ALLERGY Net: The safety of sublingual immunotherapy with one or more allergens in adults


  • A post-marketing survey on the safety of sublingual immunotherapy.

Allergy & Respiratory Diseases
Department of Internal Medicine
Padiglione Maragliano
L.go R. Benzi 10
16132 Genoa
Tel.: + 39 10 3538908
Fax: + 39 10 3538904

Sublingual immunotherapy (SLIT) is currently largely prescribed and used in many European countries, and its favourable safety profile is well ascertained. In this regard, it is well recognized from the literature that systemic and/or severe side-effects are exceptional. Nonetheless, it should be kept in mind that in Europe, SLIT is usually prescribed for a single allergen that is recognized as the principal responsible for symptoms. On the other hand, on the basis of results of the diagnostic workup, it is sometimes necessary to give SLIT for more than one allergen, when multiple allergens are clearly recognized to be the causal agents. Recently, two reports described the occurrence of anaphylaxis following the administration of multiple allergens (1, 2), thus raising concerns on the safety of multiple extracts given at the same time. For this reason, we compared the occurrence of side-effects in patients receiving SLIT with a single or multiple allergens.

Consecutive patients suffering from respiratory allergy caused by pollens (rhinitis and/or asthma) eligible for specific immunotherapy with multiple allergens, and matched patients receiving SLIT for a single allergen were followed-up by means of diary cards for the identification of side-effects (3). Sublingual immunotherapy was prescribed according to guidelines, and multiple allergens were given only when the causal role of the allergens themselves was well ascertained. The SLIT was prepared as glycerinated solution containing either one single or multiple allergens, according to the prescription. The vaccination course involved a 10-day build-up phase with a daily increasing number of drops, followed by a maintenance phase where a single-dose vial was given daily for 3 months (SLIT-One; ALK-Abellò, Linate, Italy). All patients received the first dose of SLIT at the clinic, and were then instructed to fill a diary card for adverse events. Side-effects were subdivided into: eye symptoms, rhinitis/ear itching, asthma, oral itching/swelling, gastrointestinal (nausea, vomiting, abdominal pain, diarrhea), urticaria, angioedema, and anaphylaxis. They were graded as mild (no treatment or dose adjusting), moderate (need for drugs/medical advice or dose adjusting), and severe (life-threatening/hospitalization/emergency care).

One hundred and fifty-nine patients received SLIT either for a single allergen (n = 76, 36 male, age range 16–59 years, 27 rhinitis only) or multiple allergens (n = 83, 40 male, age range 19–57 years, 30 rhinitis only) for a total of 15 347 doses. The prescribed SLITs are summarized in Table 1. There were 45 episodes in 42 patients of the first group and 51 episodes in 47 patients of the other group; thus the rate of side-effects did not differ between the groups (χ2 = NS). The reported 96 events were mainly local and appeared always in the induction phase (Table 2). Almost all the events were mild, self-limiting and required no medical intervention, but two episodes of oral angioedema, for which medical advice was required. These were judged as moderate, and successfully treated with oral antihistamines and a temporary interruption of the dose escalation. None of the patients had to stop the SLIT course and no emergency treatment with bronchodilators or adrenaline was required at all.

Table 1.   Prescribed sublingual immunotherapy
Single allergen n (%)Multi allergens n (%)
Grass38 (50)Grass + parietaria31 (37.5)
Parietaria20 (26.3)Grass + birch21 (25)
Birch15 (19.7)Grass + birch + alder + hazelnut 20 (24.5)
Ragweed2 (2.6)Grass + olive1 (1.2)
Olive1 (1.3)Grass + mugwort1 (1.2)
  Birch + hazelnut + alder9 (10.6)
Total76 (100) 83 (100)
Table 2.   Characteristics of the reported side-effects
 Single allergen 76 patients, 7296 dosesMultiple-allergens 83 patients, 8051 doses
Side-effects (episodes)
 Oral itching/swelling25 mild27 mild
 Oral angioedema1 moderate1 moderate
 Rhinitis/ear itching3 mild4 mild
 Throat irritation5 mild7 mild
 Cough6 mild7 mild
 Nausea/pain5 mild5 mild
 Generalized urticaria
Total45 episodes51 episodes
55% patients56% patients
6.6/1000 doses6.3/1000 doses

In the present postmarketing survey, we compared in a real-life setting the rate of side-effects in patients receiving SLIT for either one or two allergens. This exploratory survey was prompted by the description of anaphylactic reactions with multiple allergens (1, 2), although in these reports, more than three unrelated allergens (nonstandardized in one case) were used. In the population herein considered, no difference in the type and characteristics of side-effects was seen according to the number of allergens used (one or two). The overall number of patients is relatively small, but the reliability of the data is supported by the concordance of the figures with those reported in larger samples (3–5). Our conclusion is that SLIT with a limited number of mixed allergens does not increase the risk of side-effects, if the treatment is correctly prescribed and standardized extracts are used.