Claude MOLINA & Jacques GAYRAUD

1 Anaphylaxis: new developments
2. Pigeon breeders’ disease : utility of a provocation test
3. Long-term protection against allergy  of growing up on a farm

5. Plea for non-surgical treatment of child adenoidal hypertrophy

1.  Anaphylaxis: new developments
Theme: Emergency
Key words: Anaphylaxis, biomarkers, Patient education, Epinephrin self-injection

The Task Force of the US Academies of Allergy and Immunology has, under Phil Libermann’s leadership (JACI 2010 126 3 477-480), published a series of new recommendations on this theme.
Thus, on a physio-pathological point of view, it appears that the classic mediator cascade – histamine, leukotrienes, prostaglandins, all derived from the mast cell / basophil couple – is no longer the only culprit, so that a number of patients do not respond to epinephrine any more. It is the case for intra-vascular coagulation shock which should be treated with an anti-fibrinolytic such as tranexamic acid and for hypotension associated with anaphylaxis and producing nitric oxide calling for treatment by methylene blue. A number of biomarkers are mentioned, such the classical trypsin and histamine, but also: carboxypeptidase, and hydrolase PAF : their low serum levels being  a witness of bad prognosis.
On a clinical level the authors underline the need to maintain the subject in recumbent position until symptoms disappear, deaths having occurred after assuming prematurely an upright position
Biphasic reactions take place in one quarter of serious or even lethal cases.
Among  etiological factors, food allergy (FA) represents in  USA 30% of causes of death whereas asthma is a risk factor for severe FA. Hymenoptera sting, latex, anaesthetics, biological drugs including allergenic immunotherapy, intense practice of sport, sperm allergy, are the classic triggering agents.
Prevention depends on individual factors such as age, occupation, home location (distance to a medical centre for instance), but the most important strategy seems to be patient training, above all if the subject has presented a previous reaction to an insect sting or immunotherapy. Patients are taught to auto-inject epinephrine using a pre-filled syringe and a needle long enough to reach the muscle (ex : mg 0.15/ml 0.3 in an adult). Indications of hospitalisation in an intensive care unit and  treatment by anti-histamines, corticoids  and oxygen, are mentioned in a chart, noted in this 46-page, 310-references report.

2.  Pigeon breeders’ disease : utility of a provocation test
Theme: Respiratory allergy, Allergens
Key words: Pigeon breeders’ disease, Hypersensitivity pneumonitis, Primitive Interstitial pneumonitis, Avian Antigens provocation test, Body temperature.

The Mexican authors who published this text in 1998 under the leadership of A.Ramirez (AJRCCM 1998 158 3 862-8698), came back to it in 2010 (AJRCCM 2010 182 pages 1086-87) on the occasion of a critical study by Dr Kern, dug up by the editors who apologise for not having published it sooner.
The authors, who had observed  the frequency of bird pets in Mexican homes, had underlined in their initial report the usefulness of a provocation test induced by avian antigens, particularly in differentiating Pigeon Breeders’ Disease (PBD), which is a form of hypersensitivity pneumonitis, from Primitive Interstitial Pneumonitis (PIP) whose prognosis is more serious.
17 patients with confirmed PBD were compared to 17 PIP and 5 healthy control subjects. After the provocation test (PT) an increase in body temperature and a decrease in FVC, SaO2 and PaO2 were observed in the 17 patients with PBD and in 3 with PIP, the healthy subjects showing no reaction.
The authors undertook then a serious statistical study, which was the object of the critical letter. In their answer, they admit that, when a patient with PIP shows a negative response to the PT, one can be 100% sure that he does not have PBD. When the PT is positive, the positive predictive value, i.e. the possibility of having PBD, is higher than 80%. But the authors insist that the critical value for positive predictive value (‘cut point’) should be a 0.5° raise in body temperature, an increase which allows them to display 76% sensitivity and 81% specificity.
This discussion brings us back to the diagnosis criteria for PBD and underlines the utility, going beyond clinical and radiological signs, the value of serum precipitating antibodies, and if possible broncho-alveolar lavage, showing predominance of CD4 lymphocytes, all methods helping to avoid lung biopsy which reveals alveolar and interstitial pneumonitis  leading to chronic fibrosis.
But, as the authors also recognise, simply taking the subjects out of their home environment for 2 or 3 days leads to a decrease in many symptoms, while bringing them back home and re-exposition act as a provocation test.

3.  Long-term protection against allergy of growing up on a farm
Theme: Epidemiology
Key-words: Protection against allergy, Urbanization levels, Farming environment

Many studies have shown the low prevalence of allergic rhinitis in farmers and their children, thus deducing the allergy-protective effect of childhood farm environment, which was confirmed by several epidemiological studies.
The Swedish authors (J.Eriksson et al : Allergy 2010 65 1397-1403) wished to go further and discover whether this protection is conserved throughout adulthood and how it corresponds to different degrees of urbanization ; the level of urbanization being defined by the new living conditions, either in a small town (2 to 10,000 inhabitants), a medium-size town (over 100,000 inhabitants) or a large town such as Gothenburg (700,000 inhabitants).
In 2008 a questionnaire on respiratory health was sent to 30,000 subjects aged 16-75, of whom 29,218 could be traced and 18,087 (62%) responded. The questionnaire included questions on allergic rhinitis, asthma, respiratory symptoms and possible determinants.
The subjects were stratified into age groups of 15 years.
As expected, those who had lived on a farm during their first 5 years of life had a considerably lower prevalence of allergic rhinitis in their adulthood, and in all age groups, even among the oldest (61-75 years) and in both the 16-45 year and the 46-75 year groups.
But a significant trend of increasing prevalence was observed with increasing degrees of urbanization, independent of the protective effect of childhood in a farming environment.
As a conclusion, the authors believe that childhood life on a farm does provide a lifelong protective effect against allergic rhinitis.
But the increasing prevalence in urban surroundings can be observed as much in those raised on a farm as in those not, which proves that the deleterious influence of urbanisation is as bad for the child as for the adult, whether or not they have grown up in a farming environment.

4.  IgE allergy to cephalosporins : cross-reactivity and tolerability of other β-lactams
Theme: Drug allergy
Key words: Beta lactams, Cephalosporins, Penicillins, Monobactam, Carbapenems, Skin tests.

For several years the team of Italian allergists led by A.Romano has been interested in this theme and has undertaken a new prospective survey in 98 subjects having presented one or more reactions, of which 84 of an anaphylactic type, to cephalosporins (Cs) and who had positive skin tests to those antibiotics (JACI 2010126 5 994-999). The aim was to assess the cross-reactivity with other β-lactams such as penicillins, but also with monobactams (astreonam) and carbapenems, and the tolerability of these drugs in case of necessity.
All the patients – 68 women and 30 men of 13 to 90 years of age, all IgE allergic to Cs – underwent skin tests and serum-specific IgE assays with penicillin reagents, as well as skin tests with aztreonam, imipenem/cilastatin and meropenem .Subjects with negative tests were challenged with the last three drugs and amoxicillin (l®).
The results are the following : 25% of the subjects allergic to Cs shown positive skin tests to penicillins, and only 3.1% to aztreonam (A), 2% to imipenem/clastatin (I) and 1% to meropenem (M).
The risks of cross-reactivity with penicillins were statistically three times higher for the Cs whose side-chain structures are similar (cephalotin, cefamandole) or identical (cefaclor, cephalexine, cefatrizine) than for Cs with different side-chains (ceftriaxone, ceftazidime, cefuroxime, cefazoline, cefoperazone, cefonicid). In those cases, a preliminary positive skin test require an antibiotic different from the β-lactams, or even a desensitisation to penicillins. But a negative test removes all doubts about their use.
As to the provocation tests for A, I or M, these were negative except for one urticarial reaction to I, thus confirming their low cross-reactivity with Cs. It is then possible to conclude like the good clinicians authors, that 75% of the Cs-allergic subjects can tolerate penicillins and more than 95%  tolerate As, Is, and Ms. For the latter ones, a negative skin test allows their use with very low risk.
These conclusions are validated by the ‘Task Force on Practice Parameters’ on drug allergy (Annals of Allergy Asthma & Immunol 2010 105 259-273) representing all the US Academies of Allergy.

5.  Plea for non-surgical treatment of child adenoidal hypertrophy
Theme : Ear-Nose-Throat allergies
Key words : Aenoids, Nasal corticoids, Beclomethasone, Flunisolide, Fluticasone, Momethasone.

In a well-documented report, G.Scadding (Pediatric Allergy & Immunol 2010 21 1095-1106) recalls that adenoidal hypertrophy (AH), often associated with that of tonsils (T), are common disorders among children and can induce various problems such as snoring, nasal congestion, sinusitis, recurring middle ear otitis, and even obstructive sleep apnea. In the long run, it is even the cause of neuro-psychological or cardiovascular troubles, and growth retardation. No wonder surgical ablation is the commonest strategy, despite the detailed list of complications, which range from immediate or delayed local haemorrhage to anaesthesia complications.
That is why a number of alternatives have been suggested. The frequency of physio-pathological links between AH and allergic inflammation is underlined, particularly association with allergic rhinitis.
The intranasal use of corticosteroids (INS) was then attempted by several teams and for different drugs, always in double-bind tests.
The first trials concerned Beclomethasone in nasal spray for 2 to 4 weeks followed by 16 to 24 weeks according to the authors and at a rate of 336 to 400µg/d with significant results on AH and the symptomatic score.
With Flunisolide , a study of 178 children aged 3-6 revealed a decrease in the size of AHs, thus avoiding surgery.
Fluticasone was used by the author (unpublished study) in 40 children registered on an adenoidectomy waiting list, with no great clinical success as compared with the control group, but  histological study of the AHs showed a decrease in T-activated cells of the adenoid tissue, revealing product penetration into the AHs but not into the tonsils.
Finally, 3 randomised trials with Momethasone furoate ( 100µg/d) for periods of 6 to 8 weeks produced excellent results among which an interesting effect on an antibiotic-resistant otitis.
The unfounded fears concerning the use of INS in children for long periods of time, as well as the minimal local side effects, do not contra-indicate such treatments.
INS therefore represent an efficient alternative for a number of children. Other studies are necessary to define the most suitable INS, as well as dosage and duration of treatment.


Source:  CEFCAP
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