Follow-up study in local allergic rhinitis shows a consistent entity not evolving to systemic allergic rhinitis.

BACKGROUND: Local allergic rhinitis (LAR) is a common disease that affects 25.7% of the rhinitis population and more than 47% of patients previously diagnosed with nonallergic rhinitis. Whether LAR is the first step in the natural history of allergic rhinitis (AR) with systemic atopy or a consistent entity is unknown. OBJECTIVE: The aim was to evaluate the natural history of a population with LAR of recent onset and the development of AR and asthma. METHODS: A prospective 10-year follow-up study with initial cohorts of 194 patients with LAR of recent onset and 130 healthy controls is being undertaken. A clinical-demographic questionnaire, spirometry, skin prick test, and specific IgE to aeroallergens were done yearly. Nasal allergen provocation tests with Dermatophagoides pteronyssinus, Alternaria alternata, Olea europea, and a mix of grass pollen were performed at baseline and after 5 years. RESULTS: At disease onset, most of the patients with LAR had moderate-to-severe persistent-perennial rhinitis; conjunctivitis and asthma were the main comorbidities (51.1% and 18.8%, respectively), and D pteronyssinus was the most relevant aeroallergen (51.1%). After 5 years of follow-up, a worsening of rhinitis was detected in 26.2%, with an increase in symptom persistence and severity, and new associations with conjunctivitis and asthma. Atopy was detected by skin prick test and/or serum specific-IgE in patients with LAR (6.81%) and in controls (4.5%). CONCLUSIONS: This study shows a similar rate of development of systemic atopy in LAR and controls, which suggests that LAR is an entity well differentiated from AR. To determine the natural course of LAR more precisely, this study is in progress to complete 10 years of follow-up.

Basophil activation after nonsteroidal anti-inflammatory drugs stimulation in patients with immediate hypersensitivity reactions to these drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the drugs most frequently involved in allergic reactions of which two main types exist: IgE-mediated and crossintolerance. The diagnosis of crossintolerance reactions is often based on the drug provocation test. The potential value of the basophil activation test (BAT) was evaluated using different basophil markers in the diagnosis of patients with crossintolerance to NSAIDs and cutaneous symptoms. We studied 46 patients with crossintolerance to NSAIDs and 45 tolerant controls. BAT was performed with acetyl salicylic acid, paracetamol, diclofenac, dipyrone, naproxen, and ibuprofen at four different concentrations using CD193 and CD203c as basophil markers and CD63 as activation marker. We compared BAT results using CD193⁺ or CD193⁺ CD203c⁺ for basophil selection and found a significant increase in the stimulation index when using CD193⁺ CD203c⁺ in both patients and controls (P = 0.004 and P = 0.017, respectively). Selection of living cells only produced an increase in basophil stimulation in patients for both CD193⁺ and CD193⁺ CD203c⁺ (P < 0.001 for both), whereas in controls there was no change with CD193⁺ and a decrease with CD193⁺ CD203c⁺ (P = 0.001). We found that CD193⁺ CD203c⁺ increased the percentage of positive cases in patients and controls when compared with CD193⁺. When excluding dead cells, there was an increase of 21.7% in patients and 10% in controls. These results indicate that using CD193⁺ CD203⁺, excluding dead cells, is the best approach for BAT although this test is not recommended for the diagnosis of patients with crossintolerance to NSAIDs owing to its low sensitivity and specificity.

Immunological mechanisms underlying delayed-type hypersensitivity reactions to glatiramer acetate.

BACKGROUND: Delayed-type hypersensitivity to glatiramer acetate is rare, and the underlying immunological mechanisms are not completely understood. OBJECTIVE: To study the immunologic response in 2 patients with multiple sclerosis who developed maculopapular exanthema related with the administration of glatiramer acetate. METHODS: The allergologic study included general blood tests, viral serologic tests, and skin tests (patch and intradermal tests). The immunologic study was performed in skin biopsy specimens by immunohistochemistry and in the peripheral blood by flow cytometry and the lymphocyte transformation test. RESULTS: Skin test results were negative in both patients, and the diagnosis was confirmed by a drug provocation test. The evaluation of the acute phase showed an increase in the percentage of CD8 T lymphocytes (>50%) and the percentage of cells expressing skin-homing receptor (cutaneous lymphocyte-associated antigen) (>70%) and chemokine receptors (CCR4 and CXCR3) at T1. A positive proliferative response was observed in T lymphocytes (stimulation index [SI] = 3.5 in patient 1 and 3.59 in patient 2), especially the CD8(+) subpopulation (SI = 5.5 and 4.6 in patients 1 and 2, respectively), and NK lymphocytes (SI = 3.9 and 8.5 in patients 1 and 2, respectively) after glatiramer acetate stimulation. CONCLUSION: This study demonstrates the important role of T(H)1 cells expressing skin-homing receptors in delayed-type hypersensitivity reactions to glatiramer acetate. A lymphocyte transformation test revealed a specific glatiramer acetate recognition by T lymphocytes and NK lymphocytes.

Nasal allergen provocation test with multiple aeroallergens detects polysensitization in local allergic rhinitis.

BACKGROUND: Patients previously given a diagnosis of nonallergic rhinitis (NAR) might have a new form of local allergic rhinitis (LAR) with local production of specific IgE antibodies and a positive response to a nasal allergen provocation test (NAPT). OBJECTIVE: We evaluated an NAPT protocol using multiple aeroallergens (NAPT-M) for the detection of polysensitization to several aeroallergens in patients with LAR. METHODS: NAPT-Ms with 2 different panels of aeroallergens for patients with perennial and seasonal rhinitis were performed in 25 patients with LAR and 25 patients with NAR whose disease was diagnosed by means of NAPTs 1 year earlier. The response to nasal challenge was evaluated based on subjective (nasal-ocular symptoms) and objective (acoustic rhinometry) parameters. Nasal levels of tryptase and eosinophil cationic protein were determined by means of immunoassay at baseline, 15 minutes, and 1, 2, and 24 hours after challenge. RESULTS: NAPT-Ms showed 100% concordance with the gold standard of NAPTs with a single aeroallergen. No false-positive or false-negative responses were detected. The use of NAPT-Ms achieved 75% reduction in the total number of visits required for final diagnosis in the NAR group (from 168 to 42 visits) and a 55% reduction in the LAR group (from 144 to 65 visits) compared with NAPTs with a single aeroallergen. CONCLUSIONS: These results demonstrate that clinically relevant polysensitization to aeroallergens in patients with LAR occurred and that the NAPT-M is a useful, specific, sensitive, reproducible, and less time-consuming in vivo diagnostic test for the screening of patients with LAR.

Chloridotris(penta-fluoro-benzene-thiol-ato-κS)[tris-(4-fluoro-phen-yl)phosphine-κP]osmium(IV).

The title complex, [Os(C(6)F(5)S)(3)Cl(C(18)H(12)F(3)P)], displays a trigonal-bipyramidal Os(IV) coordination geometry with the S atoms of three thiol-ate ligands occupying the equatorial positions. The thiol-ate penta-fluoro-phenyl substituents are all placed above the equatorial plane, forming a claw-like cavity which accommodates the chloride ligand with a normal Os-Cl bond length. The phosphine ligand trans to the chloride ligand reveals a short Os-P bond length compared to other chloride-phosphine Os(IV) complexes (average = 2.40 Å). This strong bonding indicates that the inductive effect of the F atoms in the phosphine does not affect significantly its basicity, compared to triphenyl-phosphine. This feature is also consistent with the known poor trans influence of Cl(-). The crystal packing involves π-π contacts between inversion-related thiol-ate C(6)F(5) rings, with a centroid-centroid separation of 3.659 (8) Å.

Synergistic effect between amoxicillin and TLR ligands on dendritic cells from amoxicillin-delayed allergic patients.

Amoxicillin, a low-molecular-weight compound, is able to interact with dendritic cells inducing semi-maturation in vitro. Specific antigens and TLR ligands can synergistically interact with dendritic cells (DC), leading to complete maturation and more efficient T-cell stimulation. The aim of the study was to evaluate the synergistic effect of amoxicillin and the TLR2, 4 and 7/8 agonists (PAM, LPS and R848, respectively) in TLR expression, DC maturation and specific T-cell response in patients with delayed-type hypersensitivity (DTH) reactions to amoxicillin. Monocyte-derived DC from 15 patients with DTH to amoxicillin and 15 controls were cultured with amoxicillin in the presence or absence of TLR2, 4 and 7/8 agonists (PAM, LPS and R848, respectively). We studied TLR1-9 gene expression by RT-qPCR, and DC maturation, lymphocyte proliferation and cytokine production by flow cytometry. DC from both patients and controls expressed all TLRs except TLR9. The amoxicillin plus TLR2/4 or TLR7/8 ligands showed significant differences, mainly in patients: AX+PAM+LPS induced a decrease in TLR2 and AX+R848 in TLR2, 4, 7 and 8 mRNA levels. AX+PAM+LPS significantly increased the percentage of maturation in patients (75%) vs. controls (40%) (p=0.036) and T-cell proliferation (80.7% vs. 27.3% of cases; p=0.001). Moreover, the combinations AX+PAM+LPS and AX+R848 produced a significant increase in IL-12p70 during both DC maturation and T-cell proliferation. These results indicate that in amoxicillin-induced maculopapular exanthema, the presence of different TLR agonists could be critical for the induction of the innate and adaptive immune responses and this should be taken into account when evaluating allergic reactions to these drugs.