Clinical rationale for obtaining a precise diagnosis

Journal of Family Practice, April, 2004 by Leonard M. Fromer

* THE SCOPE OF THE PROBLEM

Allergic diseases present as a constellation of symptoms and signs that overlap with many nonallergic etiologies. For example, undifferentiated upper respiratory symptoms may represent seasonal or perennial allergic rhinitis. In a nonallergic patient, the same symptoms may stem from myriad etiologies, including infectious, vasomotor, or anatomic conditions. The challenge is to establish an accurate diagnosis, because appropriate management of various allergy-like symptoms may differ substantially at times. Indeed, the increasing specificity of treatments and the rising costs of pharmacotherapy lend special weight to diagnostic precision.

In the United States, 40 to 50 million people have allergic disease. (1) In 2001, for example, 12.3 million office visits were coded for chronic rhinitis, 10.1 million for allergic rhinitis, and 11.3 million for asthma (2) These numbers do not include other conditions with a possible allergic component, such as atopic dermatitis, and some cases of conjunctivitis and otitis media. Allergic diseases in some form are the sixth leading cause of chronic disease in the United States. (3)

* CLINICAL CONCEPTS

Allergy march. IgE-mediated allergic disease progresses in a predictable manner sometimes called "the allergy march" (Figure 1). The formation of IgE antibodies starts early in life, and the antibodies can often be detected before clinical symptoms emerge. Food antigens have the earliest sensitization, and it frequently precedes problems with inhalant allergens? Sasai et al showed that the presence of antibodies to egg white at 6 months of age was a strong predictor of future allergy to house dust mite (P=.0001 [level of evidence: 3]). (5) Young children with a diagnosis of atopic dermatitis and a positive family history of asthma have a 40% risk of subsequent asthma. (6)

[FIGURE 1 OMITTED]

Allergic threshold. Allergic sensitization is a cumulative process, rather than an "all or nothing" phenomenon. When the allergen load accumulates beyond an individual's threshold of tolerance, clinical symptoms become evident (Figure 2). Clinical manifestations correspond to age, with eczema predominating in the youngest age group, followed by gastrointestinal symptoms and later by respiratory symptoms. (7)

[FIGURE 2 OMITTED]

While the most recent allergen exposure precipitates symptoms, multiple allergens may be responsible for pushing a patient beyond the symptomatic threshold. For example, the patient described in Figure 2 may be sensitized to mold, dust-mite, and (;at allergens, but symptoms appeared only after a cat was obtained as a pet. Reducing the level of mold and dust-mite exposure (eg, by avoidance) may be sufficient to relieve symptoms and allow the patient to keep the cat.

The concept of the allergic threshold was suggested in studies by Boner et al of children with allergic asthma who were moved back and forth from a low-altitude, allergen-rich environment to a high-altitude (1,756 m), allergen-free environment in the Italian Alps. (8,9) Clinical improvement (ie, improved pulmonary function test results and decreased need for medication) was noted at high altitude, as were decreased serum levels of total IgE and eosinophil activation (LOE: 3).

* IS IT REALLY ALLERGY?

Despite the millions of people who have bona fide allergic disease, many millions more think they do. A study by Szeinbach et al conducted in a managed care organization suggests that as many as two-thirds of patients with allergic symptoms may be misdiagnosed. (10) The investigators identified 244 patients who were being treated with nonsedating antihistamines for allergic rhinitis. Specific IgE blood testing determined that only 35% of these patients had abnormally elevated IgE levels; the remaining 65% did not.

Thus, in this study nearly two thirds of the patients who took antihistamines presumably did not need them. Indeed, without diagnostic testing, it is often difficult to accurately differentiate allergic from nonallergic conditions. In a study by Williams et al, when the diagnosis of specific allergic sensitization by history and physical examination alone was compared with results from skin-prick and blood testing for specific IgE, the ability of allergy specialists to accurately predict allergic sensitization rarely exceeded 50% (LOE: 3). (11)

With respect to respiratory symptoms, a recent report from the Agency for Healthcare Research and Quality (AHRQ) stated, "No studies were found that specifically sought to differentiate between allergic and nonallergic rhinitis on the basis of clinical symptoms, signs on physical examination, or the presence or absence of comorbid conditions. The minimum level of testing necessary to confirm or exclude a diagnosis of allergic rhinitis has not been established in the literature.... No diagnostic test has been specifically developed to diagnose nonallergic rhinitis. Given the absence of studies to differentiate nonallergic rhinitis, diagnostic testing rather than symptoms or signs is necessary to differentiate isolated vasomotor or nonallergic rhinitis from allergic rhinitis." (12)