Development and validation of a new Spanish instrument to measure health-related quality of life in patients with allergic rhinitis: the ESPRINT questionnaire.

OBJECTIVES: To develop and validate an instrument to measure health-related quality of life (HRQOL) specific to patients with allergic rhinitis (AR) and primarily for use in Spanish and Spanish-speaking populations. METHODS: An initial item pool was generated from literature review, focus groups with AR patients, and consultations with clinical experts. Item reduction was performed using clinimetric and psychometric approaches after administration of the item pool to 400 AR patients. The resulting instrument's internal consistency, test-retest (2-4 weeks) reliability, known groups and convergent validity, and sensitivity to change were tested in a longitudinal, observational, multicenter study in 210 AR patients who also completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). RESULTS: The new questionnaire took a mean (SD) of 7.1 (5.4) minutes to answer. Floor and ceiling effects were less than 15% on all dimensions. Cronbach's alpha values and intraclass correlation coefficient values for six of the sevendimensions and the overall score exceeded 0.70. Statistically significant differences (P < 0.01) were observed on all ESPRINT-28 dimensions and the overall score between patients with mild (mean overall score 1.97, SD 0.99), moderate (mean overall score 2.78, SD 0.88), and severe AR (mean overall score 3.89, SD 0.87). Patients with persistent AR had worse scores (P < 0.05) on all dimensions than patients with intermittent AR. Correlations between the ESPRINT-28 and the RQLQ were generally as expected. Effect sizes for score changes between the two study visits ranged from 0.96 to 1.76 for individual dimensions and the overall score. CONCLUSIONS: This new, Spanish-developed instrument to measure HRQOL in AR patients has shown good reliability, validity, and sensitivity to change. It has also proved easy to use and administer.

Tolerance of a cluster schedule on the treatment of seasonal allergic respiratory disease with pollen extracts quantified in mass units.

In order to evaluate the tolerance of a cluster schedule on specific immunotherapy (SIT), 306 patients were included in a multicenter study. The patients were suffering from rhinoconjunctivitis with/without asthma, caused by sensitization to olive and/or grass pollen. SIT was administered subcutaneously according to a cluster schedule in which the maintenance dose is reached after four visits (3 weeks). The extracts were biologically standardized with major allergens quantified in mass units. Local reactions appeared in 7.2% of the patients and 1.3% of the doses. Systemic reactions (SR) were recorded in 1.2% of the doses administered to 9.5% of the patients. No anaphylactic shock was registered, and all the SR responded fully and rapidly to treatment. There was no difference in SR according to diagnosis or allergen extract used. The majority of SR occurred with the administration of vial of higher concentration (Vial 2: 7 SR (22%), Vial 3: 32 SR (78%), p < 0.05). Of the 32 SR recorded with Vial 3, 13 (41%) were immediate, with no existing association between dose administered and appearance of SR. However, of the 18 delayed SR (56%), 14 occurred after the administration of the first two doses of Vial 3 and four occurred after administration of the second two doses (78% vs 22%, p < 0.05). On the other hand, this regime realized an important saving in cost and time compared to the conventional schedule (1581 fewer doses and 2754 fewer visits were necessary to reach the optimal dose). Considering all these factors, the clinical profile of the proposed regime may be qualified as good. However, future studies are necessary in order to better adjust the schedule to avoid the delayed SR that occurred after the administration of the first two doses of Vial 3.

Persistent subcutaneous nodules in patients hyposensitized with aluminum-containing allergen extracts.

BACKGROUND: The development of persistent nodules that cause pain and itching at a vaccination or hyposensitization injection site is a rare event. These lesions have been mainly attributed to a hypersensitivity reaction to aluminum hydroxide, which is used as an absorbing agent in many vaccines and hyposensitization preparations. Patch tests with standard antigens and aluminum compounds and histopathologic and ultrastructural studies were performed on 10 patients with persistent subcutaneous nodules on the upper part of their arms after injection of aluminum-adsorbed dust and/or pollen extracts. OBSERVATIONS: The nodules appeared 1 month to 6.5 years after injections. The results of patch tests with 2% aluminum chloride were positive in five patients. Histopathologic examination revealed two different patterns: some biopsy specimens (from lesions of less than 9 months' duration) showed a pure foreign body histiocytic reaction characterized by extracellular amorphous dermal basophilic deposits with a histiocytic-macrophagic reaction; others showed a delayed hypersensitivity granulomatous reaction in association with an histiocytic foreign body response. The lesions were characterized by a unifocal or multifocal unencapsulated granulomatous reaction in the deep dermis and/or subcutaneous tissue. Eosinophilic necrotic areas surrounded by dense fibrous bands and a massive inflammatory infiltrate (lymphoid follicles, large histiocytic cells, abundant eosinophils, and some plasma cells) were observed. A granular basophilic material in extracellular spaces and within the cytoplasm of some histiocytes was also noted. Electron microscopic studies revealed intracytoplasmic and extracellular deposits of a fibrillar electron-dense material. CONCLUSIONS: Persistent subcutaneous nodules that develop after the administration of aluminum-containing preparations may show two characteristic histopathologic patterns. A pure histiocytic foreign body reaction was observed in early lesions, and a delayed hypersensitivity granulomatous reaction was seen in older lesions. No relationship between histopathologic pattern and patch test results was observed. Aluminum-free preparations should be used in patients in whom these nodules develop.

Systemic capillary leak syndrome.

Systemic capillary leak syndrome is a rare, severe disorder with a high mortality rate. It consists of the shift of fluid and proteins from the intravascular to the extravascular compartment with subsequent hypovolemic shock. We describe a 34-year-old-woman who had several episodes of generalized edema that evolved to hypovolemic shock. During the acute phase, laboratory investigations revealed marked hypoproteinemia, leukocytosis, and high levels of hematocrit and hemoglobin. A paraprotein IgG kappa chain was detected. Although different therapeutic trials were used, the patient continued to have similar episodes and she died during an acute episode 2 1/2 years after the first symptom of this disorder. The cause of systemic capillary leak syndrome is unknown. The presence of a paraprotein IgG is frequent in this group of patients.

Cyclosporine A in atopic dermatitis.

Atopic dermatitis is a chronic pruritic dermatosis that requires individualized treatment. Recent studies have shown that low-dose oral treatment with cyclosporine A may be useful in more severe forms. We report our experience with two patients who had severe atopic dermatitis. Both had high IgE concentration and satisfied Hanifin and Rajka's diagnostic criteria for atopic dermatosis. We began oral treatment at a daily dosage of 5 mg/kg divided into two doses. We monitored cyclosporine concentration in whole blood, as well as kidney and liver function. Contraindications for cyclosporine A were excluded. Clinical improvement commenced between the first and third week of treatment and was marked in one case and partial in the other. Improvement did not correlate with a reduction in serum IgE concentration. Side effects were mild (hypertrichosis, slight trembling, and gingival hypertrophy). On discontinuing treatment, clinical manifestations reappeared. We conclude that cyclosporine A may be an effective alternative for some forms of atopic dermatitis resistant to other treatments.

Coronary artery spasm and acute myocardial infarction in naproxen-associated anaphylactic reaction.

We present the case of a 43-year-old man who suffered an acute myocardial infarction after oral administration of 250 mg of naproxen, prescribed as antiinflammatory-analgesic agent after tooth extraction. Both intradermal skin test and human basophil degranulation test were positive to naproxen. These findings suggest a naproxen-associated anaphylactic reaction with concomitant coronary artery spasm and posteroinferior infarction, a clinical event previously not reported with the use of this drug.

Food allergy: identification of the major IgE-binding component of peach (Prunus persica).

Since peaches are a relatively common cause of food allergy, we set out to identify the allergens involved. With the use of a panel of 48 sera from patients allergic to peach, we demonstrate that most of the allergenicity of that fruit is confined to the skin, rather than to the flesh of peaches, and corresponds to a protein doublet with an estimated molecular weight of 8-10 kD.

Effect of astemizole on allergic asthma.

In a placebo-controlled, double-blind, crossover study with a washout phase of 2 months between each treatment period, single daily doses of 10 and 30 mg of astemizole were given to 12 patients with extrinsic asthma during 28 consecutive days. Albuterol was allowed as concurrent medication when needed. On days 0, 7, and 28 specific bronchial provocation with Dermatophagoides pteronyssinus and cutaneous tests with histamine and D. pteronyssinus extracts were carried out. The requirements of beta-agonist inhalations and the number of bronchospasm episodes were recorded throughout the study period. Inhibition of allergen-induced bronchoconstriction appeared on day 7 with 30-mg doses of astemizole, while it was not observed until day 28 with 10-mg doses. Wheal responses caused by histamine were reduced only after active treatment. The wheal response to the highest allergen concentration was reduced on days 7 and 28 after 30 mg of astemizole, whereas doses of 10 mg only caused a reduction on day 28. It is concluded that astemizole could be useful as a therapeutic agent in the treatment of certain types of asthma.

[Hypersensitivity reactions to ethylenediamine]. / Reacciones de hipersensibilidad a la etilendiamina.

Most allergic reactions to aminophylline are caused by hypersensitivity to ethylendiamine. We present 3 asthmatic patients, 2 of whom had immediate allergic symptoms after the administration of aminophylline. The third patient presented generalized erythrodermia 24 hours after receiving aminophylline. In all three cases sensitivity to ethylendiamine was observed in skin testing. These patients can tolerate other theophylline preparations not containing ethylendiamine.

[Sensitization to chymopapain in patients treated with chemonucleolysis]. / Sensibilización a la quimopapaína en pacientes tratados con quimionucleólisis.

BACKGROUND: Chemonucleolysis (intradisk administration of chymopapain) is a procedure to treat intervertebral disk hernia. Recently, its use has been questioned due to the development of anaphylactic reactions in patients sensitized to chymopapain. The prevalence of sensitization to chymopapain has been evaluated before and after chemonucleolysis, and the possibility to establish risk groups through the allergy history has been assessed. METHODS: 104 consecutive patients who were candidates to chemonucleolysis were evaluated with an allergy questionnaire, cutaneous tests to aeroallergens and to chymopapain, and chymopapain-specific IgE. The two latter tests were repeated one month after chemonucleolysis. RESULTS: Only 2 patients (1.9%) showed evidence of chymopapain sensitization before the procedure. Sixteen patients (16%) were sensitized after chemonucleolysis. None of the possible risk factors evaluated in the allergy questionnaire (atopy, drug allergy, papaya occupational exposure or use of additives, cosmetics or drugs containing papaine) were significantly related with the risk of sensitization to chymopapain. CONCLUSIONS: The prevalence of chymopapain sensitization in the study group was low. The allergy questionnaire (atopy, drug allergy, use of papaya, occupational history did not identify sensitized patients. Cutaneous tests and specific IgE are the best method to detect chymopapain sensitization. The remarkable rate of sensitization after chemonucleolysis may partially limit the usefulness of the procedure.

[Subcutaneous nodules and sensitivity to aluminum in patients undergoing hyposensitivity immunotherapy]. / Nódulos subcutáneos y sensibilidad al aluminio en pacientes con inmunoterapia hiposensibilizante.

Hypersensitivity reactions to aluminium are very rate. Sensitization has been reported to occur during continuous application of aluminium-containing antiperspirants or by aluminium adjuvants in vaccines and hyposensitization immunotherapy. We report 5 patients who developed persistent and itching subcutaneous nodules following immunotherapy. Histologically, the nodules showed a granulomatous reaction consistent with delayed hypersensitivity to aluminium. Patch tests with 2% aluminium chloride in water were positive in three patients, and positive results of patch test with other metals (nickel, cobalt) were frequently associated.

Allergenic cross-reactivity among pollens of Urticaceae.

Common antigenic determinants have been observed between Parietaria and Urtica dioica pollen. The four Parietaria pollens selected (P. judaica, P. officinalis, P. lusitanica and P. mauritanica) are shown to possess a high allergenic homology. IgE-binding structures, homologous to the P. judaica main allergenic polypeptide (Pj10), were found in the other species by immunodetection. Monoclonal antibodies specific to the Pj10 polypeptide recognized proteins from the four Parietaria pollens. Skin prick test and RAST inhibition yielded results that also indicated a high allergenic cross-reactivity among these pollens, with homologous peptides bearing common antigenic and allergenic determinants. On the other hand, U. dioica pollen showed only a slight allergenic similarity to Parietaria. The potential allergenic activity of these pollens is discussed.