How to hit the allergy target: A critical appraisal of intralymphatic immunotherapy with practical recommendations on ultrasound-guided injections.

BACKGROUND: Intralymphatic immunotherapy (ILIT) represents a promising novel approach treating allergic diseases. However, no standardized procedures or recommendations have been established or reported, despite the recognized fact that treatment efficacy relies on the ability to inject the allergen intranodally. OBJECTIVE: We aim to provide a critical appraisal of ILIT as a method of allergen immunotherapy and to deliver practical recommendations for accurate ILIT. METHODS: One hundred and seventy-three ILIT injections were performed in 28 (47%) women and 32 (53%) men with median age of 29 years (21-59). The injections were ultrasound-guided and recorded for retrospective analysis with respect to injection location, needle visibility, medication release, and patient characteristics. RESULTS: The results show that the correct positioning of the needle within the lymph node (LN) was most critical. If the whole length of the needle bevel was not inserted into the LN, substance backflush into the interstitium was observed. Selecting a more superficial LN and inserting the needle at a smaller angle towards the LN significantly improved needle visibility in the ultrasound. Longitudinal results showed that continuous practice significantly correlated with improved needle visibility and more accurate ILIT injections. CONCLUSION: Based on our results and practical experience, we propose several recommendations for LN selection and the correct handling of ultrasound probe and needle. We are confident that ILIT standardization and training will be important as to meet the goals of good safety and efficacy of ILIT.

Intralymphatic immunotherapy with birch and grass pollen extracts. A randomized double-blind placebo-controlled clinical trial.

INTRODUCTION: There is a need to evaluate the safety and efficacy of intralymphatic immunotherapy (ILIT) for inducing tolerance in patients with allergic rhinitis. METHODS: Thirty-seven patients with seasonal allergic symptoms to birch and grass pollen and skin prick test >3 mm and/or IgE to birch and timothy >0.35 kU/L were randomized to either ILIT, with three doses of 0.1 mL of birch pollen and 5-grass pollen allergen extracts on aluminium hydroxide (10,000 SQ-U/ml; ALK-Abelló) or placebo using ultrasound-guided intralymphatic injections at monthly intervals. Daily combined symptom medical score and rhinoconjunctivitis total symptom score were recorded during the peak pollen seasons the year before and after treatment. Rhinoconjunctivitis total symptom score, medication score and rhinoconjunctivitis quality of life questionnaire were recorded annually starting 2 years after treatment. Circulating proportions of T helper cell subsets and allergen-induced cytokine and chemokine production were analysed using flow cytometry and ELISA. RESULTS: There were no differences between the groups related to daily combined symptom medical score the year before and after treatment. Two years after ILIT (after unblinding), the actively treated group reported significantly fewer symptoms, lower medication use and improved quality of life than did the placebo group. After the pollen seasons the year after ILIT, T regulatory cell frequencies and grass-induced IFN-γ levels increased only in the actively treated group. CONCLUSION: In this randomized controlled trial, ILIT with birch and grass pollen extract was safe and accompanied by immunological changes. Further studies are required to confirm or refute the efficacy of the treatment.

Potential Cost Savings by Switching from Subcutaneous to Intralymphatic Insect Venom Immunotherapy.

INTRODUCTION: IgE-mediated bee venom allergy can be treated with allergen-specific immunotherapy (AIT). Subcutaneous immunotherapy (SCIT) is time and cost intensive due to the repeated consultations, but the costs are justified by the high risk of potentially life-threatening allergic reactions, including anaphylaxis. However, intralymphatic immunotherapy (ILIT) offers potential to reduce treatment costs due to a significant reduction in injections and a shorter duration of therapy. Therefore, we calculated the cost savings that arise when switching from SCIT to ILIT. METHODS: Treatment protocols for ILIT were based on previous ILIT studies. Treatment protocols for SCIT were based on routine treatment at the University Hospital Zurich (USZ). The treatment costs were calculated based on the internal hospital information system (KISIM). RESULTS: The calculations revealed a potential two-fold reduction in treatment costs if ILIT is used instead of SCIT in patients with bee venom allergy. The costs could be reduced from EUR 11,612.59 with SCIT to EUR 5,942.15 with ILIT over 5 years. CONCLUSIONS: This study shows that bee venom ILIT has a cost-benefit potential for health insurances and patients, which should encourage further ILIT studies and which should be taken into account when considering future implementation of ILIT in the standard care of venom allergy.

Evaluation of Safety, Efficacy, and Compliance of Intralymphatic Immunotherapy for Allergic Rhinoconjunctivitis: A Systematic Review and Meta-Analysis.

INTRODUCTION: Intralymphatic immunotherapy (ILIT) is an emerging type of allergen immunotherapy with fewer injections and shorter course for allergic rhinoconjunctivitis (ARC). The efficacy and safety have not been confirmed by informative and powerful evidence yet. METHODS: A systematic review and meta-analysis were conducted through electronic searching with PubMed, Web of Science, Embase, Scopus, and China National Knowledge Infrastructure (CNKI). The safety (incidence of adverse events [AEs]), compliance (percent of patients completing treatment), and clinical efficacy of ILIT were evaluated. Clinical efficacy could be assessed by improvement of subjective symptom and rescue medication use or the nasal tolerance to specific allergen. This study is registered with PROSPERO (CRD42022353562). RESULTS: 12 randomized controlled trials (RCTs) comparing ILIT with placebo and 3 trials (2 RCTs and one case-control study) comparing ILIT and SCIT were included in this review. Totally, 582 patients diagnosed as AR or ARC were enrolled. Almost all the AEs were mild-to-moderate reactions except 2 patients developed anaphylactic reactions at the intralymphatic injection dose 5,000 SQ-U in one study. ILIT got higher incidence of local AEs than placebo, but their incidence of systemic AEs was similar. ILIT was safer than SCIT (p < 0.05). Almost all the patients could complete ILIT treatment, and the most common reason for discontinuation of ILIT was AEs. The compliance of patients receiving ILIT seemed higher than patients receiving SCIT. ILIT could significantly ameliorate subjective allergic symptoms, especially for seasonal ARC, and increase nasal tolerance, similar to SCIT. CONCLUSION: ILIT was a safe and effective treatment for ARC and could achieve comparable clinical improvement with SCIT with shorter duration and higher compliance. Moreover, ILIT was safer than SCIT.

A 5-Year Open-Label Follow-up of a Randomized Double-Blind Placebo-Controlled Trial of Intralymphatic Immunotherapy for Birch and Grass Allergy Reveals Long-term Beneficial Effects.

BACKGROUND: Intralymphatic immunotherapy (ILIT) is a novel, faster alternative to conventional allergen immunotherapy (AIT). Few previous studies have evaluated its long-term effects. The objective of the present study was to complete a 5-year follow-up of a randomized double-blind placebo-controlled trial of ILIT for a combination of birch and grass allergens. METHODS: Fifty-eight patients with allergic rhinitis were treated with either placebo or a combination of ALK Alutard Birch and Grass 1000 SQ-U administered in 3 intralymphatic injections at 1-month intervals. A year after the vaccination, the symptoms induced by nasal provocation were significantly reduced. After 5-6 years, 20 out of 26 actively treated patients were followed up with a nasal provocation test (NPT) and seasonal registration of the combined symptom and medications score (CSMS), IgE and IgG4 levels in blood, and immunological markers in blood and lymph nodes and compared with 13 unvaccinated controls. RESULTS: The reduction in the NPT response with ILIT at year 1 could not be convincingly reproduced at year 5. The new CSMS scores were markedly lower among the previously treated patients than among the control group. Furthermore, grass-specific IgG4 was increased, grass-specific IgE decreased, FcεR1 on basophils was reduced, and the fraction of memory T-cells in lymph nodes increased. CONCLUSION: The combination of seasonal clinical data and immunological parameters supports the notion of a long-lasting effect of ILIT. These data support the concept of ILIT as a good alternative to traditional AIT in pollen-induced allergic rhinitis.

Efficacy of short-term combination of intralymphatic allergen immunotherapy and lokivetmab treatment in canine atopic dermatitis: A double-blinded, controlled, randomised study.

BACKGROUND: Allergen-specific immunotherapy (ASIT) is an effective therapy for canine atopic dermatitis (cAD). Intralymphatic immunotherapy (ILIT) is potentially beneficial in decreasing time to clinical effectiveness. OBJECTIVE: To compare clinical efficacy of six monthly ILIT injections combined with three monthly injections of lokivetmab (LVM) with monthly LVM monotherapy at Day (D)168. To monitor dogs treated with ILIT for an additional six months of subcutaneous immunotherapy (SCIT). ANIMALS: Thirty-six client-owned dogs with cAD. MATERIALS AND METHODS: In this double-blinded, randomised study, dogs received either six monthly injections of ILIT combined with three monthly LVM injections (ILIT group) or six monthly LVM injections (LVM group). Monthly evaluations with pruritus Visual Analogue Scale (pVAS), Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) and medication scores (MS) were undertaken. Owners completed a Quality of Life (QoL) questionnaire. Treatment success was predefined as ≥50% reduction in pVAS and CADESI-04 score ≤ 10. After D168, the ILIT group continued with SCIT until subjective assessment at 12 months. RESULTS: The treatment benchmark at D168 was achieved by 11.1% of the ILIT group and 11.8% of LVM group. A significant decrease in mean pVAS and CADESI scores was observed in both groups (p < 0.001). The ILIT group had a trend towards higher MS compared to LVM. QoL was better in LVM (p = 0.01). At 12 months subjective good-to-excellent response in 77.8% of dogs in the ILIT/SCIT group was seen. CONCLUSION AND CLINICAL RELEVANCE: The efficacy of this ILIT protocol was comparable with LVM monotherapy at six months. When ILIT was continued with SCIT, a favourable response was seen.

Intralymphatic immunotherapy with one or two allergens renders similar clinical response in patients with allergic rhinitis due to birch and grass pollen.

INTRODUCTION: There is a need for a fast, efficient and safe way to induce tolerance in patients with severe allergic rhinitis. Intralymphatic immune therapy has been shown to be effective. METHODS: Patients with severe birch and timothy allergy were randomized and received three doses of 0.1 ml of birch and 5-grass allergen extracts (10,000 SQ units/ml, ALK-Abelló), or birch and placebo or 5-grass and placebo by ultrasound-guided injections into inguinal lymph nodes at monthly intervals. Rhinoconjunctivitis total symptom score, medication score and rhinoconjunctivitis quality of life questionnaire were evaluated before treatment and after each birch and grass pollen season during three subsequent years. Circulating proportions of T helper subsets and allergen-induced cytokine and chemokine production were analysed by flow cytometry and Luminex. RESULTS: The three groups reported fewer symptoms, lower use of medication and improved quality of life during the birch and grass pollen seasons each year after treatment at an almost similar rate independently of treatment with one or two allergens. Mild local pain was the most common adverse event. IgE levels to birch decreased, whereas birch-induced IL-10 secretion increased in all three groups. IgG4 levels to birch and timothy and skin prick test reactivity remained mainly unchanged. Conjunctival challenge tests with timothy extract showed a higher threshold for allergen. In all three groups, regulatory T cell frequencies were increased 3 years after treatment. CONCLUSIONS: Intralymphatic immunotherapy with one or two allergens in patients with grass and birch pollen allergy was safe, effective and may be associated with bystander immune modulatory responses. CLINICAL TRIAL REGISTRATION: EudraCT (2013-004726-28).

Intralymphatic immunotherapy improves grass pollen allergic rhinoconjunctivitis: A 3-year randomized placebo-controlled trial.

BACKGROUND: Allergic rhinoconjunctivitis is a global health problem. Different allergen immunotherapy regimes are marketed but have low adherence because they are expensive, complex, and time-consuming. New allergen immunotherapy forms are needed. OBJECTIVE: In a 3-year follow-up double-blind randomized placebo-controlled trial, we aimed to investigate the effect of intralymphatic allergen immunotherapy (ILIT). METHODS: Patients with grass pollen rhinoconjunctivitis were treated with 3 ILIT injections and an ILIT booster 1 year later, 3 ILIT injections and a placebo booster, or 3 placebo injections and a placebo booster. Primary outcome was improvement in a combined symptom and medication score (cSMS). A novel evaluation tool with a linear regression model of cSMS and grass pollen counts was developed. Secondary outcomes were changes in grass specific immunoglobulins and skin and nasal provocation tests to grass pollen. RESULTS: A total of 36 patients were included. Log10-transformed cSMS was reduced by 0.30 (95% CI, 0.11-0.49; P = .002), equaling 48.5% (95% CI, 24.5%-62%), in the entire 3-year follow-up period, significant only in the first follow-up season but not in the second and third seasons. The regression model showed a 37% (P < .001) reduction in cSMS. The booster injection 1 year later had no additional effect. Secondary, repeated measures of IgE and IgG4 to grass showed significant between-group difference and within-group change in the ILIT groups. No change in provocation test results was found. CONCLUSIONS: ILIT gives a substantial reduction in grass pollen allergy symptoms and use of rescue medication, significant in the first season after treatment. A booster injection had no additional effect.

[The route is the destination-novel forms of application of allergen immunotherapy]. / Der Weg ist das Ziel ­ neue Applikationsverfahren der Allergenimmuntherapie.

Allergen immunotherapy (AIT) is the only causal therapy of IgE-mediated allergies if allergen avoidance is not feasible. Already well established are subcutaneous (SCIT) and sublingual (SLIT) allergen application, and recently the first oral immunotherapy (OIT) for treating peanut allergy was approved. Interesting and promising new forms of allergen administration are intralymphatic (ILIT) and epicutaneous (EPIT) immunotherapy. Immunologic and clinical efficiency in terms of tolerance induction have been investigated in animal and clinical studies, including the first phase 3 studies. The findings as well as advantages and disadvantages, potential risks and challenges that still have to be addressed before routine clinical application can be envisioned will be comprehensively presented and discussed.

Intralymphatic Immunotherapy: Update and Unmet Needs.

Allergen-specific immunotherapy (AIT) is the only allergy treatment that confers long-term symptom amelioration for patients suffering from allergy. The most frequently used allergen application route is subcutaneous injection (SCIT), commonly taken as the gold standard, followed by sublingual (SLIT) or oral (OIT) application of allergen preparations. This is an up-to-date review of the clinical evidence for a novel route of allergen application, i.e., directly into lymph nodes - intralymphatic immunotherapy (ILIT). The major advantages of ILIT over the current AIT approaches are its short duration and the low allergen doses administered. The whole treatment consists of merely 3 ultrasound-guided injections into inguinal lymph nodes 1 month apart. While the number of patients included in randomised controlled trials is still limited, the clinical results for ILIT are encouraging, but more clinical trials are needed, as well as more preclinical work for optimising formulations.

Clinical efficacy and safety of cervical intralymphatic immunotherapy for house dust mite allergic rhinitis: A pilot study.

BACKGROUND: Previous studies have demonstrated that intralymphatic immunotherapy (ILIT), a less time-consuming alternative to conventional subcutaneous immunotherapy (SCIT), is safe and effective. However, because of the private location of inguinal lymph nodes, inguinal ILIT is relatively inconvenient. We proposed a novel form of ILIT that involves 3 injections of allergen into cervical lymph nodes. The aim of this study is to determine the clinical efficacy and safety of cervical ILIT on house dust mite induced allergic rhinitis (AR) in adults. METHODS: In this study, we performed a prospective cohort study to determine the clinical efficacy and safety of cervical ILIT on house dust mite induced AR in adults, by comparing the symptom scores, quality-of-life scores (QOLS) and drug scores (use of rescue medication) before and after treatment. Meanwhile, side events were also recorded. RESULTS: Cervical ILIT elicited no moderate-severe adverse events. Patients receiving cervical ILIT experienced a significant improvement in nasal symptoms, eye symptoms and quality of life, as compared to baseline (P all <0.001). A reduction in the use of rescue medication was also demonstrated (P < 0.001). CONCLUSIONS: In this first-in-human clinical study, cervical ILIT was demonstrated safe and induced allergen tolerance after 3 injections.

Novel approaches and perspectives in allergen immunotherapy.

In this review, we report on relevant current topics in allergen immunotherapy (AIT) which were broadly discussed during the first Aarhus Immunotherapy Symposium (Aarhus, Denmark) in December 2015 by leading clinicians, scientists and industry representatives in the field. The aim of this symposium was to highlight AIT-related aspects of public health, clinical efficacy evaluation, mechanisms, development of new biomarkers and an overview of novel therapeutic approaches. Allergy is a public health issue of high socioeconomic relevance, and development of evidence-based action plans to address allergy as a public health issue ought to be on national and regional agendas. The underlying mechanisms are in the focus of current research that lays the ground for innovative therapies. Standardization and harmonization of clinical endpoints in AIT trials as well as current knowledge about potential biomarkers have substantiated proof of effectiveness of this disease-modifying therapeutic option. Novel treatments such as peptide immunotherapy, intralymphatic immunotherapy and use of recombinant allergens herald a new age in which AIT may address treatment of allergy as a public health issue by reaching a large fraction of patients.

[Innovative forms of specific immunotherapy]. / Innovative Formen der spezifischen Immuntherapie.

The clinical efficacy of allergen-specific immunotherapy depends on tolerance induction. Treatment success is currently limited by treatment-related adverse reactions. Novel approaches mainly target improvement of tolerability in addition to optimized immunogenicity. For epicutaneous immunotherapy (EPIT), commercially available treatment extracts are applied to skin via a patch. The route exhibits excellent tolerability and good clinical efficacy. The first encouraging data on a peanut EPIT were published in 2016. Intralymphatic immunotherapy (ILIT) study results show pronounced immunogenicity and persisting clinical efficacy after only three injections of a small amount of established extracts. New approaches of synthetic vaccine development focus on tolerance induction. These vaccines are genetically engineered with a precisely defined profile and can be manufactured in reproducible quality. Distinct immunogenicity of the antigenic determinants contained in the preparation as well as an optimized safety profile are expected. Grass, birch, cat, and mite vaccines are currently under investigation. Which of these approaches will gain market access is unclear up to date. Results of food immunotherapy studies reveal consistently poor tolerance and limited efficacy without encouraging perspective and are not discussed further.

IgG4 but no IgG1 antibody production after intralymphatic immunotherapy with recombinant MAT-Feld1 in human.

Allergy immunotherapy (AIT) mediates protection against allergen exposure in part due to allergen-specific antibodies. While immunization typically stimulated IgG1 and IgG2, AIT is often associated with production of IgG4. Here, twenty cat dander-sensitized patients were randomized to receive three injections of intralymphatic immunotherapy (ILIT) with MAT-Feld1 adsorbed to aluminum hydroxide or just aluminum hydroxide (placebo) in a double-blind setting (ClinicalTrials.gov NCT00718679). Whereas the clinical data, showing benefit of Mat-Feld1 ILIT was published in 2012 (Senti et al., J Allergy Clin Immunol, vol 129(5):1290-1296), the current study investigated the cat allergen-specific antibody responses. Blood was drawn prior to ILIT, as well as 1, 3, and 12 months after first ILIT. The sera were analyzed to characterize all IgG subclasses and IgE antibody responses. ILIT with MAT-Feld1 elicited high levels of total IgG that were maintained for at least 12 months. Interestingly, a strong increase in IgG4 and some increase in IgG2 were observed throughout the study, while production of cat-specific IgG1 and IgG3 was not stimulated by MAT-Feld1 ILIT. The IgE levels remained constant.

[Intralymphatic immunotherapy: An effective and safe alternative route for canine atopic dermatitis]. / Intralymphatische Immuntherapie: Eine sichere und effektive Methode zur Desensibilisierung der caninen atopischen Dermatitis.

INTRODUCTION: Allergen-specific immunotherapy (ASIT) is the only etiologic treatment of atopic dermatitis in dogs. In humans it has been shown that intralymphatic immunotherapy (ILIT) enhanced efficacy and patient compliance and reduced treatment time from 3 years to 8 weeks. As only safety data have been published yet, the aim of this study was to evaluate the clinical efficacy of ILIT in dogs. 20 atopic dogs underwent ILIT with alum-precipitated allergens administered every 4 weeks for 3 to 7 times in the popliteal lymph node. Pruritus (Hill score), CADESI (canine atopic dermatitis severety index), concurrent medications and adverse reactions were recorded initially and every 4 weeks for a total period of 24 weeks. The observed clinical response was good in 12/20 (60%) patients and improvement could be seen in some dogs already after 4 weeks. The median number of injections was 5.6. All dogs tolerated the procedure well and no adverse effects were recognized during or after ILIT. Therefore ILIT should be regarded as a safe alternative to subucaneous ASIT, enabling a faster clinical improvement with the same response rate.

INTRODUCTION: L'immunothérapie spécifique de l'allergène est le seul traitement étiologique de la dermite atopique du chien. On a pu montrer que, chez l'homme, l'immunothérapie intralymphatique (ITIL) augmente la fiabilité du traitement et permet de réduire sa durée de 3 ans à 8 semaines. Comme jusqu'à ce jour seules des données relatives à la tolérance avaient été publiées, la présente étude a pour but d'examiner l'efficacité clinique de l'ITIL chez les chiens. Vingt chiens atopiques ont été désensibilisés au moyen d'allergènes précipités à l'aluminium par ITIL dans les ganglions poplités toutes les 4 semaines. Le prurit (Hill score), le CADESI (canine atopic dermatitis severity index), les médicaments appliqués et les effets secondaires observés ont été enregistrés au début du traitement puis toutes les 4 semaines durant au total 24 semaines. 12/20 (60%) des patients ont bien répondu au traitement. L'amélioration clinique a pu être partiellement constatée après 4 semaines déjà. En moyenne, 5.6 injections ont été nécessaires. Tous les chiens ont bien toléré l'ITIL et il n'a pas été observé d'effet secondaire pendant ou après le traitement. L'immunothérapie intralymphatique semble donc une alternative sure à l'immunothérapie spécifique de l'antigène sous-cutanée et permet d'obtenir un effet plus rapide avec le même taux de réponse.

Immune regulation by intralymphatic immunotherapy with modular allergen translocation MAT vaccine.

BACKGROUND: Allergen-specific immunotherapy (SIT) faces problems related to side effects and limited efficacy. Direct administration of allergen extracts into lymph nodes induces increased specific IgG production and T-cell responses using significantly lower allergen doses. METHODS: In this study, mechanisms of immune regulation by MAT vaccines in vitro and in allergen-SIT of cat-allergic rhinitis patients, who received 3 inguinal intra-lymph node injections of MAT-Fel d 1 vaccine, were investigated in PBMC and cell cultures for specific T-cell proliferation, Fel d 1-tetramer-specific responses, and multiple immune regulatory molecules. RESULTS: MAT-Fel d 1 vaccine was efficiently internalized by antigen-presenting cells. This was followed by precaspase 1 cleavage to caspase 1 and secretion of IL-1ß, indicating inflammasome activation. Mat-Fel d 1 induced specific T-cell proliferation and an IL-10- and IFN-γ-dominated T-cell responses with decreased Th2 cytokines at 100 times lower doses than Fel d 1. Induction of immune tolerance by MAT-Fel d 1-ILIT involved multiple mechanisms of immune suppression. Early Fel d 1-specific T-cell activation was followed by full T-cell unresponsiveness to allergen after 1 year in the MAT-Fel d 1 group, characterized by increased allergen-specific T regulatory cells, decreased circulating Fel d 1 tetramer-positive cells, increased IL-10 and FOXP3 expression, and change in the HR2/HR1 ratio toward HR2. CONCLUSIONS: This study demonstrates the induction of allergen tolerance after 3 intra-lymph node injections of MAT-Fel d 1 vaccine, mediated by increased cellular internalization of the allergen, activation of inflammasome, and generation of allergen-specific peripheral T-cell tolerance.

Future Directions of Allergen Immunotherapy for Allergic Rhinitis: Experts' Perspective.

Allergen immunotherapy (AIT) is broadly used all over the world as the only available disease-modifying treatment option. The aim of this experts' perspective is to address 7 important unmet needs for the further direction of AIT and to provide the readership with the authors' positions on these topics. An international group of experts in the field of AIT have formulated 7 important aspects for the future position of AIT, performed a current literature review, and proposed a consented position on these topics. The aspects discussed and consented by the authors include: (1) alternative routes of allergen application in AIT, (2) potential of recombinant vaccines, (3) the role of allergy diagnosis based on component-resolved diagnosis for AIT composition, (4) the impact of COVID-19 vaccination for further innovations in AIT, (5) potential of combining biologics to AIT, (6) future innovations in high-risk children/adolescents, and (7) the future regulatory position on AIT. Important unmet needs and topics for AIT have been addressed in this expert review. The authors' views and personal position on these 7 aspects have also been elaborated.

Intralymphatic Immunotherapy with Ultrasound Guidance Seems to Be Associated with Improved Clinical Effect in Canine Atopic Dermatitis-A Retrospective Study of 109 Cases.

Background: Intralymphatic immunotherapy (ILIT) has been used successfully in both human and veterinary medicine as a safe and effective treatment for allergic diseases. Initially, ILIT was administered by ultrasound guidance, but palpation-based injections have become more popular among veterinary dermatologists. Data from human medicine, however, show that precise injection into the lymph node is mandatory, and injection quality clearly correlates with clinical response. Hypothesis: Our aim was to assess the impact of the injection method (ultrasound guidance versus palpation-based guidance) on clinical response in dogs with atopic dermatitis. Methods: A total of 129 canine atopic dermatitis (CAD) cases treated with ILIT between 2014 and 2022 were retrieved from the hospital clinical database. The included dogs had to receive at least three intralymphatic injections administered either by palpation or ultrasound guidance. Those cases were retrospectively assessed and compared regarding clinical response to ILIT. Results: In total, 84 dogs received ILIT by ultrasound guidance, and in 25 dogs, ILIT was injected based on palpation. The success rate of ILIT was significantly higher in the ultrasound guidance group when compared to palpation-based injections. Conclusions: Low-quality injections must be considered as a possible reason for ILIT failure in dogs. Further prospective and controlled studies are necessary to confirm these results.