February 2009
Claude MOLINA and Franz MARRACHE
• Recent advances in food allergy due to red meat
• Biphasic anaphylactic reactions after Immunotherapy
• Antibiotics for the Allergist in Clinical practice
• Inflammation and airways responsiveness in asthma
• Intradermal skin testing in inhalant allergy
Recent advances in food allergy due to red meat
Detailed histories were taken from 24 patients presenting to the University of Virginia (Prof Platts-Mills) with allergic manifestations 3 to 6 hours after ingestion of red meat J.P Commins et al. Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-a-1,3-galactose. JACI 2009; 123: 426-433).
These 18 to 74 year old, mostly male, adult individuals, reported food-induced anaphylaxis (10 cases), angioedema associated with urticaria (4 cases) or isolated urticaria (10cases) but, above all, skin itching in 15 of them.
These reactions did not occur with foodstuffs such as turkey and chicken meat, fish or in case of red meat avoidance from diet.
11 subjects had a previous history of pollinosis, 6 had house dust mite allergy.
Skin prick tests to mammalian meat using commercial extracts were only slightly positive, with a wheal of less than 4 mm in diameter. By contrast, intra dermal tests were positive. Similarly, skin prick tests were also clearly positive if fresh meat extracts were used.
Total and specific IgE levels were very high (higher than 100 IU/ml) particularly with beef, pork or lamb meat, but not with white meats (chicken, turkey) or fishes.
But the originality of this study stem from detection of elevated levels of carbohydrate-specific IgE in all of these patients. The carbohydrate was galactose á 1-3-galactose (the á –gal epitope is commonly expressed on mammalian tissues and cells and may induce severe anaphylactic reactions).
Theses IgE were also detected, by the same authors (Chang et al. NEJM 2008 ; 358 : 1109), in individuals treated with the monoclonal antibody cetuximab and allergic to this drug (we have analysed this report in our March 2008 BUA).
The treatment obviously consisted of avoidance of red meat.
However, above all, these results also strongly suggest that á-gal-specific IgE should be sought for meat allergies, or before a possible treatment with monoclonal antibodies of cetuximab type. So it is not only proteins that can elicit anaphylaxis but also, as a possibly aggravating factor, carbohydrate determinants.
Biphasic anaphylactic reactions after Immunotherapy
It is well known that biphasic anaphylactic shocks after allergen immunotherapy, although rare, may be observed in 1 to 20% of cases (S.E. Seranton et al. Incidence and characteristics of biphasic reactions after allergen immunotherapy. JACI 2009 ; 123 : 493-498). The usual risk factors include a delay in the administration of adrenalin after the initial phase and the time necessary for a favourable evolution of this initial reaction. The authors of this paper only found 4 cases published in english litterature. So they designed a prospective study and recruited subjects that had presented with an anaphylactic reaction after Immunotherapy and who had been treated with epinephrin. These patients were monitored for 24 hours and were asked to fill in a 31 –symptom scoring questionnaire. The authors statistically compared the results obtained in patients who had a biphasic reaction (BR) with those who only had an initial, early reaction.
They report their experience based upon 60 cases of systemic reactions observed in 55 patients, 14 of whom (23%) had a BR. This type of reaction was more frequent in women (P=0.03) and in the elderly (P=0.01) and require greater than 1 dose of epinephrine (P=0.001). By contrast, there was no difference between groups regarding the type of Immunotherapy, current asthma, initial symptom score, the time to symptoms, initial epinephrin injection or improvement. No specific symptom predicted BR. In any case, BR was always significantly less severe than the initial reaction (P≤0.001) and it did not occur in children.
Overall, the authors stress the need for basic precautions regarding anaphylactic shock during the injection of an allergen, namely prolonged supervision of the patient and if needed, rapid and adequate injection of adrenalin.
Ayway, this BR is benign and does not itself require additional injection of epinephrin.
We may, at this point, highlight the recommendations stated in July 2008 issue of the World Allergy Organization , from the Committee on Epinephrin headed by KSF Lockey, which consider that this key drug for the treatment of Anaphylaxis in underused and frequently given in too low doses, although the therapeutic benefits vastly exceed the risk when the product is administered in adequate doses and by intra-muscular route.
Antibiotics (AB) for the Allergist in clinical practice
This excellent review, is based upon an important literature search, the first part of which is devoted to Rhino-sinusitis and Bronchitis , the 2nd part, on Asthma and Atopic Dermatitis will be the topic of a subsequent analysis (M.S. La Shell and M.T. Tankersley. Antibiotics for the allergist (Part 1). Ann. Allergy Asthma Immunol. 2008 ; 101 : 559-567). AB are recommended in acute Rhino-sinusitis if the duration of symptoms is longer than 7 to 10 days. However, a meta-analysis of 9 randomised trials has demonstrated that 64% of adult patients may be cured without AB, in less than 2 weeks, and bearing in mind that microbiology laboratory data are of limited value for the choice of AB. This does not apply to immune-suppressed populations or to children. In these cases, and taking into account Streptococcus Pneumoniae as a frequent pathogen, it is Amoxicillin which is the first line choice, possibly associated with clavulanic acid, in order to counteract the action of â-lactamases (Augmentin ®). There are pediatric formulations of these AB. Fluoroquinolones do not yield better results and are associated with the risk of tendinitis; cephalosporins may be an alternative, but in the case of intolerance to â-lactams, one may resort to Trimethoprim-sulfamethoxazole (Bactrim ®) or erythromycin. Association with nasal corticosteroids may be useful at the beginning of the episode but, if sinusitis is confirmed by tomography, oral steroids are preferable. Finally, in case of chronic Rhino-sinusitis, the choice of AB must take into account the polymicrobial nature of infection. Macrolides, whose immuno-modulatory properties are known, are frequently used with benefit, and the treatment must be carried out for at least 3 weeks. As far as Acute Bronchitis, which is most frequently viral , AB are not recommended (with the exception of whooping cough in which macrolides or even Bactrim® are useful). Chronic Bronchitis is a different entity and the place of AB is controversial except in the case of exacerbations in which 3 principal symptoms will dictate the choice of AB: the amount of sputum, the frequency of coughing and the extent of dyspnoea. Several meta-analyses have shown the efficacy of Amoxicillin, or doxycyclin, and even 2nd and 3rd generation cephalosporins, but it seems that fluoroquinolones are more effective for prevention of relapses, whereas the amoxicillin-clavulanic acid combination is associated with adverse effects (diarrhoea). Overall, all of these studies suggest a period of observation before using AB, thus stressing that airway inflammation does not always nor merely have a bacterial aetiology.
Inflammation and airways responsiveness in asthma
Previous studies suggested that bronchial hyperreactivity (BHR), bronchial remodeling (BRM) and inflammation (INF) in asthma are interrelated. However, the persistence of BHR, in spite of treatment by anti-inflammatory drugs, has questioned the role of INF in the mechanisms of BHR, BRM and exacerbations in individuals with chronic asthma. In their experimental study, (Hewitt M, et al. Acute Exercise Decreases Airway Inflammation, but Not Responsiveness, in an Allergic Asthma Model. Am. J. Respir. Cell Mol. Biol. 2009; 40 : 83-89) the authors bring an interesting contribution to this issue. Two groups of ovalbumin (OVA)-sensitised mice were studied: the EXE group was submitted to moderate aerobic exercise after an allergen challenge test (ACT) with OVA, whereas the SED group represented the sedentary group, and did not perform physical exercise. In contrast with the SED group, the EXE group had, after the ACT, a significant reduction in the production of several mediators of INF, including KC chemokines, RANTES, MCP-1 and IL-12p40/p80, as well as a decrease in leucocyte infiltration, including eosinophils,. Similar results were seen with the Th2 cytokines, IL-5 and IL-13, as well as with PGE2 prostaglandins. By contrast, as shown after inhalation of increasing doses of metacholine, exercise did not affect the level of BHR, or markers of BRM such as hypertrophy of bronchial epithelium, airways wall thickening , or mucus production.
This dissociation between INF and BHR, after relevant physical exercise, is interesting for Sports Medicine, bearing in mind that there are in France, for instance, more than 8000 elite athletes and some of them are asthmatic or allergic. It is well known that intense exercise may trigger bronchospasm or anaphylaxis, even in absence of airways inflammation.
Intradermal Skin Testing (IST) in inhalant allergy
IST is commonly used for hymenoptera venom allergy, when the skin prick tests are negative or for drug hypersensitivity to penicillin, insulin, heparin, muscle relaxants, or chemical therapeutic agents. By contrast, it is not indicated in food allergies, or of little value in inhalant allergy, whereas SPT are sensitive and safe and have a lower risk of adverse effects.
Its place in the diagnosis of aeroallergen allergy is evaluated in a recent review by Christopher W. et al : The role of intradermal skin testing in inhalant allergy (Ann. Allergy Asthma Immunol. 2008; 101: 337-347), Details on the various aspects of IDR, in terms of criteria for positivity, concentration of solutions used, risk of adverse reactions, its pertinence versus SPT, in vitro tests, and provocation tests.
In terms of safety, the risk of adverse reactions seemed not very important, if IST is used when SPT is negative. Responses are reproducible and the degree of sensitivity allows to exclude an IgE-dependant mechanism.
However, overall, with IST we lose in specificity what we gain in sensitivity, that limits its indication to 5% of cases in which its positivity is associated with negative in vitro tests, as well as with inconclusive clinical symptoms. The pertinence of its positivity thus remains closely linked to the results of the allergen provocation test.
In contrast, a negative IST result has a high negative predictive value
In fact, use of IST varies widely among allergists . However it gains renewed interest for the study of allergen extracts with low reactivity or non-standardised allergens (fungi, trees, dog, weeds). It is also time to highlight the development of recombinant allergens as well as their high specificity which allows optimisation of the SPT sensitivity. Their usefulness must be emphasized, taking into account the great variability of IST results, as stressed by the authors of this large study.
Source: CEFCAP
You may send comments on these brief news to: cme.inallergy.online@wanadoo.fr
|
