* Doxycycline or steroids in the treatment of nasal polyps
* Anaphylaxis and asthma
* Fibronectin and repair of asthmatics’ airway epithelium
* Anti-infliximab IgE, non IgE antibodies and induction of severe anaphylactic reactions
* Chronic urticaria in children

Doxycycline or steroids in the treatment of nasal polyps

ENT teams of Belgium, Germany, the Netherlands and Australia have tried to compare the effects of oral corticosteroids (C)and Doxycycline (D) in treating chronic rhinosinusitis with nasal polyps (NP) in a randomised, double-blind, placebo-controlled trial. 47 patients were concerned.

Cs are given for 20 days in decreasing doses from 32 to 8 mg/day. D is administered during the same period at the dose of 200 mg on the first day followed by 100 mg/day once daily ; the subjects were followed for 12 weeks and assessed by nasal endoscopy for nasal peak inspiratory flow, and markers of inflammation were measured in nasal secretions : ECP (Eosinophilic Cationic Protein), IgE (Immunoglobulin E), MMP9 (Matrix Metalloproteinase 9) and in blood samples : ECP, Eosinophils, IL5α.

Results : C and D each significantly decrease nasal polyp size compared with placebo.
On a clinical level, C and D improve nasal congestion with loss of smell, and rhinorrhea with rear nasal flow. But, as for C, those symptoms recur rapidly after the last dose, unless efficiency is maintained by local treatment.
On a biological level, C effects are maximal at week 3 and last till week 8 with decreasing ECP, IL5 and IgE in nasal secretions and dropping blood eosinophils followed by a swift rebound. However D effect is more moderate but lasts until week 12 with reduced levels of ECP, MM9 and myeloperoxydase (a marker of inflammation with neutrophils).
This shows that beside D’s well known anti-microbe effects, the authors observe an unexpected anti-inflammatory effect of the treatment, going as far as inhibiting the tissue destruction underlying in mucosal inflammation.
Finally, if C and D significantly reduce the inflammatory symptoms of nasal mucosa as well as local and blood markers, D is preferable to C for a long term reduction of polyps (instead of a recurrence after 2 months with C per os).
Therefore Doxycycline deserves a significant place in the treatment of nasal polyps (possibly in association with local Cs) for its contribution to avoiding or delaying as much as possible a surgical ablation.

Key words: chronic rhinosinusitis, nasal polyps, Doxycycline, steroids

Anaphylaxis and asthma

The epidemiologic aspect of the association between these two entities is tackled by two recent publications, a European one (A.Gonzalez-Perez et al de Barcelone JACI Mai 2010 1098-1104 ) from a British database, and an American one (C.Irribaren et al :Annals of Allergy, Asthma Immunol 2010 104 5 371-377) stemming from a major health organisation in North Carolina.
In the first study, based on a filing system dating back to 1985 which includes 177,000 asthmatics aged  10 to 79 who had presented an anaphylactic episode (due to food, medications, wasp or bee stings, latex and others, by order of frequency), the incidence rates are significantly found to be 21.28 per 100,000 person-years with the no-asthma subjects and 50.45 in the asthmatic cohort, i.e. approximately twice as high.
In the study conducted in the USA, the 1996-2006 comparison of a 526,406-strong cohort of asthmatics with a control cohort aged 24 on average, matched according to sex, age and ethnic origin, the incidence of an anaphylactic episode is 19.9 per 100,000 person-years with healthy subjects and 109.0 or 5 times as high with the asthmatics.
In the British cohort the risk appears statistically greater in severe asthmas than in the moderate cases ; the incidence rate is higher with women than men ; within the asthmatics, the patients at risk include subjects suffering from rhinitis, from concomitant eczema, and users of antihistamines or steroids. It is worth noting that not a single death occurred in that cohort.
In the American cohort, the trend toward an increased anaphylactic incidence can be observed in the case of severe asthma, and in relation with some food or bee or wasp sting allergy. On the contrary the evolution of the anaphylactic episode is not influenced by the degree of severity of the asthma.
True, as underlined by European and international experts, the description of the Anaphylactic Shock as a serious/severe, fast-appearing allergic accident, with predominance of skin and respiratory symptoms, and potentially lethal, should be adopted in all countries, which is far from the case (except for the treatment in which adrenaline (epinephrine) is unanimously prescribed).
But the lesson to be learnt from those two studies is that asthma is an important risk factor of an anaphylactic episode.

Key-words: anaphylaxis, asthma

Fibronectin and repair of asthmatics’ airway epithelium

In an important experimental study based on asthmatic children’s airways, a group of Australian and American paediatricians and biologists (A.Kicic et al AJRCCM 2010 181 889-898) has analysed the repair process of airway epithelial cells (AEC) after an injury having caused a wound which is both structural and biochemical.
Normally, such a process involves the deposition by airway epithelial cells of extracellular matrix (ECM) proteins promoting migration and adhesion to the site of injury, the dysregulation of which is liable to end in epithelial remodelling.
Hence, the authors compared, in vitro, with meticulous and sophisticated techniques, AECs from 36 two-to-sixteen year-old asthmatic children who had not taken any steroids for over one month, with that of 23 atopic subjects and 53 healthy non-atopic control subjects.
After induction of a mechanical wound, they measured the time and conditions necessary for the repair.
It was observed that the repair process duration is not different between the healthy and the atopic children, but it is statistically shorter than in asthmatics.
Besides, among the ECM proteins, it is the multifunctional glycoprotein Fibronectin (FN) which is the most reduced, both in expression and quantity.
To reinforce that point, silencing of FN expression in a non-asthmatic AEC inhibits wound repair, whereas addition of FN to an asthmatic AEC restores its reparative capacity.
On the whole, FN is necessary for the normal, post-wound AEC repair. It seems natural that the maintenance of healthy AEC, a barrier against environmental aggressions, needs fast repair, all the faster with asthmatics submitted to many exogenous and inflammatory factors. But the asthmatic person’s epithelial cells produce an insufficient quantity of FN. Finally, addition of exogenous FN restores AEC’s reparative capacity.

Key-words: fibronectin, airway epithelium, extra-cellular matrix, child asthma

Anti-infliximab IgE, non IgE antibodies and induction of severe anaphylactic reactions

Infliximab (Infl) is a chimeric monoclonal antibody against TNFα, which includes a cat animal protein sequence. It is used in the treatment of inflammatory diseases with immunologic mediation : ankylosing spondylitis (ASP), rheumatoid arthritis (RA), vasculitis (VAS) among others. Anaphylactic-like reactions linked to the development of specific IgG antibodies, aiming at the animal component, have been observed. That is why Vultaggio A. et al have tried to establish it (Allergy 2010 65 657-661).
71 patients suffering from ASP, RA, or VAS, were selected and Infl infused for 2 hours at weeks 0, 2 and 6, and then every 8 weeks. A pre-treatment was administered before each infusion, with an association of 25mg of hydroxyzine and 25mg of prednisone.
The control group was composed of 20 subjects suffering from the same diseases.
The 71 patients were discriminated by their therapeutic response into respondents and non-respondents, and also sorted according to the severity of their reaction to Infl.
11 out of the 71 patients treated presented anaphylactic-like reactions, variable in intensity : light (2), moderate (4), severe (5).
Anti-Infl antibodies appearing after the 2nd or 3rd infusion were detected in 8 of them, and in 2 others, otherwise non-respondent to treatment.
For 3 cases, the antibodies were specific IgEs, with positive skin tests, and for 3 others they were specific IgMs with negative skin tests. In 2 cases the antibodies were of the IgG type. For 3 cases the reaction mechanism could not be found.
On the whole, this study confirms the existence, during the treatment and apparently with no relation to the therapeutic response, of several isotypes of anti-Infl antibodies on top of the already detected IgGs, i.e. above all IgEs with positive skin tests and IgMs. It revealed a time relation between the appearance of these antibodies and that of the anaphylactic reaction.
Given the increasing use of those biological drugs, the possibility of detecting specific IgEs, either in the serum or on the skin, seems of a great interest for the prediction and prevention of this type of accident.

Key words: Monoclonal anti-TNF??anti bodies, Infliximab, Vasculitis, rheumatoid arthritis, Anaphylactic reaction, IgE anti bodies.

Chronic urticaria in children

A group of Thai university paediatricians (Jirapongsananuruk  O. et al Ped.Allergy & Immunol 2010 21 508-514) has tried with  4-15 years-old children (94 of them) to pinpoint etiologies of a chronic urticaria (CU) defined by the apparition of typical symptomes, every day or nearly and for more than 6 weeks (excluding the cases of physical urticaria).
A priori and given the previous studies, 3 possible causes were clinically and biologically suspected: infection or parasitic infestation, collagen vascular disease, food allergy.
Eosinophilia was found in 23% of cases but parasites were only observed in 5% of the cases without clinical correlation, ESR was high in 13%. Anti-nuclear antibodies only in 2%. No clinical sign of vasculitis (usually causing the association of arthralgia and petechia or purpura). There was no change in  serum level of complement (CH50) or thyroid-stimulating hormone.
Anti-thyroglobulin, anti-microsomal antibodies, or auto-antibodies to IgE receptor (Fc€R1) were not detected.
As for food allergy, skin tests were positive in 33 subjects of which only 15 presented a significant clinical history (above all shrimps and shellfish sensitivity) ; among them 16 challenge tests turned out to be positive in 8 cases Only 4  remissions were observed, under child-adapted anti-histaminic treatment.
With all the children, the treatment comprised 4 stages, apart from avoidance of  allergen when identified :
At first Cetirizine© or  Loratadine (L) alone or associated to Hydroxysine (H) , C + L + Ranitidine® in stage 2, C + L + R + Montelukast (Singulair®) in stage 3, and finally C + L + prednisone in stage 4.
What conclusions should be drawn from this bio-clinical survey ?
1) there is little to expect from the various biological tests supposed to reveal a hypothetical auto-immunity; 2) obvious causes are rare; 3) food allergy must be systematically looked for as it can be efficiently treated; 4) the latest anti-histamines the symptomatic treatment which should be used with some interesting results; 5) whether in adults or children, urticaria is difficult to treat.
It should be noted that Levocetirizine (Xyzall®) was not used in this study.

Key-words: child chronic urticaria; food allergy; auto-immunity; anti-histamines



Source:  CEFCAP
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