Short contact with nickel causes allergic contact dermatitis: an experimental study.

BACKGROUND: Knowledge about the required duration of exposure for elicitation of allergic nickel dermatitis in nickel-allergic individuals is limited. However, it often has been proposed that short skin contact is safe. OBJECTIVES: To examine whether repeated skin contact with nickel over short time periods (3 × 10 min) can elicit allergic nickel dermatitis. METHODS: Sixteen nickel-allergic adults and 10 controls were exposed to, respectively, nickel- and aluminium-containing discs on each volar forearm and on each earlobe for 3 × 10 min. One arm was pretreated for 24 h with sodium lauryl sulfate (SLS) 0·5% under occlusion before exposure. One aluminium and one nickel exposure site were clinically evaluated, and blood flow was measured with laser Doppler flowmetry at day 2 and day 4. RESULTS: Ten of 16 (63%) nickel-allergic participants developed allergic nickel dermatitis on SLS-pretreated arm skin and three of 16 (19%) developed it on normal skin on the earlobe. On the SLS-pretreated arms of nickel-allergic participants, blood flow increased significantly more on the nickel-exposed skin than on the aluminium-exposed skin on days 2 and 4. No change in clinical reactivity or blood flow was found on normal forearm skin in nickel-allergic participants or on any skin in controls. CONCLUSIONS: This experimental study showed that relatively short repeated skin contact (3 × 10 min) with metallic nickel elicits allergic nickel dermatitis in irritated skin and at sites with previous dermatitis. The results support the restrictions in current nickel regulation.

Optimizing diagnostic tests for persulphate-induced respiratory diseases.

BACKGROUND: Persulphates from hair bleaching products are considered the major cause of occupational-rhinitis and asthma in hairdressers. The specific inhalation challenge (SIC) is considered 'reference standard' for diagnosing persulphate-induced asthma and rhinitis; however, the currently validated method of performing SIC with persulphate powder is time consuming with a duration of up to 4 days. The value of skin prick tests (SPTs) and histamine release tests (HRTs) with persulphates is unknown. The aim of this study was to establish a novel rapid SIC with persulphate powder to test for both rhinitis and asthma simultaneously in 1 day. In addition, we assessed the suitability of SPTs and HRTs for detecting persulphate-induced respiratory diseases. METHODS: The study population included 19 hairdressers with a history of work-related rhinitis and/or asthma symptoms, 12 symptomatic controls (10 with concurrent allergic asthma and rhinitis and two with non-allergic asthma), and 40 healthy controls. A previous severe asthmatic reaction and/or anaphylactic reaction to persulphates was considered an exclusion criterion for hairdressers. The 19 hairdressers and 12 symptomatic controls had SIC performed with 3 × 5 min exposures to potassium persulphate powder in a provocation chamber. All participants, including the 40 healthy controls, were subjected also to SPTs and HRTs with three persulphate salts at concentrations of 2-20 % and 0.03-1 %, respectively. RESULTS: None of the symptomatic controls had a nasal or bronchial response to SIC with potassium persulphate. Six hairdressers presented a nasal and two a bronchial response. No severe reactions occurred. No positive SPTs were recorded, neither among hairdressers, symptomatic controls, nor healthy controls. All three groups showed nonspecific non-IgE mediated histamine release to persulphates in HRT. CONCLUSIONS: The proposed method for performing SIC showed a high specificity for detecting persulphate-induced asthma and rhinitis. The rapid SIC was able to produce positive nasal and bronchial responses in symptomatic hairdressers without any severe reactions occurring. SPTs and HRTs cannot predict asthma or rhinitis caused by persulphates.

Incidence of respiratory sensitisation and allergy to enzymes among employees in an enzyme producing plant and the relation to exposure and host factors.

OBJECTIVES: Belonging to the group of high molecular weight respiratory sensitisers, microbial enzymes have been reported as a well known cause of occupational allergy, typically manifesting itself as rhinitis and/or asthma. High exposure to such high molecular weight sensitisers, and possibly also peak exposures, implies a higher risk than low exposure, but the exact relation between exposure, sensitisation and clinical allergy remains to be clarified. The authors sought to estimate the risk of respiratory enzyme allergy in an enzyme producing plant and to assess the relation between exposure indices and allergy. METHODS: Retrospective follow-up study based upon data gathered from health surveillance since 1970. 1207 employees from production and laboratories were included. The level of enzyme exposure in the relevant departments was estimated retrospectively into five exposure levels based on 10-fold increments/decrements of the threshold limit value and other exposure information. The risk was estimated in an exponential regression survival model fitted with constant intensity for subperiods of time using maximum likelihood estimation. RESULTS: During the first three years of a person's employment, the enzyme sensitisation and allergy incidence rates were 0.13 and 0.03 per person-year at risk, respectively. In the fitted models, exposure class did not correlate with the outcome variables. The risk of sensitisation decreased along the three decades, whereas the risk of allergy remained unchanged. The risk of sensitisation and allergy was doubled among smokers. Pre-employment atopy was only associated with sensitisation risk. CONCLUSION: Sensitisation to enzymes decreased during the study period, possibly reflecting improvements in the working environment. A similar decrease could not be demonstrated for allergy to enzymes. Neither of the two outcomes correlated with exposure estimates, possibly because of the low precision of the estimates.

Individuals with occupational allergy to detergent enzymes display a differential transcriptional regulation and cellular immune response.

BACKGROUND: In spite of significant safety measures, allergy to industrial enzymes remains a major concern. The increasing prevalence of occupational allergy emphasizes the need to investigate the functional properties of enzyme-exposed dendritic cells (DCs), as DCs possess a potent ability to activate allergen-specific T cells. OBJECTIVE: This study aims at elucidating the molecular mechanisms underlying allergic immune responses to lipase, an industrial enzyme. For this purpose, we studied the effect of both hypoallergenic and wild-type lipase on the transcriptional regulation in DCs and their stimulatory effect on memory CD4+ T cells. METHODS: Five individuals with documented lipase allergy were tested for specific serum IgE. DCs from these individuals, stimulated with lipases, were assayed for their ability to affect proliferation and polarization of memory T cells. The effect of lipases on transcriptional activity in DCs was evaluated using global expression analysis. RESULTS: Lipase-specific IgE levels varied considerably between donors, with donor 4 exhibiting highest levels, and a potent specific CD4+ T cell recall response was demonstrated only for donor 4. No difference was detected in cytokine profile when T cells from donor 4 were co-cultured with DCs pulsed with either hypoallergenic or wild-type lipase, as demonstrated by high IL-4 and IL-13, and low IFN-gamma production. However, the lipases induced different genetic signatures in DCs from donor 4, as compared with the non-responders. CONCLUSIONS: DCs from individuals with clinically diagnosed allergy to lipase displayed a differential response to stimulation with hypoallergenic and wild-type lipase in vitro. Only allergen-pulsed DCs from donor 4 were able to induce CD4+ T cell proliferation. The lipase-specific T cells displayed a T-helper type 2 phenotype, which was not altered by hypoallergenic lipase-pulsed DCs. Furthermore, DCs derived from donor 4 and stimulated with either of the lipases displayed different transcriptional profiles, as compared with the other donors. These signatures represent genes of potential importance for an immunoregulatory role of DC in an ongoing allergic response.

[House dust mite allergens and mite allergy in Copenhagen dwellings. A cross-sectional study]. / Støvmideallergener og mideallergi i københavnske boliger. En tvaersnitsundersøgelse.

The aim of the study was to investigate the influence of various environmental factors on occurrence of house dust mite allergens and the influence of allergen exposure on mite allergy. Ninety-two persons from a population study filled in a questionnaire, were skin prick and lung function tested and dust samples were collected from their mattresses for analyses. Two out of five patients with asthma had a positive skin reaction to house dust mite allergen in contrast to five out of 87 non-asthmatics. Fifty-nine per cent of the dust samples contained (group 1) mite allergen > 2 micrograms/g dust. Such mattresses were older (median 7 years, range 1-22) than mattresses with less allergen (median 4 years, range 1-20). In the six bedrooms reported to be humid or mouldy, mattresses contained high concentration of mite allergens. No other parameter investigated could predict the allergen contents. In almost all cases dust analyses are crucial to be able to advise patients with house dust mite allergy.

Hyponatremia following acute overdose with paroxetine.

This case illustrates severe hyponatremia following an acute overdose of paroxetine. An 83-year-old woman was admitted to our hospital after an attempt to commit suicide. She had consumed an overdose of 360 mg paroxetine. The treatment was started 3 days previously with 10 mg/day because of regular suffering from obsessive and suicidal thoughts. An initial sign of overdose was excessive vomiting. Five days late she developed hyponatremia (serum sodium 112 mmol/l) with somnolence, confusion, muscle spasms, dehydration of arms and legs and slow reflexes. Ecchymoses and myxoedema were also observed. Treatment included fluid restriction and sodium chloride infusion. Levothyroxin was prescribed and the hyponatremia resolved.

Allergy risk in an enzyme producing plant: a retrospective follow up study.

OBJECTIVE: To investigate the risk of enzyme sensitisation and clinical allergy in workers exposed to enzymes at Novo Nordisk A/S. METHODS: The study was a retrospective follow up study based on medical history and test data originally collected at routine screenings for enzyme allergy by the Occupational Health Service (OHS) of Novo Nordisk A/S during the period 1970-92. Workers were exposed to proteases, lipases, cellulases, and carboxyhydrases. Medical records of 3815 subjects were registered in the OHS database. According to criteria including possible enzyme exposure, allergy tests at the time of engagement, and participation in the allergy screening programme 1064 were selected for the present study. Outcomes were allergy symptoms, specific IgE test (radioallergosorbent test (RAST)) to enzymes, skin test reactions to common allergens and enzymes, forced expiratory volume in one second (FEV1), and forced vital capacity (FVC). Potential risk factors were smoking habits, workplace, type of job, age, and sex. RESULTS: Sensitisation occurred to all types of enzymes handled in the plant, most often in production areas and laboratories; 8.8% developed clinical enzyme allergy during the first three years of employment. The risk declined during the period. The frequency of enzyme sensitisation, expressed as RAST values > 0.5 SU, was 36%, and the frequency of significant RAST values > or = 2 SU was 8%. Ranking diagnoses of enzyme allergy by severity, the frequency of asthma was 5.3%, rhinitis 3.0%, and urticaria 0.6%. Half of the cases occurred within the first 15 months of exposure. Smoking was an independent risk factor for clinical enzyme allergy (odds ratio (OR) = 2.3 (95% exact confidence interval (95% CI) 1.4 to 3.9), measurable RAST > or = 0.5 SU (OR = 1.5 (95% CI 1.1 to 2.1)), and RAST > or = 2 SU (OR = 4.5 (95% CI 2.2 to 8.4)). Atopic predisposition at the time of engagement was not a significant risk factor for enzyme allergy. This could be due to various selection mechanisms.

Antihistamine premedication in specific cluster immunotherapy: a double-blind, placebo-controlled study.

BACKGROUND: Specific immunotherapy treatment in allergic diseases involves a risk of systemic side effects. A double-blind, placebo-controlled study was performed in 45 patients allergic to pollen to determine whether pretreatment with loratadine could reduce the number and severity of systemic reactions during the dose-increase phase of cluster immunotherapy. METHODS: The patients received cluster immunotherapy with a standardized birch (Betula verrucosa) or grass (Phleum pratense) pollen extract adsorbed to aluminum hydroxide. The immunotherapy schedule involved seven visits and 14 injections to reach a maintenance dose of 100,000 standardized quality units. Loratadine, 10 mg, or placebo tablets were administered 2 hours before the first injection at each visit. RESULTS: A total of 720 injections were given (309 injections in 21 patients receiving loratadine and 411 injections in 24 patients receiving placebo). The median numbers of injections to reach maintenance dose were 15 (range, 14 to 18) in the loratadine group and 16 (range, 14 to 23) in the placebo group (p = 0.037). The numbers of patients with systemic reactions were seven (33%) and 19 (79%) in the loratadine and placebo groups, respectively (p = 0.002). Twenty-five reductions caused by systemic reactions were observed in the placebo group in contrast to nine in the loratadine group (p = 0.047). No life-threatening systemic reactions were observed in either group. Systemic reactions were, however, more severe in the placebo group, mainly because of a significantly higher incidence of urticaria (10 vs 1, p = 0.022). CONCLUSION: Pretreatment with loratadine seems to reduce both the number and severity of systemic reactions in specific cluster immunotherapy.

Exposure chamber for allergen challenge. The development and validation of a new concept.

Exposure chambers have proven to be valuable tools in studying allergic diseases. The chamber provides a controlled environment and maintains conditions for measuring the amount of allergen inducing symptoms in allergic subjects. The aim of the present study was to develop and test an exposure chamber. The chamber was constructed as an airtight tent, made of transparent polyethylene, easy to adapt to the shape of an existing room, easy to clean, and providing exact allergen-dosage control. Airflow to the interior of the tent was controlled by a variable inlet ventilator fitted with a micropore filter and balanced by a variable high-volume air-sampler on the outlet side. Trace material and allergen were administered as aerosols with a nebulizer connected to the inlet pipe. Samples were obtained from interior surfaces and filters at the outlet. Two different methods were used to test the concept. One method used a colored, neutral trace substance (phenol red indicator) measured photometrically on extracts from filters. Secondly, house-dust mite allergen (Dermatophagoides pteronyssinus) was applied, with samples analyzed by an ELISA technique. The results demonstrated the ability of the system to administer and sample allergen with a high degree of reproducibility. A clinical pilot trial proved the capability of the system to initiate symptoms in allergic subjects.

Cardiovascular and hormonal responses to anaphylactic shock in the pig.

Cardiovascular and hormonal responses to anaphylactic shock were evaluated in anaesthetized pigs sensitized by natural exposure to Ascaris suum as verified by antibodies. In six animals with such antibodies, Ascaris antigen injection produced a plasma histamine increase of 52 (42-196) fold (median and range; P < 0.05), while four pigs without such antibodies served as controls with only insignificant increases in histamine. In the anaphylactic group, two of the animals died during the investigation due to cardiovascular collapse. In the sensitized pigs resting heart rate (HR), 104 (86-118) beats min-1, increased to 204 (164-240) beats min-1 as mean arterial pressure (MAP) decreased from 94 (83-102) to 45 (31-90) mmHg (P < 0.05). In contrast, the non-sensitized pigs maintained the resting HR of 101 (79-113) beats min-1, as MAP decreased to 50 (41-97) mmHg (P < 0.05). In the sensitized group systemic vascular resistance (SVR) fell from 1114 (843-1811) to 990 (588-1173) dyne s-1 cm-5 and then increased to 3617 (2593-4166) dyne s-1 cm-5, while in the control group there was only a reduction to a minimum value of 730 (458-1307) dyne s-1 cm-5 (P < 0.05). Thoracic electrical impedance increased only in the sensitized group [from 28.3 (24.7-31.4) to 29.9 (24.0-31.4)], indicating central volume depletion. Plasma catecholamines increased markedly only in the sensitized pigs, and plasma pancreatic polypeptide, vasopressin, aldosterone and renin responses confirmed to those established during central hypovolaemia. During anaphylaxis, this study demonstrated cardiovascular responses similar to those established during a major blood loss. However, as indicated by plasma catecholamines, sympathetic activity was many times that previously demonstrated during haemorrhage, and sympathoactivation may explain the marked vasoconstriction noted in the sensitized pigs.

Efficacy of acrivastine in the treatment of allergic rhinitis during natural pollen exposure: onset of action.

In a placebo-controlled, randomized, and double-blind 1-day field study, the efficacy and onset of action of capsule acrivastine 8 mg were evaluated in 42 patients suffering from allergic rhinoconjunctivitis elicited by natural grass pollen exposure. Before and for 2 h after treatment, the patients scored the severity of five rhinoconjunctivitis symptoms every 10 min on a 0-5 scale (0 = no symptoms; 5 = very severe symptoms). The number of sneezes was recorded, and every 30 min, measurements of nasal peak flow were made. Before treatment, there was no difference in median total symptom score (mTSS) between the acrivastine group (A) and the placebo group (P) (12 and 12, respectively). Time of onset was estimated by an exponential decay model to be 19 min (95% confidence interval 0-39 min). A statistically significant difference in percent reduction of mTSS between A and P was observed for the first time 46 min after treatment start (A = 22%, P = 0%, P < 0.05). A 50% reduction in total symptom score (TSS) was achieved within 60 min by 38% in A and 17% in P (NS), and within 80 min in 52% and 17%, respectively (P < 0.05). The median time for 50% reduction in TSS (MT50) was 80 min for A and > 120 min for P (P < 0.01). The symptom score of sneezing and number of sneezes were evaluated for periods of 30 min. The difference between A and P became statistically significant from 31-60 and 61-90 min, respectively (P < 0.05 and P < 0.01). Objective and subjective determinants in the different time intervals were well correlated. Improvement of nasal congestion was observed in A at 91-120 min, as measured by nasal peak flow.

Aeroallergen analyses and their clinical relevance. II. Sampling by high-volume airsampler with immunochemical quantification versus Burkard pollen trap sampling with morphologic quantification.

A comparison was made between the amount of airborne pollen collected by Burkard airsampler and the allergenic activity of particles trapped on glass fibre filters in an Accu-Vol high-volume airsampler. The comparison was made throughout the pollen seasons 1986 to 1989. Both airsamplers were operated 24 h a day. They were placed less than 5 m apart, and estimation of the pollen amount was made on a day-to-day basis during the pollen seasons, and on a weekly basis outside the seasons. The occurrence of the 3 clinically most important allergenic types of pollen, birch, grass, and mugwort, was analysed, and close correlations between the 2 sampling techniques were found (rs 0.5-0.8, p < 0.001). The detected range of counted pollens/m3 was: birch 0-1075, grass 0-156, and mugwort 0-44. By immunochemical analysis we found the corresponding amounts to be 0-80, 0-8, and 0-1 SQ-U/m3, respectively. Pollen counts and immunochemical estimation were compared with the symptom score recordings of allergic persons for birch season 1989 and for grass seasons 1986, 1988, and 1989. A close correlation was found for both sampling techniques for the grass seasons in 1986 and 1989 (rs 0.51-0.61, p < 0.001-0.0001), but a less significant correlation was found for the 1988 grass season, and for birch in 1989 (rs 0.24-0.34, p < 0.001-0.05).

Aeroallergen analyses and their clinical relevance. I. Immunochemical quantification of allergens by RAST-inhibition, Mab-ELISA, basophil histamine release, and counter current immuno electrophoresis.

The aim was to compare IgE and IgG4 RAST-inhibition assay (RI), monoclonal antibody ELISA (Mab-ELISA), counter current immuno electrophoresis (CCIE) and histamine release from basophil leukocytes (HR) for allergen quantification with special reference to aeroallergen detection. As components of indoor aeroallergens, cat, dog, and Derm. pter. allergen extracts were selected for the experiments. To evaluate unspecific interference, these allergens were compared mutually and with Cladosporium herbarum. Allergen extracts in varying dilutions were mixed with crushed glass fibre filter materials, eluted, recovered by centrifugation, and allergen concentration quantified by the assays. Equal sensitivity was found for both IgE- and IgG4-RI assaying cat allergen (in the range 5-50 SQ-U/ml) and dog allergen (in the range 10(2)-10(3) SQ-U/ml). The IgG4-RI assaying Derm. pter. was more sensitive (50 SQ-U/ml) than IgE-RI (2*10(3) SQ-U/ml). The ranges of allergen detection limits for the Mab-ELISA were equal for cat and Derm. pter. (10-10(2) SQ-U/ml). The range of allergen detection limits for CCIE, assaying dog were 10(4)-10(5) SQ-U/ml. The ranges of allergen detection limits for HR were equal for cat and Derm. pter. (10-10(2) SQ-U/ml), and 10(2)-10(3) SQ-U/ML for dog. Because of cross-reactivity, a minor degree of interference was observed in the IgE-RI and the HR test for the highest concentration of cat and dog allergens.

Turbuhaler: a new device for dry powder terbutaline inhalation.

The aim of this study was to compare bronchodilator response and adverse effects of terbutaline when administered with the metered dose inhaler (MDI) Bricanyl and with the dry powder inhaler Bricanyl Turbuhaler (BT). Nine adult patients with bronchial asthma participated. The study was of an open crossover design. At 30-min intervals the patients inhaled increasing doses of terbutaline (0.25 mg to 5.0 mg cumulated) from either the conventional MDI or from the BT. After each inhalation FEV1, FVC, heart rate, muscle tremor and adverse effects were recorded. Both treatments, BT and MDI, resulted in a dose-related increase in lung function, without any statistical difference. Taste sensation, muscle tremor and increase in heart rate were observed in both groups. Because of the design of the BT one may assume that inhalation failure can be avoided.

Septicemia with Agrobacterium species from a permanent vena cephalica catheter. A case report.

A case of Agrobacterium septicemia is reported in a 47-year-old woman with disseminated adenomcarcinoma mammae and a permanent vena cephalica catheter.