HLA-DRA variants predict penicillin allergy in genome-wide fine-mapping genotyping.

BACKGROUND: Immediate reactions to ß-lactams are the most common causes of anaphylactic reactions and can be life-threatening. The few known genetic factors influencing these reactions suggest a link with atopy and inflammation. OBJECTIVE: We performed a fine-mapping genome-wide association study of the genetic predictors of ß-lactam allergy to better understand the underlying mechanisms. METHODS: We studied 387 patients with immediate allergic reactions to ß-lactams and 1124 paired control subjects from Spain. We replicated the results in 299 patients and 362 paired control subjects from Italy. RESULTS: We found significant associations with the single nucleotide polymorphisms rs4958427 of ZNF300 (c.64-471G>A, P = 9.9 × 10(-9)), rs17612 of C5 (c.4311A>C [p.Glu1437Asp], P = 7.5 × 10(-7)), rs7754768 and rs9268832 of the HLA-DRA | HLA-DRB5 interregion (P = 1.6 × 10(-6) and 4.9 × 10(-6)), and rs7192 of HLA-DRA (c.724T>G [p.Leu242Val], P = 7.4 × 10(-6)) in an allelic model, with similar results in an additive model. Single nucleotide polymorphisms of HLA-DRA and ZNF300 predicted skin test positivity to amoxicillin and other penicillins but not to cephalosporins. A haplotype block in HLA-DRA and the HLA-DRA | HLA-DRB5 interregion encompassed a motif involved in balanced expression of the α- and ß-chains of MHC class II, whereas rs7192 was predicted to influence α-chain conformation. HLA-DRA rs7192 and rs8084 were significantly associated with allergy to penicillins and amoxicillin (P = 6.0 × 10(-4) and P = 4.0 × 10(-4), respectively) but not to cephalosporins in the replication study. CONCLUSIONS: Gene variants of HLA-DRA and the HLA-DRA | HLA-DRB5 interregion were significant predictors of allergy to penicillins but not to cephalosporins. These data suggest complex gene-environment interactions in which genetic susceptibility of HLA type 2 antigen presentation plays a central role.

Anticonvulsant drug hypersensitivity.

BACKGROUND: Cutaneous adverse reactions are frequently described with anticonvulsant drugs, especially with aromatic drugs such as carbamazepine, phenytoin, and phenobarbital. Patch tests could be useful for diagnosing this clinical picture. Hypersensitivity to several anticonvulsant drugs is common but unpredictable. MATERIAL AND METHODS: 15 patients from our allergy section, suffering from anticonvulsant skin allergy, were included. We describe their analitic alterations, responsible drugs, and anticonvulsants tolerated, the results of patch tests with anticonvulsant drugs (5% pet. and aq.), and skin biopsies wherever carried out. RESULTS: 23 adverse skin reactions with different anticonvulsant drugs occurred in the 15 patients: 13 resulted in fever and generalized cutaneous rash, 7 patients suffered only from cutaneous rash. There was one case of palpable purpura, one of erythema multiforme (target lesions), and another one suffered only cutaneous pruritus. Eosinophilia was found in 5 cases. Liver enzymes were elevated in 9 (7 of whom suffered fever and cutaneous rash). The responsible drugs were carbamazepine (8 adverse reactions), phenytoin (5), lamotrigine (4), phenobarbital (4), sodium valproate (1), and felbamate (1). The drugs tolerated were sodium valproate (6 patients), topiramate (4), vigabatrin (2), lamotrigine (1), clonazepam (1), and gabapentin (1). We found 12 positive patch tests: 6 with carbamazepine, 3 with phenytoin and, 1 each with lamotrigine, sodium valproate and phenobarbital. Skin biopsies were carried out in 5 patients, 4 of whom showed some characteristic findings of erythema multiforme (lymphocytic exocytosis, dyskeratotic cells, vacuolation of basal cells and pigmentary incontinence) and the other one showed a typical leucocytoclastic angitis. CONCLUSIONS: The cutaneous adverse reactions more frequently seen in our allergy section because of anticonvulsant drugs are rashes with fever. Eosinophilia and elevated levels of liver enzymes are frequently associated. This clinical picture is called "anticonvulsant hypersensitivity syndrome." The drugs implicated most frequently are carbamazepine and phenytoin. Hypersensitivity to more than one drug was variable and unpredictable. The best-tolerated drug was sodium valproate, but it was not tolerated by a patient with phenytoin and carbamazepine hypersensitivity. Patch tests are useful for diagnosing anticonvulsant hypersensitivity. The most frequently findings in the skin biopsies were typical of erythema multiforme.

A topical microemulsion for the prevention of allergic rhinitis symptoms: results of a randomized, controlled, double-blind, parallel group, multicentre, multinational clinical trial (Nares study).

BACKGROUND: Since barrier protection measures to avoid contact with allergens are being increasingly developed, we assessed the clinical efficacy and tolerability of a topical nasal microemulsion made of glycerol esters in patients with allergic rhinitis. METHODS: Randomized, controlled, double-blind, parallel group, multicentre, multinational clinical trial in which adult patients with allergic rhinitis or rhinoconjunctivitis due to sensitization to birch, grass or olive tree pollens received treatment with topical microemulsion or placebo during the pollen seasons. Efficacy variables included scores in the mini-RQLQ questionnaire, number and severity of nasal, ocular and lung signs and symptoms, need for symptomatic medications and patients' satisfaction with treatment. Adverse events were also recorded. RESULTS: Demographic characteristics were homogeneous between groups and mini-RQLQ scores did not differ significantly at baseline (visit 1). From symptoms recorded in the diary cards, the ME group showed statistically significant better scores for nasal congestion (0.72 vs. 1.01; p = 0.017) and mean total nasal symptoms (0.7 vs. 0.9; p = 0.045). At visit 2 (pollen season), lower values were observed in the mini-RQLQ in the ME group, although there were no statistically significant differences between groups in both full analysis set (FAS) and patients completing treatment (PPS) populations. The results obtained in the nasal symptoms domain of the mini-RQLQ at visit 2 showed the highest difference (-0.43; 95% CI: -0.88 to 0.02) for the ME group in the FAS population. The topical microemulsion was safe and well tolerated and no major discomforts were observed. Satisfaction rating with the treatment was similar between the groups. CONCLUSIONS: The topical application of the microemulsion is a feasible and safe therapy in the prevention of allergic symptoms, particularly nasal congestion. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01478425.

Exposición a gas CS: a propósito de un caso peculiar / Exposure to CS gas: Case study

El gas CS (o-clorobenzolideno malononitrilo) se incluye dentro del grupo de los gases lacrimógenos. La exposición a dicho gas ocurre durante su empleo como gas de defensa o antidisturbios, así como durante el entrenamiento rutinario de las fuerzas de choque especializadas. Su acción tóxica es ejercida a través de un efecto irritante sobre piel y mucosas, así como por mecanismos inmunoalérgicos. Presentamos el caso de un paciente de 24 años, perteneciente a una fuerza de choque, que consultó por lesiones cutáneas luego de una exposición a humo y dispersión de polvo de una granada de gas CS durante ejercicios de entrenamiento. Clínicamente se presentó características peculiares, referidas a sus manifestaciones cutáneas, localización y severidad de las mismas. Se analiza la etiopatogenia de las lesiones y los posibles mecanismos involucrados, diagnósticos diferenciales, así como los pilares del tratamiento frente a una exposición a gas CS...