Gianenrico Senna

Clonal mast cell disorders in patients with systemic reactions to Hymenoptera stings and increased serum tryptase levels

BACKGROUND Anaphylaxis after Hymenoptera stings has been reported in subjects with mastocytosis, but few data exist regarding disease prevalence in populations allergic to these insects. OBJECTIVE The incidence of clonal mast cell (MC) disorders in subjects with both systemic reactions to Hymenoptera stings and increased serum baseline tryptase (sBT) levels was assessed by using bone marrow (BM) aspirates and biopsy specimens. METHODS Subjects with a history of a systemic reaction caused by a Hymenoptera sting underwent the standard diagnostic work-up for Hymenoptera allergy, and sBT levels were measured. Subjects with an increased sBT level had BM evaluation that included histology/cytology, flow cytometry, and detection of KIT mutations. RESULTS Forty-four (11.6%) of 379 subjects with systemic reactions had increased sBT levels (>11.4 ng/mL), and 31 (70.5%) of these had a history of anaphylaxis. Thirty-four subjects with increased sBT levels underwent a BM analysis. Histology detected diagnostic or subdiagnostic MC infiltrates in 22 (65%) of 34 patients. Abnormal MCs were identified by means of flow cytometry and cytology in 26 (78.8%) of 33 and 20 (58.8%) of 34 subjects, respectively. A KIT mutation was detected in 17 (54.8%) of 31 subjects. The diagnosis was indolent systemic mastocytosis in 21 (61.7%) of 34 subjects and monoclonal MC activation syndrome in 9 (26.5%) of 34 subjects. All subjects with anaphylaxis had one of those 2 disorders. CONCLUSION The concomitant presence of systemic reactions (especially anaphylaxis) after Hymenoptera stings and increased sBT levels strongly suggests that a BM examination is indicated for the diagnosis of clonal MC disease.

Allergic rhinitis and asthma comorbidity: ARIA classification of rhinitis does not correlate with the prevalence of asthma

Background Allergic rhinitis and asthma comorbidity is supported by both the similar underlying pathogenesis and immunologic mechanisms. The aim of this study was to verify whether the characteristics of rhinitis classified according to the new Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines correlate with the prevalence of asthma.

How adherent to sublingual immunotherapy prescriptions are patients? The manufacturers' viewpoint

6. Bousquet PJ, Combescure C, Neukirch F, Klossek JM, Mechin H, Daures JP, et al. Visual analog scales can assess the severity of rhinitis graded according to ARIA guidelines. Allergy 2007;62:367-72. 7. Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy 2008;63(suppl 86): 8-160.

Quantitative assessment of the compliance with once‐daily sublingual immunotherapy in children (EASY Project: Evaluation of A novel SLIT formulation during a Year)

Compliance is a major determinant for allergy treatment, especially in children. Sublingual immunotherapy (SLIT) is self‐managed at home, and no quantitative data on pediatric adherence are available. We studied the compliance in a large real‐life setting. A simplified schedule of SLIT was used, consisting of a 10‐day updosing phase followed by maintenance treatment in monodose containers to be taken daily (SLITOne®). Italian specialists throughout Italy assessed the compliance in children who were newly prescribed SLIT according to guidelines. Parents were contacted with unscheduled telephone interviews at the third and sixth month of therapy and asked to count at that moment the remaining vials. Data from 71 children (38 boys, age range 2–13 yr) were enclosed in the database. Thirty had rhinoconjunctivitis, four asthma and 37 rhinoconjunctivitis + asthma. SLIT was prescribed for: mites in 57 (81%) subjects, grasses in 11 (15%) and 3 (4%) grass + olive mixture. Compliance data were available for all children at 3 months, and for 56 at 6 months. At 3 months, 85% of subjects had a compliance rate >75% (69% of them adhered >90%). At 6 months, 84% had a compliance rate >75% (66% of them adhered >90%). In four cases SLIT was discontinued for economical reasons, and in one case (1.4%) for side effects probably related to therapy. These data obtained in a quite large sample of children and in real‐life confirm that the compliance with SLITOne® is good, despite the therapy managed at home.

Economic evaluation of sublingual immunotherapy vs symptomatic treatment in adults with pollen-induced respiratory allergy: the Sublingual Immunotherapy Pollen Allergy Italy (SPAI) study

BACKGROUND Few data are available on the pharmacoeconomic aspects of immunotherapy. OBJECTIVE To evaluate, from the health care system and societal perspectives, the costs and consequences of sublingual immunotherapy (SLIT) added to pharmacotherapy compared with drugs alone for respiratory allergy. METHODS This study compared costs, clinical outcomes, and cost-effectiveness ratios of 2 strategies in the management of allergic rhinitis and asthma, namely, SLIT associated with pharmacotherapy and pharmacotherapy alone (no SLIT). A decision tree was developed and populated with epidemiologic and resource utilization data concerning approximately 2,200 patients. Direct costs included visits, tests, pharmacotherapy, immunotherapy, and hospitalizations. Indirect costs and out-of-pocket drugs were also included. Outcome was calculated as the number of improved patients and asthma cases avoided at 6 years. Sensitivity analysis was performed by varying costs and epidemiologic data. RESULTS SLIT improved the symptoms of 399 of 1,000 patients and prevented asthma in 229 of 1,000 patients compared with drugs alone. For SLIT added to pharmacotherapy and pharmacotherapy alone, the direct cost per patient at more than 6 years was Euro2,400 and Euro3,026, whereas the indirect cost was Euro1,913 and Euro3,400. CONCLUSION From both perspectives and for both effectiveness end points, SLIT is less expensive and more effective than pharmacotherapy alone.

How much specific is the association between hymenoptera venom allergy and mastocytosis

Background:  The preferential association of mastocytosis with hymenoptera sting reactions is well known, but there is no data on the prevalence of clonal mast cell disorders in subjects with severe systemic reactions due to foods or drugs.

Evidence of adherence to allergen-specific immunotherapy

Purpose of review The main feature of allergen-specific immunotherapy is its capacity to modify the natural history of the disease, reducing the development of asthma and new sensitizations after 3–4 years of treatment. For this reason, adherence to the therapy is mandatory, as happens for all chronic medical treatment. Recent findings Though subcutaneous immunotherapy is administered directly by physicians, the rate of adherence is surprisingly low, at less than 70%. The explanations for a poor subcutaneous immunotherapy adherence include inconvenience, lack of efficacy, costs and loss of working hours. Local nasal immunotherapy has a very low adherence rate (27%), due to the local nasal side effects. For sublingual immunotherapy, data are available from clinical trials and postmarketing surveys, which are favourable overall (rates of compliance >75%). Cost was the most common reason for discontinuation, followed by inconvenience, feeling of inefficacy and side effects. Summary Studies addressing the adherence to allergen-specific immunotherapy in literature are lacking. In real life, costs and patient education are crucial issues in conditioning adherence to this treatment. Reduction of costs and more efforts in education of patients and also specialists may improve the adherence to immunotherapy.

A prospective Italian survey on the safety of subcutaneous immunotherapy for respiratory allergy

Background Subcutaneous immunotherapy is effective for the treatment of respiratory allergy, and it is largely used in Italy, but no systematic safety assessment has been carried out so far.

Adherence to pharmacological treatment and specific immunotherapy in allergic rhinitis

The term compliance simply indicates how much doses of the prescribed medication are taken, whereas the term adherence implies also an agreement between patient and physician about the therapeutic plan, and it is therefore preferred. Adherence is a main problem in all long‐term treatments. Thus, it represents a problem also in the case of rhinitis, expecially concerning specific immunotherapy that must be assumed continuously for several years. Many factors can affect the adherence, depending on patient, on treatment itself and on the healthcare context, and all those factors usually interact. The adherence measured in controlled trials is usually good, but this does not reflect what happens in real life, where adherence should be preferably measured. There are few data on the adherence in real life for pharmacological treatments of allergic rhinitis (e.g. nasal steroids or antihistamines), whereas more data are available for specific immunotherapy. In this latter case, in real life, adherence seems to be far from optimal, for both sublingual and subcutaneous immunotherapy, although the recent studies agree on the fact that some interventions (i.e. patients’ education, strict follow‐up, regular contacts) could effectively improve the adherence. In this article, the literature concerning the adherence to pharmacological treatments and immunotherapy in allergic rhinitis was searched and reviewed.

Treatment of acquired cold urticaria with cetirizine and zafirlukast in combination

Acquired cold urticaria is an infrequent physical urticaria that can provoke severe systemic reactions. Histamine is the primary mediator, but leukotrienes are also involved in the pathogenesis. H(1) antihistamines are recommended as first-choice treatment, but their efficacy is sometimes unsatisfactory. On the basis of pathogenic knowledge, it can be hypothesized that a combination therapy with antihistamines and leukotriene receptor antagonists is more effective than each drug given alone. We tested this hypothesis in 2 patients with severe systemic cold urticaria poorly responsive to conventional therapy. The patients underwent 3 consecutive treatment regimens (each of 2 weeks): cetirizine (10 mg once a day); zafirlukast (20 mg twice a day); and their combination. They were clinically evaluated, after each regimen, by means of a visual analog scale and ice-cube test. The combination therapy was superior to the 2 drugs given alone, as testified by subjective and objective evaluations.