and occasionally to rubber chemicals or cornstarch in glove powder and rarely to other gloves. We gen erally test persons to the rubber chemicals with a patch test to rubber chemicals for both 20-30 min (for...

Problemsspecial considerations

Features range from mild skin rashes to severe urticaria, hypotension, broncho-spasm, abdominal pain, diarrhoea, a 'feeling of impending doom' and cardiovascular collapse. Initial hypotension is largely related to profound vasodilation, which is followed by leakage of intravascular fluid into the interstitium. Cardiac depression (thought to be caused by circulating inflammatory mediators) may also contribute to hypotension. The cardiovascular effects are exacerbated by aortocaval compression.

Management options

Immediate management of severe reactions consists of intravenous adrenaline 100 mg boluses and fluids, with management of the airway and administration of oxygen. Aortocaval compression must be avoided at all times. Any potential for adrenaline to cause uteroplacental vasoconstriction and uterine hypotony is outweighed by the restoration of cardiac output. Intravenous chlorphenamine 10 mg and hydrocortisone 200 mg may be given to reduce the effects of subsequent inflammatory mediator release. For less severe reactions (e.g. urticaria only), chlorphenamine alone may suffice.

Mechanisms Of Allergic And Allergiclike Intolerance Reactions To Foods And Food Additives

Systemic and urticaria angioedema) Urticaria from histamine- Urticaria due to a food As shown in Table 2, the most common type of IgE-mediated food reaction is cutaneous (pruritus, urticaria, or angioedema) followed by systemic anaphylaxis. In OAS, also an IgE-mediated event, itching and swelling of the mouth parts occur with direct contact Exposure to food protein usually occurs orally. Occasionally, individuals can become sensitized or, after developing a food allergy, have a reaction to re-exposure of food through either the aerosol or contact route. Examples include bakery workers who develop IgE-mediated wheat protein sensitivity (and subsequent asthma called baker's asthma) from exposure and then re-exposure to wheat flour dust. Another example is the fish-allergic individual who may develop urticaria or systemic anaphylaxis when exposed to the odor steam of cooked fish. Inhalation reactions have also been reported with crab, egg, milk, peanuts, beans, rice, and potatoes....

Food Additive Intolerance Reactions

Allergic reactions have been reported to occur to the preservative sulfites (and SO2), sodium benzoate, butylated hydroxyzole (BHA), butylated hydroxytylene (BHT), the sugar substitute aspartame, artificial colors (especially yellow, red, and blue), and the flavor enhancer monosodium glutamate (MSG). The symptoms of principal concern are urticaria and asthma. In most cases, even if it is proven that the food additive is involved in the clinical symptoms, the exact mechanism of the reaction is unknown. Very few patients have been proven to develop urticaria after ingesting food coloring agents. In sulfite-induced asthma, the principal mechanism is believed to be the inhalation of SO2 as sulfite-containing foods are chewed in the mouth. In addition, a small number of individuals have been identified who have a sulfite oxidase enzyme deficiency, which prevents metabolism of this preservative and could result in high blood levels. In a few cases of documented urticarial reactions to...

Infant Formula Substitution

A particular problem exists for infants who are allergic or intolerant to conventional cow's-milk-based formula. Although some individuals who are allergic and have urticaria can use a soy-based formula substitute, any child with a gastrointestinal problem should be given a casein protein hydrolysate infant formula. Table 8 lists the substitute infant formulas available commercially in the United States for milk allergy. Nutramigen or Alimentum is usually preferable to Pregestimil in the United States. An elemental amino acid formula should be tried in the few infants who are very sensitive to cow's milk protein and cannot tolerate casein hydrolysate formula. And the two amino-acid-based infant formulas available in the United States are Neocate and Ele Care .

How should any allergic reaction be treated

The typical presentation for a severe reaction is in a patient with prior exposure with symptoms developing soon after repeat exposure, although cross-sensitization with commercial products may permit a severe reaction on initial exposure. Respiratory symptoms include edema, especially of mucous membranes and the larynx, bronchospasm, and pulmonary edema. Cardiovascular symptoms include hypotension and tachycardia. Cutaneous manifestations include flushing and hives. These are the manifestations of the most severe, potentially fatal, IgE-mediated reaction known as anaphylaxis. Should a real or likely anaphylactic reaction be recognized, the following recommendations are made

Vivian P Hernandez TrujiUo md and Phil Lieberman md

Histamine is widely distributed throughout the body, with the highest concentrations in the lung, skin, and gastrointestinal tract. H1 receptors are the most important in producing allergic symptoms. Most first-generation antihistamines have a structural resemblance to histamine. The most important side effect of first-generation antihistamines is sedation. As a consequence, increasing numbers of second-generation antihistamines have become available. The activities of second-generation antihistamines are probably related to the fact that each of these mediators act through a G proteincoupled receptor that is analogous in structure to the receptor for histamine. The advantages of second-generation antihistamines include lack of sedation and ease of use (i.e., once-daily dosing). Antihistamines are important in the treatment of various allergic diseases. Antihistamines are the first-line therapy in the treatment of allergic rhinitis. Antihistamines are also becoming increasingly...

Allergies to Medications

As harmful and begins producing antibodies to fight it. Finally, the person takes another dose of the drug, and the allergy symptoms appear. The symptoms may appear immediately, within 1 to 2 hours, or within a few days to a week after taking the drug. Common symptoms of drug allergy include skin rash or hives, difficulty breathing, and itching. Severe drug allergies may cause seizures, loss of consciousness, or shock (see box below). If you have had a previous severe allergic reaction, you will need to carry an injecting device that contains epinephrine with you at all times, so you can inject yourself immediately if you have another allergic reaction. An injection of epinephrine can save your life. During an anaphylactic reaction, the body releases massive amounts of histamine and other powerful chemicals in response to the presence of the allergen. The blood vessels widen, causing a sudden, severe decrease in blood pressure. Other symptoms can include hives (itchy, raised, red...

Contact Dermatitis of the Eyelids

Thimerosal Allergy Reaction

Angioedema around the eyes 24 h after exposure to hair dye. Patient had a similar reaction to hair dye 2 mo previously. Fig. 2. Angioedema around the eyes 24 h after exposure to hair dye. Patient had a similar reaction to hair dye 2 mo previously. Contact allergy is a common cause of eyelid dermatitis in particular, and the allergens may reach the skin in many different ways. Common sources for allergenic sensitizers are topical pharmaceutical products (antibiotics, corticosteroids), cosmetics (fragrance components, preservatives, emulsifiers, hair-care and nail products), metals (nickel), rubber derivatives, resins (e.g., epoxy resin), and plants. Also, latex allergy (immediate-type sensitivity presenting as a contact-urticaria syndrome) was a frequent finding in such patients.

Special Forms Of Eczema And Contact Reactions Protein Contact Dermatitis

The published antigens causing protein contact dermatitis have been divided into the following categories (1) fruits, vegetables, spices, plants (including natural rubber latex) (2) animal proteins (3) grains and (4) enzymes. Atopic eczema patients commonly are sensitive to house dust, and some health care workers presenting with hand eczema (or contact urticaria) are sensitive to latex or glove powder. Such sensitivity is picked up with testing for immediate sensitivity. Several methods have been reported, including prick testing, ImmunoCAP or radioallergosorbent (RAST) testing, rub testing, scratch testing, and scratch chamber testing. Patch testing may or may not be positive. Persons with protein contact dermatitis may or may not have contact urticaria.

A survey of intermediary metabolism

Everything inside a living cell is continually moving and changing, forming and breaking down. At any instant, many or most of the cell's elementary machines - the protein molecules - are busily engaged in specialised individual activities. The proteins themselves are continually being produced and destroyed ( turned over ). At any instant, each mitochondrion, lysosome and segment of endoplasmic reticulum, every little region in the nucleus and in the cytoplasm, is buzzing with activity, each of its numerous proteins pursuing its appointed task. To describe the cell as a hive of industry would be to understate reality. The cell is a hive of hives of industry.

Other Therapeutic Uses for Cromolyn or Nedocromil

Systemic mastocytosis, a disease characterized by mast cell proliferation in multiple organ systems, usually features urticaria pigmentosa (brownish macules that transform into wheals upon stroking them) and recurrent episodes of flushing, tachycardia, pruritus, headache, syncope, abdominal pain, or diarrhea. Because it inhibits mast cell degranulation, orally administered cromolyn has some efficacy in mastocytosis, particularly for symptoms involving the gastrointestinal tract. However, cromolyn does not reduce plasma or urinary histamine levels in patients with mastocytosis.

Unconventional Theories Of Allergy

Numerous substances are tested, including the common atopic allergens, food extracts, chemicals, drugs, and hormones. Because each test substance must be administered separately to elicit symptoms, testing to multiple substances is extremely time-consuming. It has been shown, however, that patients cannot distinguish test extracts from placebo controls by this procedure, so the basis of a positive test is merely the power of suggestion. It is therefore worthless for diagnosis, and there is the potential danger that delivery by the sublingual route of an allergen to a patient with a true IgE-mediated allergy might cause life-threatening angioedema of the buccal mucosa or even systemic anaphylaxis.

Differential Diagnosis

Hypotension, pallor, diaphoresis, weakness, nausea, vomiting, and bradycardia are classically seen in these reactions. Patients lack the urticaria, pruritus, angioedema, tachycardia, and bronchospasm that are commonly seen in anaphylaxis. The characteristic bradycardia can be used as a differential diagnostic factor to distinguish these episodes from anaphylaxis. Symptoms are almost immediately reversed by recumbency and leg elevation. Other forms of shock, such as hemorrhagic, cardiogenic, and endotoxic shock, must be included in the differential diagnosis of anaphylaxis. These forms of shock, however, are usually not difficult to distinguish from anaphylaxis. The most common condition mimicking anaphylaxis is the vasodepressor (vasovagal) reaction. It is distinguished from anaphylaxis by lack of urticaria, pruritus, angioedema, tachycardia, and bronchospasm. Ingestion of saurine, which is contained in spoiled fish, can result in scombroidosis. Saurine is a histamine-like chemical...

Uses of Antihistamines

Urticaria As with allergic rhinitis, antihistamines are the drug of choice in patients with urticaria. The primary symptom in urticaria is pruritus. Antihistamines exert their major suppressive activities on this symptom. They are usually less effective in reducing wheal size. For patients with chronic urticaria, daily administration may be most effective. When H1 antihistamines alone are insufficient, addition of H2 antihistamines may improve symptom control. There are very few studies examining the use of second-generation H1 receptor antagonists in atopic dermatitis. Because of the inflammatory nature of this disease, it is expected that they would be less effective than they are in urticaria. Nonetheless, it is customary to use antihistamines in the therapy of atopic dermatitis, and because, at least a portion of the symptoms appears to be related to the release of histamine, there is strong rationale for their use. However, in the treatment of atopic dermatitis, the use of...

Natalizumab Multiple Sclerosis [6874

More common than observed with placebo. Serious hypersensitivity-like reactions were experienced in 1 of the natalizumab group. In these cases, adverse effects usually developed within two hours of the onset of the infusion. The symptoms included urticaria, fever, rash, rigors, dizziness, pruritus, nausea, flushing, dyspnea, hypotension, and chest pain. Antibodies to natalizumab are believed to be responsible, and any patient experiencing hypersensitivity should discontinue further treatment. Since adequate studies have not been performed in the pregnant, pediatric, and elderly, natalizumab is currently contraindicated in these patient populations. In addition, this drug should not be taken concurrent with medications that suppress the immune system, such as, corticosteroids the combination increases the risk for serious infections. With a dose of 300 mg to MS patients, the long half-life of 11 4 days results in a once-a-month trip to the physician for the one-hour infusion....

Approach to the Allergic Patient

Esinophil Allergic Disease

Allergy can affect virtually any organ system. Common types of presentation include conjunctivitis (eyes), rhinitis (nose), urticaria and angioedema or atopic (allergic) dermatitis (skin), asthma (lungs), and anaphylaxis (multiorgan). Evaluation of suspected allergy must include a detailed medical history, comprehensive physical examination, and appropriate diagnostic tests. Hives Hives Hives A good drug history is necessary because medications often contribute to the allergic presentation. There are many examples. Frequent use of decongestant nasal spray can lead to rebound nasal congestion, also called rhinitis medicamentosa. Over-the-counter preparations (such as aspirin or nonsteroidal anti-inflammatory compounds, vitamins, and alternative remedies and herbal supplements), often not considered medication by the patient, may be causal factors in urticaria. Likewise, angiotensin-converting enzyme inhibitors and oral or ocular p-blockers may lead to cough or worsening of asthma....

Other Food Intolerance Reactions That May Be Confused With Allergy

Reactions, such as anaphylactoid events following ingestion of scromboid fish protein, are described under Mechanisms. Urticaria may occasionally occur following ingestion of certain foods containing histamine or as histamine reactors as listed in Table 3. Examples include cheese, alcohol, red wine, or strawberries. Adverse reactions to food additives are not nearly as common as is generally believed. Reactions to BHA, BHT, benzonates, and nitrates are very rarely substantiated by objective measurements. The most common FDA-reported food additive reactions are those to aspartame, and the usual type of symptom is headache. Fifteen percent of reports of adverse effects from aspartame, however, are allergic-like, usually urticaria. Although there are two documented cases of aspartame-induced urticaria angioedema reported in the world literature, a recent large nationwide, multicenter study using DBPCFC was unable to confirm a significant association between aspartame and urticaria. The...

Diagnostic Tests in Allergy

The concept of diagnostic testing in allergy has been confusing for many years. Although there are many potential sources for the confusion, a major source has been commercial companies that market diagnostic tests as if a laboratory test could diagnose a patient with allergic disease. These companies imply that the diagnosis of allergic disease is as simple as drawing a blood sample and sending it to them. Allergic diseases can be diagnosed only from the patient's history of symptoms and compatible physical findings. Without a detailed history and physical, the results of skin tests or tests for allergen specific immunoglobulin (Ig)E are meaningless. For example, what does a positive test for cat-specific IgE mean A patient with a positive test for cat-specific IgE may be asymptomatic, have rhinitis, have asthma, or have hives from exposure to cats. The test result is meaningless without the clinical history. If the patient has a consistent history of rhinitis every time he or she is...

Metabolism And Inactivation

(1) Local allergic reactions, which are of three types. The commonest is the late-phase reaction, a biphasic IgE reaction characterized by immediate burning and pruritus with a wheal and flare at the injection site. It may resolve or become indurated, with pruritus continuing for hours to days. Two rarer forms are the Arthustype reaction, producing a pruritic painful nodule 6-8 h after injection, and the delayed hypersensitivity reaction, which is similar but appears 12-24 h after injection. The local reactions are characterized by swelling, erythema, pruritus and lipoatrophy at injection sites they usually disappear with continued treatment. Generalized allergy may produce urticaria, angioedema and, very rarely, anaphylactoid reactions if continued therapy with insulin is essential, desensitization procedures may need to be performed (Wintermantel et al., 1988). Local allergy was extremely common in the 1960s with the use of impure insulins, but the reported prevalence in patients...

Common Honey Bee Viruses

CBPV mainly attacks adult bees and causes two forms of paralysis symptoms in bees (Bailey, 1975). The most common one is characterized by an abnormal trembling of the body and wings, crawling on the ground due to the flight inability, bloated abdomens, and dislocated wings. The other form is identified by the presence of hairless, shiny, and black-appearing bees that are attacked and rejected from returning to the colonies at the entrance of the hives by guard bees. Both forms of symptoms can be seen in bees from the same colony. The variation in the disease symptoms may reflect differences among individual bees in inherited susceptibility to the multiplication of the virus (Kulincevic and Rothenbuhler, 1975 Rinderer et al, 1975).


Reactions to insulin include local or systemic reactions and insulin resistance. Although human recombinant DNA insulin appears to be less antigenic than bovine-type insulin, it can cause allergic reactions. Local reactions are the most common and are generally encountered during the first 1-4 wk of therapy. They are usually IgE-mediated and consist of mild erythema, swelling, burning, and pruritus at the injection site. These local reactions usually disappear in 3-4 wk with continued administration of insulin. Dividing the insulin dose into two or more sites or switching to a different preparation is generally helpful. If not, antihistamines may be given until the reaction disappears. Local reactions may precede anaphylactic reactions. Therefore, epinephrine should be available to these patients. Systemic reactions include urticaria, angioedema, bronchospasm, and hypotension. Most of these reactions occur upon re-starting of insulin after an interruption in therapy. In treatment of...

Radiocontrast Media

Patients who experience a reaction have urticaria. Reactions to radiocontrast media are not IgE-mediated but probably involve mast cell activation with release of histamine and other mediators. Use of nonionic, lower osmolality agents reduces the risk of a reaction. Unfortunately, their use is limited because of higher expense. In patients who receive p-adrenergic blocking agents, the reactions may be more severe and less responsive to treatment. There is no association between reaction to radiocontrast media and topical iodine solution or shellfish allergy.

Robert E Reisman md

Anaphylaxis resulting from insect stings is estimated to affect 0.3-3 of the population and is responsible for at least 40 deaths a year in the United States. In addition, increasing numbers of reactions are caused by stings of the fire ant, a nonwinged Hymenoptera present primarily in the southeastern United States. Anaphylactic symptoms are typical of those occurring from any cause. The majority of reactions in children are mild, with dermal (hives, angioedema) symptoms only. The more severe reactions, such as shock and loss of consciousness, can occur at any age, but are relatively more common in adults. After an initial anaphylactic reaction, about 60 of unselected people will continue to have reactions from subsequent re-stings. The natural history of this disease process is influenced by age and severity of anaphylaxis. Children who had dermal reactions only have a very benign course and are unlikely to have recurrent re-sting allergic reactions. People who have had severe...


The most common symptoms are dermal, generalized urticaria, flushing, and angioedema. The most severe symptoms, which may be life-threatening, include respiratory distress as a result of asthma and upper airway swelling, circulatory collapse, and shock. Other symptoms include nausea, bowel cramps, diarrhea, rarely uterine cramps, and a feeling of impending doom. Anaphylactic symptoms usually start immediately after a sting, within 10-30 min. On rare occasions reactions have started after a longer time interval.

Unusual Reactions

Serum-sickness-type reactions, characterized by urticaria, joint pain, and fever, have occurred approx 7 d after an insect sting. Individuals who have this reaction are subsequently at risk for acute anaphylaxis after repeat stings and thus are considered candidates for VIT.


The primary medication for treatment of anaphylaxis is epinephrine. Individuals at potential risk should be given epinephrine, available in preloaded syringes, (Epi-Pen, Center Laboratories, Port Washington, NY Twinject, Verus Pharmaceuticals Inc., San Diego, CA). Antihistamines, such as diphenhydramine, are also recommended and may be helpful for treatment of hives and edema.

Occupational Asthma

It is estimated that 3-5 of asthmatics will reliably worsen after the ingestion of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs). Ingestion of aspirin or other NSAIDs may provoke either of two responses respiratory responses, including bronchorrhea, rhinorrhea, bronchospasm, conjunctivitis, lacrimation, and flushing or urticaria and angioedema. Rarely, combinations of the two patterns are seen. Aspirinsensitive patients may be recognized by the presence of nasal polyps, nonallergic rhinitis, persistent sinusitis, and asthma associated with moderate eosinophilia ( 1000 mm3). The frequency of NSAID sensitivity increases with age, although children and families have been described with clear-cut reactivity. There may be a wide range of associated allergies, but many subjects (about 50 ) are not allergic. The syndrome affects males and females equally the onset of first stage involving allergic rhinitis and asthma occurs around the age of 30 yr, while the vasculitis...

Medical Therapy

Treatment guidelines have recently been developed by expert panels for both children and adults with acute sinusitis. These consensus statements emphasize that antibiotics are the primary form of treatment for acute sinusitis. For patients with uncomplicated acute bacterial sinusitis that is mild to moderate in severity (Table 4) who have not recently been treated with an antimicrobial, amoxicillinis recommended at a dose of 45 mg kg d in two divided doses. If the patient has had a history of a late-onset rash to amoxicillin (non-type-1 hypersensitivity reaction), either cefdinir (14mg kg d in one or two doses), cefuroxime (30 mg kg d in two divided doses), or cefpodoxime (10 mg kg d once daily) can be used. In cases of type 1 systemic reactions (including immediate-onset urticaria), clarithromycin (15 mg kg d in two divided doses) or azithromycin (10 mg kg d on day 1, with 5 mg kg d 4 d as a single daily dose) can be used. Alternative therapy in the penicillin-allergic patient who is...

Albert F Finn Jr md

Pathophysiology of Urticaria and Angioedema Treatment of Urticaria and Angioedema Conclusion Suggested Reading One in five individuals will suffer from hives at some point during his or her lifetime. These individuals usually look to their family doctor for help. As such, patients presenting with hives will be a common occurrence in the primary care setting. Clinicians will need to develop an approach that determines treatment needs based on triggers, duration, and underlying cause. If medications are recommended, these need to provide symptom relief however, not intolerable side effects. Short-lived episodes are generally amenable to antihistamines, though chronic urticaria requires a skilled approach. Recognition of underlying causes requires diligence, but may suggest a need for modifiers of systemic autoimmune diseases. Research efforts continue to yield information on mechanisms of pathophysiology. Key Words Angioedema anti-IgE receptor antibody autoimmune thyroid disease chronic...


First and foremost, in establishing a diagnosis the primary care clinician knows the importance of a complete history and physical examination of the patient. The patient with urticaria or angioedema typically is assigned the correct diagnostic classification following the history and physical examination. This information establishes whether the disease process is acute or chronic. Hives or swelling persisting beyond 6 wk will be assigned to the chronic designation. Questioning will reveal whether those cases with a duration of more than 6 wk represent recurrent episodes of acute urticaria following inadvertent ingestion or exposure to allergens. A history will reveal whether a child has had an acute viral prodrome and or is taking antibiotics for a presumed bacterial infection. Furthermore, a careful history will reveal medications or OTC preparations that can result in urticaria. Review of the patient's dietary history is paramount in determining whether foods in the diet or food...

Anti FcP Rl IgG

Is capable of causing degranulation from dermal mast cells. Various methods used in several laboratories have confirmed the capability of this IgG autoantibody to elicit histamine release from mast cells and basophils. These methods have included the induction of degranulation from rat basophil leukemic cells transfected with the a subunit of the IgE receptor, degranulation of human basophils, and degranulation of cutaneous mast cells. Further, the specific target of this IgG autoantibody is the a subunit of the high-affinity IgE receptor found on basophils and mast cells (Fig. 4). Studies have demonstrated this anti-IgE receptor autoantibody (Fig. 5) in approx 35-45 of patients with the diagnosis of chronic idiopathic urticaria. With this evolving insight into the autoimmune activity present in patients with chronic idiopathic urticaria, a growing consensus supports the idea that the histopathological lesions are secondary to autoantibody-dependent activation of cutaneous mast cells....

John A Anderson md

Adverse reactions to foods can be divided into those that are allergic and those resulting from food intolerance. Allergic food reactions are IgE-mediated and are usually limited to individuals with other atopic diseases such as allergic rhinitis, atopic dermatitis, and allergic asthma. The serious form of IgE-mediated reactions to food is anaphylaxis. The most common foods to cause this are peanuts, shellfish, and tree nuts. Acute urticaria from foods is also most commonly caused by these three agents. Atopic dermatitis can be related to food allergy as well. Key Words Anaphylaxis, acute urticaria, double blind placebo controlled food challenge, atopic dermatitis, food intolerance

Food Anaphylaxis

The signs and symptoms of anaphylaxis resulting from food allergy are no different from those of anaphylaxis as the result of allergy to P-lactam antibiotics, stinging insects, or natural rubber latex. The symptoms and signs may be mild or severe. Milder symptoms signs include contact urticaria, generalized pruritus, erythema, and urticaria with or without angioedema. More severe symptom signs occur with generalized systemic anaphylaxis from a food and may be multiple or single in nature. These symptoms include laryngeal edema, rhinitis with or without conjunctivitis, asthma, blood pressure decrease, or shock and possible cardiovascular collapse and death. Occasionally, additional symptoms include nausea, vomiting, abdominal cramps, diarrhea, and uterine or bladder cramps. A second food-specific anaphylactic syndrome is F-EIA. EIA is a relatively newly described physical urticaria in which vigorous exercise is associated with urticaria or shock. In half the cases, this syndrome...


Most individuals who develop food allergies have other manifestations of allergy or have family members with allergic disease. This includes atopic dermatitis, urticaria, asthma, and allergic rhinitis conjunctivitis. A history of asthma in a food-allergic individual should be considered a risk factor for possible serious life-threatening reactions of an anaphylactic nature to that food. Certain foods are associated with different types of allergic and intolerance reactions (Table 3). This should be kept in mind when taking a history of the presenting complaint. Most food anaphylactic reactions (e.g., urticaria or systemic anaphylaxis) occur within minutes (and almost always within 2 h) after exposure to the food. In these types of cases, it is often easier to pin down a likely food candidate because of the close association in time. More difficult are cases in which the problem is chronic (e.g., atopic dermatitis) and in which many nonallergic factors play a role. In studies involving...

Food Diary and Diets

Food diaries may be helpful in the patient with a history of several, but intermittent, episodes of acute urticaria or other symptoms suspected of being related to diet. If there is no obvious cause, a diary of events, including a diet for subsequent episodes, may be helpful in pinning down the ultimate diagnosis.


Systemic anaphylaxis and anaphylactoid reactions Generalized urticaria and angioedema Serum sickness-like reactions Drug fever Type I IgE-antibody-mediated (e.g., P-lactam antibiotics, insulin urticaria or anaphylaxis) Type II antitissue cytotoxic antibodies (e.g., drug-induced hemolytic anemia or thromocytopenia) Skin (e.g., pruritus, maculopapular, morbilliform and erythemic rashes, urticaria angioedema, erthema multiforme, fi xed drug eruptions, phototoxic and photoallergic reactions) Reactions to aspirin and nonsteroidal anti-inflammatory agents Reactions to enzyme inhibitors (e.g., ACE inhibitor-induced angioedema) Reactions involving histamine release (e.g., vancomycin red man syndrome)

Generalized Reaction

Anaphylaxis and anaphylactoid reactions to drugs and other therapeutic agents have the same signs and symptoms of reactions as other agents that frequently cause allergic reactions (e.g., insect stings, foods, natural rubber latex). Reactions range in severity from mild pruritus, skin erythema and urticaria angioedema to more generalized and systemic reactions of laryngeal edema, rhinitis conjunctivitis, asthma, shock, and possibly death. IgE sensitization is involved with the following drug reactions p-lactam antibiotics, insulins, protamine, blood products, chymopapain, monoclonal antibodies, vaccines, natural rubber latex used in drug-delivery systems, ethylene oxide used to clean dialysis agents, or neuromuscular agents used in anesthesia induction. Anaphylactoid reactions may occur to sulfa RCM, ASA, NSAIDs, local general anesthetics, ACE-IN, vancomy-cin, chemotherapeutic agents, protamine, and monoclonal antibodies and blood products. Other generalized allergic-like drug...

Initial Measures

Initially, when an adverse drug reaction is suspected, especially when associated with significant symptoms, the drug should be discontinued (Table 4). Any treatable signs and symptoms should then be promptly attended to. Simple pruritus and urticaria with or without angioedema will usually improve with a H antihistamine such as over-the-counter (OTC) diphehhydramine (Benadryl) 25-50 mg, two to four times daily or loratadine (Claritin) 10 mg 1-2 times daily. Prescribed nonsedating antihistamines such as cetririzine (Zyrtex) 10 mg, fexofenadine 60-180 mg, desloratadine (clarinex) 5 mg, or sedating hyroxyzine (atarax) 10-25 mg are also effective. These latter drugs are usually recommended one time daily, but may be used two times daily if the symptoms are more severe and the drugs are tolerated. Usually, systemic corticosteroids are prescribed for short periods until out patient follow-up. The type of specific medication, route and dosage will depend upon the situation. Since use of ASA...


There is no skin test or in vitro test available to confirm the presumptive diagnosis of ASA NSAID intolerance in patients who have a history of allergic-like reactions (e.g., urticaria or asthma). The usual management is to advise the individual to avoid these drugs strictly. A graded drug challenge (beginning with no more than 3 or 30 mg of ASA, depending upon the history of sensitivity, and advancing to 60, 100, 150, and 300 mg at 3-h intervals) can be done under controlled conditions, but such a challenge is usually not advocated in most clinical situations. ASA desensitization has proven successful in patients with ASA-sensitive asthma, but not with most individuals with ASA NSAID-induced urticaria, angioedema, or anaphylactoid reactions. Most allergic-like reaction to ASA or NSAID are a result of the COX-1 inhibitor portion of these drugs (see Mechanisms of Action). COX-2 inhibitor drugs have been shown to be safe in ASA-induced asthma. However, some individuals who have had...


As described under mechanisms of action, ACE-INs can be associated with either a cough or angioedema of the throat, which can be severe and life threatening. The most important aspect of acute management is to recognize the possible relationship between the clinical symptoms and signs of these conditions and the drugs. Long-term ACE-INs should be avoided. Switching to another ACE-IN or to an A-II RAS is not advised since both drug types has been shown to cause the same symptoms in some patients. The cough associated with ACE-INs (occurs in up to 25 of patients) generally resolves over a few weeks, after the drug is discontinued. Angioedema is more serious but occurs in fewer patients (0.1-0.7 ). The symptoms tend to resolve with 24-48 h after discontinuing the drug. In an emergency situation, life-threatening angioedema usually responds to epinephrine, antihistamines, antileukotrienes, corticosteroids, and possibly anticholinergic drugs. Recently it has been shown that when these...


Allergic urticaria, serum-sickness-like reactions, systemic hypersensitivity reactions Abbreviation GI, gastrointestinal. The side effect profile (Table 2) of doxycycline and minocycline also differs, most notably in the incidence of photosensitivity with doxycycline and the occurrence of hypersensitivity reactions with minocycline. Photosensitivity is very common at higher doses of doxycycline. The minocycline hypersensitivity reactions are uncommon and include urticaria, serum sickness-like reactions, and what has been termed a lupus-like reaction that in reality is probably not an activation of systemic lupus erythematosus but a generalized drug-induced reaction that resembles lupus (34).

Risk Factors

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are important causes of anaphylactoid events. These reactions are not IgE-mediated. They apparently produce anaphylactoid reactions through the aberrant mechanism of arachidonic acid, with inhibition of cyclooxygenase and subsequent increased production of leukotrienes. However, some episodes may be caused by the direct degranulation of mast cells. Adverse reactions to aspirin typically include urticaria, angioedema, asthma, chronic rhinosinusitis, and nasal polyps in sensitive individuals. Because the sensitivity persists for life, management entails strict avoidance. Acetaminophen is the alternative recommended drug. Studies have suggested that the cyclooxygenase-2 inhibitors are safe in aspirin-sensitive asthmatics, but they do not have Food and Drug Administration (FDA) approval at this time. Salsalate, choline salicylate, magnesium salicylate, and propoxyphene hydrochlo-ride are the other drugs that can be used....

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