Table of contents :

• type I hypersensitivities : T_h2 polarization

Epidemiology : by 2015, as many as 50% of all Europeans may suffer allergy
Allergies can be :
• seasonal : they are usually triggered by outdoor airborne allergens
• perennial :
The nomenclature system for allergens is defined by a designation that is composed of the first 3 letters of the  genus; a space; the first letter of the species name; a space and an arabic number. In  the event that 2 species names have identical designations, they are discriminated from one another by adding one or  more letters (as necessary) to each species designation.
The allergen may follow ...
• respiratory route (aeroallergens)

Spermatophyta (seed plants)
• Coniferopsida
• Coniferales
• Cupressaceae
• Chamaecyparis
• Chamaecyparis obtusa

=> Cha o 1
• Cryptomeria
• Cryptomeria japonica (Japanese cedar)

=> Cry j 1
• Cupressus
• Cupressus arizonica

=> Cup a 1
• Juniperus
• Juniperus ashei (Ozark white cedar)

=> Jun a 1
=> Jun a 3
• Juniperus oxycedrus (prickly juniper)

=> Jun o 2
• Magnoliophyta (a.k.a. Angiospermae, flowering plants) => pollens (expecially from anemophila plants, i.e. those which let their pollen be spread by wind, while entomophila produce far less pollen; studied by aerobiology)
• Noon pollen unit : the activity present in the saline extract from one millionth of a grain of pollen.
=> pollenoses
• eudicotyledons
• core eudicots
• Asteridae
• Ericales
• Actinidiaceae
• Actinidia
• Actinidia chinesis

=> Act c 1
• Lecythidaceae
• Bertholletia
• Bertholletia excelsa

=> Ber e 1
• euasterids I
• Lamiales
• Oleaceae
• Ligustrum
• Ligustrum vulgare (common privet)

=> Lig v 1
• Olea
• Olea europaea

=> Ole e 1
=> Ole e 2
=> Ole e 3
=> Ole e 4
=> Ole e 5
=> Ole e 6
=> Ole e 7
=> Ole e 8
• Syringa
• Syringa vulgaris (common lilac)

=> Syr v 3
• euasterids II
• Apiales
• Apiaceae
• Apium
• Apium graveolens

=> Api g 1
=> Api g 2
=> Api g 3
=> Api g 4
• Asterales (a.k.a. Compositae or daisy family)
• Asteraceae
• Asteroideae
• Anthemideae
• Artemisia spp. (mugworts)
• Artemisia vulgaris

=> Art v 1 (reacts with IgE from > 95% of patients allergic to mugworts)
• Heliantheae
• Ambrosia (ragweed)
• Ambrosia artemisiifolia (common ragweed)

=> Amb a 1
=> Amb a 2
=> Amb a 3
=> Amb a 5
=> Amb a 6
• Ambrosia psilostachya

=> Amb p 5
• Ambrosia trifida (giant ragweed)

=> Amb t 5
• Helianthus
• Helianthus annuus (common sunflower)

=> Hel a 2
• Parthenium spp.
• Rosidae
• eurosids I
• Fabales
• Fabaceae
• Papilionoideae
• Phaseoleae
• Glycine
• Glycine max (soybean)

=> Gly m 1
=> Gly m 3
• Fagales
• Betulaceae
• Alnus
• Alnus glutinosa

=> Aln g 1
=> Aln g 4
• Betula (birch)
• Betula verrucosa (a.k.a. European white birch) pollen (BP)

=> Bet v 1
=> Bet v 2
=> Bet v 3
=> Bet v 4
=> Bet v 5
=> Bet v 6 (cross-reactive with Pyr c 5)
=> Bet v 7
• Carpinus
• Carpinus betulus

=> Car b 1
• Corylus
• Corylus avellana

=> Cor a 1
• Malpighiales
• Euphorbiaceae
• Hevea
• Hevea brasiliensis (Para rubber tree)

=> Hev b 1
=> Hev b 3
=> Hev b 5
=> Hev b 6
• Hev b 6.02 / hevein
=> Hev b 8
=> Hev b 9
=> Hev b 10
=> Hev b 11 / latex chitinase : its hevein-domain displays 58% identity to hevein (Hev b 6.02).
Epidemiology ranges from 7% in general population to 17% of health care workers and > 50% of patients with spina bifida, atopics, individuals who required frequent surgical instrumentations, and all persons who have regular contact with latex products (50% in rubber workers)
Natural rubber latex (NRL) protein antigens and terpens (in rubber sterile medical gloves and rubberized clothes) absorbed onto the starch powder on the gloves)
Symptoms & signs :
=> allergic contact urticaria from latex (ACUL).
=> latex-fruit syndrome (LFS) : approximately 30-50% of individuals who are allergic to NRL show an associated hypersensitivity to some plant-derived foods, especially freshly consumed fruits :
• Persea americana (avocado)
• Musa spp. (banana)
• chestnut
• kiwi
• Prunus persica (peach)
• Lycopersicon esculentum (tomato)
• Solanum tuberosum (potato)
• bell pepper
The prevailing hypothesis is allergen cross-reactivity :
• plant defence proteins
• hevein (Hev b 6.02) cross-reacts with class I chitinases containing an N-terminal hevein-like domain
• b-1,3-glucanase cross-reacts with proteins of bell pepper
• Hev b 7 cross-react with patatin
• Hev b 11 displays 70% identity to the endochitinase from avocado
Furthermore, patients with allergy to plant-derived foods and associated pollinosis show a high frequency of IgE reactivity to the pan-allergen profilin, which may cause positive serum IgE determinations to NRL. It is not always clear whether latex sensitization precedes or follows the onset of food allergy. Symptoms vary from oral allergy syndrome to severe anaphylactic reactions, which are not uncommon.
• Mercurialis
• Mercurialis annua

=> Mer a 1
• Ricinus
• Ricinus communis

=> Ric c 1
• Rosales
• Rosaceae
• Amygdaloideae
• Prunus
• Prunus armeniaca (apricot)

=> Pru ar 1
=> Pru ar 3
• Prunus avium (sweet cherry)

=> Pru av 1
=> Pru av 3
=> Pru av 4
• Prunus domestica (garden plum)

=> Pru d 3
• Prunus persica (peach)

=> Pru p 3
• Maloideae
• Malus
• Malus x domestica (apple tree)

=> Mal d 1
=> Mal d 3
=> Mal d 4
• Pyrus
• Pyrus communis (pear)

=> Pyr c 1
=> Pyr c 3
=> Pyr c 4
=> Pyr c 5 (cross-reactive with Bet v 6)
• Urticaceae
• Parietaria
• Parietaria judaica

=> Par j 1
=> Par j 2
=> Par j 3
• eurosids II
• Brassicales
• Brassicaceae
• Arabidopsis
• Arabidopsis thaliana

=> Ara t 8
• Brassica
• Brassica juncea (Indian mustard)

=> Bra j 1
• Brassica napus (rape)

=> Bra n 1
=> Bra n 2
• Brassica rapa (field mustard)
• Sinapis
• Sinapis alba (a.k.a. Brassica hirta, white mustard)

=> Sin a 1
• Liliopsida
• Poales
• Poaceae (a.k.a. Gramineae)
• Ehrhartoideae
• Oryzeae
• Oryza
• Oryza sativa (rice)

=> Ory s 1
• PACC clade
• Chloridoideae
• Cynodonteae
• Cynodon
• Cynodon dactylon (Bermuda grass)

=> Cyn d 1
=> Cyn d 7
=> Cyn d 12
• Panicoideae
• Andropogoneae
• Zea
• Zea mays
• Zea mays subsp.mays (a.k.a. maize, Indian corn)
=> Zea m 1
=> Zea m 14
• Pooideae
• Aveneae
• Holcus
• Holcus lanatus (velvet grass)

=> Hol l 1
• Phalaris
• Phalaris aquatica (canary grass)

=> Pha a 1
=> Pha a 5
• Phleum
• Phleum pratense (timothy grass)

=> Phl p 1
=> Phl p 2
=> Phl p 5a
=> Phl p 5b
=> Phl p 6
=> Phl p 7
=> Phl p 11
• Poeae
• Dactylis
• Dactylis glomerata

=> Dac g 2
=> Dac g 3
=> Dac g 4
• Lolium
• Lolium perenne (perennial ryegrass)

=> Lol p 1
=> Lol p 2
=> Lol p 3
=> Lol p 5
• Poa
•  Poa pratensis (Kentucky bluegrass)

 => Poa p 9
• Triticeae
• Hordeum
• Hordeum vulgare

=> Hor v 1
• pollen extract : a preparation of the pollen of certain plants, such as ragweed, used in the diagnosis and treatment of inhalant allergy
Allergenic proteins are present in many parts of plants, such as grass pollen or apple skin. Although normally harmless, they cause sufferers to generate an immune response as if they had an infection. Previous research has focused on the sequence of amino acids that make up the allergens, but scientists often found that very different sequences from unrelated plants triggered almost identical allergic responses. To find out what difference protein shape makes, researchers used computer models to look at the structures of 129 common food allergens, then classified them according to their surface features. The allergens belonged to only 20 of 3,849 possible protein 'families', and just 4 families accounted for 66% of them^ref. The most active protein shapes may have developed soon after flowering plants evolved, > 100 million years ago, and been conserved throughout subsequent diversification. If a new protein belongs to one of these families, it has a higher likelihood of being an allergen. So scientists developing genetically modified plants, for example, could use the information to avoid producing proteins that might trigger allergies. The researchers now plan to catalogue the structures of further allergenic proteins, to help them understand exactly how the different shapes trigger certain immune responses. One question they want to answer is why peanut allergies can be so severe, when the related pea species pose little threat.
Web resources :
• British Aerobiology Federation (BAF)
• European Pollen Information (EPI)
• Nordisk Aerobiologisk Förening (NAF)
• Pollen Atlas by the Polish Allergy Society
• Pollen Research Unit (PRU)
• Electronic Mailbase Discussion Group : airborne-particulates
Fungi / Mycophytes
• Ascomycota
• Pezizomycotina
• Dothideomycetes
• Pleosporales
• Leptosphaeriaceae
• mitosporic Leptosphaeriaceae
• Epicoccum
• Epicoccum nigrum

=> Epi n 1
• Pleosporaceae
• mitosporic Pleosporaceae
• Alternaria
• Alternaria alternata group
• Alternaria alternata

=> Alt a 1
=> Alt a 3
=> Alt a 6
=> Alt a 7
=> Alt a 10
=> Alt a 11
=> Alt a 12
• Dothideomycetes et Chaetothyriomycetes incertae sedis
• Dothioraceae
• mitosporic Dothioraceae
• Aureobasidium
• Aureobasidium pullulans

=>
• Mycosphaerellaceae
• mitosporic Mycosphaerellaceae
• Cladosporium
• Cladosporium herbarum

=> Cla h 3
=> Cla h 4
=> Cla h 5
=> Cla h 6
=> Cla h 12
• Eurotiomycetes
• Eurotiales
• Trichocomaceae
• mitosporic Trichocomaceae
• Aspergillus
• Aspergillus fumigatus
=> Asp f 2 (> 90% of sensitized patients)
=> Asp f 3
=> Asp f 4
=> Asp f 6
=> Asp f 7
=> Asp f 8
=> Asp f 12
• => Asp f 15
• Aspergillus restrictus
=> Asp f 1
• Penicillium
• Penicillium citrinum

=> Pen c 19
• Leotiomycetes
• Helotiales
• Sclerotiniaceae
• Botryotinia
• Botryotinia fuckeliana (a.k.a. Botrytis cinerea)

=>
• Sordariomycetes
• Hypocreales
• Nectriaceae
• Nectria
• Nectria haematococca
• Fusarium solani

=> Fus s 1
• Saccharomycotina
• Saccharomycetes
• Saccharomycetales
• mitosporic Saccharomycetales
• Candida
• Candida albicans (a.k.a. Candida stellatoidea)

=> Can a 1
• mitosporic Ascomycota
• Stachybotrys
• Stachybotrys chartarum (a.k.a. Stachybotris atra, Stachybotris alternans)
=> ?
• Basidiomycota
• Hymenomycetes
• Homobasidiomycetes
• Agaricales
• Agaricaceae
• Coprinus
• Coprinus comatus (shaggy mane)

=> Cop c 2
• Ustilaginomycetes
• Exobasidiomycetidae
• Malasseziales
• Malassezia
• Malassezia furfur

=> Mal f 1
=> Mal f 2
=> Mal f 3
Metazoa
• Nematoda
• Chromadorea
• Ascaridida
• Ascaridoidea
• Anisakidae
• Anisakis
• Anisakis simplex

=> Ani s 3
• Arthropoda
• Chelicerata
• Arachnida
• Acari stools; Acariformes; Sarcoptiformes; Astigmata
• Acaroidea
• Acaridae
• Acarus
• Acarus siro

=> Aca s 13
• Tyrophagus
• Tyrophagus putrescentiae

=> Tyr p 2
• Analgoidea
• Pyroglyphidae
• Dermatophagoides
• Dermatophagoides farinae (a.k.a. American house dust mite (HDM))

=> Der f 1
=> Der f 2
=> Der f 3
=> Der f 6
=> Der f 7
• Dermatophagoides microceras

=> Der m 1
• Dermatophagoides pteronyssinus (a.k.a. European house dust mite (HDM))
• Der p 1 is a proteolytic enzyme that cleaves IL-2Ra on T cells (decreasing lymphocyte proliferation and IFN-g production), CD23 on B cells (removing inhibition on IgE synthesis), activates PAR-2 and inhibits PAR-1.
• Der p 2
• Der p 3
• Der p 4
• Der p 5
• Der p 6
• Der p 7
• Der p 8
• Der p 10
• Euroglyphus
• Euroglyphus maynei

=> Eur m 1
=> Eur m 2
=> Eur m 3
• Glycyphagoidea
• Echimyopodidae
• Blomia
• Blomia tropicalis

=> Blo t 3
=> Blo t 5
=> Blo t 12
=> Blo t 13
• Glycyphagidae
• Glycyphagus
• Glycyphagus domesticus
• Lepidoglyphus
• Lepidoglyphus destructor (a.k.a. storage mite) :

=> Lep d 1
=> Lep d 2
=> Lep d 5
=> Lep d 7
=> Lep d 10
=> Lep d 13
Staying in bed longer is a good way to keep your sheets mite-free. Dermatophagoides pteronyssinus mites feed on scales of dead human skin, soo they are often found sharing our beds. Chemical sprays are available to kill the mites, but the creatures can evolve resistance extremely quickly, and people are reluctant to spray insecticides on their beds. Changes in the domestic environment can reduce numbers of dust mites in beds : the mites race from the hot, dry end towards cooler, humid conditions as mites can't drink water like we can and have to absorb it from the atmosphere using little glands on the surface of their body. Mites cannot survive in conditions below 50% humidity, because they cannot get enough water from the atmosphere. But the extra water in the air from a quick shower can raise the humidity in a house enough to sustain the mites. People with mites should open windows or use an extractor fan after having a shower. Leaving the duvet on the bed during the day can make a big difference, because it keeps moisture in the sheets and mattress. It's best to leave the covers off. It gives you an excuse for a messy bedroom. Even better, staying in bed longer raises the temperature of the mattress enough to make the mites uncomfortable, despite the extra moisture produced by a sleeping body. And simply raising the bedroom temperature from 16°C to 18°C can cut mite numbers by a factor of 10. A typical London bed could have 80 times more mites by 2050 if the world's warming increases humidity levels as predicted. People assume that a bed is a homogeneous environment, but it's actually very variable : a single mattress can sustain up to 1.5 million mites in the right conditions
Web resources :
• Dust Mite Project
• Dust Mite Facts
• Hexapoda
• Insecta
• Hexagenia : a genus of mayflies (order Ephemeroptera)
• H. bilineata is the lake fly, a species found on the shores of Lake Erie whose cast skins may cause asthma.
• Dicondylia; Pterygota; Neoptera; Orthopteroidea; Orthoptera; Caelifera (grasshoppers => locusts)
• Locusta migratoria (migratory locust)
• Schistocerca gregaria (desert locust)
• Nomadacris septemfasciata (red locust)
=> occupational disease in research laboratories and environmental exposure during swarm of grasshoppers in Central Africa (Mauritania, Niger, and Sudan : a major locust plague in 1987 to 1989 originated in western Sudan and spread as far as India) caused mainly by inhalation of microscopic locust particles or their feces (commonly called frass). Workers rearing locusts suffered rhinitis, itching skin, bronchitis, and ultimately asthma, and generally in that sequence. Because of these problems there should be good air circulation and extraction fans in insectaries, and sometimes workers may need to wear protective masks or even respirators. A useful bibliography of insects causing inhalant allergies is given by TE Bellas (1982). Concerning the original report linking illness in Sudan to a hormone that is released by locusts during the mating season, this could be true. Studies on the desert and migratory locusts have shown that in response to crowding they become darker due to production of a neurohormone consisting of 11 amino acids. So it is possible that locusts with this hormone are more allergenic than those that have not produced it. Although allergies arising from locusts are usually reported in insectary workers who are in great physical contact with locusts, because of the incredible numbers (1000 million or more!) of locusts in locust plagues or swarms it is not surprising that other people, especially those with asthma or a predisposition to asthma develop series allergies.
• Pterygota
• Neoptera
• Endopterygota
• Diptera
• Nematocera
• Culicoidea
• Aedes
• Aedes aegypti (yellow fever mosquito)

=> Aed a 1
=> Aed a 2
=> Aed a 3
• Siphonaptera
• Pulicidae
• Pulicinae
• Ctenocephalides
• Ctenocephalides felis

=> Cte f 1
• Orthopteroidea
• Dictyoptera
• Blattaria
• Blaberoidea
• Blattellidae
• Blattellinae
• Blattella
• Blattella germanica (cockroach)

=> Bla g 1
=> Bla g 2
=> Bla g 4
=> Bla g 5
=> Bla g II
• Blattoidea
• Blattidae
• Periplaneta
• Periplaneta americana (American cockroach)

=> Per a 3
=> Per a 7
• Crustacea
• Malacostraca
• Eumalacostraca
• Eucarida
• Decapoda
• Pleocyemata
• Astacidea
• Nephropoidea
• Nephropidae
• Homarus
• Homarus americanus (American lobster)

=> Hom a 1
• Brachyura
• Eubrachyura
• Portunoidea
• Portunidae
• Charybdis
• Charybdis feriatus

=> Cha f 1
• Palinura
• Palinuroidea
• Palinuroidea
• Palinuridae
• Panulirus
• Panulirus stimpsoni

=> Pan s 1
• Chordata
• Craniata
• Vertebrata
• Euteleostomi
• Mammalia
• Eutheria
• Carnivora
• Fissipedia : epidermidis derivatives (dander) from pets (pet allergies)

Web resources : Allerpet
• Canidae
• Canis
• Canis familiaris (dog)

=> Can f 1
=> Can f 2
=> Can f 3
• Felidae
• Felis
• Felis catus (cat)

=> Fel d 1. Ex vivo Fel d 1-specific HLA-DRB1*0101-restricted CD4⁺ T cells express high levels of CCR7, CD62L, CD27, and CD28 and proportionately low levels of tissue-specific homing receptors and T_h1 and T_h2 cytokine production, placing the cells largely within the central memory subgroup^ref.
=> Fel d 2
• Perissodactyla
• Equidae
• Equus
• Equus caballus (horse)

=> Equ c 1
=> Equ c 2
=> Equ c 4
=> Equ c 5
• Rodentia
• Sciurognathi
• Muridae
• Murinae
• Mus
• Mus musculus (mouse)

=> Mus m 1
• Rattus
• Rattus norvegicus (rat)

=> Rat n 1
Pathogenesis :  pollen-associated lipid mediators, such as phytoprostanes, can modulate in vitro some DC functions by inhibiting IL-12 p70 production and potentiating their T_h2-polarizing capacity toward naive T cells seems to be in line with our observations and point out the relevance of lipid pollen fractions (either secreted or membrane associated) in influencing the adaptive DC-dependent immune response^ref.
Symptoms & signs : most animal-derived major allergens causing respiratory sensitization belong to the family of proteins called lipocalins. The current list comprises the major allergens of horse, cow, dog, mouse, rat and cockroach as well as beta-lactoglobulin of cow's milk. Their sequential identity varies but the 3D structure is conserved. They are present in body fluids and secretions. Several lipocalins are able to bind and transport small hydrophobic ligands like retinol. The immunological characteristics of lipocalin allergens are poorly known. Cow dust-derived allergen, Bos d2, which is a potent inducer of IgE production, was observed to induce the weak proliferative responses of peripheral blood mononuclear cells of asthmatic patients upon stimulation in vitro. The responses were T_h2-deviated and directed to a few epitopes in Bos d2. One of the epitopes, situated adjacent to a structurally conserved region of lipocalins, was recognized by the T cells of all patients. Computer predictions suggested that human endogenous lipocalins may contain epitopes in the corresponding region. The allergenicity of lipocalins may be associated with the adaptation of the immune system to the presence of endogenous lipocalins^{ref1, ref2}.
• if Ø > 10 mm => allergic rhinitis / anaphylactic rhinitis

Epidemiology : hay fever affects about 10-15% of adults in industrialized nations.

Symptoms : nasal obstruction, clear rhinorrhoea, sneezing, nasal congestion, itching of the eyes (conjunctivitis), soft palate, and nose, and occasional associated headache, mostly frontal. Some cases of allergic rhinitis are similar to a cold, but they usually last only 1-2 days or over 10 days. Chronic rhinitis may lead to nasal polyps (edema with eosinophil infiltration). Prevalence doesn't relate with [total IgE]_plasma.
• seasonal allergic rhinitis (SAR) / hay fever : simply focusing one's thoughts on allergen-free environments can reduce symptoms of hay fever by 33%. 79 patients with moderate to severe allergic reactions to grass or tree pollen received training on self-hypnosis.To achieve successful results using self-hypnosis one must first enter a trance-like state and then focus the mind on a particular theme. The whole process can take as little as 5 minutes. The Swiss researchers instructed the participants to imagine they were in a place where allergies do not torture them, such as on the beach or the ski slopes. The patients were encouraged to think about "glittering snow crystals", chilly temperatures and other snowy phenomena, in order to tap into as many channels of perception as possible. About 40 patients stuck with the regime for roughly 2 years, and were tested for their biological response to allergens: they were exposed to pollen and their congestion was assessed using a device that measures airflow through nasal passages. The participants were tested twice: once in the absence of self-hypnosis, and once after practising this form of therapy. Their symptoms, as measured by the congestion test and from simply asking the patients how they felt, dropped by a third thanks to hypnosis. The study is interesting, but patients may have been more influenced by their belief that the treatment would work than by the hypnosis itself : a bigger study is needed. But the results were encouraging enough to tell people to try it, because this intervention is free of side-effects. The treatment may have other benefits: some people can't afford the medicine^ref
• nonseasonal or perennial allergic rhinitis (PAR) / atopic rhinitis
Signs : edema and pallor of the turbinates, especially the inferior turbinates and the anterior tips of the middle turbinates. The turbinates may be so engorged they appear purple. The posterior turbinate tips may protrude into the nasopharynx or become irregular and look like mulberries. Red or inflamed mucosa has also been noted, especially if the allergen is a pollutant.
Laboratory examinations : sinus X-rays
Therapy : enzyme potentiated desensitization, in which b-glucuronidase (BG) is administered with low doses of mixed allergens, was proposed in the 1970s for specific immunotherapy. The BG currently commercially available in a purified and standardized preparation devoid of any allergen has been suggested as a regulator in the allergic immune response, acting on the cytokine-network of T_h2 cells. A double-blind trial with a single-dose of BG proved effective in preventing symptoms in adult patients with rhinoconjunctivitis due to grass pollens. The aim of this randomized double-blind placebo-controlled trial was to confirm the safety and effectiveness of double-dose intradermal BG immunotherapy in preventing symptoms in children suffering from chronic rhinoconjunctivitis and/or asthma due to dust mite. 125 children with dust-mite related chronic rhinoconjunctivitis and/or asthma were randomized to the BG treated group (67) or the placebo group (58). All patients were screened before treatment (TO), at BG or placebo administration (T1 and T3), and at 3 and 9 months after T1 (T2 and T4). Drug intake and bronchial, nasal and ocular symptoms were recorded in a diary. Patients in both groups completed the study and BG treatment was well tolerated without side effects. Significant differences in symptoms were observed, in particular for conjunctivitis (P= .008). The total drug intake for allergic symptoms was significantly lower in the treated group than in the placebo group (P<. 01). BG immunotherapy is efficacious, safe, and well tolerated in allergic children. Moreover, good compliance with the administration of 2 doses per year and the lack of significant side effects makes the benefit/risk ratio of this treatment particularly favorable^ref
‡
• if Ø < 10 mm => allergic or atopic tracheobronchial asthma (not to be confused with other kinds of asthma).

Epidemiology :
• prevalence = 0.8-5% (15% of children and 10% of adults in the UK) = 100-150 million people worldwide.
• USA : 15 millions; 9 million children under the age of 18; 3.8 million of those children are between 5 and 11 : of these 3.8 million, 6.3% have had an asthma attack in the last year. Children with asthma miss > 14 million school days every year, making asthma the number one cause of school absences due to chronic conditions.
• UK : between 1996 and 2003 new episodes of asthma (the mean weekly incidence of a first or new attack) fell by 46% among men and boys and by 41% among women and girls. The biggest decline was among children aged under 5 years—a fall of nearly two thirds. New episodes halved among the 5 to 24 years age group^ref.
Asthma has been increasing in prevalence in the U.S. since 1980
A broad consensus exists that in most Western countries the prevalence of asthma increased over the last four decades of the 20th century. This is based largely on repeat studies of school age children. Evidence is emerging that in recent years this trend has flattened or fallen in some countries. For example, as part of the UK arm of the international study of asthma and allergies in childhood (ISAAC), repeat studies found that self reported symptoms of asthma in 13-14 year old children had fallen by about 20% in the UK between 1995 and 2002^ref. This trend was also observed in the health survey for England between 1996 and 2001. Over the same period a similar fall in symptoms of asthma in 6-7 year old children reported by parents was seen in Melbourne^ref. On the other hand, the only available repeat survey of preschool children noted a major increase in prevalence between 1990 and 1998.4 A global picture of recent trends in children will soon be provided by the results of ISAAC phase 3, which has obtained trends in prevalence between 1995 and 2002 in more than 100 centres in 58 countries. Little information exists about long term trends in adults, but recent trends in the UK seem to be flat^ref. These data are limited by the lack of an objective measure of asthma in large populations and the reliance on surveys to elicit symptoms of wheezy breathlessness, which are likely to represent a heterogeneous group of disorders^ref. Questions about lifetime prevalence are subject to serious recall bias, and the usual compromise is to rely on the 12 month period of prevalence in an attempt to capture the intermittent nature of symptoms experienced by most people with asthma, while limiting the recall entailed and avoiding problems with labelling. Trends in the cultural perception and naming of symptoms might explain the trends observed in prevalence studies^ref, and while it remains true that without objective measures we cannot be certain how much is real and how much is artefact it seems unlikely that artefact would completely explain the observed trends. If the trend is indeed flattening or decreasing, might it be explained by trends in health care? The use of inhaled corticosteroids, an effective treatment, has increased in most countries for which data are available. Over the 1990s, sales of inhaled corticosteroids in the UK increased from 1.9 to 4.3 patient months per 10 000 population and by the late 1990s about 66% of patients with asthma treated by their general practitioner were receiving inhaled corticosteroids alone or in combination. This is one plausible explanation for the reduction in attacks of severe asthma as reflected in the fall in hospital admissions, primary care contacts for asthma attacks, and mortality that has occurred in the UK and some other Western countries over the past decade. Although this may also have had some effect on prevalence by affecting prognosis or severity, it is unlikely to explain the whole of the recent changes in prevalence, which have also been observed in milder cases and in associated atopic conditions such as hay fever and atopic eczema, which are not treated with inhaled corticosteroids^ref. More likely, the recent changes in the prevalence of asthma reflect changes in the underlying cause of asthma or its exacerbating factors. While theories abound, we must admit that neither the rise nor the recent flattening or fall in the prevalence of asthma can be explained on the basis of current knowledge. Any single explanation would need to account for both the rise and fall of the prevalence of asthma. A substantial change in prevalence would require a large change in an important risk factor to which a large proportion of the population was exposed^ref. Various explanations have been proposed to explain trends and geographical variations in asthma, including air pollution, tobacco smoke, aeroallergens, diet, and infections in early life, but none has been shown by epidemiological studies to fit the above requirements. At an individual level, the most powerful risk factor for asthma is a history of atopic disease such as atopic eczema or allergic rhinitis. However, one promising idea, the hygiene hypothesis, has not explained the epidemiology of atopy or asthma^ref. Since there is some evidence that atopic diseases tend to track together over time in populations, trends in asthma may partly reflect changes in the incidence of atopy in the population; but since the proportion of asthma cases attributable to atopy is less than one half^ref, factors unrelated to atopy must also be important. Any advance in our understanding of trends is likely to depend on the development of new theories of causation together with better methods of measuring and classifying asthma in population studies^ref.
• mortality = 2 per 100,000 / year in males, 1.5 per 100,000 in females (180,000 people per year worldwide)
Risk factors :
• intrinsic :
• female gender
• SNPs in :
• ADAM33
• C5
• GPRA
• AAA1
• arginine transporter
• arginase I
• arginase II
• nuclear erythroid 2 p45-related factor 2 (Nrf2) is a redox-sensitive basic leucine zipper transcription factor that is involved in the transcriptional regulation of many antioxidant genes. oxidative stress has been postulated to play an important role in the pathogenesis of asthma; although a defect in antioxidant responses has been speculated to exacerbate asthma severity, this has been difficult to demonstrate with certainty. Disruption of the Nrf2 gene leads to severe allergen-driven airway inflammation and hyperresponsiveness in mice. Enhanced asthmatic response as a result of ovalbumin sensitization and challenge in Nrf2-disrupted mice was associated with more pronounced mucus cell hyperplasia and infiltration of eosinophils into the lungs than seen in wild-type littermates. Nrf2 disruption resulted in an increased expression of the T_h2 cytokines IL-4 and IL-13 in BALF and in splenocytes after allergen challenge. The enhanced severity of the asthmatic response from disruption of the Nrf2 pathway was a result of a lowered antioxidant status of the lungs caused by lower basal expression, as well as marked attenuation, of the transcriptional induction of multiple antioxidant genes. The responsiveness of Nrf2-directed antioxidant pathways may act as a major determinant of susceptibility to allergen-mediated asthma^ref
• extrinsic :
• total maternal vitamin C intake during pregnancy was not statistically significantly associated with wheezing during the first year of life : however, in the second year of life, total vitamin C intake was positively associated with wheezing after adjusting for confounding variables, including total vitamin E intake. > 1 portion of fruit per day was positively associated with eczema in the second year of life. There were no consistent statistically significant associations between eczema in the first 2 years of life and total maternal intake of vitamin E, b-carotene, selenium, magnesium, copper and zinc. Maternal vitamin E intake during pregnancy was negatively associated with wheeze in the absence of a cold. In children whose mothers were atopic, there was a negative association between maternal vitamin E intake and childhood eczema^ref
• RSV and other respiratory viral infections trigger exacerbations of asthma : viral T_h1 type inflammation promotes expression of T_h2 chemokines which allow T_h2 cell recruitment even in the absence of the specific allergen-dependent activation
• exposure to NO₂, SO₂, CO, phthalates and/or tobacco smoking (the only sufficient cause if practiced in prenatal and postnatal periods). Only particles with Ø < 5 mm can reach bronchioli.
• occupational asthma :
• children with a history of ear infections were 57% more likely than other children to be diagnosed with asthma and 70% more likely to have had wheezing in the previous year. Moreover, the risk of asthma and wheezing increased as the number of ear infections rose. Factors associated with an increased risk of ear infection included higher parental education level and smoking during pregnancy. The link with higher parental education may be due to such parents being more likely to enrol their children in day-care centres, a well-known risk factor for recurrent ear infections. However, it is also possible that higher education means better access to healthcare and, therefore, such cases are simply more likely to be diagnosed and reported. Specific viruses or bacteria that cause recurrent ear infections may play a role in the development of asthma. It is also possible that antibiotics that are commonly used to treat ear infections increase the risk of asthma, but more research is needed in this area.
• several factors related to climate, including altitude, latitude, temperature and humidity, seem to affect asthma and eczema rates. But indoor relative humidity topped the list. In Western Europe, for example, for every 10% mean annual increase in indoor humidity, the prevalence of asthma symptoms reported went up by 2.7%. One explanation may be that dust mites, which may play a role in asthmatic attacks, prefer a humid environment, as does a mold that can cause allergic reactions. Less asthma is reported in countries where outdoor humidity fell below 50% for > 1 month a year, or where there were higher altitudes or greater variations in temperature^ref.
• several, but not all, studies have observed an association between antibiotics and asthma.  However, the key issue is whether these associations are causal or whether they are due to ‘reverse causation’ – that is, children who are already predisposed to asthma get more respiratory infections and thus use more antibiotics. An ecological study compared antibiotics sales in 28 countries with the prevalence of symptoms of asthma, rhinitis and eczema in 13-14 year olds in 99 centres from 28 countries. By comparing populations as a whole instead of looking at individuals within those populations, the researchers hoped to avoid the possibility of ‘reverse causation’ confounding the results. As previous studies have found an association between the level of ‘Westernization’ or ‘affluence’ of a country and asthma prevalence, the researchers also adjusted their analyses to take into account the gross national product (GNP) of each country (GNP being a readily available marker for a country’s level of affluence). In the unadjusted analyses, there is a positive correlation between per capita antibiotics sales and the prevalence of asthma, rhinitis and eczema. However, the associations between antibiotic sales and asthma were negative once the analyses had been adjusted for GNP^ref.
• it has been hypothesized that childhood asthma rise in the developed world could result at least in part from the increasing exposure of children to toxic chlorination products in the air of indoor swimming pools. Among children aged 13 to 14 years, the prevalence of wheezing by written questionnaire, of wheezing by video questionnaire and of ever asthma across Europe increased respectively by 3.39% (95% CI 1.96-4.81), 0.96% (95% CI 0.28 to 1.64) and 2.73% (95% CI 1.94-3.52) with an increase of one indoor chlorinated pool per 100,000 inhabitants. Similar increases were found when analyzing separately centres in Western or Northern Europe and for ever asthma in Southern Europe. In children aged 6 to 7 years (33 centres), the prevalence of ever asthma also increased with swimming pool availability (1.47%; 95% CI 0.21-2.74). These consistent associations were not found with other atopic diseases and were independent of the influence of altitude, climate and GDP per capita. The prevalence of childhood asthma and availability of indoor swimming pools in Europe are linked through associations that are consistent with the hypothesis implicating pool chlorine in the rise of childhood asthma in industrialized countries^ref.
• It could be hearty laugh or just a giggle, but the mere act of laughing can trigger an asthma attack. > 50% of 235 asthma patients entering a disease management program reported that their asthma could be triggered by laughter. This occurs more commonly than most doctors appreciate. In the cohort studied, 132 of 235 subjects reported that laughter was a trigger for their asthma,. Primary symptoms of laughter-induced asthma were cough, chest tightness and shortness of breath. Participants in the study filled out a list of asthma triggers. Patients were assessed for other asthma triggers, disease severity and clinical course such as emergency room visits and hospitalizations. The researchers found no differences in other asthma triggers between the 2 groups and there was no statistical difference between groups in the patients' age, duration of disease, disease severity and family history of asthma. The clinical course of asthma, number of visits to the emergency room or hospitalizations, was similar in both groups. Exercise-induced asthma was more frequent in patients with laughter-induced asthma, with 61% of subjects with laughter-induced asthma also reporting exercise-induced asthma, compared to 35% of those who did not have laughter-induced asthma. 53% of patients who said their asthma was well controlled had laughter-induced asthma. The connection between asthma-induced and exercise-induced asthma suggests the presence of a shared physiologic mechanism
Children with frequent wheezing (>= 4 episodes in the prior year) and either 1 major risk factor (a parental history of asthma or a personal history of atopic dermatitis) or 2 of 3 minor risk factors (allergic rhinitis, eosinophilia, and wheezing without colds) are thought to be at high risk^ref
Pathogenesis : bronchial airway hyperreactivity (AHR) to inhaled allergens (T_h2 cytokines produced by pulmonary V14i NKT cells crucially regulate the development of asthma and T_h2-biased respiratory immunity against nominal exogenous antigens) => epithelial disruption, subepithelial fibrosis, mucosal edema => transient or chronic bronchoconstriction due to contraction of SMCs, exudate, mucus. C/EBP-a, responsible for stopping cells proliferating, misses in bronchial smooth-muscle cells from patiens with asthma, explaining the failure of glucocorticoids to inhibit proliferation in vitro^ref. Even for uniform smooth muscle activation of a symmetric bronchial tree, the presence of minimal heterogeneity breaks the symmetry and leads to large clusters of poorly ventilated lung units. These clusters are generated by interaction of short- and long-range feedback mechanisms, which lead to catastrophic shifts similar to those linked to self-organized patchiness in nature^ref.
• Despite early findings that eosinophils are not required for pathogenesis of asthma^ref, 2 new studies do agree that eosinophils contribute to clinical asthma, although many of their findings seem to conflict^ref : in mice with a total ablation of the eosinophil lineage, increases in airway hyperresponsiveness and mucus secretion are similar to those observed in wild-type mice, but eosinophil-deficient mice are significantly protected from peribronchiolar collagen deposition and increases in airway smooth muscle^ref. Allergen challenge of a transgenic line of mice (PHIL) that are specifically devoid of eosinophils, but otherwise have a full complement of hematopoietically derived cells, demonstrates that eosinophils are required for pulmonary mucus accumulation and the airway hyperresponsiveness associated with asthma^ref.
• Patients with refractory asthma have evidence of up-regulation of the TNF-a axis. As compared with patients with mild-to-moderate asthma and controls, patients with refractory asthma had increased expression of membrane-bound TNF-a, TNFR1, and TNF-a–converting enzyme by peripheral-blood monocytes. In the clinical trial, as compared with placebo, 10 weeks of treatment with etanercept was associated with a significant increase in the concentration of methacholine required to provoke a 20 percent decrease in the FEV₁ (mean difference in doubling concentration changes between etanercept and placebo, 3.5; 95% confidence interval, 0.07 to 7.0; P=0.05), an improvement in the asthma-related quality-of-life score (by 0.85 point; 95% confidence interval, 0.16 to 1.54 on a 7-point scale; P=0.02), and a 0.32-liter increase in post-bronchodilator FEV1 (95% confidence interval, 0.08 to 0.55; P=0.01)^ref.
• 45 to 86% (mean, 63%) of the pulmonary CD4⁺CD3⁺ cells (and 73% of the CD3⁺ cells) in patients with moderate-to-severe persistent asthma were not class II MHC–restricted CD4⁺ T cells but, rather, iNKT cells that produce T_h2 cytokines (100 times the levels in the peripheral blood). In contrast, the CD4⁺ T cells found in the lungs of patients with sarcoidosis were conventional CD4⁺CD3⁺ T cells, not NKT cells; > 90% of the iNKT cells in the lungs of patients with asthma are CD4⁺ cells. Antibody to the TcRs Va24 and Vb11, although effective in identifying resting iNKT cells in peripheral blood, were less sensitive than CD1d tetramers and monoclonal antibody 6B11 in detecting iNKT cells in BALF. This finding might be due to the fact that the iNKT cells in the lungs of patients with asthma are partially activated, even in stable asthma, and that the TcR expression on iNKT cells is greatly down-regulated after the activation of iNKT cells, as shown by the high expression of mRNA^ref. This finding mirrors those in mouse models of allergic asthma showing an essential role for iNKT cells in the development of allergen-induced airway hyperreactivity^{ref1, ref2}.
Symptoms & signs : dyspnea referred as different from cardiogenic one (short inspiration followed by very long and difficult expiration, with no respiratory pause), accompanied by pulmonary overdistension, dry => wet cough, anxiety, diaphoresis. Each attack lasts 1-2 hours, usually during sleep.
• status asthmaticus : a particularly severe episode of asthma that does not respond adequately to ordinary therapeutic measures and may require hospitalization.
Patients with asthma have a higher incidence of sinusitis, nasal polyposis, nasal congestion, and olfactory disturbances : asthmatic patients also fail primary sinus surgery more frequently and require revision surgery due to a common abnormality in the respiratory epithelium of the upper and lower airway in these patients.
Laboratory examinations : see asthma ; respiratory acidosis
Grading :

	symptoms & signs	night symptoms	FEV1 or PEF	PEV daily variability	reacutizations	therapyref
						antiinflammatory	bronchodilators
mild intermittent	< 2 attacks per week	< 2 / month	> 80%	< 20%	none	none	SABA < 4 times per month (for therapy or prophylaxis)
mild persistent	3-6 attacks per week	> 2 / month	> 80%		rare	< 500 mg / die (bid/od) of inhaled beclomethasone propionate or equivalent GR agonists, or slow-releasing theophyllin, cromones, or cysLTR antagonists
moderate persistent	daily asthma	> 1 / week	60-80%		frequent	200 < inhaled beclomethasone propionate or equivalent GR agonists < 1000 mg / die (or theophyllin, SABA or cysLTR antagonists; or GR agonists > 1,000 mg / die) in fixed combinations	LABA : salmeterol seems to trigger attacks in some (3 times more patients taking the medicine died of asthma than those not taking it: risks may be greater in African-Americans)
severe persistent	continuous asthma	frequent	< 60%		frequent, severe, and impairing physical activity	inhaled beclomethasone propionate or equivalent GR agonists > 1,000 mg / die or SABA or other immunosuppressive drugs
	reacutizations (including near-fatal asthma)					2 puffs of inhaled SABA every 10-20' up to 2 hrs, mechanical ventilation if PCO2 > 45 mmHg

parameter / severity	mild	moderate	severe
dyspnea	while walking, may stay supine	while talking, prefers seated position	at rest, projected forward
conversation	dialogues	sentences	words
level of consciousness	may be agitated	often agitated	often agitated
breath rate	increased	increased	> 30 bpm
recruitment of accessory respiratory muscles and suprasternal retractions	no	yes	yes
wheezes (intensity does not relate to diameter, but silent chest marks a severe condition)	moderate end-expiratory	intense, also inspiratory	intense, also inspiratory (finally espiratory wheezes first and inspiratory wheezes then cannot be heard)
heart rate	< 100 bpm	100-120 bpm	> 120 bpm
paradoxical pulse	< 10 mmHg	+/- 10-25 mmHg	> 25 mmHg
PEF%	> 80%	60-80%	< 60%
PaO2 while on environmental air	normal	> 60 mmHg	< 60 mmHg (cyanosis)
PaCO2	< 45 mmHg	< 45 mmHg	> 45 mmHg
SaO2	> 95%	91-95%	< 90%

Therapy of reacutizations :
• O₂-therapy
• SABA (salbutamol for 5'; nebulization at a distance of 4 fingers from mouth; a spacer or a nebulizer (not a common aerosolizer) is required to create particles small enough to reach bronchioles) every 20 minutes for up to 3 times. Albuterol (salbutamol) is composed of equal amounts of 2 isomers - one active, R-albuterol, and one inactive - S-albuterol. The anti-inflammatory effects of steroids are enhanced by R-albuterol, while S-albuterol abolishes the anti-inflammatory steroid effects. If you're using this combination then your asthma should be under control and you shouldn't actually need to take your relieve medicine very often, if at all. If you're currently using salbutamol > 3 times a week, then you should be on a low-dose inhaled steroid : you'd take that regularly and you'd find that you didn't need the salbutamol
• daily therapy with inhaled corticosteroids appears to be effective in reducing symptoms in high-risk young children with frequent wheezing^{ref1, ref2, ref3, ref4, ref5, ref6}. In school-age children, treatment with inhaled corticosteroids is associated with significant improvements in various measures of asthma control; these improvements disappear within months after the inhaled corticosteroids are discontinued^{ref1, ref2, ref3, ref4}. In preschool children at high risk for asthma, 2 years of inhaled-corticosteroid therapy (fluticasone propionate 88 µg twice daily) did not change the development of asthma symptoms or lung function during a third, treatment-free year. These findings do not provide support for a subsequent disease-modifying effect of inhaled corticosteroids after the treatment is discontinued. Similary, intermittent inhaled corticosteroid therapy had no effect on the progression from episodic to persistent wheezing and no short-term benefit during episodes of wheezing in the first 3 years of life^ref
• GR agonists
• PDE4 inhibitors (teophyllin 5 mg/kg in i.v. bolus in 20 minutes, then maintenance with 0.5 mg/kg/hr with infusion pump)
• telithromycin at a daily dose of 800 mg for 10 days reduces symptoms via unclear mechanisms^ref
• do NOT use mucolytics (during acute attacks may cause bronchospasm), sedatives or b-blockers
• dried ivy (Hedera helix L.) leaf extract preparations (e.g. Prospan^®) have effects with respect to an improvement of respiratory functions of children with chronic bronchial asthma, but more far-reaching conclusions can hardly be drawn because of a meagre database, including the fact that only one primary trial included a placebo control. Further research, particularly into the long-term efficacy of the herbal extract, is needed^ref
Macroscopic anatomy : areas of pulmonary overdistension and resorption atelectasis; mucus into bronchial lumina
Microscopic anatomy : eosinophils => Charcot-Leyden crystals, Curschmann's spirals and Laënnec's pearls (soft casts of the smaller bronchial tubes expectorated) in sputum
Web resources :
• AsmaNet
• Asthma Information Center
• Asthma at CDC
• Asthma articles by New England Journal of Medicine
• Asthma Gene Database
• Asthma Zero Mortality Coalition (AZMG)
• German Asthma Information Center
• Global Allergy and Asthma European Network
• Global Initiative for Asthma (GINA)
• Interasma
• National Asthma Education Program (NAEP)
• Sandler Program for Asthma Research
• Journals :
• Pediatric Asthma Virtual Journal
Prevention : Storm van Leeuwen chamber : a room that can be kept free of airborne antigens for allergic patients (of historical interest)
• oral route
• drug allergies
• food allergies (FA) can be triggered by Eukarya :

Spermatophyta
• Magnoliophyta
• eudicotyledons
• core eudicots
• Asteridae
• euasterids I
• Solanales
• Solanaceae
• Solanum
• Solanum tuberosum (potato)

=> Sola t 2
=> Sola t 4
• euasterids II
• Apiales
• Apiaceae
• Daucus
• Daucus carota (carrot)

=> Dau c 1
• lamiids
• Lamiales
• Pedaliaceae
• Sesamum
• Sesamum indicum (sesame)

=> ?
• Rosidae
• eurosids I
• Fabales
• Fabaceae
• Papilionoideae
• Aeschynomeneae
• Arachis
• Arachis hypogaea (peanut)

=> Ara h 1
=> Ara h 2
=> Ara h 5
In the US 1.3% of adults are allergic to peanuts or tree nuts. They cause > 80% of food-induced anaphylaxis. Reaction severity may increase over time but up to 25% of young peanut allergic individuals may outgrow their peanut allergy. Peanut's allergenicity may be affected by the method of cooking, with roasted peanuts appearing more allergenic than boiled or fried peanuts. Peanut antigens do not intrinsically induce T_h2 skewing in peanut-specific lymphocytes from peanut-allergic children, but the type of response depends upon the donor’s allergic status
• Rosales
• Rosaceae (rose family)
• Rosoideae
• Fragaria
• Fragaria x ananassa (a.k.a. Fragaria chiloensis X Fragaria virginiana, strawberry)
• Liliopsida
• Commelinidae
• Poales
• Poaceae
• PACC clade
• Panicoideae
• Andropogoneae
• Zea
• Zea mays
• Zea mays subsp.mays (a.k.a. maize, Indian corn)
StarLink CBH351 was a corn variety developed by developed by Aventis CropScience genetically modified to produce a (Italic)Bacillus thuringiensis(/Italic) (Bt) endotoxin, Cry9C: allowed for animal feed, it was found in taco shells and other foods for human consumption in 2000. Allergic reactions were not confirmed, but tools for postmarket assessment were limited. Workers in agricultural and food preparation facilities have potential inhalation exposure to plant dusts and flours. In 1999, researchers found that migrant health workers can become sensitized to certain Bt spore extracts after exposure to Bt spraying.
• Pooideae
• Triticeae
• Hordeum
• Hordeum vulgare
• Hordeum vulgare subsp. vulgare (barley)
=> urticaria from beer : 10-kDa protein from barley malt, the basic ingredient used in brewing
Metazoa
• Chordata
• Craniata
• Vertebrata
• Euteleostomi
• Actinopterygii : the major allergens in fish are parvalbumins and IgE cross-recognition of parvalbumins from different fish species and cod and frog^ref has been shown. a-parvalbumin as the allergen implicated in a case of IgE-mediated anaphylaxis to fried frog leg muscle^ref. Also Anisakis simplex allergens.
• Neopterygii
• Teleostei
• Euteleostei
• Neoteleostei
• Acanthomorpha
• Paracanthopterygii
• Gadiformes, Gadidae, Gadus
• Gadus callarias (Baltic cod)

=> Gad c 1
• Protacanthopterygii
• Salmoniformes
• Salmonidae
• Salmo
• Salmo salar (Atlantic salmon)

=> Sal s 1
• Archosauria
• Aves
• Neognatha
• Galliformes
• Phasianidae
• Phasianinae
• Gallus
• Gallus gallus (chicken)

hen's egg
=> Gal d 1
=> Gal d 2
=> Gal d 3
• Mammalia
• Eutheria
• Cetartiodactyla
• Ruminantia
• Pecora
• Bovoidea
• Bovidae
• Bovinae
• Bos
• Bos taurus
=> cow's milk (85% of allergic babies are no longer so at age 3 !)
=> acute diarrhea and vomiting
=> chronic colitis and anemia
=> atopic eczema/urticaria
=> diarrhea with positive occult fecal blood test
=> Bos d 2
=> Bos d 4
=> Bos d 5
=> Bos d 6
...  wheat, soy products and tree nuts, such as almonds, pecans and brazil nuts.
Epidemiology : prevalence of food allergy in the general population, not including oral allergy syndrome, is about 1-2% = 8% of preschool children (2% of newborns suffer from either cow'smilk allergy or intolerance), 2% of older children, 1-3% of adults
While adults might tend to be allergic to fish, crustaceans, peanuts, and tree nuts, children, on the other hand, tend to be allergic to cow's milk, egg white, wheat, and soy. In Italy cow's milk > egg white > fish (0,1-0,5% in Italy)
Symptoms usually occur within 5-10', but can occur as long as 4-6 hours after ingestion
• tingling, swelling and itching of the lips, mouth and throat can begin within seconds
• nausea and vomiting
• diarrhoea
• allergic rhinitis
• acute urticaria / hives (or chronic from preservatives), angioedema
• rarely anaphylaxis
Diagnosis by skin prick test (SPT) confirmed by ...
• food elimination trial : suspected food items are eliminated from your diet one at a time for > 1-2 weeks. If you feel better when a suspected food is eliminated, your health-care provider might add that food back to your diet to see if your symptoms recur. It's helpful to keep a food diary of everything consumed, and in what amounts.
• food challenge test : a challenge test for determining food allergens; a small amount of a lyophilized preparation of the suspected allergen is administered orally and the patient is monitored for reactions such as rash, rhinorrhea, or diarrhea
• double-blind placebo control (DBPC) food challenge test requires that you swallow a pill containing the suspected allergen and another containing sugar (negative control). This test is rarely done because it must be done in a hospital setting to monitor for a serious reaction.
Prognosis : while most children outgrow food allergies, some carry them into adulthood (in particular, allergies to peanuts, tree nuts, fish and shellfish usually are not outgrown). 30 % of adults undergo remission after 2 years of allergen-free diet.
Prevention :
• don't introduce solid foods until 6 months of age
• breast-feed babies until they are at least 1 year old. However, you also will have to avoid highly allergenic foods since allergens can pass through breast milk. If breast-feeding isn't possible, discuss the choice of formula with your doctor.
• introduce new foods in small portions and one at a time. Monitor for reactions for several days before introducing the next food. Do not introduce foods that commonly cause allergies, such as peanuts, egg whites or fish until the second year of life.
• wait to give the child cow's milk until age 1 and peanuts until age 3.
• check the list of ingredients on food labels and always ask the waiter about food ingredients before eating at a restaurant.
Web resources :
• Food Allergy Advisor
• Center for Food Safety and Applied Nutrition (CFSAN) at FDA
• Food Allergy & Anaphylaxis Network (FAAN)
• Food Allergy Center
• National Conference on Children with Sensitivities (NCCS)
• Eating without casein by Beth Kevles
• systemic route through the bloodstream (=> anaphylaxis)

Aetiology :
• food allergens (33-45%) : especially eggs, seafood, nuts, grains, milk and peanuts (80%; CFR : 0.07%)
• drugs (29%)
• i.v. antimicrobials
• sulfonamides
• nitrofurantoin
• penicillin


• ampicillin
• spiramycin
• neomycin
• cephalosporins
Although allergic reactions to antibiotics account for only a small proportion of reported adverse drug reactions, they are associated with substantial morbidity and mortality and increased health care costs^{ref1, ref2, ref3}. Estimates of the prevalence of antibiotic allergy vary widely^{ref1, ref2, ref3}. Any organ may be affected, but the skin is most commonly involved. Data from the Boston Collaborative Drug Surveillance Program^ref indicate a 2.2% frequency of cutaneous drug reactions among hospitalized patients, with the antibiotics amoxicillin, trimethoprim–sulfamethoxazole, and ampicillin the most commonly implicated agents. More recently, a 6-month prospective analysis in France showed a prevalence of cutaneous drug eruptions of 3.6 per 1000 hospitalized patients; antibiotics accounted for 55% of cases^ref
Pathogenesis : allergic reactions are, by definition, immunologically mediated. A single drug may initiate multiple immune responses, and multiple antigenic determinants may be formed from a single drug^{ref1, ref2}. For instance, a major antigenic determinant and several minor determinants have been identified for penicillin^ref. T cells play a predominant role in delayed hypersensitivity reactions, including antibiotic-induced maculopapular eruptions^ref, whereas drug-specific IgE antibodies cause urticarial reactions
Symptoms & signs : highly variable in terms of the type and severity of the reaction and the organ systems affected. Factors such as the type of drug used, the nature of the disease being treated, and the immune status of the patient are all believed to play an important role in the clinical expression of these responses (Adkinson NF Jr. Drug allergy. In: Adkinson NF Jr, Yunginger J, Busse W, Bochner B, Holgate S, Simons F, eds. Middleton's allergy: principles and practice. Philadelphia: Mosby, 2003:1679-94). The most common reactions to antibiotics are maculopapular skin eruptions, urticaria, and pruritus^{ref1, ref2}. These reactions typically occur days to weeks after initial exposure to a drug (during which sensitization occurs), although on secondary exposure, the reaction usually occurs much sooner, sometimes within minutes to hours^ref. Occasionally, a hypersensitivity syndrome develops that is characterized by fever, eosinophilia, and other extracutaneous manifestations^ref.
Antibiotic-induced allergic reactions : some antibiotics also affect organs other than the skin. For instance, the combination of amoxicillin and clavulanic acid can cause cholestatic liver injury, whereas hemolysis and cytopenias, most likely caused by drug-specific antibodies, are reported with high-dose penicillin and cephalosporin therapy^ref. Severe reactions such as anaphylaxis, mediated by drug-specific IgE antibodies, are rare. Although anaphylaxis may theoretically occur with any antibiotic, only the frequency of penicillin-induced anaphylaxis is well described (1 in 5000 to 10,000 courses of drug therapy)^ref.
Special cases :
• HIV : patients infected with the HIV have a higher frequency of allergic reactions to a range of antimicrobial agents (including sulfamethoxazole, amoxicillin, clindamycin, dapsone, and amithiozone) than do persons without HIV infection^ref. Hypersensitivity to trimethoprim–sulfamethoxazole occurs in 20 to 80% of patients infected with HIV, as compared with 1 to 3% of persons not infected with HIV.16 These high rates of reaction are not well understood but may be caused by altered drug metabolism, decreased glutathione levels, or both^{ref1, ref2}
• cystic fibrosis : in approximately 30% of patients with cystic fibrosis, allergy develops to one or more antibiotics^ref. Piperacillin, ceftazidime, and ticarcillin have been most commonly implicated, with the risk being higher after parenteral administration than after oral administration. Repeated exposure to antibiotics and immune hyperresponsiveness are thought to underlie the high prevalence of allergic reactions in patients with this disease^ref.
• infectious mononucleosis : the likelihood of cutaneous reactions to penicillins and other antimicrobial agents is increased among patients with infectious mononucleosis^{ref1, ref2}. Although the mechanism of these drug reactions is not clear, the viral infection may alter the immune status of the host^ref. In such cases, the implicated agent can be readministered safely once the viral infection has resolved^ref.
Strategies and evidence :
• clinical assessment : medical history taking is critical in the evaluation of antibiotic allergy^ref and in distinguishing allergic reactions from other adverse reactions. This information is important, since overdiagnosis of allergic reactions can lead to unnecessary use of more costly antimicrobial agents and may promote the development of resistant microorganisms^ref.Whenever possible, patients who are being evaluated for possible antibiotic allergy should be encouraged to provide all medical records related to previous adverse drug reactions (Litt JZ. Litt's drug eruption reference manual: including drug interactions. 10th ed. London: Taylor & Francis, 2004)
• penicillins : urticaria, angioedema, anaphylaxis, maculopapular skin eruptions, exfoliative dermatitis, vesicular eruptions, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, serum sickness-like reactions, vasculitis, cytopenias
• cephalosporins : urticaria, angioedema, anaphylaxis, maculopapular skin eruptions, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, renal dysfunction, toxic nephropathy, hepatic dysfunction, aplastic anemia, hemolytic anemia
• sulfonamides : urticaria, angioedema, anaphaylaxis, maculopapular drug eruptions, exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, allergic myocarditis, periarteritis nodosa, serum sickness-like reactions, photosensitivity reactions
• macrolides : urticaria, angioedema, anaphylaxis, mild skin eruptions, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis
• fluoroquinolones : urticaria, angioedema, pruritus, photosensitivity, flushing, fever, chills, angioedema, erythema nodosum, anaphylaxis, hyperpigmentation
• tetracyclines : urticaria, angioedema, anaphylaxis, pericarditis, polyarthralgia, exacerbation of systemic lupus erythematosus, pulmonary infiltrates with eosinophilia
• vancomycin : anaphylaxis, drug fever, eosinophilia, skin eruptions (including exfoliative dermatitis), Stevens-Johnson syndrome, toxic epidermal necrolysis, vasculitis
Algorithm for the management of antibiotic allergy :

Nonimmune-mediated drug reactions are more common than are immune-mediated reactions. Treatment of immune-mediated reactions depends on whether the patient has a history of an immediate, IgE-mediated reaction (e.g., anaphylaxis), as compared with a delayed reaction that is mediated by T cells, antibodies, or immune complexes (categorized as type 2 to 4 hypersensitivity reactions). Skin testing is used for the detection of allergen-specific IgE antibodies. A negative response on a skin test cannot be interpreted to mean that IgE antibodies are absent except in the case of penicillin, in which case readministration of the drug in patients with a negative skin test is associated with a minimal risk of immediate reaction. Severe reactions include cytopenias, immune-complex disease, hypersensitivity syndrome, blistering rashes, and involvement of extracutaneous organs such as the liver. Treatment options are determined by the nature and severity of the reaction. In all cases, however, education and communication with the patient and the referring physician as to the detailed nature of the final diagnosis are vital to ensure the success of the management strategy and to prevent a recurrence of antibiotic allergy. Checklist for distinguishing immune-mediated reactions from nonimmune-mediated reactions :
• could the reaction have been caused by known pharmacologic actions of the drug ? The Physician's Desk Reference provides information about the nonimmune adverse reactions of many prescription drugs (toxicity, side effects, secondary effects, and drug interactions)
• was it a first-reaction dose ? Reactions that occur with the first dose either are not immunologically mediated or are an indication of previous sensitization. Sensitization can occur through previous exposure to a drug that contains antigenic determinants common to both drugs
• what was the nature of the reaction ? urticaria, angioedema, and anaphylaxis that are caused by drug-specific IgE antibodies require a period of sensitization (i.e., do not occur with the first dose). These reactions may also be caused by direct release of mast-cell mediators (nonimmune mechanism), and in such instances, the reaction may occur with the first dose. Certain antibiotics (vancomycin and the fluoroquinolones) cause direct mast-cell release in the absence of drug-specific IgE antibodies. These reactions may recur with repeated administration of the drug. Maculopapular exanthems are mediated by T cells. Certain cytopenias are immune-induced and are caused by IgG or IgM antibodies
• what was the time course of the reaction ? immediate reactions (i.e., those that occurs within minutes to hours) suggest an IgE-mediated event and are caused by preformed IgE antibodies. Drug-induced hemolysis may occur within a short time after drug administration if preformed drug-specific IgG antibodies exist. Delayed reactions (i.e. those that occur after days to weeks) suggest a drug-specific T-cell-mediated mechanism. Reactions in this category include eczematous, maculopapular, bullous, and pustular exanthems.
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