Immunotherapy

Efficacy

As far as the efficacy of immunotherapeutic desensitization is concerned, the merits of the treatment must be judged on the basis of:

• 1.

  Relief of symptoms and signs—a reduction in the response of a target organ to the specific allergen. In pollen rhinoconjunctivitis, a reduced response to the instillation of pollen into the conjunctival sac would be relevant. A reduction in the skin reaction to the specific allergen, especially a reduction in the late phase skin response (IgE-mediated), may be demonstrated. In asthma, a reduction in the specific bronchial response to inhaled allergen with an associated reduction in non-specific reactivity (measured by histamine or methacholine provocation) would indicate a response to treatment.

• 2.

  A reduction in or elimination of drug treatment.

Risks of desensitization

The risks of desensitization have to be set against the chance of benefits. The dominant risk is that of an allergic reaction. Subcutaneous injection of allergenic extracts can lead variously to:

• a transient wheal and flare at the injection site;

• a localized delayed subcutaneous swelling with itching;

• a systemic anaphylactic reaction with urticaria, asthma, and hypotension;

• anaphylactic shock.

Large local reactions should be managed by a temporary reduction in the dose of the allergen, the use of antihistamines if needed, and ice applied to the injection site. Systemic reactions may resolve spontaneously or after one injection of adrenaline.

Anaphylaxis can be fatal and requires immediate treatment and measures to prevent recurrence. The erstwhile Committee on Safety of Medicines, in a report cited below, recommended that allergenic products should only be given when facilities for full cardiopulmonary resuscitation are immediately available and that patients should be kept under medical observation for at least 2 hours after receiving an injection [ ].

There is at present no evidence of any undesirable long-term adverse effects of repeated courses of allergenic extracts, although non-allergic individuals may develop hypersensitivity, particularly when they receive extracts that contain aluminium. An isolated case of extensive subcutaneous inflammation and fibrosis with overlying skin changes was seen in a patient after 5 months of maintenance therapy [ ].

The extent and timing of the risk has been delineated in some individual studies. In 419 patients treated with extracts of grass pollen or house dust mite adsorbed on to aluminium hydroxide, local reactions occurred in 10.5% and systemic reactions in 4.8% [ ]. In a survey of 27 806 injections there were 143 (0.51%) systemic reactions, of which 83% were mild and 17% (that is five reactions) needed treatment with adrenaline [ ].

In a 10-year review (1981–91) of the reactions caused by subcutaneous immunotherapy, when 192 505 injections were given to 2206 outpatients, there were 115 systemic reactions, with no deaths. The most frequent reaction (67% of the total) was asthma with urticaria, while asthma alone occurred in 22%. Systemic reactions were much more frequent in asthmatic patients, although one-third of patients with reactions had never previously suffered from asthma. Most systemic reactions occurred during maintenance therapy. Almost always a reaction occurred within 30 minutes of the injection and was promptly controlled by routine therapy [ ].