Vernal keratoconjunctivitis: A severe allergic eye disease with remodeling changes

Vernal keratoconjunctivitis (VKC) is an unusually severe sight‐threatening allergic eye disease, occurring mainly in children. Conventional therapy for allergic conjunctivitis is generally not adequate for VKC. Pediatricians and allergists are often not familiar with the severe clinical symptoms and signs of VKC. As untreated VKC can lead to permanent visual loss, pediatric allergists should be aware of the management and therapeutic options for this disease to allow patients to enter clinical remission with the least side effects and sequelae. Children with VKC present with severe ocular symptoms, that is, severe eye itching and irritation, constant tearing, red eye, eye discharge, and photophobia. On examination, giant papillae are frequently observed on the upper tarsal conjunctiva (cobblestoning appearance), with some developing gelatinous infiltrations around the limbus surrounding the cornea (Horner‐Trantas dot). Conjunctival injections are mostly severe with thick mucus ropy discharge. Eosinophils are the predominant cells found in the tears and eye discharge. Common therapies include topical antihistamines and dual‐acting agents, such as lodoxamide and olopatadine. These are infrequently sufficient and topical corticosteroids are often required for the treatment of flare ups. Ocular surface remodeling leads to severe suffering and complications, such as corneal ulcers/scars. Other complications include side effects from chronic topical steroids use, such as increased intraocular pressure, glaucoma, cataract and infections. Alternative therapies for VKC include immunomodulators, such as cyclosporine A and tacrolimus. Surgery is reserved for those with complications and should be handled by ophthalmologists with special expertise. Newer research on the pathogenesis of VKC is reviewed in this article. Vernal keratoconjunctivitis is a very important allergic eye disease in children. Complications and remodeling changes are unique and can lead to blindness. Understanding of pathogenesis of VKC may lead to better therapy for these unfortunate patients.     

The Utility of Serum Tryptase in the Diagnosis of Food-Induced Anaphylaxis

Purpose

This study investigates the utility of serum tryptase for the confirmation of shrimp-induced anaphylaxis.

Methods

Patients with a history of shrimp allergy and positive skin prick tests (SPT) to commercial shrimp extract were recruited for shrimp challenges. Serum total tryptase was obtained at baseline and 60 min (peak) after the onset of symptoms.

Results

Thirty-nine patients were challenged. There were 12 patients with anaphylaxis, 20 with mild reactions and 7 without symptoms (control group). Characteristic features and baseline tryptase were not different among the 3 groups. The peak tryptase levels were higher than the baseline in anaphylaxis and mild reaction groups (P<0.05). The delta-tryptase (peak minus baseline) and the tryptase ratio (peak divided by baseline) in the anaphylaxis group were higher than the mild reaction and control groups (P<0.01). The optimum cut-off for peak tryptase to confirm anaphylaxis was 2.99 µg/L with 50% sensitivity, 85% specificity, 3.33 positive likelihood ratio (LR) and 0.59 negative LR. The manufacturer''s cut-off for peak tryptase was >11.4 µg/L with 17% sensitivity, 100% specificity, infinity positive LR and 0.83 negative LR. The best cut-off for delta-tryptase was ≥0.8 µg/L with 83% sensitivity, 93% specificity, 11.86 positive LR and 0.18 negative LR. The best cut-off for tryptase ratio was ≥1.5 with 92% sensitivity, 96% specificity, 23 positive LR and 0.08 negative LR.

Conclusions

The peak tryptase level should be compared with the baseline value to confirm anaphylaxis. The tryptase ratio provide the best sensitivity, specificity, positive and negative LR than a single peak serum tryptase for the confirmation of shrimp-induced anaphylaxis.     

A novel mutation of the CYBB gene resulting in severe form of X-linked chronic granulomatous disease

We evaluated a boy who had multiple Salmonella septicemia, Aspergillus pneumonia and brain abscesses. His nitroblue tetrazolium (NBT) test was reportedly abnormal. The dihydrorhodamine (DHR) flow cytometry assay was compatible with typical X-linked chronic granulomatous disease (X-CGD). CYBB analysis revealed a novel complex mutation atggacg --> ttca in exon 12 (base pairs 1532-1538). As a result, 3 amino acids Tyr 511, Gly 512 and Arg 513 were deleted and replaced by 2 amino acids, Phe and Gln. The DHR and mutation analysis of his mother showed normal DHR pattern and no mutations in exon 12 of CYBB gene. In conclusion, any children with multiple Salmonella and Aspergillus infection should be suspected of CGD. NBT test, DHR assay and gene analysis are helpful toolsto confirm the diagnosis e v en i n the case of de novo mutation.     

Pharmacokinetics of bambuterol during oral administration to asthmatic children

AIMS: To investigate dose proportionality, dosing frequency, and ethnic aspects of the pharmacokinetics of bambuterol in asthmatic children, and to discuss the relationship with previous observations in adults. METHODS: Forty-eight children in four different studies completed two double-blind bambuterol treatments each (daily doses of bambuterol hydrochloride): 12 preschool (5 mg x 2 vs 10 mg) and 12 school (10 mg vs 20 mg) Caucasians, 12 preschool (2.5 mg vs 5 mg), and 12 school (10 mg vs 20 mg) Orientals. Peak plasma concentrations and dosing interval area under curve (AUC) of bambuterol and the active metabolite terbutaline were assessed at steady state. Treatment differences were analysed statistically within each study. Differences between the studies and the relation to steady-state AUC in adults were described. RESULTS: Dose proportionality was seen for terbutaline but not for bambuterol. Twice-daily dosing (2 x AUC(0,12 h)) could not be shown to differ from once-daily dosing (AUC(0,24 h)) in the preschool Caucasians. Mean AUC of terbutaline was 128 and 242 nmol l-1 h in the preschool Caucasians (5 mg/12 h; 10 mg/24 h), 213 and 406 nmol l-1 h in the Caucasian school children (10 mg; 20 mg), 87.4 and 202 nmol l-1 h in the Oriental preschool children (2.5 mg; 5 mg), and 356 and 640 nmol l-1 h in the Oriental school children (10 mg; 20 mg). Oriental school children had higher plasma concentrations of bambuterol and terbutaline than Caucasian school children. The strict ethnic implication of the difference could not be elucidated, because demographic data were not perfectly matched. Terbutaline AUC was only moderately increased in the Caucasian school children compared with Caucasian adults. The increase was more pronounced in Oriental children and in some preschool Caucasians. The highest concentration of terbutaline, 58 nmol l-1, was seen in an Oriental school child after a 20 mg dose. CONCLUSIONS: Caucasian school children can be given bambuterol hydrochloride very much as Caucasian adults, 10 or 20 mg once daily, but Oriental preschool and school children plus preschool Caucasians should be given lower doses.     

Circadian variation of skin reactivity and allergy skin tests

Previous investigations of the circadian variation in skin reactivity suggested that results of skin tests obtained in the afternoon could vary from the results obtained in the early morning and therefore could result in a differing assessment of patient sensitivity. To determine whether this was a practical concern in the normal clinical setting, we studied 20 adults and 20 children who had skin prick tests positive (3+ or more) to short ragweed. These patients were skin tested in duplicate at 8 AM and at 4 PM with fivefold serial dilutions of short ragweed extracts (1:20 to 1:12,500, wt/vol) and of histamine hydrochloride (10 to 0.016 mg/ml). Areas of wheal and flare were recorded and measured by computed planimetry. In addition, results were also read according to a conventional scoring system. Mean wheal and erythema areas with ragweed and histamine at each dilution were compared between morning and their corresponding evening values. Although there was a trend for the morning means to be larger than evening means, no significant differences between the two sessions were observed at any dilution. Mean morning skin index scores, as calculated from the combined mean wheal and erythema areas, were larger than mean evening scores for ragweed and histamine, but the differences were not of a degree to be clinically important. This observation was also true for conventional scores. Comparing the results from the two groups of children who had their first set of skin tests performed either in the morning or afternoon session indicated that there was no evidence of a refractory state of the skin during the second test sessions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical evaluation of the "Siriraj Spacer" in asthmatic Thai children.

We designed a new, washable, and collapsible bag spacer (the Siriraj Spacer) for use with metered-dose inhalers (MDI) by Thai asthmatic patients. The Siriraj Spacer consists of a mouthpiece, a front panel to which any type of MDI could be attached and a collapsible 800 mL ringed-plastic bag. Fifteen asthmatic children (6-13 years of age) were enrolled into a randomized, double-blind, triple crossover study (spanning a period of three days) to compare the clinical effectiveness of the Siriraj Spacer with that of the Volumatic Spacer (Glaxo, Inc., Research Triangle Park, NC, U.S.A.) and with the use of MDI alone. Medication used with the active method of administration was 2 puffs of albuterol (100 micrograms/puff) while 2 puffs from placebo MDI were used with the other two methods in succession. All children were stable asthmatic patients, and had been instructed how to use MDI properly by an open mouth technique just before the initiation of the study. Spirometry (FEV1, FVC, PEFR, and FEF25-75%) was followed for six hours after the administration of albuterol. The baseline FEV1s of the three study days were within 50% to 70% of the predicted values (with baseline variability of less than 20%). Data were expressed as percentage of improvement from baseline. By an analysis of variance with repeated measures, no significant differences were observed between pulmonary function data obtained with any of the three methods of bronchodilator administration (P > .05) at any time point throughout the 6-hour period.(ABSTRACT TRUNCATED AT 250 WORDS)     

The role of disodium cromoglycate-metered dose aerosol inhaler in the management of asthma in Thai children

Metered dose aerosol inhaler of disodium cromoglycate (Intal) has been recently introduced to facilitate the ease of administration of the drug over its previous spincap formulation. We evaluated the efficacy of regular use of metered dose inhaler of disodium cromoglycate (DSCG-MDI) in the daily management of Thai asthmatic children. The study comprised nineteen children with the age range of 8-15 years (mean 11.6 years). During a two week baseline period, the patients recorded their baseline symptom scores, requirement of their asthma medications (medication scores) and their morning/evening peak flow (PEFR) readings. Thereafter, DSCG-MDI was prescribed at the dosage of two puffs (1 mg/puff) four times daily for eight weeks. Patients were examined at two week intervals at which daily score cards along with PEFR records were collected. Significant reduction in the medication scores and in the requirement for maintenance bronchodilators were noted (p less than 0.01) within two weeks of use of the DSCG-MDI. Morning and evening PEFR's increased significantly and this increase reached statistical significance at 4 weeks after the initiation of the treatment (p less than 0.01). No side effects were reported throughout the study; the aerosol was well tolerated. In this open study DSCG-MDI, at a dose of 1 mg four times daily, significantly improved asthma symptoms along with PEFR readings in Thai asthmatic children and reduced the need for concomitant asthma medications.