Specific oral immunotherapy in food allergic patients: transient or persistent tolerance?

INTRODUCTION: The first therapeutic choice for food allergy is avoidance of the responsible food, but when this approach is not possible, specific oral desensitization could be considered as a good alternative. It is not clear yet whether the acquired tolerance is transient or persistent. AIM: We report on a subset of 13 patients of a larger study, treated successfully with specific oral tolerance induction who experienced secondary loss of tolerance after a period of allergen avoidance. MATERIAL AND METHODS: Thirteen patients affected by IgE-mediated food allergy: to cow milk (3 patients), to hen egg (3 patients), to cod fish (2 patients), to peanuts (1 patient) and to corn (1 patient) confirmed by a complete allergological workup and a double-blind placebo-controlled food challenge (DBPCFC), were treated with sublingual-oral desensitization. After the interruption of the maintenance phase, the laboratory tests were performed and 12 of 13 patients underwent DBPCFC. RESULTS: Oral specific desensitization was completed successfully in all the 13 reported patients. At different times after the end of treatment, they decided, on their own initiative, to stop the ingestion of incriminated food. A new food allergen re-exposure caused adverse reactions in 12 of 13 patients. The detection of specific IgE and IgG4 during the period of allergen avoidance showed an increase in or a stable level of specific IgE and a decrease in specific IgG4 in 8 patients. CONCLUSIONS: According to our experience, the tolerance obtained through the desensitizing treatment is transient and so the regular allergen intake is necessary for its maintenance.

Latex immunotherapy: evidence of effectiveness.

INTRODUCTION: The only etiological and decisive therapy, able to influence the natural history of latex allergy is the specific desensitization. AIM: To verify the clinical efficacy and immunological changes determined by latex sublingual immunotherapy in allergic patients who underwent this treatment for at least 3 years. MATERIAL AND METHODS: We enrolled 76 patients (16 males and 60 females, mean age 34 years old) with evidence of a natural rubber latex allergy. To assess the effectiveness of the immunotherapy we performed a latex skin prick test, specific IgE and IgG4 and challenge tests before and after at least 3 years of desensitization. RESULTS: We observed a reduction in the mean diameter of the wheal area at the skin prick test and a decrease in latex specific IgE while no significant changes of latex IgG4 values were found. Moreover a reduction of symptoms and scores at the provocation tests were remarked. CONCLUSIONS: Although the primary prevention (which still remains the gold standard treatment for patients suffering from the latex allergy) sublingual immunotherapy can be offered with efficacy in addition to symptomatic treatment to selected patients.

How to actively treat food allergy.

PURPOSE OF REVIEW: In the last years, food allergy treatment is moving away from food avoidance to interventional treatments. We review here the recent developments on immunotherapy with food allergens. RECENT FINDINGS: Oral immunotherapy remains the best studied form of food immunotherapy. In 2017, further evidence has been added to its efficacy. Its mechanisms of action are under scrutiny. To reduce its side effects, studies have been dedicated to the simultaneous use of biologics, in particular omalizumab. Among the other forms of food immunotherapy that are being developed, the epicutaneous application of food allergens is promising. SUMMARY: The immunologic trajectories of the development of food tolerance may be intercepted by different forms of food immunotherapy. Research efforts aim to make these therapies feasible at the clinical level.

Profilin desensitization: A case series.

The role of profilin as an allergen has long been questioned. The capacity of profilin to induce respiratory symptoms has recently been demonstrated; moreover, over 50% of patients sensitized to profilin experienced symptoms after the ingestion of plant-derived foods, suggesting that profilin should be considered as a clinically relevant food allergen.We describe the cases of seven allergic patients with oral allergy syndrome and other adverse reactions after eating plant-derived food, that have been undergone to profilin desensitization treatment.The protocol started with a drop of profilin solution (50 µg/mL) diluted 1:10(18) in water until the highest dose of 10 drops of undiluted solution three times a week. At the end of the treatment we observed a decreased mean diameter of profilin wheal in skin prick test (SPT) in five of the seven participants and in profilin specific IgE values in six patients that repeated the test. Regarding basophil activation test (BAT) and the detection of IgG4, we do not have significant results because the tests have to be repeated in some patients. Regarding the double-blind placebo-controlled challenges, after about 10 months of induction phase all the patients showed tolerance to several foods that they previously did not tolerate.Moreover, the immunotherapy with profilin has proved to be safe because no serious adverse events have been reported in our patients.In summary, the results of this exploratory study of sublingual immunotherapy (SLIT) for profilin allergy show that it can be a promising therapeutic option that could modify the clinical reactivity of the patients to the intake of plant-derived food.

Utility of Basophil Activation Test for monitoring the acquisition of clinical tolerance after oral desensitization to cow's milk: Pilot study.

OBJECTIVE: The quantification of basophil activation by flow cytometry is a useful tool for the assessment of immediate-type responses to food allergens and the prediction of clinical tolerance in food allergy patients. The aim of this study is to investigate how the analysis of allergen-induced CD63 up-regulation by flow cytometry can be effective in monitoring the acquisition of clinical tolerance by specific oral desensitization in food allergy. To our knowledge, this is the first study to examine this topic. MATERIALS AND METHODS: Three male patients affected by cow's milk allergy underwent successful oral desensitization to cow's milk. In order to monitor the acquired clinical tolerance that occurred after treatment, we performed laboratory tests for total and specific IgE, specific IgG4 and the Basophil Activation Test (BAT) both at baseline and at the end of the desensitization protocol. RESULTS: Using a fluorescent enzyme immunoassay, the comparison of specific cow's milk antibodies before and after treatment showed a decrease of specific IgE levels, without reaching normal values, and an increase of specific IgG4 levels. A complete suppression of cow's milk proteins (α-lactoalbumin, ß-lactoglobulin and casein) induced CD63 regulation was observed in all three reported cases. CONCLUSIONS: Using flow cytometry, food allergen-specific basophil responses could be monitored in order to identify an acquired tolerance induced by desensitization treatment. Although further studies are needed to develop this important new topic, it was interesting to note that the BAT seemed to be more sensitive and characterized by a close correlation with clinical tolerance.

Allergy and psychologic evaluations of patients with multiple drug intolerance syndrome.

The multiple drug intolerance syndrome is a clinical entity characterized by adverse drug reactions to at least three drugs, chemically, pharmacologically and immunogenically unrelated, manifested upon three different occasions, and with negative allergy testing. Symptoms referred by the patients are often subjective, of neurovegetative origin. The aim of the study is to characterize patients suffering from the multiple drug intolerance syndrome from a psychological point of view, and to compare them to healthy subjects. We studied 30 women suffering from the multiple drug intolerance syndrome. All subjects underwent the following psychodiagnostic tests: (1) the State Trait Anxiety Inventory-Form Y, (2) the Zung Self-rating Anxiety Scale, (3) the Zung Self-rating Depression Scale, (4) the Quality of life enjoyment and satisfaction questionnaire, (5) the Minnesota Multiphasic Inventory-2, (6) the Toronto Alexithymia Scale. The study group was compared to 30 healthy women. When compared with the control group, our patients showed: a higher anxiety, a higher grade of depression, this difference was statistically significant (p < 0.01); a high difference (p < 0.01) between the two groups as regards somatic symptoms; a higher grade of alexithymia (p < 0.01); and a worse quality of life, in all the analyzed ambits. These findings clearly demonstrate the importance of psychological symptoms in patients with the multiple drug intolerance syndrome, and show that a complex allergy and psychological work-up is mandatory in the management of these patients.

Latex sensitization: a special risk for the obstetric population?

BACKGROUND: Previous studies have reported a greater frequency of sensitization to latex in the female population and a higher incidence of anaphylactic reactions to latex during cesarean section. In this study, the authors investigated the prevalence of latex sensitization in obstetric patients compared with nonpregnant subjects. METHODS: Two hundred ninety-four healthy pregnant women who were at term with a singleton fetus and scheduled for caesarean section (group A) were compared with 294 healthy nulliparous women with childbirth potential undergoing gynecologic surgery (group B). Before surgery, patients completed a questionnaire, and venous blood samples were collected to measure specific immunoglobulin E serum concentrations with a fluorescent enzyme immunoassay test. Skin-prick tests were performed if adverse reactions occurred during surgery. Latex allergy was diagnosed on the basis of immunoglobulin E results and/or positive skin-prick tests. RESULTS: The prevalence of latex sensitization was higher in group A than in group B (15/294, 5.1% vs. 5/294, 1.7%; P < 0.05). A significant difference in specific immunoglobulin E serum concentration was noted between pregnant and nonpregnant patients who had a positive fluorescent enzyme immunoassay test (median serum concentration: 1.93 kilounits/l; interquartile range = 2.28 vs. 0.78 kilounits/l; interquartile range = 1.07; P less than 0.05). Two patients in group A experienced an anaphylactic reaction to latex. Statistical analysis disclosed no association between latex sensitization and accepted risk factor for latex allergy. CONCLUSIONS: The authors report a higher prevalence of latex sensitization in the obstetric population than in nonpregnant subjects undergoing gynecologic surgery.

Eosinophil cationic protein: A new biomarker of coronary atherosclerosis.

AIMS: Coronary atherosclerosis is a chronic inflammatory disease, but different inflammatory biomarkers may reflect different phases of atherosclerotic plaque evolution. We aimed at assessing the role of eosinophil cationic protein (ECP), a sensitive marker of eosinophil activation, and C-reactive protein (CRP) in coronary artery disease (CAD). METHODS AND RESULTS: Consecutive anginal patients with angiographic evidence of CAD [stable angina (SA) or non-ST-elevation acute coronary syndrome (NSTE-ACS)], or with angiographically normal coronary arteries (NCA) were enrolled. The severity of CAD was graded according to Bogaty's score and coronary lesion morphology was defined as smooth or complex. Baseline ECP and high sensitivity CRP were measured in all patients. Of 198 patients (64 + or - 10 years, male 74%), 91 had SA, 57 had NSTE-ACS and 50 had NCA. ECP levels were significantly higher in SA [30 microg/L (13.8-46.9), p<0.001] and NSTE-ACS [21.8 microg/L (5.5-46.3), p=0.016] compared to NCA [9.7 microg/L (6.1-13.6)], without significant difference between SA and NSTE-ACS (p=0.45). CRP levels were significantly higher in NSTE-ACS [2.38 mg/L (1.11-11.94)] compared to SA [1.48 mg/L (0.82-2.83), p=0.03], and NCA [1.09 mg/L (0.8-2.1), p<0.001], without significant difference between SA and NCA (p=0.20). The addition of ECP to main cardiovascular risk factors improved the area under the curve from 0.88 to 0.92, p=0.007 for the angiographic diagnosis of CAD; further addition of CRP increased the area to 0.94, p=0.014. At multiple linear regression analysis ECP levels independently predicted CAD severity (p=0.001), whereas CRP levels independently predicted lesion complexity (p=0.01). CONCLUSIONS: Our study shows that ECP is a marker of CAD and that different inflammatory biomarkers reflect different phases of atherosclerotic plaque evolution.

Pre-intervention eosinophil cationic protein serum levels predict clinical outcomes following implantation of drug-eluting stents.

AIMS: Eosinophils have been identified in post-mortem studies as important players of both restenosis and thrombosis after drug-eluting stent (DES) implantation. We aimed at assessing the association between baseline levels of eosinophil cationic protein (ECP), a marker of eosinophil activation, and recurrence of clinical events in a consecutive series of patients who underwent DES implantation. METHODS AND RESULTS: Two hundred patients (age 63 +/- 10.4, males 75%) undergoing implantation of first-generation DES (Taxus or Cypher stents) were enrolled. We measured serum levels of ECP and total IgE by enzyme-linked immunosorbent assay and of C-reactive protein by high-sensitivity nephelometry prior to percutaneous coronary intervention. A clinical follow-up was planned 18 months after discharge. Major adverse cardiac events (MACEs), such as cardiac death, recurrent myocardial infarction, or clinically driven target lesion revascularization, were the endpoint of the study. Twenty-two patients (11%) had MACEs and showed higher serum levels of ECP compared with those without MACEs [30.5 (14.4-50) vs. 12.2 (4.4-31) microg/L, P = 0.004]. At simple Cox regression analysis, serum levels of ECP were a significant predictor of MACEs (hazard ratio 1.016, 95% confidence interval 1.003-1.03, P = 0.018). CONCLUSION: This study shows for the first time an association between baseline ECP levels and the occurrence of MACEs in patients undergoing implantation of DES. Further studies are warranted to establish whether in this setting ECP is a risk marker or plays a contributory pathogenetic role.

Food allergy and food intolerance: diagnosis and treatment.

Food allergy is a matter of concern because it affects about 0.5-3.8% of the paediatric population and 0.1-1% of adults, and as well may cause life-threatening reactions. Skin prick testing with food extracts and with fresh foods, the measurement of food-specific IgE, elimination diets and a double-blind, placebo-controlled food challenge are the main diagnostic procedures; many non-validated procedures are available, creating confusion among patients and physicians. The treatment of food allergy is still a matter of debate. Antihistamines, corticosteroids and, if necessary (in case of anaphylaxis), epinephrine, are the drugs of choice for the treatment of symptoms of food allergy. Sodium cromolyn may be used prophylactically even though there are no controlled studies certifying its efficacy. The only etiologic treatment of food allergy is specific desensitization. Sublingual-oral-specific desensitization has been used by our group for the treatment of food-allergic patients with a high percentage of success.

Desensitization to thalidomide in a patient with multiple myeloma.

Cutaneous reactions to thalidomide have been noted in approximately 46% of patients treated with this drug. We describe a case of a 65-year-old woman with multiple myeloma who developed fever and a generalized, itchy maculopapular rash after a 2-day treatment with thalidomide 100 mg orally. Skin prick and patch test results with thalidomide were negative, while the oral provocation test results were positive. Because thalidomide was necessary for the patient, she underwent an oral desensitization protocol, and on the fifth day, she could tolerate 100 mg of oral thalidomide. To our knowledge, this is the first report in the literature regarding this topic.

Multiple-drug intolerance syndrome: clinical findings and usefulness of challenge tests.

BACKGROUND: Multiple-drug intolerance syndrome (MDIS) is characterized by adverse reactions to several classes of chemically unrelated drugs. OBJECTIVE: To analyze all patients with a history of adverse reactions to at least 3 drugs at the Allergy Unit of Policlinico Gemelli in a 6-year period to better characterize patients with MDIS and to find safe alternative drugs. METHODS: We studied 480 patients (aged >16 years) with a history of adverse reactions to at least 3 unrelated drugs and with negative allergy test results. Patients who had experienced mild adverse reactions that remitted spontaneously underwent challenge tests without any premedication (group A). Patients with a clinical history of moderate reactions received sodium cromolyn, 500 mg, before the challenge (group B). Patients with a clinical history of severe reactions or undergoing parenteral challenges were given an antihistamine 30 minutes before the challenge (group C). RESULTS: In group A, 491 tolerance challenge tests were performed: 414 had negative results and 77 had positive results. In group B, 1,077 tolerance challenge tests were performed: 956 had negative results and 121 had positive results. In group C, 240 tolerance challenge tests were performed: 214 had negative results and 26 had positive results. Comparing the tolerance of alternative drugs in groups A and B, groups A and C, and groups B and C, no significant results were observed (P = .24, .14, and .44, respectively). CONCLUSIONS: Patients with MDIS can tolerate alternative drugs. Premedication with sodium cromolyn or oral H1-antihistamines may be useful in preventing adverse reactions.

Oral specific desensitization in food-allergic children.

The possibility of obtaining oral desensitization in patients with food allergy is still a matter of debate. We decided to evaluate the safety and efficacy of standardized protocols for oral desensitization with the most common food allergens. Forty-two children (ages up to 16 years) diagnosed as affected by food allergy (on the basis of clinical history, skin prick tests, measurement of specific IgE, and double-blind, placebo-controlled food challenge) underwent a sublingual-oral desensitizing treatment according to new standardized protocols. The control group consisted of 10 patients who followed an elimination diet. The treatment was successfully completed by 85.7% of the patients. Specific IgE showed a significant decrease, while specific IgG(4) showed a significant increase, in all treated patients. The immunological modifications observed in our patients lead us to hypothesize that oral tolerance may be mediated by the same mechanisms as those involved in traditional desensitizing treatments for respiratory and insect sting allergy.

Idiopathic chronic urticaria and celiac disease.

Idiopathic chronic urticaria (ICU) is a chronic relapsing cutaneous disease. Some case reports or studies on small series of celiac disease (CD) patients have suggested a possible association between CD and ICU. The aim of this study was to assess the prevalence of CD in a population of adults ICU patients with respect to healthy controls. We consecutively enrolled 80 patients affected by ICU and 264 blood donors as the control population without a history of ICU. Serum anti-transglutaminase IgG and anti-endomysium IgA antibodies were evaluated in all subjects. In the case of positivity to serology, diagnosis was confirmed by duodenal biopsy. One of 80 (1.25%) ICU patients were positive to both anti-transglutaminase and anti-endomysium antibodies. Duodenal biopsy showed partial villous atrophy. One control of 264 (0.38%) had CD. No statistical difference was found in the prevalence of CD between the two groups. ICU patients do not seem to bear a greater risk for CD compared to the general population.

Specific ultrarush desensitization in Hymenoptera venom-allergic patients.

BACKGROUND: Hymenoptera venom hypersensitivity is an epidemiologically important problem. The only effective treatment in the management of venom-allergic patients with a history of generalized reactions to insect sting is specific immunotherapy. OBJECTIVE: To demonstrate safety and effectiveness of a modified ultrarush desensitization protocol in venom-allergic patients. METHODS: Fifty-seven patients with Hymenoptera venom allergy underwent a specific 1-day ultrarush desensitization by the subcutaneous route, reaching the cumulative dose of 101.1 microg in 2.5 hours. The maintenance dose (100 microg) was administered after 15 days and thereafter once a month. Patients were followed up for a year. Antihistamines were withheld for 15 days before and during desensitization to not underestimate the incidence of adverse effects. RESULTS: All patients but I completed the ultrarush desensitization. (This patient discontinued the treatment because of a hypertensive crisis not related to the desensitization.) The treatment caused a rapid variation of immunological parameters (IgE, IgG4) since the 15th day. After the desensitization, skin prick test results became negative in 15 patients (27%, decrease of 3.5 log), whereas they decreased in 14 patients (25%, decrease of 1 log). Sixty-four percent showed no adverse effects. Only 7% had a mild systemic reaction. CONCLUSIONS: Ultrarush desensitization is an effective and safe therapy in the management of patients with Hymenoptera venom allergy. In fact, it provides a faster tolerance, without significant differences regarding incidence of severe adverse effects, compared with traditional and rush protocols. It can be adopted for all patients, even children and teenagers.