LTT and HLA testing as diagnostic tools in Spanish vancomycin-induced DRESS cases: A case-control study.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe T-cell-mediated off-target adverse reaction. DRESS cases caused by vancomycin have often been reported. The HLA-A*32:01 allele has been associated with genetic susceptibility to vancomycin-induced DRESS in US citizens of European descent. We have analyzed the association of the HLA-A*32:01 allele in 14 Spanish DRESS cases in which vancomycin was suspected as the culprit drug, and the lymphocyte transformation test (LTT) as an in vitro assay to evaluate vancomycin sensitization. The results were compared to vancomycin-tolerant control donors. LTT was performed in 12 DRESS cases with PBMCs from resolution samples available and in a group of 12 tolerant donors. ROC curves determined that LTT is a suitable tool to identify patients sensitized to vancomycin (AUC = 0.9646; p < 0.0001). When a stimulation index >3 was regarded as a positive result, contingency tables determined 91% sensitivity, 91.67% specificity, 91% positive predictive value, and 91.67% negative predictive value (p = 0.0001, Fisher's exact test). The HLA A*32:01 allele was determined by an allele-specific PCR assay in 14 cases and 25 tolerant controls. Among the DRESS cases, five carriers were identified (35.7%), while it was detected in only one (4%) of the tolerant donors, [odds ratio (OR) = 13.33; 95% CI: 1.364-130.3; p = 0.016]. The strength of the association increased when only cases with positive LTT to vancomycin were considered (OR = 24.0; 95% CI: 2.28-252.6; p = 4.0 × 10-3). Our results confirm the association of the risk allele HLA-A*32:01 with vancomycin-induced DRESS in Spanish cases, and support LTT as a reliable tool to determine vancomycin sensitization.

Stevens Johnson Syndrome versus Jarisch Herxheimer Reaction in an HIV Positive Patient with Secondary Syphilis.

BACKGROUND: HIV positive patients can suffer many complications due to infectious diseases. A sever drug reaction to some of the drugs involved in the treatment can overlap the symptoms of the infections, making the diagnosis very difficult. We present the case of a 28-year-old-man, HIV positive, with secondary syphilis, who developed a Stevens Johnson Syndrome (SJS) caused by one of the many drugs he received. The SJS was overlapped with a possible Jarisch Herxheimer Reaction, which complicated the diagnosis of the skin reaction. OBJECTIVE: In HIV+ patients, the overlapping of severe drug reactions and infectious diseases could be fatal, thus an accurate diagnosis is mandatory. MATERIAL AND METHODS: A Rapid Plasma Reagin Test (RPR), an ELISA test, a blood laboratory test, chest radiography and a skin biopsy were realized in order to diagnose the infectious disease and the cause of skin lesions. Intradermal tests and double blind challenge tests were realized in the allergy study. RESULTS: The laboratory tests confirmed the diagnosis of syphilis; the skin biopsy confirmed the cause of lesions, a severe allergic reaction as a SJS. The allergy study discharged all the drugs involved, except dypirone which wasn't proved in the study because of the severity of reaction, the high possibility to be the causative drug and the alternative of other similar drugs available. For the inflammatory response, HIV+ patients are especially susceptible to severe reaction, both infectious and allergic, as in this case. Thus, recent patents emphasize the interest in inflammatory molecules that cause inflammatory symptoms. CONCLUSIONS: Although the diagnose of SJS has established criteria, the possibility of overlapping with infectious illness and/or with its treatment, may complicate the diagnosis.

Immediate reactions to iodinated contrast media.

BACKGROUND: Immediate hypersensitivity reactions (IHRs) to iodinated contrast media (ICMs) remain a common clinical concern. Positive skin test and basophil activation test results suggest a specific IgE-mediated mechanism in some cases. Skin test and controlled challenge test (CCT) are useful to manage these patients. OBJECTIVE: To study clinical and allergologic features of IHRs to ICMs in a Spanish tertiary hospital during a 7-year period. METHODS: Demographic and clinical data concerning the reaction were recorded. Patients treated at the Allergy Department of Hospital General Universitario Gregorio Marañón, Madrid, Spain, underwent skin tests. In those with positive results, CCTs with an alternative skin-test-negative ICM was performed. Global reaction rate was calculated and compared for each ICM. RESULTS: A total of 342 reactions occurred in 329 patients. Cutaneous symptoms were the most common (87.7%). A total of 196 patients underwent an allergy workup, 15 (7.6%) of whom had positive skin test results. Reactions were more severe in patients with positive vs negative skin test results (grade 1, 46.7% vs 73.6%; grade 2, 33.3% vs 20.9%; grade 3, 20% vs 5.46%; P < .05). Three patients had cross-reactivity to 3 ICMs, all including ioversol and iomeprol. Six patients allergic to iopamidol tolerated ioversol and 1 tolerated iomeprol. Four patients allergic to ioversol and 1 allergic to iomeprol tolerated iopamidol. The global reaction rate was 0.2%, differing for each ICM (iopamidol, 0.14%; ioversol, 0.2%; and iomeprol, 0.4%; P < .001). Positive skin test results were found in a low percentage of patients in whom skin test-based CCT identified an alternative non-cross-reactive ICM. Low-grade cross-reactivity was found, especially between iopamidol and ioversol. Reactions were more severe in patients with positive skin test results. The reaction rate was greater for iomeprol compared with iopamidol (reaction rate, 2.8%) and ioversol (reaction rate, 2%). CONCLUSION: This study identified a possible underlying specific IgE-mediated mechanism by positive skin test result in a low percentage of patients with IHRs to ICMs. In these patients, the CCT based on skin test results was useful for identifying an alternative non-cross-reactive ICM. More studies are needed to investigate the underlying mechanism in patients with IHRs and negative skin test results.

Tolerability to nabumetone and meloxicam in patients with nonsteroidal anti-inflammatory drug intolerance.

BACKGROUND: Because nonsteroidal anti-inflammatory drug (NSAID) intolerance depends on COX-1 inhibition, preferential or selective COX-2 inhibitors have been thought to be well tolerated by these patients. OBJECTIVE: The aim of this study is to evaluate tolerability to nabumetone and meloxicam in patients with NSAID intolerance. METHODS: Seventy patients intolerant to NSAIDs were selected. Thirty subjects were patients with asthma with respiratory (rhinitis-asthma) intolerance to NSAIDs (group A); 40 patients (group B) had cutaneous-mucous (urticaria-angioedema) NSAID intolerance. Diagnosis was based on clinical histories in all patients, and it was confirmed by positive single-blind placebo-controlled oral challenge test in 36 patients. After written informed consent, a single-blind placebo-controlled oral challenge test with nabumetone in all patients (2 g except for 11 patients who reached 1 g) and meloxicam (15 mg) in 51 patients was performed. RESULTS: Of the total selected, 94.3% tolerated 1 g nabumetone. In those who reached the 2-g dose, the tolerability was 83.6%. With respect to meloxicam, 96.1% of patients, tolerated 15 mg. No significant difference in nabumetone and meloxicam tolerability was observed between groups A and B. CONCLUSION: The results of this study confirm a high percentage of tolerability to the maximum therapeutic dosage of nabumetone and meloxicam in patients with NSAID intolerance, both in those with cutaneous/mucous manifestations and in those with respiratory disease. CLINICAL IMPLICATIONS: Nabumetone and meloxicam are safe alternatives in NSAID-intolerant patients.

Sympathomimetic drug allergy: cross-reactivity study by patch test.

INTRODUCTION: Sympathomimetic (alpha-adrenergic) drugs are mainly used because of their vasoconstrictor properties, for nasal congestion, or as mydriatics. Although sympathomimetic drugs are used often, allergic reactions are rare, especially when the drugs are administered systemically. Cross-reactivity may exist among catecholamine derivatives, although reported data on this are contradictory. In this study, we investigate if there is cross-reactivity in patch tests among these drugs. MATERIAL AND METHODS: Patch tests with 10% phenylephrine and 10% pseudoephedrine in petrolatum, and 10% and 20% ephedrine, 10% phenylpropanolamine, 5% fepradinol, 1% methoxamine, and 10% oxymetazoline, all administered in dimethyl sulfoxide (DMSO), were carried out in 14 patients with a history of allergy to any of these drugs. DMSO was used as the negative control. RESULTS: All patients except one (patient number five) showed positive patch-test reactions to at least two different drugs. Nine patients (64.3%) were cross-sensitized to three or more different drugs, and 57.1% of patients were sensitized to four or more sympathomimetic drugs. Patients who experienced generalized rashes caused by orally administered pseudoephedrine had a stronger response and more cross-reactivity with other sympathomimetic drugs in patch tests than those who experienced local contact dermatitis. CONCLUSIONS: We conclude that there is cross-reactivity among the different sympathomimetic drugs tested, especially if the drug is administered systemically.

Asthma induced by canary food mix.

A 42-year-old woman reported immediate rhinoconjunctivitis, asthma, and contact urticaria while handling bird food. Skin-prick tests were positive to Lolium, Cynodon, Phragmites, Cupressus sempervirens, Cupressus arizonica, Chenopodium, sunflower pollen and seed, mugwort, chamomile, Chrysanthemum, Taraxacum, canary seed, and black seed (Guizotia abyssinica). The patient's serum-specific immunoglobulin (IgE) to Taraxacum, black seed, and canary seed was positive. Enzyme-linked immunosorbent assay inhibition studies revealed a 97 and 27% IgE-binding inhibition of whole canary food IgE by black seed and Taraxacum pollen, respectively. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis immunoblotting showed two IgE-binding protein bands of 11 and 44 kDa in the G. abyssinica extract. These two bands were totally inhibited by sunflower seed, mugwort, and Taraxacum extracts. Specific bronchial challenge with black seed extract was positive. The patient was able to feed her canary with birdseeds after she removed black seeds. We report a case of asthma caused by black seed (G. abyssinica) used as canary food in a patient previously allergic to pollen (olea europaea, grass, and mugwort) and sunflower seeds.