Acute life-threatening extrinsic allergic alveolitis in a paint controller.

BACKGROUND: Occupational diisocyanate-induced extrinsic allergic alveolitis (EAA) is a rare and probably underestimated diagnosis. Two acute occupational EAA cases have been described in this context, but neither of them concerned hexamethylene diisocyanate (HDI) exposure. AIMS: To investigate the cause of a life-threatening EAA arising at work in a healthy 30-year-old female paint quality controller. METHODS: Occupational medical assessment, workplace evaluation, airborne and biological monitoring and immunodermatological tests. RESULTS: Diagnosis of EAA relied on congruent clinical and radiological information, confirmed occupational HDI exposure and positive IgG antibodies and patch tests. The patient worked in a small laboratory for 7 years, only occasionally using HDI-containing hardeners. While working with HDI for 6 h, she developed breathlessness, rapidly progressing to severe respiratory failure. Workplace HDI airborne exposure values ranged from undetectable levels to 4.25 p.p.b. Biological monitoring of urinary hexamethylene diamine in co-workers ranged from <1.0 to 15.4 μg/g creatinine. Patch tests 8 months later showed delayed skin reaction to HDI at 48 h. Subsequent skin biopsy showed spongiotic dermatitis with infiltration of CD4(+) and CD8(+) T cells. CONCLUSIONS: We believe this is the first reported case of acute life-threatening EAA following exposure to HDI. Low concentrations of airborne HDI and relatively high urinary hexamethylene diamine suggest significant skin absorption of HDI could have significantly contributed to the development of this acute occupational EAA.

Alvéolite aux isocyanates chez une couturière [Isocyanate-induced alveolitis in a furniture manufacture worker]

A 41-year-old woman who worked in a furniture plant was admitted to hospital for acute dyspnea that had developed a few hours she marked pieces of "Alcantara" material with a heated metallic blade. The chest x-ray showed a restrictive syndrome. The lymphocyte count was high in the bronchioalveolar lavage fluid with a CD4/CD8 ratio of 0.11, leading to the diagnosis of alveolitis. Investigations at the work place allowed identification and evaluation of the causal agent. Alcantara is a synthetic fabric composed of 70% polyurethane fibers, which when burned produces isocyanate monomers. After eliminating exposure and institution of corticosteroid therapy, the outcome was good with complete recovery. The risk was eliminated by changing the work procedure. This risk has not been reported earlier for furniture manufacture.

Immuno-reactive proteins from Mycobacterium immunogenum useful for serodiagnosis of metalworking fluid hypersensitivity pneumonitis.

Metalworking fluid-associated hypersensitivity pneumonitis (MWF-HP) is a pulmonary disease caused by inhaling microorganisms present in the metalworking fluids used in the industrial sector. Mycobacterium immunogenum is the main etiological agent. Among the clinical, radiological and biological tools used for diagnosis, serological tests are important. The aim of this study was to identify immunogenic proteins in M. immunogenum and to use recombinant antigens for serological diagnosis of MWF-HP. Immunogenic proteins were detected by two-dimensional Western blot and candidate proteins were identified by mass spectrometry. Recombinant antigens were expressed in Escherichia coli and tested by enzyme-linked immunosorbent assay (ELISA) with the sera of 14 subjects with MWF-HP and 12 asymptomatic controls exposed to M. immunogenum. From the 350 spots visualized by two-dimensional gel electrophoresis with M. immunogenum extract, 6 immunogenic proteins were selected to be expressed as recombinant antigens. Acyl-CoA dehydrogenase antigen allowed for the best discrimination of MWF-HP cases against controls with an area under the receiver operating characteristics (ROC) curve of 0.930 (95% CI=0.820-1), a sensitivity of 100% and a specificity of 83% for the optimum threshold. Other recombinant antigens correspond to acyl-CoA dehydrogenase FadE, cytosol aminopeptidase, dihydrolipoyl dehydrogenase, serine hydroxymethyltransferase and superoxide dismutase. This is the first time that recombinant antigens have been used for the serodiagnosis of hypersensitivity pneumonitis. The availability of recombinant antigens makes it possible to develop standardized serological tests which in turn could simplify diagnosis, thus making it less invasive.

Allergic asthma to thaumatin : case report

Background: Thaumatin is a protein originally isolated from an African fruit (the "katemfe"), but various thaumatin-like proteins have been found in apples, grapes, kiwis and olives, etc. Thaumatin has natural sweetening properties and is about 2000 to 3000 times more potent than sucrose. It is therefore used in the food industry, particularly in the processing of low-calories sweeteners. Recently, thaumatin-like proteins have been described as a new family of allergens. Methods: We report the case of a 44-year-old woman occupationally exposed to thaumatin, who developed an allergy to it. The first symptom was an urticaria, which she presented two years after the factory she was working in (a sweeteners manufacturer), started to use thaumatin. Later on, she perceived an acute episode of a sensation of lump in the throat, persisting mild dyspnea, dysphonia and cough. Despite normal peak flow values and a normal chest examination, her general practitioner treated her with local corticoids and systemic antihistaminic drugs, which improved the symptoms. As occupational physicians, we were asked about the likelihood of an occupational disease. We visited her working place, and assessed the exposure to thaumatin. We concluded that the probability for a delayed asthma related to a thaumatin exposure was high, despite the lack of an exposure test. Results: The case was submitted to the insurance company as an occupational disease, and was accepted as such. It was therefore decided not to perform the exposure test, given the absence of true benefit for the patient, who was advised to switch job, and to avoid any exposure to thaumatin in the future. A few months later, the symptoms had completely disappeared. Conclusion: Some molecules only used in specific industry sectors, can cause health problems, such as allergy, but also toxic impairments, etc. The occupational physician, trained to find out which products and identify which molecules are involved, can contribute to the diagnosis, and help make possible a safe return to work for the patient.

Réactions cutanées allergiques et toxiques aux plantes [Allergic and toxic cutaneous reactions to plants]

Numerous professional or leisure activities expose individuals to plants susceptible to provoke contact allergies. The immunological mechanisms that are responsible for these ailments (delayed cellular reaction linked to allergic dermatitis or immediate IgE mediated reaction of the allergic urticaria) differ according to the plant families involved. A differential diagnosis must be made in the case of the even more frequent non-allergic reactions implying either a simple mechanical irritation, or a contact with toxic substances. The role of UV (phytophotodermatosis), as well as the contact allergy to wood is also evoked in this paper.

Total IgE and eotaxin (CCL11) contents in tears of patients suffering from seasonal allergic conjunctivitis.

BACKGROUND: To prospectively investigate patients with seasonal allergic conjunctivitis (SAC) during the pollen season and test associations between tears total IgE, eotaxin concentrations, and SAC severity. METHODS: Enrolled patients presented ocular symptoms and clinical signs of SAC at the time of presentation. Ocular itching, hyperaemia, chemosis, eyelid swelling, and tearing were scored, and the sum of these scores was defined as the clinical score. Conjunctival papillae were separately graded. We measured eotaxin concentration in tears by an enzyme-linked immunosorbent assay (ELISA) and total tear IgE by Lacrytest strip. RESULTS: Among thirty patients (30 eyes), 11 showed neither tear IgE nor tear eotaxin, while 15 out of 19 patients with positive IgE values presented a positive amount of eotaxin in their tears (Fisher's test: p < 0.001). The mean eotaxin concentration was 641 ± 154 (SEM) pg/ml. In patients with no amount of tear IgE, we observed a lower conjunctival papilla grade than in patients whose tears contained some amount of IgE (trend test: p = 0.032). In the 15 patients whose tear eotaxin concentration was null, tear IgE concentration was 5.3 ± 3.5 arbitrary units; in the other 15 patients whose eotaxin was positive, IgE reached 21 ± 4.3 arbitrary U (Mann-Whitney: p < 0.001). We measured 127 ± 47 pg/ml eotaxin in patients with no history of SAC but newly diagnosed as suffering from SAC, and 852 ± 218 pg/ml eotaxin in patients with a known SAC (p = 0.008). In contrast, tear IgE concentrations of both groups did not differ statistically significantly (p = 0.947). CONCLUSIONS: If IgE and eotaxin secreted in tears are major contributors in SAC pathogenesis, they however act at different steps of the process.

Clara cells drive eosinophil accumulation in allergic asthma.

Development of allergic asthma is a complex process involving immune, neuronal and tissue cells. In the lung, Clara cells represent a major part of the "immunomodulatory barrier" of the airway epithelium. To understand the contribution of these cells to the inflammatory outcome of asthma, disease development was assessed using an adjuvant-free ovalbumin model. Mice were sensitised with subcutaneous injections of 10 μg endotoxin-free ovalbumin in conjunction with naphthalene-induced Clara cell depletion. Clara epithelial cell depletion in the lung strongly reduced eosinophil influx, which correlated with decreased eotaxin levels and, moreover, diminished the T-helper cell type 2 inflammatory response, including interleukin (IL)-4, IL-5 and IL-13. In contrast, airway hyperresponsiveness was increased. Further investigation revealed Clara cells as the principal source of eotaxin in the lung. These findings are the first to show that Clara airway epithelial cells substantially contribute to the infiltration of eotaxin-responsive CCR3+ immune cells and augment the allergic immune response in the lung. The present study identifies Clara cells as a potential therapeutic target in inflammatory lung diseases such as allergic asthma.

Less mortality but more relapses in experimental allergic encephalomyelitis in CD8-/- mice.

Mice lacking in CD8 were generated from homologous recombination in embryonal stem cells at the CD8 locus and bred with the experimental allergic encephalomyelitis (EAE)-susceptible PL/JH-2u through four backcross generations to investigate the role of CD8+ T cells in this model of multiple sclerosis. The disease onset and susceptibility were similar to those of wild-type mice. However, the mutant mice had a milder acute EAE, reflected by fewer deaths, but more chronic EAE, reflected by a higher frequency of relapse. This suggests that CD8+ T lymphocytes may participate as both effectors and regulators in this animal model.

Toward Protein Biomarkers for Allergy: CD4+ T Cell Proteomics in Allergic and Nonallergic Subjects Sampled in and out of Pollen Season.

Allergy is an immunological disorder of the upper airways, lung, skin, and the gut with a growing prevalence over the last decades in Western countries. Atopy, the genetic predisposition for allergy, is strongly dependent on familial inheritance and environmental factors. These observations call for predictive markers of progression from atopy to allergy, a prerequisite to any active intervention in neonates and children (prophylactic interventions/primary prevention) or in adults (immunomodulatory interventions/secondary prevention). In an attempt to identify early biomarkers of the "atopic march" using minimally invasive sampling, CD4+ T cells from 20 adult volunteers (10 healthy and 10 with respiratory allergies) were isolated and quantitatively analyzed and their proteomes were compared in and out of pollen season (± antigen exposure). The proteome study based on high-resolution 2D gel electrophoresis revealed three candidate protein markers that distinguish the CD4+ T cell proteomes of normal from allergic individuals when sampled out of pollen season, namely Talin 1, Nipsnap homologue 3A, and Glutamate-cysteine ligase regulatory protein. Three proteins were found differentially expressed between the CD4+ T cell proteomes of normal and allergic subjects when sampled during pollen season: carbonyl reductase, glutathione S-transferase ω 1, and 2,4-dienoyl-CoA reductase. The results were partly validated by Western blotting.

Bacterial-induced protection against allergic inflammation through a multicomponent immunoregulatory mechanism.

Background Airborne microbial products have been reported to promote immune responses that suppress asthma, yet how these beneficial effects take place remains controversial and poorly understood. Methods We exposed mice to the bacterium Escherichia coli and subsequently induced allergic airway inflammation through sensitization and intranasal challenge with ovalbumin. Results Pulmonary exposure to the bacterium Escherichia coli leads to a suppression of allergic airway inflammation. This immune modulation was neither mediated by the induction of a T helper 1 (Th1) response nor regulatory T cells; however, it was dependent on Toll-like receptor 4 (TLR4) but did not involve TLR desensitisation. Dendritic cell migration to the draining lymph nodes and activation of T cells was unaffected by prior exposure to E.coli, while dendritic cells in the lung displayed a less activated phenotype and had impaired antigen presentation capacity. Consequently, in situ Th2 cytokine production was abrogated. The suppression of airway hyper-responsiveness was mediated through the recruitment of gd T cells; however, the suppression of dendritic cells and T cells was mediated through a distinct mechanism that could not be overcome by the local administration of activated dendritic cells, or by the in vivo administration of tumour necrosis factor a. Conclusion Our data reveal a localized immunoregulatory pathway that acts to protect the airways from allergic inflammation.

Hypersensitivity pneumonitis secondary to lovebirds: a new cause of bird fancier's disease.

Hypersensitivity pneumonitis (HP) is an immunologically mediated lung disease due to the repetitive inhalation of antigens. Most new cases arise from residential exposures, notably to birds, and are thus more difficult to recognise. The present authors report a 59-yr-old male who complained of dyspnoea and cough while being treated with amiodarone. Pulmonary function tests revealed restriction and obstruction with low diffusing lung capacity for carbon monoxide and partial pressure of oxygen. A high-resolution computed tomography chest scan and bronchoalveolar lavage showed diffuse bilateral ground-glass attenuation and lymphocytic alveolitis, respectively. Initial diagnosis was amiodarone pulmonary toxicity, but because of a rapidly favourable evolution, this diagnosis was questioned. A careful environmental history revealed a close contact with lovebirds shortly before the onset of symptoms. Precipitins were strongly positive against lovebird droppings, but were negative against other avian antigens. The patient was diagnosed with hypersensitivity pneumonitis to lovebirds. Avoidance of lovebirds and steroid treatment led to rapid improvement. The present observation identifies a new causative agent for hypersensitivity pneumonitis and highlights the importance of a thorough environmental history and of searching for precipitins against antigens directly extracted from the patient's environment. These two procedures should allow a more precise classification of some cases of pneumonitis, and thus might avoid progression of active undiagnosed hypersensitivity pneumonitis to irreversible fibrosis or emphysema.

Allergo-immunologie. 2 : Les réactions allergiques aux anti-inflammatoires non stéroïdiens [Allergic reactions to nonsteroidal anti-inflammatory drugs]

Allergy to nonsteroidal antiinflammatory drugs (NSAIDs) is a very common affliction, especially among patients with asthma and chronic urticaria. These reactions are most often of a non-immunological nature but related to pharmacologic intolerance and linked to arachidonic acid metabolism and leukotriene release. Therefore, crossed reactions implying all non-selective and semi-selective NSAIDs constitute the rule, especially during respiratory reactions to NSAIDs and for patients with chronic urticaria. In isolated acute urticaria, crossed reactions are difficult to predict so caution is necessary. Tolerance induction is possible, especially when aspirin has to be administered in small doses as antiplatelet agent. Finally, acetaminophen and selective NSAIDs as celecoxib are well tolerated by most of these patients. L'allergie aux anti-inflammatoires non stéroïdiens (AINS) est très fréquente, en particulier chez les asthmatiques ou dans l'urticaire chronique. Il s'agit en général de réactions non immunologiques, mais dues à une intolérance pharmacologique liée au métabolisme de l'acide arachidonique et à la formation de leucotriènes. Ainsi, les réactions croisées impliquant tous les AINS non sélectifs et semi-sélectifs sont la règle, surtout lors de réactions respiratoires aux AINS et dans l'urticaire chronique. Lors d'urticaire aiguë isolée, les réactions croisées sont difficiles à prédire, ainsi la prudence s'impose. Une induction de tolérance est possible, en particulier lorsque l'aspirine est nécessaire à dose faible, comme antiagrégant plaquettaire. Enfin, le paracétamol et les AINS sélectifs sont supportés par la grande majorité de ces patients.