Despite advances in treatment, an increase has been observed in the incidence of summer hay fever. A number of nasal steroids and newer antihistamines provide significant relief for most people with this disorder, but when these medical therapies fail, immunotherapy is a second-line option. Despite its proven efficacy, the main concern to date is whether the benefit of immunotherapy persists after it is discontinued. Durham and colleagues performed a follow-up study to evaluate the long-term efficacy of immunotherapy in patients who were previously shown to respond to this treatment.

Patients enrolled had a history of well-documented severe seasonal allergic rhinitis. They had a positive skin reaction (a wheal greater than 5 mm) to timothy grass-pollen extract and a poor response to oral antiallergy medications. These patients received a regular series of depot grass-pollen injections over a three-year period. At the end of this first phase of the study, 32 patients were still being followed. This group was then randomized to continue monthly injections of grass-pollen extract for three more years or receive placebo injections. A third group of 15 patients from the original trial continued to be followed as the control group.

Patients were monitored regularly for the presence of allergy symptoms and the need for rescue medications. The patients kept a diary of eye symptoms (itching, redness, tears), nose symptoms (sneezing, blockage, running), mouth/throat symptoms (itching, dryness) and chest symptoms (cough, wheezing, tightness), which were scored on a scale of zero to 3. Rescue medications consisted of cromolyn nasal spray, cromolyn eye drops, a nonsedating antihistamine and an albuterol inhaler. If symptoms were still not controlled, a seven-day course of prednisolone was prescribed. A scoring system was devised to quantify the medical therapy. In addition, a visual analog scale from zero to 10 was used to rate symptoms.

Additional objective testing was performed to measure allergic responses. These included skin-prick testing with the grass-allergen and conjunctival reaction to instillation of grass-pollen extract.

Lastly, punch-biopsy specimens of the skin were taken 24 hours after the injection of the allergen or placebo extract. The number of CD3+ T cells and cells containing interleukin-4 messenger RNA were identified by immunohistochemical analysis of the biopsy specimens.

The three patient groups were matched for age, sex and size of wheal reaction to the grass-allergen. During the three years of the study, scores for total hay fever symptoms, rescue medications and the visual-analog scale remained low and were similar in the patients who continued monthly immunotherapy and those who received placebo extracts. In addition, the scores were similar to those recorded during the first three years of the initial study when all patients were receiving active immunotherapy. The scores for the two groups of patients were markedly lower than the scores for the control group of 15 patients. Three patients from the treatment groups needed steroids compared with nine of the control patients. With regard to the reaction to skin-prick testing for immediate sensitivity, there was a tendency for the discontinuation group to show a 6-mm wheal at a lower allergen concentration compared with the maintenance therapy group. A similar pattern was noted with the conjunctival reaction. However, the degree of reaction was markedly lower compared with the control patients who had never received immunotherapy. A late-phase skin response (six to 24 hours) was essentially absent in both groups of immunotherapy patients. Lastly, there were markedly fewer CD3+ T cells and fewer cells containing interleukin-4 RNA in both treatment groups compared with the control group.

The authors conclude that immunotherapy for grass-pollen allergy has a sustained response for at least three years after the injections are stopped. The response is observed immunologically (documented by skin testing and cell markers) and clinically (documented by symptom scores). The authors also raise the question as to whether immunotherapy should be used earlier in the course of allergic rhinitis. It appears to have the potential to affect the patient's long-term clinical course and possibly to decrease responses to other environmental allergens.