Introduction:
Intolerance to various foods, excluding bona fide coeliac disease and lactose intolerance, represents a growing cause of patient visits to allergy clinics.
Histamine intolerance is a ...long-known, multifaceted clinical condition triggered by histamine-rich foods and alcohol and/or by drugs that liberate histamine or block diamine oxidase (DAO), the main enzyme involved in the metabolism of ingested histamine. Histamine limitation diets impose complex, non-standardized restrictions that may severely impact the quality of life of patients.
Methods:
We retrospectively evaluated 14 patients who visited allergy outpatient facilities in northern Italy with a negative diagnosis for IgE-mediated food hypersensitivity, coeliac disease, conditions related to gastric hypersecretion, and systemic nickel hypersensitivity, and who previously underwent a histamine limitation diet with benefits for their main symptoms. Serum diamine oxidase levels and the clinical response to diamine oxidase supplementation were investigated.
Results:
We found that 10 out of 14 patients had serum DAO activity <10 U/mL, which was the threshold suggested as a cutoff for probable histamine intolerance. Moreover, 13 out of 14 patients subjectively reported a benefit in at least one of the disturbances related to food intolerances following diamine oxidase supplementation. The mean value (± SD) of diamine oxidase activity in the cohort of patients with histamine intolerance symptoms was 7.04 ± 6.90 U/mL compared to 39.50 ± 18.16 U/mL in 34 healthy controls (P = 0.0031).
Conclusion:
In patients with symptoms triggered by histamine-rich food, measuring the serum diamine oxidase activity can help identify subjects who can benefit from a histamine limitation diet and/or diamine oxidase supplementation.
Properly designed, controlled studies investigating histamine intolerance that include histamine provocation are indispensable for providing insights into the area of food intolerances, which are currently primarily managed with non-scientific approaches in Italy.
Parallel follow‐up of clinical and inflammatory markers during sub‐lingual immunotherapy (SLIT) is highly beneficial. Twenty‐four children (age 4–16) monosensitized to house dust mite were randomized ...to receive either active or placebo SLIT for 1 yr in a double‐blind placebo controlled design (Marcucci et al., Allergy 2003: 58: 657–62). Thereafter, for 2 yr they all received active treatment. Symptom scores for rhinitis, asthma, and drug usage were daily recorded. Eosinophil cationic proten (ECP) and tryptase in sputum and nasal secretions, serum and nasal mite‐specific immunoglobulin E (IgE) were recorded before treatment and at 10–12 months intervals. Nasal ECP and nasal tryptase after specific nasal provocation tests were significantly reduced as compared to baseline values (p = 0.0043 and 0.0195, respectively) in the third year of active treatment. None of the other inflammatory parameters was increased. In placebo treated patients all these parameters tended to decrease only after switching to active treatment. Clinical scores did not improve in treated vs. placebo patients in the double‐blind placebo‐controlled phase of the study. In both cohorts a clinical benefit was observed as intra‐group score reduction as compared to baseline. A significant difference was reached in patients treated for 2 yr for rhinitis and asthma (p = 0.0009 and 0.0019, respectively) but not for drug usage and in patients treated for 3 yr for rhinitis, asthma, and drug usage (p = 0.0105, 0.0048, and 0.02, respectively). SLIT in children monosensitized to mites reverted the spontaneous increase in nasal IgE and in local parameters of allergic inflammation. These outcomes were followed by a consolidated clinical improvement in the second and third year of treatment.
Unconventional immune responses have been demonstrated in individuals who, despite repeated exposure to human immunodeficiency virus (HIV) infection, remain seronegative. As environmental exposure to ...pathogens and genetic background may modulate immune responses differentially, one Italian and two Asian populations of HIV-1-exposed seronegative individuals were studied. In serum samples from each group, IgG to CCR5, IgG to CD4 and IgA to gp41 were measured, which were previously described as markers of unconventional immunity in HIV-exposed seronegative Caucasians. Given the importance of conformational epitopes in virus-cell interactions, IgG to CD4-gp120 complex was also measured. It was found that markers of HIV exposure were present in all populations studied. HIV-specific humoral responses (IgA to gp41 and IgG to CD4-gp120 complex) were extremely significant predictors of HIV exposure (P<0.0001 in both cases), whereas the predictive values of anti-cell antibodies (anti-CCR5 and anti-CD4) varied between populations. Evidence is provided for the correlation of these differences with route of exposure to HIV and level of natural antibodies to cross-reactive microbial antigens. In conclusion, exposed seronegative individuals of ethnically different origins display similar signs of HIV-dependent unconventional immunity. A specific relevance must be attributed to different innate and acquired factors.
Abstract Background Allergy is determined by genetic and environmental factors. People immigrating from under-developed to industrialised countries are at higher risk of developing allergic diseases ...and immigration is as a good epidemiological model to quantify the influence of the environment. We performed the allergological assessment of 32,555 recent immigrants from different areas of the world to a polluted metropolitan area of Northern Italy. Methods We evaluated time of onset of allergic rhinitis and/or asthma, sensitisations and clinical characteristics of 395 subjects (3.74 ± 2.94 yrs, mean ± SD) from four macro-areas (Asia, Africa, East-Europe, South America) arriving to Milan, Italy from June 2005 to June 2009. Data were compared with immigrants having access to the same medical facility for any medical problem and with resident Italians living in the same area. Results Immigrants with allergic rhinitis and/or asthma days since arrival in Italy correlated with number of sensitisations (p=0.0030). Moreover, personal (2.02%) or familial (2.78%) history of allergic diseases was lower in allergic immigrants as compared to allergic residents (37.77 and 29.39%, respectively; p<0.0001 for both comparisons). Finally, the frequency of allergic immigrants from South America (63.3%) was higher than expected from the overall proportion of individuals from this macro-area who sought medical help at the same facility (40.4%; p<0.0001, OR 2.289, CI 2.1670–3.255). Conclusions Environmental factors play a relevant role in the induction of allergies in immigrants to Northern Italy. Genetics appears as a further promoting factor in the case of immigrants from South America.
Histamine release (HR) test has previously been shown to predict the presence of endogenous histamine-releasing factors in chronic spontaneous urticaria (CSU).
Twenty CSU patients unresponsive to ...antihistamine treatment were enrolled in order to evaluate the correlations between HR test results and demographic features, quality of life, disease activity, clinical course, and autologous serum and plasma skin tests (ASST and APST).
All patients with positive HR test (9/9, 100%) had a more severe disease activity at onset (urticaria activity score, UAS > 2) when compared to negative HR test patients (5/11; p = 0.04). Quality of life questionnaire's results were not substantially different between HR positive and negative subgroups at baseline (p > 0.05), and results of HR test and ASST/APST did not co-segregate (p > 0.05). After 12 months, patients with a positive HR test had a significant reduction of disease activity (p = 0.003) whereas patients with a negative HR test did not (p > 0.05), leading to disease remission and antihistamine treatment withdrawal in 67% (6/9) of positive HR test patients versus 18% (2/11) of negative HR test patients (p = 0.027).
Positive HR test may predict spontaneous CSU remission at 12 months.
In the asthmatic lung the altered expression of costimulatory molecules (CD80, CD86) by alveolar macrophages contributes to T lymphocyte activation and expansion. We hypothesized that CD80 and CD86 ...on alveolar macrophages could differentially support allergic inflammation in adult asthma. Here we studied 11 subjects with mild allergic asthma and 11 atopic non‐asthmatics as controls. Dermatophagoides‐specific T cell lines were derived from peripheral blood from each subject. Bronchoalveolar lavage with evaluation of lung inflammatory cells was performed in all individuals at baseline and 24 h after allergen challenge. The expression of CD80 and CD86 costimulatory molecules by alveolar macrophages was studied and, in parallel, the efficiency of antigen presentation was measured in terms of IL‐4 and IL‐5 production by allergen‐stimulated autologous T cells. We found that in asthmatic subjects (i) the percent of CD80+, but not CD86+ alveolar macrophages was increased at baseline and did not change following allergen challenge; (ii) CD86, but not CD80, membrane expression was up‐regulated following allergen challenge; (iii) both CD80 and CD86 were required to support Th2 cytokine production by allergen‐specific T cells, with a prevalent role of CD86 after allergen challenge. Our data indicate that alveolar macrophages deliver costimulatory signals via CD80 and CD86, which support the production of Th2 cytokines by allergen‐specific T cells. They also indicate that CD86 in vivo is up‐regulated in the 24 h following allergen exposure and that this modulation is functionally relevant.
We studied the correlations between body mass index (BMI) and percent body fat (fat%) measured by dual-photon absorptiometry (DPA) in 445 white and 242 Asian adults aged 18-94 y. In addition, ...comparisons in six circumferences and eight skinfold-thickness measurements between whites and Asians were made to explain the discrepancies. Although Asians had lower BMI, they were fatter than whites of both sexes. The correlations between fat% and BMI varied by BMI and sex and race. Comparisons in anthropometry show that Asians had more subcutaneous fat than did whites and had different fat distributions from whites. Asians had more upper-body subcutaneous fat than did whites. The magnitude of differences between the two races was greater in females than in males. Prediction equations developed for each sex and race, based on BMI alone, gave SEEs ranging from 4.4% to 5.7%. All were significantly improved to the range of 3.5-4.4% when age and several skinfold-thickness measurements were added.
The ability to mount an IgE response to allergens is a prerequisite for the development of positive allergen skin tests. Histamine is commonly used as a positive control in skin prick testing and ...provides a measure of nonspecific skin reactivity, similar to bronchial hyper-responsiveness.
To determine whether allergen responsiveness, age, gender and season of the year contribute to histamine sensitivity, 620 subjects (502 of them with at least one known sensitizing allergen and the remaining 118 non-allergic controls) were prick-tested with a panel of allergens common in the Northern Italy semi-rural area where the patients lived, and with 10 mg/ml histamine dihydrochloride.
We found higher histamine reactivity in allergic versus control individuals (median value 23.7 versus 19.8 mm2; p=0.0497). Likewise, we found in allergic subjects a correlation between allergen responsiveness in terms of number of positive allergens at skin prick test and sensitivity to histamine (mono- sensitized versus poly-sensitized subjects: p=0.0015). Moreover older age and male sex were associated with a higher response to histamine, also when separately considering allergic subjects (p<0.0001 in both cases: correlation coefficient for age versus histamine reactivity: r=0.3408). The correlation between allergen responsiveness and sensitivity to histamine was maintained also when statistically balanced for age and sex.
Allergen responsiveness, gender and age allow more accurate prediction of histamine sensitivity than either parameter alone.
We previously demonstrated that one year of sublingual immunotherapy (SLIT) with natural rubber latex (NRL) was safe and efficacious in paediatric patients with NRL allergy.
We studied 12 ...NRL-allergic children (age 4-15), previously assigned to the treated arm of a double-blind placebo controlled study, who received a commercial latex SLIT for three years. Adverse reactions were monitored. The primary end-point was the NRL glove-use test. As secondary end-points, skin prick test with NRL and NRL serum specific IgE were used.
No SLIT-related side effects were observed. A significant reduction of the glove-use score was observed after one-year treatment (5.1 +/- 4.2 vs. 14.8 +/- 5.7, p=0.0031). This parameter was further reduced in the second year since SLIT start (2.0 +/- 2.7, p=000007). After 3 years of SLIT all patients had a negative glove-use test (p<0.0001). Baseline wheal areas of skin prick test (6.8 +/- 2.5 mm2) were significantly reduced after 2 (5.3 +/- 1.8 mm2) and 3 years (4.0 +/- 1.8 mm2) of SLIT (p=0.039 and 0.027, respectively). Baseline values of serum specific IgE (23 +/- 34 KU/l) were significantly reduced after 3 years since SLIT start (6.4 +/- 5.0, p=0.0371).
Three years of latex SLIT is safe and consolidates the efficacy previously observed after one year of treatment in paediatric patients.
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