Bibliographic updates

Claude MOLINA* & Jacques GAYRAUD**

1. Allergies and mental disorders (anxiety and mood disorders)
2. Chronic urticaria (CU) and psycho-sociological factors
3. Ocular allergy (OA): recent data
4. Hand eczema (HE)
5. Gluten, Intolerance Sensitivity or Food Allergy

1. Allergies and mental disorders (anxiety and mood disorders)

Theme: Psycho allergology
Key words: Allergy, Mental disorders, Anxiety, Mood disorders, Desensitization

An US-German group of Psychologists and Psychiatrists (R.D. Goodwin et al. Clin.Exp.Allergy  December 2012 42 12 1765-1771) has investigated this association, using the data from  interviews and examinations of a German cohort of 4181 adults aged 18 to 65. As concerns the definition of mental disorders they referred to the Munich CIDI (Composite International Diagnostic Interview). In order to cover the whole range of symptoms and criteria, this CIDI was complemented by the DSM-IV world classification (Diagnostic and Statistical Manual Revision N°4) which includes mood disorders (major unipolar depression), anxiety (panic with or without agoraphobia), social and specific phobia, and generalised anxiety. All the symptoms observed in the 12 previous months were taken into account. For allergy (A), the physician-led interview covered clinical signs (hay fever, eczema, food allergy), possible laboratory tests and the desensitization treatment, completed or not.

The statistical analyses of multiple logistic regression between allergy and each mental symptom, after adjusting for age, gender, socio-economic status, then according to treatment, revealed in allergic patients a significantly higher prevalence of each mental symptom: anxiety, panic attacks, mood disorders, depression. However, the adjustment for desensitization treatment (D) made these relationships no longer significant, as if D had had a positive effect on mental disorders. Indeed, those treated for allergy had statistically less anxiety and mood disorders than those non-treated, and amongst the former those who had completed the treatment were suffering less from mental disorders than those whose treatment was incomplete.
While admitting the lacunae of this survey (absence of A objective tests or other anti-allergic treatments than D), the authors provide us the first evidence of a link between A and anxiety and mood disorders, and emphasize the impact of desensitization on these typical DSM-IV disorders.

Similarly, as concerns the asthma-anxiety relationship in teenagers, Y.Lu from Singapore (Y.Lu et al. Ped.Allergy Immunol 2012 23 707-715), after a randomised meta-analysis of 8 published studies, found a significantly higher risk of depression and anxiety in 3546 asthmatic teenagers as compared to 24884 controls, and suggested the need of early psychological intervention.

2. Chronic urticaria (CU) and psycho-sociological factors

Theme: Psycho-allergology
Key words: Chronic urticaria, Psycho-social factors

A team of Canadian researchers (Benshoshan et al Allergy 12 Nov 2012 online) undertook a considerable meta-analysis of English, Spanish and French publications--covering a period from 1st January 1935 to 1st January 2012, i.e. 77 years, and aiming to assess the contribution of psycho-social factors (PSFs) to the development and/or exacerbation of CU.

Two investigators independently reviewed all the titles and abstracts which appeared relevant, following the so-called Newcastle-Ottawa scale and, after discussion and arbitration of a third reviewer, they were able to identify 114 original studies and 17 general reviews, 67 studies with no relation to CU serving as controls. In addition they interviewed all Canadian allergists.

There are evident lacunae in CU pathogenesis...
Allergic origin is sometimes inferred from positive prick-tests and IgE in a number of cases but, generally, elimination of suspected allergen(s) does not improve the patient. Moreover, 80% of the Canadian allergists believe that these psycho-social factors are decisive and consider like the majority of publications, that the inflammatory event is more important than the allergic element. Auto-immunity is also mentioned, from the observation of auto-antibodies against IgE and Fcα RIα but without correlation to clinical symptoms.
Finally an interaction between the neuro-endocrine and the immune systems, are evoked that could be triggered by stress and all psycho-social factors (anxiety, quality of life, alexithymie, depression).                     Pooling effect sizes using random effects, analyses revealed that despite large heterogeneity, PSFs had significant overall prevalence of 46, 9 % i.e. nearly half the cases.

On the therapeutic point of view, psychotherapy, relaxation with or without hypnosis, and behavioural interventions did cause some improvement and a reduction in drug therapy to treat CU or depression. But the problem remains: are PSFs a cause or a consequence of CU? As the authors say, it’s just like the old ‘chicken and egg’ paradigm.

3. Ocular allergy (OA): recent data
Co-authors : Jean-Luc Fauquert, M.D. & Farid Marmouz, M.D.

Theme: Ocular allergy
Key words: Conjunctivitis, Seasonal conjunctivitis, Kerato-conjunctivitis, Springtime kerato-conjunctivitis, Blepharo-conjunctivitis, Giant papillary conjunctivitis

A group of French-Italian-Polish-Portuguese experts (A.Leonardi et al Allergy 2012 67 1327-1337) has just finalised a review on ocular surface hypersensitivity reactions concerning conjunctiva and cornea, requiring a close collaboration between ophthalmologists and allergists. To simplify the classification of these often complex lesions, it should be remembered that conjunctivitis may be isolated or very often associated with rhinitis: this is the hay-fever seasonal conjunctivitis, frequent, atopic, and well known. When associated with a corneal involvement, it is known as kerato-conjunctivitis (KC). This severe form usually evolves in spring and summer (spring KC, sometimes called Vernal keratoconjunctivitis, VKC). It is associated in approximately half the cases with a sensitivity, to perennial allergens, mostly domestic, sometimes seasonal. It normally disappears with puberty. However, some forms interfere with atopic keratoconjunctivitis (AKC), the other severe form which strikes teenagers or young adults and is always accompanied by eczema. Blepharo conjunctivitis (BC) presents a different clinical aspect. It can be complicated by staphylococci infection, herpes, even cataract or vision disorders if it becomes chronic. Generally, it diminishes with age. Non-atopic OA is most often represented by the giant papillary conjunctivitis (GPC), which follows an ocular surface irritation due to contact lenses or ocular prosthesis or after surgical sutures.

Ocular examination of the eyelid and above all the tarsal or limbic conjunctiva reveals either oedema, hyperaemia, follicles or papules, even erosions or fibrosis. This manage both diagnosis and aetiology. Allergy will be confirmed by the usual blood and skin tests or, in doubtful cases, by cytobiological examination of tears (eosinophils, IgE, ECP), or even, more rarely, by a conjunctival provocation test. In non IgE-dependant (BC) forms, patch tests for suspected cosmetics can be useful.

In addition to avoidance of possible allergens and immunotherapy, treatment includes protective sunglasses, cold compresses or instillation of artificial tears to reduce pruritus. Antihistamines (AHs) and over-the-counter local vasoconstrictors (naphtazoline type), Mastocyte stabilisators (nedocromil or pemirolast non-authorised in Europe) are sometimes useful. Association of local anti-H1 and anti-degranulation effects such olopatadine brings about some improvement for the most common forms. Drugs without preservatives are  in development (levocabastine: or ketotifen ): Oral antiH1 (usually 2nd generation) are sometimes associated. In seasonal or perennial conjunctivitis, local corticosteroids (fluorometholone or prednisone acetate) should be avoided whenever possible. Their use, reserved to ophthalmologists, and restricted to corneal involvement, must be short and moderate.

Finally, it should be recalled that, in general, the allergist is only consulted in second line (except in case of associated rhinitis).

4. Hand eczema (HE)

Theme: Dermato-allergy
Key words: Eczema, Irritating contact dermatitis, Allergic contact dermatitis, Atopic dermatitis

Based on a clinical case of recurring HE on the palm and dorsal sides of her hands in a young atopic nurse, a mother of 2, the author, a Dutch dermatologist, presents a complete review of this both varied and complex entity (P.J.Conrads NEJM  8 Nov 2012 367 19 1829-1837).

The thorough patient history is essential for the diagnosis but it appears that HE is often multifactorial.

The etiological classification, which comes in a detailed table, includes:
- Irritating contact dermatitis (ICD), due to repeated contact with detergents, soaps, at home or at work, or after wearing occlusive gloves;
- Allergic Contact Dermatitis, is a delayed-type reaction to a chemical substance: nickel: jewels or instruments, coins, (English dermatologists have recently protested to Royal Mint which has introduced nickel coins to cut costs) but also chromates (leather or cement), preservatives (creams or cosmetics), rubber, glues; Standard patch tests are recommended and prove 25-50% positive;
- Protein CD, in  early reaction to a protein substance (health professions: latex, or food professions: fish), often preceded by urticaria, the only case when prick tests and IgE can be useful;
- Atopic dermatitis, due to persisting or recurring childhood eczema, and often associated with the other forms (hybrid HE).

HE may be confused with other skin conditions such psoriasis (but without pruritus or vesicles) or  mycosis, which is most often unilateral.

As to the morphological classification, HE is typically vesicular and recurrent, primarily affecting of palm and lateral sides fingers, hyper-keratosic in elderly subjects, or nummular or dry and fissured on fingertips (pulpitis) but with no obvious relation to aetiology. Prompt intervention is required to avoid chronicity.

Eviction of irritants and allergens, and application of emollients (ointments are preferred over  creams) are the first indications. Wearing gloves is controversial (cotton-lined if indispensable).

Local corticosteroids are first-line pharmacologic treatments although their efficacy has not been statistically established (mometasone furoate 2 to 3 times a week is recommended). Tacrolimus and Pimecrolimus do not seem very efficacious.
As second line, phototherapy either with psoralen and UVA, or preferably with UVB, can give good results.
Retinoids which are useful in severe forms, hyperkeratosic, either per os (in capsules) or locally, are preferable to immunosuppressive (cyclosporine type) which confer a risk of adverse events (skin dryness, increase in serum lipids, teratogenesis).

5. Gluten: Intolerance,  Sensitivity or Food Allergy

Food allergy
Key words: Gluten, Celiac disease, Irritable bowel, False food allergy

Gluten (G), the major constituent of cereal flour (wheat, barley, rye) is composed of proteins (gliadin and glutenin) which may cause a range of adverse reactions.
An Italian physician (L.Elli  BMJ 2 November 2012 online) and more recently several British gastroenterologists (BMJ 6 December 2012) have noticed a huge increase in the use of the term of Gluten Sensitivity (S) which is alleged to cause non specific gastro-intestinal symptoms.
In fact, all these authors consider that the only true Intolerance to gluten, and hence justifying a gluten-free diet, is the auto-immune Coeliac disease, characterised by: histological villous atrophy of the duodenal mucosa with crypt hyperplasia, biologically, by the presence of anti-transglutaminase type 2 IgA, and genetically, by the HLA-DQ2-DQ8 haplotype.

The term, ‘S’ must be restricted to a set of digestive symptoms (abdominal pains, bloating, meteorism) often spoken of as irritable bowel syndrome. There is no anatomic or biological substratum nor objective findings to support a diagnosis of gluten susceptibility. True, this syndrome could be caused by a stimulation of the immune system (increase in IL 17) and could, in some cases, benefit from a gluten-free diet.
But this type of diet, sometimes misguidedly prescribed, constitutes a profitable market for the food industry, is not risk free and often reduces the quality of life. ‘False food allergies’ (due to additives and preservatives such as metabisulfites or glutamates) are similar,  but should be differentiated from real food allergy.

Gluten Food allergy, well-described and diagnosed by A.Moneret-Vautrin’s Nancy team (S. Denery-Papini et al. Allergy 2012 67 1023-1032) can be caused by either wheat  proteins, or gluten proteins modified by removal of the amide group (deamidated G, DG) that can be found, in food industry (cereal flours, pork sausages, soups, industrial biscuits) but also, because of their solubility, in cosmetics (creams, shampoos) responsible for contact urticaria. All the Symptoms of this Food Allergy range from urticaria to anaphylactic shock, and include exercise-induced anaphylaxis.
It should be noted that some patients, while tolerant to wheat flour, may present allergic reactions to DG whose allergenicity is due to different epitopes (omega 2, gliadine) having a strong affinity to IgE. Hence we should take this particular entity into account for the diagnosis and before proceeding with any food eviction.

Comments and questions welcome:

*Pr. Claude Molina: This email address is being protected from spambots. You need JavaScript enabled to view it.

**Dr Jacques Gayraud: This email address is being protected from spambots. You need JavaScript enabled to view it.
Last updated 25 July 2014