Prescription Of Immunotherapy Research Articles

How Molecular Diagnosis Can Change Allergen-specific Immunotherapy Prescription In A Complex Area Of Pollen Sensitization (madrid, Spain)

The identification of the disease-eliciting allergen is an essential prerequisite for the accurate prescription of Allergen-Specific Immunotherapy (SIT). The aim of this study was to evaluate whether molecular diagnosis (MD) may change indication and allergen prescription of SIT.

Polysensibilisation aux pneumallergènes : étude des profils cliniques et des modalités de prescription d’immunothérapies. Quelle immunothérapie pour les patients polysensibilisés ? Résultats d’une enquête nationale des pratiques auprès des allergologues

Purpose of the study To evaluate, in real life settings, the clinical profile and management of polysensitized patients according to the nature of allergens involved. Patients and methods Observational, prospective, multicentre, cross-sectional study conducted in France in patients older than 5 years, polysensitised and having a respiratory allergy. Sociodemographic data, history of allergy and the therapeutic approach considered were collected from September 2010 to January 2011. Results Of the 2434 polysensitized patients, included by 287 qualified doctors in allergy, 70.2% were polyallergic. Mite allergens were the most involved (77%) then grass pollen (75%) and animal dander (43%). The most frequent polyallergies were mites and grass pollen associations (39.7% of patients). Following the visit, a specific immunotherapy was prescribed to 84.3% of patients. Perennial sensitization increased the likelihood of introduction of sublingual immunotherapy (SLIT), while polysensitization was not a factor. The SLIT prescribed were mites extracts (53.3% of cases), grasses extracts (20.3%), and tree pollens extracts (12.6%). Patients received a single preparation (72.5%), with a single allergen for 86% of them, or two preparations (26.3%) with a single allergen for 97%. Conclusion Polysensitisation with polyallergy is a common feature of patients who visit. The prescription of immunotherapy was adapted to the complex profile of these patients. Desensitization was directed primarily against mites.

Allergen specificity is relevant for immunotherapy prescription in polysensitised children

The sensitization to more allergens, such as polysenitization, is becoming a frequent characteristic of allergic patients, since the childhood. However, this phenomenon is considered an obstacle to prescribe immunotherapy by many doctors. This study investigated the relevance of polysensitization in a cohort of allergic children and evaluated the number of allergen extracts prescribed for these children. There are allergens that are frequent, but not prescribed. This issue should be matter of adequate debate for Italian paediatricians.

Frequency of mold and pollen mixing in allergen immunotherapy prescriptions within a large health care system, 1990-2010

Proteolytic enzymes can be found in extracts produced from insects, mites, and molds. Loss of allergen extract potency over time may be attributed to several factors including the activity of proteolytic enzymes.1 Nelson et al2 demonstrated deleterious effects on the potency of pollen extracts when mixed with mold, with the exception of ragweed. Similarly, Grier et al3 also reported a decrease in extract recovery when combining high-protease- and low-protease–containing extracts. The most deleterious effects were seen when cockroach or mold was mixed with trees, grasses, and weeds, again with the exception of ragweed.

Characteristics of Patients with Respiratory Allergy in France and Factors Influencing Immunotherapy Prescription: A Prospective Observational Study (Realis)

To describe the sensitization profile of respiratory allergies in France, identifying factors influencing the prescription of allergen immunotherapy (AIT) [Transversal phase (T)], and assess treatment efficacy, tolerability, compliance and satisfaction [Longitudinal phase (L)]. French allergists (600) and pneumo-allergists (600) were offered participation and asked to recruit the first 20 new patients with allergic rhinitis (AR) and/or asthma, consulting for a first time allergy check-up with skin prick-test (T), and 5 patients sensitized to pollens (skin test and/or specific IgE) for whom SLIT with pollens was prescribed (L). In the T phase, 2,714 patients were recruited by 169 specialists, mostly allergists (76.5%). The majority (98%) suffered from AR, alone (57.7%) or with asthma (40.3%) and 80.3% suffered from moderate-to-severe rhinitis, mostly persistent (65.8%). Asthma, when present, was mostly intermittent (63.7%) or mild persistent (20.1%). Sensitization to house dust mites was the most common (64.5%), followed by grass pollens (61.5%), tree pollens (41.6%) and cat danders (30.5%). Poly-sensitization was seen in 73.6% of patients. AIT, mostly sublingual, was recommended in 55.6% of the patients, mostly (78.1%) because of insufficient control with symptomatic treatments. The overall impact of symptoms on QOL, positive skin test to grass pollens, ocular pruritus and/or nasal obstruction and moderate-to-severe rhinitis were significant predictors of SLIT prescription. Poly-sensitization or concomitant asthma were not seen as deterrents. Most patients consulting a specialist for allergy testing suffer from moderate-to-severe rhinitis. Treatment in current practice includes immunotherapy in half of the patients, and follows ARIA recommendations.

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

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

Recombinant allergen-based IgE testing to distinguish bee and wasp allergy

The identification of the disease-causing insect in venom allergy is often difficult. To establish recombinant allergen-based IgE tests to diagnose bee and yellow jacket wasp allergy. Sera from patients with bee and/or wasp allergy (n = 43) and patients with pollen allergy with false-positive IgE serology to venom extracts were tested for IgE reactivity in allergen extract-based tests or with purified allergens, including nonglycosylated Escherichia coli-expressed recombinant (r) Api m 1, rApi m 2, rVes v 5, and insect cell-expressed, glycosylated rApi m 2 as well as 2 natural plant glycoproteins (Phl p 4, bromelain). The patients with venom allergy could be diagnosed with a combination of E coli-expressed rApi m 1, rApi m 2, and rVes v 5 whereas patients with pollen allergy remained negative. For a group of 29 patients for whom the sensitizing venom could not be identified with natural allergen extracts, testing with nonglycosylated allergens allowed identification of the sensitizing venom. Recombinant nonglycosylated allergens also allowed definition of the sensitizing venom for those 14 patients who had reacted either with bee or wasp venom extracts. By IgE inhibition studies, it is shown that glycosylated Api m 2 contains carbohydrate epitopes that cross-react with natural Api m 1, Ves v 2, natural Phl p 4, and bromelain, thus identifying cross-reactive structures responsible for serologic false-positive test results or double-positivity to bee and wasp extracts. Nonglycosylated recombinant bee and wasp venom allergens allow the identification of patients with bee and wasp allergy and should facilitate accurate prescription of venom immunotherapy.

The natural history and epidemiology of insect venom allergy: clinical implications

Hymenoptera stings can cause severe systemic allergic reactions and occasionally fatal anaphylaxis, which contribute significantly to morbidity and deterioration in health-related quality of life. The latest epidemiological data confirm the importance of insect sting allergy as a cause of anaphylaxis. Despite the high prevalence of asymptomatic sensitization, the prevalence of sting-induced systemic reactions (SRs) is low. However, to date, no parameter has been identified that can predict who will have a future reaction and whether it will be a large local reaction or anaphylactic. The combination of several concomitant factors, which include environmental, genetics and individual factors, may account for the occurrence of a system reaction in individual patients. Several not completely known factors may be associated with the severity of systemic re-stings. As about 50% of subjects with fatal sting reactions had no documented history of a previous SR, greater insight of the natural history and risk factors is required, especially in asymptomatic sensitized subjects. For patients with SRs, prevention of future severe allergic reactions starts with referral to an emergency department, correct administration of epinephrine by medical staff, referral to an allergist and coaching for the self-administration of epinephrine. However, most insect sting victims failed to seek medical advice and hospital attendance does not always correlate with the severity of the allergic reaction. Moreover, only about one-third of patients received a prescription for self-injectable epinephrine and were officially referred to an allergist after being discharged, causing the non- or delayed prescription of specific immunotherapy. Significantly, this means that at least half of the sting fatalities in patients with a positive history could have been avoided through the timely administration of specific immunotherapy. These findings indicate the urgent need to educate the general population and doctors on the management of venom-allergic patients.

Improvement of Allergen Immunotherapy Prescriptions Using a Guideline-based Checklist

Improvement of Allergen Immunotherapy Prescriptions Using a Guideline-based Checklist

Metastatic amelanotic nodular melanoma during pregnancy

This case report presents a very aggressive course of amelanotic nodular melanoma during pregnancy resulting in death five months after delivery. A 34 year-old Caucasian woman at 19th week of the second pregnancy was diagnosed having amelanotic nodular melanoma (tumor thickness - 2.5 mm) with metastases to the regional right inguinal lymph node. Amelanotic nodular melanoma represents malignant melanocytic tumor of the skin, which clinically mimics a variety of benign and malignant skin conditions and therefore commonly leads to delayed diagnosis. Though primary tumor was excised immediately, other treatment procedures as radical lymphadenectomy and chemotherapy were delayed, and immunotherapy was not given totally. At the 29th week of pregnancy, the woman via naturalem delivered a healthy female child, and the chemotherapy was started. Since pregnancy limits the prescription of immunotherapy and chemotherapy, the prognosis for melanoma during pregnancy detected later than in the second stage is poor and can be illustrated by our reported case. Such patients seems to be at higher risk to develop metastasis of melanoma in the internal organs and occasionally even in the fetus; therefore, they should be timely informed about that.

Doctors' and Patients' Educational Levels Affect Immunotherapy Prescription

Cultural level appears to be a critical factor in the decision process of allergen-specific immunotherapy (SIT) both for doctors and patients. Thus, appropriate educational programs should be carried out to increase the number of allergic patients to be treated with SIT.

Evaluation of the IgE cross‐reactions among vespid venoms. A possible approach for the choice of immunotherapy

Hymenoptera venom allergy can be effectively cured with specific immunotherapy, thus the correct identification of the allergen is essential. In the case of multiple skin and serum positivities it is important to know if a cross-reaction among venoms is present. We studied by CAP-inhibition assays the degree of cross-reactivity between Vespula vulgaris and Polistes dominulus. Serum samples were obtained from consecutive patients with a clinical history of grade III-IV reactions to hymenoptera sting and with nondiscriminative skin/CAP positivity to both Vespula and Polistes. Inhibition assays were carried out with a CAP method, incubating the sera separately with both venoms and subsequently measuring the specific immunoglobulin E (IgE) to venoms themselves. Forty-five patients (33 male, mean age 40 years, age range 12-74, total serum IgE 242 +/- 168 kU/l) were included. Their specific IgE to Vespula and Polistes were 12.03 +/- 5.70 kU/l and 10.7 +/- 2.0 kU/l (P = NS), respectively. At the CAP-inhibition assays, in 25 patients a >75% heterologous inhibition by P. dominulus venom against V. vulgaris-specific IgE was found. In six subjects V. vulgaris venom effectively inhibited the P. dominulus-specific IgE. In the remaining 14 cases the CAP-inhibition test provided intermediate and not discriminative results. In 31/45 patients, the double sensitizations to venoms were probably the result of cross-reactions and the CAP-inhibition allowed identifying the true double sensitizations. This approach may be helpful for the correct prescription of immunotherapy in the case of V. vulgaris and P. dominulus double positivity.

In vivo and in vitro allergy diagnostics: it's time to reappraise the costs

The in vivo skin prick test (SPT) is widely considered less expensive than in vitro gamma-immunoglobulin E (IgE) determination in the diagnosis of allergy. The aim of the present paper is to evaluate the relevance of component-resolved in vitro diagnosis in comparison to extract-based diagnosis and the relative global costs in relation to clinical outcomes. For 50 individuals with suspected seasonal allergic rhinitis, we compared the costs of skin testing with those of specific IgE antibody measurement. The costs were higher for in vitro than in vivo testing. However, the clinical information obtained using recombinant reagents allowed correct identification of the sensitizing molecule. Recombinant allergens for specific IgE in vitro measurement provide more reliable information for immunotherapy prescription. This should be translated into a significant reduction in the overall costs sustained by the healthcare system.

Comparison of test devices for skin prick testing

Allergy skin testing guides developing avoidance plans and writing an immunotherapy prescription. The goal for the allergist is to apply allergen skin testing to the appropriate patient population by using a device that minimizes both false-negative and false-positive findings while minimizing patient discomfort. New skin testing devices continue to be developed with a trend toward production of multiheaded devices. Data on the performance of these devices in a head-to-head prospective fashion are limited. Our goal was to study 8 commonly used devices to compare their performance in a head-to-head fashion. In a prospective, double-blind fashion, the performance of 8 skin test devices was evaluated. Devices were tested with histamine and saline on both the arms and back of each subject. Devices were rotated over 4 testing sessions, at least a week apart, so each device was tested in each anatomic testing location. Performance elements examined included wheal, flare, pain, sensitivity, specificity, and intradevice variability. We found significant differences in all areas of device performance among all devices examined. Multiheaded devices also demonstrated significant intradevice variability and were more painful than single devices. Furthermore, multiheaded devices had larger reactions on the back, whereas single devices had larger reactions on the arms. Statistically significant differences exist among all devices tested. Providers should consider this data when choosing a device that suits their practice setting and ensure that technicians are sufficiently trained on the correct use of that device.

Foreign-body reaction due to incorrect injections of allergen extracts containing aluminum hydroxide gel

Background. – Subcutaneous allergen immunotherapy is considered as effective and safe in allergic patients. Although mild local cutaneous reactions occur frequently, the development of persistent nodules at the injection site is a rare event. We describe a case with unusual persistent nodular reactions at the sites of previous immunizations incorrectly performed via the intradermal route. Case. – A 42-year-old female presented with multiple persistent lesions on both forearms that appeared after allergen immunotherapy. Immunotherapy with an aluminum hydroxide-adsorbed mite extract had been started 3 years earlier. Prescription of immunotherapy and injections of the extract were performed in a rural private medical facility, under the supervision of a physician with no special allergy training; injections had been given erroneously intradermally rather than subcutaneously. Physical examination revealed multiple reddish, indurated cutaneous nodules at the injection sites. The diagnosis of a foreign-body granulomatous reaction was confirmed by histological examination of the lesions. Conclusions. – Intradermal injections of aluminum hydroxide-containing allergen extracts should be strictly avoided. This case emphasizes published international recommendations according to which specific allergen immunotherapy should be prescribed only by allergy specialists in order to avoid unsuitable indications and methods that can sometimes result in serious side effects.

Dose adjustments are unnecessary for local reactions occurring at immunotherapy satellite clinics

Rationale Although recent reports have found that a no dose adjustment policy for local reactions does not increase systemic reaction rates, this policy has not been examined in satellite clinics outside of the allergist's office. Methods In 9 satellite clinics from Apr 2002-Jun 2003, a no dose adjustment policy was followed for immediate and late local reactions. During this 15-month period, each suspected systemic reaction following immunotherapy was documented as part of an ongoing quality assurance program. Numbers of injections and systemic reactions were reported quarterly to the allergist prescribing the immunotherapy. Results During this 15-month period, 6,338 immunotherapy injections were administered among the 9 satellite clinics. There were a total of 43 systemic reactions resulting in a 0.68% reaction rate (43/6,338). The historical systemic reaction rate in the office of the prescribing allergist under the same no dose adjustment policy was not statistically different: 0.84% (89/10,636) vs. 0.68% (p=0.26). In addition to existing patients, a total of 84 new immunotherapy prescriptions were written for the satellite clinics during this time period by the single allergist. In general, an immunotherapy maintenance dosage of 0.5 mL 1:100 w/v was used and each maintenance vial consisted of 0.5-1 mL of each antigen. Conclusions A no dose adjustment policy at immunotherapy satellite clinics does not increase systemic reaction rates. Dose adjustments for local reactions are unnecessary and may delay achievement of a therapeutic dose, lead to patient non-compliance due to increased visits, increase costs, and place patients at an increased risk for dose administration errors.

Parietaria Profilin Shows Only Limited Cross-Reactivity with Birch and Grass Profilins

Background: In patients showing multiple reactivity to seasonal airborne allergens, a skin prick test (SPT) with Parietaria pollen scores frequently negative, suggesting that profilin from Parietaria might not share IgE-binding epitopes with profilin from botanically unrelated airborne allergens. This study investigated the immunologic cross-reactivity between profilins from Parietaria, grass and birch pollen. Methods: 36 patients hypersensitive to birch profilin, Bet v 2, underwent SPT with Parietaria, and IgE to both whole Parietaria pollen and Phleum profilin were sought in their sera by ELISA. In ELISA inhibition studies, IgE reactivity to Phleum profilin was measured before and after absorption of sera from Parietaria reactors with both whole Parietaria pollen extract, and Par j 1/Par j 2 fraction. Further, their IgE reactivity to whole Parietaria pollen was measured before and after absorption with the Par j 1/Par j 2 fraction. Results: All sera showed IgE reactivity to Phleum profilin. Only 14/36 (39%) patients had a positive SPT to Parietaria and 17/36 (47%) showed IgE to Parietaria. Absorption of sera from Parietaria reactors with whole Parietaria extract caused a marked reduction in IgE reactivity to grass profilin; in contrast, absorption of sera with the Par j 1/Par j 2 fraction did not exert any inhibitory effect on IgE reactivity to grass profilin. Absorption of sera with the Par j 1/Par j 2 fraction markedly reduced IgE reactivity to whole Parietaria extract in 8/9 cases. Conclusion: Less than 50% of patients sensitized to birch and grass profilin cross-react to Parietaria profilin. In most cases, cross-reactors are hypersensitive to major, specific Parietaria allergens as well. This findings may be of practical relevance when the prescription of specific immunotherapy is considered.