Local reactions during allergen immunotherapy do not require dose adjustment.

BACKGROUND: The recent World Health Organization position paper on allergen immunotherapy states that local reactions to immunotherapy are not predictive of subsequent systemic reactions. Nevertheless, in clinical practice dose adjustment after local reactions continues to be recommended, presumably in an effort to prevent future systemic reactions. OBJECTIVE: We sought to determine whether dose adjustment versus no adjustment for local reactions during allergen immunotherapy influences the occurrence of subsequent systemic reactions. METHODS: In a single-site allergy clinic before October 1, 1997, local reactions after allergen vaccine injection resulted in adjustment of the subsequent dose. After October 1, 1997, no dose adjustments were made for immediate and late local reactions. For the same 9-month period before and after the change in local reaction dose-adjustment policy, systemic reaction rates were compared retrospectively. For individuals experiencing a systemic reaction, local reaction rates and local reactions immediately preceding a systemic reaction were also compared before and after the policy change. RESULTS: Comparing the 9-month period (October 1996-June 1997) preceding the policy change and the 9 months (October 1997-June 1998) after the change in policy, the systemic reaction rates (0.80% and 1.01%, respectively) were not statistically different (P =.24). Among those experiencing a systemic reaction, the rate of local reactions was unchanged (7.3% and 4.7%, respectively; P =.07), and the rate of local reactions immediately preceding a systemic reaction did not increase (18.8% and 10.5%, respectively; P =.37). The sensitivity of a local reaction predicting a systemic reaction at the next immunotherapy dose was 15%. CONCLUSIONS: A local reaction is a very insensitive predictor for a subsequent systemic reaction at the next allergen vaccine dose. Dose adjustment for most local reactions is unnecessary and may delay therapy, increase costs, and put the patient at increased risk of dose administration errors.

Cross-reactivity among conifer pollens.

BACKGROUND: There are increasing reports of Cupressaceae pollinosis from various geographic areas. Cross-reactivity among a limited number of species within the Cupressaceae family has been suggested. Juniperus ashei (mountain cedar) is the leading cause of respiratory allergy in South Texas. OBJECTIVE: This study examines in vivo and in vitro cross-reactivity among 12 Cupressaceae species, one Taxodiaceae species, one Pinaceae species, and an angiosperm. METHODS: Cross-reactivity among pollen extracts of mountain cedar (MC) and the other 14 trees was investigated by: (1) prick skin testing of each tree pollen extract in ten patients with MC pollinosis. (2) Ouchterlony gel immunodiffusion employing rabbit antisera to MC. (3) IgE immunoblotting using high-titer MC pooled human sera, and immunoblot inhibition after pre-incubation with MC protein. (4) Monoclonal antibody immunoblotting using a murine monoclonal antibody with strong affinity for the gp40 major allergen of MC. RESULTS: Positive skin wheal-and-flare responses occurred to all 12 Cupressaceae and Japanese cedar (the Taxodiaceae), but not to the Pinaceae or the angiosperm. In Ouchterlony gels, lines of identity or partial identity formed between MC and all pollens except the Pinaceae and the angiosperm. Immunoblots demonstrated IgE binding to the 40 to 42 kD protein in each Cupressaceae, and to a parallel band in Japanese cedar at 43 to 46 kD. Immunoblot inhibition by MC pollen was complete for all trees. The monoclonal bound both the 40 to 42 kD protein in 11 of 12 Cupressaceae species and the 46 kD band in Japanese cedar, but bound no protein bands in the Pinaceae or the angiosperm. CONCLUSION: Pollen proteins of the 12 Cupressaceae (including MC) and the Taxodiaceae (Japanese cedar) are extensively cross-reactive. In particular, the MC major allergen, gp40, is cross-reactive with 40 to 42 kD proteins of the other Cupressaceae and with the Japanese cedar major allergen of 46 kD. Component-based immunotherapy may someday allow a standard treatment for both Juniper-allergic and C. japonica-allergic patients.

Occupational asthma in a seafood restaurant worker: cross-reactivity of shrimp and scallops.

BACKGROUND: The case of a restaurant seafood handler with IgE-mediated occupational asthma and contact urticaria to both shrimp and scallops is presented. Independent hypersensitivity to both seafoods was demonstrated by skin testing, inhalation challenge, and immunoassays. Bronchial challenge with extracts of shrimp and scallops each produced an isolated early asthmatic response. OBJECTIVE: To investigate cross-reactivity of shrimp (phylum Arthropoda) and scallops (phylum Mollusca). METHODS: Shrimp and scallops extracts were prepared from raw seafood and seafood boiling water. Distillate was collected over boiling shrimp. Specific-IgE ELISA and immunoblot assays were accomplished for shrimp and scallops extracts inhibited by each other. RESULTS: SDS-PAGE of shrimp boiling water and distillate showed similar protein patterns. SDS-PAGE and immunoblot demonstrated prominent protein allergens for shrimp boiling water at 21, 26, and 35 to 38 kD; for raw shrimp at 26 and 38 kD; for scallops boiling water at 20, 35 to 39 and 42 kD; and for raw scallops at 36 to 38 and 41 kD. Significant inhibition of the 35 to 39-kD band of each shrimp and scallops extract was demonstrated on immunoblot inhibition by seafood of the opposite phylum. IgE ELISA inhibition demonstrated 17% to 28% inhibition of shrimp by scallops and scallops by shrimp. CONCLUSIONS: Seafood allergens aerosolized during food preparation are a source of potential respiratory and contact allergens. Shrimp and scallops demonstrate significant cross-reactivity. These findings confirm that the primary cross-reactive allergen of shrimp (phylum Arthropoda) and scallops (phylum Mollusca) is the 35 to 39 kD heat-stable allergen, previously demonstrated to be muscle topomyosin in both phyla.

Isolation and characterization of the mountain cedar (Juniperus ashei) pollen major allergen, Jun a 1.

BACKGROUND: Cedar pollens are important causes of seasonal allergic disease in diverse geographic areas. OBJECTIVE: A major allergen from mountain cedar (Juniperus ashei) pollen, termed Jun a 1, was isolated and characterized. METHODS: Water-soluble pollen glycoproteins were extracted, salt precipitated, and purified with use of concanavalin A affinity chromatography or HPLC. The purified fractions were characterized by SDS-PAGE, immunoblotting, and N-terminal amino acid sequence analysis. Binding of allergen-specific IgE from the sera of cedar-hypersensitive patients was detected by ELISA and antigen-specific responses of peripheral blood T cells by tritiated thymidine incorporation. RESULTS: The major extractable cedar pollen glycoprotein had a molecular weight and N-terminal amino acid sequence that was similar to that of the major allergen Cha o 1, from Japanese cypress (Chamaecyparis obtusa), and Cry j 1, from Japanese cedar (Cryptomeria japonica). IgE from cedar-hypersensitive patients' sera bound to the isolated glycoprotein. CONCLUSION: The predominance of Jun a 1 in the soluble proteins of mountain cedar pollen and its high degree of homology with Cha o 1 and Cry j 1 make it likely to be the major allergen of this pollen. Amino acid sequence conservation also makes Jun a 1 a potential target for cross-reactivity between these pollen allergens. The observed reactivity of IgE from the sera of Japanese cedar-sensitive patients with Jun a 1 is consistent with this proposition.

Evaluation and treatment of allergic fungal sinusitis. I. Demographics and diagnosis.

BACKGROUND: Few cases of allergic fungal sinusitis have been systematically evaluated to conclusively confirm working clinical, histopathologic, and serologic diagnostic criteria. OBJECTIVES: The objective of this study was to describe 67 consecutive cases of allergic fungal sinusitis, the largest number of cases yet published. METHODS: Cases from 1 practice over 8 years were evaluated with a consistent protocol, including skin testing, serum chemistries and serologies, and surgical specimen analysis. RESULTS: All patients were atopic (100 %) and had nasal polyposis (100%). They tended to be young (33.3+/-13.1 years, mean +/-SEM), immunocompetent (92 %; remaining 8 % with low quantitative immunoglobulin but normal function), have slight female preponderance (58%), have a history of hypertrophic rhinosinusitis (100%), report nasal cast production (75%), and have developed their disease in the southwestern United States. Bipolaris spicifera was the most prevalent fungus involved (67%). Total serum IgE (mean 668 IU/mL) and fungal-specific IgG were generally elevated, whereas fungal-specific precipitins and specific IgE were generally negative despite positive fungal-specific immediate hypersensitivity skin tests. CONCLUSIONS: Patients with allergic fungal sinusitis tend to have elevated total serum IgE and fungal-specific IgG at diagnosis but not fungal-specific IgE or precipitins. Histopathologic criteria for allergic fungal sinusitis diagnosis are discussed. The southwestern United States appears to be a "hot spot" for the disease, particularly caused by B spicifera.

Evaluation and treatment of allergic fungal sinusitis. II. Treatment and follow-up.

BACKGROUND: Previous allergic fungal sinusitis case reports have speculated that oral corticosteroids might reduce the severity of disease and possibly forestall the high rate of recurrent sinus surgery. OBJECTIVES: Our objective was to comprehensively review 67 consecutive cases of allergic fungal sinusitis for their response to treatment and the utility of monitoring patient serologies during clinical follow-up. METHODS: Allergic fungal sinusitis cases from a private practice were evaluated and treated with consistent diagnostic criteria and treatment paradigms. An 8-year retrospective review of serologic parameters and clinical response to treatment with or without oral corticosteroids is described. RESULTS: The total serum IgE was found to correlate with the clinical rhinosinusitis severity (P = .0002). The fungal-specific IgG also correlated with clinical rhinosinusitis severity but less rigorously (P = .004). An increase of 10% or more in total serum IgE during follow-up was found to have significant predictive value for recurrent surgical intervention, with a sensitivity of 79%, specificity of 77%, positive predictive value of 48%, and negative predictive value of 93% (P < .0001). With the use of a modified corticosteroid treatment regimen adapted from allergic bronchopulmonary aspergillosis, as little as 2 months of oral corticosteroids after surgery provided significant clinical improvement for up to 12 months (P < .0001), although patients taking 12 months of treatment fared the best clinically (P = .03). By survival analysis, oral corticosteroids prolonged the time between subsequent sinus surgeries (P = .01) in this highly recurrent disease. No significant side effects of oral corticosteroids were observed during treatment with this dosing regimen. CONCLUSIONS: Postoperative oral corticosteroids appear to be an effective treatment option for allergic fungal sinusitis, and monitoring of total serum IgE can be helpful in the clinical follow-up of these patients.

Sudden infant death syndrome: a search for allergen hypersensitivity.

BACKGROUND: Sudden infant death syndrome (SIDS) remains a diagnosis by exclusion which leaves few if any pathologic clues to its etiology. Previous evaluations for anaphylaxis in SIDS have been few and limited. OBJECTIVE: To analyze forensic blood specimens for evidence of anaphylaxis in 51 (43 boys and 8 girls) children dying of SIDS and 13 (9 boys and 4 girls) age-matched controls who died from defined, nonanaphylactic causes. METHODS: Specimens collected over a 5-year period were assayed for (1) total IgE (IU/mL) by immunoenzymatic assay; (2) latex, cat, dust mite (Dermatophagoides farinae and Dermatophagoides pteronyssinus), milk, soy, wheat, peanuts, egg, and tomato specific-IgE by RAST; and (3) serum tryptase levels (U/L) by radioimmunoassay. RESULTS: The 51 SIDS cases (median age 3 months; range 1 to 9 months) and 13 control cases (median age 4 months; range 1 to 11 months) demonstrated similar total IgE of 9.8 +/- 1.1 IU/mL (mean +/- SEM) and 10.9 +/- 2.8 IU/mL (P = .59). The frequency of detectable (> 0.5 U/L) serum tryptase levels among SIDS cases (10/51) was similar to controls (3/13, P = .72). The frequency of positive RAST tests was 39% (20/51) in SIDS and 38% (5/13) in control subjects (P = .99). Differences in frequencies of positive RAST tests in SIDS and control cases were not statistically significant for any allergen tested. The most frequently detected allergen-specific IgE, to milk, was similar in SIDS (22%) and controls (31%, P = .48). CONCLUSIONS: Elevated tryptase levels and allergen-specific IgE (milk, soy, wheat, peanuts, egg, tomato, dust mites, cat, and latex) were demonstrated in some infant SIDS deaths but were no more common than in controls. We conclude that anaphylaxis is probably an uncommon etiology for SIDS.

Intranasal beclomethasone as an adjunct to treatment of chronic middle ear effusion.

BACKGROUND: Following otitis media, 10% to 50% of children develop residual middle ear effusion with concurrent hearing loss and potential cognitive, behavioral, and language impairment. Prophylactic antibiotics and tympanostomy tubes are currently recommended treatments for chronic middle ear effusion. OBJECTIVE: In a double-blind, placebo-controlled, randomized study of chronic middle ear effusion, we assessed the effectiveness of topical intranasal beclomethasone as an adjunct to prophylactic antibiotic therapy. METHODS: Sixty-one children, aged 3 to 11 years with persistent middle ear effusion greater than 3 months, were randomized into three treatment groups: (1) prophylactic antibiotics; (2) prophylactic antibiotics plus intranasal beclomethasone (336 micrograms/day); and (3) prophylactic antibiotics plus intranasal placebo. Patients were evaluated with aeroallergen skin tests at entry; and tympanogram, otoscopic examination, and symptom questionnaire at 0, 4, 8, and 12 weeks. RESULTS: While middle ear pressures, otoscopic examinations, and symptom scores were improved for each treatment group over 12 weeks of therapy, the beclomethasone plus antibiotics group improved all three measures more rapidly than the antibiotics-alone and placebo nasal spray plus antibiotics groups over the first 8 weeks. Only the beclomethasone group significantly improved left (P = .004) and right (P = .01) middle ear pressures over 12 weeks. Resolution of chronic middle ear effusions was more frequent in the beclomethasone group (P < or = .05 at 4 and 8 weeks). No difference in response to nasal steroids was observed between atopic and nonatopic subjects. CONCLUSIONS: We conclude that intranasal beclomethasone may be a useful adjunct to prophylactic antibiotic treatment of chronic middle ear effusion.

Aeroallergen-specific IgE changes in individuals with rapid human immunodeficiency virus disease progression.

BACKGROUND: Progression of human immunodeficiency virus type 1 (HIV-1) infection to the acquired immunodeficiency syndrome (AIDS) is associated with elevated total IgE; however, previous cross-sectional studies have differed in their assessment of concurrent changes in allergic disease prevalence. OBJECTIVE: Assessment of changes in aeroallergen-specific IgE during progression from early to late HIV disease. METHODS: Total IgE, aeroallergen-specific IgE (rye grass, ragweed, Alternaria, dust mite, and cat), IFN-gamma, IL-4, and soluble CD23 (sCD23) were measured in a longitudinal study of 20 subject who had progressed from early-HIV infection (mean CD4 lymphocyte count of 650/mm3) to AIDS (mean CD4 lymphocyte count of 40/mm3) over an average of 4 years. RESULTS: Prevalence of positive aeroallergen specific-IgE assays in early HIV disease (T1 subjects with 13 positives) decreased with progression to late disease (five subjects with nine positive, P = .057), while total IgE increased from a median of 69 to 116 IU/mL. IFN-gamma and IL-4 were unchanged, while sCD23 decreased from a median of 72 to 9 U/mL (P = .0005) with disease progression in the full cohort. In contrast to other subjects, the subgroup of individuals with total IgE > 150 IU/mL in both early and late HIV disease demonstrated an increased frequency of aeroallergen-specific IgE. CONCLUSIONS: The elevation of total IgE associated with rapid HIV-1 disease progression was unexplained by concurrent changes in aeroallergen-specific IgE, IL-4, IFN-gamma, or sCD23. Overall, aeroallergen-specific IgE expression was less prevalent with HIV-1 progression, except in those individuals with elevated total IgE both before and after progression to AIDS.

Mountain cedar allergens found in nonpollen tree parts.

BACKGROUND: Mountain cedar (Juniperus ashei) pollen is the principal aeroallergen in south central Texas from late December through February. The major mountain cedar allergen is a 40-kD glycoprotein, gp40. OBJECTIVE: To identify allergens in mountain cedar wood, leaves, and berries and to detect mountain cedar allergen in smoke from burning male or female trees. METHODS: SDS-PAGE plus mountain cedar human sIgE and monoclonal antibody immunoblots identified mountain cedar allergens within pollen and nonpollen tree part extracts. RESULTS: IgE immunoblots identified a single wood allergen at 36 kD and three berry allergens at 36, 26-27, and 21 kD, in addition to known pollen allergens. Mountain cedar monoclonal antibody bound an allergen epitope present not only on 40, 33, and 28-kD pollen allergens, but also on 36 and 32-kD wood allergens, and the 26-27-kD berry allergen. Immunoblot studies detected no mountain cedar allergen in leaves and no allergen in smoke from burning male and female trees. Allergens constituted a much smaller percentage of extractable protein in wood and berries than in pollen. CONCLUSIONS: Mountain cedar berry allergen content is too small to give credence to the ingestion of berries as a folk medicine treatment of mountain cedar pollinosis. In addition, while smoke from burning mountain cedar trees may be irritating, it contains no allergens that could cause allergic rhinoconjunctivitis.

The natural history of exposure to the imported fire ant (Solenopsis invicta).

BACKGROUND: Imported fire ants (IFA) are a common cause of insect venom hypersensitivity in the southeastern United States. The purpose of this study was to determine the sting attack rate and development of specific IgE in an unsensitized population. METHODS: Study participants consisted of 137 medical students with limited exposure to IFA-endemic areas who were temporarily training in San Antonio, Tex. Subjects were surveyed for prior IFA exposure with a questionnaire, and IFA-specific IgE was evaluated with RAST and intradermal skin testing. Evaluations were performed on arrival and reported at departure from the endemic area 3 weeks later. RESULTS: One hundred seven subjects completed the study. Field stings were reported in 55 subjects, resulting in a sting attack rate of 51%. In these 55 subjects 53 (96%) reported a pustule or a small local reaction at the sting site, one (2%) reported an isolated large local reaction, and none reported a systemic reaction. At the 3-week follow-up skin test and RAST conversions occurred in seven subjects (13%) and in one subject (1.8%), respectively. CONCLUSIONS: Even brief exposures to IFA-endemic areas result in significant sting rates and concurrent rapid development of IFA-specific IgE in 16% of stung subjects.

Pediatric adenoidal hypertrophy and nasal airway obstruction: reduction with aqueous nasal beclomethasone.

OBJECTIVE: Pediatric adenoidal obstruction of the nasal airway is associated with significant morbidity and is a frequent indication for surgery. Because efficacious medical alternatives to adenoidectomy are lacking, we assessed the potency of standard-dose topical nasal beclomethasone in reduction of adenoidal obstruction of the nasal airway. METHODS: Seventeen children, 5 to 11 years of age, exhibiting chronic obstructive nasal symptoms and a group mean (+/- SE) adenoid/choana ratio of 91 +/- 1% on rhinoscopic examination, completed an 8-week, double-blind, placebo-controlled crossover study of standard-dose aqueous nasal beclomethasone (total 336 micrograms/day) in the treatment of adenoidal hypertrophy. In a 16-week, open-label, follow-on study, subjects received beclomethasone 1 spray in each nostril twice daily (168 micrograms/day). RESULTS: Over the initial 4 weeks, improvements in the mean adenoidal obstruction of the choanae were significantly greater in the group receiving beclomethasone than in the group receiving placebo (right, -14.0% vs. +0.4%, P = .0002) (left, -15.0% vs. -2.0%, P = .0006). In the subsequent crossover 4 weeks, a significant beclomethasone carryover effect resulted in further adenoid size reduction in both treatment groups. All patients demonstrated a decrease in adenoid size with beclomethasone treatment, compared with a mixed response to placebo. Over the full 8-week crossover study, the mean (+/- SE) obstructive symptom score after beclomethasone treatment (20.5 +/- 3.0) was significantly improved compared to patients' initial (43.1 +/- 2.9) and placebo scores (31.1 +/- 4.2, P < or = .05), despite the active drug carryover effect into the placebo treatment period. Significant improvements in adenoidal obstruction and symptom scores over the 8-week crossover study were enhanced in the subsequent 16-week open-label period (P = .0001). By 24 weeks, an 82% reduction in group mean nasal obstruction symptom score accompanied a 29% mean reduction in adenoid/choana ratio. No clinical or demographic characteristic predicted a patient's degree of response to treatment. CONCLUSIONS: Properly administered aqueous nasal beclomethasone in standard doses can significantly reduce adenoidal hypertrophy and nasal airway obstructive symptoms in children.

Cross-allergenicity among celery, cucumber, carrot, and watermelon.

Cross-reactive allergens may be responsible for the clustering of food allergies seen in patients hypersensitive to fruits and vegetables. The pooled sera of six individuals were used to investigate cross-antigenicity among freshly prepared extracts of celery (Cy), cucumber (Cc), carrot (Ct), and watermelon (W). Each patient demonstrated clinical allergy to one or more study foods and, with the exception of Ct in two cases, had IgE to all four extracts by skin test or ELISA. In comparisons of each food against itself and the other three antigens, ELISA inhibition assays demonstrated allergenic similarity among Cy, Cc, Ct, and W by their similar slopes and 50% inhibition concentrations (2.0-7.3 micrograms/mL). In contrast, mountain cedar pollen (MC) produced at 50% inhibition of each food which was 10-fold higher (26.9-70.8 micrograms/mL) and had a flatter slope. Immunoblots of individual sera showed a 15-kD protein band common to all four foods. Pooled sera immunoblot inhibitions (100 and 5 micrograms/mL) demonstrated mutual inhibition of all bands in each of the four foods with the exception of a 28-kD protein of W uniquely inhibited by itself. We conclude that Cy, Cc, Ct, and W possess shared antigens that may account for clustering of these food allergies in patients.

HLA-DR4-associated nonresponsiveness to mountain-cedar allergen.

We did human lymphocyte antigen (HLA)-DR and DQ typing on 37 subjects with mountain-cedar (MC) pollinosis as defined by history and a positive skin test. Of these 37 subjects, 31 were subdivided into 18 subjects with a single positive skin test (SPST) and 13 subjects with multiple positive skin tests (MPSTs). We also typed 51 subjects without MC sensitivity or atopy as defined by history and negative skin tests to a battery of aeroallergens. We also typed 116 subjects in whom MC sensitivity had not been determined. Total IgE, Mc-specific immunoglobulin E (sIgE), and MC-sIgE binding bands by immunoblot were also determined on the subjects with SPSTs and MPSTs. No significant differences were found between the subjects with SPSTs and MPSTs for HLA type, total IgE, MC sIgE, or bands bound by MC sIgE by immunoblot. There was a strong negative relationship between HLA-DR4 and subjects with MC pollinosis; chi-square, 14.857; p = 0.0096; and odds ratio, 0.139. These findings suggest that there is no difference in genetic immunoregulation between subjects with SPSTs and MPSTs but that the presence of the DR4 gene product is associated with a decreased risk of an IgE response to MC and protection from MC pollenosis.

Objective antihistamine side effects are mitigated by evening dosing of hydroxyzine.

First-generation antihistamines have potency, pharmacokinetic, and cost advantages compared with nonsedating second-generation antihistamines. Bedtime dosing of hydroxyzine was investigated as a dosing strategy to minimize reaction time degradation and adverse subjective symptoms previously documented for hydroxyzine in divided doses. Hydroxyzine, 50 mg qhs, was compared with terfenadine, 60 mg bid, in this double-blind, placebo-controlled crossover study of 15 healthy, asymptomatic adults. Computer-based eye-hand reaction time tests of simple reaction time (SRT) and choice reaction time (CRT) were not statistically different among the three drugs. Drowsiness, dry mouth, and irritability were significant for hydroxyzine (P = .0001, .001 and .02, respectively) compared with terfenadine or placebo, but less than seen in a previous study of hydroxyzine, 25 mg bid. Symptom scores with terfenadine were comparable to placebo. Histamine skin test wheal and flare were both significantly and comparably suppressed by hydroxyzine and terfenadine (P = .0001). While wheal suppression by hydroxyzine was universal, four of the 15 subjects showed little or no suppression with terfenadine (P = .03). Although bedtime dosing of hydroxyzine did not eliminate subjective symptoms, it maintained skin H1-receptor antagonism the following morning and alleviated the prolongation of reaction times previously reported with hydroxyzine in divided doses. The significant adverse subjective symptoms and psychomotor performance degradations caused by first-generation antihistamines can be mitigated by creative dosing schedules.

Human immunodeficiency virus infection in the US Air Force: seroconversions, clinical staging, and assessment of a T helper cell functional assay to predict change in CD4+ T cell counts.

As of January 1990, 933 persons with human immunodeficiency virus type 1 (HIV-1) infection were clinically evaluated at Wilford Hall US Air Force (USAF) Medical Center. The Walter Reed HIV staging system was used in these evaluations to describe disease status and progression. Most persons were diagnosed through mandatory HIV testing in the USAF and were asymptomatic at the time of diagnosis. As of May 1990, 161 HIV-positive seroconverters (estimated overall seroconversion rate of 0.156/1000 person-years between 30 June 1988 and 1 July 1990) had been identified among active-duty USAF personnel, as they had previously tested negative for antibody to HIV. Men constitute 95% of the USAF HIV-positive population. An in vitro T helper cell functional assay was assessed to predict rate of CD4+ T cell decline over the subsequent year (mean, 15 months) in patients with greater than 200 CD4+ T cells/mm3. This assay may prove useful for prognostication and comparisons of patients in clinical trials of anti-HIV interventions.

Anaphylaxis to annatto dye: a case report.

Annatto dye is an orange-yellow food coloring extracted from the seeds of the tree Bixa orellana. It is commonly used in cheeses, snack foods, beverages, and cereals. Previously reported adverse reactions associated with annatto dye have included urticaria and angioedema. We present a patient who developed urticaria, angioedema, and severe hypotension within 20 minutes following ingestion of milk and Fiber One cereal, which contained annatto dye. Subsequent skin tests to milk, wheat, and corn were negative. The patient had a strong positive skin test to annatto dye, while controls had no response. The nondialyzable fraction of annatto dye on SDS-PAGE demonstrated two protein staining bands in the range of 50 kD. Immunoblotting demonstrated patient IgE-specific for one of these bands, while controls showed no binding. Annatto dye may contain contaminating or residual seed proteins to which our patient developed IgE hypersensitivity. Annatto dye is a potential rare cause of anaphylaxis.

Prolongation of simple and choice reaction times in a double-blind comparison of twice-daily hydroxyzine versus terfenadine.

Newer, nonsedating antihistamines provide a therapeutic alternative for the patient with allergy whose work is impaired by the side effects of traditional H1 antihistamines. To assess the differential effect of these antihistamines on reaction times and subjective symptoms, we compared terfenadine, 60 mg twice daily, to hydroxyzine, 25 mg twice daily, in a double-blind, placebo-controlled, crossover study of 16 healthy, asymptomatic adults. Simple reaction time and choice reaction time were measured with a computer-based, eye-hand, reaction-time testing apparatus. Reaction times and symptom scores were assessed 90 minutes after the fourth and tenth doses of each drug. Hydroxyzine, but not terfenadine, significantly prolonged both simple and choice reaction time (p less than or equal to 0.0001). However, decision time, the time to process one bit of spatial information, was not prolonged by either antihistamine. Therefore, hydroxyzine prolonged the interpretation and response to stimuli of the central nervous system without increasing single-bit processing time. Although terfenadine was not different from placebo for any symptom assessed, hydroxyzine produced significant drowsiness (p = 0.001), dry mouth (p = 0.022), and irritability (p = 0.021). During the 5 days of hydroxyzine administration, neither objective nor subjective symptoms demonstrated the development of tolerance. No correlation was found between subjective symptoms and prolongation of reaction times by hydroxyzine, suggesting that side effect symptoms of traditional antihistamines are unreliable predictors of objective performance. Terfenadine provides a promising therapeutic alternative to traditional antihistamines for individuals performing critical tasks.

Pediatric acquired immunodeficiency syndrome with negative human immunodeficiency virus antibody response by enzyme-linked immunosorbent assay and Western blot.

A 5-month-old white girl having persistent oral candidiasis was brought to medical attention because of acute respiratory distress, pneumonia, and hypoxia that worsened despite supportive care and antibiotics. Bronchial lavage fluid yielded Pneumocystis carinii. The diagnosis of acquired immunodeficiency syndrome (AIDS) was suspected, although enzyme-linked immunosorbent assay (ELISA) and Western blot tests were both negative for human immunodeficiency virus (HIV) antibody. Immunologic evaluation included the following results: a low normal CD4/CD8 ratio 0.88, CD4 lymphocytes 493/microL, and elevated IgA 539 mg/dL and IgM 175 mg/dL with normal IgG 492 mg/dL. Lymphocyte stimulation study results were depressed. Lymphocytes sent for culture were subsequently positive for HIV. The mother was HIV antibody positive by enzyme-linked immunosorbent assay and Western blot but belonged to no high-risk group and was asymptomatic except for chronic diarrhea. The father was HIV antibody negative. The patient was treated with pentamidine and IV gamma-globulin with good clinical response and a rapid decrease of IgM and IgA toward normal values. Subsequent candidal pneumonia and candidal esophagitis were treated successfully with amphotericin B. The patient has received prophylactic IV gamma-globulin infusions for 6 months and remains HIV negative by enzyme-linked immunosorbent assay and Western blot. This case of pediatric AIDS highlights the need to consider HIV infection in the differential diagnosis of any child with physical findings or illnesses suggestive of AIDS-related complex or AIDS, even when HIV serologic findings are negative and parents belong to no high-risk group. Parental testing for HIV antibody is suggested in such cases.