E. A. Pastorello

Atopy and intolerance of antimicrobial drugs increase the risk of reactions to acetaminophen and nimesulide in patients allergic to nonsteroidal anti‐inflammatory drugs

This study evaluated the risk factors for developing allergic reactions to alternative drugs such as acetaminophen and nimesulide in 367 patients intolerant of nonsteroidal anti‐inflammatory drugs (NSAID) compared to 243 healthy controls. All subjects were given test doses (TD) of acetaminophen and nimesulide, and age, sex, atopy, and history of reactions also to unrelated drugs were compared in those who reacted and those who were tolerant of the challenge. TD was positive in 49 of 367 (t4%) NSAID‐allergic patients and in one (0.4%) ofthe controls (f <0.001). No difference was found in age and sex between the TD‐positive and TD‐negative subjects, although a significantly larger number of females were NSAID allergic (P<0.01). Of the 367 patients, 208 had a historj of reactions only to NSAID, and 148 to NSAID and antimicrobial drugs (AMD). TD with acetaminophen or nimesulide was positive in 6% of patients intolerant only of NSAID and i n 24% of those intolerant of both NSAID and AMD, with an odds ratio of 4.82. Atopy was more frequent among patients (36%) than controls (23%) (P=0.004). among TD‐positive (51%) than TD‐negative patients (33.5%) (P<0.02), and among patients intolerant of NSAID and AMD (48%) than those intolerant only of NSAID (F=0.006). The odds ratios were, respectively, 1.87, 2.57, and 3.16. This study provides evidence that atopy and history of allergic reactions to AMD increase the likelihood of intolerance of usually well‐tolerated alternative drugs such as acetaminophen and nimesulide in subjects allergic to NSAID.

Screening the allergenic repertoires of wheat and maize with sera from double-blind, placebo-controlled food challenge positive patients.

Background:  Food allergy to wheat and maize is an increasing factor of deterioration of life quality, especially childhood and can, in rare cases, even induce anaphylaxis. Although omega‐5 gliadin from wheat and maize lipid transfer protein have been characterized as major cereal allergens on the molecular level, the list of food allergens is far to be complete.

Clinical and immunological effects of immunotherapy with alum‐absorbed grass allergoid in grass‐pollen‐induced hay fever

A double‐blind, placebo‐controlled study of immunotherapy was conducted in 19 patients with grass‐pollen hay fever to evaluate the efficacy and safety of a formalinized depot grass allergoid. The patients were assessed before and during IT by clinical (symptom‐medication scores during the grass‐ pollen season, specific nasal and skin reactivity) and immunological (specific IgE, IgG, IgG1 and IgG4 antibodies) parameters. High doses of grass allergoid, corresponding to a cumulative pre‐seasonal dosage of 46050 PNU, were administered, with only one systemic reaction. The actively treated patients had significantly lower symptom‐medication scores than placebo (p < 0.01) during the month of May and showed a significant decrease in specific skin (p < 0.01) and nasal (p < 0.05) reactivity, and a significant early increase in specific IgE (p < 0.01), IgG (p < 0.0005), IgG1 (p < 0.001) and IgG4 (p < 0.05), with a subsequent decrease of IgE and IgG1. No differences were detected in any of these parameters in the placebo group. A correlation was found between high IgG4/IgG1 ratio and the specific skin reactivity decrease (r = 0.691, p < 0.05), whereas a high IgG4/IgG1, ratio was associated with higher symptom‐medication scores (r = 0.654, p < 0.05). Possible explanations of these apparent discrepancies are proposed.

A double-blind study of hyposensitization with an alginate conjugated extract of D. pteronyssinus (Conjuvac®) in patients with perennial rhinitis

The efficacy of hyposensitization with standardised extract of Dermatophagoides pteronyssinus (D. pteronyssinus) conjugated to alginate and containing known amounts of antigen P1 (Conjuvac®) was tested in a double blind, placebo controlled, multi‐centre study in 66 adult patients with perennial rhinitis. Patients received 11 weekly injections of increasing concentrations of Conjuvac containing from 56 × 101 to 448 × 103 IU D. pteronyssinus or placebo injections of the alginate diluent to some of which 5 μg of histamine has been randomly added This was followed by 15 monthly injections of Conjuvac or placebo. The severity of nasal blockage, sneezing and rhinorrhoea was recorded twice daily in a diary and visual analogue assessments (VAS) made at each clinic visit. Nasal provocation testing (NPT) was performed with increasing concentrations of the same extract of D. pteronyssinus as used in the hyposensitization injections, and changes in nasal airways resistance measured by passive anterior rhinomanometry. VAS was recorded and NPT was performed on entry to the study and after the fifth, ninth and final monthly injection. Conjuvac injections were well tolerated. Large local reactions (> 5 cm) occurred within 30 min in only 1% of patients but later in 23%. No systemic reactions or anaphylaxis occurred within 30 min of injections, but urticaria or worsening of asthma and rhinitis was reported later in 3% of patients. A significant improvement in nasal obstruction occurred in the Conjuvac compared to the placebo treated group (P < 0.01) and there was significant increase in the percentage of patients able to tolerate provocation with the highest concentrations of D. pteronyssinus extract after nine and 15 maintenance injections of Conjuvac compared to the placebo (P 0.02, P < 0.001). Patient use of additional therapy decreased sooner in the Conjuvac treated group but was minimal in both groups after 5 months of the study.

EAACI Guidelines on Allergen Immunotherapy: Allergic Rhinoconjunctivitis.

Allergic rhinoconjunctivitis (AR) is an allergic disorder of the nose and eyes affecting about a fifth of the general population. Symptoms of AR can be controlled with allergen avoidance measures and pharmacotherapy. However, many patients continue to have ongoing symptoms and an impaired quality of life; pharmacotherapy may also induce some side‐effects. Allergen immunotherapy (AIT) represents the only currently available treatment that targets the underlying pathophysiology, and it may have a disease‐modifying effect. Either the subcutaneous (SCIT) or sublingual (SLIT) routes may be used. This Guideline has been prepared by the European Academy of Allergy and Clinical Immunologys (EAACI) Taskforce on AIT for AR and is part of the EAACI presidential project “EAACI Guidelines on Allergen Immunotherapy.” It aims to provide evidence‐based clinical recommendations and has been informed by a formal systematic review and meta‐analysis. Its generation has followed the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included involvement of the full range of stakeholders. In general, broad evidence for the clinical efficacy of AIT for AR exists but a product‐specific evaluation of evidence is recommended. In general, SCIT and SLIT are recommended for both seasonal and perennial AR for its short‐term benefit. The strongest evidence for long‐term benefit is documented for grass AIT (especially for the grass tablets) where long‐term benefit is seen. To achieve long‐term efficacy, it is recommended that a minimum of 3 years of therapy is used. Many gaps in the evidence base exist, particularly around long‐term benefit and use in children.

Allergen immunotherapy for allergic rhinoconjunctivitis: A systematic review and meta‐analysis

The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis. To inform the development of clinical recommendations, we undertook a systematic review to assess the effectiveness, cost‐effectiveness, and safety of AIT in the management of allergic rhinoconjunctivitis.

A double‐blind, placebo‐controlled study of immunotherapy with an alginate‐conjugated extract of Parietaria Judaica in patients with Parietaria hay fever

A double‐blind, placebo‐controlled study was conducted to evaluate the efficacy and safety of immunotherapy (IT) with a partially purified alginate‐conjugated extract of Parietaria judaica (Conjuvac®Parietaria, Dome/Hollister‐Stier) in patients suffering from rhinoconjunctivitis caused by Parietaria pollen. Eighteen patients (10 women, 8 men, mean age 35 years) received active treatment and 17 (10 women, 7 men, mean age 42.5 years) received placebo. Actively treated patients had significantly lower nasal symptom/medication scores (running nose P= 0.0087 and sneezing P= 0.048) during the Parietaria pollen season. Significant decreases in specific skin (P > 0.01), nasal (P > 0.05), and conjunctival (P > 0.01) reactivity to the Parietaria extract and significant increases of specific IgG (P > 0.001), IgGI (P > 0.001), and IgG4 (P > 0.001) in actively treated patients, but not in placebo, were found. IT was well tolerated, the active extract inducing five mild systemic reactions (four rhinitis and one urticaria) and placebo two (rhinitis). A significant correlation was found between low skin reactivity and high specific IgG (P= 0.0002) and IgG4 (P= 0.036). These findings indicate that IT with a partially purified P. judaica extract is an effective and safe treatment for Parietaria pollen allergy. The correlation between low immediate skin reactivity and high specific IgG and IgG4 suggests that, at least in the studied cutaneous model, these antibodies may exert a blocking effect.

Clinical evaluation of CAP System and RAST in the measurement of specific IgE

We investigated the diagnostic value of a new in vitro test, Pharmacia CAP System (Pharmacia Diagnostics AB, Uppsala, Sweden), for the quantitative measurement of allergen‐specific IgE antibodies by comparison with RAST in 2 groups of patients, 71 atopic and 48 non‐atopic. In the last 20 years RAST has supplied a good diagnostic tool, but this test presents some problems, the main one being sensitivity. The new test has a solid phase able to bind even very small amounts of specific IgE and an anti‐IgE tracer with very low cross‐reactivity with other immunoglobulins, thus presenting more favourable conditions. From the analysis of our results, Pharmaeia CAP System gave higher sensitivity (94% compared to 88% of RAST) with no loss of specificity (96% for both tests). The reliability of these results is ensured by the proper selection of patients who were all suffering from pollinosis and were clinically diagnosed as certainly hypersensitive to a single pollen. A positive trend was found between severity of asthma and levels of specific IgE for timothy. Pharmacia CAP System appears to identify a larger number of atopic patients than RAST.

Diagnostic problems due to cross‐reactions in food allergy

The immunochemical cross-reactivity of allergens is a common problem of diagnostic procedures, especially in food allergy (1). Cross-reactivity can elicit positive in vitro or in vivo allergy tests in subjects who do not display any clinical symptom, thus giving rise to the so-called asymptomatic sensitization. Cross-reactivity is an in vitro phenomenon caused by IgE antibodies directed against epitopes expressed in molecular structures from different allergenic sources, and does not always produce clinical symptoms. Cross-reactions in food allergy mainly affect specificity. Nonetheless, the positive tests in subjects who do not have symptoms cannot be simply classified as “false-positive results”, since they do not occur in nonatopic control subjects (2); therefore, their significance has yet to be fully understood. Cross-reactive allergens can be divided into three groups on the basis of the appearance/absence of resulting clinical symptoms. Group I comprises allergens which provoke clear clinical symptoms (Table l), most of which are taxonomically related, and clinical syndromes in which respiratory and food allergies are combined, such as the “birch-fruit’’ or “bird-egg’’ syndromes (3). Group I1 comprises cross-reactive allergens that do not always produce symptoms. Examples of these are profilins in the pollen-vegetable foods allergy association; cysteine proteases contained in kiwi fruit, papaya, pineapple, and mites; and the cross-reacting allergens in the “latex-fruit” syndrome. Group I11 comprises those cross-reactive allergens that do not produce symptoms, and thus seem to represent a mere in vitro phenomenon. Examples are legumes, cereals, and several differOr C. Ortolani Bizzozzero Division Niguarda Ca Granda Hospital Milan Italy

A double‐blind study of hyposensitization with an alginate‐ conjugated extract of Dermatophagoides pteronyssinus (Conjuvac®) in patients with perennial rhinitis

In a 2‐year double‐blind placebo controlled study an immunological evaluation was carried out on 33 patients (15 males, 18 females, mean age 29.2 years) with mite‐induced perennial rhinitis who were submitted to specific immunotherapy (IT) with an alginate‐conjugated extract of D. pteronyssinus. The behaviour of IgE, IgG, IgG1, and IgG4, antibodies specific to D. pteronyssinus and its major allergen Der p1, was characterized by assessment of their changes m serum, and changes in IgG in nasal secretions during the treatment. The placebo‐treated patients did not show any significant variation in the levels of specific antibodies, while in the actively treated patients we found; a statistically significant decrease (P < 0.005) of specific IgE, a statistically significant increase of specific IgG (P < 0.005), IgG1, (P < 0.005) and IgG4 (P < 0.005) in serum and a statistically significant increase (P < 0.001) of specific IgG in nasal secretions. The IgG response showed an early relative predominance of the IgG1 subclass and a late absolute predominance of IgG4 subclass, that confirmed the model of IgG4 restriction in prolonged allergen stimulation. No correlation was found between immunological and clinical data.