Intralymphatic allergen administration renders specific immunotherapy faster and safer: a randomized controlled trial.

The only causative treatment for IgE-mediated allergies is allergen-specific immunotherapy. However, fewer than 5% of allergy patients receive immunotherapy because of its long duration and risk of allergic side effects. We aimed at enhancing s.c. immunotherapy by direct administration of allergen into s.c. lymph nodes. The objective was to evaluate safety and efficacy compared with conventional s.c. immunotherapy. In a monocentric open-label trial, 165 patients with grass pollen-induced rhinoconjunctivitis were randomized to receive either 54 s.c. injections with pollen extract over 3 years [cumulative allergen dose 4,031,540 standardized quality units (SQ-U)] or 3 intralymphatic injections over 2 months (cumulative allergen dose 3,000 SQ-U). Patients were evaluated after 4 months, 1 year, and 3 years by nasal provocation, skin prick testing, IgE measurements, and symptom scores. Three low-dose intralymphatic allergen administrations increased tolerance to nasal provocation with pollen already within 4 months (P < 0.001). Tolerance was long lasting and equivalent to that achievable after standard s.c. immunotherapy (P = 0.291 after 3 years). Intralymphatic immunotherapy ameliorated hay fever symptoms (P < 0.001), reduced skin prick test reactivity (P < 0.001), decreased specific serum IgE (P < 0.001), caused fewer adverse events than s.c. immunotherapy (P = 0.001), enhanced compliance (P < 0.001), and was less painful than venous puncture (P = 0.018). In conclusion, intralymphatic allergen administration enhanced safety and efficacy of immunotherapy and reduced treatment time from 3 years to 8 weeks.

Diffuse dermal angiomatosis associated with calciphylaxis.

Diffuse dermal angiomatosis (DDA) is a reactive proliferation of vascular channels within the dermis often associated with atherosclerosis. Based on our observation of a case of calciphylaxis (CP) with extensive DDA, we investigated a new possible association and incidence of DDA in patients with CP. These 2 rare conditions had not been reported previously in the same patient. In a retrospective review of skin biopsies taken between 1988 and 2006, 11 patients with histologically proven CP were identified and the medical records were reviewed. Two cases were excluded due to inadequate specimens for a thorough histologic evaluation. Nine patients with large necrotic plaques/ulcers were included in the study. Associated diseases were end-stage renal insufficiency (n = 7), parathyroidectomy for hyperparathyroidism (n = 3), thromboembolic events (n = 3), hypertension (n = 3), and diabetes mellitus (n = 2). Histologically, all cases had some degree of diffuse dermal proliferation of vascular channels with interstitial expression of CD31, as well as subcutaneous fat necrosis and calcification with medial vascular calcification. The extent of DDA did not correlate with the gravity or severity of disease. Based on our observation, DDA is a common histological finding encountered in the dermis adjacent to necrotizing ulcers in patients with CP.

Late biliary complications in human alveolar echinococcosis are associated with high mortality.

AIM: To evaluate the incidence of late biliary complications in non-resectable alveolar echinococcosis (AE) under long-term chemotherapy with benzimidazoles. METHODS: Retrospective analysis of AE patients with biliary complications occurring more than three years after the diagnosis of AE. We compared characteristics of patients with and without biliary complications, analyzed potential risk factor for biliary complications and performed survival analyses. RESULTS: Ninety four of 148 patients with AE in Zurich had non-resectable AE requiring long-term benzimidazole chemotherapy, of which 26 (28%) patients developed late biliary complications. These patients had a median age of 55.5 (35.5-65) years at diagnosis of AE and developed biliary complications after 15 (8.25-19) years of chemotherapy. The most common biliary complications during long-term chemotherapy were late-onset cholangitis (n = 14), sclerosing cholangitis-like lesions (n = 8), hepatolithiasis (n = 5), affection of the common bile duct (n = 7) and secondary biliary cirrhosis (n = 7). Thirteen of the 26 patients had undergone surgery (including 12 resections) before chemotherapy. Previous surgery was a risk factor for late biliary complications in linear regression analysis (P = 0.012). CONCLUSION: Late biliary complications can be observed in nearly one third of patients with non-resectable AE, with previous surgery being a potential risk factor. After the occurrence of late biliary complications, the median survival is only 3 years, suggesting that late biliary complications indicate a poor prognostic outcome.

A cutaneous allergen neutralisation test that correlates with the duration of venom immunotherapy.

BACKGROUND: Despite the well-documented efficacy of Hymenoptera specific immunotherapy (SIT), there is no safe method to reliably characterise the patient level of protection. Only poor correlations between protection and allergen-specific serum immunoglobulins have been found, and a sting challenge is the only means to evaluate the efficacy of immunotherapy. Therefore, we aimed to develop a cutaneous test that measures in vivo neutralisation of the Hymenoptera venom. MATERIALS AND METHODS: Twenty-four patients with wasp venom allergy were included in the study. Wasp-specific serum IgE, IgG and IgG4 were measured by ImmunoCAP. Dilutions of the individual patient sera were intradermally injected into the forearm. Then, wasp venom extract was injected into these sites to quantitatively assess the formation of wheals and flares. RESULTS: The results show that during the course of SIT, patient sera gained the capacity to neutralise skin reactions to wasp venom extracts in vivo. The test correlated with the duration of SIT as well as with the concentration of IgG and IgG4. CONCLUSION: The in vivo neutralisation test may become a promising tool in allergy diagnostics as well as in monitoring the success of SIT in patients undergoing allergen SIT.

Der p 1 peptide on virus-like particles is safe and highly immunogenic in healthy adults.

BACKGROUND: In mice, highly repetitive antigens, such as those present on bacterial or viral surfaces, efficiently cross-link B-cell receptors and therefore induce strong IgG responses. In this study we covalently coupled a synthetic 16-amino-acid sequence of the allergen Der p 1 to a virus-like particle derived from the bacteriophage Qbeta (Qbeta-Der p 1). OBJECTIVE: We evaluated the safety and immunogenicity of Qbeta-Der p 1 in human subjects and compared different doses and routes of immunization. METHODS: In a phase I trial 24 healthy volunteers were randomly assigned to one of 4 treatment groups. Group 1 received 50 microg of Qbeta-Der p 1 intramuscularly, group 2 received 50 microg of Qbeta-Der p 1 subcutaneously, group 3 received 10 microg of Qbeta-Der p 1 intramuscularly, and group 4 received 10 microg of Qbeta-Der p 1 subcutaneously. Boosting immunizations with 10 microg were given after 1 and 3 months. Antibody titers were measured after 1, 3, 4, 6, 12, and 18 months. RESULTS: The vaccine Qbeta-Der p 1 was well tolerated. Significant IgG responses were observed 4 weeks after a single injection. Individuals receiving 50 microg of the vaccine had significantly higher IgG titers than those vaccinated with 10 microg. However, the route of immunization (subcutaneous vs intramuscular) had no effect. In the 50-microg dose group, strong antibody responses against Der p 1 with average titers of 1:2000 were obtained. CONCLUSION: Vaccination with a peptide antigen covalently coupled to highly repetitive virus-like particles represents an adjuvant-free means of rapidly inducing high antibody titers in human subjects. CLINICAL IMPLICATIONS: Allergens coupled to virus-like particles can be used to enhance the efficiency of allergen-specific immunotherapy.