High-dose pollen intralymphatic immunotherapy: Two RDBPC trials question the benefit of dose increase.

BACKGROUND: The same dosing schedule, 1000 SQ-U times three, with one-month intervals, have been evaluated in most trials of intralymphatic immunotherapy (ILIT) for the treatment of allergic rhinitis (AR). The present studies evaluated if a dose escalation in ILIT can enhance the clinical and immunological effects, without compromising safety. METHODS: Two randomized double-blind placebo-controlled trials of ILIT for grass pollen-induced AR were performed. The first included 29 patients that had recently ended 3 years of SCIT and the second contained 39 not previously vaccinated patients. An up-dosage of 1000-3000-10,000 (5000 + 5000 with 30 minutes apart) SQ-U with 1 month in between was evaluated. RESULTS: Doses up to 10,000 SQ-U were safe after recent SCIT. The combined symptom-medication scores (CSMS) were reduced by 31% and the grass-specific IgG4 levels in blood were doubled. In ILIT de novo, the two first patients that received active treatment developed serious adverse reactions at 5000 SQ-U. A modified up-dosing schedule; 1000-3000-3000 SQ-U appeared to be safe but failed to improve the CSMS. Flow cytometry analyses showed increased activation of lymph node-derived dendritic but not T cells. Quality of life and nasal provocation response did not improve in any study. CONCLUSION: Intralymphatic immunotherapy in high doses after SCIT appears to further reduce grass pollen-induced seasonal symptoms and may be considered as an add-on treatment for patients that do not reach full symptom control after SCIT. Up-dosing schedules de novo with three monthly injections that exceeds 3000 SQ-U should be avoided.

Limited beneficial effects of systemic steroids when added to standard of care treatment of seasonal allergic rhinitis.

Intramuscular injections with methylprednisolone treating allergic rhinitis (AR) have a long history. Modern guidelines are designed to dissuade this treatment, but it´s frequently used, especially in primary care. This despite of concern for side effects and lack of modern placebo-controlled studies. This study was designed to evaluate if methylprednisolone, could significantly improve symptoms of birch pollen induced AR and reduce the concomitant use of standard of care medication. Forty-two patients with birch pollen induced AR were randomized to treatment with methylprednisolone (80 mg) or placebo (NaCl 0.9%). Daily symptom- and medication scores was registered for 3 weeks. Quality of life questionnaires Sino-nasal Outcome Test-22 (SNOT-22) and Juniper Rhinoconjunctivitis Quality of Life Questionaire (Juniper RQLQ) were registered at trial start and at the end of the 3 weeks period. The combined symptom- and medication scores indicate that the methylprednisolone treated group [mean Area Under the Curve (AUC) 37.1 (SD 16.2 (95% CI 29.9-44.6))] was significantly better off than the placebo group [mean AUC 49.1 (SD 10.1 (95% CI 44.5-53.7))], p = 0.008. No significant difference between the groups were found in the SNOT-22 and Juniper RQLQ analysis. Registered side effects were few and mild. The limited beneficial effects of systemic steroids when added to standard of care in combination of its potential risk for side effects, speaks against its use for treatment of severe seasonal allergic rhinitis. The lack of difference in quality-of-life further underscores this result.

Autoimmune Pancreatitis Type 1 with Biliary, Nasal, Testicular, and Pulmonary Involvement: A Case Report and a Systematic Review.

INTRODUCTION: Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated condition associated with fibroinflammatory lesions that can occur at almost any anatomical site. It often presents as a multiorgan disease that may mimic malignancy, infection, or other immune-mediated conditions. Autoimmune pancreatitis (AIP) type 1 is the most prominent manifestation of IgG4-RD in the digestive tract, with common extra-pancreatic inflammation. We present the first patient with AIP and involvement of the testicles and nasal cavity. PATIENT AND METHODS: A case of a patient with AIP type 1 and other organ involvement (bile ducts, testicles, nasal polyps, and lungs) is described. Additionally, a systematic review of AIP type 1 with testicular and nasal involvement was conducted. RESULTS: The systematic review found two cases of AIP type 1 with testicular involvement and 143 cases with AIP type 1 with nasal cavity involvement. None of them had both testicular and nasal involvement. CONCLUSIONS: This is the first case of AIP type 1 with other organ involvement, including testicular and nasal involvement, to be described. The number of patients with nasal and testicular involvement described in the literature is low. Creating awareness of this rare clinical condition is necessary, especially due to the very effective available treatment with corticosteroids and rituximab.

A preseason booster prolongs the increase of allergen specific IgG4 levels, after basic allergen intralymphatic immunotherapy, against grass pollen seasonal allergy.

BACKGROUND: Allergen specific IgG4 levels have been monitored as a surrogate marker for the tolerance inducing effect of subcutaneous immunotherapy (SCIT) in many studies. Its accuracy at group level has been well established, but IgG4 has not yet found its place in the daily care of immunotherapy patients. METHODS: Intralymphatic immunotherapy (ILIT) is a novel route for allergy vaccination against pollen allergy, where an ultrasound-guided injection of 1000 SQ-U Alutard is given directly into a groin lymph node. The suggested standard dosing so far has been one injection with 4 weeks in-between. In total 3000 SQ-U with the treatment completed in 2 months. IgG4 was measured with Immulite technique and rhinoconjunctivitis symptoms were estimated with daily online questionnaires. Mann-Whitney U-test and Wilcoxon Signed Rank test were applied for comparisons between groups and within groups, respectively. RESULTS: The present study demonstrates that a single, preseason ILIT booster of 1000 SQ-U Alutard 5-grasses®, re-increases the allergen specific timothy-IgG4 levels, in patients already treated with ILIT before the previous pollen season. It also shows the feasibility of the ILIT-route for allergy vaccination of rhinitis patients, with or without concomitant asthma, with low degree of side effects and reconfirms high and sustained patient satisfaction. CONCLUSIONS: It is tempting to suggest that the allergen specific IgG4 levels can be used to build an intuitive algorithm for future clinical guidance of ILIT patients.Trial registration Is Intralymphatic Allergen Immunotherapy Effective and Safe?, ClinicalTrials.gov Identifier NCT04210193. Registered 24 December 2019-Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT04210193?term=NCT04210193&draw=2&rank=1.

Novel strategies for the treatment of grass pollen-induced allergic rhinitis.

INTRODUCTION: Allergic rhinitis (AR) affects over 20% of the population of Europe and the United States. Allergen immunotherapy (AIT) is currently the only form of treatment that affects symptoms and modifies the progression of disease. Established forms of AIT include subcutaneous (SCIT) and sublingual (SLIT) immunotherapy and are widely effective, yet only 2-9% of eligible patients undergo therapy, likely due to the long duration of treatment. As a result, novel, faster forms of AIT are currently under development. AREAS COVERED: This article provides an overview of AR and summarises the efficacy and mechanisms of established forms of AIT, highlighting the current drawbacks. We discuss novel strategies of AIT that have been developed in an attempt to tackle these limitations, including epicutaneous, intradermal and intralymphatic immunotherapy (ILIT), focusing on ILIT, the treatment that has been most comprehensively assessed. EXPERT OPINION: Current strategies to treat AR suffer from a poor safety profile and, importantly, lack of adherence. ILIT is a faster and safer form of AIT, with a treatment regime of only 12 weeks. Further validation is required, but ILIT, with its short and comparatively inexpensive protocol, has the potential to offer disease-modifying therapy to a larger number of patients.