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BACKGROUND: Injective immunotherapy is a well-known and recognized treatment for allergic diseases, but its safety has been questioned during recent years. Alternative administration routes have been proposed and there is a growing interest and experience in sublingual therapy. The safety of alternative routes is nonetheless a real advantage, so long as it is not counterbalanced by a loss of clinical benefit. OBJECTIVE: We have compared the efficacy of the same biologically standardized grass pollen extract administered through the injective or the sublingual route, in a group of 20 patients followed for two pollen seasons. METHODS: Both therapies were administered for 12 months according to a double-blind (double-dummy) plan; at the end of the trial the cumulative dosage of the sublingual therapy was 2.4 times higher than that of the injective therapy. Data about skin reactivity, symptoms and drugs scores during the pollen season, as well as total specific IgG and specific IgG4, during and after the trial, were obtained. RESULTS: Our data show that sublingual and injective therapy are equally effective according to subjective clinical parameters, with a statistically highly significant reduction of symptoms and drugs (P = 0.002 for symptoms and drugs in SLIT-treated patients; P = 0.002 for symptoms and P = 0.0039 for drugs in patients given injections). On the other hand, objective parameters (total specific IgG, specific IgG4, skin reactivity) changed only in patients treated with active injective therapy, with P < 0.001, P < 0.001 and P = 0.021, respectively. CONCLUSIONS: The discrepancies observed could be interpreted as a consequence of different mechanisms of actin of the two therapies or to the lack of close relationships between the clinical and the objective parameters which were considered here.
The natural exposure to house dust mites causes sensitization in genetically susceptible patients. Persistent exposure of sensitized patients causes chronic inflammation, and consequently, hyperreactivity, thus promoting the development of clinical features. Recently, intercellular adhesion molecule-1 (ICAM-1)/CD54 expression on epithelial cells triggered by allergen has been demonstrated and related to the inflammation caused by the allergic reaction. Therefore we evaluated the possible presence of inflammation (i.e., inflammatory cell infiltrate and ICAM-1/CD54 expression on epithelium) at conjunctival and nasal levels in patients with asymptomatic allergic rhinitis caused by mites, in their relatives living in the same environment, and in healthy volunteers. In addition, the possible relationship between inflammation and house dust mite allergen exposure was evaluated. Conjunctival and nasal scrapings of allergic subjects enrolled in the study showed many inflammatory cells. A mild ICAM-1/CD54 expression on conjunctival and nasal epithelium was detectable in allergic subjects, whereas relatives and healthy volunteers showed few inflammatory cells and no ICAM-1/CD54 expression on epithelial cells. A detectable level of house dust mite, sufficient to cause sensitization, was found in all houses. This study demonstrates a minimal persistent inflammation at conjunctival and nasal levels constantly detectable in patients without symptoms who are sensitized to mites and continuously exposed to the natural allergens.
BACKGROUND: sublingual immunotherapy has been recognised as safe and effective but it is still poorly documented in tree pollen allergy. Allergy to alder, birch and hazel is important in Northern European countries but its clinical relevance is increasing in Southern Europe. METHODS: thirty patients, selected and observed for one pollen season, were randomised to receive placebo (15 patients) or active treatment (15 patients). Twenty-seven patients completed the first year and 24 of them were treated with active therapy during the second year of the study in comparison to a parallel group of ten patients treated only with drugs. Symptom and drug scores during each pollen season, birch-specific IgE, changes in skin test reactivity, changes in specific Nasal Provocation Test and the daily average pollen count for the relevant trees were considered for the assessment of the efficacy of the treatment. RESULTS: both active and placebo group showed a statistically significant improvement in scores in comparison to the previous year, under a lower allergenic pressure. The improvement was higher in the active group (76.04 % reduction of drugs) but not significantly different from that registered in the placebo group (37.05 % reduction). In the open phase of the study, treated patients showed significantly better scores in comparison to the control group. No significant changes in skin reactivity, specific IgE and Nasal Provocation Test were registered. SLIT tolerance was very good. CONCLUSIONS: our data show a better but not statistically significant clinical outcome for patients actively treated with SLIT, but the placebo effect and the year-by-year variability of the environmental allergenic load in our small-size pilot study do not allow for a conclusive statement about the efficacy of this form of therapy.
BACKGROUND: specific immunotherapy for Hymenoptera Venom (VIT) is considered a life-saving treatment in insect sting allergy. A few studies with depot VIT have been published, but they are mainly focussed on patients sensitized to Apis. METHODS: this retrospective study was designed to evaluate both efficacy and safety of depot VIT for Vespula. Thirty-six patients (age range 6-73 years) with a history of systemic reactions (grade III to IV according to Mueller) after a Vespula sting, and specific sera IgE RAST to Vespula at least class 2, were administered a depot preparation of venom reaching 50 microgram as monthly maintenance dose. After the first year the maintenance dose was administered every other month. Thirty-three patients were treated for a minimum of 5 years. Reactions to any new field sting of the relevant insect were recorded during the treatment and for 6 to 24 months after its interruption. RESULTS: the treatment showed an excellent tolerance, with only a few local side effects. Thirteen patients (11 Grade IV according to Mueller before VIT) under treatment showed only local reactions after each field sting (18 field stings in total) by the relevant insect. Four patients (3 Grade IV according to Mueller before VIT) had a total of 6 field stings after the interruption of the 5-year treatment, with only local reactions. CONCLUSIONS: according to our results, and in agreement with previous published studies, VIT for Vespula spp. with depot extracts has an excellent tolerance and is clinically effective.
BACKGROUND: About 20 % of infants fed with breast-milk substitutes suffer from Gastro Esophageal Reflux (GER) and 1/3 of them also show Cow's Milk Allergy (CMA) symptoms. METHODS: We planned this study to assess by dynamic echography the usefulness of an Extensively Hydrolysed Cow's Milk Formula (eHF) in infants suffering from GER. Ten infants showing GER symptoms and 10 normal babies, all fed with breast-milk substitutes, were enrolled. Clinical symptom scores related to GER were assessed for one week. The Gastric Emptying Time (GET) was determined by means of dynamic echography after feeding with cow's milk-derived formulae and again after a week feeding with eHF in subjects previously showing GER symptoms. RESULTS: All infants with a clinical diagnosis for GER showed an abnormally high average GET in comparison to normal subjects (205 vs 124 min, p = 0.000). Switching to the eHF led to a significant clinical improvement (p = 0.0039) especially in babies skin-test and RAST positive to cow's milk, and to a significant decrease toward the normal value of the GET (167 min, p < 0.001). CONCLUSIONS: The eHF tested improves GER symptoms in infants suffering from this disease. Our experience confirms and supports the use of dynamic echography as a reliable, simple, and non-invasive diagnostic method for infants with an increased GET associated with clinical symptoms of GER.
BACKGROUND: There is compelling evidence that hemopoietic precursor cells (HPC) play a crucial role in establishing cellular inflammation in allergic diseases. Increased levels of circulating CD34+ HPC committed to the myeloid lineage have been extensively reported in allergic rhinitis, asthma and eczema, whereas CD34+ cells have been identified within the cellular infiltrates of tissues, at peripheral sites of inflammation. METHOD: We conducted a pilot study to evaluate CD34+ traffic in the peripheral blood of 22 consecutive patients (13 men and nine women; mean age 28.9 years), independently of treatment. The patients presented rhinitis, asthma, eczema, urticaria and adverse food reactions of suspected allergic origin. Allergic reactions were extrinsic in 18 patients and intrinsic in four. In 12 patients who underwent sublingual specific immunotherapy, CD34+ cells were quantified at enrollment (T0), one year later (T1) and two years later (T2). The severity of symptoms was graded on a five-point scale (0 = absence of symptoms and 4 = severe symptoms). Twenty healthy human subjects (10 men and 10 women; mean age 24.5 years) were evaluated as controls. To obtain information about the total amount of circulating HPC, independently of the lineage commitment (Lin+/-) and the degree of differentiation (CD34bright/dim), we used a modification of the Milan protocol of peripheral blood CD34+ cell estimation. The cells were analyzed using a BD FACScan or FACSCalibur and the results were expressed as the percentage of positive cells. RESULTS: CD34+ cell traffic in the control group was very low since all values were < 0.10 (median value: 0.03 %). Values in the patient group were increased in both extrinsic and intrinsic forms with a median value of 0.25 % (interquartile range: 0.13- 0.33 %). The relationship between CD34+ traffic and the severity score was highly significant (Spearman's rho = 0.954; test of Ho: CD34; independent score: Pr > t = 0.000). CONCLUSIONS: The data reported herein suggest that the method employed is effective in assessing acute allergic inflammation, as well as minimal persistent inflammation underlying an asymptomatic clinical condition. Evaluation of CD34bright/dim peripheral traffic, if confirmed by the outcomes of a multicenter study currently being planned together with traditional study of circulating IgE, could be a reliable non-invasive laboratory tool for monitoring allergic inflammation.
BACKGROUND: Injective immunotherapy is traditionally performed with a build-up phase lasting 3 to 4 months. The costs, decreasing compliance from both patients and clinicians and inconveniences due to this schedule may be overcome using different schedules. METHODS AND RESULTS: A revision of the published papers with clustered schedules has been made. Attention has been focussed on tolerance and its relationships with relevant parameters such as kind of extract (aqueous or depot), allergens and their pharmaceutical presentation, schedule followed, use or not of a premedication, clinical manifestations of patients before treatment. For a better revision, papers dealing with clustered schedules have been divided into two groups. The first group includes 20 papers not designed to study the clustered schedule but using it to study other parameters affected by specific immunotherapy. The second group includes 9 papers specifically or mainly designed to study the clustered schedule. A huge difference in the rate of side effects could be assessed among different papers, even in studies run with similar allergens from the same producer and with a similar schedule. CONCLUSIONS: Summarizing the results of the revision, the following conditions seem to lead to the optimal tolerance of the clustered schedule: use of a premedication; use of a depot preparation; use of no more than 4 administrations per cluster; administration of 1-2 clusters per week and of 4 to 6 clusters in total. These results seem promising but further efforts are required to better define the optimal clustered schedule.
BACKGROUND: Food allergy is quite common in children, but it usually trends to improve with ageing. When an individual has specific IgE to a large variety of foods (multifood allergy) the clinical picture may be of remarkable severity and the avoidance of the offending foods may lead to severe dietary impairment. We describe a case of a child with ascertained multifood allergy. METHODS: The prick-by-prick testing with fresh foods and serum IgE tests were used to evaluate the patient's sensitivity to food allergens. The clinical effect of sensitizations were evaluated by DBPCFC which was carried out for egg, fish, peanuts, walnut, fig, asparagus, orange, chicory, medlar, peach, strawberry and cherry. Each challenge was performed on a separate day. Medical assistance and resuscitation facilities were available during the whole challenge procedures. RESULTS: SPT with fresh food gave a 4 mm wheal for fig, asparagus, cherry and walnut; a 5 mm wheal for medlar and orange; a 6 mm wheal for chicory and strawberry; a 7 mm wheal for fish and peanuts; an 8 mm wheal for peach and a 9 mm wheal for egg. The RAST assay confirmed the presence of specific IgE to egg, fish, peanuts, walnut, fig, orange, strawberry, peach, and cherry. The total serum IgE was 730,6 kU/l.The DBPCFC was positive, at various degrees, for all foods tested according to skin sensitizations. CONCLUSIONS: The case herein described is a true multifood allergy, as confirmed by the DBPCFC. Multifood allergy is not common, but when present it can lead to severe dietary limitation.
BACKGROUND: The study tests the hypothesis of a reduction of priming due to tree allergy in patients sensitised to both birch/hazel and grass pollen undergoing an associated preseasonal Sublingual/Injective immunotherapy. METHODS: 36 out of 49 bisensitized candidates were pair-matched into 18 case-referent couples. During two years all patients were administered preseasonal grass-SIT and one patient in each couple received also birch/hazel-SLIT. Diary cards were fulfilled for three consecutive grass pollen seasons. Specific Nasal Provocation Test (NPT) for grass and aspecific bronchial challenge were done; sera were analyzed for specific IgE and IgG. RESULTS: During the peak of the grass pollen season both groups showed a significant improvement in total symptom-score. Conjunctivitis and cough improved significantly more in patients with associated therapies. While antihistamine score decreased significantly in both groups, antiasthmatics did only in the SLIT-SIT group. The follow-up documented a significant increase in grass- and birch-specific IgG and a decrease in grass-specific IgE. Grass-NPT threshold was clearly higher in SLIT-SIT-group (p = 0.01) and only in this group PD20 methacholine improved significantly (p < 0.05). CONCLUSIONS: Combined birch/hazel-SLIT and grass-SIT are safe and improve clinical outcomes of SIT alone in young bisensitized patients. Priming reduction is supported by specific NPT and bronchial hyperresponsiveness.
Although sublingual allergen-specific immunotherapy has been proved to be effective in the treatment of allergic diseases, controversy surrounds the means by which such a local therapy can induce systemic immunological changes. Adhesion molecules are critical in the regulation of leukocyte traffic. It has been hypothesized that allergenic extract, administered locally, may induce an up-regulation of the mucosal vessel vascular adhesion molecules (CAMs) resulting in local recruitment of circulating inflammatory cells. In the present study we investigated whether the mite antigens, Der p1 and Der p2, can modulate CAM expression of human endothelial cells (HEC). To do this, slices of whole human umbilical cord vein underwent short-term (8 hours) cultures in the presence or absence of mite antigen (baseline, unstimulated controls). Cryostatic sections of the specimens were then evaluated immunohistochemically for expression of intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) molecules. The results revealed that while Der p1 is capable of significantly up-regulating ICAM-1 and VCAM-1 on HEC, Der p2 antigen moderately up-regulates ICAM-1 expression but is ineffective in modulating VCAM-1. Although preliminary, these results clearly support the hypothesis that at least some of the effects of sublingual immunotherapy may derive from inflammatory cell recruitment at the site of allergen release.
BACKGROUND: sublingual-swallow immunotherapy has been recognized as safe and effective in adults. Different treatment schedules have been proposed and used, but the current experience in children is insufficient. We carried out a study to evaluate the clinical efficacy and the safety in children allergic to grass pollen, following different schedules. METHODS: an open study was performed with 3 parallel treated groups and a control group, each including 12 children suffering from rhinoconjunctivitis due to grass pollen. The patients underwent either a preseasonal treatment or a pre-coseasonal treatment during the grass pollen season. The analysis of the clinical outcome was based on the number of days with symptoms and/or drug consumption in the pollen peak month. RESULTS: significantly less days with symptoms and/or drug intake in all of the groups submitted to SLIT in comparison to the control group were found (p < 0.0001). Among the three schedules used, the best clinical results were obtained with the two pre-coseasonal treatments (p < 0.0001), with a preference for the schedule with the lowest maintenance dose according to the drug intake (p = 0.0267). Two patients belonging to the coseasonal schedule with the highest maintenance dose interrupted the treatment because of systemic mild side effects. CONCLUSIONS: our data suggests that in children with rhinoconjunctivitis to grass pollen, SLIT is effective and well tolerated and that the pre-coseasonal schedule should be preferred to the preseasonal treatment. According to our data, the best maintenance dose during the pollen season for children, both for tolerance and clinical outcome, corresponds to 0.4 microg of the grass major allergen Group 5 administered three times a week.
BACKGROUND: allergen-specific immunotherapy has proved to be effective in selected patients with IgE-mediated respiratory allergic diseases, and alternative routes of administration are being studied. Atopic Dermatitis (AD) is currently regarded as an allergic inflammatory disease. METHODS: we conducted a cohort study to evaluate the safety and effectiveness of sublingual-swallow immunotherapy (SLIT) in selected patients with allergic (extrinsic) AD. Thirty-five patients, 16 suffering from AD without respiratory allergic symptoms (Group A) and 19 with AD associated to mild asthma and/or rhinitis (Group B), were enrolled in the study. The severity of the skin lesions (eczema) was scored on a 0 to 4 scale (and subsequently related to the more recent SCORAD Index), where 0 indicated complete healing of the eczema and 4 indicated maximal spread of the lesions. Only patients with an eczema score of 1 to 3 were started on allergen-specific SLIT for 36 months. Eczema scores, symptoms and side effects were recorded every two months during the first 2 years and then after 36 months. After SLIT was completed, all patients attended 3 yearly follow-up visits to evaluate the long-term effects of the treatment. All patients followed a set of rules designed to control for identified confounding variables. All patients received ketotifen during the first 3 months of SLIT. RESULTS: only the complete disappearance of skin lesions (score 0) was considered to indicate effectiveness. In Group A this was observed in 12.6% of the patients after 6 months of SLIT, in 31,2% after 12 months and 68.8% after 24 months. In Group B, eczema disappeared in 0% after 6 months, in 36.8% after 12 months and 73.7% after 24 months. No patients in Group A developed asthma during SLIT, and 1 patient developed asthma 3 years after immunotherapy had ended. Three focal reactions consisting of 2 cases of mild eczema and one case of diarrhoea were recorded. One case of urticaria, due to violation of the administration schedule was the only systemic reaction observed. No life-threatening reactions appeared at any time of the study. CONCLUSIONS: the outcomes obtained, taken into account the limitations of the study design, suggest that sublingual allergen-specific immunotherapy for the treatment of the extrinsic form of Atopic Dermatitis is safe and well tolerated by patients, and may favourably affect the natural course of the disease.
We aimed to evaluate the reproducibility of the skin prick test performed with serial 1:4 dilutions of commercial standardized extracts in comparison with serum-specific IgE and the undiluted commercial extract. Twenty-four subjects sensitized to one (17 cases) or two (seven cases) inhalant allergens were selected and submitted to duplicate skin prick tests with concentrated commercial allergenic extracts or with serial 1:4 dilutions of the same extracts in two different examinations 7 days apart. Blood samples were obtained from 17 of the 24 patients for specific IgE determination. No statistically significant within-patient variations in the area of the wheal in skin prick tests done 1 week apart were found up to the eighth dilution (1:256) of the commercial allergen. On a patient-by-patient basis, only some dilutions showed a statistically significant correlation between allergen-specific IgE and the wheal area elicited by the same allergen, and a significant correlation was found between the wheal elicited by 10 mg/ml histamine and both the concentrated and diluted allergens (up to the sixth dilution). In polysensitized patients, the allergen producing the largest wheal when used in concentrated form did not produce the same result when diluted. The skin prick test with low-potency allergens was reproducible in individual patients even after a 7-day interval up to a 1:256 dilution of the commercial extract, although there was no clear correlation with allergen-specific IgE concentration. In polysensitized patients, the use of high-potency or low-potency allergens for skin prick tests can lead to different conclusions regarding the relative importance of each allergen.
Recent studies carried out by us and others have demonstrated that Fel d 1, the main cat allergen, may be passively transferred by human clothing in cat-free environments. Consequently, the monitoring of the Fel d 1 levels either in indoor environments or on allergen-contaminated clothes of sensitized cat owners should be considered an important tool in prevention strategies. The aim of this study was to evaluate the efficacy of a personal air sampler (Partrap FA 52) in capturing cat allergen from wool fabrics. Seven identical wool webs (80 x 100 cm) were put in the baskets of seven male cats for 1 week. In our laboratory each web was divided into two parts (80 x 50 cm), the first of which was then divided in two parts (40 x 50 cm) and each was vacuumed directly by one collector. The second part was dry-cleaned at a professional cleaners, divided in two parts and then vacuumed. For the dust collection from wool webs we used a fixed high volume air sampler (CF/20 Gelaire Flow Labs, Milan, Italy) and a personal collector (Partrap FA 52, Coppa Biella, Italy). Fel d 1 content was determined using a two site ELISA (ALK-Abelló Group, Madrid, Spain). Both air samplers collected cat allergens from cat-exposed wool fabrics before and after dry cleaning. There were significant differences between the levels of Fel d 1 before and after dry cleaning by using either CF/20 or Partrap FA52 and between the levels of Fel d 1 before dry cleaning using CF/20 and Partrap FA 52. The results of our study suggest that Partrap FA 52, although its air flow is half that of the CF/20, is able to collect even residual amounts of cat allergen from wool webs after dry cleaning and consequently may constitute a simple and effective means of monitoring the levels of Fel d 1 on the clothes of cat owners.
BACKGROUND: Allergy to Ambrosia is a disease of growing importance in Europe. Injective and non-injective immunotherapy have been recognised as safe and effective but no evidence is currently available for sublingual immunotherapy (SLIT) in patients sensitised to Ambrosia. This study was planned to assess the effects and the safety of SLIT in patients clinically sensitised to Ambrosia. METHODS: 19 patients clinically sensitised to Ambrosia and treated with SLIT were compared to 14 patients treated only with drugs. Diary cards with symptoms and drug consumption were filled-in by patients during the pollen season whereas specific nasal challenge and skin prick test were run two months before and after the pollen season. Patients and doctors were also asked to express their subjective assessment about symptoms and drug consumption during the season. RESULTS: SLIT-treated patients had less symptoms and a significantly minor drug intake (p = 0.04) as compared to untreated patients. Nasal challenge test improved significantly in the SLIT group (p = 0.0001) but not in the control group (p = 0.6875) with a significant difference between groups at the end (p = 0.0413) but not at the beginning of the trial (p = 0.213). The decrease in skin reactivity was significant in the control group (p = 0.0186) and highly significant in the SLIT group (p < 0.0001), with no difference between groups (p = 0.2987). Subjective assessment from both patients and doctors was favorable to SLIT (p = 0.0005 for symptoms; p = 0.0019 for drug consumption). Only one minor local side effect was registered during SLIT. CONCLUSIONS: According to our data, SLIT in patients allergic to Ambrosia is safe and able to improve both subjective and objective parameters.
House dust mite and other indoor allergens play a prominent role in the pathogenesis of asthma and other allergic diseases. Several studies have shown a close relationship between sensitisation and/or onset of asthmatic symptoms and levels of indoor allergen exposure. Aim of the study was to investigate the concentration of specific markers of the indoor allergenic pollution, such as Der p 1, Der f 1, Mite Group 2, Fel d 1 and Bla g 2. Dust samples were taken using a standard method by means of a 1200 W vacuum cleaner connected with a dust-sampling device (MITEST). A standard A4 size area has been vacuumed four times during 2 min. The concentrations of Der p 1, Der f 1, Mite Group 2, Fel d 1 and Bla g 2 were determined in dust samples from 53 different sources (office chair and carpet) using a commercial kit (DUSTSCREEN). House dust mite allergens were not always detectable in the offices. Indoor allergen concentrations (Der p 1, Der f 1, Mite Group 2, Fel d 1) were significant higher in the work station (chair) than in the carpet (p < 0.0001). Der 1 exceeded the current threshold for sensitization in about 1/4 of the samples. Der f 1 was predominant over Der p 1 according to other studies. A good correlation between the results of Der p 1 and Der f 1 was observed both in carpet and work station. Cat allergen was ubiquitous and predominantly detected in the chairs because of the employees' clothes. No appreciable levels for Mite Gr 2 and Bla g 2 were detected. Such an exposure for 8 hours in every working day may be an important occupational risk for the development of sensitization/elicitation symptoms to house dust mite. To reduce mite allergen levels are necessary preventive measure by means of specific techniques and products as barriers for preventing the direct contact with allergens.
58 patients under 12 years of age, positive to mites (Dermatophagoides pteronyssinus and D. farinae) according to prick, in vitro specific IgE and challenge tests, suffering from asthma and rhinitis, have been randomly assigned on a double blind basis to receive per os either a biologically standardized extract of mites (active therapy TA = 30 patients) or a saline buffered solution (placebo TP = 28 patients). The serologic results are interesting. The specific IgE level differences of significance are, in comparison with the placebo group. In particular, we did observe the increase of the specific IgE level in the placebo group during the autumn, whereas after 12 months and after 24 months of active treatment there was a clear (p < 0.01) decline in serum specific IgE antibody. In the active group, there was a significant increase in IgG antibodies level after 12 and 24 months and a significant increase in IgG4 level after 24 months. In the placebo group, the level of IgG antibodies was unchanged. In the actively treated patients, a significant increase of CD8+ values and a significant reduction of the ratio CD4+/CD8+ was observed.