Phase II/III clinical trial to assess the tolerability and immunological effect of a new updosing phase of Dermatophagoides mix-based immunotherapy.

BACKGROUND: Immunologically enhanced subcutaneous specific immunotherapy (SCIT) has been developed with a fast and simplified updosing phase containing equal parts of the house dust mites (HDM) Dermatophagoides pteronyssinus and Dermatophagoides farinae (Dermatophagoides mix) adsorbed on aluminum hydroxide. OBJECTIVE: To evaluate the tolerability and immunological impact of the updosing phase of this new allergen extract formulation. MATERIAL AND METHODS: We performed a multicenter, open-label, single-arm, phase II/III clinical trial. The inclusion criteria were a clinical history of rhinitis/conjunctivitis due to HDM (with/without asthma) and sensitization to HDM (positive specific IgE and skin prick test). Five updosing injections of Dermatophagoides mix (300, 600, 3000, 6000, and 15000 SQ+) were administered at weekly intervals with 1 maintenance injection (15000 SQ+) 2 weeks after the last updosing injection. Two days after each visit, patients were contacted by telephone to follow up on any adverse events. IgE-blocking factor, IgG4, and immediate skin reactivity were evaluated. RESULTS: The sample comprised 102 patients (mean [SD] age, 29.3 [7.7] years; male, 52.9%). There were 117 adverse drug reactions (ADR): 101 were local, regardless of reaction size, in 48 (47.1%) patients and 7 were systemic (all grade I) in 5 (4.9%) patients. All ADRs were mild, except for 1, which was moderate. Six weeks of treatment led to statistically significant increases in IgE-blocking factor and IgG4, as well as a significant reduction in immediate skin reactivity. CONCLUSION: This new updosing phase of Dermatophagoides mix-based immunotherapy had a good tolerability profile and induced a significant immunological effect.

Clinical-Hematological Changes and Predictors of Severity in Acute Food Protein-Induced Enterocolitis Syndrome Reactions at Oral Food Challenge: A Multicenter Observational Study.

BACKGROUND: Oral food challenge (OFC) is the criterion standard for diagnosis of acute food protein-induced enterocolitis syndrome (FPIES). No diagnostic/prognostic biomarkers are available, and OFC assessment criteria are not validated. OBJECTIVE: To assess clinical-hematological changes and predictors of severity of FPIES reactions at OFC. METHODS: This was an observational multicenter prospective study. Children aged 0 to 18 years diagnosed with acute FPIES were recruited at follow-up OFC in 12 tertiary centers in Spain and Italy. OFC outcomes (as positive/negative/inconclusive and mild/moderate/severe) were assessed on the basis of published "2017 FPIES Consensus" criteria. Clinical characteristics were recorded, and full blood cell count was done at baseline, reaction onset, and 4 hours later. Regression analysis was performed to assess predictors of severe reactions at OFC. RESULTS: A total of 81 children had positive OFC (mild in 11% [9 of 81], moderate in 61% [49 of 81], and severe in 28% [23 of 81]). Increase in neutrophils and reduction in eosinophils, basophils, and lymphocytes were observed (P < .05). OFC was inconclusive in 19 cases despite objective signs or neutrophilia. Regression analysis showed that a 2-day OFC protocol where only 25% of an age-appropriate portion is given on day 1 (not sex, age, culprit food, cumulative dose, and previous reaction severity) was associated with reduced odds of severe reaction compared with giving multiple doses in a single day. CONCLUSIONS: Distinct hematological changes may help support FPIES diagnosis. Current OFC assessment criteria may not capture the broad spectrum of acute FPIES presentations. This 2-day protocol may be associated with a reduced risk of severe reactions. Future work should aim to develop safer OFC and non-OFC diagnostics for FPIES.

Cyclical hypereosinophilia with skin manifestations and a clonal T cell population.

Hypereosinophilia is a common biological finding in clinical practice, in some cases without an identifiable cause. We describe the case of a 59-year-old woman with recurrent attacks of facial angioedema, fever, pruritic cutaneous nodules, and eosinophilia that reached up to 12.7 x 10(9) cells/L during outbreaks. She had experienced 2 episodes every month for the last 12 years, and the episodes resolved with systemic corticosteroids. Other causes of eosinophilia were ruled out. The patient showed an aberrant T cell population with a CD3-CD4+ TCR- phenotype that accounted for up to 22% of circulating lymphocytes. Analysis of the T-cell receptor (TCR) gene showed evidence of clonal rearrangement. During the episodes, this cell population produced high levels of interleukin-5, which returned to normal levels between the outbreaks. However the aberrant T cell population remained unaffected after the treatment. We suggest that lymphocyte immunophenotyping analysis should be included in the diagnostic workup of patients with hypereosinophilic syndrome, including the variant type of episodic angioedema and eosinophilia (Gleich syndrome).

Cross-reactivity among amide-type local anesthetics in a case of allergy to mepivacaine.

Among the various adverse reactions to local anesthetics, IgE-mediated reactions, particularly to the more commonly used amide group, are extremely rare. We report the case of a 39-year-old man who suffered itching and generalized urticaria with facial angioedema 15 minutes after administration of mepivacaine. Skin tests revealed a strong positive reaction to mepivacaine, lidocaine, and ropivacaine, but negative reactions to bupivacaine and levobupivacaine. Furthermore, double-blind placebo-controlled subcutaneous challenge with bupivacaine and levobupivacaine was well tolerated. We conclude that an extensive allergologic study must be carried out in rare cases of true allergic reaction to amide-type local anesthetics in order to rule out cross reactivity.

Hypersensitivity to ketoconazole.

We report a patient who experienced generalized urticaria and facial angioedema following oral administration of ketoconazole. Skin prick tests with ketoconazole and oral challenge were positive. Conjugates of ketoconazole with human serum albumin were used for the in vitro study, obtaining a positive result in the histamine release test. No significant levels of IgE antibodies to ketoconazole were found by RAST. Controls did not react to any of these tests. These results suggest that the patient developed a type I hypersensitivity reaction to ketoconazole. In this case, skin prick tests with ketoconazole and histamine release test with a conjugate of ketoconazole with human serum albumin were useful in ketoconazole hypersensitivity diagnosis. Finally, skin tests with other imidazole agents were carried out, including metronidazole, ornidazole, and fluconazole that were negative.

Allergy to natural honeys and camomile tea.

Precipitation of food allergy reactions is well known in some patients with pollinosis when they consume natural food, such as honey or camomile tea. We present 9 patients with hay fever, with or without asthma, who experienced systemic allergic reactions after ingestion of natural honeys from two local areas (Andujar and Granada) and/or camomile tea. Pollen analysis showed a high level in sunflower pollen (23.6% of pollen grains) in the honey from Andujar but not in that from Granada. The diagnosis of food and respiratory allergy was based on history, skin prick tests and specific IgE activity against pollen from Compositae. Conjunctival challenge with camomile extract also gave positive results. The above allergological tests and the inhibition studies carried out, suggest that pollen of Compositae may be responsible for allergic reactions to certain natural foods and that the reactions are mediated by an IgE-related mechanism.