Predictors of clinical effectiveness of Hymenoptera venom immunotherapy.

BACKGROUND: Treatment failure during venom immunotherapy (VIT) may be associated with a variety of risk factors, of which the relative importance is unknown. OBJECTIVE: Our aim was to evaluate the association of baseline serum tryptase concentration (BTC), mastocytosis in the skin (MIS) and of other parameters with the frequency of objective systemic reactions during in-hospital sting challenge (SC). METHODS: In this observational retrospective study, we enrolled 1532 patients (1609 cases due to double SC) with established honeybee or vespid venom allergy who had undergone VIT and a subsequent SC. Data were collected on various putative risk factors. Adult-onset MIS and/or a BTC > 20.0 µg/L was defined as clinical indicators of systemic mastocytosis. Relative rates were calculated with logistic regression models. RESULTS: Ninety-eight patients (6.4%) presented with MIS and/or BTC > 20.0 µg/L. 104 cases (6.5%) developed objective generalized symptoms during SC. In the absence of MIS, a BTC ≤ 20 µg/L did not increase the risk for VIT failure. The most important factors associated with a worse outcome were ACE inhibitor medication (OR 5.24, 95% CI 1.83-13.00, P < 0.001), honeybee venom allergy (OR 5.09, 95% CI 3.17-8.15, P < 0.001), systemic allergic reaction during VIT (OR 3.07, 95% CI 1.79-5.14, P < 0.001), and a substantial likelihood to suffer from SM (OR 2.74, 95% CI 1.37-5.22, P = 0.003), whereas a double VIT (OR 0.51, 95% CI 0.27-0.90, P = 0.027) and a longer duration of therapy (OR 0.68 per treatment month, 95% CI 0.50-0.93, P = 0.017) reduced the failure rate. CONCLUSION: The magnitude of therapeutic success correlates with type of venom, duration of therapy, and venom dose. Adult-onset MIS and/or a BTC > 20 µg/L is a significant, albeit not the strongest determinant for VIT failure. According to its odds ratio, ACE inhibitor therapy appears to be associated with the highest risk for VIT failure.

Polimorfismo del gen de aldosa reductasa y velocidad de aparición de retinopatía en diabéticos no insulinodependientes / Aldose reductase gene polymorphism and rate of appearance of retinopathy in non insulin dependent diabetic patients

Background: Recent studies suggest that polymorphisms associated to the aldose reductase gene could be related to early retinopathy in noninsulin dependent diabetics (NIDDM). There is also new interest on the genetic modulation of coagulation factors in relation to this complication. Aim: To look for a possible relationship between the rate of appearance of retinopathy and the genotype of (AC)n polymorphic marker associated to aldose reductase gene. Patients and methods: A random sample of 27 NIDDM, aged 68.1 ñ 10.6 years, with a mean diabetes duration of 20.7 ñ 4.8 years and a mean glycosilated hemoglobin of 10.6 ñ 1.6 percent, was studied. The genotype of the (AC)n, polymorphic marker associated to the 5Õ end of the aldose reductase (ALR2) gene was determined by 32P-PCR plus sequenciation. Mutations of the factor XIII-A gene were studied by single stranded conformational polymorphism, sequenciation and restriction fragment length polymorphism. Results: Four patients lacked the (AC)24 and had a higher rate of appearance of retinopathy than patients with the (AC)24 allele (0.0167 and 0.0907 score points per year respectively, p=0.047). Both groups had similar glycosilated hemoglobin (11.7 ñ 0.2 and 10.5 ñ 1.6 percent respectively). Factor XIII gene mutations were not related to the rate of appearance of retinopathy. Conclusions: Our data suggest that the absence of the (AC)24 allele of the (AC)n polymorphic marker associated to the 5Õ end of the aldose reductase gene, is associated to a five fold reduction of retinopathy appearance rate