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ABSTRACT: Hypersensitivity reactions to fluoroquinolones seem to be on the increase, especially immediate type reactions.
The aim of this study was to determine whether several conditions, including gender, age, type of reaction, time interval between the reaction and the study, type of symptoms, the specific fluoroquinolone involved in the reaction and previous confirmed hypersensitivity to betalactams or to other drugs were factors contributing to the development of hypersensitivity to fluoroquinolones.
We analysed retrospectively all patients attending our allergy department between January 2005 and December 2010 because of a reaction associated with fluoroquinolone administration. The diagnosis was confirmed by basophil activation test or drug provocation tests. In accordance with the results, patients were then classified as having hypersensitivity or non-hypersensitivity to fluoroquinolones.
A group of 218 patients was evaluated; 69 were confirmed as having hypersensitivity, 146 as non-hypersensitivity and 3 were excluded. Comparisons between groups showed that the allergic patients more often had a previous confirmed hypersensitivity to betalactams (P = 0.029), immediate reactions (P = 0.001) and anaphylaxis (P = 0.000), and moxifloxacin was the fluoroquinolone most frequently involved (P = 0.027). The logistic regression analysis showed three factors associated with the diagnosis of hypersensitivity reactions to fluoroquinolones: previous hypersensitivity to betalactams (OR: 4.571; 95% CI: 0.987-21.171; adjusted OR: 23.654; 95% CI: 1.529-365.853), immediate reactions (OR: 17.333; 95% CI: 4.374-68.691; adjusted OR: 52.493; 95% CI: 6.621-416.200) and reactions induced by moxifloxacin (OR: 3.091; 95% CI: 1.160-8.239; adjusted OR: 13.610; 95% CI: 2.419-76.565).
In patients who develop reactions to fluoroquinolones, hypersensitivity is more often confirmed in those with immediate reactions and when moxifloxacin is involved. Moreover, patients with hypersensitivity to betalactams are more prone to develop hypersensitivity reactions to fluoroquinolones.
Clinical & Experimental Allergy 05/2013; 43(5):560-7. · 5.03 Impact Factor
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ABSTRACT: Multiple Non-steroidal anti-inflammatory drugs (NSAID)-induced urticaria/angioedema is the most common manifestation of hypersensitivity reactions to NSAIDs. Diagnostic evaluation is based on the clinical history and a drug provocation test.
To evaluate the role of the clinical history in the diagnosis of multiple NSAID-induced urticaria/angioedema.
We studied a group of patients with an unequivocal history of urticaria and/or angioedema after NSAID intake. Subjects had to have had at least two episodes of cutaneous symptoms with two different COX-1 inhibitors. The diagnosis was confirmed in all cases by a drug provocation test with acetyl salicylic acid (ASA). Multivariate analysis was done by analysing different variables, including number of drugs involved, episodes and time elapsed between drug intake and symptom onset.
Of the total group of 75 cases with multiple NSAID-induced urticaria/angioedema diagnosed according to the clinical history, 76% developed a positive drug provocation test with ASA. The risk for having hypersensitivity was 17 times higher in patients who developed symptoms within the first 60 min after drug intake, 13 times higher in those who experienced reactions with more than two non-chemically related NSAIDs, and 10 times higher in women.
Drug provocation testing with ASA confirms the diagnosis of multiple NSAID-induced urticaria/angioedema in up to 92% of cases with an unequivocal clinical history, when reactions occur within 1 h and more than two different NSAIDs are involved.
Clinical & Experimental Allergy 01/2013; 43(1):85-91. · 5.03 Impact Factor
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J A Cornejo-García,
L R Jagemann,
N Blanca-López,
I Doña,
C Flores,
R M Guéant-Rodríguez,
M J Torres,
J Fernández,
J J Laguna,
A Rosado,
J A G Agúndez,
E García-Martín,
G Canto,
J-L Guéant, M Blanca
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ABSTRACT: To date, genetic studies of hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs) have been carried out mainly in aspirin-induced asthma and to a lesser extent in chronic urticaria, with no studies in patients with acute urticaria (AU), the most common entity induced by these drugs.
In this work, we analysed the association of common variants of 15 relevant genes encoding both enzymes and receptors from the arachidonic acid (AA) pathway with NSAID-induced AU.
Patients were recruited in several Allergy Services that are integrated into the Spanish network RIRAAF, and diagnosed of AU induced by cross-intolerance (CRI) to NSAIDs. Genotyping was carried out by TaqMan allelic discrimination assays.
A total of 486 patients with AU induced by CRI to NSAIDs and 536 unrelated controls were included in this large Spanish case-control study. Seven variants from 31 tested in six genes were associated in a discovery study population from Malaga (0.0003 ≤ p-value ≤ 0.041). A follow-up analysis in an independent sample from Madrid replicated three of the SNPs from the ALOX15 (rs7220870), PTGDR (rs8004654) and CYSLTR1 (rs320095) genes (1.055x10(-6) ≤meta-analysis p-value ≤ 0.003).
Genetic variants of the AA pathway may play an important role in NSAID-induced AU. These data may help understand the mechanism underlying this disease.
Clinical & Experimental Allergy 12/2012; 42(12):1772-81. · 5.03 Impact Factor
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ABSTRACT: Evidence demonstrates the existence of local allergic rhinitis (LAR) in nonatopic patients, although its prevalence in the rhinitis population remains unknown. The aim, therefore, of this study was to evaluate the prevalence, clinical characteristics, and severity of LAR in a Spanish rhinitis population, compared with patients having classical allergic rhinitis (AR) with systemic atopy or nonallergic rhinitis (NAR).
A group of 452 adult rhinitis patients were randomly selected from a total of 3860 who attended our allergy service over 1 year. A clinical questionnaire, skin prick test (SPT), spirometry, and serum total and specific IgE (sIgE) were evaluated. A nasal allergen provocation test with multiple aeroallergens (NAPT-M), including Dermatophagoides pteronyssinus, pollens, alternaria, and dog epithelia, was performed in patients with negative SPT and serum sIgE.
A total of 428 patients completed the study; 24 were excluded because of nasal hyper-reactivity. LAR was diagnosed in 25.7%, AR in 63.1%, and NAR in 11.2%. The LAR and AR patients had a similar clinical profile: a nonsmoking woman with severe, persistent perennial rhinitis frequently associated with conjunctivitis and asthma. More than 36% of LAR patients reported rhinitis onset in childhood. NAPT-M detected aeroallergen polysensitization in 37.3% of the LAR patients. Dermatophagoides pteronyssinus was the main sensitizing aeroallergen in LAR and AR (60% vs 54%, P > 0.05).
Local allergic rhinitis is a prevalent entity in patients evaluated with rhinitis. Persistent and severe symptoms associated with conjunctivitis and/or asthma and polysensitization were likely to be detected in LAR and AR.
Allergy 08/2012; 67(10):1282-8. · 6.27 Impact Factor
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ABSTRACT: Betalactam (BL) immediate-type allergy is influenced by environmental and genetic determinants, as illustrated by differences in worldwide prevalence and ethnicity from a same area and by associations with genes related to atopy.
To evaluate the association of atopy with BL allergy.
We measured specific Immunoglobulin E (IgE) against prevalent allergens and genetic predictors of atopy, IL13, IL4, IL4RA, IL4, and TNFA, in 340 patients and 340 controls from South of Spain.
Total IgE and IgE against mites were at higher concentration in patients. Patients with high total IgE and IgE against prevalent allergens had a slower decrease in BL IgE than nonatopic patients. IL4RA I50V and Q551R were associated with IgE against prevalent allergens and total IgE, respectively, and were also predictors of BL allergy.
Interacting determinants of atopy, total IgE, IgE against prevalent allergens, and IL4RA polymorphisms, contribute to the high prevalence of BL allergy in South of Spain.
Allergy 07/2012; 67(9):1181-5. · 6.27 Impact Factor
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ABSTRACT: Nonimmediate hypersensitivity reactions to iodinated contrast media (CM) are common. Allergological evaluation is necessary to confirm the diagnosis and to find a tolerated alternative. The aim of this study was to establish the role of skin testing and the drug provocation test (DPT) in the diagnosis of nonimmediate reactions to CM.
Skin intradermal testing and patch testing with delayed readings were carried out with different CM (iobitridol, iomeprol, iodixanol, iohexol, ioversol, iopramide and ioxaglate). Single-blind placebo-controlled DPT was carried out in those cases with a negative skin test. In seven cases, a skin biopsy was obtained from positive skin tests and positive DPT.
Of the 161 subjects evaluated, 34 (21.1%) were skin-test positive, 21 (50%) to Iomeprol, 7 (16.7%) to Iodixanol, 5 (11.9%) to Iobitridol, 4 (9.5%) to Ioxaglate, 3 (7.1%) to Iohexol and 1 (2.4%) to Iopramide. DPT was positive in 44 cases (34.6%) that were skin-test negative, 38 (76%) to Iodixanol, 8 (16%) to Iomeprol and 4 (8%) to Iohexol. Of 78 cases (48.4%) with confirmed hypersensitivity, 34 (43.6%) were identified by skin testing and 44 (56.4%) by DPT. Skin biopsies showed a perivascular mononuclear cell infiltrate, mainly in the dermis, with higher levels of CD4 than CD8 T lymphocytes, with expression of activation markers and skin homing receptors.
Patients with nonimmediate reactions to CM were identified by skin testing in 43.6% and by DPT in 56.4%. The method to confirm the diagnosis differed depending on the CM involved.
Allergy 05/2012; 67(7):929-35. · 6.27 Impact Factor
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ABSTRACT: Drug hypersensitivity reactions (DHRs) are among the most frequent reasons for consultation in allergy departments, and are becoming more common due to increasing prevalence and case complexity.
To study the clinical characteristics, drugs involved, diagnostic methods, and temporal variation of DHRs in a large series of patients over a 6-year period.
We included all patients attending our department between 2005 and 2010. The diagnosis was performed by in vivo and/or in vitro tests (basophil activation test and specific immunoglobulin [Ig] E in serum and drug provocation testing [DPT]) when indicated.
We evaluated 4460 patients who reported 4994 episodes (mean [SD] of 1.13 [0.36] [range, 1-3] episodes per patient). Based on clinical history, 37% of the episodes were attributed to nonsteroidal anti-inflammatory drugs (NSAIDs), 29.4% to beta-lactam antibiotics (BLs), 15% to non-BLs, and 18.4% to other drugs.Analysis of the 1683 patients (37.45%) finally confirmed as allergic showed the most frequent diagnosis to be hypersensitivity to multiple NSAIDs (47.29%), followed by immediate reactions to BLs (18.12%). There was an increase in reactions to non-BLs (from 21.2% to 31.9%; P < .03) over the study period, mainly due to an increase in allergy to quinolones (from 0.5% to 6.8%; P < .02); 44% of patients were diagnosed by clinical history, 14.6% by skin tests, 10.4% by in vitro tests, and 30.8% by DPT.
NSAIDs were the drugs most frequently involved in DHRs and the most common diagnosis was urticaria/angioedema with cross intolerance. Reactions to emerging drugs such as quinolone derivatives and radiocontrast media are becoming more common.
Journal of investigational allergology & clinical immunology: official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología 01/2012; 22(5):363-71. · 2.27 Impact Factor
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ABSTRACT: Peanut allergy is an increasingly serious disorder with a heterogeneous pattern of sensitization across different countries. In vitro diagnostic techniques may help in establishing these patterns.
To analyze the usefulness of determining specific immunoglobulin E (sIgE) with the ImmunoCAP fluorescence enzyme immunoassay (FEIA), the ImmunoCAP ISAC CRD103 microarray (ISAC), and the basophil activation test (BAT) in the molecular diagnosis of peanut allergy.
In 26 peanut-allergic patients, sIgE antibodies against allergic components were measured with FEIA, ISAC, and BAT.
The major peanut component in our population wasAra h 9.The detection of sIgE toAra h 9 using FEIA and BAT with this allergen yielded a sensitivity of 92% and 88% and a specificity of 95% and 100%, respectively. Overall diagnosis of peanut allergy by ISAC showed a sensitivity of 11% but a specificity of 95% since Ara h 9 was not present in the microarray version used. There was diagnostic agreement between the 3 techniques for the peanut allergens studied.
The determination of sIgE to Ara h 9 using FEIA and BAT offers high sensitivity and specificity in the diagnosis of peanut allergy in the Spanish population. The CRD103 version of ISAC is not of value in our region as it does not include the most common allergen, Ara h 9.
Journal of investigational allergology & clinical immunology: official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología 01/2012; 22(7):508-13. · 2.27 Impact Factor
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I Doña,
N Blanca-López,
L R Jagemann,
M J Torres,
C Rondón,
P Campo,
A I Gómez,
J Fernández,
J J Laguna,
A Rosado, M Blanca,
G Canto
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ABSTRACT: In subjects with hypersensitivity reactions with cross-intolerance to nonsteroidal anti-inflammatory drugs (NSAIDs), tolerance to selective COX-2 inhibitors has not been evaluated in large series of well-phenotyped cases.
We evaluated 252 patients with urticaria and/or angioedema caused by hypersensitivity owing to cross-intolerance to NSAIDs. In addition to the clinical history, diagnosis was confirmed by provocation to an alternative NSAID. Two groups were considered: (A) patients with cross-intolerance to NSAIDs and intolerance to paracetamol and (B) patients with cross-intolerance to NSAIDs and good tolerance to paracetamol. Etoricoxib was administered to Group A patients and to a representative sample of Group B patients. In the event of a positive response, serum tryptase levels were determined and skin biopsy was performed in five patients in each group.
Ibuprofen was the most commonly implicated drug, followed by acetylsalicylic acid (ASA). Urticaria was the most common manifestation, followed by angioedema. Most of the patients developed symptoms within 1 h. Twenty-five percent in Group A (n = 47) and 6% in Group B (n = 50) were intolerant to etoricoxib. Skin biopsy showed mast cell activation with the release of tryptase to the extracellular space but without the increase in serum tryptase levels.
Selective COX-2 inhibitors may be unsafe in subjects with urticaria and/or angioedema caused by hypersensitivity reactions to NSAIDs with cross-intolerance if they are intolerant to paracetamol. A quarter of patients who were intolerant to this drug were also intolerant to etoricoxib. In subjects with hypersensitivity to NSAIDs and intolerance to paracetamol, selective COX-2 inhibitors should be administered as a controlled, incremental dose provocation test to assess tolerance.
Allergy 08/2011; 66(11):1428-33. · 6.27 Impact Factor
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ABSTRACT: Skin testing with amoxicillin (AX) is necessary to diagnose immediate hypersensitivity reactions to this β-lactam. A commercial AX (DIA-AX) has recently become available for skin testing.
The aim of this study was to compare DIA-AX with the injectable form (INJ-AX) in patients who have well-demonstrated IgE-mediated hypersensitivity to AX.
Chemical characterization using high-performance liquid chromatography of both DIA-AX and INJ-AX reagents was performed. Patients diagnosed with an immediate allergic reaction to AX and a positive skin test to INJ-AX (N=55) were re-evaluated within 6 months by performing skin testing with INJ-AX and DIA-AX. Basophil activation test (BAT) and Radioallergosorbent test (RAST) inhibition assay using both reagents were performed in a selected group of patients.
The chemical analysis indicated that both DIA-AX and INJ-AX contained an AX compound with a purity above 95%. In the re-evaluation, 53 (96.4%) cases maintained skin test positivity to INJ-AX and were also positive to DIA-AX. Comparison of the papule area between the two reagents showed no significant differences between both reagents. BAT was performed in 30 samples and was positive to both compounds in 15 cases; no patient had a positive result to just one reagent. RAST inhibition studies using three individual cases and a pool of positive sera showed that the percentage inhibition detected with DIA-AX and INJ-AX was parallel and almost exactly the same.
This study shows that DIA-AX is equivalent to INJ-AX in terms of skin test response, as well as with in vitro immunochemical and biological tests. DIA-AX can therefore be used in the diagnosis of immediate hypersensitivity reactions.
Clinical & Experimental Allergy 08/2011; 41(11):1595-601. · 5.03 Impact Factor
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ABSTRACT: Few data on the diagnostic accuracy in pollinosis of the microarray ISAC of allergens are available.
We aim to comparatively analyse ISAC CRD103 with the whole-extract ImmunoCAP in grass and cypress pollen allergy, evaluating the suitability of the manufacturer's recommended cut-off points for both techniques.
We studied 120 atopic patients grouped into grass and cypress pollen-allergic patients and controls based on clinical history and skin prick tests. Specific IgE against Phleum pratense and Cupressus arizonica by ImmunoCAP and ISAC CRD103 were performed on all subjects.
In the grass pollen group (43 allergic/26 controls), both microarray and CAP showed high sensitivity (Se) and specificity (Sp) values (ISAC: Se 97.7, Sp 92.3; CAP: Se 95.3, Sp 96.1) for recommended cut-off points. Comparing the optimal (ISAC: 0.4 ISU; CAP: 0.33 kU/L) with the recommended cut-off points within the same technique, diagnostic agreement was observed in both techniques. Thus, CAP and ISAC showed similar diagnostic performance in grass pollen allergy when using recommended cut-off points. In cypress pollen group (12 allergic/92 controls), the microarray (Se: 91.7, Sp 91.3) showed similar Se but significantly higher Sp (P=0.034) than CAP (Se: 91.7, Sp: 80.4) using recommended cut-off points. However, although diagnostic performance of the microarray did not change when comparing the optimal (0.82 ISU) with the recommended cut-off point, CAP improved diagnosis of cypress pollen allergy, when applying the optimal (0.66 kU/L)(CAP Se: 91.7, Sp: 89.1) instead of the manufacturer's recommended cut-off point. Thus, when the most suitable cut-off point for both techniques (ISAC: 0.3 ISU; CAP: 0.66 kU/L) is selected, microarray and CAP provide equivalent diagnoses.
Component-based microarray ISAC CRD103 and whole-allergen CAP showed high Se and Sp diagnosing equally grass and cypress pollen allergy. The cut-off point for each allergen should be properly applied for both techniques.
Clinical & Experimental Allergy 07/2011; 41(10):1440-6. · 5.03 Impact Factor
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ABSTRACT: Cytotoxic T cells seem to be the main effector cells in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). However, recent data support a role of the innate immune system in the etiopathology of drug-induced cutaneous reactions. In this study, we analyzed the expression of $alpha$-defensins 1-3 in mononuclear cells from patients with SJS/TEN, drug-induced maculopapular exanthema (MPE), and healthy donors.
Allergy 03/2011; 66(3):360-7. · 6.27 Impact Factor
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ABSTRACT: Delayed reactions to iodine contrast media (CM) account for 1-3% of patients with adverse reactions to iodine CM. The cellular and molecular mechanisms of these reactions remain poorly documented. Although most of these reactions are T cell mediated, the involvement of dendritic cells (DC) has not been investigated sufficiently.
To determine whether the T cell response to iodixanol requires DC as antigen-presenting cell and, more particularly, to evaluate the changes induced by iodixanol on DC maturation and in vitro production of cytokines after drug stimulation in patients with maculopapular exanthema.
Peripheral blood lymphocytes, immature monocyte-derived DC (imDC) and skin biopsies were obtained from patients with delayed reactions to iodixanol and tolerant subjects. We studied the consequences of the interaction between DC, lymphocytes and iodixanol by phenotype analysis, proliferation and cytokine production.
A T-cell-mediated reaction was evidenced in patient biopsies, with a lymphocyte-rich, peri-vascular infiltrate. Iodixanol induced maturation of imDC from patients but not from controls, with expression of the co-stimulatory markers CD83, CD86 and CD40 and an increase in mean fluorescence intensity of CD80, CD86 and HLA-DR. In the absence of DC, positive cell proliferation to iodixanol was detected in only one patient while the addition of DC produced a positive test in five of the six patients. Similarly, the increase in cytokines (IFN-γ, IL-2, IL-6, IL-1b and TNF-α) was higher when imDC were introduced into the culture together with the culprit drug.
These results provide evidence for a DC-mediated mechanism in delayed allergic reactions to CM, influencing T cell proliferation and cytokine production. These new insights will be helpful for designing immunotherapeutic strategies and in vitro diagnostic tests of CM-delayed reactions.
Clinical & Experimental Allergy 03/2011; 41(5):657-64. · 5.03 Impact Factor
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I Doña,
N Blanca-López,
J A Cornejo-García,
M J Torres,
J J Laguna,
J Fernández,
A Rosado,
C Rondón,
P Campo,
J A Agúndez, M Blanca,
G Canto
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ABSTRACT: Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most frequently involved groups of medicines in hypersensitivity drug reactions. Two mechanisms can induce the reaction: immunological (sensitization) due to a specific IgE or T cell response and pharmacological (cyclooxygenase inhibition). The contribution of each of these mechanisms to the reactions is not well known.
To analyse a large group of subjects with confirmed hypersensitivity reactions to NSAIDs.
The drugs involved, the clinical entities induced and the time interval between drug intake and appearance of the reaction were studied. In cases where the diagnosis was not confirmed, a drug provocation test was carried out. Atopy status was also assessed with prick test and total IgE in serum.
A total of 659 patients were finally considered to have had hypersensitivity reactions to NSAIDs; 76% had cross-intolerance (CI) and 24% were selective responders (SR). The most important drugs involved in CI were propionic acid derivatives, in most cases ibuprofen, and in SR pyrazolones. In CI, the most frequent clinical entity was urticaria and angio-oedema and to a lesser extent airway involvement. The skin and airways were both involved in an important proportion of cases. The most frequent entities in SR were urticaria and/or angio-oedema followed by anaphylaxis. Atopy was significantly associated in the CI group (P<0.005).
Cutaneous hypersensitivity reactions by CI to NSAIDs are the most frequent entities induced by these compounds. In addition to aspirin, other NSAIDs are taking on a predominant role. Atopy can be a predisposing factor in patients with CI.
Clinical & Experimental Allergy 01/2011; 41(1):86-95. · 5.03 Impact Factor
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ABSTRACT: Betalactams are the commonest cause of allergic reactions mediated by either IgE or T lymphocytes in which innate and adaptive immune systems mediate the earlier stages of immunological responses. One of the links between these systems is related to the interaction between natural killer (NK) and dendritic cells (DC). We have evaluated the role of NK cells and NK-DC interaction in the immunopathological mechanisms of nonimmediate reactions to betalactams.
Patients allergic to amoxicillin (AX) (N = 17) and tolerant controls (N = 13) were included. Changes in phenotype (CD69, IFNγ, perforin, and granzyme B) in AX-stimulated NK cells, the cytotoxic activity on mature or immature DC (imDC), and the proliferation and phenotype of NK lymphocytes after culture with AX and DC were determined by flow cytometry.
Amoxicillin induced activation and increases of perforin and granzyme B (P = 0.007 and P = 0.041 respectively) but not IFNγ production in NK cells from patients. In NK subpopulations, AX induced a significant enhancement of perforin and granzyme B in CD56(dim) (P = 0.005 and P = 0.002 respectively) and of IFNγ in CD56(bright) (P = 0.001). The cytotoxic phenotype was demonstrated by an increase of annexin V only in imDC (P < 0.001). Amoxicillin also induced an increased NK proliferation with different patterns, cytotoxic or proinflammatory, depending on the presence of imDC or mature DC, respectively. No differences were observed in NK cells from tolerant controls.
These data could demonstrate the involvement of NK cells in the immunopathological mechanisms of nonimmediate allergic reactions to AX, showing that both the innate and adaptive immune systems are involved and crosstalk, producing amplification of the harmful effects observed in these drug reactions.
Allergy 12/2010; 65(12):1600-8. · 6.27 Impact Factor
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ABSTRACT: Allergic reactions to systemically administered corticosteroids seem to be infrequent considering their extensive use. The aim of the study was to evaluate the IgE response in patients with immediate allergic reactions to methylprednisolone (MP).
Four subjects who developed immediate reactions after MP administration and ten controls with good tolerance to MP administration were evaluated. Skin prick and intradermal testing were done using MP, hydrocortisone (HC), and dexamethasone (DX). If negative, a drug provocation test (DPT) was done to confirm the diagnosis and assess cross-reactivity. The in vitro IgE response was evaluated by the basophil activation test (BAT) and ImmunoCAP.
Three patients were diagnosed by the presence of a positive skin test in the immediate reading with MP, two by prick and one by intradermal testing, and one patient was skin test negative and diagnosed by DPT. All four patients had good tolerance to HC and DX. The BAT was positive for just MP in those patients with positive skin tests, with all patients being negative for HC and DX. Two patients were also ImmunoCAP positive to MP.
This study confirms the existence of immediate allergic reactions to MP and that some are mediated by specific IgE antibodies. Skin testing, ImmunoCAP and the BAT are useful to confirm the diagnosis.
Allergy 11/2010; 65(11):1376-80. · 6.27 Impact Factor
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ABSTRACT: Cytotoxic T cells seem to be the main effector cells in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). However, recent data support a role of the innate immune system in the etiopathology of drug-induced cutaneous reactions. In this study, we analyzed the expression of α-defensins 1-3 in mononuclear cells from patients with SJS/TEN, drug-induced maculopapular exanthema (MPE), and healthy donors.
DEFA1A3 gene expression was analyzed by quantitative and end-point RT-PCR. Intracellular flow cytometry, immunofluorescence and immunohistochemistry were carried out to verify α-defensin 1-3 protein expression in mononuclear cells from peripheral blood and skin infiltrates. α-Defensin 1-3 concentration was evaluated in plasma and blister fluid samples by ELISA.
We herein describe DEFA1A3 gene expression in peripheral blood mononuclear cells (PBMCs) from patients with drug-induced cutaneous diseases. Gene expression analysis unveiled transcription in CD4 and CD8 peripheral blood T cells. Protein expression was confirmed by intracellular flow cytometry in mononuclear cells from the patients, including monocytes, NK cells, and T cells from peripheral blood and blister fluid. Further analysis of protein content by flow cytometry revealed higher protein levels in CD56(+) CD3(+) lymphocytes from patients with SJS/TEN when compared to MPE and healthy donors. Immunohistological analysis was used to confirm expression in dermal infiltrates. α-Defensin levels were estimated by ELISA to be 3- to 175-fold higher in blister fluid when compared to simultaneously drawn plasma samples.
Upregulation of innate immune molecules such as α-defensins 1-3 in T cells from patients with SJS/TEN may be involved in the etiopathology of these life-threatening diseases induced by medications.
Allergy 09/2010; 66(3):360-7. · 6.27 Impact Factor
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ABSTRACT: Delayed hypersensitivity reactions to drugs can be life-threatening and constitute a growing problem in clinical practice. Although drug-specific T cells seem to be involved, the cellular and molecular bases of their aetiopathology are not fully understood.
To study the molecular mechanisms underlying the pathogenesis and the clinical heterogeneity of cutaneous delayed hypersensitivity reactions to drugs.
We characterized the gene expression profiles of peripheral blood mononuclear cells (PBMCs) isolated from patients during the acute phase of the reaction and upon resolution of clinical symptoms using a cDNA array technology. Low-density arrays were used to confirm differential expression of selected genes during the acute disease in patients and to compare gene expression in patients and exposed control donors by quantitative real-time polymerase chain reaction.
Eighty-five genes were found to be differentially expressed during the acute phase of cutaneous drug-induced delayed hypersensitivity reactions. Furthermore, 92 genes with distinct expression patterns in severe and benign diseases during the acute phase were identified. PBMCs from patients with severe bullous diseases showed a characteristic gene expression pattern with lower expression of genes encoding T cell-specific proteins and high expression of cell cycle-related genes and genes coding for inflammatory-related mediators among which several endogenous damage-associated molecular patterns (DAMPs) or alarmins were found.
Distinct gene expression profiles in PMBCs define benign and severe clinical entities. Overexpression of endogenous DAMPs in Stevens-Johnson syndrome and toxic epidermal necrolysis suggest that drugs can trigger the alarmin system in sensitized patients leading to life-threatening diseases.
British Journal of Dermatology 05/2010; 162(5):1014-22. · 3.67 Impact Factor
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ABSTRACT: Local allergic rhinitis (LAR) is characterized by in situ production of specific IgE (sIgE) antibodies and a positive response to a nasal allergen provocation test (NAPT) in the absence of atopy.
The aim of this study was to investigate the immunological mechanisms involved in the immediate and late responses after nasal exposure to Dermatophagoides pteronyssinus (DP) in patients with LAR.
A total of 40 subjects with LAR to DP were studied and compared with 50 healthy controls. Immediate and late responses to NAPT-DP were assessed using a visual analogue scale of nasal symptoms and acoustic rhinometry. Tryptase, ECP, total and sIgE-DP were measured in the nasal lavage by immunoassay at baseline, 15 min, 1, 6 and 24 h after nasal challenge.
NAPT-DP was positive in all patients, with significant increases in tryptase (45%), ECP (65%) and sIgE-DP (25%) (P<0.05). Sixty percent of the LAR patients presented an immediate response to NAPT-DP and 40% a dual response. Immediate responders showed a fast release of tryptase with a peak at 15 min after NAPT-DP, and a progressive increase in nasal ECP and sIgE-DP from 1 to 24 h after challenge, with a peak at 24 h. Dual responders presented persistently higher levels of tryptase from 15 min to 6 h after challenge, and a similar pattern of nasal release of ECP and sIgE-DP to immediate responders. There were no isolated late responders. NAPT-DP was negative in all healthy controls, with no increases in tryptase, ECP, or total and sIgE-DP in nasal secretions.
The results demonstrated the existence of immediate and dual responses to a NAPT with DP in LAR patients, with the local presence of sIgE and mast cell/eosinophil activation.
Clinical & Experimental Allergy 03/2010; 40(7):1007-14. · 5.03 Impact Factor
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ABSTRACT: Local allergic rhinitis is a newly described type of rhinitis involving nasal production of specific immunoglobulin (slg) E antibodies in the absence of atopy. It can affect patients previously diagnosed with non-allergic rhinitis. Evidence for this entity is supported by clinical symptoms, local production of slgE, a type 2 helperT cell inflammatory pattern in nasal secretions during natural exposure to aeroallergens, and a positive response to nasal allergen provocation with local nasal production of slgE to aeroallergens, tryptase, and eosinophil cationic protein (ECP). Based on these new findings, an advanced diagnostic approach is proposed in patients with symptoms suggestive of allergic rhinitis but negative results in skin prick test and serum slgE determination. Detection of local slgE in nasal secretions during natural exposure to aeorallergens and a positive nasal allergen provocation test with local production of tryptase, ECP, and slgE are useful for detecting patients with local allergic rhinitis.
Journal of investigational allergology & clinical immunology: official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología 01/2010; 20(5):364-71; quiz 2 p following 371. · 2.27 Impact Factor
