3gAllergy™
Improves Allergy Patient Care

Traditionally, allergy specialists were considered to have the primary responsibility for the diagnosis and care of allergic patients. Because of recent changes in the healthcare systems in many parts of the developed world, however, the primary care physician is now expected to make an allergy diagnosis and decide whether to treat or refer the patient to a specialist. DPC offers 3gAllergy™, an ultrasensitive, third-generation assay for the quantitative, in vitro measurement of allergen-specific IgE. 3gAllergy is a reliable, convenient tool that can help the primary care physician diagnose and monitor patients with allergic disease or qualify and refer complex cases to an allergy specialist, thereby improving patient care.

Changing diagnostic methods
The preferred diagnostic tool of allergy specialists has long been in vivo testing, typically the skin prick test. This test is a safe and sensitive procedure in the hands of a trained and skilled specialist, whose knowledge is necessary for correct interpretation. In addition, the risk of an anaphylactic reaction to the procedure requires a trained staff and a properly equipped office.

In vitro allergen-specific IgE testing began with the first-generation radioallergosorbent test (RAST), introduced in the early 1970s. It found limited acceptance among allergists and laboratories worldwide because it failed to correlate closely with the skin prick test in terms of sensitivity, specificity and reproducibility, nor did it offer the automation and system productivity that laboratories desired. The second-generation RAST, introduced in the 1980s, exhibited good correlation to skin prick testing in terms of specificity, positive predictive value (PPV) and negative predictive value (NPV),^1,2 and it offered an improved turnaround time. But it was still less sensitive than the skin prick test and still fell short of addressing laboratories' need for automation and random access. The same decade saw the advent of managed care and a broadening of the responsibility placed on the primary care physician.

Among non-allergy specialists, it is a common practice today to bypass diagnostic testing and to jump from symptoms to prescription of treatment on the assumption of allergy. But as many as two-thirds of patients with allergy-like symptoms may be misdiagnosed as allergy patients, according to a US study conducted in a managed care organization, and over 65 percent of patients who took antihistamines did not need them because they did not have allergy.³

Click image to enlarge.

Figure 1. A complete testing paradigm such as the one pictured here includes clinical diagnostic testing-either in vivo or in vitro. In vitro testing with an assay such as DPC's 3gAllergy allows for the identification of allergen-specific IgE (sIgE) and monitoring of the the treatment plan's effect on circulating sIgE levels.

A simpler solution for physicians and laboratories
In 2001, DPC introduced on its IMMULITE^® 2000 immunoassay system the first FDA-cleared, third-generation assay for allergen-specific IgE. Named 3gAllergy and now offering more than 360 allergens and allergen panels, it is a convenient tool to assist the primary care physician in arriving at a diagnosis of allergy when used in combination with a clinical examination and patient history. 3gAllergy is a safe alternative to in vivo methods and therefore particularly desirable for use with patients who have a history of anaphylactic reactions. It is well suited for patients with skin conditions such as eczema or dermatographism, and it allows testing of patients without requiring them to stop taking their allergy medications. Numerous studies demonstrate good correlation with in vivo and laboratory methods.⁴

3gAllergy also addresses the needs of the laboratory. Now available on both the IMMULITE 2000 and the IMMULITE^® 2500, it provides full automation, random access processing, a rapid turnaround time of about one hour, and consolidation of allergy testing and other immunoassays on the same platform. Because 3gAllergy is performed just like any other immunoassay, it eliminates the need for dedicated equipment or extensive training of staff.

The lowest detection limit of any specific IgE assay
3gAllergy has advanced allergy testing to a new level of precision, analytical sensitivity and functional sensitivity. Its enzyme-enhanced chemiluminescence technology detects IgE at a lower concentration than any other in vitro allergy immunoassay, for a functional sensitivity of 0.2 kU/L and a low-end detection limit of 0.1 kU/L. 3gAllergy also demonstrates linearity under dilution down to this detection limit, with dilution factors ranging from 1 to 1000 rather than from 1 to 100 as with second-generation in vitro IgE tests.⁵ What this means for patient care is that it is possible to detect allergy earlier and start treatment sooner.

Importance of diagnosing allergic disease
The incidence of allergy and asthma in both developed and developing nations is on the rise. According to WHO statistics for the year 2000, asthma afflicts 100 to 150 million people worldwide, and causes more than 180,000 deaths each year.⁶ The economic burden of the condition exceeds that of tuberculosis and HIV/AIDS combined.⁷ In the US, allergy is the sixth leading cause of chronic disease, and costs to the healthcare system total $18 billion per year; allergic diseases afflict an estimated 50 million Americans; and allergic rhinitis accounted for 14 million doctor's office visits in 2002.⁸ In Europe, allergy sufferers number 80 million.⁹

Although allergy is a common cause of disease, the less serious manifestations (such as allergic rhinitis) have not always been viewed as requiring the effort necessary to arrive at a proper diagnosis. But the progression of allergic disease is better understood today. If at one time the general perception of allergy was that it was a common but relatively minor nuisance, it must no longer be regarded as such. There is need to recognize it early and intervene to prevent progression to more serious allergic manifestations. With 3gAllergy, a convenient tool is now available to the primary care physician and the clinical laboratory to improve the quality of allergic patients' care. By correctly identifying the underlying allergens that are responsible for allergic disease and its symptoms, the physician can be alerted to strive to halt the progress of the allergy march; to address a variety of allergic conditions appropriately; and to maintain patients below their symptomatic allergic threshold.

The allergy march

Atopic dermatitis
Atopic dermatitis (AD) may present at any age, but usually appears in infancy and is one of the most common skin disorders seen in infants and children. It is often the first manifestation of the allergy march, which proceeds from AD to allergic rhinitis and asthma. The allergy march illustrates the point that IgE-mediated allergic disease often advances in a predictable manner. Clinical symptoms correspond to age, with eczema found in infants and young children, followed by gastrointestinal manifestations and, during preteen and teenage years, by respiratory conditions such as asthma. Children with atopic dermatitis and a positive family history of atopy have a 40 percent risk of developing asthma.¹⁰

One airway, one disease
It has been suggested that rhinitis and asthma are two manifestations of one syndrome.¹¹ Rhinitis, which is at least three times as common as asthma, is documented in 85 to 95 percent of patients with asthma, provided an adequate history is taken;¹¹ and studies have demonstrated that allergic rhinitis increases a patient's risk of developing asthma.¹²

Allergic rhinitis (AR) may be seasonal or perennial. Seasonal AR is also known as hay fever, while perennial AR is also known as rhinoconjunctivitis. Aeroallergens such as pollens and molds in spring, summer and/or early fall are usually the cause of seasonal AR. Seasonal AR is strongly associated with sinusitis, otitis media, nasal polyps, sleep apnea and asthma. Perennial AR symptoms are year-round and are generally related to house dust mites, animal hair or dander, and mold spores. Some patients may suffer from both seasonal and perennial AR. In these patients, the low-level monitoring of allergen-specific IgE, which is possible with 3gAllergy, affords the physician an opportunity to adopt the best treatment protocol for the patient.

Asthma is a chronic disease in which the bronchial tubes of the lungs are chronically inflamed and the muscles around these tubes tighten to constrict the airways. Acute inflammation of airways occurs as a result of exposure to aeroallergens or other asthma triggers such as stress; smoke; certain smells such as perfumes; activities such as sports; weather conditions such as dry wind or cold air; and respiratory infections such as sinus infections, flu and throat infections.

Asthma may be developed at any age, but it is routinely diagnosed in children younger than age 5 and in adults in their thirties. Fifty percent of adults with asthma suffer from allergic asthma; the number for children is close to 80 percent.¹³ That allergic asthma is a highly morbid manifestation of the allergy march, and costly to treat, underscores the need to intervene during the early manifestations of allergic disease to avert progression to this stage.

Food allergies
Although food allergies may affect people of all ages, they are more frequent in children. It is important to differentiate a food allergy from a food intolerance. Any food can act as an allergen and result in sensitization, but in children the following six foods are responsible for 90 percent of food allergy reactions: milk, peanuts, soy, egg, wheat and tree nuts (pecans, walnuts, etc.). The same list, with the addition of fish and crustaceans (shrimp, lobster, etc.), applies for adults.

In food allergy, patients may experience itching in the mouth; vomiting; diarrhea or abdominal pain; a drop in blood pressure; and, particularly in children, atopic dermatitis, eczema and hives. Allergic reactions to food may develop rapidly into anaphylaxis, a severe, life-threatening reaction. There is no cure for food allergies.

Patients who are extremely allergic and who have severe anaphylactic reactions are not candidates for skin prick testing because of the danger it poses for them. Nor is skin prick testing possible for patients affected by eczema or dermatographism. For all of these patients, blood tests such as 3gAllergy are an excellent clinical diagnostic tool.

Other allergic conditions
Additional contexts requiring the recognition of an IgE-mediated process to allow for correct, timely treatment and to prevent serious consequences include giant papillary conjunctivitis in response to contact lenses;^14,15 sensitization to a new allergen in an injected immunotherapy extract;¹⁶ drug allergy; and insect venom allergy, in which patients with a severe reaction to an insect sting may exhibit negative skin prick test results and low levels of specific IgE detectable only with a sufficiently sensitive assay.¹⁷

Allergic threshold
A polysensitized patient may have levels of IgE specific to various allergens that cumulatively are insufficient to precipitate allergic symptoms. Sensitization to a new allergen, however, or exposure to an additional allergen to which the patient is already allergic, may easily result in pushing the total allergen load over a point at which the patient experiences allergy symptoms—the allergic threshold.¹⁸ By performing allergen-specific IgE testing, the physician can identify offending allergens. 3gAllergy testing offers the possibility of monitoring the patient's allergen-specific IgE levels at low levels. Appropriate intervention can control allergy symptoms, interrupt the allergy march in children and prevent more serious allergic disease such as asthma.

Figure 2. Allergy is a cumulative threshold disease. (a) In this example, the patient is allergic to two foods, but the combined contributions of the specific IgE (sIgE) directed against the two foods is not sufficient for the manifestation of symptoms. (b) With the addition of a pollen allergen and in the absence of an avoidance protocol for any of the three allergens, the patient's cumulative sIgE concentration exceeds the threshold value and symptoms appear. (c) With the observance of an avoidance protocol, the patient's cumulative sIgE concentration drops below the threshold level and the patient's symptoms are under control.

Conclusion
Today, the primary care physician must confirm a diagnosis of allergy and decide whether the patient can receive the appropriate treatment and necessary follow-up visits or must be referred to an allergy specialist for care. In this context, 3gAllergy is a valuable diagnostic tool to assist the primary care doctor with this decision. It is reasonable to expect that in vitro allergen-specific IgE methods such as 3gAllergy can lower costs associated with treatment and management of patients who may suffer from allergic diseases, reduce inappropriate referrals to specialists, improve the quality of patient care, and help prevent progression to more morbid disease.