DRUGS

Medicines often are implicated in triggering undesired immunologic reactions. True drug allergy represents 6 –10% of all adverse drug reactions and is overreported by individuals. Most drugs are too small (
1000 Da) to incite allergic sensitization alone. To cause an allergic reaction, a reactive metabolite of the drug must bind to a macromolecular carrier for antigen processing. The drug metabolite in the carrier molecule complex is known as a hapten. This makes skin testing difficult for diagnostic accuracy. Large molecular weight drugs (heterologous antisera, insulin, streptokinase, and l-asparaginase), which are 4000 Da, and medicines that have enough distance between determinants to be bivalent (quaternary ammonium muscle relaxants and aminoglycosides), may provoke an allergic response without forming a hapten–protein complex. 

LATEX 

Natural rubber latex is a product of the rubber tree Hevea brasilensis. Sensitization is present in 75% of patients with spina bifida and 6.5% of the general population. Health care providers and patients with urological problems requiring catherization are also at increased risk. Clinical manifestations of IgE-mediated disease include allergic rhinitis, asthma, contact urticaria, and anaphylaxis. The incidence of IgE-mediated reactions to latex has declined mostly because of the development of powder-free, low-protein gloves. 

INGESTED ALLERGENS 

Food allergy is common and appears to be increasing; it can be divided into class 1 and class 2. Class 1 food allergy is considered “traditional” and occurs in the gastrointestinal tract. Class 2 food allergy is caused by allergic sensitization to inhalant allergens that cross-react with food allergens. Class 1 allergens are 10 –70 kDa and are heat, acid, and protease stable. Common class 1 allergens are cow’s milk, chicken egg, peanut, soybean, fish, and shrimp. Thirty-five percent of children with moderate to severe atopic dermatitis have an associated food allergy,15 and 6% of asthmatic children have associated food allergy. Peanut is the most common food allergy in individuals 4 years old. There has been a dramatic increase in the number of children with peanut allergy with one study noting peanut allergy prevalence of 1.4% in 2008 versus 0.8% in 2002 in the United States. Studies are currently looking at environmental factors that may result in this increased prevalence. 

Cross-reactivity between members of a food allergen group varies. Cross-reactivity between peanuts and other legumes is 5%, between tree nuts 35%, between different fish 50%, and 75% between members of the shellfish family. Cross-reactivity also occurs between aeroallergens and certain food allergy resulting in class 2 food allergies. This is known as pollen–food syndrome (previously oral allergy syndrome) and manifests as pruritus with or without angioedema of the lips, tongue, palate, and posterior oropharynx. Shared allergen sensitivities have been reported between ragweed and the gourd family (watermelon, cantaloupe, zucchini, and cucumbers) and bananas. Birch pollen shares allergen sensitivities with apples, carrots, parsnips, celery, hazelnuts, potatoes, celery, and kiwi. Tree and grass pollen share allergens with apples, tree nuts, peaches, oranges, pears, cherries, fennel, tomatoes, and carrots. Often, cooking or peeling these foods reduces symptoms of pollen–food syndrome.

Reviewing the properties of common allergens reinforces the foundation of controlling clinical allergy symptoms, which is avoidance of allergen exposure. Their properties also form the basis for developing diagnostic and therapeutic opportunities.

IMMUNOLOGY

 • An allergen is typically a protein or glycoprotein that can induce an IgE-mediated immune response with an associated clinical reaction. 

 • Size of pollen determines clinical manifestation of allergy. Particles between 20 and 60
m in diameter can be carried in the wind and cause nasal and ocular symptoms. Particles
7
m can deposit in the airways and cause symptoms of asthma. 

• True drug allergy represents 6 –10% of all adverse drug reactions. Skin testing is difficult because most drug allergens are small metabolites of the implicated drug and they must haptenize a carrier protein to induce an immune response. 

CLINICAL PEARLS

 • Most tree pollens do not have significant cross-reactivity and are released in the spring in the United States. In the upper midwestern United States, tree pollination occurs in mid to late March until May. 

• Grass pollen comes from the Poaceae family, has significant cross-reactivity, and is typically released in the late spring and early summer in the United States. In the upper midwestern United States, this time is from mid-May to the end of July. 

• Weed pollens are released mostly in the autumn in the United States with ragweed being the major allergen from August 15 to October 1 in the upper midwestern United States. 

• Global warming has shifted the floristic zones in North America to higher latitudes. Ragweed has increased in size and pollen production because of increased CO2 and temperature. 

• Fungal spores and mycelial elements are released preferentially in warm, humid environments. The first hard frost of late autumn decreases outdoor mold spores. 

• Dust mites thrive in warm, humid conditions and provide allergen through their fecal particles, enhanced by intrinsic enzymic activity. 

• Cat allergen may last in a home for up to 6 months after the source is removed. It can be isolated from saliva, urine, dander, and from sebaceous glands.

• The most common class I food allergens are cow’s milk, chicken egg, peanut, soybean, fish, and shrimp. There has been an increase in the prevalence of peanut allergy in children. 

• Pollen–food syndrome occurs because of cross-reactivity between aeroallergens and certain food proteins.